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Biomedical subjects

M Di Benedetto

Publications and source records attributed to M Di Benedetto.

At least 19 recordsLinked to original sources
PubMed2006

Role of serotonin in the regulation of the dynorphinergic system by a kappa-opioid agonist and cocaine treatment in rat CNS.

It has been shown that chronic cocaine increases prodynorphin mRNA in the caudate putamen and decreases it in the hypothalamus. In addition, treatment with a kappa-opioid receptor agonist produced the opposite effect on prodynorphin gene expression in these brain regions and also evoked a decrease in the hippocampus. It is already known that kappa-opioid receptor agonists decrease the development of sensitization to some of the behavioral effects of cocaine. The serotonin system has also been shown to regulate dynorphin gene expression and a continuous infusion of fluoxetine induced prodynorphin gene expression in the same pattern as the kappa-opioid agonist (+)(5a,7a,8b)-N-methyl-N-[7-(1-pyrrolidinyl)-1 oxaspiro[4.5]dec-8-yl]-benzeneacetamide (U-69593) in the brain regions investigated. It is interesting to note that treatment with a continuous infusion of cocaine produced different effects on this parameter. To determine whether serotonin plays a role in the regulation of prodynorphin mRNA by kappa-opioid agonists or cocaine, rats were treated with the serotonin depleter parachloroamphetamine (PCA). Beginning 24 h later, rats were treated with the selective kappa-opioid agonist U-69593 for 5 days or continuously with cocaine for 7 days and prodynorphin mRNA was measured. Prodynorphin mRNA was decreased significantly in the hypothalamus, caudate putamen, and hippocampus of rats treated with a single injection of PCA. Subsequent to PCA administration the effects of U-69593 or cocaine on prodynorphin mRNA were differentially affected across brain regions. Prodynorphin gene expression was still increased by U-69593 treatment in the hypothalamus and decreased in the caudate putamen. Cocaine treatment still produced a decrease in this parameter in the hypothalamus and an increase in the caudate putamen. In contrast, in the hippocampus, the decrease in prodynorphin mRNA produced by U-69593 was no longer evident after PCA and cocaine, which previously had no effect, now increased it in the serotonin-depleted group. These findings suggest that serotonin is necessary to maintain normal levels of dynorphin mRNA in all of the investigated brain areas and that the regulation of prodynorphin mRNA expression by chronic treatment with a kappa-opioid receptor agonist or cocaine requires serotonin in the hippocampus, but not in the hypothalamus or caudate putamen.

Animals↗
PubMed2006

Structural organization and expression of human MTUS1, a candidate 8p22 tumor suppressor gene encoding a family of angiotensin II AT2 receptor-interacting proteins, ATIP.

The Mitochondrial Tumor suppressor 1 (MTUS1) gene is a newly identified candidate tumor suppressor gene at chromosomal position 8p22. We report here that MTUS1 encodes a family of proteins whose leader member (ATIP1) was previously isolated in our laboratory as a novel interacting partner of the angiotensin II AT2 receptor involved in growth inhibition (Nouet, JBC 279: 28989-97, 2004). The MTUS1 gene contains 17 coding exons distributed over 112 kb of genomic DNA. Alternative exon usage generates three major transcripts (ATIP1, ATIP3 and ATIP4), each showing different tissue distribution. ATIP polypeptides are identical in their carboxy-terminal region carrying four coiled-coil domains. In their amino-terminal portion, ATIP polypeptides exhibit distinct motifs for localisation in the cytosol, nucleus or cell membrane, suggesting that MTUS1 gene products may be involved in a variety of intracellular functions in an AT2-dependent and independent manner. ATIP1 is ubiquitous and highly expressed in the brain. ATIP3 is the major transcript in tissues (prostate, bladder, breast, ovary, colon) corresponding to cancer types with frequent loss of heterozygosity at 8p22. Interestingly, ATIP4 is a brain-specific transcript highly abundant in the cerebellum and fetal brain. High evolutionary conservation of ATIP amino-acid sequences suggests important biological roles for this new family of proteins in tumor suppression and/or brain function.

