Influence of ethanol on the threshold for electroshock-induced seizures and electrically-evoked hippocampal afterdischarges

Summary. The anticonvulsant activity of ethanol was investigated in two representative models of experimental epilepsy. In the maximal electroshock seizure threshold test in mice, ethanol (0.5–2 g/kg i.p.) dose-dependently raised the electroconvulsive threshold for tonic seizures. In co-medication with valproate and carbamazepine, ethanol significantly increased the anticonvulsant effectiveness of both antiepileptic drugs. Subchronic premedication of ethanol did not reveal marked decrease of its additive anticonvulsant action and only tended to reduce the effectiveness of valproate and carbamazepine. No changes of the plasma levels of both antiepileptics could be detected. Furthermore, in the hippocampal afterdischarge model in rats, ethanol dose-dependently raised the focal stimulation threshold and significantly increased the anticonvulsant efficacy of co-administered carbamazepine after acute application. Subchronic premedication of ethanol tended to reduce the effectiveness of the latter. In conclusion, the present results indicated pronounced anticonvulsant effects of ethanol against generalized tonic-clonic as well as complex partial seizures which did not reveal strong tolerance after subchronic administration.     

White matter hyperintensities and chronicity of depression

OBJECTIVE: White matter hyperintensities (WMHs) on T(2)-weighted magnetic resonance imaging (MRI) of the brain are associated with advanced age and late-life depression. Most investigations predominantly found these lesions in frontal lobe and basal ganglia supporting the hypothesis of a fronto-striatal dysfunction in depression. A prospective study was undertaken to investigate the association between extent of WMHs and clinical outcome in elderly depressed patients. METHODS: Thirty-one non-demented depressed subjects underwent a 1.5 T cranial MRI scan. The MRI scans were analysed in consensus by two experienced radiologists. Each MRI scan was assessed for presence and extent of WMHs, which are differentiated in periventricular hyperintensities (PVHs) and deep white matter hyperintensities (DWMHs). A total of 21 patients of the original cohort of 31 patients were re-assessed 5 years after baseline assessment. We ascertained the severity of depressive symptoms, the longitudinal course of depression, the cognitive decline and the global assessment of functioning at follow-up visit. RESULTS: (1) Subjects with greater extent of WMHs had a significant higher Hamilton Depression Rating Scale (HAM-D) score, (2) had more severe longitudinal courses of depression (3) and had a lower Mini-Mental State Examination (MMSE) score. CONCLUSIONS: WMHs on MRI are associated with poorer outcome in elderly depressed subjects. Further studies are needed to evaluate WHMs as prognostic factor for an appropriate treatment decision-making.     

Relationship between hemoconcentration and blood coagulation responses to acute mental stress

BACKGROUND: Acute mental stress elicits reliable changes in blood coagulation factors. We studied whether stress-related changes in coagulation measures are associated with concomitant hemoconcentration. METHODS: Twenty-two men (mean age 47+/-8 years) underwent the Trier Social Stress Test (TSST) combining 13 min of task preparation, job interview, and mental arithmetic. Venous blood was obtained immediately before the preparation phase and immediately after stress to determine seven measures of coagulation and three measures of hemoconcentration. RESULTS: Clotting factor VII activity (FVII:C; 99.5+/-21.9 vs. 104.5+/-23.7 IU; p=0.016), FVIII:C (96.3+/-18.1 vs. 105.1+/-25.7 IU; p=0.008), FXII:C (95.8+/-26.7 vs. 102.6+/-26.4 IU; p=0.002), and von Willebrand factor antigen (vWF; 103.3+/-36.3 vs. 110.1+/-43.3 IU; p=0.009) all increased from baseline to poststress, with a similar statistical trend observed for d-dimer (177.6+/-85.5 vs. 180.5+/-83.9 ng/ml; p=0.058). The absolute increases in fibrinogen and in soluble tissue factor were not significant. Hematocrit (40.8+/-2.5 vs. 42.7+/-2.8; p<0.001) and hemoglobin (14.5+/-0.81 vs. 15.2+/-0.97; p<0.001) increased, and plasma volume (59.2%+/-2.5 vs. 54.6+/-4.2%; p<0.001) decreased from baseline to poststress. Unlike with heart rate (HR) and blood pressure (BP) reactivity, there emerged no significant relationship between change scores in any hemoconcentration and coagulation measure (all r values<0.4, all p values>0.05). CONCLUSION: We corroborated significant changes in coagulation measures in response to acute mental stress compatible, with the notion that stress may elicit a hypercoagulable state. However, stress hemoconcentration appears not to explain a substantial proportion in coagulation changes elicited by acute mental stress.     

Inherited factor VII deficiency: identification of two novel mutations (A191V and T239P) in the catalytic domain

We describe here five F7 mutations found in four patients without bleeding history, despite constitutional coagulation Factor VII (FVII) deficiency. All five mutations are missense and affect the catalytic domain of FVII (A191T, A191V, T239P, R224Q and M298I). The A191V and T239P mutations are novel and were found in homozygous patients with no clinical bleeding tendency. The patient diagnosed with the A191V mutation had a phenotype corresponding to a moderate type 1 FVII deficiency (FVII:C 4%, FVII:Ag 5%). The T239P mutation was found in a patient with mild type 2 FVII deficiency (FVII:C 25%, FVII:Ag 95%). Novel mutations are both in close vicinity to the charge-stabilizing system of FVII. Modeling studies allow understanding in part the molecular basis for the loss of function.     

A novel method for subarachnoid drug delivery in the medullary region of rats

This study describes a novel method for direct subarachnoid drug delivery to the medullary dorsal horn region of rats, without introducing a catheter. The reliability of the method was demonstrated by a pharmacological validation; that is, morphine administration to the medullary region blocked the nociceptive response to formalin injected in the temporomandibular joint (TMJ) region, an effect that was prevented by co-administration of naloxone. The method proposed offers many advantages over the existing methods for medullary drug delivery with catheter implantation. It is easy to be employed, it does not induce any sign of motor impairment, and it does not require the neck surgery performed to implant a catheter in the medullary dorsal horn region. Therefore, it is a useful method for subarachnoid drug delivery in behavioral trigeminal pain studies, particularly when nociceptive behavioral measures that require normal neck muscle activity to occur, such as head withdraw or head flinch, are evaluated.     

Hyperpolarized helium-3 MR imaging of pulmonary function

Recent advances in HP MR imaging contrast agents have led to novel tests of pulmonary function. Many of these tests show promise in the clinical arena.     

Potential MRI interpretation model: differentiation of benign from malignant breast masses

OBJECTIVE: Our objective was to increase the accuracy of breast MRI using a semiquantitative analysis of typical MRI features and their diagnostic potential. The prevalence of recently reported MRI signs of breast lesions were analyzed and compared with other well-known signs. CONCLUSION: New MRI features, especially from T2-weighted images, are promising for more reliable and accurate interpretation of breast lesions. Prospective studies of these findings are required to define cut-off values and test clinical practicality.