Impurity profiling in bulk pharmaceutical batches using 19F NMR spectroscopy and distinction between monomeric and dimeric impurities by NMR-based diffusion measurements

The impurity profile of production batches of fluorine-containing drugs can be characterised efficiently using 19F NMR spectroscopy. This yields the number and proportions of impurities in the bulk drug to a level of approximately equal 0.1 mole% in a few minutes of NMR experiment time. The approach has been exemplified using a partially purified batch of the steroidal product fluticasone propionate, the impurities in which include a number of dimeric species. Further distinction between the monomer and dimer impurities has been achieved through high resolution chemical shift-resolved NMR measurement of molecular diffusion coefficients on the intact mixture using 19F NMR spectroscopy. The ability of NMR-based diffusion coefficient determination to distinguish between monomeric and dimeric substances was validated using a standard mixture of authentic materials containing both monomers and dimers.     

Effect of cold pressor test and a high-chilli diet on rectosigmoid motility in irritable bowel syndrome.

AIM: Visceral hypersensitivity characterizes the irritable bowel syndrome (IBS). We evaluated the effect of a cold pressor test (CPT)--hand immersion in ice water for 1 minute, which evokes a sympathetic response--on rectosigmoid motility in patients with IBS and normal volunteers. Since many Indian patients with IBS complain of worsening of symptoms following a spicy meal, we also evaluated whether a high-chilli diet affects symptoms or changes rectosigmoid motility. METHODS: Fifteen men with IBS and 13 normal volunteers (all men) were studied. Baseline rectosigmoid manometry was done for 2 h, i.e., 1 h pre- and 1 h post-CPT. The subjects were then kept in hospital on a regular diet (approximately 5 g chilli daily) for 3 days, following which symptoms were reassessed and manometry repeated for 1 h. This was followed by a high-chilli diet (approximately 15 g/day) for 3 days, after which symptoms were reassessed and manometry repeated for 1 h. RESULTS: There was no difference in the baseline study in the pre-CPT period between patients and control subjects. CPT did not change rectosigmoid motility in either group. IBS patients had varied effect on symptoms but no change in rectosigmoid motility after the high-chilli diet. In the normal volunteers, there was increased activity in the low rectum after the high-chilli diet. CONCLUSIONS: Cold pressor test does not affect rectosigmoid motility in patients with IBS or normal subjects. A high-chilli diet has varied effect on symptoms in patients with IBS and does not affect rectosigmoid motility.     

Vesico-ureteric reflux: occurrence and long-term risks

The prevalence of vesico-ureteric reflux in the general population is unknown, but it is increased in risk groups, such as children with symptomatic urinary tract infection, schoolgirls with asymptomatic bacteriuria, first-degree relatives of patients with reflux and children with prenatal dilatation of their upper urinary tract. Children and adults with pyelonephritic renal scarring are at risk of serious long-term complications, e.g. hypertension and renal failure. Modern paediatric care, with early detection and treatment of urinary tract infections and reflux during childhood and adolescence, may improve long-term prognosis. In the adult patient with established pyelonephritic renal scarring, careful control of hypertension may retard the rate of progression, and angiotensin converting enzyme inhibitors may have renal protective properties.     

Sociodemographic Patterns of Exclusive,Dual, and Polytobacco Use Among U.S. High School Students: A Comparison of Three Nationally Representative Surveys

PurposeThis study examines sociodemographic patterns of exclusive/dual/polytobacco use among U.S. high school students using multiple national surveys.MethodsUsing three national youth surveys (Population Assessment of Tobacco and Health [PATH] Wave 4 [2016–2017], 2017 Youth Risk Behavior Survey, and 2017 National Youth Tobacco Survey), we classified tobacco products into four groups: (1) electronic nicotine delivery systems (ENDS), (2) conventional cigarettes (CCs), (3) other combustible tobacco products, and (4) smokeless tobacco products. We created 16 categories of non/exclusive/dual/polytobacco use within the past 30 days using the four product groups and calculated weighted population prevalence by sex and race/ethnicity (all surveys) and parental education and income (PATH), based on variable availability.ResultsThe results from 9,331, 12,407, and 9,699 high school students in PATH, Youth Risk Behavior Survey, and National Youth Tobacco Survey, respectively, largely agreed and pointed to similar conclusions. ENDS was the most prevalent exclusive use product (3.8%–5.2% across surveys), with CCs falling to second or third (1.2%–2.0% across surveys). By sex, exclusive, dual, and poly smokeless tobacco product use were more common for males, whereas exclusive CC use was more common for females. By race/ethnicity, non-Hispanic Whites had a higher prevalence of exclusive ENDS use and ENDS/CC dual use than non-Hispanic Blacks. As income and parental education levels increased from low to high, the prevalence of exclusive CC use decreased, whereas the prevalence of exclusive ENDS use increased.ConclusionUnderstanding sociodemographic patterns of tobacco use can help identify groups who may be at greater risk for tobacco-related health outcomes.     

