This study investigated the effects of N-acetylcysteine (NAC) on asprosin and meteorin-like protein (METRNL) levels in a rat model of lower extremity ischemia-reperfusion injury. Rats were divided into five groups: a control group, sham surgery group, NAC treatment group, ischemia-reperfusion injury group, and ischemia-reperfusion injury plus NAC treatment group. Serum and tissue levels of asprosin and METRNL were measured after 120 minutes of reperfusion. The results showed that asprosin and METRNL levels were lower in the ischemia-reperfusion injury group compared to controls, but higher in the ischemia-reperfusion injury plus NAC treatment group compared
This study investigated the protective effects of carvacrol on testicular damage caused by experimental testicular torsion-detorsion in rats. The study consisted of 4 groups of rats: a control group, a torsion group, a torsion-detorsion group, and a torsion-detorsion group treated with carvacrol. Histopathological analysis found increased damage in spermatogenic cells and decreased antioxidant levels in the torsion and torsion-detorsion groups compared to the control and carvacrol groups. Immunohistochemical staining showed increased endothelin-1 expression in the torsion and detorsion groups but not in the carvacrol group. The results suggest that carvacrol may prevent
The aim of the study was to investigate the damage created in tissue by using an in vivo isolated portal ischemia and reperfusion model in the rat liver and the effects of heparin administration on the complement system. A total of 25 male rats weighing 150-290 gr were used in the study. Following anesthesia with ketamine hydrochloride and xylazine hydrochloride, the incision area was shaved in all rats except the control group. The portal vein was isolated and clamped, and ischemia and reperfusion created. Two groups were sacrificed at the 24th hour and two at the 48th hour. Heparin was administered to one of the groups sacrificed at the 24th hour and not to the other group, and similarly one of the groups sacrificed at the 48th hour received heparin while the other did not. Biochemical and pathologic parameters were used to evaluate the damage using serum and liver tissue samples from the sacrificed rats. We used the liver GSH, MPO and C3 levels and the serum IL-6 level to evaluate the ischemia and reperfusion damage in the liver tissue. Heparin was shown to decrease the damage occurring after ischemia and reperfusion by decreasing complement activation and the MPO and IL-6 levels while increasing GSH levels as a result of the statistical analysis performed. Heparin was shown to prevent tissue damage after ischemia and reperfusion by decreasing complement activation and inflammation.
Liver ischemia/reperfusion injury, a setting in which the functional mass is ...Prof. Hesham N. Mustafa
The document discusses a study on the effects of the phosphodiesterase type-5 (PDE5) inhibitor tadalafil on liver ischemia/reperfusion injury in rats. The study found that tadalafil treatment before ischemia/reperfusion injury helped restore normal liver enzyme levels, reduced oxidative stress and inflammation in liver tissue, and decreased levels of tumor necrosis factor-alpha, interleukin-6, and intercellular adhesion molecule-1. Histological analysis also showed tadalafil treatment helped protect against liver damage. The findings suggest that modulating the inflammatory response may be one mechanism by which tadalafil provides hepatoprotection against ischemia/reperfusion injury.
This document summarizes a study that evaluated the effects of xylazine alone, lignocaine alone, and a combination of xylazine and lignocaine administered via lumbar epidural injection in water buffalo calves. The combination of xylazine and lignocaine produced the fastest onset of analgesia and the longest duration of complete analgesia of the thorax, flank, and hind limbs. It also caused the deepest level of sedation. Physiological parameters like heart rate, respiratory rate, and temperature decreased most with the combination treatment. While all treatments caused some hematological and biochemical changes, the combination generally had greater and more prolonged effects. The results suggest there may be an additive analgesic effect between epidurally administered xylazine and lign
This document provides an overview of various experimental animal models that are used to induce different disease conditions and evaluate potential treatments. It discusses models for inflammatory diseases, pyrexia, arrhythmias, hypertension, diabetes, hyperlipidemia, and tests for assessing central nervous system activity, muscle relaxation, sedation, anxiety, seizures, convulsions, and analgesia. Examples of specific animal models and procedures are provided for each condition. The models described allow for studying disease pathogenesis and testing new drug candidates before human trials.
This study analyzed early postoperative complications in 145 adult patients who received total intravenous anesthesia (TIVA) with propofol and remifentanil for elective neurosurgery. The authors found:
1) The overall incidence of shivering was 30.3%, postoperative nausea and vomiting (PONV) was 16.6%, and postoperative hypertension (blood pressure over 25% of preoperative value) was 35.2%.
2) 51% of patients experienced at least one of these complications. Complication rates varied significantly between surgical groups.
3) The intracranial vascular surgery group had the highest rates of shivering (58.8%) and PONV (29.4
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).
This study investigated whether the drug paricalcitol could reduce kidney damage caused by ischemia-reperfusion injury in rats. Rats were divided into four groups: a control group, a group given only paricalcitol, a group that underwent ischemia-reperfusion injury, and a group that received paricalcitol before undergoing ischemia-reperfusion injury. The results showed that pretreatment with paricalcitol before ischemia-reperfusion injury significantly decreased serum markers of kidney damage and oxidative stress in kidney tissue compared to rats that only underwent ischemia-reperfusion injury. Histological examination also showed less kidney tissue injury in rats pretreated with paricalcitol. Therefore, the study concluded that paricalcitol has a protective
This study investigated the protective effects of carvacrol on testicular damage caused by experimental testicular torsion-detorsion in rats. The study consisted of 4 groups of rats: a control group, a torsion group, a torsion-detorsion group, and a torsion-detorsion group treated with carvacrol. Histopathological analysis found increased damage in spermatogenic cells and decreased antioxidant levels in the torsion and torsion-detorsion groups compared to the control and carvacrol groups. Immunohistochemical staining showed increased endothelin-1 expression in the torsion and detorsion groups but not in the carvacrol group. The results suggest that carvacrol may prevent
The aim of the study was to investigate the damage created in tissue by using an in vivo isolated portal ischemia and reperfusion model in the rat liver and the effects of heparin administration on the complement system. A total of 25 male rats weighing 150-290 gr were used in the study. Following anesthesia with ketamine hydrochloride and xylazine hydrochloride, the incision area was shaved in all rats except the control group. The portal vein was isolated and clamped, and ischemia and reperfusion created. Two groups were sacrificed at the 24th hour and two at the 48th hour. Heparin was administered to one of the groups sacrificed at the 24th hour and not to the other group, and similarly one of the groups sacrificed at the 48th hour received heparin while the other did not. Biochemical and pathologic parameters were used to evaluate the damage using serum and liver tissue samples from the sacrificed rats. We used the liver GSH, MPO and C3 levels and the serum IL-6 level to evaluate the ischemia and reperfusion damage in the liver tissue. Heparin was shown to decrease the damage occurring after ischemia and reperfusion by decreasing complement activation and the MPO and IL-6 levels while increasing GSH levels as a result of the statistical analysis performed. Heparin was shown to prevent tissue damage after ischemia and reperfusion by decreasing complement activation and inflammation.
Liver ischemia/reperfusion injury, a setting in which the functional mass is ...Prof. Hesham N. Mustafa
The document discusses a study on the effects of the phosphodiesterase type-5 (PDE5) inhibitor tadalafil on liver ischemia/reperfusion injury in rats. The study found that tadalafil treatment before ischemia/reperfusion injury helped restore normal liver enzyme levels, reduced oxidative stress and inflammation in liver tissue, and decreased levels of tumor necrosis factor-alpha, interleukin-6, and intercellular adhesion molecule-1. Histological analysis also showed tadalafil treatment helped protect against liver damage. The findings suggest that modulating the inflammatory response may be one mechanism by which tadalafil provides hepatoprotection against ischemia/reperfusion injury.
This document summarizes a study that evaluated the effects of xylazine alone, lignocaine alone, and a combination of xylazine and lignocaine administered via lumbar epidural injection in water buffalo calves. The combination of xylazine and lignocaine produced the fastest onset of analgesia and the longest duration of complete analgesia of the thorax, flank, and hind limbs. It also caused the deepest level of sedation. Physiological parameters like heart rate, respiratory rate, and temperature decreased most with the combination treatment. While all treatments caused some hematological and biochemical changes, the combination generally had greater and more prolonged effects. The results suggest there may be an additive analgesic effect between epidurally administered xylazine and lign
This document provides an overview of various experimental animal models that are used to induce different disease conditions and evaluate potential treatments. It discusses models for inflammatory diseases, pyrexia, arrhythmias, hypertension, diabetes, hyperlipidemia, and tests for assessing central nervous system activity, muscle relaxation, sedation, anxiety, seizures, convulsions, and analgesia. Examples of specific animal models and procedures are provided for each condition. The models described allow for studying disease pathogenesis and testing new drug candidates before human trials.
