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M Motta

Publications and source records attributed to M Motta.

At least 19 recordsLinked to original sources
PubMed2006

Genealogy of centenarians and their relatives: a study of 12 families.

The longevity is a complex phenomenon in which specific genetic properties seem to play a role. The present study intended to reconstruct the genealogical tree of 12 subjects, being residents of one Northern and one Southern province of Italy, in order to establish the longevity of the ancestors. Detailed studies have been performed in the registry offices and the historic archives. The research method started from the identification of the centenarians on the basis of the documentation of the relevant birth document, it was continued by identifying the documents of birth, marriages and death of the parents of the centenarians. This way we proceeded systematically backwards in time. In addition, we verified the medium life span of the Italian population in the given periods of time, when the centenarians and their ascending lines had lived. These results offer clear historic-statistical evidences for the genetic basis of longevity.

Adult↗
PubMed2006

Estrogen receptor beta (ERbeta) and inhibition of prostate cancer cell proliferation: studies on the possible mechanism of action in DU145 cells.

Estrogen receptor beta (ERbeta) plays a protective role against uncontrolled cell proliferation. ERbeta is lost during prostate cancer (CaP) progression suggesting its direct involvement in contrasting tumor proliferation in this disease; however, the molecular mechanism at the basis of this effect has not been clearly defined yet. Possible molecular targets of ERbeta were assessed in DU145 cells, a CaP cell line expressing only ERbeta. Cells treated from 1 to 9 days with different doses of estradiol or diarylpropionitrile (DPN, an ERbeta-selective agonist) show a time-dependent decrease in cell proliferation. The reduced proliferation rate is accompanied by the stimulation of ERbeta expression and the increase of cyclin-dependent kinase inhibitor p21. We demonstrate that the endogenous ERbeta is one of the mediator of the antiproliferative action of estrogens enhancing the synthesis of molecules such as p21 that control cell cycle, an effect amplified by the autoregulation of ERbeta expression. Our observations suggest that CaP, when expressing a functional ERbeta, might be sensitive to the antiproliferative action of estrogens; therefore, ERbeta specific agonists might be valid candidates for new pharmacological approaches to this disease.

Blotting, Southern↗
PubMed2006

Ninth commandment: 'Thou shalt not covet thy neighbor's wife!' Penetrating trauma to the corpora cavernosa caused by gunshot.

We describe a case of gunshot wound to the corpora cavernosa caused by a low-velocity bullet in a 43-year-old man. He volunteered that his lover's husband shot him with a handgun. The bullet had penetrated the right gluteal region with no exit wound causing a right corpus cavernosum lesion. A penile colour-duplex doppler ultrasonography did not reveal injuries of the cavernosal arteries or altered peak diastolic and systolic values. A three-dimensional computed tomography study corfirmed the presence of the bullet at the root of the right corpus cavernosum and allowed to identify the curvilinear ballistic trajectory, confirming a low-velocity penetrating bullet. The patient underwent exploratory surgery with removal of the bullet and primary repair of the identified unilateral albuginea rupture. The bullet, passing through clothing, probably slowed down causing less than expected harm. The follow-up visit after 2 months showed that the penile girth was not narrowed by such a repair. With a 2-year follow-up the patient has a normal penile ultrasound morphology and a normal sexual activity.

Adult↗
PubMed2006

Circulating ghrelin level is increased in coeliac disease as in functional dyspepsia and reverts to normal during gluten-free diet.

