Similarity of plasma LH release in androgenized and normal rats following electrochemical stimulation of the basal forebrain.

Because of conflicting data in the literature, the ovulatory response to electrochemical stimulation (ECS) of the medial septal-preoptic complex was measured in pentobarbital-treated normal proestrous and androgenized female rets. Increasing the stimulus strength increases the incidence of ovulation in normal but not in androgenized rats. However, since the ovaries of androgenized rats are relatively insensitive to LH, whereas pituitary responsiveness to LH-releasing factor is normal, the response to ECS was further evaluated in terms of plasma LH. Immunoassayable plasma LH was significantly elevated 30 min after stimulation. Peak LH levels occurred 90 min after stimulation and were returning toward baseline after 120 min. There was no difference in mean plasma LH values in normal and androgenized rats at any time. Stimulation of the diagonal band of Broca, medial septum or medial preoptic area elicited similar plasma LH responses in both groups. These results indicate that the responsiveness of the medial septal-preoptic complex to ECS is not deleteriously affected by neonatal androgen treatment.     

Antitumor activity of bacteriophages in murine experimental cancer models caused possibly by inhibition of beta3 integrin signaling pathway

Bacteriophages (phages) as bacterial viruses are generally believed to have no intrinsic tropism for mammalian cells. In this study the interactions between phages and various eukaryotic cells were investigated. Binding of phages to the membranes of cancer and normal blood cells was observed. Moreover, it was shown that the wild-type phage T4 (wtT4) and its substrain HAP1 with enhanced affinity for melanoma cells inhibit markedly and significantly experimental lung metastasis of murine B16 melanoma cells by 47% and 80%, respectively. A possible molecular mechanism of these effects, namely a specific interaction between the Lys-Gly-Asp motif of the phage protein 24 and beta3-integrin receptors on target cells is proposed. It was also shown that anti-beta3 antibodies and synthetic peptides mimicking natural beta3 ligands inhibit the phage binding to cancer cells. This is in line with the well-described beta3 integrin-dependent mechanism of tumor metastasis. It is concluded that the blocking of beta3 integrins by phage preparations results in a significant decrease in tumor invasiveness.     

Central venous access device occlusions: part 2: nonthrombotic causes and treatment

Home care nurses commonly care for patients with central venous access devices (CVAD) for administration of a variety of infusion therapies. Catheter occlusion is a potential complication. In the February 2002 issue of the etiology and treatment of thrombotic occlusions were described. This month, the focus is on nonthrombotic causes of CVAD occlusion.     

The interaction between St John's wort and an oral contraceptive

OBJECTIVES: The popular herbal remedy St John's wort is an inducer of cytochrome P450 (CYP) 3A enzymes and may reduce the efficacy of oral contraceptives. Therefore we evaluated the effect of St John's wort on the disposition and efficacy of Ortho-Novum 1/35 (Ortho-McNeil Pharmaceutical, Inc, Raritan, NJ), a popular combination oral contraceptive pill containing ethinyl estradiol (INN, ethinylestradiol) and norethindrone (INN, norethisterone). METHODS: Twelve healthy premenopausal women who were using oral contraception (>3 months) received a combination oral contraceptive pill (Ortho-Novum 1/35) for 3 consecutive 28-day menstrual cycles. During the second and third cycles, the participants received 300 mg St John's wort 3 times a day. The serum concentrations of ethinyl estradiol (day 7), norethindrone (day 7), follicle-stimulating hormone (days 12-16), luteinizing hormone (days 12-16), progesterone (day 21), and intravenous and oral midazolam (days 22 and 23) were determined in serial blood samples. The incidence of breakthrough bleeding was quantified during the first and third cycles. RESULTS: Concomitant use of St John's wort was associated with a significant (P <.05) increase in the oral clearance of norethindrone (8.2 +/- 2.7 L/h to 9.5 +/- 3.4 L/h, P =.042) and a significant reduction in the half-life of ethinyl estradiol (23.4 +/- 19.5 hours to 12.2 +/- 7.1 hours, P =.023). The oral clearance of midazolam was significantly increased (109.2 +/- 47.9 L/h to 166.7 +/- 81.3 L/h, P =.007) during St John's wort administration, but the systemic clearance of midazolam was unchanged (37.7 +/- 11.3 L/h to 39.0 +/- 10.3 L/h, P =.567). Serum concentrations of follicle-stimulating hormone, luteinizing hormone, and progesterone were not significantly affected by St John's wort dosing (P >.05). Breakthrough bleeding occurred in 2 of 12 women in the control phase compared with 7 of 12 women in the St John's wort phase. The oral clearance of midazolam after St John's wort dosing was greater in women who had breakthrough bleeding (215.9 +/- 66.5 L/h) than in those who did not (97.5 +/- 37.2 L/h) (P =.005). CONCLUSION: St John's wort causes an induction of ethinyl estradiol-norethindrone metabolism consistent with increased CYP3A activity. Women taking oral contraceptive pills should be counseled to expect breakthrough bleeding and should consider adding a barrier method of contraception when consuming St Johns wort.     

