Spectrophotometric determination of lansoprazole in pharmaceuticals using bromate-bromide mixture based on redox and complexation reactions

Two sensitive spectrophotometric methods are described for the determination of lansoprazole (LPZ) in bulk drug and in capsule formulation. The methods are based on the oxidation of lansoprazole by insitu generated bromine followed by determination of unreacted bromine by two different reaction schemes. In one procedure (method A), the residual bromine is treated with excess of iron (II), and the resulting iron (III) is complexed with thiocyanate and measured at 470 nm. The second approach (method B) involves treating the unreacted bromine with a measured excess of iron (II) and remaining iron (II) is complexed with orthophenanthroline at a raised pH, and measured at 510 nm. In both methods, the amount of bromine reacted corresponds to the amount of LPZ. The experimental conditions were optimized. In method A, the absorbance is found to decrease linearly with the concentration of LPZ (r = -0.9986) where as in the method B a linear increase in absorbance occurs (r = 0.9986) The systems obey Beer's law for 0.5-4.0 and 0.5-6.0 µg mL-1 for method A and method B, respectively. The calculated molar absorptivity values are 3.97µ10(4) and 3.07µ10(4) L mol-1cm-1 for method A and method B, respectively, and the corresponding Sandell sensitivity values are 0.0039 and 0.0013 µg cm-2. The limit of detection (LOD) and quantification (LOQ) are also reported for both methods. Intra-day and inter-day precision, and accuracy of the methods were established as per the current ICH guidelines. The methods were successfully applied to the determination of LPZ in capsules and the results tallied well with the label claim and the results were statistically compared with those of a reference method by applying the Student's t-test and F-test. No interference was observed from the concomitant substances normally added to capsules. The accuracy and validity of the methods were further ascertained by performing recovery experiments via standard-addition method.

Cerimetric determination of simvastatin in pharmaceuticals based on redox and complex formation reactions

Two sensitive spectrophotometric methods are described for the determination of simvastatin (SMT) in bulk drug and in tablets. The methods are based on the oxidation of SMT by a measured excess of cerium (IV) in acid medium followed by determination of unreacted oxidant by two different reaction schemes. In one procedure (method A), the residual cerium (IV) is reacted with a fixed concentration of ferroin and the increase in absorbance is measured at 510 nm. The second approach (method B) involves the reduction of the unreacted cerium (IV) with a fixed quantity of iron (II), and the resulting iron (III) is complexed with thiocyanate and the absorbance measured at 470 nm. In both methods, the amount of cerium (IV) reacted corresponds to SMT concentration. The experimental conditions for both methods were optimized. In method A, the absorbance is found to increase linearly with SMT concentration (r = 0.9995) whereas in method B, the same decreased (r = -0.9943). The systems obey Beer's law for 0.6-7.5 and 0.5-5.0 µg mL-1 for method A and method B, respectively. The calculated molar absorptivity values are 2.7 X 10(4) and 1.06 X 10(5) Lmol-1 cm-1, respectively; and the corresponding sandel sensitivity values are 0.0153 and 0.0039µg cm-2, respectively. The limit of detection (LOD) and quantification (LOQ) are reported for both methods. Intra-day and inter-day precision, and accuracy of the methods were established as per the current ICH guidelines. The methods were successfully applied to the determination of SMT in tablets and the results were statistically compared with those of the reference method by applying the Student's t-test and F-test. No interference was observed from the common excipients added to tablets. The accuracy and validity of the methods were further ascertained by performing recovery experiments via standard addition procedure.

Polarographic study and electrode kinetics of [Zn(II) - antibiotics - cephaloglycin] system vis a vis kinetics of electrode reactions

Electrode kinetics and complex formation of Zn(II) using doxycycline, chlortetracycline, oxytetracycline, tetracycline, minocycline, amoxicillin, chloramphenicol and cephaloglycin were reported at pH = 7.30 ± 0.01 in = 1.0 molL-1 NaClO4 used as supporting electrolyte at 25.0°C. Kinetic parameters viz. transfer coefficient (α), degree of irreversibility (λ) and rate constant (k) were determined. The study showed that 'Transition state' behaves between reactant (O) and product (R) response to applied potential. The stability constants varied from 2.14 to 10.31 showing that these drugs or their complexes could be used against Zn toxicity.

