Interhemispheric and ipsilateral connections in Parkinson's disease: relation to mirror movements.

Mirror movements (MM) occur in early, asymmetric Parkinson's disease (PD). To examine the pathophysiology of MM in PD, we studied 13 PD patients with MM (PD-MM), 7 PD patients without MM (PD-NM), and 14 normal subjects. Cross-correlogram did not detect common synaptic input to motoneuron pools innervating homologous hand muscles in PD-MM patients. Transcranial magnetic stimulation studies showed no significant difference in ipsilateral motor-evoked potentials between PD-MM patients and normal subjects. The MM side of PD-MM patients showed a slower increase in ipsilateral silent period area with higher level of muscle contraction than the non-MM side and normal subjects. There was less interhemispheric inhibition (IHI) at long interstimulus intervals of 20 to 50 ms in PD-MM than PD-NM. IHI reduced short interval intracortical inhibition in normal subjects and PD-NM, but not in PD-MM. IHI significantly increased intracortical facilitation in PD-MM and PD-NM patients, but not in normal subjects. Our results suggest that MM in PD is due to activation of the contralateral motor cortex. PD-MM patients had reduced transcallosal inhibitory effects on cortical output neurons and on intracortical inhibitory circuits compared to PD-NM patients and controls. These deficits in transcallosal inhibition may contribute to MM in PD patients.     

Is chronic nitrate therapy associated with a different clinical presentation of acute coronary syndrome?

BACKGROUND: Nitrate therapy can induce ischemic preconditioning with a consequent increase in tolerance to ischemia. In the context of acute coronary syndromes (ACS), nitrates may result in a different presentation. with greater protection. OBJECTIVES: To investigate in a population of patients with ACS whether previous chronic use of nitrates results in a different presentation of ACS. METHODS: We studied 287 patients (65 +/- 13 years, 66% male) admitted to our department in the first six months of 2005 with ACS (with and without ST-segment elevation). Of these, 8% were under nitrate therapy at the time of admission. In this group, 27% presented ACS without ST-segment elevation, while in the group without nitrates this value was 58% (p = 0.005). By univariate analysis, the use of nitrates was a predictor of the preferential occurrence of non-ST-segment elevation ACS (OR 0.27, 95% CI 0.10-0.71). After correction for the potential influence of variables (age, gender, previous revascularization and smoking) by multivariate logistic regression, nitrate therapy remained a borderline predictor of clinical presentation as non-ST-segment elevation ACS (OR 0.37, 95% CI 0.13-1.04, p = 0.059). CONCLUSIONS: Previous use of nitrates was associated with a tendency to present as non-ST-segment elevation ACS. This finding may be explained by the hypothesis that nitrates induce pharmacological preconditioning, reducing the transmural extent of myocardial infarction.     

Atypical absences and recurrent absence status in an adult with Angelman syndrome due to the UBE3A mutation.

Angelman syndrome is a neurogenetic disorder resulting in refractory epilepsy and profound psychomotor retardation in its most prevalent form, caused by deletion of maternal chromosome 15q11-13. We report the case of a 29-year-old, mentally retarded man with unusual electroencephalographic changes during periods of atypical absence status epilepticus, a previously unreported manifestation of the usually milder, drug-responsive epilepsy associated with Angelman syndrome due to the UBE3A mutation.[Published with video sequences].     

Antimutagenic properties of bell and black peppers.

The wing Somatic Mutation And Recombination Test (SMART) in Drosophila melanogaster was used to study the modulating action of bell pepper (Capsicum annuum) and black pepper (Piper nigrum) in combination with the alkylating agent methyl methanesulfonate (MMS) and the promutagen agent ethyl carbamate (EC). Larvae trans-heterozygous for the third chromosome recessive markers multiple wing hairs (mwh) and flare-3 [flr(3)] were fed genotoxins alone or in combination with each of the two spices. Genetic changes induced in somatic cells of the wing's imaginal discs lead to the formation of mutant clones on the wing blade. Our results showed that bell pepper was effective in reducing the mutational events induced by EC and MMS and black pepper was only effective against EC. Pretreatment of 2-day-old larvae with the spices for 24 h followed by a treatment with EC and MMS was only effective in reducing mutations induced by EC. Suppression of metabolic activation or interaction with the active groups of mutagens could be mechanisms by which the spices exert their antimutagenic action.     

