Helicobacter pylori in gallbladder mucosa in patients with gallbladder disease

Background

Helicobacter species have been found to be associated with biliary tract diseases. This prospective study was done to determine the prevalence of H. pylori in the biliary tract of patients suffering from gallbladder disease.

Methods

Forty-nine patients undergoing laparoscopic/open cholecystectomy for benign biliary tract diseases were investigated with urea breath test for H. pylori infection of gastric antrum. Bile and gallbladder tissues were studied for presence of H. pylori by rapid urease test, histopathological examination, culture and PCR analysis. Gallbladder specimens from two patients who underwent Whipple??s operation and from 10 cadavers were studied as controls.

Results

The mean (SD) age of patients was 42.4 (11.1) years. Urea breath test was positive in 17 (34.6%) cases. Rapid urease test was negative in all the cases. There was no evidence of H. pylori infection of gallbladder on histopathological examination using H&;E, Giemsa and Warthin Starry stains. H. pylori DNA were detected in 16 patients (32.6%) and none of the 12 controls by PCR analysis (p?=?0.025). The presence of H. pylori DNA in bile and/or gallbladder was associated with positive urea breath test, (p?H. pylori infection of bile and gallbladder.

Conclusions

Nearly three quarters of patients with positive urea breath test have detectable H. pylori DNA in gallbladder tissue. The significance of these findings needs to be further evaluated.     

Gastrointestinal mucormycosis—four cases with different risk factors, involving different anatomical sites

Mucormycosis of the gastrointestinal tract is a rare infection that usually occurs in patients who are immunocompromised and carries a high mortality. We report four cases of gastrointestinal mucormycosis seen over a one year period with different presentations, risk factors and different anatomical sites of involvement. A preoperative diagnosis was made only in one patient. All underwent surgery, three survived and one died postoperatively from multiorgan failure.     

Ingestion of a carbonated beverage decreases lower esophageal sphincter pressure and increases frequency of transient lower esophageal sphincter relaxation in normal subjects

Transient lower esophageal sphincter relaxation (tLESR) and decreased basal lower esophageal sphincter (LES) pressure are postulated mechanisms of gastroesophageal reflux (GER). There is conflicting evidence on the effect of carbonated drinks on lower esophageal sphincter function. This study was conducted to assess the effect of a carbonated beverage on tLESR and LES pressure. High resolution manometry tracings (16 channel water-perfused, Trace 1.2, Hebbard, Australia) were obtained in 18 healthy volunteers (6 men) for 30 min each at baseline, and after 200 mL of chilled potable water and 200 mL of chilled carbonated cola drink (Pepsi [Pepsico India Ltd]). The sequence of administration of the drinks was determined by random number method generated by a computer. The analysis of tracings was done using TRACE 1.2 software by a physician who was unaware of the sequence of administration of fluids. The mean (SD) age of the participant was 37.3 (12.9) years. The median (range) frequency of tLESr was higher after the carbonated beverage (10.5 [0-26]) as compared to baseline (0 [0-3], p?=?0.005) as well as after water (1 [0-14], p?=?0.010). The LES pressure decreased after ingestion of the carbonated beverage (18.5 [11-37] mmHg) compared to baseline (40.5 [25-66] mmHg, p?=?0.0001) and after water (34 [15-67] mmHg, p?=?0.003). Gastric pressure was not different in the three groups. Ingestion of a carbonated beverage increases tLESr and lowers LES pressure in healthy subjects.     

Synergistic inhibition of hepatocellular carcinoma growth by cotargeting chromatin modifying enzymes and poly (ADP-ribose) polymerases

Hepatocellular carcinoma (HCC) is a particularly lethal form of cancer, yet effective therapeutic options for advanced HCC are limited. The poly(ADP-ribose) polymerases (PARPs) and histone deacetylases (HDACs) are emerging to be among the most promising targets in cancer therapy, and sensitivity to PARP inhibition depends on homologous recombination (HR) deficiency and inhibition of HDAC activity blocks the HR pathway. Here, we tested the hypothesis that cotargeting both enzymatic activities could synergistically inhibit HCC growth and defined the molecular determinants of sensitivity to both enzyme inhibitors. We discovered that HCC cells have differential sensitivity to the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and PARP inhibitor olaparib, and identified one pair of cell lines, termed SNU-398 and SNU-449, with sensitive versus resistant phenotype to both enzyme inhibitors, respectively. Coadministration of SAHA and olaparib synergistically inhibited the growth of SNU-398 but not SNU-449 cells, which was associated with increased apoptosis and accumulated unrepaired DNA damage. Multiple lines of evidence demonstrate that the hepatic fibrosis/hepatic stellate cell activation may be an important genetic determinant of cellular sensitivity to both enzymatic inhibitors, and coordinate activation or inactivation of the aryl hydrocarbon receptor (AhR) and cyclic adenosine monophosphate (cAMP)-mediated signaling pathways are involved in cell response to SAHA and olaparib treatment. CONCLUSION: These findings suggest that combination therapy with both enzyme inhibitors may be a strategy for therapy of sensitive HCC cells, and identification of these novel molecular determinants may eventually guide the optimal use of PARP and HDAC inhibitors in the clinic.     

