The effect of oral and IV ramosetron on postoperative nausea and vomiting in patients undergoing gynecological laparoscopy with total intravenous anesthesia

Purpose  Ramosetron can be administered orally as well as intravenously. We investigated the effect of oral ramosetron on postoperative nausea and vomiting (PONV) in patients undergoing gynecological laparoscopy. Methods  One hundred and twenty women were allocated randomly to one of three groups (n = 40 in each) to receive saline (control), 0.1 mg oral ramosetron (PO), or 0.3 mg IV ramosetron (IV). Total intravenous anesthesia (TIVA) with propofol and remifentanil was used in all patients. Results  The incidence of complete response (no PONV, no rescue) in the control, IV, and PO groups was: 65%, 90%, and 87.5%, respectively, during the first 1 h; and 67.5%, 87.5%, and 80%, respectively, during 1 to 24 h. Conclusion  The effect of oral ramosetron 0.1 mg was comparable to that of IV ramosetron 0.3 mg on the prevention of PONV in women undergoing gynecological laparoscopy with TIVA. Both the oral and IV forms were effective at preventing PONV during the first 1 h after surgery.     

Post-PharmD Industry Fellowship Opportunities and Proposed Guidelines for Uniformity

The focus of this paper is to examine the surge in the development of post-PharmD industry fellowships (ie, pharmacy fellowship programs sponsored by the biopharmaceutical or pharmaceutical industry). These post-PharmD training programs do not fit the currently accepted definition of a pharmacy fellowship; therefore, the authors propose a new and distinct definition to encompass these fellowships. The authors provide program examples to showcase the establishment of the post-PharmD industry fellowship institutional centers. Finally, the authors provide recommendations to create uniformity in the programs of this relatively new category of post-PharmD training.     

雌二醇水平降低对大鼠唾液腺的影响

目的 探索雌二醇水平与大鼠唾液腺之间的关系. 方法 32只雌性Wister大鼠随机分为4组:对照组、假手术组、去势组和去势并给予雌激素组.摘除雌大鼠卵巢形成绝经期大鼠模型,通过检测血清雌二醇水平,观察各组大鼠唾液腺组织的HE切片和Cu,Zn-SOD的表达量来综合分析雌二醇水平降低对鼠唾液腺的影响. 结果 与对照组、假手术组和去势并给予雌激素组相比,去势组雌二醇水平明显降低(P<0.01).组织形态学变化发现,去势并给予雌激素组腮腺腺泡发生空泡性变性;颌下腺浆液性腺导管上皮有轻度嗜酸性变化,管腔变小;舌下腺无明显变化.而去势组更为严重.免疫组化结果显示对照组和假手术组的腮腺组织中Cu,Zn-SOD呈现强阳性;颌下腺的浆液性腺导管上皮呈现强阳性,舌下腺为弱阳性.去势组和去势并给予雌激素组表达弱于对照组和假手术组,去势组表达最弱. 结论 雌激素水平降低对唾液腺组织有影响,而Cu,Zn-SOD参与了保护唾液腺组织的正常结构的过程.     

Immunolocalization of 8-OHdG and OGG1 in pancreatic islets of streptozotocin-induced diabetic rats

This study examined whether oxidative DNA damage and its repair system contribute to the occurrence of diabetes in an experimental rat model. The changed morphological findings of the 8-hydroxydeoxyguanosine (8-OHdG) and 8-oxoG-DNA glycosylase (OGG1) were examined in the pancreatic islets in streptozotocin-induced diabetic rats (60 mg/kg, i.p.). The patterns of immunolocalization were mainly observed in the periphery of the normal pancreatic islet: 8-OHdG in the nucleus and OGG1 in the cytoplasm. The altered immunolocalization of 8-OHdG and OGG1 were greatest in the first hours after streptozotocin injection, and then declined in parallel with the morphological observations of pancreatic beta cell destruction. These results suggested that increased oxidative DNA damage might play a role as the inducer of diabetes and that OGG1 may not successfully mediate DNA repair in streptozotocin-induced diabetic rat pancreas.     

