Dose-dependent effects of astaxanthin on cortical spreading depression in chronically ethanol-treated adult rats

Background: The consumption of alcoholic drinks is a frequent drug‐abuse situation, which is associated to a wide variety of pathological disturbances affecting several organs, including the brain. We have previously shown in the developing rat brain that ethanol intake facilitates the propagation of cortical spreading depression (CSD), an excitability‐related neural phenomenon present in several animal species. This electrophysiological effect was attenuated by a shrimp (Litopenaeus vannamei) carotenoids extract. Here we investigated the effects of pure astaxanthin, the main carotenoid found in shrimp, on CSD. Methods: Adult Wistar rats were treated per gavage, during 18 days, with 2.5, 10 or 90 μg/kg/d astaxanthin dissolved in ethanol (3 g/kg) and CSD was recorded on the cortical surface 1 to 3 days thereafter. Four groups, treated respectively with ethanol, distilled water and soybean oil with‐ and without astaxanthin were also studied for comparison with the ethanol + astaxanthin groups. Results: Ethanol‐treated rats displayed higher CSD‐velocities (mean values, in mm/min, per hour of recording ranging from 4.08 ± 0.09 to 4.12 ± 0.16), compared to the distilled water‐group (from 3.19 ± 0.13 to 3.27 ± 0.06). Addition of astaxanthin to ethanol lead to lower CSD‐velocities in a dose‐dependent manner, ranging from 3.68 ± 0.09 to 3.97 ± 0.22 for the 2.5 μg/kg/d‐dose, from 3.29 ± 0.09 to 3.32 ± 0.07 for the 10 μg/kg/d‐dose, and from 2.89 ± 0.13 to 2.92 ± 0.11 for the 90 μg/kg/d‐dose. The velocities of the soybean oil groups (with and without astaxanthin) were not statistically different from the 10 μg/kg/d astaxanthin + ethanol and distilled water groups. Conclusion: The results demonstrate the antagonistic effect of astaxanthin against the ethanol‐induced facilitation of CSD propagation. Probably carotenoid antioxidant properties are involved in such effects.     

Deprivation of dietary nucleotides decreases protein synthesis in the liver and small intestine in rats

BACKGROUND & AIMS: Dietary nucleotides are reported to influence the growth and functioning of the liver and small intestine. The aim of this study was to examine the mechanism by which nucleotides exert their effects in these tissues by assessing protein synthesis activity and related parameters in the presence or absence of dietary nucleotides. METHODS: Rats were fed a purified diet with or without nucleotides for 10 days. Fractional protein synthesis rate, RNA and DNA concentrations, polysome size distribution, and number of ribosomes were assessed. RESULTS: Fractional protein synthesis rates of the liver and small intestine were lower in the nucleotide-deprived group than in the control group. In the liver, RNA concentration was also lower in the nucleotide-deprived group, but values in the small intestine were similar in the two groups. In the liver, deprivation of nucleotides resulted in a reduction in the number of ribosomes and in polysome breakdown. Protein and DNA concentrations did not vary in the liver; however, the concentration of DNA was lower in the small intestine of the nucleotide-deprived group than in the control group. CONCLUSIONS: Dietary nucleotides can modulate protein synthesis in the liver and small intestine as a result of tissue-specific nucleic acid changes. (Gastroenterology 1996 Jun;110(6):1760-9)     

The formation of Ca++-dependent complexes of platelet membrane glycoproteins IIb and IIIa in solution as determined by crossed immunoelectrophoresis

Triton X-100 soluble proteins from 125I-labeled human platelets were studied by crossed immunoelectrophoresis employing a multispecific rabbit antibody raised against whole normal platelets. Emphasis was placed upon an analysis of immunoprecipitates containing 125I-labeled major membrane glycoproteins, and in particular, a prominent immunoprecipitate containing a glycoprotein antigen (s) previously designated as protein 16. SDS-polyacrylamide gel electrophoresis of protein 16 precipitated by a monospecific alloantibody. IgG L . . . , confirmed the presence of both glycoproteins IIb and IIIa. 125I-IgG L . . . , at concentration below that capable of precipitating protein 16 by itself, bound specifically to the precipitate containing protein 16 produced by the multispecific rabbit antibody. No other precipitates formed by the rabbit antibody contained either glycoprotein IIb or IIIa. When platelet proteins, incubated with optimum concentrations of ethylenediamine tetraacetic acid (EDTA) or ethyleneglycol bis (B- aminoethylether) NN1-tetraacetic acid (EGTA), were electrophoresed against the rabbit antibody, previously unobserved immunoprecipitates that contained either free glycoprotein IIb or free glycoprotein IIIa were detected. Upon readdition of excess Ca++, but not Mg++, to the same protein samples, a single immunoprecipitate containing both glycoproteins was once again observed. It is thus demonstrated that glycoproteins IIb and IIIa can form Ca++-dependent complexes (protein 16) in Triton X-100 extracts of normal platelets. The potential significance of the reversible association of these glycoproteins to normal platelet function is discussed.     

