The effect of nateglinide taken with food on gastric emptying rates in healthy subjects

OBJECTIVES: The aim of this study was to determine the effect of the timing of food intake on the pharmacokinetics and pharmacodynamics of oral nateglinide 60 mg and the effect of nateglinide on the rate of gastric emptying. METHODS: A randomized, double-blind, placebo-controlled, single-dose, 6-period, crossover study conducted in healthy male volunteers aged 18 to 50 years. On 5 occasions, subjects received a single 60-mg tablet of nateglinide at -30, -10, -5, -1, or 40 minutes from the start of a standard metal. Treatment blind was maintained by administration of placebo tablets at all other time points. On the sixth occasion, subjects received placebo tablets at all dosing time points. Each subject received acetaminophen 1 g at the beginning of the standard breakfast on each treatment day as an indicator of the rate of gastric emptying. Plasma samples were collected over a 6-hour period to determine nateglinide, glucose, insulin, and acetaminophen concentrations. RESULTS: Twelve white men with a mean (SD) age of 30 (6.8) years (range, 21-47 years) and mean (SD) weight of 73.3 (11.0) kg completed all 6 periods of the study. Nateglinide absorption was faster when administered at -5 or -10 minutes relative to food, as characterized by higher nateglinide area under the concentration-time curve from 0 to 5 hours (AUC(0-5)) and maximum plasma concentration (C(max)) values, compared with those observed at other dosing time points. Mean time to C(max) (T(max)) was also shorter when nateglinide was given at -10 minutes versus other dosing time points. Mean nateglinide half-life was similar for all 5 treatments (range, 81.3-94.6 minutes). The overall treatment effect was statistically significant for nateglinide AUC(0-5) (P = 0.031), C(max) (P = 0.001), and T(max) (P < 0.001). Insulin T(max) was shorter after nateglinide administration at -30 or -10 minutes, which was associated with lower glucose C(max) values (-30 minutes, P < 0.05) and a tendency for lower glucose AUC(0-5) values (-10 minutes, P = NS). NS). No treatment effects were observed for any of the acetaminophen indices, as demonstrated by the absence of any change in acetaminophen T(max) or C(max) value. CONCLUSIONS: Nateglinide was well tolerated and no treatment-limiting adverse events were reported in the population studied. Nateglinide administration appeared to have no effect on the rate of gastric emptying as indicated by acetaminophen indices, regardless of the time of nateglinide administration. The findings imply that the time for nateglinide administration to obtain optimal pharmacodynamic effects is prior to food consumption.     

Regional capillary and myocyte distribution in normal and exercise trained male and female rat hearts

Adult Sprague-Dawley male and female rats were exercise trained for five months by either treadmill running or swimming. Significant differences in left ventricular regional capillary density and myocyte cross-sectional area were found. In control rats the epicardial regions had greater capillary density than endocardial regions. Endocardial myocyte cross-sectional areas were greater than those of epicardial myocytes in both sexes. Male rats had larger endocardial myocytes and larger hearts than females. After exercise training, myocyte size increased in the epicardial region but not in the endocardial region, while capillary density increased significantly only in the endocardial region. Similar changes were seen in both male and female rats with comparable degrees of exercise induced hypertrophy. These data suggest that exercise training "normalizes" the distribution of capillaries in the myocardium. Capillary density increased only in the regions where myocyte cross-sectional area did not increase. Further, the effects of exercise on male and female rat hearts is not different when the degree of exercise induced hypertrophy is similar.     

Objective screening for olfactory and gustatory dysfunction during the COVID‐19 pandemic: A prospective study in healthcare workers using self‐administered testing

BackgroundSmell and taste loss are highly prevalent symptoms in coronavirus disease 2019 (COVID‐19), although few studies have employed objective measures to quantify these symptoms, especially dysgeusia. Reports of unrecognized anosmia in COVID‐19 patients suggests that self‐reported measures are insufficient for capturing patients with chemosensory dysfunction.ObjectivesThe purpose of this study was to quantify the impact of recent COVID‐19 infection on chemosensory function and demonstrate the use of at‐home objective smell and taste testing in an at‐risk population of healthcare workers.MethodsTwo hundred and fifty healthcare workers were screened for possible loss of smell and taste using online surveys. Self‐administered smell and taste tests were mailed to respondents meeting criteria for elevated risk of infection, and one‐month follow‐up surveys were completed.ResultsAmong subjects with prior SARS‐CoV‐2 infection, 73% reported symptoms of olfactory and/or gustatory dysfunction. Self‐reported smell and taste loss were both strong predictors of COVID‐19 positivity. Subjects with evidence of recent SARS‐CoV‐2 infection (<45 days) had significantly lower olfactory scores but equivalent gustatory scores compared to other subjects. There was a time‐dependent increase in smell scores but not in taste scores among subjects with prior infection and chemosensory symptoms. The overall infection rate was 4.4%, with 2.5% reported by PCR swab.ConclusionHealthcare workers with recent SARS‐CoV‐2 infection had reduced olfaction and normal gustation on self‐administered objective testing compared to those without infection. Rates of infection and chemosensory symptoms in our cohort of healthcare workers reflect those of the general public.     

