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Imino isatin derivatives; synthesis, in silico molecular dynamic study over monoamine oxidase B, ADME prediction, and in vitro cytotoxicity evaluation
No full textThe monoamine oxidase B (MAO-B) depicts an attractive drug target for the development of neuro protective agents toward the treatment of neurodegenerative diseases. The current study involved synthesis, in silico and cytotoxic evaluation of N1-alkylated-5-substituted 3-imino isatin derivatives with the proposed MAO-B inhibitory activities. The In silico molecular modeling investigation was performed through the induced fit docking, molecular mechanics-generalized born surface area, and molecular dynamic method in order to uncover the binding mode interaction and their proposed impact on the active site environment and flexibility. The synthesized compounds were characterized by spectroscopic methods. Compound 3-Imino-1-pentyl indolin-2-one (3h) with the highest free binding energy adopts an extended conformation spanning from the flavin ring location to the entrance of the substrate cavity. In this way, Ile199 adopts the �open� conformation so the two separate cavities of MAO-B active site fused and formed a single-space, which abled the compound extending to the MAO-B entrance cavity space. From consideration of the data presented in this paper, we reveal that longer N1-alkylated-3-imino isatin derivative could be proposed as inhibitor that would occupy both cavities of the MAO-B active site. Furthermore, the mentioned derivatives provided acceptable drug profiling based on in silico ADME calculation and MTT cytotoxicity test evaluation. © 2021 The Chemical Society Located in Taipei & Wiley-VCH Gmb
A closer look at pathogenesis of cerebral mucormycosis in diabetic condition: A mini review
No full textPatients with diabetes are considered a high-risk group involved with cerebral mucormycosis (CM). Due to the potential of Mucorales to invade sinuses and its rapid progression into orbit and retro-orbital areas and even brain, in most cases, CM is fatal in patients with diabetes. In the last few decades, mucormycosis and background conditions responsible for the development of its infections have received a great deal of attention. Dysfunction of innate and adaptive immune system, the increased amount of available nutrition, expression of host factors, and free iron level in plasma in diabetic ketoacidosis are among the topics that have been mostly taken into account so far. Therefore, it is important to clarify the molecular mechanisms that let the Mucorales to involve the patients with diabetes, which even at early stages of diagnosis and treatment, there is minimum chance to control the disease. © 2021 Wiley-VCH Gmb
Evaluation of Serum Immunoreactivity to Common Indigenous Iranian Inhalation and Food Allergens in Patients with Meniere�s Disease
No full textBackground: A few studies investigated the relationship between allergy and Meniere disease considering complete allergen panel. We aimed to evaluate the serum immunoreactivity in patients with Meniere�s disease (MD) compared with healthy people according to common indigenous Iranian inhalation and food allergens. Methods: Thirty-nine patients with MD referred to Rasoul Akram Hospital (Tehran, Iran) were evaluated and compared with a 41 membered control group. A panel of common inhalation and food allergens (using an immunoblotting method), as well as total immunoglobulin E (IgE) level (using the sandwich enzyme-linked immunosorbent assay method), were checked on the patients� serum. Results: The mean total IgE level was 193.85 ± 175.43 IU/ml in the patients with MD and 117.61 ± 138.05 IU/ml in the control group, which was significantly higher than the other subjects in the control group (P = .016). There was a significant difference between the two groups regarding inhalation allergens such as; sweet vernal grass, cultivated rye, cultivated oat, Russian thistle, goosefoot, and rough pigweed (P = .01�0.038). Patients with MD reported more reactive to food allergens such as; rye flour, hazelnut, pepper, citrus mix 2, potato, strawberry, and celery allergens. There was a significant relationship between Meniere and serum immunoreactivity to inhalation and food allergens (both P = .001). Conclusion: Serum total IgE level in patients with MD (in both inhalation and food allergens groups) was higher than the control group, and there was a relationship between MD and immunoreactivity to common indigenous inhalation and food allergens of Iran. © 2021 Taylor & Francis Group, LLC
Slot blotting and flow cytometry: two efficient assays for platelet antibody screening among patients with platelet refractoriness
