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Biomedical subjects

M Motta

Publications and source records attributed to M Motta.

At least 163 records · Page 9Linked to original sources

Evaluation of the biological activity of unmodified synthetic eel calcitonin rectal capsules. Comparison with intramuscular administration and placebo.

Biological activity of eel calcitonin 100 IU administered by the rectal route was evaluated in healthy volunteers by measuring plasmatic variations of cyclic adenosine monophosphate (cAMP) after a single dose and during a 21-day treatment. This formulation appears to allow a bioavailability of the drug which is half of the same dose administered intramuscularly, and to cause a prompt and significant increase of plasma cAMP, with minimal variations of calcaemia. Repeated administration shows the persistence in time of this effect. The overall conclusion is that the amount of calcitonin absorbed through the rectal mucosa seems sufficient to induce a typical biological response related to the interaction of the hormone with its specific receptors in bone.

Administration, Rectal↗

Extracorporeal shock wave lithotripsy for urinary stone disease: our experience.

The authors report results of an 18 month study on ESWL treatment for calculosis of different tracts of the urinary apparatus. Average success rate is 80%, even if it varies depending on the site and size of the calculus. Surgery and PCN are required only in cases of unsuccessful treatment or particular forms of lithiasis. ESWL has determined advanced in the treatment of renoureteral stones in the last decade. However some significant generalized complications observed in our patients at follow-up raise doubts concerning possible, unforeseable long term effects of ESWL treatment.

Adolescent↗

Intertubular capillary changes in kidney allografts: a morphologic investigation on 61 renal specimens.

A total of 61 kidney allograft specimens (51 biopsies and 10 nephrectomies) from 44 patients were investigated. Transplant glomerulopathy (TGP) was found in 38 specimens. Electron microscopy disclosed peculiar intertubular capillary changes (ITCC) in 47 specimens (all those showing TGP and nine without TGP). They were characterized by splitting and multilayering of the basement membranes. TGP and ITCC were graded and found mild (in 23 and 22 specimens), moderate (in 11 and 16 specimens), and severe (in four and nine specimens). Both worsened with time lapse from transplantation. When both were compared in single specimens, their grading was similar or, with a few exceptions, more severe for ITCC. TGP and ITCC were more frequent in biopsies with morphologic evidence of rejection and less frequent in patients treated with Cyclosporine A. Repeated biopsies and nephrectomies were studied in 10 patients and a somewhat more precocious appearance of ITCC than of TGP was found. Earlier and more severe ITCC were found in two patients who had had two transplants as compared to those with one. Morphologic similarities between TGP and ITCC suggest a common pathogenetic mechanism related to endothelial damage. The association to the histological evidence of rejection as well as the apparently protective activity of Cyclosporine A could support the involvement of an immune-mediated mechanism in agreement with what is reported in literature. The constant association of ITCC and TGP and its possible more precocious appearance enforce the diagnostic value of the former, which allows to infer the presence or the subsequent development of TGP even in biopsies where glomeruli are lacking.

Adult↗

Medical castration with zoladex: a conservative approach to premenopausal breast cancer.

For almost a century surgical castration represented the initial standard therapy for metastatic breast cancer in premenopausal women with hormone dependent tumors. Today the suppression of ovarian function can also be obtained by the administration of supraphysiologic doses of luteinizing hormone releasing hormone (LHRH) agonists. From April 1987 to February 1989, 23 premenopausal patients with advanced breast cancer (median age 39 years, range 28-52, ER positive 20, unknown 3; prior chemotherapy 17) were treated with the LHRH agonist goserelin depot (Zoladex) at the dose of 3.6 mg. every 4 weeks. Twenty-two patients were evaluable. Serum levels of 17 beta estradiol, progesterone, FSH and LH were suppressed by goserelin and fell to postmenopausal values within 8 weeks of therapy in 77% of cases. Complete response (CR) plus partial response (PR) was documented in 7 of 22 (32%) and occurred in all major sites of disease. Five patients achieved CR (soft tissue 3, viscera 2). Response rate was higher in patients not previously treated with chemotherapy (4/6). In the present series, all responses were seen in women greater than 35 years old, regularly menstruating at the start of treatment. Time to progression for the entire case series was 22 weeks and for responders 64 weeks. Oophorectomy was performed after disease progression in four patients without success. Goserelin was well tolerated. Local cutaneous dyschromia occurred in 45% and hot flushes in 82%. Treatment efficacy of goserelin is comparable to that of oophorectomy, without the psychological trauma and the morbidity related to surgical castration.