石家庄市社区综合干预预防老年人跌倒的效果评价

目的 了解石家庄市社区老年人跌倒的发生情况,并评价预防老年人跌倒干预措施的效果。方法 采用分层随机抽样方法,于2012年随机抽取石家庄市桥西区维明社区60岁及以上、居住至少满1年的836名老年人作为调查对象,进行基线调查,然后每年对社区老年人进行预防跌倒的社区综合干预,2015年再次对相同社区老年人的跌倒情况进行随访调查。结果 干预后跌倒发生率（5.7%）低于干预前（11.6%）;干预后调查对象关于"跌倒可以预防","老年人选择老花镜时是否需要验光后购买","老年人跌倒后是否应该马上扶起"的知晓率均高于干预前（均有P<0.001）,干预后调查对象在预防跌倒相关行为中关于"采取措施预防跌倒","没有因为担心跌倒而减少自己的日常活动或运动"比例均高于干预前（均有P<0.001）。结论 对社区老年人实施社区综合干预能够提高老年人预防跌倒知识知晓率及相关行为比例,并能有效降低跌倒的发生率。     

新疆维吾尔族成人支气管哮喘的影响因素研究

摘要:目的　探讨新疆乌鲁木齐市维吾尔族人群成人支气管哮喘的影响因素。方法　本研究采用成组匹配病例对照研究方法,病例组为新疆医科大学第一附属医院呼吸内科在2014年1-12月确诊的维吾尔族支气管哮喘成人患者（n＝120例）,对照组为同期体检中心健康维吾尔族体检者（n＝126例）,两组在年龄、性别相匹配。采用问卷调查的方法收集相关暴露资料,并采用单因素分析及多因素非条件Logistic回归模型分析成人支气管哮喘影响因素。结果　多因素Logistic回归分析显示,吸烟（OR＝1.88,95% CI:1.28～2.96）、家族支气管哮喘史（OR＝6.20,95% CI:2.10～18.31）、家中铺有纯毛地毯数量多（OR＝1.87,95% CI:1.18～2.95）,睡眠质量（OR＝1.46,95% CI:1.22～1.75）,患慢性支气管炎（OR＝13.43,95% CI:6.65～25.34）及过敏性鼻炎（OR＝6.27,95% CI:3.63～10.81）是维吾尔族成人支气管哮喘的主要影响因素。结论　维吾尔族成人支气管哮喘是生活方式、环境及遗传等多种因素共同作用的结果,应加强对相关影响因素的预防及治疗,减少哮喘的发生,改善哮喘患者生活质量。     

A Substance P Antagonist Increases Brain Intracellular Free Magnesium Concentration after Diffuse Traumatic Brain Injury in Rats

Objective: Magnesium (Mg) deficiency has been shown to increase substance P release and induce a pro-inflammatory response that can be attenuated with the administration of a substance P-antagonist. Neurogenic inflammation has also been implicated in traumatic brain injury (TBI), a condition where brain intracellular free magnesium (Mg_f) decline is known to occur and has been correlated with functional outcome. We therefore examined whether a substance P antagonist restores brain intracellular free magnesium concentration following TBI.

Methods: Male, adult Sprague-Dawley rats were injured using the Cernak impact acceleration model of diffuse TBI. At 30 min after injury, animals were administered either 0.25 mg/kg i.v. n-acetyl tryptophan or equal volume saline. Prior to and 4 h after induction of injury, phosphorus magnetic resonance spectra were acquired using a 7-tesla magnet interfaced with a Bruker console. Mg_f was calculated from the chemical shift of the beta ATP. Before injury, Mg_f was 0.51 ± 0.05 mM (SEM).

