Effectiveness of blended learning in pharmacy education: An experimental study using clinical research modules.

BACKGROUND &OBJECTIVES: Though there are studies to evaluate the effectiveness of blended learning in pharmacy education, most of them originate from USA and have used previous year students' scores as control. Also there is less research in comparing use of self -regulated learning strategies between blended and other learning strategies. Primary aim was to evaluate the effectiveness of blended learning on knowledge score using clinical research modules. Secondary objective was designed to compare the use of self-regulated learning strategies between blended learning, web-based e-learning and didactic teaching. MATERIALS AND METHODS: A prospective cluster randomized trial was conducted with didactic teaching as control and web-based e-learning and blended learning as interventions. The target population was final year Pharm D students. Outcome was assessed using a validated knowledge questionnaire, a motivated strategies for learning questionnaire and a feedback form. All statistical analyses were carried out using Statistical Package for Social Science (SPSS) Version 20. RESULTS: A total of 241 students from 12 colleges completed the study. Mean knowledge score of students in blended learning group was higher than those in the didactic teaching and web- based e- learning program (64.26±18.19 Vs 56.65±8.73 Vs 52.11±22.06,p<0.001).Frequency of use of learning strategies namely rehearsal, elaboration, organization and critical thinking was statistically significantly higher in the blended learning group compared to those of didactic and web-based e-learning group (p<0.05) But there were no statistically significant difference of motivational orientations between didactic and blended learning group except strategies of extrinsic goal orientation and self-efficacy. Students preferred blended learning (86.5%) over didactic and web-based e-learning. CONCLUSION: Blended learning approach is an effective way to teach clinical research module. Students of blended learning group employed all motivational and learning strategies more often than students of the didactic and web- based e-learning groups except strategies of intrinsic goal orientation, task value, control of learning belief and help seeking.

Availability, price and affordability of essential medicines for managing cardiovascular diseases and diabetes: a statewide survey in Kerala, India.

OBJECTIVE: Limited access to essential medicines (EMs) for cardiovascular disease (CVD) and diabetes is a major concern in low- and middle-income countries. We aimed to generate data on availability, price and affordability of EMs for CVD and diabetes in India. METHODS: Using WHO/HAI survey methodology, we evaluated availability and prices of 23 EMs in 30 public sector facilities (government hospitals and semi-public/government-subsidised-discount-pharmacies (GSDPs)) and 60 private retail pharmacies across six districts in Kerala state, India (November 2018 - May 2019). Median Price Ratios (MPRs) were calculated by comparing consumer prices with international reference prices. We also analysed data (collected in July 2020) on six anti-hypertensive fixed-dose-combinations (FDCs) that were designated as 'essential' by the WHO in 2019. RESULTS: Mean availability of surveyed generic EMs was 45.7% in government hospitals, 64.7% in GSDPs and 72.0% in private retail pharmacies. On average, the most-sold and highest-priced generics, respectively, were 6.6% and 8.9% costlier than the lowest-priced generics (LPG). Median MPR for LPG was 2.71 in private retail and 2.25 in GSDPs. Monthly supply of LPG would cost the lowest-paid worker 1.11 and 0.79 days' wages in private retail and GSDPs, respectively. Mean availability of the surveyed FDCs was poor (private retail: 15-85%; GSDPs: 8.3-66.7%), and the private retail prices of FDCs were comparable to the sum of corresponding constituent monotherapies. CONCLUSION: Availability of CVD and diabetes EMs fall short of WHO's 80% target in both sectors. Although availability in the private retail pharmacies was near-optimal, prices appear unaffordable compared to GSDPs. Initiatives such as mandating generic prescribing, adding the WHO-approved FDCs in local EM lists, improving price transparency, and streamlining medicine supply to ensure equitable access to EMs, especially in the public sector, are crucial in tackling Kerala's ever-increasing CVD burden.

