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Biomedical subjects

M Maestri

Publications and source records attributed to M Maestri.

At least 19 recordsLinked to original sources

Quantitative EEG analysis in post-traumatic anosmia.

Many objective and quantitative methods have been developed to create a procedure or a device to prove, describe and quantify olfactory deficit and anosmia, especially after a head trauma. Electrophysiological testing throughout olfactoelectroencephalography (olfactoEEG) is based on brain activity desynchronisation, and on the subsequent disappearance of alpha activity on the posterior regions after an olfactory stimulus. Yet traditional evaluation of EEG can be difficult, because of little or hardly detectable alpha activity on the posterior regions ('alpha rare'). The aim of this study was to evaluate the Olfactory Stop Reaction (OSR) by means of frequency band power calculation and subsequent topographical mapping in patients with post-traumatic anosmia, who presented 'alpha rare' EEG. Twenty-five consecutive patients, affected by anosmia caused by head trauma, were submitted to an EEG recording with olfactory stimulation. After signal processing and analysis, an Olfactory Stop Reaction was detected in 17 out of 25 patients; moreover, in these patients we detected a significant decrease in alpha band power in the occipital regions and an increase in theta band power on midline frontal and central regions after olfactory stimulation. In the remaining eight patients, no significant variation in band power was observed. In conclusion, an objective evaluation of the olfactory function with this method of automatic EEG signal analysis allows the limits given by psychophysical methods and traditional EEG to be overcome and attempts to fulfil the requirements for standardization of olfactory function evalution.

Adult↗

[Immunomodulation after combined spleen and kidney transplantation in swine].

AIM: Organ transplantation is the most effective treatment for several degenerative end-stage diseases. While the mainstream immunosuppression can achieve satisfactory results, the therapy has either side effects and flaws. The golden target to reach should be a stable tolerance with the transplanted organ accepted without a long term drug administration. Recent studies demonstrated a tolerogenic effect of spleen cells. Aim of this study is to evaluate a model of combined spleen and whole organ transplantation in a significant preclinical setting in swine. METHODS: Twenty-five outbred Landrace/Large-White swine underwent combined spleen/kidney transplantation (SKTx). The experiments were stratified into 3 groups per randomization. Group 1 (N=7) received kidney transplantation (KTx) alone with no immunosuppressive treatment. Group 2 (N=9) had a combined KTx and whole graft spleen Tx. Group 3 (N=9) had KTx and spleen cells (DST), injected through the portal vein. Renal lab tests were collected to evaluate the onset of rejection. Survivals were evaluated as well. The end-point of the study was at onset of kidney failure or at the limit of 60 postoperative day (POD) in non-rejecting animals. Tissue samples were collected to evaluate grade and severity of rejection. RESULTS: Controls died from kidney failure within 10(th) POD. Group 2 and 3, had a delayed renal graft rejection and an overall prolonged graft survival. Whole graft and spleen cells injection share this effect, while spleen administration through the portal route proved a superior effect, which is significant compared to controls (Kaplan Meier survival analysis P<0.05). CONCLUSIONS: These results, from a non immunosuppressed setting, suggest that spleen plays a key role as an immunomodulatory organ.

Animals↗

[Liver transplantation in swine: a model for tolerance induction].

AIM: The liver as a solid graft has a known immunological privilege. Its tolerogenic property has been demonstrated in rodents. In humans the onset of chronic rejection and the severity of such complication is less frequent after liver transplantation compared to other organs. The underlying events whose effect is graft acceptance instead of rejection should be further investigated. Their control could open new ways to decrease the need for long-term immunosuppression after transplantation of other organs. Aim of this study is to evaluate a model of liver transplantation in swine as a preliminary step for immunological studies. METHODS: Ten outbred Landrace/Large White mismatched swine underwent to liver transplantation with a simple passive portocaval jugular bypass. The onset of rejection was monitored daily by liver function test. After death or sacrifice the liver parenchyma was studied to evaluate tissue damage and inflammatory infiltrate. RESULTS: The postoperative liver function showed a critical period for organ rejection about postoperative day 5. The animals that survived longer were sacrificed with a normal biochemical hepatic function. However, histology consistently showed a pattern of mild rejection in a still preserved architecture. CONCLUSIONS: The evidence of a prolonged liver function in a rejecting model of liver transplantation makes this model suitable for studies of tolerance induction.

