Fast analysis of gross alpha with a new plastic scintillation resin.

Radionuclides analysis is a complex task, with high time and economic costs. In decommissioning activities and environmental monitoring, it is very evident, in which, to obtain an appropriate information, it is necessary to perform as many analyses as possible. The number of these analyses can be reduced using screening gross alpha or gross beta parameters. However, the currently used methods cannot give an answer as fast as it would be desired and, moreover, more than 50% of the results reported in the interlaboratory exercises fall outside the acceptance range. This work presents the development of a new material and method to gross alpha activity determination using a plastic scintillation resin (PSresin) in drinking and river water samples. A specific procedure was developed involving a new PSresin (using bis-(3-trimethylsilyl-1-propyl)-methanediphosphonic acid as an extractant) that is selective for all actinides, radium and polonium. Quantitative retention and 100% detection efficiencies were obtained at pH 2 with nitric acid. PSA value of 135 was used for α/ß discrimination. Eu was used to determine or estimate retention in sample analyses. The method developed can measure, in less than 5 h from the reception of the sample, the gross alpha parameter with quantification errors comparable or even lower to those obtained with conventional methods.

A new method based on selective fluorescent polymers (PSresin) for the analysis of 90Sr in presence of 210Pb in environmental samples.

90Sr is of major concern in emergency and environmental control plans. It is one of the main fission products in nuclear facilities and is a high-energy beta emitter that presents chemical properties similar to those of calcium. 90Sr is commonly detected using methods based on liquid scintillation counting (LSC) following a chemical separation to remove potential interferences. However, these methods generate mixed wastes (hazardous and radioactive). In recent years, an alternative strategy using PSresins has been developed. For 90Sr analysis with PSresins, 210Pb is the main interferent that should be considered, as it is also strongly retained in the PSresin. In this study, a procedure was developed involving a precipitation with iodates to separate lead from strontium before the PSresin separation. Moreover, the method developed was compared with well-established and routinely used methods based on LSC, revealing that the new method produced equivalent results in less time and with less waste generation.

Simultaneous determination of 210Pb and 90Sr and 210Po isolation in sludge samples using a plastic scintillation resin.

This study describes a new and fast method for separating 210Po from 210Pb and 90Sr, before simultaneously measuring the individual activities of the latter two radionuclides using a plastic scintillation resin (PSresin) in sludge samples taken from a drinking water treatment plant. This method speeds up the analysis process significantly by simultaneously measuring 210Pb and 90Sr in a single step. The method is reproducible and has a relative standard deviation of less than 25% for 210Pb, 210Po and 90Sr. The method was satisfactorily validated with an intercomparison sample and applied to sludge samples from a drinking water treatment plant. The minimum detectable activities for 0.9 g of sludge are 5.5 Bq/kg and 8 Bq/kg for 210Pb and 90Sr respectively when measured for 180 min, and 0.5 Bq/kg for 210Po when measured for 5000 min.

Dropout and compliance to physical exercise in menopausal osteopenic women: the European "happy bones" project.

Introduction: Decline in muscle mass and bone density seem to be two of the most disabling side effects of menopause that negatively affect women's quality of life. Promoting physical activity protocols in the workplace can represent a focal point in the prevention and management of several diseases. The study aims to evaluate the compliance and drop-out of menopausal osteopenic women engaged in combined training performed inside and outside the workplace. Strength and balance were analyzed to evaluate the effect of this protocol on osteoporosis prevention and the risk of falling. Methods: 73 menopausal women were enrolled in 5 European countries. They performed 72 lessons of a combined training proposed in the working place (IW) or sport center (SC). Results: Out of the total 39 women enrolled in the IW, 12.8% had to leave the program, while out of the 34 women enrolled in SC, 41.2% did not complete the training. According to the compliance results, 47% of women that completed the trained IW and 85% in the SC recorded high compliance (p = 0.019). Moreover, the strength of the lower limbs (p < 0.001) and static balance (p = 0.001) significantly improved in the whole group. Discussion: In conclusion, proposing well-structured training in the workplace for menopausal women seems to reduce drop-out. Strength and balance results suggest its positive impact on bone health and risk of falls, despite where it is performed.

Analysis of isotopes of plutonium in water samples with a PSresin based on aliquat·336.

