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L Alvarez

Publications and source records attributed to L Alvarez.

At least 19 recordsLinked to original sources
PubMed2007

Short communication: detection of quantitative trait loci influencing somatic cell score in Spanish Churra sheep.

Eleven half-sib ovine families, including 1,421 Spanish Churra ewes, were analyzed for 181 microsatellite markers spanning the entire autosomic ovine genome. Using a multimarker regression method, a daughter experimental design was used to identify putative quantitative trait loci (QTL) affecting the somatic cell score (SCS). Chromosome-wise significance thresholds were set empirically by permuting the phenotypic data. Marker order and genetic distances of the autosomic linkage map built for this commercial population were in accordance with the published ovine linkage map. An across-family association analysis revealed a region on chromosome 20 suggestive of evidence for a QTL. Segregation of the QTL into 2 families was inferred from the within-family analysis, and differences in the position of the suggested QTL were found between the 2 half-sib groups. This could be the result of incomplete information associated with the markers for the significant families. The location of the major histocompatibility complex in proximity to the across-family effect suggests this region may harbor a segregating QTL for the SCS in the Churra population. Studies in dairy cattle examining the SCS have reported linkage associations on corresponding bovine orthologous regions, supporting the validity of our findings.

Animals↗
PubMed2006

In vitro and in vivo effects of flubendazole on Echinococcus granulosus metacestodes.

The aim of the present work was to determine the efficacy of flubendazole (FLBZ) against Echinococcus granulosus metacestodes by using in vitro and in vivo models. Groups of 50 microcysts developed in vitro, and groups of 10 peritoneal cysts were obtained from Balb C mice with experimental secondary infections of 8 months. The cysts were placed in Leighton tubes containing 10 ml of culture medium. FLBZ was added to the medium resulting in final concentrations of 5 and 1 microg/ml for mycrocysts treatment and 10, 5, and 1 microg/ml for murine cysts treatment. In vivo treatment was performed on 20 mice that developed an experimental secondary hydatid disease over a period of 11 months. FLBZ was given (1.5 mg/kg) by the oral route once a day for 50 days. A loss of turgidity was detected in all in vitro drug treated cysts irrespective of the drug concentration or parasite origin. Inspection of treated cysts by scanning electron microscopy (SEM) revealed that the germinal layer lost it characteristic multicelular structure. These results were confirmed on the ultrastructural level by transmission electron microscopy (TEM), treated metacestodes had undergone considerable degenerative changes after the in vitro treatment. The results obtained after the in vivo treatment with FLBZ showed no significant difference between the control and treated groups related to the weight of cyst masses. However, the ultrastructural study at TEM of cysts that developed in mice from the treated group revealed alterations in the germinal layer with the presence of numerous vacuoles. With regard to the ultrastructural study at SEM, only cellular debris of the germinal layer could be seen. In conclusion, the data obtained clearly demonstrate that in vitro and in vivo treatment with FLBZ is effective against E. granulosus metacestodes.

Animals↗
PubMed2006

Social rank and response to the "male effect" in the Australian Cashmere goat.

The present study was conducted to determine if the social status of Australian Cashmere goats affects their response to the male effect in terms of LH secretion, ovulation and expression of estrus. Australian Cashmere goats were kept isolated from the males during 5 months. The index of success (SI) of each goat was calculated to establish their social rank. In the first experiment, the ten most dominant and the 10 most subordinate goats were separated from the original herd and housed in two pens (5 dominant and 5 subordinate animals in each pen). An androgenized wether was then introduced into each pen. Luteinizing hormone (LH) was measured every 20 min from 2h before to 4h after introduction of the male in the goats of first pen and from 4 to 8h after male introduction in the second pen. In the second experiment, the remaining 50 goats were exposed in their original pen to two androgenized wethers. Their association index with the males (AI) was calculated for each of these 50 goats, and the intervals from exposure to the males to the onset of estrus and to ovulation were determined. During the first 4h after male introduction, the dominant goats had more LH pulses (0.65+/-0.06 compared with 0.3+/-0.09; P<0.05) and greater LH mean concentrations (1.79+/-0.14 ng/ml compared with 1.30+/-0.15 ng/ml, P=0.05) than the subordinate animals. Although not significantly different, the AI was 35% greater for high and medium ranking goats than for low ranking animals (0.031+/-0.004, 0.032+/-0.005 and 0.023+/-0.005, respectively, P>0.05). Although the number of goats ovulating in response to male exposure was similar between dominance groups (high: 100%, medium: 94% and low ranking: 92%), the high and medium dominance goats showed a greater incidence of expression of estrus than low-dominance goats (94.4%, 89.5% and 53.8%, respectively, P<0.05). It is concluded that the social rank of the Australian Cashmere goat influences their response to the male effect in terms of early LH secretion and expression of estrus.

