Herpes simplex virus seropositivity and reactivation at delivery among pregnant women infected with human immunodeficiency virus-1

OBJECTIVE: Our purpose was to determine whether pregnant women infected with human immunodeficiency virus-1 have an increased risk of herpes simplex virus-2 seropositivity and herpes simplex virus reactivation at delivery. STUDY DESIGN: Sixty women infected with human immunodeficiency virus and 8408 other patients who were delivered at the University of Washington between 1989 and 1995 had herpes simplex virus serologic determinations at delivery. Genital herpes simplex virus cultures were obtained for 48 (80%) of the human immunodeficiency virus-infected women and 5567 (66%) of the controls. Logistic regression was used to adjust for possible confounding factors. RESULTS: Forty-five (75%) of human immunodeficiency virus-infected women and 2709 (32%) controls were seropositive for herpes simplex virus-2 (p < 0.0001). Eight percent of human immunodeficiency virus-infected women and 2% of controls had herpes simplex virus reactivation in labor (p < 0.05). CONCLUSIONS: Infection with herpes simplex virus-2 is common among pregnant women infected with human immunodeficiency virus. Herpes simplex virus reactivation complicates labor in this group more often than in other obstetric patients. The role of herpes simplex virus in perinatal human immunodeficiency virus transmission warrants further study.     

Apoptosis of late-stage erythroblasts in megaloblastic anemia: association with DNA damage and macrocyte production

An in vitro model of folate-deficient erythropoiesis has been developed using proerythroblasts isolated from the spleens of Friend virus-infected mice fed an amino acid-based, folate-free diet. Control proerythroblasts were obtained from Friend virus-infected mice fed the same diet plus 2 mg folic acid/kg diet. Our previous studies showed that, after 20 to 32 hours of culture in folate-deficient medium with 4 U/mL of erythropoietin, the folate-deficient proerythroblasts underwent apoptosis, whereas control erythroblasts survived and differentiated into reticulocytes over a period of 48 hours. The addition of folic acid or thymidine to the folate-deficient medium prevented the apoptosis of the folate-deficient erythroblasts, thereby implicating decreased thymidylate synthesis as the main cause of apoptosis in the folate-deficient erythroblasts. In the study reported here, we examined intracellular folate levels, uracil misincorporation into DNA, p53 and p21 proteins, and reticulocyte formation in erythroblasts cultured in folate-deficient or control medium. In all experiments, the folate-deficient erythroblasts cultured in folate-deficient medium gave results that varied significantly from folate-deficient erythroblasts cultured in control medium or control erythroblasts cultured in either folate-deficient or control media. Folate-deficient erythroblasts cultured in folate-deficient medium had marked decreases in all coenzyme forms of folate that persisted throughout culture, increased uracil misincorporation into DNA, persistent accumulations of p53 and p21, and decreased reticulocyte production but increased size of individual reticulocytes. A model of folate-deficient erythropoiesis based on apoptosis of late stage erythroblasts is presented. This model provides explanations for the clinical findings in megaloblastic anemia.     

Evidence from microdialysis and synaptosomal studies of rat cortex for noradrenaline uptake sites with different sensitivities to SSRIs

1. Microdialysis of the frontal cortex of freely-moving rats and uptake of [3H]noradrenaline into cortical synaptosomes were used to evaluate changes in efflux of noradrenaline in vivo and uptake of [3H]noradrenaline in vitro, respectively, induced by the selective serotonin reuptake inhibitors (SSRIs), fluoxetine and citalopram, and the tricyclic antidepressant, desipramine. 2. Noradrenaline efflux was increased during local infusion into the cortex of each of these drugs. All three agents also inhibited synaptosomal uptake of [3H]noradrenaline; this inhibition was unaffected by a substantial (50%) lesion of central 5-hydroxytrytaminergic neurones induced by intracerebroventricular infusion of 5,7-DHT (150 microg). 3. A noradrenergic lesion (70%), induced by pretreatment with the selective neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 40 mg kg(-1) i.p.), 5 days earlier, abolished the increase in noradrenaline efflux caused by local infusion of fluoxetine. In contrast, the desipramine-induced increase in efflux was greater than in non-lesioned rats whereas the effect of citalopram on noradrenaline efflux was unaffected by DSP-4 pretreatment. 4. The combined results of all these experiments suggest that there could be more than one, functionally distinct, noradrenaline uptake site in rat frontal cortex which can be distinguished by their different sensitivities to desipramine and the SSRIs, fluoxetine and citalopram.     