There is a necessity to have techniques capable to perform rapid determinations of specific radionuclides with the aim to provide fast response in emergency situations where a large number of samples need to be measured in a short time. Plastic Scintillation Resins (PSresins) raises as an adequate tool to achieve this purpose and in the present study a methodology to determine plutonium using a PSresin based on Aliquat·336 was developed. Different sample treatments have been studied under acidic conditions with an emphasis on valence adjustment treatment to achieve an effective retention within the PSresin. Under 3 M nitric acid conditions and an iron sulphamate (II) + nitrite valence adjustment, quantitative retention and 100% detection efficiency were achieved. The retention of the different interferences evaluated (238U, 230Th, 241Am, 210Pb and 99Tc) was low and therefore they do not interfere significantly in the determination of plutonium, except for 99Tc. Finally, a stable tracer to calculate the PSresin separation yield was studied, revealing that gold is suitable for this purpose. This procedure was applied to the analysis of spiked sea and river water samples, obtaining errors lower than 10% in their quantification.

PSresin for the analysis of alpha-emitting radionuclides: Comparison of diphosphonic acid-based extractants.

The analysis of radionuclides is complex, with high economic and time costs. For this reason, there is a need to develop new methods and strategies to reduce these costs. One important group in the analysis of radionuclides is the actinides, which are the main constituents assessed in the total gross alpha together with radium and radon test used to measure radioactivity in drinking water. Moreover, in nuclear dismantling processes, the possible spread of the released radionuclides has to be controlled, which is measured by many techniques, depending on the radionuclides, through scintillation. This work presents a new method to analyse actinides using plastic scintillation resins (PSresins) packed in a solid-phase extraction cartridge. The proposed method combines chemical separation and sample measurement into a single step, reducing the effort, time and reagents required for analysis as well as decreasing the amount of waste generated. The PSresins compared in this study contained three selective extractants based on methylenediphosphonic acid with different radicals, which has a high affinity for tri-, tetra-, and hexavalent actinides in dilute acids. These extractants were immobilised on plastic scintillation microspheres at a ratio of 1/1:6, producing a retention and detection efficiency of 100% for 241Am, 230Th, Uranium and 238Pu. The retention and detection efficiency were 20% and 100%, respectively, for 210Po and low for 226Ra.

[Ruptured sinus of Valsalva aneurysm and pregnancy: what anesthetic technique should be preferred for a scheduled cesarean section?]. / Aneurisma del seno de Valsalva roto y gestación. Qué técnica anestésica es preferible para una cesárea electiva?

Sinus of Valsalva aneurysm is a rare cardiac abnormality rupture the right sinus and if ruptured open into the right ventricle or atrium. Usually silent, may cause significant hemodynamic changes. Few cases of ruptured Valsalva sinus aneurysm have been reported in the literature, and the course of this condition during pregnancy and anesthetic management have scarcely been mentioned. We report the case of a primipara with a Valsalva sinus aneurysm that ruptured into the right ventricle. Cardiac function worsened as pregnancy progressed. A cesarean section under spinal anesthesia was scheduled.

[Functional profile of cephalic arch stenosis]. / Perfil funcional de la estenosis del arco de la vena cefálica.

Cephalic arch stenosis (CAS) is a unique type of vascular access stenosis. For example, the etiology of CAS is under investigation and the prevalence of CAS can be lower in diabetic patients. Three cases of CAS were identified during our vascular access stenosis surveillance program by blood flow rate measurements using the Delta-H method. We evaluated the prevalence, etiology, relationship with diabetes and functional profile of CAS. To date, this is the first functional report published about this type of stenosis.

[Prevalence and functional effect of arteriovenous fistula calcifications, evaluated by spiral CT in chronic haemodialysis patients]. / Prevalencia y efecto funcional de las calcificaciones de la fístula arteriovenosa evaluadas mediante TAC helicoidal en pacientes en hemodiálisis crónica.

