Efficacy and tolerability of hyperbaric oxygen therapy in small bowel stricturing Crohn's disease: a pilot study.

BACKGROUND/AIMS: Existing therapeutic options for complicated Crohn's disease (CD) like biologics and surgery are limited by inadequate long-term efficacy, cost, and adverse effects. Tissue hypoxia is important in CD pathogenesis and may be ameliorated with hyperbaric oxygen therapy (HBOT). We assessed the efficacy and tolerability of HBOT in small bowel stricturing CD. METHODS: This pilot study included patients of small bowel stricturing CD (from April 2019 to January 2020) who underwent HBOT. These patients were refractory to conventional medical treatment or had multiple strictures not amenable to resection. Each session of HBOT was given for 60 minutes with a pressure of 1.5-2.5 atm. Clinical, biochemical responses and Short Inflammatory Bowel Disease (SIBD) questionnaire were evaluated at 2 and 6 months, and radiological response was evaluated at 6 months. RESULTS: Fourteen patients (mean age, 42.9±15.7 years; male, 50%) were subjected to 168 HBOT sessions. Thirteen patients (92.7%) had strictures and 1 patient had enterocutaneous fistula in addition. Median number of HBOT sessions was 11 (range, 3-20) which were administered over a median of 4 weeks. Most patients tolerated it well except 1 who had hemotympanum. At 2 and 6 months of follow-up, 64.2% of patients had a clinical response, 50% and 64.2% of patients had clinical remission respectively. Steroid-free clinical remission was seen in 8 (57%) of patients with radiological improvement in 50%. There was a significant improvement in SIBD scores at 2-month follow-up (59.4 vs. 44.5, P=0.03). CONCLUSIONS: HBOT can be a safe and effective therapeutic option in patients with stricturing small bowel CD refractory to conventional medical treatment.

Does Vitamin D Improve All-cause Mortality in Critically Ill Adults? An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials.

Introduction: Vitamin D deficiency is an amendable risk factor linked to increase in mortality in critically ill patients. The aim of this systematic review was to evaluate if vitamin D supplementation reduced the mortality, and length of stay (LOS) in intensive care units (ICU) and hospitals in critically ill adults including coronavirus disease-2019 (COVID-2019) patients. Materials and methods: We searched the literature using the PubMed, Web of Science, Cochrane and Embase databases until January 13, 2022, for RCTs comparing vitamin D administration to placebo or no treatment in ICUs. The fixed-effect model was used for the primary outcome (all-cause mortality) and the random effect model for secondary objectives (LOS in ICU, hospital, mechanical ventilation). Subgroup analysis included ICU types and high vs low risk of bias. Sensitivity analysis compared severe COVID-19 vs no COVID disease. Results: Eleven RCTs (2,328 patients) were included in the analysis. Pooled analysis of these RCTs, showed no significant difference in all-cause mortality between the vitamin D and placebo groups [odds ratio (OR) 0.93, p = 0.47]. Inclusion of COVID-positive patients did not change the results (OR 0.91, p = 0.37). No significant difference was observed between the vitamin D and placebo groups in LOS in ICU (p = 0.34); hospital (p = 0.40) and mechanical ventilation duration (p = 0.7). In the subgroup analysis, there was no improvement in mortality in medical ICU (p = 0.36) or surgical ICU (p = 0.03). Neither low risk of bias (p = 0.41) nor high risk of bias (p = 0.39) reduced mortality. Conclusion: Vitamin D supplementation in the critically ill did not have statistically significant benefits on clinical outcomes in terms of overall mortality, duration of mechanical ventilation, and LOS in ICU and hospital. How to cite this article: Kaur M, Soni KD, Trikha A. Does Vitamin D Improve All-cause Mortality in Critically Ill Adults? An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials. Indian J Crit Care Med 2022;26(7):853-862.

New-onset hyperglycaemia and prolonged systemic corticosteroids therapy in mild COVID-19 patients as major risk factors for invasive mucormycosis: a preliminary study.

