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.
The role of curcumin in streptozotocin induced hepatic damage and the trans-d...Prof. Hesham N. Mustafa
Diabetic patients frequently suffer from non-alcoholic steatohepatitis. The current study aimed to investigate the role of curcumin and the response of hepatic stellate cells in streptozotocin (STZ)-induced hepatic damage. Sixty male rats were divided into three groups. The normal control injected with a citrate buffer vehicle and the diabetic control group which was injected intraperitoneally (IP) with a single-dose of streptozotocin (50mg/kg body weight) and a diabetic group was treated with an oral dose of curcumin at 80 mg/kg body weight daily for 60 days. Curcumin effectively counteracts oxidative stress-mediated hepatic damage and improves biochemical parameters. Alpha-smooth muscle actin (α-SMA) was significantly reduced, and insulin antibodies showed strong positive immunoreactivity with curcumin administration. These results optimistically demonstrate the potential use of curcumin, which is attributed to its antiradical/antioxidant activities and its potential β-cell regenerative properties. Also, it has the capability to encourage the trans-differentiation of hepatic stellate cells into insulin-producing cells for a period of time. In addition, as it is an anti-fibrotic mediator that inhibits hepatic stellate cell activation and the transition to myofibroblast-like cells, this suggests the possibility of considering curcumin's novel therapeutic effects in reducing hepatic dysfunction in diabetic patients.
The role of curcumin in streptozotocin induced hepatic damage and the trans-d...Prof. Hesham N. Mustafa
Diabetic patients frequently suffer from non-alcoholic steatohepatitis. The current study aimed to investigate the role of curcumin and the response of hepatic stellate cells in streptozotocin (STZ)-induced hepatic damage. Sixty male rats were divided into three groups. The normal control injected with a citrate buffer vehicle and the diabetic control group which was injected intraperitoneally (IP) with a single-dose of streptozotocin (50mg/kg body weight) and a diabetic group was treated with an oral dose of curcumin at 80 mg/kg body weight daily for 60 days. Curcumin effectively counteracts oxidative stress-mediated hepatic damage and improves biochemical parameters. Alpha-smooth muscle actin (α-SMA) was significantly reduced, and insulin antibodies showed strong positive immunoreactivity with curcumin administration. These results optimistically demonstrate the potential use of curcumin, which is attributed to its antiradical/antioxidant activities and its potential β-cell regenerative properties. Also, it has the capability to encourage the trans-differentiation of hepatic stellate cells into insulin-producing cells for a period of time. In addition, as it is an anti-fibrotic mediator that inhibits hepatic stellate cell activation and the transition to myofibroblast-like cells, this suggests the possibility of considering curcumin's novel therapeutic effects in reducing hepatic dysfunction in diabetic patients.
Potential role of uric acid in correlation with epidemics of hypertension and...Apollo Hospitals
Diabetic nephropathy (DN) is a microvascular complication of Type 2 diabetes mellitus. Uric acid (UA) is the end product of purine nucleotide metabolism and its primary mode of clearance is by renal excretion. Modifiable factors such as blood pressure, albuminuria, glycemic control, etc., play an important role in the progression of DN and none of them are curative. Hence, there is a pressing interest to identify other potentially modifiable factors such as UA in the progression of DN.
Evaluation of the Hepa Wash treatment in pigs with acute liver failureEnrique Moreno Gonzalez
Mortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver
support systems are still of limited success at improving survival. A new type of albumin
dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support
system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic
porcine model of ALF.
EFFECT OF DIFFERENT CHROMATOGRAPHIC FRACTION AQUEOUS AND ALCOHOLIC EXTRACTS O...Jing Zang
In recent studies Teucrium polium(T. polium ) was known as a hypoglycemic plants. But further research is needed to better understand the effect of Teucrium polium and biological active part of it. The purpose of this investigation is to examine the effect of different chromatographic fractions of aqueous and alcoholic extract of this plant on the level of insulin secretion and glucose content in hyperglycemic rat model. Also, our aim is determination of biological active fraction of aqueous and alcoholic extract of this plant. This study was carried out on the 36 rats. Hyperglycemia induced by administrating of 50 mg/kg alloxan intraperitoneally and glucose level was monitored for hyperglycemic status. Hyperglycemic was confirmed by blood glucose measurement. In each experiment 100 grams of Teucrium polium aerial parts powder were boiled with 2 Litter of distilled water for 36 h. The decoction preparation was then filtered through a gauz cloth followed by filtration through filter paper. The extract was evaporated to one-fifth of its original volume and kept at 4oC until its use. Determination of different fraction aqueous extract effect of Teucrium polium on glucose level and insulin secretion was carried out. Blood was collected from the tail of the rats. Then glucose and insulin level was evaluated. The hyperglycemic animals showed significant decrease in the blood glucose level in rats administered with fourth fraction compared with other factions. Administration of fourth fraction Teucrium polium aerial parts extract cause increase in insulin levels in alloxan-treated rats. Results suggest that treatment of fourth fraction Teucrium polium aerial parts extract may be useful in preventing the increase of glucose level in hyperglycemic rats. The interesting phenomenon of our results has shown that fourth fraction given parenterally possesses a hypoglycemic effect in alloxan hyperglycemic rats. Fourth fraction was found biological active and to be responsive to glucose challenge as evidenced by increase in insulin secretion.
Hepatoprotective Activity of Methanolic Extract of Whole Plant of Pulicaria W...IOSRJPBS
Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for liver injury. The present study was conducted to evaluate the hepatoprotective activity of methanolic extract of whole plant of Pulicaria wightiana in wistar rats. The studies were conducted using the two popular inducing agents Paracetamol (2 g/kg, p.o.) in 1% NaCMC and Carbon tetrachloride (1 ml/kg). Silymarin (100 mg/kg, p.o.) was used as reference drug in the respective models. The effect was estimated by measuring the enzymatic levels and histo- pathological studies. The methanolic extract of whole plant of Pulicaria wightiana has shown very significant hepatoprotection against both Paracetamol and CCl4 - induced hepatotoxicity study models in wistar rats. This was evidenced by marked reduction in marker enzymes in serum. Histopathological studies also confirmed the hepatoprotective nature of the extract
Liver ischemia/reperfusion injury, a setting in which the functional mass is ...Prof. Hesham N. Mustafa
Liver ischemia reperfusion is induced during sur-gical procedures like liver transplantation and re-section. Multiple mechanisms have been postulat-ed to liver damage following liver ischemia reperfu-sion injury, such as oxidative stress and inflamma-tory reactions. The present study declares the pos-sible mechanism of tadalafil, toward modulating the inflammatory response. Forty-eight rats were divided into 4 groups as follows; Sham group sub-jected to midline laparotomy only. Tadalafil group administered Tadalafil 10 mg/kg intraperitoneal 45 min before sham operation. I/R (Ischemia-reperfusion) group, rats undergo 60 min of hepatic ischemia followed by 60 min of reperfusion. Tada-lafil + I/R group rats undergo a similar pattern of I/R after the treatment with Tadalafil 10 mg/kg, 45 min before ischemia. At the end of the reperfusion, the blood samples were collected for estimation of biochemical markers including liver enzymes using colorimetric assay method and serum: TNF-α (tumor necrosis factor-α), IL-6 (interleukin 6) le-vels, ICAM- 1 (Intercellular Adhesion Molecule-1) were measured. Tissues were evaluated by semi-quantitative and morphometrical approaches. Ta-dalafil succeeded in restoring normal levels of liverenzymes and ameliorating the oxidative stress as evidenced by decreasing MDA and restoring redu-ced glutathione levels in liver tissue homogenate. Also, Tadalafil exhibits anti-inflammatory effects, as it significantly decreased the levels of TNF-α, IL6 and ICAM-1. The findings are supported by BCL-2, TNF-α immunomarkers. It is concluded that modulation of the inflammatory response might be one of the mechanisms of Tadalafil-mediated he-patoprotection, so it is recommended as an adju-vant therapy in liver surgery.Keywords: Ischemia/reperfusion injury – Oxidative stress – Apoptosis – TNF-α – BCL-2
Comparison of the Acute Hypervolemic Capacities of Erythropoietin and U-74389...CrimsonpublishersITERM
Aim: This study compared the hyper volemic capacities of erythropoietin (Epo) and antioxidant drug U-74389G based on 2 preliminary studies. The provided results at mean corpuscular volumes (MCV) levels augmentation were co-evaluated in a hypoxia re oxygenation protocol of an animal model.
