Fifteen analogues of benzenepropanamine were synthesized and evaluated for their spermicidal as w... more Fifteen analogues of benzenepropanamine were synthesized and evaluated for their spermicidal as well as microbicidal activities against Trichomonas vaginalis and Candida spp. Several compounds showed appreciable dual activities. Compound 12 exhibited good spermicidal (MEC = 0.1%) along with substantial anticandidal (MIC = 0.05%) activities, while compounds 3 and 6 showed significant microbicidal activities with moderate spermicidal effect. The SAR of these structures is being discussed here in this communication. It is concluded that suitable structural modifications in this class of compounds at 3-amino position may lead to a potent spermicide with associated microbicidal activity.
Treatment of multidrug-resistant tuberculosis has become one of the major problems in public heal... more Treatment of multidrug-resistant tuberculosis has become one of the major problems in public health. Understanding the molecular mechanisms of drug resistance has been central to tuberculosis research in recent times. DNA microarray technology provides the platform to study the genomic variations related to these mechanisms on a comprehensive level. To investigate the role of efflux pumps in drug resistance, we have constructed a custom DNA microarray containing 25 drug efflux pump genes of Mycobacterium tuberculosis (Indian Patent file no. 2071=DEL=2007) and monitored changes in the expression of these genes on exposure of common antituberculous drugs. Expression profiling of efflux pump genes in multidrug-resistant M. tuberculosis isolates showed overexpression of 10 genes following exposure to various anti-tuberculous drugs. Although two of these genes (Rv3065 and Rv2938) have already been reported to be active drug efflux pumps in M. tuberculosis in earlier studies, the increased activities of other eight efflux pump genes (Rv1819, Rv2209, Rv2459, Rv2477c, Rv2688, Rv2846, Rv2994, and Rv3728) have been demonstrated in multidrug-resistant isolates by us for the first time. After confirmation of differential expressions of these genes by real-time reverse transcription polymerase chain reaction, it was observed that a simultaneous overexpression of efflux pump genes Rv2459, Rv3728, and Rv3065 was associated with resistance to the combination of isoniazid and ethambutol, and these drugs, along with streptomycin, were identified to group together, where efflux-mediated drug resistance appears to be important in M. tuberculosis and follows a constant pattern of induction in multidrug-resistant isolates. Isoniazid and ethambutol combination was also found to be affected in 10% (6=60) of the clinical isolates in the presence of carbonyl cyanide m-chloro phenylhydrazone in resazurin microtitre plate assay, supporting the role of efflux pumps in the resistance to these drugs. Overexpression of two of the genes (Rv2477 and Rv2209) has also been observed with ofloxacin stress in M. tuberculosis.
International Journal of Leprosy and Other Mycobacterial Diseases, 2004
The present study tests the utility of the in situ hybridization procedure for M. leprae rRNA in ... more The present study tests the utility of the in situ hybridization procedure for M. leprae rRNA in the histological diagnosis of early leprosy and clinically suspect leprosy, both diagnostically demanding situations. The histological confirmation obtained with routine histopathology (Haematoxylin-Eosin staining for studying morphologic alterations and Fite-Faraco staining for demonstration of acid-fast bacilli) were 32% for early leprosy and 25% for clinically suspect leprosy. With performance of the in situ hybridization on the histologically unconfirmed cases, the positivity rates obtained were 58.8% and 55%, respectively. The results of the study confirm the utility of the procedure in the diagnostically difficult situations of early and suspect leprosy, and it is proposed that the procedure be employed in situations of clinical doubt.
Using the theory of progressive waves, an asymptotic analysis is carried out to study the propaga... more Using the theory of progressive waves, an asymptotic analysis is carried out to study the propagation of weak nonlinear waves in radiative magneto-fluids. Evolution equation governing the propagation of the waves has been derived and solved in high-frequency domain. The solution of the evolution equation in high frequency domain indicates the possibility of a wave breaking after a finite time,
Using the theory of progressive waves, an asymptotic analysis is carried out to study the propaga... more Using the theory of progressive waves, an asymptotic analysis is carried out to study the propagation of weak nonlinear waves in radiative magneto-fluids. Evolution equation governing the propagation of the waves has been derived and solved in high-frequency domain. The solution of the evolution equation in high frequency domain indicates the possibility of a wave breaking after a finite time,
This study has been carried out to get understanding of the origin among the strains of Mycobacte... more This study has been carried out to get understanding of the origin among the strains of Mycobacterium leprae in patients from Northern India by using number of tandem repeats in rpoT gene as marker. Biopsies were collected from hundred leprosy cases (paucibacillary (PB) as well as multibacillary (MB)) across the spectrum from patients attending clinic at JALMA or diagnosed in Field Unit at Ghatampur (Kanpur). These biopsies were homogenized and DNA was extracted by a physiochemical procedure. rpoT region was amplified by using the primers and conditions earlier published. Among 100 strains from Northern Indian patients, 89% exhibited the presence of three copies of the 6 bp tandem repeat in the rpoT gene, while 11% contained four copies. These profiles along with other genotyping data may help in studying the historical spread of leprosy by strains of M. leprae disseminated by various human races that migrated to Northern India from other places of Asian continent. #
