Administration-time-dependent effects of hypertension treatment on ambulatory blood pressure in patients with chronic kidney disease.

Many published prospective trials have reported clinically meaningful morning-evening, treatment-time differences in the blood pressure (BP)-lowering efficacy, duration of action, and safety of most classes of hypertension medications. Most important, it was recently documented that routine ingestion of the full daily dose of ≥1 hypertension medications at bedtime, compared with ingestion of all of them upon awakening, significantly reduces cardiovascular disease (CVD) events. Nocturnal hypertension and non-dipping (<10% decline in the asleep relative to the awake BP mean), as determined by ambulatory BP monitoring (ABPM), are frequent in chronic kidney disease (CKD) and both are associated with increased CVD risk. Here, we investigated the influence of hypertension treatment time on the circadian BP pattern and degree of BP control of hypertensive patients with CKD evaluated by 48-h ABPM. This cross-sectional study evaluated 2659 such patients (1585 men/1074 women), 64.9 ± 13.2 (mean ± SD) yrs of age, enrolled in the Hygia Project, involving primary care centers of northwest Spain and designed to evaluate prospectively CVD risk by ABPM; 1446 were ingesting all BP-lowering medications upon awakening, whereas 1213 patients were ingesting ≥1 medications at bedtime. Among the latter, 359 patients were ingesting all medications at bedtime, whereas 854 were ingesting the full daily dose of some medications upon awakening and the others at bedtime. Those ingesting all medications upon awakening had significantly higher total cholesterol and low-density lipoprotein (LDL) cholesterol than those ingesting ≥1 medications at bedtime. Moreover, patients ingesting all medications at bedtime had the lowest fasting glucose, serum creatinine, and uric acid. Ingestion of ≥1 medications at bedtime was significantly associated with lower asleep systolic (SBP) and diastolic (DBP) BP means than treatment with all medications upon awakening. The sleep-time relative SBP decline was significantly attenuated in patients ingesting all medications upon awakening (p < .001). Thus, the prevalence of non-dipping was significantly higher when all hypertension medications were ingested upon awakening (68.3%) than when ≥1 of them was ingested at bedtime (54.2%; p < .001 between groups), and even further attenuated (47.9%) when all of them were ingested at bedtime (p < .001). Additionally, the prevalence of a riser BP pattern, associated with highest CVD risk, was much greater (21.5%) among patients ingesting all medications upon awakening, compared with those ingesting some (15.7%) or all medications at bedtime (10.6%; p < .001 between groups), independent of CKD severity (disease stage). The latter group also showed a significantly higher prevalence of properly controlled ambulatory BP (p < .001) that was achieved by a significantly lower number of hypertension medications (p < .001) compared with patients treated upon awakening. Our findings demonstrate significantly lower asleep SBP and DBP means and attenuated prevalence of a blunted nighttime BP decline, i.e., lower prevalence of markers of CVD risk, in patients with CKD ingesting hypertension medications at bedtime than in those ingesting all of them upon awakening. These collective findings indicate that bedtime hypertension treatment, in conjunction with proper patient evaluation by ABPM to corroborate the diagnosis of hypertension and avoid treatment-induced nocturnal hypotension, should be the preferred therapeutic scheme for CKD.

Highly galloylated tannin fractions from witch hazel (Hamamelis virginiana) bark: electron transfer capacity, in vitro antioxidant activity, and effects on skin-related cells.

Witch hazel ( Hammamelis virginiana) bark is a rich source of both condensed and hydrolizable oligomeric tannins. From a polyphenolic extract soluble in both ethyl acetate and water, we have generated fractions rich in pyrogallol-containing polyphenols (proanthocyanidins, gallotannins, and gallates). The mixtures were highly active as free radical scavengers against ABTS, DPPH (hydrogen donation and electron transfer), and HNTTM (electron transfer). They were also able to reduce the newly introduced TNPTM radical, meaning that they included some highly reactive components. Witch hazel phenolics protected red blood cells from free radical-induced hemolysis and were mildly cytotoxic to 3T3 fibroblasts and HaCat keratinocytes. They also inhibited the proliferation of tumoral SK-Mel 28 melanoma cells at lower concentrations than grape and pine procyanidins. The high content in pyrogallol moieties may be behind the effect of witch hazel phenolics on skin cells. Because the most cytotoxic and antiproliferative mixtures were also the most efficient as electron transfer agents, we hypothesize that the final putative antioxidant effect of polyphenols may be in part attributed to the stimulation of defense systems by mild prooxidant challenges provided by reactive oxygen species generated through redox cycling.

La diferenciación territorial en los servicios farmacéuticos comunitarios en Ciudad de La Habana / Territorial differentiation in community-based pharmaceutical services in Havana

Los servicios farmacéuticos comunitarios han sido poco estudiados en Cuba. El objetivo de este trabajo es caracterizar estos servicios en la provincia Ciudad de la Habana. Fueron calculados el número de habitantes por farmacia, farmacias por habitantes, farmacia por 10 000 habitantes, habitantes por licenciado en farmacia, licenciado por 10 000 habitantes, licenciado por farmacia y farmacia por consultorios. Los resultados obtenidos permitieron identificar que los territorios de La Habana Vieja, Habana del Este, Centro Habana y Boyeros, tenían una situación desfavorable en el indicador número de habitantes por farmacia, mientras que en el municipio Cotorro, era mucho más favorable. Se apreció, además, la falta de relación entre la diferenciación territorial de la prevalencia de algunas enfermedades crónicas y la distribución de los servicios. Los resultados, mostraron, en general, una elevada heterogeneidad intermunicipal de los servicios farmacéuticos comunitarios, que se amplía en las áreas de salud. Se presentan algunas propuestas para el incremento de la eficiencia y efectividad de estos servicios.

