Prenatal exposure to airborne polychlorinated biphenyl congeners and male reproductive health.

STUDY QUESTION: Is fetal exposure to lower-chlorinated polychlorinated biphenyls (LC-PCBs) in indoor air of private homes built with PCB-containing materials associated with semen characteristics and testicular volume in adult men? SUMMARY ANSWER: We observed only marginal and inconsistent associations between maternal exposure to PCBs in indoor air and semen quality, testicular size and reproductive hormones in the adult offspring. WHAT IS KNOWN ALREADY: Recent studies have shown LC-PCBs to exhibit endocrine-disrupting properties and increase the risk of cryptorchidism. Although exposure to LC-PCBs in indoor air is relatively common, the long-term impact of prenatal exposure on male reproductive health has not yet been investigated. STUDY DESIGN, SIZE, DURATION: In this cohort study, participants were men (18+ years) whose mothers carried them while living in one of two residential areas where indoor air had been contaminated by LC-PCB evaporating from building materials in subsets of the apartments. Men were considered prenatally exposed if their mother had lived in a PCB-contaminated apartment and unexposed if their mother had lived in an uncontaminated apartment for a minimum of 1 year during the 3.6 years before conception or during the first trimester. Mothers of prenatally unexposed men could not have lived in a contaminated apartment at any point. Recruitment lasted from 2017 to 2019. In total, 73 exposed and 111 unexposed men gave a blood and semen sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: Percentage differences in semen volume, sperm concentration, total sperm count, morphologically normal spermatozoa, progressively motile spermatozoa and DNA fragmentation index (DFI) between prenatally exposed and unexposed men were estimated using negative binomial regression. Associations with total and calculated free testosterone (CFT), LH and FSH were modeled using the linear regression. Odds of small testicular volume was estimated with logistic regression. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, the results of this study were conflicting. No differences in semen volume, sperm concentration, testosterone and CFT were observed between the groups, but there were slight indications of lower total sperm count, increased FSH and risk of small testicles, alongside lower sperm DFI and a higher proportion of normal spermatozoa in men exposed to LCB-PCBs from indoor air during fetal life. There is no apparent biologically plausible explanation for the apparently improved measures of DNA fragmentation and morphology, and these findings may have occurred purely by chance. LIMITATIONS, REASONS FOR CAUTION: Owing to the indirect measure of exposure, lack of adjustment for paternal factors, the potential for self-selection due to known exposure status and fertility issues, inability to take time spent away from the residence, limited statistical power and lack of comparable literature, independent replication of the study in larger cohorts is warranted. WIDER IMPLICATIONS OF THE FINDINGS: While our findings may appear reassuring for the large number of people residing and/or working in buildings with indoor air contaminated with LC-PCBs, further efforts to understand the full range of health consequences of fetal LC-PCB exposure are needed. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the Independent Research Fund Denmark (ref no. 6110-00085B), Bispebjerg Hospital, Landsbyggefonden, Realdania (ref. no. PRJ-2017-00176), Grundejernes Investeringsfond (ref. no. 18-58) and Helsefonden (ref. no. 16-B-01-22 and 21-B-0412). K.S.H. was supported by FFIKA, Focused Research Effort on Chemicals in the Working Environment, from the Danish Government. The authors declare that they have no financial, personal or professional competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

A Comparison of Urine Dilution Ability between Adult Dominant Polycystic Kidney Disease, Other Chronic Kidney Diseases, and Healthy Control Subjects: A Case-Control Study.

