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Biomedical subjects

M Motta

Publications and source records attributed to M Motta.

At least 37 records · Page 2Linked to original sources
PubMed2005

Expression of functional ciliary neurotrophic factor receptors in immortalized gonadotrophin-releasing hormone-secreting neurones.

Ciliary neurotrophic factor (CNTF), a cytokine of the interleukin-6 superfamily, is known to exert pleiotropic actions, including regulation of food intake and permissive effects on reproduction, by facilitating the release of gonadotrophin-releasing hormone (GnRH) and gonadotrophins. CNTF activates membrane receptors (CNTF-Rs) composed of one ligand-specific binding subunit, defined CNTFR alpha, and two signal transducing subunits, termed leukaemia inhibitory factor receptor (LIFR) and gp130. However, it is not clear whether the effects of CNTF on GnRH release result from either a direct or an indirect action on GnRH-secreting hypothalamic neurones, or from a combination of these events. The hypothesis of a direct effect of CNTF was thus tested using the GT1-7 GnRH-secreting cell line. CNTF-R expression and CNTF-induced modulation of the Janus kinase (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway and of GnRH release were evaluated. GT1-7 cells were found to express CNTFR alpha, LIFR and gp130 genes, as shown by reverse transcription-polymerase chain reaction analysis, and the corresponding proteins, analysed by immunofluorescence and western blot. CNTFR alpha, LIFR and gp130 immunoreactive bands had an approximate size of 50, 190 and 130 kDa, respectively. Treatment of GT1-7 cells with 10(-12) M CNTF for 15-60 min resulted in a marked and transient increase of STAT3 phosphorylation via activation of JAK2. A 30-min exposure of GT1-7 cells to different CNTF concentrations increased the accumulation of GnRH into the culture medium, with a maximal effect at 10(-11) M. In conclusion, the present results provide new information about the regulation of the reproductive axis by CNTF, and suggest that it might operate at the hypothalamic level by directly influencing the activity of GnRH-secreting neurones, in addition to the possible indirect effects via interneurones proposed by previous studies.

Animals↗
PubMed2005

Smad proteins are targets of transforming growth factor beta1 in immortalised gonadotrophin-releasing hormone releasing neurones.

Transforming growth factor beta (TGFbeta) is one of the growth factors involved in the neuroendocrine control of the gonadotrophin-releasing hormone (GnRH) neurones. It is produced and released by the astrocytes surrounding GnRH neurones and directly controls their secretory activity. TGFbeta signalling is based on a complex of two receptors that transduces the signal through peculiar intracellular substrates, the Smad proteins, which, upon activation, move into the nucleus, and modify the transcription of TGFbeta responsive genes. The present study aimed to verify whether TGFbeta1 is able to regulate the Smad pathway in GT1-1 cells (i.e. an immortalised neuronal cell line releasing GnRH). We show that: (i) GT1-1 cells express Smad 2, 3, 4, and 7; (ii) TGFbeta1 enhances the phosphorylation of Smad 2 and 3 at short times of exposure (15-30 min); (iii) TGFbeta1 induces the synthesis of the inhibitory Smad 7 at longer times (60-120-240 min); (iv) the conditioned medium of type 1 astrocytes enhances the phosphorylation of Smad 2 and 3 in GT1-1 cells and a TGFbeta1 neutralising antibody counteracts this effect. The results indicate that Smads are targets of TGFbeta1 and that astrocytes are able to modulate Smads proteins in GT1-1 cells through the release of TGFbeta1. Taken together, the data provide new evidence that glial cells are important regulators of the GnRH neuronal activity.

Animals↗
PubMed2004

Leptin and prolactin modulate the expression of SOCS-1 in association with interleukin-6 and tumor necrosis factor-alpha in mammary cells: a role in differentiated secretory epithelium.

Leptin and its receptors have been shown to be expressed in several tissues, suggesting that this protein might be effective not only at the CNS level but also peripherally. We have previously reported that leptin and its long form receptor are expressed in the mouse mammary epithelial cell line HC11. In this study, we report a specific relationship among leptin, prolactin (PRL), interleukin-6 (IL-6), and tumor necrosis-alpha (TNF-alpha) in the modulation of the suppressor of cytokine signaling 1 (SOCS-1). Furthermore, we show that leptin and PRL are able to effectively enhance SOCS-1 gene expression in the HC11 cell line. Finally, high concentrations of leptin (100 nM) and/or PRL significantly (p<0.05) reduce the inhibitory effect of IL-6 (10 and 100 ng/ml) and TNF-alpha (10 and 100 ng/ml) on beta-casein gene expression in HC11 cells transfected with pbetacCAT, a chimeric rat-beta casein gene promoter-cloramphenicol acetyl transferase (CAT) gene construct. These results provide evidence that leptin may be an important mediator in regulating mammary gland growth and development and that this role may be related to the immune factors that are involved in inflammation.