INTRODUCTION: Vascular calcification is a common finding in patients (pts) with end-stage renal disease (ESRD). OBJECTIVE: The aim of this cross-sectional study was to investigate the prevalence and functional effect of native arteriovenous fistula AVF (feeding artery and/or arterialized vein) calcifications evaluated by spiral computed tomography (CT) in ESRD pts undergoing chronic hemodialysis (HD). PATIENTS AND METHOD: Forty-five upper limb AVF (radial 44.4% or brachial 55.6%, mean duration 65.3 +/- 80.9 months) without evidence of significant stenosis were evaluated by CT in 45 ESRD pts (mean age 63.8 +/- 13.1 yr; sex M: 71.1%, F: 28.9%; mean time on HD 53.1 +/- 51.9 months; diabetic nephropathy 15.6%). All AVF explorations were performed using the same multi-slice spiral CT scanner (HiSpeed Dual machine, GE Medical Systems). The severity of AVF calcifications was quantified by CT using the following criteria: grade I absence of calcifications, grade II isolated calcifications (<10 groups of calcification), grade III moderate calcifications (10-20 groups of calcification) and grade IV diffuse calcifications (>20 groups of calcification). Laboratory parameters analyzed: calcium, phosphorus, parathyroid hormone; calcium x phosphorus product was calculated. The same week of CT scanning, we evaluated AVF function measuring the blood flow rate (QA). We determined QA (1559.3 +/- 980.6 ml/min) by the Delta-H method (ABF-mode, HemaMetrics, USA) using the Crit-Line III monitor (68.9%) or by Doppler ultrasound (31.1%) performed by the same radiologist using a 5-8 MHz linear transducer (Sequoia machine, Siemens-Acuson); mean arterial pressure MAP (94.7 +/- 16.3 mmHg) was recorded simultaneous with QA. RESULTS: Most pts not showed AVF calcification by CT scan (grade I: 27/45, 60%). Forty percent of pts (18/45) demonstrated any degree of AVF calcification (grade II 13.3%, grade III 8.9%, grade IV 17.8%). Pts with brachial AVF showed higher mean QA compared to pts with radial AVF (1899.1 +/- 1131.8 versus 1134.5 +/- 516.4 ml/min, p=0.005), but MAP (91.2 +/- 15.8 versus 99.0 +/- 16.2 mmHg) and the prevalence of AVF calcification (32% versus 50%) were not different between both groups (p=0.11 and p=0.24, respectively). Pts with evidence of any calcification on CT scanning (grade II, III or IV) had higher time on HD (84.6 +/- 63.1 versus 24.6 +/- 20.0 months), higher AVF duration (97.7 +/- 89.3 versus 34.6 +/- 61.2 months) and similar QA (1488.3 +/- 678.9 versus 1606.6 +/- 1148.9 ml/min) compared with pts without AVF calcification (p=0.014, p=0.001 and p=0.69, respectively); no differences in MAP (95.4 +/- 13.8 versus 94.2 +/- 17.9 mmHg), prevalence of brachial AVF (44% versus 63%) or mineral metabolism parameters were found when comparing both groups (for all comparisons, p=NS). The same results were obtained when comparing pts with a high (grade III-IV: 26.7%) and a low (grade I-II: 73.3%) AVF calcification score, or when comparing pts with diffuse (grade IV) and without (grade I) AVF calcification. CONCLUSIONS: 1) The prevalence of AVF calcification by CT scan was 40%. 2) The AVF calcification was related with time on HD and AVF duration. 3) The function of fully developed AVF without stenosis and suitable for routine HD was not impaired by the presence of calcifications.

[Measurement of vascular access blood flow rate during hemodyalisis in 38 patients using the thermodilution technique. A comparative study with the Delta-H method]. / Exploración funcional del acceso vascular durante la hemodiálisis en 38 pacientes mediante la técnica de termodilución. Estudio comparativo con el método Delta-H.

