Search

Diabetes is a disease, which has assumed vital public health importance because of the complications associated with it. Various mechanisms including polyol pathway along with a complex integrating paradigm have been implicated in glucose-mediated complications. Though polyol pathway was established as a major mechanism, precise pathogenesis of these complications is not yet completely elucidated. Thus research focus was shifted towards key enzyme, aldose reductase in the pathway. Even though various compounds with aldose reductase inhibitory activity were synthesised, a very few compounds are under clinical use. However, studies on these compounds were always under conficting results and an attempt has been made to review various natural substances with aldose reductase inhibitory activity and their role in management of diabetic complications. [ABSTRACT FROM AUTHOR]

We identified twenty-two new sacubitril derivatives (5a-v) as lead compounds for various biologically active targets. These compounds were synthesized by reacting an intermediate compound (2 R ,4 S )-5-([1,1'-biphenyl]-4-yl)-4-(amino)-2-methylpentanoic acid ethyl ester hydrochloride with respective carboxylic acid (RCOOH). The molecular structures of all the newly synthesized compounds were determined by 1 H and 13 C NMR, ESI mass spectrometry, FTIR spectroscopy, and CHN analysis. Moreover, compound 5n was characterized by a single-crystal X-ray diffraction (SXRD) study to confirm the structure obtained from spectral data. All these compounds were screened for various biological functions such as antifungal, antibacterial, and anti-TB activities. Among these twenty-two compounds (5a-v), some exhibited good to moderate anti-bacterial properties. Similarly, some compounds showed moderate anti-TB and antifungal activities. In addition, the anti-TB activity of compound 5q was estimated against M. tuberculosis in a nutrient starvation model (NSM). Similarly, toxicity was examined against RAW 264.7 cells. These biological activity studies were also correlated with molecular docking studies., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: Steroids have shown its usefulness in critically ill COVID-19 patients. However, the time of starting steroid and dose tailored to severity remain a matter of inquiry due to still emerging evidences and wide-ranging concerns of benefits and harms. We did a retrospective record analysis in an apex teaching hospital ICU setting to explore optimal doses and duration of steroid therapy which can decrease mortality., Methods: 114 adults with COVID-19-ARDS admitted to ICU between 20th March-15th August 2020 were included in chart review. We did preliminary exploratory analysis (rooted in steroid therapy matrix categorized by dose and duration) to understand the effect of several covariates on survival. This was followed by univariate and multivariate Cox proportion hazard regression analysis and model diagnostics., Results: Exploratory analysis and visualization indicated age, optimal steroid, severity (measured in P/F) of disease and infection status as potential covariates for survival. Univariate cox regression analysis showed significant positive association of age > 60 years {2.6 (1.5-4.7)} and protective effect of optimum steroid {0.38(0.2-0.72)} on death (hazard) in critically ill patients. Multivariate cox regression analysis after adjusting effect of age showed protective effect of optimum steroid on hazard defined as death {0.46(0.23-0.87), LR = 17.04, (p = 2e-04)}. The concordance was 0.70 and model diagnostics fulfilled the assumption criteria for proportional hazard model., Conclusion: Optimal dose steroid as per defined 'optimum' (<24 hours and doses tailored to P/F at presentation) criteria can offer protective effect from mortality which persists after adjusting for age. This protective effect was not found to be negatively influenced by the risk of infection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Over the past decade, 3D printing in the construction industry has received worldwide attention and developed rapidly. The research and development of cement and concrete products has also become quite well-established over the years, while other sustainable materials receive considerably lower attention in comparison. This study aims to investigate the influence of the two most commonly used sustainable cementitious materials i.e., silica fume and limestone powder, on printability, thermal and mechanical properties of fly ash-Portland cement blends. Ternary blends containing Portland cement, fly ash and silica fume or limestone powder are prepared, whereas phase change material (PCM) is introduced to improve the thermal behavior. Based on the rheological properties and concurrent 3D concrete printing, improved buildability of the modified mixtures is linked to their static yield stress. Anisotropic mechanical properties are observed for 3D printed specimens, while cast specimens exhibit a maximum 41% higher compressive strength due to better material compaction. It is clear from the results that addition of silica fume and limestone powder ranged from 5% to 10%, reducing the anisotropic mechanical properties (maximum 71% and 68% reduction in anisotropic factor, respectively) in the printed specimens. The PCM addition ranged from 5% to 10% and improved thermal performance of the mixtures, as measured by a decrease in thermal conductivity (9% and 13%) and an increase in volumetric heat capacity (9% and 10%), respectively. However, the PCM-containing mixtures show around 29% reduction in compressive strength, compared to the control specimen, which necessitates new material design considering matrix strengthening methods.

