Effect of captopril on prostacyclin and nitric oxide formation in healthy human subjects: Interaction with low dose acetylsalicylic acid

1Angiotensin converting enzyme inhibitors have been suggested to act in part by potentiating the stimulatory effect of bradykinin on endothelial prostacyclin and/or nitric oxide (NO) formation. This may give rise to interaction with cyclo-oxygenase inhibiting drugs like acetylsalicylic acid, which is most often used in low doses in patients with cardiovascular diseases. 2We investigated the effects of captopril (2×25 mg day⁻¹), or ASA (1×100 mg day⁻¹), or the combination of both drugs for 7 days, on blood pressure, prostanoid and NO formation rates in a double-blind, double dummy, randomized crossover study in 13 healthy female subjects. The urinary metabolites of thromboxane A₂ (2,3-dinor-TXB₂) and prostacyclin (2,3-dinor-6-keto-PGF_1α), and PGE₂ were measured by gas chromatography/tandem mass spectrometry in urine on days 1, 6 and 7 of each medication. NO formation was assessed using urinary NO3− and cyclic GMP as indicators. 3Urinary 2,3-dinor-6-keto-PGF_1α excretion was not significantly changed by either captopril, ASA, or their combination. Urinary 2,3-dinor-TXB₂ excretion was inhibited by >80% by ASA alone or in combination with captopril (each P<0.05), but was not affected by captopril alone. Urinary PGE₂ excretion was not significantly changed by either of the treatments. Urinary NO3− and cyclic GMP excretion rates were not significantly changed by captopril, ASA, or their combination. 4Blood pressure was slightly reduced by captopril. ASA had no effect on blood pressure when given alone, nor did it modulate the effect of captopril on blood pressure during co-administration. Angiotensin II/angiotensin I ratio (index of ACE activity) was significantly decreased by captopril alone or in combination with ASA, but was unaffected by ASA alone. 5Captopril does not stimulate prostacyclin formation in healthy human subjects in a dose sufficient to substantially inhibit ACE activity. Co-administration of ASA significantly inhibits 2,3-dinor-TXB₂ excretion, but does not interfere with the blood pressure lowering effect of captopril in healthy human subjects.     

Association of Nutrition Education and Its Interaction with Lifestyle Factors on Kidney Function Parameters and Cardiovascular Risk Factors among Chronic Kidney Disease Patients in Taiwan

We evaluated the interactive effects of nutrition education (NE) and lifestyle factors on kidney function parameters and cardiovascular risk factors among chronic kidney disease (CKD) patients. This cross-sectional cohort study recruited 2176 CKD stages 3–5 patients aged > 20 years from Integrated Chronic Kidney Disease Care Network, Shuang Ho Hospital, Taiwan between December 2008 and April 2019. The multivariable regression analysis was performed to investigate the interactive effects of NE with lifestyle factors on kidney function parameters and cardiovascular risk factors. Relative excess risk due to interaction (RERI) and attributable proportion (AP) were applied to assess additive interaction. Patients who were smoking or physically inactive but received NE had better estimated glomerular filtration rate (eGFR) (β: 3.83, 95% CI: 1.17–6.49 or β: 3.67, 95% CI: 2.04–5.29) compared to those without NE. Patients with smoking and NE significantly reduced risks for having high glycated hemoglobin A_1c (HbA_1c) by 47%, high low-density lipoprotein cholesterol (LDL-C) by 38%, and high corrected calcium (C-Ca) by 50% compared to those without NE. Moreover, NE and smoking or inactive physical activity exhibited an excess risk of high C-Ca (RERI: 0.47, 95% CI: 0.09–0.85 for smoking or RERI: 0.46, 95% CI: 0.01–0.90 and AP: 0.51, 95% CI: 0.03–0.99 for physical activity). Our study suggests that CKD patients who were enrolled in the NE program had better kidney function. Thus, NE could be associated with slowing kidney function decline and improving cardiovascular risk factors.     

Bordetella pertussis Clones Identified by Multilocus Variable-Number Tandem-Repeat Analysis

Multilocus variable-number tandem-repeat analysis (MLVA) of 316 Bordetella pertussis isolates collected over 40 years from Australia and 3 other continents identified 66 MLVA types (MTs), including 6 predominant MTs. Typing of genes encoding acellular vaccine antigens showed changes that may be vaccine driven in 2 MTs prevalent in Australia.     

Most of the response elicited against Wolbachia surface protein in filarial nematode infection is due to the infective larval stage

Immune responses to the intracellular Wolbachia bacteria of filarial nematodes are thought to contribute to the pathologic process of filarial infection. Here, we compare antibody responses of subjects living in an area where lymphatic filariasis is endemic with antibody responses elicited in a murine model of filarial infection, to provide evidence that the infective larval stage (L3), not adult nematodes, are the primary inducer of responses against Wolbachia. In human subjects, antibody responses to Brugia malayi Wolbachia surface protein (WSP) are most often correlated with antibody responses to the L3 stage of B. malayi. Analysis of anti-WSP responses induced in mice by different stages of the rodent filariae Litomosoides sigmodontis shows that the strongest anti-WSP response is elicited by the L3 stage. Although adult filarial nematode death may play a role in the generation of an anti-WSP response, it is the L3 stage that is the major source of immunogenic material, and incoming L3 provide a continual boosting of the anti-WSP response. Significant exposure to the endosymbiotic bacteria may occur earlier in nematode infection than previously thought, and the level of exposure to infective insect bites may be a key determinant of disease progression.     

Microscopic diffusion anisotropy in formalin fixed prostate tissue: Preliminary findings

Diffusion tensor microimaging at 16.4 T with 40 μm isotropic voxels was used to investigate anisotropic water diffusion in prostate tissue at spatial resolution approaching the cellular scale. Nine normal glandular tissue samples were collected from the peripheral zone of six formalin fixed radical prostatectomy specimens. Fibromuscular stromal tissue exhibited microscopic diffusion anisotropy (mean fractional anisotropy range 0.47–0.66) significantly higher (P < 0.01, Student's t‐test) than in epithelium‐containing voxels (mean fractional anisotropy range 0.31–0.54) in six of the seven normal tissue samples in which both compartments could be measured. Fiber tracking demonstrated principle stromal fiber directions consistent with myocyte orientation seen on light microscopy of the same sample. Diffusion tensor microimaging may be valuable for investigation of variable results from attempts to measure diffusion anisotropy in the prostate in vivo. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.