Tourniquet application in time-critical aquatic emergencies on a moving rescue water craft (RWC): Can speed and precision coexist?

Lifeguards are the first responders to any type of aquatic incident, including rapid rescue situations such as boating and sporting accidents, animal bites/attacks, and cases involving massive bleeding. In their line of work, rescue boats such as Rescue Water Craft (RWC) are commonly utilized the aim of this study is to evaluate the time and technique of placing a tourniquet on the sled of an RWC navigating at full speed. METHODS: A randomized crossover study design was used with a sample of 44 lifeguards. The inclusion criteria required that participants be certified lifeguards with experience in RWC operations and possess knowledge of responding to massive bleeding. Two CAT tourniquet placement tests were performed. In the 1) Beach-Tourniquet (B-TQ) test: it was performed on land and in the 2) Rescue Water Craft-tourniquet (RWC-TQ) test, sailing at a cruising speed of 20 knots. The evaluation was recorded in a checklist on the steps and timing of the correct application TQ by direct observation by an expert instructor. RESULTS: The tourniquet placement on RWC was an average of 11 s slower than when placed on the beach (BT-TQ 35.7 ± 8.0 vs. 46.1 ± 10.9 s, p > 0.001). In the percentage analysis of the results on correct execution of the skills, higher values are obtained for the B-TQ test than in RWC-TQ in Distance to the wound (into 5-7 cm), band adjustment, checking the radial pulse and reporting the time of tourniquet placement (p > 0.005). CONCLUSION: The placement of a tourniquet on a RWC navigating at 20 knots is feasible, relatively quick, and technically well executed.

[Management of a first depressive episode in the primary care setting. Use of antidepressants and referrals]. / Manejo en atención primaria de un primer episodio depresivo. Uso de antidepresivos y derivaciones.

INTRODUCTION: The majority of patients who have a first depressive episode are treated by Primary Care physicians. The aim of this study was to evaluate the use of antidepressants and referrals to mental health and the treatment modifications made by psychiatrists. MATERIAL AND METHODS: A descriptive, retrospective study was conducted on patients from 64 Primary Care clinics, distributed in five Spanish provinces. The clinical history data, regarding use of antidepressants, criteria for referral, and response of psychiatric services were evaluated from June 2008 to June 2011. RESULTS: The study included 324 patients. The most commonly prescribed medication was escitalopram, with selective serotonin reuptake inhibitors (SSRI) making up 73.5% of the total. More than two-thirds (69.7%) of the patients were on treatment for at least 6 months, with no reason recorded for the 40.4% drop-outs. A large majority of professionals (76.9%) wait at least 3 weeks before modifying the medication, especially changing antidepressant. The Primary Care physicians referred 39.2% of patients to psychiatry, although much of these referrals (43.9%) had no justification. There was a lower referral rate to psychology (23.1%). An antidepressant was given to a large number of patients on multiple medications, without taking into account the risk of interactions in a high percentage. CONCLUSIONS: The Primary Care physician appropriately uses the antidepressants of the first choice, but does not pay attention to the risks in complex patients. There must be an appropriate duration of treatment and an improvement of the criteria for referral to mental health services.

Outcome of acute renal injury in diabetic mice with experimental endotoxemia: role of hypoxia-inducible factor-1 α.

The role of diabetic nephropathy in the outcome of acute renal injury (AKI) is not well defined. Herein we evaluate the outcome of lipopolysaccharide- (LPS-) induced AKI in streptozotocin-induced diabetes, as well as the potential role of Hypoxia Inducible Factor (HIF-1 α ) in this condition. Although 6 h after LPS injection all mice developed a decrease in renal function, proteinuric diabetic mice showed a better recovery of this parameter throughout the study (72 h). Both HIF-1 α and vascular endothelium growth factor (VEGF) were found to be upregulated in diabetic mice. After LPS injection, all animals showed an upregulation of these factors, although it was higher in the diabetic group. Glycated albumin (GA) was found to upregulate HIF-1 α in HK-2 cells, which resulted in increased production of VEGF. Interestingly, LPS cooperated with GA to induce HIF-1 α upregulation. In conclusion, diabetic mice display a better recovery of AKI after experimental endotoxemia. Moreover, these animals showed an increased expression of both HIF-1 α and VEGF that was reproduced by incubating renal cells with GA. Since VEGF is considered a survival factor for tubular cells, our findings suggest that diabetes displays HIF-1 α upregulation that might function as a "precondition state" offering protection from endotoxic AKI.

