荔枝核皂苷对小鼠学习记忆障碍的改善

目的:探讨荔枝核皂苷对D-半乳糖诱致小鼠学习记忆障碍的改善作用。方法:50只昆明种小鼠完全随机分为正常对照组、模型对照组、石杉碱甲组(0.4 mg/kg·d)、荔枝核皂苷低(15 g/kg·d)和高(60 g/kg·d)剂量组。上述动物除空白对照组外,均皮下(sc)注射D-半乳糖(500 mg/kg·d)8周,并于第5周起分别灌胃相应药物。采用水迷宫和自主活动仪测试小鼠学习和记忆能力,测定血清糖基化;醛糖还原酶活性;采用高效液相库仑阵列电化学检测系统检测人神经氨酸酶(NA)、多巴胺(DA)、5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)二羟苯乙酸(DOPAC)的含量变化。结果:荔枝核皂苷明显改善模型小鼠学习和记忆能力,各给药组与模型对照组相比单胺类递质含量差异无统计学意义(P>0.05)。结论:荔枝核皂苷具有改善D-半乳糖诱致小鼠学习记忆障碍的作用;其作用可能与其减少抑制对脑神经细胞的损伤作用有关。     

Validity of cardiometabolic index,lipid accumulation product,and body adiposity index in predicting the risk of hypertension in Chinese population

Objectives: Adiposity, defined by higher cardiometabolic index (CMI), lipid accumulation product (LAP), and body adiposity index (BAI), has conferred increased metabolic risk. However, the incremental utility of CMI, LAP, and BAI in association with prevalent hypertension has not been well described in a population-based setting. We hypothesized that CMI, LAP, and BAI would provide important insight into hypertension risk.

Methods: Blood pressure (BP), fasting lipid profiles, and anthropometric parameters were recorded in a cross-sectional study of 11,400 participants (mean age, 54 years; 53% women) from China. Logistic regression models were used to assess associations of CMI, LAP, and BAI with prevalent hypertension.

BAI was evaluated according to hip (cm)/[height (m)^1.5]-18; LAP was calculated separately for men [(WC-65) × TG] and women [(WC-58) × TG]; and CMI was defined by TG/HDL-C × waist-to-height ratio.

Results: CMI, LAP, and BAI were independently correlated with higher SBP and DBP, with nonstandardized (B) coefficients ranging from 1.827 to 4.590 mmHg and 1.475 to 2.210 mmHg (all P < 0.001). After adjustment for hypertension risk factors and potential confounders, CMI, LAP, and BAI, modeled as continuous measures, carried hypertension odds (95% CI) of 1.356 (1.259–1.459), 1.631 (1.501–1.771), and 1.555 (1.454–1.662) in women, respectively, per SD increment. In men, each SD increase in CMI, LAP, and BAI experienced a 31%, 65%, and 53% higher hypertension risk, respectively. Moreover, among women, the odds ratio (95% CI) for hypertension were 2.318 (1.956–2.745), 3.548 (2.985–4.217), and 3.004 (2.537–3.557) in the 4th quartile vs the first quartile of CMI, LAP, and BAI, respectively. For men, the corresponding figures were 2.200 (1.838–2.635), 3.892 (3.238–4.677), and 3.288 (2.754–3.927), respectively.

Conclusion: Measurements of CMI, LAP, and BAI provide a more complete understanding of hypertension risk related to variation in body fat distribution and pinpoint hypertensive participants in great risk of cardiovascular disease in the future.     

A randomized,double-blind study of SHP465 mixed amphetamine salts extended-release in adults with ADHD using a simulated adult workplace design

Objectives: The objective of this paper was to evaluate the efficacy, duration of effect, and tolerability of SHP465 mixed amphetamine salts (MAS) extended-release versus placebo and immediate-release MAS (MAS IR) in adults with attention-deficit/hyperactivity disorder (ADHD).

