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Biomedical subjects

M Conti

Publications and source records attributed to M Conti.

At least 181 records · Page 10Linked to original sources
PubMed1993

[Treatment of hypertrophic cardiomyopathy with a combination of carnitine and beta blockaders. Review of the literature. Description of a clinical case and long-term follow up].

In the past decade, strategies for managing heart failure have changed. The use of beta blockers, although still in the experimental stage, has proved effective in some cases. The protective action of beta-blocking agents against chronic catecholamine stimulation may be enhanced by the combination with L-carnitine. This substance plays an important and synergistic role 1) as an important source of energy due to fatty acid oxidation, and 2) by avoiding the accumulation of lipids in the myocardium. The successful follow-up of a case of dilated cardiomyopathy is critically reviewed. Treatment with the L-carnitine-propranolol combination restored cardiac function in a 52-year-old man with dilated cardiomyopathy: a 50% reduction in mitral EPSS (E Point Septal Separation), from 20 to 10 mm was obtained with the above mentioned therapy; as well as a decrease from 60 to 57 mm in diastolic diameter. Our experience suggests promising benefits in adopting beta blockers combined with L-carnitine therapy in myocardial failure secondary to dilated cardiomyopathy.

Adrenergic beta-Antagonists↗
PubMed1993

[Temporary caval filters. Indications, problems and results].

The authors report their experience with the temporary placement of inferior vena caval filters to prevent pulmonary embolism in acute deep venous thrombosis patients. Twenty devices--6 Filcard and 4 Bruneau type--were positioned and left in situ over a time period ranging 4 to 14 days (mean: 9.8). In one patient the filter was positioned and no adjunctive medical therapy given to provide protection before nephrectomy; five patients were treated with i.v. heparin that provided no vein patency but prevented disease progression. Due to failure in positioning infusion guide catheters within the thrombus, four patients were submitted to fibrinolysis and heparin therapy: when the thrombus stabilized on angiographic images, heparin alone was administered and then followed by orally administered coumarin anticoagulants. In two cases partial thrombosis resolution was achieved, but with no significant improvement in patency rate. Ten patients underwent in situ fibrinolysis: six of them exhibited moderate improvement in femoroiliac axis patency and in three patients the inferior vena cava was successfully recanalized. No patient had any clinical evidence of pulmonary embolism. One case had cranial thrombus spread which was successfully treated with fibrinolysis. In our opinion, to control possible thrombotic involvement of the device, the patients candidate for temporary inferior vena caval filters must be easy to "manage" and exhibit no contraindications fibrinolysis and anticoagulant treatment.

Humans↗
PubMed1993

[Assessment of effectiveness of a reperfusion solution in heart surgery].

Technics of myocardial protection used in cardiac surgery have been dramatically improved with the use of cardioplegic solutions. These solutions (particularly blood cardioplegic solutions) are routinely administered during open heart surgery. When unclamping the aorta, reperfusion of the ischemic heart with oxygenated blood induces reperfusion injury. Consequently, solutions capable of reducing cellular damage due to reperfusion have been designed. The effectiveness of a reperfusion solution was assessed by a randomized double-blind study including 14 patients with coronary disease. Five biochemical and physiological parameters were measured: coronary resistance, oxygen uptake, total adenine nucleotides, malonaldehyde and lactate. The solution attenuated the reperfusion phenomenon: coronary resistance remained stable, oxygen uptake was increased at the beginning of reperfusion, the pool of nucleotides was preserved and lactate production was reduced. A new study on a larger number of patients is mandatory to establish the place of this reperfusion solution in myocardial protection, particularly in the case of prolonged ischemic time.

Adenine Nucleotides↗
PubMed1993

Effects of alpha-tocopherol on antioxidant enzyme activity in human fibroblast cultures.

