- Neutrophils and reactive oxygen metabolites play a key role in microvascular injury in dermal burn wounds at 4 hours post-burn ("late phase" injury). Depletion of neutrophils or administration of hydroxyl radical scavengers significantly reduced vascular permeability.
- In contrast to its role in "early phase" injury, complement does not contribute to "late phase" dermal microvascular damage after burns, as depletion of complement did not impact vascular permeability. Blockade of C5a also did not have a protective effect.
- Development of "late phase" dermal vascular damage involves the pro-inflammatory cytokines IL-1, IL-6 and TNF-α, as blockade of these cytokines significantly
The study investigated the protective effects of losartan, an angiotensin II type 1 receptor blocker, on intestinal ischemia-reperfusion injury in rats. Forty rats were divided into four groups: sham operation, ischemia, ischemia/reperfusion (I/R), and I/R + losartan treatment. Biochemical markers and histopathological analysis of the jejunum tissue were performed. Losartan treatment reduced oxidative stress markers, inflammation, and apoptosis compared to the I/R group. This suggests losartan may protect against intestinal damage caused by ischemia-reperfusion injury.
This study investigated the effects of gallic acid on testicular injury caused by ischemia-reperfusion in a rat testicular torsion model. Forty rats were divided into four groups: a control group, a torsion group, a torsion/detorsion group, and a torsion/detorsion plus gallic acid group. Biochemical markers and immunohistochemical staining for caspase-3 and TNF-α were analyzed. The results showed that gallic acid treatment decreased oxidative stress markers, reduced apoptosis and inflammation, and helped protect testicular tissue compared to the torsion/detorsion group without treatment. The study suggests that gallic acid may be a potential therapeutic agent for testicular ischemia-reperfusion injury.
Objective: To investigate the changes in the retina due to deltamethrin toxicity and the process in cell inflammation and apoptosis.
Study Design: Sixteen Wistar albino rats were randomly divided into two groups as control (n=8) and deltamethrin (n=8) groups. Saline was given to the control group, and 0.5 mL of 5 mg/kg deltamethrin was given to the deltamethrin group for 14 days each. Blood was collected for biochemical analysis. Retinal tissue was processed for histological examination.
Results: Compared to the control group, MDA levels were high while GSH and CAT levels were low in the deltamethrin group. Histopathological analysis showed spaces between the pigment epithelium, irregularity in the delimiting membrane, degenerated ganglion, cone and bacillus cell, pyknotic nuclei, thinned inner limitation membrane, and thickened vascular wall. The control group showed FAS expression in the pigment layer limiting membranes, in the nuclei of many cone and bacillus cells, and ganglion cells in the control group sections. In the deltamethrin group, FAS expression was observed in the inner and outer limiting membranes of the pigment epithelium, cone and bacillus cells, and ganglion cell nuclei. In the control group, negative NOS expression in the pigment epithelium and outer limiting membranes, internal limitation membrane, and ganglion cells in the cone and bacillus cell nuclei were observed. In the deltamethrin group, NOS expression was positive in the pigment epithelium, cone and bacillus, and ganglion cell nuclei.
Conclusion: We suggest that deltamethrin toxicity induced apoptotic process due to increased inflammation in the retina and may cause visual impairment as a result of neural damage.
Keywords: deltamethrin, FAS, insecticides, NOS, nitric oxide synthase, retina
1) Researchers used a technique called Bacterial Enzyme Combinatorial Chemistry (BECC) to create modified forms of LPS with altered lipid A structures. 2) They screened these modified LPS molecules for their ability to activate NF-κB in human macrophage cells compared to naturally occurring pro-inflammatory LPS. 3) They identified one modified LPS molecule, created using the enzymes LpxF and PagP, that was able to strongly compete with and outcompete pro-inflammatory LPS, shifting its EC50 over 400-fold. This molecule shows promise for potentially treating septic shock.
Objective: To study the effects of resveratrol in neuronal structures in traumatic brain injury (TBI).
Study Design: Thirty rats were categorized as (1) control group (n=10), saline solution administered i.p. for 14 days, (2) TBI group (n=10), trauma induced by weight-drop model on brain, and (3) TBI+Resveratrol group (n=10), 15 minutes after injury the rats were given resveratrol (10 μmoL/kg/i.p.) for 14 days. At the end of the experiment the cerebellum was excised for routine paraffin tissue protocol. Blood samples were tested for serum biochemical markers (MDA, SOD, CAT, and GSH-x).
Results: SOD, GPx, and CAT values were lowest in the TBI group. MDA and histological scores of dilations in vessels, inflammation, degeneration in neurons, apoptosis in microglia, ADAMTS8, and GFAP expressions were highest in the TBI group. Sections of the control group showed normal cerebellar histology. The trauma group showed degenerated ganglion layer, pyknotic and apoptotic Purkinje cell nuclei. Vascular thrombus was seen in the substantia alba and substantia grisea. In the Trauma+Resveratrol group, most pa- thologies observed in the TBI group were improved. In the control group, GFAP protein was expressed in granular cells, axons, dendrites, Purkinje cells, and microglia cells. In the trauma group, increased GFAP expression was observed in glial processes, neurons, and Purkinje cells. In the Trauma+Resveratrol group, GFAP was expressed in molecular layer and glial processes. In the control group, ADAMTS-4 activity was observed in granulosa layer, glial cells, and Purkinje cells. In the trauma group, ADAMTS-4 expression was positive in Purkinje cells and glial cells. In the Trauma+ Resveratrol group, ADAMTS-4 was expressed in Purkinje cells, granular cells, and glial cells.
Conclusion: GFAP and ADAMTS-4 proteins may be involved in regeneration of damaged astroglial cells and other glial cells, Purkinje cells, and synaptic extensions. We suggest that antioxidative drugs such as resveratrol may be alternative target agents in neurological disease.
Keywords: ADAMTS-4, brain, cerebellum, GFAP, rat, resveratrol, traumatic brain injury
This study investigated the effects of spinal cord injury on the bladder tissue of rats. Twenty rats were divided into a control group and spinal cord injury (SCI) group. The SCI group exhibited statistically higher levels of oxidative stress markers (MDA, MPO), epithelial degeneration, vascular dilation, inflammation, and expression of VEGF and APAF-1 compared to the control group. The SCI group also had lower levels of the antioxidant GSH. Histological examination of the SCI group showed degeneration of epithelial cells, thickened fibrosis, dilated blood vessels, and increased VEGF and APAF-1 expression compared to the control group. The results suggest that spinal cord injury leads to increased oxidative stress, inflammation and apoptosis in
This summarizes a study that developed a modified non-biotin polymerized horseradish peroxidase (HRP) immunohistochemical method for diagnosing canine distemper virus (CDV) infection from formalin-fixed tissue samples. The method confirmed CDV infection in seven of eight suspected cases. Labelled CDV antigen was observed in various tissues including brain, spinal cord, kidney, lungs, skin, and others. Compared to microwave pretreatment alone, autoclaving followed by microwave heating produced better labelling results. The non-biotin HRP detection system produced similar results to a conventional biotin-linked system.
1) Inflammatory lung injury was observed in human volunteers after bronchial instillation of aqueous extracts of particulate matter (PM) collected from Utah Valley before and after closure of a local steel mill.
2) Exposure to extracts of PM collected when the mill was operating provoked a greater inflammatory response compared to exposure to extracts collected during the mill shutdown, as evidenced by increased cells and neutrophils in bronchial lavage fluid.
3) These findings correlate with improved health outcomes observed epidemiologically in Utah Valley during the mill shutdown, providing direct human evidence that PM effects can reflect epidemiologic associations.
The study investigated the protective effects of losartan, an angiotensin II type 1 receptor blocker, on intestinal ischemia-reperfusion injury in rats. Forty rats were divided into four groups: sham operation, ischemia, ischemia/reperfusion (I/R), and I/R + losartan treatment. Biochemical markers and histopathological analysis of the jejunum tissue were performed. Losartan treatment reduced oxidative stress markers, inflammation, and apoptosis compared to the I/R group. This suggests losartan may protect against intestinal damage caused by ischemia-reperfusion injury.
This study investigated the effects of gallic acid on testicular injury caused by ischemia-reperfusion in a rat testicular torsion model. Forty rats were divided into four groups: a control group, a torsion group, a torsion/detorsion group, and a torsion/detorsion plus gallic acid group. Biochemical markers and immunohistochemical staining for caspase-3 and TNF-α were analyzed. The results showed that gallic acid treatment decreased oxidative stress markers, reduced apoptosis and inflammation, and helped protect testicular tissue compared to the torsion/detorsion group without treatment. The study suggests that gallic acid may be a potential therapeutic agent for testicular ischemia-reperfusion injury.
Objective: To investigate the changes in the retina due to deltamethrin toxicity and the process in cell inflammation and apoptosis.
Study Design: Sixteen Wistar albino rats were randomly divided into two groups as control (n=8) and deltamethrin (n=8) groups. Saline was given to the control group, and 0.5 mL of 5 mg/kg deltamethrin was given to the deltamethrin group for 14 days each. Blood was collected for biochemical analysis. Retinal tissue was processed for histological examination.
Results: Compared to the control group, MDA levels were high while GSH and CAT levels were low in the deltamethrin group. Histopathological analysis showed spaces between the pigment epithelium, irregularity in the delimiting membrane, degenerated ganglion, cone and bacillus cell, pyknotic nuclei, thinned inner limitation membrane, and thickened vascular wall. The control group showed FAS expression in the pigment layer limiting membranes, in the nuclei of many cone and bacillus cells, and ganglion cells in the control group sections. In the deltamethrin group, FAS expression was observed in the inner and outer limiting membranes of the pigment epithelium, cone and bacillus cells, and ganglion cell nuclei. In the control group, negative NOS expression in the pigment epithelium and outer limiting membranes, internal limitation membrane, and ganglion cells in the cone and bacillus cell nuclei were observed. In the deltamethrin group, NOS expression was positive in the pigment epithelium, cone and bacillus, and ganglion cell nuclei.
Conclusion: We suggest that deltamethrin toxicity induced apoptotic process due to increased inflammation in the retina and may cause visual impairment as a result of neural damage.
