An active-control trial of lamotrigine monotherapy for partial seizures

OBJECTIVE: We report the results of a double-blind, double-dummy, active-control study designed to evaluate the efficacy and safety of lamotrigine (LTG) administered as monotherapy to adult outpatients with partial seizures. BACKGROUND: The effectiveness of LTG as add-on therapy for partial seizures in adults has previously been established. METHODS: After an 8-week baseline during which patients continued their baseline antiepileptic drug (carbamazepine or phenytoin monotherapy), 156 patients were randomly assigned to receive increasing doses of LTG (target 250 mg b.i.d.) or valproic acid (VPA; target low dose of 500 mg b.i.d.) during the first 4 weeks of an 8-week transition period. Carbamazepine or phenytoin was withdrawn over the next 4 weeks; then patients entered a 12-week monotherapy period. Study drug treatment was discontinued in patients who met predetermined escape criteria for seizure worsening. RESULTS: More patients receiving LTG were successfully maintained on monotherapy compared with patients receiving VPA (56% versus 20%; p < 0.001). The time to meet the escape criteria was also significantly longer in LTG-treated patients (median = 168 days) than in VPA-treated patients (median = 57 days; p = 0.001). The incidence of adverse events during the monotherapy period was lower than during the transition period. Four LTG patients and five VPA patients reported serious adverse events. Two of those patients experienced a rash that led to withdrawal soon after adding LTG to carbamazepine. CONCLUSIONS: We conclude that LTG is effective and well tolerated when administered as monotherapy in adult patients with partial seizures.     

Male moth sensitivity to multicomponent pheromones: Critical role of female-released blend in determining the functional role of components and active space of the pheromone

In the present study male redbanded leafroller (Argyrotaenia velutinana), cabbage looper (Trichoplusia ni), and Oriental fruit moths, (Grapholita molesta), were tested in a flight tunnel to (1) the major pheromone component, (2) theZ/E pheromone component mixtures for Oriental fruit moth and redbanded leafroller, (3) and the female-released blends, over a series of dosages. Experiments were designed to test the hypothesis that male response downwind of a female is initiated by the major component and that minor components function only to elicit behaviors close to the female during close-range approach and courtship. The results did not support this hypothesis, but rather showed that males initiated upwind flight in significantly higher percentages to the complete blends of components, at all dosages, compared to single components or partial blends. Addition of minor components also signficantly enhanced male perception of the major component at lower dosages, resulting in completed flights to dosages of the major component that alone did not elicit any upwind flight. Our results support the concept that minor components function to enhance male sensitivity to the pheromone, and the specificity of the signal. Our results also support the hypothesis that the active space of the pheromone is a function of the upper and lower concentration thresholds for the blend of components, and not simply for the major component.     

Optimization of thin-foil based phosphor screens for CCD imaging in TEM in the voltage range of 80-400 kV

The voltage dependence characteristics of thin-foil based phosphor screens in the thickness range of approximately 10-60 microns are examined for CCD imaging in transmission electron microscopy (TEM) in the voltage range of 80-400 kV. The brightest screen is obtained with a P20 layer of about 12 microns at 80 kV, and a thicker screen lowers both the screen brightness and resolution. The thickness of the brightest screen is higher at higher voltage, but other considerations for a practical CCD imaging system suggest that the P20 layer should not be greater than approximately 18 microns for the voltage range stated above.     

Myofibroblast-derived smooth muscle cells during remodelling of rabbit urinary bladder wall induced by partial outflow obstruction

BACKGROUND: Fibrosis of serosa, along with smooth muscle (SM) cell hypertrophy, has been shown to occur in the rabbit bladder after partial outflow obstruction. Identification of cells involved in the serosal thickening can be of primary interest to elucidate the functional changes that this organ undergoes. EXPERIMENTAL DESIGN: Cytoskeletal protein composition of cells present in the thickened serosa at different times from the onset of obstruction (7, 15, 30 and 60 days) was evaluated. This was accomplished by means of a panel of monoclonal antibodies specific for a number of differentiation markers of mesenchymal cells (vimentin, desmin, alpha-actin of SM type, nonmuscle (NM) and SM myosins), and by immunocytochemical and immunochemical techniques. RESULTS: The immunocytochemical study revealed that cells in serosal thickening follow a two-step maturation process from pre-existing vimentin-positive cells. In the first time period (7 to 15 days of obstruction), these cells predominantly achieved an immunophenotype corresponding to that of a specific myofibroblast subtype (i.e., containing vimentin, NM myosin, and SM alpha-actin). After 30 days from the onset of obstruction, the cytoskeletal protein content of serosal cells, as also revealed by Western blotting experiments, shifted towards that of fetal-type SM cells (i.e., presence of vimentin, NM myosin, SM alpha-actin, and SM myosin isoforms). Distribution of vimentin, desmin, SM alpha-actin, and SM myosin in tissue culture as well as the ultrastructure in vivo very closely resembled that of SM cells. Bromodeoxyuridine incorporation studies indicated that cells accumulated in the serosa of obstructed bladders did not derive, at least initially, from SM cells of the detrusor muscle. CONCLUSIONS: These findings are consistent with the existence of a differentiation process in which resident mesenchymal cells of bladder serosa may transform to myofibroblasts and, subsequently, in fetal-type SM cells during experimental outflow obstruction.     

Activity of perfluorobutyl-containing components in pheromone blend of cabbage looper moth,Trichoplusia ni

Substitution of nine hydrogens by nine fluorines in the butyl terminus of (Z)-7-dodecenyl acetate, the major component of the pheromone blend of the cabbage looper,Trichoplusia ni (Lepidoptera: Noctuidae), produces a highly volatile analog that is significantly less active as a replacement for the natural pheromone component, either alone or substituted in the sixcomponent pheromone blend of this species. When 9,9,10,10,11,11,12,12, 12-nonafluoro-(Z)-7-dodecenyl acetate (nf-Z7-12: OAc) was tested in a wind tunnel as a single component or as part of the six-component blend, males exhibited preflight activation, but they did not orient in the pheromone plume and fly upwind over a five-decade range of doses at levels comparable with those of the natural component and blend. Addition of large amounts of nf-Z7-12:OAc to the optimal dose of the natural blend also did not effect flight arrestment as when increased amounts of Z7-12:OAc were added. The nonafluoro (nf) analog of (Z)-9-tetradecenyl acetate, a minor component in theT. ni blend, did not affect male behavior when substituted in the sixcomponent blend, and substitution of both nf analogs in the natural blend produced the same results as observed for blends containing nf-Z7-12:OAc. The lack of an effect with substitution of nf-Z9-14:OAc is discussed in relation to the reported redundancy in the action of minor components inT. ni.     

Kinetics and mechanism of an NADPH-dependent succinic semialdehyde reductase from bovine brain

An NADPH-dependent succinic semialdehyde reductase has been purified from bovine brain by several chromatographic procedures. The preparation appeared homogeneous on SDS/PAGE. The enzyme is a monomeric protein with a molecular mass of 28 kDa. A number of properties of the bovine brain enzyme, such as substrate specificity, specific activity, molecular mass, optimum pH, amino acid composition, and kinetic parameters, have been determined and compared with those reported for preparations from other sources. The results indicate that the enzyme isolated from bovine brain in the present study is different from those reported for preparations from other sources. The inhibition kinetic patterns obtained when the products of the reaction or substrate analogs are used as inhibitor of the reaction catalyzed by the enzyme are consistent with an ordered sequential mechanism involving the formation of an intermediate ternary complex and in which NADPH is the first substrate to bind the enzyme.