The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (Cat) were determined in human fibroblast cultures at four concentrations of exogenous alpha-tocopherol: 0.2, 2.5, 10 and 50 micrograms/ml of culture medium, or without alpha-tocopherol. Relationships between alpha-tocopherol levels and the activities of SOD and GPx were identified. The cellular alpha-tocopherol level correlated with GPx activity (p < or = 0.01) and inversely correlated with SOD activity (p < or = 0.003), but only when alpha-tocopherol was added to the culture medium. The variations in the cellular GPx/SOD ratio depended on the level of cellular alpha-tocopherol (p < or = 0.001). Furthermore, there was a strong inverse correlation between SOD and GPx activity (p < or = 0.0001). Cat activity did not correlate either with cellular alpha-tocopherol concentration, or with SOD or GPx activity. These results underline the complex interplay between alpha-tocopherol and other antioxidant systems in human fibroblast cultures.

Catalase↗
PubMed1992

A polymerase chain reaction strategy to identify and clone cyclic nucleotide phosphodiesterase cDNAs. Molecular cloning of the cDNA encoding the 63-kDa calmodulin-dependent phosphodiesterase.

Multiple isozymes of cyclic nucleotide phosphodiesterases (PDEs) are expressed simultaneously in mammalian tissues. To identify and clone these PDEs, a polymerase chain reaction (PCR) strategy was developed using degenerate oligonucleotide primers designed to hybridize with highly conserved PDE DNA domains. Both known and novel PDEs were cloned from rat liver, the mouse K30a-3.3 lymphoma cell line, and a human hypothalamus cDNA library, demonstrating that these PCR primers can be used to amplify the cDNA of multiple PDE isozymes. One unique mouse PDE clone was found to encode a polypeptide identical with the corresponding portion of the bovine brain 63-kDa calmodulin-dependent PDE as reported in the companion article (Bentley, J. K., Kadlecek, A., Sherbert, C. H., Seger, D., Sonnenburg, W. K., Charbonneau, H., Novack, J. P., and Beavo, J. A. (1992) J. Biol. Chem. 267, 18676-18682). This mouse clone was used as a probe to screen a rat brain cDNA library for a full-length clone. The conceptual translation of the nucleotide sequence of the resulting rat clone has an open reading frame of 535 amino acids and maintains a high degree of homology with the bovine 63-kDa calmodulin-dependent PDE, indicating that this protein is likely to be the rat homolog of the 63-kDa calmodulin-dependent PDE. Expression of the full-length clone in Escherichia coli yielded a cGMP hydrolyzing activity that was stimulated severalfold by calmodulin. Northern blot analysis demonstrated that the mRNA encoding this PDE is highly expressed in rat brain and also in the S49.1 T-lymphocyte cell line. These data demonstrate that the PCR method described is a viable strategy to isolate cDNA clones of known and novel members of different families of PDE isozymes. Molecular cloning of these PDEs will provide valuable tools for investigating the roles of these isozymes in regulation of intracellular concentrations of the cyclic nucleotides.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Characterization of the structure of a low Km, rolipram-sensitive cAMP phosphodiesterase. Mapping of the catalytic domain.

