Biomedical subjects

C Orsini

Publications and source records attributed to C Orsini.

At least 19 recordsLinked to original sources

PubMed2006

Minimally invasive resection for colorectal cancer: perioperative and medium-term results in an unselected patient group at a single institution.

BACKGROUND: The use of laparoscopy for colorectal cancer resection is still controversial. METHODS: We prospectively analyzed the outcome of minimally invasive resection for colorectal cancer, performed at our institution from 1998, when laparoscopic surgery became the treatment of choice for colorectal cancer, until 2004. All patients undergoing elective resection were assessed in terms of perioperative results (duration of surgery, number of lymph nodes removed, length of specimen, rate of conversion, complications) and survival. Patients were assessed yearly with follow-up visits and telephone interviews. RESULTS: In the study period, 302 patients (mean age 66.1 years; range, 32-93 years) underwent 114 left hemicolectomies, 108 low anterior resections, 61 right hemicolectomies, 12 Miles procedures, 4 subtotal colectomies, and 3 transverse colon resections. Surgery took an average of 226 minutes (SD=71 min). The number of lymph nodes removed was 14+/-8. The conversion rate was 10%; most of the conversions were due to locally advanced cancer (15 cases) and bowel distension (7 cases). Fifteen anastomotic leaks were observed (5%). Twenty patients needed reoperation and two died: one of septic shock due to an anastomotic leak; the other of electrolyte imbalance and dehydration after peritonitis due to a bowel loop injury. Follow-up was available for 91% of patients. Cancer-related survival curves showed a 90% survival for stage II, 85% for stage III, and 10% for stage IV disease, 30 months after surgery. CONCLUSIONS: Minimally invasive laparoscopic resection for colorectal cancer enables an oncologically adequate resection with complication and survival rates that are no worse than are to be expected after traditional open surgery. Locally advanced tumor and bowel distension are the most frequent reasons for conversion to open surgery.

Adenocarcinoma↗

PubMed2006

Habituation to the test cage influences amphetamine-induced locomotion and Fos expression and increases FosB/DeltaFosB-like immunoreactivity in mice.

Pre-exposure to the testing cage (habituation or familiarization) is a common procedure aimed at reducing the interference of novelty-induced arousal and drug-independent individual differences on neural and behavioral measures. However, recent results suggest that this procedure might exert a major influence on the effects of addictive drugs. The present experiments tested the effects of repeated exposure to a test cage (1 h daily for four consecutive days) on amphetamine-induced locomotion and Fos expression as well as on FosB/DeltaFosB-like immunoreactivity in mice of the C57BL/6J and DBA/2J inbred strains that differ for the response to amphetamine, stress and novelty. Daily experiences with the test cage increased FosB/DeltaFosB-like immunoreactivity in the medial-prefrontal cortex of both strains of mice and in the caudate of mice of the C57 strain, as reported for repeated stress in the rat. Moreover, previous habituation to the test cage reduced the locomotor response to a low dose of amphetamine only in DBA mice while it reduced amphetamine-induced Fos expression in medial-prefrontal cortex, dorsal caudate and the accumbens shell of mice of the C57 strain. These results demonstrate indexes of stress-like plasticity in the brains of mice exposed to a procedure of familiarization to the testing environment. Moreover, they suggest that the procedure of daily familiarization influences the pattern of brain Fos expression induced by amphetamine. Finally, they indicate complex interactions between experience with the testing environment, genotype and drug.

Amphetamine↗

PubMed2006

Chromatic pattern-reversal electroretinograms (ChPERGs) are spared in multiple system atrophy compared with Parkinson's disease.