Materials and methods: MCV levels (MCVl) were evaluated at the 60th reoxygenation min (for groups A, C and E) and at the 120th reoxygenation min (for groups B, D and F) in 60 rats. Groups A and B received no drugs, rats from groups C and D were administered with Epo; whereas rats from groups E and F were administered with U-74389G.
Results: The first preliminary study of Epo non-significantly increased the MCVl by 0.30%+0.39% (p-value=0.4430). However, the second preliminary study of U-74389G significantly rised the MCVl by 1.60%+0.43% (p-value=0.0005). These 2 studies were co-evaluated since they came from the same experimental setting. The outcome of the co-evaluation was that U-74389G has 4.352528-fold hypervolemic potency than Epo (p-value=0.0000).
Conclusion: The anti-oxidant capacities of U-74389G accelerate the acute hypervolemic properties; presenting 4.352528-fold rise on MCVl than epo (p-value=0.0000)
Effect of Platelet Rich Plasma (PRP) Injection on the Endocrine
Pancreas of the Experimentally Induced Diabetes in Male Albino Rats: A
Histological and Immunohistochemical Study
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).
Objective: Ischemia-reperfusion (I/R) leads to reactive oxygen species formation and cell death in kidney tissue with injury and organ transplantation. Simvastatin (SIM) is an antioxidant, anti-inflammatory, and anticoagulant agent. Alterations in I/R-induced acute kidney injury model with SIM treatment were analyzed.
Study Design: Wistar rats (n=28) were grouped into Sham, Ischemia, I/R, and I/R+SIM treated. Left rat kidney renal vessels were clamped for 60 minutes for ischemia, and the I/R group had 6 hours of reperfusion. 10 mg/kg SIM was given orally for 28 days. MDA, GSH, and MPO were analyzed. Kidney tissues were paraffin embedded, and primary antibodies TNF-α and caspase-3 were applied for immunohistochemistry.
Results: In the I/R group, intense inflammatory cell infiltration around the vessels and necrosis in the glomerular structures were observed. In the treated group, proximal and distal tubular cells were found to be close to normal. Immunoexpression of caspase-3 in the ischemia group was positive in degenerative glomeruli. In the treated group, TNF-α expression was negative in the glomerular structures. MDA and MPO levels were significantly increased in ischemia and I/R.
Conclusion: We suggest that SIM treatment improved kidney tissue structure and function in a model of I/R injury.
Keywords: caspase-3; immunohistochemistry; ischemia/reperfusion; kidney; MPO; simvastatin
Potential role of uric acid in correlation with epidemics of hypertension and...Apollo Hospitals
Diabetic nephropathy (DN) is a microvascular complication of Type 2 diabetes mellitus. Uric acid (UA) is the end product of purine nucleotide metabolism and its primary mode of clearance is by renal excretion. Modifiable factors such as blood pressure, albuminuria, glycemic control, etc., play an important role in the progression of DN and none of them are curative. Hence, there is a pressing interest to identify other potentially modifiable factors such as UA in the progression of DN.
Evaluation of the Hepa Wash treatment in pigs with acute liver failureEnrique Moreno Gonzalez
Mortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver
support systems are still of limited success at improving survival. A new type of albumin
dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support
system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic
porcine model of ALF.
EFFECT OF DIFFERENT CHROMATOGRAPHIC FRACTION AQUEOUS AND ALCOHOLIC EXTRACTS O...Jing Zang
In recent studies Teucrium polium(T. polium ) was known as a hypoglycemic plants. But further research is needed to better understand the effect of Teucrium polium and biological active part of it. The purpose of this investigation is to examine the effect of different chromatographic fractions of aqueous and alcoholic extract of this plant on the level of insulin secretion and glucose content in hyperglycemic rat model. Also, our aim is determination of biological active fraction of aqueous and alcoholic extract of this plant. This study was carried out on the 36 rats. Hyperglycemia induced by administrating of 50 mg/kg alloxan intraperitoneally and glucose level was monitored for hyperglycemic status. Hyperglycemic was confirmed by blood glucose measurement. In each experiment 100 grams of Teucrium polium aerial parts powder were boiled with 2 Litter of distilled water for 36 h. The decoction preparation was then filtered through a gauz cloth followed by filtration through filter paper. The extract was evaporated to one-fifth of its original volume and kept at 4oC until its use. Determination of different fraction aqueous extract effect of Teucrium polium on glucose level and insulin secretion was carried out. Blood was collected from the tail of the rats. Then glucose and insulin level was evaluated. The hyperglycemic animals showed significant decrease in the blood glucose level in rats administered with fourth fraction compared with other factions. Administration of fourth fraction Teucrium polium aerial parts extract cause increase in insulin levels in alloxan-treated rats. Results suggest that treatment of fourth fraction Teucrium polium aerial parts extract may be useful in preventing the increase of glucose level in hyperglycemic rats. The interesting phenomenon of our results has shown that fourth fraction given parenterally possesses a hypoglycemic effect in alloxan hyperglycemic rats. Fourth fraction was found biological active and to be responsive to glucose challenge as evidenced by increase in insulin secretion.
Hepatoprotective Activity of Methanolic Extract of Whole Plant of Pulicaria W...IOSRJPBS
Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for liver injury. The present study was conducted to evaluate the hepatoprotective activity of methanolic extract of whole plant of Pulicaria wightiana in wistar rats. The studies were conducted using the two popular inducing agents Paracetamol (2 g/kg, p.o.) in 1% NaCMC and Carbon tetrachloride (1 ml/kg). Silymarin (100 mg/kg, p.o.) was used as reference drug in the respective models. The effect was estimated by measuring the enzymatic levels and histo- pathological studies. The methanolic extract of whole plant of Pulicaria wightiana has shown very significant hepatoprotection against both Paracetamol and CCl4 - induced hepatotoxicity study models in wistar rats. This was evidenced by marked reduction in marker enzymes in serum. Histopathological studies also confirmed the hepatoprotective nature of the extract
Liver ischemia/reperfusion injury, a setting in which the functional mass is ...Prof. Hesham N. Mustafa
Liver ischemia reperfusion is induced during sur-gical procedures like liver transplantation and re-section. Multiple mechanisms have been postulat-ed to liver damage following liver ischemia reperfu-sion injury, such as oxidative stress and inflamma-tory reactions. The present study declares the pos-sible mechanism of tadalafil, toward modulating the inflammatory response. Forty-eight rats were divided into 4 groups as follows; Sham group sub-jected to midline laparotomy only. Tadalafil group administered Tadalafil 10 mg/kg intraperitoneal 45 min before sham operation. I/R (Ischemia-reperfusion) group, rats undergo 60 min of hepatic ischemia followed by 60 min of reperfusion. Tada-lafil + I/R group rats undergo a similar pattern of I/R after the treatment with Tadalafil 10 mg/kg, 45 min before ischemia. At the end of the reperfusion, the blood samples were collected for estimation of biochemical markers including liver enzymes using colorimetric assay method and serum: TNF-α (tumor necrosis factor-α), IL-6 (interleukin 6) le-vels, ICAM- 1 (Intercellular Adhesion Molecule-1) were measured. Tissues were evaluated by semi-quantitative and morphometrical approaches. Ta-dalafil succeeded in restoring normal levels of liverenzymes and ameliorating the oxidative stress as evidenced by decreasing MDA and restoring redu-ced glutathione levels in liver tissue homogenate. Also, Tadalafil exhibits anti-inflammatory effects, as it significantly decreased the levels of TNF-α, IL6 and ICAM-1. The findings are supported by BCL-2, TNF-α immunomarkers. It is concluded that modulation of the inflammatory response might be one of the mechanisms of Tadalafil-mediated he-patoprotection, so it is recommended as an adju-vant therapy in liver surgery.Keywords: Ischemia/reperfusion injury – Oxidative stress – Apoptosis – TNF-α – BCL-2
Comparison of the Acute Hypervolemic Capacities of Erythropoietin and U-74389...CrimsonpublishersITERM
Aim: This study compared the hyper volemic capacities of erythropoietin (Epo) and antioxidant drug U-74389G based on 2 preliminary studies. The provided results at mean corpuscular volumes (MCV) levels augmentation were co-evaluated in a hypoxia re oxygenation protocol of an animal model.
