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Biomedical subjects

F Borella

Publications and source records attributed to F Borella.

At least 19 recordsLinked to original sources

Buprenorphine versus methadone for opioid dependence: predictor variables for treatment outcome.

The present study compared in a clinical non-experimental setting the efficacy of buprenorphine (BUP) and methadone (METH) in the treatment of opioid dependence: all the subjects included in the study showed severe long-lasting heroin addiction. Participants (154) were applicants to a 12 weeks treatment program, who were assigned to either METH (78) (mean doses 81.5 +/- 36.4 mg) or BUP (76) (mean doses 9.2 +/- 3.4 mg) treatment. Aim of the study was to evaluate patient/treatment variables possibly influencing retention rate, abstinence from illicit drugs and mood changes. METH patients showed a higher retention rate at week 4 (78.2 versus 65.8) (P < 0.05), but BUP and METH were equally effective in sustaining retention in treatment and compliance with medication at week 12 (61.5 versus 59.2). Retention rate was influenced by dose, psychosocial functioning and not by psychiatric comorbidity in METH patients. In contrast, BUP maintained patients who completed the observational period showed a significantly higher rate of depression than those who dropped out (P < 0.01) and the intention to treat sample (P < 0.05). No relationship between retention and dose, or retention and psychosocial functioning was evidenced for BUP patients. The risk of positive urine testing was similar between METH and BUP, as expression of illicit drug use in general. At week 12, the patients treated with METH showed more risk of illicit opioid use than those treated with BUP (32.1% versus 25.6%) (P < 0.05). Negative urines were associated with higher doses in both METH and BUP patients. As evidenced for retention, substance abuse history and psychosocial functioning appear unable to influence urinalyses results in BUP patients. Buprenorphine maintained patients who showed negative urines presented a significantly higher rate of depression than those with positive urines (P < 0.05). Alternatively, psychiatric comorbidity was found unrelated to urinalyses results in METH patients. Our data need to be interpreted with caution because of the observational clinical methodology and non-random procedure. The present findings provide further support for the utility of BUP in the treatment of opioid dependency and demonstrate efficacy equivalent to that of METH during a clinical procedure. BUP seems to be more effective than METH in patients affected by depressive traits and dysphoria, probably due to antagonist action on kappa-opioid receptors. Psychosocial functioning and addiction severity cannot be used as valuable predictors of BUP treatment outcome. High doses appear to predict a better outcome, in term of negative urines, for both METH and BUP, but not in term of retention for BUP patients.

Adult↗

Silybin, a new iron-chelating agent.

Silybin, a natural occurring flavolignan isolated from the fruits of Silibum marianum, has been reported to exert antioxidant and free radical scavenging abilities. It was suggested to act also as an iron chelator. The complexation and protonation equilibria of the ferric complex of this compound have been studied by potentiometric, spectrophotometric and electrochemical techniques. The formation of the complex silybin-Ga(III) in anhydrous DMSO-d6 has been studied by 1H NMR spectroscopy. Mass spectrometry and infrared spectroscopy on silybin-Fe(III) complex confirm all data obtained by 1H NMR spectroscopy. The experimental results show that silybin binds Fe(III) even at acidic pH. Different ternary complexes were observed at increasing methoxide ion concentration and their stability constants have been calculated. The results show the possible role of silybin in relation to the chelation therapy of chronic iron overload, as occurs in the treatment of Cooley's anemia.

Antioxidants↗

Alterations of protein mono-ADP-ribosylation and diabetic neuropathy: a novel pharmacological approach.

This study monitored the extranuclear endogenous mono ADP-ribosylation of proteins. At least 10 proteins were ADP-ribosylated in a crude extract from control superior cervical ganglia, and 7 were labeled in control dorsal root ganglia; whereas in the diabetic rat the extent of labeling was reduced. These data suggest that proteins of peripheral ganglia are excessively ADP-ribosylated in vivo. Treatment of diabetic animals with silybin, a flavonoid with ADP-ribosyltransferase inhibitory activity, did not affect hyperglycemia, but prevented the alterations in the extent of mono-ADP-ribosylation of proteins. This effect was associated with the prevention of substance P-like immunoreactivity loss in the sciatic nerve. In the membrane fraction of sciatic nerve Schwann cells, at least 9 proteins were ADP-ribosylated, in diabetic rats the extent of labeling was increased. A comparable increase involving the same proteins was triggered by chronic nerve injury and by corticosteroid treatment. Silybin treatment of diabetic rats prevented such an increase. We propose that the inhibition of excessive protein mono-ADP-ribosylation by silybin prevented the onset of diabetic neuropathy, while the silybin effect on mono-ADP-ribosylation of Schwann cells is likely indirect and secondary to the improvement of diabetic axonopathy.

Adenosine Diphosphate Ribose↗

Antioxidant activity of silybin in vivo during long-term iron overload in rats.