This study analyzed early postoperative complications in 145 adult patients who received total intravenous anesthesia (TIVA) with propofol and remifentanil for elective neurosurgery. The authors found:
1) The overall incidence of shivering was 30.3%, postoperative nausea and vomiting (PONV) was 16.6%, and postoperative hypertension (blood pressure over 25% of preoperative value) was 35.2%.
2) 51% of patients experienced at least one of these complications. Complication rates varied significantly between surgical groups.
3) The intracranial vascular surgery group had the highest rates of shivering (58.8%) and PONV (29.4
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).
This study investigated whether the drug paricalcitol could reduce kidney damage caused by ischemia-reperfusion injury in rats. Rats were divided into four groups: a control group, a group given only paricalcitol, a group that underwent ischemia-reperfusion injury, and a group that received paricalcitol before undergoing ischemia-reperfusion injury. The results showed that pretreatment with paricalcitol before ischemia-reperfusion injury significantly decreased serum markers of kidney damage and oxidative stress in kidney tissue compared to rats that only underwent ischemia-reperfusion injury. Histological examination also showed less kidney tissue injury in rats pretreated with paricalcitol. Therefore, the study concluded that paricalcitol has a protective
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 aimed to evaluate the protective effects of zofenopril on intestinal ischemia-reperfusion injury using a rat model. Rats were divided into five groups: sham surgery, ischemia only, ischemia-reperfusion, ischemia-reperfusion with zofenopril pretreatment, and zofenopril only. Biochemical markers of oxidative stress and apoptosis were measured in intestinal tissue samples. Histopathological examination and immunohistochemical staining for caspase-3 was also performed. Results showed that ischemia-reperfusion caused intestinal damage including mucosal destruction and cell apoptosis. Zofenopril pretreatment reduced oxidative stress markers and inhibited apoptosis, protecting against ischemia-reperfusion injury on histological and biochemical evaluation. The
This study explored whether the compound Rhein can inhibit stress in the endoplasmic reticulum and mitochondria caused by acute myocardial infarction through activating the PI3K/Akt/ERK signaling pathway. A rat model of myocardial infarction was used. Rats treated with Rhein showed improved cardiac function and reduced cardiomyocyte apoptosis compared to untreated rats. Rhein was found to inhibit expression of endoplasmic reticulum and mitochondrial proteins associated with stress and apoptosis, while elevating expression of proteins in the PI3K/Akt/ERK pathway. The results suggest Rhein can protect against myocardial damage from infarction by reducing endoplasmic reticulum and mitochondrial dysfunction through this signaling pathway.
This study examined the effects of prolonged simvastatin (SIM) treatment on ischemia-reperfusion (I/R) induced acute kidney injury in rats. Rats were divided into four groups: sham, ischemia, I/R, and I/R+SIM treated. The I/R group showed intense inflammation, necrosis, and apoptosis in kidney tissue. The I/R+SIM group showed reduced inflammation and tissue damage. Biochemical analysis found increased oxidative stress and inflammation markers in the ischemia and I/R groups compared to control, but levels in the I/R+SIM group were similar to control. Histological analysis also showed more damage in ischemia and I/R groups versus control, while the I/R+
This document summarizes methods for screening sympathomimetic and sympatholytic drugs. Sympathomimetics mimic epinephrine and stimulate the sympathetic nervous system, while sympatholytics block these effects. Screening methods include in vivo tests using cat spleens or measuring nictitating membrane prolapse in cats. In vitro tests involve measuring contractions of rabbit pulmonary arteries, rat vas deferens, or cat spleen strips in response to drugs. These assays allow evaluating sympatholytic potency by assessing the ability of test drugs to reduce contractions caused by agonists like epinephrine and norepinephrine.
This study investigated the protective effects of losartan, an AT1 receptor blocker, 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 losartan group. Biochemical assays and histopathological analysis showed that losartan prevented oxidative damage and reduced apoptosis in germ cells compared to the torsion/detorsion group, suggesting losartan has a protective role against ischemia/reperfusion injury in rat testes.
This study investigated the protective effects of allopurinol on experimentally induced ovarian ischemia-reperfusion injury in rats. Rats were divided into four groups: a sham group, an ischemia group, an ischemia-reperfusion group, and an ischemia-reperfusion + allopurinol treated group. The study found that allopurinol decreased MDA levels and increased GSH levels compared to the ischemia and ischemia-reperfusion groups, indicating it reduced oxidative load. Allopurinol also decreased caspase-3 and sFlt-1 expression, suggesting it inhibited apoptosis and protected the ovaries from damage caused by ischemia-reperfusion.
This study examined the effects of bacterial endotoxin (LPS) on myocardial function during ischemia-reperfusion injury. Rabbits were injected with increasing doses of LPS or saline prior to inducing myocardial ischemia through coronary artery occlusion. Higher LPS doses suppressed cardiac contractility and worsened injury compared to lower doses or saline. Blocking TNF-alpha prevented the additional harmful effects of LPS on cardiac function after ischemia. The findings suggest that bacterial endotoxins can exacerbate ischemia-reperfusion injury in a dose-dependent manner mediated through TNF-alpha.
This document provides details on bioassay methods for several compounds including vasopressin, digitalis, d-tubocurarine, histamine, and 5-hydroxytryptamine (5-HT).
It describes two common bioassay methods for vasopressin - the first uses rats to measure changes in blood pressure, the second uses rats and measures anti-diuretic activity. For digitalis, it outlines guinea pig and pigeon bioassays measuring the lethal dose. The d-tubocurarine bioassay uses rabbits to measure head drop or isolated frog muscle to measure contraction reduction. Histamine is assayed using guinea pig ileum or other tissues and measuring contraction. Finally, 5
Effect of carvedilol on atrial remodeling in canine model of atrial fibrillation
Authors: Jun Kishihara, Shinichi Niwano, Hiroe Niwano, Yuya Aoyama, Akira Satoh, Jun Oikawa, Michiro Kiryu, Hidehira Fukaya, Yoshihiko Masaki, Hideaki Tamaki, Tohru Izumi, Junya Ako
This study investigated the antioxidant effects of nebivolol in protecting against testicular damage caused by torsion-detorsion injury in rats. Forty rats were divided into four groups: a control group, a torsion group, a torsion/detorsion group, and a torsion/detorsion+nebivolol group. Biochemical assays and histopathological examination found that torsion-detorsion injury increased oxidative stress markers and apoptosis in testicular tissue, while administration of nebivolol before detorsion decreased oxidative stress and apoptosis. The study suggests that nebivolol has a protective effect against ischemia-reperfusion injury in the testes caused by torsion-
This study assessed the feasibility of noninvasive ventilation (NIV) in cats by comparing cardiovascular parameters, drug requirements, ventilation parameters, and blood gases between cats undergoing NIV via nasal mask and invasive ventilation via endotracheal tube. Eight healthy cats underwent 6 hours of mechanical ventilation using each method, with a minimum 9-day washout period between. All cats were effectively ventilated with both methods. There were no significant differences in cardiovascular parameters, drug requirements, or sedation scores between the two groups. However, arterial oxygen levels were higher with invasive ventilation and expiratory tidal volumes were lower with NIV due to air leaks around the nasal mask. NIV is possible in cats but does not provide cardiovascular benefits over invasive ventilation
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.
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 study investigated the effects of simvastatin treatment on a rat model of ovarian torsion and detorsion. Rats were divided into four groups: control, ischemia, ischemia-reperfusion, and ischemia-reperfusion treated with simvastatin. Ovarian tissue samples were analyzed for markers of oxidative damage (MDA and GSH-Px) and apoptosis (caspase-3 and sFlt-1 expression). Results showed that simvastatin decreased MDA levels and increased GSH levels, suggesting it reduced oxidative damage. Simvastatin also decreased caspase-3 and sFlt-1 expression, indicating it prevented cell apoptosis and regulated angiogenesis. The study concludes that simvastatin administration protects against cell
manuscript-Shenfu_ submitted version by DR. Zafar.pdfdrzafar02
Shenfu injection reduces post-resuscitation multiple organ injury in a swine model of exsanguination cardiac arrest. The study found that administering Shenfu injection after resuscitation from exsanguination cardiac arrest in swine: 1) increased survival rates; 2) improved hemodynamic parameters; and 3) reduced biomarkers of organ injury in the heart, liver, kidneys and levels of inflammatory markers, cell apoptosis, and caspase-3 expression in multiple organs. The results suggest Shenfu injection has a protective effect on multiple organs after resuscitation from exsanguination cardiac arrest.
