Susceptibility pattern and molecular type of species-specific Candida in oropharyngeal lesions of Indian human immunodeficiency virus-positive patients

A study of oropharyngeal candidiasis (OPC) in Indian human immunodeficiency virus (HIV)/AIDS patients was conducted over a period of 15 months. This study revealed that 75% of the HIV/AIDS patients had OPC. MIC testing revealed that 5% of the Candida isolates were fluconazole resistant. A correlation between CD4(+)-T-cell counts and development of OPC in HIV/AIDS patients was also observed. Molecular typing of C. albicans isolates showed that all were genetically unrelated.     

Inhibition of motility of hamster spermatozoa by protein tyrosine kinase inhibitors

Genistein, tyrphostin and piceatannol, which are specific inhibitors of protein tyrosine kinase, were screened for their effects on the motility of intact and demembranated hamster spermatozoa. Of the three inhibitors only piceatannol inhibited the motility of intact spermatozoa. None of the inhibitors had any inhibitory effect on the reactivation of motility of demembranated hamster spermatozoa. Taken together these results indicated that a protein tyrosine kinase associated with the membrane of hamster spermatozoa was probably involved in sustenance of hamster sperm motility. Therefore in the present study a membrane-associated protein tyrosine kinase was purified from a detergent-soluble extract of plasma membranes of mature hamster spermatozoa. The purification involved cation exchange chromatography on fast protein liquid chromatography (FPLC) followed by affinity chromatography either on an antiphosphotyrosine antibody agarose or poly glu-tyr agarose column. The pure protein tyrosine kinase had an apparent molecular mass of 45 kDa. The enzyme was not inhibited by genistein or herbimycin but was inhibited by piceatannol. This is the first report on the purification of a sperm plasma membrane-associated protein tyrosine kinase, an enzyme which has also been implicated in hamster sperm motility.     

The relevance of donor T cell-directed immunoglobulin G in historic sera in the age of flow cytometry

BACKGROUND: Renal transplant recipients with a positive historic cross-match due to donor T cell-directed IgG antibodies are considered to have decreased graft survival, even if their current serum is negative prior to transplantation. With the use of flow cytometric cross-match for testing current sera, false-negative results could be eliminated and the outcome of transplantation in this group of patients could be improved, assuming that immunological memory is effectively controlled with immunosuppression. METHODS: We reviewed our records to identify those patients who underwent cadaveric renal transplant, with a historic IgG positive cytotoxic T cell cross-match and a current negative flow cytometric T cell cross-match. RESULTS: Eighteen patients underwent cadaveric renal transplant in the face of a historic IgG positive T cell cross-match and a current negative flow cytometric T cell cross-match. In 14 patients treated with cyclosporine-based immunosuppression the 1-, 2-, and 3-year cumulative graft survival rates were 57, 50, and 43%, respectively. Ten of the 14 patients (71%) ultimately lost their grafts. CONCLUSIONS: Even with negative flow cytometric cross-match in current serum, a positive historic conventional cross-match suggests a high risk of graft failure.     

Molecular dynamic simulations of Co(III) and Ru(II) polypyridyl complexes and docking studies with dsDNA

The binding studies of Co(III) and Ru(II) polypyridyl complexes with dsDNA were carried out by molecular modeling studies to identify the binding interactions. The 3D structures of the metal complexes [Ru(phen)₂ippip]²⁺ (RP-ippip), [Co(phen)₂ippip]³⁺ (CP-ippip), [Ru(bpy)₂ippip]²⁺ (RB-ippip), and [Co(bpy)₂ippip]³⁺ (CB-ippip), where ippip = 4-(isopropylbenzaldehyde)imidazo[4,5-f][1,10] phenanthroline, phen = 1,10-phenanthroline, and bpy = bypyridine, were simulated using molecular dynamic simulations for stable conformers. The energy-minimized 3D structures of metal complexes were docked to the double-stranded dodecamer 5′-D(*AP * CP * CP * GP * AP * CP * GP * TP * CP * GP * GP * T)-3′. The aromatic ligand, ippip, facilitates the binding of the metal complex with DNA through intercalation. The effect of ancillary ligands, phen and bpy, was investigated. The ancillary ligands were found to be involved in bond formation with the phosphate backbone of nucleotide base pairs in metal complex–DNA docked complex. The significant interactions of metal complexes in the major groove of DNA are the prerequisite features of the metal complexes to be considered as DNA-intercalator. The molecular docking data are well substantiated by the available experimental data. The modeling results should extend knowledge about the nature of binding of these complexes with DNA.     

