Different contributions of ASIC channels 1a, 2, and 3 in gastrointestinal mechanosensory function

AIMS: Members of the acid sensing ion channel (ASIC) family are strong candidates as mechanical transducers in sensory function. The authors have shown that ASIC1a has no role in skin but a clear influence in gastrointestinal mechanotransduction. Here they investigate further ASIC1a in gut mechanoreceptors, and compare its influence with ASIC2 and ASIC3. METHODS AND RESULTS: Expression of ASIC1a, 2, and 3 mRNA was found in vagal (nodose) and dorsal root ganglia (DRG), and was lost in mice lacking the respective genes. Recordings of different classes of splanchnic colonic afferents and vagal gastro-oesophageal afferents revealed that disruption of ASIC1a increased the mechanical sensitivity of all afferents in both locations. Disruption of ASIC2 had varied effects: increased mechanosensitivity in gastro-oesophageal mucosal endings, decreases in gastro-oesophageal tension receptors, increases in colonic serosal endings, and no change in colonic mesenteric endings. In ASIC3-/- mice, all afferent classes had markedly reduced mechanosensitivity except gastro-oesophageal mucosal receptors. Observations of gastric emptying and faecal output confirmed that increases in mechanosensitivity translate to changes in digestive function in conscious animals. CONCLUSIONS: These data show that ASIC3 makes a critical positive contribution to mechanosensitivity in three out of four classes of visceral afferents. The presence of ASIC1a appears to provide an inhibitory contribution to the ion channel complex, whereas the role of ASIC2 differs widely across subclasses of afferents. These findings contrast sharply with the effects of ASIC1, 2, and 3 in skin, suggesting that targeting these subunits with pharmacological agents may have different and more pronounced effects on mechanosensitivity in the viscera.     

Cognitive characteristics and homosexuality

There have been many studies of psychological characteristics of homosexuals, but cognitive characteristics have been relatively neglected. This study investigated the verbal intelligence of 20 homosexual males, 20 heterosexual males, and 20 females, taking into account variables likely to affect verbal ability such as social class and handedness. There were no differences in overall IQ, but group differences in verbal and nonverbal ability were marked. No other differences between the groups were found. The implications are briefly discussed.     

Ischaemic brain damage in the gerbil in the absence of ''no-reflow''.

Approximately 40% of gerbils subjected to one hour of unilateral carotid artery occlusion displayed neurological abnormalities during that time. Most such animals were subsequently found to have ischaemic neuronal alterations within the territory of the ipsilateral middle cerebral artery. In contrast, impaired reperfusion ('no-reflow') rarely occurred and cannot therefore be implicated in the pathogenesis of ischaemic brain damage.     

Cyanide intoxication in Macaca mulatta: Physiological and neuropathological aspects

Sodium cyanide was infused intravenously in 11 lightly anaesthetised and spontaneously breathing M. mulatta. In most, the EEG, ECG, respiratory rate, blood pressure, cerebral venous sinus pressure, end-tidal pCO₂ and body temperature were recorded. Blood gases, pH, lactate and pyruvate were estimated in arterial and venous sinus blood samples. There was an initial hyperventilation with tetany in all animals. A rapid rate of cyanide infusion led to apnoea. An isoelectric or near-isoelectric EEG was usually precipitated by bradycardia often with additional hypotension. Neither epileptic seizures nor their EEG concomitants were seen at any stage. Three animals died of early heart failure. Brain damage was seen in 4 animals surviving up to 98 hr. White matter was involved in all. Ischaemic neuronal alterations, restricted to the striatum of one animal, were attributed to major circulatory complications. It was concluded that under these experimental conditions there is no evidence for hypoxic neuronal damage of purely histotoxic type.     

Increased risk for nonmedullary thyroid cancer in the first degree relatives of prevalent cases of nonmedullary thyroid cancer: a hospital-based study.

The genetic basis for nonmedullary forms of thyroid cancer (NMTC) is less well established than that of medullary thyroid cancer. However, epidemiological and family studies suggest that a proportion of NMTC may be due to inherited predisposition. To estimate the familial risk of thyroid cancer, we conducted a hospital-based case-control study at the Princess Margaret Hospital in Toronto, Ontario, Canada, and at 2 university hospitals in Montréal, Québec, Canada. We obtained pedigrees from 339 unselected patients diagnosed with NMTC and from 319 unaffected ethnically matched controls. Family histories of cancer were obtained from the cases and controls for 3292 first degree relatives of cases and controls. Seventeen cases (5.0%) and 2 controls (0.6%) reported at least one first degree relative with thyroid cancer. In relatives of patients with thyroid cancer, the incidence of any type of cancer (including NMTC) was 38% higher than in relatives of controls (incidence rate ratio, 1.4; 95% confidence interval, 1.1-1.7). The relative risk for thyroid cancer was 10-fold higher in relatives of cancer patients than in controls (incidence rate ratio, 10.3; 95% confidence interval, 2.2-47.6). Our findings suggest that hereditary or other familial factors are important in a small proportion of NMTC. Molecular studies are needed to determine the genetic basis of cancer susceptibility in these families.