Pharmacokinetics of synthetic atrial natriuretic peptides in normal men.

The kinetics of atrial natriuretic peptides (ANP) and the kinetic profile of their effect on blood pressure and renal hemodynamic and electrolyte excretion were investigated in 20 salt-loaded healthy volunteers during and after constant rate infusion. At steady state, mean plasma concentrations of ANP were measured at 210, 430, and 2990 pg/ml and mean systemic clearance was 2.6, 2.5, and 1.7 L/min for ANP infusion rates of 0.5, 1, and 5 micrograms/min, respectively, which corresponds to the clearance rate of other vasoactive peptide hormones. The apparent volume of distribution averaged 17 L and the mean half-life was 4.5 minutes. ANP induced dose-related effects on systemic and renal hemodynamic, as well as urinary electrolyte excretion, albeit with a time lag between onset and full effect.

Estudi comparatiu de detecció de Virus del Papiloma Humà entre pell psoriàsica i pell normal.

Existeix un debat continu sobre la rellevància del Virus del papiloma humà (VPH) en l’etiopatogènia de la psoriasi. S’ha reportat un elevat percentatge de detecció de VPH en pacients psoriàsics, sobretot el VPH5 i 36, suggerint que podrien correspondre a l’antigen causal de la cascada inmunològica. El propòsit de l’estudi és utilitzar un mètode ampli per a la detecció d’ADN tant de beta com gamma-papilomavirus en 30 biòpsies de pell psoriàsica i 30 biòpsies de pell sana. Avaluarem si els VPH són detectats de forma més freqüent en pell psoriàsica en comparació amb pell sana, i quins són els VPH específics més sobreexpresats.

Eye colour as a genetic marker for fertility and fecundity of Triatoma infestans (Klug, 1834) Hemiptera, Reduviidae, Triatominae

Eye colour of Triatoma infestans is controlled at a single autosomal locus, with black-eye as the dominant gene and red-eye as the recessive. Inheritance of these characters follows a classical Mendelian system, enabling eye colour to be used as a marker for studies of mating frequency. We found no significant differences in oviposition rates and egg hatching rates irrespective of parental phenotypes. Different mating schedules between red-eye and black-eye parents showed that eye colour did not affect mating competence. Females mated with a single male or with different males together or in succession produced similar numbers of fertile eggs, with the eye colour of the offspring reflecting exposure to the different males. We conclude that although a single mating can provide sufficient sperm for the whole reproductive life of the female, multiple matings can result in balanced assortative sperm usage from the spermatheca.

Augmented epithelial multidrug resistance-associated protein 4 expression in peritoneal endometriosis: regulation by lipoxin A(4).

OBJECTIVE: To compare the expression of the prostaglandin (PG) E(2) transporter multidrug resistance-associated protein 4 (MRP4) in eutopic and ectopic endometrial tissue from endometriosis patients with that of control subjects and to examine whether MRP4 is regulated by the antiinflammatory lipid lipoxin A(4) (LXA(4)) in endometriotic epithelial cells. DESIGN: Molecular analysis in human samples and a cell line. SETTING: Two university hospitals and a private clinic. PATIENT(S): A total of 59 endometriosis patients and 32 age- and body mass index-matched control subjects undergoing laparoscopy or hysterectomy. INTERVENTION(S): Normal, eutopic, and ectopic endometrial biopsies as well as peritoneal fluid were obtained during surgery performed during the proliferative phase of the menstrual cycle. 12Z endometriotic epithelial cells were used for in vitro mechanistic studies. MAIN OUTCOME MEASURE(S): Tissue MRP4 mRNA levels were quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and localization was analyzed with the use of immunohistochemistry. Cellular MRP4 mRNA and protein were quantified by qRT-PCR and Western blot, respectively. PGE(2) was measured in peritoneal fluid and cell supernatants using an enzyme immunoassay (EIA). RESULT(S): MRP4 was expressed in eutopic and ectopic endometrium, where it was overexpressed in peritoneal lesions and localized in the cytoplasm of glandular epithelial cells. LXA(4) attenuated MRP4 mRNA and protein levels in endometriotic epithelial cells in a dose-dependent manner, while not affecting the expression of enzymes involved in PGE(2) metabolism. Investigations employing receptor antagonists and small interfering RNA revealed that this occurred through estrogen receptor α. Accordingly, LXA(4) treatment inhibited extracellular PGE(2) release. CONCLUSION(S): We report for the first time that MRP4 is expressed in human endometrium, elevated in peritoneal endometriosis, and modulated by LXA(4) in endometriotic epithelial cells.

