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Biomedical subjects

M Conti

Publications and source records attributed to M Conti.

At least 235 records · Page 13Linked to original sources

Bleeding time is prolonged during oral anticoagulant therapy.

We have performed the BT test in 55 patients undergoing oral anticoagulant therapy monitored by means of Thrombotest (TT). Patients in steady state of anticoagulation showed longer BT than normal controls; patients in overdose phase had longer BT values than either controls or patients in steady state. After recovery the overdose phase patients showed BT values not different from those of the controls. Moreover we were able to find in our patients a significant linear correlation between BT and TT. Impairment in primary haemostasis could be due either to a scarce fibrin deposition in the haemostatic plug or to deficiency of a possible vitamin K dependent vascular "bleeding factor".

Administration, Oral↗

Is the imbalance between thrombin and plasmin activity in diabetes related to the behaviour of antiplasmin activity?

The aim of this study was to evaluate the balance between thrombin and plasmin activity in a group of 79 diabetic patients (IDDM and NIDDM). For this purpose we determined fibrinopeptide A (FPA) and B beta 15-42, specific products of thrombin and plasmin activity. Moreover we investigated the behaviour of antithrombin III and alpha 2 antiplasmin, important inhibitors of blood coagulation and fibrinolysis. Results show an increase both in FPA and B beta 15-42 in IDDM and NIDDM patients when compared to healthy controls. However the ratio between B beta 15-42 and FPA was lower than in controls indicating an imbalance between thrombin and plasmin activity. Antithrombin III levels were not different from the controls and no correlation was found with Hb A1c. alpha 2 antiplasmin was found to be higher in IDDM when compared both with NIDDM and controls. A non linear correlation was found between Hb A1c and alpha 2 AP in both diabetic groups. We conclude that the imbalance between thrombin and plasmin activity may have a role in determining fibrin deposition. These subclinical abnormalities, unrelated to vascular complications and duration of the disease, may progressively contribute to the development of the vascular complications in diabetes.

Adolescent↗

Effect of vitamin E on 2-deoxy-D-glucose uptake in human fibroblast cultures.

2-Deoxy-D-glucose (2-DOG) uptake was tested in human fibroblast cultures in the presence and absence of vitamin E. Addition of 10 micrograms/ml vitamin E to the culture medium significantly reduced this uptake for 2-DOG concentrations of 0.005 to 10 mmol/liter (P less than or equal to 0.01). The decrease of 2-DOG uptake was inversely proportional to the rise in 2-DOG concentration (P less than or equal to 0.01). The presence of vitamin E reduced by 71% the average cellular level of lipid peroxides (expressed as thiobarbituric acid reactive substances) and caused a small but significant decrease in the cholesterol concentration (P less than or equal to 0.01). These last results might explain the decrease in 2-DOG uptake observed in the presence of vitamin E.

Biological Transport↗

Long term treatment with adenosine analogs modifies the responsiveness of immature rat Sertoli cell in culture.

A1 inhibitory adenosine receptors are present in cultured Sertoli cells. Activation of these receptors by short term exposure to adenosine agonists attenuates the adenylate cyclase activity and reduces FSH stimulation of androgen aromatization to estrogen. In the present study it was investigated how long term activation of the adenosine inhibitory system affects the responsiveness of the Sertoli cell. Sertoli cells from 15- to 17-day-old Sprague-Dawley rats were incubated with medium containing adenosine deaminase (1 IU/ml) in the presence or absence of 100 nM N6-2-phenyl-isopropyl-adenosine (PIA) for 24-48 h. At the end of this pretreatment medium was changed, and cell responsiveness was measured in terms of cAMP and estrogen production. In control cells, FSH-stimulated cAMP and estradiol production were inhibited by PIA, with an EC50 of 0.70 +/- 0.13 nM. This inhibitory effect was reduced in cells that had been pretreated for 24-48 h with 100 nM PIA. The PIA concentration-response curve of pretreated cells was shifted to the right, with a 4-fold increase in the EC50. Similar effects were also evident when adenosine itself or nonmetabolizable adenosine analogs other than PIA were used in the pretreatment. In addition to these changes in the inhibitory responses, PIA pretreatment increased the response of the Sertoli cell to FSH and forskolin in terms of both cAMP accumulation and estradiol production. Potentiation of the hormonal response was due to an increase in basal and maximal stimulation without significant changes in the total stimulation. This effect was dependent on the concentration of PIA used during the pretreatment. The increase in estradiol production was also evident when cells were stimulated with (Bu)2cAMP, suggesting that adenosine analog pretreatment affects steps distal to cAMP accumulation. Moreover, the responses to both the PIA inhibitory signal and FSH stimulation were restored to control levels when pretreated cells were incubated in fresh medium in the absence of PIA for 24 h. The long term PIA effects were also blocked by pretreatment in the presence of the A1 receptor antagonist 8-[4-([([ (2-amino-ethyl)amino]carbonyl)methyl]oxy)phenyl]1,3- dipropylxanthine. These results indicate that the A1 adenosine system present in the Sertoli cell becomes refractory after prolonged exposure to adenosine analogs. Furthermore, PIA pretreatment produced a potentiation of the Sertoli cell response to stimulatory signals by affecting several steps of the cAMP-dependent pathway.

