Search PubMed⌕ Search

Biomedical subjects

R Ferrara

Publications and source records attributed to R Ferrara.

At least 19 recordsLinked to original sources
PubMed2006

New method for phosphate kinetics estimation during hemodialysis and on-line hemodiafiltration with endogenous reinfusion.

AIM: The purpose of this study was to optimize the operative and analytical methodologies to a more exact determination of intradialytic kinetics of the phosphates (P) tested in hemodialysis (HD) and in on-line hemodiafiltration with endogenous reinfusion (HFR - Hemo Filtrate Reinfusion). METHODS: The mass balance measurements of urea and P were carried out in 18 clinically stable HD patients. The effective blood flow (Qb) was measured with a Transonic monitor. The plasma was deproteinized with 10% trichloroacetic acid to prevent breakdown of the proteins and the consequent pseudohyperphosphatemia. Subsequently the supernatant containing the ultrafiltrable phosphates was made to react with a solution of ammonium molybdate for a spectrophotometric reading. RESULTS: The mean urea mass transfer in HD was 16.9 g/session and in HFR 15.4 g/session. The mean P mass transfer in HD was 726 mg/session and in HFR 679 mg/session. Nevertheless, in HFR a significant difference was verified between the clearances of P, between the plasma water side (122.4 +/- 30.8 ml/min) and the dialysate side (105.9 +/- 19.4 ml/min). CONCLUSION: As far as the P mass transfer is concerned, the data obtained is able to be superimposed with that described in the literature during HD, while in HFR it is possible to hypothesize a high efficiency, thanks to an increased output of P in relation to the phenomenon of adsorption which, although is limited, contributes to the transfer of the total mass. Based on this study and re-examining the literature on P kinetics, there is space for methodological improvement both on the operating front with careful determination of the effective Qb, and on the chemical front overcoming the inaccuracy of automatic analyzers in determining the plasma P owing to possible overestimation of phosphatemia and poor sensitivity in measuring the lower levels of P present in the dialysate and/or ultrafiltrate.

Female↗
PubMed2006

Cardiac safety of rivastigmine in Lewy body and Parkinson's disease dementias.

Cholinesterase inhibition in patients with Alzheimer's disease (AD) may affect heart rate, sometimes inducing bradycardia. Additional cardiac safety considerations apply in patients with dementia with Lewy bodies (DLB) and Parkinson's disease (PDD), in whom cardiovascular autonomic nervous system dysfunction is common. We conducted a review of the safety data available for rivastigmine in these two conditions. A modest reduction in the mean heart rate of 1.5-2 bpm was seen. No clinically meaningful treatment differences in bradycardia or ECG abnormalities were apparent. Compared with placebo, rivastigmine appeared to be associated with fewer vascular disorder adverse events (AEs) (p = 0.002) and fewer AEs of syncope (p = 0.018) in PDD patients (n = 541). A smaller randomised, placebo-controlled study of rivastigmine in DLB (n = 120) showed similar findings. Rivastigmine appears to have a favourable cardiac safety profile in PDD and DLB patients.

Aged↗
PubMed2006

Effect of on-line hemodiafiltration with endogenous reinfusion (HFR) on the calcium-phosphorus metabolism: medium-term effects.

AIM: The purpose of the study was to examine the effect of hemodiafiltration with endogenous reinfusion (HFR) compared to hemodialysis (HD) on 28 uremic patients with secondary hyperparathyroidism (2HPT) but positively selected for good and stable control of phosphatemia in order to evaluate the independent effects of dialysis treatments on bone turnover metabolism. METHODS: The study was divided into 3 periods of observation: a) HD for three months; b) HFR for three months; c) HFR for a further 3 months. We analysed the trend of: whole PTH, 1-84 PTH, 7-84 PTH, alkaline phosphatase and its bone isoenzyme, total and ionised calcium, phosphatemia, dose of phosphate binder agents, beta2-microglobulin, CRP. All the variations found were evaluated through mean values +/- SD, t-tests, multivariate analysis. RESULTS: We observed a deceleration in bone turnover characterized by a reduction of the total and bone alkaline phosphatase (IU/mL) from 92.3 +/- 82.8 and 35.8 +/- 49.8 at the end of HD to 63.4 +/- 23.9 and 16.0 +/- 8.7 at the end of HFR, respectively, and 1-84 PTH from 317.5 +/- 264.6 pg/mL at the end of HD to 287.5 +/- 258.9 pg/mL at the end of the 3rd month of HFR. Beta2-microglobulin was reduced from 32.9 +/- 16.1 mg/L at the end of HD to 26.4 +/- 8.1 mg/L already at the end of the first three months of HFR. CRP was reduced from 2.5 +/- 2.6 mg/dL at the beginning of the study to 1.3 +/- 1.7 mg/dL at the end of HFR. There were no differences with regard to: dialytic efficiency, nutritional status, calcemia, phosphatemia (maintained in the K-DOQI range for the entire duration of the study), also thanks to more careful use of phosphate chelating agents. CONCLUSION: We are of the opinion that HFR - essentially thanks to the use of ultrapure endogenous infusate - induces a deceleration in bone turnover due to 2PHT. In addition, phosphate subtraction in HFR is better compared to HD, thanks to the improvement of the anti-inflammatory conditions by removing the cytokines harmful to bone metabolism and excluding a priori the negative effects related to hyperphosphatemia.