Animals↗

REM sleep behaviour disorder in Parkinson's disease: a questionnaire-based study.

The aim of the study was to determine the clinical frequency and features of REM sleep behaviour disorder (RBD) in a large population of Parkinson's disease (PD) patients using defined diagnostic criteria both for RBD and PD. Six trained neurologists used a semistructured questionnaire based on ICSD-R diagnostic criteria for RBD to evaluate 200 PD patients and their caregivers. Interobserver reliability for the diagnosis of RBD was "substantial" (Kappa 0.65). Five patients were excluded from the study because of an MMSE lower than 25. The demographic and PD clinical features were compared in the clinically defined RBD group and in those without RBD (NRBD). Then the RBD features during the last year were analysed in the affected group. Out of 195 patients, 66 fulfilled the ICSD-R criteria for RBD; 62 patients reported RBD during the last year (frequency 31.8%). RBD features: two or more episodes per week in 35.5%; upper limb movements in 87%; lower limb movements in 79%; vocalisations during events in 85%. RBD onset was before PD in 27% of patients; 69% of the RBD group had injured themselves or their caregivers during sleep. According to multivariate analysis, RBD was associated with male gender, age and PD duration. Brief training and the use of a semistructured questionnaire may help the neurologist in dealing with sleep disturbances in PD patients. The search for RBD symptoms in PD is highly recommended, especially in patients with a long disease duration, the risk of sleep-related injuries being high.

Aged↗

[Blockade of B7:CD28 costimulatory pathway reduces the vascular damage in an experimental model of chronic rejection].

AIM: Costimulatory blockade and donor specific transfusion (DST) can catalyze tolerance of transplanted organs through a multistep adaptation between the recipient and donor immune systems. Such an in vivo process may prolong graft survival. Aim of this study was to evaluate the outcome of aortic transplantation under CTLA4Ig and DST in a mismatched model in rats. METHODS: Orthotopic aortic transplantation was performed in recipients Lewis from Wistar-Furth rats. The animals were stratified into 3 groups, according to the postoperative treatment. Group 1 had aortic transplantation only (controls, n=6), while group 2 (n=7) had a load of donor splenocytes (DST). Group 3 was treated with DST and CTLA4Ig. All the animals were sacrificed at the 60th postoperative day and the aortic specimens were prepared for histology. Intimal cells, muscular cells and lymphocyte cell infiltration were evaluated by serial counts. RESULTS: In Group 1 there was a severe chronic rejection, while group 2 showed a slower onset of chronic rejection with less inflammatory infiltrate than group 1 (P<0.05). Group 3 had the best overall outcome with lower infiltration and minimal alterations compared with groups 1 and 2. CONCLUSIONS: Costimulatory blockade and DST load can prevent the onset of chronic rejection in this experimental setting. Despite the wide availability of immunosuppressors, which makes transplantation a today's clinical routine, the solution to chronic rejection is still elusive. The synergistic role of splenocytes and costimulatory blockade raises interesting perspectives about the immunomodulatory role of spleen in tolerance induction.

Animals↗

Lormetazepam effects on daytime vigilance, psychomotor performance and simulated driving in young adult healthy volunteers.

