Antimicrobial efficacy of nanoparticle calcium hydroxide and silver nanoparticles on : An study.

Background: In root canal disinfection, intracanal medicaments play a vital role. Typical intracanal medicament, calcium hydroxide (CH), has the lowest efficacy against the biofilm of Enterococcus faecalis. Nanoparticles and their combinations may increase antimicrobial activity, making them better than conventional CH.

Homologous recombination deficiency and molecular subtype are associated with immunogenicity in ovarian cancer.

There is an unmet need for predictive biomarkers for immune checkpoint blockade in ovarian cancer. Homologous recombination deficiency (HRD) and immunoreactive molecular subtype may be associated with determinants of immunogenicity. Neoantigen load, tumor inflammation signature (TIS), immune cell infiltrates and individual immune checkpoints were assessed based on HRD status and molecular subtype.

Integrated, Integral, and Exploratory Biomarkers in the Development of Poly(ADP-Ribose) Polymerase Inhibitors.

In this article, we highlight biomarkers for poly(ADP-ribose) polymerase inhibitor (PARPi) sensitivity and resistance and discuss their implications for the clinic. We review the predictive role of a range of DNA repair genes, genomic scars, mutational signatures, and functional assays available or in development. The biomarkers used for patient selection in the specific Food and Drug Administration-approved indications for breast, ovarian, prostate, and pancreatic cancer vary across tumor type and likely depend on disease-specific DNA repair deficiencies but also the specifics of the individual clinical trials that were conducted.

Replication-dependent size reduction precedes differentiation in Chlamydia trachomatis.

Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infection. It produces an unusual intracellular infection in which a vegetative form, called the reticulate body (RB), replicates and then converts into an elementary body (EB), which is the infectious form. Here we use quantitative three-dimensional electron microscopy (3D EM) to show that C.

Nutcracker syndrome in a young female with solitary functional left ovary: a surgical challenge.

Nutcracker syndrome (NCS), a rare clinical entity, when refractory to medical management warrants surgical intervention. In the following discussion, we present a case of NCS which was managed successfully by left renal vein transposition using a decompression shunt.

Directed osteogenic differentiation of human mesenchymal stem/precursor cells on silicate substituted calcium phosphate.

Insufficient, underactive, or inappropriate osteoblast function results in serious clinical conditions such as osteoporosis, osteogenesis imperfecta and fracture nonunion and therefore the control of osteogenesis is a medical priority. In vitro mesenchymal stem cells (MSCs) can be directed to form osteoblasts through the addition of soluble factors such as β-glycerophosphate, ascorbic acid, and dexamethasone; however this is unlikely to be practical in the clinical setting. An alternative approach would be to use a scaffold or matrix engineered to provide cues for differentiation without the need for soluble factors.

Increasing strut porosity in silicate-substituted calcium-phosphate bone graft substitutes enhances osteogenesis.

Synthetic, porous silicate-substituted calcium phosphate bone graft matrices (SiCaP; 0.8 wt % Si) with varying strut porosity were applied to ovine critical-sized defect sites as either 1-2 mm microgranules (SiCaP-23G, SiCaP-32G, and SiCaP-46G) or 1-2 mm microgranules in an aqueous poloxamer carrier (SiCaP-23P, SiCaP-32P, and SiCaP-46P). Defect sites treated with SiCaP-23G or SiCaP-23P showed evidence of bone formation at 8 and 12 weeks in central zones.

Studies of benzothiophene template as potent factor IXa (FIXa) inhibitors in thrombosis.

FIXa is a serine protease enzyme involved in the intrinsic pathway of the coagulation cascade. The upstream intervention of the coagulation cascade in selectively inhibiting FIXa would leave hemostasis intact via the extrinsic pathway, leading to an optimum combination of efficacy and safety with low incidence of bleeding. We have identified 2-amindinobenzothiophene template as a lead scaffold for FIXa inhibiton based on its homology with urokinase plasminogen activator (uPA).

Structure based drug design: development of potent and selective factor IXa (FIXa) inhibitors.

