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Biomedical subjects

D E Hernandez

Publications and source records attributed to D E Hernandez.

At least 19 recordsLinked to original sources
PubMed1993

Rôle of psychosomatic factors in peptic ulcer disease.

Evidence indicates that a link between peptic ulcer disease (PUD) and selected psychosomatic factors may exist. A series of 70 consecutive male and female adult patients were categorized by peptic symptoms and divided into four groups: a) controls; b) gastric ulcer (GU); c) duodenal ulcer (DU); and d) chronic non-ulcer dyspepsia (CNUD). All patients were interviewed and asked to answer a questionnaire that included demographics, medical history and the incidence of negative life events. A decreased level of activity was a predominant finding in GU, DU and CNUD patients. Family history of PUD may be correlated with CNUD. Of interest was the finding that DU and CNUD patients presented a higher incidence of negative life events when compared to the other study groups. Negative life events that produce considerable stress may predispose to peptic symptoms in certain patients.

Adult↗
PubMed1992

A model of inflammatory bowel disease induced by 2,4-dinitrofluorobenzene in previously sensitized BALB-c mice.

The aim of this study was to develop a model of inflammatory bowel disease (IBD) induced by colonic application of 2,4-dinitrofluorobenzene in previously sensitized BALB-c mice. During the follow-up period of 30 days we observed ulcerations, haemorrhage, necrosis, and mononuclear infiltration in the colonic mucosa of previously sensitized (experimental) and, to a lesser extent, nonsensitized (control) animals. In addition, the animals in the experimental group developed adhesions, thickening of colonic segments, stenosis, and dilatation of the colon, and some animals also developed megacolon. Oedema, mononuclear infiltration, and superficial ulcerations were observed in the ileum of experimental animals and, to a lesser extent, in the control group. In addition, the animals in the experimental group developed extraintestinal changes in the liver and spleen (that is, pericholangitis and lymphofollicular proliferation). We suggest that this model of IBD may have some value for the study of early pathogenetic mechanisms of IBD and for developing new therapeutic modalities for this condition.

Animals↗
PubMed1990

Imipramine prevents gastric lesions induced by centrally administered thyrotropin-releasing hormone (TRH) in rats.

Increasing evidence indicates that thyrotropin-releasing hormone (TRH), and endogenous brain-gut peptide may play a role in experimental ulcerogenesis. Potential interactions between TRH and imipramine (a typical tricyclic antidepressant (TCA] on the development of TRH-induced gastric lesions have not been investigated. Imipramine (0.05, 0.5 and 5 mg/kg, i.p.) dose-dependently inhibited gastric lesion formation induced by intracisternal (i.c.) administration of TRH (1 micrograms). In addition, imipramine (5 mg/kg, i.p.) significantly decreased gastric acid secretion in response to i.c. TRH (1 microgram) in rats with pyloric ligation. These findings suggest the TCAs may be effective drug agents against centrally initiated gastric ulcerations. The mechanism of this response probably involves blockade of cholinergic (muscarinic) and H2 histamine receptors.

Animals↗
PubMed1990

Evidence for a role of brain thyrotropin-releasing hormone (TRH) on stress gastric lesion formation in rats.

Specific polyclonal antibodies raised against synthetic thyrotropin-releasing hormone (TRH) infused intracerebroventricularly (ICV) significantly decreased gastric lesions induced by cold restraint stress. The antiulcer effect of immunologic blockade of brain TRH was specific. Normal rabbit serum or antibodies raised against somatostatin, alpha-MSH, Leu-enkephalin, gonadotropin-releasing hormone and atrial natriuretic factor were ineffective. These findings suggest that brain TRH may play an important role in experimental stress ulcer formation.

Animals↗
PubMed1990

Administration of thyrotropin-releasing hormone into the central nucleus of the amygdala induces gastric lesions in rats.

Studies utilizing microinjections of thyrotropin-releasing hormone (TRH) were performed to determine potentially sensitive limbic brain sites to the ulcerogenic effect of TRH. Administration of TRH into the central nucleus of the amygdala (CEA) produced a high (80%) incidence of gastric lesions and also significantly stimulated acid secretion. Microinjections of TRH into other brain sites including superior colliculus, medial septum, substantia nigra and the hippocampus (CA1 area) were ineffective. Intra-CEA TRH-induced gastric lesions and acid secretion were prevented by vagotomy. These results indicate that the amygdala is of importance for mediating the ulcerogenic effect of brain TRH through peripheral vagal pathways.