OBJECTIVE: To assess the residual effects of lormetazepam on daytime vigilance, psychomotor performance and simulated driving in adult healthy volunteers. MATERIAL: Twelve subjects (7 women, 5 men), aged 27 - 38 years (mean 31). METHOD: Subjects received lormetazepam 1 mg tablet and placebo for 3 days at nighttime in a randomized, double-blind, crossover design, with a 1-week interval between medications. On the morning following the last drug administration, the subjects completed a 15-min battery of neuropsychological tests aimed at assessing memory and attention, performed simple and choice visual reaction times, and self-rated their own level of sleepiness using the Epworth sleepiness scale. Afterwards, an interactive, computer-based driving simulator (STISIM) was used to assess the effect of the study drugs on driving ability, followed by the multiple sleep latency test (MSLT). RESULTS: The findings showed that participants had similar performance when treated with lormetazepam and placebo. Indeed, as compared with baseline, neuropsychological tests, visual reaction times, sleep latency using the MSLT and driving ability showed no deterioration following either placebo or active medication. CONCLUSIONS: The data suggest that 3-day use of lormetazepam 1 mg/day neither influences daytime vigilance nor impairs psychomotor task performance and simulated driving. Results confirm previous evidence that the intermediate-acting hypnotic benzodiazepine lormetazepam is devoid of residual effects in respect to psychomotor ability. However, caution should be exercised in the interpretation of the results due to the limited sensitivity of the study.

Adult↗

Differential responses of superoxide dismutase in freezing resistant Solanum curtilobum and freezing sensitive Solanum tuberosum subjected to oxidative and water stress.

In photosynthetic tissues superoxide dismutase (SOD) plays an important role by scavenging the superoxide radical whose production is an usual reaction in chloroplast thylakoids. To test the differential response of SOD, two Andean potato species differing in frost resistance, Solanum curtilobum (frost resistant) and Solanum tuberosum (frost sensitive), were subjected to methyl viologen-mediated oxidative stress and polyethylene glycol (PEG)-induced water stress. A significant increment (approximately two-fold) in total SOD and FeSOD activity, which occupied about 50% of the total activity, was found when leaves of S. curtilobum were exposed to water stress. In contrast, the SOD activity in leaves of S. tuberosum remained unchanged. The exposure of leaves of S. curtilobum to oxidative stress increased total SOD and FeSOD activity by 350%. High correlation between SOD activity and the F(v)/F(m )ratio under both PEG induced water stress and MV-mediated oxidative stress was observed. This suggests that SOD can protect PSII from superoxide generated by oxidative and water stress. The higher SOD activity could be an important mechanism to explain why some natives Andean potato like S. curtilobum are more resistant to abiotic stresses than S. tuberosum.

Journal Article↗

Neurophysiological evaluation of vigilance in epileptic patients on monotherapy with lamotrigine.

OBJECTIVE: Limited research has focused to date on daytime sleepiness in epileptic patients treated with either conventional or newer antiepileptic drugs. We evaluated the level of vigilance in 15 consecutive, newly diagnosed and never medicated adult epileptic patients, receiving initial monotherapy with lamotrigine (LTG). METHODS: Patients underwent the Multiple Sleep Latency Test (MSLT), visual reaction times (VRT) and Stanford Sleepiness Scale (SSS) on two separate occasions, i.e. before and 2 months after LTG treatment. A group of 15 age-matched healthy volunteers was taken as control. RESULTS: At baseline, mean sleep latencies on the MSLT were comparable in epileptic patients and in controls. In patients, 2 months after monotherapy with LTG 200 mg/day, MSLT scores did not significantly change as compared with pre-treatment values. Accordingly, subjective evaluation of vigilance by the SSS and psychomotor performance by VRT were superimposable in controls and in untreated patients, and did not change in patients after LTG treatment. CONCLUSIONS: These results suggest that in adult, newly diagnosed epileptic patients initial monotherapy with LTG does not impair vigilance.

Adult↗

Oxygen delivery and oxygen tension in cerebral tissue during global cerebral ischaemia: a swine model.