Prediction of transients and control reactions in a transonic wind tunnel

This work describes a lumped parameter mathematical model for the prediction of transients in an aerodynamic circuit of a transonic wind tunnel. Control actions to properly handle those perturbations are also assessed. The tunnel circuit technology is up to date and incorporates a novel feature: high-enthalpy air injection to extend the tunnel’s Reynolds number capability. The model solves the equations of continuity, energy and momentum and defines density, internal energy and mass flow as the basic parameters in the aerodynamic study as well as Mach number, stagnation pressure and stagnation temperature, all referred to test section conditions, as the main control variables. The tunnel circuit response to control actions and the stability of the flow are numerically investigated. Initially, for validation purposes, the code was applied to the AWT ("Altitude Wind Tunnel" of NASA-Lewis). In the sequel, the Brazilian transonic wind tunnel was investigated, with all the main control systems modeled, including injection.

Control of the adrenocortical cell cycle: interaction between FGF2 and ACTH

FGF2 elicits a strong mitogenic response in the mouse Y-1 adrenocortical tumor cell line, that includes a rapid and transient activation of the ERK-MAPK cascade and induction of the c-Fos protein. ACTH, itself a very weak mitogen, blocks the mitogenic response effect of FGF2 in the early and middle G1 phase, keeping both ERK-MAPK activation and c-Fos induction at maximal levels. Probing the mitogenic response of Y-1 cells to FGF2 with ACTH is likely to uncover reactions underlying the effects of this hormone on adrenocortical cell growth.

Ethological analysis of mother-pup interactions and other behavioral reactions in rats: effects of malnutrition and tactile stimulation of the pups

Mother-pup interaction, as well as other behavioral reactions were studied during the lactation period in 24 litters of Wistar rats and their dams fed either a 16% (control - C; 12 litters) or a 6% (malnourished - M; 12 litters) protein diet. The diets were isocaloric. Throughout lactation there was a 36.4% weight loss of M dams and a 63% body weight deficit in the M pups when compared to control pups. During this period, half of the litters were exposed daily to additional tactile stimulation (CS or MS), while the other half were submitted to normal rearing conditions (CN or MN). The tactile stimulation of pups (handling) consisted of holding the animal in one hand and gently touching the dorsal part of the animal's body with the fingers for 3 min. A special camera and a time-lapse video were used to record litter behavior in their home cages. Starting at 6 p.m. and ending at 6 a.m., on days 3, 6, 12, 15, 18 and 21 of lactation, photos were taken at 4-s intervals. An increase in the frequency (154.88 ± 16.19) and duration (455.86 ± 18.05 min) of suckling was observed throughout the lactation period in all groups compared to birth day (frequency 24.88 ± 2.37 and duration 376.76 ± 21.01 min), but the frequency was higher in the C (84.96 ± 8.52) than in the M group (43.13 ± 4.37); however, the M group (470.2 ± 11.87 min) spent more time suckling as compared with the C group (393.67 ± 13.09 min). The M dams showed a decreased frequency of resting position throughout the lactation period (6.5 ± 2.48) compared to birth day (25.42 ± 7.74). Pups from the C group were more frequently observed separated (73.02 ± 4.38) and interacting (258.99 ± 20.61) more with their mothers than the M pups (separated 66.94 ± 5.5 and interacting 165.72 ± 12.05). Tactile stimulation did not interact with diet condition, showing that the kind of stimulation used in the present study did not lead to recovery from the changes induced by protein malnutrition. The changes in mother-pup interaction produced by protein malnutrition of both may represent retardation in neuromotor development and a higher dependence of the pups on their mothers. These changes may represent an important means of energy saving and heat maintenance in malnourished pups.

The antioxidant action of Polypodium leucotomos extract and kojic acid: reactions with reactive oxygen species

Two natural products Polypodium leucotomos extract (PL) and kojic acid (KA) were tested for their ability to scavenge reactive oxygen species (·OH, ·O2-, H2O2, ¹O2) in phosphate buffer. Hydroxyl radicals were generated by the Fenton reaction, and the rate constants of scavenging were 1.6 x 10(9) M-1 s-1 for KA and 1.0 x 10(9) M-1 s-1 for PL, similar to that of ethanol (1.4 x 10(9) M-1 s-1). With superoxide anions generated by the xanthine/hypoxanthine system, KA and PL (0.2-1.0 mg/ml) inhibited ·O2-dependent reduction of nitroblue tetrazolium by up to 30 and 31%, respectively. In the detection of ¹O2 by rose bengal irradiation, PL at 1.0 mg/ml quenched singlet oxygen by 43% relative to azide and KA by 36%. The present study demonstrates that PL showed an antioxidant effect, scavenging three of four reactive oxygen species tested here. Unlike KA, PL did not significantly scavenge hydrogen peroxide.