OBJECTIF: L'accès limité aux médicaments essentiels (ME) pour les maladies cardiovasculaires (MCV) et le diabète est une préoccupation majeure dans les pays à revenu faible et intermédiaire. Nous visions à générer des données sur la disponibilité, le prix et l'aspect abordable des ME pour les MCV et le diabète en Inde. MÉTHODES: En utilisant la méthodologie OMS/HAI, nous avons évalué la disponibilité et les prix de 23 ME dans 30 établissements du secteur public (hôpitaux publics et pharmacies semi-publiques/à discompte subventionnées par le gouvernement (GSDP)) et 60 pharmacies de détail privées dans 6 districts de l'Etat du Kerala, en Inde. Les ratios de prix médians (RPM) ont été calculés en comparant les prix des consommateurs aux prix de référence internationaux. Nous avons également analysé les données de six combinaisons à dose fixe (CDF) d'antihypertensives désignées ''essentielles'' par l'OMS en 2019. RÉSULTATS: La disponibilité moyenne des ME génériques étudiés était de 45,7% dans les hôpitaux publics, de 64,7% dans les GSDP et de 72,0% dans le commerce de détail privé. En moyenne, les génériques les plus vendus et les plus chers, respectivement, étaient de 6,6% et 8,9% plus chers que les génériques les moins chers (GMC). Le RPM pour les (GMC) était de 2,71 dans le secteur privé et de 2,25 dans les GSDP. L'approvisionnement mensuel en GMC coûterait au travailleur le moins payé le salaire de 1,11 et 0,79 jour de travail dans le secteur de la vente au détail privé et dans les GSDP, respectivement. La disponibilité moyenne des CDF était faible (vente au détail privée: 15% - 85%; GSDP: 8,3%-66,7%), avec des prix de détail privés comparables à la somme des monothérapies constituantes correspondantes. CONCLUSION: La disponibilité des ME pour les MCV et le diabète est inférieure à l'objectif de 80% de l'OMS dans les deux secteurs. Bien que la disponibilité dans les pharmacies de détail privées soit presque optimale, les prix semblent inabordables par rapport aux GSDP. Des initiatives telles que la prescription de médicaments génériques, l'inscription des CDF sous ME, l'amélioration de la transparence des prix, la rationalisation de l'approvisionnement en médicaments pour assurer un accès équitable aux ME, en particulier dans le secteur public, sont essentielles pour faire face à la charge toujours croissante des MCV dans le Kerala.

Effects of sedative-hypnotics on sleep quality among patients with insomnia: evidence from an observational, pre-post study in India.

BACKGROUND: Insomnia continues to be neglected globally, despite its high prevalence. Guidelines by the health regulatory agencies call for studies to evaluate the effect of sedative-hypnotics on sleep quality. METHODS: We conducted a pre-post observational study to evaluate sleep quality among 186 inpatients receiving short-term oral sedative-hypnotic therapy in a tertiary care teaching hospital in Kozhikode (Kerala), India. Using Pittsburgh Sleep Quality Index_Past-Week (PSQI_PW) questionnaire, patients were interviewed upon hospital admission and at follow up after ≥1-week of sedative-hypnotic therapy. Additionally, we interviewed 36 physicians to understand the current clinical perception about sedative-hypnotics. RESULTS: Mean (SD) age of the study patients was 59 (7.5) years. Majority (63.4%) of the patients were men. Of the various primary diagnoses for hospitalization, cardiovascular disease was the most common (22.6%, n = 49). Sedative-hypnotic therapy improved the mean (SD) PSQI_PW overall score by 6.79 points (pre: 12.70 (3.5) vs. post: 5.91 (2.8); p < 0.0001). Statistically significant improvements in sleep duration, latency, efficacy, and day dysfunction were observed. Higher proportion of study patients were prescribed benzodiazepines (73.7%) compared to zolpidem (26.3%). Patients treated with zolpidem reported higher improvements in mean overall PSQI_PW scores compared to those treated with benzodiazepines, however these differences were not statistically significant upon adjusting for age, gender and primary diagnosis for hospitalization. Qualitative interviews indicate that that physicians consider zolpidem to be safer and more efficacious. CONCLUSIONS: In our study, sedative-hypnotic therapy helped improve sleep quality among the hospitalized patients. More studies evaluating the comparative efficacy and safety of zolpidem vs. benzodiazepines - including among patient groups with varying demographic and clinical characteristics - are needed. India must develop evidence-based treatment guidelines to inform the clinical practice around the use of sedative-hypnotics.