Distribution of serotypes and evaluation of antimicrobial susceptibility among human and bovine Streptococcus agalactiae strains isolated in Brazil between 1980 and 2006

Streptococcus agalactiae is a common agent of clinical and subclinical bovine mastitis and an important cause of human infections, mainly among pregnant women, neonates and nonpregnant adults with underlying diseases. The present study describes the genetic and phenotypic diversity among 392 S. agalactiae human and bovine strains isolated between 1980 and 2006 in Brazil. The most prevalent serotypes were Ia, II, III and V and all the strains were susceptible to penicillin, vancomycin and levofloxacin. Resistance to clindamycin, chloramphenicol, erythromycin, rifampicin and tetracycline was observed. Among the erythromycin resistant strains, mefA/E, ermA and, mainly, ermB gene were detected, and a shift of prevalence from the macrolide resistance phenotype to the macrolide-lincosamide-streptogramin B resistance phenotype over the years was observed. The 23 macrolide-resistant strains showed 19 different pulsed-field gel electrophoresis profiles. Regarding macrolide resistance, a major concern in S. agalactiae epidemiology, the present study describes an increase in erythromycin resistance from the 80s to the 90s followed by a decrease in the 2000–2006 period. Also, the genetic heterogeneity described points out that erythromycin resistance in Brazil is rather due to horizontal gene transmission than to spreading of specific macrolide-resistant clones.     

Doxycycline use in patients with lymphangioleiomyomatosis: biomarkers and pulmonary function response ,

OBJECTIVE:

To assess blockade of matrix metalloproteinase (MMP)-2 and MMP-9, as well as the variation in FEV₁, in patients with lymphangioleiomyomatosis (LAM) treated with doxycycline (a known MMP inhibitor) for 12 months.

METHODS:

An open-label, single-arm, interventional clinical trial in which LAM patients received doxycycline (100 mg/day) for 12 months. Patients underwent full pulmonary function testing, a six-minute walk test, and quality of life assessment, as well as blood and urine sampling for quantification of MMP-2, MMP-9, and VEGF-D levels-at baseline, as well as at 6 and 12 months after the initiation of doxycycline.

RESULTS:

Thirty-one LAM patients received doxycycline for 12 months. Although there was effective blockade of urinary MMP-9 and serum MMP-2 after treatment, there were no significant differences between pre and post-doxycycline serum levels of MMP-9 and VEGF-D. On the basis of their response to doxycycline (as determined by the variation in FEV₁), the patients were divided into two groups: the doxycycline-responder (doxy-R) group (n = 13); and the doxycycline-nonresponder (doxy-NR) group (n = 18). The patients with mild spirometric abnormalities responded better to doxycycline. The most common side effects were mild epigastric pain, nausea, and diarrhea.

CONCLUSIONS:

In patients with LAM, doxycycline treatment results in effective MMP blockade, as well as in improved lung function and quality of life in those with less severe disease. However, these benefits do not seem to be related to the MMP blockade, raising the hypothesis that there is a different mechanism of action.     

Implementation of a protocol proposed by the Brazilian National Health Surveillance Agency for antibiotic use in very low birth weight infants

ObjectiveTo analyze the implementation of a protocol proposed by the Brazilian National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária – ANVISA) to improve sepsis diagnosis in very low birth weight newborns.MethodsThis was a prospective study that evaluated the implementation of a protocol involving clinical and laboratory criteria (hematologic scoring system of Rodwell and C-reactive protein serial measurements), recommended by ANVISA, to improve the diagnosis of neonatal sepsis in very low birth weight newborns. The study included all patients who were born and remained in the neonatal intensive care unit until discharge or death, and excluded those with congenital diseases. The main outcomes measured in newborns before (2006-2007) and after implementation of the protocol (2008) were the rates of early and late-onset sepsis, use of antibiotics, and mortality. Means were compared by Student's t-test and categorical variables were compared by the chi-squared test; the significance level for all tests was set at 95%.ResultsThe study included 136 newborns with very low birth weight. There was no difference between groups regarding general clinical characteristics in the studied periods. There was, however, a decrease in the number of diagnoses of probable early-onset sepsis (p < 0.001), use of antimicrobial regimens (p < 0.001), and overall mortality and infection-related mortality (p = 0.009 and p = 0.049, respectively).ConclusionThe implementation of the protocol allowed improvement of sepsis diagnosis by reducing the diagnosis of probable early-onset sepsis, thus promoting efficient antimicrobial use in this population.     

Saturable rate of cefatrizine absorption after oral administration to humans

This study examined the absorption kinetics of cefatrizine, an amino-beta-lactam antibiotic, after oral administration of a single 500-mg dose to 12 healthy volunteers. Plasma concentrations were determined by high performance liquid chromatography. The plots of the percentage of drug unabsorbed and the apparent rate of cefatrizine absorption as a function of time showed, first, a delay and, then, an almost constant rate of absorption with a tendency to move toward first-order kinetics at the end of the process. Three compartmental models incorporating a lag time and first-order elimination kinetics, but differing in their input rate, were used for analysis of the time course of cefatrizine plasma concentrations. The model with first-order absorption kinetics was clearly inadequate. The results were improved with the model for which the rate of absorption is constant, but a model incorporating saturable absorption kinetics of the Michaelis-Menten type improved the fit further. This last model was statistically superior to the constant-rate input model in 6 out of 12 subjects, according to the likelihood-ratio method. Because of the innovative feature of the model incorporating the Michaelis-Menten equation, simulations of the effect of altering the model parameters and the dose administered on the concentration-time profile, were performed. Different hypotheses which might explain why cefatrizine absorption kinetics fits the Michaelis-Menten equation were examined. The observation of saturable absorption kinetics is consistent with a carrier-mediated transport previously reported to occur in the gastrointestinal tract of rats.