This study examined neurons in the medulla oblongata related to gastric mucosal lesions in rats subjected to restraint water-immersion stress (RWIS). The study found that compared to controls, RWIS rats had: 1) increased cholinergic neurons in the dorsal motor nucleus of the vagus and nucleus ambiguous, and increased catecholaminergic neurons in the nucleus of the solitary tract; 2) increased oxytocin receptor- and vasopressin 1b receptor-expressing neurons in the dorsal motor nucleus and nucleus of the solitary tract; but 3) no difference in methionine-enkephalin-expressing neurons in the nucleus of the solitary tract. This suggests hyperactivity of cholinergic and cate
This study compared the use of ATL-1223, an adenosine A2A agonist, during ex vivo lung perfusion (EVLP) alone or during EVLP and reperfusion to rehabilitate non-heart-beating donor pig lungs after 12 hours of cold ischemia storage. Lungs were assigned to groups receiving DMSO (control), ATL-1223 during EVLP then DMSO (ATL-E), or ATL-1223 during EVLP and reperfusion (ATL-B). Both ATL-1223 groups had significantly higher post-operative oxygen levels compared to controls, but there was no significant difference between the ATL-1223 groups. Further investigation is needed
Background: Body of literature are becoming pronounced that pathological condition in one organ of the body might have an effect on other distal organs owing to the fact, that the entire body metabolism is orchestrated centrally.
Pathological events occurring in an organ are likely to be extended to other organs. Pretreatment that minimize these events are presumed to be beneficial to the extended organs.
Methods: Following 30 min of ischemia and 48 h of reperfusion in the kidney, rats under anesthesia were sacrificed and blood sample collected through cardiac puncture. Serum level of troponin I, and activities of total creatine kinase (CK), mass creatine kinase (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma –glutamyl transferase (GGT) were estimated spectrophotometrically.
Results: Serum troponin I increased to 0.031 ± 0.001 ng/ml in the ischemic group, and following pretreatment with Lmm (600mg/kg), serum level of troponin I decreased significantly to 0.021 ± 0.001 ng/ml (P<.05).><.05),><.05)><.05).
BACKGROUND: Sequential Epstein-Barr virus (EBV)–positive B cell lymphoma to the initial diagnosis of angioimmunoblastic T cell lymphoma (AITL) is very rare, the exact mechanism and standard therapy of which is still being explored. CASE: A 50-year-old man was admitted to our hospital in January 2014 with a three-week history of enlargement of multiple lymph nodes. His initial pathological evaluation indicated AILT. The reactivation of EBV was observed during the immunosuppression therapy for AITL, accompanied by onset of subcutaneous nodules proven to be EBV-positive diffuse large B cell lymphoma (DLBCL) based on the pathological findings of rebiopsy. The patient was successfully treated with chidamide, a histone deacetylase (HDAC) inhibitor, and rituximab.
Conclusion: The sufficient surveillance for serum EBV and repeat biopsy is necessary for patients with AITL, and this treatment modality may become an active option.
Keywords: angioimmunoblastic T cell lymphoma, Epstein-Barr virus, HDAC inhibitor, non-Hodgkin lymphoma, peripheral T cell lymphoma
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.
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Similar to Effects of N-Acetylcysteine on Meteorin-like Protein and Asprosin in an Experimental Lower Extremity Ischemia-Reperfusion Injury Model
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 aimed to evaluate the protective effects of zofenopril on intestinal ischemia-reperfusion injury using a rat model. Rats were divided into five groups: sham surgery, ischemia only, ischemia-reperfusion, ischemia-reperfusion with zofenopril pretreatment, and zofenopril only. Biochemical markers of oxidative stress and apoptosis were measured in intestinal tissue samples. Histopathological examination and immunohistochemical staining for caspase-3 was also performed. Results showed that ischemia-reperfusion caused intestinal damage including mucosal destruction and cell apoptosis. Zofenopril pretreatment reduced oxidative stress markers and inhibited apoptosis, protecting against ischemia-reperfusion injury on histological and biochemical evaluation. The
This study explored whether the compound Rhein can inhibit stress in the endoplasmic reticulum and mitochondria caused by acute myocardial infarction through activating the PI3K/Akt/ERK signaling pathway. A rat model of myocardial infarction was used. Rats treated with Rhein showed improved cardiac function and reduced cardiomyocyte apoptosis compared to untreated rats. Rhein was found to inhibit expression of endoplasmic reticulum and mitochondrial proteins associated with stress and apoptosis, while elevating expression of proteins in the PI3K/Akt/ERK pathway. The results suggest Rhein can protect against myocardial damage from infarction by reducing endoplasmic reticulum and mitochondrial dysfunction through this signaling pathway.
This study examined the effects of prolonged simvastatin (SIM) treatment on ischemia-reperfusion (I/R) induced acute kidney injury in rats. Rats were divided into four groups: sham, ischemia, I/R, and I/R+SIM treated. The I/R group showed intense inflammation, necrosis, and apoptosis in kidney tissue. The I/R+SIM group showed reduced inflammation and tissue damage. Biochemical analysis found increased oxidative stress and inflammation markers in the ischemia and I/R groups compared to control, but levels in the I/R+SIM group were similar to control. Histological analysis also showed more damage in ischemia and I/R groups versus control, while the I/R+
This document summarizes methods for screening sympathomimetic and sympatholytic drugs. Sympathomimetics mimic epinephrine and stimulate the sympathetic nervous system, while sympatholytics block these effects. Screening methods include in vivo tests using cat spleens or measuring nictitating membrane prolapse in cats. In vitro tests involve measuring contractions of rabbit pulmonary arteries, rat vas deferens, or cat spleen strips in response to drugs. These assays allow evaluating sympatholytic potency by assessing the ability of test drugs to reduce contractions caused by agonists like epinephrine and norepinephrine.
This study investigated the protective effects of losartan, an AT1 receptor blocker, 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 losartan group. Biochemical assays and histopathological analysis showed that losartan prevented oxidative damage and reduced apoptosis in germ cells compared to the torsion/detorsion group, suggesting losartan has a protective role against ischemia/reperfusion injury in rat testes.
This study investigated the protective effects of allopurinol on experimentally induced ovarian ischemia-reperfusion injury in rats. Rats were divided into four groups: a sham group, an ischemia group, an ischemia-reperfusion group, and an ischemia-reperfusion + allopurinol treated group. The study found that allopurinol decreased MDA levels and increased GSH levels compared to the ischemia and ischemia-reperfusion groups, indicating it reduced oxidative load. Allopurinol also decreased caspase-3 and sFlt-1 expression, suggesting it inhibited apoptosis and protected the ovaries from damage caused by ischemia-reperfusion.
This study examined the effects of bacterial endotoxin (LPS) on myocardial function during ischemia-reperfusion injury. Rabbits were injected with increasing doses of LPS or saline prior to inducing myocardial ischemia through coronary artery occlusion. Higher LPS doses suppressed cardiac contractility and worsened injury compared to lower doses or saline. Blocking TNF-alpha prevented the additional harmful effects of LPS on cardiac function after ischemia. The findings suggest that bacterial endotoxins can exacerbate ischemia-reperfusion injury in a dose-dependent manner mediated through TNF-alpha.
This document provides details on bioassay methods for several compounds including vasopressin, digitalis, d-tubocurarine, histamine, and 5-hydroxytryptamine (5-HT).
It describes two common bioassay methods for vasopressin - the first uses rats to measure changes in blood pressure, the second uses rats and measures anti-diuretic activity. For digitalis, it outlines guinea pig and pigeon bioassays measuring the lethal dose. The d-tubocurarine bioassay uses rabbits to measure head drop or isolated frog muscle to measure contraction reduction. Histamine is assayed using guinea pig ileum or other tissues and measuring contraction. Finally, 5
Effect of carvedilol on atrial remodeling in canine model of atrial fibrillation
Authors: Jun Kishihara, Shinichi Niwano, Hiroe Niwano, Yuya Aoyama, Akira Satoh, Jun Oikawa, Michiro Kiryu, Hidehira Fukaya, Yoshihiko Masaki, Hideaki Tamaki, Tohru Izumi, Junya Ako
This study investigated the antioxidant effects of nebivolol in protecting against testicular damage caused by torsion-detorsion injury in rats. Forty rats were divided into four groups: a control group, a torsion group, a torsion/detorsion group, and a torsion/detorsion+nebivolol group. Biochemical assays and histopathological examination found that torsion-detorsion injury increased oxidative stress markers and apoptosis in testicular tissue, while administration of nebivolol before detorsion decreased oxidative stress and apoptosis. The study suggests that nebivolol has a protective effect against ischemia-reperfusion injury in the testes caused by torsion-
This study assessed the feasibility of noninvasive ventilation (NIV) in cats by comparing cardiovascular parameters, drug requirements, ventilation parameters, and blood gases between cats undergoing NIV via nasal mask and invasive ventilation via endotracheal tube. Eight healthy cats underwent 6 hours of mechanical ventilation using each method, with a minimum 9-day washout period between. All cats were effectively ventilated with both methods. There were no significant differences in cardiovascular parameters, drug requirements, or sedation scores between the two groups. However, arterial oxygen levels were higher with invasive ventilation and expiratory tidal volumes were lower with NIV due to air leaks around the nasal mask. NIV is possible in cats but does not provide cardiovascular benefits over invasive ventilation
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.
