Mathematical model for the homeostasis of alpha-macroglobulins in the rat.

Alpha-macroglobulins (AM) are proteins that inactivate proteinases. Sodium monofluorophosphate (MFP) binds to AM and transiently changes AM plasma levels. As a consequence MFP is useful to modify AM homeostasis. A mathematical model to study the homeostasis of AM is proposed in this paper. The model describes changes in plasma concentration of AM, MFP concentration in the gastrointestinal tract, MFP plasma concentration, plasma concentration of AMMFP and includes rate constants of the processes involved in AM homeostasis. Estimation of the rate constants values was achieved using experimental and mathematical resources. The homeostasis of AM after an oral dose of 80 µmol of MFP was analyzed with a simulation tool. Experimental conditions that modify the homeostasis of AM had been simulated and validated using specific drugs that change some parameter of the system. The mathematical model describes accurately the behavior of the biological model. The results allow concluding that the simplifications made did not underestimate the main processes involved in the homeostasis and, also that the assumptions made were correct.

[Risk factors associated with the development of motor complications in Parkinson's disease. A study in a Chilean population]. / Factores de riesgo asociados con el desarrollo de complicaciones motoras en la enfermedad de Parkinson. Experiencia en poblacion chilena.

INTRODUCTION: The treatment of Parkinson's disease (PD) is based on the use of levodopa and/or dopaminergic agonists. This treatment is associated with motor complications in around 50% of the patients over 5 years of treatment. Numerous risk factors have been related to the onset of this motor complications. AIM: To describe the prevalence and risk factors associated with the occurrence of motor complications in our population. PATIENTS AND METHODS: PD patients in control in a movement disorders center were consecutively recruited. Using a multivariate logistic regression model the risk factors associated with the onset of MC were determined. RESULTS: 124 patients were evaluated. Mean age was 66,2 +/- 10,1 years, the years of PD evolution were 8,1 +/- 5,2 years, the on UPDRS score was 27,7 +/- 14,8 points. A 62% of the patients presented at least one motor complication, a 52% with wearing off and a 47,2% dyskinesias. Both motor complications were present in 39%. The multivariate analysis showed that that female sex and the dose of levodopa equivalents were the risk factors for the occurrence of dyskinesias. For the wearing off the main risk factor were the years of evolution of the PD. CONCLUSIONS: This study shows that the time of evolution of the PD is the main risk factor for the wearing off and the female sex and the dose of levodopa equivalents are the risk factor for the development of dyskinesias. These results are in agreement with the previously reported in the literature for other populations.

Factores de riesgo asociados con el desarrollo de complicaciones motoras en la enfermedad de Parkinson. Experiencia en población chilena / Risk factors associated with the development of motor complications in Parkinson disease. A study in a chilean population

Introducción. El tratamiento de la enfermedad de Parkinson (EP) se basa principalmente en el uso de levodopa y/o agonistas dopaminérgicos. Este tratamiento se asocia con complicaciones motoras aproximadamente en el 50% de los pacientes a los cinco años. Existen diversos factores de riesgo para el desarrollo de estas complicaciones descritos en otras poblaciones. Objetivo. Describir la prevalencia y factores de riesgo para la aparición de complicaciones motoras en nuestra población de portadores de EP. Pacientes y métodos. Consecutivamente se reclutaron portadores de EP. Mediante un modelo de regresión logística multivariada se determinaron los factores de riesgo asociados con el desarrollo de las complicaciones motoras. Resultados. Se evaluaron 124 pacientes, con una edad media de 66,2 ± 10,1 años, tiempo medio de evolución de la EP de 8,1 ± 5,2 años, y estado motor on mediante UPDRS-III de 27,7 ± 14,8 puntos. Un 62% presentó alguna complicación motora, un 52% deterioro de fin de dosis, un 47,2% discinesias y un 39% ambas complicaciones motoras. El análisis multivariado mostró que el sexo femenino y la dosis de equivalentes de levodopa son los principales factores de riesgo para la aparición de discinesias, mientras que el tiempo de evolución lo es para el desarrollo de deterioro de fin de dosis. Conclusiones. El tiempo de evolución de la EP es el principal factor de riesgo para el desarrollo de deterioro de fin de dosis, mientras que la dosis de fármacos dopaminérgicos y el sexo femenino son los principales para el desarrollo de discinesias. Estos resultados obtenidos en nuestra población son similares a los comunicados en otras series

