Sumatriptan is an agonist at 5-HT1P receptors on myenteric neurones in the guinea-pig gastric antrum

Sumatriptan, a 5-hydroxytryptamine(1D) (5-HT(1D))-receptor agonist used in the treatment in migraine, inhibits gastric motility via the enteric nervous system. As no studies have reported enteric neuronal 5-HT(1D) receptors, we used conventional intracellular recordings to characterize the actions of sumatriptan on 145 guinea-pig antral myenteric neurones. In 24 of 29 neurones with a 5-HT(1P) receptor-mediated depolarizing response to 5-HT, application of sumatriptan caused a dose-dependent depolarization, accompanied by increased membrane resistance and enhanced excitability. Depolarizing responses to sumatriptan occurred both in cholinergic and in nitrergic neurones. Sumatriptan did not mimic the 5-HT(3) receptor-mediated fast-depolarizing responses or 5-HT(1A) receptor-mediated inhibitory responses to 5-HT. Sumatriptan had no effect on neurones not responding to 5-HT. The depolarizing response to sumatriptan was inhibited by renzapride, but not by 5-HT(1-7) receptor antagonists. We conclude that sumatriptan behaves as an agonist at the 5-HT(1P) receptor on myenteric neurones in the guinea-pig gastric antrum. The actions of sumatriptan on gastric motility seem to be attributable to a direct action on enteric neurones.     

ATP-dependent paracrine communication between enteric neurons and glia in a primary cell culture derived from embryonic mice

Abstract  The importance of dynamic interactions between glia and neurons is increasingly recognized, both in the central and enteric nervous system. However, apart from their protective role, little is known about enteric neuro–glia interaction. The aim was to investigate neuro–glia intercellular communication in a mouse culture model using optical techniques. Complete embryonic (E13) guts were enzymatically dissociated, seeded on coverslips and studied with immunohistochemistry and Ca²⁺-imaging. Putative progenitor-like cells (expressing both PGP9.5 and S-100) differentiated over approximately 5 days into glia or neurons expressing typical cell-specific markers. The glia–neuron ratio could be manipulated by specific supplements (N2, G5). Neurons and glia were functionally identified both by their Ca²⁺-response to either depolarization (high K⁺) or lysophosphatidic acid and by the expression of typical markers. Neurons responded to ACh, DMPP, 5-HT, ATP and electrical stimulation, while glia responded to ATP and ADPβs. Inhibition of glial responses by MRS2179 suggests involvement of P2Y1 receptors. Neuronal stimulation also caused delayed glial responses, which were reduced by suramin and by exogenous apyrases that catalyse nucleotide breakdown. Conversely, glial responses were enhanced by ARL-67156, an ecto-ATPase inhibitor. In this mouse enteric co-culture, functional glia and neurons can be easily monitored using optical techniques. Glial cells can be activated directly by ATP or ADPβs. Activation of neuronal cells (DMPP, K⁺) causes secondary responses in glial cells, which can be modulated by tuning ATP and ADP breakdown. This strongly supports the involvement of paracrine purinergic communication between enteric neurons and glia.     

Use of computerized cell image analysis to characterize cell nucleus populations from normal and neoplastic renal tissues

We studied 55 renal tissue samples from 16 patients corresponding to normal (19 samples, group 1), low-grade (18 samples, group 2), and high-grade (18 samples, group 3) tumoral tissues. For this purpose, we used digital cell image analysis (the SAMBA 200 processor) to describe the morphonuclear patterns of Feulgen-stained nuclei from the 3 above-mentioned groups. Our results show that nuclear DNA ploidy is positively correlated with histopathological differentiation, which is also positively correlated with an increase in nuclear DNA heterogeneity. Morphometric and textural parameters computed on such Feulgen-stained nuclei make it possible to describe the typical morphonuclear patterns of normal, low-grade, and high-grade neoplastic renal tissues. Using multiparametric, i.e. principal-component and canonical analyses, we set up preliminary morphonuclear data banks that we used to assess the diagnosis of 6 ungraded samples. We expect that this kind of morphonuclear data banks might be helpful, on one hand, to select specific morphonuclear parameters related to patient survival, and on the other hand to establish the cytological diagnosis of deep fine-needle aspiration material, sonographically assisted, on suspicious kidneys. Such hypotheses are now under further study.     

