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Biomedical subjects

R De Giorgio

Publications and source records attributed to R De Giorgio.

At least 91 records · Page 5Linked to original sources

Differential effects of experimentally induced chronic pancreatitis on neuropeptide immunoreactivities in the feline pancreas.

The distribution and concentration of calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and gastrin-releasing peptide (GRP) immunoreactivities in the pancreas of cats with experimentally induced chronic pancreatitis and of age- and sex-matched controls were investigated. By narrowing the main pancreatic duct between the head and the body to approximately 25% of its normal diameter, we induced within 5 weeks chronic pancreatitis restricted to the body and tail. In control animals, peptide immunoreactive nerves were distributed to the islets, acini, and ducts; the latter were predominantly innervated by fibers immunoreactive for NPY, VIP, or CGRP. The vasculature received an abundant supply of NPY-, CGRP-, and, to a lesser extent, SP-containing axons. Within intrapancreatic ganglia, peptide immunoreactivities were identified in fibers and ganglion cells, with the exception of CGRP and SP immunostaining, which could be visualized only in fibers. In animals with chronic pancreatitis, the innervation pattern of each peptidergic system was comparable to that described in controls. However, there was a remarkable increase in the density and staining intensity of VIP and NPY immunoreactive fibers in the exocrine parenchyma and fibrous septa of the body and tail, where chronic pancreatitis developed. Fibers immunoreactive for CGRP and SP also were moderately denser than in controls, whereas those containing GRP immunoreactivity did not show any detectable changes. In addition, a marked increase of the immunostaining for VIP and, to a much lesser extent, for NPY and GRP, was observed in neurites supplying the head of the pancreas, which appeared devoid of histologically detectable pathological alterations. Radioimmunoassay analysis confirmed the immunohistochemical observations. The increased density of distinct peptidergic nerves in the pancreas with induced chronic pancreatitis might be the result of compensatory phenomena in response to the inflammatory process.

Animals↗

Calcitonin gene-related peptide neurons innervating the canine digestive system.

The pattern of nerve cells and fibers containing calcitonin gene-related peptide immunoreactivity (CGRP-IR) was investigated in the canine digestive tract by means of immunohistochemistry. CGRP-IR nerve fibers innervate all the layers of the gut, including the vasculature, with different densities depending on the region. CGRP-IR processes are sparse in the esophagus and stomach, where they are mostly confined to the enteric plexuses and vasculature. CGRP-IR fibers are quite abundant in the small and large intestine, where they form dense arborizations in the mucosa, and are numerous in the muscularis mucosae, deep muscular plexus and circular muscle. The myenteric and submucous plexuses of the intestine contain dense networks of CGRP-IR fibers and numerous CGRP-IR ganglion cells. On the other hand, in the enteric ganglia of the esophagus and stomach, in the intrapancreatic ganglia and in the ganglionated plexus of the gallbladder, CGRP-IR is restricted to non-varicose processes. A moderate density of CGRP-IR fibers supplies the endocrine and exocrine pancreas, and the fibromuscular layer and lamina propria of the gallbladder. The density of CGRP innervation in different regions can be summarized as follows: intestine >> pancreas and gallbladder > or = antrum > cardia > gastric corpus and distal esophagus. CGRP- and tachykinin (TK)-IRs are colocalized in a substantial population of fibers, particularly those distributed to the mucosa, muscularis mucosae and vasculature, whereas there was no evidence of colocalization in intrinsic ganglion cells. The present results suggest that (1) the CGRP innervation of the dog digestive system includes an intrinsic and an extrinsic component, and (2) CGRP- and TK-IRs are co-expressed in extrinsic nerve fibers. These findings extend previous observations in rats and guinea pigs and provide insights into the sites of action of CGRP in the digestive system of the dog, which has served as a model for CGRP functional studies.

Animals↗

Species differences in the immunoreactive patterns of calcitonin gene-related peptide in the pancreas.

