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Biomedical subjects

G Ferraro

Publications and source records attributed to G Ferraro.

At least 19 recordsLinked to original sources

Involvement of nitric oxide-soluble guanylyl cyclase pathway in the control of maximal dentate gyrus activation in the rat.

Nitric oxide/soluble Guanylyl cyclase (NO/sGC) pathway on the maximal dentate gyrus activation (MDA) was studied in rats. The cerebral NO levels were modified by administrating 7-Nitroindazole (7-NI), a selective inhibitor of neuronal NOS, and L-arginine, a precursor of the synthesis of NO. 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ), a specific inhibitor of the NO-sGC pathway, was administered to study the involvement of cGMP pathway. The epileptic activity of the dentate gyrus was obtained through the repetitive stimulation of the angular bundle; MDA parameters studied were: onset time, MDA duration and post-stimulus afterdischarge (AD) duration. 7-NI caused an increase of MDA onset time and a decrease of MDA and AD duration. L-arginine, induced an aggravation of the epileptiform phenomena. ODQ induced modifications of MDA parameters as those caused by 7-NI. Our results indicate that the nitrergic neurotransmission exerts a modulatory role in the proneness to the epileptogenic phenomena through the activation of sGC metabolic pathway.

Animals↗

Peroxidase secretion in rat submandibular glands induced by PGE2: role of cAMP and nitric oxide.

Free radicals are associated with the appearance of disorders such as tumours, CNS alterations and inflammatory pathologies. Their levels are known to be increased in inflammatory diseases due to the activity of prostaglandins, which are related to protein secretion including enzymes. Peroxidase is an oral enzyme that is implicated in the defence of the oral cavity. In this paper, investigations of the effect and mechanism of the activity of prostaglandin E2 (PGE2) on peroxidase secretion of female rat submandibular glands are reported. Results showed that PGE2 significantly increased the secretion of submandibular peroxidase and that this effect was mediated by an increase of intracellular cAMP and nitric oxide synthase activation. This could imply that prostaglandins play a modulatory role in diseases where free radicals are involved.

Animals↗

Antinociceptive activity of Eupatorium buniifolium aqueous extract.

The antinociceptive properties of the aqueous extract of Eupatorium buniifolium aerial parts were investigated in chemical and thermal models of nociception in mice. Oral doses of 250 and 500 mg/kg produced an inhibition of 42.3% and 73.9%, respectively, of the abdominal writhes induced by acetic acid in mice. This antinociceptive effect was not reversed by pretreatment with naloxone. In the formalin test, the administration of 500 and 1000 mg/kg p.o. had no effects in the first phase (0-5 min) but produced a dose-dependent analgesic effect on the second phase (15-30 min) with inhibitions of the licking time of 38.9% and 57.3%, respectively. In the hot plate test, no effect was seen at the dose of 500 mg/kg p.o.

Acetic Acid↗

1,3-dihydroxy-5-(tridec-4',7'-dienyl)benzene: a new cytotoxic compound from Lithraea molleoides.

A dichloromethane extract from the leaves of Lithraea molleoides (Anacardiaceae), an argentine medicinal plant, showed cytotoxicity on human hepatocellular carcinoma cell line. Bioassay guided fractionation of this extract led to the isolation of a new active 5-alkyl resorcinol: 1,3-dihydroxy-5-(tridec-4',7'-dienyl)benzene. Chemical structure was established based on spectroscopic data (UV, IR, MS, 1H-NMR, 13C-NMR, COSY). This compound presented cytotoxic activity on 3 human tumoral cell lines: hepatocellular carcinoma cell line-Hep G2 (IC50 +/- SD of 68 +/- 2 microM), mucoepidermoid pulmonary carcinoma cell line-H292 (IC50 +/- SD of 63 +/- 5 microM) and mammary gland adenocarcinoma cell line -MCF7 (IC50 +/- SD of 147 +/- 5).

Anacardiaceae↗

Development of a model based on body composition to predict drug kinetics; II. Application of the model to the use of digoxin in elderlies.

