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Biomedical subjects

M Bertolotti

Publications and source records attributed to M Bertolotti.

At least 19 recordsLinked to original sources
PubMed2003

Dynamics of counterpropagating pulses in photonic crystals: enhancement and suppression of stimulated emission processes.

Using numerical methods, we study the propagation of counterpropagating pulses in finite photonic crystals. We show that linear interference and localization effects combine to either enhance or suppress stimulated emission processes, depending on the initial phase difference between the input pulses. We consider the example of second harmonic generation, where we find a maximum contrast of three orders of magnitude in nonlinear conversion efficiency as a function of the input phase difference between incident pulses. We interpret these results by viewing the photonic crystal as an open cavity, with a field-dependent, electromagnetic density of modes sensitive to initial and boundary conditions.

Journal Article↗
PubMed2003

(2+1)-dimensional soliton formation in photorefractive Bi12SiO20 crystals.

(2+1)-dimensional spatial solitons in Bi12SiO20 (BSO) photorefractive crystals with large optical activity are experimentally demonstrated. The soliton formation when a Gaussian beam is injected at the input has been previously analyzed numerically and then experimentally investigated. We demonstrate analytically, numerically, and experimentally that by applying static electric biases of high values, the polarization rotation accelerates: this acceleration prevents the beam from broadening if the polarization rotation period becomes shorter than the diffraction length. Contemporary to this nonlinear optical activity, an induced birefringence affects the beam polarization state. Analysis of the polarization dynamics shows that the polarization changes nonuniformly across the beam (with a field dependent speed) until about 30-35 kV/cm; above this limit, the whole beam has just one polarization state. Representation on the Poincaré sphere of the polarization dynamics reveals the existence of a stable polarization trajectory closed around a polarization attractor that depends on the linear optical activity and on the photorefractive nonlinearity. The experimental soliton is well described by the analytical solutions already obtained [Fazio et al., Phys. Rev. E 66, 016605 (2002)].

Journal Article↗
PubMed2002

Solitonlike propagation in photorefractive crystals with large optical activity and absorption.

We have found analytical solutions of the light propagation equations in photorefractive materials with strong optical activity and absorption. These solutions show the occurrence of breathing solitons in sillenite crystals with strong optical activity and absorption in two particular orientations with respect to the external electric field. The absorption is decreasing the soliton intensity with the propagation distance (which set a limit in the soliton channel length), is increasing the breathing period, and is changing the soliton width (in inverse relations, at low and high intensities). Our experimental results confirm the analytical solutions and the numerical simulations, as well as the importance of the optical activity and absorption in solitonlike propagation.

Journal Article↗
PubMed2002

Fasting insulin and uric acid levels but not indices of iron metabolism are independent predictors of non-alcoholic fatty liver disease. A case-control study.

BACKGROUND: Non-alcoholic fatty liver disease is a common reason for hepatological consultation and may herald severe hepatic and extra-hepatic disease. The aetiopathogenesis of this condition is an area of increasing interest. AIM: To evaluate anthropometric and biochemical factors associated to non-alcoholic fatty liver disease in a case-control study. Methods. Demographic and biochemical data of 60 consecutive patients with bright liver absent-to-low alcohol consumption, no evidence of viral, genetic and autoimmune diseases, were compared to those of 60 age- and gender-matched historical controls without fatty liver by univariate and multiple logistic regression analysis. RESULTS: Patients were more often hypertriglyceridaemic, obese and diabetic than controls (p<.01). Mean values of alanine transaminase, gammaglutamyltranspeptidase, triglycerides, uric acid, fasting and log insulin, transferrin percent saturation and ferritin were significantly higher in the patients, while transferrin and quantitative insulin sensitivity check index, a quantitative insulin sensitivity index, were lower. No iron storage was found in those who underwent liver biopsy At univariate analysis the relative risk for non-alcoholic fatty liver disease significantly increased (p<0. 05) with increasing body mass index, fasting insulin, alanine transaminase, uric acid, triglycerides and gammaglutamyltranspeptidase; it decreased with increasing transferrin and quantitative insulin sensitivity check index. Multiple logistic regression analysis disclosed only fasting insulin and uric acid to be independent predictors of non-alcoholic fatty liver disease (p<0.05). CONCLUSIONS: Fasting insulin and serum uric acid levels indicating insulin resistance, but not indices of iron overload, are independent predictors of non-alcoholic fatty liver disease.

Case-Control Studies↗
PubMed2001

Simultaneously phase-matched enhanced second and third harmonic generation.