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 study investigated the effects of simvastatin treatment on a rat model of ovarian torsion and detorsion. Rats were divided into four groups: control, ischemia, ischemia-reperfusion, and ischemia-reperfusion treated with simvastatin. Ovarian tissue samples were analyzed for markers of oxidative damage (MDA and GSH-Px) and apoptosis (caspase-3 and sFlt-1 expression). Results showed that simvastatin decreased MDA levels and increased GSH levels, suggesting it reduced oxidative damage. Simvastatin also decreased caspase-3 and sFlt-1 expression, indicating it prevented cell apoptosis and regulated angiogenesis. The study concludes that simvastatin administration protects against cell
manuscript-Shenfu_ submitted version by DR. Zafar.pdfdrzafar02
Shenfu injection reduces post-resuscitation multiple organ injury in a swine model of exsanguination cardiac arrest. The study found that administering Shenfu injection after resuscitation from exsanguination cardiac arrest in swine: 1) increased survival rates; 2) improved hemodynamic parameters; and 3) reduced biomarkers of organ injury in the heart, liver, kidneys and levels of inflammatory markers, cell apoptosis, and caspase-3 expression in multiple organs. The results suggest Shenfu injection has a protective effect on multiple organs after resuscitation from exsanguination cardiac arrest.
This study examined neurons in the medulla oblongata related to gastric mucosal lesions in rats subjected to restraint water-immersion stress (RWIS). The study found that compared to controls, RWIS rats had: 1) increased cholinergic neurons in the dorsal motor nucleus of the vagus and nucleus ambiguous, and increased catecholaminergic neurons in the nucleus of the solitary tract; 2) increased oxytocin receptor- and vasopressin 1b receptor-expressing neurons in the dorsal motor nucleus and nucleus of the solitary tract; but 3) no difference in methionine-enkephalin-expressing neurons in the nucleus of the solitary tract. This suggests hyperactivity of cholinergic and cate
This study compared the use of ATL-1223, an adenosine A2A agonist, during ex vivo lung perfusion (EVLP) alone or during EVLP and reperfusion to rehabilitate non-heart-beating donor pig lungs after 12 hours of cold ischemia storage. Lungs were assigned to groups receiving DMSO (control), ATL-1223 during EVLP then DMSO (ATL-E), or ATL-1223 during EVLP and reperfusion (ATL-B). Both ATL-1223 groups had significantly higher post-operative oxygen levels compared to controls, but there was no significant difference between the ATL-1223 groups. Further investigation is needed
Background: Body of literature are becoming pronounced that pathological condition in one organ of the body might have an effect on other distal organs owing to the fact, that the entire body metabolism is orchestrated centrally.
Pathological events occurring in an organ are likely to be extended to other organs. Pretreatment that minimize these events are presumed to be beneficial to the extended organs.
Methods: Following 30 min of ischemia and 48 h of reperfusion in the kidney, rats under anesthesia were sacrificed and blood sample collected through cardiac puncture. Serum level of troponin I, and activities of total creatine kinase (CK), mass creatine kinase (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma –glutamyl transferase (GGT) were estimated spectrophotometrically.
Results: Serum troponin I increased to 0.031 ± 0.001 ng/ml in the ischemic group, and following pretreatment with Lmm (600mg/kg), serum level of troponin I decreased significantly to 0.021 ± 0.001 ng/ml (P<.05).><.05),><.05)><.05).
Similar to Effects of N-Acetylcysteine on Meteorin-like Protein and Asprosin in an Experimental Lower Extremity Ischemia-Reperfusion Injury Model (20)
BACKGROUND: Sequential Epstein-Barr virus (EBV)–positive B cell lymphoma to the initial diagnosis of angioimmunoblastic T cell lymphoma (AITL) is very rare, the exact mechanism and standard therapy of which is still being explored. CASE: A 50-year-old man was admitted to our hospital in January 2014 with a three-week history of enlargement of multiple lymph nodes. His initial pathological evaluation indicated AILT. The reactivation of EBV was observed during the immunosuppression therapy for AITL, accompanied by onset of subcutaneous nodules proven to be EBV-positive diffuse large B cell lymphoma (DLBCL) based on the pathological findings of rebiopsy. The patient was successfully treated with chidamide, a histone deacetylase (HDAC) inhibitor, and rituximab.
Conclusion: The sufficient surveillance for serum EBV and repeat biopsy is necessary for patients with AITL, and this treatment modality may become an active option.
Keywords: angioimmunoblastic T cell lymphoma, Epstein-Barr virus, HDAC inhibitor, non-Hodgkin lymphoma, peripheral T cell lymphoma
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.
Objective: The association between telomerase reverse transcriptase (TERT) promoter mutation and outcome of melanoma is unclear and controversial. We aim to conduct a meta-analysis and investigate whether the TERT promoter mutation is a prognostic factor of melanoma.
Study Design: Appropriate studies were searched in 3 databases: PubMed, Web of Science, and Embase. Pooled hazard ratios (HRs) were counted through random effects model.
Results: Heterogeneity was moderate in overall survival (OS) (I2=43.7%, p=0.059) and low in disease-free survival (DFS) (I2=0.0%, p=0.587). Sensitivity analysis indicated that the removal of any of the study did not affect the final results. Evidence for publication bias was not found (Begg’s test, p=0.281; Egger’s test, p=0.078). The pooled OS HRs from combined effects analysis was determined (HR 1.07; 95% CI 0.83–1.39, p=0.585), together with the pooled HRs of DFS (HR 1.65; 95% CI 1.02–2.66, p=0.042). TERT promoter mutation predicted a good outcome in meta-static melanoma patients (HR 0.66; 95% CI 0.46–0.96, p=0.042). The pooled HRs of combined mutation in TERT promoter and BRAF (HR 6.27; 95% CI 2.7–14.58, p=0.000) predicted a bad outcome in melanoma patients.
Conclusion: TERT promoter mutation significantly predicted poor DFS outcome but, on the contrary, predicted a good outcome in metastatic melanoma patients. The combined TERT promoter and BRAF mutation was a significant independent factor of OS in melanoma patients.
Keywords: melanoma; meta-analysis; mutation; prognosis; promoter regions, genetic; skin neoplasms; telomerase; TERT promoter mutation; TERT protein, human
Objective: In order to reduce complications accompanied with dental implant restoration, this study strives to prepare a novel sealant and lubricant that can be used in dental implant systems as well as to evaluate its characteristics.
Study Design: Chitosan (CS), β-glycerophosphate pentahydrate (β-GP), and nano silver (nAg) were used to prepare thermosensitive hydrogel. According to the different volume ratios of CS to β-GP, 3 experimental groups were established, namely 16/4, 13/7, and 10/10 groups. Their morphology, composition, and chemical properties were analyzed via SEM, EDS, and FTIR. In addition, the effect of the hydrogel on the stability of dental implant-abutment connection was investigated by removal torque test combined with dynamic cyclic loading experiment. The maximum fracture load was measured under different lubricating conditions by electronic universal testing machine. The cytotoxicity and in vitro antibacterial effect of the hydrogel were examined respectively by CCK-8 test and the spread plate method.
Results: The CS/β-GP/nAg thermosensitive hydro-gel was successfully prepared in this study, which was found to be a porous structure through SEM. The removal torque test and the dynamic cyclic loading experiment showed that the removal torque of the experimental group was greater than that of the control group. Furthermore, the single load-to-fracture test indicated that the 16/4 group had the greatest maximum bearing load. The in vitro cytotoxicity test using rat bone marrow stromal cells (rBMSCs) and human gingival fibroblast cells (hGFCs) showed no cytotoxicity in all 3 groups. The 3 experimental groups had obvious antibacterial effects against E. coli, S. aureus, and P. gingivalis.
Conclusion: A nontoxic antibacterial CS/β-GP/nAg thermosensitive hydrogel for lubricating purpose was successfully fabricated. When the volume ratio of CS to β-GP was 16/4, this thermosensitive hydrogel demonstrated better sealing and lubricating abilities and had a positive influence on the reliability of dental implant-abutment connection.
Keywords: abutment, dental implant, dental implant restoration, dental sealant, lubrication, thermosensitive hydrogel
Objective: To investigate the bond strength of resin-modified glass ionomer enhanced with bioactive glass (Activa BioActive-Base/Liner) to composite resin using different dental adhesive systems.
