Novel Piperine compound AB05 (N-5-(3,4-dimethoxyphenyl) -2E,4E pentadienylpiperidine) inhibits H1N1 influenza virus propagation in vitro

@# Pandemic H1N1 influenza virus respiratory illness has become an inevitable global health concern. With antigenic drift, it becomes necessary to have drugs over tailor-made HIN1 vaccine every year. In the current study, we screened many Piperine derivative in which, N-5-(3,4-dimethoxyphenyl)-2E,4E-pentadienylpiperidine (AB05) and was further studied for anti-H1N1influenza virus activity and compared with other stains in-vitro on MDCK cell line. Initial cytotoxic doses of AB05 for the MDCK cell line were > 25µM. The results showed a dose-dependent reduction of the viral plaque’s in the adsorption assay with EC50 of 0.33 µM. The mechanism of AB05 was by inhibition of matured viral release as evaluated by the time of virus addition with incubation of 6-10 hours. With the promising H1N1 virucidal activity of AB05, we included various strains of human influenza virus to screen AB05 inhibition of Neuraminidase (NA). The result showed 70% NA inhibition in WSN (H1N1), 90% in H3N2 & Influenza B and 49% in Tamiflu resistant H1N1). Further our In silco docking studies substantiated experimental results by showing the difference in binding and cooperation between H1N1 and N3N2. Together these observations illustrate that Piperine derivative AB05 is a promising lead molecule which needs further evaluation in animal models.

Profile of patients presenting with sustained ventricular tachycardia in a tertiary care center

Background and aim Ventricular tachycardia (VT) represents the most frequent cause of sudden cardiac death. Information on clinical characteristics, acute management and outcome of patients with sustained VT is limited in our part of world. The aim of this study was to analyze the demography, hemodynamics, ECG features, underlying disease, mode of termination and outcome of patients presenting with VT. Methods This single center cohort study represents total of 107 patients of VT enrolled over 45 months. Results Mean age was 45 years and 59 of the patients were males. Thirty three of these patients were hemodynamically unstable (31%) and 74 were stable (69%) Coronary artery disease was the most common etiological factor accounting for 39% of patients followed by non-ischemic cardiomyopathy. Determinants of hemodynamic instability were VT in course of acute myocardial infarction (8 out of fourteen) and polymorphic pattern of VT (13 out of 26). Spontaneous termination of VT occurred in seven patients, antiarrythmic drugs terminated VT in 53 of 67 patients and in remaining 45 patients VT was terminated with direct current (DC) cardioversion. Total of twenty three patients died during the hospital stay. Factors that contributed to mortality were old age, hemodynamic instability and low ejection fraction. Conclusion Ischemic heart disease remains the leading cause of VT. Hemodynamically unstable VT occurs more frequently in acute myocardial infarction and polymorphic VT. Most effective method of VT termination is DC cardioversion. Old age, hemodynamic instability and ejection fraction contribute to overall mortality in VT.

Insertion/deletion polymorphism of ACE gene in females with peripartum cardiomyopathy: A case-control study

Background The role of polymorphism of Angiotensin converting enzyme (ACE) gene and ACE activity in etiopathogenesis, prognosis, and many other clinical parameters in the various form of the cardiovascular disease has been established to some degree of certainty. The pathophysiology of Peripartum cardiomyopathy (PPCM) remains an area of active research. The main aim of our study was to see pattern of ACE- Insertion/Deletion (I/D) allele in PPCM and its implications on left ventricular performance indices. Methods This single-center case-control study included 45 cases and 70 controls. The diagnosis of PPCM was established clinically and echocardiographically. ACE genotyping was done by polymerase chain reaction (PCR) method in all subjects. Results The II, ID, and DD genotype was present in 16, 18 and 11 of subjects with PPCM and 48, 19 and 3 of controls respectively. The odds ratio for ACE-II genotype in cases vs. controls was 0.253 (95% CI = 0.114–0.558; p = 0.007), for that of II genotype was 1.93 (95% CI = 0.86–4.3; p = 0.107) and for DD genotype was 7.225 (95% CI; 1.88–27.6; p = 0.0039). Overall frequency of D allele in cases was significantly higher than controls (odds = 4.25; 95% CI = 2.01–6.7; p = 0.0001). Moreover, ejection fraction, left ventricular volume and linear dimensions were worse in patients with DD genotype. Conclusion ACE DD genotype and overall frequency of D allele is significantly higher in patients with PPCM. Also, the presence of DD genotype is associated with worse systolic performance indices measured echocardiographically.

