Kinsenoside isolated from Anoectochilus formosanus suppresses LPS-Stimulated ...Cây thuốc Việt
In the present study, we reported that kinsenoside, a major component of Anoectochilus formosanus, inhibited inflammatory reactions in mouse peritoneal lavage macrophages and protects mice from endotoxin shock. In LPSstimulated mouse peritoneal lavage macrophages, kinsenoside inhibited the inflammatory mediators, such as nitric oxide, TNF-!, IL-1", monocyte chemoattractant protein 1, and macrophage migration inhibitory factor production. Furthermore, kinsenoside decreased the formation of a nuclear factor .BYDNA complex and nuclear p65 and p50 protein levels. Kinsenoside inhibited nuclear factor .B translocation through both I.B!-dependent and -independent pathway. In contrast, it stimulated anti-inflammatory cytokine IL-10 generation and enhanced the mRNA expression of IL-10 and suppressor of cytokine signaling 3 in the same cells induced by LPS. In an animal model, both pretreatment and posttreatment of kinsenoside increased the survival rate of ICR mice challenged by LPS (80 mg/kg, i.p.). Pretreatment with kinsenoside decreased serum levels of TNF-!, IL-1", IL-10, monocyte chemoattractant protein 1, and migration inhibitory factor at 1 h after sublethal dose of LPS (40 mg/kg, i.p.) in mice. In contrast, kinsenoside enhanced serum IL-10 level at 24 h after LPS injection in mice. In conclusion, kinsenoside inhibited the production of inflammatory mediators and enhanced antiinflammatory cytokine generation. Therefore, kinsenoside can alleviate acute inflammatory hazards.
Protective Effect of Garlic Extract (Allium sativum L.) on the Liver Tissue o...BRNSS Publication Hub
Arsenic in its inorganic form is toxic and can cause severe health effects including cancers. In several
in vitro experiments, arsenic exposure has shown multiple effects at the molecular level. However, the
proper understanding of the role of arsenic in the cause of these diseases is still limited. In this work, we
demonstrated the toxicity effect of sodium arsenite in the liver tissues of freshwater fish Channa punctatus
and observed the histopathological as well as surface ultrastructural changes on it. A simultaneous study
was performed to observe the protective effect of garlic extract (Allium sativum L.) on the liver tissue of
arsenic-induced C. punctatus. The liver tissue of the control group showed a normal histoarchitecture.
The arsenic-exposed liver tissue revealed hepatic lesions in the form of cloudy swelling of hepatocytes,
vacuolar degeneration, karyolysis, dilation of sinusoids, and nuclear hypertrophy. Lesser hepatic
alternation was observed in the liver tissue of arsenic-exposed C. punctatus concurrently treated with
garlic extract. The protective effect of garlic was shown in the normalization of hepatocytes in the
arsenic-induced liver tissue.
Objective: To investigate the protective effect of lo- sartan, an angiotensin II type 1 receptor blocker with antioxidative effect on intestinal ischemia-reperfusion (I/R) injury in rats, against inflammation and apoptotic development.
Study Design: Forty male Wistar albino rats with a mean weight of 200–250 g each were divided into 4 groups: (1) Sham operation (laparotomy only, sham surgical preparation including isolation of the superior mesenteric artery [SMA] without occlusion), (2) Ischemia model with SMA closure for 2 hours, (3) I/R group (2 hours of ischemia followed by 3-hour reperfusion (SMA occlusion for 120 minutes followed by 240 minutes reperfusion), and (4) Losartan group (2 hours of ischemia, 40 mg/kg losartan was administered to the animals; losartan was dissolved in 1 mL distilled water and administered intraperitoneally after 2 hours of ischemia). Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were examined in jejunum tissue.
Results: Losartan treatment reduced the I/R-induced increase in MDA levels in the gut. Statistically, while SOD, CAT, and GSH activities decreased significantly in the I/R group, they increased in the I/R+Losartan group. Villus loss and increase in inflammation after ischemia persisted after reperfusion. Losartan treatment played a role in the reduction of inflammation and apoptosis and in the regulation of TNF-α and caspase-9 activity.
Conclusion: It has been thought that losartan in I/R may reduce mucosal damage and cell apoptosis in the direction of inflammation and may stabilize caspase-9 activity by inhibiting TNF-α stimulus.
Keywords: caspase-9, ischemia, ischemia/reperfusion, rat, reperfusion injury, TNF-α, tumor necrosis factor-alpha
Objective: To identify interstitial cells of Cajal (ICC) in the common bile duct of Kunming mice.
Study Design: Common bile ducts obtained from the Kunming mice were prepared for immunohistochemical investigations using the c-kit antibody. Immunoelectron microscopy was used to detect the expression of c-kit in the ICC of the common bile duct. Transmission electron microscopy showed ultrastructure of ICC in the murine bile duct. Reverse transcription–polymerase chain reaction (RT-PCR) and western blot were used to confirm the expression of mRNA specific for the c-kit gene and production of c-kit protein in the Kunming mice common bile duct.
Results: Immunohistochemistry revealed that ICC in the murine common bile duct are c-kit positive and the ICC are located in the tela submucosa and the tunica muscularis of the murine common bile duct and do not connect with each other. Immunoelectron microscopy confirmed the expression of Kit by ICC in the murine common bile duct. Transmission electron microscopy showed that ICC in the murine common bile duct have long processes, abundant mitochondria, plenty of smooth endoplasmic reticulum (sER), a lot of lysosomes, and dense bodies. The caveolae of ICC are distinctive. At the same time, RT-PCR indicated that the Kunming mice common bile duct expressed mRNA specific for the c-kit gene, and western blot analysis showed the evidence of production of c-kit protein in the Kunming mice common bile duct.
Conclusion: ICC are found in the Kunming mice common bile duct, which is likely to lead to the development of motility study of the common bile duct.
Keywords: common bile duct; electron microscopy; immuno-electron microscopy; interstitial cells of Cajal; intestines; smooth muscle; tyrosine kinase receptor (c-kit)
Histopathological effects of nanosilver (Ag-NPs) in liver after dermal exposu...Nanomedicine Journal (NMJ)
Objective(s):
With the advent of nanotechnology, significant progress has been made in the area of nanoscale materials such as nanosilver (Ag-Nps). These nanoparticles have a wide range of applications and been used for antimicrobial purposes for more than a century. However, little
attention has been paid to the toxicity of nanosilver wound dressing. This study was designed to investigate the possible histopathological toxicity of Ag-NPs in liver of mice during wound healing.
