Un-fractionated heparin counteracts the systemic inflammatory responses and multiple organ damages caused by endotoxaemia in sheep.

BACKGROUND: Endotoxaemia is believed to be a major cause of mortality and there are several therapeutic regimens for the treatment of this situation. OBJECTIVES: The present experimental study was conducted to evaluate acute phase response, cardiovascular and hepatorenal damages following the treatment of Ovine experimental endotoxaemia model employing unfractionated heparin (UFH). MATERIALS AND METHODS: Twenty clinically healthy 1-year-old fat-tailed ewes were randomly divided into four equal groups, comprising UFH 200, UFH 400, Ctrl+ and Ctrl-. Lipopolysaccharide (LPS) from Escherichia coli serotype O55:B5 at 0.4 µg/kg was administered intravenously to the ewes. UFH (at 200 and 400 IU/kg) was administrated to the UFH 200 and UFH 400 groups, respectively. All the ewes were evaluated clinically before and 1.5, 3, 4.5, 6 and 24 hours after LPS injection. Blood samplings were also performed at those hours. We measured serum concentrations of haptoglobin, interferon-gamma, total antioxidant status, malondialdehyde, cardiac lactate dehydrogenase, cardiac troponin-I, total bilirubin, alanine transaminase and creatinine. Serum concentrations of acute phase response, cardiovascular, hepatic and renal biomarkers and clinical parameters increased significantly following the induction of endotoxaemia in the groups receiving LPS. RESULTS: The significantly lowest concentrations of these parameters at hours 4.5 and 6 among the treatment groups belonged to the UFH 400 sheep. CONCLUSIONS: UFH could act as an anti-inflammatory mediator by decreasing inflammatory cytokines and acute phase proteins, modulating oxidative stress biomarkers and reducing multiple organ dysfunction following endotoxaemia in a dose-dependent manner. Furthermore, the anti-inflammatory effects of UFH at 400 IU/kg were significantly higher than another dose. This research examined the effect of two doses of UFH and higher doses may have more anti-inflammatory effects that require further studies.

Effects of intravenous butaphosphan and cyanocobalamin to late pregnant ewes on the metabolic indices around parturition and weight gain of their lambs after birth.

BACKGROUND: Management and control of metabolic disorders in sheep around parturition is important. and various researchers have suggested different managerial solutions. Butaphosphan and cyanocobalamin are widely used for curing metabolic disorders resulting from poor nutrition, inadequate management or diseases. OBJECTIVES: It was hypothesised that butaphosphan and cyanocobalamin could improve the metabolism of ewes around parturition. METHODS: Twenty-eight clinically healthy 3-year-old pregnant Afshari ewes from 21 days before parturition were enrolled into four equal groups: control (Ctrl), B+C1, B+C2 and B+C3. The Ctrl group only received intravenous normal saline and B+C1, B+C2 and B+C3 ewes, respectively, received an intravenous combination of 10% butaphosphan and 0.005% cyanocobalamin at 2, 4 and 6 ml/ewe, on Days 19-21, 10-12 and 1-3 before parturition. Blood samples were taken from all the ewes on Days 21, 12 and 3 before lambing at parturition day and on days 3, 12 and 21 after parturition. A body condition score of all the ewes was assessed at blood sampling days, and lambs born from the ewes were weighed at birth and every 2 weeks up to 3 months. Serum concentrations of glucose, cortisol, non-esterified fatty acids, beta-hydroxy butyric acid, triglyceride, cholesterol, high-, low- and very-low-density lipoproteins, aspartate aminotransferase and alanine aminotransferase were measured. RESULTS: This drug combination decreased circulating glucose, cortisol, lipid profile and hepatic enzymes via dose-dependent manner, 6 ml of this drug compound/ewe was more potent than 4 and 2 ml/ewe. The lambs' weight from mothers receiving 6 ml of this combination was significantly higher than those of the others. CONCLUSIONS: It may be suggested that the intravenous administration of 6 ml/ewe of this combination for 3 consecutive days in three states before parturition had prophylactic effects on metabolic disorders of ewes and enhanced the lambs weight gain after birth.

Low molecular weight heparin reduces acute phase response and multiple organ dysfunction following Ovine experimental endotoxemia model.

