Assessment of drug compliance in patients with high blood pressure resistant to antihypertensive therapy.

The persistence of high blood pressure under antihypertensive treatment (resistant hypertension) entails an increased cardiovascular risk. It occurs in three of ten treated hypertensive patients, and has several possible contributing factors, notably insufficient therapeutic adherence. There are a number of ways to evaluate whether patients take their medication as prescribed. These include interviewing the patient, pill counting, prescription follow-up, assay of drugs in blood or urine, and use of electronic pill dispensers. None is perfect. However, the essential is to discuss with the patient the importance of complying with the treatment as soon as it is prescribed for the first time, and not waiting for the appearance of resistant hypertension. The measurement of blood pressure outside the medical office and the monitoring of adherence may help to identify patients in whom hypertension is truly resistant and so to tailor the measures required to improve the control of blood pressure in the most appropriate manner.

Therapy of steroid-resistant inflammatory bowel disease.

Background and Aims: Although systemic corticosteroids are successfully administered for the induction of clinical response and remission in the majority of patients with inflammatory bowel disease (IBD) presenting with a flare, a proportion of these patients demonstrate a primary nonresponse to steroids or in the case of an initial response, they develop a resistance or a steroid dependence. Long-term therapy with corticosteroids for treatment of IBD should be avoided, given the high frequency of adverse treatment effects. Knowledge about treatment strategies in case of steroid nonresponse is therefore highly relevant. Methods: A systematic literature research was performed using Medline and Embase to summarize the currently recommended treatment strategies for steroid-resistant IBD. Results: Treatment of steroid-resistant Crohn's disease is based on the introduction of immunomodulators such as azathioprine, 6-mercaptopurine or methotrexate, the anti-TNF drugs infliximab, adalimumab and certolizumab pegol. In the case of steroid resistance in ulcerative colitis, aminosalicylates, the above-mentioned immunomodulators, infliximab, adalimumab or calcineurin inhibitors such as ciclosporin or tacrolimus may be administered. Conclusion: This review summarizes the current evidence for treating steroid-resistant IBD.

Beta-lactam resistance mechanisms of methicillin-resistant Staphylococcus aureus.

In vitro and in vivo activity of amoxicillin and penicillin G alone or combined with a penicillinase inhibitor (clavulanate) were tested against five isogenic pairs of methicillin-resistant Staphylococcus aureus (MRSA) producing or not producing penicillinase. Loss of the penicillinase plasmid caused an eight times or greater reduction in the MICs of amoxicillin and penicillin G (from greater than or equal to 64 to 8 micrograms/ml), but not of the penicillinase-resistant drugs methicillin and cloxacillin (greater than or equal to 64 micrograms/ml). This difference in antibacterial effectiveness correlated with a more than 10 times greater penicillin-binding protein 2a affinity of amoxicillin and penicillin G than of methicillin and a greater than or equal to 90% successful amoxicillin treatment of experimental endocarditis due to penicillinase-negative MRSA compared with cloxacillin, which was totally ineffective (P less than .001). Amoxicillin was also effective against penicillinase-producing parent MRSA, provided it was combined with clavulanate. Penicillinase-sensitive beta-lactam antibiotics plus penicillinase inhibitors might offer a rational alternative treatment for MRSA infections.

Enxertia in vitro na propagação de clones de Eucalyptus urophylla e E. grandis

O objetivo deste trabalho foi avaliar a eficiência da enxertia in vitro na propagação de dois clones híbridos de Eucalyptus urophylla e E. grandis. Foram utilizados porta-enxertos juvenis obtidos de sementes de E. grandis e E. urophylla germinadas in vitro. As plantas enxertadas apresentaram pegamento de até 93% aos 50 dias de idade para as combinações de enxerto e porta-enxerto. Quanto ao crescimento em altura, verificaram-se melhores resultados em relação ao porta-enxerto E. urophylla. A análise histológica das plantas enxertadas comprovou a eficiência do processo de cicatrização do calo formado na região de conexão, seguida da reconstituição vascular.

Physiological and anatomical characteristics of leaves of two clones of guarana

The objective of this work was to analyze gas exchange, photosynthetic characteristics, photochemical efficiency of photosystem II and anatomical characteristics of young plant leaves of two guarana (Paullinia cupana) clones (BRS-CG372RC and BRS-CG611RL) growing under open field. The variables of gas exchange and fluorescence of chlorophyll a were evaluated in mature leaves. The values of photosynthesis and transpiration found for BRS-CG372RC were 27% greater and 80% lesser than values found for BRS-CG611RL, respectively. The values of stomatal conductance found for the clones BRS-CG372RC and BRS-CG611RL were in the order of 224 and 614 mmol mm-2 s-1, respectively. The values of photorespiration, rate of carboxylation and rate electron transport were greater in BRS-CG372RC. The clone BRS-CG372RC exhibited stomatal density 26% greater than BRS-CG611RL. However, the area of ostiolar opening was 42% greater in BRS-CG611RL. The values of the water use efficiency in BRS-CG372RC were 134% greater than in BRS-CG611RL. High stomatal density and low stomatal conductance can be important characteristics in the selection of the clones with a good ability to assimilate carbon and optimize the use of water.

