Cell type-specific acquired protection from crystal adherence by renal tubule cells in culture

BACKGROUND: Adherence of crystals to the surface of renal tubule epithelial cells is considered an important step in the development of nephrolithiasis. Previously, we demonstrated that functional monolayers formed by the renal tubule cell line, Madin-Darby canine kidney (MDCK), acquire protection against the adherence of calcium oxalate monohydrate crystals. We now examined whether this property is cell type specific. The susceptibility of the cells to crystal binding was further studied under different culture conditions. METHODS: Cell-type specificity and the influence of the growth substrate was tested by comparing calcium oxalate monohydrate crystal binding to LLC-PK1 cells and to two MDCK strains cultured on either permeable or impermeable supports. These cell lines are representative for the renal proximal tubule (LLC-PK1) and distal tubule/collecting duct (MDCK) segments of the nephron, in which crystals are expected to be absent and present, respectively. RESULTS: Whereas relatively large amounts of crystals adhered to subconfluent MDCK cultures, the level of crystal binding to confluent monolayers was reduced for both MDCK strains. On permeable supports, MDCK cells not only obtained a higher level of morphological differentiation, but also acquired a higher degree of protection than on impermeable surfaces. Crystals avidly adhered to LLC-PK1 cells, irrespective of their developmental stage or growth substrate used. CONCLUSIONS: These results show that the prevention of crystal binding is cell type specific and expressed only by differentiated MDCK cells. The anti-adherence properties acquired by MDCK cells may mirror a specific functional characteristic of its in situ equivalent, the renal distal tubule/collecting ducts.     

Benefits of leisure-time physical activity on the cardiovascular risk profile at older age.

BACKGROUND: Intensity, frequency and duration of physical activity may contribute in different ways to the maintenance of cardiovascular health. Their relative importance may also change at different stages in life and this should be taken into account for activity recommendations. METHODS: The relationship of frequency and duration of leisure-time physical activities with cardiovascular risk factors was studied in 4942 male and 5885 female participants aged 50-69, of the German Cardiovascular Prevention Study (1984-1991). RESULTS: After adjustment for several possible confounders, women with modest levels (2-12 times per month, 0.5-2 h per week) of moderate-to-vigorous activity (> or =5 kcal/kg/h) had significantly lower systolic blood pressure (-1.8%), resting heart rate (-3.1%) and body mass index (-3.2%) values than sedentary women. Beneficial differences increased with frequency and duration of activity. Light activities (3-4.5 kcal/kg/h), conducted > or =5 times a week, were significantly associated with favourable lower diastolic blood pressure (-1.4%), resting heart rate (-2.3%) among women, and body mass index (women -2.9%, men -2.2%) among both genders. Recommended activity levels (> or =5 times, > or =3.5 h weekly) were associated with a lower prevalence of multiple risk factors (odds ratio [OR] = 0.55, 95% CI: 0.41-0.75 for men and OR = 0.44 95% CI: 0.31-0.63 for women). CONCLUSIONS: For sedentary elderly, even less physical activity than currently recommended, is likely to improve the cardiovascular risk profile.     

The theory of planned behavior: a review of its applications to health-related behaviors

PURPOSE: To review applications of Ajzen's theory of planned behavior in the domain of health and to verify the efficiency of the theory to explain and predict health-related behaviors. METHODS: Most material has been drawn from Current Contents (Social and Behavioral Sciences and Clinical Medicine) from 1985 to date, together with all peer-reviewed articles cited in the publications thus identified. FINDINGS: The results indicated that the theory performs very well for the explanation of intention; an averaged R2 of .41 was observed. Attitude toward the action and perceived behavioral control were most often the significant variables responsible for this explained variation in intention. The prediction of behavior yielded an averaged R2 of .34. Intention remained the most important predictor, but in half of the studies reviewed perceived behavioral control significantly added to the prediction. CONCLUSIONS: The efficiency of the model seems to be quite good for explaining intention, perceived behavioral control being as important as attitude across health-related behavior categories. The efficiency of the theory, however, varies between health-related behavior categories.     

Virgidivarine, a New Alkaloid of Virgilia divaricata

Virgidivarine, C (15)H (26)N (2)O (2), is a new dipiperidine alkaloid, isolated from the South African VIRGILIA DIVARICATA Leguminosae. Its systematic name is 3-carboxy-N-(4'-butenyl)-5-(2'-piperidyl) piperidine.     

Dietary fructans modulate polyamine concentration in the cecum of rats

Nondigestible but fermentable dietary fructans such as oligofructose exert many effects on gut physiology through their fermentation end products such as short-chain fatty acids. Could other metabolites be produced in the gut and contribute to the physiologic effects of dietary fructans? The aim of the study was to evaluate the influence of oligofructose on putrescine, spermidine and spermine concentrations in the cecum, the portal vein and the liver of rats and to assess their involvement in cecal enlargement and the modulation of hepatic lipid metabolism. Putrescine, spermidine and spermine were quantified by HPLC in samples obtained from male Wistar rats fed a nonpurified standard diet (controls) or the same diet enriched with 10 g/100 g oligofructose (OFS) for 4 wk. OFS-fed rats had significantly greater cecal content and tissue weights. OFS almost doubled the concentration of putrescine in the cecal contents. The concentration of all three polyamines in the cecal tissue was significantly greater than in controls. The concentration of spermidine in portal plasma was lower in rats fed OFS, whereas the treatment did not affect the polyamine concentrations in the liver. The fermentation of dietary fructans contributed to an increase in the concentration of putrescine in the gut without modifying putrescine concentration in either the portal blood or liver. Moreover, the greater levels of polyamines in cecal tissue may be related to the cell proliferation resulting from OFS fermentation in the gut.     