Protective effect of Alstonia scholaris Linn. R. Br. against Bleomycin induced chromosomal damage in cultured human lymphocytes,in vitro

It is both interesting and necessary to identify and develop nontoxic radioprotective compounds. Bleomycin (BLM), a known radiomimetic drug was used as a clastogen in the present study. The possible protective effects against BLM (15?μg/ml) induced clastogenicity by aqueous and methanolic extracts from Alstonia scholaris bark, stem and leaves were compared. The treatment of bark extracts significantly (p?2 assay was performed. Lymphocyte cultures from 12 healthy volunteers were exposed to aqueous (50?μg/ml) and methanolic (50?μg/ml) extracts of A. scholaris bark alone as well as in combination with Bleomycin under two different growth phases, G₀ and G₂. There was a statistically significant reduction (p?2 phase as compared to respective cultures exposed at G₀ phase. The highest level (p?2 phase than those at G₀ phase. This indicated that there could be certain compound(s) present in aqueous bark extracts which enhance DNA repair capacity. Therefore, the bark of A. scholaris could be further utilized to identify and bring out front line radio protective agents in the market with effective formulations.     

Formulation and In Vitro Evaluation of Ofloxacin Tablets using Natural Gums as Binders

Natural gums are economical, easily available, and useful as tablet binders. In the present investigation, an attempt was made to formulate Ofloxacin tablets using three natural binders, namely Acacia arabica, Hibiscus esculentus, and xanthan gum. Such six batches of Ofloxacin tablets were prepared by using different types and amounts of the natural binders by the wet granulation method. The tablets were analyzed for their hardness, friability, and weight variation, and in vitro release was performed in a phosphate buffer at pH 6.8. The prepared tablets were also evaluated for their various release kinetics and similarity factors f₂. The physical properties of the tablets containing the natural binders showed sufficient hardness, desirable disintegration time, and low friability. Their better percentage of drug release was observed as compared to the marketed formulation showing more than 85% drug release within 45 minutes. The in vitro release data was well-fitted into zero-order and the values of release exponent ‘n’ were between 0.303 and 0.514. The high similarity factor f₂ of 64.50 was achieved with the best batch in comparison to the marketed tablets. The results obtained indicated that the gum Acacia arabica performed as well as gelatin compared to the other binders for the Ofloxacin tablet formulation.     

Improving Adolescent Parenting: Results From a Randomized Controlled Trial of a Home Visiting Program for Young Families

