Biomedical subjects

M Conti

Publications and source records attributed to M Conti.

At least 19 recordsLinked to original sources

PubMed2006

Hyperechoic plaque: an ultrasound marker for osteoporosis in acute stroke patients with carotid disease.

BACKGROUND: Osteoporosis is a significant complication of stroke, and hip fracture after a stroke is a frequent problem. Moreover, growing evidence links vascular and bone diseases, in the form of osteoporosis associated with both atherosclerosis and vascular calcification. The aim of our study is to detect bone change in the acute phase of ischemic stroke in patients with carotid disease and to verify the correlation with carotid echogenic plaques. PATIENTS AND METHOD: Out of 245 subjects consecutively admitted to our Stroke Unit for their first ischemic stroke, we selected 49 patients with a first-ever stroke due to carotid atherosclerosis without a previous diagnosis of bone disease. We assessed risk factors for cerebrovascular disease as well as for osteoporosis, the degree of neurological deficit and disability, and bone mineral density that was quantified by bilateral hip dual energy X-ray absorbimetry. Osteoporosis was defined as a T score below -2.5. Carotid ultrasound was used to classify plaques in non-hyperechoic (grade 1) and hyperechoic plaque (grade 2). RESULTS: We found a high prevalence of low bone mass density (BMD) in our patients (18 out of 49=36.7%), without relationship to the side of paresis. According to univariate analysis evidence of osteoporosis was correlated with age (p=0.05), score of Scandinavian Stroke Scale (p=0.01) and grade 2 plaque (p=0.01). According to multivariate analysis, there was a significant positive correlation between grade 2 plaques and osteoporosis (OR=6.58; 95% CI=1.57-27.54; p=0.01), which was stronger in women (OR=18.15; 95% CI=1.80-182.83; p=0.01). The percentage of intraplaque hyperechogenicity was inversely correlated with BMD (r=-0.411, p=0.016). CONCLUSION: Osteoporosis is highly prevalent in acute atherosclerotic stroke patients. Carotid hyperechoic plaque is an independent marker of osteoporosis.

Absorptiometry, Photon↗

PubMed2006

Post-traumatic fibro-osseous lesion of the ribs: a relatively under-recognised entity.

AIM: To report the description of a rare benign osseous lesion affecting the ribs entitled post-traumatic fibro-osseous lesion (PTFOL). METHODS: Seven cases of PTFOLs were retrieved from the archives of the University Hospital of Lille. Histological slides were reviewed and lesions were classified according to the histological patterns described by McDermott et al. Clinical and follow-up data were obtained from the patients' charts. RESULTS: PTFOLs occurred principally in men (mean age 31.8 years) with a known or suspected previous chest injury for four of them. No previous cancer was noted. Radiologically, PTFOLs readily presented as an isolated expansive lucency with a sclerotic rim located on the last five ribs. A constant increased uptake of radionucleotide was noted on bone scan. Microscopically, two fibro-osseous, four xanthomatous and one mixed pattern were individualised. Lesions were characterised by a network of anastomosing bone trabeculae without osteoblast lining within a fibrous stroma. A zonal maturation from woven to peripheral lamellar bone was characterised. Central sheets of lipid-laden histiocytes were conspicuous in the xanthomatous type. For each patient, clinical follow-up was excellent, without any recurrence. CONCLUSIONS: This is the second largest series of PTFOLs, which is considered to be a dysplastic healing process after trauma. It may be symptomatic or shown by imaging studies realised for unrelated reason. PTFOL is regularly misdiagnosed with other more common lesions of the ribs, such as fibro-osseous dysplasia, osteoma osteoid and benign fibrous histiocytoma. Its recognition is of importance because no follow-up is needed after resection.

Adolescent↗

PubMed2006

Cytotoxicity of different selective serotonin reuptake inhibitors (SSRIs) against cancer cells.

