Structural exploration and study of the QSAR properties of several series of macrolide antibiotics.

In this work a fundamental and original research on the 14- membered macrolide, the aim is to predict the reactivity and biological activity of the compound studied and its derivatives. The molecular modeling methods used in our work are: MM+, PM3 and ab initio/HF(STO- 3G). These methods were used to determine the structural parameters, electronics and energy associated with molecules studied. The nature of such substituent (donor, acceptor) affects the electronic and energy parameters of basic core of the 14- membered macrolide. Indeed, this qualitative study allows us to predict the chemical reactivity of derivatives of the 14- membered macrolide and also the ketolides. A study of structure - property relationships (SPR) forthe 14- membered macrolide derivatives has been carried out for a series of bioactive derivatives of the 14- membered macrolide. QSAR studies have been performed on fifty molecules of the 14- membered macrolide as the antibiotics, multiple linear regression analysis was performed to derive QSAR models which were further evaluated internally for the prediction of activity. The developed models were cross-validated by the ‘leave one out’ technique as well as by the calculation of statistical parameters LOO. High correlation between experimental and predicted activity values was observed, indicating the validation and the good quality of the derived QSAR model

CONFORMATIONAL ANALYSIS IN 18-MEMBERED MACROLIDE ANTIBIOTICS BASED ON MOLECULAR MECHANICS.

Conformational analysis of macrolides with 18-ring membered has been carried out using molecular mechanics calculations and molecular dynamics. A high conformational mobility of no complexed macrocycles has been obtained and an important stereoselectivity has been observed for the complexed macrocycles. For 18d macrolide, which was presented by a privileged conformer with 20.1% without complex, was populated with 50.1% in presence of Fe(CO)3. For the most privileged conformer geometry; the α,β-unsaturated ester group has an s-cis conformation with a torsion angle φ1: O19-C2-C3-C4 = 14.5° for macrocycle 18d macrolide and φ1: O19-C2-C3-C4 = 25.0° for 18s macrolide. The diene group has an s-trans conformation with a torsion angle φ2:C11-C12-C13-C14 = 169.4° for 18d macrolide and φ2:C10-C11-C12-C13 = 179.5° for 18s macrolide.  L’analyse conformationnelle des macrolides à 18 chaînons a été réalisée par des calculs de mécanique moléculaire et de dynamique moléculaire. Une mobilité conformationnelle élevée a été obtenue pour les macrocycles non complexés et une stéréosélectivité importante a été observé pour les macrocycles complexés. Pour le macrolide 18d, qui a été présenté par un conformère privilégié avec 20.1% sans complexe, est devenu 50.1% en présence de Fe(CO)3 Pour la géométrie du conformère le plus privilégiée; le système d’ester α,β-insaturé, a une conformation s-cis avec un angle de torsion φ1 : O19-C2-C3-C4 = 14.5° pour le macrolide 18d et φ1 : O19-C2-C3-C4 = 25.0° pour le macrolide 18s. Le système diène a une conformation s-trans avec un angle de torsion φ2 : C11-C12-C13-C14 = 169.4° pour macrolide 18d et φ2:C10-C11-C12-C13 = 179.5° pour macrolide 18s

Taxonomy and chemical characterization of antibiotics of Streptosporangium Sg 10 isolated from a Saharan soil

A new actinomycete strain designated Sg 10, producing antimicrobial substances was isolated from an Algerian soil. Morphological and chemical studies indicated that strain Sg 10 belonged to the genus Streptosporangium. The comparison of its physiological characteristics with those of known species of Streptosporangium showed significant differences with the nearest species Streptosporangium carneum. Analysis of the 16S rDNA sequence of strain Sg 10 showed a similarity level ranging between 96.3% and 97.8% within Streptosporangium species, with S. carneum the most closely related. However, the phylogenetic analysis indicated that strain Sg 10 represent a distinct phyletic line suggesting a new genomic species. The antimicrobial activity of strain Sg 10 showed an antibacterial activity against Gram-positive bacteria as well as an antifungal one. Four active products were isolated from the culture broth using various separation procedures. On the basis of UV-VIS spectrometry, infrared spectroscopy and chemical revelations, the antibiotics were classified in the group of glycosylated aromatics

Modulation of endogenous antioxidant defense and the progression of kidney disease in multi-heritage groups of patients with type 2 diabetes: PRospective EValuation of Early Nephropathy and its Treatment (PREVENT).

