Increase in plasma leptin and Lep mRNA concentrations by food intake is dependent on insulin

The difference in pregnancy rates following intrauterine insemination (IUI) for 1 vs. 2 days in the periovulatory period has been reported as either inconsequential or favoring the use of two consecutive inseminations, 24 hours apart. Our study compared the monthly fecundity and cumulative probability of pregnancy in a large group of women (n = 123) undergoing controlled ovarian hyperstimulation and 1- or 2-day inseminations with donor sperm prepared from frozen-thawed samples. All patients underwent controlled ovarian hyperstimulation employing either clomiphene citrate in 217 cycles or human menopausal gonadotropin in 185 cycles. The choice of single or double insemination was decided by the day of the week each patient received human chorionic gonadotropin for ovulation induction. Approximately 80% of all the patients underwent both single and double insemination treatments during the 2.5-year study period. Ninety-three patients received single inseminations in 180 cycles, whereas 103 patients received double inseminations in 222 cycles. Nine clinical pregnancies were achieved in the 1-day group (5% per cycle, 9.7% per patient), while 39 pregnancies occurred in the 2-day group (17.9% per cycle, 37.9% per patient). Two and five spontaneous abortions occurred in the 1- and 2-day groups, yielding take-home baby rates of 3.9% per cycle (7.5% per patient) and 15.3% per cycle (33.0% per patient), respectively. The cumulative probability of conception over 15 cycles of treatment was consistently twice as high or higher for the 2-day group. The results of this study support the use of 2-day IUI treatment cycles when using frozen-thawed donor sperm.     

Endothelial cell injury caused by Candida albicans is dependent on iron

MRL-lpr/lpr mice spontaneously develop manifestations of autoimmunity including arthritis, vasculitis, and glomerulonephritis. The paramagnetic molecule nitric oxide has been implicated as an effector molecule in initiation and propagation of these inflammatory conditions. In this study, we utilized electron paramagnetic resonance spectroscopy to directly detect nitrosylated protein complexes as products of nitric oxide in whole blood and in kidneys of MRL-lpr/lpr mice. Electron paramagnetic resonance spectra of blood samples from MRL-lpr/lpr mice showed nitrosyl hemoglobin species. Amounts of blood nitrosyl hemoglobin in MRL-lpr/lpr mice were significantly increased as compared to age-matched control mice. Electron paramagnetic resonance spectra of MRL-lpr/lpr kidney tissue exhibited a signal characteristic of a dinitrosyl-iron-dithiolate complex at g approximately 2.04. Formation of nitrosylated nonheme protein in diseased kidneys is associated with development of glomerulonephritis in the autoimmune mice. The presence of nitrosylated nonheme protein indicates the formation of nitric oxide within the kidneys of the diseased mice signifying in situ renal nitric oxide formation.     

Evidence that the slowing caused by acute hypoxia is modality dependent

BACKGROUND: AFM (Additive Factors Method) experiments conducted with visual stimuli suggest that the slowing produced by acute hypoxia is located at the earliest preprocessing stage of information processing and that later stages are unaffected (the bottleneck hypothesis). METHODS: To determine the contribution of degraded visual functioning to slowing, we bypassed this modality and measured reaction time in an AFM paradigm to auditory (Experiment 1) and kinesthetic (Experiment 2) stimuli. In both experiments hypoxia was induced with low oxygen mixtures and arterial blood oxygen saturation (SaO2) was controlled at 65%. Task difficulty was manipulated in Experiment 1 with tones that differed in intensity and in Experiment 2 with lifted cylinders that differed in weight. RESULTS: The results for Experiment 1 showed an interaction between task difficulty and hypoxia, indicating slowing of the preprocessing stage. Slowing was not found in Experiment 2. The absence of slowing in Experiment 2 is surprising and indicates that slowing may be confined to vision and audition and may not involve later, more central, stages. We discuss the need to measure cerebral oxygenation in order to understand the sharp differences between the the bottleneck hypothesis, developed by controlling SaO2, and the more traditional behavioral model which postulates multiple cognitive deficits.     

Removal of calcium overload caused by A23187 is more dependent on glycolysis than oxidative phosphorylation

The authors present a case of cover of synthetic material by expanded skin. In a context of post-sepsis revision, this cover proved to be of excellent quality, superior to normal scalp. The specific characteristics of tissue expansion may possible explain, in this context, the superiority of the expanded skin. The authors intend to adopt a similar therapeutic approach is such a situation should arise in the future.     