Keywords: deltamethrin, FAS, insecticides, NOS, nitric oxide synthase, retina
1) Researchers used a technique called Bacterial Enzyme Combinatorial Chemistry (BECC) to create modified forms of LPS with altered lipid A structures. 2) They screened these modified LPS molecules for their ability to activate NF-κB in human macrophage cells compared to naturally occurring pro-inflammatory LPS. 3) They identified one modified LPS molecule, created using the enzymes LpxF and PagP, that was able to strongly compete with and outcompete pro-inflammatory LPS, shifting its EC50 over 400-fold. This molecule shows promise for potentially treating septic shock.
Objective: To study the effects of resveratrol in neuronal structures in traumatic brain injury (TBI).
Study Design: Thirty rats were categorized as (1) control group (n=10), saline solution administered i.p. for 14 days, (2) TBI group (n=10), trauma induced by weight-drop model on brain, and (3) TBI+Resveratrol group (n=10), 15 minutes after injury the rats were given resveratrol (10 μmoL/kg/i.p.) for 14 days. At the end of the experiment the cerebellum was excised for routine paraffin tissue protocol. Blood samples were tested for serum biochemical markers (MDA, SOD, CAT, and GSH-x).
Results: SOD, GPx, and CAT values were lowest in the TBI group. MDA and histological scores of dilations in vessels, inflammation, degeneration in neurons, apoptosis in microglia, ADAMTS8, and GFAP expressions were highest in the TBI group. Sections of the control group showed normal cerebellar histology. The trauma group showed degenerated ganglion layer, pyknotic and apoptotic Purkinje cell nuclei. Vascular thrombus was seen in the substantia alba and substantia grisea. In the Trauma+Resveratrol group, most pa- thologies observed in the TBI group were improved. In the control group, GFAP protein was expressed in granular cells, axons, dendrites, Purkinje cells, and microglia cells. In the trauma group, increased GFAP expression was observed in glial processes, neurons, and Purkinje cells. In the Trauma+Resveratrol group, GFAP was expressed in molecular layer and glial processes. In the control group, ADAMTS-4 activity was observed in granulosa layer, glial cells, and Purkinje cells. In the trauma group, ADAMTS-4 expression was positive in Purkinje cells and glial cells. In the Trauma+ Resveratrol group, ADAMTS-4 was expressed in Purkinje cells, granular cells, and glial cells.
Conclusion: GFAP and ADAMTS-4 proteins may be involved in regeneration of damaged astroglial cells and other glial cells, Purkinje cells, and synaptic extensions. We suggest that antioxidative drugs such as resveratrol may be alternative target agents in neurological disease.
Keywords: ADAMTS-4, brain, cerebellum, GFAP, rat, resveratrol, traumatic brain injury
This study investigated the effects of spinal cord injury on the bladder tissue of rats. Twenty rats were divided into a control group and spinal cord injury (SCI) group. The SCI group exhibited statistically higher levels of oxidative stress markers (MDA, MPO), epithelial degeneration, vascular dilation, inflammation, and expression of VEGF and APAF-1 compared to the control group. The SCI group also had lower levels of the antioxidant GSH. Histological examination of the SCI group showed degeneration of epithelial cells, thickened fibrosis, dilated blood vessels, and increased VEGF and APAF-1 expression compared to the control group. The results suggest that spinal cord injury leads to increased oxidative stress, inflammation and apoptosis in
This summarizes a study that developed a modified non-biotin polymerized horseradish peroxidase (HRP) immunohistochemical method for diagnosing canine distemper virus (CDV) infection from formalin-fixed tissue samples. The method confirmed CDV infection in seven of eight suspected cases. Labelled CDV antigen was observed in various tissues including brain, spinal cord, kidney, lungs, skin, and others. Compared to microwave pretreatment alone, autoclaving followed by microwave heating produced better labelling results. The non-biotin HRP detection system produced similar results to a conventional biotin-linked system.
1) Inflammatory lung injury was observed in human volunteers after bronchial instillation of aqueous extracts of particulate matter (PM) collected from Utah Valley before and after closure of a local steel mill.
2) Exposure to extracts of PM collected when the mill was operating provoked a greater inflammatory response compared to exposure to extracts collected during the mill shutdown, as evidenced by increased cells and neutrophils in bronchial lavage fluid.
3) These findings correlate with improved health outcomes observed epidemiologically in Utah Valley during the mill shutdown, providing direct human evidence that PM effects can reflect epidemiologic associations.
Objective: To evaluate the antibacterial effects of 4 different cavity disinfectants on Streptococcus mutans, Lactobacillus acidophilus, and Enterococcus faecalis bacteria in different time periods.
Study Design: The antibacterial effects of Cavity Cleanser, Tubulicid Red Label, Chloraxid 2%, and Oxygenated Water cavity disinfectant solutions on E. faecalis (ATCC 29212), S. mutans (ATCC 25175), and L. acidophilus (RSKK 03037) bacterial strains were evaluated by disk diffusion method. In the study where vancomycin antibiogram disc constituted the positive control group, physiological saline solution was used as the negative control group. Standard, sterile, blank antibiogram discs of 5 mm in diameter, in which 15 μL of each material were added, were placed on agar plates at 2.5–3 cm intervals. The inhibition zone diameters formed around the discs that were left to incubate for 24–48 hours at 37°C were measured in millimeters. Statistical analysis of the data was performed using one-way analysis of variance, Kolmogorov-Smirnov, Levene, and Bonferroni tests.
Results: At the end of the study the solutions tested showed a statistically significant antibacterial effect on all bacterial strains used (p<0.05). Cavity Cleanser disinfectant containing 2% chlorhexidine showed the highest antibacterial effect on S. mutans and L. acidophilus, and benzalkonium-containing Tubulicid Red disinfectant on E. faecalis.
Conclusion: The antibacterial effect of all cavity disinfectants used in the study was found to be higher at the end of the 48th hour than at the end of the 24th hour, but there was no statistically significant difference (p>0.05).
Keywords: antibacterial agents; antibacterial effect; cavity disinfectants; chlorhexidine; contamination; dental caries; disinfection; disc diffusion; gram-negative bacteria; gram-positive bacteria
49.Antitumour and Radioprotective activity of Alloe veraAnnadurai B
1) The study examined the anti-tumor and radioprotective effects of Aloe vera in mice.
2) In solid tumor models, Aloe vera significantly reduced tumor volume compared to the control group.
3) In radio protective studies, Aloe vera did not significantly affect body weight or hemoglobin levels in irradiated animals but did slightly increase total white blood cell count compared to radiation alone.
Objective: To investigate the effect of sildenafil on reducing the impact of hepatic ischemia/reperfusion (HIR) injury established by Pringle maneuver on the heart of rats.
Study Design: Forty Wistar albino rats were divided into 4 groups: Sham (laparotomy only), Control (laparotomy following sildenafil application), IR (ischemia/reperfusion injured by HIR), and IR+SIL (injured by HIR following sildenafil application). Ischemia was developed by clamping the hepatoduodenal ligament for 30 minutes; then reperfusion was applied for 30 minutes. Sildenafil (single dose of 50 mg/kg) was administered by oral gavage for 15 minutes before ischemia. Blood samples of rats were collected from Sham and Control groups at 60 minutes and from IR and IR+SIL groups at 30 minutes after initiation of reperfusion for biochemical analysis. Meanwhile, heart tissues were sampled for biochemical analysis. Malondialdehyde (MDA) and total antioxidant capacity (TAC) in serum samples and TAC, total oxidative capacity (TOC), and oxidative stress index in heart tissues were examined biochemically.
Results: Serum MDA levels were elevated significantly in the IR and IR+SIL groups as compared to the sham group. Sildenafil treatment inhibited MDA increase considerably in the IR+SIL group as compared to the IR group. Serum TAC levels were elevated significantly in the sildenafil and control groups (compared with sham groups) and in the IR+SIL group (compared with the IR group). TAC levels detected in heart tissue increased significantly in the IR group as compared to the sham group; however, sildenafil treatment had no effect on this increase.
Conclusion: Heart tissue was affected by HIR. It was revealed that sildenafil treatment may prevent the oxidative stress via increasing serum TAC levels in both control and IR+SIL groups.
This study examined how gene deletions and stressful environments interact to impact fitness in yeast. Single and double gene deletion strains were tested under normal and stressful conditions, including poor nutrients, high temperature, high salinity, and caffeine. The results showed that gene deletions had a relatively smaller negative impact on growth rate in stressful environments compared to normal conditions. Additionally, double deletion strains grew slightly faster than expected based on the individual gene deletions, indicating positive epistasis. This suggests that additional stresses, whether environmental or genetic, have a weaker effect when growth is already impaired. Thus interactions between stressful environments and gene deletions, as well as among gene deletions, tend to alleviate their negative impacts on fitness.
This document summarizes a study that assessed the phototoxicity of various xanthene derivatives against E. coli, S. aureus, and S. cerevisiae. Without light exposure, the compounds showed similar inherent toxicity to each organism, dependent on chemical structure. Upon illumination, the compounds demonstrated phototoxicity, with stronger effects on Gram-positive bacteria and yeast. Compounds with more halogen substituents generated higher levels of reactive oxygen and showed greater phototoxic activity. The results suggest that xanthene derivatives have potential as alternative antimicrobial agents.
The antimicrobial mechanism of ECA water against pseudomonas aeruginosa and ...Trevor William Sievert
This study investigated the antimicrobial mechanism of electrochemically activated water (anolyte) against Pseudomonas aeruginosa and Escherichia coli using SDS-PAGE protein analysis. Bacteria were treated with different concentrations of anolyte and their protein profiles analyzed via SDS-PAGE. Undiluted and 10-1 diluted anolyte were most effective, causing fewer and fainter protein bands compared to untreated bacteria, indicating protein destruction. Dilute anolyte caused extra protein bands, suggesting oxidative stress and protein fragmentation. The results provide insight into anolyte's antimicrobial action by affecting bacterial proteins.