Considerable structural similarities are present in a region of approximately 270 amino acids in most known cyclic nucleotide phosphodiesterase (PDE) sequences, opening the possibility that this region encodes the catalytic domain of the enzyme. To test this hypothesis, the structure of a high affinity cAMP PDE (cAMP-PDE) was analyzed by deletion mutations and site-directed mutagenesis. A ratPDE3 cDNA was mutated using a strategy based on fragment amplification by polymerase chain reaction. The effect of the introduced mutations was determined by expressing wild type and mutated proteins in prokaryotic and eukaryotic cells. The level of expression of the PDE protein was monitored by immunoblot analysis using two specific cAMP-PDE polyclonal antibodies and by measuring the PDE activity. After removal of a 99-amino acid region at the carboxyl terminus flanking the conserved domain, the protein retains its catalytic activity even though its Km and velocity were changed. Internal deletions at the amino terminus of this PDE showed that the enzyme activity was increased when a 97-amino acid fragment (from Tyr49 to Lys145) was removed. Further deletions within the amino terminus produced inactive proteins. Within the domain that appears essential for catalysis, 1 threonine and 2 serine residues are conserved in all PDEs. Substitutions of the invariant threonine (Thr349) present in the most conserved region with alanine, proline, or serine yielded proteins of the correct size and a level of expression comparable to the wild type PDE. However, in both expression systems used, proteins were completely devoid of the ability to hydrolyze cyclic nucleotides, except when the threonine was substituted with a serine. Conversely, mutations of 2 other conserved serine residues (Ser305 and Ser398) present in the catalytic domain either had no effect or produced changes only in Km and Vmax, but did not abolish catalytic activity. In addition, 2 histidine residues (His278 and His311) present in proximity to Thr349 appeared to be essential for the structure of the catalytic domain, since any substitution performed in these residues yielded an inactive enzyme. Mutations of a serine residue (Ser295) in the region homologous to the cAMP binding site of the regulatory subunit of the cAMP-dependent protein kinase demonstrated that this region does not have the same function in the two proteins. These data provide direct evidence that a 37-kDa domain, which in part corresponds to the region of conservation in all PDEs, contains the catalytic domain, and that threonine and histidine residues are probably involved in catalysis and/or are essential for the conformation of an active enzyme.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Mother-to-child transmission of hepatitis C virus detected by nested polymerase chain reaction.

Serum samples from eight pregnant women and their offspring were studied by nested polymerase chain reaction (PCR) for detection of hepatitis C virus (HCV) RNA to evaluate mother-to-child transmission of this virus. The mothers were all infected with human immunodeficiency virus (HIV); none showed symptoms of HCV infection. Anti-HCV antibodies were tested for by recombinant immunoblot assay. HCV viral sequences were found in five of the mothers and four of eight children, three of them at birth. Viremia was persistent in one infant who had chronic transaminase elevation and persistently remained anti-HCV-positive. The other three babies had intermittent viremia; all were asymptomatic and lost anti-HCV antibodies during follow-up. This loss of antibodies was also observed in PCR-negative infants. Thus, these results demonstrate transmission of HCV from mother to child by women coinfected with HCV and HIV. They indicate the usefulness of PCR for direct and early detection of HCV viremia in neonates.

Base Sequence↗
PubMed1992

Unique adenosine 3',5' cyclic monophosphate phosphodiesterase messenger ribonucleic acids in rat spermatogenic cells: evidence for differential gene expression during spermatogenesis.

Four cAMP phosphodiesterase (cAMP-PDE) genes (ratPDE1, ratPDE2, ratPDE3, and ratPDE4) are expressed in the rat testis (Swinnen et al., PNAS USA 1989; 86:5325). Since multiple ratPDE1 and ratPDE2 mRNAs were present in male germ cells, their developmental expression was investigated by using purified spermatogenic cell populations. RatPDE1 mRNAs (4.0 and 2.8 kb) were found to be abundant in pachytene spermatocytes. RatPDE1 mRNA levels were decreased in round spermatids and absent from condensing spermatids/residual bodies. However, multiple ratPDE2 mRNAs (4.0, 3.5, 3.1, 2.8, and 2.4 kb) were abundant in round spermatids, and lower amounts were present in condensing spermatids/residual bodies. Transcripts related to ratPDE2 were also present in mouse round spermatids. Chromatography of germ cell cytosol identified two peaks of cAMP-PDE activity. Whereas peak A was evident in all germ cell populations examined, peak B was present in pachytene spermatocytes and round spermatids, but was at the limit of detection in condensing spermatids/residual bodies. The large decrease in peak B activity in condensing spermatids/residual bodies may be related to the drop in ratPDE1 mRNA levels observed during spermatogenesis. The sustained peak A activity in condensing spermatids/residual bodies coincides with the presence of ratPDE2 mRNA in these cells and suggests that the ratPDE2 enzyme may function during spermiogenesis and in spermatozoa.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Prognosis of transient global amnesia: a long-term follow-up study.

