Ameliorative effect of certolizumab on experimentally induced acute necrotic pancreatitis in rats.

OBJECTIVE: The effects of Certolizumab, a pegylated monoclonal antibody to tumor necrosis factor α, on experimentally induced acute pancreatitis (AP) were examined. METHODS: Thirty-six Wistar Albino male rats were randomly divided into four groups. Group I was the control group and no medication administered to this group. Group II was the Certolizumab group, and 100 ml/kg serum physiologic administered into the biliopancreatic duct and a single dose of 10 µg Certolizumab was simultaneously administered intraperitoneally. Acute pancreatitis was induced with a retrograde injection of 3% Na taurocholate into the common biliopancreatic duct in the study (Group III) and treatment (Groups IV) groups. Rats were sacrificed 72 hours later. Serum amylase, lipase, lactate dehydrogenase activities, along with pancreatic histopathology, were examined. RESULTS: Certolizumab treatment significantly decreased serum amylase, lipase, and LDH levels; histopathologically edema, hemorrhage, parenchymal necrosis, fat necrosis, and infiltration scores; immunohistochemically MDA, MPO, TNF-α and Caspase-3 activity. CONCLUSION: The results support the idea that certolizumab might be beneficial for the severity of AP.

Ameliorative effect of certolizumab on experimentally induced acute necrotic pancreatitis in rats

SUMMARY OBJECTIVE: The effects of Certolizumab, a pegylated monoclonal antibody to tumor necrosis factor α, on experimentally induced acute pancreatitis (AP) were examined. METHODS: Thirty-six Wistar Albino male rats were randomly divided into four groups. Group I was the control group and no medication administered to this group. Group II was the Certolizumab group, and 100 ml/kg serum physiologic administered into the biliopancreatic duct and a single dose of 10 μg Certolizumab was simultaneously administered intraperitoneally. Acute pancreatitis was induced with a retrograde injection of 3% Na taurocholate into the common biliopancreatic duct in the study (Group III) and treatment (Groups IV) groups. Rats were sacrificed 72 hours later. Serum amylase, lipase, lactate dehydrogenase activities, along with pancreatic histopathology, were examined. RESULTS: Certolizumab treatment significantly decreased serum amylase, lipase, and LDH levels; histopathologically edema, hemorrhage, parenchymal necrosis, fat necrosis, and infiltration scores; immunohistochemically MDA, MPO, TNF-α and Caspase-3 activity. CONCLUSION: The results support the idea that certolizumab might be beneficial for the severity of AP.

RESUMO OBJETIVO: Os efeitos de Certolizumab, um anticorpo monoclonal pegilado para o fator de necrose tumoral α, na pancreatite aguda induzida experimentalmente (PA) foram examinados. MÉTODO: Trinta e seis ratos Wistar Albino foram divididos aleatoriamente em quatro grupos. O Grupo I foi considerado o grupo controle e não recebeu medicação; o Grupo II foi o grupo Certolizumab e recebeu 100 ml/kg de soro fisiológico administrado no ducto biliopancreático e dose única de 10 mg Certolizumab administrada por via intraperitoneal simultaneamente. A pancreatite aguda foi induzida com uma injeção retrógrada de uma solução de 3% taurocolato de sódio aplicada no ducto biliopancreático comum nos grupos de estudo (Grupo III) e tratamento (Grupos IV). Os ratos foram sacrificados 72 horas depois. As atividades séricas de amilase, lipase, lactato desidrogenase, juntamente com a histopatologia pancreática, foram examinadas. RESULTADOS: O tratamento com Certolizumab diminuiu significativamente os níveis séricos de amilase, lipase e LDH; edema histopatológico, hemorragia, necrose paranquimatosa, necrose gordurosa e escores de infiltração; atividade imuno-histoquímica de MDA, MPO, TNF-α e Caspase-3. CONCLUSÃO: Estes resultados suportam a ideia de que o Certolizumab pode ser benéfico para a gravidade da PA.

Effects of Certolizumab on Cerulein-Induced Acute Pancreatitis in Rats.