In the pancreas, calcitonin gene-related peptide (CGRP) immunoreactivity has been described in nerve fibers and in distinct types of islet cells. This unique, apparently species-specific cell-type expression prompted the present investigation to clarify further the pattern of CGRP immunoreactivity in different mammalian species (i.e., different strains of rats, mice, guinea pigs, rabbits, cats, dogs, pigs, and humans) commonly used for functional and anatomical studies of the pancreas by means of immunohistochemistry using three different CGRP antibodies. In each species, CGRP-immunoreactive neurites innervate the exocrine and endocrine compartments, the vasculature, and the intrapancreatic ganglia, where they form dense networks encircling unstained cell bodies. The only exception is the pig pancreas, where the islets appear to be devoid of immunoreactive fibers. The overall density of immunoreactive pancreatic axons in different species is as follows: rat, mouse, and rabbit greater than guinea pig greater than or equal to pig and cat much greater than dog and human. CGRP-immunoreactive endocrine cells appear to be restricted to the rat pancreas, where they form a subpopulation of somatostatin-containing D cells. In contrast, in mouse, guinea pig, cat, dog, and human pancreas, a homogeneous staining of the core of the islets, where insulin-producing B cells are located, was visualized in sections incubated with the rabbit CGRP antiserum at 4 degrees C, but not at 37 degrees C (an incubation temperature that does not affect the islet cell staining in the rat nor the fiber labeling in any species). Furthermore, the staining of islet B cells was not reproducible with all the CGRP antibodies used, all of which comparably stain nerve fibers in each species, and islet D cells in the rat. Immunoreactive islet cells were not visualized in pig and rabbit pancreas. These results are consistent with the hypothesis that the expression of CGRP in nerve fibers is a common feature of mammalian pancreas, whereas its expression in endocrine cells appears to be restricted to the D cells of the rat pancreas.

Animals↗

Uremia increases gastric mucosal permeability and acid back-diffusion injury in the rat.

The possibility that chronic uremia renders the gastric mucosa more susceptible to acid injury was investigated. A rat model of chronic renal failure was induced by subtotal nephrectomy. [H+] back-diffusion across the mucosa, following intragastric perfusion of 0.15N HCl or 15% ethanol in 0.15N HCl, was significantly greater in uremic than in sham-operated rats. Gastric mucous gel thickness and transmural potential difference were significantly lower in rats with renal insufficiency. Furthermore, a significantly greater acidification rate of the surface epithelial cells was found in uremic rats than in sham-operated rats during superfusion with pH 1.7 buffer. Intragastric administration of acidified ethanol or aspirin solutions markedly increased gastric mucosal blood flow (68% and 89% respectively) in the sham-operated group producing mild injury, in contrast to uremic rats, where a lesser increase in mucosal blood flow (7% and 14% respectively) was associated with more pronounced mucosal injury. It was concluded that enhanced susceptibility to acid injury in uremia is due to a reduction of function of pre-epithelial, epithelial, and postepithelial elements of the gastric mucosal barrier.

Animals↗

Pancreatic exocrine carcinoma producing adrenocorticotropic hormone.

A rare case of pancreatic exocrine carcinoma with an endocrine component secreting adrenocorticotropic hormone (ACTH) is reported and discussed in relation to other cases previously published. The patient initially presented with a severe form of diabetes, which was treated accordingly. Persistence of hyperglycemia, along with other metabolic alterations and marked hypokalemia, led to the suggestion of abnormal ACTH secretion. In this patient, however, a florid Cushing's syndrome was not observed. The patient also developed hematological alterations, mainly leukopenia and thrombocytopenia, whose origins were unclear. At autopsy, a poorly-defined mass was discovered between the body and tail of the pancreas. Standard histology showed a moderately-differentiated adenocarcinoma. Immunohistochemical analysis of the tumor specimen demonstrated the presence of some neoplastic cells immunoreactive for chromogranin A, neuron-specific enolase and ACTH. These findings are consistent with the existence of an endocrine component within the exocrine carcinoma with ACTH differentiation.

ACTH Syndrome, Ectopic↗

Patterns of innervation of vasoactive intestinal polypeptide, neuropeptide Y, and gastrin-releasing peptide immunoreactive nerves in the feline pancreas.

In this study, we performed a detailed analysis of the immunoreactive (IR) patterns and tissue distribution of vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and gastrin-releasing peptide (GRP) in the feline pancreas by means of immunohistochemical and radioimmunological techniques. Immunoreactivity for each peptide is localized to varicose nerve fibers distributed throughout the exocrine and endocrine pancreas, with some differences in the density and pattern of fiber distribution. In the acinar and stromal compartments, VIP-IR processes have a higher density than NPY- and GRP-containing fibers, the latter being the least abundant. The vasculature receives a particularly prominent NPY innervation, while GRP- and VIP-IR fibers are found occasionally in association with blood vessels. Around ducts, NPY- and VIP-IR nerves are more numerous than those positive for GRP-IR, which are quite sparse. One of the most interesting findings of the present work is the visualization of all peptide-IRs both in neuronal cell bodies and fibers within the intrapancreatic ganglia. VIP-IR is observed in virtually all ganglion cells, while GRP- and NPY-IRs are seen in a few neuronal cells. VIP and NPY tissue levels are much higher than GRP concentrations in all regions of the pancreas. VIP content in the head and body is greater than in the tail. The morphological relationship of VIP-, NPY-, and GRP-IR fibers with different pancreatic structures is consistent with specific peptidergic neural inputs in the regulation of pancreatic functions.

