Serotonin-induced increase in cAMP in ganglia isolated from the myenteric plexus of the guinea pig small intestine: Mediation by a novel 5-HT receptor

Serotonin (5-HT) is a mediator (through 5-HT_1P receptors) of slow EPSPs in myenteric ganglia of the small intestine. The effect of 5-HT can be mimicked by elevating cAMP; therefore, we tested the hypothesis that the slow EPSP-like response to 5-HT is cAMP-mediated. Guinea pig gut was enzymatically dissociated; myenteric ganglia remained intact and were collected by filtration. Neurons in the isolated ganglia retained their ability to manifest the slow EPSP-like response to 5-HT. Exposure to 5-HT raised the ganglionic level of cAMP (ED₅₀ 0.3 μM). This effect was not antagonized by the 5-HT_1P antagonist, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (100.0 μM), or mimicked by the 5-HT_1P agonist, 5-hydroxyindalpine (10.0 μM). Increases in cAMP were also evoked by the 5-HT₁ agonist, 5-carboxyamidotryptamine (10.0 μM), the 5-HT₂ agonist, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 1.0–10.0 μM), and by the 5-HT₄ agonists, renzapride (1.0–10.0 μM) and 5-methoxytryptamine (1.0–10.0 μM); however, neither the 5-HT₁/5-HT₂ antagonists, spiperone, methysergide, and methiothepin, nor the 5-HT₄ antagonist, tropisetron (ICS 205–930; 10.0 μM), were able to inhibit the rise in cAMP evoked by these compounds or by 5-HT (0.1–10.0 μM). The 5-HT-evoked elevation of cAMP was antagonized by ketanserin (10.0 μM), which also blocked the effects of 5-methoxytryptamine and DOI, but not those of renzapride. The effective concentration of DOI, however, was higher than that needed for activation of 5-HT₂ receptors, and Northern analysis using a cDNA probe encoding the rat 5-HT₂ receptor failed to reveal the presence of 5-HT₂ mRNA in myenteric ganglia, although it hybridizes with mRNA of the right size in the guinea pig brain. Compounds that failed to change levels of cAMP or to antagonize the action of 5-HT included 8-hydroxy-di-n-propylamino tetralin, R58639, R88226, and sumatriptan. It is concluded that the receptor responsible for the 5-HT-induced rise in cAMP in ganglia isolated from the guinea pig myenteric plexus is not a known subtype of 5-HT receptor. Since the pharmacology of this novel receptor is different from that of the slow EPSP-like response to 5-HT, the receptor probably does not mediate the slow EPSP. © 1993 Wiley-Liss, Inc.     

The relationship between reproductive state and "sexually" dimorphic brain areas in sexually reproducing and parthenogenetic whiptail lizards

The anterior hypothalamus-preoptic area and ventromedial hypothalamus are sexually dimorphic in the reproductively active whiptail lizard Cnemidophorus inornatus. The anterior hypothalamus-preoptic area, which is involved in the control of male-typical copulatory behaviors, is larger in males, whereas the ventromedial hypothalamus, which is involved in the control of female-typical receptivity, is larger in females. In the parthenogenetic whiptail lizard C. uniparens, which is a direct descendant of C. inornatus and exhibits both male-like and female-like pseudosexual behaviors, both brain areas are comparable in size to those of female C. inornatus. This study was conducted to determine whether these brain areas change in size in either species or sex during a time of year when these animals are reproductively inactive, or after removal of the gonads. In male C. inornatus both brain areas changed during reproductive inactivity (either seasonally or surgically induced) and became equivalent to the size characteristic of reproductively active female C. inornatus. When corrected for brain size, the anterior hypothalamus-preoptic area was significantly smaller in intact hibernating and castrated males than in intact males from the summer breeding season. Conversely, the ventromedial hypothalamus was significantly larger in intact hibernating and castrated males than in intact males from the summer breeding season. The two brain areas were not significantly different among the groups of female C. inornatus or parthenogenetic C. uniparens. These results suggest that 1) the brain of whiptail lizards may differentiate seasonally and 2) the female state may be a neutral one to which the male brain reverts during reproductive inactivity.     

