Ovariectomy Sensitizes Rat Cortical Bone to Whole-Body Vibration

This study was designed to determine the modulatory effect of estrogen on mechanical stimulation in bone. Trabecular and cortical bone compartments of ovariectomized rats exposed to whole-body vibration of different amplitudes were evaluated by peripheral quantitative computed tomographic (pQCT) analysis and histomorphometry and compared to controls not exposed to vibration. Rats underwent whole-body vibration (20 minutes/day, 5 days/week) on a vibration platform for 2 months. The control rats were placed on the platform without vibration for the same time. We divided rats into six groups: a sham control (SHAM); a sham vibrated (SHAM-V) at 30 Hz, 0.6 g; a SHAM-V at 30 Hz, 3g; an ovariectomized control (OVX); an ovariectomized vibrated (OVX-V) at 30 Hz, 0.6 g; and an OVX-V at 30 Hz, 3g. In vivo, pQCT analyses of the tibiae were performed at the start of the experiment and after 4 and 8 weeks. After 8 weeks the tibiae were excised for histomorphometric and for in vitro pQCT analyses. In the SHAM-V group, vibration had no effect upon the different bone parameters. In the OVX-V group, vibration induced a significant increase compared to the OVX group of the cortical and medullary areas (P < 0.01) and of the periosteal (P < 0.01) and endosteal (P < 0.05) perimeters at the 3 g vibration. The strain strength index increased in the OVX-V group significantly (P < 0.01) at the higher vibration. The results showed that low-amplitude, high-frequency whole-body vibration is anabolic to bone in OVX animals. The osteogenic potential is limited to the modeling of the bone cortex and depends on the amplitude of the vibration.     

Alcohol self-administration acutely stimulates the hypothalamic-pituitary-adrenal axis, but alcohol dependence leads to a dampened neuroendocrine state

Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but remaining unknown is whether functional differences in the hypothalamic-pituitary-adrenal (HPA) axis precede alcohol abuse and dependence or result from chronic exposure to this drug. Using an operant self-administration animal model of alcohol dependence and serial blood sampling, we show that longterm exposure to alcohol causes significant impairment of HPA function in adult male Wistar rats. Acute alcohol (voluntary self-administration or experimenter-administered) stimulated the release of corticosterone and its upstream regulator, adrenocorticotropic hormone, but chronic exposure sufficient to produce dependence led to a dampened neuroendocrine state. HPA responses to alcohol were most robust in 'low-responding' non-dependent animals (averaging < 0.2 mg/kg/session), intermediate in nondependent animals (averaging approximately 0.4 mg/kg/session), and most blunted in dependent animals (averaging approximately 1.0 mg/kg/session) following several weeks of daily 30-min self-administration sessions, suggesting that neuroendocrine tolerance can be initiated prior to dependence and relates to the amount of alcohol consumed. Decreased expression of corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus of the hypothalamus and reduced sensitivity of the pituitary to CRF may contribute to, but do not completely explain, neuroendocrine tolerance. The present results, combined with previous studies, suggest that multiple adaptations to stress regulatory systems may be brought about by excessive drinking, including a compromised hormonal response and a sensitized brain stress response that together contribute to dependence.     

Pharmacokinetics of intraperitoneally instilled aminophylline, terbutaline and tobramycin in pigs

Introduction: Venous catheters are sometimes difficult or even impossible to insert and may also be associated with serious complications. This study was carried out to investigate whether intraperitoneal administration of drugs may be an alternative to the intravenous route in patients with limited vascular access.
Materials and methods: Three drugs commonly in use in clinical practise, aminophylline, terbutaline and tobramycin, were administered to pigs intravenously and intraperitoneally in small volumes. Serum concentrations were analysed over a period of 6 h and pharmacokinetic key variables for each drug were calculated.
Results: Aminophylline (theophylline), terbutaline and tobramycin were absorbed from the peritoneal space and into systemic circulation. For theophylline, the concentration/time profiles after intraperitoneal and after intravenous administration were almost identical, and the intraperitoneal bioavailability was calculated to 0.94. For terbutaline and tobramycin, the intraperitoneal absorption was delayed without any initial peak. Moreover, the intraperitoneal bioavailability was lower than for theophylline (0.71 and 0.65, respectively).
Conclusion: The pharmacokinetic properties after intraperitoneal administration differed among the three drugs, but the results are encouraging and provide a basis for further investigation in humans.     