On the basis of our understanding on the binding interactions of the benzothiophene template within the FIXa active site by X-ray crystallography and molecular modeling studies, we developed our SAR strategy by targeting the 4-position of the template to access the S1 beta and S2-S4 sites. A number of highly selective and potent factor Xa (FXa) and FIXa inhibitors were identified by simple switch of functional groups with conformational changes toward the S2-S4 sites.

Pharmacodynamic and efficacy profile of TGN 255, a novel direct thrombin inhibitor, in canine cardiopulmonary bypass and simulated mitral valve repair.

Heparin-induced thrombocytopenia can be a life-threatening sequel to conventional use of unfractionated heparin in cardiopulmonary bypass (CPB). This study evaluated the pharmacokinetic/pharmacodynamic (PK/PD) and efficacy profile of a novel direct thrombin inhibitor, TGN 255, during cardiac surgery in dogs. Point-of-care coagulation monitoring was also compared against the plasma concentrations of TRI 50c, the active metabolite of TGN 255.

SEROLOGICAL DIAGNOSIS OF TOXOPLASMA GONDII INFECTION IN VARIOUS PATIENT POPULATION IN THE ARMED FORCES.

The study included 200 healthy age and sex matched controls (120 healthy volunteers and 80 healthy antenatal cases without any bad obstetric history) and 300 cases comprising patients with bad obstetric history (BOH) 80 cases, seizure or encephalitis 50 cases, cervical lymphadenopathy 30 cases, congenital deformity 30 cases, HIV infected 80 cases and patients on long term immunosuppression 30 cases. Anti-toxoplasma IgG & IgM were measured by ELISA and individuals found positive for anti Toxoplasma gondii IgM or with high titre of IgG were subjected to repeat testing after 3 weeks for rise in titre. True sero-prevalence of T gondii infection was found to be 19% and it increased with increasing age in the population.

Lipopolysaccharide and silica-stimulated mononuclear cell prostaglandin production in ulcerative colitis.

Basal, lipopolysaccharide (LPS) and silica-stimulated prostaglandin (PG) production were compared between peripheral blood mononuclear cells (PBMNC) from UC patients and healthy subjects (HS). Basal and LPS-stimulated PBMNC PGI2, but not PGE2, production was greater in UC. LPS stimulated both PGE2 and PGI2 by PBMNC from HS and UC patients.

An investigation into the effect and mechanisms of action of nicotine in inflammatory bowel disease.

Objective And Design: To determine the effect of nicotine on colonic inflammation in the trinitrobenzenesulphonic acid (TNBS) model of inflammatory bowel disease in comparison with sulphasalazine.

Materials: Male Wistar rats were used for the in-vivo and ex-vivo studies. In-vitro studies were performed using human leukemia peripheral blood monocyte cells (THP-1 cells) grown in continuous culture.

Colony stimulating factors regulate nitric oxide and prostaglandin E2 production in rat cartilage chondrocytes.

Colony stimulating factors (CSFs) are now widely used in cancer treatment and immunological disease therapy. Both granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF) are used to increase neutrophil counts in Felty syndrome. In the present study, the effects of macrophage CSF (M-CSF), G-CSF, GM-CSF and interleukin-3 (IL-3) (10 ng/ml) on the production of nitric oxide and prostaglandin E2 (PGE2) by cartilage explants were examined over 24 and 48 h.

The effect of an inhibitor of matrix metalloproteinases on colonic inflammation in a trinitrobenzenesulphonic acid rat model of inflammatory bowel disease.

Background: Recent publications have reported that matrix metalloproteinases (MMPs) are expressed in colonic tissue taken from ulcerative colitis and Crohn's disease patients.

Aim: To evaluate the effects of a matrix metalloproteinase inhibitor, marimastat, on colonic inflammation in experimental colitis induced by trinitrobenzenesulphonic acid (TNBS)-ethanol in the rat.

Methods: Rats were dosed (by mouth) for 7 days (b.

Examination of the metabolic status of rat air pouch inflammatory exudate by high field proton NMR spectroscopy.