Endotoxemia is one of the most common inflammatory situations leading to death of ruminants. Owing to the importance of this condition, several therapeutic regimens have been proposed, evaluated and implemented to treat endotoxemia. It has recently been suggested that low molecular weight heparin may be effective in treating endotoxemia. Thus, the present experimental study was conducted to evaluate the acute phase response and multiple organ dysfunction following the treatment of the Ovine experimental endotoxemia model employing this compound. In this regard, 20 clinically healthy 1-year old Iranian fat-tailed ewes were randomly divided into 4 equal groups, comprising LMWH 50, LMWH 100, Ctrl+, and Ctrl-. Lipopolysaccharide from Escherichia coli serotype O55:B5 at 0.4 µg/kg was intravenously administered to the ewes. Low molecular weight heparin (at 50 and 100 IU/kg) was administrated to LMWH 50 and LMWH 100 groups, respectively. Positive control (Ctrl+) received lipopolysaccharide and treated only by intravenous fluid without any drugs, and negative control (Ctrl-) only received intravenous fluids without lipopolysaccharide or any drugs. All the ewes were clinically evaluated before and 1.5, 3, 4.5, 6 and 24 h after lipopolysaccharide injection, and blood samplings were also performed at those hours. Serum concentrations of serum amyloid A, tumor necrosis factor-alpha, superoxide dismutase, glutathione peroxidase, creatine kinase-MB, homocysteine, total bilirubin, aspartate aminotransferase, and creatinine were measured. Serum concentrations of acute phase proteins, inflammatory cytokines, oxidative stress, cardiovascular, hepatic and renal biomarkers, and clinical parameters were significantly increased following the induction of endotoxemia in the groups receiving lipopolysaccharide. Significantly lower concentration of these markers was observed at 4.5 and 6 h after lipopolysaccharide administration in the sheep treated with LMWH compared to the Ctrl + group. In conclusion, low molecular weight heparin could act as an anti-inflammatory drug by decreasing cytokines and acute phase proteins, modulating oxidative stress biomarkers, and by reducing multiple organ dysfunction following the induction of endotoxemia by Escherichia coli serotype O55:B5 in Iranian fat-tailed sheep in a dose-dependent manner. Furthermore, the anti-inflammatory effects of low molecular weight heparin at 100 IU/kg were significantly higher than 50 IU/kg in the treatment of endotoxemic sheep.

Intravenous Administration of Butaphosphan and Cyanocobalamin Combination to Late-Pregnant Dairy Cows Reduces Their Insulin Resistance After Calving.

Dairy cows suffer insulin resistance following parturition and lactogenesis. Several researchers attempted to reduce insulin resistance via dietary and parenteral supplementations of different substances to promote metabolic performance of dairy cows. Due to mechanisms of actions of butaphosphan in combination with cyanocobalamin, we hypothesized that this compound may reduce insulin resistance of dairy cows following parturition; hence, the effects of the intravenous administration of butaphosphan and cyanocobalamin to prepartum dairy cows on their insulin resistance after calving were evaluated. Twenty-four multiparous Holstein dairy cows were enrolled 3 weeks prior to parturition and divided into four equal groups, including control (Ctrl) and butaphosphan and cyanocobalamin (B+C) 1, 2, and 3. Ctrl cows received 15 mL of 0.9% NaCl solution and B+C 1, 2, and 3 groups intravenously received 2, 4, and 6 mL/100 kg BW of 10% butaphosphan and 0.005% cyanocobalamin combination over three periods of 3 consecutive days, including 21-19, 12-10, and 3-1 days before calving, respectively. Intravenous glucose tolerance test was performed weekly 1, 2, and 3 weeks after parturition to evaluate the insulin resistance phenomenon. Circulating levels of glucose, insulin, non-esterified fatty acids (NEFA), and beta-hydroxybutyric acid (BHBA) were assessed 1, 2, and 3 weeks after calving. Ctrl cows were the most insulin-resistant group, and B+C1 group was the most insulin-sensitive, followed by B+C2 and B+C3 groups. The NEFA and BHBA levels in the B+C3 group were significantly lower than those in the other groups. In conclusion, intravenous administration of butaphosphan and cyanocobalamin to the late-pregnant dairy cows may reduce their insulin resistance after calving.

The comparative effects of dietary monensin and propylene glycol on insulin resistance of transition dairy cows.

During the transition period, dairy cows suffer from negative energy balance due to the upcoming insulin resistance as a major metabolic disturbance. We hypothesized that providing glucose precursors for transition dairy cows may reduce the insulin resistance. In this study, 24 multiparous Holstein dairy cows were enrolled 8 weeks prior to parturition and divided into 4 equal groups, including control (Ctrl), monensin (Mo), propylene glycol (PPG), and monensin plus propylene glycol (Mo + PPG). Cows from the Mo and PPG groups received 1 mg/kg body weight (BW) of monensin, daily. Cows from the PGG group received 150 g of propylene glycol, daily. Cows from the Mo + PPG group received 1 mg/kg BW of monensin and 150 g/head of propylene glycol daily and Ctrl cows received basal diet without any supplementations. Intravenous glucose tolerance test (ivGTT) was conducted weekly from 3 weeks before to 3 weeks after parturition to evaluate the insulin resistance phenomenon. Immediately after glucose administration, glucose and insulin increased significantly, and their alterations were significant during the study. Glucose and insulin were significantly higher in the Ctrl group than in the other groups, and their levels in different pre- and post-partum periods were significantly lower in the Mo + PPG group than in the other studied groups. The results of this study represented that the supplementary feeding with propionate precursors, such as monensin and propylene glycol, reduced the insulin resistance in dairy cows during the transition period. This effect is more explicit by propylene glycol than by monensin, and the combination of both reduces insulin resistance at higher rates. The use of these dietary supplements is likely to produce more propionates as the main precursor of glucose; therefore, it reduces the negative energy balance and subsequently decreases the insulin resistance. In this regard, to reduce insulin resistance, it is recommended that dairy cows during the transition period be fed with monensin and propylene glycol supplements.