Aged↗
PubMed2005

Efficacy and safety of 48 weeks of treatment with octreotide LAR in newly diagnosed acromegalic patients with macroadenomas: an open-label, multicenter, non-comparative study.

The aim of the present multicentric, open-label, non-comparative study was to evaluate the role of octreotide long-acting repeatable (LAR) as primary therapy for the treatment of GH-secreting pituitary macroadenomas. The patients received octreotide LAR 20 mg every 4 weeks for 12 weeks; afterwards the dose was confirmed or adjusted at 30 mg every 4 weeks, for the remaining 12 weeks, for responder or non-responder patients, respectively. Responder patients continued the study until 48 weeks. Twenty-one naive active acromegalic patients were enrolled. In all patients, GH profile, IGF-I levels and magnetic resonance imaging (MRI) were evaluated at baseline and during treatment. The ability of octreotide LAR to decrease mean GH < 2.5 microg/I and/or normalize IGF-I levels, adjusted for age and gender, was defined respectively as total or partial success. Total success was achieved in 5/21 (23.8%), 6/20 (30%) and 4/14 (28.6%) patients after 12, 24 and 48 weeks; partial success in 7/21 (33.3%), 9/20 (45%) and 9/14 (64%) patients at 12, 24 and 48 weeks according to GH levels, while according to IGF-I levels in 7/21 (33.3%), 7/20 (35%) and 5/14 (35.7%) patients at 12, 24 and 48 week. Tumor size was notably decreased after treatment with octreotide LAR: in 16 macroadenoma patients completing the study, the tumor sizes were 1609 +/- 1288, 818 +/- 616 (49.1 +/- 23.7%) and 688 +/- 567 mm3 (54.6 +/- 24.4%) at baseline, 24 and 48 weeks. This study shows that octreotide LAR is effective in suppressing GH/IGF-I secretion and inducing tumor shrinkage in GH-secreting macroadenomas in a 48-week treatment. Octreotide LAR could be used as primary therapy in patients harbouring large pituitary tumors, who are less likely to be cured by neurosurgery.

Acromegaly↗
PubMed2005

A portable device for continuous analysis of dissolved gaseous mercury in natural waters.

A fully automatic device for continuous analysis of DGM (Dissolved Gaseous Mercury) concentration in natural waters, controlled by a Notebook, with a resolution time of 10-15 min, equipped with an Atomic Absorption Spectrometer with a detection limit of 0.5 pg, is described. A particular feature of this instrument is the portability, making its use suitable in remote locations by means of a car battery. Comparison of the results obtained using the device in the continuous mode and in the discrete mode shows good agreement taking into consideration that water samples were collected with shifting sampling times. To compare samples collected at the same time, a second analytical device, running in the discrete mode, was used. In this case results show that measurements performed with the discrete mode are slightly higher than the continuous one. Avoiding the sample handling it was possible to reduce the contamination from external sources and to achieve low instrumental blank values (1-2 pg). The field performance of this portable instrument was tested on seawater and lagoon water, where the DGM daily behaviour was measured. In agreement with several authors, a time shifting between DGM and solar radiation intensity higher than the instrumental resolution time was noted.

