Trunk muscle strength tests to predict injuries, attrition and military ability in soldiers.

AIM: Physical fitness is related to injuries, attrition and military ability in military organisations. Therefore, all military organizations of the North Atlantic Treaty Organizations (NATO) test their employees' physical fitness at least once a year. The sit-up test is part of most of the fitness test batteries used. A possible alternative to the sit-up test is the global trunk muscle strength test (TMS). The aim of the present study was to compare the predictability of injuries, attrition and military ability between TMS and sit-up test performances. METHODS: A total of 230 male recruits in a Swiss Army fusilier company completed TMS and sit-up tests in week 1 of military training school. During the following 13 weeks, injuries, attrition and military ability data were collected. Statistical analysis included backward binary regression and receiver operating characteristic (ROC) curve analysis to compare the discriminative power of TMS and the sit-up test to predict injuries, attrition and military ability. RESULTS: ROC analysis revealed larger areas under the curve for total injuries, attrition and military ability for the TMS (areatotal injuries=0.58; areaattrition=0.60; areamilitary ability=0.59) than for the sit-up test (areatotal injuries=0.53; areaattrition=0.50; areamilitary ability=0.56). Binary logistic regression analysis revealed low body mass index, low TMS performance and cigarette smoking to be potential risk factors for injuries; while sit-up performance was extracted from the model. CONCLUSION: The TMS seems to be a valid alternative to the sit-up test in a military setting due to its appropriate results in predicting injuries in the present study.

The Swiss Army physical fitness test battery predicts risk of overuse injuries among recruits.

AIM: The aim of this study was to quantify the discriminative power of physical performance tests to recognize conscripts with enhanced risk of acute and overuse injuries in specific, physically demanding occupational specialties of the Swiss Army. The five performance tests investigated represent the Swiss Army Physical Fitness Test Battery. METHODS: Physical fitness performances were assessed during recruitment procedures prior to military service, and injury occurrences were assessed during 18 weeks of boot camp. Complete fitness and injury data of 459 volunteers from four military occupational specialties were collected. Discriminative power of volunteers' aerobic endurance capacity, trunk muscle fitness, muscle power of upper and lower extremities, and balance for predicting risk of acute injuries and for predicting risk of overuse injuries was calculated using receiver operating characteristic curve analysis. RESULTS: The presented fitness tests had no discriminative power for predicting the risk of acute injuries. However, the trunk muscle fitness test was discriminative in predicting overuse injuries in all four military occupational specialties, progressive endurance run in three, balance test in two, and standing long jump in one. Only the seated shot put had no significant power for predicting overuse injuries in all four study groups. However, for different occupational specialties, different fitness parameters were discriminative to predict overuse injuries. CONCLUSION: It is possible to conclude that the fitness tests used allow detection of conscripts with enhanced overuse injury risk in physically demanding occupational specialties and therefore provide an indicator to select suitable personnel for physically demanding jobs in a military organization.

Lead isotopes reveal bilateral asymmetry and vertical continuity in the Hawaiian mantle plume.

The two parallel chains of Hawaiian volcanoes ('Loa' and 'Kea') are known to have statistically different but overlapping radiogenic isotope characteristics. This has been explained by a model of a concentrically zoned mantle plume, where the Kea chain preferentially samples a more peripheral portion of the plume. Using high-precision lead isotope data for both centrally and peripherally located volcanoes, we show here that the two trends have very little compositional overlap and instead reveal bilateral, non-concentric plume zones, probably derived from the plume source in the mantle. On a smaller scale, along the Kea chain, there are isotopic differences between the youngest lavas from the Mauna Kea and Kilauea volcanoes, but the 550-thousand-year-old Mauna Kea lavas are isotopically identical to Kilauea lavas, consistent with Mauna Kea's position relative to the plume, which was then similar to that of present-day Kilauea. We therefore conclude that narrow (less than 50 kilometres wide) compositional streaks, as well as the larger-scale bilateral zonation, are vertically continuous over tens to hundreds of kilometres within the plume.

Tumor necrosis factor alpha and interleukin 1beta enhance the cortisone/cortisol shuttle.