Second and third harmonic generation via a chi((2)) three-wave mixing process can occur with high conversion efficiency in a one-dimensional photonic band gap structure. We find that it is possible to simultaneously achieve enhancement and exact phase-matching conditions of second harmonic and sum frequency generation, omega+2 omega-->3 omega. It is also remarkable that high conversion efficiencies persist under tuning conditions that correspond to a phase mismatch. While these conditions are quite unusual and cannot be achieved in any known bulk material, we show that they can be easily obtained in finite layered structures by using and balancing an interplay between material dispersion and the geometrical dispersion introduced by the structure.

Journal Article↗
PubMed2001

Photonic band edge effects in finite structures and applications to chi 2 interactions.

Using the concept of an effective medium, we derive coupled mode equations for nonlinear quadratic interactions in photonic band gap structures of finite length. The resulting equations reveal the essential roles played by the density of modes and effective phase matching conditions necessary for the strong enhancement of the nonlinear response. Our predictions find confirmation in an experimental demonstration of significant enhancement of second harmonic generation near the photonic band edge. The measured conversion efficiency is in good agreement with the conversion efficiency predicted by the effective-medium model.

Journal Article↗
PubMed2001

Group velocity, energy velocity, and superluminal propagation in finite photonic band-gap structures.

We have analyzed the notions of group velocity V(g) and energy velocity V(E) for light pulses propagating inside one-dimensional photonic band gap structures of finite length. We find that the two velocities are related through the transmission coefficient t as V(E)=/t/(2)V(g). It follows that V(E)=V(g) only when the transmittance is unity (/t/(2)=1). This is due to the effective dispersive properties of finite layered structures, and it allows us to better understand a wide range of phenomena, such as superluminal pulse propagation. In fact, placing the requirement that the energy velocity should remain subluminal leads directly to the condition V(g)<or=c//t/(2). This condition places a large upper limit on the allowed group velocity of the tunneling pulse at frequencies of vanishingly small transmission.

Journal Article↗
PubMed2001

Inhibition of intestinal cholesterol absorption by surfomer (alpha-olefin maleic acid) affects hepatic cholesterol synthesis and low density lipoprotein transport in hamsters fed a fat-enriched diet.

BACKGROUND: Surfomer (alpha-olefin maleic acid) reduces intestinal cholesterol absorption. AIMS: This study was performed to investigate the effect of surfomer on cholesterol synthesis and low density lipoprotein in hamsters fed a hypercholesterolaemic, lipid-enriched diet. ANIMALS AND METHODS: Male hamsters were fed a diet enriched in cholesterol (0.07%) and saturated fatty acids (coconut oil 20%); the diet was supplemented with 3% surfomer, for 1-4 weeks. Cholesterol synthesis was assessed measuring incorporation of [3H]water into tissue sterols; low density lipoprotein clearance was determined using a primed-continuous infusion of (125I)tyramine-cellobiose lipoprotein. RESULTS: Cholesterol synthesis was suppressed after 3 weeks of hyperlipidaemic diet in liver and small bowel (by 88% and 38%, respectively) and was significantly increased by supplementing the fat-enriched diet with surfomer. Low density lipoprotein-cholesterol was increased by 44% after 4 weeks of hyperlipidaemic diet, in parallel with a decrease in hepatic low density lipoprotein clearance rates (48+/-3 vs 68+/-7 microl of plasma/h per g of tissue). Concurrent treatment with surfomer for 1, 2 or 4 weeks prevented the decrease of clearance and maintained normal low density lipoprotein-cholesterol levels at all time points. CONCLUSIONS: Surfomer represents a powerful tool to investigate the impact of cholesterol absorption on sterol homeostasis. Furthermore, since surfomer appears to normalize low density lipoprotein transport in hamsters fed a diet comparable to a lipid-rich "western-style" regimen, this drug may deserve consideration as an adjunct treatment for hypercholesterolaemia in selected patient groups.

Absorption↗
PubMed2001

Suppression of bile acid synthesis, but not of hepatic cholesterol 7alpha-hydroxylase expression, by obstructive cholestasis in humans.

