Antiangiogenic activity of zinc and zinc-sorafenib combination using the chick chorioallantoic membrane assay: A descriptive study.

AIM: Zinc, a trace element, is known for downregulating several proangiogenic growth factors and cytokines. However, its antiangiogenic activity is not adequately studied. The present study was aimed to evaluate the possible antiangiogenic activity of zinc via the chick chorioallantoic membrane (CAM) assay. Furthermore, the antiangiogenic activity of the combination therapy of zinc with various doses of sorafenib, a tyrosine kinase inhibitor, was evaluated. MATERIALS AND METHODS: A pilot study was initially conducted so as to select suitable doses of zinc and sorafenib. The antiangiogenic activity after combining zinc 2.5 µg/embryo with sorafenib 1 and 2 µg/embryo was also evaluated. The antiangiogenic activity was quantified in terms of total length of blood vessels, number of junctions, number of branching points, and mean length of the blood vessels. RESULTS: Zinc 2.5 µg/embryo showed significant (P < 0.05) antiangiogenic activity, as compared to the control group. However, its effect was not comparable to that of sorafenib 2 µg/embryo. The combination of zinc 2.5 µg/embryo with sorafenib 2 µg/embryo did not show an additive/synergistic effect. The combination of zinc 2.5 µg/embryo with sorafenib 1 µg/embryo produced an antiangiogenic activity which was comparable (P > 0.05) to that of sorafenib 2 µg/embryo. CONCLUSION: Zinc caused significant antiangiogenic activity in the CAM assay. The lack of addition/synergism in the zinc-sorafenib combination could have been due to the variability in the dose/ratio selection. Addition of zinc to sorafenib therapy could improve treatment tolerability, reduce cost of therapy, and reduce the emergence of drug resistance. Future mechanistic studies could identify the exact pharmacodynamics of zinc as an angiogenesis inhibitor.

Tobacco and alcohol: the relation to pulmonary tuberculosis in household contacts.

Tuberculosis is transmitted commonly by droplet nuclei and facilitated by weak immune system. Lowered immunity may be associated with cigarette smoking, tobacco chewing and alcohol consumption. The co-relationship between these all factors to TB should be explored. This study aims to detect the hidden household contacts (HC) cases early and to examine the relative contribution of tobacco and alcohol use to the risk of TB. Across-sectional study was in Dharan among HCs. From June 2009 to May 2010, 184 index cases with sputum smear positive for AFB and their 802 HCs were included. Three sputum specimens were collected from each HCs and examined microscopically for AFB detection. AFB were detected in sputum of 13 (1.6%) HCs. The association between habits (alcohol user and smoking) and TB was found except with chewing tobacco user (P > 0.05). The risk of contact TB was 4 and 8 times greater in smoker (OR = 3.94 95% CI = 1.26-12.26, P < 0.05) and alcoholic (OR = 8.23 95% CI = 2.71-24.98, P < 0.05) HCs respectively. This study has revealed smoking and alcohols as the risk factors for tuberculosis. Effective campaign to discourage use of alcohol and tobacco, and awareness programme about the mode of transmission of TB are needed in community.

Effectiveness of an educational feedback intervention on drug prescribing in dental practice.