Adenosine↗

Thyrotropin potentiation of insulin-like growth factor-I dependent deoxribonucleic acid synthesis in FRTL-5 cells: mediation by an autocrine amplification factor(s).

Studies were undertaken to determine the mechanism(s) by which TSH and insulin-like growth factors (IGFs) act synergistically to stimulate DNA synthesis in FRTL-5 cells. As observed in previous studies, the response of these cells to a combination of TSH plus IGFs (or micromolar concentrations of insulin) greatly surpass the sum of the effects of the individual hormones when acting alone. Part of this synergism was eliminated when media containing TSH and IGF-I were replaced every 4 h with fresh media. This suggested that part of the synergism between TSH and IGF-I on cell proliferation is mediated by an amplification factor(s) (AF) released from FRTL-5 cells during incubation. The AF was not specific for thyroid cells, however, since conditioned medium from TSH treated FRTL-5 cells was also found to potentiate the mitogenic effect of IGF-I in the human fibroblast cell line GM3652. It is unlikely that the AF activity secreted by these cells in response to TSH is either IGF or an IGF-binding protein, since the anti-IGF monoclonal antibody sm 1.2 did not attenuate the synergism between TSH and high concentrations of insulin on thymidine incorporation. Analysis of thymidine incorporation into DNA at different times after different patterns of exposure to TSH, IGF-I, or TSH plus IGF-I suggested that at least part of the synergism between the two hormones resulted from increasing the number of quiescent cells recruited into the cell cycle. These results suggested that the TSH-dependent AF might be acting as a competence factor. In a preliminary screen of candidate growth factors, only fibroblast growth factor (FGF) simulated the effect of AF, and its effect was smaller than that obtained with TSH-treated FRTL-5 cells. After preincubation with TSH, FRTL-5 cells exhibited greatly increased responsivity to the mitogenic effects of IGF-I that was manifested by both increased sensitivity to IGF-I, as judged by a decreased EC50, and an increase in their maximum response. TSH pretreatment, likewise, amplified subsequent DNA synthesis in response to serum and tetradecanoyl phorbol acetate. Thus, the mitogenic effect of TSH in FRTL-5 cells is due not only its stimulation of IGF production, but also to its stimulation of one or more AF that greatly enhance the responsivity of these cells to mitogenic stimuli.

Animals↗

Follicle-stimulating hormone regulation of androgen-binding protein messenger RNA in sertoli cell cultures.