Effectiveness of a diagnostic algorithm combining clinical probability, D-dimer testing, and computed tomography in patients with suspected pulmonary embolism in an emergency department.

OBJECTIVE: The aim of our study was to assess the clinical effectiveness of a simplified algorithm using the Wells clinical decision rule, D-dimer testing, and computed tomography (CT) in patients with suspected pulmonary embolism (PE) in an Emergency Department (ED). METHODS: Patients with clinically suspected PE from the Emergency Department were included from May 2007 through December 2008. Clinical probability was assessed using the Wells clinical decision rule and a VIDAS D-dimer assay was used to measure D-dimer concentration. Patients were categorized as "pulmonary embolism unlikely" or "pulmonary embolism likely" using the dichotomized version of the Wells clinical decision rule. Pulmonary embolism was considered excluded in patients with unlikely probability and normal D-dimer test (< 500 ng/ml). All other patients underwent CT, and pulmonary embolism was considered present or excluded based on the results. Anticoagulants were withheld from patients classified as excluded, and all patients were followed up for 3 months. RESULTS: 241 patients were included in the study. The prevalence of PE in the entire population was 23.6%. The combination of unlikely probability using the dichotomized Wells clinical decision rule and a normal D-dimer level occurred in 23.6%, thus making CT unnecessary. During the followup period, no thromboembolic events were recorded and there were no deaths related to venous thromboembolic disease (3-month thromboembolic risk 0% [95% CI, 0%-8%]). CONCLUSIONS: In this study we have confirmed the effectiveness of a diagnostic management strategy using a simple clinical decision rule, D-dimer testing, and CT in the evaluation and management of patients with clinically suspected pulmonary embolism.

Diagnostic efficacy and prognostic value of serum procalcitonin concentration in patients with suspected sepsis.

BACKGROUND: Procalcitonin is released in response to bacterial infection and it is not released in Inflammatory and viral diseases. OBJECTIVE: To show the diagnostic efficacy and prognostic value of procalcitonin for sepsis. METHODS: A consecutive series of 103 patients with suspected sepsis were admitted to the intensive care unit over a 2-year period. During the first 24 hours of the admission procalcitonin, C-reactive protein, and complement proteins were determined. The diagnostic efficacy was tested with predictive values, likelihood ratios, receiver operating characteristic curves, and multiple logistic regression. The association of procalcitonin with mortality was assessed by the Multivariate Cox proportional hazards model. RESULTS: Procalcitonin had a better positive likelihood ratio than C-reactive protein -2.2 (95% confidence interval: 1.3-3.7) versus 1.1 (95% confidence interval: 0.9-1.2). Sequential Organ Failure Assessment yielded the highest discriminative value, with an area under the curve of 0.82 (95% confidence interval: 0.73-0.92), followed by procalcitonin (0.81; 95% confidence interval: 0.72-0.89). Multivariate regression analysis showed procalcitonin (adjusted odds ratio: 3.8; 95% confidence interval: 1.2-11.8) and Sequential Organ Failure Assessment score (adjusted odds ratio: 5.3; 95% confidence interval: 1.4-19.9) as the only variables independently associated with infection. Multivariate Cox regression analysis revealed that procalcitonin was not independently associated with mortality. CONCLUSIONS: The diagnostic accuracy of procalcitonin was higher than C-reactive protein and complement proteins. Procalcitonin in combination with Sequential Organ Failure Assessment was useful to diagnose infection. C-reactive protein, Sequential Organ Failure Assessment score, age, and gender showed to be helpful to improve the prediction of mortality risk, but not procalcitonin.

