Inhibition of intercellular communication between mouse hepatocytes by tumor promoters

Tumor promoters can inhibit gap junction-mediated intercellular communication in cultured cells. Since intercellular communication is thought to be important in normal cellular growth control, inhibition of intercellular communication by tumor promoters may be an important mechanism by which preneoplastic cells escape normal growth regulation and progress towards neoplasia. We have evaluated the effects of tumor promoters on intercellular communication between B6C3F1 mouse hepatocytes in primary culture. "Donor" hepatocytes were labeled with 4 microCi[5-3H]uridine/ml for 4 hr. Nonlabeled "recipient" hepatocytes were then plated onto and cocultured with the labeled donors. Hepatocyte cultures were then treated with either the tumor promoters or the solvent vehicle. After 2-24 hr, the cells were fixed and processed for autoradiography. Intercellular communication between donor and recipient hepatocytes was detected as an increase in autoradiographic grains over recipient cells in contact with donor cells, indicating the passage of labeled nucleotides from donor to recipient hepatocytes. Autoradiographic grains were not observed over recipient hepatocytes not in contact with donor cells thus indicating negligible transfer of labeled nucleotide through the medium. Intercellular communication in untreated and solvent vehicle treated hepatocytes was detected in approximately 80% of the donor-contacting recipients after 8-12 hr culture. Phenobarbital, DDT (1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane), Aroclor 1254, lindane (1,2,3,4,5,6-hexachlorocyclohexane, gamma-isomer), and TPA (12-O-tetradecanoyl phorbol-13-acetate), at noncytotoxic concentrations, significantly decreased hepatocyte intercellular communication in a dose-dependent manner.     

Postnatal development of pups from nursing rats treated with Gingko biloba

The Gingko biloba extract is contraindicated during pregnancy and lactation due to the lack of information about its effects on these reproductive phases. Previous studies have shown that G. biloba extract contains components with estrogenic and antiestrogenic activities, thus nursing dams treated with the extract of this plant could show reduction in milk production, resulting in malnutrition and poor development of pups. This work analyzes the postnatal development of pups, whose mothers were treated with G. biloba extract during the lactation period. Nursing Wistar rats received 3.5 mg/kg/day of G. biloba aqueous extract, corresponding to the highest human dose. Clinical signs of maternal toxicity were evaluated. The growth rate, viability, survival during treatment and lactation indices of the pups were calculated. The physical, motor and sensorial development of the pups was also evaluated. No maternal signs of toxicity were observed. As there were no biological differences between control and G. biloba treated pups, it is possible to assume that, in this experimental design, the administration of G. biloba aqueous extract to nursing rats during the lactation period seems to be devoid of toxic effect to mothers and to the physical, motor and sensory development of the pups.     

Lymphatic vessel density and epithelial D2-40 immunoreactivity in pre-invasive and invasive lesions of the uterine cervix

OBJECTIVE: We sought to determine the significance of lymphatic vessel density (LVD) in pre-malignant lesions and carcinomas of the uterine cervix and to evaluate the prognostic value of lymphatic invasion and D2-40 positivity in tumor cells in the three histological types of invasive lesions. The correlation of LVD, lymphatic invasion and D2-40 positivity in tumor cells with EGFR and COX-2 expressions was also evaluated. METHODS: We studied 50 cervicitis, 50 low-grade squamous intraepithelial lesions (LSIL) (CIN1), 51 high-grade squamous intraepithelial lesions (HSIL) (CIN2/CIN3), 49 invasive squamous cells carcinomas (SCC), 43 adenocarcinomas (AC) and 30 adenosquamous cells carcinomas (ASC). The immunoreaction assay was performed using the monoclonal antibody D2-40. RESULTS: Significant differences in LVD were found among all categories of pre-invasive and invasive lesions (p=0.001 and p<0.001, respectively). LVD in invasive lesions was significantly greater than in pre-invasive lesions (p<0.001) and no significant association was found between LVD in invasive lesions and both lymph node invasion and/or metastasis. D2-40 positivity in tumor cells was associated with a better prognosis in ASC cases. EGFR and COX-2 expressions in invasive lesions were not associated with LVD; however, they correlated with both lymphatic invasion and D2-40 positivity in tumor cells. CONCLUSIONS: Lymphatic neovascularization begins early in intraepithelial lesions and continues to increase towards malignancy. Both lymphatic invasion and decrease in D2-40 expression in tumor cells appear to have a prognostic value.     