Study Design: In this study, Activa BioActive-Base/Liner (ABA/BL) was placed in cylindrical cavities formed in acrylic blocks. In blocks divided into 6 groups according to the adhesive system to be applied, two-step etch-and-rinse Gluma 2 Bond (Heraeus Kulzer, Germany), one-step self-etch Gluma Self Etch (Heraeus Kulzer), universal system Gluma Universal (Heraeus Kulzer), two-step self-etch Clearfil SE Protect (Kuraray, Japan), one-step self-etch Clearfil S3 Bond Plus (Kuraray), and universal system Clearfil S3 Bond Universal (Kuraray) adhesive systems were applied on ABA/BL. After composite resin (3M ESPE Filtek Ultimate) was applied to the prepared surfaces, the specimens were placed in a universal test device and shear bond strength test was determined. Fracture types were evaluated using a stereomicroscope and scanning electron microscope. Data were analyzed by Shapiro-Wilk, two-way ANOVA, Kruskal-Wallis, and Post-Hoc Multiple Comparisons tests.
Results: In terms of bond strength values, the highest bond value was seen in the two-step self-etch (Clearfil SE Protect) group, and the lowest bond strength value was seen in the universal system (Clearfil S3 Bond Universal) group. There was no statistically significant difference between the adhesive agent groups in terms of bond strength values (p>0.05).
Conclusion: It is thought that choosing the two-step self-etch technique as an adhesive system when resin-modified glass ionomer enhanced with bioactive glass (ABA/BL) is used as the pulp capping/base material will be more appropriate in terms of bond strength.
Keywords: adhesive systems, bioactive materials, bond strength, cariostatic agents, composite resins, dental materials, fluorides, glass ionomer, glass ionomer cements, materials testing, vital pulp therapy
Objective: To analyze the sonographic features of different histopathological subtypes of borderline ovarian tumors (BOTs) confirmed by pathology, and to study the ultrasound performances of various types in borderline ovarian tumors.
Study Design: Retrospective analysis was performed on the pathological results and ultrasound projection findings of 129 patients diagnosed as BOTs by ultrasound department of our hospital from January 2012 to November 2019. All patients were confirmed by surgical pathology and scanned consecutively by the investigators using transabdominal or transvaginal ultrasound examination.
Results: Serous borderline tumors (SBOTs) were observed, and the prevalence rate (53%) was significantly higher than that of other subtypes, and the probability of bilateral lesions was higher (40%). The sonogram often showed ultrasound features of papillary neoplasm in the lesion and good internal echo (p<0.05). Mucinous borderline ovarian tumors (MBOTs) were mostly unilateral lesions (86%). The prevalence was second only to SBOTs. Histomorphological examinations were divided into gastrointestinal-type and endocervical-type. Among them, the gastrointestinal type of MBOTs were mostly unilateral, and their incidence was higher than that of endocervical-type of MBOTs. Compared with other pathological subtypes, the gastrointestinal type is more likely to show the sonographic characteristics of huge space occupying in the pelvic and abdominal cavity (mean diameter >10 cm), polycystic, multiple septums, and poor internal echo (p<0.05). The ultrasonographic features of the endocervical-type of MBOTs were similar to those of SBOTs. Compared with gastrointestinal type, the sonographic images showed smaller lesion diameter, less septal or cyst, and more papillary excrescences in the tumor (p<0.05). The borderline clear cell tumor is the intermediate transition between the clear cell adenofibroma and the clear cell carcinoma. The clinical manifestations are diverse and lack specificity. The histology of sonography was mainly solid, and the multiple microcapsules were honeycomb-like. It can also be shown as cystic. Among the 169 patients with BOTs, 20 cases of SBOTs, 17 cases of MBOTs, and 10 cases of other rare subtypes were complicated with other diseases or multiple subtypes. This study did not find significant ultrasonic characteristics were used for distinguish them from other subtypes.
Conclusion: BOTs is a common disease in women during the reproductive period. It is characterized by the development of malignant tumors. Its clinical and pathological subtypes are complex and diverse. It leads many doctors to use the terms “large pelvic mass” and “solid ovarian mass” for diagnosis because of their lack of experience and understanding.
Keywords: adenocarcinoma, mucinous; adenocarcinoma, serous; borderline ovarian tumors; diagnostic imaging; ovarian neoplasms; papillary neoplasms; prognosis; transvaginal ultrasound, ultrasonography
Objective: To evaluate the results of the effect of nebivolol on tibial bone defect and graft application in new bone development in the rat.
Study Design: Thirty Wistar albino rats were divided into 3 groups. In the Control group, tibia bone defect was created without any treatment. In the Defect+ Graft group, allograft treatment was performed by forming a 6 mm tibial bone defect. In the Defect+Graft+ Nebivolol group, alloplastic bone graft was placed in the calvarial bone defect and then nebivolol (0.34 mg/mL solution/day) treatment was intraperitoneally applied for 28 days.
Results: Histopathological examination revealed inflammation in the defect area, congestion in the vessels, degeneration in collagen fibers, and an increase in osteoclast cells. There was an increase in inflammation and blood vessel structure in graft application, and osteoblastic activity matrix formation after reorganization nebivolol application in collagen fibers. Osteonectin expression was positive in the collagen fiber and matrix, starting in the Graft group, in osteoblasts, whereas in the Nebivolol group, osteoblasts increased in osteocytes and new bone formation.
Conclusion: Nebivolol is thought to have a positive effect on osteoinductive bone growth factors and contribute to the cell-matrix interaction, in addition to the supporting effect of the graft with its antioxidative effect.
Keywords: allograft; bone; bone regeneration; disease models, animal; nebivolol; orthopedic procedures; osteonectin; rats; tibia; tibial defect
Objective: The prognostic indictors of age-related poor outcomes in patients with acute myeloid leukemia (AML) are still controversial. The aim of this work was to provide comprehensive insights into the effect of different hemocytes and to investigate the association between age and clinical features in adult patients with AML.
Study Design: A retrospective study was performed to determine the role of age in the therapeutic outcomes of AML. A total of 166 newly diagnosed adult patients’ data from January 2015 to November 2019 in Zhongshan Hospital of Xiamen University were collected and analyzed.
Results: Older patients presented a poorer prognosis (p=0.001) with shorter overall survival, which is served as age-related outcomes. Binary logistic regression demonstrated that cytogenetic risk (OR=4.508, 95% CI 2.733–7.435), leukocyte (OR=7.410, 95% CI 1.139–5.910), and bone marrow blast cells (OR=3.261, 95% CI 1.075–5.615) were independent indictors for age-related prognosis. In addition, Kaplan-Meier curve also revealed that the above factors were associated with overall survival (all p values <0.001).
Conclusion: Cytogenetic risk, leukocyte, and bone marrow blast cells are dominant factors which account for the age-related poor outcomes and shorter overall survival in AML.
Keywords: acute myeloid leukemia, adult, cytogenetic risk, hemocyte, leukemia, overall survival
This study investigated the effects of intracoronary nicorandil and tirofiban on no-reflow phenomenon and clinical outcomes in 438 patients with acute coronary syndrome undergoing percutaneous coronary intervention. Both nicorandil and tirofiban improved TIMI blood flow grades after PCI, with TIMI grade 3 flow in 85.2% and 81.4% of patients respectively. There was no significant difference in major adverse cardiac events between the two groups. The study concluded that intracoronary nicorandil can improve coronary perfusion in ACS patients, but its effect on long-term prognosis requires further research.
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)
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
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
Objective: To probe into the influence of miR-21 on the proliferation as well as apoptosis of oral squamous cell carcinoma (OSCC) and its causative role.
Study Design: We adopted microarray for detecting the differentially expressed genes in OSCC tumor tis-sues and paracancerous tissues. We assessed the link of miR-21 expression with tumor size, lymph node metastasis, and tumor differentiation. We employed CCK-8 and EdU assay for detecting the impact of miR-21 inhibitor and miR-21 mimic on Cal-27 cell proliferation, as well as TUNEL and AnnexinV-FITC/PI double staining for detecting miR-21 expression on cell apoptosis. We forecasted the possible target of miR-21 via TargetScan, as well as detected the interaction of miR-21 with PTEN via luciferase reporter experiment. The function of miR-21 expression in PTEN signaling pathway was monitored via western blot. We constructed PTEN overexpression plasmid and conducted rescue experiment to evaluate overexpressed PTEN on miR-21–induced proliferation.
Results: Microarray and RT-qPCR indicated that miR-21 expression increased demonstrably in OSCC. Subsequently, statistical analysis showed that miR-21 expression was plainly correlated with tumor size, lymph node metastasis, tumor differentiation, and smoking history. CCK-8 and EdU method exhibited that miR-21 mimics manifestly promoted Cal-27 cell proliferation, while miR-21 inhibitor blatantly inhibited Cal-27 cell proliferation. TUNEL and V-FITC/PI double staining assay showed that miR-21 inhibitor conspicuously promoted Cal-27 cell apoptosis. CCK-8 and EdU assay exhibited that overexpressed PTEN abolished the pro-proliferation influence of miR-21 mimic. TUNEL and V-FITC/PI experiments pointed out that knocking down PTEN abrogated the pro-apoptosis impact of miR-21 inhibitor.
