Experimental variability and data pre-processing as factors affecting the discrimination power of some chemometric approaches (PCA, CA and a new algorithm based on linear regression) applied to (+/-)ESI/MS and RPLC/UV data: Application on green tea extracts.

The influence of the experimental variability (instrumental repeatability, instrumental intermediate precision and sample preparation variability) and data pre-processing (normalization, peak alignment, background subtraction) on the discrimination power of multivariate data analysis methods (Principal Component Analysis -PCA- and Cluster Analysis -CA-) as well as a new algorithm based on linear regression was studied. Data used in the study were obtained through positive or negative ion monitoring electrospray mass spectrometry (+/-ESI/MS) and reversed phase liquid chromatography/UV spectrometric detection (RPLC/UV) applied to green tea extracts. Extractions in ethanol and heated water infusion were used as sample preparation procedures. The multivariate methods were directly applied to mass spectra and chromatograms, involving strictly a holistic comparison of shapes, without assignment of any structural identity to compounds. An alternative data interpretation based on linear regression analysis mutually applied to data series is also discussed. Slopes, intercepts and correlation coefficients produced by the linear regression analysis applied on pairs of very large experimental data series successfully retain information resulting from high frequency instrumental acquisition rates, obviously better defining the profiles being compared. Consequently, each type of sample or comparison between samples produces in the Cartesian space an ellipsoidal volume defined by the normal variation intervals of the slope, intercept and correlation coefficient. Distances between volumes graphically illustrates (dis)similarities between compared data. The instrumental intermediate precision had the major effect on the discrimination power of the multivariate data analysis methods. Mass spectra produced through ionization from liquid state in atmospheric pressure conditions of bulk complex mixtures resulting from extracted materials of natural origins provided an excellent data basis for multivariate analysis methods, equivalent to data resulting from chromatographic separations. The alternative evaluation of very large data series based on linear regression analysis produced information equivalent to results obtained through application of PCA an CA.

Controlled drug delivery system based on ordered mesoporous silica matrices of captopril as angiotensin-converting enzyme inhibitor drug.

In the present study, captopril-loaded ordered mesoporous SBA-15 silica matrix were produced, functionalized, and characterized to obtain an efficient formulation of controlled drug delivery system. First, the starting SBA-15 materials are examined to verify that their synthesis has been successful considering the structural properties, using XRD, FTIR, and BET methods. Second, the influence of processing parameters of ordered mesoporous matrices for the loading and release of captopril was investigated. The release of captopril was controlled by tailoring the surface properties of the mesoporous silica via functionalization. The loading and release kinetics (in vitro in simulated gastric and intestinal fluids) showed that both of them were affected by the surface properties of the mesoporous silica materials. Such a formulation shows potential as an efficient controlled drug delivery system.

Long-term immunogenicity of the new Vero cell-derived, inactivated Japanese encephalitis virus vaccine IC51 Six and 12 month results of a multicenter follow-up phase 3 study.

Japanese encephalitis (JE) is the most common viral encephalitis in Asia. IC51 is a new Vero cell-derived, inactivated JE virus vaccine with non-inferior immunogenicity (after 2 months) compared to the US-licensed vaccine JE-VAX (mouse brain-derived, inactivated) and with a more convenient (two injections instead of three) intramuscular dose schedule. Adult subjects from two studies were followed-up for comparative immunogenicity (JE-VAX) at 6 months and long-term immunogenicity of IC51 alone at 12 months. At 6 months, immunogenicity was higher with IC51 (seroconversion rate [SCR] 95%; geometric mean titer [GMT] 84) than with JE-VAX (SCR 74%; GMT 34). At 12 months, the SCR was 83% and the GMT (41) remained above the protective titer of 1:10. Most people immunized with IC51 will have protective neutralizing antibody levels for at least a year.

Pharmacokinetic based adjustment of lidocaine antiarrhythmic schedule.