Materials and Methods:
A group of 50 female BALB/c mice of about 8 weeks were randomly divided into two groups: Ag-NPs and control groups (n=25). After creating similar wound on the backs of all animals, the wound bed was treated in Ag-NPs group, with a volume of 50 microliters of the nanosilver solution (10ppm) ,and in control group, with the same amount of distilled water. The experiment lasted for 14 days. Histopathaological samplings of liver were conducted on days 2, 7 and 14 of the experiment.
Results:
Histopathological studies demonstrated time-dependent changes in mice liver treated with Ag-NPs compared to control group. Some changes include dilation in central venous, hyperemia, cell swelling, increase of Kupffer and inflammatory cells.
Conclusion:
This study suggests that use of nanosilver for wound healing may cause a mild toxicity, as indicated by time-dependent toxic responses in liver tissue. However, this issue will have to be considered more extensively in further studies
Protective Effect of β-Carotene Extracted From the Cyanobacterium Oscillatori...iosrphr_editor
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).
Kinsenoside isolated from Anoectochilus formosanus suppresses LPS-Stimulated ...Cây thuốc Việt
In the present study, we reported that kinsenoside, a major component of Anoectochilus formosanus, inhibited inflammatory reactions in mouse peritoneal lavage macrophages and protects mice from endotoxin shock. In LPSstimulated mouse peritoneal lavage macrophages, kinsenoside inhibited the inflammatory mediators, such as nitric oxide, TNF-!, IL-1", monocyte chemoattractant protein 1, and macrophage migration inhibitory factor production. Furthermore, kinsenoside decreased the formation of a nuclear factor .BYDNA complex and nuclear p65 and p50 protein levels. Kinsenoside inhibited nuclear factor .B translocation through both I.B!-dependent and -independent pathway. In contrast, it stimulated anti-inflammatory cytokine IL-10 generation and enhanced the mRNA expression of IL-10 and suppressor of cytokine signaling 3 in the same cells induced by LPS. In an animal model, both pretreatment and posttreatment of kinsenoside increased the survival rate of ICR mice challenged by LPS (80 mg/kg, i.p.). Pretreatment with kinsenoside decreased serum levels of TNF-!, IL-1", IL-10, monocyte chemoattractant protein 1, and migration inhibitory factor at 1 h after sublethal dose of LPS (40 mg/kg, i.p.) in mice. In contrast, kinsenoside enhanced serum IL-10 level at 24 h after LPS injection in mice. In conclusion, kinsenoside inhibited the production of inflammatory mediators and enhanced antiinflammatory cytokine generation. Therefore, kinsenoside can alleviate acute inflammatory hazards.
Protective Effect of Garlic Extract (Allium sativum L.) on the Liver Tissue o...BRNSS Publication Hub
Arsenic in its inorganic form is toxic and can cause severe health effects including cancers. In several
in vitro experiments, arsenic exposure has shown multiple effects at the molecular level. However, the
proper understanding of the role of arsenic in the cause of these diseases is still limited. In this work, we
demonstrated the toxicity effect of sodium arsenite in the liver tissues of freshwater fish Channa punctatus
and observed the histopathological as well as surface ultrastructural changes on it. A simultaneous study
was performed to observe the protective effect of garlic extract (Allium sativum L.) on the liver tissue of
arsenic-induced C. punctatus. The liver tissue of the control group showed a normal histoarchitecture.
The arsenic-exposed liver tissue revealed hepatic lesions in the form of cloudy swelling of hepatocytes,
vacuolar degeneration, karyolysis, dilation of sinusoids, and nuclear hypertrophy. Lesser hepatic
alternation was observed in the liver tissue of arsenic-exposed C. punctatus concurrently treated with
garlic extract. The protective effect of garlic was shown in the normalization of hepatocytes in the
arsenic-induced liver tissue.
Objective: To investigate the protective effect of lo- sartan, an angiotensin II type 1 receptor blocker with antioxidative effect on intestinal ischemia-reperfusion (I/R) injury in rats, against inflammation and apoptotic development.
Study Design: Forty male Wistar albino rats with a mean weight of 200–250 g each were divided into 4 groups: (1) Sham operation (laparotomy only, sham surgical preparation including isolation of the superior mesenteric artery [SMA] without occlusion), (2) Ischemia model with SMA closure for 2 hours, (3) I/R group (2 hours of ischemia followed by 3-hour reperfusion (SMA occlusion for 120 minutes followed by 240 minutes reperfusion), and (4) Losartan group (2 hours of ischemia, 40 mg/kg losartan was administered to the animals; losartan was dissolved in 1 mL distilled water and administered intraperitoneally after 2 hours of ischemia). Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were examined in jejunum tissue.
Results: Losartan treatment reduced the I/R-induced increase in MDA levels in the gut. Statistically, while SOD, CAT, and GSH activities decreased significantly in the I/R group, they increased in the I/R+Losartan group. Villus loss and increase in inflammation after ischemia persisted after reperfusion. Losartan treatment played a role in the reduction of inflammation and apoptosis and in the regulation of TNF-α and caspase-9 activity.
Conclusion: It has been thought that losartan in I/R may reduce mucosal damage and cell apoptosis in the direction of inflammation and may stabilize caspase-9 activity by inhibiting TNF-α stimulus.
Keywords: caspase-9, ischemia, ischemia/reperfusion, rat, reperfusion injury, TNF-α, tumor necrosis factor-alpha
Objective: To identify interstitial cells of Cajal (ICC) in the common bile duct of Kunming mice.
Study Design: Common bile ducts obtained from the Kunming mice were prepared for immunohistochemical investigations using the c-kit antibody. Immunoelectron microscopy was used to detect the expression of c-kit in the ICC of the common bile duct. Transmission electron microscopy showed ultrastructure of ICC in the murine bile duct. Reverse transcription–polymerase chain reaction (RT-PCR) and western blot were used to confirm the expression of mRNA specific for the c-kit gene and production of c-kit protein in the Kunming mice common bile duct.
