Computational binding mechanism of Mycobacterium tuberculosis UDP-NAG enolpyruvyl transferase (MurA) with inhibitors fosfomycin, cyclic disulfide analog RWJ-3981, pyrazolopyrimidine analog RWJ-110192, purine analog RWJ-140998, 5-sulfonoxy-anthranilic aci

Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. One-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), the etiologic agent of TB. In this context, TB is in the top three, with malaria and HIV being the leading causes of death from a single infectious agent, and about two million deaths are attributable to TB annually. The bacterial enzyme MurA catalyzes the transfer of enolpyruvate from phosphoenolpyruvate (PEP) to uridine diphospho-N-acetylglucosamine (UNAG), which is the first committed step of bacterial cell wall biosynthesis. In this work, 3D structural model of Mtb-MurA enzyme has been developed, for the first time, by homology modeling and molecular dynamics simulation techniques. The model provided clear insight in its structure features, i.e. substrate binding pocket, and common docking site. Multiple sequence alignment and 3D structure model provided the putative substrate binding pocket of Mtb-MurA with respect to E.coli MurA. This analysis was helpful in identifying the binding sites and molecular function of the MurA homologue. Molecular docking study was performed on this 3D structural model, using different classes of inhibitors like fosfomycin, cyclic disulfide analog RWJ-3981, pyrazolopyrimidine analog RWJ-110192, purine analog RWJ-140998, 5-sulfonoxy-anthranilic acid derivatives T6361, T6362 and the results showed that the 5-sulfonoxyanthranilic acid derivatives is showed best interaction compared with other inhibitor, taking in to this we also design a new efficient analogs of T6361 and T6362 which are showed even better interaction with Mtb-MurA than the parental5-sulfonoxy-anthranilic acid derivatives. Further the comparative molecular electrostatic potential and cavity depth analysis of Mtb-MurA suggested several important differences in its substrate and inhibitor binding pocket. Such differences could be exploited in the future for designing of a more specific inhibitor for Mtb-MurA enzym

A retrospective study on endometrial patterns in abnormal uterine bleeding

Background: To determine the type of endometrial patterns of the different age categories of women who presented as a case of abnormal uterine bleeding.Methods: This is a retrospective study conducted on 105 patients who presented with abnormal uterine bleeding who underwent fractional curettage in our hospital. The data on their age, presenting complaints, and comorbidities of all the women were collected. The patterns of endometrial changes were studied and classified.Results: The most common histopathological findings were anovulatory shedding (34.3%) and irregular shedding (18.1%). The other findings include irregular ripening, papillary endocervicitis, endocervicitis, pill endometrium, atrophic endometrium, squamous metaplasia, and endometrial hyperplasia. The most common malignant change seen was endometrioid carcinoma which was seen in women over 40 years of age.Conclusions: Histopathological examination of the endometrium shows a clear-cut differentiation between physiological and malignancy changes in the endometrium. Hence, endometrial sampling is considered the golden tool for accurate analysis of the endometrium

Assessment of drug hypersensitivity with non-irritating concentrations of antibacterial agents for allergic skin tests: a review

Hypersensitivity reactions to antibiotics are common with a prevalence of 6-10% of all adverse reactions. There is a lack of guidelines and standardization of skin tests for the screening of hypersensitivity to all antibiotics, in terms of the methodology, dose and time of evaluation of the tests. Literature from Europe and America suggests the use of non-irritating concentration (NIC) of antibiotics for skin testing such as intra dermal test (IDT), skin prick test (SPT). These are concentrations at which the drug is unlikely to produce irritation by virtue of its chemical nature resulting in false positive reactions. These concentrations have been validated by trials in their populations. Due to the increase of antibiotic resistance in our country, declaring a patient allergic to a specific class of antibiotics based on positive skin tests can further narrow the therapeutic armory. These individuals have an increased incidence of infections with resistant organisms as well as increased cost of hospitalization. This is due to the use of alternative broad spectrum antibiotics. Therefore, there is a need for a standardized protocol for the use of skin tests in screening of hypersensitivity, with validated NIC of all antibacterial agents. The aim of this article is to review literature of protocols for assessment of drug hypersensitivity with NIC of antibacterial drugs for SPT, IDT and also establish the need for research in this area in our country

Pattern of management and outcome of dengue fever in pediatric in-patients in a tertiary care hospital: a prospective observational study

Background: Dengue is one of the most important mosquito borne viral diseases presenting with varied symptomatology. A broad-angled evaluation with integration of clinical and laboratory parameters would direct the physicians through the stages of the disease process and the line of management. The objectives were to identify the pattern of management of dengue fever in pediatric in-patients and to assess the outcome.Methods: A prospective observational study was carried out in pediatric inpatients. Data were collected by intensive case record review. Patients of age group 1-18 years of both genders diagnosed of dengue fever were included. The prescribing pattern in children presenting at various stages of dengue fever was analyzed. The outcome was assessed in terms of course in hospital and duration of hospital stay.Results: A total of 110 patients diagnosed with dengue fever with one or more warning signs were admitted during the study period. Thirty percent cases had liver enzymes more than 3 times the normal and 68% patients had platelet count <1,00,000/cumm. Two cases of dengue encephalitis were reported. Most common intravenous fluid given was ringer lactate followed by isolyte P and others. Most common antibiotic prescribed was ceftriaxone followed by ampicillin and others. The symptomatic treatment given consisted of paracetamol, anti-acidity drugs and anti-emetic drugs. Vitamin K was prescribed to 41% and zinc and folic acid supplements were prescribed to 30% children. There was no correlation found between vitamin K and outcome of the disease.Conclusion: Antibiotics and vitamin K though not a part of standard World Health Organization guidelines was seen to be an important part of management. Supportive care with judicious fluid management during the critical and recovery period with continuous monitoring is required for all patients. Further comparative studies are needed to establish the role of antibiotics and other supportive measures like zinc and folic acid on the outcome of the disease