This study reports the follow-up results of 36 highly bacillated untreated BL/LL cases who were s... more This study reports the follow-up results of 36 highly bacillated untreated BL/LL cases who were serially allocated to three treatment groups. Group I patients received a modified WHO regimen (Rifampicin 600 mg once a month supervised, 50 mg of Clofazimine and 100 mg of Dapsone daily unsupervised) and BCG 0.1 mg per dose 6 monthly; group II patients received the same multi-drug treatment (MDT) and Mw (2×10 8 killed bacilli per dose) 6 monthly: group III patients received the same MDT with 0.1 ml of distilled water 6 monthly and acted as a control. Treatment was continued till smear negativity. All these three groups were comparable by their initial clinical score, bacteriological index (BI), viable bacilli as assessed by the mouse foot pad (MFP), bacillary adenosine triphoshate (ATP) content and also histologically at the time of starting treatment. All these parameters were evaluated every 6 months. The vaccines were well tolerated. All the patients in group I became smear negative by 3.5 years, in group II in 3 years whereas those in group III took 5 years. The incidence of reactions was the same in all the groups during the first 2 years, however, patients of group III (MDT+ placebo) continued to have reactions up to 3 years. No viable bacilli could be detected in the local and distal sites as estimated by MFP and bacillary ATP after 12 months in both the immunotherapy groups. These could be detected in patients on MDT alone up to 24 months of therapy. Histologically patients in both the immunotherapy groups (groups I and II) showed accelerated granuloma clearance, histological upgrading and non-specific healing without granuloma formation both at the local and distal sites and this was achieved much earlier compared to the MDT + placebo group. Thus, by the addition of immunotherapy the effective treatment period of achieving bacteriological negativity could be reduced by about 40%, time period of reactions reduced by 33% and there were no reactions and/or relapses in the 10-12 years post-treatment follow-up. (K. Katoch). relapsed patients in the above series responded to the same treatment and did not suffer from drug resistant disease.
design methods can be applied. System-level design methods structure the early phases of the desi... more design methods can be applied. System-level design methods structure the early phases of the design process by assisting the designer in developing abstract models of the system for analysing its properties. To support performance modeling, system-level design methods provide heuristics for applying certain modeling languages and performance analysis techniques. Additionally, userfriendly computer support is often supplied in the form of tools that enable efficient application of the analysis techniques by executing the constructed models.
Fifteen analogues of benzenepropanamine were synthesized and evaluated for their spermicidal as w... more Fifteen analogues of benzenepropanamine were synthesized and evaluated for their spermicidal as well as microbicidal activities against Trichomonas vaginalis and Candida spp. Several compounds showed appreciable dual activities. Compound 12 exhibited good spermicidal (MEC = 0.1%) along with substantial anticandidal (MIC = 0.05%) activities, while compounds 3 and 6 showed significant microbicidal activities with moderate spermicidal effect. The SAR of these structures is being discussed here in this communication. It is concluded that suitable structural modifications in this class of compounds at 3-amino position may lead to a potent spermicide with associated microbicidal activity.
Treatment of multidrug-resistant tuberculosis has become one of the major problems in public heal... more Treatment of multidrug-resistant tuberculosis has become one of the major problems in public health. Understanding the molecular mechanisms of drug resistance has been central to tuberculosis research in recent times. DNA microarray technology provides the platform to study the genomic variations related to these mechanisms on a comprehensive level. To investigate the role of efflux pumps in drug resistance, we have constructed a custom DNA microarray containing 25 drug efflux pump genes of Mycobacterium tuberculosis (Indian Patent file no. 2071=DEL=2007) and monitored changes in the expression of these genes on exposure of common antituberculous drugs. Expression profiling of efflux pump genes in multidrug-resistant M. tuberculosis isolates showed overexpression of 10 genes following exposure to various anti-tuberculous drugs. Although two of these genes (Rv3065 and Rv2938) have already been reported to be active drug efflux pumps in M. tuberculosis in earlier studies, the increased activities of other eight efflux pump genes (Rv1819, Rv2209, Rv2459, Rv2477c, Rv2688, Rv2846, Rv2994, and Rv3728) have been demonstrated in multidrug-resistant isolates by us for the first time. After confirmation of differential expressions of these genes by real-time reverse transcription polymerase chain reaction, it was observed that a simultaneous overexpression of efflux pump genes Rv2459, Rv3728, and Rv3065 was associated with resistance to the combination of isoniazid and ethambutol, and these drugs, along with streptomycin, were identified to group together, where efflux-mediated drug resistance appears to be important in M. tuberculosis and follows a constant pattern of induction in multidrug-resistant isolates. Isoniazid and ethambutol combination was also found to be affected in 10% (6=60) of the clinical isolates in the presence of carbonyl cyanide m-chloro phenylhydrazone in resazurin microtitre plate assay, supporting the role of efflux pumps in the resistance to these drugs. Overexpression of two of the genes (Rv2477 and Rv2209) has also been observed with ofloxacin stress in M. tuberculosis.