Results: Immunohistochemistry revealed that ICC in the murine common bile duct are c-kit positive and the ICC are located in the tela submucosa and the tunica muscularis of the murine common bile duct and do not connect with each other. Immunoelectron microscopy confirmed the expression of Kit by ICC in the murine common bile duct. Transmission electron microscopy showed that ICC in the murine common bile duct have long processes, abundant mitochondria, plenty of smooth endoplasmic reticulum (sER), a lot of lysosomes, and dense bodies. The caveolae of ICC are distinctive. At the same time, RT-PCR indicated that the Kunming mice common bile duct expressed mRNA specific for the c-kit gene, and western blot analysis showed the evidence of production of c-kit protein in the Kunming mice common bile duct.
Conclusion: ICC are found in the Kunming mice common bile duct, which is likely to lead to the development of motility study of the common bile duct.
Keywords: common bile duct; electron microscopy; immuno-electron microscopy; interstitial cells of Cajal; intestines; smooth muscle; tyrosine kinase receptor (c-kit)
Histopathological effects of nanosilver (Ag-NPs) in liver after dermal exposu...Nanomedicine Journal (NMJ)
Objective(s):
With the advent of nanotechnology, significant progress has been made in the area of nanoscale materials such as nanosilver (Ag-Nps). These nanoparticles have a wide range of applications and been used for antimicrobial purposes for more than a century. However, little
attention has been paid to the toxicity of nanosilver wound dressing. This study was designed to investigate the possible histopathological toxicity of Ag-NPs in liver of mice during wound healing.
Materials and Methods:
A group of 50 female BALB/c mice of about 8 weeks were randomly divided into two groups: Ag-NPs and control groups (n=25). After creating similar wound on the backs of all animals, the wound bed was treated in Ag-NPs group, with a volume of 50 microliters of the nanosilver solution (10ppm) ,and in control group, with the same amount of distilled water. The experiment lasted for 14 days. Histopathaological samplings of liver were conducted on days 2, 7 and 14 of the experiment.
Results:
Histopathological studies demonstrated time-dependent changes in mice liver treated with Ag-NPs compared to control group. Some changes include dilation in central venous, hyperemia, cell swelling, increase of Kupffer and inflammatory cells.
Conclusion:
This study suggests that use of nanosilver for wound healing may cause a mild toxicity, as indicated by time-dependent toxic responses in liver tissue. However, this issue will have to be considered more extensively in further studies
Protective Effect of β-Carotene Extracted From the Cyanobacterium Oscillatori...iosrphr_editor
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).
International Journal of Engineering and Science Invention (IJESI)inventionjournals
International Journal of Engineering and Science Invention (IJESI) is an international journal intended for professionals and researchers in all fields of computer science and electronics. IJESI publishes research articles and reviews within the whole field Engineering Science and Technology, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Objective: A spinal cord injury (SCI) is damage to the spinal cord either from trauma, loss of its normal blood supply, or compression from tumor or infection. In this study we focused on alterations in the bladder tissue with angiogenic and apoptotic aspects after spinal cord injury.
Study Design: Twenty Wistar Albino rats were categorized as control and SCI groups. At T7-T9 vertebras, a steel rod was dropped from 10 cm to create a spinal cord injury under anesthesia. Rats were decapitated and spinal tissue was processed to measure malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO).
Results: MDA, MPO, epithelial degeneration, vascular dilation, inflammation, VEGF, and APAF-1 expressions in the SCI group were statistically higher than those in the control group. GSH content of the SCI group was statistically lower than that in the control group. In the hematoxylin-eosin–stained sections of the control group, normal histology was observed in bladder tissue. In the SCI group, degeneration epithelial cells, thinned epithelium, increased fibrosis, dilated and congested blood vessels, and hyperplastic endothelial cells were observed. In the control group, VEGF expression was slightly observed in some epithelial cells and vascular cells. In the SCI group, VEGF expression was increased in inflammatory and vascular endothelial cells. For APAF-1 expression, the control group showed no expression. In the SCI group, APAF-1 expression was positive in degenerated epithelial cells and connective tissue cells.
Conclusion: It is thought that the urination reflex was affected due to increased inflammation in the bladder tissue, leading to alterations in the regulation and function of the muscles.
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
Hyperoxaluria Induces Oxidative DNA Damage and Results in Renal Tubular Epithelial Cell Apoptosis: A Clue to the Pathogenesis of Urolithiasis by Hasan Aydin in Experimental Techniques in Urology & Nephrology
Brazilian Red Propolis Attenuates Hypertension and Renal DamageBee Healthy Farms
Incorporating Brazilian Red Propolis in the diet of rats with reduced kidney function experienced a reduction of hypertension and renal damage. This scenario simulated Chronic Kidney Disease.and found the anti-inflammatory and antioxidant effects of Brazilian Red Propolis effective but requires additional studies to determine which mechanisms were prominent.
International Journal of Engineering and Science Invention (IJESI)inventionjournals
International Journal of Engineering and Science Invention (IJESI) is an international journal intended for professionals and researchers in all fields of computer science and electronics. IJESI publishes research articles and reviews within the whole field Engineering Science and Technology, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Objective: A spinal cord injury (SCI) is damage to the spinal cord either from trauma, loss of its normal blood supply, or compression from tumor or infection. In this study we focused on alterations in the bladder tissue with angiogenic and apoptotic aspects after spinal cord injury.
Study Design: Twenty Wistar Albino rats were categorized as control and SCI groups. At T7-T9 vertebras, a steel rod was dropped from 10 cm to create a spinal cord injury under anesthesia. Rats were decapitated and spinal tissue was processed to measure malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO).
Results: MDA, MPO, epithelial degeneration, vascular dilation, inflammation, VEGF, and APAF-1 expressions in the SCI group were statistically higher than those in the control group. GSH content of the SCI group was statistically lower than that in the control group. In the hematoxylin-eosin–stained sections of the control group, normal histology was observed in bladder tissue. In the SCI group, degeneration epithelial cells, thinned epithelium, increased fibrosis, dilated and congested blood vessels, and hyperplastic endothelial cells were observed. In the control group, VEGF expression was slightly observed in some epithelial cells and vascular cells. In the SCI group, VEGF expression was increased in inflammatory and vascular endothelial cells. For APAF-1 expression, the control group showed no expression. In the SCI group, APAF-1 expression was positive in degenerated epithelial cells and connective tissue cells.