Background and Objectives: Major adverse cardiac events (MACE) are frequent in coronavirus disease-2019 (COVID-19). Remdesivir is used worldwide for treatment in COVID-19. In this retrospective observational study, our primary objective was to assess the impact of remdesivir administration on the incidence of MACE and associated 28 day survival in critically ill patients admitted for moderate to severe COVID-19 pneumonia., Patients and Methods: We analyzed the data of 437 patients admitted in intensive care unit (ICU) and divided them into two groups: R group (received remdesivir at ICU admission) and NR group (nonremdesivir) or based on the occurrence of MACE in ICU. We followed the data until discharge, death, or 28 days postadmission. Our primary objective was to investigate the log-odds of survival with remdesivir administration and a correlation/regression analysis of MACE with remdesivir administration in all included patients., Results: The incidence of MACE was 72 among 437 patients, with 17 (9.3%) patients in R group vs 55 (21.8%) in NR group ( p <0.001). On performing correlation analysis between MACE and remdesivir administration, significant correlation coefficient of -0.168 ( p = 0.004) was obtained. On regression analysis, the odds ratio for occurrence of MACE with remdesivir administration was 0.362 (regression coefficient: -1.014, p <0.001). It indicates a 64% decrease in the log-odds of MACE and a 16% increase in the log-odds of survival with remdesivir administration. All 72 patients with MACE had expired, suggesting a high mortality risk with cardiac complications. The odds ratio for mortality due to MACE with remdesivir administration was 0.216 (regression coefficient: -1.530, p -<0.001). It indicates a 79% decrease in the log-odds of death due to MACE with remdesivir administration., Conclusion: Our study showed significant reduction in MACE and mortality benefit in patients who received remdesivir in comparison to standard treatment., How to Cite This Article: Panda R, Singh P, Jain G, Saigal S, Karna ST, Anand A, et al . Effect of Remdesivir Administration on Occurrence of Major Adverse Cardiac Events in Critically Ill COVID-19 Pneumonia: A Retrospective Observational Study. Indian J Crit Care Med 2022;26(9):993-999., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2022; The Author(s).)

Background: The outcomes in critical illness depend on disease severity, practice protocols, workload, and access to care. This study investigates the factors affecting outcomes in mechanically ventilated coronavirus disease-2019 acute respiratory distress syndrome (COVID-19 ARDS) patients admitted in a tertiary teaching hospital intensive care unit (ICU) in Central India with reference to different time periods in pandemic. This is one of the largest series of mechanically ventilated COVID-19 ARDS patients, globally., Methods: This retrospective cohort study classified the entire data into four time periods (Period 1: April 2020 to June 2020; Period 2: July 2020 to September 2020; Period 3: October 2020 to December 2020; and Period 4: January 2021 to April 2021). We performed a multivariable-adjusted analysis to evaluate predictors of mortality, adjusted for baseline-severity, sequential organ failure assessment (SOFA score) and time period. We applied mixed-effect binomial logistic regression to model fixed-effect variables with incremental complexity., Results: Among the 56 survivors (19.4%) out of 288 mechanically ventilated patients, there was an up-gradient of survival proportion (0, 18.2, 17.4, and 28.6%) in four time periods. Symptom-intubation interval (OR 1.16; 95% CI 1.03-1.31) and driving pressures (DPs) (OR 1.17; 95% CI 1.07-1.28) were significant predictors of mortality in the model having minimal AIC and BIC values. Patients aged above 60 years also had a larger effect, but statistically insignificant effect favoring mortality (OR 1.99; 95% CI 0.92-4.27). The most complex but less parsimonious model (with higher AIC/BIC) indicated the protective odds of high steroid on mortality (OR 0.59; 95% CI 0.59-0.82)., Conclusion: The outcomes in mechanically ventilated COVID-19 ARDS patients are heterogeneous across time windows and may be affected by the complex interaction of baseline risk and critical care parameters., How to Cite This Article: Saigal S, Joshi A, Panda R, Goyal A, Kodamanchili S, Anand A, et al . Changing Critical Care Patterns and Associated Outcomes in Mechanically Ventilated Severe COVID-19 Patients in Different Time Periods: An Explanatory Study from Central India. Indian J Crit Care Med 2022;26(9):1022-1030., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2022; The Author(s).)

