Hyaluronan-based nano-formulation with mesoporous silica enhances the anticancer efficacy of phloroglucinol against gastrointestinal cancers.

Gastrointestinal cancers are one among the most frequently reported cancers where colorectal and gastric cancers ranks third leading cause of cancer related death worldwide. Phloroglucinol, a well-known therapeutic agent for cancer, where its usage has been limited due to its poor water solubility and bioavailability. Hence, our study aims to synthesize and characterize Hyaluronan grafted phloroglucinol loaded Mesoporous silica nanoparticles (MSN-PG-HA). Our nano-formulation hasn't shown any teratogenic effect on Zebrafish embryos, no hemolysis and toxic effect with normal fibroblast cells with a maximum concentration of 300 µg/mL. The cumulative drug release profile of MSN-PG-HA showed a maximum drug release of 96.9 % with 5 mM GSH under redox responsive drug release, which is crucial for targeting cancer cells. In addition, the MSN-PG-HA nanoparticles showed significant a cytotoxic effect against HCT-116, AGS and SW-620 with IC50 values of 86.5 µg/mL, 80.65 µg/mL and 109.255 µg/mL respectively. Also, the cellular uptake assay has shown an increased uptake of FITC-labeled-MSN-PG-HA by HA-receptor mediated endocytosis than FITC-labeled-MSN-PG without HA modification in CD44+ gastrointestinal cancer cell lines. The ability of MSN-PG-HA to target CD44+ cells was further exploited for its application in cancer stem cell research utilizing in silico analysis with various stem cell pathway related targets, in which PG showed higher binding affinity with Gli 1 and the simulation studies proving its effectiveness in disrupting the protein structure. Thus, the findings of our study with nano-formulation are safe and non-toxic to recommend for targeted drug delivery against gastrointestinal cancers as well as its affinity towards cancer stem cell pathway related proteins proving to be a significant formulation for cancer stem cell research.

Feasibility of Using Ceftazidime-Avibactam as a Therapeutic Option for Bloodstream Infections Caused by Multidrug-Resistant Enterobacterales and Pseudomonas aeruginosa Based on Its Susceptibility Profile.

Background In the era of increased antimicrobial resistance, there are limited therapeutic options available for the treatment of bacteremia caused by multidrug-resistant organisms (MDROs). This study aims to find out the feasibility of using ceftazidime/avibactam (CZA) as a therapeutic option for bloodstream infections caused by multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa based on its susceptibility profile. Materials and methods The isolates were routinely subjected to antimicrobial susceptibility testing (AST) by an automated AST system (VITEK-2). Those isolates found as MDR (resistant to at least one drug for ≥3 antimicrobial classes) were tested against CZA by Kirby-Bauer's disk diffusion (kb-DD) method. Results A total number of 293 MDR Enterobacterales and 31 MDR P. aeruginosa isolates were included. Of these, 87.3% of isolates were found as carbapenem-resistant (CR), whereas 12.7% of isolates were found as carbapenem susceptible. About 30.6% of MDROs were susceptible to CZA. Among carbapenem-resistant organisms (CROs), CR Klebsiella pneumoniae(33.5%) is most susceptible to CZA, compared to CR P. aeruginosa(0%)and CREscherichia coli(3.2%). Among the MDR isolates that were susceptible to CZA (30.6%), the majority had poor susceptibility against other ß-lactam-ß-lactamase inhibitor (BL-BLI) agents. Among all antimicrobial agents tested against CROs, colistin (96%) was found to have the best susceptibility profile. Conclusion It is observed that CZA is an acceptable therapeutic option for the treatment of bacteremia caused by MDROs, especially CROs. Therefore, it is important for the laboratories to perform the AST for CZA if the healthcare settings intend to use CZA for the management of such "difficult-to-treat" bloodstream infections.

Bacteriuria due to Typhoidal and Nontyphoidal Salmonella: A Report of Three Cases from South India.

Urinary tract infection (UTI) with Salmonella is uncommon, accounting for merely 0.01% to 0.1% of cases of UTIs. It is reported more frequently in the presence of predisposing factors such as structural abnormalities of the urinary tract or weakened immune system. We present a case series of three patients with Salmonella bacteriuria and their susceptibility patterns. All three patients had underlying urologic features such as neurogenic bladder, chronic kidney disease, and urethral stricture, and two presented with urinary tract involvement symptoms.

The effect of hand hygiene audit in COVID intensive care units in a tertiary care hospital in South India.

BACKGROUND: In the era of COVID-19 pandemic, there is an upsurge of healthcare-associated infections (HAI) in COVID intensive care units (ICUs), which can be reduced by following proper hand hygiene (HH) practice. Performing HH auditing in COVID ICU and providing timely feedback to the stake holders is crucial to reduce HAIs. METHODS: From November 2020- April 2021, HH audit was conducted in COVID ICUs. HH complete adherence rate (HHCAR), HH partial adherence rate (HHPAR) and HH total adherence rate (HHTAR) were analyzed. Profession-specific HHTAR and moment-specific HHTAR (for each WHO moment) were also calculated. RESULTS: HHCAR, HHPAR and HHTAR were found as 30.8%, 34.5% and 65.3% respectively. There was a significant increase in the monthly HHTAR from 26.7% to 68.4% (P < .001). The profession-specific HHAR was found to be highest among doctors (67.5%) and nurses (66.4%). As the HHTAR increases there is a significant decrease in device associated infection (DAI) rate from 24.7 to 11.5 per 1,000 device days. CONCLUSIONS: Auditing HH and providing timely feedback significantly improved HH compliance. The need of the hour is to regularly conduct HH audit in COVID locations of all healthcare facilities to reduce HAI rate among the COVID- 19 infected patients in ICUs.