Increase of human plasma GABA by sodium valproate

gamma-Aminobutyric acid (GABA) was measured in the plasma of volunteers during subchronic treatment with sodium valproate (VPA). After 2 days of oral treatment with 300 mg VPA, t.i.d., the GABA concentration was increased to about 30% compared to 2 control days. This response was similar to that after 2 days of treatment with 600 mg VPA, t.i.d., whereas on the fourth day of treatment with the latter dose, a plasma GABA increase of about 90% was observed.     

Effect of melatonin on the heart rate variability caused by lesions of the dorsal hippocampus in rats

Bilateral lesions of the hippocampus induced irregular shifts of the heart rate variability in rats. The shifts could be prevented with melatonin but not with diazepam.     

Accumulation of glutamate by osmotically stressed Escherichia coli is dependent on pH

In the present study, we measured the accumulation of glutamate after hyperosmotic shock in Escherichia coli growing in synthetic medium. The accumulation was high in the medium containing sucrose at a pH above 8 and decreased with decreases in the medium pH. The same results were obtained when the hyperosmotic shock was carried out with sodium chloride. The internal level of potassium ions in cells growing at a high pH was higher than that in cells growing in a neutral medium. A mutant deficient in transport systems for potassium ions accumulated glutamate upon hyperosmotic stress at a high pH without a significant increase in the internal level of potassium ions. When the medium osmolarity was moderate at a pH below 8, E. coli accumulated gamma-aminobutyrate and the accumulation of glutamate was low. These data suggest that E. coli uses different osmolytes for hyperosmotic adaptation at different environmental pHs.     

Effects and plasma levels of propranolol and metoprolol in hyperthyroid patients

The effects and plasma concentrations of different doses of propranolol and metoprolol were studied in 34 hyperthyroid patients. The initial daily doses were propranolol 160 mg or metoprolol 200 mg. If the resting heart rate remained above 75 beats per min after treatment for 4-7 days, the dose was increased and the patient re-examined after a further 4-7 days. Propranolol (n = 17) caused a reduced heart rate, a decrease in serum 3,3',5-triiodothyronine (T3) and an increase in serum 3,3',5'-triiodothyronine (reverse T3, rT3). In 10 patients, there was no change in T3 or rT3 until the daily dose of propranolol had been increased to 240 or 320 mg. The plasma level of propranolol was significantly correlated with the decrease in T3 and the increase in rT3. Metoprolol (n = 17) caused a reduction in heart rate similar to that following propranolol. However, serum T3 was only slightly reduced even after an increase in dose to 300 or 400 mg, and serum rT3 was not altered. Metoprolol concentrations were not significantly correlated with the fall in T3. It appears that the influence of beta-blockers on T4 conversion is of little importance for the clinical improvement in hyperthyroid patients, and rather it is a consequence of beta 1-adrenergic blockade interfering with the effect of T3. In addition, the findings support the assumption that therapeutic failure with beta-blockers in hyperthyroidism may be due to suboptimal treatment, and that individualized dosage is necessary.     

Maintenance of maternal diet-induced hypertension in the rat is dependent on glucocorticoids

Recent epidemiological evidence suggests that adult cardiovascular risk is determined by birth weight and factors that influence birth weight, such as maternal nutrition. Data from animal models suggest that an interaction between nutrition and glucocorticoid hormones "programs" increased risk of adult hypertension. Increased fetal exposure to maternal glucocorticoids that is proposed to occur from a reduction in the placental barrier to maternal glucocorticoid, 11beta-hydroxysteroid dehydrogenase, is suggested to program hypertension in the resultant offspring from both glucocorticoid-treated and maternally protein-restricted rats. The extent to which postnatal glucocorticoid stimulation may influence the progression of hypertension in the offspring from protein-restricted rat dams was assessed in 6-week-old male Wistar rats, prenatally exposed to either an 18% casein (control) or 9% casein (low protein) diet. Rats from each dietary group were sham operated, adrenalectomized or adrenalectomized, and treated with 20 mg corticosterone/kg body weight per day. Before surgery, systolic blood pressure was significantly higher in the low protein-exposed rats compared with controls (165+/-3.8 versus 142+/-3.3 mm Hg, P<.0001). Adrenalectomy of the low protein-exposed animals significantly reduced the blood pressure to control levels, while corticosterone replacement restored the hypertensive state. No effect of adrenalectomy on blood pressure was observed in 18% casein controls. In both dietary groups adrenalectomy decreased brain, but not hepatic, glucocorticoid-sensitive enzyme activities and corticosterone treatment elevated activities of all enzymes. The data suggest that maternal diet-induced hypertension is dependent on an intact adrenal gland postnatally and that glucocorticoids are key trophic agents in maintaining the high blood pressure.     