BACKGROUND: Irrational use of drugs as well as inappropriate and over drug prescribing leads to unnecessary expenditures and emergence of resistant bacterial strains. Feedback intervention on drug prescribing habits and face to face educational intervention of prescription audit would be effective in rationalizing prescribing practices. OBJECTIVE: To measure the impact of educational feedback intervention on the prescribing behavior of dental surgeons. METHODS: Prospective audit of twelve hundred outpatients prescriptions in dental OPD at BPKIHS of those dental surgeon who attended the educational intervention session was collected randomly by trained persons on customized data collection sheet before and after educational intervention. RESULTS: A total 1200 prescription were collected, 300 before and 300 after intervention period at the internal of one month, three months and six months. Majority of the prescriptions (39.33%) contained four drugs but after intervention, prescriptions contained mostly one drug, 73% in first month, 78.67% in third month and 65.34% in six month. Mean number of drugs per prescription after intervention were decreased. There was increased number of generic names of drugs after intervention. Amoxicillin, Metronidazole, Chlorhexidine, Povidone iodine gargle, Nimesulide, Ibuprofen, Ibuprofen + paracetamol, and Paracetamol were most commonly prescribed by dental prescribers before and after intervention. Selection of antimicrobial was done on empirical basis which was correct because Amoxicillin concentration reaches effectively in gingival crevicular fluid and Metronidazole covered effectively against anaerobic bacteria were found in orodental infection. The uses of topical anti-infective preparation as irrigants of choice that can kill majority of micro-organisms found is root canal and dental tubules and minimize systemic use of antimicrobials. Nimesulide prescribing needs to be rationalized. CONCLUSION: Feedback educational intervention of prescription audit is effective to improve their prescribing behaviors and rationalize drug utilization pattern for the benefit of the patients.

Study of patients with painless inguinal hernia in the quality of life.

Inguinal hernias are one of the commonest surgical problems in our set up. It is a protrusion of abdominal cavity contents through the inguinal canal. This is a retrospective study done in the Department of Surgery, Nepal Medical College Teaching Hospital (NMCTH) from January 2009 to December 2010. During this period, 120 patients with painless hernia were enrolled in the study. The age range was from 30 years to 76 years with mean age of presentation at 53 years. Out of 120 patients who underwent mesh repair only 74 patients (61.7%) had visible hernia on standing and 46 patients (38.3%) had palpable impulse on cough. 90 patients (75%) were males and indirect hernia (53.3%) was more common than direct hernia. Out of 120 cases, 30 cases underwent inguinal neurectomy which on follow up had no pain at all. In other 90 cases, neurectomy was not confirmed from the operative note. In these 90 cases, 12 patients had mild pain and 10 patients had moderate to severe pain on 6 months follow up. To conclude, surgical repair is recommended for painless inguinal hernia as most of the patients develop symptoms over time and to avoid undue complications.

Signet ring cell carcinoma of the gallbladder: a case report.

Carcinoma of the gall bladder is the most common biliary tract tumor with higher incidence in females and increasing age. The risk is significantly higher in cholelithiasis. Signet ring cell carcinoma is a rare form of mucinous adenocarcinoma and has a worse prognosis. Early diagnosis is rare. We report a case of signet ring cell carcinoma of the gall bladder in a 70 years old female patient. The gross finding was yellowish white mass measuring 4 x 3.5 cm on cut surface of the gall bladder along with thickened wall. Histopathological examination of the specimen shows the sheets of signet ring cells with lateral spread through the lamina propria and large amount of extracellular mucin. There was metastasis in the retroperitoneum and mesenteric lymph node. The tumor was stage IV (according to TNM staging). Patient died 20th post operative day. Since very few cases have been reported, information regarding the behavior and prognosis of gall bladder carcinoma is limited. However it has been seen that stage III and IV carcinoma usually have worse prognosis.

Ayurvedic processed seeds of nux-vomica: neuropharmacological and chemical evaluation.

The effect of detoxification on Strychnos nux-vomica seeds by traditional processing with aloe and ginger juices (B), by frying in cow ghee (C), and by boiling in cow milk (D) was investigated. The ethanolic extracts of these samples were subjected to spontaneous motor activity (SMA), pentobarbitone-induced hypnosis, PTZ induced convulsions, diazepam-assisted protection, and morphine-induced catalepsy. All samples reduced SMA and inhibited catalepsy. The seeds processed in milk (D) showed the lowest strychnine content in the cotyledons, exhibited marked inhibition of PTZ induced convulsions and maximal potentiation of hypnosis, and were the safest (LD(50)).

Polyarthritis associated with testicular tumour.

Rarely rheumatological features may dominate and is the cause of missed or delayed diagnosis of a malignant lesion. A case is presented wherein the patient with embryonal type of testicular tumour masqueraded with symmetrical polyarthritis with small joint involvement. p53 antigen was detected in testicular tissue. Such an example is indeed unreported in literature to the best of our knowledge.