Results: By 4 hr after injury, Mg_f had significantly declined to 0.27 ± 0.02 mM in saline treated rats. In contrast, rats treated with n-acetyl tryptophan had a Mg_f of 0.47 ± 0.06 mM at 4 h after injury, which was not significantly different from preinjury values. There were no significant differences in pH between the treatment groups.

Conclusion: It seems that any beneficial effect of a substance P antagonist on functional outcome following TBI may be related to improvement in brain Mg homeostasis induced by the compound.     

Antimicrobial susceptibility of Staphylococcus aureus isolated from hospital inpatients, 2009: report from the Australian Group on Antimicrobial Resistance

In 2009, the Australian Group on Antimicrobial Resistance (AGAR) conducted a period-prevalence survey of clinical Staphylococcus aureus isolated from hospital inpatients. Thirty medical microbiology laboratories from each state and mainland territory participated. Specimens were collected more than 48 hours post-admission. Isolates were tested by Vitek2 (AST-P579 card) and by Etest for daptomycin. Nationally, the proportion of S. aureus that were MRSA was 33.6%, ranging from 27.3% in South Australia to 41.4% in New South Wales/Australian Capital Territory. Resistance to the non-beta-lactam antimicrobials was common except for rifampicin, fusidic acid, daptomycin and high-level mupirocin. No resistance was detected for vancomycin, teicoplanin, quinupristin-dalfopristin or linezolid. Resistance in the methicillin susceptible S. aureus (MSSA) was rare apart from erythromycin (12%) and absent for vancomycin, teicoplanin, daptomycin, quinupristin-dalfopristin and linezolid. The proportion of methicillin resistant S. aureus (MRSA) has remained stable since the first AGAR inpatient survey in 2005 yet during the same time frame resistance to many antimicrobials, in particular tetracycline, trimethoprim-sulphamethoxazole and gentamicin, has significantly decreased. This suggests that non-multi-resistant community-associated MRSA (CA-MRSA) clones are becoming more common in the hospital setting and replacing the long-established multi-resistant clones such as ST239-III (Aus 2/3 EMRSA). Given hospital outbreaks of CA-MRSA are thought to be extremely rare it is most likely that patients colonised at admission with CA-MRSA have become infected with the colonising strain during their hospital stay.     

高效液相色谱法测定小儿磨积片中橙皮苷的含量

目的:建立以高效液相色谱法测定小儿磨积片中橙皮苷含量的方法。方法:色谱柱为SpherisorbC18,流动相为甲醇-冰醋酸-水(25∶4∶71),检测波长为283nm,流速为2·0ml/min,柱温为50℃,灵敏度为0·16AUFS,进样量为20μl。结果:橙皮苷进样量在0·024μg~1·2μg范围内与峰面积积分值呈良好的线性关系(r=0·9999),平均回收率为99·1%(RSD=0·8%)。结论:本方法简便、快捷,灵敏度及准确度高,可为小儿磨积片质量控制提供依据。     

Epidemiology and outcomes for Staphylococcus aureus bacteraemia in Australian hospitals, 2005-06: report from the Australian Group on Antimicrobial Resistance

The Australian Group on Antimicrobial Resistance studied the epidemiology and outcomes of Staphylococcus aureus bacteraemia in selected Australian hospitals in 2005-06. Seventeen hospital-based laboratories collected basic demographic, susceptibility and patient outcome data on all cases of S. aureus bacteraemia for 5 to 24 months during the study period. There were 1,511 cases of bacteraemia documented, of which 66% occurred in males and 32% originated from vascular access devices. Bacteraemia had a community onset in 60% of cases, although 31% of these were health-care associated. Overall, 57% of episodes were health-care related. Methicillin-resistant Staphylococcus aureus (MRSA) was the responsible pathogen in 24% of instances; of these 53% were of the typical multi-resistant hospital type, and 29% were of the community-associated type. Seven per cent of all staphylococcal bacteraemias were caused by community-associated MRSA strain types, attesting to the growing size of this problem in Australia. Outcomes were available for 51% of cases and in those the all-cause mortality at 7 days or discharge (whichever came earlier) was 11.2%. Age was strongly associated with mortality; the rate for patients aged more than 60 years was 18%. Sepsis originating from intravascular access devices had a lower mortality rate of 5%. S. aureus bacteraemia is a common community and hospital infection with a significant mortality. A nationally co-ordinated program documenting the incidence and outcomes of this disease would likely lead to measures designed to reduce the incidence and improve outcomes of this disease.