Endogenously released or exogenously administered glucocorticosteroids are relevant hormones for controlling inflammation. Only 11beta-hydroxy glucocorticosteroids, but not 11-keto glucocorticosteroids, activate glucocorticoid receptors. Since we found that glomerular mesangial cells (GMC) express 11beta-hydroxysteroid dehydrogenase 1 (11beta-OHSD1), which interconverts 11-keto glucocorticosteroids into 11beta-hydroxy glucocorticosteroids (cortisone/cortisol shuttle), we explored whether 11beta-OHSD1 determines the antiinflammatory effect of glucocorticosteroids. GMC exposed to interleukin (IL)-1beta or tumor necrosis factor alpha (TNF-alpha) release group II phospholipase A2 (PLA2), a key enzyme producing inflammatory mediators. 11beta-hydroxy glucocorticosteroids inhibited cytokine-induced transcription and release of PLA2 through a glucocorticoid receptor-dependent mechanism. This inhibition was enhanced by inhibiting 11beta-OHSD1. Interestingly, 11-keto glucocorticosteroids decreased cytokine-induced PLA2 release as well, a finding abrogated by inhibiting 11beta-OHSD1. Stimulating GMC with IL-1beta or TNF-alpha increased expression and reductase activity of 11beta-OHSD1. Similarly, this IL-1beta- and TNF-alpha-induced formation of active 11beta-hydroxy glucocorticosteroids from inert 11-keto glucocorticosteroids by the 11beta-OHSD1 was shown in the Kiki cell line that expresses the stably transfected bacterial beta-galactosidase gene under the control of a glucocorticosteroids response element. Thus, we conclude that 11beta-OHSD1 controls access of 11beta-hydroxy glucocorticosteroids and 11-keto glucocorticosteroids to glucocorticoid receptors and thus determines the anti-inflammatory effect of glucocorticosteroids. IL-1beta and TNF-alpha upregulate specifically the reductase activity of 11beta-OHSD1 and counterbalance by that mechanism their own proinflammatory effect.

Asthma tests in the assessment of military conscripts.

BACKGROUND: Respiratory diseases such as asthma may affect individuals' fitness for military service. In order to assess fitness for military service in subjects with asthma symptoms at conscription, objective and reliable tests are needed. OBJECTIVE: To prospectively determine the diagnostic value of the mannitol and methacholine bronchial provocation test (BPT) as well as exhaled nitric oxide in assessing physician-diagnosed asthma in a group of Swiss Armed Forces conscripts. METHODS: Questionnaire, spirometry, BPT with methacholine and mannitol, exhaled nitric oxide (FeNO) and skin prick testing were conducted in 18-20-year-old male conscripts. Asthma was diagnosed by a military physician not involved in this study according to the medical record, results of BPT, current respiratory symptoms and use of asthma medication. RESULTS: Two hundred and eighty four subjects participated in the study. Complete data for the BPT with methacholine, mannitol and measurement of FeNO were available on 235 subjects. Forty-two conscripts (17.9%) had physician-diagnosed asthma. The sensitivity/specificity of mannitol to identify physician-diagnosed asthma was 41%/93% and for methacholine it was 43%/92%. Using a cut-off point of 36.5 p.p.b., FeNO had a similar negative predictive value to rule out physician-diagnosed asthma as BPT with mannitol or methacholine. CONCLUSION: BPT with mannitol has a sensitivity and specificity similar to methacholine for the diagnosis of physician-diagnosed asthma in military conscripts but is less costly to perform without the need to use and maintain a nebulizer.

An examination chair to measure internal rotation of the hip in routine settings: a validation study.

OBJECTIVE: To determine the performance of a newly developed examination chair as compared with the clinical standard of assessing internal rotation (IR) of the flexed hip with a goniometer. METHODS: The examination chair allowed measurement of IR in a sitting position simultaneously in both hips, with hips and knees flexed 90 degrees, lower legs hanging unsupported and a standardized load of 5 kg applied to both ankles using a bilateral pulley system. Clinical assessment of IR was performed in supine position with hips and knees flexed 90 degrees using a goniometer. Within the framework of a population-based inception cohort study, we calculated inter-observer agreement in two samples of 84 and 64 consecutive, unselected young asymptomatic males using intra-class correlation coefficients (ICC) and determined the correlation between IR assessed with examination chair and clinical assessment. RESULTS: Inter-observer agreement was excellent for the examination chair (ICC right hip, 0.92, 95% confidence interval [CI] 0.89-0.95; ICC left hip, 0.90, 95% CI 0.86-0.94), and considerably higher than that seen with clinical assessment (ICC right hip, 0.65, 95% CI 0.49-0.77; ICC left hip, 0.69, 95% CI 0.54-0.80, P for difference in ICC between examination chair and clinical assessment

Microtektites and tektites: a chemical comparison.

Elemental abundance (20 trace elements, 3 major elements) comparisons for Ivory Coast microtektites and Australasian microtektites indicate that there are distinct chemical similarities between microtektites and nearby tektites. Several trace element abundances in microtektites are quite different from those observed in Apollo 11 and Apollo 12 samples.