Conclusion: It is thought that the urination reflex was affected due to increased inflammation in the bladder tissue, leading to alterations in the regulation and function of the muscles.
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
Hyperoxaluria Induces Oxidative DNA Damage and Results in Renal Tubular Epithelial Cell Apoptosis: A Clue to the Pathogenesis of Urolithiasis by Hasan Aydin in Experimental Techniques in Urology & Nephrology
Brazilian Red Propolis Attenuates Hypertension and Renal DamageBee Healthy Farms
Incorporating Brazilian Red Propolis in the diet of rats with reduced kidney function experienced a reduction of hypertension and renal damage. This scenario simulated Chronic Kidney Disease.and found the anti-inflammatory and antioxidant effects of Brazilian Red Propolis effective but requires additional studies to determine which mechanisms were prominent.
Assessment of the immune status of nile tilapia (oreochromis niloticus) exper...sherein abdelgayed
Manal M. Zaki, Alaa E. Eissa, and Sherein Saeid (2011): Assessment of the Immune Status in Nile Tilapia (Oreochromis niloticus) Experimentally Challenged with Toxogenic / Septicemic Bacteria During Treatment Trial with Florfenicol and Enrofloxacin.World Journal of Fish and Marine Sciences(WJFMS)3(1):21-36.
Immunomodulatory effect of schisandrae oil in mouse model of autoimmune hepat...LucyPi1
Abstract Objective: To study the immunomodulatory effect of schisandra oil (SCO) in mouse model of autoimmune hepatitis induced by concanavalin A (ConA). Methods: C57BL/6 mice were divided into control group, model group and SCO group. Mice in SCO group were given SCO at 5 mg/kg by intragastric administration every day for 7 days, followed by intravenous injection of ConA at 10 mg/kg. 10 hours after ConA injection, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured by the kits, the expression of inflammatory cytokines like interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in liver was detected by real-time quantitative PCR, and the T cell activation and IFN-γ expression in spleen and MLN were examined by flow cytometry. Results: Compared with control group, each indicator in model group were significantly higher. In SCO preventive treatment group, the levels of serum ALT, AST and LDH were significantly reduced (all P < 0.001), the expression levels of inflammatory cytokines in liver were downregulated, the T cell activation in spleen and MLN was inhibited (P = 0.006 and P = 0.008), the percentages of IFN-γ+ CD8+ and IFN-γ+ CD4+ T cells were decreased, and the frequencies of Th2 and Th17 cells in spleen and MLN were also decreased at the same time. Conclusion: SCO has a protective effect on immune liver injury by inhibiting the activation of T cells and reducing the expression of inflammatory cytokines, which reflects that SCO plays a role in the immunomodulation of autoimmune hepatitis, indicating that SCO is of great significance for the maintenance of autoimmune homeostasis.
"Mechanisms of nitric oxide synthase uncoupling in endotoxin-induced acute lung injury: role of asymmetric dimethylarginine" appeared in a 2010 issue of Vascular Pharmacology and summarized Stephen M. Black's research into acute lung injury/sepsis.
Progress in liver surgery has enabled hepatectomy with concomitant venous resection for liver malignancies involving the inferior vena cava (IVC). The authors describe an alternative technique for IVC reconstruction without the need of graft.
http://www.drmarcel.com.br
Solid pseudopapillary neoplasm of the pancreas is a distinctive pancreatic neoplasm with low metastatic potential. This study examines clinical differences and prognosis between male and female patients.
http://www.drmarcel.com.br
Laparoscopic intrahepatic Glissonian technique for liver surgery. Hepatectomi...Marcel Autran Machado
The main advantage of the intrahepatic Glissonian procedure over other techniques is the possibility of gaining a rapid and precise access to the left Glissonian sheaths facilitating left hemihepatectomy, bisegmentectomy 2-3, and individual resections of segments 2, 3, and 4. The authors believe that the intrahepatic Glissonian technique facilitates laparoscopic liver resection and may increase the development of segment-based laparoscopic liver resection.
Appleby operation for pancreatic cancer. Cancer de pancreas - tratamentoMarcel Autran Machado
We described a modified Appleby operation for locally advanced distal pancreatic cancer with compromised hepatic collateral flow that needed hepatic arterial revascularization, successfully accomplished by left external iliac-hepatic arterial bypass with Dacron prosthesis.
The subtotal laparoscopic pancreatic resection can safely be performed. The da Vinci robotic system allowed for technical refinements of laparoscopic pancreatic resection. Robotic assistance improved the dissection and control of major blood vessels due to three-dimensional visualization of the operative field and instruments with wrist-type end-effectors.
Laparoscopic right trisectionectomy; Trisegmentectomia direita por video.Marcel Autran Machado
Totally laparoscopic right trisectionectomy is safe and feasible in selected patients and should be considered for patients with benign or malignant liver neoplasms. The described technique, with the use of the intrahepatic Glissonian approach and control of venous outflow, may facilitate laparoscopic
extended liver resections by reducing the technical difficulties in pedicle control and may diminish bleeding during liver transection.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- 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
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
1. ORIGINAL ARTICLE
CO2 Abdominal Insufflation Decreases Local and Systemic
Inflammatory Response in Experimental
Acute Pancreatitis
Marcel Cerqueira Cesar Machado, MD, PhD,* Ana Maria Mendon0a Coelho, PhD,*
Joilson O. Martins, PhD,Þ Sandra N. Sampietre, TSc,* Nilza A.T. Molan, BSc,*
Rosely A. Patzina, MD, PhD,* Marcel Autran Cesar Machado, MD, PhD,* and Sonia Jancar, PhDÞ
onset of the syndrome.3 The initiating event that results in the
Objectives: Acute pancreatitis (AP) is a serious disease that is am- release of inflammatory cytokines and mediators and in the
plified by an associated systemic inflammatory response. We investi- systemic inflammatory process is still incompletely understood.
gated the effect of CO2 pneumoperitoneum on the local and systemic However, it does involve the activation of several intracellular
inflammatory response in AP. signaling pathways in leukocytes and the increased expression
Methods: Acute pancreatitis was induced in Wistar rats by 5% of specific genes.
