The Interaction of Hydrochlorothiazide with Spirapril: A Novel Ace Inhibitor

In an open-label, randomized trial using a 3 x 3 Latin square design, single doses of 24 mg of the ACE inhibitor spirapril, or 50 mg hydrochlorothiazide, or their combination were given to 18 healthy male volunteers. No alteration in the area under plasma drug concentration curve (AUC), peak plasma level, time to peak level, or elimination half-life was detected for hydrochlorothiazide, spirapril, or its active metabolite, spiraprilat, during combination therapy. It was concluded that there was no significant effect of spirapril on single-dose kinetics of hydrochlorothiazide, nor of hydrochlorothiazide on single-dose kinetics of spirapril. Significant reductions in systolic blood pressure were noted 2--6 h after either spirapril or combination treatment, but no evidence of any synergistic effect of single-dose effects on blood pressure was seen during combination therapy.     

Assessment of left ventricular function: comparison between radionuclide angiography and semiquantitative two-dimensional echocardiographic analysis

Measurement of global left ventricular function is important in the follow-up of cardiac patients and is a good prognostic indicator in acute cardiac situations. We compared quantitative measurements of global left ventricular function made with radionuclide angiography (RNA) and contrast cardiac ventriculography (CVG) to visual semiquantitative estimates from two-dimensional echocardiographic images (2D-echo). Three hundred and thirty-nine consecutive patients who underwent RNA were assessed with 2D-echo within 3 months. In addition, 92 of these patients also underwent CVG (correlation of ejection fraction between CVG and RNA:r=0.82;P<0.0001). The RNA mean ejection fractions in the four 2D-echo groups (0=normal, 1=slightly, 2=moderate, or 3=severe reduced left ventricular function) differed markedly (P<0.0001); however, there was overlapping among the groups (2D-echo score/RNA ejection fraction: 0=57.3%±12.8%; 1=46.0%±12.9%; 2=29.6%±12.2%; and 3=24.6%±11.5%) and the difference between 2D-echo scores 2 and 3 was not significant. 2D-echo showed a good concordance in RNA classes (0=505; 1=35%–49%; 2=21%–34%; and 3=520% ejection fraction) 0 (133/166; 80%) and 3 (18/30; 60%) but low concordance in classes 1 (27/82; 33%) and 2 (21/61; 34%). For accurate assessment of global left ventricular ejection fraction, visual semiquantitative judgement of a 2D echocardiographic image is limited in comparison to CVG or RNA, especially in patients with a slight or moderate reduction in left ventricular ejection fraction.     

Relative importance of psychologic factors in denture satisfaction

The aim of this investigation was to explore the relative importance of psychologic variables in explaining the degree of denture satisfaction in full denture patients. A group of 125 patients who were on a waiting list to have new dentures constructed participated in this study. The patients completed the Dutch version of the Hopkins Symptom Checklist, the Dutch Personality Inventory, a denture satisfaction questionnaire and a denture complaint questionnaire. No relation was found between the personality variables and denture satisfaction as measured by the denture satisfaction questionnaire. When the different aspects of denture satisfaction were measured by means of complaint scales, satisfaction was related to personality traits. Functional complaints of the mandibular denture and complaints about a hollow face were related to the personality trait "extraversion-introversion". Vague denture complaints and complaints about a bulbous face were related to "neuroticism".     

Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by incorporation of lipid based formulations.

Astaxanthin is a carotenoid with antioxidant properties, synthesised by plants and algae, and distributed in marine seafood. Astaxanthin is also available as a food supplement, but, like other carotenoids, is a very lipophilic compound and has low oral bioavailability. However, bioavailability can be enhanced in the presence of fat. There is not much information in the literature about the pharmacokinetics of oral astaxanthin in humans. In this open parallel study, healthy male volunteers received a single dose of 40 mg astaxanthin, as lipid based formulations or as a commercially available food supplement, followed by blood sampling for further analysis of plasma concentrations. Pharmacokinetic parameters were calculated to evaluate the extent and rate of absorption from each formulation. The elimination half-life was 15.9+/-5.3 h (n=32), and showed a mono-phasic curve. Three lipid based formulations: long-chain triglyceride (palm oil) and polysorbate 80 (formulation A), glycerol mono- and dioleate and polysorbate 80 (formulation B), and glycerol mono- and dioleate, polysorbate 80 and sorbitan monooleate (formulation C), all showed enhanced bioavailability, ranging from 1.7 to 3.7 times that of the reference formulation. The highest bioavailability was observed with formulation B, containing a high content of the hydrophilic synthetic surfactant polysorbate 80.     

No evidence of an association of JC virus and colon neoplasia.