Classification accuracy of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2)-Restructured form validity scales in detecting malingered pain-related disability.

The symptom reports of individuals with chronic pain are multidimensional (e.g., emotional, cognitive, and somatic) and significantly contribute to increased morbidity and lost work productivity. When pain occurs in the context of a legally compensable event, reliable assessment of a patient's multifactorial symptom experience during psychological or neuropsychological evaluations is a necessity. The Validity Scales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) have been shown useful in identifying symptom overreporting and feigning within chronic pain samples and a number of studies have emerged supporting the use of the MMPI-2-Restructured Form (MMPI-2-RF) in the detection of simulated or feigned impairment in a variety of populations. To date, only 1 other study exists examining the ability of the MMPI-2-RF to detect exaggerated complaints using a strict operationalization of malingering exclusive to chronic pain samples. The purpose of this study was to examine the classification accuracy of MMPI-2-RF Validity Scales in a group of patients with chronic pain using a criterion-groups design. The final sample consisted of 501 clinical chronic pain patients assigned to groups based on the Bianchini, Greve, and Glynn (2005) criteria for Malingered Pain-Related Disability (MPRD). Results showed that all MMPI-2-RF Validity Scales differentiated malingerers from nonmalingerers with a high degree of accuracy. At cut-offs associated with ≥95% Specificity, Sensitivities ranged from 15% (Fs) to 60% (Response Bias Scale; RBS). This study demonstrates that the MMPI-2-RF Validity Scales are capable of differentiating intentional symptom exaggeration from genuine complaints in a sample of incentivized chronic pain patients. (PsycINFO Database Record

Liver cirrhosis induces renal and liver phospholipase A2 activity in rats.

Maintenance of renal function in liver cirrhosis requires increased synthesis of arachidonic acid derived prostaglandin metabolites. Arachidonate metabolites have been reported to be involved in modulation of liver damage. The purpose of the present study was to establish whether the first enzyme of the prostaglandin cascade synthesis, the phospholipase A2(PLA2) is altered in liver cirrhosis induced by bile duct excision. The mRNA of PLA2(group I and II) and annexin-I a presumptive inhibitor of PLA2 enzyme was measured by PCR using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as an internal standard. The mean mRNA ratio of group II PLA2/GAPDH was increased in liver tissue by 126% (P < 0.001) and in kidney tissue by 263% (P < 0.006) following induction of liver cirrhosis. The increase in group II PLA2 mRNA in cirrhotic animals was reflected by an increase in PLA2 protein and enzyme activity in both liver and kidney tissues. Since the mRNA of group I PLA2 was not detectable and Group IV PLA2 activity measured in liver and kidney tissue samples was very low and not changed following induction of cirrhosis, it is likely that the major PLA2 activity measured in liver and kidney corresponds to group II PLA2 enzyme. The mean mRNA ratio of annexin-I/GAPDH was increased in liver tissue by 115% (P < 0.05) but unchanged in kidney tissue following induction of cirrhosis. The protein content of annexin-I and -V were not affected by bile duct excision in liver and kidney tissue indicating that upregulation of group II PLA2 activity was not due to downregulation of annexin-I or -V. Group II PLA2 activity of glomerular mesangial cells stimulated by interleukin-1 beta was enhanced by bile juice and various bile salts. In conclusion, activity of group II PLA2 is upregulated partly due to enhanced transcription and translation in cirrhosis and is furthermore augmented by elevated levels of bile salts.

Impact of physical training on the ultrastructure of midthigh muscle in normal subjects and in patients treated with glucocorticoids.

Exercise-training might be a logical method to reverse muscle atrophy and weakness in patients treated with glucocorticoids. The purpose of the present investigation was to establish whether a treatment with low dose prednisone (10 +/- 2.9 mg/d) modulates the effect of a moderate strength type isokinetic training during 7 wk (21 sessions of 20 min) on "muscle efficiency" (power output/muscle mass) and on concomitant changes in ultrastructure of the thigh muscle measured by quantitative electron-microscopic morphometry. Training caused a similar increase in "muscle efficiency" in patients on prednisone (n = 9) as in normal volunteers (n = 9). In normal subjects the increase in muscle efficiency was associated with an increase in sarcoplasm, whereas in patients on prednisone the functional improvement was associated with an increase in sarcoplasm, capillaries, and mitochondria content. Thus, a therapy with low dose prednisone does not abrogate training-induced improvement of muscle efficiency but modulates the ultrastructural response of the muscle to the training.