Lack of effect of SU1498, an inhibitor of vascular endothelial growth factor receptor-2, in a transgenic murine model of retinoblastoma.

SU1498, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), has activity against retinal neovascular diseases. To determine if this drug might have clinical utility against retinoblastoma, we evaluated the effects of SU1498, as well as the expression of VEGFR-2, in a transgenic animal model of retinoblastoma. Optical coherence tomography (OCT) was evaluated as a technology to measure retinal tumors in vivo, in response to treatment. Immunofluorescence analysis was performed to evaluate the distribution and expression of VEGFR-2 in enucleated eyes from LHbetaTag transgenic mice and controls at 4, 8, 12, and 16 weeks of age. VEGFR-2 and phosphorylated (p)VEGFR-2 levels were quantitated by Western blot. OCT was used to pair 10-week-old animals based on tumor volume (n=10), and these animals were treated with 6 periocular injections of SU1498 (50mg/kg, given twice weekly) or vehicle for 3 weeks. Tumor burden was determined by histology and in vivo imaging by OCT. VEGFR-2 and pVEGFR-2 expression levels were upregulated during tumorigenesis. However, SU1498 did not significantly reduce tumor burden compared to vehicle (p=0.29). OCT imaging of one matched pair demonstrated equivalent, linear tumor growth despite treatment with SU1498. Retinal tumors can be followed non-invasively and quantitatively measured with OCT. VEGFR-2 is strongly upregulated during tumorigenesis in transgenic retinoblastoma; however, SU1498 does not decrease tumor volume in transgenic murine RB at the studied dose and route of administration.

Epidemiological and bacteriological profile of burn patients at Nepal Medical College Teaching Hospital.

This study was conducted to know the epidemiological and bacteriological profile of burn patients at Nepal Medical College Teaching Hospital. The charts of 50 burn patients admitted in department of surgery were reviewed retrospectively. All the epidemiological characteristics, mode of injury, time taken to reach hospital and involved body surface areas were noted. The charts were also reviewed for bacterial isolates from burn wounds and its sensitivity pattern for various antibiotics. Data was analyzed using the statistical package for social sciences (SPSS) for Windows. The mean age of patients was 31.8 years with male:female ratio of 1.3:1. Half of the patients were from Kathmandu. Fifty two percent of patients directly came to our hospital while rests were referred from other hospitals. The average time taken to reach hospital was 11.3 hours. Those patients who were referred from outside the valley took longer time (p = 0.002). Flame burn was the leading cause for injury (66.0%) followed by scald burn (16.0%), electric burn (14.0%) and acid burn (4.0%). Staphylococcus aureus (28.0%) was the commonest organism isolated from wound swab culture. Others were Klebsiella (16.0%), Pseudomonas (13.0%), Proteus (13.0%) and E.coli (13.0%). No growth was noted in 17.0% of patients. During the treatment, 14.0% of patients died and 4.0% left against medical advice. Remaining patients were discharged after complete recovery. Body surface area involvement was found to be a significant predictor of mortality (p < 0.001) and the length of hospital stay was significantly low for them (p = 0.05).

Detection of Genogroup I and II human picobirnaviruses showing small genomic RNA profile causing acute watery diarrhoea among children in Kolkata, India.