Regulation of bile acid synthesis, a key determinant of cholesterol homeostasis, is still incompletely understood. To elucidate the feedback control exerted on bile acid biosynthesis in humans with obstructive cholestasis, 16 patients with bile duct obstruction were studied. In vivo 7alpha-hydroxylation, reflecting bile acid synthesis, was assayed in 13 of them by tritium release analysis. Serum 27-hydroxycholesterol was determined by gas chromatography-mass spectrometry. In a subgroup, hepatic cholesterol 7alpha-hydroxylase mRNA was assayed by real-time polymerase chain reaction (PCR), enzyme activity was determined by isotope incorporation, and microsomal cholesterol content was assayed by gas chromatography-mass spectrometry. Age-matched control subjects were studied in parallel. Hydroxylation rates were lower in cholestatic patients (108 +/- 33 mg of cholesterol per day, mean +/- SEM; controls: 297 +/- 40 mg/d; P <.01). The reduction was proportional to the severity of cholestasis, and synthetic rates were normalized in 4 subjects restudied after resolution of biliary obstruction. Consistent findings were obtained by analysis of serum 7alpha-hydroxycholesterol levels. On the other hand, hepatic cholesterol 7alpha-hydroxylase mRNA, microsomal enzyme activity, and cholesterol content tended to be increased in cholestasis. Finally, serum 27-hydroxycholesterol levels were slightly reduced in cholestatic subjects and were not related with the severity of the disease. Suppression of in vivo bile acid synthesis with no corresponding reduction in tissue 7alpha-hydroxylase expression and activity is consistent with nontranscriptional, posttranslational levels of regulation; these may play a role in the feedback control of bile acid synthesis in particular conditions. Alteration of the alternate biosynthetic pathway seems unlikely according to the present data.

Aged↗
PubMed2000

Review article: effect of bile salt pool composition on hepatic and biliary functions.

The enterohepatic recirculation of bile salts exerts important regulatory effects on many hepatic, biliary and intestinal functions: such regulation is likely to depend, to a large extent, on the physical-chemical property of hydrophobicity of the recirculating pool. The present review summarizes the main experimental evidence carried out by our research group over the past two decades, in the attempt to investigate systematically the relationships between structural properties and biological effects of bile acids in humans. Hydrophobic bile acids (chenodeoxycholic acid, deoxycholic acid), but not hydrophilic acids (ursodeoxycholic acid), significantly suppressed hepatic activity of HMG-CoA reductase, the limiting step of cholesterol synthesis, and in vivo cholesterol 7alpha-hydroxylation, the limiting step of bile acid synthesis. The output of biliary cholesterol and phospholipid was also directly related to the hydrophobicity of the bile acid pool. Finally, treatment with chenodeoxycholic acid, but not with ursodeoxycholic acid, significantly decreased gall-bladder emptying rates. When turning to the in vitro model of HepG2 cells, hydrophobic bile acids were found to induce greater cytotoxic and pro-apoptotic effects. From this series of studies, we conclude that the regulatory effects of bile acids on the liver and biliary tract are largely dependent on the hydrophobic-hydrophilic balance of the recirculating bile acid pool.

Bile Acids and Salts↗
PubMed2000

[Psychological assistance in organ transplantation].

The aim of this report is introducing with a series of psychological, psychiatric and psychosocial problems, that can arise, at every point, in the procedure of organ transplantations. Different areas of intervention are considered: the assistance to the patients and their families during the pre- and post-operative periods; the evaluation of transplant recipients' quality of life; ethical and psychological problems of living kidney donation; psychosocial support to donors' families; the training of the intensive therapy units to entertain relationships with donors' relatives; the delicate psychological aspects of transplantation during childhood. The sense of awareness about these matters is growing in Italy too, and many initiatives of psychological and psychiatric help are being developed in collaboration with several transplantation centres.

Adult↗
PubMed1999

Dispersive properties of finite, one-dimensional photonic band gap structures: applications to nonlinear quadratic interactions.

We discuss the linear dispersive properties of finite one-dimensional photonic band-gap structures. We introduce the concept of a complex effective index for structures of finite length, derived from a generalized dispersion equation that identically satisfies the Kramers-Kronig relations. We then address the conditions necessary for optimal, phase-matched, resonant second harmonic generation. The combination of enhanced density of modes, field localization, and exact phase matching near the band edge conspire to yield conversion efficiencies orders of magnitude higher than quasi-phase-matched structures of similar lengths. We also discuss an unusual and interesting effect: counterpropagating waves can simultaneously travel with different phase velocities, pointing to the existence of two dispersion relations for structures of finite length.

Journal Article↗
PubMed1998

Serum time course of naltrexone and 6 beta-naltrexol levels during long-term treatment in drug addicts.