Molecular epidemiology of methicillin-resistant Staphylococcus aureus from 4 Cuban hospitals.

During a 1-year period, 87 methicillin-resistant Staphylococcus aureus isolates were collected from 4 major Cuban hospitals for epidemiological analysis. The majority (86%) were related to the community-associated USA300 clone, whereas the remaining belonged to a new clone ST72-V. Interestingly, no hospital-associated clone was found in these Cuban hospitals.

Vigor de clones de umezeiro e pessegueiro 'Okinawa' propagados por estacas herbáceas

O objetivo deste trabalho foi avaliar o vigor de três clones de umezeiro (Prunus mume Sieb. et Zucc.) e do pessegueiro 'Okinawa' [Prunus persica (L.) Batsch], propagados por estacas herbáceas, em condições de campo. O experimento foi conduzido em blocos ao acaso, com quatro tratamentos (genótipos) e cinco repetições. As plantas foram espaçadas 0,5 m entre si. O pessegueiro 'Okinawa' apresentou maior diâmetro do tronco, em relação aos clones de umezeiro. Na análise conjunta das variáveis, o Clone 10 revela-se o menos vigoroso, indicando a possibilidade de sucesso como porta-enxerto ananizante para pessegueiro.

LB11058, a new cephalosporin with high penicillin-binding protein 2a affinity and activity in experimental endocarditis due to homogeneously methicillin-resistant Staphylococcus aureus.

LB11058 is a new synthetic cephalosporin with good affinity for staphylococcal penicillin-binding protein 2a (PBP2a). LB11058 was tested in vitro and in rats with experimental aortic endocarditis against three methicillin-resistant Staphylococcus aureus (MRSA) strains, one penicillinase-negative strain (strain COL), and two penicillinase-producing strains (COL-Bla+ and P8-Hom). The MICs of LB11058 for the organisms were 1 mg/liter. The MICs of vancomycin and ceftriaxone were 1 and >/=64 mg/liter, respectively. In population analysis profiles, none of the MRSA strains grew at >/=2 mg of LB11058/liter. Rats with endocarditis were treated for 5 days. LB11058 was highly bound to serum proteins in rats (>/=98%). However, binding was saturable above a threshold of 250 mg/liter. Therefore, continuous concentrations of 250 mg/liter in serum were infused to ensure a free fraction (>/=5 mg/liter) above the drug's MIC for the entire infusion period. Control treatments included simulation of human serum kinetics produced by intravenous vancomycin (1 g twice daily, free drug concentration above MIC, >/=90% of infusion period) or ceftriaxone (2 g/24 h, free drug concentrations above the MIC, 0% of infusion period). LB11058 successfully treated 10 of 10 (100%) and 13 of 14 (93%) of rats infected with COL-Bla+ and P8-Hom, respectively. This was comparable to vancomycin (sterilization of 8 of 12 [66%] and 6 of 8 [75%] rats, respectively). Ceftriaxone was inactive. Low concentrations of LB11058 (5 and 10 mg/liter, continuously infused) in serum were ineffective, as predicted by the pharmacodynamic parameters. At appropriate doses, LB11058 was highly effective both in vitro and in vivo. This finding supports the development of this beta-lactam with high PBP2a affinity for the treatment of MRSA infections.

Glucocorticoid-induced MIF expression by human CEM T cells.

Macrophage migration inhibitory factor (MIF) is an upstream activator of the immune response that counter-regulates the immunosuppressive effects of glucocorticoids. While MIF is released by cells in response to diverse microbial and invasive stimuli, evidence that glucocorticoids in low concentrations also induce MIF secretion suggests an additional regulatory relationship between these mediators. We investigated the expression of MIF from the human CEM T cell line, which exists in two well-characterized, glucocorticoid-sensitive (CEM-C7) and glucocorticoid-resistant (CEM-C1) variant clones. Dexamethasone in low concentrations induced MIF secretion from CEM-C7 but not CEM-C1 T cells by a bell-shaped dose response that was similar to that reported previously for the release of MIF by monocytes/macrophages. Glucocorticoid stimulation of CEM-C7 T cells was accompanied by an MIF transcriptional response, which by promoter analysis was found to involve the GRE and ATF/CRE transcription factor binding sites. These data support a glucocorticoid-mediated MIF secretion response by T cells that may contribute to the regulation of the adaptive immune response.

Networking of differentially expressed genes in human cancer cells resistant to methotrexate

BACKGROUND: The need for an integrated view of data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance, we constructed biological association networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). METHODS: Seven cell lines representative of different types of cancer, including colon cancer (HT29 and Caco2), breast cancer (MCF-7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. Genes deregulated in common between the different cancer cell lines served to generate biological association networks using the Pathway Architect software. RESULTS: Dikkopf homolog-1 (DKK1) is a highly interconnected node in the network generated with genes in common between the two colon cancer cell lines, and functional validations of this target using small interfering RNAs (siRNAs) showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of genes differentially expressed in the two breast cancer cell lines. siRNA treatment against UGT1A also showed an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was overexpressed among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. CONCLUSIONS: Biological association networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using siRNA technology against these three genes showed chemosensitization toward MTX.

