Characteristics and programme-defined treatment outcomes among childhood tuberculosis (TB) patients under the national TB programme in Delhi

Background

Childhood tuberculosis (TB) patients under India''s Revised National TB Control Programme (RNTCP) are managed using diagnostic algorithms and directly observed treatment with intermittent thrice-weekly short-course treatment regimens for 6–8 months. The assignment into pre-treatment weight bands leads to drug doses (milligram per kilogram) that are lower than current World Health Organization (WHO) guidelines for some patients.

Objectives

The main aim of our study was to describe the baseline characteristics and treatment outcomes reported under RNTCP for registered childhood (age <15 years) TB patients in Delhi. Additionally, we compared the reported programmatic treatment completion rates between children treated as per WHO recommended anti-TB drug doses with those children treated with anti-TB drug doses below that recommended in WHO guidelines.

Methods

For this cross-sectional retrospective study, we reviewed programme records of all 1089 TB patients aged <15 years registered for TB treatment from January to June, 2008 in 6 randomly selected districts of Delhi. WHO disease classification and treatment outcome definitions are used by RNTCP, and these were extracted as reported in programme records.

Results and Conclusions

Among 1074 patients with records available, 651 (61%) were females, 122 (11%) were <5 years of age, 1000 (93%) were new cases, and 680 (63%) had extra-pulmonary TB (EP-TB)—most commonly peripheral lymph node disease [310 (46%)]. Among 394 pulmonary TB (PTB) cases, 165 (42%) were sputum smear-positive. The overall reported treatment completion rate was 95%. Similar reported treatment completion rates were found in all subgroups assessed, including those patients whose drug dosages were lower than that currently recommended by WHO. Further studies are needed to assess the reasons for the low proportion of under-5 years of age TB case notifications, address challenges in reaching all childhood TB patients by RNTCP, the accuracy of diagnosis, and the clinical validity of reported programme defined treatment completion.     

Transformation of some hydroxy amino acids to other amino acids.

It has been observed that beta-hydroxy-alpha-amino acids are transformed into other amino acids, when heated in dilute solutions with phosphorous acid, phosphoric acid or their ammonium salts. It has been shown that as in the case of previously reported glycine-aldehyde reactions, glycine also reacts with acetone to give beta-hydroxyvaline under prebiologically feasible conditions. It is suggested, therefore, that the formation of beta-hydroxy-alpha-amino acids and their transformation to other amino acids may have been a pathway for the synthesis of amino acids under primitive earth conditions.     

Peroxynitrite and nitric oxide differ in their effects on pig coronary artery smooth muscle

Peroxynitrite generated in arteries fromsuperoxide and nitric oxide (NO) may damage their function. Here, wecompare the effects of peroxynitrite and peroxynitrite/NO-generatingagents SIN-1 (3-morpholinosydnonimine hydrochloride), SNAP(S-nitroso-N-acetyl-penicillamine), SNP (sodiumnitroprusside), and NONOate (spermine NONOate) on pig coronary artery.Deendothelialized artery rings were pretreated with these agents andthen washed before examining their contractility. Pretreatment with allagents (200 µM) results in a decrease in the force of contraction inresponse to the sarco(endo)plasmic Ca²⁺ (SERCA) pumpinhibitor cyclopiazonic acid (CPA): SNAP > NONOate  peroxynitrite  SIN-1 > SNP. Pretreatment with SNAP,NONOate, or SIN-1 also inhibits the force of contraction produced with 30 mM KCl, with SNAP being the most potent. Including catalase plussuperoxide dismutase (SOD) during the preincubation has no effect. Including an NO scavenger[2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide] or a guanylate cyclase inhibitor(1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) partially protects against SNAP. Pretreatment of cultured cells with peroxynitrite, but not with SNAP, inhibits the Ca²⁺transients produced in response to CPA. Pretreating isolated membranevesicles with peroxynitrite inhibits the Ca²⁺ uptake due tothe SERCA pump, with all the other agents being less effective. Thusperoxynitrite and NO both inhibit the CPA-induced contractions indeendothelialized artery rings, peroxynitrite by damage to the SERCApump and NO possibly by a step downstream from the increase incytosolic Ca²⁺.

     

Pseudomonas cepacia lipase--mediated transesterification reactions of hydrocinnamates

Use of lipase from Pseudomonas cepacia in transesterifcation reactions of ethyl hydrocinnamate with different alcohols has been examined. Among the alcohols tested, viz., n-butanol, iso-amyl alcohol, benzyl alcohol, n-octanol and 1-phenylethanol, only n-butanol yielded the transesterified product. Among the solvents tested, viz., n-heptane, n-hexane, cyclohexane, toluene, diisopropylether and n-butanol, the initial rate of transesterification proceeded in the order cyclohexane > n-heptane > n-hexane > diisopropylether > n-butanol > toluene. Using hexane as the solvent and a substrate to enzyme ratio of 1:5, the substrate to alcohol ratio was varied to maximize the yield. n-Butyl hydrocinnamate was obtained in 92% yield in 48 hr by employing a 1:1 (wt/wt) ratio of ethyl hydrocinnamate to lipase and a 1:5 (vol/vol) ratio of ethyl hydrocinnamate to n-butanol in hexane.     