Idiopathic Parkinson's disease (IPD) patients have abnormal visual evoked potentials (VEPs) and pattern electroretinograms (PERGs), attributed to dopaminergic transmission deficiency in visual pathway, probably the retina. VEP abnormalities are not reported in multiple system atrophy (MSA). The aim of this study was to investigate and compare chromatic (Ch) red-green (R-G) and blue-yellow (B-Y), and luminance yellow-black (Y-Bk) PERGs in patients with MSA and IPD. We investigated 6 MSA patients (mean age: 62+/-7.4 years) not undergoing any pharmacological treatment, as well as 12 early IPD patients (mean age: 60.1+/-8.3 years) and 12 age-matched normal observers. ChPERGs were recorded monocularly in response to full-field equiluminant R-G, B-Y and Y-Bk horizontal gratings. In MSA only responses to R-G stimuli showed minimal insignificant changes (slight but not significant amplitude reduction without any significant latency delay); no significant abnormality was detected for B-Y and luminance Y-Bk stimuli. By contrast, in IPD all responses were reduced in amplitude and delayed in latency, above all for B-Y stimuli. Present data indicate that both chromatic and achromatic PERGs are virtually unaffected in MSA, whereas in early IPD they are clearly impaired, suggesting different pathogenic retinal mechanisms and a useful simple tool for distinguishing MSA from IPD.

Aged↗

PubMed2005

Susceptibility to conditioned place preference induced by addictive drugs in mice of the C57BL/6 and DBA/2 inbred strains.

RATIONALE: In previous studies, we have demonstrated that mice of the inbred strain C57BL/6J (C57) are more susceptible to amphetamine-induced conditioned place preference (CPP) than DBA/2J (DBA) mice. Moreover, we also observed parallel strain differences for the locomotor-stimulant effects of the drug. However, other studies have reported either no difference or opposite strain differences for cocaine- and morphine-induced CPP as well as for the locomotor effects of these drugs, suggesting that amphetamine-related behavioral phenotypes might depend on a specific pharmacological action of the psychostimulant. OBJECTIVES: This study was aimed at testing strain differences for cocaine- and morphine-related behavioral phenotypes in the same experimental protocol and conditions previously used for amphetamine. METHODS: C57 and DBA mice were tested for CPP induced by cocaine (0, 5, 10, and 20 mg/kg) and morphine (0, 5, 7.5, and 10 mg/kg). Locomotor activity data were simultaneously obtained by measuring distance moved during all different CPP phases and unconditioned locomotor activity, behavioral sensitization and conditioned hyperactivity were measured together with CPP. RESULTS: (a) Either cocaine or morphine promoted significant CPP at lower doses in C57 than in DBA mice; (b) only drug-trained C57 mice showed a significant CPP compared with the control group; and (c) only C57 mice showed dose-dependent effects of cocaine on CPP. Moreover, there was no relationship between drug-induced CPP and locomotion. CONCLUSIONS: The results demonstrate that C57 and DBA mice differ in their sensitivity to cocaine- and morphine-induced CPP and suggest that the two strains differ in sensitivity to the positive incentive properties of drugs of abuse.

Analgesics, Opioid↗

PubMed2004

Distinct patterns of Fos expression induced by systemic amphetamine in the striatal complex of C57BL/6JICo and DBA/2JICo inbred strains of mice.

Mice from the inbred strains C57BL/6 and DBA/2 are characterized by striking differences in their behavioral response to addictive drugs. We used Fos expression as a tool to reveal strain differences in the postsynaptic effects of amphetamine (AMPH; 2.5 mg/kg) within the nucleus accumbens (NAc) (core and shell) and the dorsal caudate (dorsomedial and dorsolateral). AMPH stimulated Fos expression in all striatal regions of mice from both strains. However, while C57BL/6 showed a higher Fos response than DBA/2 mice in both NAc shell and core, the opposite was true for the dorsolateral caudate. The effects of AMPH were prevented by D1 blockade in all striatal regions of both strains and mimicked by the D1 agonist, SKF82958 (0.1 mg/kg), in both regions of the caudate and in the NAc shell, but not in the core. Our results suggest that the functional heterogeneity of the striatal complex is under genetic control and that this control may implicate DA transmission and corticostriatal interactions.

Amphetamine↗

PubMed2004

Locating polyps by endoscopy with or without videolaparoscopy, radioguided occult colonic lesion identification or magnetic endoscopic imaging: the way forward to complete polyp removal.