The final dilution of urine is regulated via aquaporin-2 water channels in the distal part of the nephron. It is unclear whether urine dilution ability in autosomal dominant polycystic kidney disease patients (ADPKD patients) differs from other patients with similar degree of impaired renal function (non-ADPKD patients). The purpose of this case control study was to measure urine dilution ability in ADPKD patients compared to non-ADPKD patients and healthy controls. Methods. Eighteen ADPKD, 16 non-ADPKD patients (both with chronic kidney disease, stage I-IV), and 18 healthy controls received an oral water load of 20 ml/kg body weight. Urine was collected in 7 consecutive periods. We measured free water clearance (CH2O), urine osmolality, urine output, fractional excretion of sodium, urine aquaporin2 (u-AQP2), and urine epithelial sodium channel (u-ENaC). Blood samples were drawn four times (at baseline, 2 h, 4 h, and 6 hours after the water load) for analyses of plasma osmolality, vasopressin, renin, angiotensin II, and aldosterone. Brachial and central blood pressure was measured regularly during the test. Results. The three groups were age and gender matched, and the patient groups had similar renal function. One hour after water load, the ADPKD patients had an increased CH2O compared to non-ADPKD patients (2.97 ± 2.42 ml/min in ADPKD patients vs. 1.31 ± 1.50 ml/min in non-ADPKD patients, p0.029). The reduction in u-AQP2 and u-ENaC occurred earlier in ADPKD than in non-ADPKD patients. Plasma concentrations of vasopressin, renin, angiotensin II, and aldosterone and blood pressure measurements did not show any differences that could explain the deviation in urine dilution capacity between the patient groups. Conclusions. ADPKD patients had a higher CH2O than non-ADPKD patients after an oral water load, and u-AQP2 and u-ENaC were more rapidly reduced than in non-ADPKD patients. Thus, urine-diluting capacity may be better preserved in ADPKD patients than in non-ADPKD patients.

Urine concentration ability is reduced to the same degree in adult dominant polycystic kidney disease compared with other chronic kidney diseases in the same CKD-stage and lower THAN in healthy control subjects - a CASE control study.

BACKGROUND: Concentration of the urine is primarily regulated via vasopressin dependent aquaporin-2 water channels in the apical membrane of kidney principal cells. It is unclear whether urine concentration ability in ADPKD differs from other patients with similar degree of impaired renal function (non-ADPKD patients). The purpose of this case control study was to measure urine concentration ability in ADPKD patients compared to non-ADPKD patients and healthy controls. METHODS: A seventeen hour long water deprivation test was carried out in 17 ADPKD patients (CKD I-IV), 16 non-ADPKD patients (CKD I-IV), and 18 healthy controls. Urine was collected in 4 consecutive periods during water deprivation (12 h, 1 h, 2 h and 2 h, respectively) and analyzed for osmolality (u-Osm), output (UO), fractional excretion of sodium (FENa), aquaporin2 (u-AQP2) and ENaC (u-ENaC). Blood samples were drawn trice (after 13-, 15-, and 17 h after water deprivation) for analyses of osmolality (p-Osm), vasopressin (p-AVP), and aldosterone (p-Aldo). RESULTS: U-Osm was significantly lower and FENa significantly higher in both ADPKD patients and non-ADPKD patients compared to healthy controls during the last three periods of water deprivation. During the same periods, UO was higher and secretion rates of u-AQP2 and u-ENaC were lower and at the same level in the two groups of patients compared to controls. P-AVP and p-Osm did not differ significantly between the three groups. P-Aldo was higher in both groups of patients than in controls. CONCLUSIONS: Urine concentration ability was reduced to the same extent in patients with ADPKD and other chronic kidney diseases with the same level of renal function compared to healthy controls. The lower urine excretion of AQP2 and ENaC suggests that the underlying mechanism may be a reduced tubular response to vasopressin and aldosterone. TRIAL REGISTRATION: Current Controlled Trial NCT04363554 , date of registration: 20.08.2017.

Effect of 3% saline and furosemide on biomarkers of kidney injury and renal tubular function and GFR in healthy subjects - a randomized controlled trial.