Dibenzo[a,l]pyrene-induced DNA adduction, tumorigenicity, and Ki-ras oncogene mutations in strain A/J mouse lung

Dibenzo[a,l]pyrene (DB[a,l]P), an environmental polycyclic aromatic hydrocarbon, is the most potent carcinogen ever tested in mouse skin and rat mammary gland. In this study, DB[a,l]P was examined for DNA adduction, tumorigenicity, and induction of Ki-ras oncogene mutations in tumor DNA in strain A/J mouse lung. Groups of mice received a single i.p. injection of 0.3, 1.5, 3.0, or 6.0 mg/kg DB[a,l]P in tricaprylin. Following treatment, DNA adducts were measured at times between 1 and 28 days, while tumors were counted at 250 days and analyzed for the occurrence of point mutations in codons 12 and 61 of the Ki-ras oncogene. DB[a,l]P in strain A/J mouse lung induced six major and four minor DNA adducts. Maximal levels of adduction occurred between 5 and 10 days after injection followed by a gradual decrease. DB[a,l]P-DNA adducts in lung tissue were derived from both anti- and syn-11,12- dihydroxy-13,14-epoxy- 11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE) and both deoxyadenosine (dAdo) and deoxyguanosine (dGuo) residues in DNA as revealed by cochromatography. The major adduct was identified as a product of the reaction of an anti-DB[a,l]PDE with dAdo in DNA. DB[a,l]P induced significant numbers of lung adenomas in a dose- dependent manner, with the highest dose (6.0 mg/kg) yielding 16.1 adenomas/mouse. In tricaprylin-treated control animals, there were 0.67 adenomas/mouse. Based on the administered dose, DB[a,l]P was more active than other environmental carcinogens including benzo[a]pyrene. As a function of time-integrated DNA adduct levels, DB[a,l]P induced lung adenomas with about the same potency as other PAHs, suggesting that the adducts formed by DB[a,l]P are similar in carcinogenic potency to other PAHs in the strain A/J mouse lung model. Analysis of the Ki- ras mutation spectrum in DB[a,l]P-induced lung tumors revealed the predominant mutations to be G-->T transversions in the first base of codon 12, A-->G transitions in the second base of codon 12, and A-->T transversions in the second or third base of codon 61, concordant with the DNA adduct profile.      

Early stage nasopharyngeal carcinoma: radiotherapy dose and time factors in tumor control

OBJECTIVE: To evaluate radiotherapy dose and length of treatment in the control of early stage nasopharyngeal carcinoma (NPC) treated with a combination of external radiotherapy and brachytherapy, MATERIALS & METHODS: We reviewed the records of 133 patients with early stage nasopharyngeal carcinoma (stage I or II, AJC/UICC staging system) who received definitive radiotherapy in Chang Gung Memorial Hospital from 1979 to 1991. The median follow-up time was 7.1 years with a minimum of 2 years. All patients were treated with megavoltage external radiotherapy to the nasopharynx area (63-72 Gy) followed by high dose rate intracavitary brachytherapy (5-16.5 Gy in one to three fractions, spaced 1-2 weeks apart). The median total dose and time of irradiation was 75 Gy (69.8-81.4 Gy) and 11.6 weeks (7.8-20 weeks) respectively. Survival analysis was used to examine the effect of several variables on prognosis. RESULTS: The 5-year rates were 86.4% for local control, 84.7% for disease free survival, 88.5% for actuarial survival and 84.2% for overall survival. The treatment group (combination of time and dose of irradiation) was the most important prognostic factor according to Cox's proportional hazard model. Patients receiving radiation at a total dose of < or = 75 Gy completed in < 12 weeks showed the best prognosis. CONCLUSION: Treatment time and total treatment dose are both important factors in treating early stage NPC. Decreasing the total radiation time to < 12 weeks and not exceeding a radiation dose of 75 Gy gave the best results.      

A multi-biomarker approach to study the effects of smoking on oxidative DNA damage and repair and antioxidative defense mechanisms

Carcinogenesis,      

CYP1A2 and NAT2 genotype/phenotype relations and urinary excretion of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a human dietary intervention study.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking, and is subsequently metabolically activated by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). Respective genes encoding for these enzymes, display polymorphic distribution in the human population and are thus believed to cause interindividual differences in cancer risk susceptibility. The present study investigated the influence of dietary exposure and CYP1A2 and NAT2 genotypes and phenotypes on differential urinary PhIP excretion levels in 71 human volunteers after consumption of either a high (7.4 ng/g) or low (1.7 ng/g) dose of PhIP. Urinary PhIP excretion levels were found to reflect recent dietary exposure levels, with average levels of 174% (high dose group) and 127% (low dose group), as compared to pre-feed levels. Urinary caffeine metabolite ratios were significantly different between the two NAT2 genotypes, whereas for CYP1A2, the apparent difference in metabolic ratios between the genotypes was statistically non-significant. Significant correlations were firstly found between the CYP1A2-164A-->C (CYP1A2*1F) polymorphism and differential urinary PhIP excretion levels. Although the found correlations are driven primarily by a small number of subjects possessing the homozygous variant constellation, the strong influence of this genotype indicates that the CYP1A2*1F polymorphism could play an important role in human cancer risk susceptibility.