Endoscopic polypectomy is the gold standard for the treatment of colorectal polyps. In the case of non-palpable lesions or to complete polyp removal, the lesions are located intra-operatively. With the advent of laparoscopy, identifying their position is even more important because there is no opportunity for intestinal palpation. Several methods of preoperative endoscopic marking have been proposed using different types of tattooing and recently using clips followed by ultrasonography detection. Innovative methods are analysed; magnetic endoscopic imaging is a reliable and accurate method for determining the anatomical position of the tip of the endoscope during colonoscopy. Radioguided colonic lesion identification needs a gamma detection probe. Endoscopic removal can be converted to endo-laparoscopic rendezvous, failing which, laparoscopic resection is a reliable and safe choice, offering all the advantages of minimally invasive surgical techniques.

Adult↗

PubMed2002

Viral and non-viral gene therapy partially prevents experimental cisplatin-induced neuropathy.

Sensory neuropathies are a frequent and dose-limiting complication resulting from treatment with cisplatin. Neurotrophin-3 (NT-3) promotes the survival of the large fiber sensory neurones that are impaired in cisplatin-induced neuropathy, and may therefore serve as a preventive agent. However, the short half-life of recombinant NT-3 after systemic administration limits its clinical applications. We compared two muscle-based gene transfer strategies for the continuous delivery of NT-3 to the bloodstream in an experimental model of cisplatin-induced neuropathy. Electrophysiological studies showed that the intramuscular injection of an adenovirus encoding NT-3 partially prevented the cisplatin-induced increase in sensory distal latencies. Similar effects were observed in cisplatin-treated mice that received intramuscular injections of a plasmid encoding NT-3 associated with in vivo electroporation. The two techniques were well tolerated and induced only slight muscle toxicity. Measurement of renal function, weight and survival showed that neither technique increased the toxicity of cisplatin. Our study shows that gene therapy, using either a viral or a non-viral vector, is a promising strategy for the prevention of cisplatin-induced neuropathy.

Adenoviridae↗

PubMed2001

Continuous delivery of neurotrophin 3 by gene therapy has a neuroprotective effect in experimental models of diabetic and acrylamide neuropathies.

Neurotrophic factors (NFs) are promising agents for the treatment of peripheral neuropathies such as diabetic neuropathy. However, the value of treatment with recombinant NF is limited by the short half-lives of these molecules, which reduces efficiency, and by their potential toxicity. We explored the use of intramuscular injection of a recombinant adenovirus encoding NT-3 (AdNT-3) to deliver sustained low doses of NT-3. We assessed its effect in two rat models: streptozotocin (STZ)-induced diabetes, a model of early diabetic neuropathy characterized by demyelination, and acrylamide experimental neuropathy, a model of diffuse axonal neuropathy which, like late-onset human diabetic neuropathy, results in a diffuse sensorimotor neuropathy with dysautonomy. Treatment of STZ-diabetic rats with AdNT-3 partially prevented the slowing of motor and sensory nerve conduction velocities (p < 0.01 and p < 0.0001, respectively). Treatment with AdNT-3 of acrylamide-intoxicated rats prevented the slowing of motor and nerve conduction velocities (p < 0.001 and p < 0.0001, respectively) and the decrease in amplitude of compound muscle potentials (p < 0.0001), an index of denervation. Acrylamide-intoxicated rats treated with NT-3 had higher than control levels of muscle choline acetyltransferase activity (p < 0.05), suggesting greater muscle innervation. In addition, treatment of acrylamide-intoxicated rats with AdNT-3 significantly improved behavioral test results. Treatment with AdNT-3 was well tolerated with minimal muscle inflammation and no detectable general side effects. Therefore, our results suggest that NT-3 delivery by adenovirus-based gene therapy is a promising strategy for the prevention of both early diabetic neuropathy and axonal neuropathies, especially late axonal diabetic neuropathy.

Acrylamides↗

PubMed2001

MUSEAP, a novel reporter gene for the study of long-term gene expression in immunocompetent mice.