Breast Neoplasms↗

Effect of unilateral vagotomy on serum gonadotropin concentration in rats with two testes and in hemicastrates.

The effect of right- or left-sided vagotomy on serum gonadotropin secretion was studied in rats with two testes and in hemicastrates. Right-sided vagotomy in animals with two testes in situ induced a very marked rise in serum LH levels. Left-sided vagotomy was also accompanied with a slight increase in LH secretion. The difference in serum LH levels between right-and left-sided vagotomized animals was significant. FSH levels were unaffected by either right- or left-sided vagotomy. Removal of the right or of the left testis resulted in a significant increase in serum gonadotropin levels. Unilateral vagotomy in hemicastrates did not alter the hemicastration-induced changes in serum gonadotropin hormone levels. These data indicate that the vagus nerve might have a modulatory role in the control of LH secretion in rats with two testes but not in hemicastrates. The different response in LH levels after right-sided and left-sided vagotomy suggests a functional asymmetry of the vagus nerve in the regulation of LH secretion.

Animals↗

Substance P-like immunoreactive nerve fibers of the human laryngeal mucosa--preliminary report.

Substance P (SP) is considered a primary sensory transmitter and is widely distributed within the autonomic nervous system. This study is concerned with the distribution of SP-like immunoreactive nerve fibers in the human larynx. Individual SP-like immunoreactive nerve fibers were detected in the subepithelial connective tissue of the laryngeal mucosa, in the ventricular and subglottic glandular regions and in a few nervous ganglia in the deep connective tissue. No intraepithelial SP-like immunoreactive fibers were present in our material.

Humans↗

[Evaluation of the risk of hepatitis delta virus (HDV) infection in a population of hemodialyzed patients: significance of the determination of anti-delta antibodies in the blood].

Hepatitis delta virus (HDV) is a defective virus which requires the helper function of hepatitis B virus (HBV) for replication. HDV infection occurs only during or after HDV infection. Viral infection spreads parenterally in both cases. However, it has been reported that the risk of HDV infection is limited to hemodialysed patients, unlike the risk of HBV infection. In order to verify these findings the Authors studied 108 patients undergoing periodical hemodialytic treatment in order to study the delta antibodies present in their blood. Sixty-one of these subjects had received previous blood transfusions, 15 were HBsAg positive and 7 positive for other serological markers of the hepatitis B virus. None of the subjects examined was positive for anti HDV. Our results agreed with the literature reporting an incidence of positive HDV serological markers limited to hemodialyzed patients. The Authors observed that the behaviour of the HDV serological markers can vary from patient to patient and that it is impossible to furnish diagnosis of HDV infection after HBV and HDV clearance. Since these factors can lead to underestimation of the real incidence of HDV infection in hemodialyzed patients, the Authors underline the need to perform long term epidemiological studies and to investigate all the HDV serological markers.

Antibodies, Viral↗

[Cutaneous tuberculosis with multifocal visceral involvement].

The case of a young Senegalese man who developed a form of cutaneous tuberculosis associated with a disseminated disease, successfully treated with appropriate antitubercular chemotherapy is reported. We found Mycobacterium Microti in the cutaneous ulcers, the only organism isolated after many cultural and microscopical examinations of different exudates and tissues. This mycobacterium was considered up to now to be pathogenic to rodents, but not man. Its possible pathogenicity to man (under certain situations) is also suggested, and it is expected that this possibility will be supported by other reports in the near future. In addition, stress is laid on the problems of diagnosis and classification of the cutaneous tuberculosis, so uncommon in the Western Hemisphere, and its possible association with leprosy.

Antitubercular Agents↗

Antihormonal activities of 5 alpha-reductase and aromatase inhibitors.