UNLABELLED: Interest in tissue oxygen (PtiO2) monitoring is increasing. However the exact interactions between ptiO2, systemic and cerebral variables are a matter of debate. Particularly, the relationship between ptiO2, cerebral oxygen supply and consumption needs to be clarified. We designed a model to achieve progressive Cerebral Blood Flow (CBF) reduction through 3 steps: 1. baseline, 2. CBF between 50-60% of the baseline, 3. CBF < 30% of the baseline. In 7 pigs, under general anaesthesia, Cerebral Perfusion Pressure (CPP) and CBF were reduced through the infusion of saline in a lateral ventricle. PtiO2 and CBF were monitored respectively through a Clark electrode (Licox, GMS) and laser doppler (Peri-Flux). Blood from superior sagittal sinus and from an arterial line was simultaneously drawn to calculate the artero-venous difference of oxygen (AVDO2). Brain oxygen supply was calculated by multiplying relative CBF change and arterial oxygen content. PtiO2 reflected CBF reductions, as it was 27.95 (+/- 10.15) mmHg during the first stage of intact CBF, declined to 14.77 (+/- 3.58) mmHg during the first CBF reduction, declined to 3.45 (+/- 2.89) mmHg during the second CBF reduction and finally fell to 0 mmHg when CBF was completely abolished. CBF changes were also followed by a decline in O2 supply and a parallel increase in AVDO2. CONCLUSION: This model allows stable and reproducible steps of progressive CBF reduction in which ptiO2 changes can be studied together with oxygen supply and consumption.

Animals↗

[Whole pancreatic transplantation and islet transplantation. Experiment notes].

BACKGROUND: The results of pancreas transplantation have greatly improved in recent years. The path to further improvements goes through extensive experimental researches. METHODS: This study describes the effects of different procedures as hemodynamic asset and postoperative outcome. Twenty-nine swine underwent a total pancreatectomy, and were stratified into five groups. Group one (n = 5) served as control. Group two (n = 7) was autotransplanted. Group three (n = 6) and group four (n = 6) underwent allotransplantation; the first without immunosuppression and the second treated with cyclosporine and steroids. In group five (n = 5) Langerhans Islets transplantation was performed. RESULTS: Survival was different depending on which methodology was applied. The postoperative survival was 7 +/- 2 days in group one, 24 +/- 16 days in group two, 17 +/- 7 days in group three, 27 +/- 8 days in group four and 12 +/- 6 days in group five. CONCLUSIONS: The postoperative glucose control was normal in group two and group four while a severe diabetes appeared in group one (group 1 vs group 2: p < 0.05) and in group three during acute graft rejection after the 12th postoperative day (group 3 vs group 4: p < 0.05). Glycemia was slightly controlled in group five. The intraoperative hemodynamic status was evaluated at the time of pancreatectomy, harvesting, revascularization, and when surgery was over. Among the different parameters studied (mean arterial and pulmonary pressure, pulmonary wedge pressure, central venous pressure, cardiac output, oxygen extraction ratio, systemic vascular resistance, oxygen delivery and oxygen consumption), a statistically significant difference between group one and group five (p < 0.05) was observed.

Animals↗

Augmenter of liver regeneration enhances the success rate of fetal pancreas transplantation in rodents.

BACKGROUND: Treatment of fetal pancreas (FP) isografts with insulin-like growth factor-I greatly improves the rate of conversion to euglycemia in diabetic rats. Complete knowledge of other factors that may facilitate the engraftment and function of FP in vivo is still embryonic. Augmenter of liver regeneration (ALR) is a newly described polypeptide growth factor found in weanling rat livers. ALR has trophic effects on regenerating liver. We studied the effects of in situ administration of this agent on FP isografts in rats. METHODS: Streptozotocin-diabetic Lewis rats (blood glucose > 300 mg/dl) received 16 FP isografts transplanted intramuscularly. ALR was delivered from day 1 through day 14, in doses of 40 or 400 ng/kg/d. Animals were followed for 3 months with serial weights and blood glucose monitoring. These animals were compared with those treated with vehicle alone. RESULTS: Of the group treated with ALR at 40 ng/kg/day for 14 days, 89% (eight of nine) were euglycemic (P=0.0003). Of the group treated with ALR at 400 ng/kg/day for 14 days, 88% (seven of eight) were euglycemic (P=0.0007). Of the group treated with vehicle alone, none of the six were euglycemic. Euglycemia is defined here as glucose < 200 mg/dl for 3 days. Pathology of the intramuscular transplant site showed patches of islet tissue embedded in fat. These patches demonstrated insulin immunoreactivity. CONCLUSIONS: Diabetes was reversed in a significantly greater proportion of FP + ALR-treated recipients than those animals treated with vehicle alone. Local delivery of growth factors may be used as an adjunct to FP transplantation to improve the rate of success. This in situ model may be useful to further evaluate other soluble factors.