Effects of dietary supplementation of bentonite and Saccharomyces cerevisiae cell wall on acute-phase protein and liver function in high-producing dairy cows during transition period.

The aim of this study was to investigate the efficacy of dietary endotoxin binders [bentonite (BEN) and Saccharomyces cerevisiae cell wall (SCW)] on acute-phase protein (APP) response and liver function in cows during the transition period. Twenty-four multiparous Holstein cows were randomly assigned to one of four treatment groups. The experimental groups consisted of (1) the basal diet (BD) + SCW, (2) BD + SCW + BEN, (3) BD + BEN, and (4) BD (control). Blood samples were taken at 1, 3 and 4 weeks before and 1 and 3 weeks after parturition and serum concentrations of non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), glucose, haptoglobin (Hp), serum amyloid A(SAA), albumin, g-glutamyl transferase (GGT), aspartate aminotransferase (AST), cholesterol, iron, and lipopolysaccharide (LPS) were measured. The concentrations of LPS, SAA, albumin, and Hp in the blood were within reference range at all times. The level of blood LPS was not high enough to initiate an APP response. Mean BHBA concentration was highest at 1 week after calving. For NEFA, the pattern was similar, with a peak at 1 week after calving. Cholesterol concentration was lower in the SCW group, probably due to a lower lipoprotein concentration. Mean AST concentration was highest at 1 week after calving, especially in the SCW + BEN group. The results of a current study showed that, if the carbohydrate level is not high in the diet to cause rumen acidosis, it is not profitable to supplement BEN and SCW for adsorbing endotoxins in the diet, in transition cows.

The comparative efficacy of tyloxapol versus pentoxifylline against induced acute phase response in an ovine experimental endotoxemia model.

The effective treatments of endotoxemia are necessary to prevent high mortality rates. Hence, the present study was performed to clarify the antiendotoxic effects of tyloxapol and pentoxifylline in experimentally induced endotoxemia in sheep. Thirty clinically healthy 1-year-old Iranian fat-tailed ewes were randomly divided into six equal experimental (n = 5) groups, comprising Negative and Positive control, Tyloxapol 1, Tyloxapol 2, Pentoxifylline 1 and Pentoxifylline 2. Phenol extracted lipopolysaccharide from Escherichia coli serotype O55:B5 was infused at 2 µg/kg intravenously. Tyloxapol (200 and 400 mg/kg) and pentoxifylline (30 and 60 mg/kg) were injected to Tyloxapol and Pentoxifylline groups, respectively, at 90 min after endotoxemia induction over 60 min along with intravenous fluids. Blood samples were collected from all ewes prior and 1.5, 3, 4.5, 6, 24 and 48 h after lipopolysaccharide injection and sera and plasmas were separated, subsequently. Haptoglobin, serum amyloid A, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), superoxide dismutase and glutathione peroxidase were measured in all samples. Serum concentrations of haptoglobin, serum amyloid A, TNF-α and IFN-γ in Tyloxapol 1 and 2 and Pentoxifylline 1 and 2 groups were significantly lower than Positive control one after hour 3. There were no significant differences among Tyloxapol and Pentoxifylline groups (P > 0.05). Superoxide dismutase and glutathione peroxidase activities in Tyloxapol 1 and 2 and Pentoxifylline 1 and 2 groups were significantly lower than Positive control one after hour 3. There were no significant differences among Tyloxapol 1 and 2 and Pentoxifylline 1 and 2 groups (P > 0.05). Tyloxapol and pentoxifylline act as the anti-inflammatory mediators by decreasing pro-inflammatory cytokines and hepatic APPs and modulating oxidative enzymes activity after endotoxemia induction in sheep. Furthermore, their efficacies at different doses were significantly similar together and both drugs don't induce their effects by dose dependent manner and the anti- and pro-inflammatory effects of them were statistically similar.

Chronic arsenic toxicity in sheep of Kurdistan province, western Iran.

