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21.
Poonam Yash Gupta Nikesh Gupta Snigdha Singh Lidong Wu Bhupender Singh Chhikara Manmeet Rawat Brijesh Rathi 《Medicinal research reviews》2018,38(5):1511-1535
Over time, several exciting advances have been made in the treatment and prevention of malaria; however, this devastating disease continues to be a major global health problem and affects millions of people every year. Notably, the paucity of new efficient drug molecules and the inevitable drug resistance of the malaria parasite, Plasmodium falciparum, against frontline therapeutics are the foremost struggles facing malaria eradication initiatives. According to the malaria eradication agenda, the discovery of new chemical entities that can destroy the parasite at the liver stage, the asexual blood stage, the gametocyte stage, and the insect ookinete stage of the parasite life cycle (i.e., compounds exhibiting multistage activity) are in high demand, preferably with novel and multiple modes of action. Phenotypic screening of chemical libraries against the malaria parasite is certainly a crucial step toward overcoming these crises. In the last few years, various research groups, including industrial research laboratories, have performed large‐scale phenotypic screenings that have identified a wealth of chemical entities active against multiple life stages of the malaria parasite. Vital scientific and technological developments have led to the discovery of multistage inhibitors of the malaria parasite; these compounds, considered highly valuable starting points for subsequent drug discovery and eradication of malaria, are reviewed. 相似文献
22.
Aadish Rawat Parikshit Singh Anupam Jyoti Sanket Kaushik Vijay Kumar Srivastava 《Chemical biology & drug design》2020,96(2):731-744
Amoebiasis is a parasitic infectious disease caused by the enteric protozoan Entamoeba histolytica, a leading basis of deaths accounted to parasites, succeeding malaria and schistosomiasis. Conventional treatment methodologies used to deal with amoebiasis mainly rely on the administration of anti‐amoebic compounds and vaccines but are often linked with substantial side‐effects on the patient. Besides, cases of development of drug resistance in protozoans have been recorded, contributing further to the reduction in the efficiency of the treatment. Loopholes in the efficacious management of the disease call for the development of novel methodologies to manage amoebiasis. A way to achieve this is by targeting the essential metabolic processes of ‘encystation’ and ‘excystation’, and the associated biomolecules, thus interrupting the biphasic life cycle of the parasite. Technologies like the CRISPR‐Cas9 system can efficiently be exploited to discover novel and essential molecules that regulate the protozoan's metabolism, while efficiently manipulating and managing the known drug targets, leading to an effective halt and forestall to the enteric infection. This review presents a perspective on these essential metabolic processes and the associated molecules that can be targeted efficaciously to prevent the transmission of amoebiasis, thus managing the disease and proving to be a fruitful endeavour. 相似文献
23.
24.
BACKGROUND: Although many studies have investigated the safety and tolerability of ibuprofen or acetaminophen (paracetamol) use in children, few have specifically examined the association of ibuprofen or acetaminophen and the occurrence of asthma in pediatric populations. OBJECTIVES: The primary objective of this literature review was to ascertain whether ibuprofen use exacerbates the symptoms of asthma or asthma-related adverse events in febrile children, and how it compares with acetaminophen use. The secondary objective was to develop an algorithm that allows for the consideration of ibuprofen treatment in children by health care professionals. METHODS: Twelve electronic databases (MEDLINE, EMBASE, Cochrane Database, DARE, British Nursing Index, CBIB, Derwent Drug File, International Pharmaceutical Abstracts, Pharm-Line, CINAHL, PASCAL, SCZZ-SciSearch) were searched from their year of inception to June 2007, to identify English-language articles pertaining to ibuprofen or acetaminophen use in the asthmatic pediatric population. The following search terms were used: asthma, child, pediatric, pediatrics, ibuprofen, Nurofen, Brufen, Motrin, Advil, propionic acid, paracetamol, and acetaminophen. RESULTS: Of 472 articles retrieved, 3 were relevant for the development of the algorithm. Two were subanalyses of a major randomized controlled trial (RCT), the Boston University Fever Study. Therefore, some overlap should be noted. The third article was another RCT. Other studies and review articles identified were used for the discussion. Findings from the literature analysis indicated that the use of ibuprofen in the pediatric population does not exacerbate asthma morbidity. Two of the studies demonstrated that ibuprofen was associated with a lower risk for asthma morbidity in febrile children with or without asthma compared with acetaminophen. In one study, ibuprofen use was associated with a lower relative risk for hospitalization (0.63) and outpatient visits (0.56) for asthma compared with acetaminophen. In the second study, acetaminophen use was associated with the exacerbation of wheezing in febrile children. This observation was corroborated by the findings of other studies that revealed an increased risk for asthma, wheezing, and other atopic outcomes with acetaminophen use. CONCLUSIONS: The evidence reviewed in this article suggests a low risk for asthma-related morbidity associated with ibuprofen use in children and a possible protective and therapeutic effect compared with acetaminophen. The findings also suggest that acetaminophen use in children is associated with an increased risk for wheezing. The pediatric algorithm developed might serve as a guide for health care professionals in assessing suitability for ibuprofen use in children. 相似文献
25.