Picobirnaviruses (PBVs) with bisegmented small RNA genome profile (1.75 and 1.55kbp for segment 1 and 2, respectively) were detected from 1999 to 2003 in faecal specimens of acute watery diarrhoea cases, largely children (n=20) and an adult in Kolkata, India. Varying degrees of dehydration necessitated their visit to hospital for further treatment and management of acute watery diarrhoea. PBV was associated with rotavirus (n=3) or astrovirus (n=3) and with both in one case. No co-infection with norovirus, sapovirus or adenovirus was detected in the picobirnavirus positive cases. No co-infection with parasites (Cryptosporidium spp., Giardia spp., Entamoeba spp., helminths) or bacteria (Vibrio spp., Shigella spp., Escherichia coli) was detected among the picobirnavirus positive cases. There was a single instance of co-infection with Salmonella spp. (n=1). PBVs not associated with serious diarrhoea illness and showing large genome profile (2.3-2.6 and 1.5-1.9kbp for segment 1 and 2, respectively) have earlier been reported in adult individuals and recently among children from a slum community in Kolkata, India. The short genome profile PBVs associated with acute watery diarrhoea may be another emerging diarrhoeagenic virus in Kolkata, India. Molecular characterization using reported primers PicoB25-PicoB43 for Genogroup I and PicoB23-PicoB24 for Genogroup II in RT-PCR showed the presence of Genogroup I PBVs (n=6) and Genogroup II PBVs (n=5), while some could not be amplified (n=3) with these primers. Sequence analysis of Genogroup I amplicons indicated remarkable sequence heterogeneity. After more than a decade, four PBV positives of Genogroup II were detected during this study. Phylogenetic analysis showed varying degree of genetic diversity amongst PBV strains from Kolkata and other countries.

Pre- & post-treatment evaluation of immunological features in Indian visceral leishmaniasis (VL) patients with HIV co-infection.

BACKGROUND & OBJECTIVE: The risk of human immunodeficiency virus (HIV) co-infection in patients with visceral leishmaniasis (VL) or kala-azar in endemic areas has posed a major challenge in control programmes. We undertook this study to identify the high risk groups vulnerable to Leishmania-HIV co-infection in VL endemic State of Bihar, India. Further, immunological responses were also evaluated in these patients before and after treatment for VL to see the immune impairment associated with CD4 T cell count. METHODS: A total of 1511 subjects attending Voluntary Counselling and Testing Centre (VCTC) at Patna, Bihar were included in this study. VL was confirmed by splenic or bone marrow aspirates testing for parasite. HIV states was confirmed by two kits. Immunological parameters (CD4, CD8, IFN-gamma, IL-4) were studied in co-infection patients. RESULTS: Of the 280 (18.53%) HIV-positive individuals, eight were diagnosed serologically and pathologically as VL patients co-infected with HIV. The humoral and cellular immune responses were evaluated in 18 Indian VL patients with (n = 8) or without HIV (n = 10) and 10 HIV seropositive subjects. Among the eight confirmed cases of VL, false negative direct agglutination test (DAT) result was observed in two who had HIV co-infection (sensitivity 80%), while none in 10 other VL cases who were HIV negative (sensitivity 100%). A very low CD4 cell count was observed in VL cases that had HIV co-infection compared to HIV negative VL or controls. All VL cases with or without HIV infection had lower Th1/Th2 ratio compared to controls. VL patients with or without HIV infection responded well to anti-leishmanial/anti-retroviral therapy with considerable degree of immunological reconstitution. INTERPRETATION & CONCLUSION: A different immune response was noticed in patients with co-infection of HIV and Leishmania. Anti-leishmanial drug treatment led to improvement in immunological response in co-infected patients. Further studies need to be done to see the effect of combined therapy for VL and HIV on immunological parameters in these patients.

Dose-dependent therapeutic antiinfectives from ethnomedicines of bay islands.

BACKGROUND: The methanol extract of Ophirrhiza nicobarica, Alstonia macrophylla and Mallotus peltatus, ethnomedicines of Little Andaman, were investigated for antiinfective, antiinflammatory and antioxidant activities. METHODS: Toxicity was determined in cells and in an animal model. Antiviral, antibacterial and antifungal activity was determined by plaque reduction, disc diffusion and agar dilution methods. The antiinflammatory and antioxidant activities were also studied. RESULTS: O. nicobarica at 300 microg ml(-1) showed anti-HSV activity while M. peltatus and A. macrophylla showed antibacterial activity at 64-1,000 microg ml(-1). Both extracts showed significant dose-dependent antiinflammatory and antioxidant activity at nontoxic concentrations. CONCLUSION: The alkaloid, flavonoid and beta-sitosterol isolated from bioactive parts had a dose-dependent therapeutic efficacy, justifying their use. Further study is required to know the mechanism of action.