Cell membrane ion transporters expression and activity are altered in cancer cells and these phenotypic alterations offer potential targets for cancer therapies. Among the therapeutic agents affecting cell membrane transporters, serotonin reuptake inhibitors (SSRIs) have been shown to have anticancer potential. In this work, we have compared two SSRIs, one very specific for serotonin reuptake transporters (paroxetine) and another which also inhibit norepinephrine and dopamine transporters (venlafaxine), for their ability to counteract growth of various murine and human cancer cell lines. We found that paroxetine has cytotoxic activity against tumor cells, both of murine or human origin in the micromolar concentration range, whereas venlafaxine has not. A neurotransmitter receptor mediated mechanism of action appears thus unlikely for SSRIs cytotoxicity on cancer cells. With ranges of SSRIs cytotoxicity on cancer cells defined, limits in their possible applicability in cancer therapy is discussed.

Animals↗

PubMed2005

Arthroscopic biceps tendon tenodesis: the anchorage technical note.

Treatment of long head biceps (LHB) tendon pathology has become an area of renewed interest and debate among orthopaedic surgeons in recent years. The background of this manuscript is a description of biceps tenodesis which ensure continual dynamic action of the tendon which depresses the head and impedes lateral translation. A new technique has been developed in order to treat LHB tendon irreversible structural abnormalities associated with cuff rotator lesions. This technique entails the construction of a biological anchor between the LHB and supraspinatus and/or infraspinatus tendons according to arthroscopic findings. The rationale, although not supported by biomechanical studies is to obtain a triple, biomechanical effect. The first of these biomechanical effects which we try to promote through the procedure of transposition is the elimination of the deviation and oblique angle which occurs as the LHB completes its intra-articular course prior to reaching the bicipital groove. Furthermore, we have found this technique extremely useful in the presence of large ruptures of the rotator cuff with muscle retraction. The most common complication associated to this particular method, observed in less than 3%, is failed biological fixation which manifests as subsidence of the tenodesis and consequent descent of the tendon with evident aesthetic deformity.

Arthroscopy↗

PubMed2005

Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study.

OBJECTIVE: The influence of postprandial blood glucose on diabetes complications is intensively debated. We aimed to evaluate the predictive role of both fasting and postprandial blood glucose on cardiovascular events in type 2 diabetes and the influence of gender. METHODS: In a population of 529 (284 men and 245 women) consecutive type 2 diabetic patients attending our diabetes clinic, we evaluated the relationships, corrected for cardiovascular risk factors and type of treatment, between cardiovascular events in a 5-yr follow-up and baseline values of hemoglobin A1c (HbA1c) and blood glucose measured: 1) after an overnight fast, 2) after breakfast, 3) after lunch, and 4) before dinner. Continuous variables were categorized into tertiles. RESULTS: We recorded cardiovascular events in 77 subjects: 54 of 284 men (19%) and 23 of 245 women (9.4%). Univariate analysis indicated that cardiovascular events were associated with increasing age, longer diabetes duration, and higher HbA1c and fibrinogen in men, and higher systolic blood pressure, albumin excretion rate, HbA1c, and all blood glucose values in women. Smoking was more frequent in subjects with events. When all blood glucose values and HbA1c were introduced simultaneously in the models, only blood glucose after lunch predicted cardiovascular events, with hazard ratio of the third tertile vs. the first and the second tertiles greater in women (5.54; confidence interval, 1.45-21.20) than in men (2.12; confidence interval, 1.04-4.32; P < 0.01). CONCLUSIONS: Postprandial, but not fasting, blood glucose is an independent risk factor for cardiovascular events in type 2 diabetes, with a stronger predictive power in women than in men, suggesting that more attention should be paid to postprandial hyperglycemia, particularly in women.

Aged↗

PubMed2005

Effectiveness of frequency-modulated electromagnetic neural stimulation in the treatment of painful diabetic neuropathy.