Animals↗
PubMed2004

Alterations in the immune system of children from mothers treated with immunosuppressive agents during pregnancy.

Many of the immunosuppressive drugs that are used during pregnancy can cross the placental barrier and enter the foetal circulation, with a possible impact on the foetal immune system. We have evaluated the immune function of children born from mothers treated with immunosuppressants for connective tissue diseases. A total of nine babies, whose six mothers had been taking cyclosporine A (two), azathioprine (one) and dexamethasone (three) during pregnancy, together with 14 babies from mothers with similar diseases but who had not been treated (controls) were investigated. Complete blood count, IgA, IgG, IgM, IgG subclasses, and lymphocyte subpopulations were determined in all cases. Moreover, serum levels of anti-HBsAg and presence of autoantibodies (ANA, ENA) were also evaluated. Patients were tested at a mean age of 11 months (range, 1-17). Only a minor proportion of our patients displayed low values for age (mainly, IgA and IgG2), but none of the parameters tested resulted significantly different in patients than in controls. All children responded satisfactorily to hepatitis B vaccination. Although our results are preliminary, we conclude that prenatal exposure to immunosuppressive drugs does not have a profound effect to the developing immune system. More data and a longer follow-up are needed to confirm these results.

Adult↗
PubMed2004

Synthesis, characterization, and cytotoxic activity of copper(II) and platinum(II) complexes of 2-benzoylpyrrole and X-ray structure of bis[2-benzoylpyrrolato(N,O)]copper(II).

Copper(II) and platinum(II) complexes of 2-benzoylpyrrole (2-BZPH) were synthesized and characterized with IR, 1H and 13C NMR spectroscopies and coordination geometry with ligands arranged in transoid fashion. The crystal structure of [Cu(II)(2-BZP)2] was determined by X-ray diffraction. Death of complex treated Jurkat cells was measured by flow cytometry. The bis-chelate complexes [Cu(II)(2-BZP)2] and [Pt(II)(2-BZP)2] adopt square-planar coordination geometry with ligands, arranged in transoid fashion. Concentrations of 1-10 microM Platinum(II) complexes reduced cell survival from 100% to 20%, in contrast to the copper(II) complex which caused no cell death at a concentration of 10 microM. While the Pt(II) complexes may have damaged DNA to induce cell death, treatment with the Cu(II) complex did not induce Jurkat cell death.

Antineoplastic Agents↗
PubMed2004

Free and bound leptin in prepubertal children with Down's syndrome and different degrees of adiposity.

OBJECTIVE: To evaluate plasma total, free (FL) and protein-bound (BL) leptin in children with Down's syndrome (DS) and different degrees of adiposity and its relationship with thyroid stimulating hormone (TSH), free thyroxine (FT(4)), and free triiodothyronine (FT(3)). SUBJECTS: A total of 24 prepubertal clinically euthyroid DS children. METHODS: Plasma leptin, TSH, FT(4), and FT(3) concentrations were determined by immunometric/radioimmunologic assays. FL and BL were evaluated by fast protein liquid chromatography. RESULTS: In DS children, leptin circulates in two fractions, corresponding to BL and FL. The amount of BL and FL is negatively and positively correlated to body mass index (BMI), respectively. Plasma leptin concentrations correlate with BMI, but not with TSH, FT(4), and FT(3). CONCLUSIONS: In prepubertal DS children, leptin circulates as both BL and FL, correlates with adiposity and its concentration appears independent of thyroid function.

Adipose Tissue↗
PubMed2004

Our experience with nifedipine and prednisolone as expulsive therapy for ureteral stones.

OBJECTIVES: We evaluated the effect of nifedipine associated with prednisolone in ureteral stone passage. MATERIAL AND METHODS: In our department we enrolled 50 patients with radiopaque ureteral stones. Stone size was 15 mm or less. The patients were divided into two groups: group I included 25 patients who received 30 mg oral treatment of slow-release nifedipine (for a maximum of 20 days) and 25 mg of prednisolone (for a maximum of 10 days) daily. Group II was made up of 25 patients who received 25 mg of prednisolone daily. On request, both groups could use non-steroidal anti-inflammatory drugs. RESULTS: The mean expulsion time was 6 days in group I and 10 days in group II. The average stone size was 12 mm in group I and 12.8 mm in group II. Six patients suspended therapy in group I (5 erythema, 1 stomachache), and seven in group II (3 because of intolerable pain, 4 stomachache). The expulsion success rates were 68% in group I and 81% in group II. CONCLUSIONS: For ureteral stones that do not cause an emergency situation, such as obstructive uropathy, infection or intolerable pain, we suggest expulsive medical treatment with nifedipine and prednisolone, if there are no contraindications to drug use.