BACKGROUND & AIMS: Hepatic iron toxicity may be mediated by free radical species and lipid peroxidation of biological membranes. The antioxidant property of silybin, a main constituent of natural flavonoids, was investigated in vivo during experimental iron overload. METHODS: Rats were fed a 2.5% carbonyl-iron diet and 100 mg.kg body wt-1.day-1 silybin for 4 months and were assayed for accumulation of hepatic lipid peroxidation by-products by immunocytochemistry, mitochondrial energy-dependent functions, and mitochondrial malondialdehyde content. RESULTS: Iron overload caused a dramatic accumulation of malondialdehyde-protein adducts into iron-filled periportal hepatocytes that was decreased appreciably by silybin treatment. The same beneficial effect of silybin was found on the iron-induced accumulation of malondialdehyde in mitochondria. As to the liver functional efficiency, mitochondrial energy wasting and tissue adenosine triphosphate depletion induced by iron overload were successfully counteracted by silybin. CONCLUSIONS: Oral administration of silybin protects against iron-induced hepatic toxicity in vivo. This effect seems to be caused by the prominent antioxidant activity of this compound.

Adenosine Triphosphate↗

Experimental diabetic neuropathy. Inhibition of protein mono-ADP-ribosylation prevents reduction of substance P axonal transport.

The extranuclear endogenous mono-ADP-ribosylation of proteins in cellular fractions from retinas of control and diabetic rats was studied. At least six proteins were ADP-ribosylated in the crude extract, membrane and cytosolic fractions from control preparations, whereas in diabetic rats the number of labeled proteins and the extent of labeling were highly reduced. Treatment of diabetic animals with silybin, a flavonoid with ADP-ribosyltransferase inhibitory activity, did not affect hyperglycemia, but prevented the alterations of the extent of ADP-ribosylation of the 38 K cytosolic, 39 K, 40 K membrane and 39 K, 41 K and 42 K crude extract proteins. These data suggest a hyperactivity of extranuclear endogenous protein mono-ADP-ribosylation in the diabetic rat retina, and that treatment with silybin inhibits such enzyme activity, thus improving the extent of ADP-ribosylation. Sciatic nerve axonal transport of substance P was reduced markedly in diabetic rats, and inhibition of mono-ADP-ribosylation with silybin prevented such a loss in spite of high blood glucose levels. These results suggest that the abnormal endogenous ADP-ribosylation of proteins might play a role in the onset of diabetic peripheral neuropathy and its inhibition may represent a novel pharmacological approach to the treatment of diabetes complications.

Adenosine Diphosphate Ribose↗

Delaying effects of dietary eicosapentaenoic-docosahexaenoic acids on development of "fatty streaks" in hypercholesterolaemic rabbits. A morphological study by scanning electron microscopy.

Besides causing functional and clinical damage, hypercholesterolaemia also causes morphological alterations of vascular endothelium. Rabbits fed a diet with 1% cholesterol for 4, 6, or 8 weeks are experimental models for hypercholesterolaemia, with pathological structural changes in vascular luminal surface. Morphological investigation by scanning electron microscopy was performed to reveal the tridimensional growth of these lesions and the differences in this growth induced by concomitant dietary assimilation of fish-oil (2 g/day). Macroscopic reduction in fatty-streak production was clearly seen in rabbits fed fish-oil. Scanning electron microscopy confirmed that the area of intimal lesions was only 21 +/- 6% in this group, while in the group fed cholesterol without fish oil, the lesioned area attained 76 +/- 5%. Endothelial swelling was less marked, probably due to reduced intracellular lipid accumulation into the foam cells. Adherent macrophages were also fewer. The differences might be correlated with protection against the lipoproteins' atherogenic effects and to hemorheological benefits produced by the Omega-3 fatty acid (85%) present in fish-oil.

Animals↗

Modulation of urokinase receptors on human synovial cells and osteoarthritic chondrocytes by diacetylrhein.

On the basis of both 125I-labelled urokinase-like plasminogen activator binding analysis and transmission electron microscopy of an urokinase-gold complex, we have shown the presence of specific receptors for human urokinase on the cell membrane of human synovial cells. By radio-ligand binding experiments we have shown the existence of similar receptors on the surface of human chondrocytes. In both cases the specific binding is attributable to interaction between the receptor and the A chain of the ligand, as previously shown in other cell model systems. Treatment of synoviocytes with 1,8-diacetoxy-anthraquinone-3-carboxylic acid (diacetylrhein) is able to reduce the number of surface urokinase receptors. At the same time the drug can reduce the fibrinolytic activity released into the culture medium of human synovial cells. Preliminary data indicate that chondrocytes from osteoarthritic patients have a larger number of urokinase receptors than chondrocytes of normal patients. Diacetylrhein can restore the receptor number to normal levels; the amount of urokinase in the synovial fluid of ostroarthritic patients is also reduced. We conclude that the use of this drug has the chance to significantly modify the natural history of osteoarthritis.

