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Biomedical subjects

G Ferraro

Publications and source records attributed to G Ferraro.

At least 55 records · Page 3Linked to original sources

[Histopathologic examination of the intervertebral lumbar disk. Evaluation of its usefulness and limitations].

A retrospective clinical-pathological review of 192 lumbar intervertebral discs removed via an interlaminar approach or percutaneous nucleotomy from patients suffering from sciatic pain was carried out in order to assess if routine examination is useful. Only for a case of our series, which showed ill defined features at preoperative neuroradiologic imaging, an intraoperative pathologic examination was necessary. Immunohistochemical study was never required. A routine examination with a hematoxilin-eosin stain was sufficient also to recognize postoperative scar in patients reoperated. In conclusion we think that routine examination of the intervertebral disc is a procedure which is not expensive and useful to assess the nature of the lesion in reoperated patients and in rare cases showing unclear radiologic pattern.

Female↗

Argentine plant extracts active against polymerase and ribonuclease H activities of HIV-1 reverse transcriptase.

Lipophilic and hydrophilic extracts of four Argentine plants (Gamochaeta simplicaulis Cabr. 1, Achyrocline flaccida Wein. D. C. 2, Eupatorium buniifolium H. et A. 3, and Phyllanthus sellowianus Muell. Arg. 4) were examined in vitro for their ability to inhibit the polymerase and ribonuclease H (RNase H) activities of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) (wild and Y181C mutant types). The active extracts were also examined as inhibitors of viral replication in HLT4LacZ-1IIIB cell cultures, evaluating their cytotoxicity in parallel. Infusions 2I and 4I, among the crude extracts, showed the highest activity. These extracts were refractioned into four fractions; 2I4 and 4I4 were active as inhibitors of DNA-polymerase (wild and Y181C types) and RNase H activities. These fractions were potent as inhibitors of viral replication and were not cytotoxic. Refractionation of 2I4 yielded five new fractions, two of which, 2I4-4 and 2I4-5, showed notable activity. Refractionation of 4I4 yielded for new fractions; of these, 4I4-3 and 4I4-4 were active. The marked biological activity found in the infusion of A. flaccida and P. sellowianus makes them sufficiently attractive to be considered in the combined chemotherapy of the disease.

Anti-HIV Agents↗

Antiviral activity in Argentine medicinal plants.

In an ethnopharmacological screening of selected medicinal plants used in Argentina for the treatment of infectious diseases, aqueous extracts of five species were assayed in vitro to detect antiviral activity against herpes simplex virus type 1 (HSV-1), respiratory syncytial virus (RSV) and adenovirus serotype 7 (ADV-7). Polygonum punctatum, Lithraea molleoides, Sebastiania brasiliensis and Sebastiania klotzschiana but not Myrcianthes cisplatensis showed in vitro antiherpetic activity with 50% effective dose (ED50) ranging from 39 to 169 microg/ml. P. punctatum, L. molleoides and M. cisplatensis showed antiviral activity against RSV with ED50 ranging from 78 to 120 microg/ml. None of the extracts had antiviral activity against ADV-7. The differences between their maximal non cytotoxic concentration and their antiviral activity values were high enough to justify further analysis.

Adenoviruses, Human↗

Diuretic activity of an aqueous extract of Phyllanthus sellowianus.

Phyllanthus sellowianus Muell. Arg. (Euphorbiaceae) is used widely as a hypoglycemic and diuretic agent in South American folk medicine. In order to assess the diuretic activity of this plant, test animals were treated with a single oral administration of an aqueous extract (5% w/v) of the stem bark of P. sellowianus (400 mg/kg body weight), which produced after 8 h a significant increase in the urinary excretion. In the studies on acute toxicity in mice neither mortality nor neurobehavioral or autonomic profile changes could be observed.

Animals↗

Nitric oxide and glutamate interaction in the control of cortical and hippocampal excitability.