A comparative study of patient experiences of conventional fluoroscopic and four-hour ambulatory urodynamic studies

We assessed several emotional variables in patients experiencing conventional urodynamic and ambulatory urodynamic monitoring (AUM) to verify the hypothesis that AUM is tolerated as well as conventional urodynamics. A total of 33 women and 7 men from 23 to 72 years of age who were undergoing both procedures were prospectively included in this study. Prior to and immediately after the procedures, each patient completed a self-administered questionnaire. Answers were given on a visual analogue scale. The degree of anxiety was higher for conventional urodynamics than for AUM (p = 0.045), while the degree of boredom experienced during AUM was higher than that during conventional urodynamics (p= 0.013). There was no significant difference in the degree of shame or bother experienced by the patients during the two procedures. In general, patients tolerated both examinations extremely well. The examiner-rated degree of intolerance during conventional urodynamics was influenced by the subjective pain score (p=0.001), while all other emotional variables except bother were not significantly related with the degree of intolerance during AUM (p=0.007). A total of 74.4% and 84.6% responded that they were willing to repeat conventional urodynamics and AUM, respectively, which were not significantly different. Although AUM produced a significantly higher level of boredom than conventional urodynamics, our data demonstrates that patients are as tolerant of AUM as they are of conventional urodynamic procedures.     

An unusual case with membranous lipodystrophy in a hypertensive patient with transepidermal elimination

Membranous lipodystrophy represents a peculiar type of fat necrosis that is present in patients with various types of skin disease. It is characterized by the presence of microcysts and macrocysts and is lined by amorphous eosinophilic material with a crenelated arabesque appearance. These findings have been associated with lupus erythematosus, diabetes mellitus, erythema nodosum, trauma, etc. We report a case of a 43-year-old woman who had a red to purple asymptomatic indurated plaque, approximately seven cm in diameter and on the left arm. She was a chronic hepatitis B antigen carrier and had hypertension for four years. Histopathology of the biopsied lesion showed transepidermal elimination of altered collagen and elastic fibers, as well as membranous lipodystrophy changes. There were hypertensive vascular changes including lymphohistiocytic infiltration around the vascular wall, swelling of endothelial cells, increased thickness of the vascular walls, and narrowing of the lumen. We report a case showing transepidermal elimination with membranous lipodystrophy. We carefully suggest that the secondary phenomenon of transepidermal elimination was associated with membranous lipodystrophy and degenerate connective tissues.     

Simplified EM grid vitrification is a convenient and efficient method for mouse mature oocyte cryopreservation

This study was performed to evaluate the efficiency of simplified EM grid vitrification, skipping the step of removing the cryoprotectant (5.5M EG + 1.0M sucrose) droplet on the grid after loading oocytes, compared to conventional cryopreservation protocols for mouse mature oocytes. Firstly, the recovery, survival, fertilization and hatching rates of simplified EM grid vitrification were compared with those of the slow freezing method using 1.5M DMSO. Then, conventional EM grid vitrification was compared with simplified EM grid vitrification. Simplified EM grid vitrification showed higher survival, fertilization and hatching rates than those of the slow freezing method (85.6% vs. 63.2%; 51.0% vs. 22.3%; 38.7% vs. 12.5%, p < 0.01, respectively). Moreover, simplified EM grid vitrification showed higher recovery, survival and fertilization rates than those of conventional EM grid vitrification (100% vs. 95.0%, p=0.024; 90.0% vs. 78.9%, p=0.033; 56.7% vs. 38.7%, p=0.021, respectively). Hatching rate tended to be higher for simplified EM grid vitrification compared to conventional EM grid vitrification (41.1% vs. 24.1%). In conclusion, simplified EM grid vitrification is a convenient and efficient method for cryopreservation of mouse mature oocytes, compared to conventional EM grid vitrification and slow freezing methods.     