Materials and methods: MCV levels (MCVl) were evaluated at the 60th reoxygenation min (for groups A, C and E) and at the 120th reoxygenation min (for groups B, D and F) in 60 rats. Groups A and B received no drugs, rats from groups C and D were administered with Epo; whereas rats from groups E and F were administered with U-74389G.
Results: The first preliminary study of Epo non-significantly increased the MCVl by 0.30%+0.39% (p-value=0.4430). However, the second preliminary study of U-74389G significantly rised the MCVl by 1.60%+0.43% (p-value=0.0005). These 2 studies were co-evaluated since they came from the same experimental setting. The outcome of the co-evaluation was that U-74389G has 4.352528-fold hypervolemic potency than Epo (p-value=0.0000).
Conclusion: The anti-oxidant capacities of U-74389G accelerate the acute hypervolemic properties; presenting 4.352528-fold rise on MCVl than epo (p-value=0.0000)
Effect of Platelet Rich Plasma (PRP) Injection on the Endocrine
Pancreas of the Experimentally Induced Diabetes in Male Albino Rats: A
Histological and Immunohistochemical Study
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).
Objective: Ischemia-reperfusion (I/R) leads to reactive oxygen species formation and cell death in kidney tissue with injury and organ transplantation. Simvastatin (SIM) is an antioxidant, anti-inflammatory, and anticoagulant agent. Alterations in I/R-induced acute kidney injury model with SIM treatment were analyzed.
Study Design: Wistar rats (n=28) were grouped into Sham, Ischemia, I/R, and I/R+SIM treated. Left rat kidney renal vessels were clamped for 60 minutes for ischemia, and the I/R group had 6 hours of reperfusion. 10 mg/kg SIM was given orally for 28 days. MDA, GSH, and MPO were analyzed. Kidney tissues were paraffin embedded, and primary antibodies TNF-α and caspase-3 were applied for immunohistochemistry.
Results: In the I/R group, intense inflammatory cell infiltration around the vessels and necrosis in the glomerular structures were observed. In the treated group, proximal and distal tubular cells were found to be close to normal. Immunoexpression of caspase-3 in the ischemia group was positive in degenerative glomeruli. In the treated group, TNF-α expression was negative in the glomerular structures. MDA and MPO levels were significantly increased in ischemia and I/R.
Conclusion: We suggest that SIM treatment improved kidney tissue structure and function in a model of I/R injury.
Keywords: caspase-3; immunohistochemistry; ischemia/reperfusion; kidney; MPO; simvastatin
Protective effects of commelina benghalensis linn (root) extract on ethanol i...IJSIT Editor
The present study was undertaken to investigate the protective effect and possible mechanism of
alcoholic (AlE) and aqueous extract (AqE) from Commelina benghalensis root (CB) on EtOH-induced hepatic
injury in Wistar rat. Hepatotoxic parameters studied in vivo include serum transaminases (AST, and ALT),
ALP, bilirubin, protein, lipid profile (Cholesterol, triglyceride, VLDL and HDL) and level of antioxidants
together with histopathological examination. Liv 52® was used as a reference hepatoprotective agent
(5ml/kg-1b.w.). AlE and AqE (200 mg/kg-1b.w.) on oral administration decreased the level of AST, ALP, ALT,
bilirubin, cholesterol, triglyceride, VLDL, MDA and increased the level of protein, HDL and antioxidants (SOD,
GSH and CAT) in rats being treated with ethanol (EtOH). Pentobarbitone -induced sleeping time study was
carried out to verify the effect on microsomal enzymes Histopathological observations confirmed the
beneficial roles of MF against EtOH-induced liver injury in rats. Possible mechanism may involve their
antioxidant activity
Biochemical and Toxicological Investigations of 5-Fluorouracil, Nimesulide, a...BRNSS Publication Hub
The objective of this study was biochemical and toxicological investigations of 5-fluorouracil (5-FU), nimesulide, and ascorbic acid (Vitamin C) in Wistar rats with hepatocellular carcinoma in. Results showed that DENA increased the level of alpha fetoprotein (AFP), alkaline phosphatase (ALP), serum glutamic oxaloacetate transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), and total bilirubin which was decreased by the various combinations of 5-FU to normal. On the other hand, DENA resulted in decrease of blood glucose level, DFN decreased more than DF, and DFC showed results similar to DFN, while DFNC led to increased AFP, ALP, SGOT, SGPT, and total bilirubin levels to normal. Histopathological evaluations showed normal architecture of tissues of rat liver in normal group. Lesser damage of hepatocytes and low index of necrosis were in pre- and post-treated group of 5-FU+DF, DFN+DFC groups. DFNC treated group exhibited histological features resembling normal control animals.
Prophylactic role of coenzyme Q10 and Cynara scolymus L on doxorubicin-indu...Prof. Hesham N. Mustafa
Objective: The study aims to evaluate the protective effects of coenzyme Q10 (CoQ10) and Cynara scolymus L (CS) on doxorubicin (dox)-induced toxicity.
Materials and Methods: Sixty male rats were divided into six groups. Group 1 as a control. Group 2 received dox (10 mg/kg) intraperitoneally. Group 3 received CoQ10 (200 mg/kg). Group 4 received CS (500 mg/kg). Group 5 received CoQ10 (200 mg/kg) and dox (10 mg/kg). Group 6 received CS (500 mg/kg) and dox (10 mg/kg). The rats were then evaluated biochemically and immunohistochemically.
Results: Dox produced a significant deterioration of hepatic and renal functional parameters. Moreover, an upsurge of oxidative stress and nitrosative stress markers. The expression of alpha-smooth muscle actin (α-SMA) was increased and proliferating cell nuclear antigen (PCNA) expression was decreased. Administration of CoQ10 and CS resulted in a significant improvement of hepatic and renal functional parameters, and an improvement of both α-SMA and PCNA.
Conclusion: It is concluded that pretreatment with CoQ10 and CS is associated with up-regulation of favorable protective enzymes and down-regulation of oxidative stress. That can be advised as a supplement to dox-treated patients.
