Paternal effects acting during the first cell cycle of human preimplantation development after ICSI.

BACKGROUND: The ability of human embryos to undergo normal development has been shown previously to be subject to strong paternal (sperm-derived) effects. This study was undertaken to determine whether paternal influences on human embryo quality are detectable as early as the first cell cycle after fertilization. METHODS: The quality of zygotes and cleaving embryos resulting from sibling donor oocytes fertilized by sperm from different patients were compared in a donor oocyte-sharing programme. RESULTS: Fertilizations with sperm from certain individuals repeatedly resulted in the formation of high proportions of zygotes with abnormal pronuclear morphology that subsequently tended to cleave slowly and to show extensive fragmentation and blastomere irregularities. This phenomenon was observed with oocytes from two different donors for each of these individuals and contrasted with normal developmental performance of embryos resulting from sibling oocytes fertilized by sperm from other men with similar basic sperm characteristics. Fertilization rates were not related to these differences. CONCLUSIONS: These data point to a very early onset of paternal effects that condition human embryo development. These effects may be both of genetic (related to the minor gene activity of the male pronucleus) or epigenetic (related to the sperm-derived oocyte-activating factor or sperm centrosome) origin.     

Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex

Weak transcranial direct current stimulation (tDCS) of the human motor cortex results in excitability shifts which occur during and after stimulation. These excitability shifts are polarity-specific with anodal tDCS enhancing excitability, and cathodal reducing it. To explore the origin of this excitability modulation in more detail, we measured the input–output curve and motor thresholds as global parameters of cortico-spinal excitability, and determined intracortical inhibition and facilitation, as well as facilitatory indirect wave (I-wave) interactions. Measurements were performed during short-term tDCS, which elicits no after-effects, and during other tDCS protocols which do elicit short- and long-lasting after-effects. Resting and active motor thresholds remained stable during and after tDCS. The slope of the input–output curve was increased by anodal tDCS and decreased by cathodal tDCS. Anodal tDCS of the primary motor cortex reduced intracortical inhibition and enhanced facilitation after tDCS but not during tDCS. Cathodal tDCS reduced facilitation during, and additionally increased inhibition after its administration. During tDCS, I-wave facilitation was not influenced but, for the after-effects, anodal tDCS increased I-wave facilitation, while cathodal tDCS had only minor effects. These results suggest that the effect of tDCS on cortico-spinal excitability during a short period of stimulation (which does not induce after-effects) primarily depends on subthreshold resting membrane potential changes, which are able to modulate the input-output curve, but not motor thresholds. In contrast, the after-effects of tDCS are due to shifts in intracortical inhibition and facilitation, and at least partly also to facilitatory I-wave interaction, which is controlled by synaptic activity.     

Melatonin prevents focal rat cerebellum injury as assessed by induction of heat shock protein (HO-1) following subarachnoid injections of lysed blood

The present paper studies a marker of oxidative stress such as heme oxygenase-1 (HO-1), the main heat shock protein. HO-1 expression was induced in the focal region of the cerebellum following experimental subarachnoid hemorrhage (SAH). Lysed blood was injected into the subarachnoid space or cisterna magna region of adult rats. The experimental groups used were: (1) animals injected with lysed blood alone; (2) animals injected with saline alone; (3) lysed blood plus melatonin (10 mg/kg body weight(BW)); (4) lysed blood plus melatonin (10 mg/kg BW injected 1 h before SAH); (5) lysed blood plus melatonin (5 mg/kg BW injected 1 h before SAH); (6) lysed blood plus vitamin E (Trolox; 30 mg/kg BW injected simultaneously); (7) lysed blood plus vitamin E (30 mg/kg BW injected 1 h before SAH); and (8) lysed blood plus vitamin E (15 mg/kg BW injected 1 h before SAH). Animals were sacrificed 24 h later. Injection of lysed blood induced an overexpression of HO-1. Both, melatonin and vitamin E were able to prevent the expression of the heat shock protein. However, in terms of efficiency, the antioxidant capability of melatonin was clearly higher than that exhibited by vitamin E. The results presented in this study show that antioxidants, especially melatonin, prevent focal regions of injury as assessed by heat shock protein expression in a rat model of SAH.     

Cardiovascular and Mood Responses to Quantified Doses of Cigarette Smoke in Oral Contraceptive Users and Nonusers

Previous research suggests that the female sex hormones may moderate cardiovascular and mood responses to cigarette smoking and abstinence. To test this possibility, acute effects of cigarette smoking on cardiovascular reactivity and mood were examined in 12 oral contraceptive users and 12 nonusers across two menstrual phases (early and late cycle). After overnight deprivation, each participant attended two sessions in which they first sham-smoked and then smoked two standard cigarettes, via a quantified smoke delivery system. Oral contraceptive users exhibited larger cigarette smoking-induced increases in heart rate compared with nonusers. In addition, cigarette smoking-induced cardiovascular changes varied with both the phase of the menstrual cycle and oral contraceptive use. No menstrual phase-dependent effects were observed for tobacco withdrawal symptoms, premenstrual symptoms, or moods prior to smoking. Cardiovascular hyperreactivity to cigarette smoke in oral contraceptive users may help explain the mechanisms by which smoking and oral contraceptive use contribute to an elevated risk for coronary heart disease.     