BACKGROUND: It is controversial whether serum ghrelin concentration is altered in coeliac disease and whether this alteration is related to nutritional impairment or to inflammatory changes of duodenal mucosa. AIM: To investigate clinical and histopathological variables affecting circulating ghrelin in coeliac patients by comparison with dyspeptic patients and with healthy controls. METHODS: We measured serum ghrelin and obtained gastric and duodenal biopsies in 44 coeliac patients before and after 1-year gluten-free diet, in 39 dyspeptic patients and 53 healthy controls. RESULTS: Serum ghrelin concentration was significantly higher in coeliac (531 +/- 29 pg/mL, P < 0.05) and in dyspeptic patients (526 +/- 14 pg/mL, P < 0.01) than in healthy controls (451 +/- 8 pg/mL), and body mass index was significantly lower in coeliac (20 +/- 1) and in dyspeptic patients (20 +/- 1) than in healthy controls (22 +/- 1, P < 0.05). In coeliac patients serum ghrelin concentration was not related to the severity of duodenal lesions. Serum ghrelin reverted to normal (399 +/- 30 pg/mL) and body mass index increased significantly (0.6 +/- 0.1 kg/m(2) increase, P < 0.05) during gluten-free diet despite persistent duodenal lymphocytic infiltration. CONCLUSIONS: Ghrelin concentration is increased and body mass index is decreased in coeliac and in dyspeptic patients irrespective of presence and severity of duodenal inflammation. Nutritional impairment is a key factor in elevating plasma ghrelin levels in coeliac disease.

Adult↗
PubMed2006

Leptin concentration in plasma and in milk during the interpartum period in the mare.

The aim of this work is to investigate on plasma profiles of leptin and estradiol 17beta during the interpartum period and leptin concentrations in the milk and in the colostrum during the period from parturition to the successive delivery in mare. Leptin plasma concentration varied from 5.1+/-2.3 ng/ml after the first parturition (week 0) to 3.0+/-0.7 at week 21 (p<0.05), then it increased to maximal level at week 49 (6.9+/-1.0 ng/ml, p<0.05). Leptin concentration in the colostrum and in the milk has been significantly (p<0.05) higher than that in plasma samples at week 1 (milk 8.8+/-2.3 versus plasma 5.2+/-0.6 ng/ml) and between week 12 and 17. This difference may be explained with a local leptin production at mammary level and supports a role of leptin in the mammary gland and/or in foal intestine. Estradiol 17beta increased from week 15 (17.9+/-2.3 pg/ml) up to 487.9+/-67.7 pg/ml at week 43. Plasma estradiol 17beta rise anticipated by 4 weeks plasma leptin increase and it does not seem to be positively correlated to leptin secretion.

Animals↗
PubMed2006

Normal neuropsychological development in children with congenital complete heart block who may or may not be exposed to high-dose dexamethasone in utero.

BACKGROUND: Antenatal and postnatal treatment with dexamethasone (DEX) may negatively affect the neuropsychological development in children. Maternal anti-Ro/Sjögren's syndrome A (SSA) antibodies may also be associated with learning disabilities in offspring. OBJECTIVE: To assess neuropsychological development in babies exposed to very high dosages of DEX in utero, whose mothers were anti-Ro/SSA positive. METHODS: 13 children with congenital complete heart block (CHB) (11 exposed and 2 not exposed to DEX) and 3 healthy siblings, all of anti-Ro/SSA-positive women, were evaluated. 11 preschool-aged children (5 boys) were assessed using Griffiths Mental Development Scales. 5 school-aged children (2 boys) were examined using Wechsler Intelligence Scale for Children-Revised to check IQ and reading tests to explore the existence of learning disabilities or dyslexia. None of the children had had major neonatal complications, although those with CHB had to be paced at different intervals from birth. RESULTS: The children had been exposed in utero to a mean total dose of 186.6 mg DEX. IQ levels were always normal (mean IQ 105.1, standard deviation (SD) 9.5). Only one child had a learning disability, of borderline clinical significance, but this child had never been exposed to DEX. CONCLUSION: No negative effects were found on the neuropsychological development in this cohort of children, even if they had been exposed to maternal anti-Ro/SSA antibodies and to very high dosages of DEX (much higher than those used to improve fetal lung maturity). These findings might be of interest in view of the large number of infants exposed in the past to repeated antenatal courses of steroids.

Antibodies, Antinuclear↗
PubMed2006

Thymidine-phosphorothioate oligonucleotides induce activation and apoptosis of CLL cells independently of CpG motifs or BCL-2 gene interference.