The role of chemokines and chemokine receptors in eosinophil activation during inflammatory allergic reactions

Chemokines are important chemotactic cytokines that play a fundamental role in the trafficking of leukocytes to sites of inflammation. They are also potent cell-activating factors, inducing cytokine and histamine release and free radical production, a fact that makes them particularly important in the pathogenesis of allergic inflammation. The action of chemokines is regulated at the level of agonist production and processing as well as at the level of receptor expression and coupling. Therefore, an analysis of the ligands must necessarily consider receptors. Eosinophils are target cells involved in the allergic inflammatory response since they are able to release a wide variety of mediators including CC and CXC chemokines and express their receptors. These mediators could damage the airway epithelial cells and might be important to stimulate other cells inducing an amplification of the allergic response. This review focuses on recently emerging data pertaining to the importance of chemokines and chemokine receptors in promoting eosinophil activation and migration during the allergic inflammatory process. The analysis of the function of eosinophils and their chemokine receptors during allergic inflammation might be a good approach to understanding the determinants of asthma severity and to developing novel therapies.

High incidence of adverse reactions to initial antiretroviral therapy in Brazil

A concurrent prospective study was conducted from 2001 to 2003 to assess factors associated with adverse reactions among individuals initiating antiretroviral therapy at two public referral HIV/AIDS centers in Belo Horizonte, MG, Brazil. Adverse reactions were obtained from medical charts reviewed up to 12 months after the first antiretroviral prescription. Cox proportional hazard model was used to perform univariate and multivariate analyses. Relative hazards (RH) were estimated with 95% confidence intervals (CI). Among 397 charts reviewed, 377 (95.0%) had precise information on adverse reactions and initial antiretroviral treatment. Most patients received triple combination regimens including nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. At least one adverse reaction was recorded on 34.5% (N = 130) of the medical charts (0.17 adverse reactions/100 person-day), while nausea (14.5%) and vomiting (13.1%) were the most common ones. Variables independently associated with adverse reactions were: regimens with nevirapine (RH = 1.78; 95% CI = 1.07-2.96), indinavir or indinavir/ritonavir combinations (RH = 2.05; 95% CI = 1.15-3.64), female patients (RH = 1.93; 95% CI = 1.31-2.83), 5 or more outpatient visits (RH = 1.94; 95% CI = 1.25-3.01), non-adherence to antiretroviral therapy (RH = 2.38; 95% CI = 1.62-3.51), and a CD4+ count of 200 to 500 cells/mm³ (RH = 2.66; 95% CI = 1.19-5.90). An independent and negative association was also found for alcohol use (RH = 0.55; 95% CI = 0.33-0.90). Adverse reactions were substantial among participants initiating antiretroviral therapy. Specially elaborated protocols in HIV/AIDS referral centers may improve the diagnosis, management and prevention of adverse reactions, thus contributing to improving adherence to antiretroviral therapy among HIV-infected patients.

Functional changes of dendritic cells in hypersensivity reactions to amoxicillin

A better understanding of dendritic cell (DC) involvement in responses to haptenic drugs is needed, because it represents a possible approach to the development of an in vitro test, which could identify patients prone to drug allergies. There are two main DC subsets: plasmacytoid DC (pDC) and myeloid DC (mDC). β-lactams form hapten-carrier conjugates and may provide a suitable model to study DC behavior in drug allergy reactions. It has been demonstrated that drugs interact differently with DC in drug allergic and non-allergic patients, but there are no studies regarding these subsets. Our aim was to assess the functional changes of mDC and pDC harvested from an amoxicillin-hypersensitive 32-year-old woman who experienced a severe maculopapular exanthema as reflected in interleukin-6 (IL-6) production after stimulation with this drug and penicillin. We also aim to demonstrate, for the first time, the feasibility of this method for dendritic cell isolation followed by in vitro stimulation for studies of drug allergy physiopathology. DC were harvested using a double Percoll density gradient, which generates a basophil-depleted cell (BDC) suspension. Further, pDC were isolated by blood DC antigen 4-positive magnetic selection and gravity filtration through magnetized columns. After stimulation with amoxicillin, penicillin and positive and negative controls, IL-6 production was measured by ELISA. A positive dose-response curve for IL-6 after stimulation with amoxicillin and penicillin was observed for pDC, but not for mDC or BDC suspension. These preliminary results demonstrate the feasibility of this methodology to expand the knowledge of the effect of dendritic cell activation by drug allergens.

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.