Environmental Monitoring↗
PubMed2004

Importance of the biogenic organic matter in photo-formation of dissolved gaseous mercury in a culture of the marine diatom Chaetoceros sp.

Laboratory experiments on DGM production under light/dark cycles in a culture of the marine diatom Chaetoceros sp. spiked with 200 ng l(-1) of mercury have been performed. DGM formation has been investigated also in the cell exudates, obtained by filtration of the cell culture. Results show that the cell culture and the filtrate give the same value of DGM production (2.24+/-0.88 pg min(-1) l(-1) and 2.23+/-0.02 pg min(-1) l(-1), respectively) in the light (40 W m(-2)), values much higher than to those obtained in the medium culture alone. A significant DGM production has been measured in dark conditions both in the cell culture (0.48+/-0.11 pg min(-1) l(-1)) and in the filtrate (0.85+/-0.10 pg min(-1) l(-1)). The results highlight that the organic compounds released by the cell in the culture medium play a fundamental role in the DGM photo-formation processes.

Cell Culture Techniques↗
PubMed2004

Immediate (overnight) switching from carbamazepine to oxcarbazepine monotherapy is equivalent to a progressive switch.

This study compared immediate (overnight) and progressive switching to oxcarbazepine monotherapy in patients with partial seizures unsatisfactorily treated with carbamazepine monotherapy. Patients were randomised to either an overnight (n = 140) or a progressive switch (n = 146) from carbamazepine to oxcarbazepine monotherapy at a dose ratio of 1:1.5. The difference between the two switch groups in the mean monthly seizure frequency supported the equivalence of overnight and progressive switching (difference of 0.02 excluding outliers; 95% confidence interval (CI) -0.74, 0.78). Following the switch from carbamazepine to oxcarbazepine, there was a reduction in median monthly seizure frequency in both the overnight group (from 1.5 to 0; P = 0.0005) and the progressive group (from 1.0 to 0.4; P = 0.003). The proportion of seizure-free patients increased from 38 to 51% (P = 0.002) and 39 to 49% (P = -0.01) in the overnight and progressive groups, respectively. In addition, the proportion of patients experiencing no clinically significant adverse events did not differ between the two switch methods (difference of 2.5; 95% CI -4.1, 9.0). For patients who are unsatisfactorily treated with carbamazepine monotherapy, overnight switch to oxcarbazepine monotherapy is as effective and well tolerated as a progressive switch, therefore allowing simple and flexible individualised treatment. Switching to oxcarbazepine monotherapy appears to be beneficial for patients who are unsatisfactorily treated with carbamazepine monotherapy, independently of the switch method used.

Adolescent↗
PubMed2003

Improving mercury flux chamber measurements over water surface.

A modified floating flux chamber was designed and used to measure mercury evasional fluxes in a coastal area of the Mediterranean Sea in different meteo-marine conditions during the hours of maximum insolation (PAR intensity 360-430 W m(-2)) in the summer season. The chamber has been modified providing a flap at the inlet port preventing the back-flow of air from the interior of the chamber. Results demonstrate that the modified flux chamber gives flux values noticeably higher both in rippled sea conditions (mean value 7.88 +/- 1.45 ng m(-2) h(-1)) and in rough sea conditions (mean value 21.71 +/- 2.17 ng m(-2) h(-1)) with respect to those obtained by using the unmodified chamber (respectively 5.23 +/- 0.67 and 14.15 +/- 1.03 ng m(-2) h(-1)).

Air↗
PubMed2002

Photo-induced formation of dissolved gaseous mercury in coastal and offshore seawater of the Mediterranean basin.

The first measurements on the daily trend of dissolved gaseous mercury (DGM) concentration determined in coastal and offshore waters of the Mediterranean basin are reported. Marked daily behaviour tracking solar radiation has been observed at the coastal sampling station with DGM values ranging from 11.0 to 38.9 pg/l. Contrary to these observations the DGM values in offshore water samples (11.9-20.0 pg/l) were independent of the sampling time, thus identifying the absence of higher levels during the hours of maximum insolation. The availability of Hg2+ substrate necessary for the photo-reaction processes of DGM formation has been evaluated by measuring the reactive mercury concentration. In offshore waters the lower DGM concentrations are attributable to the substrate as a limiting factor. The highest concentration of DOC measured in coastal seawater with respect to the offshore one could moreover enhance the reaction rates of DGM production through the formation of inorganic mercury complexes and weaker organic associations.