[Differences in the synthesis pattern of vasoactive factors in gestational hypertension and preeclampsia]. / Diferencias en el patrón de síntesis de factores vasoactivos en la hipertensión gestacional y en la preeclampsia.

BACKGROUND AND OBJECTIVE: The gestational hypertension -HG- and preeclampsia -P- are hypertensive diseases whose pathogenic mechanism has not been determined yet. The aim of this work is to define some patterns of vasoactive factors release that allow to explain the origin of the differences between both entities. DESIGN: Prospective case-control study. MATERIAL AND METHODS: Two groups of target patients were consecutively selected, GH (n=21) and P patients (n=21). Every patient was matched with a pregnant of similar age and week of pregnancy. Two control groups were obtained, one respect to the GH and another one respect to the P group. A biochemistry, blood cell count, coagulation and quantification of vasoactive factors endothelin, nitrites and GMPc were performed in every woman. Results of GH and P groups were compared with their respective control group with the paired Student's t Test. RESULTS: Both systolic and diastolic arterial pressures were higher in hypertensive pregnants (GH and P) than in their respective controls. Moreover, blood endothelin and GMPc were higher in GH and P. GH pregnants showed decreased norepinephrine and increased epinephrine urinary excretion , as well as an increased plasma nitrites concentration than control group. P patients did not show statistically significant differences in catecholamines urinary excretion nor in plasma nitrites concentration respect their control group. CONCLUSION: There are relevant differences in the synthesis patterns of vasoactive factors between gestational hypertension and preeclampsia. These differences could account for a decreased tissue perfusion in preeclampsia and could also contribute to the genesis of the renal dysfunction of this entity.

Phosphocalcic metabolism after biliopancreatic diversion.

BACKGROUND: Malabsorptive techniques to treat morbid obesity have been followed by alterations in phosphocalcic metabolism. Knowledge of the preoperative situation is important to assess the influence of these techniques on phosphocalcic metabolism and to consider treatments for these alterations. METHODS: 61 consecutive morbidly obese patients (50 women, 11 men, age 19 to 63 years) having had biliopancreatic diversion (BPD) were studied in a prospective manner. Preoperative and postoperative levels of calcium, phosphorus, 25-hydroxyvitamin D, tartrate resistant acid phosphate, plasma parathormone (PTH), tubular absorption of phosphate, and urinary calcium and pyridinolines were analyzed, as well as the potential risk factors for their alterations. Follow-up of all patients was a minimum of 4 years. RESULTS: Before BPD, 42.3% of patients presented an increase in PTH and 54% a decrease in the 25-OH vitamin D, but the values of calcium and plasma phosphorus maintained at normal level. 81.8% of the patients with an increase in the PTH maintained high levels after BPD, while 60% of those with a normal preoperative PTH also presented hyperparathyroidism 4 years after the intervention. A correlation between the levels of plasma PTH and body mass index was not found. CONCLUSION: Morbid obesity is accompanied by a high percentage of hyperparathyroidism. BPD produces malabsorption of vitamin D during the first years, favoring the persistence or appearance of hyperparathyroidism. It is important to recognize and treat the secondary hyperparathyroidism. The postoperative period could necessitate more energetic interventions to get more efficient control of the phosphocalcic metabolism.

The parathyroid hormone-related protein system and diabetic nephropathy outcome in streptozotocin-induced diabetes.