taurocholate intraductal injection. Carbon dioxide pneumoperitoneum Some investigators in the early 1970s proposed that these
was applied for 30 minutes before the induction of AP. Inflammatory mediators could be found in the ascitic fluid in AP and therefore
parameters were evaluated in the peritoneum (ascites, cell number, and advocated peritoneal lavage for the treatment of this disease.4,5
tumor necrosis factor > [TNF->]), serum (amylase, TNF->, interleukin-6 Furthermore, a number of experiments demonstrated the
[IL-6], and IL-10), pancreas (myeloperoxidase [MPO] activity, cyclo- toxicity of the pancreatitis-associated ascitic fluid to liver mito-
oxygenase 2 and inducible nitric oxide synthase expression, and his- chondria and to the kidneys causing acute renal failure.6Y8
tological diagnosis), liver, and lung (mitochondria dysfunction and MPO Pancreatic injury leads to activation and leakage of pan-
activity). creatic enzymes into the organ interstitium and accumulation in
Results: Abdominal insufflation with CO2 before induction of AP pancreatic and peripancreatic tissues and peritoneal cavity.9
caused a significant decrease in ascites volume, cells, and TNF-> in the Resident peritoneal macrophages are an important source
peritoneal cavity and in serum TNF-> and IL-6 but not IL-10 levels. of TNF->.10 Macrophages obtained from the peritoneal cavity of
In the pancreas, this treatment reduced MPO activity, acinar and fat animals undergoing AP produce higher levels of TNF-> when
necrosis, and the expression of inducible nitric oxide synthase and cyclo- exposed to lipopolysaccharide (LPS) than their controls.11
oxygenase 2. There were no significant differences on serum amy- It has also been shown that injection of trypsin into the
lase levels, liver mitochondrial function, and pulmonary MPO between peritoneal cavity stimulates the production of TNF-> and IL-1.12
groups. These studies have suggested that the peritoneum may play an
Conclusions: Our data demonstrated that CO2 pneumoperitoneum important role in the systemic inflammatory response in AP.12,13
reduced pancreatic inflammation and attenuated systemic inflammatory Previous studies have demonstrated that peritoneal macro-
response in AP. This article suggests that CO2 pneumoperitoneum plays phages stimulated with LPS have a significant decrease in TNF->
a critical role on the better outcome in patients undergoing laparoscopic and IL-1 production when exposed to CO2 in vitro.14
pancreatic surgery. Moreover, it has been reported that CO2 insufflation pre-
Key Words: acute experimental pancreatitis, carbon dioxide, treatment reduces the plasma levels of TNF-> and IL-6 and
pneumoperitoneum, SIRS, inflammation increases survival after LPS-contaminated laparotomy.15 The
authors of this study suggested that the local tissue acidifica-
(Pancreas 2009;00: 00Y00)
tion caused by peritoneal CO2 insufflation might explain the
decrease in local and systemic inflammatory response mediated
by peritoneal macrophages.
S evere acute pancreatitis (AP) is one of the most serious
diseases with high morbidity and mortality. The pancreatic
injury is amplified by an associated systemic inflammatory re-
On the other hand, experience with laparoscopic pancreatic
surgery is growing exponentially worldwide, with lower sys-
temic inflammatory response and reduction of postoperative
sponse syndrome (SIRS) that is ultimately responsible for the pancreatic fistulas being reported.16
morbidity and mortality related to this disease.1,2 In the present study, we investigated the effect of CO2
Systemic inflammatory response syndrome is character- pneumoperitoneum on local and systemic inflammatory re-
ized by elevated serum levels of cytokines such as interleukin-1 sponse during AP.
(IL-1), IL-6, IL-8, tumor necrosis factor > (TNF->), and nitric
oxide (NO) that greatly increase in the serum early after the
MATERIALS AND METHODS
From the *Department of Gastroenterology, and †Medical School and Im-
munology, Institute of Biomedical Sciences, University of Sao Paulo, Sao
˜ ˜ Animals
Paulo, Brazil. Adult male Wistar rats weighing 230 to 270 g were housed
Received for publication September 5, 2008; accepted July 24, 2009. in individual cages and kept under standard conditions (12 hours
Reprints: Marcel Cerqueira Cesar Machado, MD, PhD, R. Peixoto Gomide,
515 13 andar Jd Paulista, Zip Code: 01409-001 Y Sao Paulo-SP,
˜
of light-dark cycle and temperature between 22 and 28-C) with
Brazil (e-mail: amcoelho@usp.br). free access to a standard rat chow and water ad libitum. The
Copyright * 2009 by Lippincott Williams & Wilkins experimental protocol was approved by the ethics commission
Pancreas & Volume 00, Number 00, Month 2009 www.pancreasjournal.com 1
2. Machado et al Pancreas & Volume 00, Number 00, Month 2009
of the Hospital das Clınicas: Sao Paulo University. Surgical
´ ˜ Sample Preparations
anesthesia was induced with ketamine chloride (Ketalar; Parke At 2 hours after AP induction, animals were killed. Serum
Davis, Sao Paulo, Brazil).
˜ samples were assayed for amylase,19 TNF->, IL-6, and IL-10
Reagents levels by a solid-phase sandwich enzyme-linked immune ab-
sorbent assay. Volume, levels of TNF->, and cell number were
All chemical reagents were obtained from Sigma Chemical,
determined in ascitic fluid. Cyclo-oxygenase (COX2) and in-
Co (St Louis, Mo). Tumor necrosis factor >, IL-6, and IL-10
ducible nitric oxide synthase (iNOS) protein expressions and
were assayed with kits from Biosource International (Camarillo,
myeloperoxidase (MPO) activities were analyzed in homoge-
Calif ).
nates of pancreas at 2 hours, and pulmonary MPO was analyzed
Induction of AP at 2 and 24 hours after AP induction. Hepatic tissue was col-
Acute pancreatitis was induced by retrograde injection of lected for evaluation of oxidation and phosphorylation of liver
0.5 mL of 5% sodium taurocholate in saline into the main pan- mitochondria. A portion of the pancreas was fixed in 10% buff-
creatic duct during 1 minute at constant rate by using an infu- ered formalin for histological analysis.
sion pump. A clamp was applied to the proximal part of the
Cell Counting of Peritoneal Cells
hepatic duct during the injection.17,18
Ten milliliters of cooled phosphate-buffered saline solution
Experimental Groups was injected into the abdominal cavities, and the peritoneum was
Animals were randomized to the following experimental massaged. The peritoneal lavage fluid was recovered by peri-
groups: toneal puncture. The lavage fluid was centrifuged at 250g for
Group 1: Ten control rats, nonmanipulated; 10 minutes, and the cell pellet was resuspended in phosphate-
Group 2: Ten control rats, with CO2 pneumoperitoneum buffered saline. Cells were counted in a Neubauer chamber.
