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Biomedical subjects

M R Costa

Publications and source records attributed to M R Costa.

At least 19 recordsLinked to original sources
PubMed2005

Risk factors for type 2 diabetes in women attending menopause clinics in Italy: a cross-sectional study.

OBJECTIVE: To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause. SUBJECTS: Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms. METHODS: Cross-sectional study with no exclusion criteria. Type 2 diabetes was defined according to National Diabetes Data Groups Indications and the fasting blood glucose at an oral glucose tolerance test within the previous year. RESULTS: Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged < 50 years, the multivariate odds ratios (OR) of type 2 diabetes were 1.31 (95% confidence interval (CI), 0.99-1.74) for women aged 50-52 years, 1.66 (95% CI, 1.27-2.17) at 53-56 years and 2.84 (95% CI, 2.20-3.67) in women aged > or = 57 years. Type 2 diabetes was less frequently reported in more educated women (OR high school/university vs. primary school = 0.44 (95% CI, 0.36-0.55)). Being overweight was associated with an increased risk of type 2 diabetes. In comparison with women reporting a low level of physical activity, the multivariate OR of type 2 diabetes was 0.67 (95% CI, 0.54-0.84) for women reporting regular physical activity. In comparison with premenopausal women, the multivariate OR of type 2 diabetes was 1.38 (95% CI, 1.03-1.84) in women with natural menopause. This finding was present also after allowing for the potential confounding effect of age. The multivariate OR of diabetes for users of hormonal replacement therapy was 0.58 (95% CI, 0.46-0.73). CONCLUSIONS: This large cross-sectional study suggests that postmenopausal women are at higher risk of type 2 diabetes after allowance for the effect of age. Other main determinants of risk of type 2 diabetes in women around menopause were low socioeconomic status and being overweight. Diabetes was found less frequently in those taking hormone replacement therapy.

Age Distribution↗
PubMed2002

Synthesis, characterization and biodistribution of bisphosphonates Sm-153 complexes: correlation with molecular modeling interaction studies.

Bisphosphonates (BPs) are characterized by a P-C-P backbone structure and two phosphonic acid groups bonded to the same carbon, and are established as osteoclast-mediated bone resorption inhibitors. The nature of the groups attached to the central carbon atom are responsible in determining the potency of bisphosphonates as anti-resorption drugs. However, it is not yet clear the exact relationship between their molecular structure and pharmacologic activities. In this study, molecular geometries of pamidronate, alendronate and neridronate, differing only in the length of the aliphatic chains, were predicted by molecular mechanics and their interactions with hydroxyapatite, the main bone mineral component, were examined. We report the synthesis and radiochemical characterization of 153Sm complexes with pamidronate, alendronate and neridronate. Hydroxyapatite binding and biodistribution studies of these complexes have shown a good correlation with the theoretical molecular modeling interaction studies. So, it is possible to conclude that computational chemistry techniques are a good approach to evaluate specific interactions and may play a relevant role in determining the relative ability of BPs to mineral bone, and open new perspectives to the design of new BPs with increased pharmacological activity. These techniques could be extended to BPs as ligands to carrier radioactive metals, aiming for new bone therapeutic radiopharmaceuticals.

Alendronate↗
PubMed2001

Expression and function of ganglioside 9-O-acetyl GD3 in postmitotic granule cell development.

We have shown previously that the Jones monoclonal antibody (Jones mAb) recognizes 9-O-acetyl GD3 expressed during periods of neuronal migration and neurite outgrowth in the developing rat nervous system. In the present study we investigated the expression of this ganglioside in the developing cerebellum and correlated this expression with granule cell migration. Electron microscopic immunocytochemistry revealed that around the peak of cerebellar neuronal migration (7-day-old rat), 9-O-acetyl GD3 was localized at the contact sites between migrating granule cells and radial glia in the external granular layer and prospective molecular layer. In addition, using microexplant and slice cultures of the postnatal rat cerebellum, we tested whether the ganglioside detected by our antibody contribute to the regulation of neuronal migration in the cerebellar cortex. We have shown that the Jones mAb blocks the migration of neurons in a dose-dependent manner. These findings suggest strongly that 9-O-acetyl GD3 is involved in granule cell migration in the developing cerebellum.