Animals↗
PubMed2006

Biochemical response to bisphosphonate therapy in pagetic patients with skull involvement.

The aims of this study were to compare the response to therapy in disease activity in pagetic patients with and without skull involvement and the usefulness of bone markers in the evaluation of these patients. Forty patients with Paget's disease treated with tiludronate and 26 healthy controls were included. Serum total and bone alkaline phosphatases (TAP, BAP), procollagen I N propeptide (PINP), and urinary N- and C-terminal cross-linking telopeptides of collagen I (NTX, alpha-alpha CTX, and beta-beta CTX) were measured at baseline and 6 months after therapy. The extent of the disease was evaluated using the Coutris' index. Pagetic patients were classified into three groups: patients with skull involvement (G-I, n = 12), patients without skull involvement (G-II, n = 28), and a subgroup of patients from G-II without skull involvement but with similar disease extent to G-I (G-III, n = 10). At baseline, patients from G-I showed significantly higher values in most markers compared to G-II. alpha-alpha CTX was the marker with the highest values in all groups. Moreover, monostotic patients with skull involvement showed higher serum baseline values of TAP per unit of affected area than monostotic patients without skull involvement. After therapy, the percentage of patients with markers within the normal range was lower in G-I than in G-II and G-III. In conclusion, pagetic patients with skull involvement showed a marked increase in bone turnover and a lower response to therapy.

Adult↗
PubMed2006

Drug transport mechanisms in helminth parasites: passive diffusion of benzimidazole anthelmintics.

Anthelmintic molecules must reach their receptors inside target parasites to exert the pharmacological effect. Available data suggest that the main route of entry of antiparasitic drugs into helminth parasites would be through their external surface. However, it is unclear if trans-tegumental/cuticular penetration is the most important way of entry of benzimidazole (BZD) anthelmintics into their target parasites compared to oral ingestion. The relative involvement of active and passive transport mechanisms has not been defined. The goal of the work reported here was to determine the main processes involved in the entry of BZD anthelmintic molecules into the three main classes of helminth parasites. Adult specimens of Moniezia benedeni (cestode), Fasciola hepatica (trematode) and Ascaris suum (nematode) were incubated in Kreb's Ringer Tris buffer (pH 7.4, 37 degrees C) (1g parasite/10 ml incubation medium) for 15, 45, and 90 min, respectively, in the presence of a concentration gradient of either fenbendazole (FBZ), oxfendazole or triclabendazole sulphoxide (TCBZSO) (1-30 mol/ml, n=4). Dead helminth specimens were also incubated with the same drug concentration gradient. Specimens of F. hepatica with the oral route closed off by ligation were incubated with TCBZSO in the presence or absence of bovine serum albumin. After the incubation time elapsed, samples of parasite material were chemically extracted and prepared for high performance liquid chromatography analysis to measure drug/metabolite concentrations. Equivalent drug concentrations were measured within ligated and non-ligated liver flukes, demonstrating that BZD do mainly penetrate by trans-tegumental diffusion. The higher the concentration of BZD molecules in the incubation medium, the greater their concentration recovered within the helminth parasites. High correlation coefficients (>0.98) were obtained between initial drug concentration in the incubation medium and those measured inside the nematode, cestode, and trematode parasites. FBZ concentrations recovered from tissues of dead cestodes/nematodes over time were significantly greater compared to those measured in living parasites. These differences in drug diffusion may be related to the morphological/functional properties of the parasite's external surfaces. The outcome of the work reported here indicates that passive drug transfer through the external helminth surface is the main transport mechanism accounting for BZD accumulation into target parasites.

Animals↗
PubMed2006

Inherited thrombophilia is associated with deep vein thrombosis in a Colombian population.