The pharmacokinetics of naltrexone have been scarcely explored in patients during chronic treatment despite the observation that the pharmacological effect of the drug is related to its plasma concentrations. In this study we investigated the time course of serum levels of naltrexone and its active metabolite, 6 beta-naltrexol, in 13 heroin addicts (3 F, 10 M; age 22-32 years) in the 24 h after 100 mg of naltrexone orally. Six patients were studied once, at different times during chronic treatment, whereas in seven patients the study was done at the beginning and after 1 month of naltrexone treatment. Four of these patients also repeated the study after 3 months of naltrexone treatment. Serum naltrexone and 6 beta-naltrexol were assayed by GLC with a nitrogen-phosphorus detector. Our results showed large differences among patients in serum naltrexone and 6 beta-naltrexol levels. On the other hand, there were no differences in serum time course of both substances in the same patient over 3 months. Peak levels and AUCs of naltrexone were lower than those of 6 beta-naltrexol in ten addicts and higher than those of the metabolite in three patients. No significant differences in the apparent half-lives of the two drugs were detected among groups. These data are consistent with the occurrence of a decreased first-pass metabolism of naltrexone in three patients leading to a larger availability of an oral dose. The increased bioavailability of the drug is not very important for opioid receptor antagonist activity but may play a role in naltrexone treatment safety.

Administration, Oral↗
PubMed1998

Influence of age and sex on serum concentrations of total dimeric activin A.

Several studies have shown that activin A is secreted in substantial amounts into the systemic circulation. The changes that occur during menstrual cycle and pregnancy suggest a correlation with reproductive function. At present, however, no definitive evidence has confirmed this pattern throughout adult life; moreover, neither the origin nor the physiological implications of this circulating growth factor have been clearly defined. The aim of the present study was to evaluate whether circulating concentrations of activin A change in adult men and women according to age and sex, and to examine the possible correlation with serum concentrations of FSH. Total dimeric activin A was measured using a specific two-site enzyme immunoassay in serum specimens collected from a cohort of normal individuals enrolled in an epidemiological survey. A group of men (n = 106) and one of women (n=151) were subdivided into six age groups (20-30, 30-40, 40-50, 50-60, 60-70 and 70-90 years). In a small group of 8 men and 11 women, serum concentrations of activin A were evaluated twice, in specimens collected at an interval of 10 years. Serum FSH concentrations were also measured in all specimens. Serum concentrations of activin A were not significantly different in men and women and showed an age-related progressive increase between 20 and 50 years of age (P<0.01, those aged 40-50 compared with those aged 20-30 years). After the age of 50 years, activin A concentrations remained in the same range of values in women, whereas they increased significantly in men, reaching peak values between 70 and 90 years (P<0.01 compared with the group aged between 20 and 50 years). From the age of 50 years, activin A concentrations were significantly greater in men compared with those in women in the corresponding age groups (P<0.001). Activin A concentrations correlated with age in men, but not in women. No significant correlation between concentrations of activin A and FSH was found in either sex. Activin A concentrations in specimens collected 10 years apart showed an increase in seven of eight men, but not in women. Finally, no significant variations of activin A concentrations were observed when fertile and postmenopausal women were compared. The present data indicate that circulating concentrations of activin A vary according to age; furthermore, men older than 50 years have greater concentrations than women. These changes, which occur irrespectively of FSH concentrations, indicate that circulating activin A is not a hormone of the reproductive axis.

Activins↗
PubMed1997

Effect of taurohyodeoxycholic acid on biliary lipid secretion in humans.

This study aimed to determine the effect in humans of taurohyodeoxycholic acid, a 6alpha-hydroxylated bile acid with hydrophilic properties, on bile lipid secretion. Four cholecystectomized patients who had gallstones and an interrupted enterohepatic circulation were intraduodenally infused with taurohyodeoxycholic and tauroursodeoxycholic acids on separate occasions at a dose of 0.8 to 1 g/h for 3 hours. In hourly bile samples collected for 8 hours after the beginning of the infusion, biliary bile acid composition (by high-performance liquid chromatography), biliary lipid concentrations (by standard methods), and distribution of biliary carriers (by gel chromatography) were evaluated. Blood liver function tests were performed before and after the infusions. Taurohyodeoxycholic and tauroursodeoxycholic acids became the predominant biliary bile acids in all patients except for one infused with taurohyodeoxycholic acid. Taurohyodeoxycholic acid stimulated significantly greater (P < .05) cholesterol and phospholipid secretion per unit of secreted bile acid (0.098 and 0.451 micromol/micromol, respectively) compared with tauroursodeoxycholic acid (0.061 micromol/micromol for cholesterol and 0.275 micromol/micromol for phospholipids). The secretory ratio between phospholipid and cholesterol was significantly higher after infusion of taurohyodeoxycholic acid (3.88 micromol/micromol) compared with taroursodeoxycholic acid (3.09 micromol/micromol) (P < .05). Biliary enrichment with taurohyodeoxycholic acid was positively related with percent concentration of phospholipids but not with that of cholesterol. The opposite trend was observed in tauroursodeoxycholic acid-enriched biles. In both taurohyodeoxycholic acid- and tauroursodeoxycholic acid-rich bile, 80% to 90% of cholesterol was carried in a gel-chromatographic fraction corresponding to an apparent molecular weight of 80 to 200 kd. No alteration in liver function test results was observed after taurohyodeoxycholic acid infusion. In conclusion, taurohyodeoxycholic acid stimulates greater cholesterol and phospholipid secretion than tauroursodeoxycholic acid, but with a higher phospholipid/cholesterol secretory ratio. In bile enriched with both bile acids, biliary cholesterol is transported in non-micellar aggregates. Finally, in the conditions of our study, taurohyodeoxycholic acid was not hepatotoxic.

