Changes in psychiatric comorbidity during early postsurgical period in patients operated for medically refractory epilepsy--a MINI-based follow-up study.

PURPOSE: The purpose of this study was to assess axis-I DSM-IV psychiatric disorders in patients at baseline and 3 months after surgery for medically refractory temporal lobe epilepsy. METHOD: The Mini International Neuropsychiatric Interview (MINI) and Quality of Life in Epilepsy Inventory-10 (QOLIE-10) were evaluated before and 3 months after surgery in 50 consecutive patients (21 females, 29 males) with medically refractory temporal lobe epilepsy (persistent seizures>2/month, despite treatment with ≥2 appropriate drugs in adequate doses for ≥2 years) who underwent surgery [anterior temporal lobectomy with amygdalo-hippocampectomy (for mesial temporal sclerosis in 40), electrocorticography-guided lesionectomy (for other lesions in 10)]. RESULTS: Twenty-six patients (52%) had an axis-I psychiatric disorder [26% depressive disorder, 28% anxiety disorder] at baseline, while 30 (60%) patients had an axis-I psychiatric disorder [28% depressive disorder, 28% anxiety disorder] at 3 months after surgery. Twenty percent developed a new psychiatric disorder, while 12% showed improvement postsurgery. Mean QOLIE-10 scores improved from 23.78 to 17.80 [24 (48%) patients showed ≥5-point improvement]. Thirty-four (68%) patients had no seizure, 6 (12%) had non-disabling seizures, while 2 (4%) had disabling seizures after surgery. High frequency of seizures prior to surgery (p<0.038) and seizure occurrence after surgery (p<0.055) predicted the presence of psychiatric disorders after surgery. No clinical characteristic could predict development of new psychiatric disorder after surgery. CONCLUSION: Psychiatric dysfunction in the early postsurgery period is seen in nearly half of patients undergoing surgery for temporal lobe epilepsy, is mild in nature, and does not adversely affect quality of life but may cause significant clinical problems when it arises de novo postsurgery.

Theory of gas hydrates: effect of the approximation of rigid water lattice.

One of the assumptions of the van der Waals and Platteeuw theory for gas hydrates is that the host water lattice is rigid and not distorted by the presence of guest molecules. In this work, we study the effect of this approximation on the triple-point lines of the gas hydrates. We calculate the triple-point lines of methane and ethane hydrates via Monte Carlo molecular simulations and compare the simulation results with the predictions of van der Waals and Platteeuw theory. Our study shows that even if the exact intermolecular potential between the guest molecules and water is known, the dissociation temperatures predicted by the theory are significantly higher. This has serious implications to the modeling of gas hydrate thermodynamics, and in spite of the several impressive efforts made toward obtaining an accurate description of intermolecular interactions in gas hydrates, the theory will suffer from the problem of robustness if the issue of movement of water molecules is not adequately addressed.

In vivo bioavailability studies of sumatriptan succinate buccal tablets.

UNLABELLED: BACK GROUND AND THE PURPOSE OF STUDY: Sumatriptan succinate is a Serotonin 5- HT1 receptor agonist, used in treatment of migraine. It is absorbed rapidly but incompletely when given orally and undergoes first-pass metabolism, resulting in a low absolute bioavailability of about 15%. The aim of this work was to design mucoadhesive bilayered buccal tablets of sumatriptan succinate to improve its bioavailability. METHODS: Mucoadhesive polymers carbopol 934 (Carbopol), HPMC K4M, HPMC K15M along with ethyl cellulose as an impermeable backing layer were used for the preparation of mucoadhesive bilayered tablets. In vivo bioavailability studies was also conducted in rabbits for optimized formulation using oral solution of sumatriptan succinate as standard. RESULTS: Bilayered buccal tablets (BBT) containing the mixture of Carbopol and HPMC K4M in the ratio 1:1 (T1) had the maximum percentage of in vitro drug release within 6 hrs. The optimized formulation (T1) followed non-Fickian release mechanism. The percentage relative bioavailability of sumatriptan succinate from selected bilayered buccal tablets (T1) was found to be 140.78%. CONCLUSIONS: Bilayered buccal tablets of sumatriptan succinate was successfully prepared with improved bioavailability.

Bacterial phytoene synthase: molecular cloning, expression, and characterization of Erwinia herbicola phytoene synthase.

Phytoene synthase (PSase) catalyzes the condensation of two molecules of geranylgeranyl diphosphate (GGPP) to give prephytoene diphosphate (PPPP) and the subsequent rearrangement of the cyclopropylcarbinyl intermediate to phytoene. These reactions constitute the first pathway specific step in carotenoid biosynthesis. The crtB gene encoding phytoene synthase was isolated from a plasmid containing the carotenoid gene cluster in Erwinia herbicola and cloned into an Escherichia coli expression system. Upon induction, recombinant phytoene synthase constituted 5-10% of total soluble protein. To facilitate purification of the recombinant enzyme, the structural gene for PSase was modified by site-directed mutagenesis to incorporate a C-terminal Glu-Glu-Phe (EEF) tripepetide to allow purification by immunoaffinity chromatography on an immobilized monoclonal anti-alpha-tubulin antibody YL1/2 column. Purified recombinant PSase-EEF gave a band at 34.5 kDa upon SDS-PAGE. Recombinant PSase-EEF was then purified to >90% homogeneity in two steps by ion-exchange and immunoaffinity chromatography. The enzyme required Mn(2+) for activity, had a pH optimum of 8.2, and was strongly stimulated by detergent. The concentration of GGPP needed for half-maximal activity was approximately 35 microM, and a significant inhibition of activity was seen at GGPP concentrations above 100 microM. The sole product of the reaction was 15,15'-Z-phytoene.