AIMS/HYPOTHESIS: The largely unsatisfactory results reported for the pharmacological treatment of diabetic neuropathy has spurred the search for alternative therapies. The aim of this study was to evaluate the efficacy of frequency-modulated electromagnetic neural stimulation (FREMS) as a novel treatment for painful diabetic neuropathy. METHODS: Patients (n=31) with painful neuropathy associated with decreased nerve conduction velocity (<40 m/s) and increased vibration perception threshold (>25 V) were enrolled in a randomised, double-blind, crossover study designed to compare the effects of FREMS with those of placebo. Each patient received two series of ten treatments of either FREMS or placebo in random sequence, with each series lasting no more than 3 weeks. The primary efficacy end point was the change in pain measured by a visual analogue scale (VAS). RESULTS: FREMS induced a significant reduction in daytime and night-time VAS pain score (all p<0.02). Furthermore, FREMS induced a significant increase in sensory tactile perception, as assessed by monofilament; a decrease in foot vibration perception threshold, as measured by a biothesiometer; and an increase in motor nerve conduction velocity (all p<0.01). No significant changes were observed after placebo. Comparison of measurements at the 4-month follow-up with those at baseline revealed that a significant benefit persisted for all measures that showed an improvement at the end of treatment, with an additional improvement in quality of life evaluated by the Short Form-36 questionnaire (all p<0.05). No significant side effects were recorded during the study. CONCLUSIONS/INTERPRETATION: FREMS is a safe and effective therapy for neuropathic pain in patients with diabetes and is able to modify some parameters of peripheral nerve function.

Cross-Over Studies↗

PubMed2005

Inactivation of the mouse adenylyl cyclase 3 gene disrupts male fertility and spermatozoon function.

Mammalian spermatids and spermatozoa express functional G protein-coupled receptors. However, bicarbonate-regulated soluble adenylyl cyclase (AC), the major AC present in these cells, is not directly coupled to G proteins. To understand how G protein-coupled receptors signal in spermatozoa, we investigated whether a conventional transmembrane cyclase is present and biologically active in these cells. Here, we provide evidence for expression of type 3 AC (AC3) in male germ cells and describe the effects of disruption of the AC3 gene on fertility and function of mouse spermatozoa. As previously reported in rat, AC3 mRNA is expressed in mouse testes and localized, together with soluble AC mRNA, mainly in postmeiotic germ cells. AC3 protein was detected by immunolocalization in round and elongating spermatids in a region corresponding to the developing acrosome and was retained in the mature spermatozoa of the epididymis. Forskolin caused a small increase in cAMP production in mouse spermatozoa, but this increase could not be detected in the AC3(-/-) mice. Inactivation of the AC3 gene did not have overt effects on spermatogenesis; however, AC3(-/-) males were subfertile with only three litters generated by 11 males over a period of 6 months. When used in in vitro fertilization, spermatozoa from these AC3(-/-) mice produced few embryos, but their fertilizing ability was restored after removal of the zona pellucida. Despite an apparently normal structure, these spermatozoa had decreased motility and showed an increase in spontaneous acrosome reactions. These data support the hypothesis that AC3 is required for normal spermatid or spermatozoa function and male fertility.

Adenylyl Cyclases↗

PubMed2005

Thymidine phosphorylase gene mutations in patients with mitochondrial neurogastrointestinal encephalomyopathy syndrome.

The mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome is characterized by the association of gastrointestinal and neurological symptoms. It is a rare autosomal recessive mitochondrial disorder with multiple mitochondrial DNA deletions and/or depletion. It is caused by thymidine phosphorylase (TP) gene mutations resulting in a complete abolition of TP activity. We tested 31 unrelated patients presenting either with a complete MNGIE syndrome (8 patients), a severe intestinal pseudo-obstruction (10 patients), and multiple deletions and/or depletion of mitochondrial DNA (13 patients). All the tested patients presenting with a complete MNGIE had increased thymidine levels in plasma and urine, and no TP activity. The group with pseudo-obstruction syndrome had normal or partial reduction of TP activity. We found pathogenic mutations on TP gene only in the MNGIE syndrome group: all the MNGIE patients were compound heterozygous or homozygous for mutations in the TP gene. Eight of these mutations are yet unreported, confirming the lack of genotype/phenotype correlation in this syndrome. Enzymatic activity and thymidine level are thus rapid diagnosis tests to detect MNGIE affected patients prior to genetic testing for patients with gastrointestinal symptoms.

Adult↗

PubMed2005

Definition of an uptake pharmacophore of the serotonin transporter through 3D-QSAR analysis.

