Comparative evaluation of bioglass with calcium sulphate β-hemihydrate for the treatment of intraosseous defects—a clinico-radiological study

Background

The aim of the present clinical and radiological study was to compare bioglass and calcium sulphate β-hemihydrate in the treatment of intraosseous defect in chronic periodontitis.

Method

A total of 50 subjects with bilaterally symmetrical periodontal osseous defects with probing pocket depth = 5 mm and intraosseous defects ≥ 3 mm as seen on the radiographs were undertaken for the study. In one site (group A) bioactive glass was placed in defect and in contralateral site (group B) calcium sulphate β-hemihydrate was used in the defect site.

Results

Clinical improvement was noted in all patients at the end of study. Both the groups showed reduction in probing pocket depth, increase in clinical attachment level, and reduction in osseous defect. Both materials were effective in achieving osseous gain.

Conclusion

The osseous gain in group A subjects was 58.93%, whereas in group B subjects it was 48.56%. Calcium sulphate β-hemihydrates showed promising results and were cost effective.     

Interaction studies of E. coli uracil phosphoribosyltransferase with 5-fluorouracil for potent anti cancer activity

Uracil phosphoribosyltransferase (UPRT) enzyme has immense potential in prodrug-mediated cancer therapy. Molecular docking and enzyme inhibition studies are important for understanding drug–protein interaction in modern drug design. Herein, we experimentally determined the enzyme inhibition constant (K _i) of 5-fluorouracil (5FU)—a competitive inhibitor of uracil, on UPRT purified from Escherichia coli. In silico experiments were performed on X-ray crystallography structure of UPRT to establish ligand protein interactions, where uracil and its selective inhibitor 5FU were docked computationally to the active site of UPRT enzyme. DOCK 5.2 was employed to dock the ligands to 1,250 molecular dynamics (MDs) snapshots of UPRT. The results highlighted the key residues of UPRT involved in the binding with the ligands. The findings are important for rational design of mutant E. coli UPRT with high selectivity towards the prodrug for suicide gene therapy.     

Chromone linked nitrone derivative induces the expression of iNOS2 and Th1 cytokines but reduces the Th2 response in experimental visceral leishmaniasis

In our previous work we have shown that the novel synthetic chromone derivative could effectively inhibit the Leishmania donovani replication in vitro and in vivo with less cytotoxicity on murine splenocytes. The aim of the present study is to explore the possible mechanism of anti-leishmanial effect of C-(6-methyl-4-oxo-4H-1-benzopyran-3-yl)-N-(p-tolyl) nitrone (designated as NP1) in vitro and in vivo in experimental visceral leishmaniasis caused by L. donovani. The cytotoxic effect of this derivative was studied in murine peritoneal macrophages by MTT method. NP1 at a dose of 17.06 μM showed 50% inhibition on L. donovani promastigotes but found less cytotoxic to the RAW 264.7 cells. Even the higher concentration of IC50 (up to four fold) did not exert much cytotoxic effect on RAW 264.7. Interestingly, NP1 at lower concentration (8.53 μM) could inhibit 50% of intracellular amastigotes in murine peritoneal macrophages. L. donovani is known to exert its pathogenic effects mainly by the suppression of NO generation and subversion of the cellular inflammatory responses in the macrophages. NP1 was found to induce a potent host-protective immune response by enhancing NO generation and iNOS2 expression at mRNA level and by up-regulating proinflammatory cytokines such as IL-12 and IFN-γ and limiting the expression of IL-10 in vivo. The NO dependent killing was further confirmed in iNOS^?/? mice compared to wild type. In agreement with the fact, induced synthesis of IL-12 and IFN-γ and associated down-regulation of IL-10 by the treatment of NP1 clearly indicated the possibility of novel strategy of drug development against Leishmania infection.     

Peripheral blood stem cells used to augment autologous bone marrow transplantation

Peripheral blood stem cells (PBSC) were used to augment autologous bone marrow transplantation (ABMT), aiming to hasten engraftment after high dose treatment in a group of heavily pretreated patients. PBSC were obtained by leukapheresis during the rebound after standard chemotherapy. In 11 patients aged 7-17 years, high dose chemotherapy consisted of busulphan 16 mg/kg orally with melphalan 160 mg/m2 intravenously for seven patients, and melphalan 200 mg/m2 intravenously alone for four. The median number of granulocyte-macrophage colony forming units in the reinfused PBSC was 3.42 x 10(4)/kg (3.03-18.01) and bone marrow 12.4 x 10(4)/kg (4.16-28.6). Neutrophil recovery to > or = 0.5 x 10(9)/l and platelet transfusion independence occurred at a median of 14 days (11-18) and 22 days (9-84) respectively. In five patients the early engraftment was transient with neutrophils again dropping below 0.5 x 10(9)/l then slowly recovering. There was one toxic death due to sepsis. PBSC harvesting in these children was undertaken without interrupting routine chemotherapy and without the use of bone marrow growth factors. In some patients PBSC failed to influence engraftment and the use of combined chemotherapy and growth factor priming for PBSC collection may give improved results.     

