An 8-month adapted motor activity program in a young CMT1A male patient.

Background: It is unclear whether prolonged periods of training can be well tolerated. In Charcot-Marie Tooth disease (CMT). We report the effects of an 8-month, adapted motor activity (AMA) program in a 16-years-old CMT1A male patient. The program included strength, mobility, and balance training (two sessions per week, 1 h per session). Measures: Walking ability and walking velocity (Six-Minute Walking Test-6MWT, Ten Meters Walking Test-10 mW T), balance (Y-Balance Test-YBT, Berg Balance Scale-BBS), functional mobility (Short Physical Performance Battery-Short physical performance battery), fatigue (Checklist Individual strength questionnaire - CIS20R), health and quality of life (Short Form Health Survey 36 questionnaire-SF-36) were evaluated in three moments: before (T0), after 5 (T1) and 8 (T2) months of adapted motor activity. Dorsal and plantar foot flexion strength (Maximal Voluntary Contraction-maximum voluntary contraction) and neuromuscular functions (Electromyography-sEMG, interpolated twitch technique-ITT) were measured at T1 and T2. Results: Relative to T0, an amelioration of walking ability (6MWT, +9,3%) and balance (with improvements on Y-balance composite normalized mean reach of the right and left limb of 15,3% and 8,5%, respectively) was appreciable. Relative to T1, an increase in foot strength in three out of four movements (right plantar flexion, +39,3%, left plantar flexion, +22,7%, left dorsal flexion, 11,5%) was observed. Concerning voluntary muscle activation, a greater recruitment in the left, unlike right, medial gastrocnemius was observed. Conclusion: Results suggest the safety of an 8-month AMA program in a young patient affected by CMT1A.

Venetoclax-Related Neutropenia in Leukemic Patients: A Comprehensive Review of the Underlying Causes, Risk Factors, and Management.

Venetoclax is a Bcl-2 homology domain 3 (BH3) mimetic currently approved for the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) that has proven to be highly effective in reinstating apoptosis in leukemic cells through the highly selective inhibition of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2). Clinically, venetoclax has provided lasting remissions through the inhibition of CLL and AML blasts. However, this activity has often come at the cost of grade III/IV neutropenia due to hematopoietic cells' dependence on Bcl-2 for survival. As life-threatening infections are an important complication in these patients, an effective management of neutropenia is indispensable to maximize patient outcomes. While there is general consensus over dose reduction and scheduling modifications to minimize the risk of neutropenia, the impact of these modifications on survival is uncertain. Moreover, guidelines do not yet adequately account for patient-specific and disease-specific risk factors that may predict toxicity, or the role combination treatment plays in exacerbating neutropenia. The objective of this review is to discuss the venetoclax-induced mechanism of hematological toxicity, the potential predictive risk factors that affect patient vulnerability to neutropenia, and the current consensus on practices for management of neutropenia.

Exercise, Nutrition, and Supplements in the Muscle Carnitine Palmitoyl-Transferase II Deficiency: New Theoretical Bases for Potential Applications.

Carnitine palmitoyltransferase II (CPTII) deficiency is the most frequent inherited disorder regarding muscle fatty acid metabolism, resulting in a reduced mitochondrial long-chain fatty acid oxidation during endurance exercise. This condition leads to a clinical syndrome characterized by muscle fatigue and/or muscle pain with a variable annual frequency of severe rhabdomyolytic episodes. While since the CPTII deficiency discovery remarkable scientific advancements have been reached in genetic analysis, pathophysiology and diagnoses, the same cannot be said for the methods of treatments. The current recommendations remain those of following a carbohydrates-rich diet with a limited fats intake and reducing, even excluding, physical activity, without, however, taking into account the long-term consequences of this approach. Suggestions to use carnitine and medium chain triglycerides remain controversial; conversely, other potential dietary supplements able to sustain muscle metabolism and recovery from exercise have never been taken into consideration. The aim of this review is to clarify biochemical mechanisms related to nutrition and physiological aspects of muscle metabolism related to exercise in order to propose new theoretical bases of treatment which, if properly tested and validated by future trials, could be applied to improve the quality of life of these patients.