The serotonergic system plays a critical role in a wide variety of physiological and behavioral processes. Dysregulation of the tightly controlled extracellular concentration of serotonin (5-hydroxytryptamine, 5-HT) appears to be at the origin of a host of metabolic and psychiatric disorders. Since the plasma membrane 5-HT transporter (SERT) is the major protagonist in regulating extracellular 5-HT concentration, SERT is the target of most drugs interacting with the serotonergic system. Unfortunately, some of the drugs towards SERT (e.g. amphetamine derivatives) interfere with cell homeostasis leading to cell toxicity. Developing new SERT ligands devoid of any side-effect represents a major priority in the treatment of 5-HT-associated pathologies. Here, we report structure-activity relationships (SAR) and three-dimensional QSAR (3D-QSAR) studies of a library of 121 compounds including 5-HT analogs, harmanes, benzothiazoles, indanones, amphetamine derivatives and substrate-type 5-HT releasers, with the goal of identifying the structural determinants crucial for SERT uptake. In the absence of data about the bioactive form of 5-HT, conformational analysis of 5-HT was performed using quantum chemistry calculations. This led to three 5-HT stable conformers with anti, -gauche and +gauche side-chain conformation. These conformers, used as templates for superimposition with all the library compounds, enabled the design of a reliable 6-points pharmacophore representative of SERT uptake activity. Molecular dynamics (MD) simulations performed with compounds that are efficiently, moderately, poorly or not transported by SERT allowed to assess the validity of our pharmacophore. Altogether, our data provide for the first time a reliable pharmacophore of SERT uptake activity, which may help to the design of new drugs targeting SERT.

Adult↗

PubMed2004

Dose-dependent insulin regulation of insulin-like growth factor binding protein-1 in human endometrial stromal cells is mediated by distinct signaling pathways.

IGF binding protein-1 (IGFBP-1) is a major product of decidualized human endometrial stromal cells and decidua, and as a modulator of IGF action and/or by independent mechanisms, it regulates cell growth and differentiation and embryonic implantation in these tissues. IGFBP-1 secretion is primarily stimulated by progesterone and cAMP and is inhibited by insulin and IGFs. The signaling pathways mediating the latter are not well defined, and the current study was conducted to determine which pathways mediate the effects of insulin on IGFBP-1 mRNA and protein expression by human endometrial stromal cells decidualized in vitro by progesterone. Cells were cultured and treated with different combinations of insulin; wortmannin, an inhibitor of the phosphatidylinositide-3-kinase (PI3-kinase) pathway; and PD98059, an inhibitor of the MAPK pathway. IGFBP-1 mRNA was determined by real-time PCR, and protein secretion in the conditioned medium was measured by ELISA. Activation of the PI3-kinase and the MAPK pathways was assessed by the detection of phosphorylated AKT and ERK in Western blots, respectively. Insulin inhibited IGFBP-1 mRNA and protein secretion in a dose-dependent fashion, with an ED(50) for the latter 0.127 ng/ml (21.6 pm). Inhibitor studies revealed that at low doses, insulin acts through the PI3-kinase pathway, whereas at higher levels it also activates the MAPK pathway in the inhibition of IGFBP-1. The data demonstrate that human endometrium is a target for insulin action in the regulation of IGFBP-1. At physiological levels insulin likely plays a homeostatic role for energy metabolism in the endometrium, and in hyperinsulinemic states, insulin action on the endometrium may activate cellular mitosis via the MAPK pathway and perhaps predispose this tissue to hyperplasia and/or cancer.

Adult↗

PubMed2004

Epidermal growth factor family members: endogenous mediators of the ovulatory response.