applied for 30 minutes at a pressure of 4 mm Hg, not submitted
to AP; Myeloperoxidase Activity
Group 3: Forty-six rats without treatment before the in- Myeloperoxidase activity was used as an indicator of
duction of AP; neutrophils’ infiltration into tissues. Samples of pancreatic and
Group 4: Forty-six rats with CO2 pneumoperitoneum ap- pulmonary tissue were homogenized with a Polytron homog-
plied for 30 minutes at a pressure of 4 mm Hg before the in- enizer using a homogenization buffer that contains 0.5%
duction of AP.15 hexadecyltrimethyl ammonium bromide, 5-mmol/L EDTA and
50-mmol/L phosphate at pH 6.0. Homogenized samples were
Mortality Study sonicated and centrifuged (3000g for 30 minutes) at 4-C. Mye-
Animals of groups 1 (n = 20) and 2 (n = 20) were observed loperoxidase activity in the supernatant was assayed by mea-
for 7 days after induction of AP for mortality analysis. suring the change in A460 resulting from the decomposition of
FIGURE 1. Effect of CO2 insufflation on the peritoneal inflammation induced by AP. Acute pancreatitis was induced in rats by intraductal
instillation of 0.5 mL of 5% taurocholic acid. One group received abdominal insufflation with CO2 30 minutes before induction of
AP: volume of ascites (A), number of peritoneal cells (B), and levels of TNF-> in ascitic fluid (C). Data are expressed as mean T SEM of
10 animals per group. *P G 0.001.
2 www.pancreasjournal.com * 2009 Lippincott Williams & Wilkins
3. Pancreas & Volume 00, Number 00, Month 2009 CO2 Pneumoperitoneum on Acute Pancreatitis
200-mmol/L glycine, pH 3.0, for 10 minutes, washed with
TBS-T 3 times for 30 minutes each, and reprobed with A-actin
(1:10,000), followed by antimouse secondary antibody (1:2000).
The band densities were determined by densitometric analysis
using the AlphaEase FC program. Density values of bands were
normalized to the total A-actin present in each lane and were
expressed in percentage of control.
Oxidation and Phosphorylation of
Liver Mitochondria
Liver mitochondria were prepared as previously de-
scribed.22 Mitochondrial oxygen consumption was measured
polarographically23 using a Gilson 5/6H Oxygraph (Gilson
Medical Electronics, Middleton, Wis) in a closed reaction vessel
fitted with a Clark oxygen electrode (Yellow Springs Instru-
ments, Yellow Springs, Ohio) at 28-C. The respiratory control
rate (RCR), considered an index of oxidative and phosphory-
lative mitochondrial function, was calculated by the rate of
oxygen consumption in the presence of adenosine diphosphate
(state 3, S3) over the consumption in the absence of adenosine
diphosphate (state 4, S4).24 Respiratory S3 and S4 were mea-
sured and reported as nanogram atoms of oxygen per milligram
of mitochondrial protein per minute. Mitochondrial protein
content was determined by the method of Lowry et al.25
Histological Analysis of the Pancreas
Pancreas tissue was sliced in 5-Km sections and stained
with hematoxylin/eosin. Histological assessment was performed
by a pathologist unaware of the experimental design.
FIGURE 2. Effect of CO2 on the systemic inflammation induced
by AP. Acute pancreatitis was induced in rats by intraductal
instillation of 0.5 mL of 5% taurocholic acid. One group received
abdominal insufflation with CO2 30 minutes before induction of
AP: serum levels of TNF-> (A), levels of IL-6 (B), and levels of IL-10
(C). Data are expressed as mean T SEM of 10 animals per group.
*P G 0.05.
H2O2 in the presence of O-dianisidine. Results were expressed
as optical density at 460 mm.20,21
Expression of Inducible NO and Cyclo-Oxygenase
Protein content in the supernatant of pancreas homoge-
nates was determined using the BCA protein assay reagent kit
(Pierce), according to the protocol provided by the manufac-
turer. Samples containing 20 Kg of protein were separated on
10% sodium dodecyl sulfateYpolyacrylamide gel electrophoresis
gels and were transferred to nitrocellulose membrane using the
Bio-rad Mini-Gel System and Trans-Blot SD-Semidry Transfer
Cells. For immunoblotting, the nitrocellulose membranes were
incubated in TBS-T buffer (150-mmol/L NaCl, 20-mmol/L Tris,
1% Tween 20, pH 7.4) containing 5% nonfat dried milk for
1 hour. The blot was treated with 1:1000 dilutions of rabbit
polyclonal antibodies to COX2 or rabbit antiserum iNOS for
2 hours at room temperature, then washed 3 times with TBS-T,
and incubated with 1:2000 dilutions of peroxidase-conjugated FIGURE 3. Effect of CO2 on the expression of COX2 and iNOS
monoclonal antirabbit immunoglobulin G for 1 hour at room and in the pancreas. Acute pancreatitis was induced in rats by
temperature. Protein bands at 72 kd (COX2) or at 130 kd (iNOS) intraductal instillation of 0.5 mL of 5% taurocholic acid. One
group received abdominal insufflation with CO2 30 minutes
were identified by comparison with Rainbow Protein Molecu- before induction of AP. The expression of COX2 and iNOS was
lar Weight Markers. The immunocomplexed peroxidase-labeled assessed by Western blot analysis. Illustration of the Western
antibodies were visualized by an ECL chemiluminescence kit blot represents 1 of 4 independent experiments. Expression of
following the manufacturer’s instruction (Amersham) and ex- protein was quantified by the AlphaEase FC software. Values are
posed to photographic film. Finally, blots were stripped with mean and SEM of 4 animals per group. *P G 0.001.
* 2009 Lippincott Williams & Wilkins www.pancreasjournal.com 3
4. Machado et al Pancreas & Volume 00, Number 00, Month 2009
2.5 5 foci
3 6 foci
3.5 7 foci
4 8 foci or more
Statistical Analysis
Results are reported as mean values with SEM. Continuous
variables (amylase, TNF->, IL-6, IL-10, peritoneal cells, COX2
and iNOS expression, MPO activity, and oxidation and phos-
phorylation of liver mitochondria) between groups were com-
pared by using unpaired Student t test. Histological analysis was
determined using the Mann-Whitney U test.