The problem of developing androgen antagonists has been tackled so far only by synthesizing steroids able to displace testosterone and other androgens from their specific receptor sites. The observation that testosterone has to be converted intracellularly either to 5 alpha-reduced metabolites (DHT, 3 alpha-diol, etc.) or to estrogens, in order to become fully active on androgen-dependent structures (both central and peripheral), has opened the possibility of creating molecules which prevent these conversions, and which could then block the actions of testosterone. The availability of these new compounds has allowed a better understanding of the selective physiological role of each of the metabolites of testosterone, and to provide the basis for the development of new hormone antagonists to be used in those clinical conditions for which an inhibition of the actions of testosterone is foreseen. The usefulness of these enzyme inhibitors is underlined by some examples described in this paper. The results obtained may permit the formulation of the following conclusions: (1) The conversion of testosterone to its 5 alpha-reduced metabolites occurring in the neuroendocrine structures may represent an essential step for the appearance of the inhibitory feedback effect testosterone exerts on LH secretion; (2) Testosterone exhibits its negative feedback effect on FSH secretion as such and not following the local aromatization to estrogens; (3) Testosterone exerts its effect on the intrahypothalamic stores of LHRH acting as such and not following its local conversion either to 5 alpha-reduced metabolites or to estrogenic molecules; (4) Some of the new enzyme inhibitors (e.g. 4-OH-A) may represent an interesting tool for the treatment and/or the prevention of BPH and possibly of other androgen-dependent diseases (prostate carcinoma, acne etc.), as shown by their ability to prevent the in vitro conversion of testosterone to its 5 alpha-reduced metabolites both in the normal prostate of the rat and in the human BPH tissue.

Animals↗

Testosterone and the control of hypothalamic GnRH.

The aim of the present study was to test the hypothesis that the restoring effect of testosterone on hypothalamic GnRH stores in orchidectomized rats might be linked to the intrahypothalamic transformation of the hormone into estrogenic metabolites. To this purpose, advantage has been taken of the availability of the potent antiestrogen, tamoxifen (TMX). Different groups of adult male rats castrated since 4 weeks were submitted to a 6-day treatment with testosterone propionate (TP, 2 mg/rat daily); TMX (50 or 200 micrograms/rat daily); or TP (2 mg/rat daily) plus TMX (50 or 200 micrograms/rat daily). The animals were sacrificed 24 h after the last injection, and hypothalamic GnRH content was measured by radioimmunoassay. The results have confirmed the ability of TP to counteract the decreasing effect of orchidectomy on hypothalamic GnRH stores, and have shown that TMX does not have any intrinsic activity on this parameter. Furthermore, TMX at either dose used in the present experiments, was found not to be able to abolish the restoring effect of TP on MBH-GnRH stores. It is concluded that the action of testosterone on hypothalamic GnRH does not require the conversion of the hormone into estrogens.

Animals↗

Evaluation of the nature of mildly prolonged prothrombin times.

Twenty-one asymptomatic individuals with a mildly prolonged prothrombin time (greater than 2 SD from the prothrombin time of the reference plasma) were found to have a mild isolated factor VII (F VII) defect (mean 38.8 U/dl; SD 13.2). Factor VII antigen levels were also found to be reduced (mean 45.5 U/dl; SD 7.8) in 13 of them. These figures were compared with those of 50 normals and 28 obligatory heterozygotes for F VII deficiency. The phenotypical behaviors in the propositi were found to be equal to those of the F VII congenital deficiency heterozygotes: the discrepant one (VII+) and the nondiscrepant one (VII-/R). Fifteen families of the propositi could also be studied, totalling 55 additional individuals; in 25 of them (ten pedigrees) a mild F VII deficiency was found showing the same phenotypical features of the corresponding propositi. We therefore believe that these individuals with mild F VII deficiency can be considered as heterozygotes for the defect, since the other vitamin K-dependent clotting factors were normal; the defect is transmitted throughout the kindred with the same mode of inheritance as F VII congenital deficiency; and F VII:C and F VII:Ag levels are highly comparable with those of known obligatory heterozygotes for F VII deficiency. On the grounds of a careful statistical analysis we propose a formula which allows a discrimination between the two phenotypes of the heterozygotes for F VII congenital deficiency. In addition it is suggested that sensitive tissue thromboplastins should be used to pick up these mild defects.