BACKGROUND: Diabetes is the western world's leading cause of end-stage renal disease. Glucose-dependent, oxidative stress is linked to the development of renal inflammation and sclerosis, which, in animal models of diabetes, can be prevented by anti-oxidative treatment. Patients of non-Caucasian heritage have low activity of the selenoprotein, antioxidant enzyme, glutathione peroxidase (GPx) and its co-factor vitamin E, which may be linked to their increased propensity to developing end-stage renal disease. RESEARCH DESIGN AND METHODS: We have designed a double-blind, randomized, placebo controlled study with selenium and/or vitamin E versus placebo as the interventions for patients with type 2 diabetes and chronic kidney disease (CKD) stages 1-3. A 2 × 2 factorial design will allow a balanced representation of the heritage groups exposed to each intervention. The primary biochemical outcome is change in GPx activity, and clinical outcome measure is the actual, rate of-and/or percentage change in estimated glomerular filtration rate (eGFR) from baseline. Analysis will be with a marginal model for longitudinal data using Generalized Estimating Equations corrected for measures of baseline serum antioxidant enzyme activities (GPx, superoxide dismutase and catalase), micronutrient levels (vitamins E and C), measures of inflammation (interleukin 6, c-reactive protein and monocyte chemoattractant protein-1) and markers of oxidative damage (plasma 8-isoprostaglandin F2α and urinary 8-hydroxydeoxyguanosine). EXPECTED RESULTS: The study will assess the relationship between GPx activity, oxidative stress, inflammation and eGFR. It will test the null hypothesis that antioxidant therapy does not influence the activity of GPx or other antioxidant enzymes and/or alter the rate of change in eGFR in these patient groups. CONCLUSIONS: Outcome data on the effect of antioxidants in human diabetic renal disease is limited. Previous post hoc analyses have not shown a beneficial effect of vitamin E on renal function. A recent trial of a pharmaceutical antioxidant agent, improved eGFR, but in patients with advanced diabetes-related chronic kidney disease its use was associated with an increased incidence of cardiovascular events. We will explore whether the nutritional antioxidants, vitamin E and selenium alone, or in combination in patients at high risk of renal disease progression, forestalls a reduction in eGFR. The study will describe whether endogenous antioxidant enzyme defenses can be safely modified by this intervention and how this is associated with changes in markers of oxidative stress. Trial registration ISRCTN 97358113. Registered 21st September 2009

Ethnic differences in the +405 and -460 vascular endothelial growth factor polymorphisms and peripheral neuropathy in patients with diabetes residing in a North London, community in the United Kingdom.

BACKGROUND: There are marked ethnic differences in the susceptibility to the long-term diabetic vascular complications including sensory neuropathy. The vascular endothelial growth factor (VEGF) +405 (C/G) and -460 (T/C) polymorphisms are associated with retinopathy and possibly with nephropathy, however no information is available on their relationship with peripheral neuropathy. Therefore, we examined the prevalence of these VEGF genotypes in a multi-ethnic cohort of patients with diabetes and their relationship with evident peripheral diabetic neuropathy. METHODS: In the current investigation, we studied 313 patients with diabetes mellitus of African-Caribbean, Indo-Asian and Caucasian ethnic origin residing in an inner-city community in London, United Kingdom attending a single secondary care centre. Genotyping was performed for the VEGF +405 and VEGF -460 polymorphisms using a pyrosequencing technique. RESULTS: Forty-nine patients (15.6%) had clinical evidence of peripheral neuropathy. Compared to Caucasian patients, African-Caribbean and Indo-Asian patients had lower incidence of neuropathy (24.6%, 14.28%, 6.7%, respectively; P = 0.04). The frequency of the VEGF +405 GG genotype was more common in Indo-Asian patients compared to African-Caribbean and Caucasian patients (67.5%, 45.3%, 38.4%, respectively; p ≤ 0.02). The G allele was more common in patients with type 2 diabetes of Indo-Asian origin compared to African-Caribbean and Caucasian origin (p ≤ 0.02). There was no difference between the ethnic groups in VEGF -460 genotypes. The distributions of the VEGF +405 and VEGF -460 genotypes were similar between the diabetic patients with and without neuropathy. CONCLUSIONS: In this cohort of patients, VEGF +405 and VEGF -460 polymorphisms were not associated with evident diabetic peripheral neuropathy, however an association was found between VEGF +405 genotypes and Indo-Asian which might have relevance to their lower rates of ulceration and amputation. This finding highlights the need for further investigation of any possible relationship between VEGF genotype, circulating VEGF concentrations and differential vulnerability to peripheral neuropathy amongst diabetic patients of different ethnic backgrounds