Background and Purpose: Rapid surge of invasive mucormycosis has surprised the Indian healthcare system amidst the coronavirus disease-19 (COVID-19) pandemic. Hence, there is an urgent need to find the risk factors for the sudden rise in cases of invasive mucormycosis among COVID-19 patients. This study aimed to find crucial risk factors for the sudden surge of invasive mucormycosis in India. Materials and Methods: This case-control study included 77 cases of COVID-19 associated mucormycosis (CAM) who matched the controls (45 controls) in terms of age , gender, and COVID-19 disease severity. The control group included subjects that matched controls without mucormycosis confirmed by reverse transcription-polymerase chain reaction at our tertiary care center during April-May 2021. Probable predisposing factors, such as duration of diabetes mellitus (DM), history of recent hospitalization, duration of hospital stay, mode of the received oxygen supplementation, and use of steroids, zinc, vitamin c, and any other specific drugs were collected and compared between the two groups. Moreover, the laboratory parameters, like glycated hemoglobin (HbA1c), highly sensitive C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR) were analyzed to find out the significant association with CAM. Results: DM (Odds ratio=7.7, 95% CI 3.30-18.12; P=<0.0001) and high glycated hemoglobin level (HbA1c>7.5 gm %) (odds ratio=6.2, 95% CI 1.4-26.7; P=0.014) were significant risk factors for the development of invasive mucormycosis among the COVID-19 cases. A higher number of mild COVID-19 cases developed CAM, compared to the moderate to severe cases (59.7% vs 40.3%). Use of systemic corticosteroids (odd ratio=5 with 95% CI 1.5-16.9; P=0.007) was found to be a risk factor for invasive mucormycosis only in mild COVID-19 cases. Use of oxygen, zinc, and vitamin C supplementation, and proprietary medicine did not lead to a significant risk of invasive mucormycosis in cases, compared to controls. Cases with invasive mucormycosis had a higher level of inflammatory markers (hs-CRP and ESR, P=<0.001 and 0.002, respectively), compared to the controls. Conclusion: Uncontrolled and new-onset DM and the use of systemic corticosteroids in mild cases were significantly associated with a higher risk of invasive mucormycosis in COVID-19 cases. There should be a strong recommendation against the use of systemic corticosteroids in mild COVID-19 cases.

Fractions of Boswellia Serrata Suppress LTA4, LTC4, Cyclooxygenase-2 Activities and mRNA in HL-60 Cells and Reduce Lung Inflammation in BALB/c Mice.

BACKGROUND: Purified fractions from a Boswellia serrata Roxb. Ex. Colebr. (Burseraceae) extract (ETOH and DCM) contain biologically active compounds that are well known for having inflammation inhibitory properties. In this work, the purified fractions were tested in-vitro for LTC4, LTA4 and COX-2 activities using ELISA and qPCR was performed to determine gene regulation in human leukemia (HL-60) Cells. Two D-imaging tomography was performed to determine the anti-inflammatory activities of the fractions in BALB/c mouse model of lung inflammation. OBJECTIVE: To evaluate anti-inflammatory activities of bioactive compounds of Boswellia serrata purified fractions. METHODS: In-vitro MTT assay was performed in HL-60 cell lines for measuring the toxicity/ viability of the cells. ELISA tests were performed for evaluating LTA4, LTC4 and COX-2 activities. qPCR was performed to evaluate the expression of mRNA in HL-60 cells. In-vivo experiments were performed in OVA sensitized and challenged BALB/c mice at two doses of Boswellia serrata purified fraction containing 6% Boswellic acid of 50 and 100mg/kg body weight were given orally and the standard drug dexamethasone (DXA, 4 mg/kg body weight) and reduction in lung inflammation was assessed by using an IVIS Xenogen in-vivo fluorescence imaging system. RESULTS: A purified fraction of Boswellia serrata ETOH extracts reduced leukotriene-C4-synthase activity by 52%, leuktotriene-A4-hydrolase activity by 22% and COX-2 activity by 99% with an IC50 of 12.5µg/ml. Intragastric administration of the purified fraction of Boswellia serrata at two doses of 50mg/kg b.w. and 100mg/kg b.w., respectively along with 2-3% HPMC resulted in a ~51% (P value <0.01) reduction in OVA induced lung inflammation in BALB/c mice as observed by imaging tomography. Treatment of the OVA challenged mice with standard drug dexamethasone (DXA) reduced inflammation by ~66% with significant value (P<0.0001). CONCLUSION: The present study describes that Boswellia serrata ethanolic extracts purified fraction (ETOH-BS) possess significant anti-inflammatory activities in HL-60 and in BALB/c and further supports for its use as Ayurvedic medicines traditionally in the treatment of lung disorders including allergy and asthma.

The Role of Leukotrienes Inhibitors in the Management of Chronic Inflammatory Diseases.

BACKGROUND: Leukotrienes are powerful mediators of inflammation and interact with specific receptors in target cell membrane to initiate an inflammatory response. Thus, Leukotrienes (LTs) are considered to be potent mediators of inflammatory diseases including allergic rhinitis, inflammatory bowel disease and asthma. Leukotriene B4 and the series of cysteinyl leukotrienes (C4, D4, and E4) are metabolites of arachidonic acid metabolism that cause inflammation. The cysteinyl LTs are known to increase vascular permeability, bronco-constriction and mucus secretion. OBJECTIVES: To review the published data for leukotriene inhibitors of plant origin and the recent patents for leukotriene inhibitors, as well as their role in the management of inflammatory diseases. METHODS: Published data for leukotrienes antagonists of plant origin were searched from 1938 to 2019, without language restrictions using relevant keywords in both free text and Medical Subject Headings (MeSH terms) format. Literature and patent searches in the field of leukotriene inhibitors were carried out by using numerous scientific databases including Science Direct, PubMed, MEDLINE, Google Patents, US Patents, US Patent Applications, Abstract of Japan, German Patents, European Patents, WIPO and NAPRALERT. Finally, data from these information resources were analyzed and reported in the present study. RESULTS: Currently, numerous anti-histaminic medicines are available including chloropheneremine, brompheniramine, cetirizine, and clementine. Furthermore, specific leukotriene antagonists from allopathic medicines are also available including zileuton, montelukast, pranlukast and zafirlukast and are considered effective and safe medicines as compared to the first generation medicines. The present study reports leukotrienes antagonistic agents of natural products and certain recent patents that could be an alternative medicine in the management of inflammation in respiratory diseases. CONCLUSION: The present study highlights recent updates on the pharmacology and patents on leukotriene antagonists in the management of inflammation respiratory diseases.

