Assessment of oral bioavailability and preclinical pharmacokinetics of DRF-6196, a novel oxazolidinone analogue, in comparison to linezolid.

The aim of this study was to determine the bioavailability of a novel oxazolidinone, DRF-6196, in mice and rats following intravenous (i.v) and oral dosing and to compare the pharmacokinetics with those obtained following linezolid dosing. Blood samples were drawn at predetermined intervals up to 24 h post-dose after either DRF-6196 or linezolid administration. The concentrations of DRF-6196 and linezolid in various plasma samples were determined by a HPLC method. Following oral administration maximum concentrations of DRF-6196 were achieved within 0.5 h irrespective of the species. While the doses increased in the ratio of 1 : 3 : 10, mean Cmax and AUC(0-infinity) values in mice for DRF-6196 increased in the ratio of 1 : 3.87 : 8.53 and 1 : 2.51 : 9.24, respectively. Both the Cmax and AUC(0-infinity) values increased almost proportional to the dose administered in mice. Following i.v administration, the concentration of DRF-6196 declined in a bi-exponential fashion with terminal elimination half-life of 1.5 h irrespective of the species. The systemic clearance and volume of distribution of DRF-6196 in mice were 1.14 L/h/kg and 0.66 L/kg, respectively after i.v administration, while the respective values in rats were 0.61 L/h/kg and 0.41L/kg, respectively. Elimination half-life ranged between 0.8-1.5 h. Absolute oral bioavailability of DRF-6196 was found to be 80-96% across the test dose range. Although plasma levels of DRF-6196 were lesser compared to linezolid in the initial hours, it may not have any consequences on the clinical effectiveness of the molecule.     

Targets and management of hypertension in heart failure: focusing on the stages of heart failure

Hypertension is highly prevalent worldwide and is the major risk factor for heart failure (HF). More than half of the patients with HF in Asia suffer from hypertension. According to the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America HF guideline, there are four stages of HF, including at risk for HF (stage A), pre‐HF (stage B), symptomatic HF (stage C), and advanced HF (stage D). Given the high prevalence of hypertension as well as HF and the stronger association between hypertension and cardiovascular diseases in Asians compared to the west, measures to prevent and alleviate the progression to clinical HF, especially controlling the blood pressure (BP), are of priority for Asian populations. After reviewing evidence‐based studies, we propose a BP target of less than 130/80 mmHg for patients at stages A, B, and C. However, relatively higher BP may represent an opportunity to maximize guideline‐directed medical therapy (GDMT), which could potentially result in a better prognosis for patients at stage D. Traditional antihypertensive drugs are the cornerstones for the management of hypertension at stages A and B. Notably, calcium channel blockers (CCBs) are inferior to other drug classes for the preventing of HF, whereas diuretics are superior to others. For patients at stage C, GDMT is essential which also helps the control of BP. In particular, sodium‐glucose cotransporter‐2 (SGLT2) inhibitors are newer therapies recommended for the treatment of HF and presumably even in hypertension to prevent HF. Regarding patients at stage D, GDMT is also recommended if tolerable and measures should be taken to improve hemodynamics.     

Seroprevalence to common infectious abortifacient and infertility causing agents in the dairy herds of India

Background:Information on the prevalence of infectious agents in dairy farms forms the basis for formulating a suitable control strategy; especially in endemic situations. Aims:A cross-sectional study was undertaken to determine the prevalence of six economically important bovine diseases, causing reproductive disorders including bovine abortion in organized dairy herds in India. Methods:A total of 1,075 animals (cattle and buffaloes) from 09 dairy farms were screened by ELISA tests. Results:Bovine viral diarrhoea (BVD) was the most prevalent (56.5%) disease followed by infectious bovine rhinotracheitis (IBR) (45.4%). Prevalence of Q-fever (5.4%) and neosporosis (6.1%) were less on the farms. Although 16.3% of the samples turned positive for brucellosis, the contribution of calf-hood vaccination (B. abortus S19 vaccine) to the prevalence of antibodies cannot be ruled out. The overall prevalence of bovine anaplasmosis, known to cause sporadic abortions in dairy herds, was 34.1% in the 9 farms with a prevalence of less than 20% in 5 farms. Infection of multiple abortifacient (seroprevalence to more than two pathogens) was recorded in 56.8% of animals. A very strong association was observed between BVD and brucellosis (Odds ratio 14.2; P<0.001). Further, a positive association was also seen between seroprevalence of IBR and anaplasmosis, and neosporosis and Q fever (P<0.05). Conclusion:Viral diseases were found to be more common in the dairy herds than bacterial and protozoan diseases. Increased susceptibility of IBR seropositive cows to other bacterial and viral infections was observed.Key Words: Abortion, Bovine viral diarrhoea, Brucellosis, Infectious bovine rhinotracheitis, Neosporosis     

Self-biased photodetector using 2D layered bismuth triiodide (BiI3) prepared using the spin coating method