This document summarizes a study that evaluated mitochondrial DNA (mtDNA) fragmentation as a potential time-temperature integrator for monitoring safety and quality in dry roasted peanuts. MtDNA fragmentation was measured using quantitative PCR (qPCR) and compared to reduction of the Salmonella surrogate Enterococcus faecium and changes in peanut color (Hunter L value) during roasting. While E. faecium reduction curves were highly repeatable, mtDNA fragmentation did not correlate linearly with time at a given temperature. Dissection of individual peanuts also showed differential heating effects depending on peanut part. The researchers determined that mtDNA fragmentation as measured by qPCR was too variable for validation of dry roasted peanut processes but could help evaluate heat penetration through
Combined effect of solar drying and gamma radiation on the microbiological qu...Nii Korley Kortei
This study evaluated the combined effect of solar drying and gamma irradiation on the microbiological quality of dried oyster mushrooms (Pleurotus ostreatus) stored at room temperature. Mushrooms were dried using a solar dryer to 12-14% moisture content. Samples were then gamma irradiated at doses from 0-2 kGy. Initial microbial counts for total viable count, Bacillus cereus, yeasts and molds ranged from 1.2-5.3, 0.95-1.4, 0-1.39, and 0-0.8 log CFU/g, respectively. Solar drying and irradiation resulted in an average 0.55 and 0.38 log reduction of total viable count
This study compared the contractile response patterns of ergot alkaloids isolated from tall fescue in bovine lateral saphenous veins. The ergoline alkaloids lysergic acid, lysergol, and ergonovine produced quicker contractile responses that began relaxing immediately, while the ergopeptine alkaloids ergovaline, ergotamine, ergocristine, ergocryptine, and ergocornine had slower, more persistent contractile responses with little to no relaxation over 120 minutes. The different classes of alkaloids produced significantly different contractile response patterns in the veins. Persistent vasoconstriction by certain ergot alkaloids may
Alopecia areata is a common cause of hair loss seen in 3.8% of patients in dermatology clinics and in 0.2% to 2.0% of the general US population. The pathology of the disease remains poorly understood. Hair loss in alopecia areata can range from a single patch to 100% loss of body hair. When hair regrowth occurs in alopecia areata, the new hair may demonstrate pigment alterations, but a change in hair texture (i.e, curly or straight) has rarely been reported as a consequence of alopecia areata.
Biochemical Monitoring of Detoxifying Enzyme Levels in Field Population of Mo...BRNSS Publication Hub
The major cause of resistance mechanism in mosquitoes is the detoxification and degradation of
insecticides by overproduction of various metabolic enzymes. Quantitative metabolic enzyme assays
of carboxylesterases (α and β), mixed function oxidases (MFO), and glutathione S-transferases (GST)
have been commonly used in the detection of insecticide resistance due to its sensitive nature even at low
frequencies. For the present study, larval strains of Culex quinquefasciatus Say and Aedes aegypti (L) were
collected from the Cochin Corporation, Kerala, India, and were assayed to organophosphate temephos
and carbamate propoxur. The resistance ratio of median lethal time for temephos and propoxur from the
field population of C. quinquefasciatus and A. aegypti is higher than the laboratory population. Elevated
levels of α and β esterase enzyme were observed with the ratio of 1.6 and 1.54 for C. quinquefasciatus
and 1.51 and 1.47 for A. aegypti. In Culex mosquitoes, 1.71, and in Aedes, 1.64 fold increase in GST
enzyme level and 1.38 and 1.3 fold increase for the MFO level determined. The study results revealed
the urgent needs of improving the vector control methods by introducing alternative techniques and
strategies against mosquitoes.
- Experiments tested the effect of extracellular self-DNA (exDNA) and heterologous DNA on the growth of 6 species from different taxonomic groups, including bacteria, fungi, algae, plants, protozoa and insects.
- Treatments with conspecific exDNA produced a concentration-dependent growth inhibition in all species, whereas heterologous DNA did not cause inhibition except in one bacterial species.
- The results suggest exDNA may have a general inhibitory effect on biological systems, providing a potential mechanism for self-inhibition and negative feedback observed in different organisms. Further investigation is needed to understand the molecular mechanisms of this effect.
This document describes a project aimed at synthesizing and characterizing novel achiral and chiral ionic liquids containing ester and amide functionality. The ionic liquids were evaluated for their antimicrobial toxicity and biodegradability. Some of the ionic liquids exhibited low toxicity and were readily biodegradable by microorganisms. The suitable ionic liquids were then employed as reaction media in catalytic reactions and as electrolytes in dye-sensitized solar cells, demonstrating their potential as environmentally-friendly solvents.
Biomarker is an objective measure that has been evaluated and confirmed either as an indicator of physiologic health, a pathogenic process or a pharmacologic response to a therapeutic intervention. Biomarkers, whether produces by normal healthy individuals or by individuals affected by specific systemic diseases, are tell tale molecules that could be used to monitor health status, disease onset, treatment response and outcome.The biomarkers can help for the determination of present as well as future disease activity along with diagnosis and previous periodontal diseases.
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The document provides guidance on appropriate online communication. It states that people should behave online as they would in person by being polite, respectful, and avoiding sharing anything they wouldn't say publicly. It also advises being careful with private communications as they may be forwarded without consent. Users should avoid responding to anger online and use proper grammar to effectively convey their message. Sarcasm and jokes can be misunderstood so clarification or emojis may be needed. Personal details should only be shared with known users to avoid becoming a target.
It's all about about rhythm - UX research & design proposal for a park in Sa...Marco Trevisani
Alfredo Nieves-Moreno and Marco Trevisani-Montresor propose a community engagement project in Ciudadela, Puerto Rico to integrate the diverse activities in Santurce and make Ciudadela the cultural center. They will research the community to design experiences promoting connections between residents, businesses, and neighborhoods. The project could include designing Parque San Mateo park and a creative marketplace in Ciudadela to involve the community and showcase Ciudadela and Putnam Bridge as leaders in Santurce's revival. The proposal aims to build consensus and trust through community-focused development.
The document provides guidance on appropriate online communication. It states that people should behave online as they would in person by being polite, respectful, and avoiding sharing private information or messages that could be misinterpreted or forwarded without consent. It also advises taking time before responding angrily online, avoiding all caps which can be seen as shouting, and being mindful that jokes and sarcasm may not translate well without tone of voice or body language cues. Personal information should only be shared with known users to avoid becoming a target.
Rap/hip hop conventions include casual or gangster clothing, references to violence, sex, drugs, and explicit language. Colors are typically black, grey or brown. Pop features young singers performing exaggerated love songs aimed at teens, with happy imagery, dance beats, and occasional rap sections. Rock involves tattooed male artists with unusual hair and unposed, gritty magazine covers dealing with explicit but non-objectifying lyrics about hate. Dance features club/party scenes with short skirts, makeup, dancing, drinking, flashing lights, and DJs over consistent beats that increase and decrease in pace.
Social media refers to broadcasting messages to a wide audience, while social networking involves interacting with individuals. Specifically, social media channels spread information to the masses, whereas social networks connect people. LinkedIn is an example of a social networking site that allows users to connect based on shared interests and workplaces. YouTube exemplifies social media as a platform for broadcasting videos to broad audiences.
The document analyzes and interprets the symbolism and meanings represented in the mastheads of several grime/rap media brands. It finds that most use dark backgrounds combined with bright colors like orange to represent both the hard lives of artists but also convey a message of hope. Bright colors and fonts are used to signify hope and opportunity for success. One masthead without dark elements may symbolize that artists signed to it have already "made it." The analysis concludes most aim to show hope for artists despite current challenges through use of contrasting dark and light colors and bold outlines.
The document outlines the key elements that are commonly found on magazine covers, including the masthead, date, variety of fonts used, strapline, cover line, main image, secondary images, use of house style colors, and barcode with price. While actor images are usually the main cover feature, this particular magazine uses a graphic image instead. The layout demonstrates the standard conventions for presenting essential information on magazine covers.
Objective: To evaluate the antibacterial effects of 4 different cavity disinfectants on Streptococcus mutans, Lactobacillus acidophilus, and Enterococcus faecalis bacteria in different time periods.
Study Design: The antibacterial effects of Cavity Cleanser, Tubulicid Red Label, Chloraxid 2%, and Oxygenated Water cavity disinfectant solutions on E. faecalis (ATCC 29212), S. mutans (ATCC 25175), and L. acidophilus (RSKK 03037) bacterial strains were evaluated by disk diffusion method. In the study where vancomycin antibiogram disc constituted the positive control group, physiological saline solution was used as the negative control group. Standard, sterile, blank antibiogram discs of 5 mm in diameter, in which 15 μL of each material were added, were placed on agar plates at 2.5–3 cm intervals. The inhibition zone diameters formed around the discs that were left to incubate for 24–48 hours at 37°C were measured in millimeters. Statistical analysis of the data was performed using one-way analysis of variance, Kolmogorov-Smirnov, Levene, and Bonferroni tests.
Results: At the end of the study the solutions tested showed a statistically significant antibacterial effect on all bacterial strains used (p<0.05). Cavity Cleanser disinfectant containing 2% chlorhexidine showed the highest antibacterial effect on S. mutans and L. acidophilus, and benzalkonium-containing Tubulicid Red disinfectant on E. faecalis.
Conclusion: The antibacterial effect of all cavity disinfectants used in the study was found to be higher at the end of the 48th hour than at the end of the 24th hour, but there was no statistically significant difference (p>0.05).
Keywords: antibacterial agents; antibacterial effect; cavity disinfectants; chlorhexidine; contamination; dental caries; disinfection; disc diffusion; gram-negative bacteria; gram-positive bacteria
49.Antitumour and Radioprotective activity of Alloe veraAnnadurai B
1) The study examined the anti-tumor and radioprotective effects of Aloe vera in mice.
2) In solid tumor models, Aloe vera significantly reduced tumor volume compared to the control group.
3) In radio protective studies, Aloe vera did not significantly affect body weight or hemoglobin levels in irradiated animals but did slightly increase total white blood cell count compared to radiation alone.
Objective: To investigate the effect of sildenafil on reducing the impact of hepatic ischemia/reperfusion (HIR) injury established by Pringle maneuver on the heart of rats.
Study Design: Forty Wistar albino rats were divided into 4 groups: Sham (laparotomy only), Control (laparotomy following sildenafil application), IR (ischemia/reperfusion injured by HIR), and IR+SIL (injured by HIR following sildenafil application). Ischemia was developed by clamping the hepatoduodenal ligament for 30 minutes; then reperfusion was applied for 30 minutes. Sildenafil (single dose of 50 mg/kg) was administered by oral gavage for 15 minutes before ischemia. Blood samples of rats were collected from Sham and Control groups at 60 minutes and from IR and IR+SIL groups at 30 minutes after initiation of reperfusion for biochemical analysis. Meanwhile, heart tissues were sampled for biochemical analysis. Malondialdehyde (MDA) and total antioxidant capacity (TAC) in serum samples and TAC, total oxidative capacity (TOC), and oxidative stress index in heart tissues were examined biochemically.