Journal Article↗
PubMed2002

Mercury exposure and elimination rates in captive bottlenose dolphins.

Mercury concentrations in fish, faeces and exhaled air were investigated in order to evaluate total mercury exposure through the gut in captive bottlenose dolphin and excretion via intestine and pulmonary routes. Results showed that faeces account for elimination of 34-48% of dietary mercury; while only 0.9-1.2% of alimentary mercury is eliminated through exhaled air. The remaining 51.2-65.3% of ingested mercury, ranging approximately between 266 and 339 microg per day, is retained within the organism. The complexation of mercury with selenium, forming insoluble tiemannite granules, is discussed as an important mechanism, complementary to excretion, by which odontocetes are able to cope with elevated alimentary exposure to mercury.

Animals↗
PubMed2002

Effects of rivastigmine on cognitive function in dementia with lewy bodies: a randomised placebo-controlled international study using the cognitive drug research computerised assessment system.

This study was designed to assess the effects of rivastigmine (Exelon) on the cognitive functioning of patients suffering from dementia with Lewy bodies. This was a prospective, multi-centre, randomised, double-blind, placebo-controlled exploratory study conducted at sites in the UK, Spain and Italy. The treatment period was 20 weeks with a 3-week posttreatment follow-up. The primary outcome measures were the Cognitive Drug Research (CDR) computerised assessment system and the Neuropsychiatric Inventory. Testing was conducted prior to dosing and then again at weeks 12, 20 and 23. Analysis of the data from the 92 patients who completed the study identified a significant pattern of benefits of rivastigmine over placebo on the CDR system. These benefits were seen on tests of attention, working memory and episodic secondary memory. Taking attention for example, patients given placebo showed a significant deterioration from predosing scores at 12 and 20 weeks, whereas patients on rivastigmine performed significantly above their predosing levels. These effects were also large in magnitude, the decline under placebo at week 12 being 19%, while the improvement under rivastigmine was 23%. The clinical relevance of this 23% improvement was that it took the patients 33% towards being normal for their age on this assessment of attention. These benefits to cognitive function were accompanied by a significant improvement of the other primary outcome measure, the Neuropsychiatric Inventory. Three weeks after discontinuation of rivastigmine, most parameters of cognitive performance returned to predrug levels.

Aged↗
PubMed2001

Cytochrome CYP2E1 phenotyping and genotyping in the evaluation of health risks from exposure to polluted environments.

Humans are exposed to over 70,000 man-made chemicals including drugs, food additives, herbicides, pesticides, and industrial agents. It is well established that environmental chemicals are the cause of numerous human diseases including cancer. In most cases, chemical carcinogens require metabolic activation, which is mainly achieved by P450s enzymes. CYP2E1 is of clinical relevance because it is inducible by ethanol, and it metabolizes many common organic solvents such as benzene, alcohols and halogenated solvents. Therefore, alteration in the level of CYP2E1 might influence the health effects of the environmental pollutants. This hypothesis needs to be validated by epidemiological studies and the objective of the "Biomed-2" project was to develop new tests to assess the individual metabolic capacity of workers exposed to volatile organic compounds in order to predict their occupational risk. In vivo chlorzoxazone 6-hydroxylation was validated as a non-invasive and selective test for the determination of liver CYP2E1 activity. Preliminary data in workers exposed to organic solvents indicated that chlorzoxazone metabolism may be a biomarker of occupational exposure to organic solvents. Other approaches, such as use of salicylate as catalytic probe or measurement of catalytic activity in lymphocytes, were not conclusive. Attempts to use CYP2E1 genotyping for estimating human risks from chemical exposure did not bring convincing data as genetic polymorphism of CYP2E1 could not be clearly related to its catalytic activity.

Animals↗
PubMed2001

Inactivation of rat liver cytochrome P450 (P450) by N,N-dimethylformamide and N,N-dimethylacetamide.