No full textBackground and Objectives: Frequent platelet transfusion may lead to the formation of alloantibodies and immune-mediated platelet destruction. Currently, identifying economic and effective screening methods is necessary for the management of platelet transfusion while different tests were recommended. The present study aims to challenge the performance of slot blotting (SB) and flow cytometry (FC) assays in detecting immune platelet refractoriness. Materials and Methods: Sera from 118 patients who received blood components and were clinically suspected of platelet refractoriness were enrolled. Platelet-reactive antibodies were explored in parallel by SB, FC and monoclonal antibody-specific immobilization of platelet antigens (MAIPA) techniques. In a further study, chloroquine-treated platelets were incubated with MAIPA-positive serum, and then, the results of the SB and FC techniques were compared. Results: Using MAIPA as a reference, antibodies were detected in 51 sera, with specificity for human leucocyte antigens (HLA), human platelet antigens (HPA) or both HLA/HPA, in 27, 18 and 6 patients, respectively. The sensitivity and specificity of SB and FC were 86·3, 88·1, 82·4 and 95·5, respectively. The Spearman correlation revealed significant (P < 0·001) correlations between FC (r = 0·763) and SB (r = 0·738) with MAIPA. In respect to HPA antibody detection, SB had 83·3 sensitivity and 92·6 specificity compared to 91·7 and 96·3 for FC while both approaches are acceptable (P < 0·001, r = 0·69; P < 0·001, r = 0·773) and can be recommended. Conclusions: The present study acknowledges that among the used methods, the flow cytometry's performance is the most appropriate, but slot blotting, with acceptable sensitivity, can be used as an acceptable and convenient procedure for platelet antibody screening. © 2020 International Society of Blood Transfusio
Prophylactic use of tranexamic acid for decreasing the blood loss in elective cesarean section: A placebo-controlled randomized clinical trial
No full textIntroduction: Tranexamic acid is used as a known treatment of post-partum hemorrhage both in natural vaginal deliveries and cesarean sections, but its use in elective cesarean as a prophylactic measure to decrease the blood loss is not so common. Objective: This clinical trial evaluates the efficacy and safety of tranexamic acid in decreasing the bleeding in women undergoing elective cesarean section. Method: 200 term singleton pregnant women who were scheduled for elective cesarean section were randomized to 2 groups and received a bolus of 1 gm tranexamic acid if body weight was 90 kg diluted in 15 ml of 5 dextrose intravenously, or 5 ml of distilled water in 15 ml of 5 dextrose as placebo (before skin incision). Intra-operative and post-operative blood loss and hemoglobin levels were compared. Results: Tranexamic acid decreased the mean blood loss by 25.3 in our studied women. Mean volume of intra-operative blood loss was 391.1 (±67.4) ml in tranexamic acid group and 523.8 (±153.4) ml in control group which was statistically significant lesser with a 132.7 ml difference. Rate of >1000 ml and >500 ml bleeding and need to blood transfusion were also statistically significant lower in tranexamic acid group., mean hemoglobin level was statistically significant lower in placebo group than tranexamic acid group (11.77 ± 0.50 versus 11.31 ± 0.56) 6 h after cesarean section. No adverse reaction was documented. Conclusion: Prophylactic use of intravenous tranexamic acid decreases the blood loss safely in women undergoing elective cesarean section. © 2020 Elsevier Masson SA
Computer aided diagnosis system using deep convolutional neural networks for ADHD subtypes
No full textBackground: Attention deficit hyperactivity disorder (ADHD) is a ubiquitous neurodevelopmental disorder affecting many children. Therefore, automated diagnosis of ADHD can be of tremendous value. Unfortunately, unlike many other applications, the use of deep learning algorithms for automatic detection of ADHD is still limited. Method: In this paper, we proposed a novel computer aided diagnosis system based on deep learning approach to classify the EEG signal of Healthy children (Control) from ADHD children with two subtypes of Combined ADHD (ADHD-C) and Inattentive ADHD (ADHD-I). Inspired by the classical approaches, we proposed a deep convolutional neural network that is capable of extracting both spatial and frequency band features from the raw electroencephalograph (EEG) signal and then performing the classification. Result: We achieved the highest classification accuracy with the combination of β1, β2, and γ bands. Accuracy Recall, Precision, and Kappa values were 99.46, 99.45, 99.48, and 0.99, respectively. After investigating the spatial channels, we observed that electrodes in the Posterior side had the most contribution. Conclusions: To the best of our knowledge, all previous multiclass studies were based on fMRI and MRI imaging. Therefore, the presented research is novel in terms of using a deep neural network architecture and EEG signal for multiclass classification of ADHD and healthy children with high accuracy. © 202