INTRODUCTION: Periodic QA measurement is the preferred way for VA surveillance in end-stage renal disease (ESRD) patients (pts). OBJECTIVE: The aims of this study were to measure QA by TDT and to compare the functional results with Delta-H method. PATIENTS AND METHODS: We measured Q(A) non invasively in 38 VA (mean VA duration: 48.7 +/- 69.8 months) during HD in 38 stable ESRD (mean age 63.8 +/- 15.1 yr, mean time on HD 47.6 +/- 53.9 months, diabetic nephropathy 18.4%) pts by the TDT. Fourteen pts (36.8%) had history of previous VA that were ipsilateral to the VA under study in most cases (11/14, 78.6%). Thirteen pts (34.2%) had history of any comorbidity (coronary artery or cerebrovascular or peripheral vascular diseases). Q(A) was calculated from the recirculation values obtained by means of the blood temperature monitor (BTM), integrated into the Fresenius Medical Care 4008-S machine, at normal and reverse configurations of the HD blood lines. Q(A) was measured within the first hour of two consecutive HD sessions (the values were averaged). Mean arterial pressure MAP and distance between needles (DBN) were measured simultaneous with Q(A). In addition, the VA blood flow was also determined by Delta-H method using Crit-Line III Monitor (ABF-) between 1000 and 1500 ml/min. The mean DBN and MAP were 6.2 +/- 2.9 cm, 91.9 +/- 12.4 mmHg, respectively. Mean Q(A) was similar for pts with mean MAP<100 mmHg (n=26) and for pts with mean MAP>or=100 mmHg (n=12) (p=0.85). Pts with diabetic nephropathy showed lower mean Q(A) (836.1 +/- 395.8 ml/min) compared to the remaining pts (1,245.9 +/- 449.9 ml/min) (p=0.033). No differences in mean Q(A) was found when pts with any comorbidity and without comorbidities were compared (p=0.62). Brachial AVF tended to have higher mean Q(A) (1,323.6 +/- 465.3 ml/min) compared to radial AVF (1,017.4 +/- 447.3 ml/min) (p=0.052). Pts with history of previous VA showed higher mean Q(A) (1,410.6 +/- 377.7 ml/min) compared to the remaining pts (1,030.4 +/- 458.7 ml/min) (p=0.013). No correlation was found between mean Q(A) and: mean age, DBN, MAP, Kt/V index, time on HD and VA duration. Mean Q(A) obtained by TDT was not different when compared with mean ABF determined by Delta-H method (1,151.3 +/- 479.0 ml/min) (p=0.89). The calculated values of VA blood flow obtained by TDT were highly correlated with those determined by the Delta-H method (intraclass correlation coefficient =0.95, p<0.001). CONCLUSIONS: The TDT is an indicator of QA during HD. The functional profile of VA was worse in pts with diabetic nephropathy or without history of previous VA. The VA blood flow values obtained by TDT and Delta-H techniques correlated highly with each other.

[Pregnancy in recipients of kidney transplantation: effects on mother and child]. / Embarazo en receptoras de trasplante renal: efectos en la madre y en el niño.

When the field of transplantation was first developing, physicians worried about the teratogenicity of immunosuppressive medications and considered pregnancy ill-advised. The purpose of this study is to analyze pregnancy after kidney transplantation and their consequences on mother, graft and child. We review ten pregnant women with kidney transplantation, average of 29 years old and 44 months post-kidney transplantation. The mean glomerular filtration rate was 64 ml/min and the immunosuppression was with prednisone and tacrolimus. We analyze outcomes of different variables before and during pregnancy, and after labour. Pregnancy finished in nine of ten patients. Three patients needed cesarean section and only one patient had a miscarriage on the first term. Blood arterial pressure increased at the end of pregnancy and the creatinine level was stable with a few increase of proteinuria at the third term. We increased the tacrolimus dose to obtain the correct blood levels and any rejection was detected. We had only one patient with preeclampsia that we solved with a cesarean section. Labours were a mean of 37.2 weeks and the mean birth weight of infant was 2,809 grams. Two newborns had prematurity without structural malformations. Pregnancy after kidney transplantation is safe with prednisone and tacrolimus when the renal function is good, proteinuria doesn't exist and blood pressure is controlled.

[Prophylactic and pre-emptive therapy for cytomegalovirus infection in kidney transplant patients using oral valganciclovir]. / Tratamiento profiláctico y anticipado de la infección por citomegalovirus en pacientes trasplantados renales mediante valganciclovir oral.

UNLABELLED: Prophylactic and pre-emptive therapy with oral valganciclovir for cytomegalovirus infection in renal transplant recipients. BACKGROUND: Cytomegalovirus infection is a very important health problem in solid organ transplant recipients (SOT). Once-daily valganciclovir has been shown to be as clinically effective and well tolerated as oral ganciclovir tid in the prevention of CMV infection in high risk SOT recipients. METHODS: The aim of the present study was to evaluate the incidence and severity of CMV disease in 150 renal transplant recipients that received either prophylactic [high risk group (HR), N = 66] or pre-emptive [low risk group (LR), N = 84] therapy with oral valganciclovir (900 mg/day vo) for three months according to their basal risk. Patients were monitored for signs and symptoms of CMV disease and CMV plasma viral load was assessed weekly. RESULTS: A total of 31 patients (47%) of the HR and 26 patients (31%) of the LR presented a positive CMV PCR result. Twelve patients (14.3%) in the LR that had a high viral load (CMV PCR > 1,000 copies/mL) but remained asymptomatic received pre-emptive therapy. Four patients (4.7%) in the LR, after an average time of 35 days after transplant and two patients (4.5%) in the HR, after prophylactic treatment was completed, developed CMV disease. The disease was mild-moderate in most of the cases. Those patients that developed CMV disease responded to treatment with iv ganciclovir for 14 days followed by treatment with oral valganciclovir for up to three months. CONCLUSION: Prophylactic treatment with oral valganciclovir for CMV prevention is only required in high risk solid organ transplant recipients.