Effects of a toxin from the mucus of the caribbean sea anemone (Bunodosoma granulifera) on the ionic currents of single ventricular mammalian cardiomyocytes

The effects were studied of a toxin (Bainh) isolated from the secretion of the Caribbean sea anemone Bunodosoma granulifera on electrical and mechanical activities of rat ventricular muscle. The effects on the ionic currents of single rat and dog ventricular cardiomyocytes were studied using the whole-cell recording patch-clamp technique. In the concentration range from 1 to 10 mg/ml, Bainh increased the force of contraction and induced an increase in action potential duration of ventricular multicellular preparations. In single cardiomyocytes, at concentrations up to 10 mg/ml Bainh showed no significant effects on the sodium current. However, at 0.5–1 mg/ml it increased the L-type Ca current (I_CaL) by 25–50%. This increase in I_CaL was not voltage dependent and was reversible after washout. The transient outward current was not significantly affected by Bainh (1–10 mg/ml). In this concentration range, Bainh markedly (≈75%) increased the inward-going rectifier current, I_K1. This effect that was not voltage dependent and was fully reversible upon returning to control solution. It is suggested that these effects on ionic currents could explain the positive inotropic action of Bainh on cardiac multicellular preparations.     

Sustained-release theophylline-uniphyllin in nocturnal asthmatics

For a period of six months, we collected 12 cases of nocturnal asthmatics (7 males, 5 females); their ages ranged from 20 to 66 (the average age is 49). We found that administration of Uniphyllin (10 mg/kg) once a day at 6 PM could maintain the blood level of theophylline within therapeutic range at least 12 to 24 hrs. The peak expiratory flow rate of the 6 cases we collected, were significantly improved. The result of pharmokinetic parameters: 1) The average of a single dose (12 cases) is AUC (ug. hr/ml) 275.1 +/- 62. k; Kel (hr-1) 0.068 +/- 0.019; Ka (hr-1) 0.33 +/- 0.07); Tmax (hr) 6.3 +/- 1.4; T 1/2 (hr) 11.2 +/- 4.4; Clearance/F (ml/kg/hr) 37.9 +/- 9.0.2). The average of steady state (12 cases) is Css (mg/L) 5. 7 +/- 2.6; Cmax-Cmin (mg/L) 10.09 +/- 1.46.3). The average of relative bioavailability (3 cases) is 82%, 83%, 102%. However, the extent of absorption data is available for only 3 subjects. There are too few subjects to draw any meaningful conclusions about this relative bioavailability. Four cases show slight symptoms, including 1 case of dizziness, 2 cases of nausea, and 1 case gaseousness. It is suggested that the drug be administered at about 6-8 PM to coincide peak levels in the early morning in nocturnal asthmatics.     

Aging reverts to juvenile conditions the synaptic connectivity of cerebral cortical pyramidal shafts.

Quantitative analysis of the total number and distribution of dendritic spines along the apical shafts of layer V cerebral cortical pyramids has been performed on aging rats (90-120 to 1,135 days old) and on rats during the period of early and late development (10-80 days). As expected from previous work, present results show that the total number of dendritic spines along the shafts increase from 10 to 80 days, after which it starts to gradually decrease until the last age studied (1,135 days). The quantitative analysis of the effect of aging on the relative decrease of dendritic spines shows that this decrease starts being homogeneous along the whole length of the apical shafts and that from a certain age onwards, estimated according to present results in 400 days, this effect is significantly more pronounced in layers IV and III-II than in deep layers. Furthermore, the comparison made between the distribution of dendritic spines along the apical shafts of pyramidal neurons of old and young animals has shown that aging produces a regression of this distribution to juvenile conditions.