A series of 30 novel diamino phenyl chloropicolinate fettered carboxamides, urea, and thiourea derivatives were synthesized by coupling of methyl 4-amino-6-(2-aminophenyl)-3-chloropyridine-2-carboxylate with different acid chlorides, urea, and thiourea moieties, respectively. All of these compounds were characterized by 1 H and 13 C nuclear magnetic resonance spectroscopy, CHN analysis, and high-resolution mass spectra for confirmation of the structures. Two compounds were also characterized by single-crystal X-ray diffraction analysis to confirm the structures obtained by spectral analysis. All these 30 compounds were tested for their in vitro antimycobacterial activity using the microplate alamar blue assay method against Mycobacterium tuberculosis . Five compounds have shown good minimum inhibitory concentration (MIC) values with low cytotoxicity when compared with the reference drugs. Moreover, some of the compounds have high MIC values compared with isoniazid, rifampicin, and so forth and also had shown good reign in the spread of bacteria by the nutrient starvation model. These antimycobacterial activity results have shown a good correlation with molecular docking model analysis with the inhibitors MurB by exhibiting strong interactions. Some of these compounds could be promising candidates against M. tuberculosis for future preclinical agent drug development., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: Aldose reductase (AR) and Advanced glycation end product (AGE) are known to play important roles in the development of diabetic complications. The inhibitors of AR and AGE would be potential agents for the prevention of diabetic complications., Objective: The present study was aimed to evaluate the aldose reductase (AR) and advanced glycation end product (AGE) inhibitory potential of pterostilbene for its possible role in the treatment of diabetic complications such as cataract., Materials and Methods: The compound was studied for its inhibitory activity against rat lens AR (RLAR) and rat kidney AR (RKAR) in vitro along with its ability to inhibit the formation of AGEs. Anticataract activity of pterostilbene was demonstrated using sugar induced lens opacity model in isolated cattle lens. Further, the involvement of pterostilbene in galactosemia in rats was investigated by assessing the key markers in the polyol pathway and the results were compared with that of a potent AR inhibitor, fidarestat., Results: Pterostilbene exhibited inhibitory activity against RLAR and RKAR with IC50 values of 5.49 mg/ml (21.4 mM) and 6.40 mg/ml (25.02 mM), respectively. In sugar-induced lens opacity model, pterostilbene displayed a significant protective effect by preventing opacification and formation of polyols in cattle lens. Besides, the compound exhibited in vivo inhibition of galactitol accumulation in lens and sciatic nerves of galactose fed rats., Conclusion: The results obtained in the study underline the potential of pterostilbene as possible therapeutic agent against long-term diabetic complications., (Copyright © 2018 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.)

