Effect of rufloxacin on in-vitro proliferation and differentiation of human mononuclear cells.

We investigated the effects of rufloxacin, a new, long acting fluoroquinolone, on the growth and differentiation of human peripheral blood mononuclear cells (MNC) stimulated with T- and B-cell mitogenic agents. Rufloxacin inhibited 3H-thymidine incorporation into MNC stimulated with phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) in a dose-dependent manner. The concentrations of rufloxacin required to inhibit 1/2 maximal proliferation of T- and B-cells were 62 and 33.5 mg/L respectively. Rufloxacin, at clinically achievable serum levels (less than 10 mg/L), was found not to inhibit PHA-induced T-cell differentiation as assessed by IL-2 production, IL-2 receptor expression and the expression of cell differentiation markers (CD4 and CD8). However, higher concentrations of rufloxacin (10 and 50 mg/L) markedly inhibited B-cell differentiation in-vitro as determined by the measurement of immunoglobulin production by MNC stimulated with PWM. The clinical relevance of our in-vitro findings remains to be elucidated.     

Nevirapine derivatives with broad-spectrum chemotherapeutic properties for the effective treatment of HIV/AIDS.

A series of nevirapine derivatives has been synthesized in an effort to enhance the spectrum of chemotherapeutic properties for the effective treatment of AIDS and AIDS-related opportunistic infections. The nevirapine derivative bearing isoniazid moiety (3a) was found to be the most potent compound with EC50 of<0.0636 microM, CC50 of>1000 microM and selectivity index of>15,723 which also exhibited 90% inhibition against Mycobacterium tuberculosis at 6.25 microg/ml. Compound 3c showed 100% inhibition against M. tuberculosis and also exhibited potent antibacterial activity against 24 pathogenic bacteria with MIC less than 1 microg/ml.     

Characterization of autoantibodies against sulfatide from a V-gene phage-display library derived from patients with systemic lupus erythematosus

Sulfatide, ceramide galactosyl-3'-sulfate, is mainly present in nervous tissue, kidney, testis, red blood cells, platelets and granulocyte. Antibodies to sulfatide are present in many patients with demyelinating peripheral neuropathy, HIV infection and systemic lupus erythematosus and may account for some of the clinical manifestations. To evaluate the effect of such antibodies, we have constructed a phage-display antibody fragment library from the lymphocytes of patients with systemic lupus erythematosus. Sulfatide-reactive phage were selected by absorption and elution on sulfatide liposomes and soluble single chain variable fragment (ScFv) were isolated from individual colonies and tested in an ELISA assay for binding to bovine brain sulfatide. Five ScFv clones that bound sulfatide were isolated. Two of the clones, PH5 and PA38, bound sulfatide but not phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin or ceramide. These two clones also bound sulfatide from human red blood cells. The DNA encoding the fragments was sequenced, revealing predicted polypeptides of 19 kDa for PH5 containing only variable heavy (VH) sequences, and 31 kDa for PA38, with both VH and variable light (VL) sequences. Although they had similar antigen specificities, the VH domains of the two clones were derived from different heavy-chain families. The clustered mutational patterns in the complementarity-determining region (CDR) of the heavy chains in both clones suggest that the V-domains are the products of antigen-driven B cell clonal maturation leading to the development of sulfatide-binding specificity. These results show the presence of sulfatide-specific antibodies in lupus patients, and allow us to test the possibility that the interaction of the antibodies with sulfatide may contribute to some of the symptoms. In addition, the antibodies provide useful reagents to test the role of sulfatide in pathophysiological processes.     

Thromboelastography as a perioperative measure of anticoagulation resulting from low molecular weight heparin: a comparison with anti-Xa concentrations

Low molecular weight heparin (LMWH) is commonly used to prevent postoperative thromboembolism. Currently, there is no convenient test to measure the degree of anticoagulation from LMWH. This prospective study examines the relationship of thromboelastography and serum anti-Xa concentration in patients treated with enoxaparin. Twenty-four adult patients scheduled for orthopedic surgery using epidural anesthesia were enrolled. Epidural catheters were removed the morning after surgery before the commencement of subcutaneous enoxaparin 30 mg twice daily. Venous blood samples were obtained at 1) the induction of anesthesia (baseline), 2) immediately before the third dose of enoxaparin postoperatively (Day 2-trough), 3) 4 h after the third dose postoperatively (Day 2-peak), and 4) immediately before the fifth dose postoperatively (Day 3-trough). Whole blood samples were obtained for thromboelastography, activated clotting time, and anti-Xa level analyses at each of the four time intervals. At the four sample intervals, the r time (mean +/- SEM). (20 +/- 1, 25 +/- 2, 51 +/- 6, 31 +/- 3 mm) and the k time (9 +/- 0. 7, 12 +/- 1, 27 +/- 5, 14 +/- 2 mm) of the thromboelastograph were significantly correlated with the expected peak and trough levels of LMWH and serum anti-Xa levels (P: < 0.05). At the Day 3-trough, thromboelastograph r times exceeded the normal range in 6 of 25 patients (25%). Prolongation of r time and k time on postoperative Day 3 may indicate an exaggerated response to LMWH. Thromboelastography is a test that could potentially correlate with the degree of anticoagulation produced by low molecular weight heparin. Implications: Thromboelastography is a test that could potentially correlate with the degree of anticoagulation produced by low molecular weight heparin. The r time from the thromboelastogram correlates with serum anti-Xa concentration.     

