Haemoglobin E/Beta Thalassaemia- A Study in BSMMU

Background: Thalassaemias and haemoglobinopathies have been found sporadically in every ethnic group and geographic region, they occur with particularly high frequency from the shores of the Mediterranean and Africa through the Middle East, the Indian subcontinent, Burma and Southeast Asia. Objective: The study was designed to find out the incidence of HbE/beta thalassaemia in BSMMU. Method: A total of 700 patients suspected to have been suffering from haemolytic anaemia were included in the study. Patients having evidence of haemolysis in peripheral blood film were selected for reticulocyte count and haemoglobin electrophoresis in cellulose acetate membrane at pH 8.6. Result: The study group of 700 patients underwent Hb-electrophoresis of which only 52 (7.4%) cases were diagnosed as HbE/beta thalassaemia. Out of 52 cases, 34 (65.4%) patients were found symptomatic and the remaining 18 (34.6%) patients were asymptomatic. Out of 34 symptomatic cases of HbE/beta thalassaemia, only 14 cases needed blood transfusion. Among the 14 patients, only 8 patients needed more than 10 units of transfusion and 6 patients needed frequent transfusion that is two units of blood in every month. Conclusion: It is clearly evident from the present and other studied so far carried out in this Indian subcontinent and South-East Asia that hereditary haemolytic anaemia due to globin chain defects are quite common in this region, especially in Bangladesh and are responsible for considerable morbidity and mortality. Key words: Thalassaemia; Haemoglobinopathies; HbE/beta thalassemia. DOI: 10.3329/bsmmuj.v2i2.4762 BSMMU J 2009; 2(2): 78-8

Arthritis as a presentation of acute leukemia

A 14 year old boy presented with 3 months history of low back pain as well as pain and swelling of both knee joints. The pain was inflammatory in nature. He was thoroughly evaluated but no underlying cause was detected. However, the boy was treated with NSAIDs and sulphasalazine. A few weeks later he developed anemia and took the blood transfusion. Then he developed fever and the joint pain re-appeared. On examination, the patient was found moderately anemic, positive bony tenderness and splenomegaly. Musculoskeletal examination revealed right knee joint effusion. The investigation revealed pancytopenia. Bone marrow morphology and immunophenotyping revealed acute lymphoblastic leukemia. We treated the patient according to modified UKALL-2003 protocol and patient condition improved and arthritis disappeared

Arthritis as a presentation of acute leukemia

A 14 year old boy presented with 3 months history of low back pain as well as pain and swelling of both knee joints. The pain was inflammatory in nature. He was thoroughly evaluated but no underlying cause was detected. However, the boy was treated with NSAIDs and sulphasalazine. A few weeks later he developed anemia and took the blood transfusion. Then he developed fever and the joint pain re-appeared. On examination, the patient was found moderately anemic, positive bony tenderness and splenomegaly. Musculoskeletal examination revealed right knee joint effusion. The investigation revealed pancytopenia. Bone marrow morphology and immunophenotyping revealed acute lymphoblastic leukemia. We treated the patient according to modified UKALL-2003 protocol and patient condition improved and arthritis disappeared

Frequency of consanguineous marriage among the thalassaemia major patients in Bangabandhu Sheikh Mujib Medical University

Thalassaemia is a commonly occurring hereditary disorder. There is a high prevalence of thalassaemia disease in South-East Asia as well as Bangladesh. It is an autosomal recessive disorder, so consanguineous marriage is a very important factor for this disease. Mutated beta globin gene of haemoglobin from both parents is responsible for this disease to occur. But when the number of thalassaemia carriers is miserably high, then only avoidance of consanguineous marriage can’t prevent the birth of children with thalassaemia major. So, this cross sectional study was conducted among 120 diagnosed (by haemoglobin electrophoresis or high performance liquid chromatography) thalassaemia major patients in the Department of Haematology, Bangabandhu Sheikh Mujib Medical University, Dhaka from July 2019 to May 2020. History from each patient was taken and blood samples were collected from their parents to confirm carrier state by haemoglobin electrophoresis. Blood samples were also collected from patients and their parents toperform complete blood count and peripheral Blood Film. This study showed the mean age of the participants was 15±9.34 and 73 (60.8%) patients were male and 47 (39.2%) were female. About, 71% of the study population lived in urban area, 81 (67%) patients were transfusion dependent thalassaemia patients. 15% thalas- saemia major patients had the history of consanguinity of their parents. Among the parents of the thalassaemia major patients, 62.5% were Beta thalassaemia trait (heterozygous state), 25.83% parents were Hb E trait ( heterozygous state), 7.08% parents were suffering from Beta Thalassaemia Major(homozygous state) and 11 (4.58%) parents were suffering from Hb E/Beta Thalassaemia which is a compound heterozygous state. Though consanguinity is a very influential factor, but the most important causative factor is the presence of high number of thalassaemia carrier in the population. So, it’s a burning issue for the nation to perform a routine carrier screening for all rather than focusing on consanguinity only, to lessen the burden of thalassaemia disease in Bangladesh. BSMMU J 2022; 15(1): 25-2