BACKGROUND: Chloride is speculated to have nephrotoxic properties. In healthy subjects we tested the hypothesis that acute chloride loading with 3% saline would induce kidney injury, which could be prevented with the loop-diuretic furosemide. METHODS: The study was designed as a randomized, placebo-controlled, crossover study. Subjects were given 3% saline accompanied by either placebo or furosemide. Before, during and after infusion of 3% saline we measured glomerular filtration rate (GFR), fractional excretion of sodium (FENa), urinary chloride excretion (u-Cl), urinary excretions of aquaporin-2 (u-AQP2) and epithelial sodium channels (u-ENaCγ), neutrophil gelatinase-associated lipocalin (u-NGAL) and kidney injury molecule-1 (u-KIM-1) as marker of kidney injury and vasoactive hormones: renin (PRC), angiotensin II (p-AngII), aldosterone (p-Aldo) and arginine vasopressin (p-AVP). Four days prior to each of the two examinations subjects were given a standardized fluid and diet intake. RESULTS: After 3% saline infusion u-NGAL and KIM-1 excretion increased slightly (u-NGAL: 17 ± 24 during placebo vs. -7 ± 23 ng/min during furosemide, p = 0.039, u-KIM-1: 0.21 ± 0.23 vs - 0.06 ± 0.14 ng/ml, p <  0.001). The increase in u-NGAL was absent when furosemide was given simultaneously, and the responses in u-NGAL were not significantly different from placebo control. Furosemide changed responses in u-KIM-1 where a delayed increase was observed. GFR was increased by 3% saline but decreased when furosemide accompanied the infusion. U-Na, FENa, u-Cl, and u-osmolality increased in response to saline, and the increase was markedly pronounced when furosemide was added. FEK decreased slightly during 3% saline infusion, but simultaneously furosemide increased FEK. U-AQP2 increased after 3% saline and placebo, and the response was further increased by furosemide. U-ENaCγ decreased to the same extent after 3% saline infusion in the two groups. 3% saline significantly reduced PRC, p-AngII and p-Aldo, and responses were attenuated by furosemide. p-AVP was increased by 3% saline, with a larger increase during furosemide. CONCLUSION: This study shows minor increases in markers of kidney injury after 3% saline infusion Furosemide abolished the increase in NGAL and postponed the increase in u-KIM-1. The clinical importance of these findings needs further investigation. TRIAL REGISTRATION: (EU Clinical trials register number: 2015-002585-23 , registered on 5th November 2015).

Short-term telemedical home blood pressure monitoring does not improve blood pressure in uncomplicated hypertensive patients.

Telemonitoring of home blood pressure measurements (TBPM) is a new and promising supplement to diagnosis, control and treatment of hypertension. We wanted to compare the outcome of antihypertensive treatment based on TBPM and conventional monitoring of blood pressure. Participants were recruited from a prevalence study among citizens aged 55-64 years in the municipality of Holstebro, Denmark. The study was a randomized, controlled, unblinded 3 months' trial. In the intervention group, antihypertensive treatment was based on TBPM with transmission of the measurements and subsequent communication by telephone or e-mail. In the control group, patients received usual care. Primary outcome was reduction in daytime ambulatory blood pressure measurements (ABPM) from baseline to 3 months' follow-up. Of 375 participants randomized, primary outcome data were available for 356 (95%). In both groups, daytime ABPM decreased significantly. The decrease in daytime ABPM in the intervention group was systolic/diastolic, -8±12/-4±7 mm Hg. This did not differ significantly from the control group's -8±13/-4±8 mm Hg. An equal number of participants obtained normal daytime ABPM, in the intervention group 17% (31/175) versus control 21% (37/181), P=0.34. We found that both TBPM patients and controls achieved a significant blood pressure reduction in this randomized, controlled, unblinded 3-month trial. We found no difference in blood pressure reduction or number of patients reaching blood pressure goals. Further information and education of some general practitioners seem to be relevant regarding blood pressure management and control of hypertension.

Lipid-modified G4-decoy oligonucleotide anchored to nanoparticles: delivery and bioactivity in pancreatic cancer cells.

KRAS is mutated in >90% of pancreatic ductal adenocarcinomas. As its inactivation leads to tumour regression, mutant KRAS is considered an attractive target for anticancer drugs. In this study we report a new delivery strategy for a G4-decoy oligonucleotide that sequesters MAZ, a transcription factor essential for KRAS transcription. It is based on the use of palmitoyl-oleyl-phosphatidylcholine (POPC) liposomes functionalized with lipid-modified G4-decoy oligonucleotides and a lipid-modified cell penetrating TAT peptide. The potency of the strategy in pancreatic cancer cells is demonstrated by cell cytometry, confocal microscopy, clonogenic and qRT-PCR assays.

Improving organic tandem solar cells based on water-processed nanoparticles by quantitative 3D nanoimaging.

Organic solar cells have great potential for upscaling due to roll-to-roll processing and a low energy payback time, making them an attractive sustainable energy source for the future. Active layers coated with water-dispersible Landfester particles enable greater control of the layer formation and easier access to the printing industry, which has reduced the use of organic solvents since the 1980s. Through ptychographic X-ray computed tomography (PXCT), we image quantitatively a roll-to-roll coated photovoltaic tandem stack consisting of one bulk heterojunction active layer and one Landfester particle active layer. We extract the layered morphology with structural and density information including the porosity present in the various layers and the silver electrode with high resolution in 3D. The Landfester particle layer is found to have an undesired morphology with negatively correlated top- and bottom interfaces, wide thickness distribution and only partial surface coverage causing electric short circuits through the layer. By top coating a polymer material onto the Landfester nanoparticles we eliminate the structural defects of the layer such as porosity and roughness, and achieve the increased performance larger than 1 V expected for a tandem cell. This study highlights that quantitative imaging of weakly scattering stacked layers of organic materials has become feasible by PXCT, and that this information cannot be obtained by other methods. In the present study, this technique specifically reveals the need to improve the coatability and layer formation of Landfester nanoparticles, thus allowing improved solar cells to be produced.