Psychiatric Co-morbidity in Patients With Irritable Bowel Syndrome at a Tertiary Care Center in Northern India

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a chronic psycho-physiological disorder. It is considered to be the most common functional gastrointestinal disorder, and about 50–90% of IBS patients have associated psychiatric co-morbidity. We aimed to study psychiatric co-morbidities in patients with IBS visiting a tertiary care center. METHODS: This was a cross-sectional case-control study conducted over a duration of one and a half years from January 2014 to July 2015. Patients were selected from the out-patient department of gastroenterology. About 160 patients with IBS who fulfilled the inclusion criteria and who gave written informed consent were selected as study cases. The healthy attendants of cases were selected as controls. A total of 200 controls were selected. Rome-III criteria were used to diagnose IBS. For diagnosing psychiatric disorders, we used the Mini International Neuropsychiatric Interview Schedule Plus. RESULTS: Mean age of our cases and controls was 39.7 ± 11.4 and 37.7 ± 9.6 years, respectively. Females outnumbered males in our cases as well as their controls by a ratio of 2:1 approximately. Psychiatric disorders were seen in 84.4% of IBS patients as compared to 41.5% in controls. Major psychiatric disorders seen in our patients were generalized anxiety disorders (30.0%) and depression (28.0%). CONCLUSIONS: The majority of patients with IBS who present to a tertiary care center have co-morbid psychiatric disorders. We need to screen these patients for such co-morbidities and develop a holistic approach for better outcome in such cases.

In vitro genotoxicity of pyridine in human lymphocytes

This work was carried out to study the genotoxicity of pyridine in vitro on human leucocyte culture. Cyclophosphamide, a well-known carcinogen was used as positive control. The four different concentrations of pyridine and cyclophosphamide showed breaks and pulverization of chromosomes in dose dependent manner. Higher number of pulverization was observed with higher concentration of pyridine [3.25ug/mL]. Based on this data, our results confirm that both pyridine and its precursor showed genotoxicity against human lymphocytes

Rapid and simple DNA extraction protocol from goat rumen digesta for metagenomic analysis

In contrast to the traditional culturing techniques and microscopy that have led to the identification and characterization of only about 15-20% of the rumen microbes till date, nucleic acid-based molecular approaches are rapid, reproducible, and allow both the qualitative and quantitative assessment of microbial diversity. The aim of this study was to develop a simple, rapid and effective extraction protocol for the recovery of high-molecular-weight and cloneable metagenomic DNA [mDNA] from goat rumen contents. An efficient method was devised to isolate highmolecular- weight mDNA [>23kb] that was pure and cloneable after isolation in a relatively short period [3.5 h]. This is the first report wherein purification of isolated mDNA could be passed. The purity and cloneability of mDNA was found to be possible with the successful restriction digestion, 16S rDNA PCR amplification of the isolated mDNA and mDNA library construction.The screening of 1600 clones from the metagenomic library revealed one clone with adistinct hydrolytic activity on carboxymethyl cellulose [CMC] agar suggesting its endoglucanase activity. Agarose gel electrophoresis showed aDNA insert of [TILDE]1.5kb size on digestion with BamH1. The metagenomic clones offer a prodigious non-conventional means to explore the genetically untapped resources from nature

Clinical evaluation of efficacy and safety of α-keto analogs of essential amino acids supplementation in patients of chronic kidney disease.