Introduction. The treatment of Parkinson’s disease (PD) is based on the use of levodopa and/or dopaminergic agonists. This treatment is associated with motor complications in around 50% of the patients over 5 years of treatment. Numerous risk factors have been related to the onset of this motor complications. Aim. To describe the prevalence and risk factors associated with the occurrence of motor complications in our population. Patients and methods. PD patients in control in a movement disorders center were consecutively recruited. Using a multivariate logistic regression model the risk factors associated with the onset of MC were determined. Results. 124 patients were evaluated. Mean age was 66,2 ± 10,1 years, the years of PD evolution were 8,1 ± 5,2 years, the on UPDRS score was 27,7 ± 14,8 points. A 62% of the patients presented at least one motor complication, a 52% with wearing off and a 47,2% dyskinesias. Both motor complications were present in 39%. The multivariate analysis showed that that female sex and the dose of levodopa equivalents were the risk factors for the occurrence of dyskinesias. For the wearing off the main risk factor were the years of evolution of the PD. Conclusions. This study shows that the time of evolution of the PD is the main risk factor for the wearing off and the female sex and the dose of levodopa equivalents are the risk factor for the development of dyskinesias. These results are in agreement with the previously reported in the literature for other populations

Analgesic activity of Ugni molinae (murtilla) in mice models of acute pain.

Leaf extracts of Ugni molinae Turcz. (Myrtaceae) are used in Chilean folk medicine as analgesic and anti-inflammatory. The antinociceptive effect of dichloromethane (DCM), ethyl acetate (EA) and methanol (ME) leaf extracts was assessed by intraperitoneal, oral and topical administration in writhing, tail flick, and tail formalin tests in mice. The extracts showed a dose-dependent antinociceptive activity in all the assays under different administration routes. The ED(50) values for the different tests for the DCM, EA, ME extract and reference drug (ibuprofen) were as follows. Writhing test in acetic acid (i.p. administration): 0.21, 0.37, 1.37 and 0.85mg/kg, respectively; tail flick test (oral administration): 199, 189, 120 and 45.9mg/kg. The EC(50) values for tail flick test were (topical administration): 2.0, 0.35, 1.4 and 8.2% (w/v), respectively; and the topical analgesic effects were (formalin assay) 75.5, 77.5, 31.6 and 76.5%, respectively. Ugni molinae extracts produce antinociception in chemical and thermal pain models through a mechanism partially linked to either lipooxygenase and/or cyclooxygenase via the arachidonic acid cascade and/or opioid receptors. Flavonoid glycosides and triterpenoids have been isolated from the plant and can be associated with the observed effect. Our results corroborate the analgesic effects of Ugni molinae, and justify its traditional use for treating pain.

Hamster sperm glycine receptor: evidence for its presence and involvement in the acrosome reaction.

Recent reports have provided evidence for the presence of amino acid neurotransmitter receptor/chloride channels in human and porcine spermatozoa and their involvement in the acrosome reaction (AR). In this work we investigated whether a glycine receptor (GlyR) was present in golden hamster sperm, and whether it had a role in the hamster AR. The neuronal GlyR agonist glycine, stimulated in a dose-dependent manner, the AR of hamster spermatozoa previously capacitated for at least 3 hr. This stimulation was completely inhibited by 50 microM (+)-bicuculline and by concentrations of strychnine as low as 10-50 nM; both agents are antagonists of neuronal GlyR when used at the concentrations reported in this study. beta-Alanine, another agonist of the neuronal GlyR, also stimulated the AR. The AR-stimulatory effect of this compound was completely abolished by 50 nM strychnine. The inhibitory effect of strychnine on the glycine-induced hamster sperm AR was completely overcome by subsequent treatment with the calcium ionophore ionomycin, demonstrating that the strychnine effect was specific for GlyR. Additional binding studies with (3)[H]-strychnine, the typical radioligand used to detect GlyR in several cells, demonstrated for the first time the presence of specific binding sites for strychnine in the hamster spermatozoa. Interestingly, binding increased during in vitro capacitation, particularly in those sperm suspensions showing high percentages of AR. Taken together these results strongly suggest the presence of a GlyR in the hamster spermatozoa, with a role in the AR when activated.