Keywords: Alpha-smooth muscle actin, doxorubicin, nitrosative, oxidative, proliferating cell nuclear antigen
ABSTRACT
Background:The main objective of the study is to determine the anti-arthritic effect of whole plant ethanolic extract of Polygonum glabrum
belonging to the family Polygonaceae in Female wistar rats using the Freund’s Complete Adjuvant (FCA) model . Methods:The plants areal
parts were collected near Tirupathi hills, Chittoor district of Andhra Pradesh in India. The Phytoconstituents were identified through the
chemical tests. Ethanol (95%) was used to obtain the whole plant extraction through Soxhlet extractor. Female SD rats were used for antiarthritic
screening. Arthritis was induced using FCA, and the anti-arthritic effect of the ethanolic extract of P.glabrum was studied at doses
of 250 and500 mg/kg. The effects were compared with those of indomethacin (10 mg/kg). At the end of the study, theliver enzyme levels were
determined and a radiological examination was carried out. Results and Discussion:The preliminary phytochemical analysis of the ethanolic
extract of Polygonum glabrum showed the presence of alkaloids, tannins, flavonoids and saponins. P. glabrum at 250 and 500 mg/kg
significantly inhibited the FCA-induced arthritis in the rats. This was manifested by as a decrease in the paw volume. The arthritic control
animals exhibited a significant decrease in body weight compared with control animals without arthritis. P. glabrum treated animals showed
dose dependent reduction in decrease in body weight and arthritis.At the same time, P.glabrum significantly altered the biochemical and
haematological changes induced by FCA (P < 0.05). The anti-arthritic effect of P.glabrum was comparable with that of Indomethacin.
Conclusion:The whole plant extract of P.glabrum showed significant anti-arthritic activity against FCA-induced arthritis in female Wistar
rats.
A 5-year old boy, with an established diagnosis of a topic
dermatitis, previously treated by topical corticosteroids and emollient cream with a good improvement, developed widespread papules on his legs, hands and forearm that appeared 5 months ago.
Methods: Retrospectively, the file records of the patients who underwent sleeve gastrectomy were examined. Demographic features, Body Mass Index (BMI), the mouth opening, Mallampati score, thyromental distance, sternomental distance, neck circumference measurements and videolaryngoscopic examination results were recorded Results: In a total of 140 consecutive patients (58 male, 82 female) were included in the study. The mean age of the study participants was 35.40 ± 9.78 and the mean BMI of the patients was 44.33 ± 7.52 kg/m2
. The mean mouth opening of the patients was 4.82 ± 0.54 cm
and the mean neck circumference was 43.52 ± 4.66 cm. The mean thyromental distance was 8.02 ± 1.00 cm and the mean sternomental distance was16.58 ± 1.53 cm. Difficult intubation was determined in 8 (5.7%) patients. In logistic regression analysis, age (p : 0.446), gender (p : 0.371), BMI (p : 0.947), snoring (p : 0.567), sleep apnea (p : 0.218), mouth opening (p : 0.687), thyromental distance (p :0.557), sternomental (p : 0.596) and neck circumference (p : 0.838) were not the independent predictors of difficult intubation. However, Mallampati score (p : 0.001) and preoperative direct laryngoscopy findings (p : 0.037) performed in outpatient clinic were the significant
predictors of difficult intubation. Interestingly, all patients with grade 4 laryngoscopy findings had difficult intubation.
Introduction: Laparoscopic surgery has been performed in Mexico since 1989, but no reports about training tendencies exist. We conducted a national survey in 2015, and here we report the results concerning training characteristics during the surgical residence of the respondents. Materials and Methods: A prospective study was conducted through a survey questioning demographic data, laparoscopic training during pre and post surgical residency and other of areas of laparoscopic practice. The sample was calculated and survey piloted before
application. Special interest in this report was placed on type and quality of training received. Data are reported in percentages.
Heterotopic Ossification (HO) is defined as pathological bone formation at locations where bone normally does not exist. The
presence of HO has been found to be a rare complication after stroke in several studies, whereas there are only sporadic references relating HO to Cerebral Palsy (CP) and few for CP and stroke. No effective treatment for HO has yet been found, whereas the cellular and molecular mechanisms have not been completely understood. Therefore, increased awareness among physicians is required, as a challenge for early diagnosis and treatment. A case of a male patient with CP, who developed HO on the paretichip joint following an ischemic stroke is presented.
Objectives: To assess the practice of food hygiene and safety, and its associated factors among street food vendors in urban areas of Shashemane, West Arsi Zone, Oromia Ethiopia, 2019.
Methods: Cross-sectional study design was applied from December 28, 2019 to January 27, 2020. Data was collected from 120 food handlers, which were selected by purposive sampling techniques. Information was gathered from interview and field observation by conducting food safety survey and using questionnaires via face to face interview. The collected data was entered using Epi Data 3.1 and finally, it was analyzed using SPSS VERSION 20.
A Division I football athlete experienced acute posterior leg pain while pushing off on the line of scrimmage. Ultrasound (US) showed a midsubstance plantaris tendon rupture, an injury that, to our knowledge, has only been described once before in the medical literature [1]. US was also used to assist with rehab progression and return to previous level of activity, which was achieved three weeks after the injury. While there currently are no guidelines regarding return to sport after this injury, this case demonstrates that once pain is controlled and ROM restored, progression through rehabilitation and return to elite level sport is simply based on symptoms.
Type 1 Diabetes (T1D), is a severe disease, representing 5-10% of all reported cases of diabetes worldwide. Fulminant Type 1 Diabetes Mellitus (FT1D) is a subtype of type 1 diabetes mellitus that is largely characterized by the abrupt onset of Diabetic Ketoacidosis (DKA) and severe hyperglycemia without insulin defi ciency. Viral infections have been hypothesized to play a major role in the pathogenesis of Fulminant Type 1 Diabetes Mellitus (FT1D) through the complete and rapid destruction of pancreatic beta cells. Coxsackie viral infection has been detected in islets of 50% of the pancreatic tissue recovered from recent-onset Type 1 Diabetes (T1D) patients. In this report we have highlighted a case where the patient developed a Group B Coxsackie virus infection culminating in the development of Fulminant Type 1 Diabetes Mellitus (FT1D).
Methods: Cercariae are released by infected water snails. To determine the occurrence of cercariae-emitting snails in SchleswigHolstein, 155 public bathing places were visited and searched for fresh water snails. Family and genus of the collected snails were determined and the snails were examined for the shedding of cercariae, using a standard method and a newly developed method.
Objective: To generate preliminary information about of enteroviruses and Enterovirus 71 (EV71) in patients with aseptic meningitis in Khartoum State, Sudan.
Method: Cerebrospinal fluid specimens were collected from 89 aseptic meningitis patients from different Khartoum Hospitals
(Mohammed Alamin Hamid Hospital, Soba Teaching Hospital, Omdurman Military Hospital, Alban Gadeed Teaching Hospital and Police Hospital) within February to May 2015. Among these 89 patients, 43 (48%) were males and 46 (52%) were females. The patient’s age ranged between 1 day and 30 years old. The collected specimens were assayed to detect enteroviruses and EV71 RNA using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) technique
Femoral hernias, comprise 2% to 4% of all hernias in the inguinal region, and occur most commonly in women. Th ey present typically with a mass below the level of the inguinal ligament. The sac may contain preperitoneal fat, omentum, small bowel, or other structures and have a high rate of incarceration and strangulation due to the small size of the hernia neck orifice, requiring emergency surgery. We present the case of a 54-year-old female patient with intestinal occlusion due to incarcerated femoral hernia, repaired by laparoscopic approach, that gave the patient the opportunity to attend her daughter’s wedding the same day.