Glucocorticoid deficiency increases phospholipase A2 activity in rats.

An important mechanism for the antiinflammatory effect of pharmacological doses of glucocorticoids is the inhibition of arachidonic acid release from phospholipids by phospholipase A2 (PLA2). As a corollary, one might predict that low endogenous concentrations of glucocorticoids favor inflammatory disease states. Indeed, clinical and experimental observations revealed an association between glucocorticoid deficiency and disease states caused by immunological and/or inflammatory mechanisms. The purpose of the present investigation was to study the regulation of PLA2 mRNA, protein, and enzyme activity in adrenalectomized (ADX) rats where glucocorticoid concentrations were below physiological levels. The mRNA of group I and II PLA2 were measured by PCR. Group II PLA2 mRNA was increased by 126 +/- 9% in lung tissue of ADX rats, whereas group I PLA2 was increased only by 27 +/- 1.5%. The increase in group II mRNA in ADX rats was reflected by a corresponding increase of group II PLA2 protein (70-100%) in lung, spleen, liver, and kidney. This increase was reversed by the administration of exogenous corticosterone. After ADX, the percentage increase in total PLA2 activity was higher than that of mRNA or PLA2 protein, suggesting that the activity of the enzyme was modulated by inhibitors or activators. The concentration of lipocortin-I, an inhibitor of PLA2 enzyme was strongly correlated with the activity of PLA2 in the tissues (lung, spleen, liver, and kidney). In all these tissues, the concentrations of lipocortin-I declined after ADX. Thus upregulation of PLA2 enzyme and downregulation of lipocortin-I might account for the enhanced inflammatory response in hypoglucocorticoid states.

Reduced activity of 11 beta-hydroxysteroid dehydrogenase in patients with cholestasis.

Enhanced renal sodium retention and potassium loss in patients with cirrhosis is due to activation of mineralocorticoid receptors (MRs). Increased aldosterone concentrations, however, do not entirely explain the activation of MR in cirrhosis. Here, we hypothesize that cortisol activates MRs in patients with cholestasis. We present evidence that access of cortisol to MRs is a result of bile acid-mediated inhibition of 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2), an MR-protecting enzyme that converts cortisol to cortisone. Twelve patients with biliary obstruction and high plasma bile acid levels were studied before and after removal of the obstruction. The urinary ratio of (tetrahydrocortisol + 5 alpha-tetrahydrocortisol)/tetrahydrocortisone, a measure of 11 beta-HSD2 activity, decreased from a median of 1.91 during biliary obstruction to 0.78 at 4 and 8 weeks after removal of the obstruction and normalization of plasma bile acid concentrations. In order to demonstrate that bile acids facilitate access of cortisol to the MR by inhibiting 11 beta-HSD2, an MR translocation assay was performed in HEK-293 cells transfected with human 11 beta-HSD2 and tagged MR. Increasing concentrations of chenodeoxycholic acid led to cortisol-induced nuclear translocation of MR. In conclusion, 11 beta-HSD2 activity is reduced in cholestasis, which results in MR activation by cortisol.

Selective enhancement of gene transfer by steroid-mediated gene delivery.

The incorporation of transgenes into the host cells' nuclei is problematic using conventional nonviral gene delivery technologies. Here we describe a strategy called steroid-mediated gene delivery (SMGD), which uses steroid receptors as shuttles to facilitate the uptake of transfected DNA into the nucleus. We use glucocorticoid receptors (GRs) as a model system with which to test the principle of SMGD. To this end, we synthesized and tested several bifunctional steroid derivatives, finally focusing on a compound named DR9NP, consisting of a dexamethasone backbone linked to a psoralen moiety using a nine-atom chemical spacer. DR9NP binds to the GR in either its free or DNA-crosslinked form, inducing the translocation of the GR to the nucleus. The expression of transfected DR9NP-decorated reporter plasmids is enhanced in dividing cells: expression of steroid-decorated reporter plasmids depends on the presence of the GR, is independent of the transactivation potential of the GR, and correlates with enhanced nuclear accumulation of the transgene in GR-positive cells. The SMGD effect is also observed in cells naturally expressing GRs and is significantly increased in nondividing cell cultures. We propose that SMGD could be used as a platform for selective targeting of transgenes in nonviral somatic gene transfer.

Purification and characterization of a 34-kDa, heat stable glycoprotein from Synadenium grantii latex: action on human fibrinogen and fibrin clot.