Animals↗
PubMed1991

Treatment of experimental cryptococcosis with SCH 39304 and fluconazole.

The efficacy of two triazoles, SCH 39304 and fluconazole, in the treatment of disseminated cryptococcosis in Wistar rats was determined. A total of 160 rats were inoculated intracardiacally with 2 x 10(5) cells of Cryptococcus neoformans. Both drugs were administered by gavage once daily, at three doses (8, 16, and 32 mg/kg/day). Two treatment schedules were followed: (i) treatment began 1 week after infection and continued for 3 weeks and (ii) prophylaxis treatment began 3 days before infection and continued an additional 3 weeks. Evaluation was based on (i) macroscopic examination of lungs, (ii) microscopic examination of brains and lungs, (iii) histopathology of brains and lungs, and (iv) determination of number of CFU in brains. The number of CFU was the best measure of activity. SCH 39304 was more active than fluconazole in both regimens, and, prophylactically, SCH 39304 was able to achieve biological cures.

Animals↗
PubMed1990

[Methodologic and therapeutic approach to patients in shock].

The authors extensively review pathophysiology and clinical aspects of the several forms of shock. Then they report a statistical evaluation of the incidence of the different shocks in the Campania area and an analysis of the therapeutic protocols used in several medical centers. From January 1983 to May 1986, 212 patients in shock have been followed: 90 patients with hypovolemic shock; 81 patients with cardiac shock; 24 patients with shock caused by abnormal peripheral distribution; 17 patients with obstructive shock; Furthermore, from January to May 1986, in a multicenter cooperative study (69 medical centers evenly distributed all over Italy) operational factors that could be considered prognostic factors have been investigated utilizing a questionnaire. Finally the authors extensively discuss the therapeutic management of shock proposing new therapeutic protocols based on recent knowledge concerning the pathophysiology of the several clinical features investigated.

Anaphylaxis↗
PubMed1984

Cyclic AMP-dependent phosphorylation of the alpha subunit of the sodium channel in synaptic nerve ending particles.

In purified preparations of voltage-sensitive sodium channels, the alpha subunit is selectively phosphorylated by cAMP-dependent protein kinase (Costa, M. R. C., Casnellie, J. E., and Catterall, W. A. (1982) J. Biol. Chem., 7918-7921). We have developed methods to measure sodium channel phosphorylation in both lysed synaptosomal membranes and intact synaptosomes. Incubation of lysed synaptosomal membranes with exogenously added catalytic subunit of cAMP-dependent kinase and [gamma-32P]ATP resulted in rapid phosphorylation of the alpha subunit as detected by specific immuno-precipitation, sodium dodecyl sulfate-gel electrophoresis, and autoradiography. Analysis of tryptic phosphopeptides revealed five major sites of reaction. The level of phosphorylation of these sites on the sodium channel in intact synaptosomes was monitored using a rephosphorylation method in which those sites not phosphorylated in situ were labeled with [gamma-32P]ATP and exogenously added protein kinase after lysis of the synaptosomes. Incubation of synaptosomes with 8-Br-cAMP completely blocked labeling of the alpha subunit in rephosphorylation indicating marked stimulation of phosphorylation of the sites on the sodium channel in situ. Phosphorylation was complete in 15 s and all four of the tryptic phosphopeptides detected under these conditions could be phosphorylated in situ. These results show that the sodium channel can be rapidly phosphorylated by endogenous cAMP-dependent protein kinase in intact synaptosomes. In addition, since ATP and protein kinase are only available inside the synaptosomes, they also show that the alpha subunit is a transmembrane polypeptide exposed on both sides of the synaptosomal membrane. The functional consequences of 8-Br-cAMP-stimulated phosphorylation were examined using ion flux and neurotoxin-binding methods. Binding of saxitoxin and scorpion toxin were unaffected, but neurotoxin-activated 22Na+ influx mediated by the sodium channel was reduced 16 to 26% (P less than 0.01) under various experimental conditions. The potential physiological significance of this action is considered.