Background: The objective was to evaluate the efficacy and safety of α-keto analogs of essential amino acids (KAA) as a supplement in chronic kidney disease (CKD). Methods: A prospective comparative study was conducted in patients of CKD of a tertiary care center of North India. Patients were randomly divided into two interventional groups. Group I (control) was advised conservative management and placebo while Group II (KAA) given conservative management along with KAA (600 mg, thrice daily) for 12 weeks. Hemogram, renal function tests, lipid profiles were done, and adverse effects were recorded at 0, 4, 8, and 12 weeks of treatment. Results: There was progressive improvement in clinical features in both groups after 12 weeks of treatment, but KAA group showed more marked improvement as compared with the control group. Both groups showed gradual improvement in the biochemical parameters as compared to their pre-treated values, which was more marked in KAA supplemented group. There was a reduction in blood glucose, blood urea, serum creatinine, and 24 h total urine protein. There was an increase in hemoglobin, 24 h total urine volume and glomerular filtration rate. KAA group showed significant (p<0.05) improvement in lipid profiles as compared with the control group. There was no statistical difference in two groups with respect to side-effects (p>0.05). Conclusion: KAA supplementation along with conservative management is efficacious and safe in preventing the progression of disease in patients of CKD.

Study of serum interleukin (IL) 18 and IL-6 levels in relation with the clinical disease severity in chronic idiopathic urticaria patients of Kashmir (North India)

BACKGROUND: Chronic urticaria is termed as idiopathic if there is an absence of any identifiable causes of mast cell and basophil degranulation. Various cytokines have been found to be involved in inflammatory processes associated with chronic idiopathic urticaria, including interleukin (IL) 18 and IL-6. OBJECTIVE: To evaluate any possible correlation of IL-18 and IL-6 cytokines with the clinical disease severity in chronic idiopathic urticaria (CIU). METHODS: IL-18 and IL-6 levels of CIU patients (n = 62) and healthy controls (n = 27) were assessed by commercially available enzyme linked immunosorbent assay kits following the manufacturer's protocols. RESULTS: Serum IL-18 concentration (mean ± standard deviation [SD], 62.95 ± 36.09 pg/mL) in CIU patients and in healthy controls (54.35 ± 18.45 pg/mL) showed no statistical significance (p > 0.05). No statistically significant difference (p > 0.05) was observed between autologous serum skin test (ASST) positive and ASST negative patients with regard to the serum IL-18 levels either. Similarly, serum IL-6 concentration (0.82 ± 4.6 pg/mL) in CIU patients and in healthy controls (0.12 ± 1.7 pg/mL), showed no statistical significance (p > 0.05). Also, comparison between positive and ASST negative patients with regard to the serum IL-6 levels was statistically nonsignificant (p > 0.05). However, statistical significance was found both in IL-18 and IL-6 concentrations in certain grades with regard to the clinical disease severity of urticaria. CONCLUSION: There is no significant association as such found between IL-18 and IL-6 levels with CIU, however, these cytokines may help in predicting the clinical disease severity in CIU. Hence, these cytokines may indicate a potential role as a biomarker to assess the disease severity in CIU.

Lymphoma presenting as severe left ventricular systolic dysfunction: a case report

Lymphoma involving the heart is rare. This is a case report on non- Hodgkin lymphoma where the patient presented for the first time with heart failure and severe left ventricular systolic dysfunction due to lymphoma infiltrating the heart muscle and had simultaneous bilateral involvement of kidneys. This type of presentation has never been described in world literature and is the first reported case

Chemotherapeutic potential of Boerhaavia diffusa Linn: A review.

Boerhaavia diffusa Linn. has been shown to exhibit a wide range of medicinal properties for the treatment of diabetes, inflammation, stress, hepatotoxicity, jaundice and heart failure. The extraordinary antioxidant, hepatoprotective, antibiotic, antidiabetic and anticarcinogenic properties of B. diffusa have attracted pioneers in the field of science and medicine. Moreover, the therapeutic importance of this plant, which is due to presence of polyphenols and flavanoids, makes this plant medically more important to be exploited by clinicians and scientists to gain more insight into its biological and medicinal properties. The present review on B. diffusa focuses over the chemical compositions and its ethno-medicinal uses, linked from ancient times to the present with a scope of development in future. Furthermore, a recent update on mechanistic approaches of B. diffusa has also been discussed, which could be helpful for the researchers working in this field. Eventually, based on its antioxidant and antidiabetic characteristics, it is hypothesized that B. diffusa might exhibit antiglycating properties as well.