Walking after stroke. Measurement and recovery over the first 3 months

Sixty surviving patients had their walking ability and speed assessed regularly over the first 3 months after an acute stroke. Sixty-four matched controls were studied to allow categorisation of speed as 'slow' or 'normal'. Fourteen patients never had any significant loss of walking speed; fifteen patients never recovered the ability to walk and one patient remained dependent upon verbal support. Of the 30 showing significant recovery, only 10 regained normal speed, and 8 remained dependent upon a physical aid at 3 months. Plotting individual recovery curves of walking speed over time showed the wide range of change which may be expected. It is argued that timing of gait over 10 metres is a valid reliable measure that is currently underused.     

The contribution of optimism and quality of life to depression in an acute coronary syndrome population.

BACKGROUND: Numerous longitudinal studies have revealed that depression following an acute cardiac event poses a risk factor for poor cardiac outcomes. It is therefore important to identify modifiable predictors of depression in order to develop a variety of interventions with this population. AIMS: The aim of the present research was to determine whether the relationship between optimism and depressive symptoms was mediated by self-reported quality of life (QOL) in acute coronary syndrome patients. METHODS: Two weeks following hospital discharge (Time 1) 59 participants completed a self-report questionnaire. Four weeks later (Time 2), 49 of these participants completed the same questionnaire. RESULTS: At Time 1, the relationship between optimism and depressive symptoms was partially mediated by functional QOL and symptom QOL. Furthermore, the relationship between Time 1 optimism and Time 2 depressive symptoms was partially mediated by Time 1 functional QOL. When each of the Time 1 variables were used to predict Time 2 depressive symptoms, only optimism continued to predict depressive symptoms over and above the influence of Time 1 depressive symptoms and other covariates. CONCLUSION: These findings suggest the underlying importance of optimism in influencing depressive symptoms in acute coronary syndrome patients, and indicate that optimism and perceptions of functional QOL may be a possible rehabilitation target for this population.     

Neutropenic enterocolitis. Clinical diagnosis and treatment.

Review of the consultation records of the Gastrointestinal Surgical Oncology service at Roswell Park Memorial Institute from 1982 to 1987 revealed 22 patients with a clinical diagnosis of neutropenic enterocolitis. Ninety-one percent of the patients had hematologic malignancies, and 95% were receiving cytotoxic chemotherapy. Sixteen patients were treated nonsurgically; 11 died. Of those 11 cases, autopsies were performed in 9. At autopsy, the clinical diagnosis was confirmed in four cases; four cases were found to have normal intestinal tracts, and one case had a small bowel volvulus. In none of the four cases for which autopsy proved neutropenic enterocolitis was transmural bowel necrosis or perforation found. Laparotomy was performed in six patients; three survived. The clinical diagnosis was verified in four of the six patients. Neutropenic enterocolitis must be considered a diagnosis of exclusion. Care of these patients should be individualized. Nonoperative management with bowel rest, decompression, nutritional support, and broad spectrum antibiotics is recommended initially. Operative intervention is recommended for those with perforation or those whose condition deteriorates clinically during close, frequent observation.     

Effectiveness of two palliative support teams.

The palliative care of 227 consecutive patients by two support teams was measured according to 17 key indicators in the Support Team Assessment Schedule (STAS), an instrument previously developed and validated for use in these settings. Mean time in care was 71 days (range 1-547); 56 per cent of patients died at home, 26 per cent in hospital, 18 per cent in a hospice. Totalled ratings (sum of 15 items, excluding two items owing to missed ratings) improved in 83 per cent of cases, remained unchanged in 3 per cent and deteriorated in 13 per cent. The main problems which the STAS identified at referral were family anxiety, symptom control, patient anxiety and communication between patient and family. Fifteen of the 17 items showed significant improvements (Wilcoxon Z ranged from -3.18 to -8.20, p less than 0.00005) between referral ratings and ratings for the last week of the patient's life; family anxiety and spiritual needs did not. Patient anxiety and symptom control, although improved, also remained relatively severe at death. These results demonstrate the value of measuring key indicators and indicate areas where improvement in palliative care is needed.