Layered bismuth triiodide (BiI₃) is a 2D material that has emerged as an ideal choice for optical sensors. Although BiI₃ has been prepared using vacuum-based deposition techniques, there is a dearth of research studies on synthesizing this material using chemical route. The present work uses a facile spin coating method with varying rotation speeds (rpm) to fabricate BiI₃ material thin films for photodetection applications. The structural, optical, and morphological study of BiI₃ thin films prepared at 3000–6000 rpm were investigated. XRD analysis indicates formation of BiI₃ films and revealed that BiI₃ has a rhombohedral crystal structure. FESEM analysis showed that BiI₃ films prepared at different rpm are homogeneous, dense, and free from cracks, flaws, and protrusions. In addition, films show an island-like morphology with grain boundaries having different grain sizes, micro gaps, and the evolution of the granular morphology of BiI₃ particles. The UV spectroscopy and photoluminescence analysis revealed that BiI₃ films strongly absorb light in the visible region of spectra with a high absorption coefficient of ∼10⁴ cm⁻¹, have an optical band gap of ∼1.51 eV. A photodetector was realised using fabricated BiI₃ film obtained at an optimum spin speed of 4000 rpm. It showed rapid rise and decay times of 0.4 s and 0.5 s, a responsivity of ∼100 μA W⁻¹, external quantum efficiency of 2.1 × 10⁻⁴%, and detectivity of ∼3.69 × 10⁶ Jones at a bias voltage of 0 V. Our results point towards a new direction for layered 2D BiI₃ materials for the application in self-biased photodetectors.

Layered bismuth triiodide (BiI₃) is a 2D material that has emerged as an ideal choice for optical sensors.     

DABCO-promoted highly diastereo- and regioselective construction of C-3 functionalized spirooxindoles via [3 + 2] cycloaddition of 2-aryl/heteroarylidene-1H-indene-1,3(2H)-diones with N-2,2,2-trifluoroethylisatin ketimines at ambient conditions

The application of 2-aryl/heteroarylidene-1H-indene-1,3(2H)-dione as an activated olefin source in the DABCO-catalyzed [3 + 2] cycloaddition with N-2,2,2-trifluoroethylisatin ketimines has been disclosed. This highly efficient 1,3-dipolar cycloaddition reaction offered a variety of trifluoro methyl group bearing spiro-pyrrolidine linked oxindoles with four consecutive stereocentres in good to excellent yield and excellent diastereoselectivity. The synthetic practicality of the protocol was established by demonstrating the enantioselective construction of spiro-pyrrolidine-oxindoles with two vicinal spiro-quaternary chiral centres in good yield excellent enantioselectivity (>90% ee) by using ultralow loading of quinine as the catalyst at room temperature.

A highly chemo- and regioselective construction of spiropyrrolidine oxindole is devised via DABCO catalysed [3 + 2] cycloaddition reaction.     

Right lower quadrant abdominal mass: A case report

Right lower quadrant mass in the abdomen has many causes, but gastric perforation is rare. We discuss a 65‐year‐old lady who presented with a history of pain in her abdomen followed by swelling in her right lower abdomen. During the evaluation, a diagnosis of gastric perforation was made.     

Subchronic toxicity and mutagenicity/genotoxicity studies of Irvingia gabonensis extract (IGOB131)

African Bush Mango from Irvingia gabonensis is a West African culinary fruit and the mucilage from this fruit seed is used to make traditional soups and sauces. Extract from the kernel (IGOB131) has been claimed for its health benefits. In the present investigations, potential adverse effects, if any, of IGOB131 were investigated in dose–response 90-day study and genotoxicity studies. In the subchronic study, Sprague Dawley rats (20/sex/group) were gavaged with I. gabonensis extract (IGOB131) at dose levels of 0, 100, 1000 and 2500 mg/kg body weight (bw)/day for 90-days. No treatment-related changes in clinical signs, functional observations, mortality, ophthalmologic observations, body weights, body weight gain or feed consumption were noted. Similarly, hematological, clinical chemistry, urine analysis parameters, and organ weights did not reveal any toxicologically significant treatment-related changes. No treatment-related macroscopic and microscopic abnormalities were noted at the end of treatment period. The mutagenicity as evaluated by Ames assay, in vitro and in vivo chromosomal aberration test and in vivo micronucleus assay did not reveal any genotoxicity of IGOB131. The results of subchronic toxicity study suggest the no-observed-adverse-effect level (NOAEL) for I. gabonensis extract (IGOB131) as ?2500 mg/kg bw/day, the highest dose tested.     

Outcomes for patients with infantile idiopathic scoliosis by casting table type

Purpose:Serial casting is an effective treatment for infantile idiopathic scoliosis. The most common casting table types are Mehta, Risser, and spica tables. We compared major curve correction between patients with infantile idiopathic scoliosis treated using pediatric hip spica tables versus Risser or Mehta tables.Methods:In this multicenter retrospective study, we included 52 children younger than 3 years (mean ± standard deviation age, 1.6 ± 0.68 years) treated with ≥2 consecutive casts for infantile idiopathic scoliosis between September 2011 and July 2018. We compared major curve angle (measured using the Cobb method) before and after treatment and improvement in curve angle between the spica tables group (n = 12) and the Risser or Mehta tables group (n = 40). The primary outcome was the difference in percentage correction of the major curve according to radiographs taken after first casting and at final follow-up.Results:The mean major curve was 47° ± 18° before casting. A median of six casts (range: 2–14) were applied. Mean follow-up after treatment initiation was 22 months (range: 7–86 months). At baseline, the major curve was significantly larger in the spica tables group (58°) than in the Risser or Mehta tables group (43°) (p = 0.01). We found no differences in the percentage curve correction in the spica tables group versus Risser or Mehta tables group after first casting or at final follow-up.Conclusion:Serial casting was associated with substantial major curve correction in patients with infantile idiopathic scoliosis. Curve correction did not differ between patients treated with a spica table versus a Risser or Mehta table.Level of Evidence:Level III, retrospective cohort study