After the detection of arsenic (As) toxicity in sheep from Ebrahim-abad and Babanazar villages in Kurdistan province, the concentration of this element in drinking water, cultivated soil, alfalfa hay, wool, and blood samples was evaluated. Total As concentrations ranged from 119 to 310 µg/L in drinking water, 46.70-819.20 mg/kg in soil 1.90-6.90 mg/kg in vegetation 1.56-10.79 mg/kg in sheep's wool, and 86.30-656 µg/L in blood samples. These very high As contents, in all parts of the biogeochemical cycle, exceed the recommended normal range for this element compared with a control area. Results indicate that As has moved through all compartments of the biogeochemical cycle by way of direct or indirect pathways. The present investigation illustrated decreased packed cell volume and hemoglobin in sheep from the As-contaminated zone. It was concluded that sheep from the contaminated areas suffer from anemia. Chronic As exposure of the liver was determined by liver function tests. For this purpose, blood aspartate transaminase (AST) and alanine transaminase (ALT) were measured. The results show that serum ALT and AST activities are increased significantly (p < 0.01) in the sheep population exposed to As in the contaminated zone. Moreover, chronic As exposure causes injury to hepatocytes and damages the liver.

Genetic characterization and phylogenetic analysis of Trypanosoma evansi in Iranian dromedary camels.

Whole blood samples were collected from 117 male clinically healthy Camelus dromedarius aged between 6 months to 18 years from several farms in Yazd Province of Iran. Trypanosoma evansi-affected camels were detected by Giemsa-stained blood smears, and the positive blood samples (4 out of 117) were submitted to PCR examination and phylogenetic analysis. Basic Local Alignment Search Tool data of the obtained complete internal transcribed spacer (ITS) sequences revealed that they corresponded to those of T. evansi, Thailand cattle isolate (AY912276) with the homology of 99 %. Both phylogenetic trees generated by ITS1 and complete ITS were unable to clearly show inter- and intraspecific genetic diversity of Trypanosoma spp. isolates. The phylogenetic tree inferred from the ITS2 nucleotide sequences (569 bp) clearly showed the genetic diversity of the parasites. Phylogenetic and molecular analyses of this region showed that two distinct genotypes of T. evansi in Iranian dromedary camels are present. In contrast to the ITS1 and ITS2 regions, multiple alignment of the nucleotide sequence of the 5.8S rRNA showed a high degree of sequence conservation during evolution in various Trypanosoma spp.

Anti-inflammatory effects of insulin regular and flunixin meglumine on endotoxemia experimentally induced by Escherichia coli serotype O55:B5 in an ovine model.

BACKGROUND: Endotoxemia is a major cause of mortality in large animals and there are several therapeutic regimens for the treatment of endotoxemia. Recent studies have suggested the anti-inflammatory effects of insulin in endotoxemic human and laboratory animal models but to the best of our knowledge there is no report on the possible therapeutic effect of insulin in large animal endotoxemia. OBJECTIVE: This experiment was conducted to evaluate the anti-inflammatory effects of insulin regular compared with flunixin meglumine on the treatment of endotoxemia in sheep. METHODS: Lipopolysaccharide from Escherichia coli was administered intravenously to ewes. Anti-inflammatory effects of flunixin meglumine (at 2.2 mg/kg) and insulin regular (at 1.5 and 3 IU/kg) were evaluated by determination of serum concentrations of acute phase proteins, inflammatory cytokines and oxidative stress biomarkers. RESULTS: Insulin regular at 3 IU/kg controlled the acute phase response following endotoxemia induction. The anti-inflammatory potency of insulin regular at 3 IU/kg was significantly higher than at 1.5 IU/kg and of flunixin meglumine at 2.2 mg/kg (P < 0.05). CONCLUSION: Insulin regular induces its anti-inflammatory effects in a dose-dependent manner. Intravenous use of insulin regular can be a potential new therapeutic regimen for endotoxemia in large animal medicine.

A survey of seasonal infestation with Przhevalskiana larvae in slaughtered goats and sheep in South-Western Iran.

In this research slaughtered sheep and goats were investigated during August 2003-July 2004 at a slaughterhouse in Masjed-Soleyman, South-Western Iran. The number of infested animals with Przhevalskiana larvae and their age and sex was recorded. Collected larvae from infested animals were stored in Alcohol-Glycerin solution and were studied to determine their morphological properties and species. The data was analyzed by the chi-square test. Rate of infestation was 0.2 and 5.3% in sheep and goats, respectively. Infestation rate in male and female goats and sheep was significantly different (p<0.05). Prevalence of hypodermosis in sheep was significantly different in spring and winter, while infestation prevalence in goats was significantly different in four seasons of the year. Myiasis was seen more frequent in 2-3 and 1-2-year-old age groups of sheep and goats, respectively. The causative agents of goat and sheep hypodermosis were Przhevalskiana aegagri and Przhevalskiana crossii. The onset of fly activity was from late June to mid July.