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Healthy brains display a wide range of firing patterns, from synchronized oscillations during slow-wave sleep to desynchronized firing during movement. These physiological activities coexist with periods of pathological hyperactivity in the epileptic brain, where neurons can fire in synchronized bursts. Most cortical neurons are pyramidal regular spiking (RS) cells with frequency adaptation and do not exhibit bursts in current-clamp experiments (in vitro). In this work, we investigate the transition mechanism of spike-to-burst patterns due to slow potassium and calcium currents, considering a conductance-based model of a cortical RS cell. The joint influence of potassium and calcium ion channels on high synchronous patterns is investigated for different synaptic couplings (gsyn) and external current inputs ( I ). Our results suggest that slow potassium currents play an important role in the emergence of high-synchronous activities, as well as in the spike-to-burst firing pattern transitions. This transition is related to the bistable dynamics of the neuronal network, where physiological asynchronous states coexist with pathological burst synchronization. The hysteresis curve of the coefficient of variation of the inter-spike interval demonstrates that a burst can be initiated by firing states with neuronal synchronization. Furthermore, we notice that high-threshold (IL) and low-threshold (IT) ion channels play a role in increasing and decreasing the parameter conditions (gsyn and I ) in which bistable dynamics occur, respectively. For high values of IL conductance, a synchronous burst appears when neurons are weakly coupled and receive more external input. On the other hand, when the conductance IT increases, higher coupling and lower I are necessary to produce burst synchronization. In light of our results, we suggest that channel subtype-specific pharmacological interactions can be useful to induce transitions from pathological high bursting states to healthy states.

Objective: To radiographically evaluate individuals who underwent opening wedge proximal tibial osteotomy, with the aim of analyzing the proximal tibial slope in the frontal and sagittal planes, and the patellar height., Method: The study included 22 individuals who were operated at the National Traumatology and Orthopedics Institute (INTO) for correction of varus angular tibial deviation using the opening wedge osteotomy (OWO) technique with the Orthofix monolateral external fixator. Patients with OWO whose treatment was completed between January 2000 and December 2006 were analyzed. The measurement technique consisted of using anteroposterior radiographs with loading and lateral views with the operated knees flexed at 30°., Results: There were no statistically significant differences between the pre and postoperative tibial slope and patellar height values in the patients evaluated., Conclusion: Opening wedge proximal tibial osteotomy is a technique that avoids the problems presented by high proximal tibial osteotomy, since it is done without causing changes to the extensor mechanism, ligament imbalance or distortions in the proximal tibia.

The aim of this work was to verify the effects of methanol (MeOH) and hydroalcoholic (HA) extracts and their respective partition phases obtained from white mangrove (Laguncularia racemosa (L.) C.F. Gaertn.) leaves on human thrombin activity. Among the extracts and phases tested, only the ethyl acetate and butanolic partitions significantly inhibited human thrombin activity and the coagulation of plasma in the presence of this enzyme. Chromatographic analyses of the thrombin samples incubated with these phases revealed that different compounds were able to interact with thrombin. The butanolic phase of the MeOH extract had the most potent inhibitory effects, reducing enzymatic activity and thrombin-induced plasma coagulation. Two glycosylated flavonoids in this partition were identified as the most potent inhibitors of human thrombin activity, namely quercetin-3-O-arabinoside (QAra) and quercetin-3-O-rhamnoside (Qn). Chromatographic analyses of thrombin samples incubated with these flavonoids demonstrated the chemical modification of this enzyme, suggesting that the MeOH extract contained other compounds that both induced structural changes in thrombin and diminished its activity. In this article, we show that despite the near absence of the medical use of mangrove compounds, this plant contains natural compounds with potential therapeutic applications.

Cefuroxime (CFU) is a semi-synthetic cephalosporin with a relatively broad-spectrum antimicrobial activity, and belongs to the second generation of cephalosporins. Regarding the quality control of medicines, a validated microbiological assay for determination of cefuroxime sodium in pharmaceutical formulations has not been reported yet. With this purpose, this paper reports the development and validation of a simple, sensitive, accurate and reproducible agar diffusion method to quantify CFU sodium in injectable formulations. The assay is based on the inhibitory effect of CFU upon the strain of Staphylococcus aureus ATCC 6538P used as test microorganism. The results were treated statistically by analysis of variance and were found to be linear (r=0.9998) in the selected range of 8.0-32.0 microg/ml; precise [repeatability: relative standard deviation (RSD)=1.56%; intermediate precision: between-day RSD=1.27%; between analyst RSD=1.13%] and accurate (101.58%). The bioassay specificity was studied by evaluation of degraded sample at 50 degrees C with analysis at 0, 24 and 48 h in parallel with the pharmacopeial liquid chromatography method for CFU. The results demonstrated the validity of the proposed bioassay, which allows reliable quantitation of CFU sodium in pharmaceutical samples and therefore can be used as a useful alternative methodology for the routine quality control of this medicine.