Animals↗

Reversibility of gastrointestinal motor abnormalities in chronic intestinal pseudo-obstruction.

A 43-year-old man with chronic intestinal pseudo-obstruction is presented. He had undergone two laparotomies in an attempt to eliminate the cause of repeated episodes suggestive of obstruction. Gastrointestinal manometry showed severe abnormalities compatible with the diagnosis of chronic intestinal pseudo-obstruction. Laboratory tests indicated the presence of intestinal malabsorption and villous atrophy. A gluten-free diet accompanied by 10 days of treatment with tetracycline and 2 short periods of treatment with cisapride led to gradual, but apparently complete, resolution of the pseudo-obstructive syndrome. Repeated manometric studies showed progressive normalization of both the fasting and postprandial upper gastrointestinal motor pattern.

Adult↗

Primary non-Hodgkin's T-cell lymphoma of the esophagus. A case with peculiar endoscopic ultrasonographic pattern.

We report a case of primary esophageal non-Hodgkin's T-cell lymphoma in a young white female. At admission, endoscopy revealed large, irregularly shaped, esophageal ulcerations with super imposed candidiasis. Endoscopic ultrasonography to assess submucosal alterations and periesophageal involvement revealed a diffuse hypoechogenic thickening (up to 5 mm) of the esophageal wall, a pattern consistent with lymphomatous infiltration. Definitive diagnosis was made with the aid of histology and immunohistochemistry.

Adolescent↗

Tissue distribution and innervation pattern of peptide immunoreactivities in the rat pancreas.

The distribution of calcitonin gene-related peptide (CGRP), substance P/tachykinin (SP/TK), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) and gastrin-releasing peptide (GRP) immunreactivities (IR) in the rat pancreas was investigated using radioimmunoassay and immunohistochemistry. CGRP, NPY and VIP tissue contents are much higher than GRP and SP/TK concentrations. Peptide-containing nerves are distributed to both the exocrine and endocrine pancreas. However, differences exist in terms of density and targets of innervation for each peptidergic system. In the acini and through the stroma, fibers IR for CGRP, NPY and VIP are greater than GRP- and SP/TK-containing processes. The vasculature is supplied by a prominent NPY, CGRP and, to a lesser extent, SP/TK innervation. VIP-IR is found occasionally, and GRP-IR is never detected, in fibers associated with blood vessels. Around ducts, CGRP- and NPY-positive neurites are greater than SP/TK- greater than or equal to VIP-IR fibers, whereas GRP-containing nerves are not visualized. In the islets, the density of peptidergic nerves is: VIP-, GRP- greater than or equal to CGRP-IR greater than NPY or SP/TK. In intrapancreatic ganglia. VIP- and, to a lesser extent, NPY-IRs are found in numerous neuronal cell bodies and in nerve fibers; GRP-IR is present in numerous nerve processes and in few cell bodies; CGRP- and SP/TK-IRs are detected only in fibers wrapping around unlabeled ganglion cells. The majority of CGRP-IR fibers contain SP/TK-IR. The existence of differential patterns of peptidergic nerves suggests that peptides exert their effects on pancreatic functions via different pathways.

Animals↗

Clinical use of manometry for the diagnosis of intestinal motor abnormalities.

Digestive symptoms suggestive of intestinal motor disorders, such as abdominal pain and distension, fullness, vomiting, constipation and diarrhoea, are very common and non-specific, and may be clinical manifestations of both organic and functional diseases. Both radiology and endoscopy are important in the diagnosis of structural gastrointestinal lesions that can affect motility and offer indirect signs of impaired gastrointestinal functions, but the diagnosis of gut motility disorders currently relies on the manometric assessment of contractile activities. Small bowel manometry helps to identify normal motility features and consequently to identify abnormal motor patterns. Small bowel manometry can help to differentiate mechanical obstruction from pseudo-obstruction and neurogenic from myogenic motor disorders. Manometry is an invasive technique which is not well accepted by patients and requires specific skills from investigators. Also, manometric assessment is limited to referral centres with a specific interest in the field of digestive functions, in general, and motility, in particular. Only patients who remain undiagnosed after extensive traditional work-up and fail repeated courses with medical therapy should be referred for the manometric test. Understanding the underlying pathophysiologic mechanisms of abnormal motility and developing new therapies are the goals of the current research in this fascinating field of medicine.

