Na and K movements across the membranes of frog skin epithelia associated with transient current changes

Summary The ionic composition of the current crossing each membrane of the frog skin epithelia during a) the positive and transient current responses elicited by sudden addition of Na ions to the outer Na free medium b) the negative and transient current responses observed when Na loaded preparations are suddenly exposed to outer Na free solution was determined using isotopic techniques. It is shown that Na ions carry the current across the outer membrane while K ions are mainly involved in the transfert of charges across the inner membrane. The amount of Na accumulated by the epithelial cells during the responses is correlated to the area under the transient part of the current responses. Determinations of²⁴Na uptake at different time of these transient positive responses show that the unidirectional Na influx across the outer membrane decreases as a function of time. It is suggested that the intracellular Na concentration might control the Na uptake mechanism across the outer membrane. During the negative responses, the Na efflux into the outer medium is highly correlated, either in time course or magnitude, to the current response. Both Na efflux and negative current are sensitive to amiloride, suggesting that the mechanism of Na uptake by the frog skin also is able to promote Na movement out of the epithelial cells.     

Effect of age, ethnicity, and glucocorticoid use on tacrolimus pharmacokinetics in pediatric renal transplant patients

Tacrolimus has become an effective alternative to cyclosporine as a component of primary immunosuppression in pediatric renal transplant patients, but the information on the pharmacokinetic characteristics of tacrolimus in young patients is still limited. The primary objective of this study was to determine the effect of patient age, ethnicity, and concurrent steroid administration on tacrolimus pharmacokinetics in pediatric renal transplant patients. The study population consisted of 30 pediatric patients, age 1.5-18.6 yr, who received a kidney transplant between July 1999 and February 2004. After twice daily dosing was stabilized based on clinical judgment, at least 5 days postoperatively, tacrolimus levels were drawn prior to, and 1, 2, 4, 8, and 12 h after the morning dose. The mean dose of tacrolimus was 0.12 mg/kg/dose. Mean trough level was 11.9 +/- 5.0 ng/mL. Mean area under the curve (AUC) was 192 +/- 84 with a range of 78-360 h x (ng/mL). The correlation between trough level and AUC was only fair (r = 0.74); later time points correlated better with AUC, and an excellent correlation (r = 0.96) was obtained between the mean of trough and 2-h level (C(2)) and AUC. There was a negative correlation between age and dose per body weight (r = -0.68). African-American patients had marginally lower drug exposure with similar dosing. Three age groups (<5, 5-12, and >12 yr) were compared with respect to dosing and AUC. Despite similar AUC in all three groups, the mean dose per kg required to achieve the AUC was 2.7- and 1.9-fold higher in the <5 and 5-12-yr groups, respectively, compared with the >12-yr group. Nine of the 30 patients were on a totally steroid-free regimen. Their tacrolimus dose and trough levels were similar to those of steroid-exposed patients, but their mean AUC was 41% higher. Our results show an inverse correlation between age and required tacrolimus dose, wide interindividual variation, and greater exposure with steroid-free regimen despite no change in trough level.     

Alteration of CD44 and cadherins expression: possible association with augmented aggressiveness and invasiveness of endometrial carcinoma

Cadherins and CD44 isoforms are transmembrane glycoproteins with diverse functions in cell-cell and cell-matrix interactions and may be a determinant of invasive and metastatic behavior in carcinomas. The immunohistochemical expression of cadherins and CD44 in tissue samples from 15 normal endometrium and 33 endometrial adenocarcinomas were examined. The immunohistochemical analysis was performed using the monoclonal antibody HECD-1 against E-cadherin and the polyclonal antibody against N-cadherin. In addition, the monoclonal antibodies 2C5, which binds to CD44s and all of the variants encoded by exons 3-10; 3G5, which is specific for CD44v3; and 2F10, which is specific for CD44v6 were used. E-cadherin (P=0.0001) and N-cadherin (P<0.001) expressions were statistically lower in endometrial adenocarcinoma than in normal endometrium. In contrast, an overexpression of CD44 isoforms (P<0.01) and CD44v3 (P<0.01) expressions was found in endometrial adenocarcinomas compared with normal endometrium. No difference was noted for CD44v6. An association was found between a decrease in E-cadherin expression and the occurrence of local recurrent and nodal metastasis. An association was found between CD44 overexpression, lymph space involvement, and myometrial invasion. Our results suggest that cadherin and CD44 expressions in endometrial carcinomas may have a prognostic value. Alteration of CD44 seems to be related to local invasion, while alteration of E-cadherin seems to be associated with dissemination of the disease.     

Evidence that male smoking affects the likelihood of a pregnancy following IVF treatment: application of the modified cumulative embryo score

