Attentional modulation of the cardiac defense response in humans

How cardiac components of the defense reaction are modulated by attentional factors related to sensory intake versus sensory rejection was examined. Forty-eight men participated in a test of the heart rate response to three presentations of an intense auditory stimulus while performing one of three attentional tasks during the 80 s following stimulus onset: (a) internal (rejection) task, (b) external (intake) task, and (c) no task. Results showed a potentiation of the defense response only under the external attention condition. We concluded that defensive reactions, far from provoking the rejection of the aversive stimulus, require allocation of attention to processing that stimulus in detail.     

Constitutive Secretion of Interleukin-6 by Human Decidual Stromal Cells in Culture. Regulatory Effect of Progesterone

PROBLEM : Although several studies have demonstrated that decidual stromal cells (DSC) can secrete cytokines in culture, none of these studies documented the purity of the cultures. Since other cells of the decidua, such as macrophages and epithelial cells, also produce cytokines, it is important to ensure purity of the culture so that cytokine production can be ascribed with confidence to DSC. METHOD : DSC from early human pregnancies were highly purified and maintained in culture. Basal secretion by these cells of IL-6, together with other cytokines considered critical for pregnancy (IL-1β, TNFα and IFNγ), was measured with immunological techniques. RESULTS : We found that DSC in culture produce insignificant quantities of IL-1β, TNFá and IFNΓ, but appreciable amounts of IL-6. The production of this later cytokine was, however, inhibited by the effect of progesterone. CONCLUSIONS : Basal production of IL-6 by DSC may be involved in physiological functions at the maternal-fetal interface. Nevertheless, the secretion of this cytokine is regulated by progesterone, probably to prevent excessive production of this cytokine from triggering an inflammatory response that might compromise pregnancy.     

Role of presynaptic purinoceptors and cyclic AMP on the noradrenaline release in cat cerebral arteries

Field electrical stimulation (ES), K+ (50 mM) or ionophore X-537A (0.01 mM) induced tritium release from cat cerebral arteries preincubated with [3H]noradrenaline (NA). Adenosine and AMP (0.5 mM) did not modify tritium release caused by ionophore X-537A, but these agents and ATP (0.5 mM) significantly reduced that elicited by ES and K+; this reduction was antagonized by 1-methyl-3-isobutylxanthine (MIX; 0.05 mM). Inosine (0.5 mM) and the agonist of purinergic A2-receptors, 5'N-ethyl-carboxamide adenosine (NECA; 0.5 mM) had no effect, but the agonist of purinergic A2-receptors L-N6-phenylisopropyl adenosine (L-PIA; 0.1 mM) diminished tritium efflux caused by ES and K+. The adenosine inhibition of ES-induced radioactivity release was not affected by indomethacin (0.05 mM). MIX (0.05 mM) increased tritium release evoked by ES and K+. Agents that increase intracellular cyclic (c)AMP levels, such as dibutyryl cAMP (0.5 mM), the phosphodiesterase inhibitor Ro 20-1724 (0.1 mM), and the activators of adenylate cyclase, forskolin (0.005 mM) and NaF (2 mM) reduced tritium secretion elicited by ES and K+. However, the intracellular increase of cyclic GMP (cGMP) caused by 8-Br-cGMP did not affect this secretion. Dipyridamole (0.05 mM) and the adenosine deaminase inhibitor erythro-9-2-hydroxy-3 nonyl adenosine (EHNA; 0.1 mM) also produced inhibition of tritium secretion elicited by ES and K+. Dipyridamole reduced both the uptake of [3H]NA and [3H]adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)     