Conclusion: miR-21 contributes to OSCC cell proliferation via targeting PTEN and inhibits its apoptosis.
Keywords: Akt/PKB signaling pathway; apoptosis; biomarkers, tumor; carcinoma, squamous cell; cell line, tumor; cell proliferation; microRNAs; miR-21; miRNA-21; mouth neoplasms; oral cancer; oral squamous cell carcinoma; proliferation; real time PCR
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
Objective: Tongue squamous cell carcinoma (TSCC) is a prominent type of oral cancer. Despite the numerous research studies on SCC and microRNAs (miRs), the relation between TSCC and miR-135b-5p is poorly discussed. This experiment aims to find out the possible effect of miR-135b-5p on TSCC with the network of its downstream genes.
Study Design: TSCC tissues and adjacent normal tissues were harvested. Then, expression of miR-135b-5p and AT-rich interactive domain‑containing protein 1A gene (ARID1A) and the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) pathway was analyzed. After the transfection of miR-135b-5p inhibitor and its negative control into TSCC cells, functional assays were employed to measure cell proliferation, apoptosis, and cycle. Next, the target relation between miR-135b-5p and ARID1A was confirmed. In addition, the fact that miR-135b-5p promoted TSCC development via mediating ARID1A was demonstrated by functional rescue experiment.
Results: miR-135b-5p was upregulated in TSCC tissues and cells, while ARID1A was suppressed (p< 0.05). Silenced miR-135b-5p discouraged TSCC cell proliferation, improved apoptosis, induced cell cycle arrest, and increased ARID1A expression while inactivating the PI3K/AKT axis (p<0.05). Furthermore, knockdown of ARID1A reversed the impacts on TSCC cell proliferation and apoptosis exerted by silencing miR-135b-5p.
Conclusion: This research supported that silenced miR-135b-5p impeded TSCC proliferation and apoptosis by promoting ARID1A and inactivating the PI3K/AKT axis, which may provide some indications for TSCC alleviation.
Keywords: apoptosis; ARID1A; ARID1A protein, human; carcinoma, squamous cell; cell line, tumor; cell proliferation; drug resistance, neoplasm; microRNA-135b-5p; microRNAs; PI3K/AKT pathway; neoplasm metastasis; neoplastic stem cells; proliferation; protein binding; tongue; tongue squamous cell carcinoma
Objective: To investigate the immunohistochemical staining of hypoxia-inducible factor 1-alpha (HIF-1α) and Ki-67 expression in the placenta of pregnant women with placenta previa and placenta accreta.
Study Design: Thirty placentas (10 normotensive, 10 placenta previa, and 10 placenta accreta) were processed for routine histological tissue processing. The biochemical parameters of patients were recorded. Placentas were stained with hematoxylin-eosin and HIF-1α and Ki-67 immunostaining.
Results: Normal histology was observed in placentas of normotensive pregnant women. Placenta previa sections showed increased syncytial knots, intervillous hemorrhage, fibrin accumulation, and hyalinization. In placenta accreta sections, increased syncytial nodes, vascular dilation/congestion, fibrin accumulation, and hyalinization were observed. Normotensive placentas showed no HIF-1α expression. In placenta previa tissues, high HIF-1α expression was observed in vascular endothelial cells, villous stromal cells, and syncytial knots. High HIF-1α expression was recorded in villous stromal cells and cytotrophoblast cells in placenta accreta. In normotensive placental tissues, no Ki-67 expression was observed. In placenta previa sections, high Ki-67 expression was observed mostly in root villi stromal cells and some endothelial cells. High Ki-67 expression was observed mostly in villi stromal cells of placenta accreta.
Conclusion: It is thought that HIF-1α is an important regulatory gene in the development of villus in trophoblast invasion such as placenta accreta and previa, while Ki-67 will play a key role in the development of abnormal placenta with its stimulating effect on inflammatory cell development and angiogenesis in accreta and preeclampsia.
Objective: To examine the oropharynx of patients with ectodermal dysplasia showing maxillary retrusion and mandibular protrusion with a short and concave facial structure using cone-beam computed tomography method. Ectodermal dysplasia refers to the congenital disorder defined by the abnormal development of the structure originating from the ectoderm.
Study Design: In order to examine the oropharynx airway, measurements and statistical evaluations were made in 3 levels in sagittal and transversal directions on three-dimensional cone beam computed tomography images obtained from 14 individuals divided into 2 groups as Ectodermal Dysplasia group (n=7) and Control group (n=7).
Results: As a result of statistical analysis, no statistically significant difference was found between the groups at any level or direction in metric measurements performed on all 3 planes taken at the sagittal and transversal levels (p>0.05).
Conclusion: Our findings on ectodermal dysplasia are similar to Class III malpositions that show similarity with ectodermal dysplasia.
Objective: Diabetic nephropathy is one of the most serious complications of diabetes mellitus. It develops in approximately one-third of diabetic patients, years after the onset of metabolic abnormalities.
Study Design: The biopsy specimens were evaluated with the focus on light microscopy. The aim of our study was to reveal differences in the details and the frequency of occurrence of individual histomorphological changes in diabetic nephropathy and other glomerulonephritides.
Results: Diabetic nephropathy accounted for 14 out of 82 analyzed biopsies. Isolated thickening of the glomerular basement membrane was not present in any case, but along with some degree of mesangial expansion, hypercellularity or glomerulosclerosis was seen in 12 out of 14 findings of diabetic nephropathy. In other glomerular diseases, mesangial changes, but without glomerular basement membrane thickening, were the most frequent findings. In addition to glomerular lesions, some of the tubular, interstitial, and vascular changes were seen in 13 out of 14 patients with diabetic nephropathy. In other glomerulonephritides the combination of all these changes was a rare finding.
Conclusion: There are cases where immunofluorescence and electron microscopy cannot be performed or their results are not helpful. In such cases we must rely on light microscopic histomorphological changes.
The document describes an experiment that aimed to establish a model of cardiomyocyte hypertrophy using cultured neonatal rat cardiomyocytes treated with angiotensin II (Ang II). The effects of rutin treatment on various markers of hypertrophy were then observed. Rutin treatment inhibited Ang II-induced increases in cardiomyocyte surface area, intracellular calcium levels, and expression of hypertrophy marker proteins. Rutin also inhibited decreases in calcium ATPase activity and nitric oxide levels caused by Ang II. The results suggest rutin has protective effects against Ang II-induced cardiomyocyte hypertrophy, potentially by regulating intracellular calcium handling and nitric oxide signaling.
This study investigated the expression of Caspase-12 and ADAMTS-5 in placental samples from 15 pregnant women with placenta previa and 15 healthy pregnant women. Histopathological examination found significant degeneration and apoptotic changes in the placenta previa group. Immunohistochemical analysis showed increased expression of ADAMTS-5 and Caspase-12 in the placenta previa group. The researchers concluded that increased expression of these proteins, which are involved in extracellular matrix development, inflammation, and angiogenesis, may negatively impact maternal function and fetal development in placenta previa.
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4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
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2. White adipose tissue is the major synthesis site of
ASP. Following its synthesis, ASP is released into
the blood, and its plasma concentration increases
during fasting. Besides peripheral target tissues,
ASP can also cross the blood-brain barrier and
have an effect on the central nervous system. ASP
has been reported to have systemic effects, and this
molecule is increasingly gaining popularity among
researchers.3 Meteorin-like protein (METRNL) is
a hormone released into the circulation mainly
after the skeletal muscle and adipose tissue are
exposed to cold or exercise.4 Increased circulating
METRNL results in increased energy expenditure
in the whole body and improves glucose tolerance
in people with obesity.5 In our study, changes in
skeletal muscle and serum levels of ASP and
METRNL were investigated using N-acetylcysteine
(NAC), a powerful antioxidant, in rats with experi
mentally induced IR injury.
Materials and Methods
This study received ethical approval from the local
Animal Research Ethics Committee (Decision No.
2020/01; Date: January 15, 2020) and was con
ducted in the Experimental Research Center.
The rats used in this study were maintained at
22–25°C room temperature with 12 hours of light
(7:00–19:00) and 12 hours of darkness (19:00–7:00).
They were fed in specially constructed cages the
bottoms of which were cleaned daily. Feed was
given in steel containers and drinking water (tap
water) was given in glass bottles. The same stan
dard rat feed was given to all rats, ad libitum water
and food intake was ensured, and the animals
were taken care of by cleaning their containers
daily. In total, 30 male Wistar Albino rats aged
8–10 weeks were divided into 5 groups as follows:
Group I (Control group) (n=6). No procedure was
applied to the rats in this group during the ex-
periment.