The development of venous thromboembolism is influenced by a variety of genetic and environmental risk factors. A few studies have ascertained whether thrombophilic defects are risk factors for venous thromboembolism in Latin American populations with a variable degree of admixture, such as the Colombian population. To address this issue, we conducted a case-control study involving 100 consecutive patients with deep vein thrombosis and 114 healthy controls from the Hospital Universitario San Vicente de Paúl, Medellín, Colombia. Activated protein C resistance (APC resistance) was detected in 25/99 patients vs. 6/114 controls (OR = 6.08, 95% CI = 2.23-17.47). Ten of 100 patients carried the factor V Leiden mutation vs. 1/114 controls (OR = 12.56, 95% CI = 1.61-267). APC resistance was associated with the factor V Leiden mutation in only 10/25 patients. The prothrombin G20210A mutation was found in 4/100 patients, but none of the controls (P < 0.05). There was no significant difference in the proportion of homozygous carriers of methylenetetrahydrofolate reductase C677T variant among patients and controls. In conclusion, in our studied population, factor V Leiden, APC resistance, and prothrombin G20210A were associated with an increased risk of deep vein thrombosis. However, the frequencies of these thrombophilic defects and of APC resistance associated with factor V Leiden was lower than the corresponding frequencies previously reported for Caucasian populations. Further study is required to assess the influence of ethnicity on thrombophilia.

Activated Protein C Resistance↗
PubMed2006

Identification of a new leucine haplotype (ALQ) at codon 154 in the ovine prion protein gene in Spanish sheep.

Genetic susceptibility to scrapie is closely linked to variations at codons 136, 154, and 171 of the prion protein (PRNP) gene. This association between the PRNP genotype and susceptibility to scrapie is the basis of breeding programs for scrapie resistance in different countries. In this paper, we describe the method used with 2 Spanish dairy sheep breeds (Churra and Castellana) to ascertain the initial status of protection against scrapie as a first step toward adapting their breeding schemes to include resistance as a complementary selection criterion. The procedure for genotype identification is based on multiplex minisequencing methodology and has been shown to be accurate, easy to interpret, and to have a medium throughput. The frequency of the ARQ allele was similar in the 2 populations at nearly 70%. The ARR allele, associated with resistance in the homozygous state, reaches around 23% in Churras and nearly 20% in Castellanas. The high-risk VRQ allele appeared at a relatively low frequency in both breeds. No other haplotypes were found in these 2 breeds. Furthermore, in this screening we found a new allele carrying leucine at codon 154. This new genetic variant might play a role in susceptibility to scrapie because codon 154 belongs to a region considered to have an important role in conformational conversion of the cellular to the pathogenic protein.

Alleles↗
PubMed2006

Influence of prion protein genotypes on milk production traits in Spanish Churra sheep.

The aim of this work was to analyze the possible relationships between milk production traits and prion protein genotypes in Spanish Churra sheep. For this purpose, 2 analyses were carried out. First, an association study was performed of the prion protein genotypes of 12,533 Churra ewes and their milk yield, protein percentage, fat percentage, and somatic cell score as phenotypes, followed by a quantitative trait loci screening on the chromosome where the prion protein gene was located in this population. The latter analysis was carried out using 8 genetic markers (7 microsatellites and the prion protein genotypes) spanning ovine chromosome 13 using a daughter design. Regarding genotype frequencies, the most frequent allele was ARQ (75.90%), which linked with a high susceptibility to scrapie, followed by the resistant haplotype, ARR (18.16 %). The frequency of the most susceptible allele, VRQ, was around 1%. No evidence of association or linkage between prion protein genotypes and milk traits has been detected in Churra sheep. These results indicate that increasing the ARR frequency in Churra population will not have an adverse effect on selection for milk traits included in the breeding objectives. However, the low allele frequencies for ARR should be considered in the initial stages to prevent possible bottlenecks in future genetic progress.

Alleles↗
PubMed2006

[Vascular access outcome in patients aged over 75 years].

