醋酸环丙孕酮／炔雌醇复方片剂在人体的药代动力学

目的建立人血浆中醋酸环丙孕酮的HPLC—ESI—MS测定方法和丹酰氯衍生化血浆中炔雌醇的HPLC—APCI—MS测定方法,测定女性志愿者口服复方醋酸环丙孕酮片1片后的药代动力学参数,并对受试制剂和参比制剂的生物等效性进行评价。方法血浆样品中的炔雌醇以乙酸乙酯提取后,与丹酰氯发生衍生化反应,进行HPLC—APCI—MS分析,流动相为10mmol·L-1乙酸铵缓冲液（1％甲酸）-甲醇（3：97）。检测离子分别为m／z530．3（炔雌醇的丹酰氯衍生物）、m／z404．3（内标,对羟基联苯的丹酰氯衍生物1。结果在10．43～625．8Pg·ml-1范同内炔雌醇的丹酰氯衍生物与内标的丹酰氯衍生物峰面积比值与浓度呈良好的线性关系,最低定量限为10．43pg·ml-1结论本实验建立的分析方法灵敏、准确、简便,且统计学结果表明两种制剂生物等效。     

Naringenin stimulates cholecystokinin secretion in STC-1 cells

BACKGROUND/OBJECTIVES

Cholecystokinin (CCK), a hormone or neuropeptide, is secreted in response to intraluminal nutrients by enteroendocrine I-cells of the intestine and has important physiological actions related to appetite regulation and satiety. The stimulation on CCK secretion from the intestine is of potential relevance for body weight management. Naringenin (4'',5,7-trihydroxyflavanone) and its glycoside naringin (naringenin 7-rhamnoglucoside) have been reported to have many biological functions. In the current study, we investigated the question of whether naringenin and naringin could stimulate CCK secretion and then examined the mechanisms involved in CCK release.

MATERIALS/METHODS

STC-1 cells were used as a model of enteroendocrine cells. CCK release and changes in intracellular Ca²⁺ ([Ca²⁺]_i) were measured after incubation of cells with naringenin and naringin for 1 h.

RESULTS

Naringenin caused significant (P < 0.05) stimulation of CCK secretion, but naringin did not. In addition, regarding the secretory mechanisms, naringenin-induced CCK secretion involved increases in [Ca²⁺]_i, influx of extracellular Ca²⁺, at least in part, and activation of TRP channels, including TRPA1.

CONCLUSION

Findings of this study suggest that naringenin could have a role in appetite regulation and satiety.     

Twenty-four-hour ambulatory blood pressure in men and women aged 17 to 80 years: the Allied Irish Bank Study.

In order to determine reference values for ambulatory blood pressure, a sample of 815 healthy bank employees (399 men and 416 women), aged 17-79 years, were investigated. Ambulatory blood pressure was recorded over 24 h, taking measurements at 30-min intervals. Blood pressure was also measured by trained observers in the clinic. Ambulatory blood pressure in the 815 subjects averaged 118/72 mmHg over 24 h, 124/78 mmHg during the day (1000-2259 h) and 106/61 mmHg at night (0100-0659 h). Office blood pressure, measured by an observer, was 4/2 mmHg lower (p less than 0.0001) than daytime ambulatory pressure. The 95th centiles for the daytime ambulatory pressure in men were: 114/88 mmHg for the age group 17-29 years (n = 107); 143/91 mmHg from 30-39 years (n = 123); 150/98 mmHg from 40-49 years (n = 109); and 155/103 mmHg in 50-79 year old men (n = 60); for the corresponding age groups in women, the 95th centiles of the daytime pressure were: 131/83 mmHg (n = 174); 132/85 mmHg (n = 149); 150/94 mmHg (n = 55); and 177/97 mmHg (n = 38).     

