Phulen Sarma

Therapeutic potential of arachidonyl trifluromethyl ketone, a cytosolic phospholipaseA2 IVA specific inhibitor, in cigarette smoke condensate-induced pathological conditions in alveolar type I & II epithelial cells

Cigarette smoke is responsible for multiple disorders and causes almost 10 million annual deaths globally but underlying mechanisms are still underexplored. Continuous exposure of Cigarette smoke condensate (CSC) leads to cytosolic phospholipase A2 (cPLA2) mediated high free radicals where cPLA2s seems to play crucial role in generated various patho-physiological conditions such as chronic inflammation, oxidative stress and cancer. In this view, we assessed the therapeutic potential of arachidonyl trifluromethyl ketone (ATK), a cPLA2 inhibitor, via pharmacological inhibition of most expressible CSC-induced cPLA2 group IVA in type-I and type-II alveolar epithelial cells. The In Vitro inhibitory effect of ATK on CSC-induced PLA2 activity and its cellular role were assessed in terms of cell viability, fluorescein diacetate (FDA) dye uptake assay for membrane integrity, reactive oxygen species (ROS)/reactive nitrogen species (RNS) levels and pro apoptotic as well as anti apoptosis markers via flow cytometry, along with extracellular signal-regulated kinases (ERK) levels using enzyme-linked immunosorbent assay (ELISA). The experimental findings demonstrated that ATK acts as potent inhibitor of cPLA2 activity and shown its effectiveness as therapeutic agent by significantly mimicking CSC-induced levels of free radicals, primary apoptosis, ratio of pro-apoptotic/apoptotic proteins and levels of ERK whereas protected cells from loss of cell viability and membrane integrity. Thus, this study is an important step towards the opening up of avenues for the applicability of the cPLA2 isoform specific inhibitors such as ATK for pre-clinical and clinical studies and could be beneficial during smoking-induced lung pathological conditions.

Specifically targeted antimicrobial peptides: A new and promising avenue in selective antimicrobial therapy

The human body is colonized by more than 100 trillion microbes, which comprise the human microbiome.[1] The microbiome consists of more than 1000 species of bacteria, and Bacteroidetes and Firmicutes were the dominant phyla. Diversity of gut microbiota is quite huge compared to other body sites, and variation is seen in the gut microbiota constituents even among healthy adult humans.[2] The bacterial mass comprises only 1%–3% of the human body mass. This is because of their small size. Although the comparative mass is less, the number of microbes is 10 times more than the number of human cells.[3]

mHealth technologies in clinical trials: Opportunities and challenges

105 The exponential growth and advancement of mobile and wireless technologies and increasing network coverage and novel opportunities for integration in the existing health systems have fueled the rapid development of mobile health technologies for the promotion of quality health care. The scope of digital health, as per the US Food and Drug Administration, includes mobile health – mHealth, information technology, wearables, telehealth, telemedicine, and personalized medicine.[1] As defined by the World Health Organization Global Observatory for eHealth, mHealth – a component of eHealth – is a medical and public health practice assisted by mobile devices such as cellular phones including smartphones, monitoring devices, personal digital assistants, and other wireless technologies.[2] The practice of mHealth relies on device’s core as well as advanced utilities and applications including voice communications, text messaging, third‐ and fourth‐generation (3G and 4G) mobile broadband technologies, Bluetooth, and global positioning system (GPS) among others. The use of mobile devices has progressively become ubiquitous and increasingly indispensable in our day‐to‐day lives. Since 2014, mobile devices have outnumbered the world population, with the former multiplying at rates five times that of the latter.[3] Going by the projections, by 2021, there will be 1.5 mobile devices per capita, amounting to a total of 11.6 billion devices, and the average mobile connection speed globally will be >20 megabits/s.[4] Pew Research Center reports increasing rates of Internet usage and smartphone ownership in emerging and developing nations.[5] Between 2013 and 2015, the median smartphone ownership rates nearly doubled in emerging countries. The worldwide mobile health app market has been estimated to be valued at 28.32 billion USD in 2018 and is projected to reach a value in excess of 100 billion in the next 5 years.[6]

CYP2E1 activity and children with obesity: possible confounding factors: CYP2E1 activity and children with obesity: possible confounding factors

Lots of factors can influence CYP2E1 activities, e.g. thyroid status, different types of anaemia (fanconi anaemia and sideroblastic anaemia), etc. Alcohol is a known inducer of CYP2E1, therefore a justifiable duration of abstinence is required before the subjects are enrolled into a study for normalization of CYP2E1 activity. In this letter we address these confounding factors and their role in CYP2E1 activity.