Super sural neurofasciocutaneous flaps in acute traumatic heel reconstructions

Conventional reversed sural flaps have been used to cover heel defects; however, the experience of the authors indicates that the reach of these flaps falls just short of the critical area to be covered. With the limitation being the location of the flap (the middle third of the leg), the authors thought that if the flap territory were extended proximally, they would have a super flap with immense potential. Nevertheless, the critical question remained, "How far?" The massive earthquake in January of 2001 in Gujarat, India, made medical personnel pressed for time, manpower, resources, and other ancillary supports. The authors were forced to make some innovations in their management of extensive heel defects. On the basis of preexisting anatomic studies, they developed the possibility of using distally based neuroskin flaps of huge dimensions that extend well beyond the conventional confines. The versatility of this extended, reversed, neuro-fasciocutaneous flap in regard to its reliability and safety, despite its huge dimensions, is commendable. The hallmarks of this successful extended sural flap, which the authors used to cover large heel defects, were basically accurate understanding of the anatomy and the use of Doppler to map the perforators and the lesser saphenous vein for inclusion in the lie of the pedicle. The authors share their experience of five cases of difficult heel reconstructions salvaged with this flap, which made them attempt to define maximum flap dimensions that can be harvested. The authors learned that the flap can be extended proximally to include the entire upper one-third of the leg posteriorly, drastically improving its reach and size, without compromising safety. The largest flap used measured 17 x 16 cm, far more than ever reported in the literature. The flaps truly deserve the classification of "super," which is usually reserved for Ponten's flaps.     

1,2,3-Triazole Derivatives as an Emerging Scaffold for Antifungal Drug Development against Candida albicans: A Comprehensive Review

Candida infections are most prominent among fungal infections majorly target immunocompromised and hospitalized patients and cause significant morbidity and mortality. Candida albicans is the notorious and most prevalent among all pathogenic Candida strains. Its emerging resistance toward available antifungal agents making it hard to tackle and emerging as global healthcare emergency. Simultaneously, 1,2,3-triazole nucleus is a privileged scaffold that is gaining importance in antifungal drug development due to being a prominent bioactive linker and isostere of triazole based antifungal class core 1,2,4-triazole. Numerous reports have been updated in scientific literature in last few decades related to utilization of 1,2,3-triazole nucleus in antifungal drug development against Candida albicans. Present review will shed light on various preclinical studies focused on development of 1,2,3-triazole derivatives targeting Candida albicans along with brief highlight on clinical trials and newly approved drugs. Structure-activity relationship has been precisely discussed for each architect along with future perspective that will help medicinal chemists in design and development of potent antifungal agents for tackling infections derived from Candida albicans.     

Biological treatment of textile dye acid violet-17 by bacterial consortium in an up-flow immobilized cell bioreactor

AIMS: To develop a cost effective and efficient biological treatment process for small scale textile processing industries (TPI) releasing untreated effluents containing intense coloured Acid violet-17 (AV-17), a triphenyl methane (TPM) group textile dye. METHODS AND RESULTS: The samples collected from effluent disposal sites of TPI were used for selective enrichment of microbial populations capable of degrading/decolourizing AV-17. A consortium of five bacterial isolates was used to develop an up-flow immobilized cell bioreactor for treatment of feed containing AV-17. The bioreactor, operating at a flow rate of 6 ml x h(-1), resulted in 91% decolourization of 30 mg AV-17/l with 94.3 and 95.7% removal of biochemical oxygen demand and chemical oxygen demand of the feed. Comparison of the input and output of the bioreactor by UV-visible, thin layer chromatography and (1)H-nuclear magnetic resonance spectroscopy indicates conversion of the parent dye into unrelated metabolic intermediates. SIGNIFICANCE: These results will form a basis for developing 'on-site' treatment system for TPI effluents to achieve decolourization and degradation of residual dyes.     

Constitutive α-amylase producing mutant and recombinant haploid strains of thermophilic fungusThermomyces lanuginosus

Morphological, developmental and antimetabolite-resistant mutants of T. lanuginosus were characterized and used for screening with the aim to develop constitutive alpha-amylase-hyperproducing strains. The protoplast fusion of two spontaneous mutants of T. lanuginosus, characterized as asporulating and resistant to 2-deoxy-D-glucose (2DG), resulted in sporulating, 2DG sensitive heterokaryotic fusants. A recombinant haploid strain F64fB developed there from produced alpha-amylase constitutively in glucose-containing medium. Constitutive alpha-amylase-hyperproducing mutant (III8) obtained after cyclic mutagenesis and screening yielded approximately 20 fold more alpha-amylase in a glycerol-containing medium than the wild strain.     

High-throughput SNP genotyping by single-tube PCR with Tm-shift primers

Despite many recent advances in high-throughput single nucleotide polymorphism (SNP) genotyping technologies, there is still a great need for inexpensive and flexible methods with a reasonable throughput. Here we report substantial modifications and improvements to an existing homogenous allele-specific PCR-based SNP genotyping method, making it an attractive new option for researchers engaging in candidate gene studies or following up on genome-wide scans. In this advanced version of the melting temperature (Tm)-shift SNP genotyping method, we attach two GC-rich tails of different lengths to allele-specific PCR primers, such that SNP alleles in genomic DNA samples can be discriminated by the Tms of the PCR products. We have validated 306 SNP assays using this method and achieved a success rate in assay development of greater than 83% under uniform PCR conditions. We have developed a standalone software application to automatically assign genotypes directly from melting curve data. To demonstrate the accuracy of this method, we typed 592 individuals for 6 SNPs and showed a high call rate (>98%) and high accuracy (>99.9%). With this method, 6-10,000 samples can be genotyped per day using a single 384-well real-time thermal cycler with 2-4 standard 384-well PCR instruments.