Female cigarette smoking has been implicated as having a detrimental effect on in-vitro fertilization (IVF) outcomes mediated through: (i) a diminished ovarian reserve (DOR), and (ii) an elevated pregnancy loss. Research is sparse regarding the effect of male smoking. The objective of this retrospective cohort study was to investigate the effect of male and female smoking on: (i) the collective quality of embryos selected for uterine transfer, and (ii) the likelihood of achieving an ongoing pregnancy at 12 weeks. A total of 498 consecutive IVF treatment cycles were analysed. Female smokers were significantly younger (P < 0.05) and achieved a better modified cumulative embryo score (mCES) (P < 0.05) than female non-smokers. Female age correlated inversely with the number of oocytes collected (r = -0.42, P < 0.01) and the number of oocytes in turn was important in terms of predicting mCES. The decreasing number of oocytes aspirated with increasing age was of a significantly stronger magnitude for female smokers than for female non- smokers (P < 0.05). Multiple logistic regression was used to determine whether smoking affected the likelihood of achieving a 12-week pregnancy. The mCES, tubal infertility and male smoking were found to be significant. Male smoking interacted with male age (P = 0.0164), indicating for male smokers a decrease of 2.4% in the likelihood of achieving a 12-week pregnancy with every 1-year increase in age. This is the first study to show that male smoking has a deleterious effect on pregnancy outcome among IVF patients. Our study supports the increased risk of DOR but fails to support the elevated incidence of pregnancy loss among female smokers. A reduced pregnancy rate was associated with male smoking possibly through pre-zygotic genetic damage. The growing realization of a paternal component of reproductive impairment suggests that studying the male is necessary.      

Magnetic resonance imaging of cerebral arteriovenous malformations

Magnetic resonance imaging (MRI) was performed in 15 patients with small to very large supratentorial arteriovenous malformations (AVMs). Unlike non-contrast infused computed tomographic (CT) scanning, MRI demonstrated the AVM in all cases. The nidus had a characteristic honeycomb appearance, and in all cases feeding arteries and deep or superficial draining veins were demonstrated without intervening bone artifact. The relationship of the AVM to surrounding cortical areas, deep nuclei, important white matter tracts, and the ventricular system was well appreciated. These characteristics make MRI useful for the diagnosis of cerebral AVMs and add to the accuracy of systems that grade operability on the basis of the angiographic demonstration of size, location, depth, arterial supply, and venous drainage. In many cases, based on the MRI appearance of the AVM and its relationship to important brain structures, the lesion can be deemed inoperable or unsuitable for other forms of treatment, making angiography unnecessary. Thus, the superior anatomical and morphological resolution of MRI, the lower false-negative rate, and the independence from x-ray and contrast material make MRI more useful than CT scanning for the diagnosis of AVMs and as an aid in the management of specific cases.     

血管紧张素Ⅱ及牛磺酸对体外培养乳鼠肥大心肌细胞心律失常发生的作用

在培养７２ｈ的乳鼠心肌细胞，血管紧张素Ⅱ（ａｎｇｉｏｔｅｎｓｉｎⅡ，ＡｇｎⅡ）１，１０，１００和１０００ｎｍｏｌ·Ｌ－１时，可浓度依赖性地增加细胞搏动频率；而牛磺酸５，１０和２０ｍｍｏｌ·Ｌ－１不影响心肌细胞搏动频率，但能浓度依赖性地拮抗ＡｎｇⅡ１００ｎｍｏｌ·Ｌ－１加快心肌细胞搏动频率的作用。ＡｎｇⅡ１００ｎｍｏｌ·Ｌ－１连续作用７ｄ引起的培养乳鼠肥大心肌细胞搏动频率加快，动作电位ＡＰＡ升高，ＡＰＤ５０和ＡＰＤ９０延长，ＳＣＬ缩短；哇巴因５０ｎｍｏｌ·Ｌ－１诱发的心肌细胞搏动节律失常发生率高于常规培养组。牛磺酸２０ｍｍｏｌ·Ｌ－１可抑制ＡｎｇⅡ引起的上述改变，并降低哇巴因诱发的心律失常发生率。     

Laparoscopic staging of early ovarian carcinoma

PURPOSE OF REVIEW: A European randomized trial on early stage ovarian cancer confirmed the importance of accurate staging to select candidates for adjuvant chemotherapy. Since early-stage disease is often discovered incidentally, staging is not always carried out or inadequately performed at the time of primary surgery. Laparoscopy was reported more than 10 years ago as a method of performing the staging procedure while avoiding the morbidity from a classical midline incision. RECENT FINDINGS: Several teams have recently published their results on laparoscopic staging. Updated results of an earlier series in addition to other recent studies are discussed. All highlight the advantages and limits of the method. SUMMARY: Complete laparoscopic management seems feasible in selected cases of apparently early stage ovarian cancer. Re-staging procedures remain an ideal indication for laparoscopy in early adnexal carcinomas. Due to the critical nature of the information obtained, this approach should only be reserved for teams trained in advanced laparoscopy.     

Overexpression of phosphoinositide-specific phospholipase Cgamma in NIH 3T3 cells promotes transformation and tumorigenicity

Phosphoinositide-specific phospholipase Cgamma (PLCgamma) is a key regulatory enzyme that binds to the phosphoryl-tyrosine residues in the cytoplasmic domain of certain activated receptors and catalyses the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] forming IP3 and diacylglycerol (DAG) in response to several mitogenic factors. Previously, we determined that microinjected PLCgamma induces DNA synthesis in G0-arrested NIH 3T3 cells, suggesting the possibility that PLCgamma may have an oncogenic potential. In this report, we demonstrate that overexpression of PLCgamma in NIH 3T3 cells results in altered growth properties and cellular transformation. The PLCgamma/3T3 transfectants do not require serum growth factors to proliferate, display anchorage-independent growth in soft agar and induce tumors when transplanted into nude mice. These findings suggest that overexpression of PLCgamma facilitates the transformation of NIH 3T3 cells. Furthermore, PLCgamma expression and activity have been shown to be elevated in many human tumors. Thus, PLCgamma signaling may contribute to the promotion and/or progression of human cancers.