Search

Herein, we report series of isatin-based oxo-spiro chromene Schiff's bases, synthesized by condensing 2,7-diamino-2'-oxospiro[chromene-4,3'-indoline]-3-carbonitrile with aromatic aldehydes using efficient acid catalyst, silica sulfuric acid (SSA). Spectroscopic techniques have corroborated the formation of desired products. Derivatives were screened in vitro for antibacterial and anticancer activities. Molecular docking was also performed to predict the possible mode of action of these derivatives. [ABSTRACT FROM AUTHOR]

A series of new Betti bases, 1-{(aryl)[(5-methyl-1,3-thiazol-2-yl)amino]methyl}naphthalen-2-ols, have been synthesized via one-pot three-component reaction of aromatic aldehydes, 5-methyl-1,3-thiazol-2-amine, and naphthalen-2-ol in glycerol in the presence of silica sulfuric acid (SSA) as a catalyst. The synthesized compounds were evaluated for their in vitro antibacterial activity against S. aureus, B. subtilis, E. coli, and P. aeruginosa using ciprofloxacin as a standard drug. Molecular docking analysis ascertained that the anti-microbial potential of these derivatives is determined by inhibition of DNA gyrase. In silico ADMET analysis of the title compounds was also performed. [ABSTRACT FROM AUTHOR]

A series of novel oxo-spiro chromene Schiff's bases were synthesized by condensing 2,7-diamino-2'-oxospiro[chromene-4,3'-indoline]-3-carbonitrile, and series of aromatic aldehydes. Spectrochemical techniques have corroborated the formation of desired products. Derivatives were screened in vitro for antibacterial and anticancer activities. Molecular docking analysis was also performed to predict the possible mode of action of these derivatives. The docking analysis ascertained that these derivatives regulate the antimicrobial potential via inhibition of DNA gyrase and anticancer potential via inhibition of CDK 6. Among all the synthesized compounds, Nitro derivatives have exhibited eminent anticancer and antibacterial activities. [ABSTRACT FROM AUTHOR]

Inhibitors are an impediment to the effective management of haemophilia B ( HB), but there is limited understanding of the underlying genetic risk factors. In this study we aim to understand the role of F9 gene mutations on inhibitor development in patients with HB. Mutations in the F9 gene were identified and HLA typing performed for five boys with severe HB. Data from the CDC Haemophilia B Mutation Project ( CHBMP) database were used to assess association between F9 gene mutation type and inhibitor development. Analysis of the CHBMP database showed that larger disruptions in the F9 gene are associated with a higher life-time prevalence of inhibitors. We detected the following mutations in the five subjects, including four novel mutations: Nonsense in three patients (c.223 C>T; p.Arg75* in two siblings, c.553 C>T; p.Glu185*); Splice site in two patients (c.723 + 1 G>A, c.278-27 A>G); Missense in one patient (c.580 A>G, p.Thr194Ala; c.723 G>T; p.Gln241His). Of the two siblings only one responded to immune tolerance induction ( ITI). These siblings have identical F9 gene mutations but differ with respect to the HLA alleles. Interestingly, an analysis of peptide- MHC binding affinities shows a significantly higher (one-sided unpaired t-test, P = 0.0018) median affinity for FIX-derived peptides in the sibling that responded to ITI. We conclude that the nature of the F9 gene mutation may be an important risk factor for the development of inhibitors. In addition, the HLA alleles of the individual patients, in conjunction with the mutation type, could be a predictor for the development of inhibitors as well as the response to ITI. [ABSTRACT FROM AUTHOR]

Background: Ethyl alcohol exerts both positive and negative effects on the cardiovascular system. Alcoholic cardiomyopathy, produced by direct or indirect mechanisms, is well-documented. An important, but seldom appreciated effect is an increase in iron deposition in the myocardium, which can add to the cardiac dysfunction. The present study was planned to document the pathological features and iron levels in the cardiac tissue of patients who were chronic alcoholics and correlate these characteristics with the liver pathology and iron content. Materials and Methods: An autopsy-based prospective study of 40 consecutive patients compared with ten age matched controls (no history of alcohol intake). Histopathological changes like the morphology of the cardiac myocytes, degree of fibrosis (interstitial, interfiber, perivascular, and replacement), presence of inflammatory cells, increased capillary network, and adipose tissue deposition were noted and graded. These were also correlated with the liver pathology. The iron content in the heart and liver were measured by using calorimetry. Results: All cases had increased epicardial adipose tissue with epicardial and endocardial fibrosis, prominence of interstitial and interfiber fibrosis, myofiber degeneration, and increased capillary network; this was particularly prominent in patients with cirrhosis. Elemental iron level in heart tissue was raised in the cases relative to controls. Conclusions: Alcohol produces subclinical changes in the myocardium, with an increased iron content, which may be the forerunner for subsequent clinical cardiac dysfunction. [ABSTRACT FROM AUTHOR]

The article characterizes the morphology of a ligated loop model of Salmonella enterica serotypeTyphimurium infection in rhesus macaques and verifies the occurrence of Salmonella-induced cell death in healthy and simian immunodeficiency virus (SIV)-infected macaques. Results showed the histopathology scores for hemorrhage, cell death, blunting of villi, epithelial loss, edema and neutrophil infiltration. The study examined the kinetics of tissue invasion and the features of cell death.