Trachyspermum ammi Seeds Supplementation Helps Reverse Scopolamine, Alprazolam and Electroshock Induced Amnesia.

The present study was designed to explore the beneficial effects of successive 10 days administration of Trachyspermum ammi seed's powder (TASP) along with diet (at the dose of 0.5%, 1.0% and 2.0% w/w) on learning and memory of mice. A total of 306 mice divided in 51 equal groups were employed in the study. Passive avoidance paradigm (PAP) and Object recognition Task (ORT) were employed as exteroceptive models. The brain acetylcholinesterase activity (AChE), serum cholesterol, brain monoaldehyde (MDA), brain reduced glutathione (GSH) and brain nitrite were estimated and Alprazolam, Scopolamine and Electroshock induced amnesia was employed to describe the actions. Treatment of TASP significantly increased step down latency of PAA and significantly increased discrimination index of ORT in groups with or without amnesia when compared to respective control groups. Furthermore, TASP administration resulted in significant fall in brain AChE activity, brain MDA level and brain nitrite level with simultaneous rise in brain GSH level, thereby decreased oxidative damage. A significant decrease in serum cholesterol was also observed. Ajowan supplementation may prove a remedy for the management of cognitive disorders owing to have pro-cholinergic, antioxidant and hypo-lipidemic activities.

Estrogenic and serotonergic butenolides from the leaves of Piper hispidum Swingle (Piperaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Our previous work has demonstrated that several plants in the Piperaceae family are commonly used by the Q'eqchi Maya of Livingston, Guatemala to treat amenorrhea, dysmenorrhea, and pain. Extracts of Piper hispidum Swingle (Piperaceae), bound to the estrogen (ER) and serotonin (5-HT7) receptors. AIM OF THE STUDY: To investigate the estrogenic and serotonergic activities of Piper hispidum extracts in functionalized assays, identify the active chemical constituents in the leaf extract, and test these compounds as agonists or antagonists of ER and 5-HT7. MATERIALS AND METHODS: The effects of the Piper hispidum leaf extracts were investigated in estrogen reporter gene and endogenous gene assays in MCF-7 cells to determine if the extracts acted as an estrogen agonist or antagonist. In addition, the active compounds were isolated using ER- and 5-HT7 receptor bioassay-guided fractionation. The structures of the purified compounds were identified using high-resolution LC-MS and NMR spectroscopic methods. The ER- and 5-HT7-agonist effects of the purified chemical constituents were tested in a 2ERE-reporter gene assay in MCF-7 cells and in serotonin binding and functionalized assays. RESULTS: Three butenolides including one new compound (1) were isolated from the leaves of Piper hispidum, and their structures were determined. Compound 1 bound to the serotonin receptor 5-HT(7) with IC(50) values of 16.1 and 8.3 microM, respectively, and using GTP shift assays, Compound 1 was found to be a partial agonist of the 5-HT(7) receptor. The Piper hispidum leaf extracts, as well as Compounds 2 and 3 enhanced the expression of estrogen responsive reporter and endogenous genes in MCF-7 cells, demonstrating estrogen agonist effects. CONCLUSIONS: Extracts of Piper hispidum act as agonists of the ER and 5-HT(7) receptors. Compound 1, a new natural product, identified as 9,10-methylenedioxy-5,6-Z-fadyenolide, was isolated as the 5-HT(7) agonist. Compounds 2 and 3 are reported for the first time in Piper hispidum, and identified as the estrogen agonists. No inhibition of CYP450 was observed for any of these compounds in concentrations up to 1 microM. These activities are consistent with the Q'eqchi traditional use of the plant for the treatment of disorders associated with the female reproductive cycle.

Spasmolytic activity of a herbal drug isolated from Tephrosia purpurea in guinea pigs.

We investigated the spasmolytic activity of herbal drugs isolated from Tephrosia purpurea on guinea pigs for the treatment of asthma in India. For this investigation, the herbal drug was extracted with 70% ethanol in soxhlet apparatus. After purification and isolution, the drug was used in experimental animals to observe prophylactic activity. For anaphylactic activity, horse serum 0.5 ml along with triple antigen (0.5 ml) was induced in guinea pigs. To observe prophylactic activity, male guinea pigs weighing about 250-450 gms were killed by cervical dislocation and the trachea was isolated. Each trachea was cut in to six segments. Each segment consists of three cartilage rings. Each end of tracheal muscles was attached to the bronchospasm transducers for isometric recording of the tension charges on a polygraph. The results of experiments clearly showed the spasmolytic activity of the drug. The preliminary phytochemical investigation, however shows the presence of glycoside saponins.