PURPOSE: We investigated the role of nitric oxide (NO) as a new neurotransmitter in the control of excitability of the hippocampus and the cerebral cortex, as well as the possible functional interaction between NO and the glutamate systems. METHODS: The experiments were performed on anesthetized rats. The bioelectrical activities of the somatosensory cortex and the CA1 region of the hippocampus of these rats were recorded. Pharmacologic inhibition of NO synthase (NOS) through the nonselective and brain-selective inhibitors, N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), was performed. RESULTS: The treatments caused the appearance of an interictal discharge activity in both the structures. The latency of induction and the duration of the interictal discharge activity were strictly related to the dose of NOS inhibitor used. In some cases, after L-NAME treatment at high doses, it was possible to note spike and wave afterdischarge activity in the hippocampus. All the NOS inhibitor-mediated excitatory effects were abolished by intraperitoneal (i.p.) pretreatment with the N-methyl-D-aspartic acid (NMDA) receptor antagonists (DL-2-amino-5-phosphonovaleric acid, 2-APV; dizolcipine, MK-801) and partly suppressed after the i.p. injection of the non-NMDA antagonist (6-cyano-7-nitroquinoxaline-2,3-dione; CNQX). CONCLUSIONS: All data showed that the reduction of NO levels in the nervous system causes the functional prevalence of the excitatory neurotransmission, which is probably due to an NMDA overactivity caused by the absence of the NO-mediated modulatory action. Thus, it is possible to hypothesize a neuroprotective role for NO, probably through a selective desensitization of the NMDA receptors.

Animals↗

Etoposide, l-leucovorin and fluorouracil (ELF) regimen in metastatic gastric cancer: a phase II study.

The role of chemotherapy in metastatic gastric cancer (MGC) is predominantly palliative, therefore regimens with mild toxicity and acceptable activity should be preferred. The combination of etoposide, leucovorin and 5-fluorouracil (ELF) is suitable chemotherapy in this situation. We have enrolled 33 patients with MGC, using the following chemotherapy schedule: l-leucovorin 150 mg/m2 10 minute i.v., followed by etoposide 120 mg/m2 50 minute i.v., followed by 5-fluorouracil 500 mg/m2 10 minute i.v. on days 1-3, every 22 days. All patients are valuable for response, toxicity and survival. Two patients achieved complete response (6%), 10 patients (30%) had a partial response (PR), 9 patients (27%) had stabilization of disease (SD) and 12 patients had disease progression (PD). The median survival for all patients was 6 months (range, 1 to 40+). ELF was well tolerated, the main toxicity being myelosuppression. No toxic deaths occurred. In conclusion, the ELF regimen in our trial demonstrated, in this kind of patient, moderate activity in the absence of relevant toxicity, confirming its suitability in patients in generally poor condition.

Adult↗

Human defunctionalized colon: a histopathological and pharmacological study of muscularis propria in resection specimens.

Despite the regression of "diversion colitis," temporary functional disorders after bowel continuity restoration could be caused by changes in the smooth muscle of excluded segments; however, studies on the muscularis propria have yielded contradictory results. This study was aimed at evaluating possible histopathological changes in muscular layers and motility of the defunctionalized human colon. Ten patients with defunctionalized colorectum (group A) and 10 controls (group B) underwent restorative or primary resection surgery. Strips were taken proximal to the colostomy (specimens A1) and the defunctionalized segment (specimens A2), and from the proximal (specimens B1) and distal extremity (specimens B2) of resected colons. Measurements of the thickness of the muscularis propria and of the volume density of the myenteric plexus, as well as of spontaneous motility and responses to electrical and pharmacological stimulation were taken. The muscularis propria was thicker in A2 than in A1 specimens (P = 0.004) and in B2 than in B1 specimens (P = 0.007). No differences were recorded either in the myenteric plexus volume density or in colonic motility. No differences were recorded in intergroup comparisons. As no structural or functional changes related to defunctionalization were found, clinical disorders after colorectal restoration could rather result from underlying colonic pathology and/or incomplete distal colon resection.

Case-Control Studies↗

Relationship between fundic endocrine cells and gastric acid secretion in hypersecretory duodenal ulcer diseases.