Amphibian Proteins↗
PubMed1984

Phosphorylation of the alpha subunit of the sodium channel by protein kinase C.

The alpha subunit of the purified voltage-sensitive sodium channel from rat brain is rapidly phosphorylated to the extent of 3-4 mol phosphate/mol by purified protein kinase C. The alpha subunit of the native sodium channel in synaptosomal membranes is also phosphorylated by added protein kinase C as assessed by specific immunoprecipitation and polyacrylamide gel electrophoresis of labeled membranes. Our results suggest coordinate regulation of sodium channel phosphorylation state by cAMP-dependent and calcium/phospholipid-dependent protein kinases.

Animals↗
PubMed1982

Selective phosphorylation of the alpha subunit of the sodium channel by cAMP-dependent protein kinase.

The alpha subunit of the sodium channel purified from rat brain is rapidly and selectively phosphorylated by the catalytic subunit of cAMP-dependent protein kinase to a level of 3 to 4 mol of 32P/mol of saxitoxin-binding activity. The rate of phosphorylation is comparable to that of the synthetic peptide analog of the phosphorylation site of pyruvate kinase, one of the best substrates for cAMP-dependent protein kinase. An endogenous cAMP-dependent protein kinase that is present in the partially purified sodium channel preparations also selectively phosphorylates the alpha subunit. The specificity and rapidity of the phosphorylation reaction are consistent with the hypothesis that the alpha subunit is phosphorylated by cAMP-dependent protein kinase in vivo.

Amphibian Proteins↗
PubMed1982

Characterization of variant neuroblastoma clones with missing or altered sodium channels.

Variant neuroblastoma cell clones were selected for resistance to the cytotoxic effects of neurotoxins that cause persistent activation of sodium channels. Three classes of variant clones were obtained: sodium channel-deficient clones, which have markedly reduced numbers of functional sodium channels; scorpion toxin-resistant clones, which have sodium channels with an altered interaction with scorpion toxin; and parental-type clones, which have functional sodium channels similar to the ones from N18 cells but have other heritable alterations that confer toxin resistance. The frequency of conversion to all three variant phenotypes was enhanced by treatment with the missense mutagen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), suggesting that all three variant phenotypes are the result of mutational events. Incorporation of [35S]methionine into the alpha-subunit of the sodium channel (Mr = 270,000; pI = 5.8 +/- 0.2) was studied in normal and variant clones by affinity chromatography on wheat germ agglutinin/Sepharose followed by analysis of labeled polypeptides by 1- and 2-dimensional gel electrophoresis. Sodium channel-deficient clones do not synthesize the alpha-subunit of the sodium channel, suggesting that mutations in these clones block expression of the gene for this protein subunit. The scorpion toxin-resistant clone LV10 synthesizes an alpha-subunit which has a molecular weight and pI similar to those of the parental clones within the resolution of the methods used.

Animals↗
PubMed1979

Presence of free cyclic AMP receptor protein and regulation of its level by cyclic AMP in neuroblastoma-glioma hybrid cells.

Neuroblastoma-glioma hybrid cells of line 108CC-5 were found to contain high levels of soluble adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase activity and high levels of two specific cAMP receptor proteins, RI and RII. Treatment of the hybrid cells with dibutyryl cAMP increased the level of RI but did not significantly affect the level either of RII or of cAMP-dependent protein kinase activity. The effect of dibutyryl cAMP could be mimicked by prostaglandin E1 and 3-isobutyl-1-methylxanthine, both of which are known to raise cAMP levels in neuroblastoma-glioma hybrid cells. Both in control as well as in dibutyryl cAMP-treated cells, RII but not RI was associated with cAMP-dependent protein kinase. Several lines of evidence suggest that RI represents the free regulatory subunit of type I cAMP-dependent protein kinase. The presence of this regulatory subunit as free cAMP receptor protein in neuroblastoma-glioma hybrid cells may be of significance with respect to the regulation of growth and differentiation in tumor cells.