UNLABELLED: We report a retrospective study on the results of 132 native fistulas, 12 grafts and 27 tunneled catheters followed during 30 months in 144 patients on hemodialysis. The results were compared according to patient age: 75 years or over (n = 58, 80.3 +/- 3.5) vs below 75 years (n = 86, 59.5 +/- 13.3). Gender, presence of diabetes and type of fistula were also included in the analysis. RESULTS: There were no statistically significant differences between both groups in the use of tunneled catheters or grafts (8.6% vs 5.8% y 5.2% vs 10.5% respectively), primary failure of native fistulas (7.1% in those aged 75 years or over vs 25.5% in patients below 75 years), rate of thrombosis (0.03 vs 0.09/patient year at risk respectively) or number of percutaneous or surgical procedures in order to maintain the fistula patency (0.11 vs 0.16/patient year at risk respectively). At the same time no differences were seen in the primary, primary assisted and secondary patency of the native fistulas. The mean age of the patients when the first access fistula was created was different according to the area of surgery (74.9 +/- 9.3 for the elbow vs 64.9 +/- 16.2 years for the forearm, p < 0.005). Diabetes was an unfavourable factor for primary (HR Cox 2.08, p < 0.05) or secondary (Log Rank, p <0.05) patency. CONCLUSION: The vascular access for hemodialysis in elderly patients presents a similar evolution to that seen in younger populations if the access creation is based on an exhaustive study, including ecodoppler of the vascular map and the use of more proximal fistulas if necessary. Therefore the more frequent use of grafts or catheters in elderly patients is not justified.

Age Factors↗
PubMed2005

In vitro effects of flubendazole on Echinococcus granulosus protoscoleces.

The aim of the present work was to determine the in vitro protoscolicidal effect of flubendazole (FLBZ) against Echinococcus granulosus. Protoscoleces of E. granulosus were incubated with FLBZ at concentrations of 10, 5 and 1 microg/ml. The first signs of FLBZ-induced damage were observed 3 days post-incubation. A clear protoscolicidal effect, reducing the vitality of protoscoleces to 35.6+/-0.7%, was observed after 18 days of incubation. After 25 days of FLBZ incubation (5 microg/ml), the percentage of vital protoscoleces was 13.9+/-5.9%. Protoscolex mortality was 100% (10 and 1 microg/ml) and 0.7+/-0.7% (5 microg/ml) after FLBZ incubation for 30 days. Results of vitality tests were consistent with the tissue damage observed at the ultrastructural level. The primary site of damage was the tegument of the parasite. The morphological changes included contraction of the soma region, formation of blebs on the tegument, rostellar disorganization, loss of hooks and destruction of microtriches. The data reported in this article demonstrate a clear in vitro effect of FLBZ against E. granulosus protoscoleces.

Animals↗
PubMed2005

XAS evidence of As(V) association with iron oxyhydroxides in a contaminated soil at a former arsenical pesticide processing plant.

The molecular-level speciation of arsenic has been determined in a soil profile in the Massif Central near Auzon, France that was impacted by As-based pesticides by combining conventional techniques (XRD, selective chemical extractions) with X-ray absorption spectroscopy (XAS). The arsenic concentration is very high at the top (>7000 mg kg(-1)) and decreases rapidly downward to a few hundreds of milligrams per kilogram. A thin layer of schultenite (PbHAsO4), a lead arsenate commonly used as an insecticide until the middle of the 20th century, was found at 10 cm depth. Despite the occurrence of this As-bearing mineral, oxalate extraction indicated that more than 65% of the arsenic was released upon dissolution of amorphous iron oxides, suggesting a major association of arsenic with these phases within the soil profile. Since oxalate extraction cannot unambiguously distinguish among the various chemical forms of arsenic, these results were confirmed by a direct in situ determination of arsenic speciation using XAS analysis. XANES data indicate that arsenic occurs mainly as As(V) along the soil profile except for the topsoil sample where a minor amount (7%) of As(III) was detected. EXAFS spectra of soil samples were fit by linear combinations of model compounds spectra and by a shell-by-shell method. These procedures clearly confirmed that As(V) is mainly (at least 80 wt %) associated with amorphous Fe(III) oxides as coprecipitates within the soil profile. If any, the proportion of schultenite, which was evidenced by XRD in a separate thin white layer, does not account for more than 10 wt % of arsenic in soil samples. This study emphasizes the importance of iron oxides in restricting arsenic dispersal within soils following dissolution of primary As-bearing solids manufactured for use as pesticides and released into the soils.

Arsenic↗
PubMed2005

The role of type I and type II 5' deiodinases on hexachlorobenzene-induced alteration of the hormonal thyroid status.