Background The development of susceptibility to secondary pathogenic infections in the oral cavity during HIV infection is likely to result from or coincide with deterioration of the local mucosal immune system. Methods We have utilized the SIV model to investigate the kinetics and magnitude of oral pathogenesis during systemic dissemination of intravenously inoculated SIVmac251. Results Viral replication was detected in oropharyngeal lymph nodes at 6 weeks post-infection and shown to be coincident with a broad scale loss of growth factor receptor transcription in the oral mucosa, providing multiple avenues for blocking the normal activity of apoptosis inhibitors that function through Bcl2- and p53-dependent pathways. Conclusions Our findings suggest that the normal balance between cell death and regeneration may be rapidly disrupted in the oral mucosa during the early stages of immunodeficiency virus infection, setting the stage for continuing deterioration of immune function and the development of susceptibility to secondary infections. [ABSTRACT FROM AUTHOR]

AIMS: This study was conducted to evaluate the outcomes of assisted reproductive technology (ART) procedures, viz., intrauterine insemination (IUI), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in males with impaired spermatogenesis. SETTINGS AND DESIGN: The subjects of the study were infertile couples who were undergoing ART treatment due to male factor indications. The project was designed to correlate the outcome of the ART treatment and its efficacy in different study groups. METHODS: Males were grouped as: 1. oligozoospermia (n = 153), 2. asthenoteratozoospermia (n = 158), 3. obstructive azoospermia (n = 110) and 4. nonobstructive azoospermia (n = 58). Patients from groups 1 and 2 were considered for IUI, IVF and ICSI. Those from group 3 were considered for IVF and ICSI and the 4th group underwent only ICSI treatment. RESULTS: Oligozoospermia showed lower pregnancy rates with IUI than with both IVF and ICSI. An average minimum native and postharvest count was obtained to get an acceptable IUI outcome. Asthenoteratozoospermia had the lowest pregnancy rate with IUI as compared to IVF, whereas ICSI showed significantly higher pregnancy rates in this group. Obstructive azoospermia showed significant improvement with ICSI over IVF. In nonobstructive azoospermia, ICSI resulted in a 27.58% pregnancy rate. CONCLUSION: The IUI outcome was impressive though less effective whereas there was no difference between the IVF and ICSI outcomes in oligozoospermia. In asthenoteratozoospermia, ICSI showed a significant advantage over IUI and IVF, with IUI resulting in poor outcome in this group. In obstructive azoospermia, ICSI had a distinct advantage over IVF whereas in nonobstructive azoospermia, ICSI, the only option, was found to be effective and helpful in achieving an acceptable pregnancy rate. [ABSTRACT FROM AUTHOR]

Background In vitro and clinical observations in HIV-infected patients receiving interferon α therapy have shown a reduction in HIV loads. Limited investigations have explored the innate or adaptive immune responses of IFN- α on SIV replication in vivo. Methods Seven chronically infected rhesus macaques were given pegylated IFN- α2a ( n = four) or saline ( n = three) injections once weekly for 14 weeks. Weekly peripheral blood samples were taken for safety parameters, viral load determinations, and measurements of innate and adaptive immune responses. Results Pharmacokinetic measurements demonstrated therapeutic peg-IFN- α levels for the initial period of therapy and IFN- α inducible antiviral molecules were increased sporadically in the PBMC mRNA of the treatment group. Despite the demonstrable effect of the IFN- α injections, the treatment had no effect on plasma viral RNA levels. Conclusions This work demonstrates that while short term IFN- α therapy induces innate antiviral immunity, it does not dramatically enhance or suppress viral replication. However, studies in the SIV model to determine therapeutic potential of chronic IFN- α therapy for the treatment of HIV will require macaque specific cytokines. [ABSTRACT FROM AUTHOR]

Background Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4+ T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4+ memory subsets or lost and fail to regenerate during ART. Methods Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. Results Changes in proliferative CD4+ memory subsets during infection accelerated their depletion. This reduced the central memory CD4+ T-cell pool and contributed to slow CD4+ T-cell restoration during ART. Conclusion There was a lack of restoration of the CD4+ central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection. [ABSTRACT FROM AUTHOR]

