XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

http://academic.oup.com/milmed/article-pdf/146/7/506/24126715/milmed-146-7-506.pdf

Goodman and Gilman's The Pharmacological Basis of Therapeutics

Male circumcision for HIV prevention in young men in Kisumu, Kenya : a randomised controlled trial. Commentary

Background: A substantial proportion of patients receiving fibrinolytic therapy for myocardial infarction with ST-segment elevation have inadequate reperfusion or reocclusion of the infarct-related artery, leading to an increased risk of complications and death. Methods: We enrolled 3491 patients, 18 to 75 years of age, who presented within 12 hours after the onset of an ST-elevation myocardial infarction and randomly assigned them to receive clopidogrel 8300-mg loading dose, followed by 75 mg once daily) or placebo. Patients received a fibrinolytic agent, aspirin, and when appropriate, heparin (dispensed according to body weight) and were echeduled to undergo angiography 48 to 192 hours after the start of study medication. The primary efficacy end point was a composite of an ocluded infarct-related artery (defined by a Thrombolysus in Myocardial Infarction flow grade of 0 or 1) on angiography or death or recurrent myocardial infarction before angiography. Results: The rates of the primary efficacy end point were 21.7 percent in the placebo group and 15.0 percent in the clopidogrel group, representing an absolute reduction of 6.7 percentage points in the rate and a 36 percent reduction in the odds of the end point with clopidogrel therapy (95 percent confidence interval, 24 to 47 percent; P<0.001). By 30 days, clopidogrel therapy reduced the odds ol the composite end point of death from cardiovascular causes, recurrent myocardial infarction, or recurrent ischemia leading to the need for urgent revascularization by 20 percent (from 14.1 to 11.6 percent, P=0.03). The rates of major bleeding and intracranial hemorrhage were similar in the two groups. Conclusions: In patients 75 years of age or younger who have myocardial infarction with ST-segment elevation and who receive aspirin and a standard fibrinolytic regimen, the addition of clopidogrel improves the patency rate of the infarct-related artery and reduces ischemic complications.

Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a cardioprotective phytochemical occurring in many plant products. In this study, a new series of imine congeners of resveratrol has been synthesized in which the imine moiety replaced the double bond in the structure of resveratrol. In addition, the in vitro antiplatelet activity of these resveratrol derivatives has been evaluated against adenosine diphosphate (ADP), arachidonic acid (AA), and collagen as platelet aggregation inducers. In general, the synthesized compounds were active as antiplatelet agents, and, therefore, the imine functional group may be considered as an effective replacement for a double bond in resveratrol for developing new and promising antiplatelet drugs.

/pdf/synthesis-of-imine-congeners-of-resveratrol-and-evaluation-gacrhgaww7.pdf

Synthesis of Imine Congeners of Resveratrol and Evaluation of Their Anti-Platelet Activity

Background: The biotransformation of steroids by fungal biocatalysts has been recognized for many years. There are numerous fungi of the genus Aspergillus which have been shown to transform different steroid substances. The possibility of using filamentous fungi Aspergillus brasiliensis cells in the biotransformation of androsta-1,4-diene-3,17-dione, was evaluated. Methods: The fungal strain was inoculated into the transformation medium which supplemented with androstadienedione as a substrate and fermentation continued for 5 days. The metabolites were extracted and isolated by thin layer chromatography. The structures of these metabolites were elucidated using 1 H-NMR, broadband decoupled 13 C-NMR, EI Mass and IR spectroscopies. Results: The fermentation yielded one reduced product: 17β-hydroxyandrost-1,4-dien-3-one and two hydroxylated metabolites: 11α-hydroxyandrost-1,4-diene-3,17-dione and 12β-hydroxyandrost-1,4-diene-3,17-dione. Conclusions: The results obtained in this study show that A. brasiliendsis could be considered as a biocatalyst for producing important derivatives from androstadienedione.