Apoptosis in keratinocytes is not dependent on induction of differentiation

The aim of this study was to determine a reliable procedure for the quantification of organic acids, alcohol soluble sugars and sugar alcohols in fruit flesh by means of a rapid GLC method, without resorting to methoximation of sugars and employing apricot as a model. The use of two internal standards, an accurate derivatization and a proper calibration of the GLC conditions allowed an accurate quantitative analysis of the compounds detected in the unknown samples. This simple procedure improves the speed of preparation of the trimethylsilyl derivatives and is highly reproducible. Variability was found between years for each of the five cultivars studied and for each compound in terms of absolute values, whereas the percentage incidence of the single sugars as a total was more stable over the two years of observation.     

NO-cGMP pathway accentuates the decrease in heart rate caused by cardiac vagal nerve stimulation

The role of the cardiac muscarinic-receptor-coupled nitric oxide (NO) pathway in the cholinergic control of heart rate (HR) is controversial. We investigated whether adding excessive NO or its intracellular messenger cGMP could significantly modulate the HR response to vagal nerve stimulation (VNS) in the anesthetized rabbit and isolated guinea pig atria. The NO donor molsidomine (0.2 mg/kg iv) significantly enhanced the decrease in HR seen with right VNS (5 Hz, 5 V, 30 s) in vivo. A qualitatively similar effect was seen with the NO donor sodium nitroprusside (SNP; 10 and 100 microM) during VNS in vitro. This effect was still present when the baseline shift in HR caused by SNP was eliminated by using the specific hyperpolarization-activated current antagonist 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)-pyrimidinium chloride (ZD-7288, 1 microM). The accentuated decrease in HR with SNP during VNS was mimicked by the stable analog of cyclic GMP, 8-bromoguanosine 3',5'-cyclic monophosphate (0.5 mM). This, however, was not seen with bath application of the stable analog of acetylcholine, carbamylcholine chloride (100 nM). We conclude that excessive NO enhances the magnitude of the decrease in HR caused by VNS. This effect appears to involve a presynaptic action via a cGMP-dependent pathway because it was not mimicked by bath-applied carbamylcholine chloride.     

Nicotine induced c-fos expression in the striatum is mediated mostly by dopamine D1 receptor and is dependent on NMDA stimulation

Serum humoral immune response to Cryptosporidium parvum was evaluated in six species: mouse, rabbit, lamb, calf, pig and man. Electrophoretic and immunoblot analysis showed that specific animal antibody response appeared between Day 4 and Day 15 post inoculation. The two main target antigens had apparent molecular weights of 15-17 and 23 kDa. They were recognised by each species studied. Serum IgA intensively recognised the 15-17 kDa antigen, except in rabbit. This study demonstrates that these two antigens are consistent targets of humoral immune response and can therefore be of great interest in studies of therapy/prophylaxis.     

Activation of the Ca2+ message system by parathyroid hormone is dependent on the cell cycle

To verify whether the heterogeneous intracellular calcium ([Ca2+]i) responses to PTH observed in the UMR 106-01 osteogenic sarcoma cells are secondary to cell cycle asynchrony or to genotypic differences within the population, we synchronized cell monolayers at the G1/S boundary using a sequential thymidine-aphidicolin block. Video image analysis of fura-2-loaded cells revealed that PTH (10(-7) M) induced transient increases of [Ca2+]i preferentially in cells in S phase (82% response frequency, n = 63; 286 +/- 33% of baseline, n = 29), whereas cells in G1 phase responded poorly to PTH (10% response frequency, n = 51; 140 +/- 8% of baseline, n = 5). In contrast, cell exposure to 2% fetal calf serum was followed by [Ca2+]i transients in 83% (n = 42) of cells in G1 phase, but in only 25% (n = 63) of cells in S phase, with similar response amplitude. Hormonal responsiveness was heterogeneous in small clones obtained from single UMR 106-01 cells, with response frequency similar to that observed in nonsynchronized cultures. Pretreatment with either La3+, nifedipine, or pertussis toxin reduced both frequency and amplitude of PTH response in S phase to levels close to G1 phase, whereas there was no significant difference in inositol trisphosphate generated by PTH stimulation in either phase. Therefore, the heterogeneous [Ca2+]i responses of UMR 106-01 cells to hormonal stimulation is dependent on the phase of the cell cycle, rather than on genotypic heterogeneity. The switch from the G1 to the S phase mode of response is driven by active coupling between the PTH receptor and a Ca2+ channel through a pertussis toxin-sensitive G protein.     