Methods: Adults with ADHD Rating Scale, Version IV (ADHD-RS-IV) scores ≥24 were randomized to SHP465 MAS (50 or 75 mg), placebo, or 25 mg MAS IR in a double-blind, three-period, crossover study using a simulated adult workplace environment. On the final day of each 7-day treatment period, efficacy was assessed for 16 h postdose. Primary efficacy analyses for Permanent Product Measure of Performance (PERMP) total score averaged across all postdose assessments and each postdose time point were conducted in the intent-to-treat population using a mixed linear model. Secondary end-points included PERMP problems attempted and answered correctly and ADHD-RS-IV scores based on clinician ratings of counselor observations using the Time Segment Rating System and participant self-report. Tolerability assessments included treatment-emergent adverse events (TEAEs) and vital signs.

Results: Least squares mean (95% CI) treatment differences (combined 50/75 mg SHP465 MAS–placebo) significantly favored SHP465 MAS over placebo for PERMP total score averaged across all postdose assessments (18.38 [11.28, 25.47]; P < .0001) and at each postdose assessment (all P < .02). Nominal superiority of MAS IR over placebo for PERMP total score averaged across all postdose assessments was observed (nominal P = .0001); treatment differences between SHP465 MAS and MAS IR were not significant (nominal P = .2443). The two most frequently reported TEAEs associated with SHP465 MAS were insomnia (36.5%) and anorexia (21.2%). Mean increases in pulse and blood pressure with SHP465 MAS exceeded those of placebo.

Conclusions: SHP465 MAS (combined 50/75 mg) significantly improved PERMP total score versus placebo, with superiority observed from 2 to 16 h postdose. The tolerability profile of SHP465 MAS was similar to previous reports of SHP465 MAS in adults with ADHD.

Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT00928148 identifier is NCT00928148.     

DPOAE level mapping for detecting noise-induced cochlear damage from short-duration music exposures

Distortion product otoacoustic emission (DPOAE) level mapping provides a comprehensive picture of cochlear responses over a range of DP frequencies and f₂/f₁ ratios. We hypothesized that individuals exposed to high-level sound would show changes detectable by DPOAE mapping, but not apparent on a standard DP-gram. Thirteen normal hearing subjects were studied before and after attending music concerts. Pure-tone audiometry (500-8,000 Hz), DP-grams (0.3-10 kHz) at 1.22 ratio, and DPOAE level maps were collected prior to, as soon as possible after, and the day after the concerts. All maps covered the range of 2,000-6,000 Hz in DP frequency and from 1.3 to -1.3 in ratio using equi-level primary tone stimuli. Changes in the pure-tone audiogram were significant (P ≤ 0.01) immediately after the concert at 1,000 Hz, 4,000 Hz, and 6,000 Hz. The DP-gram showed significant differences only at f₂ = 4,066 (P = 0.01) and f₂ = 4,348 (P = 0.04). The postconcert changes were readily apparent both visually and statistically (P ≤ 0.01) on the mean DP level maps, and remained statistically significantly different from baseline the day after noise exposure although no significant changes from baseline were seen on the DP-gram or audiogram the day after exposure. Although both the DP-gram and audiogram showed recovery by the next day, the average DPOAE level maps remained significantly different from baseline. The mapping data showed changes in the cochlea that were not detected from the DP-gram obtained at a single ratio. DPOAE level mapping provides comprehensive information on subtle cochlear responses, which may offer advantages for studying and tracking noise-induced hearing loss (NIHL).     

Calendering as a direct shaping tool for the continuous production of fixed-dose combination products via co-extrusion

In this study calendering is used as a downstream technique to shape monolithic co-extruded fixed-dose combination products in a continuous way. Co-extrudates with a metoprolol tartrate-loaded sustained-release core and a hydrochlorothiazide-loaded immediate-release coat were produced and immediately shaped into a monolithic drug delivery system via calendering, using chilled rolls with tablet-shaped cavities. In vitro metoprolol tartrate release from the ethylcellulose core of the calendered tablets was prolonged in comparison with the sustained release of a multiparticulate dosage form, prepared manually by cutting co-extrudates into mini-matrices. Analysis of the dosage forms using X-ray micro-computed tomography only detected small differences between the pore structure of the core of the calendered tablet and the mini-matrices. Diffusion path length was shown to be the main mechanism behind the release kinetics. Terahertz pulsed imaging visualized that adhesion between the core and coat of the calendered tablet was not complete and a gradient in coat thickness (varying from 200 to 600 μm) was observed. Modulated differential scanning calorimetry and X-ray diffraction indicated that the solid-state properties of both drugs were not affected by the calendering procedure.     