Results: Serum MDA levels were elevated significantly in the IR and IR+SIL groups as compared to the sham group. Sildenafil treatment inhibited MDA increase considerably in the IR+SIL group as compared to the IR group. Serum TAC levels were elevated significantly in the sildenafil and control groups (compared with sham groups) and in the IR+SIL group (compared with the IR group). TAC levels detected in heart tissue increased significantly in the IR group as compared to the sham group; however, sildenafil treatment had no effect on this increase.
Conclusion: Heart tissue was affected by HIR. It was revealed that sildenafil treatment may prevent the oxidative stress via increasing serum TAC levels in both control and IR+SIL groups.
This study examined how gene deletions and stressful environments interact to impact fitness in yeast. Single and double gene deletion strains were tested under normal and stressful conditions, including poor nutrients, high temperature, high salinity, and caffeine. The results showed that gene deletions had a relatively smaller negative impact on growth rate in stressful environments compared to normal conditions. Additionally, double deletion strains grew slightly faster than expected based on the individual gene deletions, indicating positive epistasis. This suggests that additional stresses, whether environmental or genetic, have a weaker effect when growth is already impaired. Thus interactions between stressful environments and gene deletions, as well as among gene deletions, tend to alleviate their negative impacts on fitness.
This document summarizes a study that assessed the phototoxicity of various xanthene derivatives against E. coli, S. aureus, and S. cerevisiae. Without light exposure, the compounds showed similar inherent toxicity to each organism, dependent on chemical structure. Upon illumination, the compounds demonstrated phototoxicity, with stronger effects on Gram-positive bacteria and yeast. Compounds with more halogen substituents generated higher levels of reactive oxygen and showed greater phototoxic activity. The results suggest that xanthene derivatives have potential as alternative antimicrobial agents.
The antimicrobial mechanism of ECA water against pseudomonas aeruginosa and ...Trevor William Sievert
This study investigated the antimicrobial mechanism of electrochemically activated water (anolyte) against Pseudomonas aeruginosa and Escherichia coli using SDS-PAGE protein analysis. Bacteria were treated with different concentrations of anolyte and their protein profiles analyzed via SDS-PAGE. Undiluted and 10-1 diluted anolyte were most effective, causing fewer and fainter protein bands compared to untreated bacteria, indicating protein destruction. Dilute anolyte caused extra protein bands, suggesting oxidative stress and protein fragmentation. The results provide insight into anolyte's antimicrobial action by affecting bacterial proteins.
This document summarizes a study that evaluated mitochondrial DNA (mtDNA) fragmentation as a potential time-temperature integrator for monitoring safety and quality in dry roasted peanuts. MtDNA fragmentation was measured using quantitative PCR (qPCR) and compared to reduction of the Salmonella surrogate Enterococcus faecium and changes in peanut color (Hunter L value) during roasting. While E. faecium reduction curves were highly repeatable, mtDNA fragmentation did not correlate linearly with time at a given temperature. Dissection of individual peanuts also showed differential heating effects depending on peanut part. The researchers determined that mtDNA fragmentation as measured by qPCR was too variable for validation of dry roasted peanut processes but could help evaluate heat penetration through
Combined effect of solar drying and gamma radiation on the microbiological qu...Nii Korley Kortei
This study evaluated the combined effect of solar drying and gamma irradiation on the microbiological quality of dried oyster mushrooms (Pleurotus ostreatus) stored at room temperature. Mushrooms were dried using a solar dryer to 12-14% moisture content. Samples were then gamma irradiated at doses from 0-2 kGy. Initial microbial counts for total viable count, Bacillus cereus, yeasts and molds ranged from 1.2-5.3, 0.95-1.4, 0-1.39, and 0-0.8 log CFU/g, respectively. Solar drying and irradiation resulted in an average 0.55 and 0.38 log reduction of total viable count
This study compared the contractile response patterns of ergot alkaloids isolated from tall fescue in bovine lateral saphenous veins. The ergoline alkaloids lysergic acid, lysergol, and ergonovine produced quicker contractile responses that began relaxing immediately, while the ergopeptine alkaloids ergovaline, ergotamine, ergocristine, ergocryptine, and ergocornine had slower, more persistent contractile responses with little to no relaxation over 120 minutes. The different classes of alkaloids produced significantly different contractile response patterns in the veins. Persistent vasoconstriction by certain ergot alkaloids may
Alopecia areata is a common cause of hair loss seen in 3.8% of patients in dermatology clinics and in 0.2% to 2.0% of the general US population. The pathology of the disease remains poorly understood. Hair loss in alopecia areata can range from a single patch to 100% loss of body hair. When hair regrowth occurs in alopecia areata, the new hair may demonstrate pigment alterations, but a change in hair texture (i.e, curly or straight) has rarely been reported as a consequence of alopecia areata.
Biochemical Monitoring of Detoxifying Enzyme Levels in Field Population of Mo...BRNSS Publication Hub
The major cause of resistance mechanism in mosquitoes is the detoxification and degradation of
insecticides by overproduction of various metabolic enzymes. Quantitative metabolic enzyme assays
of carboxylesterases (α and β), mixed function oxidases (MFO), and glutathione S-transferases (GST)
have been commonly used in the detection of insecticide resistance due to its sensitive nature even at low
frequencies. For the present study, larval strains of Culex quinquefasciatus Say and Aedes aegypti (L) were
collected from the Cochin Corporation, Kerala, India, and were assayed to organophosphate temephos
and carbamate propoxur. The resistance ratio of median lethal time for temephos and propoxur from the
field population of C. quinquefasciatus and A. aegypti is higher than the laboratory population. Elevated
levels of α and β esterase enzyme were observed with the ratio of 1.6 and 1.54 for C. quinquefasciatus
and 1.51 and 1.47 for A. aegypti. In Culex mosquitoes, 1.71, and in Aedes, 1.64 fold increase in GST
enzyme level and 1.38 and 1.3 fold increase for the MFO level determined. The study results revealed
the urgent needs of improving the vector control methods by introducing alternative techniques and
strategies against mosquitoes.
- Experiments tested the effect of extracellular self-DNA (exDNA) and heterologous DNA on the growth of 6 species from different taxonomic groups, including bacteria, fungi, algae, plants, protozoa and insects.
- Treatments with conspecific exDNA produced a concentration-dependent growth inhibition in all species, whereas heterologous DNA did not cause inhibition except in one bacterial species.
- The results suggest exDNA may have a general inhibitory effect on biological systems, providing a potential mechanism for self-inhibition and negative feedback observed in different organisms. Further investigation is needed to understand the molecular mechanisms of this effect.
This document describes a project aimed at synthesizing and characterizing novel achiral and chiral ionic liquids containing ester and amide functionality. The ionic liquids were evaluated for their antimicrobial toxicity and biodegradability. Some of the ionic liquids exhibited low toxicity and were readily biodegradable by microorganisms. The suitable ionic liquids were then employed as reaction media in catalytic reactions and as electrolytes in dye-sensitized solar cells, demonstrating their potential as environmentally-friendly solvents.
Biomarker is an objective measure that has been evaluated and confirmed either as an indicator of physiologic health, a pathogenic process or a pharmacologic response to a therapeutic intervention. Biomarkers, whether produces by normal healthy individuals or by individuals affected by specific systemic diseases, are tell tale molecules that could be used to monitor health status, disease onset, treatment response and outcome.The biomarkers can help for the determination of present as well as future disease activity along with diagnosis and previous periodontal diseases.
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The document provides guidance on appropriate online communication. It states that people should behave online as they would in person by being polite, respectful, and avoiding sharing anything they wouldn't say publicly. It also advises being careful with private communications as they may be forwarded without consent. Users should avoid responding to anger online and use proper grammar to effectively convey their message. Sarcasm and jokes can be misunderstood so clarification or emojis may be needed. Personal details should only be shared with known users to avoid becoming a target.
It's all about about rhythm - UX research & design proposal for a park in Sa...Marco Trevisani
Alfredo Nieves-Moreno and Marco Trevisani-Montresor propose a community engagement project in Ciudadela, Puerto Rico to integrate the diverse activities in Santurce and make Ciudadela the cultural center. They will research the community to design experiences promoting connections between residents, businesses, and neighborhoods. The project could include designing Parque San Mateo park and a creative marketplace in Ciudadela to involve the community and showcase Ciudadela and Putnam Bridge as leaders in Santurce's revival. The proposal aims to build consensus and trust through community-focused development.
The document provides guidance on appropriate online communication. It states that people should behave online as they would in person by being polite, respectful, and avoiding sharing private information or messages that could be misinterpreted or forwarded without consent. It also advises taking time before responding angrily online, avoiding all caps which can be seen as shouting, and being mindful that jokes and sarcasm may not translate well without tone of voice or body language cues. Personal information should only be shared with known users to avoid becoming a target.
Rap/hip hop conventions include casual or gangster clothing, references to violence, sex, drugs, and explicit language. Colors are typically black, grey or brown. Pop features young singers performing exaggerated love songs aimed at teens, with happy imagery, dance beats, and occasional rap sections. Rock involves tattooed male artists with unusual hair and unposed, gritty magazine covers dealing with explicit but non-objectifying lyrics about hate. Dance features club/party scenes with short skirts, makeup, dancing, drinking, flashing lights, and DJs over consistent beats that increase and decrease in pace.
Social media refers to broadcasting messages to a wide audience, while social networking involves interacting with individuals. Specifically, social media channels spread information to the masses, whereas social networks connect people. LinkedIn is an example of a social networking site that allows users to connect based on shared interests and workplaces. YouTube exemplifies social media as a platform for broadcasting videos to broad audiences.
The document analyzes and interprets the symbolism and meanings represented in the mastheads of several grime/rap media brands. It finds that most use dark backgrounds combined with bright colors like orange to represent both the hard lives of artists but also convey a message of hope. Bright colors and fonts are used to signify hope and opportunity for success. One masthead without dark elements may symbolize that artists signed to it have already "made it." The analysis concludes most aim to show hope for artists despite current challenges through use of contrasting dark and light colors and bold outlines.
