Cerebral blood flow changes in normal aging: Spect measurements

Global and regional cerebral blood flow (CBF) were evaluated with single photon emission computerized tomography (SPECT) utilizing both ¹³³Xenon (¹³³Xe) (47 subjects, 47–82 years old) and ⁹⁹Tc-hexamethylpropyleneamine oxime (⁹⁹Tc-HMPAO) (27 subjects, 47–80 years old). The ¹³³Xe results showed: among total subjects, no age-related decline in global CBF, but a significant regional decline in the occipital lobe (p < 0.05); among men, significant age-related declines in global, frontal, temporal, occipital and right hemisphere CBF (all p < 0.05); among women, no age-related decline in global or regional CBF. The ⁹⁹Tc-HMPAO results showed no age-related decline in either global or regional perfusion among total subjects, men or women. These results suggest that age-related global and regional (including frontal lobe) CBF declines do not occur in healthy control subjects after the age of 45 years. However, gender differences in age-related CBF changes warrant further study.     

Effect of diazepam on successive negative contrast in one-way avoidance learning.

The effect of administration of diazepam on successive negative contrast in one-way avoidance learning was examined in rats. Contrast was induced by shifting rats from a large reward, 30 s spent in the safe compartment, to a small reward, 1 s spent in the safe compartment. IP administration of 2 mg/kg diazepam eliminated this negative contrast. Moreover, this effect is dose dependent, with doses of 2 and 2.5 mg/kg, but not 0.5 mg/kg, effective in reliably reducing contrast. These results suggest the existence of similar or common underlying mechanisms in both aversive and appetitive contrast effects; they are discussed in light of the current theories of frustrative nonreward and as a mean of studying the behavioral and biological mechanisms of anxiety.     

Ischemic stroke complicating cardiac catherization: case report.

Ischemic stroke occurs in 0.2-0.4% of patients undergoing left heart catheterization, and is responsible for 5-10% of the mortality associated with the procedure. The main predisposing factors for this complication are female gender, complex atherosclerotic plaques in the ascending aorta, and peripheral arterial disease. The possibility of timely intervention with reperfusion therapy supports close clinical monitoring during the immediate post-catheterization period. The cardiologist should be familiar with the various types of stroke reperfusion therapy and its indications according to the time interval between catheterization and the stroke. The decision should be discussed with neurology and neuroradiology.     

Pregnancy outcome associated with natural family planning (NFP): scientific basis and experimental design for an international cohort study

Although natural family planning (NFP) is a form of contraception without ostensible maternal risks (other than pregnancy), potential fetal risks could exist if aging gametes are involved in inadvertent fertilization. In the following report, we first review animal studies firmly establishing that aging sperm and aging oocytes (delayed fertilization) cause chromosomal abnormalities in mammals and other species. We next review human studies associating decreased coital frequency with trisomy and studies of NFP populations that generally show no increased frequency of anomalous offspring or spontaneous abortions. Our rationale for initiating an international cohort study is presented, along with the experimental design selected. Preliminary findings indicate that the experimental design chosen will indeed provide information allowing NFP safety to be assessed definitively.

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Resumen Aunque la planificación familiar natural (PFN) es una forma de anticoncepción sin riesgos maternos ostensibles, (fuera del embarzo) podrían existir posibles riesgos fetales di gametos que están envejeciendo son inadvertidamente fertilizados. La primera revisión de estudios en animales establece firmemente que espermatozoides y oocytos en envejecimiento (fertilización tardía), causan anormalidades cromosómicas en mamíferos y otras especies. A continuación revisamos estudios en humanos que asocian la disminución de la frecuencia coital con trisomía, y estudios de poblaciones practicando PFN que generalmente no muestran aumento en la frecuencia de descendientes anormales o de abortos espontáneos. Presentamos nuestras razones para iniciar el estudio de una cohorte internactional ademas del diseño experimental elegido proveerá información alegando que la inocuidad de la PFN sea definitivamente valorada.

