Microbial profile and antibiotic sensitivity pattern in acute bacterial cholangitis

Introduction  

The changing antimicrobial sensitivity pattern of causative organisms poses a therapeutic challenge in treating patients with acute cholangitis. We therefore evaluated the microbial profile and sensitivity pattern to antibiotics in patients with acute bacterial cholangitis.     

A novel approach to the synthesis of 1,2,3-triazoles and their SAR studies

Abstract  

A series of biologically active 4-acetyl-2-aryl-5-methyl-1-vinyl-2,3-dihydro-1H-1,2,3-triazole derivatives has been synthesized. The compounds were synthesized in excellent yields (80–85%) and the structures were established on the basis of corresponding IR, ¹H NMR, and elemental analysis data. The purity has been ascertained on the basis of chromatographic resolution using acetic acid-toluene (4:6 v/v) as binary eluent. All the compounds (4a–l) have been tested for their antifungal activity against a representative panel of fungal microbes. These synthesized compounds exhibited significant activities against A. niger, C. albicans, C. azyma, and A. flavus. For all the tests conducted, voriconazole was used as the control drug. The hydrophobic parameter (log P) also has been quantized for correlation of structure with biological activity, and a critical evaluation of structure-activity relationship (SAR) has been performed.     

Genetic characterization of type A foot-and-mouth disease virus 3A region in context of the reemergence of VP359-deletion lineage in India

The 3A region of foot-and-mouth disease virus has been implicated in host range and virulence. Here we analyzed the 3A region of serotype A virus in view of the emergence of a variant group in India with an amino acid deletion at an antigenically critical position of capsid protein, VP3. The 3A region exhibited extreme variability with 38% of the amino acid positions showing substitutions and the C-terminal third (127–151) region was most flexible. Genotype inclusive grouping of type A foot-and-mouth disease virus as observed in 1D region based phylogeny was much less apparent at 3A region possibly due to independent evolution of nonstructural and structural protein coding regions. Akin to the 1D region, the VP3⁵⁹-deletion group maintained its phylogenetic distinctness even at the 3A region and was found to be diverging with time. Twelve lineage specific signature amino acid residues, of which four were identified to be experiencing positive selection, indicates fixation of advantageous mutations in a lineage specific manner. Six positions, all located in the hypervariable C-terminal third, were identified to be under positive selection and were presumed to be imparting the virus certain advantage accounting for its adaptability to wide host spectrum and rapid dissemination. A significant change of Q₄₄H was noted only in the older lineage (VIIb) of the deletion group at a position where Q₄₄R mutation is associated with guinea pig adaptation. As this site has been detected to be under positive selection, such a lineage specific substitution is thought to have imparted certain temporary advantage to the virus during its possible adaptation in wild or some understudied domestic hosts and must not have seriously compromised fitness upon readaptation in bovines. A conserved hydrophobic transmembrane domain from position 59 to 76 could be predicted which possibly anchors 3A to intracellular membranes for successful interaction with RNA replication complex.     

Antibody specific to 43 kDa excretory-secretory antigenic peptide of Taenia solium metacestode as a potential diagnostic marker in human neurocysticercosis

Recent studies suggest excretory-secretory (ES) antigen specific antibody detection tests to be of promising utility in laboratory diagnosis of many parasitic diseases in human including neurocysticercosis (NCC). The objective of the present study was to characterize the ES antigens collected from in vitro culture of Taenia solium metacestode larvae, and to identify specific ES peptides as diagnostic markers. Three ES peptides viz., 67 kDa, 43 kDa and 32 kDa, were found to be diagnostic for NCC based on high sensitivity and specificity of their reactivity to either serum or cerebrospinal fluid (CSF) specimens. More remarkably, the 43 kDa ES peptide was found reactive with CSF and serum specimens from confirmed NCC patients with absolute specificity and a high sensitivity (88.23% in serum and 89.28% in CSF). This peptide was also detected by sera and CSF from clinically suspected NCC patients but with a decreased sensitivity correlating with the decreasing order of the certainty of diagnosis as per a criteria proposed earlier. The 43 kDa ES peptide is suggested to be an important peptide of diagnostic utility in NCC.     

Screening of Plumbago Species for the Bio-active Marker Plumbagin

Three locally available Plumbago species (Plumbago auriculata, Plumbago rosea and Plumbago zeylanica) have been quantitatively screened for the bioactive marker plumbagin by high performance thin layer chromatography. In general, the root parts were found to be the rich sources for plumbagin. Most significantly, P. rosea was found to accumulate maximum plumbagin in the roots. In contrast, P. auriculata and P. zeylanica are high yielding species for the leaf and stem parts, respectively. Studies have also been extended to evaluate some P. rosea samples collected from southern India and a traditional medicine, Chitrakadi vati, which contains P. zeylanica as the major constituents.     