Administration, Oral↗
PubMed2004

ESWL: Comparing two analgesic techniques. Our experience.

OBJECTIVE: We compared the effects of intramuscular analgesia versus intramuscular analgesia associated with topical application of Luan (gel containing lidocaine 1%) on the efficacy of extracorporeal shockwave lithotripsy (ESWL). MATERIAL AND METHODS: From January 2001 to November 2002, 300 patients (mean age 46) were treated for kidney or upper ureteral radiopaque stones with ESWL, using a Dornier Compact Delta magneto lithotripter. The patients were divided into two groups: group A, 180 patients, received intramuscular analgesia with Ketorolac 30 mg, Tramadolo 100 mg and, during treatment, intravenous betametasone 4 mg. Group B, 120 patients, received the same pharmacological treatment associated with topical application of Luan. RESULTS: At 3 months, the stone-free rate in group A was 61% compared with 79% in group B. The energy of treatment was less than 13 kV in group A and less than 15 kV in group B. CONCLUSIONS: For ESWL treatment of kidney stones of 20 mm or less and ureteral stones of 15 mm or less, we suggest local analgesia with topical Luan and intramuscular analgesia. This approach increases the success rate of ESWL and reduces the discomfort associated with treatment.

Administration, Topical↗
PubMed2004

Pregnancy in patients with rheumatic diseases: psychological implication of a chronic disease and neuropsychological evaluation of the children.

As a consequence of the general improvement in the diagnosis and management of rheumatic diseases, patients achieve a better quality of life, with the possibility of a normal family life including one or more pregnancies. It is important, therefore, to consider the psychological aspects of these mothers' life and the influence of their chronic disease on their children is development. Several papers have reported the impact of systemic lupus erythematosus (SLE) on the quality of life. They found higher incidence of anxiety (from 15 to 45%) and depression (from 25 to 47%) compared to the general population. We have investigated the psychological influence of SLE on family planning, and we observed that it can interfere with physiological phenomena such as parenthood and the upbringing of children. The children of lupus mothers have a normal intelligence level for their age. What is emerging, however, is an increased incidence of learning disabilities compared to the general population. This observation suggests the importance of an early neuropsychological examination, in order to identify the children needing particular care. Therefore, psychological support seems to be an important help in the counseling of patients with rheumatic disease and in the future life of their children.

Adult↗
PubMed2004

European register of babies born to mothers with antiphospholipid syndrome.

This prospective multicentric register was initiated by the European Forum of Antiphospholipid Antibodies (APL) in 2003 after approval by local ethic committees. This register allows the investigation of infants after written informed parental consent. It collects mothers' clinical pattern of antiphospholipid syndrome (APS), course and outcome of pregnancy, treatment and immunological status. For the babies, clinical and immunological examinations are performed at birth; neurodevelopmental conditions followed up to five years. A re-evaluation of lupus anticoagulant (LA), anticardiolipin (ACL) or other antibodies will be done if they are positive at birth to follow their kinetics. A descriptive and a case control study of babies with versus without APL at birth will be possible after the inclusion of 300 cases.

Antiphospholipid Syndrome↗
PubMed2004

Neuropsychological development of children born to patients with systemic lupus erythematosus.

To verify the neuropsychological development in the offspring of patients with systemic lupus erythematosus (SLE), 47 children (23 male and 24 female) from affected women were studied. The tests applied were related to the children's ages: Griffiths scale up to four years, WPPSI and metaphonological tests (MP, evaluating the phonological consciousness) from four to six years of age, WISC-R test and Rey test (evaluating the visual-space abilities) from six years onwards; finally, specific tests for the diagnosis of learning disabilities (LD) between the ages of seven and 13. Intelligence levels were always normal (mean IQ score 106.32; median 104; SD 9.05). Three out of eight examined children failed MP, therefore may develop LD and will need further evaluation later. Fourteen children were specifically studied for LD and three reported scores lower than normal, but only two (who were brothers) were defined dyslexic. Antiphospholipid antibodies (aPL) were positive in the mothers of the three children with impaired LD tests. Other maternal autoantibodies or drugs administered during pregnancy did not seem to be related to LD. In conclusion, maternal SLE does not impair intelligence levels, but may increase the occurrence of LD particularly in male children (2/8 males examined, 25%). Both maternal aPL and genetic background may have pathogenetic implications.