28 Days repeated oral dose toxicity test of aqueous extracts of mahwangyounpae-tang,a polyherbal formula

Mahwangyounpae-tang (MT), consisting of 22 types of herbal extracts has been used for thousands of years in Korean traditional medicine for the oral treatment of respiratory diseases including asthma. As part of a safety evaluation of MT extract for use in asthma, the 28 day repeat oral dose toxicity of an aqueous MT extract was evaluated at 800, 400 and 200 mg/kg per day dose levels. The results showed that no significant toxicological changes were observed when 200 and 400 mg/kg per day of MT extract was administered to rats. But when the dose was increased to 800 mg/kg per day, increases of body weights, food consumptions, and heart and kidney weights were observed with hypertrophy of heart and tubular necrosis of kidney. Besides this, no other signs of toxicity were observed. Based on these results, it can be concluded that the no observed adverse effect level of MT extract is 400 mg/kg per day. Therefore, the use of MT is expected to be safe because 30 mg/kg was shown to be pharmacologically effective in mice and the high dose heart and kidney findings are not considered to represent any safety concern for humans.     

Prediction of drug particle size and content uniformity in low-dose solid dosage forms

Drug particle size distribution has a profound impact to the content uniformity in low-dose solid drug products. We derived theoretically the skewness of potency distribution as a function of particle size distribution and target dose. It was demonstrated that both skewness and coefficient of variation diverge simultaneously with inverse square root of the target dose. This scaling relation was observed in recent experiment and was verified by Monte Carlo (MC) simulation, which was employed for the first time to solve for the full potency distribution from a random retrieving model. When tested against the criteria from USP 〈905〉 uniformity of dosage units, MC simulation showed a striking anisotropic distribution of the data. This suggests a full-scale consideration of the potency distribution is necessary for evaluating the impacts from particle size distribution and the dose, as compared against the normality assumption used before. A nomograph of the median particle size and the dose that meets a 99% pass rate was constructed for the specification of particle size or the lowest dose limit. Furthermore, we showed quantitatively the lowest dose limit can be drastically reduced if a cut-off size is imposed by removing oversized particles.     

Thaliporphine ameliorates cardiac depression in endotoxemic rats through attenuating TLR4 signaling in the downstream of TAK-1 phosphorylation and NF-κB signaling

Thaliporphine was found to ameliorate endotoxin-induced circulatory failure and mortality in rodents. The aims of the present study were to assess whether thaliporphine could improve cardiac function in endotoxemic rats and to investigate the underlying mechanisms. Cardiac function was evaluated by pressure–volume loop analysis in pentobarbital-anesthetized rats 24 h after intravenous injection of lipopolysaccharide (LPS) (4 mg/kg) with or without thaliporphine (1 mg/kg, iv). The intracellular Ca²⁺ transients, nitric oxide (NO), and reactive oxygen species (ROS) in enzymatically isolated ventricular cells were measured by fluorescent indicators. Western blotting was used to analyze the change of protein expression in response to LPS with or without thaliporphine in rat ventricle, H9C2 and Raw264.7 cells. Cardiac depression was found to coincide with the decreased intracellular Ca²⁺ transients and the increased expression of nitrotyrosine on SERCA2 in rat ventricles after 24-h endotoxemia. Thaliporphine decreased intracellular NO and ROS level in ventricular cells and the nitrosylation of SERCA2, which resulted in recovering the functional properties of intracellular Ca²⁺ handling and cardiac contraction. In H9C2 cells, LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) could be attenuated by thaliporphine. In Raw264.7 cells, thaliporphine attenuated LPS-induced TAK-1 phosphorylation and IκBα degradation in association with the inhibition of inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-α) expression and the production of NO and ROS. In conclusion, thaliporphine ameliorates LPS-induced cardiac depression through attenuating TLR4 signaling in the downstream of TAK-1 phosphorylation and NF-κB signaling in both cardiomyocytes and macrophage to prevent cardiac SERCA2 from nitrosylation by peroxynitrite via decreasing iNOS and TNF-α expression.