Effectiveness of treatments for hypertension in a sample of Colombian patients

Hypertension represents a high health cost because of its prevalence, its low level of diagnosis and control, and its role as a primary risk factor for other cardiovascular diseases. According to the JNC 7 report, hypertensive individuals have blood pressures of 140/90 mm Hg or higher; recommended treatment reduces these values to below 120/80 mm Hg. Co-morbidity and the presence of other risk factors must also be considered. In a random sample of 458 hypertensive patients from 6 Colombian cities, the effectiveness, tolerance and adherence to treatment was compared in cases with treatment of at least one year's duration. During routine blood pressure examinations, trained nurses obtained patient consent and additional anthropometric data, such as including co-morbidity, risk factors, antihypertensive medication prescribed, dosages and usage of unrelated medications. Some of the data were retrieved from the patients' medical histories. The average age of the patients was 57.6 +/- 13 years, with 67.5% women; 92% with complete adherence to the treatment and 59% not reporting adverse events associated with the medication. Forty-four percent were treated with antihypertensive monotherapy with the most commonly prescribed medications as follows (in order): hydrochlorothiazide, verapamil, enalapril, metoprolol and propanolol. Forty-five percent (n=207) were control patients, 35% were in a hypertensive stage 1 and 19.7% were in stage 2. Multivariate analysis showed that uncontrolled hypertension was significantly associated with geriatrics receiving a combination of antihypertensive medication and residence in three cities--Ibagué, Barranquilla and Manizales--where smaller daily doses of hypertensive medications are prescribed. Health care teams are advised to adjust doses carefully to obtain clearly defined therapeutic objectives.     

Differential effect of nitric oxide on glutathione metabolism and mitochondrial function in astrocytes and neurones: implications for neuroprotection/neurodegeneration?

Primary culture rat astrocytes exposed to the long acting nitric oxide donor (Z)-1-[2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO) for 24 h approximately double their concentration of glutathione (GSH) and show no sign of cell death. In contrast, GSH was depleted by 48%, and significant loss of mitochondrial respiratory chain complex activity and cell death were observed in primary culture rat neurones subjected to DETA-NO for 18 h. Northern blot analysis suggested that mRNA amounts of both subunits of glutamate-cysteine ligase (GCL), the rate-limiting enzyme in GSH synthesis, were elevated in astrocytes following nitric oxide (NO) exposure. This correlated with an increase in astrocytic GCL activity. Neurones on the other hand did not exhibit increased GCL activity when exposed to NO. In addition, the rate of GSH efflux was doubled and gamma-glutamyltranspeptidase (gamma-GT) activity was increased by 42% in astrocytes treated with NO for 24 h. These results suggest that astrocytes, but not neurones, up-regulate GSH synthesis as a defence mechanism against excess NO. It is possible that the increased rate of GSH release and activity of gamma-GT in astrocytes may have important implications for neuroprotection in vivo by optimizing the supply of GSH precursors to neurones in close proximity.     

Talisia esculenta lectin and larval development of Callosobruchus maculatus and Zabrotes subfasciatus (Coleoptera: Bruchidae)

Bruchid larvae cause major losses in grain legume crops throughout the world. Some bruchid species, such as the cowpea weevil and the Mexican bean weevil, are pests that damage stored seeds. Plant lectins have been implicated as antibiosis factors against insects, particularly the cowpea weevil, Callosobruchus maculatus. Talisia esculenta lectin (TEL) was tested for anti-insect activity against C. maculatus and Zabrotes subfasciatus larvae. TEL produced ca. 90% mortality to these bruchids when incorporated in an artificial diet at a level of 2% (w/w). The LD(50) and ED(50) for TEL was ca. 1% (w/w) for both insects. TEL was not digested by midgut preparations of C. maculatus and Z. subfasciatus. The transformation of the genes coding for this lectin could be useful in the development of insect resistance in important agricultural crops.     

Molecular and biochemical characterization of a highly stable bacterial laccase that occurs as a structural component of the Bacillus subtilis endospore coat

