Conformational Evaluation of Indol-3-yl-N-alkyl-glyoxalylamides and Indol-3-yl-N,N-dialkyl-glyoxalylamides

Restricted rotation in indol-3-yl-N-alkyl- and indol-3-yl-N,N-dialkyl-glyoxalylamides can in principle give the syn-periplanar and anti-periplanar rotamers. In asymmetrically disubstituted glyoxalylamides, steric effects lead to the occurrence of both rotamers, as observed by NMR spectroscopy. The predominant peak corresponds with the anti rotamer, in which the bulkier alkyl group is orientated trans to the amide carbonyl group. In monoalkylated glyoxalylamides, only one set of peaks is observed, consistent with the presence of only one rotamer. Crystal structures of 5-methoxyindole-3-yl-N-tert-butylglyoxalylamide, indole-3-yl-N-tert-butylglyoxalylamide, and indole-3-yl-N-isopropylglyoxalylamide reported here reveal a syn conformation held by an intramolecular N-HO hydrogen bond.

Some reactions of hydroperoxides in the presence of cyclic phosphate esters

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Asymmetric reactions of organosilicon compounds and properties of novel optically active organosilanes

Partial reduction of racemic methoxysilanes by 1:1 complexes of lithium aluminium hydride with optically active cinchona and ephedra alkaloids give optically active silanes and methoxysilanes. Optical yields depend on the groups attached to silicon and the alkaloid used but in some cases approach 50%, The method has been used to prepare novel optically active organosilanes, possessing an asymmetric silicon centre, which are either inaccessible by any of the other available routes or would require a time consuming preparation. Such compounds are of use in the study of the mechanism of substitutions at silicon. Attempts have been made to rationalize the results of the asymmetric reductions in terms of differences in sterio and electronic interactions in diastereoisomeric transition states. Circular dichroism and optical rotatory dispersion spectra have been obtained for the optically active products in an attempt to elucidate the absolute configurations of the novel asymmetric organosilanes. The results from these studies provide a useful addition to the data so far accumulated for asymmetrically perturbed aromatic chromophores. Nuclear magnetic resonanoe studies of diastereoisomaric (-)-menthoxysilanes show that these compounds possess resonances extremely useful in the determination of optical purities for asymmetric organosilanes which possess an aromatic group. The effect of variable temperature on the spectra has revealed evidence for the conformational preferences in these compounds. Other diastereoisomeric alkoxysilanes have been prepared and their n.m.r.spectra studied in the hope of establishing trends. Exploratory studies for other asymmetric reactions proceeding at silicon have proved unfruitful.

Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes:a randomized double-blind placebo-controlled 102-week trial

Aims: To assess initial pharmacotherapy of Type 2 diabetes with the sodium-glucose cotransporter-2 inhibitor dapagliflozin. Methods: This double-blind, placebo-controlled trial, randomly allocated people with Type 2 diabetes aged 18-77 years and inadequate glycaemic control on diet and exercise [HbA1c 53-86 mmol/mol (7.0-10.0%)] to receive placebo (n = 75) or dapagliflozin monotherapy 2.5 mg (n = 65), 5 mg (n = 64) or 10 mg (n = 70) once daily in the morning. After 24 weeks, low-dose double-blind metformin 500 mg/day was added to the placebo group regimen (placebo+low-dose metformin group). Changes in HbA1c level, fasting plasma glucose and body weight, as well as adverse events, were assessed over 102 weeks. Results: Of the 274 participants randomized, 167 completed the study (60.9%). At 102 weeks, significant differences vs placebo+low-dose metformin with dapagliflozin 5 and 10 mg were observed for HbA1c (-5.8 mmol/mol [-0.53%], P = 0.018; and -4.8 mmol/mol [-0.44%], P = 0.048), respectively); and for FPG (-0.69 mmol/L, P = 0.044; and -1.12 mmol/l, P = 0.001, respectively). For body weight, the difference between the dapagliflozin 10-mg group and the placebo+low-dose metformin group was significant (-2.60 kg; P = 0.016). Hypoglycaemic events were uncommon, with rates of 5.3% for placebo+low-dose metformin group and 0-4.6% for the dapagliflozin groups. Genital infections and urinary tract infections were more common in the dapagliflozin groups than in the placebo+low-dose metformin group. Conclusions: Dapagliflozin as monotherapy in treatment-naïve people with early Type 2 diabetes improved glycaemic control and reduced weight without increasing hypoglycaemia over 102 weeks. Dapagliflozin may provide an alternative initial pharmacotherapy in such people.