Large aneurysm of innominate vein: extremely rare cause of mediastinal mass

Aneurysms of the innominate vein are extremely rare. Fifteen such cases have been reported in literature. They may be asymptomatic or may present as a mediastinal mass with compression of adjacent structures or may present with vascular complications like thromboembolism or rupture. We present a case of large innominate vein aneurysm presenting as a mediastinal mass that was surgically excised through a left thoracotomy without use of cardiopulmonary bypass.     

Mild and highly efficient copper (II) sulfate catalyzed one pot synthesis of 2-aryl benzimidazole using atmospheric air as an oxidant and its antibacterial study

A simple, efficient, and environmentally benign method has been developed for the synthesis of 2-substituted benzimidazole using one pot reaction of o-phenylenediamine with substituted aldehydes in good to excellent yields under mild conditions using low catalyst loading (CuSO₄ as the selective catalyst) and atmospheric air as an oxidant. All synthesized compounds were evaluated for their in vitro anti bacterial activity against six microorganisms: Staphylococcus aureus (ATCC 11632), Streptococcus feacalis (clinically isolated), Bacillus cerus (MTCC 7350), Escherichia coli (ATCC 35218), Salmonella typhi (ATCC15499), and Pseudomonas aeruginosa (ATCC 23564). It was observed that all compounds exhibited good to moderate activity as compared to standard drug. The easy setup and purification procedure of this sustainable method and biological importance makes it appealing for bulk industry applications.     

Automated radiochemical synthesis of pharmaceutical grade [18F]FLT using 3-N-Boc-5′-O-dimethoxytrityl-3′-O-nosyl-thymidine precursor and its Sep-Pak® purification employing selective elution from reversed phase

Pharmaceutical grade 3′-deoxy-3′-[¹⁸F]fluorothymidine [¹⁸F]FLT was synthesized using 3-N-Boc-5′-O-dimethoxytrityl-3′-O-nosyl-thymidine (BOC-Nosyl) precursor, in the general purpose TRACERlab FX modules. Purification of [¹⁸F]FLT, via solid phase extraction (SPE) after radiosynthesis, using a combination of different SPE cartridges, yielded satisfactory results, with radiochemical and chemical purity >99%. While the non-decay corrected radiochemical yield (RCY) with 20 mg (24 μmole) of BOC-Nosyl precursor was found to be 6.80 ± 0.16%, the decay corrected radiochemical yield (RCY) was 9.95 ± 0.24%. Residual acetone, acetonitrile, and ethanol levels were found to be 22.97 ± 0.76, 109.08 ± 0.93, and 7,666.45 ± 3.7 ppm, respectively. A simplified method for solid-phase purification of [¹⁸F]FLT was developed, circumventing the need for HPLC purification. Biodistribution in C57BL/6 mice with B16F10 cell line-induced melanoma showed tumor to blood ratio of ~3.8 at 90 min. PET/CT imaging of normal rabbit injected with [¹⁸F]FLT shows selective uptake in the bone marrow and small intestine. [¹⁸F]FLT was found to be excreted through the kidneys and get collected in the urinary bladder, 120 min post injection. PET/CT imaging performed in rabbit model at 30, 60, 90, and 120 min post [¹⁸F]FLT injections showed concordance with tissue distribution kinetics of mice tumor model.     

Evaluation of subclinical hypothyroidism in ambulatory children with controlled epilepsy on valproate monotherapy

There are conflicting reports in the literature about the influence of valproate on thyroid function. A cross-sectional study was performed to determine the prevalence of subclinical hypothyroidism in ambulatory children aged 3 to 15 years with controlled epilepsy receiving valproate monotherapy for at least 6 months. Fifty-seven consecutive children with controlled epilepsy on valproate monotherapy and 52 healthy age- and sex-matched control children were studied. Thyroid-stimulating hormone, free thyroxine, antithyroid peroxidase antibodies, and serum valproic acid levels were measured. There was a significantly high (P = .012) prevalence of subclinical hypothyroidism (26%) in those receiving valproate monotherapy compared with healthy controls (7.7%). Median duration of valproate therapy was significantly higher (P = .039) in the subclinical hypothyroidism group (21 months, range 6-36) compared with those without subclinical hypothyroidism (14 months, range 6-25). Results of the present study suggest higher prevalence of subclinical hypothyroidism in children with controlled epilepsy on long-term valproate monotherapy.