Platelet-melanoma cell interaction is mediated by the glycoprotein IIb- IIIa complex

A human malignant melanoma cell line (M3Dau) was observed by electron microscopy to interact directly with human platelets and induced platelet aggregation. Fab fragments of a monoclonal antibody MoAb (LYP18), directed against the platelet glycoprotein (GP) IIb-IIIa complex, inhibited platelet-melanoma interactions and platelet-platelet aggregation. M3Dau melanoma cells bind LYP 18 and synthesize IIb-IIIa- like GPs. When the melanoma cells were preincubated with LYP 18, tumor- platelet interaction did not occur, suggesting that the interaction may be mediated by the IIb-IIIa-like GPs present on the melanoma cell surface. Glanzmann's thrombasthenic platelets, lacking GPIIb and IIIa, did not interact with melanoma cells, indicating that the platelet GPIIb-IIIa complex is also necessary for the platelet-melanoma cell interaction. This work demonstrates the importance of the IIb-IIIa-like GPs, present on M3Dau melanoma cells, in mediating tumor-platelet interactions.     

Congenital heart surgery

In reviewing selected publications on congenital heart disease management for 1990 and 1991, some topics have been chosen for discussion, including isolated patent ductus arteriosus, coarctation of the aorta, critical aortic stenosis in early infancy, hypoplastic left-heart syndrome, pulmonary artery banding, Fontan procedures, pulmonary atresia and intact ventricular septum, Ebstein's anomaly, tetralogy of Fallot, transposition of the great vessels, and others.     

Clinical features of patients with choledocholithiasis showing high levels of aminotransferases]

BACKGROUND/AIMS: We aimed to determine the clinical features of patients with common bile duct (CBD) stones with high serum levels of AST or ALT. METHODS: A retrospective review of 93 patients with CBD stones was done. Clinical characteristics, diameters of CBD, and prior diagnosis before endoscopic retrograde cholangiopancreatography (ERCP) were assessed between two groups (group 1 with serum AST or ALT levels > or =400 IU/L and group 2 with AST and ALT < or =100 IU/L). RESULTS: Nineteen patients in group 1 and 17 patients in group 2 were enrolled. The most common presenting symptom was abdominal pain in both groups. Patients in group 1 was about 14 years younger than group 2 (p=0.003). The duration of symptoms in group 1 and group 2 were 4.1 and 36.8 days, respectively (p=0.005). The diameter of CBD was smaller in group 1 (11.4 mm) than in group 2 (16.3 mm) (p=0.001). Most patients were diagnosed as CBD stones by abdominal ultrasound or computed tomography before ERCP, except two patients in group 1 who were diagnosed as hepatitis initially. All of the patients were recovered by stone removal through ERCP and antibiotics treatment. There were inverse correlations between the diameter of CBD and AST or ALT levels (r=-0.517, p=0.002 and r=-0.504, p=0.002, respectively). CONCLUSIONS: CBD stones with high levels of AST or ALT are frequently observed in younger patients with shorter duration of symptoms and a smaller diameter of CBD. ERCP seems to be a valuable method in the diagnosis and treatment of these patients.     

The attitude toward xenocorneal transplantation in wait‐listed subjects for corneal transplantation in Korea

Shortage of donor cornea is a significant problem in Asia, and xenocorneal transplantation is being actively studied to alleviate this problem. However, the attitudes of subjects who await corneal transplants toward xenocorneal transplantation are not known at all. Thus, this study aimed to investigate the attitudes of subjects on the waiting lists for corneal transplants, toward corneal xenotransplantation. A telephone questionnaire survey comprising six items was conducted in 132 subjects among the wait‐listed individuals (n = 590) who were awaiting corneal transplantation or had undergone corneal transplantation at Seoul National University Hospital from July, 2003 to August, 2012. Among six inquiries, four questions were used to analyze attitudes toward corneal xenotransplantation. Each question pertained to (1) the acceptance of xenocorneal transplantation, (2) willingness to participate in clinical trials, (3) worries in xenocorneal transplantation, and (4) the concern of self‐identity or social life after xenocorneal transplantation. To analyze demographic factors influencing the question, the subjects were arbitrarily divided into two groups: the young (age < 60 yr, n = 58) and the elderly (age ≥ 60 yr, n = 74) or the less‐educated (n = 53) and the well‐educated with high school diploma, college graduation, or higher education (n = 79). Collected demographic data were analyzed as influencing factors on each question using a chi‐square and logistic regression tests. In this study, 42.4% of the subjects (n = 56) expressed favorable views on xenocorneal transplantation using porcine corneas to cure visual loss from corneal blindness. Among those subjects expressing favorable views (n = 56), the willingness to participate in clinical trials, knowing they and their spouses must undergo long‐term surveillance, was 62.5% (n = 35). There were 76.5% of subjects (n = 101) expressing worries regarding xenocorneal transplantation, while 28.8% of subjects (n = 38) expressed their concerns about self‐identity or social life after xenotransplantation. Younger subjects expressed more worry about xenotransplantation than elderly subjects. The well‐educated expressed less concern over self‐identity and social life than the less‐educated. This survey among subjects who are wait‐listed for corneal transplant or who have received a corneal transplant demonstrates that there is an interest in xenocorneal transplantation as an alternate procedure, although there are worries about the procedure that should be further explored in educational campaigns and future studies of the general population.     