糖尿病视网膜病变和心脏衰竭的风险

微血管病变可能在糖尿病心肌病的发病机理中起比较重要作用，是糖尿病患者心脏衰竭的主要原因。糖尿病视网膜病变作为糖尿病微血管并发症，能否预示心脏衰竭的发生？此项基于人群的研究包括1，021个中年2型糖尿病患者，研究开始时他们有正常的。肾脏功能，无临床冠状动脉疾病或心衰。有125个参与者（12．8％）患有糖尿病视网膜病变。     

The dissociation rate of estrogen receptor alpha from the consensus estrogen response element

The rate of dissociation of recombinant, purified human estrogen receptor alpha (ERalpha) from a fluorescein-labeled DNA containing the consensus vitellogenin ERE sequence (F-vitERE) was determined in real time using fluorescence anisotropy. The complex of estradiol-occupied ERalpha with F-vitERE had an apparent dissociation rate of 1.48+/-0.06x10(-2) s(-1) and a half-life of 46.6 s at room temperature. The dissociation rate was characterized by a single exponential decay, suggesting that ER dissociates from the DNA as a preformed dimer, rather than as two individual monomers. The association rate of estradiol-occupied ERalpha for the F-vitERE was calculated as 7x10(6) M(-1) s(-1) based on the dissociation rate measured and previous determinations of the equilibrium dissociation constant (Kd) in similar assay conditions (Ozers et al., 1997). In buffer containing various concentrations of salt, the rate of dissociation of estradiol-occupied ERalpha from F-vitERE was accelerated by increasing salt concentrations. Compared to estradiol-occupied ERalpha, the rate of dissociation of unoccupied ERalpha from the F-vitERE was very similar, indicating that estradiol occupancy does not affect the dissociation rate of ERalpha from the ERE.     

Blood donors who are repeatedly reactive for hepatitis C virus on enzyme immunoassay and positive on recombinant immunoblot assay: evidence of failure to identify some risk factors

BACKGROUND: Despite the introduction of surrogate testing and subsequent antibody testing of donor blood, transmission of hepatitis C virus (HCV) still occurs. The institution from which this report originates is a medical center, and many of the blood donors have also been seen as patients at the institution. This provided an opportunity for comparison of donor questionnaire responses and medical history information and for correlation of those findings with HCV test results. STUDY DESIGN AND METHODS: HCV polymerase chain reaction (PCR) testing was performed on nine stored frozen sera from donors or former donors with previous positive results on HCV enzyme immunoassay (EIA) (first- or second-generation) and recombinant immunoblot assay (RIBA) (first- or second-generation). The medical histories were also reviewed for 22 of 23 such HCV EIA-repeatedly reactive, RIBA-positive donors and 88 randomly chosen HCV-negative donors. The lifestyle information was compared with the donors' responses on the blood donation questionnaires. The data were then correlated with available clinical and laboratory evidence of HCV transmission to transfusion recipients. RESULTS: For eight donors, there were no recipients of their blood to be assessed. For 9 of the remaining 15 donors, there were recipients who were tested for HCV. Recipients of blood from 5 of these 9 donors were repeatedly reactive for HCV; while recipients of blood from 4 donors were not. Donor PCR positivity correlated with apparent transmission (p = 0.047). Twelve of 20 HCV EIA-positive donors for whom history and questionnaires were available for comparison had at least one suggestive lifestyle or established risk factor in their medical records, while none of 88 HCV-negative controls did (p < 0.0001). The data did not indicate that paid donation correlated with failure to disclose these factors. CONCLUSION: Despite more explicit and intrusive donor questioning, it is still not possible to identify all possible risk factors at donations, though many donors who do not disclose all their risk factors are eliminated from the pool by the increasingly sensitive donor tests. As long as tests are not completely foolproof, workers must be vigilant regarding the ability to elicit complete information on a donor's risk. Further study is required to determine the best way(s) to do so.