Circadian rhythm of plasma corticosteroids in heroin dependent subjects

The circadian rhythm of corticosteroid secretion was investigated in six heroin dependent subjects by measuring plasma corticosteroids at 09.00 hours and 24.00 hours. All results were within the normal range and it seems unlikely that chronic heroin dependence affects the hypothalamic control of corticosteroid secretion.     

Drug output from nebulizers is dependent on the method of measurement

The objective of this study was to determine whether current regulatory methods for assessing the output of nebulizers are appropriate for the delivery of nebulized steroid suspensions to patients. We studied a conventional jet nebulizer (the Intersurgical Cirrus), an open-vent nebulizer (the Medicaid Sidestream) and a breath-enhanced nebulizer (the Pari LC Plus), using a constant sampling flow or a sinusoidal pump to represent the breathing pattern of children from 6 months to adulthood. Recovery of budesonide released from the nebulizers onto filters was reduced when using breathing simulation compared with constant flow, and this reduction was greatest for the conventional nebulizer (Cirrus, 103 microg with constant flow to 4.4 microg with a 50 mL tidal volume; Pari, 176 microg to 25 microg). The open-vent nebulizer deposited very little budesonide on the filter at lower tidal volumes (4.5 microg with a 50 mL tidal volume), possibly because the enhanced flow of aerosol laden air was greater than the inspiratory flow from the breathing simulator. The output of the LC plus was reduced at high flow, from 176 microg at 20 L x min(-1) to 93 microg at 60 L x min(-1). Overall, the measured output varied by up to 700%, depending on the method used. These results suggest that breathing patterns dramatically alter the measured output of different nebulizers and that breathing simulation should be included as part of their assessment.     

Effect of clonidine on changes in plasma catecholamine concentrations and oxygen consumption caused by the cold pressor test

A range of different drugs can cause renal problems, and reactions to the radiocontrast material administered for diagnostic tests are well known. This review describes factors that put patients at risk of kidney damage from drug use and outlines how to clinically diagnose adverse reactions. The most appropriate way to deal with drug-induced renal toxicity is through prevention.     

Effects of dextran, gelatine and homologous plasma on circulation in shock caused by severe anemia in the dog

Irreversible shock is produced in 28 anaesthetized mongrel dogs by withdrawal of erythrocytes and substitution by dextran, gelatine or plasma to an average Hb of 4.5g%. In contrast to other shock models cardiac output and perfusion pressure are not decreased by this preparation. In order to maintain arterial blood pressue above 90 mm Hg significantly more gelatine than dextran or serum has to be infused. There is no difference in hemodynamic responses after treatment with dextran or gelatine respectively. Both groups treated with colloidal solutions have the same survival rate of 38%. In the serum substituted dogs, however,survival rate is significantly greater (83%). Very likely this is due to a greater buffer capacity preventing severe acidosis, which is observed in the animals treated with colloidal solutions.     

Why is the cesarean delivery rate so high in Alabama? An examination of risk factors, 1991-1993

A new autosomal recessive mutation of the house mouse developed generalized alopecia associated with breakage of abnormal hair shafts. This mutation, named 'lanceolate hair' (symbol: lah), arose in a mutagenesis experiment using ethylnitrosourea. Hair shafts were short with a focal degeneration at the breakpoint characterized by a pronounced enlargement at the apex, resembling a lance head. Plucked hair fibers were 2.0 to 3.5 mm in length with a normal base, suggesting that there was a synchronized developmental defect. Histologic examination of anagen follicles revealed abnormal cornification of the matrix region with degeneration resulting in the focal hair shaft deformity. Catagen follicles showed pronounced follicular dystrophy but telogen follicles were almost normal. There was a marked, persistent thickening of the epidermis associated with a non-scarring, relatively non-inflammatory ichthyosiform dermatitis. These features are found in the Netherton's syndrome of the human, for which this mouse mutation may represent a model. The lah mutation has been localized to the centromeric end of mouse Chromosome 18.