Adolescent↗
PubMed2004

Neonatal outcome in patients with rheumatic disease.

Rheumatic autoimmune diseases have a higher prevalence in women, particularly during their childbearing age. Due to improved management, an increasing number of patients plan and carry out one or more pregnancies. Therefore, a growing interest is being paid to the possible consequences of maternal disease and associated treatment on the fetus and newborn infant. If maternal disease is characterized by the presence of IgG isotype autoantibodies, these can cross the placenta with possible antibody-mediated damage to the fetus. This is typically the case of the so called neonatal lupus erythematosus (NLE); a similar mechanism has been shown in infants of patients with immune thrombocytopenic purpura (ITP) and, less frequently, in those from mothers with antiphospholipid syndrome (APS). Indeed, this last condition is often responsible for placental, rather than neonatal, pathology. In addition, immunosuppressive and other drugs administered to the mothers during pregnancy and lactation might affect the fetal and neonatal immune system development. Finally, mothers disease and/or treatment could be related to neuropsychological alteration reported in some of their children.

Antiphospholipid Syndrome↗
PubMed2004

"Ultrashort" control of hypothalamic hormones secretion: a brief history.

Some 30 years ago we proposed that the synthesis of the hypothalamic releasing factors (RFs) might be influenced by changes of their own titers in the general circulation and in the hypothalamus. At that time the dominating concept was that there were two different hypothalamic RFs controling respectively follicle-stimulating hormone (FSHRF) and luteinizing hormone (LHRF). The possible existence of the first "ultrashort" feedback system was proposed on the basis of the observation that in male rats castrated, to eliminate the "long" feedback effect of testosterone, and then hypophysectomized, to abolish the possible "short" feedback effect of pituitary hormones on the hypothalamus, the intrahypothalamic levels of FSHRF resulted to be higher than in controls. Following a treatment with an hypothalamic extract, the intrahypothalamic stores of FSHRF returned to pre-operation levels, suggesting that a factor present in the hypothalamic extract might exert an inhibitory influence on the synthesis of FSHRF. In 1987, we confirmed these findings using an in vitro perfusion system of rat hypothalamic tissue, where the amount of gonadotropin-releasing hormone (GnRH) released was measured in the effluent. When a GnRH analog was added to the perfusion medium, both the spontaneous and the stimulated release of GnRH were totally obliterated. The presence of specific binding sites for GnRH has been clearly demonstrated in GnRH neurons. It is becoming consequently attractive the hypothesis that paracrine interactions might occur among GnRH neurons, entertaining an "ultrashort" feedback control of GnRH secretion.

Animals↗
PubMed2004

Sexual differentiation of the brain: role of testosterone and its active metabolites.

The sex-related morphological differences of many brain nuclei are mainly determined by the hormonal environment present during embryonic development. These morphological differences are at the basis of the gender-specific secretion of many hypothalamic and pituitary hormones, of sexual and aggressive behavior, etc. It is known that, at least in rodents, testosterone (T) secreted by the fetal testes plays a key role in the permanent organization of the developing central nervous system (CNS) toward masculine patterns. The main aspect concerning the mechanism of action of T is that the brain, and especially the hypothalamus, possesses the enzymes that transforms this hormone into compounds which amplify (dihydrotestosterone) or differentiate (estrogens) its action; these enzymatic systems are the 5alpha-reductase and the aromatase respectively. In this short review are summarized the main results obtained in our and other laboratories concerning some characteristics of the two enzymatic pathways in the developing CNS and the possible dimorphism in their expression during ontogenesis. On the basis of diseases in which alterations of the normal levels and/or of the mechanism of action of gonadal hormones during embryogenesis are present, in the last part of the paper some hypotheses on the possible influence of T metabolites in the sexual differentiation of the human brain are also drawn.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2003

Aldosterone receptor antagonists: biology and novel therapeutical applications.