Is lipid accumulation product a better cardiovascular risk predictor in elderly individuals than anthropometric measures?

IntroductionPopulation aging is associated with increased prevalence of cardiovascular diseases that have a significant impact on overall morbidity and mortality. Insulin resistance (IR) and visceral obesity are risk factors for vascular damage and cardiometabolic diseases.AimsEstimating the correlation between lipid accumulation product (LAP) and IR in elderly individuals and comparing them to traditional anthropometric indices.MethodsCross-sectional study comprising 411 individuals >60 years, who were treated in a primary care service. Body mass index (BMI), neck circumference (NC), waist circumference (WC), hip circumference (HC), arm circumference (AC), sagittal abdominal diameter (SAD) and waist-hip ratio (WHR) were recorded. IR was estimated based on HOMA-IR (homeostasis model assessment IR index). LAP^a index was calculated as [WC-65]×[triglyceride (TG)] in men, and as [WC-58]×[TG] in women, whereas LAP^b was calculated by using the minimum WC values recorded for the current sample, i.e., 61.5 cm for women and 71.5 cm for men.ResultsThere was correlation among LAP^a (0.506), LAP^b (0.515) and HOMA-IR. LAP was better correlated to HOMA-IR and showed higher area under the curve than BMI, NC, WHR and SAD. Based on the receiver operating characteristic curve analysis, LAP^b≥47.40 and LAP^a≥52.5 were the best cut-off values used to identify individuals with IR presenting 68.8% and 68.2% sensitivity, and 68.6% and 68.6% specificity, respectively.ConclusionLAP may be a useful and simple clinical marker to assess cardiometabolic risk factors in the elderly population treated at a primary care service.     

Primary amenorrhea associated with hirsutism, acanthosis nigricans, dermoid cysts of the ovaries and a new type of insulin resistance

We describe a 15 1/2 year old presenting with primary amenorrhea, hirsutism, acanthosis nigricans and insulin resistance. Ovarian vein catheterization studies revealed bilateral excess plasma testosterone and androstenedione secretion, and at surgery multiple dermoid cysts of both ovaries were found in association with polycystic ovaries. The suggestion that the dermoid cysts may be causative in the evolution of the polycystic ovarian disease has been made. The mechanism of the insulin resistance appears to be at the post receptor level. The acanthosis nigricans diminished following surgery with normalization of the plasma androgens.     

Measurement of the average radiation dose to the local skin and thyroid gland during intracranial aneurysm coil embolization

IntroductionIntracranial aneurysm coil embolisation is a fluoroscopically guided procedure associated with high radiation dose. The increase in the number of coil embolisation procedures raises concern for the amount of radiation and the associated radiation risks to the patients. This research study was conducted to determine the average radiation dose to patients’ thyroid glands and local skin during intracranial aneurysm coil embolisation and to establish preliminary local diagnostic reference levels for this procedure. In this paper, local skin dose refers to the absorbed radiation dose on the areas of the skin exposed to radiation during intracranial aneurysm coil embolisation, namely neck, face and scalp.MethodsThis study employed air-kerma area product meters to determine the local skin dose and diagnostic reference levels during intracranial aneurysm coil embolisation. In addition, thyroid radiation doses were measured using thermo-luminescent dosimeters on a phantom during simulation of embolisation procedures.ResultsThe local skin doses as determined by air-kerma area product ranged between 33 and 125 Gy.cm2. The mean thyroid dose was 9.87 mGy. The established local diagnostic reference level was 52.1 Gy cm², 17.8 min’ fluoroscopy time and 503 image frames.ConclusionThe average air-kerma area product values and the proposed diagnostic reference levels were lower than most published values for intracranial aneurysm coil embolisation.Implications for practiceThe established local diagnostic reference levels are recommended for use as radiation dose optimisation tool at the research site. The findings of this study cannot be generalised or applied to other hospitals. The complexity of the embolisation procedures was not classified for this study. Further research on diagnostic reference levels for intracranial aneurysm coil embolisation, taking into account the complexity of the procedures, is recommended.