Diagnosis, Differential↗

[Nosography of the Laurence-Moon-Bardet-Biedl syndrome].

The Author presents two cases of Laurence-Moon-Bardet-Biedl syndrome, characterized from a rare psychopathologic symptom consisting in a state of delirium (first case); by lack of obesity and oligophrenia (first case), and of familiarity (second case).

Adult↗

Neurotensin: a physiological regulator of exocrine pancreatic secretion?

The aim of the present review was to evaluate the effects of neurotensin on the exocrine pancreatic secretion. Neurotensin immunoreactivity has been identified in the central nervous system and also in the digestive system, where it is found in specific endocrine cells of the intestinal mucosa (N cells), in nerve fibers of the enteric nervous system and in intrapancreatic ganglia (both in nerves and cell bodies). Studies in laboratory animals and in humans have demonstrated that the ingestion of a meal causes a significant release of neurotensin into the circulation and that exogenous administration of low doses of the peptide strongly stimulates exocrine pancreatic secretion. These findings, together with the demonstration that the immunoneutralization of circulating neurotensin significantly reduces the pancreatic secretory response to a meal, suggest that neurotensin is a physiological regulator of exocrine pancreatic secretion.

Animals↗

Synovial expression of vasoactive intestinal peptide in polymyalgia rheumatica.

OBJECTIVE: Polymyalgia rheumatica (PMR) is an inflammatory disease that typically affects elderly people. Its clinical hallmark is the severity of pain in the shoulder and pelvic girdle. Mild to moderate synovitis and/or bursitis of the joints involved has been described. Neuropeptides are involved in nociception and modulation of inflammatory reaction. To evaluate whether neuropeptides have a role in PMR pathophysiology, we studied the expression of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and somatostatin (SOM) in shoulder synovial tissues of PMR patients. METHODS: Synovial expression of neuropeptides was investigated by immunohistochemical analysis, in two groups of PMR patients: the first one at the onset of disease and the second one after corticosteroid treatment, and in other joint diseases, rheumatoid arthritis (RA) and osteoarthritis (OA). RESULTS: The only significant expression of VIP was found in PMR and, to a lesser extent, in RA synovial tissue. In PMR, we observed VIP immunostaining both in the lining layer and in the sublining area. In patients on corticosteroid treatment VIP lining layer expression was not significantly different while VIP positive cells in the sublining area were almost absent. CONCLUSION: Local VIP production in PMR synovial tissue might contribute to the typical musculoskeletal discomfort and it may have a role in the immunomodulation of synovial inflammation.

Aged↗

Rifaximin and Helicobacter pylori eradication.

In this study, we tested the effectiveness of Rifaximin, a surface antibiotic which is not absorbed when given orally, in the eradication of Helicobacter pylori (HP). The drug was combined in triple therapy either with Amoxicillin and Omeprazole or with Erythromycin-ethylsuccinate and Omeprazole. Twenty-three patients complaining of dyspeptic symptoms and gastric infection due to HP were evaluated. The patients were randomly given one of the following therapeutic protocols: Rifaximin susp. 600 mg/day x 3/day (at least two hours after meals: 10:00 am, 2:00 pm, 9:00 pm), Amoxicillin tab. 1 g x 2/day (at least two hours after meals: 10:00 am, 9:00 pm), Omeprazole tab. 40 mg/day (in the morning before breakfast) (protocol A) and Rifaximin susp. 600 mg/day x 3/day and Erythromycin-ethylsuccinate tab. 600 mg x 3/day (at least two hours after meals: 10:00 am, 2:00 pm, 9:00 pm), Omeprazole tab. 40 mg/day (in the morning before breakfast) (protocol B). Both therapeutic protocols were prescribed for two weeks. At least one month after the end of the treatment the patients were controlled to ascertain eradication of the infection. The follow-up carried out after treatment showed that HP infection was eradicated in 6 of 10 patients in the first group (protocol A) and in 1 of 10 in the second group (protocol B). These patients were HP-negative in all the tests performed: histological, CP-TEST, culture test. The data collected showed a reasonable level of effectiveness of the protocol using the combination Rifaximin-Amoxicillin and Omeprazole. However, they do not differ from the reported data in the literature which show a similar effectiveness of the combination Omeprazole-Amoxicillin at the same doses. Different formulations that makes it possible for the drug to reach these "protected areas" would probably be more effective.

Adolescent↗