Adolescent↗

Evaluation of factor VII antigen in factor VII congenital deficiencies with a new ELISA assay.

An evaluation of a new Enzyme Linked Immunosorbent Assay (ELISA) factor VII:Ag assay in factor VII congenital deficiencies was carried out. This assay was compared to factor VII:C assay and the Inhibitor Neutralization Assay (INA) for factor VII:Ag, both in normals and F VII-deficient patients. The correlations between ELISA F VII:Ag and VII:C, as well as the one between INA F VII:Ag and VII:C, were good (r = .86 and .81, respectively). The correlation between the two immunologic methods of assay in normals was fairly good (r = 0.73, P less than 0.001); whereas in mild F VII deficiencies (heterozygotes for F VII deficiencies), the two methods correlated very well (r = .96). In the severe deficiencies, ELISA F VII:Ag assay allowed the evaluation of F VII protein levels below 1 u/dl. The sensitivities of the INA and ELISA assays were evaluated by creating artificially prepared plasmas containing serial amounts of purified F VII: INA was unable to pick up F VII protein levels lower than 75 ng/ml, whereas the ELISA assay could detect up to 5 ng of F VII.

Adult↗

Aging and the hypothalamo-pituitary-testicular axis in the rat.

Several experiments have been performed in order to clarify the mechanisms through which aging in male rats brings about profound modifications of the neuroendocrine system (reduced pulsatile secretion of LH and FSH, decreased serum levels of gonadotropins and testosterone, etc.). (1) It has been found that the number of mu opioid receptors decreases significantly in the hypothalami of old male rats; the substitution therapy with testosterone is ineffective in increasing the number of mu opioid receptors. These data suggest that the decrease of hypothalamic mu opioid receptors is not due to a decline of serum testosterone levels, but appears to be an independent phenomenon. (2) K opioid receptors increase significantly in the amygdala and in the thalamus of old male rats. These results show that aging, in addition to mu receptors, affects also the number of K receptors in selected areas of the brain. The increase of the number of K receptors in the amygdala might have some bearing on the decrease of serum gonadotropins observed in aged rats, since the amygdala is involved in the nervous circuitry influencing the hypothalamo-pituitary-gonadal axis. (3) The study of the release of LHRH from the hypothalamus of old male rats with an in vitro perfusion system shows that the release of the hormone is comparable in young and old animals, both in basal and in K+ stimulated conditions. These results indicate that the hypothalamus of old male rats retains the capacity of releasing LHRH both in basal and in stimulated conditions. (4) It has been observed that the number of LHRH receptors at the level of the anterior pituitary is significantly reduced in old male rats. This finding might explain the low serum levels of gonadotropins and testosterone in aged rats, due to a lack of an adequate response of the pituitary to hypothalamic LHRH.

Aging↗

Effect of oestrus cyclicity on the number of brain opioid mu receptors in the rat.

The present experiments have been performed in order to analyse whether the binding characteristics of brain opioid receptors of the mu type vary during the different phases of the oestrous cycle in the female rat. To this purpose different groups of females with a regular 4-day oestrous cycle were killed by decapitation in different phases of their oestrous cycle, i.e. at 10.00 and 16.00 h of the first and second day of dioestrus, at 10.00, 12.00, 14.00, 16.00 18.00 and 20.00 of the day of pro-oestrus, and at 10.00, 12.00 14.00, 16.00 and 18.00 of the day of oestrus. The total brains, after discarding the cerebellum, were homogenized and crude membrane preparations were obtained. On these preparations the maximal binding capacity (Bmax, index of the number of receptors) and the constant of affinity (Ka) for dihydromorphine, a typical ligand of mu opioid receptors were evaluated. Serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were measured by specific radioimmunoassays in order to exactly ascertain the different phases of the oestrous cycle. The results obtained show that the number of mu opioid receptors in the whole brain presents significant changes during the different phases of the oestrous cycle. In particular, an increase in the concentration of these receptors was observed at 12.00 h of the day of pro-oestrus and at 18.00 h of the day of oestrus; these fluctuations of the number of mu receptors were not accompanied by any change of their affinity for the ligand.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