Background: Data mining techniques are used to mine unknown knowledge from huge data. Microarray gene expression (MGE) data plays a major role in predicting type of cancer. But as MGE data is huge in volume, applying traditional data mining approaches is time consuming. Hence parallel programming frameworks like Hadoop, Spark and Mahout are necessary to ease the task of computation., Objective: Not all the gene expressions are necessary in prediction, it is very essential to select important genes for improving classification accuracy. So feature selection algorithms are parallelized and executed on Spark framework to eliminate unnecessary genes and identify only predictive genes in very less time without affecting prediction accuracy., Methods: Parallelized hybrid feature selection (HFS) method is proposed to serve the purpose. This method includes parallelized correlation feature subset selection followed by rank-based feature selection methods. The selected subset of genes is evaluated using parallel classification algorithms. The accuracy values obtained are compared with existing rank-weight feature selection, parallelized recursive feature selection methods and also with the values obtained by executing parallelized HFS on DistributedWekaSpark., Results: The classification accuracy obtained with the proposed parallelized HFS method is 97% and 79% for gastric cancer and childhood leukemia respectively. The proposed parallelized HFS method produced ~ 4% to ~ 15% improvement in classification accuracy when compared with previous methods., Conclusion: The results reveal the fact that the proposed parallelized feature selection algorithm is scalable to growing medical data and predicts cancer sub-types in lesser time with higher accuracy.

RBM4 participates in cell differentiation by regulating tissue-specific alternative pre-mRNA splicing. RBM4 also has been implicated in neurogenesis in the mouse embryonic brain. Using mouse embryonal carcinoma P19 cells as a neural differentiation model, we observed a temporal correlation between RBM4 expression and a change in splicing isoforms of Numb, a cell-fate determination gene. Knockdown of RBM4 affected the inclusion/exclusion of exons 3 and 9 of Numb in P19 cells. RBM4-deficient embryonic mouse brain also exhibited aberrant splicing of Numb pre-mRNA. Using a splicing reporter minigene assay, we demonstrated that RBM4 promoted exon 3 inclusion and exon 9 exclusion. Moreover, we found that RBM4 depletion reduced the expression of the proneural gene Mash1, and such reduction was reversed by an RBM4-induced Numb isoform containing exon 3 but lacking exon 9. Accordingly, induction of ectopic RBM4 expression in neuronal progenitor cells increased Mash1 expression and promoted cell differentiation. Finally, we found that RBM4 was also essential for neurite outgrowth from cortical neurons in vitro. Neurite outgrowth defects of RBM4-depleted neurons were rescued by RBM4-induced exon 9-lacking Numb isoforms. Therefore our findings indicate that RBM4 modulates exon selection of Numb to generate isoforms that promote neuronal cell differentiation and neurite outgrowth., (© 2016 Tarn et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

To enhance patient compliance toward treatment in diseases like diabetes, usually a combination of drugs is prescribed. Therefore, an anti-diabetic fixed-dose combination of 2.5 mg of linagliptin 500 mg of metformin was taken for simultaneous estimation of both the drugs by reverse phase-high performance liquid chromatography (RP-HPLC) method. The present study aimed to develop a simple and sensitive RP-HPLC method for the simultaneous determination of linagliptin and metformin in pharmaceutical dosage forms. The chromatographic separation was designed and evaluated by using linagliptin and metformin working standard and sample solutions in the linearity range. Chromatographic separation was performed on a C18 column using a mobile phase of 70:30 (v/v) mixture of methanol and 0.05 M potassium dihydrogen orthophosphate (pH adjusted to 4.6 with orthophosphoric acid) delivered at a flow rate of 0.6 mL/min and UV detection at 267 nm. Linagliptin and metformin shown linearity in the range of 2-12 μg/mL and 400-2400 μg/mL respectively with correlation co-efficient of 0.9996 and 0.9989. The resultant findings analyzed for standard deviation (SD) and relative standard deviation to validate the developed method. The retention time of linagliptin and metformin was found to be 6.3 and 4.6 min and separation was complete in <10 min. The method was validated for linearity, accuracy and precision were found to be acceptable over the linearity range of the linagliptin and metformin. The method was found suitable for the routine quantitative analysis of linagliptin and metformin in pharmaceutical dosage forms.