High pulse pressure is not associated with abnormal activation of the renin-angiotensin-aldosterone system in repaired aortic coarctation.

We investigated the relationship between pulse pressure (PP)--a surrogate marker of arterial stiffness-and activity of the renin-angiotensin-aldosterone system (RAAS) in adult patients with repaired coarctation and normal left ventricular (LV) function. A total of 114 patients (44 (26-74) years, 13 (0.1-40) years at repair) and 20 healthy controls were examined with 24-h ambulatory blood pressure monitoring, echocardiography, vasoactive hormone levels and magnetic resonance of the thoracic aorta. Forty-one patients (36%) were taking antihypertensives (28 RAAS inhibitors). Fifty-one had mean 24-h blood pressures >130/80 mm Hg. Hypertension was not associated with age at repair (P=0.257). Patients had higher PP and LV mass compared with controls (52±11 vs. 45±5 mm Hg and 221±71 vs. 154±55 g, respectively; both P<0.05). Differences were more pronounced in the presence of recoarctation, but independently of RAA levels. Even normotensive patients had higher LV mass than controls. LV mass and recoarctation were correlated with PP levels. In conclusion, adult patients with repaired coarctation have increased PP and LV mass compared with controls. PP increased with increasing recoarctation. Hypertension was present also in the absence of recoarctation. These changes could not be explained by abnormal activation of the RAAS.

Renal and hormonal effects of systemic nitric oxide inhibition in patients with congestive heart failure and in healthy control subjects.

BACKGROUND: The significance of basal renal nitric oxide (NO) availability in the regulation of renal perfusion and sodium excretion in human congestive heart failure (CHF) has not been described previously. METHODS AND RESULTS: We studied the effects of acute systemic NO synthesis inhibition with N(G)-monomethyl-L-arginine (L-NMMA) in 12 patients with CHF and 10 healthy control subjects (CON) in a randomized placebo-controlled study. Effect parameters were renal plasma flow (RPF), renal vascular resistance (RVR), glomerular filtration rate (GFR), urine sodium excretion and plasma levels of vasoactive hormones. L-NMMA was associated with a significant decrease in RPF (CON-LNMMA: -13 ± 3% [P = .014]; CHF-LNMMA: -17 ± 7% [P = .017]) and a profound increase in RVR in both CHF and CON (CON-LNMMA: +26 ± 6% [P = .009]; CHF-LNMMA: +37 ± 70% [P = .005]). Significant decreases in sodium excretion were found in both CHF-LNMMA and CON-LNMMA. Relative changes from baseline were not statistically different between CHF-LNMMA and CON-LNMMA. After L-NMMA, RPF values correlated inversely with plasma aldosterone in CHF-LNMMA (P = .01). L-NMMA induced an increase in A-type natriuretic peptide (ANP) only in CHF-LNMMA (+18 ± 8%; P = .035), which correlated significantly with basal ANP levels (P = .034). CONCLUSIONS: There was no difference in the renal response to L-NMMA in CHF vs CON, suggesting that the impact of NO on renal perfusion and sodium excretion is maintained in stable CHF. We suggest that NO influences the release of ANP during high levels of atrial stretch in CHF.

Acute effects of atorvastatin on glomerular filtration rate, tubular function, blood pressure, and vasoactive hormones in patients with type 2 diabetes.