Challenges constraining availability and affordability of insulin in Bengaluru region (Karnataka, India): evidence from a mixed-methods study.

INTRODUCTION: Considering limited global access to affordable insulin, we evaluated insulin access in public and private health sectors in Bengaluru, India. METHODS: Employing modified WHO/HAI methodology, we used mixed-methods analysis to study insulin access and factors influencing insulin supply and demand in Bengaluru in December 2017. We assessed insulin availability, price and affordability in a representative sample of 5 public-sector hospitals, 5 private-sector hospitals and 30 retail pharmacies. We obtained insulin price data from websites of government Jan Aushadhi scheme (JAS) and four online private-sector retail pharmacies. We interviewed wholesalers in April 2018 to understand insulin market dynamics. RESULTS: Mean availability of insulins on India's 2015 Essential Medicine List was 66.7% in the public sector, lower than private-sector retail (76.1%) and hospital pharmacies (93.3%). Among private retailers, mean availability was higher among chain (96.7%) than independent pharmacies (68.3%). Non-Indian companies supplied 67.3% products in both sectors. 79.1% products were manufactured in India, of which 60% were marketed by non-Indian companies.In private retail pharmacies, median consumer prices of human insulin cartridges and pens were 2.5 and 3.6 times, respectively, that of human insulin vials. Analogues depending on delivery device were twice as expensive as human insulin. Human insulin vials were 18.3% less expensive in JAS pharmacies than private retail pharmacies. The lowest paid unskilled worker would pay 1.4 to 9.3 days' wages for a month's supply, depending on insulin type and health sector. Wholesaler interviews suggest that challenges constraining patient insulin access include limited market competition, physicians' preference for non-Indian insulins, and the ongoing transition from human to analogue insulin. Rising popularity of online and chain pharmacies may influence insulin access. CONCLUSION: Insulin availability in Bengaluru's public sector falls short of WHO's 80% target. Insulin remains unaffordable in both private and public sectors. To improve insulin availability and affordability, government should streamline insulin procurement and supply chains at different levels, mandate biosimilar prescribing, educate physicians to pursue evidence-based prescribing, and empower pharmacists with brand substitution. Patients must be encouraged to shop around for lower prices from subsidized schemes like JAS. While non-Indian companies dominate Bengaluru's insulin market, rising market competition from Indian companies may improve access.

Evaluation of Supportive Care Management Outcomes in Cancer Chemotherapy: A Prospective Observational Study in a Tertiary Care Teaching Hospital in South India.

AIMS: Evaluation of supportive care management of cancer patients experiencing drug-related problems (DRPs) is a challenge because it might increase the cost due to additional therapy. The main objectives of this study were to estimate chemotherapy-associated drug-related hospital admissions in the department of medical oncology and to estimate the cost of managing chemotherapy-associated DRPs. SETTINGS AND DESIGN: This study is a prospective observational study. SUBJECTS AND METHODS: Patients with chemotherapy-related DRPs were prospectively identified from the patient's medical records. The contribution of DRPs and cost incurred due to each hospitalization was assessed. STATISTICAL ANALYSIS USED: Data were analyzed using SPSS® 20.0 version. RESULTS: Out of 55 patients analyzed for DRPs, 25 (45.5%) patients in the age group of 51-60 years experienced DRPs most frequently. Most commonly occurring DRP was adverse drug reactions 42 (76.4%), which were more frequent in females. DRPs were maximum with alkylating agents 15 (27.3%) and the least with hormonal agents 1 (1.8%). The mean length of hospitalization was 9.6 ± 6.5 days. The total direct medical cost was Rs. 31,540 ± 42,476, of which medicine cost accounted for Rs. 16,550 ± 25,404, constituting a major share of the total medical costs. CONCLUSIONS: Pharmacists can provide better patient care by identifying and preventing DRPs and reducing drug-related morbidity and mortality.