JC virus (JCV) is an ubiquitous human polyomavirus that frequently resides in the kidneys of healthy individuals and is excreted in the urine of a large proportion of the adult population. Polyomaviruses are associated with disease largely in immunocompromised individuals (progressive multifocal leukoencephalopathy). Colorectal cancers can show chromosome instability and it was hypothesized that JCV may account for some of this instability. We screened urine from 45 healthy donors and 233 colorectal cancer/normal tissue pairs for the presence of JCV sequences using a Taqman assay. This assay could detect 1 virus genome in 10 human genomes. In the urine samples, we found an infection rate of approximately 70%. The JCV isolates in these samples could be categorized into four JCV types (2B, 4, 7, and 8), none of which had a rearranged regulatory region. Among the colon tissues, one normal tissue (<0.5%) and none of the matched tumors tested positive for JCV. There is no evidence in these data to indicate that JCV is the cause of genetic instability in colorectal cancer.     

Mammographic density in relation to daidzein-metabolizing phenotypes in overweight, postmenopausal women.

Circulating hormones are associated with mammographic density, an intermediate marker of breast cancer risk. Differences in circulating hormones, including estrone and testosterone, have been observed in premenopausal women based on their capacity to metabolize daidzein, an isoflavone found predominantly in soybeans. Equol and O-desmethylangolensin (O-DMA) are products of intestinal bacterial metabolism of daidzein. There is interindividual variability in the capacity to produce daidzein metabolites; individuals can be equol producers or non-producers and O-DMA producers or non-producers. We tested the hypothesis that daidzein-metabolizing phenotypes are associated with mammographic density. Participants were recruited from among 92 sedentary, postmenopausal women, ages 50 to 75 years, who participated in a 1-year physical activity intervention. Pre-intervention mammographic density was determined using a computer-assisted, gray-scale thresholding technique. Fifty-five of these women consumed supplemental soy protein (>10 mg daidzein/d) for 3 days and collected a first-void urine sample on the fourth day to determine daidzein-metabolizing phenotypes. Equol and O-DMA concentrations were measured using gas chromatography-mass spectrometry. Associations between daidzein-metabolizing phenotypes and percent mammographic density were adjusted for age, maximum adult weight, gravidity, family history of breast cancer, and serum follicle-stimulating hormone and free testosterone concentrations. Mammographic density was 39% lower in equol producers compared with non-producers (P = 0.04). O-DMA producers had mammographic density 69% greater than non-producers (P = 0.05). These results suggest that particular intestinal bacterial profiles are associated with postmenopausal mammographic density, and these associations are not entirely explained by differences in reproductive or anthropometric characteristics or circulating hormones.     

Flavonoids and breast cancer risk in Italy.

Few epidemiologic studies have investigated the potential relation between flavonoids and breast cancer risk. We have applied recently published data on the composition of foods and beverages in terms of six principal classes of flavonoids (i.e., flavanones, flavan-3-ols, flavonols, flavones, anthocyanidines, and isoflavones) on dietary information collected in a large-case control study of breast cancer conducted in Italy between 1991 and 1994. The study included 2,569 women with incident, histologically confirmed breast cancer, and 2,588 hospital controls. Odds ratios (OR) and 95% confidence intervals were estimated by multiple logistic regression models. After allowance for major confounding factors and energy intake, a reduced risk of breast cancer was found for increasing intake of flavones (OR, 0.81, for the highest versus the lowest quintile; P-trend, 0.02), and flavonols (OR, 0.80; P-trend, 0.06). No significant association was found for other flavonoids, including flavanones (OR, 0.95), flavan-3-ols (OR, 0.86), anthocyanidins (OR, 1.09), as well as for isoflavones (OR, 1.05). The findings of this large study of an inverse association between flavones and breast cancer risk confirm the results of a Greek study.     

Delivery and stability of LHRH and Nafarelin in human skin: the effect of constant/pulsed iontophoresis.

Poor absorption and stability of peptides are the major obstacles concerning the development of therapeutically relevant iontophoretic devices for the transdermal delivery of peptides. The present study examined the impact of constant and pulsed (direct/alternating) current profiles on the transport and stability of two decapeptides LHRH and Nafarelin. The stability of these peptides was studied in a physiological buffer solution, with electrical current, and when the peptide solution was exposed to the stratum corneum or to the epidermal/dermal side of human skin. Pulsed direct current profile was shown to be the most efficient in transporting both LHRH and Nafarelin across the human epidermis. Furthermore, the percentage of intact LHRH in the receiver phase was slightly higher when a pulsed current profile was used. Both the peptides were stable in a physiological buffer and under the influence of current, but LHRH was degraded especially in contact with the dermal side of the skin. Altogether five hydrolytic degradation products of LHRH were observed, and they were identified by LC-ESI/MS and LC-ESI/MS/MS. No degradation products of Nafarelin were observed. It is concluded that the pulsed direct current profile may provide at least a partial solution for the transdermal delivery of peptides in terms of improved transport efficacy and peptide stability.