Synergistic synthesis of quasi-monocrystal CdS nanoboxes with high-energy facets

Hollow nanostructures with a highly oriented lattice structure and active facets are promising for catalytic applications, while their preparation via traditional approaches contains multiple steps and is time and energy consuming. Here, we demonstrate a new one-step strategy involving two complementary reactions which promote each other; it is capable of producing unique hollow nanoparticles. Specifically, we apply synergic cooperation of cation exchange and chemical etching to attack PbS nanosized cubes (NCs) and produce CdS quasi-monocrystal nanoboxes (QMNBs) which possess the smallest dimensions reported so far, a metastable zinc-blende phase, a large specific surface area, and particularly high-energy {100} facets directly visualized by aberration-corrected scanning transmission electron microscopy. These properties in combination allow the nanoboxes to acquire exceptional photocatalytic activities. As an extension of the approach, we use the same strategy to prepare Co9S8 and Cu7.2S4 single-crystal hollow nanooctahedrons (SCHNOs) successfully. Hence, the synergic reaction synthesis strategy exhibits great potential in engineering unique nanostructures with superior properties.

Understanding the risk of hypoglycaemia in older individuals with diabetes

Introduction: Although older individuals are more prone to hypoglycaemia, it is not known if they have sufficient understanding of the risks of hypoglycaemia or the factors that predispose to it. We evaluated the effectiveness of hypoglycaemia education and examined the factors that increased susceptibility to hypoglycaemia among older people with diabetes. Methods: Forty-five patients (male/female) aged >65 years and known to have diabetes were identified through outpatient clinics at a secondary care hospital. Information relating to education received, awareness of hypoglycaemia and associated risk factors was collected using a standard questionnaire. Additionally, data regarding demographics, treatment regimes, patient attitudes, hypoglycaemic awareness and risks and barriers to self-management of diabetes was collected. Patients were categorised as low, moderate and high risk based on their responses. Independent sample t-tests and Analysis of Variance were carried out to identify factors contributing to high hypoglycaemic risk. Results: Overall, 70% of the patients reported receiving education about hypoglycaemia from health professionals and 95% of them reported good understanding of hypoglycaemia and were able to self-test. Proportion of women receiving education was, however, lower than men (52% women versus 88% men). Compared with men, women were less likely to recognise (59 versus 73%), or act appropriately to a hypoglycaemic episode (59 versus 78%). The mean number of hypoglycaemic episodes per year (41 versus 12) and the duration of hypoglycaemia (9.9 versus 6.3 min) was also greater among women compared with men. The duration of diabetes (P = 0.018), female gender, type 1 diabetes (0.002) and lack awareness of medications causing hypos (P = 0.006) were strong predictors of hypoglycaemia risk. Conclusions: There are significant gaps in education around hypoglycaemia in older people with diabetes. Women, people with longer duration and type 1 diabetes in particular, need additional attention and future educational initiatives need to address these issues.  

Increased risk of diabetes mellitus among persons with psychotic symptoms:results from the WHO World Health Survey

OBJECTIVE: To analyze with a symptom-based approach the relationship between psychosis and diabetes mellitus in the general population. METHOD: Nationally representative samples from the World Health Organization (WHO) World Health Survey, totaling 224,743 randomly selected adults 18 years and older from 52 countries worldwide, were interviewed to establish the presence of psychotic symptoms and diabetes mellitus. Presence of psychotic symptoms was established using questions pertaining to positive symptoms from the psychosis screening module of the Composite International Diagnostic Interview. Presence of diabetes was established with a response of "yes" to the question, "Have you ever been diagnosed with diabetes (high blood sugar)?" The World Health Survey was conducted between 2002 and 2004. RESULTS: An increasing number of psychotic symptoms was related to increasing likelihood of diabetes mellitus (OR = 1.27; 95% CI, 1.24-1.30). As compared to no symptoms, at least 1 psychotic symptom substantially elevated the risk (OR = 1.71; 95% CI, 1.61-1.81). In people with a lifetime diagnosis of schizophrenia or psychosis, the prevalence of diabetes was higher in those with current psychotic symptoms (7.3% vs 5.2%; OR = 1.65; 95% CI, 1.21-2.26), suggesting that the persistence of symptoms over time could play a central role. After controlling for different potential confounders, there was a clear increase in the probability of having diabetes as the number of psychotic symptoms increased. The relationship between psychotic symptoms and diabetes was tested with multiple mediation models and path analyses for categorical outcomes. Only body mass index appeared as a relevant mediator in a model with a good fit (ie, χ21 = 3.2, P = .0742; comparative fit index = 0.999). CONCLUSIONS: Psychotic symptoms are related to increased rates of diabetes mellitus in nonclinical samples, independent of several potential confounders-including a clinical diagnosis of psychosis or schizophrenia, previous antipsychotic treatment, depression, lifestyle, and individual or country socioeconomic status. The findings highlight the worldwide relevance of the problem and the importance of identifying the specific paths of this association.