Small Supernumerary Marker Chromosome (sSMC) is a rare genetic condition marked by the presence of an extra chromosome to the 46 human chromosomes. This case report describes a 4 year old child with SSMC on the 46th chromosome. The child presented with delayed speech and language development, seizures and mild developmental delay. Speech and Language evaluation was carried out and management options are discussed.
A catheter is a thin tube made from medical grade materials that serve a broad range of functions, but mainly catheters are medical devices that can be inserted in the body to treat disease or perform surgical procedures. Catheters have been inserted into body cavities, ducts, or vessels to allow for drainage, administration of therapeutic fluids or gases, operational access for surgery. Catheters help perform tasks in various systems such as cardiovascular, urological, gastrointestinal, neurovascular, and ophthalmic systems. A dataset of 12 patients with varying “weights” and “heights” was recorded along with the lengths of their catheter tubes. This data set was found from two revered statistical textbooks on linear regression and the Department of Scientific Computing at Florida State University. This data set was not able to be linked to any particular clinical or experimental research studies, but the data set can be used to help catheter manufacturers and medical professionals better decide on what particular catheter lengths to use for patients knowing only their height & weight. These research insights could be helpful to healthcare professionals that have patients with incomplete or no healthcare records
to decide what catheter length to use. The main investigative inquiry that needed to be answered was how does patient weight & height influence catheter length together and separately? We conducted linear regression and other statistical analysis procedures in R program & Microsoft Excel and discovered that this data exhibited a quality called multi collinearity. With multi collinearity, all predictors (2 or more
independent variables) are not significant in an all encompassing linear aggression, but the predictors might be significant in their own individual linear regressions. Individual linear regression analyses were conducted for both patient height & weight to see how much they both contribute to varying catheter length. Patient weight was found to be more impatful than patient height in relationship to catheter length, even though height and weight are a classical example of multi collinearity predictors.
Bovine mastitis has a negative impact through economic losses in the dairy sector across the globe. A cross sectional study was carried out from September 2015 to July 2016 to determine the prevalence of bovine mastitis, associated risk factors and isolation of major causative bacteria in lactating dairy cows in selected districts of central highland of Ethiopia. A total of 304 lactating cows selected randomly from five districts were screened by California Mastitis Test (CMT) for subclinical mastitis. Based on CMT result and clinical examination, over all prevalence of mastitis at cow level was 70.62% (214/304).
Two hundred fourteen milk samples collected from CMT positive cows were cultured for isolation of major causative bacteria. From 214 milk samples,187 were culture positive and the most prevalent isolates were Staphylococcus aureus 42.25% (79/187) followed by Streptococcus agalactiae 14.43%
(27/187). Other bacterial isolates were included Coagulase Negative Staphylococcus species 12.83% (24/187), Streptococcus dysgalactiae 5.88% (11/187), Escherichia coli 13.38% (25/187) and Entrococcus feacalis 11.23% (21/187) were also isolated. Moreover, age, parity number, visible teat abnormalities,husbandry practice, barn fl oor status and milking hygiene were considered as risk factors for the occurrence of bovine mastitis and they were found significantly associated with the occurrence of mastitis (p < 0.05). The findings of this study warrants the need for strategic approach including dairy extension that focus on enhancing dairy farmers’ awareness and practice of hygienic milking, regular screening for subclinical mastitis, dry cow therapy and culling of chronically infected cows.
Kratom is an herbal product that is derived from Southeast Asian Mitragyna speciose tree leaves [1-10]. This compound is used for many purposes such as stimulation, euphoria, or analgesia [1-10]. It has been recently identified as a drug of abuse by the United States Drug Enforcement Administration [2,8]. Side-effects from this compound have not been well documented. We describe a case of a 36-year-old female who develop nephrotoxicity after taking an herbal supplement. She took kratom as an adjunctive therapy for back pain management. She developed right upper quadrant pain and nausea. Laboratory tests showed elevated liver enzymes without evidence of bile duct obstruction. Liver enzymes normalized several weeks after Kratom discontinuation. We advise clinicians to be vigilant about Kratom’s hepatotoxic potential on patient health.
The assessment, diagnosis and treatment of critically ill patients is extremely challenging. Patients often deteriorate whilst being
reviewed and their rapidly changing pathophysiology barrages healthcare professionals with new data. Furthermore, comprehensive assessments must be postponed until the patient has been stabilised. So, important data and interventions are often missed in the heat of the moment. In emergency situations, suboptimal management decisions may cause signifi cant morbidity and mortality. Fortunately, standardisation and careful design of documentation (i.e. proformas and checklists) can enhance patient safety. So, I have developed a series of checklist proformas to guide the assessment of critically ill patients. These proformas also promote the systematic recording and presentation of information to facilitate the retrieval of the precise data required for the management for critically ill patients. The proformas have been modifi ed extensively over the last twenty years based on my personal experience and extensive consultation with colleagues in several world-renowned centres of excellence. The proformas were originally developed for use in the intensive therapy unit
or high dependency unit. However, they have been adapted for use by outreach teams reviewing patients admitted outside of critical care areas. The use of these tools can direct eff orts to provide appropriate organ support and provides a framework for diagnostic reasoning.
Systemic Hypertension (HTN) accounts for the largest amount of attributable Cardiovascular (CV) mortality worldwide. There are several factors responsible for the development of HTN and its CV complications. Multicenter trials revealed that risk factors responsible for Micro Vascular Disease (MVD) are similar for those attributable to Coronary Artery Disease (CAD) which include tobacco use, unhealthy cholesterol levels, HTN, obesity and overweight, physical inactivity, unhealthy diet, diabetes, insulin resistance, increasing age and genetic predisposition. In addition, the defective release of Nitric Oxide (NO) could be a putative candidate for HTN and MVD. This study reviewed the risk stratification of hypertensive population employing cardiac imaging modalities which are of crucial importance
in diagnosis. It further emphasized the proper used of cardiac imaging to determine patients at increased CV risk and identify the management strategy. It is now known that NO has an important effect on blood pressure, and the basal release of endothelial Nitric Oxide (eNOS) in HTN may be reduced. Although there are different forms of eNOS gene allele, there is no solid data revealing the potential role of the polymorphism of the eNOS in patients with HTN and coronary vascular diseases. In the present article, the prevalence of eNOS G298 allele in hypertensive patients with micro vascular angina will be demonstrated. This review provides an update on appropriate and justified use of non-invasive imaging tests in hypertensive patients and its important role in proper diagnosis of MVD and CAD. Second, eNOS gene allele and its relation to essential hypertension and angina pectoris are also highlighted.
Methods: Two groups were selected by non-probability random sampling technique including case group of 154 patients with
suspected dengue (fever>2days and <10days) and control group of 146 patients with febrile illness other than dengue. Clinical,hematological and serologic markers of cases and control groups were analyzed. The frequency distribution was used to compare categorical serologic markers and paired sample T test was applied for hematologic variables before and after treatment of dengue using SPSS version 21.
Researchers from Utrecht recently published yet another paper on the use of Magnetic Resonance Imaging (MRI)demonstrating an additional failed attempt to understand the importance of qualitative versus quantitative imaging, and anatomic versus physiologic imaging. Th e implications of this failure here cannot be overstated.
Introduction: Stroke is an even more dramatic major public health problem in young people. Goal of the study: Contribute to the knowledge of strokes in young people. Methodology: This was a retrospective study carried out over a period of 02 years (January 2017 to December 2018) including the files of patients aged 18 to 49 years hospitalized for any suspected case of stroke in the Neurology department of the University Hospital
Center of the Sino-Central African Friendship (CHUSCA) of Bangui.