Administration of lidocaine, 200 mg/day i.m. or 275 mg orally, decreased sudden death after myocardial infarct (from 20.7% to 10.3%) although such schedules are not considered adequate to guarantee efficient plasma levels. Inclusion of lidocaine in a polyethylene matrix assured a slow release and complete disappearance of known side effects. Lidocaine was administered 200 mg intramuscularly to hospitalized patients every 6 h or 275 mg oral tablets to healthy volunteers every 8 h and plasma levels evaluated. Plasma levels after oral administration to healthy volunteers showed a great variability, so that it was not possible to draw a statistically significant conclusion about the accumulation of lidocaine in a period of 1 week. In coronary artery disease patients, plasma levels slowly increased with time, but clinical signs indicated, in some cases, a much more rapid accumulation. The therapeutic efficiency at low repeated doses was explained as a consequence of a slow accumulation on the one hand and of the addition of the action of MEGX, the major metabolite of lidocaine, on the other hand.

The effects of TAB and of adrenergic blocking drugs on the course of the experimental irradiation disease.

The experiment is aimed at establishing the consequences of the endotoxic stress (TAB) associated with alpha- or beta-adrenergic selective blocking drugs on the course of the acute irradiation disease in rats (700R, gamma rad Co60). TAB administered before or after irradiation, alone or associated with propranolol, increases the surviving rate at 30 and 60 days from exposure as compared to the controls (LD 95/30 days). Generally, dibenzyline has unfavourable effects on mortality and survival rate at the mentioned intervals. Based on the data obtained, an adrenergic component is analysed in achieving the survival increase by TAB and beta-adrenergic blocking substances; a hypothesis about the mechanisms involved is advanced.

Some pharmacological correlations of hypothermia induced by anticholinesterasics.

The investigations have been performed on Wistar rats intoxicated with paraoxon in toxic sublethal doses. There have been measured the variations of rectal temperature at various time periods following the anticholinesterase agent. The authors established the pharmacodynamic correlations of paraoxon-induced hypothermia with cholinesterase reactivators (toxogonin, isonitrosine), anticholinergic substances (atropine, butylscopolamine), carbamic anticholinesterase (eserine, neoeserine) and chlorpromazine. The efficiency of atropine and cholinesterase reactivators in antagonization of hypothermia induced by organophosphorics on the one hand, and only of atropine against hypothermia induced by carbamates on the other hand allow the hypothesis of a central cholinergic mechanism, predominantly muscarinic, involved in hypothermia induced by anticholinesterasics and of a direct correlation of this mechanism with phosphorylation or carbamylation processes of cerebral cholinesterases.

Effects of training to heat and cold in the neonatal period on the body temperature response of adult rats.

Forty infant albino rats were divided into four groups. Group I was exposed 15 minutes daily for one month to a dry ambient temperature of +40 degrees C +/- 1 degree C and group II was exposed to 10 - 20 minutes daily to an ambient temperature of - 10 degrees C +/- 2 degrees C. Groups III and IV served as controls. When they had grown adult the animals of the experimental groups were exposed once to the temperature to which they had been trained. Basal temperature was measured and the temperature curve was recorded for 30 - 60 minutes after removing the animals from the hot or cold environment. Values were compared with those found in the control groups. The statistically processed results show that daily exposure to heat and cold does not influence the basal temperature of adult animals but impairs functional tests and resistance to limit temperature exposure. Thus, compared with controls, animals trained to cold developed a significantly lower hypothermia, whereas the animals trained to heat responded by a temperature rise equalling in height and duration that of controls when they were exposed to +40 degrees C, but displayed a significantly poorer resistance to lethal hyperthermic shock. The paper ends with a discussion of the mechanisms involved in these late effects, which are probably due to the impaired maturation of the pituitary-adrenal system in the neonatal period.

A polarographic study of the pre-sodium type catalytic hydrogen wave exhibited by selenocystine.

Selenocysteine, formed by reduction of selenocystine at the DME at about -0.6 V in an ammoniacal buffer, produces a pre-sodium catalytic hydrogen wave. The effects on this wave of variation of several physico-chemical parameters such as selenocystine concentration, mercury column height, buffer capacity and concentration, and ionic strength, have been studied. The results obtained all support the conclusion that the wave is of pre-sodium type. The partially protonated species of selenocysteine seem to be catalytically active. An analytical determination of selenocystine in the presence of selenocysteine, based on this study, is proposed.