ETHANOL ELIMINATION IN ALCOHOL-TREATED PREGNANT RATS

The effects of chronic intake of alcohol on ethanol eliminationwere studied in 20-day pregnant rats, in their foetuses, andin virgin rats. Experimental animals received ethanol in drinkingwater (from 10% to 25% in 2 months) (alcohol group), whereascontrols drank only water. At the end of chronic exposure, alcoholdehydrogenase activity was determined in stomach and liver andcytochronse P-450 was measured in liver. In a complementaryassay, the same experimental groups of rats were given an acutedose of ethanol (2 g/kg body wt, 25% w/v) either intragastricallyor intraperitoneally, at the end of the chronic exposure, todetermine first-pass ethanol metabolism and pharmacokineticparameters of its elimination. Significant differences werefound between alcohol and control groups for liver and stomachalcohol dehydrogenase activity in pregnant rats. Only in virginsdid chronic alcohol treatment significantly increase the livercytochrome P-450 content. In virgin rats, the first-pass metabolismof ethanol was lower in the alcohol group than in control. Bycontrast, in control rats, the first-pass of ethanol was lowerin pregnant, than in virgin, rats. The metabolic rate of ethanolelimination (mg/kg body wt/hr) was clearly enhanced in alcoholicvirgin rats, demonstrating that this model of chronic alcoholisminduces metabolic tolerance to ethanol. In alcoholic pregnantrats, a surprisingly low theoretical volwne of body ethanoldistribution (55 ml/100 g body wt vs. 80 ml/100 g body wt inthe other groups) masked their metabolic tolerance to ethanol.This preliminary study should be taken into account when evaluatingthe effects of chronic or/and acute alcohol intake during pregnancyon the circulating ethanol levels in foetuses and on futuredevelopment of the foetal alcohol syndrome.     

A novel homozygous mutation at the GAA gene in Mexicans with early-onset Pompe disease

Glycogen-storage disease type II, also named Pompe disease, is caused by the deficiency of the enzyme acid alpha-glucosidase, which originates lysosomal glycogen accumulation leading to progressive neuromuscular damage. Early-onset Pompe disease shows a debilitating and frequently fulminating course. To date, more than 300 mutations have been described; the majority of them are unique to each affected individual. Most early-onset phenotypes are associated with frameshift mutations leading to a truncated alpha-glucosidase protein with loss of function. Founder effects are responsible from many cases from few highprevalence world regions. Herein we described two apparently unrelated cases affected with classical early-onset Pompe disease, both pertaining to a small region from Central Mexico (the State of San Luis Potosí), the same novel homozygous frameshift mutation at gene GAA (c.1987delC) was demonstrated in both cases. This GAA gene deletion implies a change of glutamine to serine at codon 663, and a new reading frame that ends after 33 base pairs, which leads to the translation of a truncated protein. This report contributes to widen the knowledge on the effect of pathogenic mutations in Pompe disease. Here we postulate the existence of a founder effect.Key words: Early-onset Pompe disease, Acid maltase deficiency, Founder effectGlycogen storage disease type II (Online Mendelian Inheritance in Man, OMIM, accession number 232300), also called Pompe disease, was described by Johannes C. Pompe in 1932. The disorder is caused by a deficiency of the enzyme acid alpha-glucosidase (acid maltase, EC 3.2.1.20, Swiss) which originates lysosomal glycogen accumulation leading to lysosomal swelling, cellular damage and dysfunction (1-3). Affected individuals develop progressive neuromuscular damage, showing a debilitating and frequently fulminating course on the classical, early-onset type of the disease. Other main findings are hypertrophic cardiomyopathy, hypotonia, hepatomegaly, macroglossia, feeding problems and breath difficulty. Currently it is recognized that the late form of Pompe disease has a very variable phenotype that can be confused with a wide range of neuromuscular, pulmonary and cardiovascular diseases with mild, moderate or severe symptoms that present either alone or combined (4-6).Pompe disease has an autosomal recessive inheritance and it is caused by more than 300 mutations that occur all over the gene coding for acid alpha-glucosidase (GAA) located at locus 17q25.2q25.3. The molecular phenomenon responsible of the different types of clinical expression occur by the presence of two either homozygous or compound heterozygous pathogenic mutations in early-onset Pompe cases, whereas late-onset Pompe have one variant and one pathogenic mutation (7). The majority of disease-causing mutations are unique; nonetheless, relatively frequent mutations have been described in certain populations with a possible founder effect traced from the original mutated carrier to the newly occurring cases. Affected cases have been described worldwide with a few high-prevalence regions like South-Africa, Taiwan and Holland (1, 8-10).Herein, we described two unrelated cases affected with classical early-onset Pompe disease, both pertaining to the same small Mexican region, with the same novel homozygous frameshift mutation at gene GAA (c.1987delC), identified by complete gene sequencing.     

A case of optic atrophy possibly induced by quinoline in acrodermatitis enteropathica

A 2-year-old girl with acrodermatitis enteropathica, developed optic atrophy during quinoline treatment (600 mg/day, later gradually increased to 1700 mg/day; a total dose of 280 g was given). The optic atrophy developed rapidly 9 months after the start of the quinoline treatment. The right eye was blinded and developed a convergent strabismus. Eight months after the quinoline had been stopped, the left eye began a slow and partial recovery of vision with an improvement in the appearance of the optic disc.