Alternative Splicing↗
PubMed2006

Alterations in prodynorphin gene expression and dynorphin levels in different brain regions after chronic administration of 14-methoxymetopon and oxycodone-6-oxime.

Previous studies showed that opioid drugs-oxycodone-6-oxime and 14-methoxy-5-methyl-dihydromorphinone (14-methoxymetopon)-produced less respiratory depressive effect and slower rate of tolerance and dependence, respectively. It was also reported that morphine decreased the prodynorphin gene expression in the rat hippocampus, striatum and hypothalamus. In this study, we determined the prodynorphin gene expression and dynorphin levels in selected brain regions of opioid tolerant rats. We found that in the striatum morphine decreased, while oxycodone-6-oxime increased and 14-methoxymetopon did not alter the prodynorphin gene expression. In the nucleus accumbens, morphine and oxycodone-6-oxime did not change, while 14-methoxymetopon increased the prodynorphin gene expression. In the hippocampus both oxycodone-6-oxime and 14-methoxymetopon enhanced, whereas morphine did not alter the prodynorphin gene expression. In the rat striatum only oxycodone-6-oxime increased dynorphin levels significantly in accordance with the prodynorphin mRNA changes. In the hippocampus both opioid agonists increased the dynorphin levels significantly similarly to the augmented prodynorphin gene expression. In ventral tegmental area only 14-methoxymetopon increased dynorphin levels significantly. In nucleus accumbens and the temporal-parietal cortex the changes in the prodynorphin gene expression and the dynorphin levels did not correlate. Since the endogenous prodynorphin system may play a modulatory role in the development of opioid tolerance, the elevated supraspinal dynorphin levels appear to be partly responsible for the reduced degree of tolerance induced by the investigated opioids.

Animals↗
PubMed2006

Mutation analysis of the 8p22 candidate tumor suppressor gene ATIP/MTUS1 in hepatocellular carcinoma.

A high frequency of allelic loss affecting chromosome 8p and a minimal region of deletion at p21-22 have been previously reported in hepatocellular carcinoma (HCC), suggesting that at least one tumor suppressor gene is present in this region. In this study, we assessed whether the angiotensin II AT2 receptor interacting protein (ATIP)/mitochondrial tumor suppressor gene (MTUS1), a gene newly identified at position 8p22, may be a candidate tumor suppressor gene mutated in HCC. We searched for alterations in the 17 coding exons of ATIP/MTUS1 by means of denaturating high-performance liquid chromatography and sequencing, in 51 HCC tumors and 58 cell lines for which loss of heterozygosity status was known. Five major nucleotide substitutions were identified, all located in exons used by the ATIP3 transcript which is the only ATIP transcript variant expressed in liver. These nucleotide variations result in amino-acid substitution or deletion of conserved structural motifs (nuclear localisation signal, polyproline motif, leucine zipper) and also affect exonic splicing enhancer motifs and physiological splice sites, suggesting potential deleterious effects on ATIP3 function and/or expression.

Amino Acid Substitution↗
PubMed2005

Chronic and acute effects of 3,4-methylenedioxy-N-methylamphetamine ('Ecstasy') administration on the dynorphinergic system in the rat brain.