OBJECTIVES: To evaluate the effects of certolizumab, a pegylated monoclonal antibody to tumor necrosis factor α (TNF-α), on experimentally induced acute pancreatitis. METHODS: Healthy Wistar Albino male rats (n = 36) were randomly divided into 4 groups (9 rats in each group): group 1, control group; group 2, certolizumab group; group 3, cerulein group; and group 4, cerulein + certolizumab group. Acute edematous pancreatitis was induced via intraperitoneal injection of 80-µg/kg cerulein (20 µg/kg, 4 times at 1-hour intervals) in groups 3 and 4. Certolizumab (10 µg) was intraperitoneally administered in groups 2 and 4. Serum levels of amylase, lipase, TNF-α, and lactate dehydrogenase were evaluated. Histopathology and immunohistochemistry of the pancreatic tissue for assessing the activities of malondialdehyde, myeloperoxidase, TNF-α, and caspase-3 were also performed after 72 hours. RESULTS: Certolizumab treatment significantly decreased the serum levels of amylase, lipase, and lactate dehydrogenase. Histopathological edema, hemorrhage, parenchymal necrosis, and infiltration scores were also decreased, along with a decrease in malondialdehyde, myeloperoxidase, TNF-α, and caspase-3 activities. CONCLUSION: This study suggests that certolizumab is a beneficial treatment mode for reducing the severity of acute pancreatitis.

Coagulation profile, haematological and biochemical changes in kids naturally infected with peste des petits ruminants.

The aim of this study was to examine the coagulation profile in peste des petits ruminant (PPR) in kids. Five kids from a group of 150 animals (72 goats and 78 kids) were brought to the Veterinary Medical Teaching Hospital from a farm in Burdur province (Turkey) with nasal and ocular discharges and diarrhea. Fifteen goats and 41 kids had died due to diarrhea and three kids were presented to the Department of Pathology for diagnosis. Blood samples were taken from 12 ill animals (infected group) for haematological and biochemical analysis. In addition, five healthy kids were examined from another healthy flock (control group). Leukocyte and lymphocyte numbers of infected group showed significant declinations in comparison to control group (≤0.001). Haemorrhages in all organs of digestive system and small haemorrhagic areas in liver were caused to decrease in erythrocyte and haematocrit values (p ≤ 0.001) in infected group. Concentrations of blood urea nitrogen (BUN) (p ≤ 0.01) and creatinine (p ≤ 0.001) in infected group were significantly higher than control group. Compared to control group, significant increases were determined in serum concentrations of alkaline phosphatase (ALP) (p ≤ 0.01), aspartate aminotransferase (AST) (p ≤ 0.001) and alanine aminotransferase (ALT) (p ≤ 0.001) in the infected group. No significant differences were observed between the infected and control groups for serum gamma glutamyl-transferase (GGT) concentration value. In our study, thrombocytopenia (p ≤ 0.001) together with prolonged activated partial thromboplastin time (APTT; p ≤ 0.01) and prothrombin time (PT; p ≤ 0.001) may show that disseminated intravascular coagulopathy which can occur in kids with PPR.

Ameliorative effect of adalimumab on experimentally induced acute pancreatitis in rats.

OBJECTIVES: In this study, the effects of adalimumab (ADA), a fully humanized IgG1 monoclonal antibody to tumor necrosis factor α, on experimentally acute pancreatitis (AP) were examined. METHODS: Healthy Wistar rats (n = 32) were randomly divided into 4 groups: group 1, AP; group 2, AP + ADA; group 3, control (physiologic saline), and group 4, physiologic saline + ADA (n = 8/group). Acute pancreatitis was induced with a retrograde injection of 3% sodium (Na)-taurocholate into the common biliopancreatic duct. Adalimumab was simultaneously administered at 50 mg/kg intraperitoneally for groups 2 and 4. Physiologic saline was administered instead of Na-taurocholate for non-AP groups. After 24 hours, serum amylase, lactate dehydrogenase, pancreatic myeloperoxidase, and malondialdehyde activities, along with pancreatic histopathology, were examined. RESULTS: Adalimumab treatment significantly decreased serum amylase activity (AP, 2778.25 ± 298.80; AP + ADA, 2143.13 ± 221.69; control, 1541.00 ± 148.39; ADA, 1143.00 ± 256.30 U/L; P < 0.001), lactate dehydrogenase activity (AP, 2978.37 ± 364.65; AP + ADA, 2582.75 ± 164.23; control 931.25 ± 135.93; ADA, 582.62 ± 99.37 U/L; P < 0.001), myeloperoxidase activity (AP, 1.44 ± 0.20; AP + ADA, 0.86 ± 0.01; control, 0.60 ± 0.17; ADA, 0.41 ± 0.00 U/g of wet tissue; P < 0.001), malondialdehyde activity (AP, 16.94 ± 3.98; AP + ADA, 7.66 ± 2.27; control, 9.07 ± 1.00; ADA, 3.58 ± 0.30 nmol/g; P < 0.01), and total histopathologic scores (AP, 2.75 ± 0.16; AP + ADA, 1.50 ± 0.19; control, 0.00 ± 0.00; ADA, 0.00 ± 0.00; P < 0.001). CONCLUSIONS: These results support the idea that adalimumab might be beneficial for severity of AP.