Carcinoembryonic antigen (CEA): demonstration of a partial identity between CEA and a normal glycoprotein.

The carcinoembryonic antigen of the human digestive tract (CEA), described by Gold as a glycoprotein specific for digestive carcinomatous and foetal tissues, was found to have common antigenic determinants with a glycoprotein of smaller size extracted from normal adult tissues. This observation suggests that only a part of the CEA molecule carries the onco-foetal specificity. It also has practical implications regarding the radioimmunoassay for CEA used for the diagnosis of certain carcinomas.

Mast cells are dispensable for normal and activin-promoted wound healing and skin carcinogenesis.

The growth and differentiation factor activin A is a key regulator of tissue repair, inflammation, fibrosis, and tumorigenesis. However, the cellular targets, which mediate the different activin functions, are still largely unknown. In this study, we show that activin increases the number of mature mast cells in mouse skin in vivo. To determine the relevance of this finding for wound healing and skin carcinogenesis, we mated activin transgenic mice with CreMaster mice, which are characterized by Cre recombinase-mediated mast cell eradication. Using single- and double-mutant mice, we show that loss of mast cells neither affected the stimulatory effect of overexpressed activin on granulation tissue formation and reepithelialization of skin wounds nor its protumorigenic activity in a model of chemically induced skin carcinogenesis. Furthermore, mast cell deficiency did not alter wounding-induced inflammation and new tissue formation or chemically induced angiogenesis and tumorigenesis in mice with normal activin levels. These findings reveal that mast cells are not major targets of activin during wound healing and skin cancer development and also argue against nonredundant functions of mast cells in wound healing and skin carcinogenesis in general.

Obésité et fertilité ne font pas bon ménage [The impact of obesity on fertility]

There are many negative impacts of obesity on fertility. Obese couples present decreased sperm count, decreased ovulation and conception rates, increased erectile dysfunction and spontaneous abortion rate as well as increased maternal and foetal complications of pregnancy. Moreover, obesity tends to decrease response to fertility treatments. Fortunately, intensive lifestyle modifications can restore fertility while decreasing pregnancy complications risk. With the increasing trend of obesity to affect young populations, taking care of these infertile couples rapidly is capital to restore fertility and decrease its related pregnancy complications.

Acquired auditory agnosia in childhood and normal sleep electroencephalography subsequently diagnosed as Landau-Kleffner syndrome: a report of three cases.

Aim  We report three cases of Landau-Kleffner syndrome (LKS) in children (two females, one male) in whom diagnosis was delayed because the sleep electroencephalography (EEG) was initially normal. Method  Case histories including EEG, positron emission tomography findings, and long-term outcome were reviewed. Results  Auditory agnosia occurred between the age of 2 years and 3 years 6 months, after a period of normal language development. Initial awake and sleep EEG, recorded weeks to months after the onset of language regression, during a nap period in two cases and during a full night of sleep in the third case, was normal. Repeat EEG between 2 months and 2 years later showed epileptiform discharges during wakefulness and strongly activated by sleep, with a pattern of continuous spike-waves during slow-wave sleep in two patients. Patients were diagnosed with LKS and treated with various antiepileptic regimens, including corticosteroids. One patient in whom EEG became normal on hydrocortisone is making significant recovery. The other two patients did not exhibit a sustained response to treatment and remained severely impaired. Interpretation  Sleep EEG may be normal in the early phase of acquired auditory agnosia. EEG should be repeated frequently in individuals in whom a firm clinical diagnosis is made to facilitate early treatment.

Social influences on fertility : a comparative mixed methods study in eastern and western Germany

This article uses a mixed methods design to investigate the effects of social influence on family formation in a sample of eastern and western German young adults at an early stage of their family formation. Theoretical propositions on the importance of informal interaction for fertility and family behavior are still rarely supported by systematic empirical evidence. Major problems are the correct identification of salient relationships and the comparability of social networks across population subgroups. This article addresses the two issues through a combination of qualitative and quantitative data collection and analysis. In-depth interviewing, network charts, and network grids are used to map individual personal relationships and their influence on family formation decisions. In addition, an analysis of friendship dyads is provided.

Préservation de la fertilité masculine et cancer [Fertility preservation and cancer in the male].