Effectiveness of clinical pharmacist intervention on health-related quality of life in chronic obstructive pulmonary disorder patients - a randomized controlled study.

WHAT IS KNOWN AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD), a preventable and treatable disease, has been described as '10% medication and 90% education'. Extreme physician scarcity limits the implementation of quality healthcare delivery in India. We conducted this study to evaluate the effectiveness of clinical pharmacist intervention on health-related quality of life (HRQoL) in patients with COPD in an Indian tertiary care hospital. METHODS: An open-labelled randomized controlled study was conducted over a 3-year period, at Kasturba Medical College Hospital, Manipal, India, after obtaining institutional ethics clearance (IEC 88/2012). The study was registered with the Indian clinical trial registry (CTRI/2014/08/004848). Patients were randomly assigned to two groups (intervention group [IG] and control group [CG]) by envelope method. St. George's Respiratory Questionnaire (SGRQ) was used to assess the HRQoL. The pharmacist intervention laid emphasis on (i) importance of medication compliance, (ii) need for smoking cessation, (iii) simple exercise, (iv) proper use of inhaler devices and (v) need for timely follow-up by pulmonary medicine department. SGRQ assessment was repeated at 6, 12, 18 and 24 months. RESULTS: Of 328 patients with COPD screened during the study period (March 2012 to June 2013), 260 (79%) were recruited. Of these, 202 (78%) patients completed follow-up (98 in CG and 104 in IG). Both groups were matched for baseline, sociodemographics and clinical characteristics. SGRQ scores and its subscales (symptoms, activity and impact) improved significantly after the pharmacist intervention in IG at follow-up (P < 0·001). WHAT IS NEW AND CONCLUSION: Our randomized controlled study shows that pharmacist intervention improved the HRQoL of patients with COPD in India. The generalizability of our results requires exploration even within other settings in India. Nonetheless, our results provide support for a greater involvement of pharmacists in the care of patients with COPD.

Multi-target drugs to address multiple checkpoints in complex inflammatory pathologies: evolutionary cues for novel "first-in-class" anti-inflammatory drug candidates: a reviewer's perspective.

Inflammation is a complex, metabolically expensive process involving multiple signaling pathways and regulatory mechanisms which have evolved over evolutionary timescale. Addressing multiple targets of inflammation holistically, in moderation, is probably a more evolutionarily viable strategy, as compared to current therapy which addresses drug targets in isolation. Polypharmacology, addressing multiple targets, is commonly used in complex ailments, suggesting the superior safety and efficacy profile of multi-target (MT) drugs. Phenotypic drug discovery, which generated successful MT and first-in-class drugs in the past, is now re-emerging. A multi-pronged approach, which modulates the evolutionarily conserved, robust and pervasive cellular mechanisms of tissue repair, with AMPK at the helm, regulating the complex metabolic/immune/redox pathways underlying inflammation, is perhaps a more viable strategy than addressing single targets in isolation. Molecules that modulate multiple molecular mechanisms of inflammation in moderation (modulating TH cells toward the anti-inflammatory phenotype, activating AMPK, stimulating Nrf2 and inhibiting NFκB) might serve as a model for a novel Darwinian "first-in-class" therapeutic category that holistically addresses immune, redox and metabolic processes associated with inflammatory repair. Such a multimodal biological activity is supported by the fact that several non-calorific pleiotropic natural products with anti-inflammatory action have been incorporated into diet (chiefly guided by the adaptive development of olfacto-gustatory preferences over evolutionary timescales) rendering such molecules, endowed with evolutionarily privileged molecular scaffolds, naturally oriented toward multiple targets.

South-Asian population has a higher likelihood for diabetes risk for statins regardless of potency.

Higher potency statins are associated with increased risk of new-onset diabetes (NOD) in Western populations. South-Asians phenotype, with certain unique features such as young onset of diabetes and lower threshold for diabetes risk factors, present a higher likelihood for NOD risk for statins regardless of potency.

Impact of diabetic foot ulcer on health-related quality of life: A cross-sectional study.