Treatment of male Wistar rats with hexachlorobenzene (HCB) (1000 mg/kg b.w.) for 3-30 days decreases circulating levels of thyroxine (T4) but does not affect triiodothyronine (T3). Time courses were determined for 5' deiodinase type I (5' D-I) activity in thyroid, liver, and kidney and 5' deiodinase type II (5' D-II) activity in brown adipose tissue (BAT) to test the possibility that increased deiodinase activity might contribute to the maintenance of the serum T3 level. Specific 5' D-I activity was increased in the thyroid at 21 days and thereafter. No significant changes were observed in the liver, however, total 5' D-I activity in this tissue was increased at 30 days of treatment as a consequence of liver weight enhancement. HCB decreased kidney 5' D-I activity after 15 days, and BAT 5' D-II activity after 21 days of treatment. Total body 5' D-I activity was significantly increased by 30 days of HCB-treatment. HCB increased the activity of hepatic T4 uridine diphosphoglucuronosyl transferase (UDPGT) in a time-dependent manner, without changes in T3 UDPGT. We propose that increased T4 to T3 conversion in the thyroid and in the greatly enlarged liver may account for the maintenance of serum T3 concentration in hypothyroxinemic HCB-treated rats.

Adipose Tissue, Brown↗
PubMed2005

Bilateral subthalamotomy in Parkinson's disease: initial and long-term response.

We conducted an open label pilot study of the effect of bilateral subthalamotomy in 18 patients with advanced Parkinson's disease. In seven patients, the first subthalamotomy pre-dated the second by 12-24 months ('staged surgery'). Subsequently, a second group of 11 patients received bilateral subthalamotomy on the same day ('simultaneous surgery'). Patients were assessed according to the CAPIT (Core Assessment Program for Intracerebral Transplantation) protocol, a battery of timed motor tests and neuropsychological tests. Evaluations were performed in the 'off' and 'on' drug states before surgery and at 1 and 6 months and every year thereafter for a minimum of 3 years after bilateral subthalamotomy. Compared with baseline, bilateral subthalamotomy induced a significant (P < 0.001) reduction in the 'off' (49.5%) and 'on' (35.5%) Unified Parkinson's Disease Rating Scale (UPDRS) motor scores at the last assessment. A blind rating of videotape motor exams in the 'off' and 'on' medication states preoperatively and at 2 years postoperatively also revealed a significant improvement. All of the cardinal features of Parkinson's disease as well as activities of daily living (ADL) scores significantly improved (P < 0.01). Levodopa-induced dyskinesias were reduced by 50% (P < 0.01), and the mean daily levodopa dose was reduced by 47% at the time of the last evaluation compared with baseline (P < 0.0001). Dyskinesias occurred intraoperatively or in the immediate postoperative hours in 13 patients, but were generally mild and short lasting. Three patients developed severe generalized chorea that gradually resolved within the next 3-6 months. Three patients experienced severe and persistent postoperative dysarthria. In two, this coincided with the patients exhibiting large bilateral lesions also suffering from severe dyskinesias. No patient exhibited permanent cognitive impairment. The motor benefit has persisted for a follow-up of 3-6 years. This study indicates that bilateral subthalamotomy may induce a significant and long-lasting improvement of advanced Parkinson's disease, but the clinical outcome was variable. This variability may depend in large part on the precise location and volume of the lesions. Further refinement of the surgical procedure is mandatory.

Activities of Daily Living↗
PubMed2005

Transient bone marrow oedema of the knee.

OBJECTIVE: To evaluate the role of MRI in the diagnosis of transient bone marrow oedema of the knee. DESIGN: All cases were analysed with plain film and MR. Bone scan was performed to one of them. Laboratory tests were obtained in all 8 cases and core decompression was performed in two cases. PATIENTS: The study includes 8 patients, 7 men and 1 woman with ages ranging from 33 to 74 years with severe knee pain, tenderness and slightly limited range of motion. RESULTS AND CONCLUSIONS: Radiographs were unremarkable in terms of osteopenia because they were obtained early in the course of the disease and proved to be of no value in the diagnosis. MR is the imaging modality of choice showing low signal intensity in T1WI and increased signal intensity in T2WI with no joint destruction, fractures, bone death, periostitis or cortical disruption. Bone scan showed increase uptake of the affected area. Laboratory tests were normal. Spontaneous resolution was the rule. It should not be a diagnosis of exclusion and it should be ruled out every time a patient presents with pain and limited range of motion in the absence of history of trauma.

Adult↗
PubMed2005

Kidney-specific proteins in patients receiving aprotinin at high- and low-dose regimens during coronary artery bypass graft with cardiopulmonary bypass.