The document outlines the key elements that are commonly found on magazine covers, including the masthead, date, variety of fonts used, strapline, cover line, main image, secondary images, use of house style colors, and barcode with price. While actor images are usually the main cover feature, this particular magazine uses a graphic image instead. The layout demonstrates the standard conventions for presenting essential information on magazine covers.
The document discusses the personality traits of the Kardashian family that have contributed to their success as entrepreneurs. It outlines the big five personality traits of openness, extraversion, agreeableness, conscientiousness, and neuroticism. Each Kardashian sister exhibits traits that help explain their business ventures, with Kim being organized and detail-oriented, Khloe enjoying attention and social situations, and Kourtney generating new ideas. As a family, they have effectively leveraged their combined personalities and reality television fame into clothing lines, boutiques, and other brands.
The document discusses the euro currency used by European Union countries. It explains that countries lose control over interest rates and exchange rates when joining the eurozone, as the European Central Bank sets rates for the entire bloc. However, there are also benefits to businesses and consumers from using a single currency, such as increased cross-border trade, lower borrowing costs, price stability, and greater job opportunities throughout Europe. Overall, the euro provides economic advantages but also means individual countries can no longer adjust rates for their own economic situations.
This document outlines a 4-step process to create a personal brand mantra: 1) Identify emotional modifiers to describe your personality; 2) Choose a descriptive modifier to specify your focus or audience; 3) List what you do or will do; 4) Combine the lists into a short, memorable phrase no more than 5 words that communicates who you are and inspires you. Following these steps helps craft a clear, simple statement of your personal brand.
Digital identity refers to a person's collective online presence across websites, while digital footprint is the traceable record of a user's internet interactions. Your digital footprint consists of the websites you visit and all online content you create or consume, including social media posts, reviews, and search histories. Both your digital identity and footprint can be used to build a profile about you and your online behaviors. It is important to manage your digital identity and footprint carefully to avoid potential issues like job loss that may occur from information publicly available online.
- Silver nanoparticles (Ag-NPs) were applied daily to wounds on mice to examine effects on healing.
- Levels of TGF-β, C3, RF, and CRP - markers of inflammation - were significantly lower in mice treated with Ag-NPs, indicating Ag-NPs suppressed the innate immune system and reduced inflammation.
- Wounds treated with Ag-NPs showed less scarring after 14 days and healed more quickly than untreated wounds, demonstrating that Ag-NPs accelerate wound healing by decreasing inflammatory responses.
Leishmania amazonensis INFECTION INDUCES CHANGES IN POTASSIUM PERMEABILITY OF...Mariela Marín
1. The document examines how Leishmania amazonensis infection affects the membrane potential and potassium permeability of macrophage-like cells.
2. It finds that infected macrophages initially depolarize but then hyperpolarize over time as infection progresses, shifting their membrane potential. This hyperpolarization is accompanied by an increase in inward potassium currents.
3. The changes are specific to infection by the parasite and differ from those seen due to phagocytosis of latex beads. The hyperpolarization and increased inward currents during later infection suggest the parasite modifies ion transport properties of macrophages to benefit its survival.
This study examines the antimicrobial and antibiofilm activity of a 5-kDa peptide fraction isolated from the coelomocytes (immune cells) of the sea urchin Paracentrotus lividus. The peptide fraction, called 5-CC, showed inhibitory activity against both Gram-positive and Gram-negative bacteria, as well as fungi, with minimum inhibitory concentrations ranging from 253.7 to 15.8 mg ml-1. 5-CC also inhibited the formation of Staphylococcus aureus and Staphylococcus epidermidis biofilms. At sub-MIC concentrations, 5-CC inhibited the formation of young (6-hour) and mature (24-hour) biofilms of
vascular insulin and IGF-1 in diabetic woundsSaeed Aghdam
This document summarizes a study examining the role of vascular endothelial insulin/IGF-1 signaling in skin wound healing. The study found that deleting the insulin receptor and IGF-1 receptor specifically in endothelial cells of mice (DKOIVE mice) did not significantly impact skin vessel homeostasis under normal conditions. However, when the skin was wounded, DKOIVE mice showed strongly reduced neovascularization during wound healing compared to controls, accompanied by reduced granulation tissue formation. This indicates that endothelial insulin/IGF signaling is essential for neovascularization during wound healing and implies its reduction directly contributes to impaired healing associated with diabetes.
This study investigated age-related changes in the function of primary afferent neurons in the skin by recording the responses of C-fiber nociceptors to mechanical and chemical stimuli from young and aged rats. The mechanical threshold was higher in aged skin, and latency to chemical stimuli tended to be longer. However, the number of discharges induced by chemicals was not different between age groups. Young rats displayed stronger and longer sensitization to mechanical stimuli after chemical exposure compared to aged rats. This showed decreased mechanical and chemical responses in aged rat skin C-fibers.
2014 increasing survival study of kidney hek-293 tOscar Moreno
This document summarizes a study that examined the effects of magnetic field stimulation on the growth of Human Embryonic Kidney 293 cells (HEK-293T cells). The cells were exposed to magnetic field vortices at frequencies between 100-2500 Hz and field intensities of 1.13-4.13 mT. A nanofluid containing gadolinium was also added to the cells. Flow cytometry analysis after 72 hours found that cell survival increased by 12.89% in the exposed cells compared to the unexposed control cells. The results suggest that magnetic field stimulation may activate cellular mechanisms that promote increased cell survival. Further experiments are still needed to fully understand the magnetic effects on cell growth.
This document summarizes various methods used to evaluate anti-inflammatory drugs. It describes animal models used to induce and measure inflammation, including UV erythema, rat paw edema, and cotton pellet assays. Key mediators of inflammation like histamine, bradykinin, and prostaglandins are discussed. Tests to measure drug effects on leukocyte adhesion and superoxide production are also presented. The document provides an overview of the development process for the anti-inflammatory drug piroxicam and signs of both acute and chronic inflammation.
Heat stress affects the kinetics of olfactory responses in rats. The study found that exposing rats to high temperatures of 45°C for 25 minutes significantly increased their body temperatures and caused faster rise and decay times of electrical responses in the olfactory epithelium to odorants. Heat stress also increased blood levels of lipopolysaccharides and free vesicles but did not change most cytokine levels, except for an increase in IL-10. This suggests heat stress causes strong, irreversible modulation of olfactory responses that is consistent with effects seen in other neurons and sensory systems.
This study investigated whether S-methylcysteine (SMC), a metabolite of monohalomethanes, contributes to their neurotoxicity. The researchers found that:
1) High concentrations of SMC (10-2 M) reduced synaptic responses in hippocampal slices, an effect that was partially reversible.
2) In organotypic hippocampal cultures, 24 hour exposure to 5x10-5 M SMC compromised membrane integrity in the dentate gyrus, while lower concentrations increased population spike amplitudes and repetitive discharges without affecting membrane integrity.
3) In dissociated hippocampal neurons, SMC reduced GABA-induced currents, acting as a competitive GABAA receptor antagonist with
The role of surface charge of ISCOMATRIX nanoparticles on the type of immune ...Nanomedicine Journal (NMJ)
Abstract
Objective(s):
ISCOMATRIX vaccines have now been shown to induce strong antigen-specific cellular or humoral immune responses to a broad range of antigens of viral, bacterial, parasite or tumor. In the present study, we investigated the role of ISCOMATRIX charge in induction of a Th1 type of immune response and protection against Leishmania major infection in BALB/c mice.
Materials and Methods:
Positively and negatively charged ISCOMATRIX were prepared. BALB/C mice were immunized subcutaneously, three times with 2-week intervals, with different ISCOMATRIX formulations. Soluble Leishmania antigens (SLA) were mixed with ISCOMATRIX right before injection. The extent of protection and type of immune response were studied in different groups of mice.
Results:
The group of mice immunized with negatively charged ISCOMATRIX showed smaller footpad swelling upon challenge with L. major and the highest IgG2a production compared with positively charged one. The mice immunized with positively charged ISCOMATRIX showed the lowest splenic parasite burden compared to the other groups. Cytokine assay results indicated that the highest level of IFN- γ and IL-4 secretion was observed in the splenocytes of mice immunized with negatively charged ISCOMATRIX as compared to other groups.
Conclusion:
The results indicated that ISCOMATRIX formulations generate an immune response with mixed Th1/Th2 response that was not protective against challenge against L. major.
High Intensity of Continuous Ultrasound in the Skin Repair Process in Rats: R...inventionjournals
Healing is a complex process involving different steps. Any change in one of them interferes with the normal repair process causing functional, morphological and aesthetic problems in the scar. Therapeutic ultrasound is a widely used and studied resource for cutaneous repair. However, divergences and parameters cause further scientific investigations. The experimental research sought to verify the effects of the high intensity of the therapeutic ultrasound in the cutaneous healing process of rats in the different stages 3, 7 and 21 days. Methodology: 60 animals, male rats, young adults, were irradiated in one SHAM group and another group with 3MHz continuous and intensity 2.0W / cm² for 5 minutes, 24 h after surgery. Results: The high intensity of the TUS in the continuous mode promoted burns, necrosis and poor healing in the irradiated areas. Conclusion: The high intensity of continuous TUS irradiated for 5 minutes was not therapeutic in skin repair of rats
Treatment of Purulent Wounds Immobilized Antisepticsinventionjournals
An experimental study of the wound healing abilities of immobilized forms of m and x lorgeksidinairamistinabigluconate on various bases in the treatment of purulent wounds. Results of the study showed the benefits of using a combination of m with m etronidazolomiramistinaized and immobilized on sodium carboxymethylcellulose and the preparation of chlorhexidine digluconate with m etiluratsilom immobilized on polymethylsiloxanepolyhydrates compared with ointment "Aevomekol."
This study investigated how hypoxia and lipopolysaccharide (LPS) affect autophagy in mouse-derived dendritic cells. The researchers found that hypoxia induced autophagy in the cells, as evidenced by increased autophagosome formation and expression of autophagy-related proteins LC3, Beclin1, and HIF-1α. Administration of LPS under hypoxic conditions further enhanced autophagy flux. Hypoxia upregulates HIF-1α, which plays an important role in activating autophagy. This study provides insight into how hypoxic environments stimulate autophagy in dendritic cells through the HIF-1α pathway and how LPS can augment
The document provides an overview of the immune system and inflammation. It discusses the inflammatory response process, including the vascular and cellular stages. It describes the signs of inflammation (rubor, tumor, calor, dolor, functio laesa) and cells involved in inflammation like neutrophils, eosinophils, basophils, and monocytes. It also discusses mediators of inflammation like kinins, complement system, histamine, serotonin, arachidonic acid metabolites, platelet activating factor, cytokines, and nitric oxide. Finally, it covers acute phase response, types of inflammation (acute vs chronic), and factors that influence wound healing.
