Protein tyrosine phosphatase 1B inhibitors as antidiabetic agents - A brief review.

Diabetes mellitus and obesity are one of the most common health issues spread throughout world and raised the medical attention to find the new effective agents to treat these disease state. Occurrence of the drug resistance to the insulin and leptin receptor is also challenging major issues. The molecules that can overcome this resistance problem could be effective for the treatment of both type II diabetes and obesity. Protein Tyrosine Phosphatase (PTP) has emerged as new promising targets for therapeutic purpose in recent years. Protein Tyrosine Phosphatase 1B (PTP 1B) act as a negative regulator of insulin and leptin receptor signalling pathways. Several approaches have been successfully applied to find out potent and selective inhibitors. This article reviews PTP 1B inhibitors; natural, synthetic and semi-synthetic that showed inhibition towards enzyme as a major target for the management of type II diabetes. These studies could be contributing the future development of PTP 1B inhibitors as drugs.

Geochemical evaluation and the mechanism controlling groundwater chemistry using chemometric approach and groundwater pollution index (GPI) in the Kishangarh city of Rajasthan, India.

This study is primarily focused on delving into the geochemistry of groundwater in the Kishangarh area, located in the Ajmer district of Rajasthan, India. In pursuit of this research goal, the sampling locations were divided into three parts within the Kishangarh region: Badgaon Rural (KSGR), Kishangarh Urban (KSGU), and the Kishangarh RIICO marble industrial area (KSGI). Various analytical methods have been executed to assess the suitability of groundwater for various purposes based on pH, electric conductivity, total dissolved solids, hardness, salinity, major anions, and cations. The ionic trend of anions and cations was found as HCO3- > Cl- > SO42- > NO3- > Br- > NO2- > F- and Na+ > Ca2+ > Mg2+ > K+, respectively. Applying statistical techniques such as principal component analysis (PCA) and Pearson correlation matrix analysis (PCMA) makes it evident that the physicochemical attributes of water sourced from the aquifers in the study area result from a blend of diverse origins. In addition, Gibbs, Piper, Durov, and scatter plots were used to assess groundwater's geochemical evolution. Piper plot demonstrated the two types of groundwater facies, Na-HCO3- and Na-Cl, implying significant contributions from evaporitic dissolution and silicate weathering. Also, the scatter plots have evaluated the impression of mine acid leachate, evaporitic dissolution, and silicate weathering to upsurge salt formation in the groundwater. The pollution risk evaluation within the study area was conducted using the groundwater pollution index (GPI). This index revealed a prominent concern for pollution, particularly in the northern segment of the study region. As a result, it can be inferred that the fine aeolian sand and silt formations in the northern part are relatively more vulnerable to contamination.

Reactivation of Tuberculosis in the Setting of COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) was declared a pandemic by WHO in March 2020. The causative organism has since undergone a series of mutations. COVID-19 primarily being a respiratory illness causes pre-existing pulmonary diseases to show worse clinical outcomes. About one-third of the world's population is thought to be infected with latent Mycobacterium tuberculosis (MTB). Both previous and newly developed tuberculosis (TB) infection are risk factors for COVID-19 and are associated with poor outcomes. T lymphocytes play a pivotal role in defense against MTB and with evidence suggesting depletion of T lymphocytes in COVID-19, it can be postulated that COVID-19 can increase the risk of reactivation of latent TB.  Given that a large population around the globe is infected with latent tuberculosis, it is interesting to study and note cases where the virus leads to the reactivation of latent tuberculosis infection. Herein, we present a 76-year-old Brazilian male recently treated for COVID-19 pneumonia, presenting with new-onset cough and weakness diagnosed with latent MTB reactivation.

A Rare Yet Morbid Complication of Endotracheal Intubation: Tracheal Rupture.

Tracheal tears are an uncommon phenomenon that can occur due to infection, blunt or penetrating trauma or iatrogenic causes secondary to endotracheal intubation or procedures such as bronchoscopy. Post-intubation tracheal laceration is a very rare yet serious complication with high morbidity and mortality rates. Here, we report the case of a 53-year-old woman with a medical history of hypertension who presented with complaints of facial swelling after undergoing arthroscopic debridement of the coracoacromial ligament as well as partial resection of the acromion for impingement of the right shoulder under general anaesthesia. The patient was found to have extensive pneumomediastinum, subcutaneous emphysema, and a large tracheal tear. We aim to highlight this rare complication of endotracheal intubation, discuss the presenting signs and symptoms, and explore the various management options. LEARNING POINTS: Iatrogenic tracheal laceration after intubation is a rare but life-threatening complication.Prompt recognition and treatment is required to reduce morbidity and mortality.

Vasopressor-Induced Digital Ischemia.