Aged↗
PubMed1997

Cholecystokinin increases bile acid synthesis with total parenteral nutrition but does not prevent stone formation.

Total parenteral nutrition (TPN) is associated with cholestasis and gallstones. Gallbladder stasis may be important in the development of gallstones, and cholecystokinin (CCK) to stimulate gallbladder contraction has been proposed as a treatment to prevent this complication. We studied in vivo bile acid synthesis and bile acid output in miniswine on TPN to test whether daily CCK improves bile acid output and normalizes bile acid profiles with TPN. Nine miniswine were nutritionally maintained with TPN for 4 weeks; four pigs received CCK (0.1 mg/kg) iv daily. In vivo bile acid synthesis was measured with injection of 7 alpha-tritiated cholesterol. An increase in tritiated water reflects the activity of 7 alpha-hydroxylation, the rate-limiting step in bile acid synthesis. At the end of 4 weeks, bile was collected and bile acid output and bile salt profiles were determined. One of five animals on TPN developed gallstones while two of four receiving daily CCK developed stones. In vivo bile acid synthesis decreased with TPN (controls, 63 +/- 9 mg/24 hr versus TPN, 13 +/- 4 mg/24 hr) and increased in TPN animals with CCK treatment (TPN-CCK, 105 +/- 35 mg/24 hr). Bile acid profiles are changed with TPN with more secondary bile acids, this was not improved with CCK. CCK improved bile acid synthesis and bile acid output but failed to prevent gallstone formation or normalize bile salt profiles. In addition to promoting gallbladder contraction, CCK may have a stimulatory effect on bile acid synthesis. CCK alone did not prevent gallstone formation.

Animals↗
PubMed1997

Effect of liver cirrhosis on the systemic availability of naltrexone in humans.

BACKGROUND/AIMS: Naltrexone is a competitive opiate antagonist with high hepatic extraction. It is used for detoxification treatment for heroin addicts and has been proposed as a possible treatment of pruritus in cholestasis. Such patients are likely to have impaired liver function, underscoring the need to understand the pharmacokinetic behavior of naltrexone in liver disease. These studies were undertaken to evaluate the effect of liver cirrhosis on the plasma time-course of naltrexone. METHODS: A total of 18 patients were investigated: seven migraine patients with normal liver function regarded as controls and 11 patients with liver cirrhosis (six with decompensated disease and five with preserved liver function). A bolus of 100 mg of naltrexone was administered orally in the morning, after an overnight fast. Blood samples were taken in basal conditions and at fixed intervals, up to 24 h after administration. Serum levels of naltrexone and of its major active metabolite, 6 beta-naltrexol, were assayed by reversed-phase HPLC analysis. RESULTS: In control subjects, circulating concentrations of naltrexone were always much lower than those of 6 beta-naltrexol (area under the curve: naltrexone, 200 +/- 97 ng/ml x 24 h; 6 beta-naltrexol, 2467 +/- 730 ng/ml x 24 h, p < 0.01). In severe cirrhosis serum levels of 6 beta-naltrexol increased more slowly, so that circulating levels of naltrexone during the first 2-4 h after drug intake were higher than those of 6 beta-naltrexol (6 beta-naltrexol/naltrexone ratio at 2 h: controls, 10.91 +/- 4.80; cirrhosis, 0.39 +/- 0.18, p < 0.01). The area under the curve for naltrexone (1610 +/- 629 ng/ml x 24 h) was significantly greater than in controls, whereas that for 6 beta-naltrexol (2021 +/- 955 ng/ml x 24 h) was not significantly different. Patients with compensated cirrhosis showed an intermediate pattern. No differences in elimination half-life of the two drugs were detected among the groups. CONCLUSIONS: Our data suggest the occurrence of important changes in the systemic availability of naltrexone and 6 beta-naltrexol in liver cirrhosis; such alterations are consistent with lesser reduction of naltrexone to 6 beta-naltrexol and appear to be related to the severity of liver disease. This must be considered when administering naltrexone in conditions of liver insufficiency.

Adult↗