Nephrotoxicity of cadmium-metallothionein: protection by zinc and role of glutathione

BACKGROUND: In vitro studies have shown an antiproliferative effect of tumor necrosis factor (TNF) against various nonsmall cell lung carcinoma (NSCLC) cell lines. However, clinical trials of combined interleukin-2 and TNF-alpha in patients with advanced NSCLC have demonstrated both conflicting and disappointing results. METHODS: Immunohistochemical (IHC) staining was performed on formalin fixed, paraffin embedded tissues from 39 bronchogenic adenocarcinomas and 32 squamous cell carcinomas using polyclonal antibodies against TNF-alpha, TNF-beta, TNF-R1, and TNF-R2 proteins. IHC positivity was correlated with tumor stage, grade, and patient survival. RESULTS: Significant coexpression of TNF-alpha, TNF-beta, TNF-R1, and TNF-R2 was observed in NSCLC (significance range, P < 0.001-0.02). Although immunoreactivity for TNFs remained high in all tumor stages, a loss of TNF-R expression was found in advanced NSCLC (P < 0.006 for TNF-R1 and P < 0.003 for TNF-R2), suggesting down-regulation of TNF-Rs in the process of tumor progression. When all stages were considered together, immunoreactivity for TNF-beta(P < 0.001), TNF-R1, and TNF-R2 (both P < 0.001) significantly correlated with favorable outcome in univariate analysis. However, when stages were studied separately, an association between immunopositivity for TNF-Rs and favorable prognosis was found only in NSCLC without distant metastasis (P < 0.04 and P < 0.005 for TNF-R1 and TNF-R2 in Stage I [according to the American Joint Committee on Cancer staging system] disease, and P < 0.03 and P < 0.02 for TNF-R1 and TNF-R2 in Stage III disease). On multivariate analysis, increased expression of TNF-R1 (P < 0.003) and TNF-R2 (P < 0.001) as well as tumor stage (P < 0.001) independently predicted favorable outcome in patients with NSCLC. CONCLUSIONS: Although NSCLC exhibits strong coexpression of TNF-alpha, TNF-beta, TNF-R1, and TNF-R2, there is a loss/down-regulation of TNF receptors in high stage tumors. TNF-R1 and TNF-R2 positivity independently predicts favorable outcome in NSCLC, particularly in tumors with no clinically distant metastasis. The current study supports a role for TNFs and their receptors in the evolution and progression of NSCLC.     

Direct evidence for histamine H3 receptor-mediated inhibition of norepinephrine release from sympathetic terminals of guinea pig myocardium

AIM: To study the histamine H3 receptors mediated inhibition of norepinephrine (NE) release from cardiac sympathetic terminals of guinea pig isolated atria. METHODS: Release of NE induced by electric field stimulation (50 mA, 5 ms) in the bath solution was measured by HPLC-ECD. RESULTS: The release of NE caused by field stimulation was attenuated by (R)-alpha-methyl-histamine (alpha-MeHA, 0.1 nmol.L-1(-10) mumol.L-1) in a concentration-dependent manner. Thioperamide concentration-dependently antagonized the inhibition of alpha-MeHA. Blockade of H1, H2, alpha 2, beta 2-receptors failed to prevent the inhibitory effect of alpha-MeHA. Thioperamide (1 nmol.L-1(-10) mumol.L-1), when used alone, concentration-dependently facilitated the release of NE evoked by field stimulation. CONCLUSION: The presynaptic histamine H3-receptors inhibited the NE release from cardiac sympathetic terminals.     

The changes of lipids, lipoproteins and apolipoproteins in plasma in ischemic stroke

Contents of lipids (cholesterol CS, triglycerides) as well as levels of CS of lipoproteins of different density and of apolipoproteins A1 and B were measured in blood serum of 31 patients in different periods after of ischemic stroke. The majority of the indices studied were significantly decreased in men in acute periods of the stroke, especially in 8-21 days after the stroke development. Meanwhile, the levels of lipids, CS lipoproteins of both low and very low densities were increased later. Contents of CS of antiatherogenic lipoproteins of high density (HDLP) was low in different periods after the development of disorders of cerebral circulation. This confirms the concept that low level of HDLP is one of the risk factors of ischemic stroke. Decrease of the levels of both lipids and CS of lipoproteins of different density was more pronounced in patients with more severe atherosclerotic damages of the main cerebral arteries. Disorders of metabolism of lipoproteins in ischemic disorders of cerebral circulation are discussed with reference to literary data taking into consideration their heterogeneity. Genetically determined pathology of certain apolipoproteins plays a key role factor in the development of early atherosclerosis and in the elucidation of biochemical markers of the primary damages of cerebral vessels.     

Therapy of multidrug-resistant typhoid fever with oral cefixime vs. intravenous ceftriaxone

We randomly allocated 80 children with suspected multidrug-resistant tyhpoid fever to therapy with either cefixime or ceftriaxone. Of these, an alternative diagnosis was subsequently made in 10 children and another 10 were excluded because cultures were negative. In 9 cases the typhoidal organisms isolated were susceptible to first-line drugs. In all, 50 children were randomly allocated to receive therapy with either intravenous ceftriaxone (65 mg/kg/day once daily, Group A, n = 25) or oral cefixime (10 mg/kg/day divided every 12 hours, Group B, n = 25) for 14 days. The two groups were comparable in their clinical characteristics, duration and severity of illness at the time of admission. The time to defervescence was comparable in both groups (8.3 +/- 3.7 vs. 8.0 +/- 4.1 days, P = not significant). An equal number (3 in each group) failed to respond and underwent a change in therapy. Three children in Group A and one in Group B relapsed. No adverse effects were seen in either group during the course of therapy. Our data suggest that oral cefixime can be used as effectively as parenterally administered ceftriaxone for management of typhoid fever in children.