The improvement of gene therapy vectors would benefit from the availability of a reporter gene that can be used for long-term studies in immunocompetent laboratory animals. We describe the construction and characterization of a novel reporter gene, murine secreted embryonic alkaline phosphatase (MUSEAP). We demonstrate by gene transfer in skeletal muscle of immunocompetent mice that MUSEAP is efficiently secreted and detected in the bloodstream and that injection of an increasing dose of DNA leads to a dose-dependent increase of plasma MUSEAP activity. We also show that the expression of MUSEAP under the control of a constitutive promoter is stable for 1 year and that the activity of MUSEAP in the bloodstream reflects the changes in the transcription rate of its gene. These properties make MUSEAP the only reporter gene that can be used for somatic gene transfer into immunocompetent mice in order to study the impact of gene transfer vectors of metabolic, developmental or environmental factors on long-term gene expression.

Alkaline Phosphatase↗

PubMed2001

Partial prevention of cisplatin-induced neuropathy by electroporation-mediated nonviral gene transfer.

Cisplatin-induced sensory peripheral neuropathy is the dose-limiting factor for cisplatin chemotherapy. We describe the preventive effect of NT-3 delivery, using direct gene transfer into muscle by in vivo electroporation in a mouse model of cisplatin-induced neuropathy. Cisplatin-induced neuropathy was produced by weekly injections of cisplatin (five injections). Two doses of plasmid DNA encoding murine NT-3 (pCMVNT-3) were tested (5 and 50 microg/animal/injection). Cisplatin-treated mice were given two intramuscular injections. The first injection of pCMVNT-3 was given 2 days before the first injection of cisplatin and the second injection 2 weeks later. Six weeks after the start of the experiment, measurement of NT-3 levels (ELISA) demonstrated significant levels both in muscle and plasma. We observed a smaller cisplatin-related increase in the latency of the sensory nerve action potential of the caudal nerve in pCMVNT-3-treated mice than in controls (p < 0.0001). Mean sensory distal latencies were not different between the 5- and 50- microg/animal/injection groups. Treatment with gene therapy induced only a slight muscle toxicity and no general side effects. Therefore, neurotrophic factor delivery by direct gene transfer into muscle by electroporation is of potential benefit in the prevention of cisplatin-induced neuropathy and of peripheral neuropathies in general.

Animals↗

PubMed2001

Pharmacological evidence of muscarinic-cholinergic sensitization following chronic stress.

RATIONALE: Although much evidence supports a major role of brain cholinergic transmission in memory consolidation processes, little is known about cholinergic functioning under environmental pressure. OBJECTIVES: The present experiments were aimed at investigating possible functional adaptation of muscarinic receptors promoted by a chronic stressful procedure in an inbred strain of mice highly susceptible to stress. METHODS: We tested the effects of post-trial administration of a cholinergic agonist and a muscarinic antagonist on the retention of a passive avoidance task in control animals and compared these effects with those observed following food restriction. RESULTS: Food restriction enhanced the facilitatory effects of oxotremorine and reduced the impairing effects of atropine on memory consolidation. CONCLUSION: Our results support the view that chronic sensitization of muscarinic receptors occurs following chronic stress.

Animals↗

PubMed2001

A dopamine partial agonist and antagonist block amphetamine self-administration in a progressive ratio schedule.

A recently characterized class of compounds, dopamine partial agonists, have been suggested as potential therapeutic candidates for pharmacological intervention in psychostimulant addiction. These drugs bind to dopamine receptors with high affinity and low intrinsic activity and are thought to behave as functional antagonists in conditions of high dopaminergic tone, and as agonists in conditions of low receptor occupancy by dopamine. The aim of the present study was to characterize the effects of terguride, a partial dopamine agonist at the D2 receptor subtype, on intravenous self-administration of amphetamine in a progressive ratio schedule and to compare it with the effects produced by the dopamine D2 antagonist eticlopride and the dopamine D2 full agonist quinpirole. Terguride at the doses of 0.2 and 0.4 mg/kg i.p. significantly decreased the maximum number of responses delivered for a single injection of amphetamine ("breaking point"), an effect similar to that produced by the antagonist eticlopride (0.01-0.1 mg/kg s.c.). In contrast, administration of quinpirole (0.1-1 mg/kg s.c.) did not significantly modify the breaking point for amphetamine responding. Also, terguride dose-dependently increased responding for amphetamine self-administration on a continuous reinforcement schedule. These data further confirm the effects of terguride on psychostimulant self-administration and indicate that under these conditions partial dopamine agonists act as functional dopamine receptor antagonists.