/pdf/fungal-transformation-of-androsta-1-4-diene-3-17-dione-by-sgesblcoy9.pdf

Fungal transformation of androsta-1,4-diene-3,17-dione by Aspergillus brasiliensis

A drug-like molecule could be considered as a congregation of small fragments which are chemically linked to each other and the biological effect of such molecule is due to the contribution of these small fragments working together. This molecular unit has been constructed gradually through a multi-step synthesis route. Assessment of the biological activity of all the intermediary compounds of a multi-step synthesis process helps to track down the emergence of biological activity alongside the synthesis process and the results provide valuable clues about the SAR of the compounds. Furthermore unanticipated findings may be encountered if such approach is exercised. A two-step synthesis route was employed to make a few 2-aminopyrimidines from their corresponding enamine precursors. Both aminopyrimidines and enamines were subjected to antiproliferative and antimicrobial tests. Hit compounds with acceptable activities were found in both aminopyrimidine and enamine series. With respect to antimicrobial activity, enamine series were found more promising. This experiment sets an example for the applicability of our new approach called "Synthesis route-based hit identification" as a tool in medicinal chemistry to increase the hit rate in drug discovery processes.

Introducing "synthesis route-based hit identification approach" as a tool in medicinal chemistry and its application in investigating the antiproliferative and antimicrobial effects of 2- aminopyrimidine derivatives

The outbreak of the second severe acute respiratory syndrome coronavirus (SARS-CoV-2) known as COVID-19 has caused global concern. No effective vaccine or treatment to control the virus has been approved yet. Social distancing and precautionary protocols are still the only way to prevent person-to-person transmission. We hope to identify anti-COVID-19 activity of the existing drugs to overcome this pandemic as soon as possible. The present study used HEX and AutoDock Vina softwares to predict the affinity of about 100 medicinal structures toward the active site of 3-chymotrypsin-like protease (3Clpro) and RNA-dependent RNA polymerase (RdRp), separately. Afterwards, MOE software and the pharmacophore-derived query methodology were employed to determine the pharmacophore model of their inhibitors. Tegobuvir (19) and compound 45 showed the best binding affinity toward RdRp and 3Clpro of SARS-CoV-2 in silico, respectively. Tegobuvir -previously applied for hepatitis C virus- formed highly stable complex with uncommon binding pocket of RdRp (E total: -707.91 Kcal/mol) in silico. In addition to compound 45, tipranavir (28) and atazanavir (26) as FDA-approved HIV protease inhibitors were tightly interacted with the active site of SARS-CoV-2 main protease as well. Based on pharmacophore modelling, a good structural pattern for potent candidates against SARS-CoV-2 main enzymes is suggested. Re-tasking or taking inspiration from the structures of tegobuvir and tipranavir can be a proper approach toward coping with the COVID-19 in the shortest possible time and at the lowest cost.

In silico prediction of SARS-CoV-2 main protease and polymerase inhibitors: 3D-Pharmacophore modelling.

Magnesium is an essential metal that has important roles in physiological function of the body organs. Ethambutol is an oral antitubercular agent with chelating effects owing to its chemical structure. The aim of present study is to determine whether ethambutol usage can alter serum magnesium concentration in patients with pulmonary tuberculosis. Sixty patients with diagnosis of pulmonary tuberculosis were enrolled in the study. Blood samples were obtained before treatment from patients. Ten days after starting anti tuberculosis therapy, second blood samples were obtained. The amounts of serum magnesium were determined in all samples by spectrophotometric method. Statistical analysis showed that serum magnesium concentrations at baseline (0.61± 0.08 mmol/l) and at day 10 (0.62± 0.11 mmol/l) were not different. It is possible that ethambotol does not affect magnesium concentration in tuberculosis patients, however further studies about the other cationic trace elements are recommended.

http://ijpr.sbmu.ac.ir/article_785_59307cd288c429c7a906ae7e0cc504d5.pdf

Farzad Kobarfard

Papers

Synthesis of Imine Congeners of Resveratrol and Evaluation of Their Anti-Platelet Activity

Fungal transformation of androsta-1,4-diene-3,17-dione by Aspergillus brasiliensis

Introducing "synthesis route-based hit identification approach" as a tool in medicinal chemistry and its application in investigating the antiproliferative and antimicrobial effects of 2- aminopyrimidine derivatives

In silico prediction of SARS-CoV-2 main protease and polymerase inhibitors: 3D-Pharmacophore modelling.

Effect of Antituberculosis Regimen Containing Ethambutol on Serum Magnesium Level in Pulmonary Tuberculosis Patients