We compared antisense phosphorothioate oligonucleotides (PS-ODN) that target BCL-2 such as Genasense (G3139-PS), with other PS-ODN or phosphodiester-ODN (PO-ODN) in their relative capacity to induce apoptosis of chronic lymphocytic leukemia (CLL) B cells in vitro. Surprisingly, we found that thymidine-containing PS-ODN, but not PO-ODN, induced activation and apoptosis of CLL cells independent of BCL-2 antisense sequence or CpG motifs. All tested thimidine-containing PS-ODN, irrespective of their primary sequences, reduced the expression of Bcl-2 protein and increased the levels of the proapoptotic molecules p53, Bid, Bax in CLL cells. Apoptosis induced by thymidine-containing PS-ODN was preceded by cellular activation, could be blocked by the tyrosine-kinase inhibitor imatinib mesylate (Gleevec), and was dependent on ABL kinase. We conclude that thymidine-containing PS-ODN can activate CLL cells and induce apoptosis via a mechanism that is independent of BCL-2 gene interference or CpG motifs.

Amino Acid Chloromethyl Ketones↗
PubMed2006

Peripheral levels of BDNF and NGF in primary headaches.

Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), have been implicated in the generation and modulation of pain. To investigate whether alterations in neurotrophin levels can be detected in subjects suffering from nociceptive disorders, such as primary headaches, we determined the peripheral (platelet and plasma) levels of BDNF and NGF in patients suffering from migraine, with or without aura, or cluster headache (CH), in the interictal phase, and in healthy volunteers. All primary headaches patients studied showed significantly decreased platelet levels of BDNF (migraine vs. controls P<0.001; CH vs. controls P<0.01), while a selective reduction of platelet NGF was observed in migraine sufferers and not in CH patients compared with control subjects (migraine vs. controls P<0.001). These changes were not accompanied by significant modifications of neurotrophin plasma levels. Our findings show for the first time that changes in peripheral levels of neurotrophines (BDNF and NGF) occur in patients suffering from different types of primary headaches, suggesting a potential involvement of BDNF and NGF in the pathophysiology of these disorders, and raising the possibility that differences in peripheral neurotrophins may help to distinguish migraine biologically from CH.

Adult↗
PubMed2006

Impact of in utero environment on the offspring of lupus patients.

The number of patients affected by systemic lupus erythematosus (SLE) that decide to have children has greatly increased probably because of recent improvements in the diagnosis and management of the disease. This has stimulated our interest in defining the outcome of children, focusing both on neonatal problems and long term development. SLE patients still carry a risk of pregnancy loss. However, due to careful monitoring and treatment by a multidisciplinary team, the number of losses has dramatically decreased, but an increased number of preterm deliveries is still a problem. Neonatal lupus is linked to the presence of anti-Ro/SS-A and anti-La/SS-B antibodies in the mother, although other factors probably of fetal origin are important. Neonatal lupus is a complex condition whose most serious manifestation is the congenital heart block (CHB). Usually, children with complete CHB need permanent pacing, but apparently do not have neuropsychological problems. Studies focusing on the neuropsychological development of SLE offspring show an increased number of learning disabilities in children with normal intelligence levels. Fetal consequence of maternal treatment need to be considered choosing non teratogenic drugs, but the withdrawal of medications just because the patient is pregnant should be avoided to avoid SLE flares.

Central Nervous System↗
PubMed2006

Characterization of T-cell population in children with prolonged fetal exposure to dexamethasone for anti-Ro/SS-A antibodies associated congenital heart block.

The objectives of the study were to characterize the production, function and survival of T lymphocytes of children with prolonged fetal exposure to dexamethasone for anti-Ro/SS-A antibodies associated congenital complete heart block. The analysis of thymic function, studied by measuring the level of T-cell receptor excision circles, was performed by real time PCR, the composition of T-cell subpopulation was evaluated by flow cytometry and the T-cell diversity was assayed by heteroduplex analysis. T-cell competence was gauged at two functional levels by determining the proliferation and the number of T-cell divisions and by measuring gamma-interferon production after mitogenic stimulation. We observed that the thymic output, distribution of T-cell subsets, thymidine incorporation, number of T-cell divisions, and y-interferon production were comparable to those of age-matched control. On the contrary, heteroduplex analysis demonstrated the presence of both polyclonal and oligoclonal peripheral T-cell repertoires. In conclusion, the analysis of the T-cell compartment in children with prolonged intrauterine exposure to high dose dexamethasone did not disclose any relevant abnormality, except a restriction of T-cell receptor diversity in some patients.