Amygdala↗
PubMed1990

Brain ACTH prevents stress gastric lesions in rats.

This study evaluated the effect of ACTH and several ACTH fragments on the development of gastric glandular lesions induced by cold-restraint stress in rats. Intracerebroventricular administration of ACTH1-39 dose-dependently (0.1-10 micrograms) inhibited stress gastric lesion formation. Studies with smaller molecular weight forms of ACTH (in a dose equimolar to 10 micrograms of ACTH1-39) revealed that ACTH1-13 and ACTH1-10 were also protective. The ACTH fragments ACTH5-10, ACTH34-39 and ACTH1-17 were without effect. Immunoneutralization of endogenous brain ACTH1-39 significantly increased stress gastric lesion severity. Antisera raised against synthetic somatostatin, gonadotropin-releasing hormone, and L-enkephalin were ineffective. These results with ACTH coupled with our previous demonstration of a protective effect of beta-endorphin suggest that specific brain pro-opiomelanocortin gene products modulate gastric mucosal integrity in response to stress.

Adrenocorticotropic Hormone↗
PubMed1990

Inhibition of neurotensin-induced miosis by blockade of ocular dopamine pathways.

In previous work we have determined that intracameral (IC) administration of neurotensin (NT) produces strong miosis in rabbits. However, the pharmacological mechanism of this response remains undetermined. Blockade of alpha and beta-adrenoceptor subtypes with phenoxybenzamine and propranolol, blockade of M1 muscarinic receptors with atropine or blockade of mu opioid receptors with naloxone did not affect NT-induced miosis. Of interest however was the observation that destruction of ocular dopamine (DA) nerve endings with 6-hydroxydopamine (6-OHDA) + desmethylimipramine (DMI), or blockade of D-2 DA receptors with haloperidol significantly inhibited the miotic response to IC NT. These findings indicate that an intact iridic DA pathway is required for the expression of NT-induced miosis.

Animals↗
PubMed1989

Imipramine prevents stress gastric glandular lesions in rats.

Intraperitoneal (i.p.) administration of imipramine dose-dependently inhibited gastric lesions induced by 3 h of cold restraint stress. The high dose of imipramine (5 mg/kg) almost completely abolished gastric lesion formation, and also suppressed acid secretion in rats with pyloric ligation. Intracisternal imipramine (1 microgram) was also protective. These findings suggest that tricyclic antidepressants may play an important role in preventing the deleterious effects of stress on the gut.

Analysis of Variance↗
PubMed1989

Immunohistochemical demonstration of neurotensin and tyrosine hydroxylase in iris nerves of the rabbit eye.

In previous studies we have provided evidence that intracameral administration of neurotensin (NT), an endogenous tridecapeptide, produces strong miosis in the rabbit. The presence of NT immunoreactivity was investigated in rabbit iris whole mounts by light microscopic immunohistochemistry, and its distribution in the iris compared to that, of tyrosine hydroxylase (TH). A few scattered NT-positive cell bodies were localized in the dilator muscle. Both, the NT cell bodies and processes appeared parallel to the muscle cells. Extensive branching of NT-containing cell processes was observed in connection with the sphincter muscle. These NT-positive fibers formed a dense, randomly oriented network throughout the sphincter muscle cells. The distribution of TH immunoreactivity was similar to that of NT-positive cell processes, except that no TH-positive cell bodies were detected in any of the iris structures examined. Moderate branching of TH-positive fibers was observed in the dilator and sphincter iris muscles. These findings provide neuroanatomical support for an important role of NT in pupillary physiology. Its similar topographical distribution with TH suggests that NT and dopamine may be co-localized, as it has already been described in brain.

Animals↗
PubMed1989

Increased dopamine receptor binding in duodenal mucosa of duodenal ulcer patients.

High-affinity and saturable membrane-bound dopamine binding sites have been characterized in rat and human gastrointestinal tissues. Although their role in experimental ulcerogenesis has been suggested, dopamine receptor activity in peptic ulcer disease has not been investigated. Radioligand binding studies were performed with mucosal tissue homogenates obtained from the antrum and duodenum of six male healthy volunteers and six male duodenal ulcer patients. The binding assay was performed in triplicate with a crude membrane fraction using [3H]dopamine as a ligand at a final concentration of 1 nM at 22 degrees C in the dark. Nonspecific binding (which usually comprised about 30% of total binding) was determined in the presence of a 100-fold excess of unlabeled dopamine. A significant (P less than 0.05) increase of [3H]dopamine binding was found in duodenal mucosa of duodenal ulcer patients. [3H]Dopamine binding in stomach (antrum) of normal and duodenal ulcer patients did not differ significantly. These findings provide preliminary evidence for a role of dopamine receptors in duodenal ulcer and suggest that biochemical abnormalities of gut dopamine function may be operative in the pathogenesis of peptic ulcer disease.