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
ANTI-INFLAMMATORY AND ANALGESIC EFFECTS OF METHANOLIC EXTRACT OF Afrofritomia...paperpublications3
Abstract: Methanolic extract of the leaf of Afrofritomia sylvestris was investigated for its anti-inflammatory and analgesic effects. The extract was evaluated using carragenaan-induced paw oedema in rats (anti-inflammatory effect) as well as acetic acid-induced writhing (analgesic effect) in mice, after intra-peritoneal injection of the extract (250mg/kg, 500mg/kg and 1000mg/kg). The negative control animals were given normal saline (10ml/kg) and the effects were compared with that of Acetylsalicylic acid (100mg/kg), as a positive control drug. Each experiment consisted of twenty five animals divided into 5 groups of 5 animals each. Tail immersion reaction time and Naloxone antagonism of the extracts and morphine were further used to investigate the mode of action of the analgesic activity of the leaf. The extract significantly inhibited carageenan-induced hind paw inflammation in rats (P<0.05-0.01)><0.01). The methanolic extract failed to raise the pain threshold of mice towards heat stimulus and Naloxone did not show any significant antagonism (blocking effect) against the extract in the tail immersion experiment, thus ruling out the involvement of opioid receptors in the mechanism of analgesic action of the extract. Phytochemical analyses of the plant show the presence of flavonoids, alkaloids, saponins, tannins, steroids, triterpenes and cyanogenic glycosides. The LD50 of the extract was determined to be 3050+223.65mg/kg using the method of Tainter and Miller.In this study, methanolic extract of Afrofritomia sylvestris leaf was found to possess significant anti-inflammatory and analgesic effects in the tested models.
Hypothermia therapy is the standard treatment for hypoxic ischemic encephalopathy (HIE). Mild hypothermia between 34-35°C is initiated within 6 hours and continued for at least 72 hours. This decreases cerebral metabolic rate, excitatory neurotransmitter release, apoptosis, and vascular permeability. Hypothermia reduces mortality and neurodevelopmental disability in HIE. Other promising therapies target oxidative stress, calcium channels, excitatory amino acids, nitric oxide, and apoptosis, but require further study. Stem cell transplantation may also have potential as a future regenerative therapy for HIE.
This document provides a literature review on burn rehabilitation. It begins with definitions of burns and epidemiology. It then discusses skin anatomy, classification of burns, pathological changes from burns, assessment of burns, outcome measures, and treatment phases. The treatment phases include emergent, acute, and chronic phases. Various treatment modalities are discussed for each phase, including fluid resuscitation, wound care, splinting, scar management, and exercise. Reference sources supporting the information are also provided.
1) L. major proteins (LMP) completely stopped spontaneous contractions of cultured rat cardiomyocytes, which resumed contracting after washing with saline.
2) LMP significantly decreased force of contractions in guinea pig ileum strips stimulated with nicotine in a dose-dependent manner, but had no effect on strips stimulated with acetylcholine. Contractions resumed after washing.
3) LMP also reduced contractions of guinea pig uterine strips stimulated with oxytocin, and of electrically stimulated guinea pig ileum strips, in a dose-dependent manner. Contractions resumed after washing in all cases.
IJAR-9267 BM AFCs Published in 1 4 2016mohamed galal
1. The study evaluated the avidity of the tetanus immune response in mice after vaccination with tetanus toxoid (TT) vaccine via intraperitoneal or subcutaneous routes.
2. Results showed that the antibody level and avidity index were higher in mice that received the intraperitoneal vaccination compared to subcutaneous.
3. Examination of germinal centers in the spleen revealed that they peaked at day 10 post-vaccination and then deteriorated by day 33, suggesting their role in generating high affinity plasma cells and memory B cells is time-limited.
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8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
DECLARATION OF HELSINKI - History and principlesanaghabharat01
This SlideShare presentation provides a comprehensive overview of the Declaration of Helsinki, a foundational document outlining ethical guidelines for conducting medical research involving human subjects.
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
The skin is the largest organ and its health plays a vital role among the other sense organs. The skin concerns like acne breakout, psoriasis, or anything similar along the lines, finding a qualified and experienced dermatologist becomes paramount.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Mercurius is named after the roman god mercurius, the god of trade and science. The planet mercurius is named after the same god. Mercurius is sometimes called hydrargyrum, means ‘watery silver’. Its shine and colour are very similar to silver, but mercury is a fluid at room temperatures. The name quick silver is a translation of hydrargyrum, where the word quick describes its tendency to scatter away in all directions.
The droplets have a tendency to conglomerate to one big mass, but on being shaken they fall apart into countless little droplets again. It is used to ignite explosives, like mercury fulminate, the explosive character is one of its general themes.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
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Ravage et al.
in distant organs, as well. The systemic effects occur in cases with extensive
thermal trauma, but can be seen even in burn injuries covering only one quarter
of the total body surface area (TBSA). In a second-degree thermal injury model
in rats involving 25-30% TBSA, secondary lung injury has been observed. Till,
et al. (1983) described systemic complement activation, as detected by reductions in hemolytic activity of individual complement components (C3, C4, C6)
and crossed immunoelectrophoresis analysis of the conversion of serum C3
(2). Chemotaxis assays showed C5a-mediated activation of blood neutrophils
to occur, as well. Secondary accumulation of polymorphonuclear leukocytes
(PMN) has been shown to occur in lung tissues, followed by development of
acute pulmonary injury, related to production of neutrophil-derived toxic oxygen metabolites (2). Employing the same animal model of dermal burn injury,
PMN influx into lung tissues was reduced substantially (up to 77%) using antibodies to adhesion molecules (LFA-1, Mac-1, ICAM-1, E and L-selectin) (3).
The process of local edema formation in the burn wound appears to be more
complex, as it involves both the direct effect of heat and the consequences of
inflammatory mediators locally generated in response to the thermal insult. It
has been shown that under conditions of limited thermal, chemical or physical
trauma, two waves of increased vascular permeability occur in the skin (4). The
"early phase" of increased permeability—approximately one hour after thermally
injury—was shown to develop as a result of complement activation with anaphylatoxin release and mast cell secretion of histamine. This lead to an enhancement
of xanthine oxidase activity and increased production of oxygen radicals, damaging endothelial cells (5). This one hour injury has been shown to be neutrophil
independent (6).
The pathophysiology of "late phase" dermal microvascular injury (at
approximately four hours post-burn) is less well understood. The delay in onset
of this injury would indicate that a series of elaborate events must take place
before maximal tissue damage is achieved. Recent data from our group suggest
that, in contrast to the "early phase" edema formation, blood neutrophils are
involved in the pathogenesis of the "late phase" injury. Since antibodies to neutrophils, as well as, to E- and L-selectin and ICAM-1 were shown to effectively
reduce vascular leakage in the dermal burn wound at four hours post-burn (3),
we sought to clarify the mechanism for neutrophil recruitment and infiltration by
focusing on the upstream inflammatory mediators that may regulate these events.
The current studies were designed to elucidate the role of the cytokines IL-6,
IL-1 and TNFa, as well as complement, and to further clarify the role of neutrophils in the development of microvascular injury in the second-degree, "late
phase" dermal burn wound. Here, we present evidence which demonstrates that
the four hour burn injury is complement independent, involves the proinflammatory cytokines IL-6, IL-1 and TNFa and may result from the tissue-damaging
effects of neutrophil-derived reactive oxygen species.
3. Mediators of Injury in Dermal Burn Wounds
621
MATERIALS AND METHODS
Animal Model of Thermal Injury
The experimental burn model used in the present study has been described previously (2, 6,
7). Adult male, specific pathogen-free Long-Evans rats (300-350 g, Marian Sprague-Dawley, Indianapolis, Indiana) were used in all experiments. Ketamine hydrochloride (100 mg/kg body weight)
(Fort Dodge Laboratories, Fort Dodge, Iowa) and xylazine (13 mg/kg body weight) (Bayer Corporation, Shawnee Mission, Kansas) were administered intraperitoneally and intramuscularly, respectively, throughout the experiment. This ensured that the animals were properly anesthetized for the
entire procedure, from the induction of the burn injury to the time of sacrifice. The skin over the
lumbrosacral and dorsal flank areas was shaved and exposed to 70°C water for 30 s. This resulted
in a deep second-degree skin burn involving 25 to 30% of the total body surface area. Animals
were sacrificed at 4 h by cervical dislocation. Control animals were exposed to 22°C water. All
experiments were in accord with the standards in The Guide for the Care and Use of Laboratory
Animals, and were supervised by veterinarians from the Unit for Laboratory and Animal Care of
the University of Michigan Medical School.
Measurement of Microvascular Injury. Local microvascular injury was assessed by measurement of extravasation of radiolabeled bovine serum albumin ( 125 I-BSA) into the burned skin. Immediately prior to thermal injury, burn or sham-treated animals received an intravenous injection of 0.5
uCi of 125I-BSA in 0.5 ml sterile phosphate buffered saline (PBS). Using a template, four uniform
skin samples, each one square inch in size, were excised from the burned area on each animal. For
calculations of the permeability index, the amount of radioactivity ( I25 I-BSA) in skin biopsies was
compared to the amount of radioactivity present in 1.0 ml of blood obtained from the inferior vena
cava at the time of sacrifice (4 h).