Targeted photothermal therapy of melanoma in C57bl/6 mice using Fe3 O4 @Au core-shell nanoparticles and near-infrared laser
Get PDFBackground: Gold nanoshells can be tuned to absorb a particular wavelength of light. As a result, these tunable nanoparticles (NPs) can efficiently absorb light and convert it to heat. This phenomenon can be used for cancer treatment known as photothermal therapy. In this study, we synthesized Fe3 O4 @Au core-shell NPs, magnetically targeted them towards tumor, and used them for photothermal therapy of cancer. Objective: The main purpose of this research was to synthesize Fe3 O4 @Au coreshell NPs, magnetically target them towards tumor, and use them for photothermal therapy of cancer. Material and Methods: In this experimental study, twenty mice received 2 � 106 B16-F10 melanoma cells subcutaneously. After tumors volume reached 100 mm3,the mice were divided into five groups including a control group, NPs group, laser irradiation group, NPs + laser group and NPs + magnet + laser group. NPs were injected intravenously. After 6 hours, the tumor region was irradiated by laser (808 nm, 2.5 W/cm2, 6 minutes). The tumor volumes were measured every other day. Results: The effective diameter of Fe3 O4 @Au NPs was approximately 37.8 nm. The average tumor volume in control group, NPs group, laser irradiation group, NPs + laser irradiation group and NPs + magnet + laser irradiation group increased to 47.3, 45.3, 32.8, 19.9 and 7.7 times, respectively in 2 weeks. No obvious change in the average body weight for different groups occurred. Conclusion: Results demonstrated that magnetically targeted nano-photothermal therapy of cancer described in this paper holds great promise for the selective destruction of tumors. © 2021, Shriaz University of Medical Sciences. All rights reserved
Recurrence of a neuroendocrine tumor of adrenal origin: a case report with more than a decade follow-up
Full text linkBackground: Neuroendocrine tumor (NET) with adrenocorticotropic hormone (ACTH) secretion are very rare. To our knowledge, no follow-up study is published for ACTH-secreting NET, regardless of the primary site, to show second occurrence of tumor after a long follow-up, following resection of primary tumor. Case presentation: Here, we describe a 49-year-old-man with cushingoid feature, drowsiness and quadriparesis came to emergency department at December 2005. Laboratory tests revealed hyperglycemia, metabolic alkalosis, severe hypokalemia, and chemical evidence of an ACTH-dependent hypercortisolism as morning serum cortisol of 57 μg /dL without suppression after 8 mg dexamethasone suppression test, serum ACTH level of 256 pg/mL, and urine free cortisol of > 1000 μg /24 h. Imaging showed only bilateral adrenal hyperplasia, without evidence of pituitary adenoma or ectopic ACTH producing tumors. Importantly, other diagnostic tests for differentiating Cushing disease (CD) from ectopic ACTH producing tumor, such as inferior petrosal sinus sampling (IPSS), corticotropin releasing hormone (CRH) stimulation test, octreotide scan or fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan were not available in our country at that time. Therefore, bilateral adrenalectomy was performed that led to clinical and biochemical remission of hypercortisolism and decreased ACTH level to < 50 pg/mL, findings suggestive of a primary focus of NET in adrenal glands. After 11 years uncomplicated follow up, the ACTH level elevated up to 341 pg/mL and re-evaluation showed a 2 cm nodule in the middle lobe of the right lung. Surgical excision of the pulmonary nodule yielded a carcinoid tumor with positive immunostaining for ACTH; leading to decrease in serum ACTH level to 98 pg/mL. Subsequently after 7 months, serum ACHT levels rose again. More investigation showed multiple lung nodules with metastatic bone lesions accompanied by high serum chromogranin level (2062 ng/mL), and the patient managed as a metastatic NET, with bisphosphonate and somatostatin receptor analogues. Conclusion: This case of surgically-treated NET showing a secondary focus of carcinoid tumor after one decade of disease-free follow-up emphasizes on the importance of long-term follow-up of ACTH-secreting adrenal NET. © 2021, The Author(s)