Animals↗
PubMedDate not supplied

Factors associated with climacteric symptoms in women around menopause attending menopause clinics in Italy.

OBJECTIVE: To obtain data on correlates of climacteric symptoms in women around menopause attending menopause clinics in Italy. METHODS: Since 1997 a large cross sectional study has been conducted on the characteristics of women around menopause attending a network of first level menopause outpatient's clinics in Italy. A total of 66,501 (mean age 54.4 years) women are considered in the present paper. RESULTS: The odds ratios of moderate and severe hot flashes/night sweats were lower in more educated women and (for severe symptoms only) in women reporting regular physical activity. Depression, difficulty to sleep, forgetfulness and irritability tended to be less frequent in more educated women and (depression only) in women reporting regular physical activity. Parous women reported more frequently these symptoms. CONCLUSIONS: This large study confirms in Southern European population that low education, body mass index and low physical activity are associated with climacteric symptoms. Parous women are at greater risk of psychological symptoms.

Adult↗
PubMedDate not supplied

Blood culture as a parameter of treatment effectiveness in experimental histoplasmosis of the hamster.

The aim of this study was to determine the value of blood culture as a parameter of treatment effectiveness in experimental histoplasmosis. A total of thirty five hamsters, weighing approximately 120g, were inoculated intracardially with 0.1 ml of a suspension containing 4 x 10(7) cells/ml of the yeast phase of H. capsulatum. Treatments were started one week after the infection and lasted for 3 weeks. The azoles, (itraconazole, saperconazole and fluconazole) were administered once a day by gavage, at a dose of 8 mg/kg; Amphotericin B was given intraperitoneally every other day at a dose of 6mg/kg. Blood samples (1 ml) were obtained by heart punction from the 4th day after infection and were seeded in Sabouraud honey-agar and BHI-agar. The hamsters that survived were killed one week after treatment completion and the following criteria were considered for treatment evaluation: 1) rate of spontaneous death, at the end of the experience; 2) microscopic examination of Giemsa smears from liver and spleen and 3) determination of CFU in spleen cultures. Amphotericin B was the most effective drug, with negative blood cultures at day 20, negative spleen cultures in all cases and all the animals survived until the end of the study. Fluconazole was the less effective drug, blood cultures were positive during the whole experience, spleen cultures showed a similar average of CFU when compared with the control animals and 42.8% of these animals died. Saperconazole and itraconazole showed a similar activity, with survival of all hamsters and negative blood cultures at 23 and 26 days respectively. Blood culture seems to be valuable parameter for treatments' evaluation in experimental histoplasmosis of the hamster.

Amphotericin B↗
PubMedDate not supplied

[The etiology and epidemiology of dermatophytoses in Goiânia, GO, Brazil].

Dermatophytoses are superficial infections that may lead to lesions of keratinized tissues, like skin, hair and nails. A total of 6068 individuals from Goiânia, GO, with suspected dermatophytic lesions were examined over a period of five years (1993-1997) in order to determine the incidence and etiology of dermatophytosis. Material collected from different body parts was submitted to direct microscopic examination using KOH, cultured in Sabouraud agar and microscopically examined for colony morphology, with the identification of 1595 dermatophytes. Trichophyton rubrum (37.4%), T. mentagrophytes (36.4%) and Microsporum canis (16%) were the species most frequently isolated. Dermatophytes were more frequently found producing lesions in the feet (30.5%), inguinal and crural regions (17.8%) and glabrous body regions (15.5%). The distribution of the different infected body sites was determined in terms of the respective etiologic agents found. Better hygiene conditions and an early diagnosis are the most important tools to control and reduce the incidence of dermatophytosis in Goiânia, GO.

Adolescent↗