The prodynorphin system is implicated in the neurochemical mechanism of psychostimulants. Exposure to different drugs of abuse can induce neuroadaptations in the brain and affect opioid gene expression. The present study aims to examine the possibility of a common neurobiological substrate in drug addiction processes. We studied the effects of single and repeated 3,4-methylenedioxy-N-methylamphetamine ('Ecstasy') on the gene expression of the opioid precursor prodynorphin, and on the levels of peptide dynorphin A in the rat brain. Acute (8 mg/kg, intraperitoneally) 3,4-methylenedioxy-N-methylamphetamine markedly raised, two hours later, prodynorphin mRNA levels in the prefrontal cortex, and in the caudate putamen, whereas it decreased gene expression in the ventral tegmental area. Chronic (8 mg/kg, intraperitoneally, twice a day for 7 days) 3,4-methylenedioxy-N-methylamphetamine increased prodynorphin mRNA in the nucleus accumbens, hypothalamus and caudate putamen and decreased it in the ventral tegmental area. Dynorphin A levels increased after chronic treatment in the ventral tegmental area and decreased after acute treatment in the nucleus accumbens, prefrontal cortex and hypothalamus. These findings confirm the role of the dynorphinergic system in mediating the effects of drugs of abuse, such as 3,4-methylenedioxy-N-methylamphetamine, in various regions of the rat brain, which may be important sites for the opioidergic mechanisms activated by addictive drugs.

Animals↗
PubMed2003

Inhibition of epidermoid carcinoma A431 cell growth and angiogenesis in nude mice by early and late treatment with a novel dextran derivative.

We investigated the effect of a new dextran derivative, phenylacetate carboxymethyl benzylamide dextran (NaPaC), on epidermoid carcinoma A431 cells secreting a large quantity of angiogenic factor, vascular endothelial growth factor (VEGF). In vitro, NaPaC inhibited the proliferation of A431 cells (IC(50)=5 micro M). Also, NaPaC decreased the binding of radiolabelled VEGF(165) to endothelial cells (IC(50)=0.2 micro M). In vivo, we explored the effects of NaPaC (15 mg kg(-1)) on A431 xenograft growth starting the drug administration at the time of tumour cell inoculation (early treatment) and 1 week later, when tumours were well established (late treatment). Early treatment was more efficient on tumour inhibition (70% vs control) than late treatment (50% vs control). Early and late NaPaC-treatment increased the aponecrosis in tumour by 70 and 30%, respectively. Whatever treatment, NaPaC inhibited the intratumour endothelial cell density in the same manner. In contrast, vessel area was decreased only when NaPaC was injected early (35%). These results show that NaPaC has a potent inhibitory effect, dependent on treatment outset, on epidermoid carcinoma growth associated with an intratumour microvascular network diminution and an aponecrosis increase. As this drug is nontoxic at efficient dose, it offers interesting perspectives for the therapy of malignant lesions.

Animals↗
PubMed2002

[Hypernatremia. Etiopathogenetic classification and description of a rare clinical case].

On the basis of a rare case of hypernatremia, the essential lines which allow a correct diagnostic and therapeutic approach to hypernatremia are underlined. Hypernatremia is classified according to the patient's state of hydratation and on the content of sodium as: hypovoloemic, euvolemic and hypervolemic. Even the concentrations of sodium in urine are often of great importance for a correct diagnosis. The patient studied suffered from hypernatremia, which is based on genetical factors. The state of dehydration, together with hypovolemia and acute tubular necrosis secondary to rhabdomyolisis, were the causes of hypernatremia. The above mentioned causes were resolved but an enterocutaneous fistula showed to be the cause, quite rare, of hypernatremia. It is suggested that this rare cause should always be mentioned when diagnosing hypernatremia; which it is important since this cause could be solved with an operation. All this was useless in our case since the patient had a drastic deterioration of his general clinical conditions.

Algorithms↗
PubMed2001

Sodium phenylacetate enhances the inhibitory effect of dextran derivative on breast cancer cell growth in vitro and in nude mice.

Sodium phenylacetate (NaPa) and carboxymethyl benzylamide dextran derivative (CMDB(LS4)) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDB(LS4)may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose- and time-dependent manner. The addition of CMDB(LS4)potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDB(LS4)and NaPa concentrations. In nude mice, CMDB(LS4)(150 mg kg(-1)) or NaPa (40 mg kg(-1)) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDB(LS4)and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDB(LS4)action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDB(LS4)added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDB(LS4)involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of dextran derivatives with NaPa to inhibit the breast tumour growth.