Background: This report describes a unique case of a patient that developed psychotic symptoms believed to be secondary
to a tentorial meningioma with associated hydrocephalus. These psychotic symptoms subsequently abated with placement of a
ventriculoperitoneal shunt. Case description: 60-year-old female was admitted to an inpatient psychiatric facility on a psychiatric involuntary commitment petition due to progressive paranoia, homicidal ideation and psychosis. The work up showed a calcified six cm tentorial meningioma with associated hydrocephalus. The patient initially rejected treatment but later became amenable to placement of Ventriculoperitoneal Shunt
(VPS).
More from SciRes Literature LLC. | Open Access Journals (20)
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
2. International Journal of Hepatology & Gastroenterology
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INTRODUCTION
Liver transplantation is the most important treatment option for
both acute and terminal period liver disorders [1]. Improvements in
surgical technique and the immunosuppressive treatments used after
transplantationprolongsurvivalbutalsoleadtovariouscomplications
[1]. These complications include hemorrhage, gall bladder leakage,
bile fistula, bile duct stenosis, and vascular complications such as
portal vein or hepatic artery thrombosis [1,2].
Minimizing the duration and effect of hepatic ischemia after the
Pringle maneuver and keeping inflammatory events under control
has become increasingly important to protect liver functions during
surgery in recent years [3]. The Pringle maneuver leads to hepatic
problems related to ischemia and reperfusion but the mechanism
is not fully clear. Ischemia can develop due to arterial or venous
occlusion. Vascular bed stasis is present in venous occlusion. The
Pringle maneuver can be extended to 60-90 minutes at present but
longer durations can lead to severe hepatic destruction and even
shock and death [3]. Portal venous ischemia has also been reported to
be fatal after 60 minutes in rats [4].
Polymorphonuclear Leukocyte (PMNL) activation, oxygen
free radical formation, cytokine secretion, complement activation
and eicosanoid production are the main results of ischemia and
reperfusion damage. These mediators have been found at abnormally
high levels in the circulation in patients with ischemia and reperfusion
damage and their presence leads to the development of clinical signs
and symptoms [5].
Heparin is an antithrombotic agent known to increase the
survival rate in sepsis, shock, ischemia and reperfusion models [6,7].
Heparin has also been shown to prevent complement activation
through the alternative route and decrease activation of the classic
complement route with its C1 esterase inhibitor effect [8]. Heparin is
known to play a role in decreasing inflammation in the ischemia and
reperfusion model in this way [9]. It has been reported to decrease
tissue damage by inhibiting complement activation after ischemia
reperfusion damage [8,10].
The aim of this experimental study was to investigate whether
heparin decreases tissue damage through complement inhibition in
hepatic ischemia and reperfusion damage created via the portal vein.
MATERIALS AND METHODS
The experimental study protocol was realized in accordance
with the guidelines of the “National Institutes of Health Guide for
the Care and Use of Laboratory Animals” after ethical and scientific
approval from the Başkent University Medical Faculty Experimental
Research Committee. The rats used in the experiment were obtained
from the Experiment Animals Production Center affiliated with
the Başkent University Research Center. This study was conducted
at the Başkent University Experimental Research Center. A total
of 25 (Wistar Albino) male rats weighing 150-290 gr were used in
the study. They were transferred from the production center to the
study center one week before the study started and prepared for the
experiment by being kept at a stable environment (at 22°C) for 12
hours under daylight conditions and 12 hours under night conditions
each day and being given standard rat food. The rats to be used in
the experiment were left fasting and allowed to drink only water for
12 hours beforehand. Anesthesia was ensured by intraperitoneal
administration of 50 mg/kg Ketamine Hydrochloride (Ketalar®
Eczacibaşi Warner-Lambert İlaç Sanayi, Levent, Istanbul) and 7 mg/
kg Xylazine Hydrochloride (Rompun®
Bayer Şişli, Istanbul) under
aseptic conditions . The subjects were divided into five main groups.
Group 1 (control group = 5)
The group where the parameters would be observed without
administration of heparin or formation of ischemia reperfusion
damage.
Group 2 (n = 5)
The group that was sacrificed 24 hours after the formation of
ischemia reperfusion damage without the administration of the
therapeutic drug.
Group 3 (n = 5)
The group that was sacrificed 24 hours after ischemia reperfusion
damage was created and administration of heparin (Nevparin®
Mustafa Nevzat Ilaç Sanayii, Gayrettepe, Istanbul).
Group 4 (n = 5)
The group that was sacrificed 48 hours after the formation of
ischemia reperfusion damage without the administration of the
therapeutic drug.
Group 5 (n = 5)
The group that was sacrificed 48 hours after ischemia reperfusion
damage and administration of heparin.
The rats were weighed before the procedure. The incision site was
shaved after anesthesia. Skin antisepsis was provided with povidone
iodine and the arms and legs were fixed on the operating device. The
device was held at a 30 degree incline to prevent the aspiration risk
and the subject draped under sterile conditions with the incision site
ABSTRACT
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.
Keywords: Liver; Heparin; Ischemia; Reperfusion
3. International Journal of Hepatology & Gastroenterology
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exposed. A midline incision was preferred. Following the laparotomy,
the small intestines were taken out of the abdomen and the portal
peduncle observed. Subsequently, the portal vein was isolated and
dissected and then separated from the hepatic artery and biliary tract.
Ischemia creation
Ischemia was created with a microvascular clamp placed on
the portal vein so as to avoid pressure on the hepatic artery (Figure
1). Ischemia duration was 60 minutes. The microclamp was then
removed and reperfusion was provided. Each rat was kept under
a heat lamp during this period in order to prevent heat loss. The
incision was closed in 2 layers using 3.0 silk at the end of the surgery.
The rats were not fed orally until the effects of anesthesia passed.
Heparin administration
A 1200 IU/kg dose of heparin was administered from the tail vein
right before ischemia was created.
Blood samples were taken from the inferior vena cava for
biochemical investigation. The tissue samples taken from the liver
were placed into sterile containers of known weight. The serum IL-6
levels and liver tissue GSH levels were measured as biochemical
parameters at the Başkent University Hospital’s Biochemical
Laboratory and recorded on the information form of each rat. Tissue
samples taken from the left lobe of the liver were kept at -86°C until
biochemical analyses were performed. The inferior vena cava blood
samples were immediately centrifuged at 1500 g for 15 minutes to
separate the serum for cytokine analyses and kept at -86°C until the
analysis. All biochemical analyses were performed as dual studies.
Serum TNF-α and IL-6 levels were measured with the ELISA method
by using commercial kits (Biosource International Inc, California,
USA; TNF-α: KRC3011 and IL-6: KRC0061) while cytokine analysis
was with the “solid phase sandwich ELISA” method.
Liver tissue homogenates were prepared by using a glass
homogenizer inside 0.15 M KCl (10%, w/v) for reduced glutathione
(GSH) analyses in tissue samples. Tissue MDA concentration was
used as the lipid peroxidation marker according to the method
identified by Beuge and Aust [11]. Tissue GSH concentrations were
evaluated using the tissue sulfhydryl group determination method of
Ellman [12]. Protein analysis in tissue homogenates was according to
the method of Lowry, et al. [13].
Pathology evaluation
The liver tissue sample was covered with sterile gauze previously
soaked with 0.9% Saline and sent to Başkent University Hospital’s
Pathology Department inside a Petri Box for C3 evaluation in
the fresh sample with the IF method. C3 (FITC-Conjugated
Rabbit Anti-Human C3a Complement Code No. F 0201 Lot. 075
BIOKEM) presence was then investigated in liver tissue with the
Immunofluorescent (IF) method. The study groups were monitored
for 24 and 48 hours and the complement-dependent effects of
heparin in the liver were investigated. The C3 levels in fresh liver
tissue samples were determined with the IF method. The effects of
heparin on the C3 level in the liver were evaluated.
