A novel heterozygote allele in caprine melanocortin 1 receptor (MC1R) gene: an association with heat stress traits.

Climate change negatively influences the productive and reproductive abilities of goats. There is a need to understand the relationship between heat stress and genes that may aid in the development of climate-resilient goats. Melanism variation in goats plays a role in thermoregulation, in which the melanogenic genes have a pleiotropic effect on the regulation of physiological responses and behavior that are altered due to heat stress in the animals. Thus, the present study was conducted to establish a possible association between the coat color gene (MC1R) and heat stress characteristics. The physiological responses and cortisol levels were recorded in forty different coat-colored goats. The genotyping of the animals revealed four SNPs at the 183rd (C/T), 332nd (C/G), 748th (G/T), and 801st (C/G) positions, among which the black and brown goat populations had novel SNPs at the 332nd position. Eight haplotypes were constructed, and an association study revealed that haplotypes (CCGG, TCGG, and CCTC) that were linked to white animals had lower cortisol values, rectal temperature, skin temperature, and respiration rate. The multivariate and cluster analyses revealed that the white goats were distinct from the rest of the goats. In addition, the docking results revealed the residues that were forming the interaction complex, which could play a role in melanogenesis in the animals and, in turn, the heat stress ability of the goats. Altogether, the results of the present study could pave the way for more research into coat color genes and their relationship with heat stress traits.

HSF1 and GM-CSF expression, its association with cardiac health, and assessment of organ function during heat stress in crossbred Jersey cattle.

The study aimed to evaluate the differential expression of HSF1 and GM-CSF mRNA in PBMCs and correlate it with myocardial injury in crossbred Jersey heifers during heat stress. The study also assessed the effect of heat stress on cardiac electrical activity, vascular health, liver function and kidney function. The experiment was conducted in two phases: for heat stressed animals; HS in June (THI ranged from 80.0 to 89.8) and for control group i.e. not exposed to heat stress in January (THI ranged between 70.1 and 71.4). Results of the study revealed that the relative abundance of HSF1 and GM-CSF mRNA increased significantly (P < 0.05) in HS. Serum cardiac biomarkers such as CK-MB, AST and CRP were significantly elevated (P < 0.05) in HS. cTnI was detected 'positive' in nineteen out of twenty four cases in HS. Correlation of HSF1 and GM-CSF expression with concentration of LDH, CKMB, CRP and AST in HS was negative but non-significant (P > 0.05). Significant (P < 0.05) ECG findings in HS were increased heart rate, decreased RR interval, decreased PR interval, decreased QRS amplitude and decreased amplitude of P wave. Marked reduction (P < 0.05) in serum cholesterol and triglyceride levels was observed in HS. ALP, AST, bilirubin and urea levels in serum were significantly elevated (P < 0.05) in HS. In conclusion, cardiac enzymes in serum were significantly elevated in HS indicating myocardial injury. HSF1 and GM-CSF mRNA expression alone was inadequate in conferring cytoprotection to cardiac cells in HS. Cardiac electrical activity, vascular status, liver and kidney function were significantly altered in HS.

An in vivo and in silico analysis of novel variation in TMBIM6 gene affecting cardiopulmonary traits of Indian goats.

Transmembrane Bax Inhibitor Motif-containing 6 (TMBIM6) gene acts as calcium leak channel and negatively regulates autophagy and autophagosome formation. The TMBIM6 gene was amplified and searched for variation in three different goat populations (i.e. Black Bengal, Ganjam and Raighar) of Odisha state of the India. The result indicated two substitutions i.e. 55th position (C55T) and 95th position (C95A) in the amplified region of the gene resulting in change of amino acids (Leu > Phe and Thr > Asn). The identified SNPs were combined to form haplotypes and animals were grouped accordingly. Structural analysis showed minor changes (5%) in between mutant and wild TMBIM6 protein structures. However, any functional variation could not be identified with respect to the calcium ligand and open pore state. But an alteration of calcium binding site was found. The binding interaction of calcium with the TMBIM6 protein was hydrophobic in nature in closed state whereas hydrophilic in open pore stage. The stress releasing function was the result of calcium leakage controlled by amino acids coded by exon 4 and exon 5 regions of TMBIM6 gene. The effect of breed and haplotype on cardiopulmonary traits was studied. The data on cardiopulmonary traits of body i.e. rectal temperature, skin temperature, heart rate and respiration rate were recorded when ambient temperature usually remained the highest. The statistical analysis showed, significant difference in rectal temperature, skin temperature and respiration rate among these goat populations. The haplotypes (CC and TA) were found to have a significant (P < 0.05) effect on rectal temperature, skin temperature and respiration rate. However, any such significant effect could not be identified in recorded heart rate. The objective of the present study to identify the genetic variations in TMBIM6 gene having significant effect on cardiopulmonary traits which can be further uses as the molecular markers to improve heat tolerance mechanism in goats.