GSTT1 and GSTM1 Gene Polymorphisms as Major Risk Factors for Asthma in a North Indian Population

Background

According to the National Family Health Survey, asthma is one of the leading diseases in India. In order to understand the complexity of asthma, the susceptibility genes need to be targeted for their association. Glutathione S-transferases play a major role in the detoxification of metabolites of oxidative stress resulting in inflammation and asthma. In the present study, the hypothesis that GSTT1 and GSTM1 gene polymorphisms are associated with asthma was examined.

Methods

This is the first study to investigate the role of GSTT1 and GSTM1 gene polymorphisms in asthma pathogenesis in a North Indian population. A total of 824 subjects were recruited, of which 410 were asthma patients, including 323 patients suffering from allergic rhinitis. The other 414 recruits were healthy controls from regions of North India. Multiplex PCR was used for genotyping the GSTT1 and GSTM1 gene polymorphisms.

Results

The GSTT1 null allele was more prevalent in asthma patients (40?%) than in the control subjects (13.3?%), which yielded a nearly fourfold risk towards asthma with odds ratio (OR) (95?% CI)?=?4.35 (3.04–6.24), χ²?=?75.34, and p?=?0.000. The GSTM1 polymorphism also revealed a greater prevalence of the GSTM1 null allele in asthma patients (46.6?%) than in controls (39.4?%). Statistical analysis yielded a marginal risk toward asthma with OR (95?% CI)?=?1.34 (1.01–1.79), χ²?=?4.37, and p?=?0.036.

Conclusions

Polymorphisms as a result of deletions in the GSTT1 and GSTM1 genes confer an increased risk towards asthma thereby suggesting the protective role of these functional genes in the development of the disease.     

Rare association of eventration of left hemidiaphragm with ipsilateral thyroid agenesis

Eventration is a well-known congenital malformation of the diaphragm, usually asymptomatic and diagnosed incidentally on chest radiography. It is sometimes associated with a number of other congenital syndromes and anomalies. We report a rare case of eventration of left hemidiaphragm associated with gastric volvulus, ipsilateral thyroid agenesis and microphthalmia.     

Reserpine modulates neurotransmitter release to extend lifespan and alleviate age-dependent Aβ proteotoxicity in Caenorhabditis elegans

Aging is a debilitating process often associated with chronic diseases such as diabetes, cardiovascular and neurodegenerative diseases like Alzheimer's disease (AD). AD occurs at a very high incidence posing a huge burden to the society. Model organisms such as C. elegans become essential to understand aging or lifespan extension - the etiology, molecular mechanism and identification of new drugs against age associated diseases. The AD model, manifesting Aβ proteotoxicity, in C. elegans is well established and has provided valuable insights. Earlier, we have reported that Reserpine, an FDA-approved antihypertensive drug, increases C. elegans lifespan with a high quality of life and ameliorates Aβ toxicity in C. elegans. But reserpine does not seem to act through the known lifespan extension pathways or inhibition of its known target, vesicular monoamine transporter, VMAT. Reserpine's mode of action and the pathways it activates are not known. Here, we have evaluated the presynaptic neurotransmitter(s) release pathway and identified acetylcholine (ACh) as the crucial player for reserpine's action. The corroborating evidences are: i) lack of lifespan extension in the ACh loss of function (hypomorphic) - synthesis (cha-1) and transport (unc-17) mutants; ii) mitigation of chronic aldicarb effect; iii) lifespan extension in dopamine (cat-2) and dopamine and serotonin (bas-1) biosynthetic mutants; iv) no rescue from exogenous serotonin induced paralysis in the AD model worms; upon reserpine treatment. Thus, modulation of acetylcholine is essential for reserpine's action.