Integrin-mediated mechanotransduction pathway of low-intensity continuous ultrasound in human chondrocytes

Chondrocytes are mechanosensitive cells that require mechanical stimulation for proper growth and function in in vitro culture systems. Ultrasound (US) has emerged as a technique to deliver mechanical stress; however, the intracellular signaling components of the mechanotransduction pathways that transmit the extracellular mechanical stimulus to gene regulatory mechanisms are not fully defined. We evaluated a possible integrin/mitogen-activated protein kinase (MAPK) mechanotransduction pathway using Western blotting with antibodies targeting specific phosphorylation sites on intracellular signaling proteins. US stimulation of chondrocytes induced phosphorylation of focal adhesion kinase (FAK), Src, p130 Crk-associated substrate (p130Cas), CrkII, and extracellular-regulated kinase (Erk). Furthermore, pre-incubation with inhibitors of integrin receptors, Src, and MAPK/Erk kinase (MEK) reduced US-induced Erk phosphorylation levels, indicating integrins and Src are upstream of Erk in an US-mediated mechanotransduction pathway. These findings suggest US signals through integrin receptors to the MAPK/Erk pathway via a mechanotransduction pathway involving FAK, Src, p130Cas, and CrkII

Presence of Phytol, a Precursor of Vitamin E in Chaetomorpha Antinnina

Phytol, a precursor of vitamin E was identified from green algae Chaetomorpha antinnina collected from Chullickal, Kochi Kerala coast, using GC-MS. Phytol is an acyclic diterpene alcohol that can be used as a precursor for the manufacture of synthetic forms of vitamin E and vitamin K1. The compound 3,7,11,15-tetramethylhexadec-2-en-1-ol also known as phytol  which exist  naturally only in single isomeric form having molecular formula C20H40O and molecular mass 296. From the total ion chromatogram more than twenty peaks were observed, the mass spectrum of the peak at Rt 21.53 was resolved and the major fragmentations were noted. Major fragmentation were m/z 71 the base peak, m/z 296 the molecular ion peak, m/z 43, m/z 57, m/z 81, m/z 95, and m/z 123. It was found that there are some other compounds apart from this identified phytol which are more complicated in structure and cannot be characterised using GC-MS. Phytol is reported to have both antimicrobial and anticancer activities. The green algae Chaetomorpha antinnina can be proposed to be a good natural source for production of phytol

A Comprehensive Survey of Deep Learning: Advancements, Applications, and Challenges

Artificial intelligence's "deep learning" discipline has taken off, revolutionizing a variety of industries, from computer vision and natural language processing to healthcare and finance. Deep learning has shown extraordinary effectiveness in resolving complicated issues, and it has a wide range of potential applications, from autonomous vehicles to healthcare. The purpose of the survey to study deep learning's present condition, including recent advancements, difficulties, and constraints since the subject is currently fast growing. The basic ideas of deep learning, such as neural networks, activation functions, and optimization algorithms, are first introduced. We next explore numerous topologies, emphasizing their distinct properties and uses, including convolutional neural networks (CNNs), recurrent neural networks (RNNs), and generative adversarial networks (GANs). Further concepts, applications, and difficulties of deep learning are all covered in this survey paper's thorough review. This survey aid the academics, professionals, and individuals who want to learn more about deep learning and explore its applications to challenging situations in the real world

Stability Studies of Crude Plant Material of Bacopa monnieri and Its Effect on Free Radical Scavenging Activity

Stability study of the crude plant material of Bacopa monnieri has been carried out as per ICH guidelines and its effect on free radical scavenging activity was studied by DPPH, ABTS radical scavenging assays and Deoxyribose degradation assay. The dried whole plant material of B. monnieri was kept in stability chambers at 40°C and 75% relative humidity in case of accelerated studies and at 30°C and 65% relative humidity for long term studies. Real time studies samples were stored at room temperature. Samples were taken out at periodic intervals, extracted in methanol to observe the HPTLC profiles and to study free radical scavenging activity. Results of antioxidant assays indicated that the samples of long term studies showed better antioxidant activity than the samples of accelerated and real time studies. Key words: Brahmi; accelerated study; long term study; real time study; free radical scavenging activity Abbreviations: BM: Bacopa monnieri; AS: Accelerated studies; LS: Long term studies; RT Real time studiesPratibha Srivastava et al. Stability Studies of Crude Plant Material of Bacopa monnieri and Its Effect on Free Radical Scavenging Activity. J Phytol 2/8 (2010) 103-109