BACKGROUND: Acid hypersecretion is associated with duodenal ulcer disease in the following conditions: Zollinger-Ellison syndrome (ZES) and antral gastrin cell hyperfunction (AGCH) due to hypergastrinaemia, or hypersecretory duodenal ulcer (HDU) without hypergastrinaemia. AIM: To evaluate whether quantitative changes in fundic ECL and D cells may be involved in acid hypersecretion. PATIENTS AND METHODS: Seven ZES, six AGCH and six HDU Helicobacter pylori-positive patients were compared. Basal (BAO) and pentagastrin-stimulated gastric acid secretions (PAO), and morphometry of fundic ECL and D cells were performed. The six AGCH and six HDU patients were investigated again using the same tests 1 year after H. pylori eradication. RESULTS: Median PAO values were no different in all the hypersecretory conditions studied. The median volume density of ECL cells in ZES was significantly higher than in controls (2.75, range 1.74-5.8 vs. 0.73, 0.52-1.11: P < 0.05), whereas it was in the control range in AGCH and HDU patients (0.77, range 0.20-1.39 and 0.99, range 0.42-1.51; respectively). The count of fundic D cells was significantly lower in AGCH patients than in all other investigated groups (median 0.16, range 0.1-0.52; P < 0.05). Cure of infection in AGCH and HDU patients did not modify the ECL cell volume density, whereas a significant increase in the count of fundic D cells was observed in AGCH patients. Thus, the ECL/D cell index was significantly affected in AGCH patients (P < 0.05), being higher during H. pylori infection (median 6, range 0.7-9.25) than after the cure (median 2.12, range 1.10-3.5). BAO and PAO were not affected by H. pylori eradication in either group. CONCLUSIONS: The study provides evidence, for the first time, that quantitative alterations in the fundic endocrine cells are not involved in acid hypersecretion of patients with hypersecretory states, and that eradication of H. pylori does not restore normal acid secretion values.

Adult↗

Changing strategies of lung biopsies in diffuse lung diseases: the impact of video-assisted thoracoscopy.

The aims of this report were: 1) to compare the strategy of bioptic approach in Italy during the last 4 yrs with a previous period; and 2) to compare efficacy and safety of video-assisted thorascopic lung biopsy (VTLB) versus OLB. We retrospectively evaluated: 1) the strategy of the bioptic approach in the Milan Sarcoid Clinic in the years 1992-1995 (201 patients) versus 1988-1991 (197 patients); and 2) data from 65 VTLB procedures in the years 1992-1995 versus 68 OLB procedures in the years 1988-1991 performed in patients with diffuse lung disease. It was found that the use of OLB (17-9%), mediastinoscopy (15-5%), and scalene node biopsy (20-7%) decreased, whereas transbronchial biopsy (TBB) increased (11-17%). VTLB biopsy is now performed in 17% of patients. VTLB compares favourably with OLB as there is less need for analgesia (7.5+/-7.5 versus 17.5+/-8.0 methadone mg i.m.: p<0.001), lower blood loss (61+/-58 versus 156+/-84 mL in the first postoperative day: p<0.001), and shorter postoperative stay (4.7+/-1.6 versus 5.7+/-1.4 days: p<0.001). Specimen adequacy (98.6 versus 985%) and diagnostic accuracy (86.1% VTLB, versus 92.6% OLB: p>0.05) were the same in the two groups. In conclusion, video-assisted thoracoscopic lung biopsy is replacing both mediastinoscopy and open lung biopsy. It is at present the best option when a surgical procedure is required for histological confirmation of diffuse lung disease.

Adult↗

Endocrine cell growths in atrophic body gastritis. Critical evaluation of a histological classification.

The aim of the present study was to evaluate the correspondence of the classification of non-antral endocrine cell growths proposed by Solcia and co-workers with clinical features and non-endocrine mucosal changes. For this purpose, 94 cases of newly diagnosed atrophic body gastritis were investigated using endoscopic biopsies and compared with 18 control subjects. The patients were subdivided into the following four groups according to the most severe pattern of endocrine cell proliferation found in the body mucosa, as shown by chromogranin A immunostaining: group 1, normal pattern (7 cases, 7.5 per cent); group 2, simple hyperplasia (6 cases, 6.5 per cent); group 3, linear hyperplasia (24 cases, 25.8 per cent); group 4; micronodular hyperplasia (56 cases, 60.2 per cent). Adenomatoid hyperplasia was found in only one case, thus precluding further analysis. Patients in groups 1 and 2 had lower acid secretion, higher gastrin level, and higher mean scores in all histopathological variables of chronic gastritis considered by the Sydney system when compared with controls, but did not differ among them in any parameter investigated. When compared with groups 1 and 2, patients of groups 3 and 4 showed higher values of circulating gastrin, higher scores of glandular atrophy, and lower values of acid secretion and of mononuclear and neutrophil inflammatory cell infiltration. Moreover, group 4 patients differed significantly from those of group 3 in their higher gastrin levels and atrophy scores, and lower scores of neutrophil cell infiltration. On the basis of these results, it is proposed that for practical purposes the normal and the simple hyperplasia patterns may be incorporated into a single group. It is concluded that this classification in its simplified form, based on a qualitative histological approach, shows clinical relevance without the need to perform expensive, time-consuming morphometric evaluations.

Adult↗

Lateral habenula and hippocampus: a complex interaction raphe cells-mediated.

The study has shown an excitatory influence exerted by lateral habenula (LH) on hippocampal pyramidal cells. The modulatory influence is paradoxically serotonine-mediated; in fact all LH stimulation effects were abolished by intrahippocampal iontophoretic methysergide application. The data suggest the involvement of dorsal raphe nucleus. In fact, the dorsal raphe nucleus stimulation caused on hippocampus an expected inhibitory effect antagonized by intrahippocampal iontophoretic methysergide application. In the context of this neural structure we have highlighted a disinhibitory relation between two types of cells: slow serotonergic efferent neurones and fast GABAergic interneurones. The disinhibitory hypothesis is also supported by the following experimental tests performed on both slow and fast raphe cells: a) LH stimulation at low and high frequencies; b) iontophoretic administration of NMDA and GABA; c) LH stimulation during intraraphe iontophoretic injection of 2-APV (NMDA antagonist) and bicuculline (GABA antagonist).

2-Amino-5-phosphonovalerate↗

Pancreatic-polypeptide cell hyperplasia associated with pancreatic or duodenal gastrinomas.

An immunohistochemical investigation of pancreatic-polypeptide (PP) cells in the PP-rich region of the pancreas, of ventral embryological origin, was performed in three female patients affected by or previously operated on for functioning duodenal or pancreatic gastrinomas not associated with multiple endocrine neoplasia syndrome. A pronounced PP-cell hyperplasia showing histological patterns of endocrine cell dysplasia and focal adenomatosis as defined by Jaffe et al was found in all cases. Morphometric analysis showed that in these patients the fraction of ventral-type pancreatic lobules occupied by PP-immunoreactive cells was 14.77 +/- 5.73%, 8.94 +/- 2.92%, and 10.83 +/- 5.64%, respectively. These values were three to five times higher than the upper values found in controls (mean, 2.20%; range, 1.54 to 2.93%; P < .0001). PP-cell hyperplasia may contribute for the increased circulating levels of PP found in gastrinoma patients. In this regard, elevation of fasting blood PP was found in one of four determinations done in one patient, indicating that PP-cell hyperplasia may be responsible for, at least, transient PP hypersecretion. In one of our patients, PP-cell hyperplasia was found 15 years after normalization of gastrin levels by removal of a single pancreatic gastrinoma. This finding is against a trophic role for hypergastrinemia in the development of PP-cell hyperplasia. In one of two patients in whom the pancreatic regions of dorsal embryological origin (ie, body and tail of the gland) were examined, ventral-type, PP-rich islets were frequently encountered, a finding at variance with their exceptional detection in control cases. This finding suggests that PP cell hyperplasia of the PP-rich pancreatic region may be a feature of a more diffuse disorder of PP cell development in the pancreas of gastrinoma patients.

Aged↗

Neuroendocrine proliferation in the gastric mucosa: biological behaviour and management.

Neuroendocrine proliferation of gastric mucosa is commonly encontered in routine gastric biopsies and is an indirect effect of modern drugs suppressing acid secretion. The process is virtually circumscribed to the ECL cell, the most common endocrine cell of the oxyntic mucosa, and is dependent on the trophic effect of the concomitant hypergastrinemia in most cases. It starts in the form of hyperplastic lesions that in some cases evolves into dysplasia and neoplasia. Gastrin has promoting but not transforming properties for such ECL cell tumour induction. Proven or potential transforming factors include the allelic loss of the MEN-1 suppressor gene at 11q13, the still unknown factor(s) associated with atrophic corporal gastritis in which overexpression of BCL-2 likely plays a favouring role by prolonging ECL exposure to mitogens, and agents with still unclarified role, such as basic fibroblast growth factor, human chorionic gonadotropin-alpha and transforming growth factor-alpha. Gastric neuroendocrine tumours independent of the trophic effect of gastrin are less frequent but more malignant. Their pathogenesis and precursor lesions are ignored.

Carcinoid Tumor↗

Lateral habenular influence on dorsal raphe neurons.

Previously, we have demonstrated that lateral habenula (LH) modulates the bioelectric activity of the hippocampus through the dorsal raphe nucleus functional involvement. In this study we have, preliminarily, electrophysiologically identified two types of raphe neurons: "slow" (S cells, serotonergic in nature); and "fast" (F cells, presumably GABAergic in nature). Then, we have shown that LH electrical stimulation at lower frequency induced an excitation of S and F neurons. LH stimulation at higher frequency inhibited only S neurons. Furthermore, iontophoretic NMDA excited S and F neurons. The excitatory effects of LH stimulation were antagonized by the iontophoretic 2-APV (NMDA antagonist). Iontophoretic GABA inhibited only S neurons. Iontophoretic bicuculline antagonized the LH-induced inhibition os S neurons. The data suggested a direct (NMDA-mediated) and indirect (through the F GABAergic inhibitory interneuron) influence of the LH on the serotonergic efferent neuron.

2-Amino-5-phosphonovalerate↗

Involvement of BCL-2 oncoprotein in the development of enterochromaffin-like cell gastric carcinoids.

To evaluate the involvement of the apoptosis-suppressing protein BCL-2 in the gastrin-dependent mechanism of induction of gastric enterochromaffin-like (ECL) cell carcinoids, the endocrine cell of the oxyntic mucosa were immunohistochemically investigated in (a) 10 normogastrinemic subjects with histologically normal gastric mucosa; (b) 22 patients with endocrine cell hyperplasia and affected by hypergastrinemic conditions with different risk of gastric carcinoid development, such as sporadic Zollinger-Ellison syndrome (sZES; n = 9), ZES associated with multiple endocrine neoplasia-1 (MEN-1; n = 4), and atrophic fundal gastritis (AFG; n = 9); (c) 14 patients with ECL gastric carcinoids accounting for a total of 31 tumors investigated. In the normal oxyntic mucosa, BCL-2 was consistently expressed by a subset of endocrine cells accounting for 50.0% (median; range, 24.6-74.0%) of the total number of endocrine cells immunostained for chromogranin A (CgA) in consecutive sections. BCL-2 immunoreactive cells were located mostly in the middle mucosal layer, suggesting a role for the protein during downward migration of maturing endocrine cells. No BCL-2 immunoreactivity was found in other specialized gastric epithelial cells. Expression of BCL-2 by hyperplastic oxyntic endocrine cells (mostly ECL cells) varied in parallel with the risk of carcinoid development. In fact, the ratio of BCL-2- to CgA-immunoreactive cells was reduced (median, 4.6%; p less than 0.0001; range, 0.9-42.0%) in sZES, a condition showing virtually no risk, unchanged (median, 55.6%; range 29.4-83.8 %) in cases of MEN-1/ZES with intermediate risk, and increased (median 87.6%; p less than 0.014; range, 48.8-199.4%) in cases of AFG, a condition at the highest risk of carcinoid. In ECL cell carcinoids, BCL-2 expression varied markedly from one tumor to another even in the same patient and was low or absent in most cases. In both hyperplastic and neoplastic ECL cells, an inverse relation between BCL-2 expression and CgA immunoreactivity, that is, the cell granule content, was found. These results suggest that BCL-2 expression by hyperplastic ECL cells is independent of the influence of serum gastrin and may contribute to the development of ECL cell carcinoid tumors by extending cell exposure to oncogenic factors. Once a carcinoid tumor is established, BCL-2 expression becomes inconsistent.

Adult↗