Pathological and immunohistochemical examinations of the pancreas in subacute endosulfan toxicity in rabbits.

OBJECTIVES: Pancreas pathology in subacute endosulfan toxicity and the effect of vitamin C in rabbits were studied. METHODS: : Twenty-four rabbits in 4 groups were used. The rabbits in group END were given a daily sublethal dose (1 mg/kg of body weight) of endosulfan in corn oil by oral gavage for 6 weeks. Group END+C received the same dose of endosulfan and also vitamin C (20 mg/kg) every other day. Group OIL+C received oral corn oil daily and vitamin C (20 mg/kg) every other day. Group OIL received corn oil daily by oral gavage throughout the experiment. Serum amylase, lipase, and glucose levels were analyzed 1 week after the last treatment. Histopathological and immunohistochemical methods were used. RESULTS: The amylase levels were normal, but the lipase levels were increased in all the groups. Marked increases in glucose levels were observed in the END and the OIL+C groups. Microscopy examination of the pancreases indicated degenerative changes in the END group. The pancreases of the END+C group were relatively normal in appearance. The immunohistochemistry of the pancreas showed marked decreases in proinsulin-, insulin-, and amylin-secreting cells and slight decreases in glucagon-secreting cells, whereas cells expressing caspase 3 increased. CONCLUSION: Endosulfan can cause toxic effects on rabbit pancreases, but vitamin C has an ameliorative effect.

Effects of etanercept on sodium taurocholate-induced acute pancreatitis in rats.

In this study, we examined the effects of etanercept (ETA) on experimentally induced pancreatitis. Acute pancreatitis was induced with Na taurocholate. ETA was simultaneously administered to treatment groups. Serum amylase and lipase activity, pancreatic histopathology, apoptosis, malondialdehyde (MDA), and myeloperoxidase enzyme activity (MPO) were assessed. Although rats in the groups 1, 2, and 3 were sacrificed 24h later, groups 4, 5, and 6 were sacrificed 5 days later. ETA treatment significantly decreased serum amylase activity (nontreated, 2636.16+/-191.94; treated, 1898.71+/-262.53; control, 506.28+/-17.31 U/L, P<0.001), lipase activity (nontreated, 3049.67+/-972.65; treated, 2538.85+/-660.45; control, 88.57+/-7.54 U/L, P<0.001), histopathologic score (nontreated, 5.43+/-0.43; treated, 2.57+/-0.20; control, 0.71+/-0.18, P<0.001), MDA (nontreated, 105.77+/-13.29; treated, 92.89+/-10.39; control, 41.26+/-2.54 nmol/g, P<0.001), and MPO (nontreated, 0.64+/-1.15; treated, 0.59+/-0.13; control, 0.17+/-0.02 units/g/wet weight, P<0.001) activity in 24-h groups. In 5-day groups, ETA treatment decreased amylase activity (nontreated, 738.67+/-48.60; treated, 497.14+/-47.25; control, 389.00+/-9.17 U/L, P<0.001), lipase activity (nontreated, 101.33+/-39.32; treated, 34.57+/-7.29; control, 23.42+/-2.12 U/L, P<0.001), histopathologic score (nontreated, 5.43+/-0.43; treated, 3.71+/-0.68; control, 0.00+/-0.00, P<0.001), MDA (nontreated, 67.91+/-4.28; treated, 60.91+/-3.57; control, 14.85+/-1.16 nmol/g, P<0.001), and MPO (nontreated, 0.36+/-0.04; treated, 0.27+/-0.02; control, 0.14+/-0.02 units/g/wet weight, P<0.001) activity. Caspase-positive cells numbers around the necrosis significantly decreased by ETA treatment in both 24-h groups (nontreated, 74.28+/-3.26; treated, 67.00+/-1.15; control, 3.85+/-0.63, P<0.001) and 5-day groups (nontreated, 79.85+/-3.01; treated, 47.85+/-5.76; control, 2.22+/-0.63, P<0.001). These results showed that ETA has an ameliorating effect on sodium taurocholate-induced acute necrotic pancreatitis.

Evaluation of changes in serum lipoprotein and apolipoprotein patterns in cows with ketosis.