Measurement of Skin Myeloperoxidase (MPO) Content. Local accumulation of neutrophils
was assessed by measurement of myeloperoxidase in skin biopsies. Animals received burn or sham
treatment as described above. At time of sacrifice (4 h), four 4 mm punch biopsies from standardized
areas of the wound were taken from each animal and instantly frozen in liquid nitrogen. The biopsies
were homogenized in 500 ul of PBS pH 7.4, containing 0.1% Tween 20, sonicated on ice and
insoluble material removed by centrifugation at 3000 rpm for 10 min. 5 ul of tissue extract (PBS
pH 7.4 and 0.1% Tween 20) were incubated with 100 ul of 2,2'-Azino-di-[3-ethylbenzthiozoline
sulfonate (6)] diammonium salt solution (ATBS substrate) (Boehringer Mannheim, BIOCHEMICA,
Germany) and the maximum velocity of the substrate/MPO chromogenic reaction (Vmax) measured
by monitoring the 96 well low-protein binding flat bottom plates (Corning Glass Works, Corning,
New York) at 405 nm over a two minute period (BioTek Elx808 microplate reader) (BIO-TEK
Instruments, INC., Winooski, Vermont). Kinetic calculations were performed using KC3 software
(BIO-TEK Instruments, Inc.). MPO concentrations in samples were determined using a standard
curve of purified MPO (CALBIOCHEM, San Diego, California). MPO values are reported as units
of activity/biopsy.
Interventional Studies
Cytokine Blockade. Irrelevant IgG antibody, anti-mouse IL-6 polyclonal antibody, and antirat IL-10 monoclonal antibody were obtained from R&D Systems, Minneapolis, Minnesota. Antirat TNFa polyclonal antibody were purchased from PeproTech, INC., Rocky Hill, New Jersey. In
4. 622
Ravage et al.
each case, antibodies were given in a total amount of 500 ug per animal, in 0.5 ml sterile PBS,
administered intravenously in two equal doses at 30 and 120 min post-burn.
Complement Depletion. Cobra venom factor (CVF) was purified from crude lyophilized
cobra venom (Naja naja kaouthia) (Sigma Chemical Company, St. Louis, Missouri) by ion exchange
chromatography and gel filtration (8). Complement depletion was achieved by serial intraperitoneal
injections of 4 X 20 units CVF in 12 h intervals, resulting in undetectable levels of serum hemolytic
complement activity (CH50 Assay). The experiments were performed 12 h after the final injection
of CVF.
C5a Blockade. Isolation of polyclonal antibody to C5a was performed as described by Mulligan, et al. (9). Briefly, animals were immunized with rat C5a. Obtained serum was IgG purified by
acid elution of Sepharose G beads (Pharmacia Biotech AB, Uppsala, Sweden), followed by extensive
dialysis against PBS. Characterization of the anti-rat C5a antibody was performed by immunoprecipitation and Western blot analysis showing a single band at 14 kDa. This antibody was given in
a total amount of 400 ug per animal, administered intravenously in two equal doses at 30 and 120
min post-burn.
Neutrophil Depletion. Neutrophil depletion was induced by the intraperitoneal injection of
1.0 ml of rabbit antiserum to rat PMN (Accurate, Westbury, New York) 16 h prior to the experiment.
This procedure reduced neutrophil counts in peripheral blood by >90 percent.
Hydroxyl Radical Scavenger Administration. Dimethyl thiourea (DMTU) (Sigma Chemical
Co.) (1000 mg/kg body weight) in 1.0 ml sterile PBS was injected intraperitoneally 10 min prior
to thermal injury. Dimethyl sulfoxide (DMSO) (Sigma Chemical Co.) (500 ug) in 1.0 ml sterile
PBS was injected intraperitoneally 10 min prior to thermal injury. The effectiveness of the chosen
concentrations of scavengers was demonstrated in earlier studies (7).
Statistical Analysis. Data sets were analyzed using one-way ANOVA. Individual group
means were compared with the Tukey multiple comparison test. All values were expressed as mean
± SEM. Significance was assigned where P < 0.05. For percentage change between groups, values obtained from negative controls were subtracted from each data point. Statistical analysis was
performed using SigmaStat 2.0 (Jandel Scientific Software, San Rafael, California).
RESULTS
Protective Effects of Neutrophil Depletion in Dermal Burn Injury. Neutropenia was achieved by intraperitoneal injection of antiserum to rat PMN.
Extravasation of 125I-bovine serum albumin into the skin 4 h after thermal trauma
was used to measure tissue injury. The results of neutropenia on the development
of increased vascular permeability in the skin are shown in Figure 1. Negative
controls had a permeability index of 0.049 ± 0.039. Neutrophil depletion was
associated with a 58% (P < 0.001) attenuation of the dermal vascular permeability four hours after thermal injury (permeability index of 0.405 ± 0.038 in
neutrophil depleted rats versus an index of 0.898 ± 0.039 in nontreated rats).
Thus, availability of PMNs seems to be required for the full development of
dermal microvascular injury four hours after thermal trauma.
Failure of Complement Depletion to Protect Against Dermal Microvascular Injury. Complement depletion was induced with CVF as described above.
Extravasation of 125I-bovine serum albumin into the skin four hours after ther-
5. Mediators of Injury in Dermal Burn Wounds
623
Fig. 1. Effects of complement depletion and neutrophil depletion on dermal vascular injury 4 h
after thermal trauma to skin as measured by leakage of 125I-labeled bovine serum albumin. For
each vertical bar, N = 4.
mal trauma was used to assess tissue injury. The results of complement depletion
on the development of increased vascular permeability in the skin are shown in
Figure 1. Complement depleted rats had a permeability index of 0.88 ± 0.065
versus an index of 0.898 ± 0.039 in non-treated rats (PN.S). Thus, complement
depletion was not associated with a significant reduction in dermal vascular permeability compared with positive controls.
Failure of C5a Blockade to Protect Against Dermal Microvascular Injury.
In the presence of antibody to C5a, vascular permeability index was calculated.
Anti-C5a-treated rats had an index of 0.89 ± 0.054, as compared with an index of
6. 624
Ravage et al.
Fig. 2. Effects of cytokine blockade on dermal vascular injury 4 h after thermal trauma to skin as
measured by leakage of 125I-labeled bovine serum albumin. For each vertical bar, n = 5 or higher.
and 0.89 ± 0.047 in positive controls (PN.S.). C5a blockade was not associated
with a significant reduction in dermal vascular permeability compared with positive controls. Thus, C5a does not seem to be required for dermal microvascular
injury four h after thermal trauma, providing further evidence that development
of the "late phase" burn wound is complement independent.
Protective Effects of Cytokine Blockade Against Dermal Microvascular
Injury. Protection against increased vascular permeability in skin 4 h after thermal injury was evaluated through the use of blocking antibodies to cytokines.
Vascular permeability index was calculated as described above. The negative
control skin permeability index was 0.049 ± 0.002; this value increased to 0.885
± 0.048 in positive controls, as shown in Figure 2. Treatment with anti-IL-6 was
7. Mediators of Injury in Dermal Burn Wounds
625
Fig. 3. Effects of hydroxyl radical scavengers on dermal vascular injury 4 h after thermal trauma
to skin as measured by leakage of 125I-labeled bovine serum albumin. For each vertical bar, n = 4.
associated with a 53% (P < 0.001) reduction in dermal vascular permeability to
0.47 ± 0.031. Treatment with antibody to IL-1 resulted in a decrease of dermal
vascular permeability by 34% (P < 0.001) to a value of 0.63 ± 0.068. Similarly, animals treated with anti-TNFa had a mean dermal vascular permeability
index of 0.60 ± 0.068, which was 37% (P < 0.001) lower than the positive control group. Thus, dermal microvascular injury at four hours after thermal trauma
requires the cytokines IL-6, IL-1 and TNFa for full development.
Protective Effects of Hydroxyl Radical Scavengers in the Skin Burn Wound.
The effects of hydroxyl radical scavengers on vascular permeability in skin
4 h after thermal injury was assessed by determination of vascular permeability index. The data are shown in Figure 3. Treatment with dimethyl thiourea
(DMTU) was associated with a 56% (P < 0.001) reduction in vascular perme-
8. 626
Ravage et al.
Table 1. Protection Against Neutrophil Influx into Thermally Injured Skin
Treatment
No. of
animals
None
anti-IL-6
anti-IL-1
anti-TNFoi
anti-PMN
4
4
4
4
4
MPO Value
(x ± SEM)
23.81
8.70
9.34
7.41
6.94
± 0.20
+0.81
± 1.60
±0.11
± 0.33
Significance
(P values)
Change
(%)a
<0.001
<0.001
<0.001
<0.001
<0.001
-67
-64
-73
-75
a
For percentage change between groups, values obtained from negative controls were subtracted
from each data point.
ability as compared to the positive controls (0.426 + 0.070 for DMTU treated
rats, 0.898 ± 0.039 in non-treated rats). Treatment with dimethyl sulfoxide
(DMSO) resulted in a 46% (P < 0.001) reduction in dermal vascular permeability (0.508 ± 0.081 with DMSO treatment, 0.898 ± 0.039 without). Thus,
blockade of hydroxyl radicals results in a marked protective effect on dermal
microvascular injury four hours after thermal trauma, indicating an important
role for these radicals in the "late phase" local burn injury.
Role of PMN in the Dermal Burn Wound. Skin samples from injured animals treated with irrelevant antibodies or specific antibodies directed against the
cytokines IL-6, IL-1 and TNFa or against rat PMNs were collected and assessed
for MPO activity as a measure of tissue accumulation of neutrophils. Negative
control animals showed values of MPO content of 1.31 ± 0.019, increasing to
23.8 ± 0.20 in samples from positive controls. The results of interventional studies of vascular leakage (Figure 1) were noticeably similar to PMN accumulation
in these treatment groups (Table 1). Anti-IL-6 treated animals showed a MPO
value of 8.7 ± 1.6 which represents a 67% (P < 0.001) reduction in PMN accumulation. Anti-IL-1-treated animals showed a 64% (P < 0.001) decrease in MPO
value to 9.3 ± 3.2. Anti-TNFa-treated animals displayed an MPO value of 7.4
± 0.23, a reduction of 73% (P < 0.001) as compared to positive controls. As
would be expected, neutrophil depletion resulted in a 75% (P < 0.001) reduction in MPO value to 6.9 ± 0.66. Therefore, blockade of IL-6, IL-1 and TNFa
greatly reduced tissue MPO activity, demonstrating a clear requirement for these
cytokines in neutrophil accumulation during the "late phase" dermal burn injury.