Studies have reported that health-related quality of life (HRQoL) is adversely affected by diabetic foot ulcer (DFU). There is a paucity of data on the effects of foot ulcers on HRQoL of diabetes patients in our population. Because South-Asians, especially Indians, have unique features related to diabetes and its complications, generalizing the data about their effect on HRQoL from any other part of the world is not a pragmatic approach. This study evaluated the impact of foot ulcers on HRQoL of diabetes patients. This cross-sectional study, conducted in Kasturba Hospital, Manipal (coastal South India), included 200 DFU patients in a study group (SG) and 200 diabetes patients in a control group (CG). The RAND-36 questionnaire was employed for evaluating HRQoL scores for the patients in both groups. DFU patients also completed the Diabetic Foot Ulcer Scale-Short Form questionnaire. Independent t-test was used to test the differences in mean scores. Results found that both CG and SG have "poor" HRQoL (mean score <50) on all the subscales except for two in CG. There is a statistically significant difference between groups (P < 0.05) on all eight of the subscales of HRQoL. For both CG and SG, the Physical Component Summary domain score (44.9 ± 6.3 v 28.4 ± 3.4) and Mental Component Summary domain score (42.5 ± 3.8 v 29.5 ± 7.1) were poor. There were significant differences between CG and SG for both mean Physical Component Summary score and Mental Component Summary score of HRQoL (p < 0.05). The Diabetic Foot Ulcer Scale-Short Form found that HRQoL is very poor for DFU patients on all six domains. The study concludes that DFU patients have very poor HRQoL compared with diabetic patients. Likewise, the diabetic foot is associated with severely impaired HRQoL in both physical and mental health aspects. This study will help to develop a patient education model for DFU patients by looking at the various HRQoL domains that are adversely affected by the presence of foot ulcer.

Sexual violence in India: addressing gaps between policy and implementation.

The savage Delhi rape of 16 December 2012 was instrumental in generating the Verma Report that framed policies for amending the Criminal Laws related to sexual violence, professionalizing forensic/medical examination of victims, and sensitizing the police, electorate and the educational sectors. Unfortunately, even after a year, the Indian Home Ministry has abysmally failed to implement most recommendations, even underutilizing budgetary allocations. This article addresses gaps in governance systems and offers solutions to the problem of sexual violence in India.

Antidiabetic activity of benzopyrone analogues in nicotinamide-streptozotocin induced type 2 diabetes in rats.

Benzopyrones are proven antidiabetic drug candidate in diabetic drug discovery. In this view novel synthetic benzopyrone analogues were selected for testing in experimental diabetes. Type 2 diabetes (T2D) was induced in Wistar rats by streptozotocin (60 mg/kg, i.p.) followed by nicotinamide (120 mg/kg i.p.). Rats having fasting blood glucose (FBG)>200 mg/dL, 7 days after T2D-induction, are selected for the study. Test compounds and standard treatment were continued for 15 days. FBG, oral glucose tolerance test (OGTT), and insulin tolerance test (ITT) were determined on 21st day after induction of T2D. Plasma lipids and serum insulin were estimated. Homeostatic model assessment (HOMA-IR) was then calculated from serum insulin. Rats were sacrificed and pancreas was isolated for histopathological observations. Oxidative stress markers were estimated in liver homogenate. Quercetin, a natural product with benzopyrone ring, showed significant hypoglycemic activity comparable to glibenclamide. Treatment with test compounds lowered the FBG and insulin resistance was significant alleviated as determined by OGTT, HOMA-IR, and ITT. There was significant normalisation of liver antioxidant enzymes compared to diabetic rats indicating that all the synthesised benzopyrone analogues are beneficial in reducing oxidative stress and are on par with the standard quercetin and glibenclamide in experimental T2D.

Antidiabetic activity of 3-hydroxyflavone analogues in high fructose fed insulin resistant rats.

