Barriers to the hospital treatment among Bede snake charmers in Bangladesh with special reference to venomous snakebite.

Snakebite envenoming is a potentially life-threatening global public health issue with Bangladesh having one of the highest rates of snakebite cases. The Bede, a nomadic ethnic group in Bangladesh, traditionally engages in snake-related business such as snake charming. The Bede relies on their own ethnomedicinal practitioners for snakebite treatment while there is a lack of concrete evidence on the effectiveness of such ethnomedicinal treatment. To identify the barriers to the utilization of biomedical treatment for snakebite we conducted interviews with 38 Bede snake charmers, who have experienced snakebite, and six family members of those who died of snakebite. Our results show that four critical barriers, Accessibility, Affordability, Availability, and Acceptability (4As), prevented some of the Bede from seeking biomedical treatment. Moreover, we found that a few Bede died of a snakebite every year. There are survivors of snakebite who were able to receive biomedical treatment by overcoming all of the 4As. Our results provide insights into the current state of snakebite treatment in Bangladesh and can inform the development of more effective and accessible treatment options for those affected. Partnership between the public sector and the Bede community has the potential to make a significant impact in reducing snakebite morbidity and mortality in Bangladesh.

Anti-Trypanosoma cruzi activity of Coptis rhizome extract and its constituents.

BACKGROUND: Current therapeutic agents, including nifurtimox and benznidazole, are not sufficiently effective in the chronic phase of Trypanosoma cruzi infection and are accompanied by various side effects. In this study, 120 kinds of extracts from medicinal herbs used for Kampo formulations and 94 kinds of compounds isolated from medicinal herbs for Kampo formulations were screened for anti-T. cruzi activity in vitro and in vivo. METHODS: As an experimental method, a recombinant protozoan cloned strain expressing luciferase, namely Luc2-Tulahuen, was used in the experiments. The in vitro anti-T. cruzi activity on epimastigote, trypomastigote, and amastigote forms was assessed by measuring luminescence intensity after treatment with the Kampo extracts or compounds. In addition, the cytotoxicity of compounds was tested using mouse and human feeder cell lines. The in vivo anti-T. cruzi activity was measured by a murine acute infection model using intraperitoneal injection of trypomastigotes followed by live bioluminescence imaging. RESULTS: As a result, three protoberberine-type alkaloids, namely coptisine chloride, dehydrocorydaline nitrate, and palmatine chloride, showed strong anti-T. cruzi activities with low cytotoxicity. The IC50 values of these compounds differed depending on the side chain, and the most effective compound, coptisine chloride, showed a significant effect in the acute infection model. CONCLUSIONS: For these reasons, coptisine chloride is a hit compound that can be a potential candidate for anti-Chagas disease drugs. In addition, it was expected that there would be room for further improvement by modifying the side chains of the basic skeleton.

Mini-review on the properties and possible applications of therapeutic oxygen carrier Hemarina-M101.

Therapeutic Oxygen Carriers (TOCs) have been studied in the past for utilization in resuscitation fluid, treatment of organ ischemia, and as an alternative to red blood cell transfusion. One TOC, Hemarina-M101, seems promising in transplantation and oxygenation due its capability as a non-immunogenic, nontoxic, high-oxygen-carrying capacity TOC with little to no side effects. This mini-review focuses on Hemarina-M101 and explores its characteristics and possible utilities through past and recent studies.

Tolerance to FVIII: Role of the Immune Metabolic Enzymes Indoleamine 2,3 Dyoxigenase-1 and Heme Oxygenase-1.

The occurrence of neutralizing anti-FVIII antibodies is a major complication in the treatment of patients affected by hemophilia A. The immune response to FVIII is a complex, multi-factorial process that has been extensively studied for the past two decades. The reasons why only a proportion of hemophilic patients treated with FVIII concentrates develop a clinically significant immune response is incompletely understood. The "danger theory" has been proposed as a possible explanation to interpret the findings of some observational clinical studies highlighting the possible detrimental impact of inflammatory stimuli at the time of replacement therapy on inhibitor development. The host immune system is often challenged to react to FVIII under steady state or inflammatory conditions (e.g., bleeding, infections) although fine tuning of mechanisms of immune tolerance can control this reactivity and promote long-term unresponsiveness to the therapeutically administered factor. Recent studies have provided evidence that multiple interactions involving central and peripheral mechanisms of tolerance are integrated by the host immune system with the environmental conditions at the time of FVIII exposure and influence the balance between immunity and tolerance to FVIII. Here we review evidences showing the involvement of two key immunoregulatory oxygenase enzymes (IDO1, HO-1) that have been studied in hemophilia patients and pre-clinical models, showing that the ability of the host immune system to induce such regulatory proteins under inflammatory conditions can play important roles in the balance between immunity and tolerance to exogenous FVIII.

Molecular Mechanisms of Inhibitor Development in Hemophilia.

The development of neutralizing antibodies in hemophilia is a serious complication of factor replacement therapy. These antibodies, also known as "inhibitors", significantly increase morbidity within the hemophilia population and lower the quality of life for these patients. People with severe hemophilia A have an overall 25-40% lifetime risk of inhibitor development, compared to that of 5-15% lifetime risk in those with moderate/mild hemophilia A. The risk is lower in hemophilia B population (about 1-5%) and occurrence of inhibitors is almost only seen in patients with severe hemophilia B. The understanding of the pathophysiological mechanism leading to the development of inhibitors in patients with hemophilia has improved considerably over the last 2 decades. Identification of early biomarkers which predict inhibitor development in previously untreated patients with hemophilia will assist in risk identification and possible early intervention strategies. In this review, we aim to summarize the molecular mechanisms of inhibitor development in hemophilia and to identify potential areas in need of further investigation.

Inferior vena cava syndrome in neonates: An evidence-based systematic review of the literature.

Neonatal inferior vena cava syndrome (IVCS), though uncommon, is associated with significant morbidity and mortality. Information on risk factors, diagnosis, treatment, and outcomes is limited. This review comprised 61 neonates across 33 reports. Thrombosis occurred in 98% and 42% involved a central venous catheter. Diagnosis was mainly established by ultrasound in 82%. Therapeutically, heparin was employed in 36% and thrombolysis in 18% of the cases. The overall mortality was 23%. An algorithm of clinical signs, investigation, and management is presented. Well-designed prospective studies are needed to establish a concrete investigational approach to neonatal IVCS and institute safe, evidence-based treatment.