International Journal of Leprosy and Other Mycobacterial Diseases, 2004
The present study tests the utility of the in situ hybridization procedure for M. leprae rRNA in ... more The present study tests the utility of the in situ hybridization procedure for M. leprae rRNA in the histological diagnosis of early leprosy and clinically suspect leprosy, both diagnostically demanding situations. The histological confirmation obtained with routine histopathology (Haematoxylin-Eosin staining for studying morphologic alterations and Fite-Faraco staining for demonstration of acid-fast bacilli) were 32% for early leprosy and 25% for clinically suspect leprosy. With performance of the in situ hybridization on the histologically unconfirmed cases, the positivity rates obtained were 58.8% and 55%, respectively. The results of the study confirm the utility of the procedure in the diagnostically difficult situations of early and suspect leprosy, and it is proposed that the procedure be employed in situations of clinical doubt.
Using the theory of progressive waves, an asymptotic analysis is carried out to study the propaga... more Using the theory of progressive waves, an asymptotic analysis is carried out to study the propagation of weak nonlinear waves in radiative magneto-fluids. Evolution equation governing the propagation of the waves has been derived and solved in high-frequency domain. The solution of the evolution equation in high frequency domain indicates the possibility of a wave breaking after a finite time,
Using the theory of progressive waves, an asymptotic analysis is carried out to study the propaga... more Using the theory of progressive waves, an asymptotic analysis is carried out to study the propagation of weak nonlinear waves in radiative magneto-fluids. Evolution equation governing the propagation of the waves has been derived and solved in high-frequency domain. The solution of the evolution equation in high frequency domain indicates the possibility of a wave breaking after a finite time,
This study has been carried out to get understanding of the origin among the strains of Mycobacte... more This study has been carried out to get understanding of the origin among the strains of Mycobacterium leprae in patients from Northern India by using number of tandem repeats in rpoT gene as marker. Biopsies were collected from hundred leprosy cases (paucibacillary (PB) as well as multibacillary (MB)) across the spectrum from patients attending clinic at JALMA or diagnosed in Field Unit at Ghatampur (Kanpur). These biopsies were homogenized and DNA was extracted by a physiochemical procedure. rpoT region was amplified by using the primers and conditions earlier published. Among 100 strains from Northern Indian patients, 89% exhibited the presence of three copies of the 6 bp tandem repeat in the rpoT gene, while 11% contained four copies. These profiles along with other genotyping data may help in studying the historical spread of leprosy by strains of M. leprae disseminated by various human races that migrated to Northern India from other places of Asian continent. #
This study reports the follow-up results of 36 highly bacillated untreated BL/LL cases who were s... more This study reports the follow-up results of 36 highly bacillated untreated BL/LL cases who were serially allocated to three treatment groups. Group I patients received a modified WHO regimen (Rifampicin 600 mg once a month supervised, 50 mg of Clofazimine and 100 mg of Dapsone daily unsupervised) and BCG 0.1 mg per dose 6 monthly; group II patients received the same multi-drug treatment (MDT) and Mw (2×10 8 killed bacilli per dose) 6 monthly: group III patients received the same MDT with 0.1 ml of distilled water 6 monthly and acted as a control. Treatment was continued till smear negativity. All these three groups were comparable by their initial clinical score, bacteriological index (BI), viable bacilli as assessed by the mouse foot pad (MFP), bacillary adenosine triphoshate (ATP) content and also histologically at the time of starting treatment. All these parameters were evaluated every 6 months. The vaccines were well tolerated. All the patients in group I became smear negative by 3.5 years, in group II in 3 years whereas those in group III took 5 years. The incidence of reactions was the same in all the groups during the first 2 years, however, patients of group III (MDT+ placebo) continued to have reactions up to 3 years. No viable bacilli could be detected in the local and distal sites as estimated by MFP and bacillary ATP after 12 months in both the immunotherapy groups. These could be detected in patients on MDT alone up to 24 months of therapy. Histologically patients in both the immunotherapy groups (groups I and II) showed accelerated granuloma clearance, histological upgrading and non-specific healing without granuloma formation both at the local and distal sites and this was achieved much earlier compared to the MDT + placebo group. Thus, by the addition of immunotherapy the effective treatment period of achieving bacteriological negativity could be reduced by about 40%, time period of reactions reduced by 33% and there were no reactions and/or relapses in the 10-12 years post-treatment follow-up. (K. Katoch). relapsed patients in the above series responded to the same treatment and did not suffer from drug resistant disease.
design methods can be applied. System-level design methods structure the early phases of the desi... more design methods can be applied. System-level design methods structure the early phases of the design process by assisting the designer in developing abstract models of the system for analysing its properties. To support performance modeling, system-level design methods provide heuristics for applying certain modeling languages and performance analysis techniques. Additionally, userfriendly computer support is often supplied in the form of tools that enable efficient application of the analysis techniques by executing the constructed models.
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