C3 level determination
Samples taken from the fresh liver tissue were frozen in frozen
section gel (Tissue freezing Medium/ JUNG) at -60°
C and 6 μ sections
placed on poly-lysine coated slides at -20°
C. The sections were kept
in acetone for 10 minutes. Once the acetone was vaporized, they
were incubated with C3 Antibody (C3-b Complement/FITC-Rabbit
Anti-Human/BİOKEM) at room temperature in an environment
without light for 3 hours. The sections were then washed with distilled
water and dried. They were covered with fluorescent covering gel
(Fluorescent Mounting Medium/BIOKEM) and evaluated under
the fluorescent microscope. The investigation was conducted by
a single pathologist from the Başkent University Hospital and the
samples graded semi quantitatively between +1 and +3 according to
IF staining severity.
MPO STUDY
The 3 μ thick sections from paraffin blocks were placed on poly-
L-lysine-coated slides and then kept in the oven at 56°C for 14 hours
before being placed in xylene and alcohol for 30 minutes each. The
slides were then washed under tap water and transferred into Citrate
Buffer Solution (pH = 6.0). They were boiled at moderate temperature
for 20 minutes and kept at room temperature for 20 minutes. The
section were then incubated at room temperature for 2 hours with
a 1:300 dilation of MPO (Myeloperoxidase DAKO polyclonal
rabbit A 0398) and undiluted ready-to-use primary antibody INOS
(INOS Rabbit polyclonal antibody RB-9242-R7) using the avidin-
biotin complex method. Finally, the reaction was made visible using
chromogen 3.3-diamino-benzidine-tetrahydrochloride.
STATISTICAL ANALYSIS
The SPSS 9.0 software program was used for the statistical
analyses of study results. Mean and standard deviations, which are
central distribution criteria in statistical analysis, were calculated
and intragroup differences of the nominal values determined using
Fisher’s exact chi-square test for non-parametric data. A p value <0.05
was considered significant. The Kruskal-Wallis and Mann-Whitney
U tests were used to analyze values obtained with measurement. For
the groups where the difference was found to be significant with the
Kruskal-Wallis test, we used the Mann-Whitney test to analyze the
significance between two groups and p values <0.015 were accepted
as significant following Bonferroni correction.
RESULTS
Biochemical findings
The results obtained from the study were biochemically
categorized (Table 1).
Figure 1: Ischemia was created with a microvascular clamp placed on the
portal vein so as to avoid pressure on the hepatic artery.
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A statistically significant difference was found between all groups
in terms of IL-6 (p = 0.001). Statistically significant differences were
found between the groups sacrificed at 24 hours with and without
heparin administration in pairwise comparison between the
groups (p = 0.004). No statistically significant difference was found
between the groups sacrificed at 48 hours with and without heparin
administration (p > 0.017).
A statistically significant difference was found between all groups
in terms of GSH (p = 0.001).Statistically significant differences were
found between the groups sacrificed at 24 and 48 hours with and
without heparin administration in pairwise comparisons (p = 0.002).
A statistically significant different was found between all groups
in terms of MPO (p = 0.001).
Statistically significant differences were found between the groups
sacrificed at 24 and 48 hours with and without heparin administration
in pairwise comparisons (p = 0.001)
A statistically significant different was found between all groups
in terms of MPO (p = 0.001)
Statistically significant differences were found between the groups
sacrificed at 24 and 48 hours with and without heparin administration
in pairwise comparisons (p = 0.002)
Pathology findings
C3 levels in liver tissue with the IF method: C3 levels in
livertissue as determined with the IF method are presented (Table 2).
C3 staining in the group without heparin administration (group 2
and 4) was stronger than in the groups administered heparin (group
3 and 5), (Figure 2).
A statistically significant difference was found between the groups
in terms of C3 staining (p = 0.001).
DISCUSSION
Interventions on the liver lead to changes that are consistent
with the ischemia and reperfusion model. While cell damage occurs
during the ischemic period, this damage is further increased during
the reperfusion period that follows. The damaging factors include
oxygen free radicals, leukocyte migration and activation, sinusoidal
endothelial cell damage, irregular microcirculation, and activation of
the coagulation system and complement system [14,15].
Ischemia and reperfusion damage is an important pathological
process leading to hepatic damage following shock and hepatic
surgery. The hepatic damage caused by ischemia and reperfusion
damage is believed to be through the pro-inflammatory cytokines
and other inflammatory mediators secreted from the activated
leukocytes. Therapeutic inhibition of leukocyte activation is therefore
useful in preventing this hepatic damage. Inhibition of TNF-α
production could be effective in preventing such damage. TNF-α
plays an important role in the new microcirculatory distribution
due to microthrombus formation. This microthrombus formation
further increases TNF-α production in the hepatic damage caused
by ischemia and reperfusion damage, leading to a vicious cycle as
regards microcirculatory distribution. Heparin has also been shown
to prevent neutrophil activation through increased hepatic PGI2 and
Table1: IL-6, GSH, MPO mean and standard error values are presented in table 1.
IL-6 (pg/ ml) GSH (nmol/
mg-protein)
MPO
Necrosis Involvement
Control 72.94 ± 55.56 23.58 ± 6.44 4.00 ± 8.94 5.00 ± 0.00
Heparin (-) 24th
Hour
120.44 ± 141.98 31.22 ± 7.42 10.00 ± 22.36 21.25 ± 4.78
Heparin (+)
24th Hour
3.26 ± 7.28 38.42 ± 8.08 0.00 ± 0.00 9.00 ± 2.23
Heparin (-) 48th
Hour
46.14 ± 41.13 25.74 ± 8.69 16.00 ± 23.02 22.00 ± 2.73
Heparin (+)
48th Hour
21.34 ± 47.71 30.44 ± 2.08 0.00 ± 0.00 9.00 ± 2.23
Table 2: Liver tissue C3 levels with the immunofluorescent method.
Order
No
Groups Weight
(gr)
Procedure
Performed
Samples Taken
Pathology
Liver Tissue C3 Levels with the
Immunofluorescence Method.
1 Group 1 180
Control group
Negative
2 160 Negative
3 160 Negative
4 150 Negative
5 150 Negative
6 Group 2 190 Ischemia and
reperfusion
damage at
the 24th
hour
sacrifice
without heparin
administration
Negative
7 210 Diffuse +++ at vessel wall
8 205 Diffuse +++ at vessel wall
9 210 Focal + at vessel wall
10 200 Negative
11 Group 3 280 Ischemia and
reperfusion
damage at
the 24th
hour
sacrifice
with heparin
administration
Negative
12 240 Focal + at vessel wall
13 195 Negative
14 220 Negative
15 250 Focal + at vessel wall
16 Group 4 205 Ischemia and
reperfusion
damage at
the 48th
hour
sacrifice
without heparin
administration
Focal ++ at vessel wall
17 190 Negative
18 190 Focal ++ at vessel wall
19 180 Focal + at vessel wall
20 285 Negative
21 Group 5 290 Ischemia and
reperfusion
damage at
the 48th
hour
sacrifice
with heparin
administration
Focal + at vessel wall
22 200 Negative
23 250 Negative
24 205 Negative
25 180 Focal + at vessel wall
Figure 2: C3 staining in the groups.
5. International Journal of Hepatology & Gastroenterology
SCIRES Literature - Volume 3 Issue 2 - www.scireslit.com Page - 054
to decrease the hepatic damage caused by ischemia and reperfusion.