FSH plays an important role in testicular Sertoli cell differentiation and function in spermatogenesis. Previous studies using rat androgen-binding protein (ABP) as a marker of FSH action on Sertoli cells have demonstrated in vivo and in vitro regulation of ABP. We now have extended these studies to examine FSH regulation of ABP mRNA using Northern blot hybridization. In the immature rat testicular ABP mRNA [1.7- and 2.3-kilobase (kb) species] increased with age and reached a maximum 20 days postpartum, coincident with an increased plasma FSH concentration. To determine the direct effect of FSH on Sertoli cells, we examined ABP mRNA in vitro. In Sertoli cell-enriched cultures FSH was found to maintain the major 1.7-kb ABP RNA transcript level over 5 days of treatment in a dose-dependent manner, whereas in the absence of FSH, ABP mRNA declined with time in culture. The ABP mRNA maintenance by FSH was accompanied by higher concentrations of secreted immunoreactive ABP, which declined in the absence of FSH. This FSH effect on ABP mRNA and secreted ABP was mimicked by the cAMP analog (Bu)2cAMP. After the decline of ABP mRNA during culture, administration of FSH did not result in a detectable increase in the 1.7-kb ABP mRNA within 3 days, whereas cAMP and c-fos mRNA were rapidly induced within 15 min. On the contrary, the level of the minor hybridizing ABP mRNA (2.3 kb) was altered by FSH, indicating differential regulation of the 1.7- and 2.3-kb hybridizing species. Also, after FSH deprivation, tissue plasminogen activator and inhibin alpha mRNA were substantially increased within 6 h of FSH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen-Binding Protein↗

[Cardiological aspects of pregnancy in women with tetralogy of Fallot. Description of a case of multiple pregnancies and review of the literature].

A case report concerning a patient who received a late surgical correction of a tetralogy of Fallot, at the age of 26, and then had the chance of two pregnancies with no or little risk. The patient was severely cyanotic (erythrocytes 6,440,000/ml-Ht 58.3%-Hb 19.5 g/100 ml) with balanced pressures between the two ventricular cavities and 72 mmHg gradient between right ventricle and pulmonary artery. Before the operation two pregnancies resulted in abortions: the former was before the correction of the cardiac malformation and the latter just after. Then two pregnancies were successful and both the newborn males were healthy and completely free from congenital diseases, and in particular cardiac. Brief examination of literature.

Adult↗

[Some analytical aspects of mescaline].

Mescaline was extracted from a vegetal powder, seazed on the "Côte d'Azur", then analyzed by several techniques (thin layer chromatography, infra-red spectrometry, gas chromatography/mass spectrometry) and determined by high performance liquid chromatography with methyl-amphetamine as internal standard. The powder contained 0.76% of mescaline. The presence of a possible isomer was noted in the powder as well as in a "old" sample of mescaline.

Chromatography, Thin Layer↗

[Effects of i.v. nicardipine in the treatment of hypertensive crisis].

The availability of i.v. nicardipine has urged us to prove this drug in the treatment of hypertensive attacks (SAP greater than or equal to 210 mmHg and/or DAP greater than or equal to 110 mmHg). Two groups of patients (each made up of ten subjects) were treated with 2 mg and 5 mg respectively of i.v. nicardipine injected for 4 min while mean systolic and diastolic arterial pressure and heart rate were registered until three hours. I.V. nicardipine administration induced in both groups of patients a decrease in systolic pressure from 20 to 30% while diastolic arterial pressure decreased from 15 to 18% in the first group and from 20 to 25% in the second one. Heart rate showed an initial mild increase following arterial vasodilator action of nicardipine whereas it decreased significantly from 120 min in the presence of an unchanged hypotensive effect of the drug. One patient did not respond to nicardipine while another felt chest pain and palpitations. In conclusion our results are satisfactory and argue for the inclusion of nicardipine among the drugs that may be considered useful for the treatment of hypertensive attacks.

Acute Disease↗

[Echocardiographic diagnosis of rupture of the interventricular septum and release into the wall of the left ventricle (with formation of pseudoaneurysm) in inferior myocardial infarction].

A case of inferior myocardial infarction in a 77 years old woman suffering from angina pectoris for 8 years, is reported. The clinical course was complicated by mild heart failure secondary to interventricular septum repture, diagnosed by Doppler-echocardiography. The patient was discharged in III-IV NYHA class with medical therapy. Then, unstable hemodynamic conditions and episodes of angina pectoris occurred again. Five months after acute myocardial infarction, echocardiography confirmed the interventricular septum defect. An echocardiographic control, performed 17 months after the acute episode, documented, besides previous data, the presence of a pseudoaneurysm of the inferior wall with a large cavity in communication with the left ventricle.