The pathophysiology of the diabetic kidney (e.g., hypertrophy, increase urinary albumin excretion (UAE) is still ill-defined. Parathyroid hormone-related protein (PTHrP) is overexpressed in several nephropathies, but its role remains unclear. We evaluated the effect of high glucose on PTHrP and the PTH1 receptor (PTH1R) protein (by Western blot and immunohistochemistry) in the kidney of mice ith streptozotocin-induced diabetes, and in several mouse renal cells in vitro. Diabetic mice showed a significantly increased renal expression of PTHrP and PTH1R proteins with 2-8 weeks from the onset of diabetes. These animals exhibited an intense immunostaining for both proteins in the renal tubules and glomeruli. Using transgenic mice overexpressing PTHrP targeted to the renal proximal tubule, we found a significant increase in the renal hypertrophy index and in UAE in these diabetic mice relative to their control littermates. Moreover, logistic regression analysis showed a significant association between both PTHrP and PTH1R protein levels and UAE in all diabetic mice throughout the study. High-glucose (25 mm) medium was found to increase PTHrP and PTH1R in tubuloepithelial cells, mesangial cells and podocytes in vitro. Moreover, this increase in PTHrP (but not that of PTH1R) was inhibited by the AT1 receptor antagonist losartan. Collectively, these results indicate that the renal PTHrP/PTH1R system is upregulated in streptozotozin-induced diabetes in mice, and appears to adversely affect the outcome of diabetic renal disease. Our findings also suggest that angiotensin II might have a role in the PTHrP upregulation in this condition.

Retinoids as a potential treatment for experimental puromycin-induced nephrosis.

1 Puromycin aminonucleoside (PAN)-induced nephrosis is a model of human minimal change disease. In rats, PAN induces nephrotic-range proteinuria, renal epithelial cell (podocyte) damage, infiltration of mononuclear leukocytes, and apoptosis of several renal cell types. 2 Retinoic acid (RA) modulates a wide range of biological processes, such as inflammation and apoptosis. Since renal damage by PAN is characterized by inflammatory infiltration and epithelial cell death, the effect of treatment with all-trans RA (tRA) was examined in the PAN nephrosis model and in the cultured differentiated podocyte. 3 Treatment with tRA 4 days after PAN injection did not inhibit the proteinuria peak but reversed it significantly. However, treatment with tRA both before and 2 days after the injection of PAN protected the glomerular epithelial cells, diminishing the cellular edema and diffuseness of the foot process effacement. Preservation of the podocyte architecture correlated with the inhibition of proteinuria. The anti-inflammatory effect of tRA was evidenced by the inhibition of PAN-induced interstitial mononuclear cell infiltration and the decreased renal expression of two molecules involved in monocyte infiltration: fibronectin and monocyte chemoattractant protein-1. TUNEL assays showed that tRA inhibited the PAN-induced apoptosis of cultured differentiated mouse podocytes. 4 We conclude that tRA treatment may prevent proteinuria by protecting the podocytes from injury and diminishing the interstitial mononuclear infiltrate in the model of PAN nephrosis. Retinoids are a potential new treatment for kidney diseases characterized by proteinuria and mononuclear cell infiltration.

Bone mass, bone metabolism, gonadal status and body mass index.

Weight and gonadal status are the main determinants of bone mass in women. Because of this it is important to study which influences it more. The effect of weight (expressed as body mass index, BMI) and gonadal status of women on total-body bone mineral content (TBBMC) and regional bone mineral content (BMC) was investigated. A total of 373 normal women (mean age 48.9 +/- 13.4 years) were studied: 171 postmenopausal women (mean age 59.3 +/- 9.5 years; years since menopause 11.3 +/- 6.7 years); 76 perimenopausal women (mean age 48.9 +/- 2.2 years); and 126 premenopausal women (mean age 34.7 +/- 7.4 years). In all the women, TBBMC and regional BMC were determined by dual-energy X-ray absorptiometry. Also biochemical markers of bone metabolism (total alkaline phosphatase and tartrate-resistant acid phosphatase) and serum estrone and estradiol were determined. When the women were stratified by gonadal status and BMI, thin women (BMI <20 kg/m2) had significantly lower TBBMC and regional BMC, lower gonadal steroid concentration and higher levels of biochemical markers than overweight (BMI 25-30 kg/m2) and obese (BMI >30 kg/m2) women, regardless of gonadal status. Overweight and obese women had findings suggestive of increased parathyroid activity, but greater bone mass. Weight rather than gonadal steroid concentration is the main determinant of bone mass in women regardless of gonadal status.

