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71.
Sahana K.S. Prakash R.M. Saldanha Supriya Kushwah Anitha S. Prabhu 《The Indian journal of tuberculosis》2018,65(3):195-199
Introduction
In spite of having BCG vaccination and tuberculosis control program for the last 50 years, prevalence of tuberculosis continues to be high in India. Inadequate diagnostic methods, suboptimal treatment and monitoring, and the lack of vigilant reporting system are some of the contributing factors for the failure of TB control.Objectives
To know the current practices among local pediatricians regarding management of TB.Materials and methods
Field based cross sectional study. All the registered pediatricians who were practicing in Mangalore, (list – local IAP branch) were included in the study. A structured Questionnaire on signs and symptoms of TB, diagnosis, strategies adopted in treatment, MDR tuberculosis and reporting of cases to RNTCP was asked. Management practice standards according to the Updated National Guidelines for Pediatric Tuberculosis in India, 2012, RNTCP guidelines in consensus with IAP, latest at the time of the study.Results
50 pediatricians participated in the study with 62% having an attachment to the teaching institution. More than 50% identified all the symptoms of TB. 64% were sending chest X-ray, Mantoux test and gastric lavage/induced sputum examination for AFB to diagnose TB. 22% were not stressing for AFB examination. Still 16% told serological tests as one of the diagnostic modality. 52% were not aware about the diagnosis of latent TB. In 16% of their cases ATT was on a trial basis. Only 52% of the clinicians are adhering to updated national (RNTCP) guidelines. 30% felt still there are drawbacks in the current RNTCP guidelines. 72% knew the correct definition of MDR tuberculosis. But only 36% of them knew the diagnostic method (gene expert/CB NAAT) of confirming the MDR TB.Conclusion
Management practices are found to be still suboptimum. Better engagement of the private sector is urgently required to improve TB management practices and to prevent diagnostic delay and drug resistance. 相似文献72.
Zhuang Z Johnson RE Haracska L Prakash L Prakash S Benkovic SJ 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(14):5361-5366
To ensure efficient and timely replication of genomic DNA, organisms in all three kingdoms of life possess specialized translesion DNA synthesis (TLS) polymerases (Pols) that tolerate various types of DNA lesions. It has been proposed that an exchange between the replicative DNA Pol and the TLS Pol at the site of DNA damage enables lesion bypass to occur. However, to date the molecular mechanism underlying this process is not fully understood. In this study, we demonstrated in a reconstituted system that the exchange of Saccharomyces cerevisiae Poldelta with Poleta requires both the stalling of the holoenzyme and the monoubiquitination of proliferating cell nuclear antigen (PCNA). A moving Poldelta holoenzyme is refractory to the incoming Poleta. Furthermore, we showed that the Poleta C-terminal PCNA-interacting protein motif is required for the exchange process. We also demonstrated that the second exchange step to bring back Poldelta is prohibited when Lys-164 of PCNA is monoubiquitinated. Thus the removal of the ubiquitin moiety from PCNA is likely required for the reverse exchange step after the lesion bypass synthesis by Poleta. 相似文献
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Maha Abdalla Harika Sabbineni Roshini Prakash Adviye Ergul Susan C Fagan Payaningal R Somanath 《British journal of pharmacology》2015,172(16):4173-4188
Background and Purpose
Interstitial lung disease accounts for a group of chronic and progressive disorders associated with severe pulmonary vascular remodelling, peripheral vascular rarefaction and fibrosis, thus limiting lung function. We have previously shown that Akt is necessary for myofibroblast differentiation, a critical event in organ fibrosis. However, the contributory role of the Akt-mTOR pathway in interstitial lung disease and the therapeutic benefits of targeting Akt and mTOR remain unclear.Experimental Approach
We investigated the role of the Akt-mTOR pathway and its downstream molecular mechanisms in chronic hypoxia- and TGFβ-induced pulmonary vascular pruning and fibrosis in mice. We also determined the therapeutic benefits of the Akt inhibitor triciribine and the mTOR inhibitor rapamycin for the treatment of pulmonary fibrosis in mice.Key Results
Akt1−/− mice were protected from chronic hypoxia-induced peripheral vascular pruning. In contrast, hyperactivation of Akt1 induced focal fibrosis similar to TGFβ-induced fibrosis. Pharmacological inhibition of Akt, but not the Akt substrate mTOR, inhibited hypoxia- and TGFβ-induced pulmonary vascular rarefaction and fibrosis. Mechanistically, we found that Akt1 modulates pulmonary remodelling via regulation of thrombospondin1 (TSP1) expression. Hypoxic Akt1−/− mice lungs expressed less TSP1. Moreover, TSP1−/− mice were resistant to adMyrAkt1-induced pulmonary fibrosis.Conclusions and Implications
Our study identified Akt1 as a novel target for the treatment of interstitial lung disease and provides preclinical data on the potential benefits of the Akt inhibitor triciribine for the treatment of interstitial lung disease. 相似文献76.