Animals↗

[Kidney-pancreas transplantation. Clinical results in 23 consecutive patients].

Immunosuppressive approaches to combined kidney-pancreas tx include quadruple therapy with either antilymphocyte globulin (ATG) or OKT3 for a short period (7-14 days) immediately after transplantation. Maintenance therapy with prednisone, azathioprine and cyclosporin is then used to ensure the long-term survival of the graft. This study reports 23 cases of combined kidney-pancreas tx under ATG induction (n = 7) and OKT3 induction (n = 16). Both groups had maintenance therapy with azathioprine, prednisone and cyclosporin. The follow-up was 12 months. Graft loss was 3 out of 7 vs 1 out of 16 (p < 0.05) for the kidney and 3 out of 7 vs 3 out of 16 for the pancreas in ATG treated vs OKT3 treated patients respectively. There were two deaths in the ATG group and one in the OKT3 group; two patients died with functioning graft, one in each group. The one year actuarial survival was 87% for graft and patient, 83% for kidney and 77% for pancreas. Combined kidney-pancreas tx with ATG or OKT3 have a similar outcome. OKT3 allows a longer period before the onset of rejection. There is a trend in survivals which suggests a better survival in OKT3 treated recipients. Infections and other complications were similar in ATG and OKT3 patients.

Adult↗

[Treatment of the nephrotoxicity of immunosuppressive drugs with insulin-like growth factor-I].

BACKGROUND: Delayed graft function is a common and severe complication after cadaveric kidney transplantation. Besides a more complicated postoperative course, DGF can worsen the overall graft survival. In particular, DGF enhances the nephrotoxicity of mainstream immunosuppressants cyclosporine and FK506. This study evaluates a new therapeutical approach to the treatment of DGF related nephrotoxicity, based on the administration of IGF-I. METHODS: Sixty inbred Lewis rats underwent a bilateral clamping of the renal pedicles (20') as standard damage. The animals were stratified in six groups, according to the postoperative treatment. Group 1 served as control and received only the standard ischemic injury. Cyclosporine and FK506 were added in groups 3 and 5. Groups 2, 4 and 6 had the same treatment of groups 1, 3, 5 respectively, plus the administration of IGF-I. Blood samples were drawn daily to evaluate creatinine and BUN for 7 days. RESULTS: The rats treated with IGF-I had significantly better values compared to the respective controls (2-way ANOVA, p < 0.05). CONCLUSIONS: In conclusion, IGF-I improves the nephrotoxicity of mainstream immunosuppressants in this model. Its use is potentially beneficial for transplantation.

Animals↗

[The hemodynamic effects of the in-vivo administration of insulin-like growth-factor I].

BACKGROUND: Recent studies have demonstrated that IGF-I has several biological activities that correlate with the GH axis, by acting as a cell protecting factor and a promoting compound in different tissues and organs. Our latest findings have demonstrated a potential application of IGF-I in the treatment of postischemic renal injury, which frequently appears after a kidney transplant. The beneficial effect of the renal postoperative recovery probably correlates with the regulation of the vascular tone, in which IGF-I plays a role with other cytokines. However, this rises the question whether IGF-I has any effect on the general hemodynamic status. This study was designed to underline the intraoperative hemodynamic effect of exogenous IGF-I in an experimental setting of renal transplantation in swine. METHODS: Twelve female swine underwent a left renal autotransplantation. At the reperfusion the animals were separated in two groups. Group one served as control. Group two received 400 micrograms of IGF-I (added to the flushing solution). The animals were kept under complete hemodynamic monitoring over the operation. RESULTS: Among the different parameters studied (mean arterial pressure, mean pulmonary arterial pressure, pulmonary wedge pressure, central venous pressure, cardiac output, oxygen extraction ratio, systemic vascular resistance, oxygen delivery and oxygen consumption), any statistically significant difference between group one and two were observed. CONCLUSIONS: While the clinical administration of IGF-I requires further studies, the in vivo administration of this peptide is apparently well tolerated, and does not cause any hemodynamic instability to the operation.