Can a determination of tartrate-resistant acid phosphatase predict postmenopausal loss of bone mass?

BACKGROUND: A study was carried out over a 24-month interval to determine if an initial measurement of serum tartrate-resistant acid phosphatase would be predictive of bone mass loss quantified by dual-energy X-ray absorptiometry, as total bone mineral content and total bone mineral content corrected for weight. DESIGN: Sixty-two women were studied (at onset: mean age 59.7 +/- 8.9 years, 10.8 +/- 8.8 years since menopause; at conclusion: mean age 61.9 +/- 8.8 and 13.0 +/- 8.7 since menopause). RESULTS: A paired Wilcoxon test showed a small, but significant, increase in weight (P < 0.05) and decrease in height (P < 0.05). Total bone mineral content and total bone mineral content corrected for weight decreased (P < 0.005 and 0.0001, respectively). Serum tartrate-resistant acid phosphatase increased (P < 0.005). Single-regression analysis showed that the per cent bone mass loss observed between the first and second body bone mineral content measurements correlated negatively with the first serum tartrate-resistant acid phosphatase determination (r = -0.62, P < 0.0001). Changes in tartrate-resistant acid phosphatase correlated negatively with changes in total bone mineral content (r = -0.79, P < 0.0001). In a multiple regression analysis of per cent change in bone mass against initially important variables such as age, years since menopause, weight, and tartrate-resistant acid phosphatase, only tartrate-resistant acid phosphatase was significant (P < 0.0001). The sensitivity and specifity of tartrate-resistant acid phosphatase for evaluating bone loss were 86% and 78%, respectively, and the area under the curve was of 0.83 (95% CI 0.71-0.95). CONCLUSION: These results show that a simple measurement of serum tartrate-resistant acid phosphatase can help to predict the potential rate of bone mass loss in women.

Spiral CT findings in active and remission phases in patients with Crohn disease.

PURPOSE: The purpose of this study was to evaluate the radiologic findings in helical CT (HCT) that can be useful to differentiate patients with active Crohn disease (CD) from those in the remission phase. METHOD: Fifty patients diagnosed with cases of CD were classified into active or remission phases (n = 37 and n = 13, respectively) according to clinical criteria and laboratory data. All of them underwent an abdominal HCT exploration. The following radiologic findings were evaluated: thickness, density and enhancement of the bowel wall, presence of "target" or "double halo," mesenteric involvement, and possible complications. RESULTS: All patients in the active phase had pathologic findings on HCT. The wall thickness was 8.5 (SD 3.2) and 6.5 mm (SD 4 mm) in active and remission phases, respectively (p = 0.06). Target was present in seven patients (19%) with active disease and in five patients (38.5%) in the remission phase (p = 0.15). Density of the wall in the active phase was 95 HU and in the remission phase 65 HU (p < 0.002). Mesentery was involved in 89.2% of patients in the active phase and 38% of patients in the remission phase (p < 0.001). The complications observed in patients with active-phase disease were abscesses in nine (24%), phlegmons in two, fistulas in three, intestinal obstruction in two, and pancreatitis in one. CONCLUSION: A normal HCT rules out that a patient with CD is in the active phase of disease. The presence of significant bowel wall enhancement and mesentery involvement assists in the differentiation of patients in the active phase from those in remission. HCT is also effective to assess the presence of complications, which are indicative of the active phase.

Prognostic value of carcinoembryonic antigen, CA 19-9 and CA 72-4 in gastric carcinoma.