The Bacillus subtilis endospore coat protein CotA shows laccase activity. By using comparative modeling techniques, we were able to derive a model for CotA based on the known x-ray structures of zucchini ascorbate oxidase and Cuprinus cereneus laccase. This model of CotA contains all the structural features of a laccase, including the reactive surface-exposed copper center (T1) and two buried copper centers (T2 and T3). Single amino acid substitutions in the CotA T1 copper center (H497A, or M502L) did not prevent assembly of the mutant proteins into the coat and did not alter the pattern of extractable coat polypeptides. However, in contrast to a wild type strain, both mutants produced unpigmented colonies and spores unable to oxidize syringaldazine (SGZ) and 2'2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). The CotA protein was purified to homogeneity from an overproducing Escherichia coli strain. The purified CotA shows an absorbance and a EPR spectra typical of blue multicopper oxidases. Optimal enzymatic activity was found at < or =pH 3.0 and at pH 7.0 for ABTS or SGZ oxidation, respectively. The apparent K(m) values for ABTS and SGZ at 37 degrees C were of 106 +/- 11 and 26 +/- 2 microm, respectively, with corresponding k(cat) values of 16.8 +/- 0.8 and 3.7 +/- 0.1 s(-1). Maximal enzyme activity was observed at 75 degrees C with ABTS as substrate. Remarkably, the coat-associated or the purified enzyme showed a half-life of inactivation at 80 degrees C of about 4 and 2 h, respectively, indicating that CotA is intrinsically highly thermostable.     

Immunocytolocalization of tryptophan decarboxylase in Catharanthus roseus hairy roots

We investigated the intracellular distribution of tryptophan decarboxylase (TDC) (EC 4.1.1.28) in Catharanthus roseus hairy roots using immunofluorescence and immunogold techniques. TDC was detected by immunofluorescence localization in the cytosol and in the apoplastic region of the meristematic cells of the roots, with a slight enrichment in the epidermal cells of the root cap and in the meristematic region. In the enlargement zone, TDC was localized only in the first three layers of the cortex. In the maturation zone, the enzyme was not present. Immunogold studies confirmed that the enzyme was localized in the cytosol of the meristematic region, and intense gold labeling was found in the apoplastic zone. A protein fraction isolated from the apoplastic zone and assayed for TDC activity showed high activity.     

Prophylactic corticosteroid to prevent pain flare in bone metastases treated by radiotherapy

BackgroundThe aim of this study was to evaluate the effectiveness of prophylactic corticosteroids to prevent pain flare (PF) in bone metastases treated with radiotherapy performing a meta-analysis of randomized clinical trials (RCT).Materials and methodsRCTs were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through June 2020. We followed the PRISMA and MOOSE guidelines. A meta-analysis was performed to assess if corticosteroids reduce the PF, pain progression, and the mean of days with PF compared with the placebo. A p-value < 0.05 was considered significant.ResultsThree RCTs with a total of 713 patients treated were included. The corticosteroids reduced the occurrence of early PF 20.5% (51/248) versus 32% (80/250) placebo, OR = 0.55 (95% CI: 0.36–0.82, p = 0.002). The mean days of PF were reduced to 1.6 days (95% CI: 1.3–1.9, p = 0.0001). Prophylactic corticosteroids had more patients with no PF and no pain progression, OR = 1.63 (95% CI: 1.14–2.32, p = 0.007). No significant corticosteroids effect was observed for pain progression (p = ns) and late PF occurrence (p = ns).ConclusionProphylactic corticosteroids reduced the incidence of early PF, the days with PF, resulting in a superior rate of patients with no PF and no pain progression, but with no significant benefit for reducing pain progression or late PF occurrence.     

Azilsartan Reduced TNF-α and IL-1β Levels,Increased IL-10 Levels and Upregulated VEGF,FGF, KGF,and TGF-α in an Oral Mucositis Model

Oral mucositis (OM) is a common complication of treatments for head and neck cancer, particularly radiotherapy with or without chemotherapy. OM is characterised by oral erythema, ulceration, and pain. The aim of this study was to evaluate the effect of azilsartan (AZT), an angiotensin II receptor antagonist, on 5-fluorouracil (5-FU)-induced oral mucositis (OM) in Syrian hamsters. OM was induced by the intraperitoneal administration of 5-FU on experimental days 1 (60mg/Kg) and 2 (40mg/Kg). Animals were pretreated with oral AZT (1, 5, or 10 mg/kg) or vehicle 30 min before 5-FU injection and daily until day 10. Experimental treatment protocols were approved by the Animal Ethics Committee Use/CEUA (Number 28/2012) of the UFRN. Macroscopic analysis and cheek pouch samples were removed for histopathologic analysis. Myeloperoxidase (MPO), Malonyldialdehyde (MDA), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), and tumour necrosis factor-alpha (TNF-α) were analysed by Enzyme Linked Immuno Sorbent Assay (ELISA). Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), and transforming growth factor (TGF)-α were measured by immunohistochemistry. Analysis of variance followed by Bonferroni’s test was used to calculate the means of intergroup differences (p ≤ 0.05). Treatment with 1 mg/kg AZT reduced levels MPO (p<0.01), MDA (p<0.5) and histological inflammatory cell infiltration, and increased the presence of granulation tissue. AZT treatment at 1 mg/kg reduced the TNF-α (p<0.05) and IL-1β (p<0.05) levels, increased the cheek pouch levels of IL-10 (p<0.01), and upregulated VEGF, FGF, KGF, and TGF-α. Administration of AZT at higher doses (5 and 10 mg/kg) did not significantly reverse the OM. AZT at a dose of 1 mg/kg prevented the mucosal damage and inflammation associated with 5-FU-induced OM, increasing granulation and tissue repair.     