[Quality of life of patients with rheumatoid arthritis undergoing out-patient treatment with TNF inhibitors]. / Calidad de vida en pacientes con artritis reumatoide en tratamiento ambulatorio con anti-TNF.

OBJECTIVE: To assess the quality of life of patients with rheumatoid arthritis undergoing out-patient treatment with TNF inhibitors (etanercept and adalimumab). METHOD: Observational, descriptive and multi-centre study. A specific validated questionnaire was used (QOL-RA Scale) in its Spanish version, with complete confidentiality ensured. To measure the reliability of the results, the Cronbach Alpha Coefficient was used. A descriptive analysis was carried out to compare the results obtained with those obtained from studies in the USA and Colombia. RESULTS: A total of 82 patients were selected who mainly consisted of married housewives who had not undergone any previous studies. The average amount of years from diagnosis was 11.81 years (SD: 7.30) and the average duration of treatment with TNF inhibitors was 1.71 years (SD: 1.03). The results of the questionnaire were: physical ability 5.42 (SD: 1.67), pain 5.10 (SD: 1.83), social life 7.08 (SD: 1.96), support 7.45 (SD: 2.10), mood 6.02 (SD: 2.03), stress 5.50 (SD: 2.01), arthritis 5.15 (SD: 1.86), health 5.50 (SD: 1.77). The results obtained were similar to those from the USA, although they showed a lower score for mood and stress categories. However, the high score in the support and social-life categories was more similar to that obtained with the Colombian questionnaire. All patients considered their quality of life to have improved with the use of TNF inhibitors. CONCLUSIONS: The quality of life in patients with Rheumatoid Arthritis is low, determined by pain and symptoms of depression. The patients believe that TNF inhibitors have improved their quality of life.

Using specific recombinant gonadotropins to induce spermatogenesis and spermiation in the European eel (Anguilla anguilla).

New specific European eel (Anguilla anguilla) recombinant gonadotropins (aarGths) produced in the ovarian cells of Chinese hamsters (CHO) were used to induce maturation in captive male eels. In the first experiment, five different hormonal treatments were assayed: one group was given a constant dose of recombinant European eel follicle-stimulating hormone (aarFsh; 4 µg/fish) for 9 weeks, and the second group received a constant dose of recombinant European eel luteinizing hormone (aarLh; 2 µg/fish) also for 9 weeks. The other three groups were injected with different combinations of both aarGths (some doses constant, some variable). All five treatments stimulated androgen synthesis, but the increase was more pronounced in the fish treated with a combination of both aarGths. Unlike aarLh, aarFsh alone was able to induce spermiation, the best results were achieved in the fish that were treated with a constant dose of aarFSH and an increasing dose of aarLH, with spermiation being induced (20% motile cells) despite the fact that these fish were immature at the start of the experiment. In order to improve sperm quality, a second experiment was performed. Immature males received three constant doses of aarFsh (2.8, 1.4 or 0.7 µg/fish) and increasing doses of aarLh (every 3 weeks; 1, 2, 6 µg/fish). All the treatments induced spermiation, however the best sperm quality (with ≥50% motile cells) was observed in the males treated with the highest dose of aarFsh. In conclusion, these specific recombinant gonadotropins have demonstrated their capacity to induce spermatogenesis and spermiation in vivo in a teleost fish, the European eel.

Cutaneous changes during prolonged application of 12-O-tetradecanoylphorbol-13-acetate on mouse skin and residual effects after cessation of treatment.