Binding Sites↗
PubMed1989

Neurobiology of brain-gut interactions. Implications for ulcer disease.

Clinical and laboratory evidence indicates that the brain exerts major control on the gastrointestinal tract. Specific brain loci and circuits that send efferent viscerotropic projections to the gut have been described. A variety of aminergic and peptidergic neurotransmitters have been shown to occur along these cerebrogastrointestinal pathways and to influence motor and secretory functions of the gut. Some of the newly identified peptides have been shown to influence the development of gastroduodenal ulcers. Findings with thyrotropin-releasing hormone (TRH) indicate that this endogenous tripeptide induces a full spectrum of gut effects, prominent among which is production of gastric ulcers. By contrast, other peptides including beta-endorphin, neurotensin, and bombesin induce gut effects opposite to those of TRH, namely, inhibition of gastric acid and motility and prevention of experimental ulcers. These laboratory findings suggest that ulcer disease may represent a brain-driven event, which may be the result of a neurochemical imbalance within the brain. Further neurobiological research will generate additional data on brain-gut interactions and will probably disclose new information to explain certain functional and organic disorders of the gut.

Animals↗
PubMed1989

Effect of dopamine on amylase secretion from guinea pig pancreatic acinar cells in vitro.

Dopamine has been shown to effect pancreatic flow, protein output and amylase secretion in a variety of species. However, there is conflicting evidence regarding the role of dopamine on amylase release in vitro. Specific studies were conducted to evaluate the effect of dopamine and to compare its effects with other substances on basal- and secretagogue-stimulated amylase secretion in a guinea pig dispersed pancreatic acinar cells preparation. Dopamine (10(-6) M) induced a small, but significant (P less than 0.05) increase of amylase secretion. Established secretagogues (10(-6) M) including bombesin, cholecystokinin-octapeptide (CCK-8) and carbachol as anticipated induced significantly larger responses. Other substances tested (10(-6) M) including thyrotropin-releasing hormone (TRH) and muscimol were without effect. Complete dose-response studies (10(-11)-10(-3) M) in the presence of bombesin, CCK-8 and carbachol revealed that dopamine does not affect amylase release in response to these secretagogues. These findings suggest that dopamine is a weak stimulant of amylase secretion in vitro, and that it may therefore play a minor role in regulation of pancreatic enzyme secretion. Several factors including vascular, hormonal and neural have been implicated in regulation of pancreatic exocrine secretion. In particular, autonomic nervous system activity, notably cholinergic, has been shown to affect the secretory status of the pancreatic acinar cell. In addition, several biologically active peptides including bombesin, cholecystokinin (CCK), secretin, vasoactive intestinal peptide (VIP), substance P, gastrin and stimulation of cholinergic (muscarinic) receptors with carbachol have been shown to stimulate pancreatic enzyme secretion both in vivo and in vitro. Certain controversy regarding the role of the sympathetic nervous system in regulation of pancreatic exocrine secretion does exist. For example, several studies with agonists and antagonists of noradrenergic and dopaminergic receptor subtypes suggest a stimulatory effect on pancreatic fluid, electrolyte and enzyme secretion. However, these responses are species-specific and variations inherent to the model have been described. Dopamine administration has been shown to stimulate pancreatic bicarbonate and enzyme secretion in a variety of species including mice, dogs, and man. Radioligand binding studies with 3H-dopamine have revealed the presence of high- and low-affinity dopamine binding sites in dog pancreatic acinar cells. Stimulation of these receptors has been correlated with dose-dependent increases in intracellular cAMP levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Amylases↗
PubMed1988

Thyrotropin-releasing hormone: medullary site of action to induce gastric ulcers and stimulate acid secretion.