High field proton (1H) NMR spectroscopy was employed to investigate the metabolic status of rat air pouch inflammatory exudates obtained subsequent to the induction of inflammation with carrageenan, and the 1H NMR profiles of these fluids were compared and contrasted with those of inflammatory human synovial fluid, rat plasma and human serum. The characteristic biochemical features obtained from 1H NMR analysis of these exudates consisted of (1) substantially elevated levels of lactate (11.40+/-1.

Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis.

Background: Reactive oxygen species may mediate tissue injury in inflammatory bowel disease. Aminosalicylates have antioxidant activity and the antioxidants, superoxide dismutase and allopurinol, are of reported benefit in inflammatory bowel disease.

Aim: To develop a convenient technique for testing the antioxidant potential of standard and novel therapeutic agents for use in inflammatory bowel disease.

Generation of lipid peroxidation products in culinary oils and fats during episodes of thermal stressing: a high field 1H NMR study.

The oxidative deterioration of glycerol-bound polyunsaturated fatty acids (PUFAs) in culinary oils and fats during episodes of heating associated with normal usage (30-90 min at 180 degrees C) has been monitored by high field 1H NMR spectroscopy. Thermal stressing of PUFA-rich culinary oils generated high levels of n-alkanals, trans-2-alkenals, alka-2,4-dienals and 4-hydroxy-trans-2-alkenals via decomposition of their conjugated hydroperoxydiene precursors, whereas only low concentrations of selected aldehydes were produced in oils with a low PUFA content, lard and dripping when subjected to the above heating episodes. Samples of repeatedly used, PUFA-rich culinary oils obtained from restaurants also contained high levels of each class of aldehyde.

The role of the contractile fibroblast in the capsules around tissue expanders and implants.

The occurrence, structure and contractility of myofibroblasts in the capsules around tissue expanders and static implants has been studied in the rat, pig and humans. The capsules showed a characteristic layered structure with myofibroblasts being the predominant cell type. Capsular strips contract in vitro in a manner characteristic of fibroblast contraction.

High resolution proton NMR investigations of rat blood plasma. Assignment of resonances for the molecularly mobile carbohydrate side-chains of 'acute-phase' glycoproteins.

An intense broad resonance at 2.14 ppm present in high field (400, 500 and 600 MHz) Hahn spin-echo 1H-NMR spectra of rat blood plasma, but absent from those of human blood plasma is attributable to the presence of terminal O-acetylsialate sugars in the molecularly mobile carbohydrate side-chains of 'acute-phase' glycoproteins (predominantly alpha 1-acid glycoprotein). The presence of such alternative acetylsugars in the carbohydrate side-chains of rat plasma glycoproteins are of much physiological and experimental significance in view of the regular use of these animals in model systems of human inflammatory conditions.

Assessment of a human recombinant manganese superoxide dismutase in models of inflammation.

We evaluated a novel human recombinant preparation of manganese superoxide dismutase (MnSOD) for anti-inflammatory and anti-oxidant activity compared with a copper zinc (CuZn) SOD preparation. The results showed that administration of MnSOD (50, 100 and 200 micrograms kg-1) in the Freund's Complete Adjuvant (FCA) mediated paw oedema model suppressed the inflammation at 4 hours by 43, 25 and 43% (P < 0.001, P < 0.

Effect of endothelin-1 on croton oil-induced granulation tissue in the rat. A pharmacologic and immunohistochemical study.

Background: To date no attempts have been made to determine the role of the endothelial cell derived product, endothelin-1 (ET-1) in granulation tissue development. This study investigates the cellular immunolocalization of ET-1 and its pharmacologic effect on myofibroblast-mediated rat croton oil-induced granulation tissue contraction.

Experimental Design: The distribution, cellular localization and temporal production of ET-1 in the tissues was determined by immunohistochemistry at days 7, 14, 21, and 28.

New areas for therapeutic intervention in the treatment of rheumatic disease.

Anti-rheumatic therapy has been targeted against the symptoms arising from chronic inflammation of the joint. This has resulted in the extensive use of non-steroidal anti-inflammatory drugs. It is now becoming apparent that these agents have no beneficial effect on disease progression.