The epidermal and dermal effects of protracted 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment (2 micrograms TPA twice weekly) of Sencar mouse skin were studied using cell kinetics and morphometric techniques. In addition, regression of TPA-induced changes was evaluated after cessation of 56 topical applications. During the first week of treatment a reactional hyperplasia, characterized by cell damage, edema, and acute inflammation in both epidermis and dermis, occurred. This picture changed gradually during the following 3 weeks: an epidermal hyperplasia devoid of involutional or inflammatory features was accompanied by a moderate to mild chronic inflammation of the dermis and a hyperplasia of the hair follicles. This remained throughout the experimental period until the topical TPA treatment ceased. Although TPA induced papillomas in only 5% of the animals (maximum = 2 papillomas/animal and no carcinomas), all sustained marked epidermal hyperplasia of approximately 4 to 5 times the normal thickness, and increased the number and volume of hair follicles. The [3H]thymidine pulse-labeling index of the basal layer was approximately 32% (normal congruent to 6%). The level of dark keratinocytes remained constant; i.e., 8% of the basal cells were identified as dark cells during the entire experiment. At the subepidermal level the dermal thickness and total cellularity increased, although the proportion of the different cell types changed during the treatment. The mast cell population increased remarkably. After TPA treatment ceased, most of these parameters regressed abruptly during the first 2 weeks. Two to 4 months later, the epidermis was slightly thinner, and the labeling index was 50% lower than normal (2.8%). This study shows that prolonged repetitive TPA applications induced a steady-state hyperplasia without tachyphylaxis, and that this alteration regressed rapidly after treatment ceased. In addition, labeling-index values lower than normal were reached soon after normalization, suggesting that a possible selection of keratinocytes, dependent on TPA for proliferation, took place during the chronic administration of topical TPA. The number of hair follicle, capillary vessels, mast cells, and the dermal thickness never reached normal values after treatment. These important changes in the dermis and hair follicles indicate that the target cells for tumor promoters are not confined to the epidermis alone, and that these tissues could participate actively in carcinogenesis directly, either as tumor-originating tissues (hair follicles), or as inducers or helpers of neoplastic growth (connective tissue cells).

Expression of epidermal growth factor receptor, polyamine levels, ornithine decarboxylase activity, micronuclei, and transglutaminase I in a 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis model.

The expression of epidermal growth factor receptor and transglutaminase type I, polyamine (putrescine, spermidine, and spermine) levels, ornithine decarboxylase activity, and micronuclei occurrence were assessed in the 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch model to elucidate the role and timing of changes in different growth and differentiation markers during carcinogenesis. DMBA (0.5%) in heavy mineral oil was applied to the right buccal pouch 3 times per wk for up to 16 wk; controls received heavy mineral oil alone. Hamsters were killed after 0, 4, 8, and 16 wk. Frozen tissue was chemically analyzed for polyamine levels and ornithine decarboxylase activity and was also used for immunohistochemical analysis of transglutaminase I. Paraffin-embedded sections were used for epidermal growth factor receptor immunohistochemical determinations and for micronucleated cell assays. Hyperplasia was detected by histological analysis at 4 wk, dysplasia with or without papillomatous changes at 8 wk, and squamous cell carcinoma at 16 wk. Epidermal growth factor receptor was not expressed in the normal buccal epithelial layer, at a moderate level in both the superficial keratin and basal cell layers in hyperplastic epithelium, and at very high levels in both dysplasia and squamous cell carcinoma. Transglutaminase I was expressed at a limited level in normal buccal mucosa, was expressed at a low level in the basal layer of hyperplastic lesions, was somewhat elevated in dysplasia, and was markedly enhanced in squamous cell carcinoma. Putrescine and spermidine levels and ornithine decarboxylase activity increased dramatically after 8 and 16 wk of DMBA. Micronucleated cells increased after 4 wk of DMBA treatment, that high level sustained during all stages of carcinogenesis. We suggest that these biological markers could be excellent intermediate end points in assessing the effects of various chemopreventive agents to be tested in the hamster buccal pouch model and in human clinical trials.

Salidiuretic action by genistein in the isolated, perfused rat kidney.