Statins improve cardiovascular survival in both nondiabetic and diabetic patients, but diabetic patients benefit more, in both primary and secondary prevention. Statins seem to have multiple effects beyond cholesterol lowering, that is, pleiotropic effects that may include changes in renal function. This study tests the hypothesis that acute treatment with atorvastatin may change glomerular filtration rate, tubular function, vasoactive hormones, blood pressure, and pulse rate in patients with type 2 diabetes. In an acute, randomized, placebo-controlled, double-blinded, crossover trial, the effects of atorvastatin on renal function, vasoactive hormones, blood pressure, and pulse rate are measured in 21 patients with type 2 diabetes. Patients are randomized to either 2 doses of atorvastatin 80 mg or placebo before 2 different study days. Treatment with atorvastatin induces a significant reduction in fractional sodium excretion compared with placebo, and sodium clearance tends to be reduced. No significant differences in glomerular filtration rate, albumin/creatinine ratio, vasoactive hormones, and blood pressure by acute treatment with atorvastatin are found in diabetic patients. Acute treatment with atorvastatin reduces renal fractional sodium excretion in patients with type 2 diabetes. No changes are measured in glomerular filtration rate, albumin/creatinine ratio, vasoactive hormones, and blood pressure.

Glomerular filtration rate and blood pressure are unchanged by increased sodium intake in atorvastatin-treated healthy men.

OBJECTIVE: Improved cardiovascular survival during statin treatment might be due to effects in addition to cholesterol lowering. We hypothesize that sodium intake affects renal function and vasoactive hormones in atorvastatin-treated healthy subjects. METHODS: In a randomized, placebo-controlled, double-blind, crossover study we measured the effect of a moderate change in sodium intake on glomerular filtration rate (GFR), blood pressure (BP), renal tubular function, plasma concentrations of vasoactive hormones and urinary excretion of aquaporin-2 (u-AQP2) in 22 healthy subjects. The subjects were randomized to standardized fluid intake and diet corresponding to the need for calories in the 4 days before each of the 2 examination days. In one of the periods they were randomized to receive sodium chloride tablets (2 g) thrice daily for 4 days. Two doses of atorvastatin (80 mg) were given; one at 2200 h the evening before the study day, the other at 0830 h in the morning. RESULTS: 24-h urinary sodium excretion increased by 23%. GFR and BP were unchanged. Sodium clearance, fractional excretion of sodium and u-AQP2 increased, whereas free water clearance decreased during high sodium intake. PRC and aldosterone were suppressed during the high sodium diet. CONCLUSIONS: A change in dietary sodium intake of approximately 100 mmol daily does not change GFR and BP in atorvastatin-treated healthy men. The lack of change in BP might reflect that the subjects studied were not sodium sensitive, or that atorvastatin treatment modified sodium sensitivity.

Abnormally increased nitric oxide synthesis and increased endothelin-1 in plasma in patients with obstructive sleep apnoea.

OBJECTIVE: Obstructive sleep apnoea (OSA) is a risk factor for cardiovascular morbidity and mortality. The mechanism is unknown, but endothelial dysfunction might contribute. We tested the hypothesis that patients with OSA have abnormal nitric oxide (NO) synthesis, which results in an abnormal response in blood pressure, renal hemodynamics, renal tubular function and vasoactive hormones in response to inhibition of the NO synthesis with L-NMMA. MATERIAL AND METHODS: A randomized, placebo-controlled, single-blinded, crossover study was done in 13 OSA patients and 14 controls. We measured changes in systolic and diastolic blood pressure (SBP and DBP), pulse rate, glomerular filtration rate, renal plasma flow, fractional excretion of sodium and lithium and plasma concentrations of vasoactive hormones after injection of L-NMMA and placebo. RESULTS: L-NMMA induced a significant increase in SBP and DBP in both groups. The placebo-corrected increase in DBP was more pronounced in patients with OSA than in controls (9 (5-11) versus 3 (1-6) mmHg; p=0.01). Endothelin-1 (ET-1) was significantly higher in patients compared with controls (1.1 (1.0-1.3) versus 0.8 (0.7-0.9) pg/mL; p<0.01). In controls, L-NMMA induced a small increase in ET-1, while no changes were seen in patients. The placebo-corrected change in ET-1 was lower in patients compared to controls (-01 (-0.3-0.0) versus 0.1 (0.0-0.1) pg/mL; p=0.04). CONCLUSIONS: Patients with OSA have abnormally increased NO synthesis and an increased unresponsive level of ET-1 in plasma. This might be due to an imbalance between NO synthesis and ET-1 production.

Increased nocturnal sodium excretion in obstructive sleep apnoea. Relation to nocturnal change in diastolic blood pressure.