Antibodies, Antinuclear↗
PubMed2006

Gonadotropin-releasing hormone (GnRH) receptors in tumors: a new rationale for the therapeutical application of GnRH analogs in cancer patients?

Gonadotropin-Releasing Hormone (GnRH) is the hypothalamic decapeptide which plays a key role in the control of reproductive functions. By binding to specific receptors present on the pituitary gonadotropes, GnRH regulates gonadotropin release and, consequently, steroid hormone secretion from the gonads. When given continuously and at high doses, GnRH agonists suppress the pituitary gonadal axis through the down-regulation and desensitization of its own receptors. Based on this rationale, pituitary GnRH receptors represent the target for the successful utilization of GnRH agonists (that are more stable than the native peptide) for the treatment of hormone-dependent tumors (e.g., prostate, breast, endometrial, ovarian cancers). The observation that GnRH receptors are expressed in steroid-dependent tumors, and that their activation reduces cell proliferation and metastatic behavior of cancer cell lines, both in vitro and in vivo (when inoculated into nude mice), indicates a possible additional and more direct antitumor activity for these compounds. Interestingly, GnRH receptors have been shown to be expressed also in androgen-independent prostate carcinoma, as well as in tumors that are not classically considered hormone-related (e.g., melanoma), suggesting a clinical utility of the administration of GnRH analogs also in these tumors. More recently, GnRH agonists have been proposed as useful carriers to target cytotoxic drugs or toxins to cancer cells displaying the specific GnRH receptors. A second form of GnRH (designated GnRH-II) has been discovered in most vertebrates, including humans. GnRH-II has been suggested to act through a 'putative' cognate type II GnRH receptor, which is distributed in different tissues, both normal and tumoral. In humans, a full-length functional type II GnRH receptor has not been found. Therefore, its functions as well as its possible utility as a molecular target for a GnRH-II based therapy in oncology still has to be clarified. This review will focus on the role of GnRH receptors in the control of tumor growth, progression and dissemination. It will also be discussed whether the presence of these receptors might represent an additional rationale for the clinical utility of GnRH analogs as anticancer drugs.

Animals↗
PubMed2006

GnRH agonists and antagonists decrease the metastatic progression of human prostate cancer cell lines by inhibiting the plasminogen activator system.

Prostate cancer (PCa) growth initially depends on circulating androgens. Gonadotropin-releasing hormone (GnRH) agonists are currently used for the treatment of PCa. However, after an initial responsiveness to hormonal deprivation, PCa progresses and metastasizes. Recently, also GnRH antagonists have been used for clinical trials in patients with PCa and the results seem promising. The components of the plasminogen activator (PA) system (urokinase-type PA, uPA; PA inhibitors, PAI-1/2; uPA receptor, uPAR) have been implicated in the local degradation of the extracellular matrix (ECM) and PCa progression. The aim of this study was to test the possible effects of the treatment with an agonist (Leuprolide, GnRH-A) and an antagonist (Cetrorelix, GnRH-ANT) of GnRH on the expression and activity of uPA and PAI-1 in the conditioned media of DU145 and PC3, two PCa androgen-independent cell lines. The involvement of the PA system in the control of cellular migration was also investigated. The results obtained in DU145 and PC3 cells show that both GnRH-A and GnRH-ANT: i) inhibit cell proliferation; ii) significantly decrease the enzymatic activity and the secretion of uPA; iii) significantly increase the protein levels of PAI-1; iv) induce a significant decrease of the migratory and invasion PCa capabilities. This study suggests that GnRH analogues exhibit not only an antiproliferative effect, but also an anti-metastatic action exerted through the inhibition of the activity of PA system and might provide a rational basis for the development of clinical strategies for those tumours that progress towards an androgen-independent condition characterized by a higher metastatic potential.