The applicability of a kinetic model for the prediction of steady-state blood levels, based on body composition as assessed by bioelectric impedance analysis (BIA), was applied to a population of elderly patients, candidates for digoxin therapy. Elderlies, all >70 years of age, underwent standard laboratory and clinical evaluation but no further characterization of liver or renal function. These 72 patients were given 0.125 mg digoxin for 5 days, in order to reach steady-state levels. Treatment was then interrupted and samples were collected 2 and 48 h after the last administration. Plasma digoxin levels were determined both by the immunochemical method with TDX and according to the BIA method described in the accompanying paper. Plasma levels calculated and measured in 2 h samples did not differ statistically, but levels were about 15% higher in the directly measured samples. There was a similar underestimation, i.e. about 15%, for the 48 h calculated levels. However, only approximately 5% of the levels were outside of the 95% confidence intervals as determined from the directly measured levels. These findings indicate that digoxin levels, calculated based on a BIA evaluation, may be sufficiently reliable, in the majority of patients, to allow direct determination of the more appropriate doses of digoxin.

Aged↗

Antinociceptive and antiinflammatory activities of Artemisia copa extracts.

The aqueous extract from aerial parts of Artemisia copa Phil. (Compositae), was evaluated for antinociceptive activity using writhing, formalin, and hot-plate tests in mice. A dose-related antinociceptive response was obtained in the writhing test at doses of 500 and 1000 mg/kg p.o. (percentage of inhibition 23.3 and 52.70, respectively). The extract also inhibited the second phase of formalin test (38.81%) and this effect was not antagonized by pretreatment with naloxone 5mg/kg i.p. Furthermore, no significant effect was obtained in the hot-plate test. Dichloromethane and ethanolic extracts, were analyzed for antiinflammatory activity with the carrageenan-induced paw edema in rats and the ear edema induced by 12-O-tetradecanoylphorbol-13 acetate (TPA) and arachidonic acid (AA) in mice. Both extracts showed antiinflammatory activity in the TPA (88 and 54%), and the ethanolic extract showed a 37% inhibition in AA test. No effects were seen at doses of 300 mg/kg p.o. and 100 mg/kg i.p. in the carrageenan test. The results obtained indicate that A. copa has analgesic and topical antiinflammatory activities that supports the folk medicinal use of the plant.

Acetic Acid↗

Flavonoids from Achyrocline satureioides with relaxant effects on the smooth muscle of Guinea pig corpus cavernosum.

Ethanol extract of the aerial parts of Achyrocline satureioides (Lam.) DC. (Asteraceae) showed a significant, dose dependent, relaxant effect on the smooth muscle of corpus cavernosum strips, obtained from Guinea pig (65.5 +/- 4.1% of relaxation at the dose of 25.0 mg/ml). Bioassay guided fractionation of this extract furnished two flavonoids, quercetin and quercetin 3-methyl ether, with important vasorelaxing effects on the corpus cavernosum strips (79.8 +/- 8.4 and 66.0 +/- 4.8% of relaxation respectively at the dose of 0.075 mg/ml). Two methyl derivatives of quercetin obtained by synthesis, quercetin 3,7,3',4'-tetramethylether and quercetin 3,5,7,3',4'-pentamethylether, showed similar relaxant effects at the dose of 0.075 mg/ml (86.4 +/- 8.5 and 67.31 +/- 1.4% of relaxation respectively). The results show that the ethanol extract of A. satureioides and the assayed compounds exhibit significant vasorelaxing properties. Additionally, it is shown that the number of methyl groups in the quercetin nucleus has no significant influence on the effectiveness of these compounds.

Animals↗

Induction chemotherapy to weekly paclitaxel concurrent with curative radiotherapy in stage IV (M0) unresectable head and neck squamous cell carcinoma: a dose escalation study.