Common variable immunodeficiency syndrome with chronic diarrhoea.

Common variable immunodeficiency syndrome (CVID) is a heterogeneous disorder characterised by diminished levels of IgG, IgA and/or IgM, and recurrent bacterial infections. Sinopulmonary infections are most commonly reported followed by gastrointestinal (GI) infections. GI tract represents the largest immune organ with abundance of lymphoid cells, its involvement can manifest variably ranging from asymptomatic involvement to florid symptoms and signs. Diffuse nodular lymphoid hyperplasia (DNLH) of the GI tract is characterised by numerous small polypoid nodules of variable size in the small intestine, large intestine or both. It is commonly seen in association to immunodeficiency states such as CVID, IgA deficiency and chronic infections due to Giardia lamblia and Helicobacter pylori and cryptosporidiosis. Repetitive antigenic stimulation leads to lymphoid hyperplasia. We herein describe a case of DNLH of the intestine and another case of duodenal cytomegalovirus (CMV) infection associated with CVID.

Gastrointestinal Histoplasmosis: A Case Series.

Histoplasmosis is an invasive mycosis caused by inhalation of the spores of dimorphic fungi Histoplasma capsulatum. The disease manifests in the lung as acute or chronic pulmonary histoplasmosis and in severe cases gets disseminated in multiple organs like skin, adrenal gland, central nervous system, lymph node, liver, spleen, bone marrow, and gastrointestinal tract. It occurs most commonly in immunodeficient patients like HIV-positive patients and transplant recipients, while immunocompetent hosts are affected rarely. In cases of gastrointestinal histoplasmosis, the samples are collected for culture and biopsy should be sent for histopathological examination for definitive diagnosis. We conducted a retrospective study of colonic biopsies performed in the department of gastroenterology in a tertiary care hospital of north India from January 2014 to December 2015. Five cases of colonic histoplasmosis were diagnosed on histopathology out of which 4 patients were from north India while 1 patient was from Myanmar. The patients presented with various complaints, including loose stools, diarrhea, altered bowel habits, and gastrointestinal bleeding. The prognosis is very good after early and aggressive treatment while the disease is fatal if it remains untreated. In our study, 2 patients died within few days of diagnosis due to delay in the diagnosis, dissemination, and associated complications. Other patients were started on amphotericin B deoxycholate and are under follow-up. An early diagnosis of gastrointestinal histoplasmosis is important as appropriate treatment leads to long-term survival while untreated cases are almost fatal.

Expression and secretory profile of buffalo fetal fibroblasts and Wharton's jelly feeder layers.

The present study examined the comparative expression and secretory profile of vital signaling molecules in buffalo fetal fibroblasts (BFF) and Wharton's jelly (BWJ) feeder layers at different passages. Both feeder layers were expanded up to 8th passage. Signaling molecules viz. bone morphogenetic protein 4 (BMP4), fibroblast growth factor 2 (FGF2), leukemia inhibitory factor (LIF) and transforming growth factor beta 1 (TGFB1) and pluripotency-associated transcriptional factors (POU5F1, SOX2, NANOG, KLF4, MYC and FOXD3) were immunolocalized in the both feeder types. A clear variation in the expression pattern of key signaling molecules with passaging was registered in both feeders compared to primary culture (0 passage). The conditioned media (CM) was collected from different passages (2, 4, 6, 8) of both the feeder layers and was quantified using enzyme-linked immunosorbent assay (ELISA). Concomitant to expression profile, protein quantification also revealed differences in the concentration of signaling molecules at different time points. Conjointly, expression and secretory profile revealed that 2nd passage of BFF and 6th passage of BWJ exhibit optimal levels of key signaling molecules thus may be selected as best passages for embryonic stem cells (ESCs) propagation. Further, the effect of mitomycin-C (MMC) treatment on the expression profile of signaling molecules in the selected passages of BFF and BWJ revealed that MMC modulates the expression profile of these molecules. In conclusion, the results indicate that feeder layers vary in expression and secretory pattern of vital signaling molecules with passaging. Based on these findings, the appropriate feeder passages may be selected for the quality propagation of buffalo ESCs.