Survival was evaluated using the Kaplan-Meier method and
was analyzed for significance with the log-rank test (Cox-Mantel)
and Wilcoxon test.
P G 0.05 was considered significant.
The GraphPad Prism Software (GraphPad Software, San
Diego, Calif ) was used for statistical analysis.
RESULTS
CO2 Pneumoperitoneum Effect on the
Peritoneal Inflammation
During AP, there is accumulation of ascitic fluid in the
peritoneal cavity when compared with animals of the control
FIGURE 4. Effect of CO2 on the pancreas. Acute pancreatitis
was induced in rats by intraductal instillation of 0.5 mL of 5%
taurocholic acid. One group received abdominal insufflation with
CO2 30 minutes before induction of AP: MPO activity measured
in homogenates of pancreas samples (A), acinar pancreatic
necrosis (B), and fat pancreatic necrosis (C). Data are expressed
as mean T SEM of 10 animals per group. *P G 0.05.
The severity of acinar and fat necrosis was analyzed in
accordance with Schmidt et al.26 A scale of 0 to 4 was used
according to the following histological scoring criteria:
Acinar necrosis
0 Absent
0.5 Focal occurrence of 1 to 4 necrotic cells/high-power field
(HPF)
1 Diffuse occurrence of 1 to 4 necrotic cells/HPF
1.5 Same as 1 + focal occurrence of 5 to 10 necrotic cells/HPF
2 Diffuse occurrence of 5 to 10 necrotic cells/HPF
2.5 Same as 2 + focal occurrence of 11 to 16 necrotic cells/HPF
3 Diffuse occurrence of 11 to 16 necrotic cells/HPF (foci of
confluent necrosis)
3.5 Same as 3 + focal occurrence of more than 16 necrotic cells/
HPF
4 More than 16 necrotic cells/HPF (extensive confluent
necrosis)
Fat necrosis
0 Absent
0.5 1 focus
1 2 foci FIGURE 5. Reduction in acinar pancreatic necrosis 2 hours after
1.5 3 foci AP. A, Group without pretreatment. B, Group pretreated with
2 4 foci abdominal insufflation with CO2. Hematoxylin/eosin staining.
4 www.pancreasjournal.com * 2009 Lippincott Williams & Wilkins
5. Pancreas & Volume 00, Number 00, Month 2009 CO2 Pneumoperitoneum on Acute Pancreatitis
nonmanipulated group. A significant decrease in the volume of
ascitic fluid was observed in animals pretreated with abdominal
insufflation of CO2 when compared with animals without pre-
treatment (P G 0.05; Fig. 1A).
Figure 1C shows that, after 2 hours of AP induction, the
number of cells in the peritoneum was not significantly different
from that found in the control group. Carbon dioxide peritoneal
insufflation significantly reduced the number of cells in both
control and AP groups (P G 0.05).
In this model of AP, we found TNF-> in the ascites
(Fig. 1B), and pretreatment with CO2 significantly reduced the
total amount of peritoneal TNF-> (P G 0.05).
CO2 Pneumoperitoneum Effect on the
FIGURE 7. Effect of CO2 on animals’ survival. Acute pancreatitis
Systemic Inflammation was induced in rats by intraductal instillation of 0.5 mL of 5%
We found TNF->, IL-6, and IL-10 in the serum after taurocholic acid. One group received abdominal insufflation with
2 hours of AP induction. Treatment with CO2 caused a sig- CO2 30 minutes before induction of AP. The Kaplan-Meier curve
nificant decrease on serum levels of TNF-> (Fig. 2A) and IL-6 for the 2 groups is shown. Mortality was observed for 7 days after
(Fig. 2B) when compared with the nontreated group (P G 0.05). AP induction. P 9 0.05.
There was no significant difference in serum levels of IL-10
(Fig. 2C).
However, a marked reduction of TNF->/IL-10 ratio was Already at 2 hours of AP induction, we observed a sig-
observed after treatment with CO2 (6-fold). These results in- nificant reduction in acinar and fat necrosis in the group of
dicate that there is a prevalence of anti-inflammatory activity in animals pretreated with CO2 abdominal insufflation (Figs. 4B
the CO2-treated group compared with the nontreated group. and C). Figure 5 illustrates the reduction in acinar pancreatic
The elevated serum amylase levels found in the AP group necrosis 2 hours after AP in the group pretreated (Fig. 5B) with
(7.7 T 0.2 vs. 17.5 T 0.8 U/mL in control and AP groups, re- abdominal insufflation with CO2 compared with the group
spectively) were not affected by CO2 treatment. without pretreatment (Fig. 5A). Fat necrosis was undetectable in
the CO2-treated group.
CO2 Pneumoperitoneum Effect on
CO2 Pneumoperitoneum Effect on Lung and Liver
Pancreas Inflammation
After 2 hours of AP induction, we detected MPO activity in
The iNOS and COX2 enzymes were induced during in-
lung homogenates indicating that AP induced neutrophils’
flammatory conditions and were used here as markers of in-
infiltration into the lung (0.018 T 0.002 vs 0.084 T 0.007 for
flammation. We found the expression of both enzymes in the
control and AP groups, respectively). Treatment with CO2 did
pancreas after 2 hours of AP induction. Carbon dioxide treat-
not affect the lung MPO activity either after 2 hours or after
ment suppressed the expression of both enzymes (Fig. 3).
24 hours (Fig. 6).
To evaluate neutrophils’ infiltration into the pancreas, we
Also, we found that AP affected the liver because decreased
measured the MPO activity in tissue samples. We found neg-
mitochondrial oxidation and phosphorylation were observed
ligible MPO activity in the control group, whereas in the AP
(RCR: 4.02 T 0.14, S3: 99.41 T 3.63, S4: 24.73 T 0.90 nmol/mg
group, it was clearly detected. The group with CO2 abdominal
protein per minute vs RCR: 2.82 T 0.12, S3: 104.37 T 8.58,
insufflation pretreatment had a significant reduction in pancre-
S4: 37.01 T 2.43 nmol/mg protein per minute for control and
atic MPO activity compared with group without pretreatment
AP groups, respectively). Pretreatment with CO2 did not sig-
(Fig. 4A).
nificantly affect these parameters.