Cross‐reactivity between decellularized porcine corneal lamellae for corneal xenobridging and subsequent corneal allotransplants

The purpose of this study is to investigate cross‐reactivity between hypertonic saline‐treated decellularized porcine corneal lamellae for corneal xenobridging and subsequent corneal allotransplants. Five Chinese rhesus macaques, which had undergone anterior partial thickness corneal transplantation using hypertonic saline‐treated decellularized porcine corneal lamellae in preceding experiments, were used as recipients for subsequent full‐thickness corneal allografts. To determine whether sensitization of recipients to xenoantigens leads to cross‐reactivity against alloantigens, we compared; (i) allogeneic one‐way mixed lymphocyte reaction (MLR) of peripheral blood mononuclear cells (PBMCs) from xeno‐sensitized recipients with that of PBMCs from naïve rhesus macaques, and (ii) amounts of IgG antibodies that bound to the PBMCs of a rhesus panel (five monkeys) before and after xeno‐sensitization. Graft survival and immunologic profiles including memory T‐cell subsets and donor rhesus‐specific antibodies were also evaluated. No hyperacute or acute rejection was observed within a month of subsequent allotransplantation in any recipient. Alloreactivity by MLR was not different between xeno‐sensitized rhesus recipients and naïve rhesus monkeys. Panel‐reactive IgG antibodies were unchanged after xeno‐sensitization, and no change in donor rhesus‐specific antibodies was observed in any recipient. No significant changes in memory T‐cell subsets were observed during the early post‐operative period in any recipient. Decellularized porcine corneal lamellae may not increase cross‐reactivity to alloantigens, and thus, porcine corneal lamellae may be used as a bridge to subsequent corneal allografting.     

Serum ferritin levels are positively associated with bone mineral density in elderly Korean men: the 2008–2010 Korea National Health and Nutrition Examination Surveys

A possible negative effect of iron overload on bone metabolism has been suggested by the fact that patients with hemochromatosis, thalassemia, and sickle cell anemia have lower bone mineral density than the general population. However, the influence of iron overload on bone health in the general population is uncertain. The aim of this study was to investigate the relationship between serum ferritin levels and bone mineral density (BMD) in elderly Koreans. A total of 2,943 subjects aged 65 years and over who participated in the 2008–2010 Korea National Health and Nutrition Examination Surveys were included in this study. Age, physical activity, current smoking status, alcohol consumption, education level, household income, and dietary assessment were surveyed by a face-to-face interview. BMD was measured at the lumbar spine and femur by dual-energy X-ray absorptiometry, and other biochemical markers, including serum ferritin, 25-hydroxyvitamin D₃, serum alkaline phosphatase, and parathyroid hormone, were assayed. After adjusting for age and body mass index, we found an association between BMD of the total lumbar spine, total femur, and femur neck and levels of alkaline phosphatase, parathyroid hormone, vitamin D₃, and daily intake of calcium and protein. Serum ferritin levels were positively associated with BMD of the total lumbar spine, total femur, and femur neck after adjusting for all covariates in men, but not in women. This study suggests a positive association between serum ferritin levels and BMD in elderly South Korean men without hematologic disorders. Further study is warranted to verify the effects of iron on bone metabolism.