Analysis of Variance↗

Insulin-like growth factor-I ameliorates delayed kidney graft function and the acute nephrotoxic effects of cyclosporine.

BACKGROUND: Delayed graft function (DGF) is a relatively common complication after cadaveric renal transplantation. The adverse effect of DGF on long-term graft survival has lead to intensive efforts to reduce ischemic graft injury. In this study we examined the effects of a new protective treatment based on insulin growth factor (IGF)-I. We evaluated the impact of the treatment on renal recovery and on the nephrotoxicity that is a common side effect of mainstream immunosuppressants. Because therapy with IGF-I or the analog des(1-3)IGF-I is effective in treating experimental ischemic renal failure, these peptides may be useful as perspective clinical treatments. METHODS: We have addressed three areas relating to the potential use of IGF-I and its analog des(1-3)IGF-I. First, because of the immunogenic properties of IGF-I, we assessed the effect of des(1-3)IGF-I on the rejection of skin allografts in Lewis rats. Next we determined whether treatment with des(1-3)IGF-I influences the early function of transplanted kidneys in a model of DGF induced by a combination of warm and cold ischemia. Finally we tested whether IGF-I protects against acute cyclosporine nephrotoxicity. RESULTS: Des(1-3)IGF-I did not accelerate the rejection of the skin grafts (P=0.57). The administration of this peptide in a model of syngenic renal transplant improved the early function of the graft. Postoperative values of creatinine and blood urea nitrogen were significantly better (P<0.05) in treated animals. IGF-I also ameliorated the nephrotoxicity of cyclosporine, with better values of creatinine and blood urea nitrogen (P<0.05). CONCLUSIONS: In evaluating this study it should be recognized that the animal models studied, although widely used, differ from the human condition. However, IGF-I and des(1-3)IGF-I exhibit properties that strongly suggest their value in preventing clinical DGF, and they deserve further studies.

Animals↗

Regimens of IGF-I treatment in fetal pancreas transplantation.

Transplantation of fetal pancreas (FP) is a potential treatment for diabetes mellitus. FP has remarkable proliferative capacity and may be induced to expand sufficiently to provide a functional beta cell mass in adult recipients. We have demonstrated that local delivery of recombinant insulin-like growth factor-I (IGF-I) onto FP isografts is sufficient to reverse streptozotocin-induced diabetes in animals receiving as few as 4 fetal pancreata. In this current study we investigated other regimens of IGF-I delivery in an attempt to define whether its effects on FP required local delivery or whether other, more clinically feasible, forms of treatment would suffice. In our model, diabetic Lewis rats received isografts of 16 FP into the anterior thigh intramuscular (IM) site. In the group of FP recipients treated with vehicle alone, no animals converted to euglycemia (0/8). When the IM site was pretreated locally with 14 days of continuous IGF-I administration (69 micrograms/kg per day) prior to FP transplantation, 100% of the recipients (10/10) became euglycemic with a mean interval from transplant to euglycemia of 35 +/- 15 days (P < 0.001 when compared to vehicle alone). No significant advantage over the vehicle alone group was gained either when the FP tissue was cultured for 48 hr in the presence of IGF-I (100 micrograms/ml) and then implanted (27% conversion to euglycemia, 3/11) or when FP isografts were treated with continuous subcutaneous delivery of IGF-I (69 micrograms/kg per day over 14 days) distant from the transplant site (0% conversion to euglycemia, 0/6). IGF-I increased the rate of conversion to euglycemia either when delivered locally to FP isografts or when delivered to the transplant bed prior to transplantation. This suggests an active role of the IGF-I-treated transplant bed in the success of FP transplantation.

Animals↗