DISCUSSION
Our data indicate that development of the late phase of microvascular leakage (four h post-burn) in thermally injured rat skin requires the pro-inflammatory
9. Mediators of Injury in Dermal Burn Wounds
627
cytokines IL-6, IL-1 and TNFa. The ability of blocking antibodies to each of the
aforementioned cytokines to attenuate both vascular injury and polymorphonuclear leukocyte (PMN) influx into the burn wound suggests that these cytokines
represent upstream mediators in this inflammatory process. These cytokines may
affect vascular endothelial cells (EC), which are known to actively participate
in the development of inflammatory reactions by controlling fluid leakage and
promoting adhesion and activation of leukocytes, or target PMN. With regard to
IL-1 and TNFa, there is a large body of evidence detailing the ability of these
cytokines to activate EC to synthesize and express adhesion molecules (10-14).
The adhesion molecules ICAM-1 and E- and L-selectin have previously been
shown to be required for full development of vascular injury in the "late phase"
edema formation of thermally injured rat skin (3). In addition, IL-1 and TNFa
have been shown to induce cellular production of IL-6 (15, 16).
There are several ways in which IL-6 may exert pro-inflammatory effects
on increased vascular permeability and PMN influx in acute local thermal injury.
There is in vitro evidence that IL-6 increases endothelial permeability by rearranging actin filaments and by changing the shape of endothelial cells (17). Biffl,
et al., have demonstrated that with platelet-activating factor, IL-6 potentiates
PMN priming and delays PMN apoptosis (18, 19), both effects which contribute
to PMN-mediated tissue damage. Furthermore, Mullen et al. demonstrated that
IL-6 is capable of interacting synergistically with TNFa to augment the effect
of TNFa on PMN phagocytosis and superoxide production in vitro (20). The
authors hypothesized IL-6 to be a more distal mediator of the cytokine cascade,
which may modulate an inflammatory response to trauma initiated by other, more
proximal cytokines. This supports our data which show IL-6 blockade to be the
most effective of the cytokine interventions in reducing dermal vascular injury
after thermal trauma. Lastly, expression of ICAM-1 on myocytes is induced by
IL-6 in a cardiac ischemia/reperfusion injury model (21). Given the established
role of ICAM-1 and E- and L-selectin in the development of "late phase" edema
in thermally injured skin, it is possible that IL-6 may exert a similar effect on
EC in the pathogenesis of burns, resulting in increased PMN recruitment and
infiltration into injured tissues.
PMN depletion resulted in a significant decrease in both vascular leakage
and PMN accumulation in skin at 4 h. This is in contrast to the 1 h burn wound
for which PMN involvement was not required (7). The delay in burn wound
edema formation may be explained by the time necessary for the cytokine cascade to cause expression of adhesion molecules in the injured skin and activate
PMNs. The notion that increased tissue damage then results from PMN-derived
reactive oxygen species is supported by our data showing the ability of hydroxyl
radical scavengers in these experiments to reduce vascular injury. The fact that
PMN depletion, or any of the other interventions, was only able to result in a
maximum reduction of approximately 60% in vascular leakage is most likely
10. 628
Ravage et al.
due to the possibility that a large percentage of injury and cell death (approximately 40%) is directly heat-related. A similar phenomenon was observed in the
assay of skin MPO content.
It is known that the burn model utilized in these experiments produces systemic complement activation that initiates a series of events leading to the "early
phase" edema formation in the burned skin. Interestingly, neither complement
depletion nor C5a blockade was able to attenuate local vascular permeability
at four hours. In this case, the effects of cytokines and PMNs may be able to
produce maximal injury even in the absence of complement. Another possibility
is that the role of complement is fulfilled in the early phase, whereas the late
phase is more dependent on the ensuing inflammatory reaction. Despite the fact
that our data does not support a role for complement in the "late phase" burn
wound, a complete lack of involvement of complement components cannot be
stated. Recently, studies have revealed local complement production in numerous
and varied tissues in an ischemia/reperfusion injury in rabbit (22). Complement
proteins may be present in thermally injured tissue and contributing to the development of the 4 h injury, but were not effectively blocked by our antibody to
C5a or were able to be produced in significant amounts in skin, though serum
complement levels were undetectable following treatment with CVF. Administered in one dose immediately prior to induction or thermal trauma, 400 ug of
anti-C5a was able to slightly, though not significantly, reduce vascular leakage
at four hours (data not shown).
We therefore conclude that the development of the "late phase" dermal vascular injury following thermal trauma to the skin is largely mediated by the
pro-inflammatory actions of cytokines, in particular IL-6. IL-6 may modulate
the effects of TNFa and IL-1, resulting in EC expression of E- and L-selectin
and ICAM-1. IL-6 also may act directly on EC to alter cell structure and/or
promote upregulation of adhesion molecules. PMN-generated reactive oxygen
species appear to be responsible for the local tissue damage. Complement does
not appear to play a significant role, if any, in the pathogenesis of the "late phase"
second-degree burn wound.
REFERENCES
1. MANN, R. and D. HEIMBACH. 1996. Prognosis and treatment of burns. West. J. Med.
165:215-220.
2. TILL, G. O., C. BEAUCHAMP, D. MENPACE, W. TOURTELLOTTE Jr., R. KUNKEL, K. J. JOHNSON,
and P. A. WARD. 1983. Oxygen radical dependent lung damage following thermal injury of rat
skin. J. Trauma. 23:269-273.
3. MULLIGAN, M. S., G. O. TILL, C. W. SMITH, D. C. ANDERSON, M. MIYASAKA, T. TAMATANI,
R. F. TODD, III, T. B. ISSEKUTZ, and P. A. WARD. 1994. Role of leukocyte adhesion molecules
in lung and dermal vascular injury after thermal trauma of skin. Am. J. Pathol. 144:1008-1015.
11. Mediators of Injury in Dermal Burn Wounds
629
4. DEMLING, R. H. 1985. Burns. N. Engl. J. Med. 313: 1389-1398.
5. FREIDL, H. P., G. O. TILL, O. TRENTZ, and P. A. WARD. 1989. Roles of histamine, complement
and xanthine oxidase in thermal injury of skin. Am. J. Pathol. 135:203-217.
6. TILL, G. O., L. S. GUILDS, M. MAHROUGUI, H. P. FREIDL, O. TRENTZ, and P. A. WARD. 1989.
Role of xanthine oxidase in thermal injury of skin. Am. J. Pathol. 135:195-202.
7. TILL, G. O., J. R. HATHERILL, W. w. TOURTELLOTTE, M. J. LUTZ, and P. A. WARD. 1985. Lipid
peroxidation and acute lung injury after thermal trauma to skin: Evidence of a role for hydroxyl
radical. Am. J. Pathol. 135:195-202.
8. BALLOW, M. and C. G. COCHRANE. 1969. Two anti-complementary factors in cobra venom.
Hemolysis of guinea pig erythrocytes by one of them. J. Immunol. 103:944-952.
9. MULLIGAN, M. S., E. SCHMID, B. BECK-SCHIMMER, G. O. TILL, H. P. FRIEDL, R. B. BRAUER,
T. E. HUGLI, M. MIYASAKA, R. L. WARNER, K. J. JOHNSON, and P. A. WARD. 1996. Requirement and role of C5a in Acute Lung Inflammatory Injury in Rats. J. Clin. Invest. 98:503-512.
10. PROBER, J. S. and R. S. COTRAN. 1990. The role of endothelial cells in inflammation. Transplantation. 50:537-544.
11. BEVILACQUA, M. P., J. S. PROBER, D. L. MENDRICK, R. S. COTRAN, and M. A. GIMBRONE, JR.
1987. Identification of an inducible endothelial-leukocyte adhesion molecule. Proc. Natl. Acad.
Sci. U.S.A. 84:9238-9242.
12. BEVILACQUA, M. P., S. STENGELIN, M. A. GIMBRONE, and B. SEED. 1989. Endothelial leukocyte
adhesion molecule 1: An inducible receptor for neutrophils related to complement regulatory
proteins and lectins. Science 243:1160-1165.
13. OSBORN, L., C. HESSION, R. TIZARD, C. VASSALLO, S. LUHOWSKYJ, G. Cm-Rosso, and R.
LOBB. 1989. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced
endothelial protein that binds to lymphocytes. Cell 60:577-584.
14. DUSTIN, M. A. and T. A. SPRINGER. 1988. Lymphocyte function-associated antigen-1 (LFA-l)
interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms
for lymphocyte adhesion to cultures endothelial cells. J. Cell Biol. 107:321-331.
15. CONTENT, J., L. DE WIT, P. POUPART, G. OPDENAKKER, J. VAN DAMME, and A. BILLIAU. 1985.
Induction of a 26-kDa-protein mRNA in human cells treated with and interleukin-1-related,
leukocyte-derived factor. Eur. J. Biochem. 152:253-257.
16. KASID, A., E. P. DIRECTOR, and S. A. ROSENBERG. 1989. Regulation of interleukin-6 (IL-6)
by JL-2 and TNF-a in human peripheral blood mononuclear cells. Ann. N.Y. Acad. Sci.
557:564-566.
17. MARUO, N., I. MORITA, M. SHIRAO, and S. MUROTA. 1992. IL-6 increases endothelial permeability in vitro. Endocrinology 131:710-714.
18. BIFFL, W. L., E. E. MOORE, F. A. MOORE, V. S. CARL, F. J. KIM, and R. J. FRANCIOSE.
1994. Interleukin-6 potentiates neutrophil priming with platelet-activating factor. Arch. Surg.
129:1131-1136.
19. BIFFL, W. L., E. E. MOORE, F. A. MOORE, and C. C. BARNETT. 1996. Interleukin-6 delays neutrophil apoptosis via a mechanism involving platelet-activating factor. J. Trauma 40:575-579.
20. MULLEN, P. G., A. C. J. WINDSOR, C. J. WALSH, A. A. FOWLER, III, and H. J. SUGARMAN.
1995. Tumor necrosis factor-a and IL-6 selectively regulate neutrophil function in vitro. J. Surg.
Res. 58:124-130.
21. YOUKER, K., C. W. SMITH, D. C. ANDERSON, D. MILLER, L. H. MICHAEL, R. D. ROSSEN, and
M. L. ENTMAN. 1992. Neutrophil adherence to isolated adult cardiac myocytes: Induction by
cardiac lymph collected during ischemia and reperfusion. J. Clin. Invest. 89:602-609.
22. YASOJIMA, K., K. S. KILGORE, R. A. WASHINGTON, B. R. LUCCHESI, and P. L. MCGEER. 1998.
Complement gene expression by rabbit heart: Upregulation by ischemia and reperfusion. Circ.
Res. 82:1224-1230.