Weekly administration of topotecan–paclitaxel as second-line treatment in ovarian cancer

Purpose To investigate the weekly administration of topotecan combined with paclitaxel in pretreated advanced ovarian cancer patients; our objectives were to determine efficacy, toxicity and survival Methods The chemotherapy agents, topotecan and paclitaxel were administered on a weekly basis for 3 consecutive weeks, every 28 days. The plan was to give three courses (each course included three once-weekly infusions). The dose of topotecan was 1.75 mg/m² and of paclitaxel 70 mg/m². Results From January 2004 until January 2006, 45 patients were enrolled in this multicenter trial; 44 patients were evaluable for response and toxicity. The median age was 60 years old (range 39–82 years) and performance status was 0–2. Thirty-nine patients were in stage III and 5 in stage IV. All patients had been pretreated with carboplatin or cisplatin in combination with paclitaxel. Complete and partial responses were seen in 39% of the patients, stable disease in 43% and progressive disease in 18%; median survival time was 9 months, range 2–24+ months, (95% CI: 7.9–10.2). There was a notable absence of grade 3 toxicity except for neutropenia in 11% of the patients. Conclusion The combination of topotecan and paclitaxel administered on a weekly basis is a well-tolerated chemotherapy schedule. The response rate of 39% is quite high for patients with pretreated ovarian cancer.     

Optimizing bioavailability in the treatment of Parkinson's disease

The bioavailability of drugs used to treat chronic diseases such as Parkinson's disease may have important implications for their clinical utility. Drugs with low bioavailability may cause a wide variation in clinical response between patients and even in the same patient. In addition, numerous factors - including gender, age, and gastric motility - may affect a drug's bioavailability. This is especially important in patients with Parkinson's disease, who develop response fluctuations as the disease progresses. Strategies that may improve the bioavailability of levodopa, the most efficacious medication for Parkinson's disease, include coadministering levodopa with carbidopa, a decarboxylase inhibitor, or with a catechol-O-methyltransferase inhibitor or using an alternative route of administration. Other adjunctive therapies used to treat Parkinson's disease have a wide range of bioavailabilities, which may also affect clinical outcomes. The bioavailability of adjunctive medications may be improved by the use of alternative formulations as well, such as orally disintegrating tablets or transdermal delivery. Considering bioavailability of a medication when prescribing drugs to treat Parkinson's disease may improve patient response and minimize adverse effects.     

Early-phase pharmacokinetics of enteral and parenteral nimodipine in patients with acute subarachnoid haemorrhage – a pilot study

Objective The pharmacokinetics of nimodipine following enteral administration in the early phase after subarachnoid haemorrhage (SAH) has not been described. If a sufficient absorption could be achieved with enterally administered nimodipine, this would be more feasible dosage form and result in a significant reduction in pharmaceutical costs given that the parenteral formulation of nimodipine currently used is tenfold more expensive than the enteral formulation. Methods This was a pilot study in which 17 patients with aneurysmal SAH were randomly assigned to receive nimodipine within 24 h after initial bleeding either as an 60 mg tablet/suspension at 4-h intervals, or as a continuous intravenous infusion of 2 mg/h. Serum nimodipine concentrations were measured during the 4 h following the first dose, and at 24 and 72 h on a validated gas chromatography mass spectrometer (GC-MS). Results Nimodipine AUC values (expressed in μg min/ml) were lower in the eight SAH patients receiving enteral nimodipine [AUC_0–4 range: 0.13–5.4 (median: 0.32); AUC_24–28 range: 0.16–6.1 (0.71); AUC_72–76 range: 0.47–20.6 (1.9)] than in the nine patients receiving a continuous intravenous infusion of nimodipine [AUC_0–4 range: 2.4–4.9 (3.4), p = 0.059; AUC_24–28 range: 4.7–10.3 (7.3), p = 0.001; AUC_72–76 range: 3.4–8.6 (6.9), p = 0.001]. In three of five good-grade SAH patients receiving nimodipine tablets the AUC values were comparable to those of the intravenous administration, but in two good-grade patients with tablets and in all three poor-grade (Hunt&Hess, grade IV) SAH patients receiving the suspension, the rate and extent of nimodipine absorption was negligible. Conclusion This pilot study indicates that the rate and extent of nimopidine absorption following enteral administration in some acute SAH patients could be negligible, and this may particularly be the case in patients with a decreased level of consciousness.     