Aim of the Study: n-Hexanic and ethanolic extracts from twelve plants (Brugmansia suaveolens Brecht. et Presl., Eupatorium laevigatum Lam., Galinsoga parviflora Cav., Iresine herbstii Hook., Kalanchöe tubiflora Hamet-Ahti, Petiveria alliacea L., Pluchea sagittalis (Lam.) Cabrera, Piper regnellii DC., Schinus molle L., Sedum dendroideum Moç et Sessé ex DC., Waltheria douradinha St. Hill., Xanthium cavanillesii Schouw.) used in traditional South Brazilian medicine as wound healing agents were investigated in various biological assays, targeting different aspects in this complex process., Materials and Methods: The extracts were investigated on NF-kappaB DNA binding, p38alpha MAPK, TNF-alpha release, direct elastase inhibition and its release as well as on caspase-3. Fibroblasts migration to and proliferation into the wounded monolayers were evaluated in the scratch assay, the agar diffusion test for antibacterial and the MTT assay for cytotoxic effects., Results: The hydrophilic extracts from Galinsoga parviflora, Petiveria alliacea, Schinus molle, Waltheria douradinha and Xanthium cavanillesii as well as the lipophilic extract of Waltheria douradinha turned out to be the most active ones., Conclusions: These results increase our knowledge on the wound healing effects of the investigated medicinal plants. Further studies are necessary to find out the effective secondary metabolites responsible for the observed effects.

The development and validation of a reversed-phase liquid chromatographic (LC) method for the determination of sibutramine hydrochloride monohydrate in capsules is described. An isocratic LC analysis was performed on a reversed-phase RP-18 column (250 x 4.6 mm id, 5 microm particle size). The mobile phase consisted of methanol-water-triethylamine (80 + 20 + 0.5, v/v/v), with pH adjusted to 5.65 with 85% phosphoric acid, and was pumped at a constant flow rate of 1.0 mL/min. Measurements were made at a wavelength of 223 nm. The calibration curve was linear over the range of 15-40 microg/mL [correlation coefficient (r2) = 0.9998]. The relative standard deviation (RSD) value for intraday precision was 0.84%. The RSD value for interday precision was 0.90%. Recoveries ranged from 99.64 to 100.66%. No interferences from the excipients were observed. Because of its simplicity and accuracy, the method is suitable for routine quality control analysis of sibutramine in capsules.

Ceftazidime (CFZ) is a broad spectrum parenteral beta-lactam antibiotic of the cephalosporin family. This paper reports the development and validation of an agar diffusion microbiological assay using the cylinder-plate method for determination of CFZ in powder for injection. The validation carried out yielded good results in terms of linearity, precision, accuracy, selectivity, and robustness. The assay is based on the inhibitory effect of CFZ upon the strain of Pseudomonas aeruginosa ATCC 27853 used as the test microorganism. The results of the assays were treated statistically by analysis of variance and were found to be linear (correlation coefficient = 0.999998) in the selected range of 8.0-32.0 microg/mL; precise [repeatability: relative standard deviation (RSD) = 1.11%; intermediate precision: between-day RSD = 1.37% and between-analyst RSD = 1.41%]; and accurate. The selectivity of the bioassay was evaluated by analysis of degraded samples at 50 degrees C, and the results were compared with a pharmacopeial liquid chromatographic method at the time 0, 24, and 48 h. The results demonstrated the validity of the proposed bioassay, which allows reliable quantitation of CFZ in pharmaceutical samples and can be used as a useful alternative methodology for CFZ analysis in routine quality control.

A simple, sensitive and specific agar diffusion bioassay for the antibacterial enrofloxacin was developed. Using a strain of Staphylococcus aureus ATCC 6538P as the test organism, enrofloxacin at concentrations ranging from 3.2 to 12.8 microg ml(-1) could be measured in injection. A prospective validation of the method showed that method was linear (r = 0.99998), precise (R.S.D. = 0.27) and accurate (it measured the added quantities). The method shows results that confirm its precision, not differing significantly the other method described in the literature. We conclude that microbiological assay is satisfactory for quantitation of in vitro antibacterial activity of enrofloxacin.

A high-performance liquid chromatography isocratic procedure was developed for the assay of cefetamet pivoxil hydrochloride in drug substance and powder for oral suspension. The method validation yielded good results and included the range, linearity, precision intra- inter-day, accuracy, specificity, LOD and LOQ values. The chromatographic system consisted of a C(18) absorbosphere column (150 x 4.6 mm i.d., 5 microm particle size), a mobile phase composed of water-acetonitrile-methanol-phosphate buffer, pH 3.5 (50:35:10:5, v/v), flow rate of 1.5 ml min(-1) and UV detection at 254 nm. The relative standard deviation varied between 0.03 and 1.76%, and accuracy of 100.09% was found. Calibration curve was linear from 30.0-80.0 microg ml(-1); its correlation coefficient was 0.99989., (Copyright 2002 Elsevier Science B.V.)

A simple, rapid and sensitive high-performance liquid chromatographic (HPLC) method was developed for the assay of enrofloxacin in raw material and injection. The validation method yielded good results and included the range, linearity, precision, accuracy, specificity, recovery, limit of detection (LOD) and limit quantification (LOQ) values. The HPLC separation was carried out by reversed phase chromatography on a C-18 absorbosphere column (150 x 4.6 mm i.d. 5 microm particle size) with a phase composed of sodium acetate (pH 4.7; 0.1 M): acetonitrile (60:40, v/v; pH 5.0), pumped isocratically at a flow rate of 1.5 ml min(-1). The effluent was monitored at 278 nm with the eluting solvent. The calibration graph for enrofloxacin was linear from 10.0 to 80.0 microg ml(-1).