Recent studies suggest that a dysregulation of the aldosterone system is involved in the pathophysiology of different cardiovascular diseases, including myocardial failure and several cases of essential hypertension. In both rat models and in humans, aldosterone action has been shown to induce heart remodeling and interstitial and perivascular fibrosis of the myocardium. For these reasons, a rationale for the use of aldosterone antagonists (ARAs) of the spirolactone family, which have been available for decades in the treatment of aldosterone excess syndromes, has now emerged. Moreover, the recent validation of their use, in combination with the current therapy, for the treatment of these cardiovascular diseases by trials like the RALES Study has further strenghtened this approach. The development of compounds, like eplerenone, with a greater selectivity for mineralocorticoid receptors, seems promising also in terms of reduction of endocrine side effects. The addition of aldosterone antagonists to the conventional therapy of myocardial failure and of selected cases of hypertension thus appears beneficial, resulting in an improved survival rate and a reduced incidence of cardiac complications. This review article, after a brief recall of the physiology of the aldosterone system, addresses the emerging role of aldosterone in cardiovascular diseases, considers the pharmacology of ARAs and the novel therapeutical applications of these compounds in hypertension and heart failure.

Aldosterone↗
PubMed2003

Role of Ca 15-3 in patients with biochemically suspected prostate cancer and multiple negative ultrasound-guided prostate biopsies.

Ca 15-3 is an aspecific tumor marker characteristic of cancer proliferation. Elevated serum levels seem to be closely correlated with cancer progression in non-urological tumors. This study assessed the role of Ca 15-3 as an aspecific tumor marker in patients with borderline prostate-specific antigen (PSA) biochemically suspected of prostate cancer (PCa) and with multiple negative prostate biopsies. The study is based on prospective analysis of 103 patients: (a) 33 patients (group A) presented lower urinary tract symptoms secondary to BPH with normal serum PSA values, DRE and TRUS negative for suspected PCa; (b) 31 patients (group B) with histologically diagnosed PCa; (c) 39 patients (group C) with borderline serum PSA values, DRE and TRUS normal, two ultrasound (US)-guided random prostate biopsies negative for PCa. Ca 15-3 was determined in the entire study series by the IRMA method, using as range the values proposed for the investigated non-urological tumors (38 UI/l).Ca 15-3 was within normal range in all group A patients (control), while the values were elevated in 27/31 of group B patients (PCa) and in 11/39 of group C (PCa suspected) patients. A third biopsy was performed in all 39 group C patients with borderline PSA and it was PCa-positive in 13 patients (33.3%, subgroup C3). In this series Ca 15-3 was increased in 9 of 13 patients (subgroup C3alpha), while the remaining four patients (subgroup C3beta) presented values within the normal range. On 26 group C patients who were negative for PCa to third biopsy (subgroup C4), 24 patients had Ca 15-3 levels within normal range (subgroup C4alpha) with histologic findings of BPH in 23 cases and granulomatous chronic prostatitis in one case, while two patients (subgroup C4beta) had elevated Ca 15-3 concentrations associated with lymphoplasmacytic chronic prostatitis. We hypothesize that Ca 15-3, as a specific tumor marker, could be an interesting and inexpensive second step diagnostic tool for PCa in patients with borderline PSA and multiple negative prostate biopsies, as it could indicate whether a repeated biopsy should be performed in a short time, having excluded other concomitant tumors. However, further prospective studies will be necessary to confirm this hypothesis.

Adenocarcinoma↗
PubMed2003

Early use of Nasal-BiPAP in two infants with Congenital Central Hypoventilation syndrome.

AIM: To reduce the problems caused by prolonged artificial ventilation in babies with Congenital Central Hypoventilation syndrome (CCHS). METHODS: Two term infants with CCHS, weighing 4030 g and 3100 g, respectively, at the beginning of treatment and aged 53 and 31 d, respectively, were successfully ventilated with a Nasal Bilevel Positive Airway Pressure (N-BiPAP) device. RESULTS: In the first patient the tcPO2 recordings (mean +/- SD) during sleep were 46 +/- 12 mmHg before using N-BiPAP and 58 +/- 13 mmHg after using the device, while those for tcPCO2 were 75 +/- 9 mmHg and 49 +/- 11 mmHg, respectively. In the second patient tcPO2 during sleep was 42 +/- 3 mmHg before, and 55 +/- 5 after N-BiPAP, and for tcPCO2 the recordings were 119 +/- 24 mmHg and 55 +/- 6 mmHg, respectively, showing a significant improvement. One infant had persistent gastro-oesophageal reflux, and frontal skin abrasion caused by the face mask. Nevertheless, these complications did not necessitate the discontinuation of N-BiPAP ventilation, thus precluding prolonged use of intubation and tracheotomy. CONCLUSION: In infants with CCHS, early use of non-invasive, positive-pressure ventilation with N-BiPAP, in association with careful monitoring, can decrease problems caused by prolonged intubation and tracheotomy.

Apnea↗