The prognostic value of preoperative serum levels of carcinoembryonic antigen (CEA), CA 19-9 and CA 72-4 tumor markers was investigated in patients with gastric cancer. Eighty-two patients who underwent surgical resection of gastric cancer were entered in the study. Correlation analyses showed that CA 72-4 was more frequently positive in patients with advanced tumors (p = 0.04), lymph node invasion (p = 0.02), liver metastasis (p = 0.02) and peritoneal involvement (p = 0.03). CA 19-9 was more frequently positive in patients with advanced tumors (p = 0.01) and with serosal (p = 0.04), lymph node (p = 0.008) and peritoneal involvement (p = 0.02). CEA was more frequently positive in patients with liver metastasis (p = 0.03). Low 3-year cumulative survival was significantly associated with elevated serum levels of CA 72-4 (p = 0.004), CA 19-9 (p = 0.001) and CEA (p < 0.001). Age, tumor stage and CA 72-4 provided prognostic information in the multivariate analysis. Patients with elevated serum levels of CA 72-4 showed a 4.2 times higher risk of death than patients with low levels of the marker. Our results suggest that CA 72-4 has prognostic value in gastric cancer, and patients with a high preoperative serum level of CA 72-4 have a greater risk of death due to gastric cancer.

Behavior of phalangeal bone ultrasound in normal women with relation to gonadal status and body mass index.

The behavior of phalangeal bone ultrasound was studied, measured by amplitude-dependent speed of sound (Ad-SOS) in meters per second, in 324 normal women (mean age 48.9 +/- 13.7 years) classified by gonadal status (premenopausal, perimenopausal and postmenopausal) and body mass index (BMI, thin, normal, overweight and obese). Ad-SOS differed significantly with gonadal status and BMI (p<0.0001 for all). In the overall group of women, Ad-SOS correlated negatively with age (r=-0.84, p<0.0001), weight (r=-0.16, p<0.005), BMI (r=-0.27, p<0.0001), and tartrate-resistant acid phosphatase concentration (TRAP) (r=-0.35, p<0.0001). The negative correlation remained significant in the groups separated by gonadal status, but to a lesser extent. After adjusting for confounding variables such as age and weight, Ad-SOS was dependent on age (but not on weight or BMI) in the overall group of women and in the gonadal status groups. In conclusion, Ad-SOS values differed significantly with gonadal status and BMI, and correlated negatively with TRAP. The plot of Ad-SOS against age differed significantly with gonadal status as well as BMI.

[Usefulness of the percentage of free prostatic specific antigen in the differential diagnosis between benign prostatic hyperplasia and prostate cancer]. / Utilidad de la fracción libre del antígeno prostático específico en el diagnóstico diferencial entre hiperplasia prostática benigna y cáncer de próstata.

BACKGROUND: PSA (prostatic specific antigen) is the most used tumor marker to monitor prostate cancer (PC). It is an acceptably sensitive test. Molecular forms of PSA give a chance to improve its specificity. We have evaluated the usefulness of the ratio free PSA/total PSA (f-PSA/t-PSA%) to diagnose prostate cancer, in the range between 4 and 20 ng/ml; i.e. the interval in which values overlap for patients with PC and benign prostatic hyperplasia (BPH) in our environment. PATIENTS AND METHODS: Prospective study on 269 patients, 73 with PC and 196 with BPH. Both t-PSA and f-PSA were determined using microparticles enzyme immune assay (MEIA) with AXSYM (Abbott) analyzer. RESULTS: Statistically significant differences were evidenced in f-PSA/t-PSA% for patients with PC vs. BPH; but that did not happen for t-PSA values. Sensitivity and specificity values were established for different cut-off points. ROC curve analysis proved diagnostic efficacy was better for f-PSA/t-PSA% than for t-PSA. CONCLUSIONS: f-PSA/t-PSA percentage is a useful tool for the differential diagnosis between PC and BPH. A ratio lower than 12% selects a population with high risk of cancer. A percentage over 18% is useful to avoid or delay the indication of biopsy.