Effect of fish oil on offensive and defensive factors in gastric ulceration in rats.

The effect of fish oil (FO) derived from Scomberoides commersonianus containing omega-3 polyunsaturated fatty acids was studied on gastric ulcers and as well as on offensive and defensive factors in gastric mucosal damage, following experimental gastric ulceration. FO significantly reduced the severity of ulceration in gastric ulcers induced by aspirin, cold-restraint stress (CRS), alcohol, and pylorus ligation. The results also indicated the potentiality of FO in maintaining the integrity of gastric mucosa by virtue of its effect on both offensive and defensive gastric mucosal factors. It decreased the offensive acid-pepsin secretion and augmented the defensive factors like mucin secretion, cellular mucus and life span of mucosal cells following pylorus ligation. FO significantly increased activity of anti-oxidant enzymes (catalase and glutathione peroxidase) and decreased lipid peroxidation in gastric mucosa of CRS rats. The study indicates the beneficial role of FO in gastric ulceration by inhibition of offensive mucosal factors and oxidative stress, and augmentation of defensive mucosal factors.

An epidemiological study on risk factors of diabetes mellitus among patients attending a medical college hospital in Kolkata, West Bengal.

Two hundred and thirty cases of diabetes mellitus were selected in a case-control fashion by applying systemic random sampling technique taking 20% of the patients attending the diabetic clinic of Calcutta National Medical College during the period from January to June, 2003 to find out association and risks of some socio-economic and demographic factors with the occurrence of diabetes mellitus. Controls were selected from the patients admitted in the department of surgery in the same period. Factors like physical activity, socio-economic status, residential status, family history and obesity have shown statistically significant association with diabetes. For physical activity the estimated relative risk is maximum in case of sedentary worker where the odd's ratio was 9.4. So far other factors are concerned the estimated relative risk of diabetes was 5.1 in case of urban population, 6.2 in case of positive family history, 2.5 in case of upper and upper middle classes, and 2.4 in case of obesity in comparison to their respective reference category.

Oxidants and ocular tumors.

Serum superoxide dismutase and catalase assays were performed using spectrophotometry in 60 adults and children with benign or malignant tumors and in controls. There was a statistically significant difference in the antioxidative status of children with intraocular tumors (primary retinoblastoma) compared with children without tumors. The difference was not significant in adults. These enzymes may be of value in the early diagnosis of malignant intraocular tumor, especially retinoblastoma.

Polymorphism of HIV-1 gag (p17) gene from female sex workers in Calcutta, India.

HIV-1 subtype C is the major subtype in India as evidenced from the analysis of specific regions within envelope and gag gene. The matrix protein (p17) of HIV-1 which is involved in several functions like the viral RNA transport, nuclear localization, assembly of pre-integration complex into host nucleus has been used to study the strain diversity among female sexworkers in Calcutta. The gene encoding for the HIV-1 matrix protein, p17 was amplified by nested polymerase chain reaction (PCR) from blood samples of HIV-1 seropositive female sex workers (FSW) in Calcutta, India. Genes of twenty-two samples were sequenced and the phylogenetic analysis with different global strains showed that the majority (seventeen) was clustered with Indian type C. A few samples were found to be close to other C subtypes isolated from South Africa, China and Myanmar. The comparison of Calcutta samples with the samples from other regions of India along with other non-asian subtype C sequences clearly revealed a different cluster of Indian sequences. The two samples, cal 242 and cal 709 was found to be the most divergent type and showed close relatedness with African C subtypes.

Multiplex PCR assay for rapid detection and genotyping of Helicobacter pylori directly from biopsy specimens.

We developed and evaluated a simple, novel multiplex PCR assay for rapid detection of Helicobacter pylori infection and for the determination of vacA and cagA genotypes directly from gastric biopsy specimens. This assay did not require culturing of strains or extraction of DNA from biopsy samples. This multiplex PCR assay would be of particularly great value for laboratories in developing countries.