Previous studies showed that epidermal growth factor (EGF) and TGFalpha mimic the action of LH on the resumption of oocyte maturation. We tested whether EGF-like agents, such as amphiregulin (AR), epiregulin (ER), and betacellulin (BTC), also mediate the LH stimulation of the ovulatory response in the rat. LH induced transient follicular expression of AR, ER, and BTC mRNA, reaching a maximum after 3-h incubation. Furthermore, the addition of ER, AR, and BTC to the culture medium could mimic some of LH actions. AR and ER fully simulated LH-induced resumption of meiosis in vitro, whereas BTC was less effective. To study the putative involvement of EGF-like factors in mediation of LH signal, the effect of the EGF receptor kinase inhibitor AG1478 was tested. When added with LH, AG1478, but not its inactive analog AG43, reduced EGF receptor phosphorylation and oocyte maturation compared with follicles treated with LH only. In addition to the inhibition of resumption of meiosis, AG1478 administration into the bursa (3 microg/bursa) resulted in 51% (P < 0.0005) inhibition of ovulation in the treated ovaries, compared with the untreated contralateral ones, as well as to the vehicle-treated ovaries (P < 0.02). LH, as well as ER, induced the expression of genes associated with the ovulatory response like rat hyaluronan synthase-2, cyclooxygenase-2, and TNFalpha-stimulated gene 6 mRNA, whereas AG1478 inhibited this effect of LH. Release of EGF-like factors from the membrane is dependent on activated metalloproteases. Indeed, Galardin, a broad-spectrum metalloprotease inhibitor, but not a specific matrix metalloprotease 2 and 9 inhibitor, suppressed meiotic maturation induced by LH. Conversely, meiotic maturation induced by ER was not affected by Galardin, thus, supporting the notion that LH releases follicular membrane-bound EGF-like agents. In summary, EGF-like factors such as ER, AR, and BTC seem to mediate, at least partially, the LH stimulation of oocyte maturation, ovulatory enzyme expression, and ovulation.

Amphiregulin↗

PubMed2004

Dynamics of vibrofluidized granular gases in periodic structures.

The behavior of a driven granular gas in a container consisting of M connected compartments is studied employing a microscopic kinetic model. After obtaining the governing equations for the occupation numbers and the granular temperatures of each compartment we consider the various dynamical regimes. The system displays interesting analogies with the ordering processes of phase separating mixtures quenched below their critical point. In particular, we show that below a certain value of the driving intensity the populations of the various compartments become unequal and the system forms clusters. Such a phenomenon is not instantaneous, but is characterized by a time scale tau which follows a Vogel-Vulcher exponential behavior. On the other hand, the reverse phenomenon which involves the "evaporation" of a cluster due to the driving force is also characterized by a second time scale which diverges at the limit of stability of the cluster.

Journal Article↗

PubMed2004

[Blast injury. Acute blindness caused by thoracoabdominal compression trauma].

Blindness can be the consequence of trauma, which until now had only been described in cases involving direct facial or cranial trauma. In our case a 53-year-old street worker became irreversibly blind after a thoracoabdominal compression trauma. The investigations performed were inconclusive regarding the cause of blindness. We postulate a massive increase in venous blood pressure with capillary stasis and consequent optic nerve damage. Fat emboli syndrome or posterior ischemic optic neuropathy could be causes, but unrealistic for this case. It still comes into question why such a mechanism has not been seen in other blast injury cases. In the end, the additional factor that resulted here in complete irreversible blindness remains unclear.

Abdominal Injuries↗

PubMed2004

Pure post-stroke cerebellar cognitive affective syndrome: a case report.

Cerebellar pathology commonly shows important motor signs and less evident cognitive dysfunction. The 'cerebellar cognitive affective syndrome' is characterised by impairment on executive function, spatial cognition, language and behaviour. We report the case of a man with acute onset of transitory motor features and severe mental disorders. Cranial CT and brain MRI revealed extended cerebellar lesions. Neuropsychological assessment disclosed deficits of attention, executive function and memory. Auditory event-related potentials showed abnormal P300. These data suggest a pure "cerebellar cognitive affective syndrome"and strengthen the hypothesis of cerebellar cognitive function modulation.

Aged↗

PubMed2004

Impact of trisomy 21 on human trophoblast behaviour and hormonal function.