Mortality Study
Figure 7 shows decrease in mortality in CO2-treated group
(8/20, 40%) compared with the nontreated group (12/20, 60%);
however, it did not reach statistical significance.
DISCUSSION
It became clear since the 1990s that AP is associated with
the production of inflammatory cytokines that are implicated in
the development of systemic inflammatory response.27,28
As has been previously shown, macrophages are an im-
portant source of IL-1A and TNF->.29 These cells are con-
centrated in the liver, lung, spleen, lymph nodes, and lining of
the serosal membrane of the peritoneum and may be stimulated
during AP by leakage of activated pancreatic enzymes.12 It has
also been described that depletion of the cellular component
FIGURE 6. Effect of CO2 on pulmonary MPO activity. Acute from the peritoneal cavity by lavage previous to induction of
pancreatitis was induced in rats by intraductal instillation of 0.5 mL
of 5% taurocholic acid. One group received abdominal
AP reduces the toxicity of ascitic fluid without changing the
insufflation with CO2 30 minutes before induction of AP. The MPO severity of the pancreatic lesions. The authors report that more
activity measured in homogenates of lung samples 2 and 24 hours than 90% of the depleted cells were macrophages.30
after AP induction. Data are expressed as mean T SEM of 10 Recently, it has been demonstrated that CO2 pneumoper-
animals per group. P 9 0.05. itoneum could modify the inflammatory response to abdominal
* 2009 Lippincott Williams & Wilkins www.pancreasjournal.com 5
6. Machado et al Pancreas & Volume 00, Number 00, Month 2009
injury. Indeed, recent reports have shown that CO2 pneumoper- The lung MPO activity and the liver mitochondrial oxidation
itoneum attenuates the acute-phase response in sepsis produced and phosphorylation were similar in the treated and nontreated
by LPS injection or by cecal-ligation puncture.31,32 Carbon di- groups.
oxide abdominal insufflation pretreatment not only significantly We also observed a decrease in mortality in the CO2-treated
suppressed the plasma levels of the proinflammatory cytokine group (8/20, 40%) compared with the nontreated group (12/20,
IL-6 but also increased survival in animals with a LPS- 60%); however, this difference did not reach statistical sig-
contaminated laparotomy.15 These effects explain why laparo- nificance. Thus, there is a tendency of protection by CO2 treat-
scopic cholecystectomy is followed by reduced plasma levels of ment. This effect might become more relevant in conditions of
IL-6 when compared with cholecystectomy by laparotomy.33 milder pancreatitis or perhaps in pancreatitis induced by dif-
The effect of CO2 peritoneal insufflation is probably more im- ferent stimuli.
portant than the size of incision.15 In a previous study, it has been shown that CO2 abdominal
In the present study, CO2 abdominal insufflation pretreatment insufflation pretreatment increased survival after an LPS-
decreased the systemic inflammatory response induced by AP contaminated laparotomy.15 In that study, the systemic inflam-
(Figs. 1B, C and 2A, B). Serum levels of TNF-> and IL-6 were matory response was secondary to the stimulation mainly of
significantly reduced in the CO2 pneumoperitoneum group when peritoneal macrophages, whereas in AP, systemic inflammatory
compared with the control group. However, the serum levels of response is supposed to be due also to stimulation of mac-
the anti-inflammatory cytokine, IL-10, were similar between rophages from extra peritoneal sites by cytokines, enzymes, and
groups (Fig. 2C). When the ratio of TNF->/IL-10 was calculated, it other substances released in the circulation from damaged
clearly showed prevalence of anti-inflammatory activity in the pancreatic tissue.34,35 Indeed, we have previously demonstrated
CO2-treated group. This indicates that CO2 pneumoperitoneum that in AP there is an up-regulation of NO production by
influences the SIRS consequent to AP. nonparenchymal liver cells and an inhibition of Kupffer cell
Previous studies demonstrated that CO2 pneumoperitoneum microbicidal activity by the platelet-activating factor released
reduced TNF-> and IL-6 production, whereas it upregulated the during AP.36
anti-inflammatory cytokine IL-10 in animals whose peritoneal The effects of CO2 pneumoperitoneum are durable but
cavity was instilled with LPSs during laparotomy.32 Further reversible,14 producing a prophylactic effect against subsequent
studies evaluating the influence of CO2 pneumoperitoneum AP. Therefore, if an endoscopy for stone removal from common
pretreatment in LPS-contaminated laparotomy model, however, bile duct needs to be performed, it should better be done during
did not demonstrate any significant changes in IL-10.15 These the laparoscopic cholecystectomy to reduce the inflammatory
findings could be explained by the timing that blood samples response if an AP follows the procedure.
were harvested for cytokine determinations because IL-10 Whereas CO2 pneumoperitoneum pretreatment reduces the
generally peaks earlier.15 systemic inflammatory response in AP, CO2 pneumoperitoneum
The CO2 treatment also markedly affected the peritoneal after the induction of AP did not result in decrease of cytokine
inflammation: it reduced the volume of ascitic fluid and the total release.37,38
peritoneal TNF->. The number of cells in the peritoneum was The main causes of morbidity and mortality after pancreatic
similar in the AP and control groups at 2 hours, and the CO2 surgery are related to AP with consequent pancreatic fistula and
insufflation reduced the cell number in both groups. This effect systemic inflammation. Our data demonstrated that CO2 ab-
could be attributed to the adhesion of peritoneal cells to the dominal insufflation attenuates systemic inflammatory response
serosal lining. in AP with a reduction of proinflammatory cytokines TNF-> and
The inflammatory response in the pancreas was also re- IL-6 without a significant change in serum IL-10. It also reduces
duced by CO2 treatment. Inflammation involves activation of the inflammation both in the pancreas and in the peritoneal
intracellular signaling pathways, which leads to increased ex- cavity. This article suggests that CO2 pneumoperitoneum plays
pression of specific genes such as those for iNOS and COX2. a critical role on the better outcome in patients undergoing
Thus, these enzymes can be used as markers of inflammation. laparoscopic pancreatic surgery.
The results presented show that CO2 insufflation before in-
duction of AP suppressed the expression of these enzymes
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