Cyclosporine increases local glomerular synthesis of reactive oxygen species in rats: effect of vitamin E on cyclosporine nephrotoxicity.

BACKGROUND: We report an investigation of the effects of cyclosporine (CsA) on kidney function, the glomerular synthesis of reactive oxygen species, the peroxidation of lipids, and the levels of thromboxane B2 (TXB2). The effect of the simultaneous administration of the antioxidant vitamin E (Vit E) and CsA in rats was also evaluated. METHODS: Adult male Wistar rats were treated for 30 days with CsA (30 mg/kg/day), with Vit E (0.05 mg/ml), with CsA plus Vit E, or with the vehicle used for administration of CsA, namely 12.6% ethanol. RESULTS: CsA induced kidney failure and increased the glomerular synthesis of superoxide anion, H2O2, malonyldialdehyde, and TXB2. Vit E minimized the adverse effects of CsA on kidney function and the glomerular synthesis of these compounds. CONCLUSIONS: Our results suggest that the acute decrease in glomerular filtration rate induced by CsA might be mediated by the synthesis of reactive oxygen species and subsequent peroxidation of lipids, which increases the levels of TXB2. Treatment with Vit E prevented these effects, suggesting a possible role for antioxidants in the prevention of CsA nephrotoxicity.

Total and regional bone mass and biochemical markers of bone remodeling in metastatic prostate cancer.

BACKGROUND: The osteolytic activity of metastases of prostate cancer was evaluated in relation to total body bone mineral content (TBBMC) and regional bone mineral content (RBMC). METHODS: Bone mass was determined by dual-energy X-ray absorptiometry (DXA). Tartrate-resistant acid phosphatase (TRAP) was measured as a biochemical marker of bone resorption. RESULTS: In 32 patients (mean age 72+/-4 years) compared with 32 controls (mean age 73+/-5 years), there were significant differences in TRAP (P < 0.0001), TBBMC (P < 0.0001), and RBMC in the pelvis (P < 0.0001), legs (P=0.0001), and trunk (P<0.05), but not in the arms and head (P=ns). In the overall group of subjects, the correlation between TBBMC and TRAP was r=-0.68, P < 0.0001. The correlations remained significant in the patient and control groups separately. CONCLUSIONS: The loss of bone mass observed in patients with metastatic prostate cancer was caused mainly by the predominance of bone resorption in the osteoblastic metastases.

Cyclosporin A-induced hydrogen peroxide synthesis by cultured human mesangial cells is blocked by exogenous antioxidants.

Cyclosporin A (CsA) is the immunosupressor most widely used in transplanted patients for preventing organ rejection, but it has some toxic side effects in vascular beds and kidney. The purpose of this work was to study if H2O2, a reactive oxygen species, is involved in the CsA-induced toxic effects on kidney in vitro. Human mesangial cells (HMC) in culture were incubated in presence of CsA (10[-5]-10[-8]M) and H2O2 was measured by flow cytometry. The specificity of the probe used in this method was demonstrated as fluorescence was not detected when superoxide anion generated through a Xanthine-Xanthine oxidase system was present, but fluorescence was noted when H2O2 was present in the incubation medium, both directly and after addition of superoxide dismutase to the medium thus promoting H2O2 synthesis. CsA induced a significant dose and time-response increased H2O2 synthesis by cultured HMC. This increase appeared 5 min after CsA addition, being maximal between 15-45 min at CsA concentration of 10(-7)M. When HMC were preincubated with antioxidants as vitamin E or selenium, the CsA-induced H2O2 production was partially blocked. In addition, selenium also induced an increased activity of glutathion peroxidase in HMC after 24 hours of incubation, suggesting that it exerted its H2O2 scavenging action through the modulation of the activity of this enzyme.