77.
Lakkireddy Prakash Malipeddi Himaja Belly Ramakrishna Yadav Arumalla Maheshwara Reddy 《Scientia pharmaceutica》2015,83(3):453-463
Cost-effective isolation methods were developed on preparative HPLC, flash LC, and simulated moving bed (SMB) to prepare the process impurity, 3-(aminomethyl)-5-methylhex-4-enoic acid (4-ene impurity), of pregabalin. By a thorough experimental study on the different isolation techniques available, it was concluded that SMB was the most cost-effective. Hence, it was a continuous chromatography that utilized the advantage of SMB so that a high quantity of the impurity was generated in a short period of time. SMB was equipped with eight reversed-phased columns and was used to separate the process impurity of pregabalin. The effects of flow rate in zone 2 (Q2) and 3 (Q3), as well as switching time, on the operating performance parameters like purity, productivity, and desorbent consumption were studied. Operating conditions leading to more than 90% purity in the raffinate outlet stream were identified, together with those achieving optimal performance. All of these developed methods are novel, cost-effective, and can be applied to the isolation of other process- and stability-related impurities of pregabalin. 相似文献
78.
Vinblastine a DNA non-intercalating agent has wide application against several human neoplasms, and found to cause cytogenotoxicity. In this study, clastogenotoxicity of vinblastine (1.5?mg/kg b w) and its prevention by caffeine at different doses (25, 50 and 100?mg/kg b w) administered intraperitoneally was assessed in in vivo mice. It was found that micronucleus level had decreased significantly (up to 28.8%) in 100?mg caffeine treated group at 30?h post treatment. However, it did not exhibit protective effect against chromosomal aberration in spaermatogonial cells at 24?h post treatment. The frequencies of aberrant primary spermatocytes had decreased significantly in 25 and 100?mg caffeine at 4th week of post treatment. Similarly, in 100?mg of caffeine administered, abnormal sperm level had reduced (4.01%) significantly at 8th week post treatment. Thus, caffeine decreased the vinblastine induced chromosomal aberrations and mitotic index in bone marrow cells. In conclusion, this study shows that caffeine exerts protective effect against vinblastin induced cytogenotoxicity. Further studies on molecular mechanism are interesting in order to develop it as an effective drug in cancer chemotherapy. 相似文献
79.
George M. Varghese Jeshina Janardhanan Sanjay K. Mahajan David Tariang Paul Trowbridge John A.J. Prakash Thambu David Sowmya Sathendra O.C. Abraham 《Emerging infectious diseases》2015,21(1):64-69
Scrub typhus, an acute febrile illness that is widespread in the Asia-Pacific region, is caused by the bacterium Orientia tsutsugamushi, which displays high levels of antigenic variation. We conducted an investigation to identify the circulating genotypes of O. tsutsugamushi in 3 scrub typhus–endemic geographic regions of India: South India, Northern India, and Northeast India. Eschar samples collected during September 2010–August 2012 from patients with scrub typhus were subjected to 56-kDa type-specific PCR and sequencing to identify their genotypes. Kato-like strains predominated (61.5%), especially in the South and Northeast, followed by Karp-like strains (27.7%) and Gilliam and Ikeda strains (2.3% each). Neimeng-65 genotype strains were also observed in the Northeast. Clarifying the genotypic diversity of O. tsutsugamushi in India enhances knowledge of the regional diversity among circulating strains and provides potential resources for future region-specific diagnostic studies and vaccine development. 相似文献
80.
Nair Aswin M. Mathew John Goel Ruchika Chebbi Pramod Mathew Ashish Jacob Arvind G. Yadav Bijesh Rebekah Grace Prakash John A. J. Danda Debashish 《Clinical rheumatology》2021,40(7):2805-2819
Clinical Rheumatology - Consensus on treatment of idiopathic inflammatory myositis (IIM), particularly with regard to flares and interstitial lung disease (ILD), does not exist. We studied the... 相似文献