Design,Synthesis, Biological Screening,and Molecular Docking Studies of Piperazine-Derived Constrained Inhibitors of DPP-IV for the Treatment of Type 2 Diabetes 下载免费PDF全文
Ram N. Kushwaha Rohit Srivastava Akansha Mishra Arun K. Rawat Arvind K. Srivastava Wahajul Haq Seturam B. Katti 《Chemical biology & drug design》2015,85(4):439-446
Novel piperazine-derived conformationally constrained compounds were designed, synthesized, and evaluated for in vitro Dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. From a library of compounds synthesized, 1-(2-(4-(7-Chloro-4-quinolyl)piperazin-1-yl)acetyl)pyrrolidine ( 2g ) was identified as a potential DPP-IV inhibitor exhibiting better inhibitory activity than P32/98, reference inhibitor. The in vivo studies carried out in STZ and db/db mice models indicated that the compound 2g showed moderate antihyperglycemic activity as compared to the marketed drug Sitagliptin. A two-week repeated dose study in db/db mice revealed that compound 2g significantly declined blood glucose levels with no evidence of hypoglycemia risk. Furthermore, it showed improvement in insulin resistance reversal and antidyslipidemic properties. Molecular docking studies established good binding affinity of compound 2g at the DPP-IV active site and are in favor of the observed biological data. These data collectively suggest that compound 2g is a good lead molecule for further optimization studies. 相似文献
26.
Srivastava Sharad Tiwari Surabhi Srivastava Nishi Verma Shikhar Rawat Ajay Kumar Singh 《Proceedings of the National Academy of Sciences, India. Section B.》2019,89(3):1057-1066
Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Centella asiatica (L.) Urb. (Apiaceae) with high commercial value is an important herb in traditional Indian... 相似文献
27.
Surjit Singh Deepti Suri Roosy Aulakh Anju Gupta Amit Rawat Rohit Manoj Kumar 《Clinical rheumatology》2014,33(11):1675-1679
Survival and outcomes have improved considerably among patients with juvenile dermatomyositis (JDM) in the west. However, mortality continues to be high in the developing world. There is paucity of literature on this aspect of JDM from developing countries. We reviewed case files of all patients with JDM registered in the Pediatric Rheumatology Clinic, Advanced Pediatrics Centre at the Post Graduate Institute of Medical Education and Research, Chandigarh, during the period 1993–2013. Seventy-six children were diagnosed to have inflammatory myopathy during this period. Of these, 63 had JDM, 3 had polymyositis while 10 had an overlap syndrome. We had reported 2 deaths out of 33 (8.3 %) patients with JDM in 2004, and over the last 9 years, we have encountered five more deaths in this group, thereby accounting for a mortality rate of 11.1 % (7/63) over two decades of follow-up. In these five children now being described, the mean duration between onset of symptoms and institution of appropriate therapy was 9.2 months. Four children (80 %) had severe muscle weakness needing nasogastric tubes at the onset, three (60 %) had cutaneous ulcers and three (60 %) had superadded infections. Two children (40 %) had gastrointestinal vasculitis and one of these developed an intestinal perforation. Three patients (60 %) had progressive pulmonary disease and air leak was identified in two of them. Although the prognosis for survival in JDM has steadily improved, in our experience the disease remains a serious illness and still carries significant mortality in the context of a developing country. 相似文献
28.