The role played by oral antioxidant therapies in preventing and treating preeclampsia: An updated meta-analysis

AimsPerforming an up-to-date meta-analysis of oral antioxidant therapies and determining whether they are effective in preventing and/or treating preeclampsia (PE).Data synthesisSearch was performed in PubMed, CENTRAL, LILACS, Web of Science, and ScienceDirect databases. The risk of bias was assessed based on using Cochrane Collaboration's tool. A funnel plot was created, and Egger's and Peter's test was carried out to assess publication bias in the primary outcome of prevention studies. The overall quality of the evidence was assessed based on using the Grading of Recommendations Assessment, Developing and Evaluation (GRADE) tool; a formal protocol was published in the PROSPERO database (registration number CRD42022348992). In total, 32 studies were taken into consideration for analysis purposes; 22 studies focused on investigating preeclampsia prevention methods, whereas 10 focused on its treatment. Significant results associated with the incidence of preeclampsia were observed in prevention studies comprising 11,198 subjects and 1106 events in the control groups, as well as 11,156 subjects and 1048 events in the intervention groups (relative risk [RR]: 0.86, 95% confidence interval [CI]: [0.75, 0.99], P = 0.03; I² = 44%, P = 0.02). With respect to outcomes associated with treatment studies, only intrauterine growth restriction has shown significant effects. Egger's and Peter's test has evidenced publication bias. Six outcomes in prevention studies were classified as having low quality and two as having moderate quality, whereas all three outcomes assessed in treatment studies were classified as having moderate quality.ConclusionsAntioxidant therapy has shown beneficial effects on preeclampsia prevention; moreover, the positive impact of this therapy on intrauterine growth restriction was observed during the disease treatment.     

2018~2020年某口腔专科医院麻醉药品使用情况分析

目的了解某口腔专科医院麻醉药品的临床使用情况,为促进临床合理使用麻醉药品及其规范化管理提供参考。方法采用回顾性分析方法,对2018~2020年某口腔专科医院麻醉药品使用情况进行统计与分析。结果2018~2020年,该院麻醉药品销售金额占药品销售总金额的比例分别为3.86%、3.90%和4.02%;共使用6种麻醉药品,绝大部分用于住院全麻手术患者的麻醉诱导和麻醉维持,少数用于门诊全麻手术的麻醉诱导和麻醉维持,极少数用于门诊、住院癌痛患者的镇痛;麻醉药品使用以注射用盐酸瑞芬太尼和枸橼酸舒芬太尼注射液为主,二者销售金额之和占麻醉药品销售总金额的比例在三年中分别为99.84%、99.85%和99.87%,DDDs之和占麻醉药品总DDDs的比例在三年中分别为98.14%、97.55%和98.26%。结论该院麻醉药品使用较为稳定、合理,绝大部分用于全麻手术麻醉诱导和麻醉维持,符合口腔专科医院收治患者的药物镇痛特点。全麻手术用麻醉药品是该院麻醉药品使用管理的重点。     

利伐沙班片经鼻胃管给药方式的体外试验研究

目的：以利伐沙班为例,对临床上需鼻饲管给药的品种,建立体外药学研究的方法,以指导自制制剂与参比制剂在特定给药条件下的药学行为的一致性。方法：模拟临床给药,对影响给药的项目：沉降试验、粒径分析试验和回收试验进行研究。结果：沉降试验、粒径分析试验及回收试验结果可靠,表明本次所选自制制剂与参比制剂经鼻饲管给药过程中,沉降体积一致、粒度分布一致、回收结果一致。结论：所选方法可指导同类品种鼻胃管给药的体外研究。