Background Although the majority of drug-naïve HIV-infected patients develop acquired immunodeficiency syndrome (AIDS), a small percentage remains asymptomatic without therapeutic intervention. Methods We have utilized the simian immunodeficiency virus (SIV)-infected rhesus macaque model to gain insights into the molecular mechanisms of long-term protection against simian AIDS. Results Chronically SIV-infected macaques with disease progression had high viral loads and CD4+ T-cell depletion in mucosal tissue and peripheral blood. These animals displayed pathologic changes in gut-associated lymphoid tissue (GALT) and mesenteric lymph node that coincided with increased expression of genes associated with interferon induction, inflammation and immune activation. In contrast, the animal with long-term asymptomatic infection suppressed viral replication and maintained CD4+ T cells in both GALT and peripheral blood while decreasing expression of genes involved in inflammation and immune activation. Conclusions Our findings suggest that reduced immune activation and effective repair and regeneration of mucosal tissues correlate with long-term survival in SIV-infected macaques. [ABSTRACT FROM AUTHOR]

Aims: To assess the influence of smoking on the type of age related macular degeneration (AMD) lesion causing visual impairment in a large cohort of patients with AMD at a tertiary referral UK centre. Methods: Prospective, observational, cross sectional study to analyse smoking data on 711 subjects, of western European origin, in relation to the type of AMD lesion present. Colour fundus photographs were graded according to a modified version of the international classification. Multiple logistic regression analysis was performed, adjusting for age and sex using the statistical package SPSS ver 9.0 for Windows. χ² tests were also used to assess pack year and ex-smoker data. Results: 578 subjects were graded with neovascular AMD and 133 with non-neovascular AMD. There was no statistically significant association found between smoking status or increasing number of pack years and type of AMD lesion. The odds of "current smokers" compared to "non-smokers" developing neovascular rather than non-neovascular AMD when adjusted for age and sex was 1.88 (95% CI: 0.91 to 3.89; p=0.09). Conclusions: Smoking is known to be a risk factor for AMD and this study suggests that smokers are at no more risk of developing neovascular than atrophic lesions. [ABSTRACT FROM AUTHOR]

To purify and evaluate the molecular changes associated with an aspartic protease (Cathepsin D) in human semen from infertile subjects. Cathepsin D was purified from normo-, oligo- and azoospermic semen, by a procedure involving detergent solubilisation, affinity chromatography and gel filtration chromatography. The enzyme from normo-, oligo- and azoospermic samples was purified 86, 60 and 44 fold respectively. The purified enzyme appeared as a single band on SDS as well as on native PAGE irrespective of the pathological conditions. The molecular weight of Cathepsin D from oligospermic and normospermic samples was 40 kDa while that of azoospermic sample was found to be 43 kDa. The enzyme was inhibited by pepstatin while other proteinase inhibitors and metal ions did not have any effect. Purified Cathepsin D from azoospermic sample differs from normospermia and oligospermia. [ABSTRACT FROM AUTHOR]

Aims: To determine the molecular basis and describe the phenotype of an atypical retinal dystrophy in a family presenting with bilateral, progressive central visual loss. Methods: Family members were examined. Investigations included Goldman perimetry, electrophysiology, and autofluorescence imaging. Candidate gene screening was performed using SSCP and sequence analysis. The proband's lymphoblastoid cells were examined for protein expression. Results: Fundal examination of the proband, his mother, and brother revealed peripopillary and macular atrophy. Autosomal dominant retinal dystrophy was suspected, but less severe disease in the mother led to screening for mutations in X linked genes. A 4 bp microdeletion in exon 3 of the RP2 gene, segregating with disease, was identified. No RP2 protein expression was detected. Conclusion: The distinct phenotype in this family, caused by this frameshifting mutation in RP2, broadens the phenotypic spectrum of X linked retinitis pigmentosa. The absence of RP2 protein suggests that loss of protein function and not novel gain of function could account for the atypical phenotype. A definitive diagnosis of X linked retinitis pigmentosa permits appropriate genetic counselling with important implications for other family members. Clinicians should have a low threshold for screening RP2 in families with retinal dystrophy, including posterior retinal disease, not immediately suggestive of X linked inheritance. [ABSTRACT FROM AUTHOR]

The article presents a test of schemes for textile finishing agents on the fibre. The flame-proof finishes has negative result in chlorine test however, positive in both nitrogen and phosphorous. The finish has a soft handle and gives a characteristic smell when burnt. In the fluorine testing for water-repellent finishes such as oil-repellent finish and velan-type, the oil remains as a small drop and does not spread which indicates a positive result with negative nitrogen. Moreover, reactant-type resins give a positive nitrogen test and a very weak or negative amino-group test.

The article focuses on the case of a 62-year-old woman who developed a suprachoroidal hemorrhage after addition of clarithromycin to her warfarin medication. It is indicated that the patient, who has chronic atrial fibrillation, lost anticoagulant control due to the interaction between the two drugs. Key information regarding the chemical structure and mechanisms of the drugs are further discussed.

Seven cases of suspected haemorrhage In pre-existing adenoma or cyst in the thyroid showed serum thyroglobulin (tg) levels phenomenonly elevated. The serum tg leveis reduced remarkably within one to three montha. During this period all patients were treated with thyroxin. It is concluded that serial serum thyroglobulin determinations may be useful in confirming the clinical suspicion of haemorrhage in the thyroid. [ABSTRACT FROM AUTHOR]