Structure-based computational peptide design methods have gained significant interest in recent years owing to the availability of structural insights into protein−protein interactions obtained from the crystal structures. The majority of these approaches design new peptide ligands by connecting the crucial amino acid residues from the protein interface and are generally not based on any predicted receptor−ligand interaction. In this work, a peptide design method based on the Knob−Socket model was used to identify the specific ligand residues packed into the receptor interface. This method enables peptide ligands to be designed rationally by predicting amino acid residues that will fit best at the binding site of the receptor protein. In this, specific peptide ligands were designed for the model receptor CD13, overexpression of which has been observed in several cancer types. From the initial library of designed peptides, three potential candidates were selected based on simulated energies in the CD13 binding site using the programs molecular operating environment and AutoDock Vina. In the CD13 enzymatic activity inhibition assay, the three identified peptides exhibited 2.7−7.4 times lower IC 50 values (GYPAY, 227 μM; GFPAY, 463 μM; GYPAVYLF, 170 μM) as compared to the known peptide ligand CNGRC (C1−C5) (1260 μM). The apparent binding affinities of the peptides (GYPAY, K i = 54.0 μM; GFPAY, K i = 74.3 μM; GYPAVYLF, K i = 38.8 μM) were 10−20 times higher than that of CNGRC (C1−C5) (K i = 773 μM). The double reciprocal plots from the steady-state enzyme kinetic assays confirmed the binding of the peptides to the intended active site of CD13. The cell binding and confocal microscopy assays showed that the designed peptides selectively bind to the CD13 on the cell surface. Our study demonstrates the feasibility of a Knob−Socket-based rational design of novel peptide ligands in improving the identification of specific binding versus current more labor-intensive methods.
This study was carried out to improve the dissolution properties of loratadine by solid dispersion technique. A series of solid dispersions of loratadine in PVP K-30 (1:1, 1:3 and 1:5) were prepared by kneading technique. The prepared solid dispersions were characterized by various physicochemical properties (fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscopy) and the dissolution characteristics were compared with loratadine and the physical mixtures of loratadine. It was revealed from the physicochemical analyses that there was a good compatibility between drug and carrier. On the other hand, the drug release from the prepared binary solid dispersions was significantly enhanced in comparison to both drug alone and the physical mixtures. Finally solid dispersion of loratadine: PVP K-30 prepared as 1:5 ratio was found to be described by non-Fickian release mechanism and was selected as the best formulation in this study.
Background: Blue Rubber Bleb Nevus syndrome (BRBNS) is a rare disorder, that results in congenital cutaneous hemangiomas of the skin and gastrointestinal tract. Although asymptomatic, the nevi present as soft, non-mobile, dark blue, compressible papules. Clinically it presents as iron deficiency anemia due to occult gastrointestinal bleeding. Case presentation: A 22-year-old female patient presented with complaints of shortness of breath, fatigue, and palpitation for 2 months. On examination, she had a pale effect and widespread hemangiomas on her lips, hands, and feet. Laboratory results revealed iron deficiency anemia with hemoglobin (Hb) of 2.1 gm/dl and histopathology results of the hemangioma specimen showed angiokeratomas. Based on clinical manifestations and laboratory results, the patient was diagnosed with a case of BRBNS. The patient was transfused with red cell concentrate her symptoms improved but on the first follow-up visit her Hb again dropped to 8.6 mg/dl. Conclusion: A high suspicion of BRBNS diagnosis should be considered if a patient presents with iron deficiency anemia and multiple cutaneous hemangiomas. Further screening should be done to explore internal bleeding and hemangiomas.
Noise is considered as a sound of independent loudness and an environmental pollutant, produces in conjunction with various anthropogenic activities and becomes hazardous to all living being. In this aspect, the research determined a noise inventory for urban and rural settings in Khulna District of Bangladesh and identified the relevant sources from which the noise produced such as urbanization, industrialization and motorization activities. Sound level meters and questionnaires were used for noise measurement and public perceptions regarding noise pollution in 2005 respectively. The research finds out higher values than the Bangladesh standard almost every sensitive areas like hospitals and schools. The identified noise-levels have the significant impacts on physical and mental health of the stakeholders particularly to the senior citizens, students and children. In addition, the research makes a comparison of noise levels between urban and rural settings, where the comparison shows that noise-levels are closely related with traffic volume, vehicles number, its quality and composition such as trucks, buses, auto rickshaws, construction activities, various machineries and other such tools and activities. The research also analyzes the people’s perception on the noise effects of both urban and rural areas to find out a sustainable remedial measure. The health effects include suffering from headache, bad-temper, sleeplessness, aggravation, hearing problems and other relevant diseases.
Background:Thyroid diseases and diabetes mellitus are the two most common endocrine disorders encountered in clinical practice. Type 2 diabetes mellitus (T2DM) has an intersecting underlying pathology with thyroid dysfunction. Insulin and thyroid hormones are intimately involved in cellular metabolism and thus excess or deficit of either of these hormones result in the functional derangement of the other.Despite the absence of definite guidelines regarding screening for thyroid dysfunction in diabetic patients, in the view of this incidence together with the mutual effect of the common two endocrinopathies on each other and the increased risk of complications in diabetic patients in the setting of abnormal thyroid dysfunction, a systematic approach to thyroid testing in diabetic patients is favorable. Methods:A Cross sectional descriptive observational study was performed at a tertiary care centre.Patients of 30 years and older with known type 2 DM without thyroid disorders between March 2018 to September 2018 were included in this study by purposive sampling technique.A total of 100 patients were included in the study. Results:Among the study patients, 13(26%) had thyroid abnormalities, 8 cases were male and 5 cases were female. Thyroid abnormality was associated with duration of DM. The mean duration of disease was 6.28±2.57 years in patients with normal thyroid profile group and 10.92±8.13 years in patients with abnormal thyroid profile (hypothyroidism or hyperthyroidism) group. Patients with poor glycemic control prone to develop endocrinopathies like thyroid abnormality. HbA1c also shows the positive correlation with thyroid abnormality in type 2 diabetes patients. Regarding the definition of thyroid abnormality, 7% patients had Primary hypothyroidism, 2% Subclinical hypothyroidism and 3% primary hyperthyroidism and single case subclinical hyperthyroidism. Conclusion: Our results demonstrate that hypothyroidism is the common thyroid disorder in type 2 DM patient. It seems that unidentified thyroid dysfunction could positively impact diabetes and its complications. The ability to diagnose and treat unsuspected thyroid dysfunction in these patients may greatly enhance the quality of life. Hence the need to detect such cases where thyroid dysfunction contributes to morbidity and where it is the cause for poor control of the associated conditions. Bangladesh J Medicine 2022; 33: 193-201
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