A Rare Case Report of Non-toxigenic Corynebacterium diphtheriae Bloodstream Infection in an Uncontrolled Diabetic With Peripheral Vascular Disease.

Corynebacterium diphtheriae usually causes respiratory diphtheria, which is considered as a disease of toxemia but never bacteremia. Over the last few decades, cutaneous diphtheria has been increasingly reported owing to the emergence of the non-toxigenic strain, which causes locally necrotic and ulcerative lesions. Bacteremia is very rare, but the existing evidence in the literature suggests that the organism can rarely cause invasive infections such as septicemia, endocarditis, and osteoarthritis. Here, we present a rare case of C. diphtheriae causing bloodstream infections in an elderly diabetic with peripheral vascular disease, which was diagnosed incidentally on routine blood culture owing to automated identification systems viz matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) confirmed with conventional methods, and susceptibility was performed using automated VITEK 2 system (BioMérieux, Marcy-l'Étoile, France), which has aided in the timely management.

Taurine enhances the metabolism and detoxification of ethanol and prevents hepatic fibrosis in rats treated with iron and alcohol.

The study examines the effects of taurine on the metabolism and detoxification of ethanol in liver fibrosis induced by simultaneous administration of iron carbonyl (0.5%, w/w) and ethanol (6g/(kgday)). Ethanol and iron administration caused liver damage and fibrosis as evidenced by liver histology and biochemical profile in plasma. Over accumulation of iron and a loss in taurine in hepatic tissue was observed in fibrotic animals. The activities of alcohol dehydrogenase and aldehyde dehydrogenase were significantly reduced in these rats compared to control. Adaptive induction of activities of Cytochrome P4502E1 (CYP2E1) and aniline hydroxylase accompanied by the reduction in glutathione-S-transferase, DT-diaphorase and glyoxalases I and II was observed. Taurine administration (2% in drinking water) ameliorated the effects of ethanol and iron. Hepatic damage and fibrosis were reduced in taurine-supplemented rats. Thus taurine has the potential for the treatment of alcoholic liver fibrosis.

Oxidative and nitrosative stress in experimental rat liver fibrosis: Protective effect of taurine.

Taurine (TAU) has protective effects on experimental liver fibrosis. The present study investigates whether benefits of TAU are mediated through attenuation of oxidative and nitrosative stresses. Liver fibrosis was induced in male Wistar rats by simultaneous administration of iron (0.5%, w/w) and ethanol (6g/kg/day) for 60 days consecutively. Significant increases in thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, protein carbonyl content and loss of non-protein, protein and total thiols were observed in the liver of iron plus alcohol-fed rats. Nitrosative stress was marked by increased levels of S-nitrosothiols and decreased nitrite content. Accumulation of nitrated and oxidatively modified proteins in liver was further evidenced by immunohistochemical localization with specific antibodies for 4-hydroxynonenol (4-HNE), 3-nitrotyrosine (3-NT) and dinitrophenol (DNP). Decrease in mitochondrial ion-transport enzymes and disturbances in calcium and iron levels were also observed in these rats. TAU administration (2% (w/v) in drinking water) significantly reduced the levels of lipid hydroperoxides, TBARS, protein carbonyl with concomitant elevation in thiol levels. The presence of 4-HNE, 3-NT and DNP-protein adducts was minimal. TAU also improved mitochondrial enzyme activities and regulated iron and calcium levels. These results show that the restorative effect of taurine in fibrosis involves amelioration of protein and lipid damage by decreasing oxidative and nitrosative stresses.

Regression of liver fibrosis by taurine in rats fed alcohol: effects on collagen accumulation, selected cytokines and stellate cell activation.

The antifibrogenic effect of taurine in experimental liver fibrosis has been shown. The role of taurine to abate fibrogenic mediators and collagen deposition during liver fibrosis induced by simultaneous administration of iron carbonyl (0.5% w/w) and alcohol (6 g/kg/day) was investigated in this study. Liver histology, the levels of inflammatory cytokines, stellate cell activation, oxidative stress and collagen content were assessed. Liver fibrosis and a rise in collagen content in ethanol plus iron-fed rat were evident from van Gieson and Masson's trichrome staining respectively. Hepatic myeloperoxidase activity and plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were markedly elevated. This was associated with an imbalance in the oxidant-antioxidant system, increased expression of transforming growth factor-ß(1) (TGF-ß(1)) and stellate cell activation suggested by α-smooth muscle actin (α-SMA) localization. This condition was protected in the presence of taurine. Taurine lowered the levels of IL-6, TNF-α and peroxidation products and the expression of α-SMA, desmin and TGF-ß(1) and improved the antioxidant status. A positive relationship between hepatic collagen with iron and lipid peroxides and an inverse relationship between collagen and glutathione were noted. It is concluded that taurine reduces iron-potentiated alcoholic liver fibrosis by curtailing oxidative stress, production of inflammatory and fibrogenic mediators and activation of stellate cells.