Ethnic differences in antioxidant defence in patients with type 2 diabetes mellitus

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Mobile telemonitoring for achieving tighter targets of blood pressure control in patients with complicated diabetes: a pilot study

Abstract BACKGROUND: Hypertension is a major risk factor for the long-term complications of diabetes. Mobile, self-measurement of blood pressure is emerging as a method to manage blood pressure in general, but its impact in patients with diabetes is unclear. METHODS: We randomized 137 patients with diabetes and hypertension to either mobile telemonitoring (n = 72) or usual care (n = 65). Clinic blood pressure was recorded at baseline and after 6 months. Patients in the intervention arm transmitted weekly blood pressure readings wirelessly, using adapted sensors via mobile phones to a central server. Clinicians received the data in real-time and using a web-based application provided management advice to the patient and their physicians. RESULTS: Systolic blood pressure fell significantly in the patients in the intervention group (mean [95% confidence interval], -6.5 [-0.8 to -12.2] mm Hg; P = 0.027) and remained unchanged in the control group (2.1 [9.3 to -5.0] mm Hg; P = 0.57). Patients within the intervention arm of African origin seemed to benefit more from the intervention. In addition, those who achieved a systolic blood pressure of <120 mm Hg had lower average blood sugars than those with higher readings (7.8 [SD 1.6] vs. 8.9 [SD 2.2] mmol/L; P = 0.02). CONCLUSIONS: In patients with diabetes, mobile telemonitoring has potential for delivering intensified care to improve blood pressure control, and its use may be associated with reduced exposure to hyperglycemia

Evaluation of a mobile phone telemonitoring system for glycaemic control in patients with diabetes

We conducted a randomized controlled trial using mobile health technology in an ethnically diverse sample of 137 patients with complicated diabetes. Patients in the intervention group (n = 72) were trained to measure their blood glucose with a sensor which transmitted the readings to a mobile phone via a Bluetooth wireless link. Clinicians were then able to examine and respond to the readings which were viewed with a web-based application. Patients in the control arm of the study (n = 65) did not transmit their readings and received care with their usual doctor in the outpatient and/or primary care setting. The mean follow-up period was 9 months in each group. The default rate was higher in the patients in the intervention arm due to technical problems. In an intention-to-treat analysis there were no differences in HbA(1c) between the intervention and control groups. In a sub-group analysis of the patients who completed the study, the telemonitoring group had a lower HbA(1c) than those in the control group: 7.76% and 8.40%, respectively (P = 0.06)

B-Cell Lymphoma of the Mandible: A Case Report

Introduction The mandible is an infrequent localisation of primary osseous non-Hodgkin's lymphomas. Few cases of mandibular non-Hodgkin's lymphomas (NHL) have been reported. Case Report A rare condition of primary malignant non-Hodgkin's lymphoma of the mandible in 53-year-old man, was reported at the Department of Maxillofacial and Plastic Surgery in Charles Nicolle Hospital (Tunis, Tunisia). Histologic and Immunohistochemical (IHC) examination Confirmed a B-Cell lymphoma. Discussion The purpose of this report is to describe this rare case of NHL of the mandible, explore the diagnosis and workup, and discuss treatment strategies. In this localisation, neither the clinical features nor the radiologic appearances are often pathognomonic. Conclusion Particular care must be taken to consider lymphoma in the differential diagnosis because this uncommon lesion can pose significant diagnostic problems and is frequently misdiagnosed