Sadhana Awsathi Vinita Rawat Chandra Mohan Singh Rawat Vandana Semwal Sunil Janki Bartwal 《Indian Journal of Community Medicine》2014,39(2):94-97
Background:
In March 2013, cases of acute hepatitis were reported from Lalkuan, Nainital district. We investigated the outbreak to identify the source of infection and to facilitate control measures.Objectives:
To study the distribution of hepatitis cases, to find the source of infection, and to initiate the control measures in the affected area.Materials and Methods:
We defined a case of acute hepatitis as those cases that had jaundice with at least one of the following symptoms: Dark urine, fever, pain in abdomen, vomiting, and loss of appetite in the affected area between January and March 2013. Door-to-door survey was carried out. Thirteen blood samples were randomly collected from jaundice cases for immunoglobulin M (IgM) antibody for hepatitis A virus (HAV) and hepatitis E virus (HEV). Water samples were collected to test residual chlorine.Results:
Total 2,785 individuals were surveyed; of which 240 were suffering from acute viral hepatitis (attack rate (AR) = 8.61%). Out of 13 serum samples, 10 were found positive for HEV IgM antibodies and three cases had IgM antibodies for both HAV and HEV, which confirmed a hepatitis E outbreak. The difference in attack rate of hepatitis of both the sexes was statistically significant (P < 0.001). The attack rate was significantly higher in age groups >12 years of age (P < 0.001). Environmental investigation also confirmed the sewage contamination of drinking water in the distribution system. The attack rate was much higher (29.4%) among those who were exposed to the leaking pipeline than the nonexposed (χ2 = 574.26, P < 0.01).Conclusion:
HEV was confirmed as the major etiological agent in this outbreak that was transmitted by contaminated drinking water. The recognition of early warning signals, timely investigation, and application of specific control measures can contain the outbreak. 相似文献29.
The causative agent of tuberculosis (TB), Mycobacterium tuberculosis and more recently totally drug-resistant strains of M. tuberculosis, display unique mechanisms to survive in the host. A four-drug treatment regimen was introduced 40 years ago but the emergence of multidrug-resistance and more recently TDR necessitates the identification of new targets and drugs for the cure of M. tuberculosis infection. The current efforts in the drug development process are insufficient to completely eradicate the TB epidemic. For almost five decades the TB drug development process remained stagnant. The last 10 years have made sudden progress giving some new and highly promising drugs including bedaquiline, delamanid, and pretomanid. Many of the candidates are repurposed compounds, which were developed to treat other infections but later, exhibited anti-TB properties also. Each class of drug has a specific target and a definite mode of action. These targets are either involved in cell wall biosynthesis, protein synthesis, DNA/RNA synthesis, or metabolism. This review discusses recent progress in the discovery of newly developed and Food and Drug Administration approved drugs as well as repurposed drugs, their targets, mode of action, drug-target interactions, and their structure-activity relationship. 相似文献
30.
Amit Rawat Surjit Singh Deepti Suri Anju Gupta Biman Saikia Ranjana Walker Minz Shobha Sehgal Kim Vaiphei C. Kamae K. Honma N. Nakagawa K. Imai S. Nonoyama K. Oshima N. Mitsuiki O. Ohara Koon-Wing Chan Yu Lung Lau 《Journal of clinical immunology》2014,34(1):58-67
Chronic granulomatous disease (CGD) results from an inherited defect in the phagocytic cells of the immune system. It is a genetically heterogenous disease caused by defects in one of the five major subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. There is a paucity of data from India on CGD. We herein describe the clinical features in 17 children with CGD from a single tertiary referral center in India. A detailed analysis of the clinical features, laboratory investigations and outcome of 17 children 7 with X-linked (XL) and 10 with autosomal recessive (AR) form was performed. Diagnosis of CGD was based on an abnormal granulocyte oxidative burst evaluated by either Nitroblue Tetrazolium (NBT) test or flow cytometry based Dihyrorhodamine 123 assay or both. The molecular diagnosis was confirmed by genetic mutation analysis in 13 cases. The mean age at diagnosis and the age at onset of symptoms was significantly lower in children diagnosed with XL- CGD compared those with AR disease. Mutations were detected in CYBB gene in 6 patients with XL-CGD and NCF-1 gene mutations were observed in 7 cases of AR- CGD. The course and outcome of the disease was much worse in children diagnosed with X-linked form of disease compared to AR forms of the disease; 4/7 (57 %) children with X-CGD were dead at the time of data analysis. This is one of the largest series on chronic granulomatous disease from any developing country. 相似文献