Synthesis, Cytotoxic and Anti-bacterial studies of some novel derivatives of N'-[(2E)-3-phenylprop-2-en-1-yl]-2-(quinolin-8-yloxy) acetohydrazide.

An efficient method for preparing chalcones, commencing from acetohydrazide and substituted aromatic aldehydes, have been developed. The reaction of acetohydrazide with substituted aldehydes in the presence of ethanol to yield chalcones 4(a-j) and further the compounds thus obtained were identified by IR, 1H NMR and Mass spectral data and have been screened for their anti-cancer and anti-microbial activity. All the compounds shown significant anti-bacterial activity against S. aureus, B. Subtilis, S. typhi and E. coli and potent anti-fungal activity against A. Niger and C. Albicans. Further moderate activity against carcinoma cells.

Vancomycin resistant enterococcal sepsis in an acute myeloid leu kemic patient

Neutropenic fever is an important cause of morbidity and mortality during therapy of acute myeloid leukemia. Patients with acute myeloid leukemia are at increased risk of acquiring vancomycin resistant enterococcal infection and its treatment remains problematic. Vancomycin therapy for more than 7 days is usually associated with inducible vancomycin-resistant enterococcal infections. We report a case of vancomycin resistant enterococcal sepsis in a patient of acute myeloid leukemia

Physical mapping, expression analysis and polymorphism survey of resistance gene analogues on chromosome 11 of rice.

Rice is the fi rst cereal genome with a fi nished sequence and a model crop that has important syntenic relationships with other cereal species. The objectives of our study were to identify resistance gene analogue (RGA) sequences from chromosome 11 of rice, understand their expression in other cereals and dicots by in silico analysis, determine their presence on other rice chromosomes, and evaluate the extent of polymorphism and actual expression in a set of rice genotypes. A total of 195 RGAs were predicted and physically localised. Of these, 91.79% expressed in rice, and 51.28% expressed in wheat, which was the highest among other cereals. Among monocots, sugarcane showed the highest (78.92%) expression, while among dicots, RGAs were maximally expressed in Arabidopsis (11.79%). Interestingly, two of the chromosome 11-specifi c RGAs were found to be expressing in all the organisms studied. Eighty RGAs of chromosome 11 had signifi cant homology with chromosome 12, which was the maximum among all the rice chromosomes. Thirty-one per cent of the RGAs used in polymerase chain reaction (PCR) amplifi cation showed polymorphism in a set of rice genotypes. Actual gene expression analysis revealed post-inoculation induction of one RGA in the rice line IRBB-4 carrying the bacterial blight resistance gene Xa-4. Our results have implications for the development of sequence-based markers and functional validation of specifi c RGAs in rice.

Age related changes in the rat adrenal gland during prenatal period; [study-1]

Adrenals are complex and important glands of dual character in mammals. The growth of the rat adrenal gland is relatively slower than the general body growth. To observe the age related changes in the adrenal gland of the albino rat during prenatal period. SETTING: Albino rats used were obtained from Animal House of BMSI, JPMC, Karachi. Twenty four fetuses of 15,17,19 and 21 days of gestation were used by dividing into four groups [A to D] each composing 6 fetuses. METHODS: Right adrenals were dissected free, fixed and then stained with 1% toluidine blue solution to study under light microscope. Were dissected free, fixed and then stained with 1% toluidine blue solution to study under light microscope. RESULTS AND CONCLUSIONS: The adrenals showed continuous growth throughout the study. The pancenchymal zonation of cortex started on 15th day and developed on 21st day. In all the cortical zones, the predominance of desk cells over the light cells was observed irrespective of age group studied. The mitotic activity was maximum at the time of birth in both the zones of cortex. The lipid globules in the cortex started developing on 21st day. The medulla appeared distinctly on the 19th day. Both myelinated and unmyelinated nerve fibers were observed in between the cortical cells traversing the whole thickness of cortex from capsule to the medulla