Antineoplastic Agents, Hormonal↗
PubMed2006

[Mechanical characteristics of the human bladder wall and application of the results in a finite elements model to study the pelvic floor].

AIM: There is no radiological method capable of providing a real-time, dynamic 3D illustration of the pelvic organs and supporting structures during stress, physiological regressions and pathological alterations. This paper describes the determination of the mechanical characteristics of the human bladder, the application of the results in a numerical 3D finite elements model of the pelvis and the processing of the model in the presence or absence of urethro-pelvic and pubo-vescical ligaments supporting the pelvis. METHODS: A 3D numerical finite element model of the human pelvis has been realised starting from CT image and Mimics (Materialise), Rhinoceros (Robert Mc Neel and Associates), Patran (MSC) e Marc (MSC) programs. The mechanical characteristic of human bladder specimen have been studied in vitro drawn up from human bladder removed for neoplasia. Results have been introduced in a numeric model. After the definition of bond and load applied, we made the simulation and numerical structural analysis with and without some ligaments that link pelvic fascia and urethra at the pubis. RESULTS: The study of mechanical data of bladder reports structural differences between lateral wall, trigone wall and anterior wall in correlation to the topographical disposition of fibres of detrusor and its thickness. Dynamics investigation performed in the absence of cervical urethra ligaments of suspension and pelvic fascia showed that the anatomical deflections of pelvic fascia modified the distributions of loads toward centripetal deviation, stressing even more the perineal area and the sphincter tract. CONCLUSIONS: The study shows that trigone is the area with the greatest stiffness in comparison with other areas of the bladder and that it has the greatest strength to tensile loads. This study has shown that pelvic fascia, urethropelvic and pubovescical ligaments are cardinal supports that cannot be neglected in a dynamic numerical analysis. Dynamic simulation of the model in the absence of the ligaments confirms the role of surgical techniques used for their reconstruction following their section during radical surgery.

Biomechanical Phenomena↗
PubMed2005

Diabetes mellitus in the elderly: diagnostic features.

The new diagnostic criteria of the diabetes do not consider the age of the subjects. It has been demonstrated that the fasting glucose values as well as the glycemia levels after oral glucose load increase with age. Therefore, it is necessary to evaluate whether the new diagnostic criteria are valid for the elderly subjects also. In spite of the findings that among the subjects with fasting glycemia of 126-140 mg/ml subsequent controls after long times often revealed the presence of impaired fasting glucose (IFG) and numerous cases with IFG displayed values <110 mg/dl after longer times, the present authors accept the new diagnostic criteria even for the elderly subjects. However, they emphasize the importance of distinguishing diabetes in the elderly in subclasses, such as clinically manifest diabetes, mild diabetes and diabetic glucose tolerance (DGT) type, in order to establish the early diagnosis of diabetes, and therefore, to prevent the chronic vascular complications.

Aged↗
PubMed2005

Incidence of prostate cancer in Sicily: results of a multicenter case-findings protocol.

OBJECTIVE: To establish the incidence of prostate cancer (PCa) in Sicily in patients who entered an early detection protocol. METHODS: From February 2002 to February 2004, 16,298 subjects aged 40-75 entered the protocol. Patients with suspicious DRE, PSA>10 ng/ml, PSA<or=2.5 ng/ml, from 2.6 to 4 ng/ml or from 4.1 to 10 ng/ml with F/T PSA of <or=15%, <or=20% and <or=25% respectively underwent needle biopsy according to an extensive protocol. RESULTS: 3266 patients were eligible for biopsy; PSA was <or=4 in 12.7% and <or=10 ng/ml in 63.9% of patients. A PCa was found in 1171 cases (36.9%) with a relationship between PCa incidence and PSA and age respectively (chi2-test, p<0.0001); 51.8% of patients with PCa had a PSA<10 and 8.8% a PSA<4 ng/ml; 49% were clinically staged as T1c. The estimated odds ratios for each age group showed increased risk for PCa in the fourth decade with PSA between 2.6 and 4 ng/ml (12.5 times higher) and in the fifth decade with PSA between 4.1 and 10 ng/ml (6.2 times higher). CONCLUSIONS: Age and serum PSA levels are the major risk factors for PCa. On their basis it is possible to modulate the most suitable timing for early diagnosis in individual patients.