Amphetamine↗

PubMed2001

Dopamine partial agonist reverses amphetamine withdrawal in rats.

Decreased motivation to work for a natural reward is a sign of amphetamine withdrawal and is thought to be associated with hypofunction of the mesolimbic dopamine system. During withdrawal from repeated amphetamine administration, rats showed reduced responding for a sweet solution in a progressive ratio schedule. Repeated systemic treatment with terguride (0.2 and 0.4 mg/kg, i.p.) twice daily during the first four days of amphetamine withdrawal reversed the decrease in responding for the sweet solution. These results suggest that dopamine partial agonists, possibly due to their agonistic-like actions under these conditions, are a potential therapeutic approach for the acute withdrawal stage of the amphetamine addition cycle.

Amphetamine↗

PubMed2001

Equiluminant red-green and blue-yellow VEPs in multiple sclerosis.

The primate visual system is composed by two color-opponent pathways--red-green (R-G) and blue-yellow (B-Y)--subserved by the so-called parvo- and koniocellular streams respectively. The authors' aim was to compare the relative involvement of chromatic visual subsystems in multiple sclerosis (MS). In 30 MS patients with different forms of MS they recorded visual evoked potentials (VEPs) to onset (300 msec) and offset (700 msec) of equiluminant R-G and B-Y sinusoidal gratings of different contrast (90% and 25%). Equiluminance was established psychophysically by establishing the R-G and the B-Y color ratio at which chromatic gratings alternating at 15 and 10 Hz respectively had minimum visibility. The negative wave at stimulus onset with a peak latency of 120 to 160 msec was evaluated. Ordinary VEPs to luminance (LUM) contrast (black-white reversing checkerboards of 15' check size and 50% contrast) were also recorded for comparison. Latencies of R-G VEPs were abnormal in 53.3% and 58.3% of patients at 90% and 25% contrast respectively, whereas abnormal B-Y VEPs were 56.6% and 48.3%. Latencies of LUM VEPs were abnormal in 45% of patients. Interocular latency asymmetries were abnormal in 59.2% and 33.3% of patients for R-G, and 51.8% and 62.9% for B-Y. Latency asymmetries for LUM VEP were abnormal in 46.4% of patients. The higher rate of VEP abnormalities found with equiluminant chromatic stimuli compared with achromatic stimuli confirms the general vulnerability of color-opponent visual pathways in MS, even if the number of patients with abnormal findings was not significantly different when both test conditions were compared. VEPs to R-G and B-Y equiluminant stimuli appear to be involved approximately to the same extent.

Adolescent↗

PubMed2000

Identification of a ras oncogene peptide that contains both CD4(+) and CD8(+) T cell epitopes in a nested configuration and elicits both T cell subset responses by peptide or DNA immunization.

Mutations in ras proto-oncogenes are commonly found in a diversity of malignancies and may encode unique, non-self epitopes for T cell-mediated antitumor activity. In a BALB/c (H-2(d)) murine model, we have identified a single peptide sequence derived from the ras oncogenes that contained both CD8(+) and CD4(+) T cell epitopes in a nested configuration. This peptide reflected ras sequence 4-16, and contained the substitution of Gly to Val at position 12 ¿i.e., 4-16(Val12)¿. Mice immunized with this 13-mer peptide induced a strong antigen (Ag)-specific CD4(+) proliferative response in vitro. In contrast, mice inoculated with the wild-type ras sequence failed to generate a peptide-specific T cell response. Additionally, mice immunized with the ras 4-16(Val12) peptide concomitantly displayed an Ag-specific CD8(+) cytotoxic T lymphocyte (CTL) response, as determined by lysis of syngeneic tumor target cells incubated with the nominal 9-mer nested epitope peptide ¿i.e., 4-12(Val12)¿, as well as lysis of tumor target cells expressing the corresponding ras codon 12 mutation. Analysis of the Valpha- and Vbeta-chains of the T cell receptor (TCR) expressed by these CTL revealed usage of the Valpha1 and Vbeta9 subunits, consistent with the TCR phenotype of anti-ras Val12 CTL lines produced by in vivo immunization with the nominal peptide epitope alone. Moreover, immunization with the nested epitope peptide, as compared to immunization with either the 9-mer CTL peptide alone or an admixture of the 9-mer CTL peptide with an overlapping 13-mer CD4(+) T cell helper peptide ¿i.e., 5-17(Val12)¿ lacking the class I N-terminus anchor site, enhanced the production of the CD8(+) T cell response. Finally, immunization with plasmid DNA encoding the ras 4-16(Val12) sequence led to the induction of both Ag-specific proliferative and cytotoxic responses. Overall, these results suggested that a single peptide immunogen containing nested mutant ras-specific CD4(+) and CD8(+) T cell epitopes: (1) can be processed in vivo to induce both subset-specific T lymphocyte responses; and (2) leads to the generation of a quantitatively enhanced CD8(+) CTL response, likely due to the intimate coexistence of CD4(+) help, which may have implications in peptide- or DNA-based immunotherapies.