Characterization of myenteric neuropathy in the jejunum of spontaneously diabetic BB-rats

Abstract  Decreased gastric expression and function of neuronal nitric oxide synthase (nNOS) has been proposed as a potential mechanism underlying diabetic gastroparesis. As gastric nNOS expression is vagally controlled, these changes might occur secondarily to vagal neuropathy. In addition, it is unclear whether other inhibitory neurotransmitters are also involved. We used the type 1 diabetic BioBreeding (BB)-rat model to study jejunal motor control and nNOS expression, which is independent of the vagus. Jejunal segments were used for in vitro contractility studies, and measurement of nNOS expression after 8 or 16 weeks of diabetes compared with age- and sex-matched controls. Unlike electrical field stimulation and acetylcholine (ACh)-induced contractions, non-adrenergic non-cholinergic (NANC) relaxations were significantly reduced in diabetic rats. In contrast to control rats, NANC relaxations in diabetic rats were N _ω-nitro- l -arginine methyl ester ( l -NAME) insensitive. Jejunal nNOS expression was significantly decreased in diabetic rats. Both in diabetic and in control animals, l -NAME resistant relaxations were sensitive to P₂-receptor antagonists. In the jejunum of spontaneously diabetic rats, decreased nitric oxide responsiveness and decreased nNOS protein expression occur while purinergic transmission is unaffected. These findings indicate that nitrergic enteric neuropathy may be a primary dysfunction in diabetes, independent from vagal dysfunction.     

Adolescent physical performance and adult physical activity in Flemish males

Limited information is available about the associations between adolescent fitness levels and adult physical activity. In the present study, these associations are investigated using different indicators of physical activity. It is hypothesized that both health‐ and performance‐related fitness characteristics, observed during the adolescent period, contribute equally to the explained variance in adult physical activity levels. Subjects were 109 Flemish males followed over a period of 27 years from 13 to 40 years of age in the Leuven Longitudinal Study on Lifestyle Fitness and Health. Performance and health‐related fitness characteristics were observed during the growth period and at 40 years of age. The Work Index, Leisure Time Index, and Sport Index of the Baecke questionnaire were used as indicators of physical activity together with triaxial accelerometry. Multiple regression and discriminant analyses contrasting extreme quintiles of activity groupings were used to analyse the associations. Only the Baecke Sport Index showed consistent significant associations (R² = 0.03 to R² = 0.23) with adolescent fitness levels observed at 13, 15, and 18 years. When upper and lower quintiles were contrasted, fitness characteristics observed at the three age levels during adolescence were significantly different for each of the three indices of the Baecke questionnaire at 40 years of age. Lowest associations (R² = 0.09 to R² = 0.17) were found for the Work Index, followed by the Leisure Time Index (R² = 0.12 to R² = 0.28) and Sport Index (R² = 0.25 to R² = 0.43). Highest associations were evident for the 18‐ to 40‐year interval. Performance‐ and health‐related fitness characteristics explain equally well the variance in physical activity indicators. Am. J. Hum. Biol. 13:173–179, 2001. © 2001 Wiley‐Liss, Inc.     

Bevacizumab reverses need for liver transplantation in hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by mucocutaneous and visceral telangiectasia. Hepatic involvement with vascular malformations may lead to portal hypertension, biliary ischemia, and high-output cardiac failure. Liver transplantation is indicated for life-threatening disease but carries significant risk from surgery and chronic immunosuppression. We report a case of a 47-year-old woman with HHT successfully treated with the vascular endothelial growth factor (VEGF) antibody bevacizumab. The patient was referred for consideration of liver transplantation because of hepatic HHT leading to high-output cardiac failure, diuretic resistant ascites, cholestasis, and malnutrition. As she was considered a high-risk candidate for transplantation, she underwent 6 courses of bevacizumab (5 mg/kg) over 12 weeks. A dramatic improvement in her clinical state was observed after 3 months with reversal of cholestasis, resolution of cardiac failure and ascites, and improvement in nutritional status with a 10% dry weight increase. Treatment induced a marked reduction in liver vascularity and halving of her liver volume from 4807 to 2269 mL over 6 months. This was associated with normalization of her cardiac output from 10.2 to 5.1 L/minute. Correspondingly, she ceased diuretic medications, returned to full-time work, and was delisted as a transplant candidate. She remains well 6 months after completing treatment. In conclusion, antagonism of VEGF receptors led to a dramatic regression of hepatic vascular malformations and reversal of high-output cardiac failure and complications of portal hypertension in this patient with HHT. Bevacizumab may potentially alleviate the need for liver transplantation in this group of patients.     

Palliative inpatients in general hospitals: a one day observational study in Belgium

Background  

Hospital care plays a major role at the end-of-life. But little is known about the overall size and characteristics of the palliative inpatient population. The aim of our study was to analyse these aspects.     

MR findings in cardiac amyloidosis

OBJECTIVE: The objective of our study was to describe a combination of features on MRI specific to cardiac amyloidosis. CONCLUSION: Cardiac amyloidosis is a common cause of infiltrative heart disease. The combination of subtle widespread heterogeneous myocardial enhancement on delayed postcontrast inversion recovery T1-weighted images, which may initially be dismissed as a technical error, with ancillary features of restrictive cardiac disease is highly suggestive of cardiac amyloidosis.