Altered Levels of Serum Zinc and Cadmium in Patients with Chronic Vesiculobullous Hand and Feet Dermatitis

Micronutrients serve many important functions in our body and altered levels of heavy and trace metals are associated with cutaneous and systemic disorders. Vesicular palmoplantar eczema is an entity whose etiopathogenesis is a mystery. In this prospective case-noncase study blood levels of Zinc and Cadmium in 37 patients of chronic vesiculobullous hand dermatitis were estimated and compared with 40 noncases with similar age and gender distributions. Low serum Zinc levels were found in patients as compared to noncases. The mean difference of serum Zinc between the case and noncase groups was 27.26; the mean value of serum Zinc between the two groups was statistically significant ( < 0.0001). However, elevated Cadmium levels were detected in only 5 patients and in none of the noncases. The mean concentration of serum Cadmium was 2.32 ± 0.38 g/dL, with a range of 1.90-2.80 g/dL for the five cases in whom Cadmium was detected. Various toxic and trace metals can interact by influencing each other's absorption, retention, distribution, and bioavailability in the body. The clinical significance of this finding lies in the possible beneficial role of Zinc supplementation in the therapy of chronic vesiculobullous hand dermatitis

The Intervention of tert-Butylhydroquinone Protects Ethanol-Induced Gastric Ulcer in Type-II Diabetic Rats: Role of Nrf2 pathway

Ethanol consumption increases the prevalence of gastric ulcer (GU) in rats with type 2 diabetes (T2D). Induction of GU by absolute ethanol (5 mL/kg or 3.94 g/kg) in the animal model resembles human ulcer characteristics. The aim was to investigate the role of the Nrf2 pathway in the treatment of GU in diabetic condition. The rats were exposed to absolute ethanol before one hour of sacrifice and T2D was induced by combined exposure of high-fat diet and low dose streptozotocin. Pre-treatment of tBHQ (25 and 50 mg/kg), metformin (500 mg/kg) and omeprazole (20 mg/kg) were given once daily for last three consecutive weeks. In ethanol-exposed diabetic rats, pretreatment with tBHQ, omeprazole, and metformin reduced gastric mucosal lesion, ulcer index, histological alterations, MDA level and apoptosis. Further, the intervention of tBHQ, omeprazole and metformin improved the integrity of the stomach mucosa, glutathione, gastric pH, collagen and goblet cells. tBHQ treatment improved ethanol-induced alterations of Nrf2, catalase, HSP70, NF-κB and endothelin-1 expressions in diabetic rats. In diabetic conditions, the incidence of GU is increased due to elevated levels of ROS, inflammatory mediators, depleted levels of cellular antioxidants, altered gastric parameters. The tBHQ intervention could be a rational strategy to protect these changes.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis

The liver injury leads to an inflammatory response, which causes the activation of hepatic stellate cells (HSCs) that further secrete ECM proteins and play an important role in liver fibrosis. Moreover, the inflammatory response is a driving force for fibrogenesis, which is triggered by many types of injuries. Exaggerated inflammatory immune responses are mediated by cytoplasmic protein complexes known as inflammasomes, which are involved in many chronic liver diseases. Inflammasomes are pattern recognition receptors (PRRs) that can sense any microbial motifs known as pathogen-associated molecular patterns (PAMPs), and host- or environmental-derived stress signals known as damage-associated molecular patterns (DAMPs). The inflammasomes cause caspase-mediated proteolytic cleavage of pro-IL-1β and pro-IL-18 into active IL-1β and IL-18. In this review, we provide a comprehensive summary of the important roles of NLRP3 inflammasome in the pathogenesis of liver fibrosis with an emphasis on several direct and indirect pathways responsible for the NLRP3 inflammasome-mediated HSCs activation and fibrogenesis. In addition, we discuss the general pharmacological and genetics strategies for the inhibition of NLRP3 inflammasome activation and its downstream signaling with examples of emerging pharmacotherapeutics, targeting the NLRP3 inflammasome signaling as well as a possible way to develop effective and safer NLRP3 inflammasome inhibitors

Altered Levels of Serum Zinc and Cadmium in Patients with Chronic Vesiculobullous Hand and Feet Dermatitis

Micronutrients serve many important functions in our body and altered levels of heavy and trace metals are associated with cutaneous and systemic disorders. Vesicular palmoplantar eczema is an entity whose etiopathogenesis is a mystery. In this prospective case-noncase study blood levels of Zinc and Cadmium in 37 patients of chronic vesiculobullous hand dermatitis were estimated and compared with 40 noncases with similar age and gender distributions. Low serum Zinc levels were found in patients as compared to noncases. The mean difference of serum Zinc between the case and noncase groups was 27.26; the mean value of serum Zinc between the two groups was statistically significant (p<0.0001). However, elevated Cadmium levels were detected in only 5 patients and in none of the noncases. The mean concentration of serum Cadmium was 2.32±0.38 μg/dL, with a range of 1.90–2.80 μg/dL for the five cases in whom Cadmium was detected. Various toxic and trace metals can interact by influencing each other’s absorption, retention, distribution, and bioavailability in the body. The clinical significance of this finding lies in the possible beneficial role of Zinc supplementation in the therapy of chronic vesiculobullous hand dermatitis