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Resumé Bien que le planning familial naturel (PFN-NFP) soit une forme de contraception ne présentant pas de risques manifestes pour la mère (autres qu'une grossesse), il pourrait y avoir des risques potentiels pour le foetus si des gamètes âgés sont par inadvertance fécondés. Nous passons en revue tout d'abord des études effectuées sur des animaux, établissant fermement que le sperme veillissant et les oocytes vieillissants (fécondation retardée) provoquent des anomalies chromosomales chez les mammifères et d'autres espèces. Nous examinons ensuite des études sur des humains, qui associent diminution coitale et trisomie, et des études de populations pratiquant le PFN, qui ne révèlent généralement pas de fréquence accrue d'enfants anormaux ou d'avortements spontanés. Cette communication expose la raison pour laquelle nous avons entrepris une étude sur une cohorte internationale, ainsi que le concept d'expérimentation que nous avons choisi. Les constatations préliminaires indiquent que ce concept fournira véritablement des informations qui permettront d'évaluer de façon définitive la sécurité du PFN.

     

Increased susceptibility of spinal muscular atrophy fibroblasts to camptothecin-induced cell death

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions or mutations in the telomeric copy of the survival motor neuron (SMN1) gene. Although the SMN protein has been implicated in the biogenesis of ribonucleoprotein complexes and RNA processing, it is not clear how these functions contribute to the pathogenesis of SMA. To gain a further understanding of SMN function, we have investigated its role in cell survival in skin fibroblasts derived from SMA patients and age-matched controls. SMA fibroblasts exposed to camptothecin, a specific inhibitor of DNA topoisomerase I, consistently showed cell death at a lower concentration than normal controls. Treatment with other cell death-inducing agents did not cause differences in survival of SMA fibroblasts as compared with control fibroblasts. Camptothecin treatment resulted in activation of caspase-3 with generation of the caspase-3 cleavage product, poly ADP-ribose polymerase (PARP). Depletion of SMN protein by RNA interference in control fibroblasts increased caspase-3 activity, whereas transfection of SMA fibroblasts with wild-type SMN decreased caspase-3 activity. Our data demonstrate that SMA fibroblasts are more prone to some, but not all, death-stimuli. Vulnerability to death-stimuli is associated with decreased levels of SMN protein and is mediated by activation of caspase-3.     

Coxsackievirus infection of the pancreas: evaluation of receptor expression, pathogenesis, and immunopathology

Coxsackievirus type B (CVB) infection of the pancreas induces a massive cellular infiltrate composed of natural killer cells, T cells, and macrophages and leads to the destruction of exocrine tissue. The physiological manifestations of pancreatic CVB infection are correlated with viral tropism; the virus infects acinar cells but spares the islets of Langerhans. Here we evaluate the mechanisms underlying pancreatic inflammation and destruction and identify the determinants of viral tropism. T-cell-mediated immunopathology has been invoked, along with direct virus-mediated cytopathicity, to explain certain aspects of CVB-induced pancreatic disease. However, we show here that in the pancreas, the extent of inflammation and tissue destruction appears unaltered in the absence of the cytolytic protein perforin; these findings exclude any requirement for perforin-mediated lysis by natural killer cells or cytotoxic T cells in CVB3-induced pancreatic damage. Furthermore, perforin-mediated cytotoxic T-cell activity does not contribute to the control of CVB infection in this organ. In addition, we demonstrate that the recently identified coxsackie-adenovirus receptor is expressed at high levels in acinar cells but is barely detectable in islets, which is consistent with its being a major determinant of virus tropism and, therefore, of disease. However, further studies using various cell lines of pancreatic origin reveal secondary determinants of virus tropism.     

Unidirectional block in a computer model of partially coupled segments of cardiac Purkinje tissue

The initiation of a reentrant circuit requires a zone of slow conduction and a zone of unidirectional block. This study used computer model conditions under which partial coupling between segments of cardiac Purkinje tissue resulted in unidirectional block. The structure used was one-dimensional and divided into three segments: a middle segment of variable length coupled to two long (semi-infinite in concept) segments. The DiFrancesco-Noble equations represented the ionic currents of the membrane. The results show that the possibility of unidirectional block depends on the size of the middle segment and the coupling resistances between the segments. No combination of coupling resistances allowed unidirectional block for middle segments with a length of two space constants (4 mm) or longer. Unidirectional block occurred for many combinations of coupling resistances as the length of the middle segment decreased to around half a space constant (1 mm). The number of length combinations that caused unidirectional block decreased again as segment length further decreased. These results provide a possible mechanism of unidirectional block for situations where islands of viable tissue are connected through nonviable tissue, such as in a healed myocardial infarction.     

Post-coital administration of levonorgestrel and post-fertilization events in the new-world monkey Cebus apella

Sir, The paper by Ortiz et al. (2004), which concludes that ‘Post-coitaladministration of levonorgestrel does not interfere with post-fertilizationevents in