Efficacy of immune sera from human immunoglobulin transgenic mice immunized with a peptide mimotope of Cryptococcus neoformans glucuronoxylomannan

The efficacy of antibody mediated immunity against Cryptococcus neoformans has not been established experimentally for human antibodies. Our group has previously shown that immunization with a conjugate consisting of a peptide mimotope of the C. neoformans capsular polysaccharide glucuronoxylomannan (GXM), P13, and diphtheria toxoid (P13-DT) prolonged survival of transgenic mice with human immunoglobulin loci, XenoMouse mice, which were challenged with a lethal dose of C. neoformans. In the study reported herein, we determined the efficacy of human antibodies in the sera of immunized XenoMouse mice against C. neoformans in passive transfer experiments in na?ve BALB/c mice. Survival studies were performed with sera from XenoMouse mice expressing human IgG2/kappa (G2/k mice) or IgG4/kappa (G4/k mice) that had been immunized with P13-tetanus toxoid (TT)/Alhydrogel with or without CpG, and G2/k mice that had been immunized with P13-DT/Alhydrogel/CpG or Alhydrogel/CpG, obtained on day 7 (early sera) and days 30 or 35-59 (late sera) after primary immunization. Compared to mice receiving sera from G2/k-PBS-treated mice, the survival of na?ve mice was prolonged by both early and late sera from G2/k-P13-DT/Alhydrogel/CpG-immunized mice, but only late sera from G2/k-P13-TT/Alhydrogel/CpG-immunized mice. Late, but not early sera from G2/k-Alhydrogel/CpG-immunized mice also prolonged survival. For all sera, prolongation of survival was associated with GXM-specific serum IgM. Sera from G2/k mice that received P13-TT without CpG, and all groups of G4/k mice had low to undetectable levels of antibody to GXM and were not protective. Our findings suggest that GXM-specific human IgM may be a functional mediator of protection against C. neoformans.     

Molecular analysis of the cytoadherence phenotype of a Plasmodium falciparum field isolate that binds intercellular adhesion molecule-1

The ability of Plasmodium falciparum-infected erythrocytes to adhere to endothelial receptors and sequester in diverse host organs is an important pathogenic mechanism. Cytoadherence is mediated by variant surface antigens, which are referred to as PfEMP-1 and are encoded by var genes. The extracellular regions of PfEMP-1 contain multiple conserved cysteine-rich domains that are referred to as Duffy-binding-like (DBL) domains. Here, we analyze the adhesive phenotype of an Indian P. falciparum field isolate, JDP8, which binds ICAM-1 but does not bind CD36. This is a unique cytoadherence phenotype because P. falciparum strains that bind ICAM-1 described thus far usually also bind CD36. Moreover, binding to both receptors is thought to be important for static adhesion under flow. The ICAM-1 binding population of P. falciparum JDP8 adheres to endothelial cells under flow despite poor binding to CD36. We have also identified an expressed var gene, JDP8Icvar, which mediates the ICAM-1 binding phenotype of JDP8. Expression of different regions of JDP8Icvar on the surface of COS-7 cells followed by binding assays demonstrates that the ICAM-1 binding domain maps to the DBL2betaC2 domain of JDP8Icvar. Sequence comparison with two previously identified ICAM-1 binding domains of PfEMP-1, which also map to DBLbetaC2 domains, suggests that diverse P. falciparum isolates use a structurally conserved domain to bind ICAM-1. It thus appears that functional constraints may place limits on the extent of sequence diversity in receptor-binding domains of PfEMP-1.     

Effects of Intensive Blood Pressure Treatment on Acute Kidney Injury Events in the Systolic Blood Pressure Intervention Trial (SPRINT)

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Clinical,Biochemical, Tumoural and Mutation Profile of VHL- and MEN2A-Associated Pheochromocytoma: A Comparative Study

World Journal of Surgery - To compare clinical, biochemical, tumoural and mutational characteristics of Von Hippel Lindau Syndrome (VHL)-associated pheochromocytoma (PCC) to multiple endocrine...