Synthetic 3-hydroxyflavone analogues (JY-1, JY-2, JY-3, JY-4), were tested for antidiabetic activity in high-fructose-diet-fed (66 %, for 6 weeks) insulin-resistant Wistar rats (FD-fed rats). The fasting blood glucose, insulin, creatinine and AGEs were decreased to near normal upon treatment with test compounds. Insulin resistance markers such as HOMA-IR, K-ITT, plasma triglycerides, lipids, endogenous antioxidant defense and glycogen were restored in FD-fed rats after treatment with 3-hydroxyflavones. It is known that insulin resistance is partly because of oxidative stress and hence antioxidant activity was determined. They exhibited significant in vitro DPPH and ABTS radical scavenging activity (IC50: 10.66-66.63 µM). Test compounds inhibited ROS and NO production in RAW 264.7 cells (IC50: 10.39-42.63 µM) and they were found as potent as quercetin. Further, the test compounds inhibited lipid peroxidation at low concentrations (IC50: 99.61-217.47 µM). All test compounds at concentrations 100-200 µM protected calf thymus DNA-damage by Fenton reaction. In addition, test compounds inhibited protein glycation in different in vitro antiglycation assays. JY-2 showed maximum potency in all the stages of glycation which was comparable to the standard quercetin and aminoguanidine. Test compounds also enhanced the glucose uptake by L6 myotubes at an EC50 much lower than that of quercetin. Thus the synthetic 3-hydroxyflavones were found to have good antidiabetic activity by pleotropic and multimodal suppression of insulin resistance and enhancement of glucose uptake by skeletal muscles. These compounds are non-toxic at the doses tested. Further, the combined antioxidant and antiglycation activities of these molecules have complementary benefits in management of diabetes.

A multimodal Darwinian strategy for alleviating the atherosclerosis pandemic.

The conflict between our 'primitive' genes and 'modern' lifestyle probably lies at the root of several disorders that afflict modern man. Atherosclerosis, which is relatively unknown among contemporary hunter-gatherer populations, has reached pandemic proportions in recent times. Being an evolutionary problem with several inter-related pathologies, current therapeutic strategy for treating atherosclerosis has inherent limitations. Reviewing evolution-linked risk factors suggests that there are four aspects to the etiology of atherosclerosis namely, decreased intestinal parasitism, oversensitivity of evolutionarily redundant mast cells, chronic underactivation of AMPK (cellular energy sensor) and a deficiency of vitamin D. A combination of these four causes appear to have precipitated the atherosclerosis pandemic in modern times. Man and worms co-existed symbiotically in the past. Massive de-worming campaigns could have disrupted this symbiosis, increasing nutritional availability to man (pro-obesity) at the cost of decreased immunotolerance (pro-atherogenicity). A reduction in helminth-induced chronic TH2 activation could also have enhanced TH1 polarization, eventually disrupting the reciprocal regulation of TH1/TH2 balance and resulting in atherosclerosis. The riddance of helminth infestations may have rendered mast cells immunologically redundant, making them oversensitive to inflammatory stimuli, thereby playing a pro-atherogenic role. AMPK activation exerts pleiotropic anti-atherogenic effects, such as suppression of fatty acid, cholesterol, protein synthesis, reduction of vascular smooth muscle proliferation, etc. As energy deficit is the chief stimulus for AMPK activation, the over-nourished modern man appears to be suffering from chronic underactivation of AMPK, legitimising the unrivalled supremacy of metformin, the oldest prescribed antidiabetic drug. The fact that humans evolved in the sunny tropics suggests that humans are selected for high vitamin D levels. Vitamin D deficiency is now linked to several conditions including increased risk of CV disorders, diabetes, etc. The manifold decrease in vitamin D levels in modern man justifies a need for supplementation. We therefore hypothesize that a judicious combination of mast cell stabilization, AMPK activation, vitamin D supplementation, and moderation in hygiene practices could be an evolution-based multimodal strategy for both preventing and mitigating the pandemic of atherosclerosis.

Topical application/formulation of probiotics: will it be a novel treatment approach for diabetic foot ulcer?