Surface plasmon resonance based biosensor: A new platform for rapid diagnosis of livestock diseases.

Surface plasmon resonance (SPR) based biosensors are the most advanced and developed optical label-free biosensor technique used for powerful detection with vast applications in environmental protection, biotechnology, medical diagnostics, drug screening, food safety, and security as well in livestock sector. The livestock sector which contributes the largest economy of India, harbors many bacterial, viral, and fungal diseases impacting a great loss to the production and productive potential which is a major concern in both small and large ruminants. Hence, an accurate, sensitive, and rapid diagnosis is required for prevention of these above-mentioned diseases. SPR based biosensor assay may fulfill the above characteristics which lead to a greater platform for rapid diagnosis of different livestock diseases. Hence, this review may give a detail idea about the principle, recent development of SPR based biosensor techniques and its application in livestock sector.

Early primary prophylaxis with beta-blockers does not prevent the growth of small esophageal varices in cirrhosis: a randomized controlled trial.

BACKGROUND: The efficacy of portal pressure reduction by beta-blockers and the utility of serial hepatic venous pressure gradient (HVPG) measurements for the management of small (≤5 mm) esophageal varices in patients of cirrhosis are not clear. AIMS: The study had the following aims: to study (1) the effect of propranolol on the growth of small varices and (2) whether single or serial HVPG measurements result in a better outcome compared to no measurement in patients with small varices. METHODS: Consecutive cirrhosis patients with small varices, without any history of variceal bleed, were randomized to receive propranolol or placebo and to undergo no HVPG, only baseline HVPG, or serial HVPG measurements. RESULTS: A total of 150 cirrhotics (cirrhosis predominantly viral or alcohol induced) were included (77 in the beta-blocker and 73 in the placebo group). Baseline characteristics were similar. The actuarial 2-year risk of growth of varices (primary endpoint) was 11 and 16% in the propranolol and placebo group, respectively (P = 0.786). Variceal bleeding and mortality were also comparable in the two groups. Similarly, the outcome was not influenced by HVPG measurements (whether serial, only baseline, or no HVPG). A bilirubin level of ≥1.5 mg/dl was found to be an independent predictor of variceal progression. CONCLUSIONS: In cirrhotics with small esophageal varices, nonselective beta-blockers are unable to prevent the growth of varices, variceal bleed, or mortality. HVPG monitoring of these patients did not change the outcome; however, the role of HVPG-guided therapy modification needs to be studied.

Liver and spleen stiffness in patients with extrahepatic portal vein obstruction.

PURPOSE: To evaluate liver stiffness (LS) and spleen stiffness (SS) in patients with extrahepatic portal vein obstruction (EHPVO). MATERIALS AND METHODS: Institutional research board approval and informed consent were obtained. LS and SS were measured in 65 consecutive patients with EHPVO. Patients underwent endoscopy, liver biopsy, liver function tests, abdominal ultrasonography, a detailed history, and examination. LS and SS measurements were also obtained in 50 age-matched healthy control subjects. Comparisons were made by using the Student t test, Mann-Whitney test for quantitative data, and χ(2) or Fisher exact test for qualitative data. RESULTS: Sixty-five patients with EHPVO (with a bleed, n = 45; without a bleed, n = 20; mean age, 25.4 years ± 10.7 [standard deviation]; 29 men, 36 women) were enrolled. Twenty-two (34%) had hypersplenism. LS (P = .001) and SS (P = .01) were higher in patients with EHPVO (6.7 kPa ± 2.3 and 51.7 kPa ± 21.5, respectively) than in control subjects (4.6 kPa ± 0.7 and 16.0 kPa ± 3.0, respectively). Patients who had a bleed had higher SS than did those without a bleed (60.4 kPa ± 5.4 vs 30.3 kPa ± 14.2, P = .01). There was no significant difference in age (26.7 years ± 10.4 vs 22.5 years ± 9.8, P = .8) and median duration of disease (4.5 years [range, 1-26 years] vs 6.0 years [range, 1-22 years], P = .23) in patients with a bleed versus those without. With a cutoff of 5.9 kPa for LS, sensitivity and specificity for detection of a variceal bleed were 67% and 75%, respectively. An SS cutoff of 42.8 kPa yielded sensitivity and specificity of 88% and 94%, respectively. CONCLUSION: LS and SS were higher in patients with EHPVO than in control subjects, and patients with a history of a bleed had a higher SS than did those without a bleed.

