Synthesis, antimycobacterial activities and phototoxic evaluation of 5H-thiazolo[3,2-a]quinoline-4-carboxylic acid derivatives

Thirty four novel 7-fluoro/nitro-1,2-dihydro-5-oxo-8-(sub)-5H-thiazolo[3,2-a]quinoline-4-carboxylic acids were synthesized from 2,4-dichlorobenzoic acid and 2,4-dichloro-5-fluoroacetophenone by multi step reaction, evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC2) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the synthesized compounds, 8-[6-[[(1,1-dimethylethoxy)carbonyl]amino]-3-azabicyclo[3.1.0]hex-3-yl]-1,2-dihydro-7-nitro-5-oxo-5H-thiazolo[3,2-a]quinoline-4-carboxylic acid (10q) was found to be the most active compound in vitro with MIC of 0.08 microM and <0.08 microM against MTB and MDR-TB respectively. Compound 10q was found to be 4.5 and >570 times more potent than isoniazid against MTB and MDR-TB respectively. In the in vivo animal model 10q decreased the bacterial load in lung and spleen tissues with 2.51 and 3.71-log10 protections respectively at the dose of 50 mg/kg body weight.     

First detection of measles genotype D7 from India

National Institute of Virology, India has instituted molecular surveillance of measles strains in the country. In phased manner, three major cities Pune, Chennai and Bangalore were covered. Throat swab and urine from suspected measles cases from Chennai and Pune and freshly frozen brain tissues, CSF from suspected SSPE case from Bangalore were subjected to RNA extraction and Measles N&H gene RT-PCR as per WHO standard protocols. PCR positive products were sequenced. Sequence alignment and phylogenetic analysis was carried out using WHO standard reference sequences. Virus isolation was attempted using B95a cell line. Measles genotype D7 was detected from two classical measles cases (Chennai and Pune) and in a fulminant SSPE case (Bangalore). This is the first detection of measles genotype D7 from India.     

Molecular mechanisms underlying occult hepatitis B virus infection

Chronic hepatitis B virus (HBV) infection is a complex clinical entity frequently associated with cirrhosis and hepatocellular carcinoma (HCC). The persistence of HBV genomes in the absence of detectable surface antigenemia is termed occult HBV infection. Mutations in the surface gene rendering HBsAg undetectable by commercial assays and inhibition of HBV by suppression of viral replication and viral proteins represent two fundamentally different mechanisms that lead to occult HBV infections. The molecular mechanisms underlying occult HBV infections, including recently identified mechanisms associated with the suppression of HBV replication and inhibition of HBV proteins, are reviewed in detail. The availability of highly sensitive molecular methods has led to increased detection of occult HBV infections in various clinical settings. The clinical relevance of occult HBV infection and the utility of appropriate diagnostic methods to detect occult HBV infection are discussed. The need for specific guidelines on the diagnosis and management of occult HBV infection is being increasingly recognized; the aspects of mechanistic studies that warrant further investigation are discussed in the final section.     

Removal of Pb (II) by Immobilized and Free Filaments of Marine <Emphasis Type="Italic">Oscillatoria</Emphasis> sp. NTMS01 and <Emphasis Type="Italic">Phormidium</Emphasis> sp. NTMS02

Pb²⁺ removal ability of the immobilized and free filaments of marine cyanobacteria Oscillatoria sp. NTMS01 and Phormidium sp. NTMS02 was studied using batch experiments. Biosorption of lead by immobilized filaments was studied as a function of pH (2, 4, 6, 8, 10), contact time (5–180 min) and initial lead concentration (1, 3, 5, 7 mg/L) and the removal efficiency of free filaments was studied by culturing in the marine medium with the initial concentration (1, 3, 5, 7 mg/L) at pH 7 and incubated for 10 days. The maximum percentage removal was observed at 25 min for immobilized Oscillatoria sp. NTMS01 and 30 min for immobilized Phormidium sp. NTMS02. At 4th and 6th day of incubation, 89% and 77% removal was observed at 1 mg/L of initial lead concentration by free filaments of Oscillatoria sp. NTMS01 and Phormidium sp. NTMS02 respectively and further the removal was decreased with increasing concentration. Chlorophyll-a content was decreased in a dose dependent manner. About 40 and 50% reduction of chlorophyll-a was observed at higher concentration in Oscillatoria sp. NTMS01 and Phormidium sp. NTMS02 respectively. The adsorption capacity of immobilized Oscillatoria sp. NTMS01 was found to be (Q_max) 217.39 which is comparatively higher than other sorbents. The Pb²⁺ removal efficiency was performed as described in terms of Langmuir and Freundlich isotherms. These organisms is found to fit better by the Langmuir isotherms.     