Objectives. Our aim was to estimate the effects of Healthy Families Massachusetts, a statewide home visiting program serving first-time adolescent parents, on parenting, child development, educational attainment, family planning, and maternal health and well-being.Methods. We used a randomized controlled trial design to randomly assign the 704 participants to a group receiving home visiting services or a control group. Between 2008 and 2012, telephone and in-person interviews were conducted and administrative data obtained at 12 and 24 months after enrollment. Intention-to-treat analyses compared group differences across 5 outcome domains: parenting, child health and development, educational and economic achievement, family planning, and parental health and well-being.Results. The home visiting program had a positive influence on parenting stress, college attendance, condom use, intimate partner violence, and engagement in risky behaviors. No negative findings were observed.Conclusions. A paraprofessional home visiting program specifically targeting young mothers appears effective in domains of particular salience to young parents and their infants and toddlers. Expanding participation in the program appears a worthy goal for program administrators and policymakers.Home visiting to promote the well-being of infants, toddlers, and their parents has gained increasing public attention over the past 30 years, moving from a promising service to one with considerable evidence supporting its continued implementation and future expansion.1–3 This change in status was codified in 2010 with the authorization of the Maternal, Infant, and Early Childhood Home Visiting Program within the Affordable Care Act (Pub L No. 111–148). At least 75% of the funds for this program, which supports home visiting in at-risk communities, are reserved for programs implementing one of the 17 service models designated as evidence based by the Home Visiting Evidence of Effectiveness initiative of the US Department of Health and Human Services.4 In addition, thousands of individual home visiting programs operate under myriad auspices across the country.The sole unifying feature across the 17 evidence-based models is the locus of service delivery. Otherwise, there is great variability in program goals (e.g., reducing child maltreatment, enhancing birth outcomes), service modalities (e.g., a single postpartum visit, weekly visits over 5 years), staffing (e.g., paraprofessionals, nurses), and target populations (e.g., high risk, universal).5Across and within evidence-based models, impact findings also vary widely. For the domains in which meta-analyses have detected effects (e.g., parenting; child health, development, and school readiness; maternal health and well-being; education and economic self-sufficiency; family violence),6–13 the story line is inconsistent, providing accumulating but scattershot evidence supporting home visiting as a general service approach5,14 rather than a single, uniform enterprise. Indeed, a review of home visiting evaluation findings suggests measured, nuanced, and context-specific interpretations that should guide program developers, frontline staff, and researchers in articulating and measuring what is achievable and meaningful, program to program, for the populations and communities served.15In this study, we assessed impact results from a randomized, controlled trial of Healthy Families Massachusetts (HFM), the only universal statewide home visiting program that specifically targets and wholly serves first-time young parents; reflecting the Five-Tiered Approach to evaluation,16,17 we detailed program processes, model fidelity, participants’ use of the program, and profiles of relationships between home visitors and clients. Here we describe the main program effects 12 and 24 months after enrollment on 28 indicators grouped into 5 outcome domains: parenting, child development, education, family planning, and maternal health and well-being.     

The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.     

美托洛尔治疗右室流出道室性早搏的效果观察

目的：观察美托洛尔对起源于右室流出道室性早搏的疗效。方法：选择起源于右室流出道的室性早搏患25例，给予美托洛尔治疗，剂量从6．25mg开始，无不良反应后，逐渐加量，最大剂量每天100－150mg，疗程3个月，用药前后查12导联体表心电图、24小时动态心电图及结合临床症状进行评定。结果：①临床症状评定：胸闷心悸25例，治疗后减轻20例，有效率为80％；焦虑20例，治疗后症状均消失，有效率为100％；头晕14例，治疗后减轻12例，有效率为85．7％。②室性早搏评定：25例中达到室性早搏抑制率70％有11例，有效率为44％；平均室性早搏抑制率为45．6％，6例成对室性早搏抑制率为80％，3例短阵室速消失，平均心率降低12．6／min。③生化指标：血糖、胆固醇、甘油、三酯治疗前后无明显改变。④2例因血压低未加药量。结论：美托洛尔治疗起源于右室流出道室性早搏疗效肯定，尤其对运动后早搏增多疗效较好，临床太改善较显，观察中未发现明显不良反应，无致心律失常现象。     

Trends in weights,heights, BMI and comparison of their differences in urban and rural areas for Iranian children and adolescents 2–18‐year‐old between 1990–1991 and 1999

Background Secular trends in height and weight are interesting because in middle‐ and low‐income countries they are a marker for changes in population health. The present study aims to evaluate the secular trend in height and weight and body mass index (BMI) of Iranian children and adolescents aged 2–18 years old between 1990–1991 and 1999 and compare the magnitude of urban–rural differences during this period for the first time in an Asian country. Methods Data from two national health surveys in 1990–1991 and 1999, of 22 349 and 25 196 weight and height measures of Iranian children and adolescents were used to study the trend and compare its difference in urban and rural children. Logarithmic transformation of weight, height and BMI was modelled as a polynomial in age for urban and rural boys and girls in each survey separately. The trend in urban and rural growth indexes (weight, height and BMI) and also the comparisons of urban–rural differences between two national surveys were tested in logarithmic scale using a weighted form of Z statistic for comparison of two means adjusted for age groups. Results Urban and rural boys and girls became taller and heavier (P≤ 0.02) with no change of BMI (P > 0.05) during the period. There was not any significant difference between the magnitudes of urban–rural difference between two surveys (P≥ 0.61). Conclusion Although generally positive weight and height trend was observed among urban and rural residents, the magnitude of their differences was not changed.