OBJECTIVE: The mechanisms involved in the development and maintenance of hypertension in obstructive sleep apnoea (OSA) are not clear. We hypothesized that OSA patients have an abnormal renal handling of sodium and water during the night. MATERIAL AND METHODS: We studied 29 OSA patients and 19 healthy controls at night with serial determinations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), arginine vasopressin (AVP), aldosterone (Aldo), fractional urinary excretion of sodium (FE(Na)), free water clearance (C(H2O)), urinary excretion of aquaporin 2 (u-AQP2), systolic blood pressure (SBP), diastolic blood pressure (DBP) and oxygen saturation. RESULTS: OSA patients had a higher FE(Na) (0.6 (0.4-1.0) versus 0.4 (0.3-0.6) %; p = 0.017), SBP (129 (114-145) versus 114 (106-122) mmHg; p = 0.001) and DBP (81 (72-87) versus 71 (65-74) mmHg; p<0.001) than healthy controls at night. In hypertensive OSA patients, the FE(Na) correlated significantly with the change in nocturnal DBP (r (2) = 0.411; p = 0.010). Mean level of AVP during the night was higher in OSA patients compared with healthy controls (1.1 (0.8-1.4) versus 0.8 (0.6-1.1) pmol/L; p = 0.033) and correlated with SBP. ANP, BNP, Aldo, C(H2O) and u-AQP2 were the same in OSA and controls. CONCLUSIONS: We conclude that the higher fractional excretion of sodium in OSA is most likely attributable to pressure natriuresis. The correlation between mean AVP and blood pressure suggests that AVP may be part of the pathogenetic mechanism underlying hypertension in these patients.

Increased urinary aquaporin-2 excretion in response to furosemide in patients with chronic heart failure.

OBJECTIVE: Patients with chronic heart failure (CHF) have decreased ability to excrete water and increased urinary excretion of aquaporin-2 (U-AQP2). The natriuretic and diuretic effects of furosemide are antagonized by an increased reabsorption of sodium and water in the collecting ducts. It is unknown whether aquaporin-2 (AQP2) renal water channels are involved in this compensatory reabsorption. We tested the hypothesis that U-AQP2 increases after a single intravenous dose of furosemide in CHF patients. MATERIAL AND METHODS: In a randomized, single-blind, placebo-controlled, crossover study, we measured the effect of furosemide (80 mg) on U-AQP2, urine volume, free water clearance (C(H2O)) and fractional excretion of sodium (FE(Na)) in 12 CHF patients. Plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), atrial (ANP) and brain natriuretic peptides (BNP) were measured during the study. U-AQP2 and hormones were determined by radioimmunoassays. RESULTS: Furosemide increased U-AQP2 (140 %), urine volume (280 %), C(H2O) (95 %) and FE(Na) by a factor of 15 (p<0.008 for all), and also AVP (51 %), PRC, Ang II (86 %) and Aldo (59 %) (p<0.021 for all). ANP and BNP did not change. CONCLUSIONS: In CHF, furosemide increased the vasopressin level, which stimulated water reabsorption via the APQ2 water channels. This is most likely a compensatory phenomenon in addition to the increase in the renin-angiotensin system to prevent excess loss of sodium and water. However, both these effects were overridden by the effect of furosemide, as shown by increased free water clearance and sodium excretion.

Urinary excretion of alpha-GST and albumin in rheumatoid arthritis patients treated with methotrexate or other DMARDs alone or in combination with NSAIDs.

OBJECTIVE: To evaluate the effect of methotrexate (MTX) and other disease-modifying anti-rheumatic drugs (DMARDs) alone or in combination with non-steroidal anti-inflammatory drugs (NSAIDs) on the urinary excretion of alpha-glutathione S-transferase (alpha-GST) and albumin in rheumatoid arthritis (RA) patients. METHODS: Nineteen RA patients starting treatment with MTX were followed for 1 year with measurements of urinary alpha-GST, urinary albumin, and urinary and plasma creatinine at the start of treatment, and after 16, 28, and 52 weeks. A larger group of RA patients (n = 72) undergoing long-term treatment with different DMARDs was compared with 79 healthy controls regarding urinary alpha-GST and albumin. alpha-GST was quantified by an enzyme immunoassay. Urine albumin was measured turbidimetrically. RESULTS: The urine-alpha-GST/urine-creatinine ratio and the urine-albumin/urine-creatinine ratio did not change during 52 weeks of treatment with MTX. The long-term DMARD-treated RA patients and the healthy controls were comparable with regard to the urine-alpha-GST/urine-creatinine ratio and the urine-albumin/urine-creatinine ratio. All patients had preserved renal function as assessed by plasma creatinine, and none had proteinuria using urine dipstick methods. CONCLUSION: DMARD-treated RA patients with normal serum creatinine had no detectable renal injuries assessed by the urinary excretions of alpha-GST and albumin.