Predicting thyroxine requirements following total thyroidectomy

Objective Optimal thyroxine replacement following total thyroidectomy is critical to avoid symptoms of hypothyroidism. The aim of this study was to determine the best formula to determine the initiated replacement dose of levothyroxine immediately following total thyroidectomy. Design Prospective study. All patients were initiated on 100 μg levothyroxine and titrated to within the reference range for TSH and free T4. Correlations to height, weight, age, lean body mass (LBM), body surface area (BSA) and body mass index (BMI) were calculated. Patients One hundred consecutive adult patients underwent total thyroidectomy for non‐malignant disease. Measurements Comparison between three methods of levothyroxine dose prediction, aiming for a levothyroxine dose correct to within 25 μg of actual dose required. Results Correlations were seen between levothyroxine dose and patient age (r = ?0·346, P < 0·01), bodyweight (r = 0·296, P < 0·01), LBM (r = 0·312, P < 0·01), BSA (r = 0·319, P < 0·01) and BMI (r = 0·172, P < 0·05). A regression equation was calculated (predicted levothyroxine dose = [0·943 × bodyweight] + [?1·165 × age] + 125·8), simplified to (levothyroxine dose = bodyweight ? age + 125) pragmatically. Initiating patients empirically on 100 μg post‐operatively showed that 40% of patients achieved target within 25 μg of their required dose; this increased to 59% when using a weight‐only dose calculation (1·6 μg/kg) and to 72% using the simplified regression equation. Conclusions A simple calculated regression equation gives a more accurate prediction of initiated levothyroxine dose following total thyroidectomy, reducing the need for outpatient attendance for dose titration.     

Polychlorinated Biphenyl (PCBs)-Induced Oxidative Stress Plays a Critical Role on Cerebellar Dopaminergic Receptor Expression: Ameliorative Role of Quercetin

Polychlorinated biphenyls (PCBs) exposure produces profound damage to the developing as well as adult central nervous system. Locomotor activities which are closely linked to dopaminergic neurotransmission are often impaired in PCBs toxicity. Targeting PCBs-induced oxidative stress using natural antioxidants is an attractive approach. Quercetin, a flavonoid is a safe and potent neuroprotective antioxidant. In this study, we sought to examine the protective role of quercetin against PCBs-induced neurodegeneration and dysfunction of dopaminergic receptors in the cerebellar region of adult male rats. They were divided into four groups. Group I received only vehicle (corn oil) intraperitoneally (i.p); Group II received Aroclor 1254 at a dose of 2?mg/kg bwt/day (i.p); Group III received Aroclor 1254 (i.p) and simultaneously quercetin (50?mg/kg bwt/day) through gavage; Group IV received quercetin alone (gavage). After 30?days treatment, rats were euthanized. The cerebellum was dissected from each rat brain, the levels of hydrogen peroxide, lipid peroxidation, protein carbonyl content, and activities of creatine kinase, acetylcholine esterase, membrane-bound ATPases were evaluated. Expressions of dopaminergic receptors and tyrosine hydroxylase in cerebellum were studied by semi-quantitative RT-PCR and western blot analysis, respectively. The PCBs-induced neurodegeneration was assessed by histological studies. Results proclaim that PCBs disturb dopaminergic receptors and also causes neurodegeneration in cerebellum via production of ROS. Simultaneous quercetin treatment had scavenged the free radicals induced by PCBs and protected dopaminergic receptors dysfunction in rat cerebellum.     

Subcutaneous administration of alemtuzumab in patients with highly active multiple sclerosis

Alemtuzumab is an anti-CD52 monoclonal antibody with remarkable efficacy in relapsing multiple sclerosis (MS). In clinical trials and off-label use in MS, alemtuzumab has been administered intravenously (IV). Alemtuzumab is approved for chronic lymphoid leukemia as IV. Oncology guidelines recommend alemtuzumab subcutaneous (SC) over IV. There is no report of alemtuzumab SC in MS. We report two patients with highly active relapsing MS who were treated with SC alemtuzumab, had significant improvement and tolerated SC alemtuzumab well without the typical infusion-associated adverse events. SC alemtuzumab in MS warrants further studies as this may enhance patient convenience and minimize infusion-associated adverse events.     

Case Report: A Technique to Remove a Jammed Locking Screw from a Locking Plate

Background  

Locking titanium plates revolutionized the treatment of osteoporotic and metaphyseal fractures of long bones. However as with any innovation, with time new complications are identified. One of the problems with titanium locking plates is removal of screws, often attributable to cold welding of screw heads into the locking screw holes. Several techniques have been described to overcome this problem. We describe a new easy technique to remove a jammed locking screw in a locking plate that is easily reproducible and suggest an algorithm to determine the method to remove screws from locking plates.     

Bicondylar tibial fractures: Internal or external fixation?

Bicondylar fractures of the tibia, representing the Schatzker V and VI fractures represent a challenging problem. Any treatment protocol should aim at restoring articular congruity and the metaphyseo-diaphsyeal dissociation (MDD)—both of these are equally important to long-term outcome. Both internal and external fixations have their proponents, and each method of treatment is associated with its unique features and complications. We review the initial and definitive management of these injuries, and the advantages and disadvantages of each method of definitive fixation. We suggest the use of a protocol for definitive management, using either internal or external fixation as deemed appropriate. This protocol is based on the fracture configuration, local soft tissue status and patient condition. In a nutshell, if the fracture pattern and soft tissue status are amenable plate fixation (single or double) is performed, otherwise limited open reduction and articular surface reconstruction with screws and circular frame is performed.     

Possible relationship among socio-economic determinants,knowledge and practices on lymphatic filariasis and implication for disease elimination in India

Objective  

To assess the socio-economic determinants, knowledge and practices on lymphatic filariasis in India and discuss the implications for elimination.