The community-based pharmaceutical services have not been thoroughly studied in Cuba. The objective of this paper is to characterize these services in the City of Havana province using the estimation of the number of inhabitants per drugstore, of drugstores per inhabitant, of drugstores per 10 000 pop., of inhabitants per Bachelor of Pharmacy, of Bachelors per 10 000 pop., of Bacherlors per drugstore and of drugstores per doctor's offices. The results made it possible to identify Old Havana, Eastern Havana, Centro Habana and Boyeros municipalities as the territories that faced the most unfavorable situation in terms of number of inhabitants per drugstore whereas the situation of Cotorro municipality was much more favorable. Territorial differentiation in the prevalence of some chronic diseases and the distribution of services were unrelated. Generally, the results showed great inter-municipal heterogeneity of community-based pharmaceutical services, being more extensive in the health areas. Some proposals for increasing efficiency and effectiveness of these services were put forward.

A recombinant enolase from Anisakis simplex is differentially recognized in natural human and mouse experimental infections.

A 1,963-bp cDNA was isolated from an Anisakis simplex cDNA library by immunoscreening with a hyperimmune rabbit serum raised against a crude extract of A. simplex L3 larvae. The open reading frame encodes a putative protein of 436 amino acid residues, which exhibits high similarity (70-80%) to enolase molecules from various other organisms, including helminth parasites. After subcloning and expression of the A. simplex cDNA in PGEX-4T-3, the resulting glutathione S-transferase fusion protein, purified by glutathione-Sepharose-4B chromatography, showed functional enolase activity. The immunogenicity of the recombinant A. simplex enolase was analyzed by immunoblotting using sera obtained from (a) mice immunized with crude extracts (CE) of A. simplex, or other nematode species, (b) mice immunized with excretory-secretory (ES) antigens from A. simplex, or (c) mice infected with L3 larvae by the intraperitoneal route. In addition, we used ELISA, to investigate the presence of IgG1 and IgE antibodies against this molecule in sera from patients infected with A. simplex. Mouse sera obtained after infection with L3 or raised against CE antigens, but not sera raised against ES antigens, showed strong reactivity with the recombinant A. simplex enolase. We also obtained good reactivity in Western blotting with sera from mice immunized with CE antigens from Ascaris suum and Toxocara canis, but not with sera from mice immunized with CE antigens from Trichuris muris, Trichinella spiralis or Hysterothylacium aduncum. In contrast to the experimental infections/immunizations in mice, we were unable to detect anti-enolase IgE antibodies in sera from human patients infected with A.simplex (15 sera), and the levels of anti-enolase IgG1 antibodies in these sera were low and apparently nonspecific. These results seem to indicate that, during natural infection in humans, A. simplex larvae do not offer sufficient antigenic stimulus to induce anti-enolase antibodies.

Monoclonal antibodies raised in Btk(xid) mice reveal new antigenic relationships and molecular interactions among gp53 and other Trichinella glycoproteins.

Tyvelose-bearing glycoproteins or Trichinella spiralis Group 1 antigens (TSL-1 antigens) are thought to be key molecules in the immunobiology of Trichinella. In the present study, we investigated the binding characteristics of several mAbs produced in Btk(xid) immunodeficient mice that recognise gp53 and some other minor glycoproteins of this parasite. The data obtained reveal the existence of an O-glycan/peptide epitope (recognised by mAb US8) common to all TSL-1 glycoproteins, as well as a specific interaction between the TSL-1 antigen gp53 and other unknown Trichinella glycoproteins in the 35-40 kDa range (these latter react with mAbs US8 and US9, but not with mAb US5). Some of the epitopes recognised by our mAbs are differentially expressed in Trichinella species: the epitope recognised by mAb US5 on gp53 (another O-glycan/peptide epitope) is present only in T. spiralis, whereas those recognised by mAbs US8 and US9 (peptide epitopes) are present in encapsulated Trichinella species. The data obtained also reveal that gp53 is synthesised and glycosylated in beta-stichocytes only. The possible relevance of these findings is discussed.

Presencia de lectinas, taninos e inhibidores de proteasas en algas marinas de las costas Venezolanas / Presence of lectins, tannins and protease inhibitors in Venezuelan marine algae

Se estudió la presencia de lectinas, taninos e inhibidores de proteases, en 27 especies de algas colectadas en barreras coralinas de cuatro regiones de Venezuela. Sólo seis de las especies estudiadas, presentaron actividad hemaglutinante atribuible a lectinas, obteniéndose los mayores títulos de hemaglutinación com eritrocitos tratados con pronasa. En cuatro de las especies, las lectinas fueron inhibidas por más de un azúcar sencillo y por la mucina de glándula submaxilar de bovino: Caulerpa sertularioides, Enteromorpha intestinalis, Codium repens y Codium isthmocladum (Chlorophyta). La lectina de Grateloupia filicina fue inhibida solamente por NAcGal. Ninguno de los compuestos probados inhibió la hemaglutinación causada por Halimeda opuntia. El tratamiento de los extractos con polivinilpolipirrolidona eliminó la actividad hemaglutinante de las algas pardas y rojas, menos en dos especies de rodofitas: Grateloupia filicina e Hypnea cervicornis, lo que hace presumir la presencia de lectinas en ambas. Los taninos presentes en las Phaeophyta y Rhodophyta estudiadas son aparentemente del tipo florotaninos con un mayor contenido en las primeras. Sólo se encontró actividad inhibidora de tripsina en: Padina gymnospora (Phaeophyta) y Acantophora spicifera (Rhodophyta). En ningún caso se encontró actividad inhibidora contra subtilisina.