This study evaluated the hypothesis that the dorsal motor nucleus (DMN) of the brainstem may mediate the ulcerogenic and acid-stimulatory effects of thyrotropin-releasing hormone (TRH) in rats. To accomplish this, intra-DMN microinjections of TRH (50 and 500 ng) were performed and their effects on acid secretion and gastric ulcer formation evaluated in the pylorus-ligation model. The high (500 ng), but not the low dose of TRH (50 ng) produced gastric glandular lesions in 64% of the rats with a mean severity index (no. of ulcers/rat) of 6.4 +/- 0.98 and significantly increased gastric acid output. The ulcerogenic and gastric secretory response to intra-DMN TRH was site-specific. We conclude that presynaptic TRH fibers may modulate vagal activity at the level of the DMN and propose that descending TRH pathways may play a role in experimental ulcerogenesis through acid hypersecretion.

Animals↗
PubMed1988

Influence of thyroid states on stress gastric ulcer formation.

Thyroid hormones exert a critical developmental and regulatory role on the morphology and biochemistry of gastrointestinal mucosal cells. However, the relationship between thyroid function and stress gastric lesion formation remains undetermined. This study was designed to test the hypothesis that thyroid states may affect the acute development of gastric lesions induced by cold-restraint stress. Normal (euthyroid), hyperthyroid (200 micrograms of T4 i.p. x 7 days) and hypothyroid (thyroidectomized) rats were used. Gastric lesion incidence and severity was significantly (p less than 0.05) increased in hypothyroid rats, whereas in contrast hyperthyroid rats developed significantly less gastric lesions. As anticipated, plasma levels of thyroxin (T4) were significantly (p less than 0.01) elevated in hyperthyroid rats, and undetectable in hypothyroid rats. Acute pretreatment with i.p. cimetidine (100 mg/Kg), but not T4 (200 micrograms/Kg) 1 h prior to stress completely prevented gastric lesions formation in hypothyroid rats. Finally, binding of 3H-dihydroalprenolol to beta-adrenergic receptors on brain membranes prepared from frontal cortex was reduced by 20% in hypothyroid rats after 3 h of stress. These and other data contained herein suggest that thyroid hormones contribute to modulate the responsiveness of the gastric mucosa to stress. The increased rate of ulcerogenesis observed in hypothyroid rats appears to be mediated by gastric acid secretion. The central mechanism of this response may involve decreased brain nonadrenergic receptor function.

Animals↗
PubMed1987

Dopamine receptors in human gastrointestinal mucosa.

Dopamine is a putative enteric neurotransmitter that has been implicated in exocrine secretory and motility functions of the gastrointestinal tract of several mammalian species including man. This study was designed to determine the presence of dopamine binding sites in human gastric and duodenal mucosa and to describe certain biochemical characteristics of these enteric receptor sites. The binding assay was performed in triplicate with tissue homogenates obtained from healthy volunteers of both sexes using 3H-dopamine as a ligand. The extent of nonspecific binding was determined in the presence of a 100-fold excess of unlabeled dopamine. Scatchard analysis performed with increasing concentrations of 3H-dopamine (20-500 nM) revealed a single class of saturable dopamine binding sites in gastric and duodenal mucosa. Binding parameters obtained from the regression lines of the Scatchard plots of gastric mucosa of males were Bmax = 73.4 +/- 4.0 pmoles/mg protein; KD = 154 +/- 20 nM and Bmax = 95 +/- 13.6 pmoles/mg protein and KD = 826 +/- 200 nM in females. In duodenal mucosa of males these parameters were Bmax = 63.9 +/- 15.9 pmoles/protein; KD = 235 +/- 53 nM and Bmax = 83.2 +/- 19.4 pmoles/mg protein; KD = 568 +/- 104 nM in females. The results of this report demonstrate the presence of specific dopamine receptors in human gastric and duodenal mucosa. These biochemical data suggest that molecular abnormalities of these receptor sites may be operative in the pathogenesis of important gastrointestinal disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Dopamine↗
PubMed1987

Brain vasoactive intestinal peptide: a potent stimulant of gastric acid secretion.

Vasoactive intestinal peptide (VIP) belongs to a rapidly expanding family of cerebrogastrointestinal oligopeptides. This report describes a potent dose-, time- and vagus-dependent stimulation of gastric acid secretion by brain VIP. Physiologic evidence favoring a role of VIP on acid secretion was provided by the finding that immunoneutralization of endogenous brain VIP produced a significant decrease of acid secretion. These and other data contained herein suggest that the mechanism by which central VIP stimulates acid secretion appears to involve peripheral cholinergic pathways.

Animals↗