Long term retention of retigabine in a cohort of people with drug resistant epilepsy.

PURPOSE: To assess the utility of retigabine (RTG) for epilepsy in clinical practice at a single UK tertiary centre. METHODS: We identified all individuals who were offered RTG from April 2011 to May 2013. We collected demographics, seizure types, previous and current antiepileptic drugs (AEDs), starting and maximum attained daily dose of RTG, clinical benefits, side effects, and reason to discontinue RTG from in- and outpatient encounters until February 28, 2014. RESULTS: 145 people who had failed a median of 11 AEDs took at least one dose of RTG. One year retention was 32% and decreased following the safety alert by the US Federal Drug Administration (FDA) in April 2013. None became seizure free. 34 people (24%) reported a benefit that was ongoing at last assessment in five (3%). The most relevant benefit was the significant reduction or cessation of drop attacks or seizure-related falls in four women, this persisted at last assessment in two. The presence of simple partial seizures was associated with longer retention, as was a higher attained dose of RTG. Adverse effects were seen in 74% and largely CNS-related or nonspecific and affected the genitourinary system in 13%. CONCLUSION: Retention of RTG was less favourable compared to data from open label extension studies of the regulatory trials. In comparison with historical data on similar retention audits retention of RTG at one year appears to be less than lamotrigine, topiramate, levetiracetam, pregabalin, zonisamide, and lacosamide, and slightly higher than gabapentin.

Viabilidade econômica de diferentes sistemas de sangria em clones de seringueira

O objetivo deste trabalho foi avaliar o desempenho produtivo e os aspectos econômicos de três clones de seringueira [Hevea brasiliensis (Willd. ex Adr. de Juss.) Muell. Arg.], sob nove sistemas de sangria. O experimento foi instalado sob delineamento de blocos ao acaso com parcelas subdivididas no tempo. Os tratamentos principais foram os clones PR 255, RRIM 600 e GT 1, submetidos aos seguintes sistemas de sangria: ½S d/3 6d/7.11m/y.ET 2,5% Pa La 8/y; ½S d/3 6d/7.11m/y.ET 5,0% Pa La 8/y; ½S d/4 6d/7.11m/y.ET 2,5% Pa La 8/y; ½S d/4 6d/7.11m/y.ET 5,0% Pa La 8/y; ½S d/5 6d/7.11m/y.ET 2,5% Pa La 8/y; ½S d/5 6d/7.11m/y.ET 5,0% Pa La 8/y; ½S d/7 6d/7.11m/y.ET 2,5% Pa La 8/y; ½S d/7 6d/7.11m/y.ET 5,0% Pa La 8/y e ½S d/2 6d/7.11m/y (testemunha). As variáveis estudadas foram: perímetro do caule, produtividade de borracha seca e secamento do painel. Também foi avaliada a viabilidade econômica dos sistemas de sangria. Observaram-se maior produtividade e rentabilidade dos sistemas ½S d/3.ET 2,5% 8/y para os clones PR 255 e RRIM 600 e ½S d/7.ET 2,5% 8/y para o clone GT 1, comparados com a testemunha. A maior e a menor porcentagem de secamento do painel foram observadas nos sistemas ½S d/3 ET 5,0% 8/y e ½S d/7.ET 5,0% 8/y, respectivamente.

Sistemas de explotação de seringueira utilizados em clones asiáticos Prang Besar no Oeste paulista

O objetivo deste trabalho foi avaliar o desempenho produtivo e os aspectos fisiológicos e econômicos de quatro clones asiáticos Prang Besar de seringueira [Hevea brasiliensis (Willd. ex A. Juss.) Muell. Arg.], sob diferentes sistemas de sangria. O experimento foi instalado na Fazenda Santa Gilda, Município de Guararapes, SP, em delineamento de blocos ao acaso, com parcelas subdivididas no tempo. Os tratamentos principais foram os clones PB 260, PB 235, PB 330 e PB 217, submetidos a nove sistemas de sangria: ½S d/3.ET 2,5% 8/y; ½S d/3.ET 5% 8/y; ½S d/4.ET 2,5% 8/y; ½S d/4.ET 5% 8/y; ½S d/5.ET 2,5% 8/y; ½S d/5.ET 5% 8/y; ½S d/7.ET 2,5% 8/y; ½S d/7.ET 5% 8/y e ½S d/2 (testemunha). As variáveis avaliadas foram: perímetro do caule, produção de borracha seca, secamento do painel; foi avaliada, também, a viabilidade econômica. Os resultados mostram a superioridade econômica dos sistemas ½S d/5.ET 2,5% 8/y e ½S d/7.ET 5% 8/y, para o clone PB 260; ½S d/7.ET 2,5% 8/y para o clone PB 235; e ½S d/3.ET 2,5% 8/y e ½S d/3.ET 5% 8/y, para os clones PB 330 e PB 217, comparados com a testemunha. A menor incidência de secamento do painel foi observada no sistema ½S d/7.ET 5% 8/y, exceto para o clone PB 235.