Primary prophylaxis of gastric variceal bleeding comparing cyanoacrylate injection and beta-blockers: a randomized controlled trial.

BACKGROUND & AIMS: Gastric variceal bleeding is severe and is associated with high mortality. We compared the efficacy of cyanoacrylate injection and beta-blockers in primary prophylaxis of gastric variceal bleeding. METHODS: Cirrhotics with large gastroesophageal varices type 2 with eradicated esophageal varices or large isolated gastric varix type 1, who had never bled from gastric varix, were randomised to cyanoacrylate injection (Group I, n=30), beta-blockers (Group II, n=29) or no treatment (Group III, n=30). Primary end-points were bleeding from gastric varix or death. RESULTS: The actuarial probability of bleeding from gastric varices over a median follow-up of 26 months was 13% in Group I, 28% in Group II (p=0.039), and 45% in Group III (p=0.003). The actuarial probability of survival was higher in the cyanoacrylate compared to the no-treatment group (90% vs. 72%, p=0.048). The median hepatic venous pressure gradient (HVPG) was increased in Group I (14-15 mm Hg, p=0.001) and III (14-16 mm Hg, p=0.001) but decreased in Group II (14 to 12 mm Hg, p=0.001) during follow-up. Size of gastric varix >20 mm, a MELD score ≥17, and presence of portal hypertensive gastropathy predicted 'high risk' of first bleeding from gastric varices. CONCLUSIONS: Primary prophylaxis is recommended in patients with large and high risk gastric varices to reduce the risk of first bleeding and mortality. Cyanoacrylate injection is more effective than beta-blocker therapy in preventing first gastric variceal bleeding.

Endoscopic cyanoacrylate injection versus beta-blocker for secondary prophylaxis of gastric variceal bleed: a randomised controlled trial.

BACKGROUND AND AIMS: Bleeding from gastric varices is often severe and difficult to manage. Endoscopic injection of gastric varices with cyanoacrylate is effective in prevention of rebleeding. The efficacy of beta-blockers in secondary prophylaxis of gastric variceal bleed has not been well studied. A comparison of the efficacy of beta-blocker treatment and cyanoacrylate injection for the prevention of gastric variceal rebleeding was carried out. METHODS: Patients with gastro-oesophageal varices type 2 (GOV2) with eradicated oesophageal varices or isolated gastric varices type 1 (IGV1) who had bled from gastric varices were randomised to cyanoacrylate injection (n=33) or beta-blocker treatment (n=34). Baseline and follow-up upper gastrointestinal endoscopy and hepatic venous pressure gradient (HVPG) measurements were performed. Primary end points were gastric variceal rebleeding or death. RESULTS: The probability of gastric variceal rebleeding rate in the cyanoacrylate group was significantly lower than in the beta-blocker group (15% vs 55%, p=0.004) and the mortality rate was lower (3% vs 25%, p=0.026) during a median follow-up of 26 months. The median baseline and follow-up HVPG in the cyanoacrylate group were 15 (10-23) and 17 (11-24) mm Hg (p=0.001) and for the beta-blocker group 14 (11-24) and 13 (8-25) mm Hg (p=0.003). While no patient showed reduction of HVPG in the cyanoacrylate group, in the beta-blocker group 12 of 28 (42%) patients were responders, of which 5 (41% of responders) bled. On multivariate analysis, treatment method, portal hypertensive gastropathy and size of the gastric varix >20 mm independently correlated with gastric variceal rebleeding. Gastric variceal rebleeding independently correlated with mortality. CONCLUSIONS: Cyanoacrylate injection is more effective than beta-blocker treatment for the prevention of gastric variceal rebleeding and improving survival.

Equal efficacy of endoscopic variceal ligation and propranolol in preventing variceal bleeding in patients with noncirrhotic portal hypertension.