Group II (Sham group) (n=6). Laparotomy and ab-
dominal aortic dissection were performed on the
rats in this group. The amount of stress applied
and the duration of the surgical procedure were
the same as that in the other groups.
Group III (N-Acetylcysteine group) (n=6). A single
dose of 150 mg/kg NAC was administered intra
peritoneally to the rats in this group 120 minutes
before the end of the experiment.
Group IV (Ischemia-Reperfusion group) (n=6). The
infrarenal abdominal aorta was exposed by immo
bilizing the rats in the supine position and per
forming laparotomy in the midline of the abdo-
men. Later, the infrarenal abdominal aorta was
clipped using a nontraumatic microvascular clamp
for 120 minutes, followed by opening the clips
and terminating the experiment after 120 minutes
of reperfusion.
Group V (Ischemia-Reperfusion+N-Acetylcysteine
group) (n=6). The infrarenal abdominal aorta was
exposed by immobilizing the rats in the supine
position and performing laparotomy in the mid-
line of the abdomen. Later, the infrarenal abdom
inal aorta was clipped using a nontraumatic
microvascular clamp for 120 minutes, followed
by opening the clips, administering a single dose
of 150 mg/kg NAC intraperitoneally, and termi
nating the experiment after 120 minutes of reper-
fusion.
Anesthesia was achieved using intramuscular
administration of 30 mg/kg ketamine hydrochlo
ride (Ketalar; Pfizer, Groton, Connecticut, USA)
and 3 mg/kg xylazine hydrochloride 37 (Rompun;
Bayer, Leverkusen, Germany).
The rats were anesthetized with additional
doses of the anesthetic (1/3 of the initial dose)
when necessary, while ensuring spontaneous ac
tivity of their respiratory muscles throughout the
procedure. To prevent possible hypothermia, the
operation was performed in the supine position
under a heating lamp. The skin was prepared asep
tically, and laparotomy was performed in the mid-
line of the abdomen. To maintain fluid balance,
10 mL warm saline was administered into the
physiological peritoneal cavity. The abdominal
aorta was accessed by pulling the intestines to
the left with wet gas. To achieve anticoagulation,
150 U/kg heparin (Nevparin; Mustafa Nevzat I
∙
laç
San, Istanbul, Turkey) was administered intra
venously through the tail vein 2 minutes before
placing the aortic clamp. A lower extremity ische
mia rat model was created by placing a non
traumatic micro
vascular clamp on the infrarenal
abdominal aorta. The absence of vascular flow
was confirmed using a HADECO brand ES-101 EX
model handheld doppler device on the distal side
of the clamp. The abdominal incision was closed
to minimize heat and fluid loss. The induced is-
chemia was observed for 120 minutes. After oc-
clusion, the abdomen was reopened and the mi-
68 Analytical and Quantitative Cytopathology and Histopathology®
Ozguler and Ustunel
3. crovascular clamp in the infrarenal abdominal
aorta was removed, followed by reperfusion for
120 minutes. To evaluate the ischemia and reper
fusion procedure with aortic clamping, handheld
doppler device was used to confirm the loss of
flow in the distal aorta during the clamping pro-
cedure. Similarly, to evaluate the reperfusion, a
handheld doppler device was used to confirm the
maintenance of flow in the distal aorta after clamp
removal.
Retrieval of Samples
At the end of the experiment, following intracar-
diac blood collection under anesthesia from the
rats of all groups, muscle tissues of the lower ex
tremity were removed rapidly. The blood samples
were centrifuged at 4,000 rpm for 5 minutes, and
the sera obtained were kept at −80°C until further
analysis.
The muscle tissue samples were fixed in 10%
formaldehyde solution for immunohistochemical
analysis. After fixing, the samples were washed
using tap water and were analyzed using rou
tine histological analysis. The tissues were embed
ded in paraffin blocks cut into 4–6 µm thick sec
tions that were then placed on polylysine-coated
slides.
Biochemical Analysis
Total Oxidant Status Measurement. Serum total oxi
dant status (TOS) levels were measured using a
Rel Assay Total Oxidant Status Test Kit (Mega Tip,
Gaziantep, Turkey).6
Serum METRNL and ASP Measurement. Serum lev
els of METRNL (Rat METRNL ELISA kit, SunRed
201-11-3875, China) and ASP (Rat Asprosin ELISA
kit, SunRed 201-11-5748, China) were measured
using ELISA.
Immunohistochemical Analysis
The 4–6 µm thick sections retrieved from the
paraffin blocks were placed on polylysine-coated
slides. Deparaffinized tissues were passed through
graded series of alcohol and boiled in a citrate buf
fer solution of pH 6 in a microwave oven (750 W)
for 7+5 minutes for antigen retrieval. After boil
ing, the tissues were kept at room temperature for
approximately 20 minutes to cool down, washed
3× using phosphate-buffered saline (PBS; P4417,
Sigma-Aldrich, USA) for 5 minutes each time, and
incubated for 5 minutes with hydrogen peroxide
block solution (Hydrogen Peroxide Block, TA-125-
HP, Lab Vision Corporation, USA) to prevent
endogenous peroxidase activity. The tissues were
again washed 3× using PBS for 5 minutes each
time. After applying Ultra V Block (TA-125-UB,
Lab Vision Corporation, USA) solution to the tis
sues for 5 minutes to prevent background stain-
ing, METRNL and ASP were diluted to 1/200 and
incubated with primary antibodies (METRNL Po-
lyclonal Antibody, PAH662Ra01, CLOUD-CLONE
Corp., Katy, Texas, USA) and with antiasprosin
antibody (FNab09797, Fine Test, China) for 60
minutes at room temperature in a humid envir-
onment. After this, the tissues were washed using
PBS as previously mentioned and incubated
with the secondary antibody (Biotinylated Goat
anti-Polyvalent (anti-mouse/rabbit IgG), TP-125-
BN, Lab Vision Corporation, USA) for 30 min
utes at room temperature in a humid environ
ment. Then, the tissues were washed using PBS
as previously mentioned, incubated with strepta
vidin peroxidase (TS-125-HR, Lab Vision Corpo
ration, USA) for 30 minutes at room temperature
in a humid environment, and then kept in PBS.
3-amino-9-ethylcarbazole (AEC) Substrate+AEC
Chromo
gen (AEC Substrate, TA-015 and HAS,
AEC Chromogen, TA-002-HAC, Lab Vision Cor-
poration, USA) solution was dropped on the tis
sues, and after detecting the image signal under
the light microscope, the tissues were washed with
PBS. The tissues that were counterstained with
Mayer’s hematoxylin were passed through PBS
and distilled water and covered with an appropri
ate closure solution (Large Volume Vision Mount,
TA-125-UG, Lab Vision Corporation, USA). For
negative control, PBS was applied in the other
tissues instead of the primer in the same way. The
prepared tissues were then examined, evaluated,
and photographed under a Leica DM500 micro
scope (Leica DFC295).
A histoscore was defined based on the preva-
lence (0.1: <25%, 0.4: 26–50%, 0.6: 51–75%, 0.9:
76–100%) and severity (0: none, +0.5: very little,
+1: low, +2: moderate, +3: severe) of immunoreac-
tivity. Histoscore = prevalence×severity.
Statistical Analyses
SPSS version 22 (IBM Corp. Released 2013. IBM
SPSS Statistics for Windows, Version 22.0. IBM
Corp., Armonk, New York, USA) was used for
statistical analyses. Numerical measurements were
presented as median and minimum-maximum.
Volume 43, Number 2/April 2021 69
N-Acetylcysteine on Meteorin-like Protein and Asprosin
4. The Kruskal-Wallis test was used for general com
parisons between more than 2 groups. The Mann-
Whitney U test was used for comparison between
2 groups. The statistical significance level was set
at 0.05 in all tests.
Results
Biochemical Findings
Serum TOS Levels. In the biochemical analysis
performed for evaluating the serum TOS levels of
all groups as compared with the control group,
no statistically significant difference was observed
between the Sham (p=0.548) and NAC (p=0.167)
groups; however, a statistically significant increase
was observed in the TOS levels of the IR group
(p=0.002). In addition, when compared with the
IR group, a statistically significant decrease in the
TOS levels was observed in the IR+NAC group
(p=0.024) (Table I).
Serum METRNL Levels. In the biochemical analy
sis performed for evaluating the serum METRNL
levels of all groups as compared with the control
group, no statistically significant difference was
observed between the Sham (p=0.229) and NAC
(p=0.133) groups; however, a statistically signifi
cant decrease was observed in the METRNL lev
els of the IR group (p=0.010). In addition, when
compared with the IR group, a statistically signifi
cant increase in the METRNL levels was observed
in the IR+NAC group (p=0.009) (Table I).