Safety,tolerability, and effectiveness of oral zonisamide therapy in comparison with intramuscular adrenocorticotropic hormone therapy in infants with West syndrome

West syndrome is a distinct, infantile onset, epileptic encephalopathy, associated with poor neurodevelopmental outcome. The present study was designed as a randomized, open-label, pilot study to evaluate the safety, feasibility, and effectiveness of oral zonisamide therapy in comparison with adrenocorticotropic hormone therapy in infants with West syndrome. Thirty infants with West syndrome were randomized to receive treatment with either synthetic, intramuscular adrenocorticotropic hormone (30–60 IU) or oral zonisamide (4–25 mg/kg/day). The study participants had a long treatment lag and preponderance of male sex (90%). The primary effectiveness outcome measure was the cessation of epileptic spasms at 2 weeks of initiation of therapy and persistent till 6 weeks as per West Delphi consensus statement recommendations. Comparison of efficacies of zonisamide versus adrenocorticotropic hormone was as following: the cessation of epileptic spasms (27% vs. 40%, p = 0.70), resolution of hypsarrhythmia at 14 days (20% vs. 33%, p = 0.68) and resolution of hypsarrhythmia at 6 weeks (36% vs. 71%, p = 0.14). Overall, the study observed a poor efficacy of both adrenocorticotropic hormone and zonisamide therapy, which is probably due to long treatment lag and a high proportion of structural aetiology. However, oral zonisamide appeared to be safe and tolerable in the study.     

Vitamin D deficiency in childhood — A review of current guidelines on diagnosis and management

Vitamin D deficiency has emerged as a significant public health problem throughout the world. Even in the Indian context,it has been reported to be present in majority of children in spite of wide availability of sunlight. Recent guidelines have defined vitamin D status as severe deficiency, deficiency, sufficiency and risk for toxicity as 25(OH)D levels <5, <15, >20 and >50ng/mL, respectively.The manifestations of deficiency may vary from hypocalcemic seizures, tetany in infancy and adolescence to florid rickets in toddlers. Treatment is necessary for all individuals with deficiency whether symptomatic or not and consists of vitamin D supplementation as Stoss therapy or daily or weekly oral regimens with equal efficacy and safety, combined with calcium supplements. Routine supplementation starting from newborn period is being increasingly endorsed by various international organizations. Prevention by sensible sunlight exposure, food fortification and routine supplementation are the currently available options for tackling this nutritional deficiency.     

Clostridium and Bacillus Binary Enterotoxins: Bad for the Bowels,and Eukaryotic Being

Some pathogenic spore-forming bacilli employ a binary protein mechanism for intoxicating the intestinal tracts of insects, animals, and humans. These Gram-positive bacteria and their toxins include Clostridium botulinum (C2 toxin), Clostridium difficile (C. difficile toxin or CDT), Clostridium perfringens (ι-toxin and binary enterotoxin, or BEC), Clostridium spiroforme (C. spiroforme toxin or CST), as well as Bacillus cereus (vegetative insecticidal protein or VIP). These gut-acting proteins form an AB complex composed of ADP-ribosyl transferase (A) and cell-binding (B) components that intoxicate cells via receptor-mediated endocytosis and endosomal trafficking. Once inside the cytosol, the A components inhibit normal cell functions by mono-ADP-ribosylation of globular actin, which induces cytoskeletal disarray and death. Important aspects of each bacterium and binary enterotoxin will be highlighted in this review, with particular focus upon the disease process involving the biochemistry and modes of action for each toxin.     

Clinical Anatomy of the Ligament of the Head of Femur

The ligament of the head of femur (LHF) has gained clinical attention recently and is reported to contribute to hip stability. This study explores its morphology and morphometry, information that may help inform surgical decision making. Gross anatomical dissections were undertaken on 229 embalmed hips from European (n = 105) and Thai (n = 124) adult cadavers to examine LHF anatomy. Ligament morphometry was statistically compared at different sites, between sexes and sides. The origin of ligamental arteries and absence of the ligament were documented. The LHF was pyramidal or quadrangular in shape. Sub‐synovial fibrous bands originated from the transverse acetabular ligament, edges of the acetabular notch, and acetabular floor; less frequently from the hip joint capsule. Distally, the ligament flattened and converged onto the fovea capitis. The ligament was 22.3 ± 4.4 mm long and was significantly wider (P = 0.001) and thicker (P = 0.0003) at the fovea, compared to its mid‐zone. Branches of the obturator artery entered the acetabular foramen inferomedially and penetrated the middle third of the LHF. Blood vessels ran within the LHF and appeared to enter the fovea. The ligament was absent in 2.8% of Thai hips and there were no significant sex or side differences in ligament dimensions. The morphology of the LHF is complex. While individual variation was apparent, blood vessels were seen in the distal ligament. Precise information on LHF morphometry and attachment sites will help inform appropriate graft dimensions and choice of fixation sites necessary for ligament reconstruction. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc.