PubMed Health⌕ Search

Biomedical subjects

B Rosa

Publications and source records attributed to B Rosa.

15 recordsLinked to original sources

Brain concentrations of kynurenic acid after a systemic neuroprotective dose in the gerbil model of global ischemia.

1. Kynurenic acid (KYNA) is a kynurenine metabolite and a broad spectrum excitatory amino acid antagonist that has been shown to be neuroprotective in models of cerebral ischemia, when administered exogenously. However, the actual concentration required in the CNS to evoke significant neuroprotection has never been assessed. 2. The purpose of this study was to address this question in the gerbil model of forebrain ischemia. KYNA (400-1600 mg/kg) or vehicle were administered i.p. 15 min before 5 min bilateral carotid occlusion. 3. Seven days after reperfusion, ischemia-induced hippocampal nerve cell loss (95% in vehicle-treated) was significantly lower in KYNA-treated gerbils (65% and 52% at 1000 and 1200 mg/Kg, respectively, P < 0.01). Treatment with 1000 mg/kg produced brain KYNA concentrations that were dramatically elevated (135.9 and 42.3 microM in CSF and whole brain, vs 0.032 and 0.16 microM in controls, at 15 min after ischemia), as measured in a separate group of transcardially-perfused gerbils. Cerebral KYNA concentrations tended to return to basal values 2 hours after reperfusion. 4. These results indicate that KYNA has a marked neuroprotective effect in a model of forebrain ischemia. This activity is associated with KYNA concentrations in the brain and CSF that are compatible with the in vitro affinity of the compound for ionotropic glutamate receptors.

Animals↗

Pharmacological characterization of FCE 27262, a combined thromboxane synthase inhibitor and PGH2/TXA2 receptor antagonist.

The literature supports the hypothesis that the association of a thromboxane (TX)A2 synthase inhibitor and a PGH2/TXA2 receptor antagonist has a superior antithrombotic effect when compared to both aspirin and single agent alone; a compound endowed with the dual mechanism of action might therefore be of therapeutic value for the management of thrombotic disorders. FCE 27262, an imidazol-1-yl-ethylideneaminooxypentanoic acid, displaces in vitro the binding of [3H]SQ 29,548 to washed human platelets (IC50 = 6.0 +/- 0.6 x 10(-8) M) and antagonizes human platelet aggregation induced by U 46619 in PRP with an IC50 (95% confidence limits) of 4.5(3.3-5.1) x 10(-7) M. It also selectively antagonizes the isolated vessel contraction induced by U 46619. In the rat aorta the Kb (95% confidence limits) was 1.6(0.6-4.3) x 10(-7) M. Additionally it inhibits in vitro TXB2 production in rat and human whole blood, the IC50 being, respectively, 5.9(3.3-9.6) x 10(-8) M and 3.8(2.9-5.0) x 10(-8) M. When administered orally to fed rats it also inhibits ex vivo TXB2 production in whole blood during clotting, the ID50 being 0.62(0.4-0.8) mg/kg. Both in vitro and ex vivo the effect of FCE 27262 on TXA2 synthase was selective, the production of PGE2, the product of a different isomerase from the common precursors, PG-endoperoxides, being concomitantly enhanced. In a canine model of electrically-induced coronary thrombosis, FCE 27262 (1 mg/kg i.v.) inhibits ex vivo TXB2 synthesis (> 95%), antagonizes U 46619-induced platelet aggregation and prolongs occlusion time (controls: 72 +/- 8 min, FCE 27262: 215 +/- 38 min; p < 0.01). In the same model both aspirin (5 mg/kg i.v.) and a pure PGH2/TXA2 receptor antagonist (L 670596), at a dose giving a similar degree of TXA2 synthase inhibition and receptor blockade, respectively, are significantly less effective. Thus, FCE 27262 combines thromboxane synthase inhibition and PGH2/TXA2 receptor antagonism in one molecule, resulting in enhanced antithrombotic activity. FCE 27262 thus may be an appropriate pharmacological tool to test the therapeutic potential of the dual mechanism of action.

Animals↗

Evidence for a direct vasoconstrictor effect of big endothelin-1 in the rat kidney.

Inhibition of endothelin-1 (ET-1)-converting enzyme has been suggested as a strategy for blocking ET-1-mediated vasoconstriction. However, it is unclear whether its putative substrate, bigET-1, is an inactive precursor. Thus, we compared in the rat the effects of ET-1 and bigET-1 on renal vascular resistance (RVR) in vitro (isolated perfused kidney, n = 15) and in vivo (Doppler shift technique, n = 23) when injected i.v. or in the rat renal artery (i.a.), before and after metalloprotease inhibition with phosphoramidon (30 mg/kg i.v.). In vitro, the ET-1/bigET-1 potency ratio for the RVR increase was 175; in vivo (i.v.) it was approximately 7 (ED50: 99 and 692 pmol/kg, respectively; P < 0.01). Unlike that of ET-1, the bigET-1 effect started slowly (peak effect at 15 min). On i.a. injection, the ED50 of ET-1 was lower but that of big ET-1 was unchanged (ED50: 28 and 706 pmol/kg, respectively). Moreover, the effect of i.a. bigET-1 on RVR was biphasic, with a dose-related rapid increase followed by a slowly developing further rise. Phosphoramidon completely inhibited the hemodynamic effects of i.v. bigET-1, but abolished only the second phase of the response when given i.a. It also significantly enhanced the effect of ET-1. We conclude that in the rat: (1) bigET-1 may affect RVR by both a direct effect and through phosphoramidon-sensitive conversion to ET-1; (2) the direct vasoconstrictor effect of bigET-1 might be expressed during endothelin-converting enzyme inhibition; (3) metalloproteases are involved in ET-1 degradation.

Animals↗

Amplified pulmonary metastases of a rat rhabdomyosarcoma in response to nitrosourea treatment.

Repeated observations in our laboratory show that the chloroethylnitrosourea of cysteamine ( CNCC ) induces slowed tumor growth rate and decreased lymph node metastasis in rats bearing a rhabdomyosarcoma but concomitantly enhances metastatic dissemination in the lung. Tumors obtained by sc graft of tumor cells, in syngeneic rats, gave a reproducible pattern of metastases at nodal and pulmonary sites after a 60-80-day period. CNCC was administered orally at a dose of 50 mg/kg once a week for 5 weeks beginning at the time of tumor appearance. Forty-five of 46 CNCC -treated rats had lung metastases with 95 (+/- 9.7) nodules; in the control group 29 of 41 rats had lung metastases with 7 (+/- 1.5) nodules. This amplifying effect was found after treatment with two other nitrosoureas (chlorozotocin and hydroxyethylchloroethylnitrosourea ) but not with cyclophosphamide and methotrexate. Lung metastatic amplification was also observed after treatment of the 13762 mammary adenocarcinoma in Fischer rats and treatment of nickel-induced soft tissue tumor. Several hypotheses have been proposed. The dissociated effect of nitrosourea on local tumor, lymph nodes, and pulmonary metastases does not support the concept of systemic immunosuppression as the main mechanism of this phenomenon, but a decrease of local immunological defenses exerted by NK cells, for example, could be possible. Alternatively, a direct effect of the drug on lung tissue, especially lesions of endothelial tissue, could be responsible for the observed effect. Nitrosourea treatment of rats after surgical excision of the tumor, as adjuvant chemotherapy, was responsible for an amplification effect in association with local recurrences. From this fact we hypothesized that nitrosourea treatment could modify the equilibrium of cell subpopulations in the tumor by selecting highly metastatic drug-resistant variants. Although the mechanism of the amplifying effect of nitrosoureas has not been elucidated, our study shows a possible risk in the use of these drugs for inductive or adjuvant chemotherapy.

Adenocarcinoma↗

Effect of 13 cis retinoic acid on early precancerous antigenic goblet-cell modifications and induction of cancer during 1,2-dimethylhydrazine carcinogenesis in rats.

The possible effect of oral 13 cis retinoic acid (13-cis-RA) on the carcinogenic process induced by 28 weekly s.c. injections of 1,2-dimethylhydrazine (DMH) in 34 Wistar rats was investigated. Using immunohistology, precancerous and cancerous stages were compared with the same stages induced by DMH without additional 13-cis-RA in 33 rats. M1 antigens, which characterize modifications in goblet-cell differentiation occurring early in rat colonic carcinogenesis, were used to investigate the possible effect of retinoids on differentiation during precancerous stages. From 3-20 weeks after the start of the experiment, no significant differences were observed in the timing of M1 antigens in the 2 groups of rats. It was also observed that 13-cis-RA had no effect on histological lesions associated with precancerous mucosa, nor on the occurrence of intestinal adenocarcinomas. Thus, under these conditions, oral administration of 13-cis-RA did not significantly inhibit precancerous or cancerous stages of intestinal carcinoma development.

1,2-Dimethylhydrazine↗

Intestinal metaplasia and carcinomas of the human stomach: an immunohistological study.

Rabbit immunization with duodenal or colonic high molecular weight components allowed us to distinguish three new M3 antigens associated with intestinal goblet cells; these were denoted as M3SI, M3D, and M3C. Using immunoperoxidase staining, the anti-M3SI serum labeled all goblet cells in the small intestine, and a certain number of them in the colon, mainly in its proximal part. The anti-M3D serum reacted primarily with the goblet cells of the duodenal villosities, and the anti-M3C serum with all goblet cells of the large, but not the small, intestine. Moreover, the M3C antigen was recovered in some goblet cells of the fetal duodenum, in association with the two other markers. Only the M3D and the M3SI antigens were observed in the normal duodenum and intestinal metaplasia (IM) of benign gastric mucosa. In contrast, IM adjacent to gastric carcinomas, whatever their histological type, contained the M3C antigen in addition to M3D and M3SI antigens, and thus showed an antigenic pattern similar to fetal duodenum. Some gastric carcinomas, especially those with intestinal-like differentiation, produced the colonic M3C antigen as the neighboring IM. Thus, these two tissues displayed common differentiation features, which could be related to fetal duodenum rather than to adult colon.

Antigens, Neoplasm↗

Early oncofetal antigenic modifications during rat colonic carcinogenesis.

M1 antigens, associated with adult rat surface gastric epithelium and which are present in fetal but not adult distal colon, were investigated in this colonic mucosa during carcinogenesis. Fifty Wistar rats were given s.c. injections of 1,2-dimethylhydrazine for 28 weeks. Using an immunohistochemical method, M1 antigens associated with goblet cells were shown to be present after 2 weeks of 1,2-dimethylhydrazine treatment in histologically normal mucosa and then in 78% of mucinous hyperplasia and polypoid-like glands, in 54% of hyposecreting glands, in 58% of dysplasias, Grades 1 and 2, in two of 12 dysplasias, Grade 3, and in five of five transitional mucosas adjacent to carcinoma. The production of sialomucins associated with M1 antigens was often seen in the same histological lesion, although not always associated in the same goblet cells. The number of these histological lesions as well as the production of M1 antigens increased with the number of injections. Thus, these antigenic changes of an oncofetal nature can be regarded as early transformations of goblet cell differentiation in colonic mucosa subjected to chemical carcinogen.

Adenocarcinoma↗

[Congenital mesoblastic nephroma. Study of five cases and review of the literature (author's transl)].

Mesoblastic nephroma (individualized by Bolande in 1967) is a congenital renal tumor sometimes locally and regionally aggressive but never giving metastases, in contrast with nephroblastoma. It almost always occurs in the newborn. Therefore, every renal tumor discovered before twelve months must evoke mesoblastic nephroma. No preoperative adjuvant treatment must be used in infants under six months old. Considering five personal observations and review of literature, the authors expose the main etiologic and clinical characteristics of the disease, the gross and microscopic features which allow its diagnosis and the histogenetic theories of this curious lesion, probably border-line between neoplasias and dysplasias of renal parenchyma.

Child, Preschool↗

Pancreatic exocrine function in rosacea.

As some rosacea patients complain of gastrointestinal troubles and the administration of pancreatic extracts ameliorates both dyspepsia and skin lesions, the pancreatic exocrine function in 21 subjects affected with rosacea has been investigated by means of the secretin-cerulein infusion test. 21 healthy controls have been studied for comparison. No difference was found between rosacea and control subjects for flow rate, bicarbonate and chymotrypsin concentration and output, while lipase concentration and output was significantly lower in rosacea patients, with a decrease ranging from 18.5 to 66% of normal values. Therefore, a deficient lipase secretion could be responsible, at least partly, for the clinical manifestations of rosacea.

Adult↗

Effect of graded doses of PGE2 on pancreatic exocrine secretion of bicarbonate, chymotrypsin and cyclic nucleotides during i.v. infusion of secretin in man.

We have previously reported that PGE2 inhibits pancreatic enzyme secretion during Secretin-Caerulein infusion, but differing results have also been reported. In this study 10 tests were performed in 5 healthy volunteers as follows: each subject received secretin (GIH) 2 CU/Kg-h by continuous infusion for 2 hours and, several days later, Secretin at the same dose plus PGE2 (Upjohn) in step-wise doses (0.04-0.08-0.12 gamma/Kg min) increasing every thirty min form 30' to 120' min. Duodenal juice was collected in 10 min samples. The volume of each sample was recorded and bicarbonate, chymotrypsin, cAMP and cGMP contents were determined. Statistical evaluation was performed by Student's "t" test for paired data and the regression test. PGE2 significantly decreased chymotrypsin concentration under Secretin. Both cyclic AMP and GMP Secretin-induced secretions were significantly increased by the highest dose of PGE2. No correlation was found in the behaviour of bicarbonate, chymotrypsin and cyclic nucleotides, but it must be noted that our data concern duodenal contents and not pure pancreatic secretion.

Adult↗

Lymphocyte subpopulations bearing different surface markers in non-Hodgkin lymphoma.

Lymphoid cells isolated from peripheral blood and lymph nodes were examined by using the rosette test with sheep erythrocytes (E), the immunofluorescent staining of the surface immunoglobulins (SmIg), the rosette test with mouse C 57 BL erythrocytes (Em and a combined test (SmIg + E). These studies were performed in 143 patients with various subtypes of non-Hodgkin lymphoma and in 110 controls. In the control group the following percentage of cell types was obtained: 1) blood (n = 110): T-68 +/- 12, B- 20 +/- 3, O- 11 +/- 7, BT- 1 +/- 1.4, Em+ cells--9 +/- 7, C3+ cells--21 +/- 3, 2) lymph nodes (n = 23): T- 66 +/- 10, B- 17 +/- 10, O- 15.7 +/- 9, BT- 0.8 +/- 1.7. In non-Hodgkin lymphoma lymph nodes a statistically significant increase of null and B cells- was noted in comparison to the controls (p less than 0.001). Similar changes were observed in the blood of non-Hodgkin lymphoma patients in which the leukocyte count exceeded 10(3)/microliter, whereas in the cases with low leukocythosis the B-T values were within the nomal range. It is concluded that the marker studied does allow to differentiate in most cases between the non-Hodgkin lymphoma and other disorders of the lymphoid system. They also give additional information about the more exact nature of the lymphoid malignancies.

Binding Sites↗

[Contribution of clinical, biohumoral, morphological and instrumental parameters to the diagnosis of some chronic liver diseases].

A comparative study concerning the diagnostic importance of clinical, humoral, morphological and instrumental parameters had been carried out on 105 patients affected by chronic liver disease (51 cases with liver cirrhosis, 15 with metastatic tumors, 10 with liver steatosis and 29 with chronic hepatitis). The final diagnosis of the patients used for the comparison was formulated considering the greatest numbers of data. The results of this study can be drawn as follows: --clinical and laboratory data show satisfactory diagnostic value principally in patients suffering from liver cirrhosis (90 per ceny) and metastatic tumors (93 per cent); --peritoneoscopy appears to be generally the most useful procedure with the most significance value above all in cirrhotic patients; --morphological examination in biopsy specimen results of the greatest importance in patients affected by chronic hepatitis and hepatosteatosis while rather high has been the percentage of false negatives in secondary tumors of the liver (40 per cent) and cirrhosis (68 per cent); --scintiphotoscanning is generally less useful as a diagnostic tool than peritoneoscopy a part of the cases of metastatic tumors. In such a condition the diagnostic power of both the procedures results to be identical; --it may be concluded that an integrating diagnostic information generally results to be the most precise and maximally capable of reducing the number of false negatives. In individual cases, of course, the less important procedure shows to have the maximum of diagnostic capacity.

Biopsy, Needle↗

The behavior of Italian family physicians regarding the health problems of women and, in particular, family planning (both contraception and NFP).

The hospital-centered trend that has dominated medical culture and the management of health care during this entire century has, in the last few years, undergone a reversal in Italy. Conditions in other countries suggest that similar changes have or will become increasingly common. The family physician today manages many of the functions previously handled by hospitals and specialists. In the field of reproductive health, family physicians are responsible not only for diagnosis and treatment, but also for prevention and education. The present study considers this new context with the objective of investigating the knowledge and behavior of Italian family physicians in the field of women's health, with particular regard to family planning (including natural family planning), through (1) a qualitative study (focus groups) of a small group of family physicians and (2) a questionnaire sent to 500 family physicians throughout Italy. The results of the focus group are summarized in the form of obstacles that the family physician finds in providing family planning services and proposals for change. The results indicate that because of their holistic approach, the family physician is an appropriate provider of family planning services although continued use of specialists' services, changes in logistics of the family physicians' practice, increased gender sensitivity, and additional training and information are necessary. The results of the questionnaire (121 responses, 24.2%) indicate that the Italian family physician currently lacks certain important information about family planning and would require logistical support to provide these services but is interested in acquiring information and is an appropriate family planning provider. An additional challenge for encouraging family practitioners to provide natural methods is that they favor a "medical" approach rather than a "behavioral" one in their treatment preferences for several other conditions.

Contraception↗

Urinary cytology for carcinoma in situ of the urinary bladder.

The urinary cytologies of 14 nonpapillary carcinomas in situ of the urinary bladder were reviewed. Cytologic malignancy was often diagnosed before any clinical manifestation or cytoscopic lesion could be perceived. The cytologic characteristics of this lesion as previously described in the literature were confirmed: the background was usually clean and the tumor cells were numerous and relatively monomorphic, with many atypias. Taking into consideration the limitations discussed, urinary cytology should be regarded as having great accuracy in the early diagnosis of in situ carcinoma of the urinary bladder.

Carcinoma in Situ↗