The purpose was to determine the maximum tolerated dose (MTD) of weekly paclitaxel with concurrent, daily irradiation in patients with unresectable head and neck squamous cell carcinoma previously submitted to induction chemotherapy. Patients with stage IV, and unresectable tumor and/or node/s were enrolled. Nine male patients were submitted to a course of paclitaxel 175 mg/m2 day 1 and cisplatin 75 mg/m2 day 2 given every 3 weeks for three courses. Curative radiotherapy (RT) started 3 weeks after the last cycle of chemotherapy with the goal of delivering a total dose of 66-70 Gy. During RT weekly paclitaxel was administered for 6 courses if feasible; paclitaxel was given according to a dose escalation schema in cohorts of three patients. Dose level A, 30 mg/m2; dose level B, 40 mg/m2; dose level C, 50 mg/m2. During weekly paclitaxel the major toxicity was mucositis that required a treatment break in two of three patients in dose level C; mucositis grade 4 required interruption of paclitaxel administration in all these patients. RT can be given in a continuous fashion with weekly paclitaxel after induction chemotherapy. The MTD of weekly paclitaxel was 40 mg/m2.

Aged↗

Argentinian plant extracts with relaxant effect on the smooth muscle of the corpus cavernosum of guinea pig.

Extracts of different polarity from Baccharis trimera, Haplopappus rigidus Huperzia saururus, Maytenus ilicifolia, Satureja parvifolia and Senecio eriophyton were tested for their relaxant activity on smooth muscle using L-phenylephrine precontracted strips of corpus cavernosum obtained from Guinea pigs. Highly significant and dose dependent results were obtained with the dichloromethane extracts of H. saururus (87% of relaxation at the dose of 10 mg/ml), S. parvifolia (95% of relaxation at 2.5 mg/ml) and S. eriophyton (94% of relaxation at 5 mg/ml). Similar effects were observed with the methanol extracts of H. saururus (88% of relaxation at 10 mg/ml) and S. parvifolia (84% of relaxation at 10 mg/ml). These results were comparable to those obtained with the dichloromethane and methanol extracts of the well known Mexican species Turnera diffusa. Moreover, the aqueous extract of H. rigidus and the aqueous and methanol extracts of S. eriophyton were highly effective in a dose dependent manner (more than 90% of relaxation at the dose of 10 mg/ml). Significant results, but with a lower overall relaxant activity (about 70% of relaxation at 10 mg/ml), could also be obtained with the aqueous extract of S. parvifolia and with the dichlormethane and methanol extracts of B. trimera and M. ilicifolia. The positive controls with Sildenafil citrate at doses ranging from 0.35 to 35 microg/ml yielded moderate effects (up to 46% of relaxation at 35 microg/ml). The effects observed in the present study seem to validate the folk medicinal use of the tested plants and open new ways in the search for natural products with vasodilatory effects.

Animals↗

Effects of Ginko Biloba and caspase inhibitors on brain ischemia in the Mongolian Gerbil.

AIM: Data reported in previous studies and our own previous experience have led us to explore the mechanism of and the degree of protection afforded by Ginko Biloba in a model of cerebral ischemia in the Mongolian Gerbil evaluating histological and neurological effects in this rodent. METHODS: Mongolian Gerbils were divided into experimental groups: Group A consisted of animals subjected only to experimental ischemia; 5 minutes occlusion of the carotid arteries. Group B consisted of animals subjected to experimental ischemia and to a dose of Ginko Biloba, given intraperitoneally immediately before the surgical procedure. Group C consisted of animals subjected to experimental ischemia and to a dose of Ginko Biloba, given intraperitoneally immediately after the surgical procedure. Group D consisted of animals subjected to experimental ischemia and to a dose of the caspase inhibitors z-VAD.FMK and z-DEVD.FMK injected intracerebroventricularly through the right hemisphere before the surgical procedure. Group E consisted of animals subjected to experimental ischemia and to a dose of caspase inhibitors injected after the surgical procedure. Group F consisted of Sham-operated animals. Histological controls were done by H and E and the TUNEL method in the frontal cortex and caudate-putamen. RESULTS: The percentage of normal cells was not statistically significant at analysis with H and E, whereas the TUNEL method showed good protection with Ginko Biloba and caspase inhibitors, when the latter is given in the reperfusion phase. These data were in agreement with data obtained at neurological examination. CONCLUSION: We could say that cellular morphology is in itself an untrustworthy tool for judging the effects of ischemia and protective drugs; the TUNEL method may add important information about the different components of cellular death; the reperfusion phase may be critical for apoptotic phenomena; Ginko Biloba might protect neurons of the frontal cortex from both necrotic and apoptotic death in this model of ischemia.