Aged↗

Signal transduction in the Sertoli cell: serum modulation of the response to FSH.

Immature Sertoli cells of the testicular seminiferous tubule maintain the expression of their differentiated phenotype when cultured in unsupplemented medium. In preliminary experiments we observed that foetal bovine serum (FBS) stimulates polyphosphoinositides (PI) hydrolysis in Sertoli cells. We then evaluated the effect of serum on the function of the immature Sertoli cell in culture, in terms of cAMP and estrogen production. Treatment of Sertoli cells for 30 min with 1-10% FBS had no effect on basal cAMP accumulation but abolished the response to FSH. The serum concentration producing half-maximal inhibition of the FSH-dependent cAMP accumulation was 0.5-1%. Comparison of the FSH-dose-response in the absence or presence of serum showed a decreased maximal response when serum was present. Sertoli cells exposed to serum were also less responsive to the beta-adrenergic agonist isoproterenol, to cholera toxin, and to forskolin. The serum inhibition was rapidly reversed upon removal of serum or incubating the cells with the phosphodiesterase inhibitor MIX (methyl-isobutyl-xanthine). Similarly to what observed with cAMP, serum affected androgen aromatization stimulated by FSH, isoproterenol, cholera toxin, forskolin and dibutyryl cAMP. These data indicate that factors present in serum can act as modulators of the Sertoli cell function in vitro by rapidly and reversibly inhibiting the cAMP and steroidogenic response of the Sertoli cell to FSH.

Animals↗

Molecular cloning of rat homologues of the Drosophila melanogaster dunce cAMP phosphodiesterase: evidence for a family of genes.

To study the structure and function of cyclic nucleotide phosphodiesterases (PDEs) involved in mammalian gametogenesis, a rat testis cDNA library was screened at low stringency with a cDNA clone coding for the Drosophila melanogaster dunce-encoded PDE as a probe. This screening resulted in the isolation of two groups of cDNA clones, differing in their nucleotide sequences (ratPDE1 and ratPDE2). In the rat testis, RNA transcripts corresponding to both groups of clones were expressed predominantly in germ cells. Additional screenings of a Sertoli cell cDNA library with a ratPDE2 clone as a probe led to the isolation of two more groups of clones (rat-PDE3 and ratPDE4). Unlike ratPDE1 and ratPDE2, these clones hybridized to transcripts present predominantly in the Sertoli cell. In the middle of the coding region, all four groups of clones were homologous to each other. The deduced amino acid sequences of part of this region were also homologous to the D. melanogaster dunce PDE and to PDEs from bovine and yeast. These data indicate that a family of genes homologous to the D. melanogaster dunce-encoded PDE is present in the rat and that these genes are differentially expressed in somatic and germ cells of the seminiferous tubule. These findings provide a molecular basis for the observed heterogeneity of cAMP PDEs.

3',5'-Cyclic-AMP Phosphodiesterases↗

The mRNA encoding a high-affinity cAMP phosphodiesterase is regulated by hormones and cAMP.

To elucidate the mechanisms by which hormones regulate cAMP phosphodiesterases (PDEs), a group of cDNA clones that had been isolated from a rat Sertoli cell library were characterized. These cDNAs are derived from a single gene (ratPDE3). The deduced amino acid sequence of the ratPDE3 cDNA corresponds to a 66,200-Da protein homologous to other testicular PDEs, to the Drosophila melanogaster dunce-encoded cAMP PDE, and to bovine and yeast PDEs. Expression of ratPDE3 in eukaryotic and prokaryotic cells leads to the appearance of a cAMP PDE with properties identical to the cAMP PDE purified from Sertoli cells. Although of different size, transcripts corresponding to ratPDE3 were present in all organs studied. In the immature Sertoli cell in culture, the level of mRNA transcripts of ratPDE3 was increased more than 100-fold by follicle-stimulating hormone or N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate treatment. Stimulation of ratPDE3 mRNA by N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate was also observed in a C6 glioma cell line. These data demonstrate that cAMP regulates the expression of one of its own degrading enzymes by an intracellular feedback mechanism that involves changes in mRNA levels.

3',5'-Cyclic-AMP Phosphodiesterases↗