Anthraquinones↗

Effects of tetroxoprim and sulfadiazine on T lymphocyte proliferation and gamma-interferon production.

The in vitro effects exerted by tetroxoprim and sulfadiazine on T lymphocyte proliferation were evaluated at drug concentrations equal to and twice the plasmatic peak level of each drug. The two drugs did not exert any significant effect on spontaneous and mitogen (PHA) or monoclonal antibody (MAb anti-CD3) induced T lymphocyte proliferation at the studied concentrations, both when tested separately and combined. In addition the two compounds did not significantly interfere in gamma-interferon (IFN-gamma) production.

Adult↗

New isosorbide 5-mononitrate derivative with hypotensive activity.

Synthesis and pharmacological properties of the 5-fluoro-nicotinic ester with isosorbide-5-mononitrate 3 are reported. The new compound shows an in vitro activity on rabbit aortic helical strips five times higher than isosorbide-5-mononitrate. The hypotensive activity in guinea-pigs of 3 is markedly superior to that of 5-ISMN. In the rat 3 shows a bioavailability and an acute toxicity inferior to those of 5-ISMN after oral administration.

Animals↗

Synthesis and hypolipidemic activity of some new esters of glycerol and 2-O-methyl-glycerol with nicotinic and 5-fluoro-nicotinic acids.

A series of new esters of glycerol and 2-O-methyl-glycerol with nicotinic and 5-fluoro-nicotinic acids were synthesized and their hypolipidemic activities were comparatively tested. The two most interesting compounds, 5 and 12, show a higher activity than both nicotinic and 5-fluoro-nicotinic acids in the following experimental models: Triton and olive oil hyperdyslipemia and tests on old rats.

Animals↗

Ureteropelvic junction obstructions: prenatal diagnosis and neonatal surgery in 47 cases.

In a series of 150 patients with congenital urologic disorders diagnosed in utero and managed in the neonatal period from 1980 to 1985, 48 cases were ureteropelvic junction obstructions. One was a false positive, and 47 were documented pyelocaliceal distension and retention; 12 of them were bilateral. Five cases had a spontaneous resolution. Three had a nephrectomy performed (destroyed kidney). Fifty kidneys have been operated on (Anderson-Hynes dysmembered pyeloplasty). Ninety percent of the cases are reported as clinically, biologically, and radiologically fair. Six percent postoperative complications are reported. The authors pointed out the great interest in neonatal repair of this condition, using microsurgical techniques without stent or nephrostomy. A comparison is made of the overall results with an identical series of older patients operated on during the same period.

Female↗

The Mayer-Rokitansky syndrome. Report of 5 cases.

Five cases of uterus didelphys, unilateral imperforate vagina and ipsilateral renal agenesis are reported with a follow-up from 1 to 5 years. Diagnosis included typical revelation at puberty (2 cases) but also in the first months of life (2 cases). One case was only diagnosed at the age of 6 years, and the presence of an ectopic ureter was noted in the imperforate vagina. The authors point out the necessity of precise evaluation and careful management in order to maintain an intact reproductory tract. Simple excision of the septum is recommended which can most of the time be done by the vaginal approach.

Adolescent↗

Pharmacokinetics of PTT-119 in man.

The pharmacokinetics of PTT-119, a new alkylating agent, was studied in 8 advanced cancer patients. PTT-119 disappeared rapidly from plasma after administration at a dose of 3 mg/kg by i.v. bolus injection. The HPLC method shows plasma levels of m-bis (dichloroethyl)amino-phenyl-L-alanine which is the major metabolite of PPT-119. Elimination of the drug from plasma can be described by a one-compartment model. Mean values of 77.8 min for the half-life, 510.8 ml/min for the total plasma clearance and 0.69 l/kg for the volume of distribution were found.

Aged↗

Structural and biochemical alterations in the dorsal horn of the spinal cord caused by peripheral nerve lesions.

Substance P and Met-enkephalin were detected by radioimmunoassay and immunocytochemistry in the rat lumbar spinal cord. The sciatic nerve was lesioned by resecting a piece and the proximal stump was either ligated, for limiting neurite outgrowth, or intraperitoneally sutured, allowing the formation of a large neuroma. Ten days post lesioning both peptide levels dropped approximately 50% and the punctate immunoreactivity decreased in the dorsal horn. Lesioning both sciatic nerves did not accelerate nor increase the extent of peptide loss compared to monolateral lesions. Immunocytochemistry showed that after bilateral lesioning also the punctate immunoreactivity in the dorsal horn decreased less drastically. However, FRAP staining of the dorsal horn decreased according to the lesion paradigms, mono- and bilaterally with the same intensity. Therefore nerve lesions trigger the process, but the peptidergic loss seems intraspinally regulated. In addition, both kinds of abnormal neurite outgrowth similarly altered peptide levels and distribution in the spinal cord. Our data suggest that pain states related to peripheral nerve lesions may be due to opiate peptide loss rather than to neuroma.

Animals↗