Vitamin D insufficiency in Greenlanders on a westernized fare: ethnic differences in calcitropic hormones between Greenlanders and Danes.

We studied the influence of age, gender, latitude, season, diet and ethnicity on plasma 25-hydroxyvitamin D 25 OHD, PTH, 1,25-dihydroxyvitamin D, vitamin D-binding protein, bone-specific alkaline phosphatase, and osteocalcin levels in 46 Greenlanders living in Nuuk (64 degrees N) on a traditional fare (group A), 45 Greenlanders living in Nuuk on a westernized fare (group B), 54 Greenlanders (group C), and 43 Danes (Group D) living in Denmark (55 degrees N) on a westernized fare. Blood specimens were drawn both summer and winter. Vitamin D insufficiency (plasma 25 OHD <40 nmol/l) was common in all four study groups during summer (23-74%) and winter (42-81%). Compared to groups A and D, vitamin D insufficiency was significantly more frequent in groups B and C. In all groups, summer levels of 25 OHD were above winter levels. Multiple regression analysis revealed a significant effect of ethnicity. Compared to Danes, Greenlanders had higher 1,25-dihydroxyvitamin D levels, but lower 25 OHD and PTH levels despite relatively low plasma calcium concentrations. In addition to ethnicity, 25(OH)D levels were influenced by age, season (summer > winter), and diet (a traditional Inuit diet>westernized diet). Ethnic differences exist between Greenlanders and Danes. Our results suggest that Greenlanders may have an inherent lower "set-point" for calcium-regulated PTH release or an enhanced renal 1,25(OH)(2)D production. In addition to ethnicity, age, season, and diet were important determinants of vitamin D status. Changes from a traditional to a westernized fare are associated with a reduced vitamin D status in Greenlanders. Vitamin D supplementation should be considered.

Accuracy of telemedical home blood pressure measurement in the diagnosis of hypertension.

This study was conducted to compare the accuracy of clinic blood pressure (CBP) and telemedical home blood pressure (HBP) measurement in the diagnosis of hypertension in primary care. The study subjects were 411 patients with average CBP > or =140 mmHg systolic or > or =90 mmHg diastolic, who performed telemedical HBP measurement (5 days, four times daily) and ambulatory blood pressure (ABP) monitoring in random order. Main outcome measure was the agreement of CBP and HBP with daytime ABP. CBP was much higher than daytime ABP and average HBP (P<0.001) with no difference between the latter two. The correlation between CBP and ABP was weak (systolic: r=0.499, diastolic: r=0.543), whereas strong correlations existed between HBP and ABP (systolic: r=0.847, diastolic: r=0.812). A progressive improvement in the strength of the linear regression between average HBP of single days and ABP was obtained from day 1 to day 4, with no further benefit obtained on the fifth day. The HBP readings taken at noon and in the afternoon showed significantly stronger correlations with ABP than the blood pressures measured in the morning and in the evening. In conclusion, the accuracy of telemedical HBP measurement was substantially better than that of CBP in the diagnosis of hypertension in primary care. HBP most accurately reflected ABP on the fourth day of monitoring, and the readings at noon and in the afternoon seemed to be most accurate.

Effect of an acute oral lithium intake on urinary Aquaporin-2 in healthy humans with and without simultaneous stimulation with hypertonic saline infusion.