Peripheral mononuclear blood cells contribute to the obesity-associated inflammatory state independently of glycemic status: involvement of the novel proinflammatory adipokines chemerin,chitinase-3-like protein 1, lipocalin-2 and osteopontin

Inflammation is a critical contributor to the pathogenesis of metabolic disorders with adipose tissue being crucial in the inflammatory response by releasing multiple adipokines with either pro- or anti-inflammatory activities with potential functions as metabolic regulators. Peripheral blood mononuclear cells (PBMC) have been proposed as representative of the inflammatory status in obesity. The aim of the present study was to evaluate the contribution of PBMC to the obesity-associated chronic inflammation analyzing the expression of novel adipokines. Samples obtained from 69 subjects were used in the study. Real-time PCR determinations were performed to quantify gene expression levels in PBMC of novel adipokines including chemerin, chitinase-3-like protein 1 (YKL-40), lipocalin-2 (LCN-2) and osteopontin (OPN), and their circulating concentrations were also determined by ELISA. We show, for the first time, that PBMC gene expression levels of chemerin (P < 0.0001), chitinase-3-like protein 1 (P = 0.010), lipocalin-2 (P < 0.0001) and osteopontin (P < 0.0001) were strongly upregulated in obesity independently of the glycemic state. Circulating concentrations of these adipokines followed the same trend being significantly higher (P < 0.05) in obese normoglycemic and type 2 diabetic patients compared to lean volunteers and also associated (P < 0.05) with their corresponding mRNA levels in PBMC. These results provide evidence that alterations in inflammation-related adipokines are manifest in PBMC, which might contribute to the low-grade chronic inflammation that characterizes obesity.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-015-0460-8) contains supplementary material, which is available to authorized users.     

Circulating CXCR5+CD4+ T Follicular-Like Helper Cell and Memory B Cell Responses to Human Papillomavirus Vaccines

Through the interaction of T follicular helper (Tfh) cells and B cells, efficacious vaccines can generate high-affinity, pathogen-neutralizing antibodies, and memory B cells. Using CXCR5, CXCR3, CCR6, CCR7, PD1, and ICOS as markers, Tfh-like cells can be identified in the circulation and be classified into three functionally distinct subsets that are PD1⁺ICOS⁺, PD1⁺ ICOS^-, or PD1^-ICOS^-. We used these markers to identify different subsets of CXCR5⁺CD4⁺ Tfh-like cells in response to highly immunogenic and efficacious vaccines for human papillomaviruses (HPV): Cervarix and Gardasil. In this small study, we used PBMC samples from 11 Gardasil recipients, and 8 Cervarix recipients from the Vaccine Research Center 902 Study to examine the induction of circulating Tfh-like cells and IgD^-CD38^HiCD27⁺ memory B cells by flow cytometry. PD1⁺ICOS⁺ CXCR3⁺CCR6^-CXCR5⁺CD4⁺ (Tfh1-like) cells were induced and peaked on Day (D) 7 post-first vaccination, but not as much on D7 post-third vaccination. We also observed a trend toward increase in PD1⁺ICOS⁺ CXCR3^-CCR6^-CXCR5⁺CD4⁺ (Tfh2-like) cells for both vaccines, and PD1⁺ICOS⁺ CXCR3^-CCR6⁺CXCR5⁺CD4⁺ (Tfh17-like) subset was induced by Cervarix post-first vaccination. There were also minimal changes in the other cellular subsets. In addition, Cervarix recipients had more memory B cells post-first vaccination than did Gardasil recipients at D14 and D30. We found frequencies of memory B cells at D30 correlated with anti-HPV16 and 18 antibody titers from D30, and the induction levels of memory B cells at D30 and PD1⁺ICOS⁺Tfh1-like cells at D7 post-first vaccination correlated for Cervarix. Our study showed that induction of circulating CXCR5⁺CD4⁺ Tfh-like subsets can be detected following immunization with HPV vaccines, and potentially be useful as a marker of immunogenicity of vaccines. However, further investigations should be extended to different cohorts with larger sample size to better understand the functions of these T cells, as well as their relationship with B cells and antibodies.