BACKGROUND AND OBJECTIVE: The aim was to determine whether the administration of aprotinin can cause deleterious effects on renal function in cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Sixty consecutive patients with normal preoperative renal function undergoing elective coronary artery bypass surgery with CPB using the same anaesthetic; CPB and surgical protocols were randomized into three groups. Patients received placebo (Group 1), low-dose aprotinin (Group 2) or high-dose aprotinin (Group 3). Renal parameters measured were plasma creatinine, alpha1-microglobulin and beta-glucosaminidase (beta-NAG) excretion. Measurements were performed before surgery, during CPB and 24 and 72 h, and 7 and 40 days postoperatively. RESULTS: In the three groups, alpha1-microglobulin and beta-NAG excretions significantly increased during CPB, at 24 and 72 h, and 7 days postoperatively (P < 0.05) and had returned to preoperative levels at postoperative day 40. Plasma creatinine levels were within normal values at times recorded. In Groups 2 and 3, alpha1-microglobulin excretion during CPB was significantly higher than in Group 1 (P < 0.001), and 24h after surgery it still remained significantly higher in Group 3 compared to Groups 1 and 2 (P < 0.05). CONCLUSIONS: Aprotinin caused a significant increase in alpha1-microglobulin excretion but not in beta-NAG excretion during CPB, which may be interpreted as a greater renal tubular overload without tubular damage. This effect persisted for 24 h after surgery when high-dose aprotinin doses had been administered. Creatinine plasma levels were not sensitive to detect these prolonged renal effects in our study.

Acetylglucosaminidase↗
PubMed2005

Toxoplasma gondii infections in chickens from Venezuela: isolation, tissue distribution, and molecular characterization.

The prevalence of Toxoplasma gondii, in free-ranging chickens is a good indicator of the prevalence of T. gondii oocysts in the soil because chickens feed from the ground. The prevalence of T. gondii in 46 free-range chickens (Gallus domesticus) from Venezuela was determined. Antibodies to T. gondii were assayed by the modified agglutination test (MAT). Antibodies were found in 16 (32%) chickens with titers of 1:5 in 1, 1:10 in 2, 1:40 in 2, 1:80 in 2, 1:160 in 2, 1:320 in 3, 1: 640 in 2, and 1:1,280 or higher in 2. Hearts, pectoral muscles, and brains of 13 chickens with MAT titers of 1:40 or more were bioassayed individually in mice. Tissues of each of 3 chickens with titers of 1:5 or 1:10 were pooled and bioassayed in mice. Tissues from the remaining 30 seronegative chickens were pooled and fed to 1 T. gondii-free cat. Feces of the cat were examined for oocysts; it did not shed oocysts. Toxoplasma gondii was isolated from 12 of 13 chickens with MAT titers of 1:40 or more. Toxoplasma gondii was isolated from pooled tissues of 1 of 2 chickens with titers of 1:10. Eight of these 13 isolates were virulent for mice. Genotyping of 13 of these isolates using the SAG2 locus indicated that 10 were type III, and 3 were type II. Phenotypically and genetically these isolates were different from T. gondii isolates from North America and Brazil. This is the first report of isolation of T. gondii from chickens from Venezuela.

Agglutination Tests↗
PubMed2005

[Optimization of use of levodopa in Parkinson's disease: role of levodopa-carbidopa-entacapone combination].

Levodopa remains the mainstay treatment for Parkinson's disease (PD). Chronic treatment is associated with motor complications (MC) that marred the clinical benefit of levodopa. These problems and experimental data in cell cultures indicating a neurotoxic effect of levodopa have led to the idea of delaying the introduction of levodopa treatment for as long as possible. We here review recent data regarding the mechanism of action of levodopa and its application in clinical practice on the light of the marketing of the combination levodopa-carbidopa- entacapone. Accumulated evidence indicates that MC are mainly the consequence of disease severity governing the degree of dopaminergic depletion and the "pulsatile" dopaminergic stimulation provided by levodopa short plasma half-life. There is no in vivo or clinical evidence of a relevant neurotoxic effect of levodopa. In fact, the recent ELLDOPA study may suggest a neuroprotective effect. Entacapone reduces homocysteine plasma levels which could provide a mechanism to reduce cell death in PD. Currently, the combination levodopa-carbidopa-entacapone is particularly indicated for the treatment of "wearing off" fluctuations. Experimental evidence suggests that early treatment with levodopa-carbidopa-entacapone may substantially ameliorate the incidence of MC. Such a clinical study in "de novo" patients is underway. At present, the combination levodopa-carbidopa-entacapone is indicated when levodopa is judged necessary.

Akathisia, Drug-Induced↗