Amino Acid Chloromethyl Ketones↗

Hepatoprotective activity of Achyrocline satureioides(Lam) D. C.

Aerial parts of Achyrocline satureioides(Lam) D. C. (Asteraceae) are used in folk medicine as infusions or decoctions for the management of several diseases including gastrointestinal and hepatic disorders. These data and the presence of flavonoids and caffeoyl derivatives have led us to study its hepatoprotective and choleretic activities. The hepatoprotective activity was evaluated in the bromobenzene- (BB-) induced hepatotoxicity model in mice through the measurement of the serum levels of alanine-aminotransferase (ALT) and aspartate transaminase (AST), thiobarbituric acid reacting substances (TBARS) and glutathione levels. The aqueous extract of the aerial parts of A. satureioides administered before BB, at the dose of 300 mg kg(-1)p.o., demonstrated significant inhibition (P< 0.01) in the BB increase of liver ALT and AST and in the BB-induced increase of liver TBARS content. Also it was able to significantly increase (P< 0.05) the depleted levels of liver glutathione. In addition, at the same dose, a significant increase (P< 0.01) in the bile flow of rats was found. The results obtained with the aqueous extract of A. satureioides support its use in popular medicine as a hepatoprotective and digestive agent, and the effects might be mediated through the antioxidant and choleretic activities.

Alanine Transaminase↗

Influence of nitric oxide on the spontaneous activity of globus pallidus neurones in the rat.

Previous observations have suggested a role for nitric oxide in the activity of the globus pallidus, but this functional involvement has not yet been tested in vivo. The extracellular activity of single units of the globus pallidus was recorded, and neuronal nitric oxide synthase was inhibited by systemically administering 7-nitro-indazole to a group of anaesthetised rats. Forty-five per cent of cells responded with a decrease in the firing rate. In another group of rats, the microiontophoretic administration of 3-morpholino-sydnonimin-hydrochloride (a nitric oxide donor) induced an increase in neuronal firing rate (24/28 cells), whereas the administration of N-omega-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor) reduced the activity of pallidal neurones (8/11 cells). No electrophysiological differences between drug-sensitive and -insensitive neurones were evidenced. An excitatory role of nitric oxide in controlling the level of spontaneous activity of globus pallidus neurones is suggested, without any influence upon the discharge pattern.

Action Potentials↗

Antinociceptive effect of the aqueous extract of Balbisia calycina.

The aqueous extract from the aerial parts of Balbisia calycina (Gris.) A.T. Hunziker et Ariza (Ledocarpaceae), was evaluated for antinociceptive activity using the abdominal constriction, hot plate and formalin tests. The extract was administered orally to male mice at doses of 200, 400 and 800 mg/kg. A dose-dependent antinociceptive effect of the extract was obtained with the abdominal constriction test at doses of 400 and 800 mg/kg. This antinociceptive effect was not reversed by pretreatment with naloxone. No significant response was obtained with the hot plate test. With the formalin test doses of 400 and 800 mg/kg had no significant effect during the first phase of the test (0-5 min), while with the dose of 800 mg/kg, a significant inhibition during the second phase (15-30 min) was observed. The phytochemical investigation of the aqueous extract of B. calycina revealed the presence of the flavonoids luteolin, avicularin and hyperoside. The possible involvement of these flavonoids (specially luteolin) in the antinociceptive action is discussed.

Analgesics↗

Cytotoxic effect of Argentine medicinal plant extracts on human hepatocellular carcinoma cell line.

Methanolic extracts from Achyrocline satureioides (Dc.) Lam, Aristolochia macroura Gomez, Lithraea molleoides (Vell.) Engl., Schinus molle L., unlike those from Celtis spinosa Spreng, Chenopodium ambrosioides L., Petiveria alliacea L., and Plantago major L. showed cytotoxic activity against a human hepatocellular carcinoma cell line, Hep G2. Schinus molle L. was the most active (IC50=50+/-7 microg/ml). These results call for further studies of these extracts.

Anacardiaceae↗