Adult↗
PubMed2005

Delayed inhibition of Nogo-A does not alter injury-induced axonal sprouting but enhances recovery of cognitive function following experimental traumatic brain injury in rats.

Traumatic brain injury causes long-term neurological motor and cognitive deficits, often with limited recovery. The inability of CNS axons to regenerate following traumatic brain injury may be due, in part, to inhibitory molecules associated with myelin. One of these myelin-associated proteins, Nogo-A, inhibits neurite outgrowth in vitro, and inhibition of Nogo-A in vivo enhances axonal outgrowth and sprouting and improves outcome following experimental CNS insults. However, the involvement of Nogo-A in the neurobehavioral deficits observed in experimental traumatic brain injury remains unknown and was evaluated in the present study using the 11C7 monoclonal antibody against Nogo-A. Anesthetized, male Sprague-Dawley rats were subjected to either lateral fluid percussion brain injury of moderate severity (2.5-2.6 atm) or sham injury. Beginning 24 h post-injury, monoclonal antibody 11C7 (n=17 injured, n=6 shams included) or control Ab (IgG) (n=16 injured, n=5 shams included) was infused at a rate of 5 microl/h over 14 days into the ipsilateral ventricle using osmotic minipumps connected to an implanted cannula. Rats were assessed up to 4 weeks post-injury using tests for neurological motor function (composite neuroscore, and sensorimotor test of adhesive paper removal) and, at 4 weeks, cognition was assessed using the Morris water maze. Hippocampal CA3 pyramidal neuron damage and corticospinal tract sprouting, using an anterograde tracer (biotinylated dextran amine), were also evaluated. Brain injury significantly increased sprouting from the uninjured corticospinal tract but treatment with monoclonal antibody 11C7 did not further increase the extent of sprouting nor did it alter the extent of CA3 cell damage. Animals treated with 11C7 showed no improvement in neurologic motor deficits but did show significantly improved cognitive function at 4 weeks post-injury when compared with brain-injured, IgG-treated animals. To our knowledge, the present findings are the first to suggest that (1) traumatic brain injury induces axonal sprouting in the corticospinal tract and this sprouting may be independent of myelin-associated inhibitory factors and (2) that post-traumatic inhibition of Nogo-A may promote cognitive recovery unrelated to sprouting in the corticospinal tract or neuroprotective effects on hippocampal cell loss following experimental traumatic brain injury.

Analysis of Variance↗
PubMed2005

Increased expression of CD152 (CTLA-4) by normal T lymphocytes in untreated patients with B-cell chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) have defects in both cellular and humoral immunity. Since CD152 (CTLA-4) plays a critical role in downregulating T-cell responses, we studied the expression of surface and cytoplasmic CD152 (sCD152 and cCD152, respectively) in freshly isolated T cells from treatment-naïve patients with CLL. CD4+ and CD8+ T cells from these patients demonstrated significantly increased sCD152 and cCD152 compared to normal donors. Furthermore, these patients had an increased proportion of the regulatory CD4(+)/CD25(+)/CD152+ subset that correlated with advanced Rai stage, unfavorable cytogenetics and low serum IgG and IgA levels. The expression of sCD152 by T cells also correlated with ZAP-70 expression by CLL B cells. The proportion of CD4(+)/CD25+ cells was also correlated with unmutated immunoglobulin heavy chain variable gene status. Blockade of CD152 with monoclonal antibody (mAb) in proliferation assays was associated with potent T-cell proliferation in response to autologous and allogeneic CD40-activated CLL B cells. In summary, T cells from patients with CLL may be primed for anergy by expressing increased amounts of CD152; anti-CD152 mAb may represent a therapeutic opportunity to enhance an immune response against autologous leukemia cells.

Adult↗