Evaluation of cholinesterase level in an endemic population exposed to malathion suspension formulation as a vector control measure

The manuscript describes a study on the blood cholinesterase (ChE) level in an exposed population at different interval of time after spraying with malathion suspension (SRES) use for kala-azar vector control in an endemic area of Bihar, India. The toxicity of a 5 percent malathion formulation in the form of a slow release emulsified suspension (SRES) was assessed by measuring serum ChE levels in spraymen and in the exposed population.The study showed a significant decrease in ChE levels in the spraymen (p < 0.01) after one week of spraying and in exposed population one week and one month after of spraying (p < 0.01), but was still within the normal range of ChE concentration, one year after spraying, the ChE concentration in the exposed population was the same as prior to spraying (p > 0.01). On no occasion was the decrease in ChE level alarming. A parallel examination of the clinical status also showed the absence of any over toxicity or any behavioural changes in the exposed population. Hence, it may be concluded that 5 percent malathion slow release formulation, SRES, is a safe insecticide for use as a vector control measure in endemic areas of kala-azar in Bihar, India so long as good personal protection for spraymen is provided to minimize absorption and it can substitute the presently used traditional DDT spray.

HIV type 1 subtypes circulating in eastern and northeastern regions of India.

Genetic subtyping has been a powerful tool in tracking the global spread of HIV. To determine the HIV-1 subtypes circulating in eastern and northeastern regions of India blood samples were collected from female sex workers in Calcutta and intravenous drug users (IDUs) in Manipur. Fifty-four samples from Calcutta and 25 samples from Manipur were analyzed for HIV-1 subtyping by heteroduplex mobility assay (HMA). Twenty-six samples from these regions were sequenced. HMA and sequencing of the samples from these regions revealed subtype C as the major subtype, circulating within both eastern and northeastern regions. In Manipur, subtype ThaiB was also detected as the second major subtype. Some of the IDUs from Manipur were found to be dual infected with subtype C and ThaiB.

Antimicrobial and anti-inflammatory activity of folklore: Mallotus peltatus leaf extract.

Since ages Mallotus peltatus (Geist) Muell. Arg. var acuminatus (Euphorbiaceae) leaf and stem bark is used in folk medicine to cure intestinal ailments and skin infections. In several intestinal ailments, localized inflammation is of common occurrence and hence we have evaluated the antimicrobial as well as anti-inflammatory activity of M. peltatus leaf extract. The crude methanol extract of M. peltatus leaves was found to be active against Staphylococcus aureus, Staphylococcus saprophyticus, Streptococcus faecalis, Bacillus subtilis, Escherichia coli and Proteus mirabilis and the dermatophytic fungi Microsporum gypseum. The minimum inhibitory concentration (MIC) ranges from 128 to 2000 microg ml(-1) for bacteria and 128 mg ml(-1) for fungi, while the minimum bactericidal concentration (MBC) was 2-4-fold higher than MIC. The methanol-water fraction of the extract showed similar activity against Staphylococcus, Streptococcus, Bacillus and Proteus isolates. The anti-inflammatory activity of the extract against carrageenan (acute model) and dextran-induced (subacute model) rat paw oedema and cotton pellet-induced granuloma (chronic model) in rats were studied using indomethacin (10 mg kg(-1)), a nonsteroid anti-inflammatory drug, as standard. The methanol extract at 200 and 400 mg kg(-1), and the n-butanol fractions A and B at 25 mg kg(-1), exhibited significant anti-inflammatory activity in Albino rats, compared with indomethacin. Phytochemical study revealed the presence of tannins, saponins, terpenoids, steroids and reducing sugars in the crude extract while the n-butanol fractions showed the presence of ursolic acid, beta-sitosterol and some fatty acids as major compounds. Further study with fractions showed that the antibacterial and anti-inflammatory activity is due to either fraction A (ursolic acid) alone or the combination of fractions A and B (beta-sitosterol and fatty acids) of the extract.