Heparin decreases this hepatic damage not only by inhibiting TNF-α
production but also by increasing endothelial PGI2 production
[16,17]. The fact that we did not find a difference between the groups
for serum TNF-α levels could be due to the short half-life. More
accurate results could be obtained by investigating tissue TNF-α
levels.
Significant differences were found between the groups in the
statistical analysis performed for serum IL-6 levels (p = 0.001).
Statistically significant differences were found between Group 2
and Group 3 in pairwise comparisons (p = 0.004). No statistically
significant differences were found in pairwise comparisons conducted
between the other groups (p > 0.017). The maximum increase in serum
IL-6 level was in Group 2. The maximum decrease in serum IL-6 level
was in Group 3. When Group 4 and 5 were compared, no statistically
significant difference was found. This result is explained with the rapid
increaseinserumcytokinesafterischemiaandreperfusion,decreasing
to basal values at the 48th hour sacrifice due to the very short half-life.
Although no statistically significant difference was found, IL-6 levels
in the group sacrificed at the 48th
hour were lower than in the control
group. The IL-6 blood level reached is directly proportional to the
amount of tissue damage and is therefore a valuable tissue damage
indicator. The high IL-6 level found in Group 2 in our study indicates
a high degree of tissue destruction in this group. The decrease in
Group 3 could indicate decreased tissue destruction with the effect of
heparin. The blood level of IL-6 increases during ischemia [14].
MDA in liver tissue reflects the presence of lipid peroxidation due
to the free oxygen radicals in tissues following ischemia reperfusion
and thus cellular damage [18]. The lack of a statistical difference
between our groups for MDA results suggests that the ischemia that
was created did not affect all liver tissue due to the presence of hepatic
artery flow. However, one must remember that MDA is not specific.
The consumption of glutathione through conjugation during
ischemia and reperfusion damage is one of the causes of cellular
GSH level reduction. The decrease in the glutathione amount is
compensated by biosynthesis in hepatocytes or exogenous GSH
intake. The decrease in intracellular GSH increases GSH biosynthesis
through an adaptive cellular response at an early stage [19]. A decrease
in the high GSH level is considered to indicate mitochondrial damage
and weakening of the intracellular defense system. Heparin sulfate
proteoglycans bind to the cell surface and inhibit the damage created
by free oxygen radicals. The GSH levels were highest in Group 3 in our
study and higher here than in Group 2. This result shows that heparin
decreases oxidative damage and increases the level of antioxidant
enzymes. No significant difference was found when Group 4 and 5
were compared. The reason for the decrease in tissue GSH levels in
Group 4 and 5 could be increased oxidative stress as a result of the
decreased lipid peroxidation caused by active neutrophils in these
groups and thus inadequate GSH enzyme system activation. This
result indicates that heparin reduces oxidative stress in the first 24
hours and leads to the maintenance of high GSH levels. Elucidating
the mechanism of this effect will require more advanced studies.
One of the most important indicators of leukocyte migration
into tissue that leads to tissue damage is the tissue MPO level.
Myeloperoxidase is released from the primary granules of leucocytes
and catalyzes the reaction of hypochloric acid formation that is
harmful to tissue with the chloride ions of hydrogen peroxide [20,21].
Toxic digestive enzymes such as neutrophil elastase, lactoferrin,
β-glucuronidase, N-acetylglucosaminidase, and in particular MPO
are released with neutrophil degranulation. This reaction causes
tissue destruction and decreased immune resistance [20,21]. MPO
activity is considered to be a sensitive quantitative indicator of
neutrophil sequestration and has been found to be associated
with acute liver damage in many studies based on the ischemia-
reperfusion model [22]. We evaluated MPO activity of liver tissue
with the immunohistochemical method based on data showing a
relationship between MPO activity and number of neutrophils in the
tissue [20]. Evaluation of the MPO activity of the liver tissue revealed
a statistically significant difference between the groups (p = 0.003).
Increased MPO activity was observed in the groups not administered
heparin. Low MPO activity was found in most control group subjects.
The groups with the most increase in tissue MPO activity were those
where ischemia was created without heparin administration. Tissue
necrosis was also observed in these groups. There was a decrease in
the MPO and no tissue necrosis in the groups administered heparin.
These results suggest that heparin can prevent ischemia-related
damage in the liver by decreasing cytokines and that this action is
independent of the complement system [23,24]. Our results were
consistent with the literature. The MPO and IL-6 levels also reflect
tissue damage. We observed heparin to decrease tissue damage as
reflected in the reduced MPO and IL-6 levels in our study. Heparin
could be producing an immunosuppressive effect through its anti-
complement action. It has been shown to have a tissue-protective
effect at doses of 400 to 2000 IU/kg in various ischemia and
reperfusion models [15]. We found mortality to increase at heparin
doses of 1200 IU/kg and above in the ischemia and reperfusion
model in pilot studies while creating our experimental model and
therefore determined our heparin dose as 1200 IU/kg. The reason for
administering heparin as a single intravenous bolus is that heparin
infusion requires immobilization of the rat causing additional stress.
We considered that stress could affect many parameters of our study
and therefore used a single intravenous bolus.
Heparin can decrease hepatic damage independently of its
anticoagulant effect. Heparin and derivatives also have an effect on
the complement system and the most important one is inhibition of
the alternative route through C3b. Inhibition of complement and its
derivatives by heparin has been demonstrated with residual C3 [25].
C3 inhibition then inhibits the production of C3a, C5a and MAC
(C5b-9) that increase leukocyte chemotaxis. Heparin is a C1 inhibitor
and prevents complement activation through the classic route [26].
C1 inhibitors have shown damage-decreasing effects in models where
experimental ischemia and reperfusion damage were created in the
liver, myocardium and brain [14,27]. The protective effect of C1
inhibitors in human myocardial ischemia and reperfusion damage
has been demonstrated [27]. This protective effect suggests that this
substance may play a role in ischemia and reperfusion damage in
other organs. However, the exact mechanism of these effects of C1
inhibitors is not yet clear. Specific inhibition of MAC formation can
also play a protective role against ischemia and reperfusion damage in
certain tissues. Heparin has been shown to inhibit C3 convertase and
C5b-9 [28,29]. We did not include C5b-9 in our study as the other
studies were performed in humans and not in rats [28,29].
Heparin has been found to show a protective effect by inhibiting
complement in kidney tissue with the C3 IF staining technique in an
experimental ischemia reperfusion model [15]. We aimed to show the
relationship between heparin and complement with the IF method
in the rat liver in this study. Complement staining in Group 2 and 4
6. International Journal of Hepatology & Gastroenterology
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(the groups that were not administered heparin) was more intense
than in Group 3 and 5 (the groups administered heparin). Group
2 complement staining was more intense than in Group 3. Diffuse
involvement of the vessel wall was seen in group 2 while there was
no involvement or only focal involvement in Group 3. Complement
staining was more intense in Group 4 than in Group 5. Complement
staining was less intense in the groups administered heparin. Our
results have demonstrated the anti-complement effect of heparin.
Portal vein thrombosis after liver transplantation is a rare
complication. However, it needs to be diagnosed and treated early
in symptomatic patients as it carries a risk of mesenteric ischemia.
Retransplantation may be required if it occurs in the early period
after liver transplantation. Heparin and coumadin are used in the
treatment of portal vein thrombosis. We showed heparin to decrease
the ischemia and reperfusion damage that occurs after portal vein
clamping in this study. The results of the clinical use of heparin can
be better evaluated in cases of portal vein thrombosis occurring after
liver transplantation.
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