Serum ASP Levels. In the biochemical analysis
performed for evaluating the serum ASP levels
of all groups as compared with the control group,
no statistically significant difference was observed
between the Sham (p=0.262) and NAC (p=1.00)
groups; however, a statistically significant decrease
was observed in the ASP levels of the IR group
(p=0.002). When compared with the IR group, a
statistically significant increase in the ASP levels
was observed in the IR+NAC group (p=0.010)
(Table I).
Immunohistochemical Findings
METRNL Immunoreactivity. The examination of
immunohistochemical staining under the light
microscope for METRNL immunoreactivity result
ed in the observation of METRNL immunoreac
tivity in muscle tissue myocytes (black arrow).
Compared to the control group (Figure 1a), there
was no statistically significant difference between
the Sham (Figure 1b) (p=0.394) and NAC (Figure
1c) (p=0.394) groups in terms of METRNL immu
noreactivity, but there was a statistically signifi-
cant decrease in METRNL immunoreactivity in
the IR group (Figure 1d) (p=0.002). When com-
pared with the IR group, a statistically significant
increase in METRNL immunoreactivity was ob
served in the IR+NAC group (Figure 1e) (p=
0.002), and METRNL immunoreactivity was not
observed in the negative control (Figure 1f) (Ta-
ble II).
ASP Immunoreactivity. The examination of immu
nohistochemical staining under the light micro
scope for ASP immunoreactivity resulted in the
observation of ASP immunoreactivity in muscle
tissue myocytes (black arrow).
When compared with the control group (Fig
ure 2a), there was no statistically significant dif-
ference in the ASP immunoreactivities of the
Sham (Figure 2b) (p=0.589) and NAC (Figure 2c)
(p=0.818) groups, but there was a statistically sig
nificant decrease in the ASP immunoreactivity of
the IR group (Figure 2d). When compared with
70 Analytical and Quantitative Cytopathology and Histopathology®
Ozguler and Ustunel
Table I Serum Total Oxidant Status, Meteorin-like Protein, and Asprosin Levels
Total oxidant status Meteorin-like protein
(µmol/L) (ng/mL) Asprosin (ng/mL)
Group Median (min-max) Median (min-max) Median (min-max)
Control 7.88 (7.23–8.22) 2.52 (2.30–2.86) 39.21 (30.69–48.49)
Sham 7.92 (6.89–8.01) 2.18 (1.49–2.47) 44.99 (36.71–49.93)
NAC 7.11 (7.23–8.22) 1.97 (1.88–2.06) 41.41 (34.36–48.47)
IR 11.75 (10.09–13.44)a 0.68 (0.25–1.24)a 22.19 (17.98–26.12)a
IR+NAC 8.75 (8.71–9.89)b 2.11 (1.24–2.47)b 44.39 (41.03–48.65)b
Values are presented as median (min-max).
aCompared with the control group.
bCompared with the IR group (p<0.05).
5. the IR group, a statistically significant increase
in ASP immunoreactivity was observed in the
IR+NAC group (Figure 2e) (p=0.017), and ASP
immunoreactivity was not observed in the nega-
tive control (Figure 2f) (Table II).
Discussion
IR injury is a pathology wherein complex inflam
matory processes are involved in the process of
reestablishing blood flow to areas with impaired
circulation. The regional and systemic effects of
free oxygen radicals cause major damage. NAC,
a glutathione precursor, is a molecule that has
been reported to be beneficial in IR injuries be-
cause it prevents oxidative damage at the molec
ular level.7 In the IR model created in our study,
the increase in TOS levels and the significant
decrease in TOS levels in the NAC-administered
group are in line with previously reported data.1,7
In addition, the lower levels of TOS in the control
and sham groups as compared with the IR group
suggest that IR injury significantly increases oxi
dant molecules.
METRNL is a recently discovered molecule
which is produced in the adipose tissue. METRNL
has been reported to reduce lipid-mediated inflam
matory response and insulin resistance through
activation of 5′ AMP-activated protein kinase
(AMPK) or PPARγ signaling pathways in the ske
letal muscles of mice.5
In the H9C2 cell line, METRNL has been shown
to reduce oxidative stress-induced myocardial
damage by activating the AMPK-PAK2 pathway,
which attenuates the effects of oxidative stress
on the endoplasmic reticulum, thereby reducing
cardiomyocyte apoptosis. Hence, METRNL has
been suggested for the treatment of myocardial
ischemia.8 In another study on the H9C2 cell line,
METRNL reduced the harmful effects of doxoru
bicin, which causes oxidative damage on cardiac
cells.9 In the same study it was shown that while
the protective effects of METRNL were evident,
the antitumor potential of doxorubicin was also
preserved. Hence, it can be assumed that the anti
apoptotic characteristic of METRNL is cell type–
specific.
Similar to the results of these studies, in our
study METRNL decreased in response to increased
TOS in the tissue and serum in the IR model,
suggesting that exogenous supplementation of
METRNL in cell cultures can protect cardiomyo
cytes and skeletal muscle, thereby providing effec
Volume 43, Number 2/April 2021 71
N-Acetylcysteine on Meteorin-like Protein and Asprosin
Table II Meteorin-like Protein and Asprosin Immunoreactivity
Histoscore
Meteorin-like protein Asprosin
Group Median (min-max) Median (min-max)
Control 0.90 (0.80–2.70) 0.40 (0.30–0.60)
Sham 1.05 (0.60–1.80) 0.35 (0.20–0.45)
NAC 1.80 (0.80–2.70) 0.42 (0.10–0.60)
IR 0.42 (0.30–0.80)a 0.10 (0.10–0.20)a
IR+NAC 1.05 (0.80–1.80)b 0.30 (0.20–0.45)b
Values are presented as median (min-max).
aCompared with the control group.
bCompared with the IR group (p<0.05).
Figure 1
Meteorin-like protein
immunoreactivity of the study
groups.
6. tive protection against IR injury. It is also known
that a significant amount of METRNL is synthe
sized in the skeletal muscle during exercise.10 The
reduction in METRNL to its normal levels in the
period following NAC administration strengthens
the link between METRNL and oxidative stress.
In addition, changes in circulation indicate that
METRNL may also be effective in distal organ
pathologies of IR injury.
ASP, a hormone synthesized in the white adi-
pose tissue, regulates hepatic glucose release.2
In addition, ASP has been reported to cross the
blood-brain barrier, stimulate orexigenic neurons
through G protein–related pathways, and inhibit
anorexigenic neurons.11 ASP has been shown to be
present in various tissues, such as liver, pancreas,
kidney, testis, skeletal muscle, and heart.12,13 The
biological effect of ASP on the liver depends on
the G protein receptor, resulting in glucose pro
duction and release.2 It has been reported that
beta cells are also synthesized under hyperlipid-
emic conditions.14 In addition, it has been shown
that the expression of superoxide dismutase in-
creases via activation of the ERK1/2 signaling
pathway in mesenchymal stromal cells treated
with ASP.15 In another study, ASP was found to
inhibit the production of malondialdehyde and
oxidation products in mouse cardiomyocytes.16
With this effect, ASP inhibits cell death by de-
creasing the level of reactive oxygen radicals.
Contrary to the protective effects of ASP on the
heart, ASP increases free oxygen radicals and pro
inflammatory cytokines via toll-like receptor in
beta cells.14 Therefore, it may be thought to cause
the loss of ASP beta cells. It has been claimed that
METRNL and ASP can be biomarkers in differ
entiating between malignant mesothelioma and
benign diseases.13 Jung et al17 suggested that, con
trary to its effects on the heart, ASP has no effect
on the formation of free oxygen radicals in the
skeletal muscles. However, the receptor that ASP
binds to in the skeletal muscles has not yet been
elucidated.3 The data on the effects of ASP on
skeletal muscles and IR injury is preliminary and
conflicting. This is because ASP is a newly discov
ered protein. In our experiment, the reduction in
ASP levels in the oxidative environment of IR in-
jury and the elevation in ASP levels in NAC or
control groups will provide key insights for future
studies on this topic.
It has long been known that adipokines and
myokines are effective in inflammatory pro
cesses.3,8,18,19 We demonstrated changes in the
tissue and serum levels of METRNL and ASP,
which are newly identified adipokines, in lower
extremity IR injury. We proved their presence
in the skeletal muscle immunohistochemically. In
addition, the simultaneous changes in the levels
of METRNL and ASP in the serum and the region
of IR injury suggest that the IR injury may be
the source of the circulating levels of these mole
cules. Hence, we believe that ASP and METRNL
may be useful in the diagnosis or treatment of
lower extremity injuries, which are an important
clinical pathology as they cause both local and dis
tal organ damage.
72 Analytical and Quantitative Cytopathology and Histopathology®
Ozguler and Ustunel
Figure 2
Asprosin immunoreactivity of
the study groups.
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total oxidant status. Clin Biochem 2005;38:1103-1111
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N-Acetylcysteine on Meteorin-like Protein and Asprosin