BACKGROUND & AIMS: Variceal bleeding increases morbidity and mortality among patients with noncirrhotic portal hypertension (NCPH). Blockers of ß-adrenergic receptor signaling and endoscopic variceal ligation (EVL) have been used to prevent recurrence of bleeding, based on data from cirrhotic patients. We compared the efficacy and safety of the ß-blocker propranolol with that of EVL in preventing the recurrence of variceal bleeding in patients with NCPH. METHODS: Consecutive patients with NCPH with a history of variceal bleeding in the past 6 weeks were assigned randomly to groups treated every 3 weeks with EVL (n = 51) or propranolol (until they had a resting heart rate of 55 beats per minute or to a maximum of 320 mg/day; n = 50). Primary end points were recurrence of variceal bleeding or death. Secondary end points were complications of EVL in patients given EVL, variceal eradication after EVL, variceal recurrence after EVL, or a decrease in variceal grade in patients given propranolol. RESULTS: After a median follow-up period of 23 months, rates of recurrence of bleeding were similar between the groups (EVL, 23.5%; propranolol, 18%; P = .625). The actuarial probability of remaining free of bleeding recurrence was similar between the groups. No deaths occurred in either group. Of the patients given propranolol, 47% had a decrease in the grade of varices and none experienced bleeding. Adverse events were minor and comparable between groups (EVL, 12%; propranolol, 18%; P = .635). CONCLUSIONS: EVL was not more effective than the ß-blocker propranolol for the secondary prophylaxis of variceal bleeding in patients with NCPH.

Clinical, laboratory, and hemodynamic parameters in portal hypertensive gastropathy: a study of 254 cirrhotics.

BACKGROUND: Portal hypertensive gastropathy (PHG) is the most common gastric mucosal injury in patients with liver cirrhosis. It is a cause of both acute and chronic upper gastrointestinal bleeding even in the absence of esophageal or gastric varices. The pathogenesis of PHG is unclear. It is not known whether PHG correlates more with portal hypertension or with liver dysfunction. It is also not clear whether altered vascular hemodynamics occurring in PHG is purely a local phenomenon of the stomach or is it a part of a generalized vascular abnormality of cirrhosis and portal hypertension. AIM: In the first part of our study, we aimed to assess any correlation of various clinical and laboratory parameters relating to portal hypertension and liver dysfunction with the presence or absence of PHG. In the second part of our study we examined whether systemic and pulmonary hemodynamics is significantly altered in patients with PHG. PATIENTS AND METHODS: In this retrospective study, the records of consecutive cirrhotic patients who had undergone complete portal, systemic, and pulmonary hemodynamic assessments were analyzed. We excluded patients who had had endoscopic variceal ligation, endoscopic sclerotherapy, cyanoacrylate glue injection or surgery for portal hypertension, patients on beta-blockers, and patients with gastric antral vascular ectasia. Clinical, laboratory, and hemodynamic parameters were compared between patients with and without PHG. RESULTS: Two hundred and fifty-four patients were included in the study (mean age 44.3+/-12.6 y, 82% males). One hundred and three (41%) patients had a history of upper gastrointestinal bleeding. Alcohol, hepatitis B, and cryptogeny were the most common etiologies (27% each). One hundred and forty (55%) patients had PHG. Variables significantly associated with PHG on univariate analysis were history of gastrointestinal bleed, ascites, high bilirubin, deranged prothrombin time, higher variceal grade, high Child-Pugh score, and high hepatic venous pressure gradient. However, on multivariate analysis only Child-Pugh class C, large variceal size, and hepatic venous pressure gradient greater than 12 mm Hg were independently associated with the presence of PHG. Patients with PHG were significantly more vasodilated as indicated by the high mean cardiac index (5.3+/-2.3 vs. 4.6+/-1.9 L/min/m, P=0.012), mean cardiac output (8.9+/-4.0 vs. 7.6+/-3.2 L/min, P=0.004), low median systemic vascular resistance [869 (252-2651) vs. 974 (403-2590) dyn.s/cm, P=0.012], and low median pulmonary vascular resistance [51 (6-226) vs. 63 (6-512) dyn.s/cm, P=0.003]. CONCLUSIONS: PHG is more often associated with advanced portal hypertension and advanced liver failure. The presence of PHG also indicates the existence of an additional vasodilation to already existent hemodynamic anomalies seen in portal hypertension as evidenced by a higher cardiac index and output and lower systemic and pulmonary resistance compared with patients without PHG. Thus, PHG is not merely a local phenomenon in gastric mucosa but also a severe manifestation of generalized vascular alterations of cirrhosis and portal hypertension.