A long-term follow-up study was performed on patients with transient global amnesia (TGA) in order to evaluate the prognosis, the recurrence rate and the occurrence of stroke and dementia. 102 patients (57 women, 45 men; mean age 62.8 +/- 9.4 years) were prospectively included and followed up. The follow-up duration ranged between 12 and 241 months with an average value of 82.2 +/- 51.1 (mean +/- SD). The death rate showed no difference from that of sex- and age-matched subjects. TGA recurred in 19 cases (18.63%). Only 4 patients suffered subsequent stroke, and only 3 showed intellectual deterioration. TGA prognosis was shown to be better than that of RIA and lacunar patients.

Adult↗
PubMed1992

Multivariate analysis of the variables affecting left ventricular filling in normal subjects.

Pulsed Doppler measurements of left ventricular filling (LVF), two-dimensional and M-mode echocardiograms were performed in 189 healthy subjects, in order to evaluate factors influencing LVF Doppler indexes in normal subjects. LVF Doppler indexes (peak E, peak A, peak E/peak A, deceleration rate of peak E (ED) were related by univariate and multivariate analyses with the following parameters: age, sex, heart rate, systolic and diastolic blood pressure, aortic root and left atrial dimensions, left ventricular mass index, left ventricular shortening fraction. The stepwise analysis showed that age by itself explained up to 18% of peak E variance, 50% of peak A variance, 61% of peak E/peak A variance and 25% of ED variance. The other variables entered into the regression, slightly improved the predictive power (less than 10%). In conclusion, age is the major independent factor affecting LVF in normal subjects, although other variables show significant correlation also after age adjustment.

Age Factors↗
PubMed1992

Dementia associated with lacunar infarction.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the number of patients with lacunar lesions who develop dementia and to evaluate in patients with and without dementia the relevance of risk factors for cerebrovascular disease, the occurrence of leukoaraiosis, the volume and location of vascular lesions, the size of ventricular and subarachnoid spaces, and stroke recurrence. METHODS: One hundred eight patients in whom computed tomograms revealed lacunar lesions that could account for their clinical neurological pictures were followed up for an average of 4 years after their first lacunar stroke. RESULTS: Twenty-five patients (23.1%) developed dementia. The prognosis regarding occurrence of dementia during the follow-up period, evaluated by the Kaplan-Meier method, was significantly worse in subjects with the greatest evidence of cerebral atrophy (p less than 0.009) and in subjects who underwent new focal cerebrovascular episodes (p less than 0.000001). No differences were seen in the frequency of vascular risk factors or the site or volume of lesions between the demented and nondemented groups. CONCLUSIONS: Patients with lacunar infarcts suffer from dementia 4-12 times more frequently than the normal population. Cerebral atrophy and recurrent stroke, as well as other as-yet unclarified factors, are involved in producing dementia.

Aged↗
PubMed1992

Protective activity of silipide on liver damage in rodents.

The activity of silipide, a silybin-phosphatidylcholine complex (IdB 1016), was tested in different models of liver damage in rodents. After oral administration, silipide exhibited a significant and dose-related protective effect against the hepatotoxicity induced by CCl4, praseodymium, ethanol and galactosamine. The ED50 values for inhibition of the rise in ASAT and ALAT levels caused by CCl4 and praseodymium and for antagonism of the increase in liver triglycerides caused by ethanol ranged from 93 to 156 mg/kg (as silybin). At a dose of 400 mg/kg (as silybin), silipide was also active in protecting against paracetamol-induced hepatotoxicity. Silybin and phosphatidylcholine at doses equivalent to those contained in the active doses of silipide failed to show any significant protective activity in these models. The liver protective effect of silipide is probably related to its antioxidant activities and to a stimulating effect on the hepatic synthesis of RNA and proteins.

Acetaminophen↗