Although trisomy 21 (T21) is the most frequent genetic abnormality and some maternal serum markers for this fetoplacental aneuploidy are of placental origin, little is known of its impact on placental development. We therefore studied the influence of T21 on trophoblast behaviour. Using cultured cells from 46 human T21 pregnancies, we confirmed the defective morphological and functional differentiation of the villous cytotrophoblast in this setting; indeed, villous cytotrophoblast cells aggregate normally but fuse inefficiently to form the syncytiotrophoblast. This is in part related to the abnormal oxidative status of the T21 cytotrophoblast, characterized by a gene dosage-related increase in SOD-1 (copper-zinc superoxide dismutase) expression and activity. This was associated with a significant (P < 0.01) increase in catalase activity but no significant change in glutathione peroxidase activity. On the basis of these in vitro findings and studies of large panels of maternal serum, we propose a pathophysiological explanation for trisomy 21 maternal serum markers of placental origin.

Adult↗

PubMed2004

Clinical pharmacology of intraperitoneal cisplatin-based chemotherapy.

The management of intraperitoneal tumors, especially when confined to the peritoneal cavity and/or associated with malignant ascites, requires the use of intraperitoneal (i.p.) cisplatin-based chemotherapy. This therapeutic approach, enabling high concentrations of drug and long duration of tumor tissue exposure, while generating a systemic exposure similar to that obtained with intravenous (i.v.) infusion, significantly improves therapeutic ratio. Nowadays, as feasibility issues are easy to overcome, intraperitoneal chemotherapy provides a safe, effective treatment for the management of peritoneal disease, particularly ovarian carcinoma. In this paper we review pharmacological issues of intraperitoneal cisplatin-based chemotherapy in order to provide a ready to use information collection for clinical practice and ongoing research.

Cisplatin↗

PubMed2004

Characterization of focal liver lesions in real time using harmonic imaging with high mechanical index and contrast agent levovist.

OBJECTIVE: The aim of this study was to characterize focal hepatic lesions using agent detection imaging and Levovist. MATERIALS AND METHODS: Sixty-five patients (21 male and 44 female; age range, 8-82 years; mean +/- standard deviation, 58.1 +/- 14.5 years) were independently evaluated by two observers in a blinded manner using stored sonographic images. Seventy-five lesions were found: 15 hepatocellular carcinomas, nine focal nodular hyperplasias, two adenomas, 21 hemangiomas, 23 metastases, and five regenerative nodules. Nine patients were excluded (six because of technical failures, three with unproven diagnoses). New high-mechanical-index software was used to reveal power harmonic responses from contrast microbubble destruction. After a venous bolus injection of 4 g of Levovist at a strength of 400 mg/mL, delayed imaging was used to study lesion enhancement in the arterial, portal, and parenchymal phases. Two comparisons were made. The first was between the B-mode image and the first contrast-enhanced image after the flash. The second was between color Doppler sonograms and real-time contrast-enhanced perfusion images. RESULTS: Contrast-enhanced images after the flash and real-time contrast-enhanced images revealed more information for the characterization of the lesion than did gray-scale and color Doppler images (p < 0.0001, Wilcoxon's signed rank test). Different types of lesions showed statistically significant differences in enhancement during each of the three vascular phases (p < 0.005, Kruskal-Wallis test). Lesions with lower contrast enhancement were metastases and regenerating nodules. Good agreement was present between the two observers; differences were not statistically significant (p > 0.05). CONCLUSION: Agent detection imaging with Levovist increased diagnostic confidence in the characterization of focal hepatic lesions as compared with standard sonography.

Adolescent↗

PubMed2003

Stroke in young adults: epidemiology.

Stroke in the young is rather rare. The absolute proportion of juvenile stroke is strongly linked to the structure of the population. In western European countries, with a high prevalence of old and very old people, less than 5% of strokes occur in subject under 45 years. The incidence is about 10 in 100,000 in several Italian studies. In Italy, about 3,300 new cases of juvenile stroke occur each year. Higher incidence rates have been found in the United States and developing countries. Subarachnoid hemorrhage prevails in young cases, compared with the total population of stroke patients. In the subgroup of patients with cerebral infarction, inter-atrial septum defects and inherited thrombophilic disorders seem to play an important role.

Adolescent↗