Molecular and serological evaluation of surface antigen negative hepatitis B virus infection in blood donors from Venezuela

Surface antigen negative hepatitis B virus (HBV) infection was evaluated in Venezuela, by molecular characterization of blood samples positive for antibodies to core antigen (anti-HBc) and negative for surface antigen (HBsAg) in blood donors (residual infections). HBV DNA was found in 11/258 samples (4.3%), and was significantly associated with high levels of anti-HBc antibodies (>25 UI/ml, P < 0.05), while no correlation was found between the presence of HBV DNA and the levels of anti-HBs. Synonymous and non-synonymous mutations were found in the HBV surface region (but not vaccine escape mutants) and in the precore/core region (precore mutants in 2/7 samples and 33-45 bp deletions near the N-terminal core region in 4/19 samples). While HBV genotype F prevails among HBsAg positive samples from blood donors in Venezuela, residual infection isolates were mainly genotypes A and D. Phylogenetic analysis of viral surface and core region revealed discrepancies in genotype designation in 6/9 samples, suggesting the presence of mixed infection or recombination. In conclusion, HBV residual infection in Venezuela does not seem to be frequently observed in HBV genotype F. This type of infection is frequently associated with variants exhibiting mutations in the surface gene that might be affecting the correct recognition by commercial tests, with precore mutants and with core internal deletions. These variants do not seem to cause severe liver disease, and on the contrary, were found circulating at low viremia.     

Hemostatic coronary risk factors in a healthy population of Maracaibo,Venezuela

The purpose of the present work was to determine the plasma concentrations of fibrinogen and Von Willebrand Factor (VWF) as well as platelet aggregation, in an apparently healthy population of 306 men and 41 women, 33 to 65 years of age, workers of the national oil industry (PDVSA, Maracaibo), as a base investigation in a 5-year prospective national collaborative study. The participants were previously subjected to a thorough clinical examination with cardiovascular evaluation and laboratory tests. Clottable fibrinogen and VWF concentrations were determined in platelet poor plasma, the last one by immunoclectrophoresis, and a multimeric analysis of VWF was performed on those plasmas with concentrations higher than 150 U/dL by SDS agarose electrophoresis, followed by cellulose membrane transference. Platelet aggregation was studied in platelet rich plasma with no addition of stimulants and after collagen and ristocetin were added. Forty per cent of men and 65.8% of women, showed fibrinogen concentrations above 300 mg/dL (p < 0.01) and 12.2% of men and 15.4% of women had VWF values higher than 150 U/dL, with normal multimeric distribution. Fourteen individuals presented spontancous platelet aggregation and increased aggregation in 12 and 13 of them, after induction with collagen and ristocetin respectively. Comparing these findings with those of previous collaborative studies from other countries, the present results could mean that an important proportion of the population here studied, could be at risk for a future coronary event; however, as these are the base findings in Maracaibo, the significance of our results will be better evaluated at the end of the five year study.     

Monosomy 15 in chronic myelomonocytic leukemia. description of a case and review of the literature

We report a 89-year-old female diagnosed with chronic myelomonocytic leukemia (CMMoL) presenting with a monosomy 15. To our knowledge, this is the second reported case of CMMoL with monosomy 15. On the other hand, monosomy 15 in complex karyotypes is a frequent chromosome aberration in myelodysplastic syndromes, particularly in refractory anemia with excess of blasts.     

Adenosine A2A Receptor Agonists Promote More Rapid Wound Healing Than Recombinant Human Platelet–Derived Growth Factor (Becaplermin Gel)

Animal studies of the topical application of adenosine A _2A receptor agonists show that it promotes wound closure. To further confirm the efficacy of adenosine A _2A receptor agonists as promoters of wound healing, we compared the effect of MRE0094, a novel selective adenosine A _2A receptor agonist, to CGS-21680, a reference selective adenosine A _2A receptor agonist, as well as to recombinant human platelet–derived growth factor (0.01% Becaplermin gel), an agent currently used to promote healing of diabetic ulcers, on wound closure in healthy BALB/C mice. Wounds (12 mm diameter) were created on the dorsum of mice (two per mouse) and then treated daily with vehicle, 0.01% Becaplermin gel, or different doses of the adenosine A _2A receptor agonists. The wound margins were traced onto plastic sheets, and the wound areas were digitized, quantitated, and compared. We found that application of MRE0094 (1 g/wound and 10 g/wound) and CGS-21680 (1 g/wound and 5 g/wound) achieved 50% wound closure significantly more rapidly than control application (day 1.9, 1.9, 3.5, 3.2, respectively, versus control day 4, p < 0.05 ANOVA). Surprisingly, neither higher nor lower concentrations of CGS-21680 affected the rate of wound closure, as compared to control. In contrast, Becaplermin gel did not increase the rate at which wounds closed (50% closure by day 7.2, p = NS versus control). These data confirm our prior observations that adenosine A _2A receptor agonists promote wound closure, and they suggest that these agents may be as effective if not more effective than Becaplermin gel for the treatment of poorly healing wounds.