Background: Various mechanisms with a complex integrating paradigm have been implicated in diabetic complications. The present study was aimed to evaluate the aldose reductase (AR) and advanced glycation end products (AGEs) inhibitory activity of resveratrol (RSV) and its potential in the treatment of diabetic complications such as cataract and nephropathy., Methods: RSV was studied for its inhibitory activity against rat lens AR (RLAR) and rat kidney AR (RKAR) in vitro along with its ability to inhibit formation of AGEs. Anticataract activity of RSV was demonstrated using sugar induced lens opacity model in isolated cattle lens. Furthermore the involvement of RSV in streptozotocin-induced diabetic nephropathy was investigated by assessing the key markers of kidney function along with the formation of AGEs. The potent AR inhibitor, fidarestat was as a standard., Results: RSV exhibited inhibitory activity against RLAR and RKAR with IC50 values of 4.99 μg/ml (21.9 μM) and 5.49 μg/ml (24.5 μM), respectively. It also showed a significant inhibition of AGEs formation in vitro. In sugar-induced lens opacity model, RSV displayed a significant protective effect preventing opacification and formation of polyols in cattle lens. RSV significantly improved glycaemic status and renal function in diabetic rats with a significant decrease in the formation of AGEs in the kidneys., Conclusions: The results obtained in this study underline the potential of RSV as a possible therapeutic agent against long-term diabetic complications., (Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Objective: This study was aimed to investigate the beneficial effects of quercetin (QCT) against trinitrobenzene sulfonic acid (TNBS) induced clinical, morphological, and biochemical alterations in rats., Materials and Methods: Colitis in rats was induced by administration of TNBS (25 mg dissolved in 0.25 ml of 30% ethanol) 8 cm into the rectum of the rat using a catheter. The animals were divided into six experimental groups (n = 6); naive (saline only without TNBS administration), control (saline + TNBS), standard (sulfasalazine 25 mg/kg + TNBS), QCT (25) (QCT 25 mg/kg + TNBS), QCT (50) (QCT 50 mg/kg + TNBS), QCT (100) (QCT 100 mg/kg + TNBS). Sulfasalazine (25 mg/kg) and QCT (25, 50 and 100 mg/kg) were administered per oral for 11 days and the colonic damage was evaluated in terms of macroscopical (body weight, stool consistency, rectal bleeding, and ulcer index) and biochemical parameters (myeloperoxidase activity, lipid peroxidation, nitrite, and glutathione)., Results: Treatment with QCT (50, 100 mg/kg) for 10 days following TNBS administration significantly attenuated the clinical, morphological, and biochemical alterations induced by TNBS, whereas it was found to be not effective at its lower dose (25 mg/kg) throughout the experimental protocol., Conclusion: QCT attenuates the clinical, morphological and biochemical alterations induced by TNBS possibly via its antioxidant mechanism.

Background: Inflammatory bowel disease (IBD) is characterized by most common symptoms such as rectal bleeding. Lack of specific, curative treatments tempted us to evaluate the therapeutic efficacy of quercetin against acetic acid induced IBD like symptoms., Methods: Animals were randomly divided into five groups (n = 6): naive, control, sulphasalazine and quercetin, and were pretreated for three days. Colitis was induced by intra-rectal administration of 3% acetic acid., Results: Pretreatment with sulphasalazine or quercetin significantly attenuated the biochemical and morphological alterations in the colon induced by acetic acid in rats., Conclusions: The findings of the study suggest the possible role of quercetin as therapeutics in IBD., (Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

A new indolo[3,2-b]quinoline alkaloid glycoside, jusbetonin (1), and three known alkaloids, namely, 10H-quindoline (2), 6H-quinindoline (3), and 5H,6H-quinindolin-11-one (4), have been isolated from the leaves of Justicia betonica. The structure of 1 was established on the basis of 1D and 2D NMR ((1)H-(1)H COSY, HMQC, and HMBC) and HRFABMS data. Compound 1 is the first example of a glycosylated indolo[3,2-b]quinoline alkaloid, while compound 4 was isolated for the first time from a natural source.

An unusual secolignan glycoside, juspurpurin (1), and a new arylnaphthalene glycoside, justalakonin (2), together with eight known lignans were isolated from the whole plants of Justicia purpurea. Compound 1 is the first glycoside of a rare group of secolignans. The structures of the new compounds 1 and 2 were established using 1D and 2D NMR ((1)H-(1)H COSY, HMQC, and HMBC) spectral data and by chemical transformations.