Improvement in cancer treatments resulted in an increased number of men surviving cancer. Quality of life has become an important issue in these patients. Anti cancer treatments might have transient or definitive harmful effects on male fertility. Sperm cryoconservation is currently the only proven method to preserve fertility in patients undergoing oncologic treatment. It should be proposed to every patient at reproductive age before chemotherapy, radiotherapy or any surgery involving reproductive tract. Despite low use rate, this simple method could allow patients presenting infertility after treatment to father a child.

Plasma angiotensin-(1-8) octapeptide measurement to assess acute angiotensin-converting enzyme inhibition with captopril administered parenterally to normal subjects.

The blood pressure (BP), heart rate (HR), and humoral effects of single intravenous (i.v.) doses of the angiotensin-converting enzyme (ACE) inhibitor captopril was investigated in five normotensive healthy volunteers. Each subject received at 1-week intervals a bolus dose of either captopril (1, 5, and 25 mg) or its vehicle. The study was conducted in a single-blind fashion, and the order of treatment phases was randomized. The different doses of captopril had no acute effect on BP and HR. They induced a dose-dependent decrease in plasma ACE activity and plasma angiotensin II levels. The angiotensin-(1-8) octapeptide was isolated by solid-phase extraction and high-performance liquid chromatography (HPLC) prior to radioimmunoassay (RIA). All three doses of captopril reduced circulating angiotensin II levels within 15 min of drug administration. Only with the 25-mg dose was the angiotensin II concentration below the detection limit at 15 min and still significantly reduced 90 min after drug administration. Simultaneous and progressive decreases in plasma aldosterone levels were observed both with ACE inhibition and during vehicle injection, but the relative fall was more pronounced after captopril administration. No adverse reaction was noticed. These results demonstrate that captopril given parenterally blocks the renin-angiotensin system in a dose-dependent manner. Only with the dose of 25 mg was the inhibition of plasma-converting enzyme activity and the reduction of plasma angiotensin II sustained for at least 1 1/2 h.

Notch signaling is required for normal prostatic epithelial cell proliferation and differentiation.

Notch pathway is crucial for stem/progenitor cell maintenance, growth and differentiation in a variety of tissues. Using a transgenic cell ablation approach, we found in our previous study that cells expressing Notch1 are crucial for prostate early development and re-growth. Here, we further define the role of Notch signaling in regulating prostatic epithelial cell growth and differentiation using biochemical and genetic approaches in ex vivo or in vivo systems. Treatment of developing prostate grown in culture with inhibitors of gamma-secretase/presenilin, which is required for Notch cleavage and activation, caused a robust increase in proliferation of epithelial cells co-expressing cytokeratin 8 and 14, lack of luminal/basal layer segregation and dramatically reduced branching morphogenesis. Using conditional Notch1 gene deletion mouse models, we found that inactivation of Notch1 signaling resulted in profound prostatic alterations, including increased tufting, bridging and enhanced epithelial proliferation. Cells within these lesions co-expressed both luminal and basal cell markers, a feature of prostatic epithelial cells in predifferentiation developmental stages. Microarray analysis revealed that the gene expression in a number of genetic networks was altered following Notch1 gene deletion in prostate. Furthermore, expression of Notch1 and its effector Hey-1 gene in human prostate adenocarcinomas were found significantly down-regulated compared to normal control tissues. Taken together, these data suggest that Notch signaling is critical for normal cell proliferation and differentiation in the prostate, and deregulation of this pathway may facilitate prostatic tumorigenesis.

Bacillus subtilis alpha-phosphoglucomutase is required for normal cell morphology and biofilm formation.

Mutations designated gtaC and gtaE that affect alpha-phosphoglucomutase activity required for interconversion of glucose 6-phosphate and alpha-glucose 1-phosphate were mapped to the Bacillus subtilis pgcA (yhxB) gene. Backcrossing of the two mutations into the 168 reference strain was accompanied by impaired alpha-phosphoglucomutase activity in the soluble cell extract fraction, altered colony and cell morphology, and resistance to phages phi29 and rho11. Altered cell morphology, reversible by additional magnesium ions, may be correlated with a deficiency in the membrane glycolipid. The deficiency in biofilm formation in gtaC and gtaE mutants may be attributed to an inability to synthesize UDP-glucose, an important intermediate in a number of cell envelope biosynthetic processes.