Magnetic resonance spectroscopy imaging-directed transrectal ultrasound biopsy increases prostate cancer detection in men with prostate-specific antigen between 4-10 ng/mL and normal digital rectal examination

Objectives: To evaluate the ability of magnetic resonance spectroscopic imaging to improve prostate cancer detection rate. Methods: A retrospective analysis was carried out of 278 men with prostate-specific antigen in the range of 4–10 ng/mL and normal digital rectal examination who underwent transrectal ultrasound-guided prostate biopsy. Outcomes were compared between men who had a standard biopsy versus those who also underwent a prebiopsy magnetic resonance spectroscopic imaging. Men with an abnormal voxel on magnetic resonance spectroscopic imaging had standard transrectal ultrasound biopsies plus biopsies directed to the abnormal voxels. Results: The study group (n = 140) and control group (n = 138) were similar in baseline parameters, such as mean age, prostate size and mean prostate-specific antigen. The overall cancer detection in the magnetic resonance spectroscopic imaging positive group (24.4%) was more than double that of the control group (10.1%). On comparing the magnetic resonance spectroscopic imaging results with the transrectal ultrasound biopsy findings, magnetic resonance spectroscopic imaging had 95.6% sensitivity, 41.9% specificity, a positive predictive value of 24.4%, a negative predictive value of 98% and an accuracy of 51.4%. Conclusions: Magnetic resonance spectroscopic imaging-directed transrectal ultrasound biopsy increases the cancer detection rate compared with standard transrectal ultrasound biopsy in patients with normal digital rectal examination and elevated prostate-specific antigen in the range of 4–10 ng/mL

Comparative chemical profiling of purified and unpurified Strychnos nux-vomica Linn seeds: An attempt to reduce toxic Brucine content

Vishamusthi (Strychnos nux-vomica Linn.), a medicinal plant described as Upavisha (semi-poisonous) group of Ayurvedic Pharmacopoeia of India. Vishamusthi has widely been used and being practiced in several illness namely nervous debility, paralysis, weakness of limbs, sexual weakness, dyspepsia and etc. Ayurveda practices strictly recommend the use of Vishamusthi in therapeutics only after proper shodhana (purificatory procedure) through specific medias such as Gomutra (cow’s urine), Godugdha (cow’s milk), Goghrita (cow’s ghee), and etc. Although various shodhana procedures are recommended in Ayurvedic treatise, but updated scientific researches regarding the shodhana methods are lacking. The present study was undertaken to investigate the physicochemical and phytochemical parameters, quantitative estimation of brucine using cutting edge research tools such as high-performance thin layer chromatography (HPTLC), liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) analyses of Vishamusthi seeds before and after purification. The remarkable changes have been observed in different physicochemical parameters, HPTLC, HPLC, GC-MS and LC-MS chromatographic profiling before and after shodhana process of Vishamusthi seeds. Quantitative HPLC studies revealed that the process of shodhana resulted in depletion of toxic brucine (chief poisonous constituent of Vishamusthi seeds) reduced to 79.66% in chloroform extract and 64.54% in ethanol extract after shodhana process

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Not AvailableAn absolute or relative deficiency of pancreatic β-cells mass and functionality is a crucial pathological feature common to type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Glucagon-like-peptide-1 receptor (GLP1R) agonists have been the focus of considerable research attention for their ability to protect β-cell mass and augment insulin secretion with no risk of hypoglycemia. Presently commercially available GLP1R agonists are peptides that limit their use due to cost, stability, and mode of administration. To address this drawback, strategically designed distinct sets of small molecules were docked on GLP1R ectodomain and compared with previously known small molecules GLP1R agonist. One of the small molecule PK2 (6-((1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-6H-indolo[2,3-b]quinoxaline) displays stable binding with GLP1R, induces GLP1R internalization and increasing cAMP levels. PK2 also increases insulin secretion in the INS-1 cells. The oral administration of PK2 protects against diabetes induced by multiple low-dose streptozotocin (STZ) administration by lowering high blood glucose levels. Similar to GLP1R peptidic agonists, treatment of PK2 induces β-cell replication and attenuate β-cell apoptosis in STZ treated mice. Mechanistically, this protection was associated with decreased thioredoxin interacting protein (TXNIP) expression, a potent inducer of diabetic β-cell apoptosis and dysfunction. Together, this report describes a small molecule, PK2, as an orally active non peptidic GLP1R agonist that has efficacy to preserve or restore functional β-cell mass.Not Availabl