Animals↗

PubMed2000

Abolition and reversal of strain differences in behavioral responses to drugs of abuse after a brief experience.

Inbred strains of mice are largely used to identify the genetic basis of normal and pathological behaviors. This report demonstrates that a moderate period of food shortage, an ecologically common experience, can reverse or abolish strain differences in behavioral responses to the abused psychostimulant amphetamine. The period of food shortage occurred when the animals were mature and was terminated before the administration of amphetamine. Strain differences in behavior appear highly dependent on environmental experiences. Consequently, to identify biological determinants of behavior, an integrated approach considering the interaction between environmental and genetic factors needs to be used.

Amphetamine↗

PubMed2000

Stable transduction of actively dividing cells via a novel adenoviral/episomal vector.

Many gene therapy indications would benefit from vectors capable of achieving efficient in vivo delivery and long-term transgene expression in either dividing or nondividing cells. Such vector systems are not yet available. To achieve both goals, we have used noncytotoxic E1- and E4-deleted adenoviral vectors as vehicles for delivering an Epstein-Barr virus-based self-replicating episome (replicon) via Cre/loxP site-specific recombination. Co-infection of human cells with a proreplicon-encoded and a Cre-expressing adenovirus resulted in efficient delivery and excision of a functional replicon in the absence of vector-induced cytotoxicity. In addition, replication and nuclear retention of the replicon in the cell progeny translated into a prolonged transgene expression in actively dividing cells, both in vitro and in vivo. Combining desired features from different viruses within a single hybrid vector system should expand the range of clinical indications currently amenable to gene transfer.

Adenoviruses, Human↗

PubMed1998

Long-term effects of postnatal manipulation on emotionality are prevented by maternal anxiolytic treatment in mice.

This study investigated the role of maternal behavior on the long-term effects of postnatal manipulation (15 min of daily separation from the dam and exposure to clean bedding from Day 1 to Day 14 of postnatal life) on emotionality in the mouse. Mothers were treated with an antianxiety agent (Chlordiazepoxide: 5 mg/kg), daily upon removal of the litter from the nest. Emotionality in adult offspring was tested in the elevated plus maze. Mice manipulated during postnatal development were more explorative and less anxious than unhandled mice, but this effect was not observable in the offspring of Chlordiazepoxide-treated dams. No effect of maternal Chlordiazepoxide was observed in unhandled offspring. The pharmacological treatment of the mother did not affect either pups' ultrasonic calling during separation, or maternal behavior far apart from the daily manipulation sessions. By contrast, Chlordiazepoxide-treated dams were less responsive toward pups upon reunion following daily separation. This alteration of dams' behavior was not related to alterations in the amount of ultrasonic calls emitted by pups during reunion. Finally, when dams were daily injected with Chlordiazepoxide far apart from pups' removal, the pharmacological treatment was devoid of effects. These results support the view that the mother-infant interaction which follows separation plays a major role in determining the effects of postnatal manipulations on adult emotionality.

Age Factors↗