Structure-function studies of the tridecapeptide mating pheromone of Saccharomyces cerevisiae

An analog of α-factor, the Saccharomyces cerevisiae tridecapeptide mating pheromone (Trp-His-Trp-Leu-Gln-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr), in which the side chains of Lys7 and Gln10 were covalently linked, was synthesized using solid phase methodologies. The structure of the peptide was verified by chemical analyses. Cyclo7,10[Nle12]α-factor caused growth arrest and morphological alterations in S. cerevisiae MATa cells qualitatively identical to those induced by linear pheromone and was one-fourth to one-twentieth as active as the linear α-factor depending upon the S. cerevisiae strain tested. Competion binding studies were consistent with the relative activities of the linear and cyclic peptides. Hydrolysis of the cyclic peptide by the target cells did not lead to opening of the ring and was less rapid than that of linear α-factor. The α-factor antagonist des-Trp1-[Ala3,Nle12]α-factor reversed the activity of the cyclic analog, and cyclo7,10[Nle12]α-factor was not active at the restrictive temperature in a temperature-sensitive receptor mutant. These results support the conclusion that the cyclic α-factor occupies the same binding site within the receptor as is occupied by the natural pheromone. The cyclic α-factor represents a rare example of an agonist among covalently constrained congeners of small linear peptide messengers. Amino- and carboxy-terminus truncated peptides were derived from linear- and cyclic-α-factor using aminopeptidase M or carboxypeptidase A. Their structures were verified by chemical analyses. des-Trp1- or des-Tyr13- linear or cyclic α-factor peptides showed reduced agonist activity. des-Trp1,His2-linear or cyclic peptides were antagonists of α-factor activity. des-Nle12,Tyr13 linear or cyclic α-factor peptides exhibited synergistic activity with α-factor (increased the growth inhibition of S. cerevisiae caused by α-factor), although neither compound showed any agonist activity when tested alone. The exact mechanism of action of the synergistic peptides is still unkown

Influence of membrane lipid composition of Staphylococcus aureus on susceptibility to parabens.

The relationship between staphylococcal lipid composition and resistance to parabens was investigated. Chloroform-methanol extractable lipids were determined gravimetrically. Phospholipid and fatty acid fractions were studied using thin layer chromatography, gas liquid chromatography and mass spectrometry. Consistent quantitative differences were found among the total lipid, phospholipid and fatty acid compositions of sensitive and resistant strains. Most notable was the fact that, in paraben resistant strains, the percentage of total lipid and the phosphatidyl glycerol fraction of phospholipids were greater than in paraben sensitive strains. Furthermore, paraben resistant strains showed decreases in cyclopropane-ring containing fatty acids as compared with sensitive strains. Since significant differences in total lipid, phospholipid and fatty acid fractions were noted, it was suggested that the resistance of Staphylococcus aureus to parabens was related to membrane lipid composition

Oxytocin as a treatment for high-risk psychosis or early stages of psychosis: a mini review

Individuals at clinical high risk for psychosis (CHR-P) present as help-seeking individuals with social deficits as well as cognitive and functional impairment and have a 23–36% risk of transition to first-episode psychosis. The therapeutic role of intranasal oxytocin (ΟΤ) in psychiatric disorders has been widely studied during the last decades, concerning its effects on social behavior in humans. A literature search was conducted via Pubmed and Scopus, using the search terms “oxytocin” and “psychosis.” Six studies were included in the current review. There were differences in terms of demographics, intervention type, and outcome measures. ΟΤ may affect the social cognition skills of people at prodromal and early stages of psychosis, but its effect on clinical symptoms is ambiguous. Because of the high level of heterogeneity of existing studies, more original studies are needed to examine and clarify whether OT improves high-risk and early psychosis populations

Factors Associated with Ulcer Healing and Quality of Life in Patients with Diabetic Foot Ulcer

A prospective nonrandomized cohort study on consecutive diabetic patients with foot ulcer was undertaken to assess the factors associated with the healing process or limb salvage and evaluate the impact of their treatment on their quality of life. Quality of life was evaluated using Diabetic Foot Ulcer Scale–Short Form (DFS-SF) questionnaire before and after treatment. A total of 103 diabetic patients with ulcer (mean age 69.7 ± 9.6 years, 77% male) were treated and followed up for 12 months. Ulcer healing, minor amputation, and major amputation rates were 41%, 41%, and 18%, respectively, while the mortality rate was 18%. Ulcer healing was associated with University of Texas wound grade 1 and the Study of Infections in Diabetic feet comparing Efficacy, Safety and Tolerability of Ertapenem versus Piperacillin/Tazobactam trial’s diabetic foot infection wound score. Limb loss was associated with nonpalpable popliteal artery, longer in-hospital stay, and delay until referral. Quality of life was improved in all domains of DFS-SF (P < .0001) throughout the cohort of our patients regardless of their outcome, and no outcome (healing, minor amputation, or major amputation) was superior to other. Significant improvement was observed in all domains of hygiene self-management after consultation during the follow-up period

The effect of hypoxia on carbohydrate metabolism in man

Available from British Library Document Supply Centre- DSC:DXN060362 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Psychological effects of amenorrhea , due to hyperprolactinemia, for women aged between 18 to 45 years old, who suffer from psychotic disorder and receive typical or atypical antipsychotic medications