Treatment of chronic conditions like diabetic foot ulcer (DFU) is challenging due to increased susceptibility for infection and delayed wound healing. Complexity of existing therapy, adverse effects and microbial resistance emphasizes the need of an alternative approach for the management of DFU. The increasing body of evidence associated with probiotic application in diverse disease states merits its use in wound healing and infection too. Different probiotic strains have shown their efficacy in various infections like gut infections, oral infections and urogenital infections. Experimental studies have demonstrated probiotics' ability for gastric ulcer healing. Underlying mechanism of the above therapeutic effects of probiotics involves modulation of local and systemic immunity. The hypothesis is based on the concept that mechanism of anti-infective and ulcer healing action of probiotics will be similar in peripheral wounds and ulcers as on any other part of the body. This paper focuses on the hypothesis that topical applications/formulation of probiotics may be effective for the treatment of diabetic foot ulcers.

Synbiotic formulation of probiotic and lactulose combination for hepatic encephalopathy treatment: a realistic hope?

Gut-produced ammonia plays a vital role in the pathogenesis of hepatic encephalopathy because cirrhotic liver fails to clear toxic metabolites. Small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhosis add to the pathogenesis. Lactulose is a mainstay in the treatment of hepatic encephalopathy. Another benefit of lactulose is its prebiotic effect on probiotics that reduce the activity of bacterial urease, resulting in decreased hyperammoneamia and increased elimination of ammonia and other nitrogenous waste through enteric toxin reduction technology. Synbiotic formulation of probiotic and lactulose can synergistically/additively reduce ammonia production, increase utilization and excretion of ammonia and other nitrogenous wastes, thereby improving the well-being of patients with hepatic encephalopathy. We hypothesize that oral administration of a synbiotic formulation prepared from a combination of selected microbial strains of probiotics and lactulose will offer additional protection against hepatic encephalopathy via intra-intestinal extraction of toxic solutes in patients with cirrhosis.

6b,11b-Dihydroxy-6b,11b-dihydro-7H-indeno[1,2-b]naphtho[2,1-d]furan-7-one (DHFO), a small molecule targeting NF-κB, demonstrates therapeutic potential in immunopathogenic chronic inflammatory conditions.

6b,11b-Dihydroxy-6b,11b-dihydro-7H-indeno[1,2-b]naphtho[2,1-d]furan-7-one (DHFO), an easily synthesisable, orally bioavailable and relatively non-toxic small molecule synthesised in our lab, was previously reported to possess anti-oxidant, 5-lipoxygenase inhibitory, anti-inflammatory and peripheral analgesic activities. The present work deals with exploration of DHFO's efficacy in immunopathogenic chronic inflammatory conditions - arthritis and allergy. In carrageenan-induced inflammatory air pouch, which resembles the arthritic synovium, DHFO effectively reduced inflammatory redness and swelling and neutrophil infiltration. In complete Freund's adjuvant-induced arthritis, DHFO significantly decreased paw oedema and nitrite levels with efficacy comparable to diclofenac. DHFO inhibited neutrophil activation (observed as decreased myeloperoxidase levels), in both the in vivo models of inflammation. Interestingly, DHFO did not ulcerate the gastrointestinal tract, while diclofenac was observed to be extremely ulcerogenic. In antigen-induced active and passive anaphylaxis (allergy) models, DHFO dose-dependently prevented mesenteric mast cell (MC) degranulation with efficacy comparable to ketotifen. DHFO also inhibited compound 48/80 (C48/80)-induced paw oedema and peritoneal MC degranulation. DHFO stabilised p815 murine MCs stimulated by C48/80 and calcium ionophore-A23187, indicating an action downstream of calcium mobilisation. DHFO's anti-allergic mechanism could be two-pronged involving (1) inhibition of IgE production and/or (2) MC stabilisation. DHFO inhibited lipopolysaccharide (LPS)-induced pro-inflammatory mediator release (ROS, NO, IL-6 levels) and COX2 expression in RAW264.7 murine macrophages. Protein expression studies confirmed DHFO's ability to reduce nuclear levels of NF-κB in LPS-stimulated macrophages. Thus, DHFO is a promising non-ulcerogenic synthetic small molecule lead for immunopathogenic chronic inflammatory conditions.