Serum and Cerebrospinal Fluid Pharmacokinetics of Intravenous and Oral Lamivudine in Human Immunodeficiency Virus-Infected Children

We studied the pharmacokinetics of intravenously and orally administered lamivudine at six dose levels ranging from 0.5 to 10 mg/kg of body weight in 52 children with human immunodeficiency virus infection. A two-compartment model with first-order elimination from the central compartment was simultaneously fitted to the serum drug concentration-time data obtained after intravenous and oral administration. The maximal concentration at the end of the 1-h intravenous infusion and the area under the concentration-time curve after oral and intravenous administration increased proportionally with the dose. The mean clearance of lamivudine (± standard deviation) in the children was 0.53 ± 0.19 liter/kg/h (229 ± 77 ml/min/m² of body surface area), and the mean half-lives at the distribution and elimination phases were 0.23 ± 0.18 and 2.2 ± 2.1 h, respectively. Clearance was age dependent when normalized to body weight but age independent when normalized to body surface area. Lamivudine was rapidly absorbed after oral administration, and 66% ± 25% of the oral dose was absorbed. Serum lamivudine concentrations were maintained above 1 μM for ≥8 h of 24 h on the twice daily oral dosing schedule with doses of ≥2 mg/kg. The cerebrospinal fluid drug concentration measured 2 to 4 h after the dose was 12% (range, 0 to 46%) of the simultaneously measured serum drug concentration. A limited-sampling strategy was developed to estimate the area under the concentration-time curve for concentrations in serum at 2 and 6 h.     

神经生长因子对小鼠突触体内Ca^2＋水平的调节作用

观察了多次海马内微注射ＮＧＦ对小鼠突触体内游离钙水平的影响，并在离体情况下观察ＮＧＦ对ＥＧＴＡ和ＣａＣｌ２分别造成突触体内低钙和高钙状态的调节作用。结果如下：（１）在体实验表明，一定剂量的ＮＧＦ可显著降低老年小鼠海马突触体内游离钙水平（Ｐ＜００５）；（２）离体实验表明，当突触体游离钙水平降低时，适当剂量的ＮＧＦ具有升高游离钙水平的作用；而突触体内游离钙水平升高时，则ＮＧＦ有降低游离钙水平的作用。提示ＮＧＦ对游离钙水平的双向调节作用可能是ＮＧＦ改善老年性记忆衰退的作用机制。     

Herpetic croup: two case reports and a review of the literature

Croup is an acute infectious illness usually occurring in children; it is characterized by brassy cough and stridor. The main pathogens include mainly parainfluenza and influenza viruses. Recently there have been reports of prolonged croup caused by the herpes simplex viruses. We report two cases of prolonged croup due to herpes simplex types 1 and 2. We also review and summarize the reported pediatric cases of herpetic croup.     

Induced luteolysis in the primate: rapid loss of luteinizing hormone receptors

The molecular mechanisms involved in luteolysis are still unclear in the primate. This study aimed to investigate the effect of induced luteolysis on the ovarian luteinizing hormone (LH) receptor and the steroidogenic enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the marmoset monkey. Luteolysis was induced in the mid-luteal phase either directly by systemic prostaglandin F2alpha (PGF2alpha), or indirectly by LH withdrawal using systemic gonadotrophin releasing hormone antagonist (GnRHant) treatment. The LH receptor was studied by isotopic mRNA in-situ hybridization and in-situ ligand binding and 3beta-HSD expression was studied using isotopic mRNA in-situ hybridization and immunohistochemistry. Induced luteolysis was associated with a reduction in the expression of LH receptor (P < 0.0001) and 3beta-HSD mRNA, closely followed by a reduction in the LH receptor (P < 0.05) and 3beta-HSD protein concentrations within 24 h. There were no differences in the findings whether luteolysis was induced with PGF2alpha or GnRHant. This study shows that disparate mechanisms to induce luteolysis in the primate result in an identical rapid loss of the LH receptor and 3beta-HSD. In conclusion, induced luteolysis leads to rapid loss of the steroidogenic pathway in luteal cells.      

Lung surfactant-associated glycoproteins and proteolipids in human amniotic fluids evaluated by dot immunobinding assays

Dot immunobinding assays for the quantitation of two classes of proteins associated with lung surfactant phospholipids in human amniotic fluid are described. With the use of these assays it was determined that the two classes of surfactant proteins accumulate in the amniotic fluid at the same rate. The concentrations of disaturated phosphatidylcholine and the surfactant-associated proteins are less closely correlated. Centrifugation of amniotic fluids either before or after freezing resulted in a loss ranging from 10 to 35 percent of both surfactant disaturated phosphatidylcholine and proteins depending on the relative centrifugal force used. Preterm amniotic fluids contained significantly less of both surfactant-associated proteins, as well as disaturated phosphatidylcholine, than did term amniotic fluids which suggests that the use of these specific protein markers may enhance the assessment of fetal lung maturity.     

Reduced cell proliferation in fetal lung after maternal administration of pilocarpine. A scintillation autoradiographic study

Fetuses were obtained on the 28th gestational day from pregnant New Zealand white rabbits treated daily, on the 24th through the 27th gestational day, with pilocarpine HCl, 5 mg/kg in saline, or saline alone. Lung fragments from these fetuses were incubated for two hours in medium containing ³H-thymidine. Scintillation autoradiography of 1-μm-thick sections of these fetal lungs revealed that the lung tissue from pilocarpine-treated fetuses had significantly lower labelled cell indices for both alveolar epithelial cells and interstitial cells. These results indicate that pilocarpine treatment promotes differentiation of immature cells in the fetal lung at the expense of cell proliferation.     

Spermicidal activity of chelated complexes of bis(cyclopentadienyl)vanadium(IV)

Transition metal complexes containing vanadium IV have been shown to modulate the cellular redox potential and catalyse the generation of reactive oxygen intermediates (ROI). Since sperm function is exquisitely susceptible to ROI, we examined the effects of stable chelate complexes of vanadocenes on human sperm motility. We synthesized seven structurally distinct chelate complexes of bis(cyclopentadienyl)vanadium(IV) with bidentate ligands [i.e. vanadocene acetylacetonato monotriflate (VDacac), vanadocene hexafluoro acetylacetonato monotriflate (VDHfacac), vanadocene N-phenyl benzohydroxamato monotriflate (VDPH), vanadocene acethydroxamato monotriflate (VDH), vanadocene catecholate (VDCAT), vanadocene bipyridino ditriflate (VDBPY), and vanadocene dithiocarbamate monotriflate (VDDTC)], and evaluated their spermicidal activity using computer-assisted sperm analysis (CASA; Hamilton-Thorne). All seven chelate complexes of vanadocene elicited potent spermicidal activity at micromolar concentrations (EC50 values: 3.9-106 microM) without affecting the sperm acrosome integrity. The catecholate and acetylacetonate complexes of vanadocene were the most active and the bipyridyl complex the least active with an order of efficacy VDCAT > VDacac > VDDTC > VDPH > VDH > VDHfacac > VDBPY. The spermicidal activity of chelate complexes of vanadocenes was rapid and irreversible since the treated spermatozoa underwent apoptosis, as determined by the flow cytometric analysis of mitochondrial membrane potential, surface annexin V binding assay, in-situ nick-end labelling of sperm nuclei, and confocal laser scanning microscopy. These results provide unprecedented evidence that chelate complexes of vanadocene with bidentate ligands have spermicidal and apoptosis inducing properties. These vanadocene complexes, especially VDacac, may be useful as contraceptive agents.