The urinary isoflavonoid genistein inhibits membrane Na-K-Cl cotransporters at similar concentrations as furosemide, but the significance of this action is unknown. Genistein was therefore investigated in rats for its potential salidiuretic actions. In the isolated, perfused rat kidney, genistein induced a maximal salidiuretic action similar to that of furosemide but was 3 to 5 times less potent than furosemide in terms of active doses (natriuresis EC50, 237+/-92 versus 56+/-20 micromol/L for genistein and furosemide, respectively). Genistein and furosemide had no additive salidiuretic actions. Genistein had no significant effect on glomerular filtration rate but was able to significantly reduce renal vascular resistance with respect to vehicle isolated perfused kidney. Indomethacin (10 micromol/L), a blocker of prostaglandin biosynthesis, reduced salidiuresis and renal vasorelaxation by genistein. Subcutaneous genistein (15 mg/kg) induced a statistically significant increase in diuresis and natriuresis with respect to vehicle during the first 6 hours of administration in rats. In conclusion, genistein compares well with furosemide in vitro for its salidiuretic profile and potency in the isolated perfused rat kidney and is also natriuretic by the subcutaneous route in the rat. Further studies are required to investigate potential natriuretic and perhaps hypotensive actions of dietary genistein.

Soy isoflavonoids exhibit in vitro biological activities of loop diuretics.

Intake of soyfoods containing isoflavonoids is related to positive effects on heart and kidney diseases. Urinary equol, a potent inhibitor of Na+-K+-2Cl- cotransport, originates from the metabolism of daidzein by intestinal bacteria. Loop diuretics (eg, furosemide), acting through inhibition of Na+-K+-2Cl- cotransport, are used to maintain adequate blood volume. In the present work, we compare isoflavonoids' inhibition of cotransport and effects on the function and hemodynamics of isolated perfused rat kidneys with those of furosemide. Equol [IC50 (half-maximal inhibitory concentration): 23.6 +/- 3.6 micromol/L], genistein (IC50: 34.8 +/- 2.6 micromol/L), and daidzein (IC50: 140.0 +/- 24 micromol/L) inhibited bumetanide-sensitive rubidium uptake in LLC-PK1 cells. The IC50 of equol and genistein was close to that of furosemide (IC50: 10.3 +/- 2.7 micromol/L). Furosemide, equol, and genistein stimulated water, sodium, and potassium excretion by isolated rat kidneys in the same temporal pattern. None of the isoflavonoids significantly increased the glomerular filtration rate, but genistein induced significant vasorelaxation. We conclude that isoflavonoids exhibit biological activities of furosemide in vitro, at concentrations similar to those reported for other in vitro effects. More research is needed to evaluate the participation of cotransport inhibition by isoflavonoids in the healthful effects claimed for soy intake.

Renal and vascular actions of equol in the rat.

BACKGROUND: The urinary isoflavonoid equol inhibits membrane Na-K-Cl cotransporters at similar concentrations to those at which furosemide inhibits them, but the significance of this action is not known. OBJECTIVE: To investigate the potential salidiuretic and vascular actions of equol in the rat. METHODS: Renal functioning was assessed in vitro in the isolated perfused kidney and in vivo in conscious rats. The vascular contractility of isolated aorta was assessed. RESULTS: In the isolated perfused kidney equol was concentrated 50- to 70-fold in the urinary fluid, it was 3-4 times less potent than furosemide at increasing diuresis, natriuresis and kaliuresis (the difference was due to its higher protein-binding affinity), and it induced a modest but significant increase in glomerular filtration rate. In vivo, orally administered equol was a modest natriuretic agent, about 8-fold less potent than orally administered furosemide (in molar terms). In isolated aortic rings precontracted by administration of phenylephrine, administration of equol relaxed the contracted aorta at 10-fold lower concentrations (concentration for half-maximal activity 58.9 +/- 16 micromol/l, n = 3) than did furosemide (concentration for half-maximal activity 633 +/- 145 micromol/l, n = 3). CONCLUSIONS: Equol is a modest natriuretic and vasorelaxant agent in the rat. Further studies are required in order to investigate the potential natriuretic and perhaps hypotensive actions of dietary equol precursors (daidzein).

Natriuretic effect of equol.

A furosemide-sensitive Na-K-Cl cotransporter (NKCC2 isoform) accounts for almost all luminal NaCl reabsorption in the thick ascending limb of Henle's loop (TALH). The activity of this transport protein is regulated by humoral factors known as cotransport inhibitory factors. One family of these compounds is represented by the urinary phytoestrogens equol and genistein, which inhibit cotransport fluxes at concentrations similar to furosemide. Moreover, they possess salidiuretic potency similar to furosemide in the isolated perfused rat kidney, but are less potent than furosemide (in vivo). Thus, dietary phytoestrogens can be responsible, at least in part, for the low blood pressure of vegetarians.