N,N-dimethylformamide (DMF), an organic solvent widely used in industry, is bioactivated by cytochrome P450 (P450) to reactive metabolites which are believed to be responsible for the hepatotoxicity observed in animals and humans. A decrease of the activating enzyme has been reported in rats treated with DMF, although the specific P450 isoform(s) involved and the nature of the reactive species responsible for this and the other toxic effects are still being investigated. In the present work, the effect of DMF and of the structurally related N,N-dimethylacetamide (DMAc) on the activating enzyme and the nature of the reactive species involved in the mechanism of P450 inactivation by the two chemicals were investigated in vitro. Incubation of liver microsomes from pyridine-induced rats with either substrate resulted in a dose-dependent (0-20 mM) loss of P450 (up to 28 and 24% for DMF and DMAc, respectively), microsomal haem (up to 24 and 20% for DMF and DMAc, respectively), but not protoporphyrin IX content. Moreover, bubbling of CO through the incubation mixture gave almost complete protection against substrate-dependent P450 inactivation, and the spin trapping agent N-tert-butyl-alpha-phenylnitrone, but neither glutathione nor vitamin C, provided a significant protection against DMF- or DMAc-dependent haem loss. Finally, electron spin resonance analysis of microsomal incubations in presence of DMF or DMAc showed spectral evidence for a carbon centered radical intermediate. The results indicate, overall, that both compounds are metabolized in vitro by P450, probably CYP2E1, to free radical metabolites which attack the haem prosthetic group, leading to suicidal enzyme inactivation.

Acetamides↗
PubMed2001

Bioactivation and toxicity in vitro of HCFC-123 and HCFC-141b: role of cytochrome P450.

The bioactivation and cytotoxicity in vitro of 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123) and 1,1-dichloro-1-fluoroethane (HCFC-141b), two replacements for some ozone-depleting chlorofluorocarbons (CFC), were investigated in rat liver microsomes and isolated rat hepatocytes. Both compounds were activated by cytochrome P450 to reactive metabolites, as indicated by: (i) the depletion of exogenous and cellular glutathione, (ii) the increased LDH release from hepatocytes, (iii) the loss of microsomal P450 content and activities, and (iv) the formation of free radical species observed in the presence of the two compounds. Moreover, the formation of two stable metabolites and an increased production of conjugated dienes, a marker of lipid peroxidation, were observed for both HCFC-123 and HCFC-141b. The biotransformation of both compounds by pyridine- and phenobarbital-induced rat liver microsomes and the inhibition of LDH release by 4-methylpyrazole and troleandomycin indicate that P450 2E1, 2B and, possibly, also 3A are the isoforms involved in the bioactivation and toxicity of HCFC-123 and HCFC-141b in the rat.

Animals↗
PubMed2001

Daily trend of dissolved gaseous mercury concentration in coastal seawater of the Mediterranean basin.

A daily trend of DGM concentration in shallow coastal seawater has been measured in an area of the Mediterranean basin. Values up to 47 pg/l were determined for a photosynthetically active radiation (PAR) intensity of 350 W/m2. The lowest value (18 pg/l) has been observed before sunrise. A linear relationship between the PAR intensity and DGM production has been highlighted in an experiment on seawater samples exposed for 10 min to solar radiation. The processes involved in DGM production and losses are discussed.

Environmental Monitoring↗
PubMed2001

Spreading of HIV-specific CD8+ T-cell repertoire in long-term nonprogressors and its role in the control of viral load and disease activity.

Long-term non-progressors (LTNP) represent a minority of human immunodeficiency virus (HIV) infected individuals characterized by stable or even increasing CD4+ T-cell count and by stronger immune responses against HIV than progressors. In this study, HIV-specific effector CD8+ T cells, as detected by both a sensitive ex vivo enzyme-linked immunospot (ELISPOT) assay and specific major histocompatibility complex (MHC) peptide tetramers, were at a low frequency in the peripheral blood of LTNP, and recognized a lower number of HIV peptides than their memory resting cell counterparts. Both factors may account for the lack of complete HIV clearance by LTNP, who could control the viral spread, and displayed a higher magnitude of cytotoxic T lymphocyte (CTL) responses than progressors. By combining cell purification and ELISPOT assays this study demonstrates that both effector and memory resting cells were confined to a CD8+ population with memory CD45RO+ phenotype, with the former being CD28- and the latter CD28+. Longitudinal studies highlighted a relatively stable HIV-specific effector repertoire, viremia, and CD4+ T-cell counts, which were all correlated with maintenance of nonprogressor status. In conclusion, the analysis of HIV-specific cellular responses in these individuals may help define clear correlates of protective immunity in HIV infection.

Adult↗