Familial hypercholesterolaemia: what’s new?

Autosomal Dominant Familial Hypercholesterolaemia (FH) is the commonest inherited disorder of lipoprotein metabolism. Untreated monogenic FH caused by mutations in the LDLR, APOB or PCSK9 genes result in early onset cardiovascular death (below the age of 60 years). In the UK the prevalence of heterozygous FH is 1 in 270 and homozygous FH is 160,000 approximately.The introduction of statins nearly three decades ago has altered the natural history of FH, with a significant reduction of cardiovascular related morbidity and mortality. There is increasing evidence that early childhood interventions such as lifestyle choices, healthy eating and commencing statins by the age of 10 years would potentially prevent early onset cardiovascular disease and mortality in monogenic FH. The medium term safety of statins in children has been demonstrated. The UK paediatric FH register data has shown that children with FH are less obese than the normal population and the register aims to monitor the longer-term safety of statins in children with FH. Child-parent screening would potentially benefit the child and enables identifying a parent with FH, before the onset of a life threatening cardiovascular event. In addition, genetic cascade testing of relatives of an affected individual has been shown to be highly cost effective.We review the current literature with brief updates on genetics, the UK paediatric FH register data, published recommendations for the management of homozygous and heterozygous FH, lipid lowering therapies in children and screening for FH in childhood.     

Prognostic factors for recurrence of gastrointestinal bleeding due to Dieulafoy's lesion

AIM: To analyze the effectiveness of the endoscopic therapy and to identify prognostic factors for recurrent bleeding.METHODS: Retrospective study of patients with gastrointestinal bleeding secondary to Dieulafoy’s lesion (DL) from 2005 to 2011. We analyzed the demographic characteristics of the patients, risk factors for gastrointestinal bleeding, endoscopic findings, characteristics of the endoscopic treatment, and the recurrence of bleeding. We included cases in which endoscopy described a lesion compatible with Dieulafoy. We excluded patients who had potentially bleeding lesions such as angiodysplasia in other areas or had undergone other gastrointestinal endoscopic procedures.RESULTS: Twenty-nine patients with DL were identified. Most of them were men with an average age of 71.5 years. Fifty-five percent of the patients received antiaggregatory or anticoagulant therapy. The most common location for DL was the stomach (51.7%). The main type of bleeding was oozing in 65.5% of cases. In 27.6% of cases, there was arterial (spurting) bleeding, and 6.9% of the patients presented with an adherent clot. A single endoscopic treatment was applied to nine patients (31%); eight of them with adrenaline and one with argon, while 69% of the patients received combined treatment. Six patients (20.7%) presented with recurrent bleeding at a median of 4 d after endoscopy (interquartile range = 97.75). Within these six patients, the new endoscopic treatment obtained a therapeutic success of 100%. The presence of arterial bleeding at endoscopy was associated with a higher recurrence rate for bleeding (50% vs 33.3% for other type of bleeding) [P = 0.024, odds ratio (OR) = 8.5, 95% CI = 1.13-63.87]. The use of combined endoscopic treatment prevented the recurrence of bleeding (10% vs 44.4% of single treatment) (P = 0.034, OR = 0.14, 95% CI = 0.19-0.99).CONCLUSION: Endoscopic treatment of DL is safe and effective. Adrenaline monotherapy and arterial (spurting) bleeding are associated with a high rate of bleeding recurrence.