3T3 Cells↗
PubMed2001

Could 99mTc-MIBI be used to visualize the apoptotic MCF7 human breast cancer cells?

Defects in key components of apoptotic pathways provide a survival advantage to cells and have been implicated as important factors in tumorogenesis. As therapeutic drug-induced apoptosis is a key component in treatment of most cancers, alterations in apoptotic pathways may be critical to drug resistance. The question is: would it be possible to distinguish apoptotic cells and resistant cells with a same radiotracer? In this study, we investigated the ability of sodium phenylacetate (NaPa), a natural cytostatic proapoptotic metabolite, to induce apoptosis in MCF7 human breast cancer cells. Then, we tested the 99mTc-MIBI accumulation in these apoptotic cells. Annexin V-FITC was used to identify apoptotic cells by flow cytometry. Ours results demonstrated that a 72 hr treatment of MCF7 cells with 40 mM NaPa induced apoptosis in 60% of cells. In a parallel way, 99mTc-MIBI accumulation in NaPa treated cells decreased for concentrations higher than 20 mM NaPa. Thus, 99mTc-MIBI accumulation decreased correlatively with the increasing percentage of apoptotic cells obtained by treatment of MCF7 cells with NaPa. These data demonstrate that NaPa induced apoptosis in MCF7 cells and that 99mTc-MIBI is a negative tracer of apoptosis: the more MCF7 cells were engaged in the apoptotic pathway, the more 99mTc-MIBI accumulation decreased in these MCF7 apoptotic cells.

Apoptosis↗
PubMed2000

Plasmatic endothelin-1 levels in hyperthyroid patients before and after antithyroid therapy.

BACKGROUND: The Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced by endothelial cells in many vascular diseases probably as a response to vessel damage. In hyperthyroidism as in other endocrinological diseases elevated ET-1 plasma levels have been found. METHODS: The effect of antithyroid therapy on ET-1 plasmatic levels was evaluated by measuring ET-1 plasma levels before and 2 and 6 months after treatment with methimazole in 14 patients affected by hyperthyroidism. RESULTS: The hyperthyroid patients had significantly higher ET-1 levels than the controls (18.85 +/- 5.7 vs 10.9 +/- 2.1 pg/ml), while after treatment no difference was found. The ET-1 plasma levels of hyperthyroid patients correlated closely with the raised thyroid metabolic activity independently of its cause. It is possible that the increased ET-1 levels in hyperthyroid patients are the expression of blood vessel damage caused by high thyroid hormone levels. CONCLUSIONS: Moreover the results of this study could suggest that, in future, ET-1 plasmatic levels might be considered as a functional thyroid index in hyperthyroid diseases.

Adult↗
PubMed1996

American Association of Electrodiagnostic Medicine guidelines for outcome studies in electrodiagnostic medicine.

Based on a review of the literature and the clinical research experience of the authors and reviewers, the AAEM proposes 17 criteria which should be used to construct and evaluate diagnostic and/or therapeutic outcome studies for patients with symptoms and signs of neuromuscular diseases. Neuromuscular diseases are defined as diseases that cause pathology and/or dysfunction of the sensory, motor, and/or autonomic nerve offers and/or muscles.

Association↗
PubMed1989

Suction cup ground and reference electrodes in electrodiagnosis.

An alternative to the taped-disc surface electrodes typically used during monopolar and concentric needle electromyographic studies has been investigated. The use of suction cup surface electrodes in place of the taped metal disc surface electrodes increases patient and operator safety and enhances patient comfort and operator efficiency. A two-channel EMG, with a single active needle and two reference electrodes, was done on patients routinely referred for electromyographic studies. The motor units were stored and compared. Similarly, baseline noise was stored and compared. This study shows that no distortion of motor unit potentials in typically measured parameters, nor alteration in baseline "noise" occurs when using the suction cup electrode in place of the taped metal discs. The safer, more comfortable suction cup surface electrodes do not distort the motor unit potentials that electromyographers are accustomed to interpreting.