In patients who are critically ill and in circulatory shock, substantial dosages of vasopressors including norepinephrine and Neosynephrine are often required to sustain blood pressure. While these medications are necessary and can be lifesaving, they are often associated with several complications related to severe vasoconstrictions. One of these known but underreported side effects is digital ischemia (DI). DI refers to a decrease in digital perfusion. It is a rare and uncommon phenomenon that can lead to significant consequences and unfortunately can result in amputation of the digits. Herein, we report an unfortunate female with septic shock secondary to acute bowel ischemia who developed bilateral digital necrosis while on norepinephrine.

Detection of African genotype in Hyalomma tick pools during Crimean Congo hemorrhagic fever outbreak, Rajasthan, India, 2019.

Crimean Congo hemorrhagic fever (CCHF) is a zoonotic viral disease presenting with fever and hemorrhagic manifestations in humans. After several outbreaks of CCHF being reported from Gujarat since 2011 till 2019 and from Rajasthan in 2014 and 2015, the present study reports the CCHF outbreak which was recorded from five human cases in three districts Jodhpur, Jaisalmer, and Sirohi of Rajasthan state since August 2019 till November 2019. A high percent of positivity was recorded in livestock animal samples for the CCHFV IgG antibody. CCHF virus (CCHFV) positive human blood samples and Hyalomma tick pool samples were sequenced using next-generation sequencing method. Two different M segment genotypes, encoding glycoprotein precursor, were identified from tick pools in the study: first from Asian and second from African lineage. The L gene (polymerase) and the S gene (nucleocapsid) clustered in the Asian lineage. The present study illustrates the existence of two different CCHFV lineages being circulating within the Hyalomma tick pools in the Rajasthan state, India. We also observed 3.56% amino acid changes between the death and the survived case of CCHFV in the M gene. This report also sets an alarm to enhance human, tick and livestock surveillance in other districts of Rajasthan and nearby states of India. Biosafety measures, barrier nursing along with the availability of personal protective equipment and ribavirin drug will always be a mainstay in preventing nosocomial infection for proper case management.

Platelet-activating factor (PAF)-antagonists of natural origin.

Presently herbal medicines are being used by about 80% of the world population for primary health care as they stood the test of time for their safety, efficacy, cultural acceptability and lesser side effects. The discovery of platelet activating factor antagonists (PAF antagonists) during these decades are going on with different framework, but the researchers led their efficiency in studying in vitro test models. Since it is assumed that PAF play a central role in etiology of many diseases in humans such as asthma, neuronal damage, migraine, cardiac diseases, inflammatory, headache etc. Present days instinctively occurring PAF antagonist exists as a specific grade of therapeutic agents for the humans against these and different diseases either laid hold of immunological or non-immunological types. Ginkgolide, cedrol and many other natural PAF antagonists such as andrographolide, α-bulnesene, cinchonine, piperine, kadsurenone, different Piper species' natural products and marine origin plants extracts or even crude drugs having PAF antagonist properties are being used currently against different inflammatory pathologies. This review is an attempt to summarize the data on PAF and action of natural PAF antagonists on it, which were evaluated by in vivo and in vitro assays.

Role of PPARg2 transcription factor in thiazolidinedione-induced insulin sensitization.

OBJECTIVES: Adipose tissue is the key regulator of energy balance, playing an active role in lipid storage and metabolism and may be a dynamic buffer to control fatty acid flux. Peroxisome proliferator-activated receptor gamma isoform-2 (PPARg2), an isoform of the nuclear hormone receptor superfamily, has been implicated in almost all aspects of human metabolic alterations such as obesity, insulin resistance, type-2 diabetes and dyslipidaemia. The PPARg2 isoform is highly present in adipose tissue where it functions as a thrifty phenotype, which promotes adipocyte differentiation and triglyceride storage. Thiazolidinediones, antidiabetic drugs, induce insulin sensitivity by controlling adipokines. The thiazolidinediones bind with PPARg2 in adipocytes and exert an agonist effect by enhancing adipogenesis and fatty acid uptake. Thiazolidinediones stimulate PPARg2, by which they down-regulate tumour necrosis factor-α, leptin, interleukin-6 and plasminogen and also enhance insulin sensitivity. The aim of this work is to define role of PPARg2 transcription factor in thiazolidinedione-induced insulin sensitization. KEY FINDINGS: The PPARg2 alters the transcription of the target gene. This altered gene transcription results in the up-regulation of insulin-sensitizing factors and down-regulation of insulin-resistant factors. The variant Pro12Ala of the PPARg2 gene is an important modulator in metabolic control in the body. Thiazolidinediones stimulate PPARg2 transcription factor by which PPARg2 binds to responsive elements located in the promoter regions of many genes and modulates their transcriptive activity. There is a strong mutual relationship between receptor binding and agonism, which is evidence of the insulin-sensitizing target of thiazolidinediones in PPARg2. This evidently increases the biological potency of the glucose-lowering effect of thiazolidinediones in vivo as well as their antidiabetic activity. CONCLUSIONS: PPARg2 transcription factor plays an important role in treatment of type-2 diabetes with thiazolidindiones. The variant Pro12Ala of the PPARg2 gene promotes the activity of thiazolidinediones in minimizing insulin resistance. Transcriptional activity of Pro12Ala variant improves the activity of insulin. Thus thiazolidinediones promote the phosphorylation of PPARg2 to induce insulin sensitivity.

