Isradipine Twice Daily Lowers Blood Pressure Over 24 H

The objective of this study was to compare the effects of isradipine and placebo on blood pressure (BP) at the end of the dosing interval (‘trough'). Following a three-week placebo period, 187 patients who had previously shown a response to treatment with isradipine (based on office BP measurements) were randomized to double-blind treatment with 2.5 mg isradipine twice daily or placebo for six weeks. Four of these patients withdrew from the study during the double-blind phase because of adverse events (one taking isradipine and three taking placebo). Blood pressure during the double-blind study was always measured 12 h after drug administration (trough values). The rate of normalization [defined as diastolic BP (DBP) ≤ 90 mm Hg] was 52/96 (54%) in the isradipine-treated group compared with 30/87 (33%) in the placebo group. A further 12/96 (12%) patients taking isradipine showed a fall in DBP of ≥ 10 mm Hg, although their DBP was still not < 90 mm Hg, compared with 5/87 (6%) patients receiving placebo. This difference was statistically significant (P = .003). Thus, isradipine in a dose of 2.5 mg twice daily lowers blood pressure over 24 h. Am J Hypertens 1991;4:131S-134

Ceftriaxone for the Treatment of Chronic Bacterial Prostatitis:A Case Series and Literature Review

Chronic bacterial prostatitis is increasingly difficult to treat due to rising antimicrobial resistance limiting oral treatment options. In this case series, 11 men with CBP (including patients with urological comorbidities) due to multi-resistant E. coli were treated with once-daily ceftriaxone intravenously for 6 weeks. Nine patients were clinically cured at 3 months follow up. No early withdrawal of medication due to side effects occurred. A literature review was conducted to describe the prostate pharmacokinetics of ceftriaxone and its use in prostatic infection. In conclusion, ceftriaxone can be considered an appropriate treatment of chronic bacterial prostatitis

Nonsteroidal anti-inflammatory drug use and Alzheimer's disease risk: the MIRAGE Study

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAID) use may protect against Alzheimer's disease (AD) risk. We sought examine the association between NSAID use and risk of AD, and potential effect modification by APOE-ε4 carrier status and ethnicity. METHODS: The MIRAGE Study is a multi-center family study of genetic and environmental risk factors for AD. Subjects comprised 691 AD patients (probands) and 973 family members enrolled at 15 research centers between 1996 and 2002. The primary independent and dependent variables were prior NSAID use and AD case status, respectively. We stratified the dataset in order to evaluate whether the association between NSAID use and AD was similar in APOE-ε4 carriers and non-carriers. Ethnicity was similarly examined as an effect modifier. RESULTS: NSAID use was less frequent in cases compared to controls in the overall sample (adjusted OR = 0.64; 95% CI = 0.38–1.05). The benefit of NSAID use appeared more pronounced among APOE-ε4 carriers (adjusted OR = 0.49; 95% CI = 0.24–0.98) compared to non-carriers, although this association was not statistically significant. The pattern of association was similar in Caucasian and African Americans. CONCLUSIONS: NSAID use is inversely associated with AD and may be modified by APOE genotype. Prospective studies and clinical trials of sufficient power to detect effect modification by APOE-ε4 carrier status are needed

Modification of Cu surface with picosecond laser pulses

High purity, mirror-polished polycrystalline Cu surface was treated with single picosecond laser pulses at fluence levels close to the single-pulse modification threshold. The induced surface topography and sub-surface changes were examined with scanning and transmission electron microscopy, respectively. The analysis showed an increased absorption of laser energy on the microscopic surface topography inhomogeneities, even at a fluence level below the modification threshold. Many features, like spikes, bubbles, spheres, as well as small periodic ripples at the bottom of scratches, reveal a significant influence of melting and eruptive relaxation of the absorbed laser energy on the final appearance of the surface. Further, it was found that thermal stresses result in twinning to a depth of few tens of nanometers under the surface. Voids at this depth have been observed as well. The results of the observations provide new insights into the early stages of the picosecond laser pulse modification of metals, especially metals witha weak electron-phonon coupling. (C) 2014 Elsevier B.V. All rights reserved

Next-generation muscle-directed gene therapy by in silico vector design

There is an urgent need to develop the next-generation vectors for gene therapy of muscle disorders, given the relatively modest advances in clinical trials. These vectors should express substantially higher levels of the therapeutic transgene, enabling the use of lower and safer vector doses. In the current study, we identify potent muscle-specific transcriptional cisregulatory modules (CRMs), containing clusters of transcription factor binding sites, using a genome-wide data-mining strategy. These novel muscle-specific CRMs result in a substantial increase in muscle-specific gene transcription (up to 400-fold) when delivered using adeno-associated viral vectors in mice. Significantly higher and sustained human micro-dystrophin and follistatin expression levels are attained than when conventional promoters are used. This results in robust phenotypic correction in dystrophic mice, without triggering apoptosis or evoking an immune response. This multidisciplinary approach has potentially broad implications for augmenting the efficacy and safety of muscle-directed gene therapy

Changes in the ceIl membrane of Lactobacillus bulgaricus during storage following freeze-drying

The mechanism of inactivation of freeze-dried Lactobacillus bulgaricus during storage in maltodextrin under controlled humidity was investigated. Evidence is presented supporting the hypothesis that membrane damage occurs during storage. A study on the lipid composition of the cells by gas chromatography showed a decrease in the unsaturated and saturated fatty acid content of the cell. Further evidence indicating membrane damage includes a decrease in membrane bound proton-translocating ATPase activity

In Vitro Proliferation of Adult Human Beta-Cells

A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1) analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide

Omics analysis of educated platelets in cancer and benign disease of the pancreas

Pancreatic ductal adenocarcinoma (PDAC) is traditionally associated with thrombocytosis/hypercoagulation and novel insights on platelet-PDAC “dangerous liaisons” are warranted. Here we performed an integrative omics study investigating the biological processes of mRNAs and expressed miRNAs, as well as proteins in PDAC blood platelets, using benign disease as a reference for inflammatory noise. Gene ontology mining revealed enrichment of RNA splicing, mRNA processing and translation initiation in miRNAs and proteins but depletion in RNA transcripts. Remarkably, correlation analyses revealed a negative regulation on SPARC transcription by isomiRs involved in cancer signaling, suggesting a specific ”education” in PDAC platelets. Platelets of benign patients were enriched for non-templated additions of G nucleotides (#ntaG) miRNAs, while PDAC presented length variation on 3′ (lv3p) as the most frequent modification on miRNAs. Additionally, we provided an actionable repertoire of PDAC and benign platelet-ome to be exploited for future studies. In conclusion, our data show that platelets change their biological repertoire in patients with PDAC, through dysregulation of miRNAs and splicing factors, supporting the presence of de novo protein machinery that can “educate” the platelet. These novel findings could be further exploited for innovative liquid biopsies platforms as well as possible therapeutic targets