Intestinal dysmotility and enteric neurochemical changes in a Parkinson's disease rat model.

Gastrointestinal disorders, constipation in particular, are the most common non-motor dysfunctions affecting Parkinson's disease (PD) patients. We have previously reported that rats bearing unilateral nigrostriatal lesion caused by 6-hydroxydopamine (6-OHDA) stereotaxic injection develop severe constipation together with a region-specific decrease of neuronal nitric oxide synthase (nNOS) in enteric neurons of the lower intestinal tract. Here, we extend these observations on other enteric neuronal subpopulations, investigating also the propulsive activity of isolated colonic specimens. Four weeks post 6-OHDA injection, lesioned rats showed a significant increase of vasoactive intestinal polypeptide (VIP) concomitant with the reduced expression of nNOS in the myenteric plexus of distal ileum and proximal colon; in particular VIP increased in a subpopulation of neurons actively expressing nNOS. On the other hand, choline acetyltransferase (ChAT) was not modified in any of the intestinal segments analyzed. Interestingly, we found a reduced expression of dopamine receptor type 2 (D2R) in proximal (-66.8%) and distal (-54.5%) colon, together with reduced peristalsis efficiency (decrease in intraluminal pressure and frequency of peristaltic events) in the 6-OHDA-lesioned rats. The selective depletion of dopaminergic nigrostriatal neurons is associated with changes in the expression of enteric inhibitory neurotransmitters, as well as of the D2R in intestinal specific regions. Moreover, 6-OHDA-lesioned rats demonstrated altered colon propulsive activity referable to the D2R decrease. Our findings unveil subtle mechanisms underlying the enteric neurochemical plasticity events evoked by disruption of the normal brain-gut cross-talk, giving a peculiar point of view on the pathophysiology of the severe constipation that frequently affects PD patients.

Intercambiabilidad entre equivalentes terapéuticos de lamotrigina. Réplica / Interchangeability among therapeutics equivalents of lamotrigine. Reply

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Influence of enzyme inducing antiepileptic drugs on the pharmacokinetics of levetiracetam in patients with epilepsy.

To assess whether levetiracetam elimination is influenced by enzyme inducing antiepileptic drugs (EIAEDs), serum levetiracetam levels were determined at frequent intervals after a single oral 1000mg dose in 15 subjects co-medicated with EIAEDs and 15 matched controls. The EIAED group showed a higher levetiracetam oral clearance (p=0.01) and a shorter half-life (p=0.02) than controls. Although the magnitude of interaction is relatively modest, it could have clinical significance for some patients.

[Interchangeability among therapeutics equivalents of lamotrigine in the treatment of refractory epilepsy patients: risks and benefits]. / Intercambiabilidad entre equivalentes terapéuticos de lamotrigina en pacientes con epilepsia refractaria: riesgos y beneficios.

INTRODUCTION: Epilepsy is a condition characterized by signs and symptoms of neurological disorder. Lamotrigine has been widely used, mainly due to their greater tolerability and lower rate of drug interactions with other antiepileptic drugs however the newest antiepileptic drugs have high cost to patient. In Brazil there are three different sort of pharmaceutical equivalents (reference, generic and similar), and the Brazilian health care authorities offers to users the possibility to receive them free of charge. Moreover these pharmaceutical equivalents can change during the treatment of epilepsy because this authorities buy the cheapest by public tender two or three times a year. AIM: To evaluate the clinical and laboratory findings related to the most frequently used therapeutic equivalents of lamotrigine (reference drugs and similar products). PATIENTS AND METHODS: Two similar formulations (A and B) and one reference (C) were tested in nine epileptic refractory patients. The study was divided into three periods of 42 days, one for each formulation, and medical data about the frequency of seizures, the occurrence of side effects and measurement of plasma concentrations of lamotrigine were collected. RESULTS: The average number of seizures/week and plasma concentration of lamotrigine for formulations A, B and C were not statistically significant differences. Three patients during the use of the formulation C presented mild and transitory side effects. CONCLUSION: Similar or reference drugs showed satisfactory results, however the interchangeability among the formulations raise the difficulty for the management of seizures in refractory epilepsy.