Extended administration of the association of zidovudine plus ritonavir during rat pregnancy: maternal and fetal effects

The purpose of the study was to evaluate at term, the effects of the association of zidovudine/ritonavir administered during the entire period of rat pregnancy. Forty pregnant EPM-1 Wistar rats were divided randomly into four groups: one control (drug vehicle control, n=10) and three experimental treated with an oral solution of zidovudine/ritonavir (Exp 1 = 10/20 mg/kg bw, n = 10; Exp 2 = 30/60 mg/kg bw, n=10; Exp 3 = 90/180 mg/kg bw, n=10) from day 0 up to day 20 of pregnancy. Maternal body weights were recorded at the start of the experiment and at the 7th, 14th and the 20th day thereafter. At term (20th day) the rats were anesthetized and, upon laparotomy and hysterotomy, the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded. The collected fetuses and placentae were weighed, and the concepts were examined under a stereoscopic microscope for external malformations. The maternal body gain and the mean fetal weight at term were both significantly lower (p < 0.01 and p < 0.0001, respectively) in the experimental groups compared to the control. The recorded resorptions were higher in Exp 2 and Exp 3 groups than in the control group. The other parameters were not affected. The exposure of pregnant rats at term to a 1:2 association of zidovudine plus ritonavir resulted in a significant reduction in maternal body weight gain and increased rate of fetal resorption.     

Effectiveness of fetal fibronectin testing compared with digital cervical assessment of women with preterm contractions

The purpose of this study is to determine the effectiveness of fetal fibronectin (FFN) compared to assessment of cervical dilation (CD) in clinical management of women with symptomatic preterm labor (PTL). Pregnant women presenting to Thomas Jefferson University Hospital between May 1, 2001 and November 30, 2002 with symptomatic PTL underwent FFN sampling and had a complete clinical evaluation including a pelvic bimanual examination. Inclusion criteria were singleton pregnancy, gestational age (GA) between 24 (0) and 33 (6) weeks, CD < 3 cm, and intact amniotic membranes. FFN samples were sent out and results were available within 4-12 hours. Clinical management including tocolysis, antenatal steroids, and hospitalization was determined based on digital CD assessment and FFN status. A dilated cervix was defined as CD > 1 cm. Ninety-three patients were included. Spontaneous preterm delivery (SPTD) at < 37 weeks occurred in 20 of 93 (21.5%) patients. Medical therapy use was significantly higher in patients with dilated cervix than in those with a closed cervix (all P values < 0.05). Tocolysis and steroid use in FFN-negative patients and FFN-positive patients were not significantly different. Furthermore, tocolytic use was higher in FFN-negative patients than in women with positive FFN (50% versus 42.1%; P = 0.53). Use of antenatal steroids was similar in patients with CD >/= 1 cm and a positive FFN (54.5% versus 47.4%; P = 0.92). Compared with FFN-negative patients, women with closed cervix were less likely to undergo interventions. In symptomatic PTL patients, CD determined clinical management more than FFN status. Overall, the use of FFN was not effective in decreasing "unnecessary" clinical interventions.     

The mediator role of unmet needs on quality of life in myeloma patients

Quality of Life Research - The diagnosis of multiple myeloma (MM) has a significant impact on patients. This study analyzed the mediating role of patients’ unmet needs in the relationship...     

Resistance Exercise Training Improves Metabolic and Inflammatory Control in Adipose and Muscle Tissues in Mice Fed a High-Fat Diet

This study investigates whether ladder climbing (LC), as a model of resistance exercise, can reverse whole-body and skeletal muscle deleterious metabolic and inflammatory effects of high-fat (HF) diet-induced obesity in mice. To accomplish this, Swiss mice were fed for 17 weeks either standard chow (SC) or an HF diet and then randomly assigned to remain sedentary or to undergo 8 weeks of LC training with progressive increases in resistance weight. Prior to beginning the exercise intervention, HF-fed animals displayed a 47% increase in body weight (BW) and impaired ability to clear blood glucose during an insulin tolerance test (ITT) when compared to SC animals. However, 8 weeks of LC significantly reduced BW, adipocyte size, as well as glycemia under fasting and during the ITT in HF-fed rats. LC also increased the phosphorylation of Akt_Ser473 and AMPK_Thr172 and reduced tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL1-β) contents in the quadriceps muscles of HF-fed mice. Additionally, LC reduced the gene expression of inflammatory markers and attenuated HF-diet-induced NADPH oxidase subunit gp91phox in skeletal muscles. LC training was effective in reducing adiposity and the content of inflammatory mediators in skeletal muscle and improved whole-body glycemic control in mice fed an HF diet.