OBJECTIVE: Animal experiments have shown that lithium interferes with the formation of Aquaporin-2 in the distal renal tubuli. The effect of lithium on formation of renal water channels has not been studied in healthy humans. The aim of this study was to test the hypotheses that a single oral dose of lithium will reduce the formation of water channels both with and without stimulation with hypertonic saline infusion, and that this effect can be detected by measurement of urinary excretion of Aquaporin-2 (u-AQP2). METHODS: In healthy subjects, Study 1 (n = 11) and Study 2 (n = 12), urine was collected in 6 and 7 periods between 08.00 and 14.00, respectively, and blood samples were drawn at 30- to 60-min intervals. The study medication was given at 09.00; u-AQP2 was determined by radioimmunoassay. RESULTS: In Study 1 neither u-AQP2 nor urinary output were significantly changed by lithium. In Study 2, u-AQP2 was increased by hypertonic saline infusion in parallel with an increase in arginine vasopressin. At the end of the study, u-AQP2 was increased by 30% with placebo but only by 13% with the 600 mg lithium dose, and urinary output was significantly higher after 600 mg lithium than after placebo and 300 mg lithium. CONCLUSIONS: U-AQP2 was not significantly changed after a single oral dose of lithium. The antidiuretic response to hypertonic saline infusion was reduced when lithium was given. It is suggested that lithium increases urinary output by inhibiting trafficking of renal water channels in healthy humans.

Urinary aquaporin-2 in healthy humans and patients with liver cirrhosis and chronic heart failure during baseline conditions and after acute water load.

BACKGROUND: Patients with liver cirrhosis and chronic heart failure (CHF) have a reduced capacity to excrete water. Studies in healthy humans have shown that an acute water load reduces the excretion of aquaporin-2 in urine (u-AQP-2). We wanted to test the hypothesis that an acute water load reduces u-AQP-2 less in patients with liver cirrhosis or CHF than in healthy humans. METHODS: Fourteen healthy subjects, 14 patients with liver cirrhosis, and 14 patients with CHF were given an oral water load of 20 mL/kg. Urine was collected every 30 minutes for 4 hours for analysis of u-AQP-2. Blood samples were drawn at the beginning and at the end of the study for analysis of arginine vasopressin (AVP). u-AQP-2 was determined by radioimmunoassay. RESULTS: During the study period, urinary output was 22.8% higher than water intake in the healthy controls and increased 14-fold from baseline, but in patients with liver cirrhosis and CHF urinary output was 14% and 24% less than the intake, while urinary output increased 7- and 19-fold from baseline, respectively. u-AQP2 decreased significantly more in patients with CHF (39%) than in healthy controls (17%) but it was unchanged in those with liver cirrhosis. AVP decreased 46% in patients with CHF, but was unchanged in healthy controls and those with liver cirrhosis. A 24-hour urinary excretion of AQP-2 was significantly elevated in patients with CHF (median, 25.7 nmol/mol creatinine) compared to healthy controls (15.7 nmol/mol creatinine) and those with liver cirrhosis (17 nmol/mol creatinine). CONCLUSION: The excretion of AQP-2 in urine is abnormal both in liver cirrhosis in which we find less suppression of u-AQP2 by an acute water load and in CHF in which we find a high baseline level and an exaggerated suppression of u-AQP2 by an acute water load.

Twenty-four-hour blood pressure among Greenlanders and Danes: relationship to diet and lifestyle.

BACKGROUND: Greenlanders have a lower rate of cardiovascular mortality and morbidity than Danes, possibly due to lower blood pressure. However, 24-h blood pressure has never been measured in Greenlanders. The aim of this study was to compare the 24-h blood pressure of Greenlanders and Danes, and to analyse the influence of Arctic food and lifestyle on blood pressure. METHODS: Four groups of healthy subjects were recruited for the study. Group I: Danes in Denmark consuming European food; group II: Greenlanders in Denmark consuming European food; group III: Greenlanders in Greenland consuming mainly European food; and group IV: Greenlanders in Greenland consuming mainly traditional Greenlandic food. All subjects underwent a physical examination, laboratory screening of blood and urine samples, and completed a questionnaire on diet, physical activity, smoking status, intake of alcohol, liquorices, vitamins and minerals. Twenty-four-hour blood pressure was measured. RESULTS: It was found that 24-h diastolic blood pressure was lower in Greenlanders than in Danes for the whole 24-h period and during both day and night-time, whereas systolic blood pressure was the same (mean 24-h blood pressure with 95% CI: Danes 123/75 mmHg (120/73-127/77), Greenlanders 122/ 69 (119/68-124/70)). Among Greenlanders, blood pressure increased with age and male gender, and systolic blood pressure increased with body mass index (BMI). No association with diet was found. The difference between the two populations persisted after controlling for age, gender, BMI, outdoor temperature, and lifestyle factors. CONCLUSION: Greenlanders have a lower 24-h diastolic blood pressure than Danes, and it is suggested that genetic factors are mainly responsible for the lower blood pressure level among Greenlanders.