Intercambiabilidad entre equivalentes terapéuticos de lamotrigina en pacientes con epilepsia refractaria: riesgos y beneficios (AU) / Interchangeability among therapeutics equivalents of lamotrigine in the treatment of refractory epilepsy patients: risks and benefits

Introducción. La epilepsia es una enfermedad caracterizada por signos y síntomas de trastornos neurológicos. La lamotrigina se ha utilizado ampliamente debido, sobre todo, a su gran tolerabilidad y su inferior tasa de interacciones farmacológicas con otros antiepilépticos; sin embargo, los antiepilépticos más recientes tienen un elevado coste para el paciente. En Brasil, hay tres tipos diferentes de equivalentes farmacéuticos (de referencia, genéricos y similares), y las autoridades sanitarias brasileñas ofrecen a los usuarios la posibilidad de recibirlos de forma gratuita. Además, estas equivalencias farmacéuticas pueden cambiar durante el tratamiento de la epilepsia porque las autoridades adquieren las más económicas mediante concurso público, dos o tres veces al año. Objetivo. Evaluar los datos clínicos y de laboratorio relacionados con los equivalentes terapéuticos de lamotrigina usados con más frecuencia (medicamentos de referencia y productos similares). Pacientes y métodos. Se probaron dos formulaciones similares (A y B) y una de referencia (C) en nueve pacientes epilépticos resistentes al tratamiento. El estudio se dividió en tres períodos de 42 días, uno para cada formulación, y se recopilaron datos sobre la frecuencia de las crisis epilépticas, la aparición de efectos secundarios y la medición de las concentraciones plasmáticas de lamotrigina. Resultados. Las diferencias en el promedio de crisis epilépticas por semana y la concentración plasmática de lamotrigina para las formulaciones A, B y C no fueron estadísticamente significativas. Tres pacientes presentaron efectos secundarios leves y transitorios durante el uso de la formulación C. Conclusión. Los medicamentos similares o de referencia mostraron unos resultados satisfactorios; sin embargo, la intercambiabilidad entre las formulaciones eleva el grado de dificultad para el tratamiento de las crisis en la epilepsia refractaria (AU)

Introduction. Epilepsy is a condition characterized by signs and symptoms of neurological disorder. Lamotrigine has been widely used, mainly due to their greater tolerability and lower rate of drug interactions with other antiepileptic drugs however the newest antiepileptic drugs have high cost to patient. In Brazil there are three different sort of pharmaceutical equivalents (reference, generic and similar), and the Brazilian health care authorities offers to users the possibility to receive them free of charge. Moreover these pharmaceutical equivalents can change during the treatment of epilepsy because this authorities buy the cheapest by public tender two or three times a year. Aim. To evaluate the clinical and laboratory findings related to the most frequently used therapeutic equivalents of lamotrigine (reference drugs and similar products). Patients and methods. Two similar formulations (A and B) and one reference (C) were tested in nine epileptic refractory patients. The study was divided into three periods of 42 days, one for each formulation, and medical data about the frequency of seizures, the occurrence of side effects and measurement of plasma concentrations of lamotrigine were collected. Results. The average number of seizures/week and plasma concentration of lamotrigine for formulations A, B and C were not statistically significant differences. Three patients during the use of the formulation C presented mild and transitory side effects. Conclusion. Similar or reference drugs showed satisfactory results, however the interchangeability among the formulations raise the difficulty for the management of seizures in refractory epilepsy (AU)