P-glycoprotein Inhibition for Optimal Drug Delivery

P-glycoprotein (P-gp), an efflux membrane transporter, is widely distributed throughout the body and is responsible for limiting cellular uptake and the distribution of xenobiotics and toxic substances. Hundreds of structurally diverse therapeutic agents are substrates to it and it impedes the absorption, permeability, and retention of the drugs, extruding them out of the cells. It is overexpressed in cancer cells and accountable for obstructing cell internalization of chemotherapeutic agents and for developing transporter mediated resistance by cancer cells during anti-tumor treatments. As it jeopardizes the success of drug delivery and cancer targeting, strategies are being developed to overcome P-gp mediated drug transport. This concise review represents a brief discussion on P-gp mediated drug transport and how it hinders the success of various therapies. Its main focus is on various strategies used to tackle this curb in the field of drug delivery and targeting

Development of Floating-Mucoadhesive Microsphere for Site Specific Release of Metronidazole

Purpose: The purpose of this study was to develop and evaluate metronidazole loadedfloating-mucoadhesive microsphere for sustained drug release at the gastric mucosa.Methods: Alginate gastroretentive microspheres containing metronidazole were preparedby ionic gelation method using sodium bicarbonate as gas forming agent, guar gum asmucoadhesive polymer, and Eudragit L100 as drug release modifier. Carbopol was used forincreasing the bead strength. The microspheres were characterized by scanning electronmicroscopy and evaluated by means of drug entrapment efficiency, in vitro buoyancy, andswelling studies. In vitro mucoadhesion and drug release studies were carried out in order toevaluate site specific sustained drug release.Results: All formulations showed 100% buoyancy in vitro for a prolonged period of time.Amount of guar gum influenced the properties of different formulations. The formulationcontaining drug and guar gum at a ratio of 1:0.5 showed the best results with 76.3% drugentrapment efficiency, 61.21% mucoadhesion, and sustained drug release. Carbopol wasfound to increase surface smoothness of the microspheres.Conclusion: Metronidazole mucoadhesive-floating microspheres can be effectively usedfor sustained drug release to the gastric mucosa in treatment of upper GIT infection

Marine Polysaccharide-Based Immunomodulatory Hydrogels for Attenuation of Immune Response in Cell Therapy for Type-1 Diabetes

The encapsulation of pancreatic islets in hydrogels is of topical interest for its potential for treatment of type-1 diabetes. Clinical investigations have demonstrated only partial success of traditional immunoisolation by physical exclusion. This limitation highlights a complementary approach in the form of local immunomodulation for long-term islet survival.The present work focused on the development of an immunomodulatory hydrogel system for islet encapsulation. The anti-inflammatory and cell-protective properties of fucoidan and carrageenans suggest their potential to inhibit immune cell activation and to act as biological cues to support islet survival. Consequently, fucoidan and carrageenans were functionalised with methacrylate groups and the immunomodulatory properties were assessed. The polysaccharides were crosslinked with methacrylate-functionalised poly(vinyl alcohol) (PVA-MA) in order to fabricate biosynthetic hydrogels using UV photopolymerisation. Two hydrogel configurations were fabricated, one with low crosslink density for islet encapsulation and the other with high crosslink density for size-based exclusion. The former, which encapsulated pancreatic islets, was characterised by cell survival and functionality testing. The latter was characterised by the permeation of IgG and IL-1β, two harmful inflammatory molecules.The results demonstrated that fucoidan is an effective immunomodulatory agent that downregulates molecules responsible for islet dysfunction, particularly the expression of CD86, which is a major co-stimulatory molecule that contributes to the activation of T cells. Fucoidan also significantly decreased cellular nitric oxide production and demonstrated effective scavenging (>90%) of superoxide free radicals. In contrast, the carrageenans exhibited only the latter two effects. The hydrogel of high crosslink density was effective in blocking permeation of IL-1β in ~24 h while allowing permeation of BSA. The favourable effects of fucoidan were shown by the hydrogel of low crosslink density, which revealed high beta cell survival and glucose-stimulated insulin secretion over a period of 32 days. Further, fucoidan-based hydrogels protected beta cells from cytokine-induced cell death after 48 h of incubation.The present work confirms the effectiveness of fucoidan as an immunomodulatory agent and a biological cue for beta cell survival and function, suggesting its potential for clinical applications

Arthritis as a presentation of acute leukemia

A 14 year old boy presented with 3 months history of low back pain as well as pain and swelling of both knee joints. The pain was inflammatory in nature. He was thoroughly evaluated but no underlying cause was detected. However, the boy was treated with NSAIDs and sulphasalazine. A few weeks later he developed anemia and took the blood transfusion. Then he developed fever and the joint pain re-appeared. On examination, the patient was found moderately anemic, positive bony tenderness and splenomegaly. Musculoskeletal examination revealed right knee joint effusion. The investigation revealed pancytopenia. Bone marrow morphology and immunophenotyping revealed acute lymphoblastic leukemia. We treated the patient according to modified UKALL-2003 protocol and patient condition improved and arthritis disappeared