Action Potentials↗
PubMed1988

Hypoglossal nerve conduction in normal subjects.

A nerve conduction method is demonstrated for cranial nerve XII, the hypoglossal nerve. Submandibular surface stimulation is performed while recording over the anterior surface of the tongue. There were 30 normal adult subjects and 60 hypoglossal nerves studied. Evoked response parameters are reported as follows: mean latency 2.2 +/- 0.4 msec, mean amplitude 3.8 +/- 1.6 mV (baseline to peak, best of 5 responses). This nerve conduction method is reliable and should expand the electrophysiological assessment of XII cranial nerve motor function.

Adult↗
PubMed1986

New criteria for sensory nerve conduction especially useful in diagnosing carpal tunnel syndrome.

This article reports a technique for determining new standard values for median sensory nerve latencies, amplitudes, and durations. Use of these values should significantly improve the ability to diagnose carpal tunnel syndrome and to reduce the number of false negative results. Forty-five median sensory nerves of 30 neurologically healthy subjects were evaluated with rigid techniques and temperature control at stimulation and recording points. Latencies for antidromic and orthodromic conduction from wrist-to-thumb, wrist-to-index finger, wrist-to-middle finger, and wrist-to-ring finger (all 14 cm distances) are reported. Conduction time for nerve impulses through the transcarpal segment via ulnar and radial nerves was also measured for comparison with median nerve latencies. In addition to latency measurements, characteristics of electrical responses evoked by stimulation were described. These include amplitude of the recorded response measured from baseline to negative peak and from negative peak to positive peak, duration of the negative response wave (from baseline to return to baseline) and duration measured from onset of the negative wave to the positive peak. According to our data, a distal median nerve sensory latency of more than 3.3 ms (the mean of 2.9 ms plus two standard deviation values of 0.18 ms) when measured to the peak of the negative wave is indicative of abnormality.

Adult↗
PubMed1985

Isolation of Mycobacteria from drinking water in Palermo.

Mycobacteria other than tuberculosis (MOTT) were isolated from 20 of 54 samples (37%) of tap water collected in Palermo in the period April-July 1984. The 55 isolates were M. gordonae (40), M. scrofulaceum (9), MAIS organisms (3), M. fortuitum (2), M. non photochromogenic (1). M. gordonae was isolated from 16 of the 20 positive samples and in five of them in association to other MOTT. A study of MOTT spread in other levels of piping system, showed, as already reported in similar studies, that some places, like taps and tanks, are probably favourable to more or less persistent MOTT colonization.

Disease Reservoirs↗
PubMed1984

Neuropathy in end-stage renal disease secondary to primary renal disease and diabetes.

A study was undertaken to critically observe electrophysiologic findings in patients with end-stage renal disease (ESRD) secondary to primary renal disease (PRD) and to compare these with data recorded from patients with ESRD secondary to diabetes mellitus. Motor and sensory nerve conduction velocity studies were performed on 56 patients; 16 parameters were investigated and laboratory data recorded. Our findings reveal that diabetic uremics have more severe peripheral neuropathy electrophysiologically than nondiabetics, indicating that the diabetic component of neuropathy sustains its influence even in the presence of end-stage renal neuropathy. The sural latency and amplitude, median sensory latency and amplitude, H-reflex and facial latency were significantly involved parameters in nondiabetic and diabetic patients. The facial nerve was found to be a sensitive indicator of uremic neuropathy. In 28 nondiabetic uremic patients the mean facial latency was 3.8 +/- 0.5msec compared to 28 diabetic uremic patients with a mean of 5.0 +/- 0.4msec.

Adolescent↗