OBJECTIVE: To detect changes in serum lipoprotein and apolipoprotein profiles via precipitation and electrophoresis in ketotic cows and in those cows treated with different methods. ANIMALS: 21 cows with clinical and subclinical ketosis, 7 healthy cows in the early lactation period, and 7 healthy cows in the nonlactation period. PROCEDURES: Ketotic cows were allocated into 3 groups; the first group was treated with dextrose and dexamethasone, the second group with dextrose and prednisolone, and the third group with dextrose and insulin. The beta and alpha lipoproteins were precipitated with dextran sulfate-magnesium chloride in ketotic cows after treatment and healthy cows in the nonlactation and lactation periods. The serum samples, precipitates, and supernatants were examined via agarose gel electrophoresis for detection of alterations in serum lipoproteins. Subsequently, alterations in serum apolipoproteins were detected via SDS-PAGE of precipitates. RESULTS: Compared with serum beta and alpha lipoprotein concentrations in healthy cows during nonlactation, those in cows during lactation were higher; however, those in cows with ketosis were lower. The SDS-PAGE analysis of serum beta lipoproteins revealed that apolipoprotein E (approx 36 and 40 kDa) decreased in ketotic cows, in comparison with healthy cows in the nonlactation and lactation periods, but increased after treatment. Decreases in apolipo-protein B (approx 222 kDa), apolipoprotein A-I (19 and 24 kDa), apolipoprotein A-IV (55 kDa), apolipoprotein C-III (8.8 and 10.2 kDa), and albumin (66 kDa) concentrations were detected in ketotic cows, in comparison with the healthy cows in the lactation period. CONCLUSIONS AND CLINICAL RELEVANCE: Serum lipoprotein and apolipoproteins may routinely be determined via precipitation and electrophoresis in the diagnosis and treatment of ketosis.

Clinicopathological studies on facial eczema outbreak in sheep in Southwest Turkey.

After very hot summer, 22 sheep from 5 different flocks consisting of approximately 150-200 animals each were diagnosed with facial eczema in September 2005, in southwest Turkey. Photophobia, corneal opacity, severe ulcers of the facial skin, especially localized around the eyes and mouth, and 3% mortality were the most prominent clinical symptoms. GGT levels of the animals were very high and varying between 261- 328 U/l. While the activities of ALT and total bilirubin were elevated and AST was normal in affected sheep. Total bilirubin level was higher than normal. Seven of the 22 sheep were euthanatized and necropsy was performed on all of these animals. Severe icterus, hepatomegaly, enlarged gallbladder, congestion of mesenteric vessels were the common necropsy findings. Histopathological changes of the liver included necrosis of the hepatocytes, cholangiohepatitis characterized by mononuclear inflammatory cell infiltrate in the portal area and mild to severe fibrosis around bile ducts. A diagnosis of sporidesmin toxicosis was made based on the histopathology of the livers, the elevation in liver enzymes, and the development of cutaneous lesions consistent with photosensitization and high spore counts in the ruminal contents. Surviving sheep were treated with procaine penicillin + dihidrostreptomycin sulfate, multivitamin complexes and flunixin meglumine. Additionally, zinc sulphate was also given at a dose of 6 gr per 100 lt drinking water for 28 days. All treated sheep recovered. Pasture spore counts were between 96,300- 267,500 spores/g grass.

Effect of insufficient insulin treatment in streptozotocin-induced diabetes mellitus.

OBJECTIVES: In this study, we investigated clinically, pathologically, and immunohistochemically the effect of insufficient short-acting insulin treatment on streptozotocin (STZ)-induced diabetes mellitus in rats. METHODS: Three groups composed of 10 rats each were studied as follows: (1) a group that received only STZ (50 mg/kg) (STZ group); (2) a group that received 50 mg/kg STZ and, after 12 hours, 8 IU of short-acting insulin treatment (STZ + INS group), repeated every night for 5 days; and (3) a control group. Ketonuria and blood glucose levels were examined every day. Blood was obtained from 2 rats from each group, and necropsy was performed every day during the 5-day period. RESULTS: Hyperglycemia was observed in the STZ and STZ + INS groups 24 hours after, but levels were higher in the STS + INS group than those in the STZ-only group. Histopathology was similar in the STZ and STZ + INS groups, and degeneration was observed in both groups, but immunohistochemistry revealed a more severe reduction in insulin-secreting cells in the STZ + INS group than that in the STZ group. There were no hyperglycemia and histopathological or immunochemical alteration in the control group. CONCLUSIONS: This study showed that insufficient short-acting insulin treatment can increase the diabetogenic effect of STZ in rats.