Role of fetuin-A in atherosclerosis associated with diabetic patients.

OBJECTIVES: Fetuin-A is a circulating glycoprotein, formed in the liver. It regulates bone remodelling and calcium metabolism. Fetuin-A has adipogenic properties, so fat accumulation in the liver may be associated with higher levels of fetuin-A. Fetuin-A is an inhibitor of the phosphorylation of the insulin receptor tyrosine kinase. KEY FINDINGS: High concentrations of fetuin-A in humans causes insulin resistance. Insulin sensitivity is also found to be increased in fetuin-A knockout mice. Fetuin-A has been shown to cause insulin resistivity in type-2 diabetes mellitus and worsens the pro-atherogenic milieu. SUMMARY: Fetuin-A should be considered as a hepatic bio-marker. Vascular diseases like atherosclerosis are major causes of disability in patients with diabetes mellitus.

The target-specific transporter and current status of diuretics as antihypertensive.

The currently available diuretics increase the urinary excretion of sodium chloride by selective inhibition of specific sodium transporters in the loop of Henle and distal nephron. In recent years, the molecular cloning of the diuretic-sensitive sodium transporters at distal convoluted tubule has improved our understanding of the cellular mechanisms of action of each class of diuretics. Diuretics are tools of considerable therapeutic importance. First, they effectively reduce blood pressure. Loop and thiazide diuretics are secreted from the proximal tubule via the organic anion transporter-1 and exert their diuretic action by binding to the Na(+)-K(+)-2Cl(-) co-transporter type 2 in the thick ascending limb and the Na(+)-Cl(-) co-transporter in the distal convoluted tubule, respectively. Recent studies in animal models suggest that abundance of these ion transporters is affected by long-term diuretic administration. The WHO/ISH guidelines point out that diuretics enhance the efficacy of antihypertensive drugs and will most often be a component of combination therapy.

Wound-healing activity of ethanolic and aqueous extracts of Ficus benghalensis.

Wound healing is the process of repair that follows injury to the skin and other soft tissues. Following injury, an inflammatory response occurs and the cells below the dermis (the deepest skin layer) begin to increase collagen (connective tissue) production. Later, the epithelial tissue (the outer skin) is regenerated. There are three stages to the process of wound healing: inflammation, proliferation, and remodeling. Traditionally, Ficus benghalensis is used for wound healing. Since no detailed scientific data are available regarding the wound-healing activity of F. benghalensis, the present study was designed to explore the same. The wound-healing efficacy of ethanolic and aqueous extracts of F. benghalensis was evaluated in excision and incision wound models. The parameters studied include rate of wound contraction, period of complete epithelialization, and tensile strength of incision wound. Student's t test was used to analyze the results obtained from the present study and P<0.05 was considered significant. Both the ethanolic and aqueous extracts of F. benghalensis were found to possess significant wound-healing activity, which was evidenced by decrease in the period of epithelialization, increase in the rate of wound contraction and skin-breaking strength. The present study has demonstrated that the ethanolic and aqueous extracts of F. benghalensis have properties that render them capable of promoting accelerated wound-healing activity compared with placebo control.

Anti-inflammatory activity of aqueous extract of Beta vulgaris L.

The present study deals with the investigation of phytochemically evaluated aqueous extract of leaves of Beta vulgaris for its anti-inflammatory activity. The anti-inflammatory activity was evaluated by carrageenan induced rat paw oedema method for acute inflammation and cotton pellet granuloma method for chronic inflammation. The standard drug used was indomethacin (10 mg/kg) for both the models. In both methods, aqueous extract at a dose level of 1000 mg/kg has shown significant activity which is comparable to that of the standard.

Ocular inserts - Advancement in therapy of eye diseases.

The ocular insert represents a significant advancement in the therapy of eye disease. Ocular inserts are defined as sterile, thin, multilayered, drug-impregnated, solid or semisolid consistency devices placed into the cul-de-sac or conjuctival sac, whose size and shape are especially designed for ophthalmic application. They are composed of a polymeric support that may or may not contain a drug. The drug can later be incorporated as dispersion or a solution in the polymeric support. They offer several advantages as increased ocular residence and sustained release of medication into the eye. The insert includes a body portion sized to position within a lachrymal canaliculus of the eyelid. The inserts are classified according to their solubility as insoluble, soluble, or bioerodible inserts. The release of drug from the insert depends upon the diffusion, osmosis, and bioerosion of the drug, and this article is an attempt to present a brief about this newer drug delivery system.