Introduction: Hyperprolactinemia comprises one of the most frequent consequences of antipsychotic medication and it can have many adverse clinical effects, like amenorrhea, that occurs to women of reproductive age, after being treated with typical and also many of the atypical antipsychotics. Objective: This study aims to investigate the psychological effects and the attitude towards menstruation of psychotic women who suffer from antipsychotic medication induced hyperprolactinaemia that leads to amenorrhea, related to hyperprolactinemic women who have not reported amenorrhea. Materials and Methods: Two hundred and sixty three (263) females, diagnosed with a psychotic disorder (DSM-IV-TR), 18-45 years old, were examined. The patients were under treatment with either risperidone or haloperidol or olanzapine or quetiapine. Blood- sampling was conducted, in order to measure the levels of prolactin in serum. The quantitative determination was made by Chemiluminescence Immuno Assay (CLIA). Then, two self- report psychometric instruments were distributed, the Symptom- Checklist – 90- R (SCL-90-R) questionnaire and the Menstrual Attitude Questionnaire (MAQ). All data were analyzed and the scales and subscales of the questionnaires were compared using the MANOVA model ( Multivariate Analysis of Variance).Results: 139 out of 263 women were found with hyperprolactinemia. Strong statistical signifi-cance arouse between hyperprolactinaemia and the four antipsychotic agents (prisperidone>olanzapine>quetiapine, p ρισπεριδόνη> ολανζαπίνη >κουετιαπίνη, p<0,0005).Oι γυναίκες που εμφάνισαν αμηνόρροια ασχολούνται περισσότερο με σωματικά ενοχλήματα, εμφανίζουν ψυχαναγκαστικά καταναγκαστικά συμπτώματα, καταθλιπτικές-αγχώδεις διαταραχές, αισθήματα θυμού, εκδηλώσεις επιθετικότητας, φοβίες, παρανοειδή τρόπο σκέψης και λιγότερο αιτιάσεις προσωπικής ανεπάρκειας σε σύγκριση με μη αμηνορροϊκές ασθενείς (p<0,0005). Ακόμη, δε θεωρούν την έμμηνο ρύση τόσο ενοχλητικό γεγονός, και ενώ δεν μπορούν να προβλέψουν την έναρξη της, αρνούνται τις επιδράσεις στον οργανισμό τους. Συμπέρασμα: Η υπερπρολακτιναιμία και η επακόλουθη αμηνόρροια έχουν σημαντικές επι-πτώσεις στην ψυχική υγεία καθώς και στη στάση απέναντι στην έμμηνο ρύση των γυναικών της αναπαραγωγικής ηλικίας που πάσχουν από ψυχωσικές διαταραχές. Τα παραπάνω αποτελέσματα έχουν ερευνητική σημασία, καθώς δεν υπάρχουν παρόμοιες μελέτες στη βιβλιογραφία, αλλά και κλινική, αφού η σωστή αντιμετώπιση θα βελτιώσει όχι μόνο την πορεία αλλά και τη ζωή των ασθενών

1680-P: Impact of Diabetic Environment on Sclerostin Levels in Adult Patients with Type 1 Diabetes Mellitus

Introduction: The aim of this study is to examine sclerostin levels in uncomplicated patients T1DM and its correlation with bone metabolism. Methods/Design: We studied 118 (M/F:53/65) uncomplicated T1DM patients (Group-D) aged &amp;gt;20 and &amp;lt;50 years, diabetes duration&amp;gt;5 years and 50 healthy controls matched for age, sex and body mass index (BMI)(Group-C). In both groups Sclerostin, β-crosslaps, TP1NP and HbA1c were measured and the mean HbA1c of the last 5 years was calculated (HbA1c-5). BMD at lumbar spine (LS), femoral neck (FN) and total hip (HIP) by dual energy X-ray absorptiometry (DXA) was measured. Results: In Group-D, mean age was 35.4±10.3years, age of diagnosis was 19.2±9.8years, disease duration was 16.6±9.5years, mean HbA1c and HbA1c-5 were 7.8±1.4%, 7.4±1.1, respectively. Z-scores were lower in the Group-D compared to controls in all the 3 regions [(LS: p=0.009), (FN: p=0.000), (HIP: p=0,000)]. Lower sclerostin levels, but not statistically significant, were observed in group-D compared to group-C (D: 19.0±11.6 vs. C: 23.3±13.6, p=0.059). No difference was found between sexes. Β-CrossLaps was significantly lower in the D-group (D: 198.9±19.6 vs. C: 262.5±53.6, p=0.001), but no significant difference was observed in TP1NP (D: 50.34±30.98 vs. C: 58.47±30.74, p=0.256) between the two groups. Regression analysis showed: a negative correlation between sclerostin and bone markers (βCrosslaps: r=-0.0288, p=0.003, TP1NP: r=-0.0255, p=0.009). No correlation was observed between sclerostin and glycemic control. A positive correlation was found between sclerostin and patients’ age (r=0.490, p=0.000) and between sclerostin and BMD in both LS and FN (LS: r=0.311, p=0.001, FN: r=0.183, p=0.049). Conclusion: Sclerostin levels were lower, but not statistically significant, in T1DM patients compared to controls. Sclerostin was positively correlated with BMD and negative correlation was found with both bone turnover markers. No correlation was found with the metabolic control. Disclosure E. Barmpa: None. A. Bargiota: None. </jats:sec