Terlipressin-induced peripheral ischemic gangrene in a diabetic patient

Terlipressin is used commonly in the management of hepatorenal syndrome and acute variceal bleeding. Like its parent compound vasopressin, it is also notorious for its ischemic complications. Terlipressin-induced ischemic complications can virtually affect any part of the body, but the incidence of serious complications is less than its parent compound vasopressin. Here, we report a case of terlipressin-induced peripheral ischemic gangrene in a diabetic male, which ultimately led to death of the patient.

Are your capsules vegetarian or nonvegetarian: An ethical and scientific justification

Capsules are important component of day to day health management. But recently an issue came up whether the capsule you are using is of vegetarian or non-vegetarian origin. Capsule shell can be divided into vegetarian and non-vegetarian origin on the basis of their origin. Gelatin capsule shell are typically of animal origin and HPMC or starch based shells are of vegetarian origin. CDSCO received one proposal to replace all non veg capsule with capsule of vegetarian origin. CDSCO has invited comments from different stakeholders regarding this. So, in this editorial, we are addressing different issues lying behind veg and non-veg capsules and scientific justification of the same.

Congenital malformation and autism spectrum disorder: Insight from a rat model of autism spectrum disorder

AIMS AND OBJECTIVES: The primary aim was an evaluation of the pattern of gross congenital malformations in a rat model of autism spectrum disorder (ASD) and the secondary aim was characterization of the most common gross malformation observed. MATERIALS AND METHODS: In females, the late pro-oestrous phase was identified by vaginal smear cytology, and then, they were allowed to mate at 1:3 ratio (male: female). Pregnancy was confirmed by the presence of sperm plug in the vagina and presence of sperm in the vaginal smear. In the ASD group, ASD was induced by injecting valproic acid 600 mg/kg (i.p.) to pregnant female rats (n = 18) on day 12.5 (single injection). Only vehicle (normal saline) was given in the control group (n = 12). After delivery, pups were grossly observed for congenital malformations until the time of sacrifice (3 months) and different types of malformations and their frequency were noted and characterized. RESULTS: In the ASD group, congenital malformation was present in 69.9% of the pups, whereas in the control group, it was 0%. Male pups were most commonly affected (90% in males vs. only 39.72% in female pups). The tail deformity was the most common malformation found affecting 61.2% pups in the ASD group. Other malformations observed were dental malformation (3.82%), genital malformation (3.28%) and paw malformation (1.1%). Hind limb paralysis was observed in one pup. The tail anomalies were characterized as per gross appearance and location of the malformation. CONCLUSION: In this well-validated rat model of ASD, congenital malformation was quite common. It seems screening of congenital malformations should be an integral part of the management of ASD, or the case may be vice versa, i.e., in the case of a baby born with a congenital deformity, they should be screened for ASD.

Development in Assay Methods for in Vitro Antimalarial Drug Efficacy Testing: A Systematic Review

The emergence and spread of drug resistance are the major challenges in malaria eradication mission. Besides various strategies laid down by World Health Organization, such as vector management, source reduction, early case detection, prompt treatment, and development of new diagnostics and vaccines, nevertheless the need for new and efficacious drugs against malaria has become a critical priority on the global malaria research agenda. At several screening stages, millions of compounds are screened (1,000–2,000,000 compounds per screening campaign), before pre-clinical trials to select optimum lead. Carrying out in vitro screening of antimalarials is very difficult as different assay methods are subject to numerous sources of variability across different laboratories around the globe. Despite this, in vitro screening is an essential part of antimalarial drug development as it enables to resource various confounding factors such as host immune response and drug–drug interaction. Therefore, in this article, we try to illustrate the basic necessity behind in vitro study and how new methods are developed and subsequently adopted for high-throughput antimalarial drug screening and its application in achieving the next level of in vitro screening based on the current approaches (such as stem cells).