Latex glycoprotein (LGP) from Synadenium grantii latex was purified by the combination of heat precipitation and gel permeation chromatography. LGP is a heat stable protein even at 80 degrees C showed a sharp single band both in SDS-PAGE as well as in native (acidic) PAGE. LGP is a monomeric protein appears as single band under reducing condition. It is a less hydrophobic protein showed sharp single peak in RP-HPLC with retention time of 13.3 m. The relative molecular mass of LGP is 34.4 kDa. CD spectrum of LGP explains less content of alpha-helix (7%), and high content of beta-pleated sheets (48%) and random coils (46%). The N-terminal sequence of LGP is D-F-P-S-D-W-Y-A-Y-E-G-Y-V-I-D-R-P-F-S. Purified LGP is a fibrinogen degrading protease hydrolyses all the three subunits in the order of Aalpha, Bbeta and gamma. The hydrolytic pattern is totally different from plasmin as well as thrombin. LGP reduces recalcification time from 165 to 30 s with citrated human plasma but did not show thrombin like as well as factor Xa-like activity. Although LGP induces procoagulant activity, it hydrolyses partially cross-linked fibrin clot. It hydrolyses all the subunits of partially cross-linked fibrin clot (alpha- chains, beta-chain and gamma-gamma dimer). LGP is a serine protease, inhibited by PMSF. Other serine protease inhibitors, aprotinin and leupeptin did not inhibit the caseinolytic activity as well as fibrinogenolytic activity. We report purification and characterization of a glycoprotein from Synadenium grantii latex with human fibrino(geno)lytic activity.

[Calcific uremic arteriolopathy]. / Explodierende Nekrosen.

The history of a patient with calcific uremic arteriolopathy is discussed. The hypothetical pathogenesis and the therapeutic approach is revised.

Drosophila serpin 27A is a likely target for immune suppression of the blood cell-mediated melanotic encapsulation response.

Avirulent strains of the endoparasitoid Leptopilina boulardi succumb to a blood cell-mediated melanotic encapsulation response in host larvae of Drosophila melanogaster. Virulent wasp strains effectively abrogate the cellular response with substances introduced into the host that specifically target and effectively suppress one or more immune signaling pathways, including elements that control phenoloxidase-mediated melanotic encapsulation. The present study implicates involvement of the Drosophila Toll pathway in cellular innate immunity by regulating the serine protease inhibitor Serpin 27A (Spn27A), which normally functions as a negative regulator of phenoloxidase. The introduction of Spn27A into normally highly immune competent D. melanogaster larvae significantly reduced their ability to form melanotic capsules around eggs of L. boulardi. This study confirms the role of Spn27A in the melanization cascade and establishes that this pathway and associated blood cell responses can be activated by parasitization. The activation of phenoloxidase and the site-specific localization of the ensuing melanotic response are such critical components of the blood cell response that Spn27A and the signaling elements mediating its activity are likely to represent prime targets for immune suppression by L. boulardi.

Superoxide anion generation in Drosophila during melanotic encapsulation of parasites.

Quinoid precursors of melanin and/or reactive oxygen species (ROS) generated during melanogenesis have been implicated as cytotoxic molecules in the immune responses of insects against their internal metazoan parasites. No study has yet identified the killing components produced in conjunction with melanotic encapsulation responses, or explained how cytotoxic molecules generated in the open circulatory system of an insect can selectively destroy foreign tissues. Strains of Drosophila melanogaster with differing immune capabilities against the wasp parasitoid Leptopilina boulardi were examined for superoxide anion (O2-.) formation during parasitization. Elevated levels of O2-. were produced by immune reactive (R-strain) hosts during melanotic encapsulation of the parasitoid, but not by susceptible (S-strain) hosts in which the parasitoid developed unmolested. Both a superoxide dismutase (SOD)-deficient strain (cSODn108, red/TM3/Sb Ser) and a catalase (CAT)-deficient strain (Catn1) also produced melanotic capsules and elevated levels of O2-. when infected, but these reactions were unsuccessful and the parasitoids survived, indicating that neither the quinoid precursors of melanin nor O2-. per se were cytotoxic. Immune incompetence in SOD-deficient and CAT-deficient hosts is attributed in part to defects in hydrogen peroxide (H2O2) metabolism, and/or the inability of these metalloenzyme-deficient strains to initiate the metal-mediated reductive cleavage of H2O2 required for the production of the cytotoxic hydroxyl radical (.OH). The role proposed for O2-. in Drosophila cellular immunity is one of potentiating the formation of .OH. Melanin, which contains both oxidizing and reducing components, may serve a dual role in producing O2-. and sequestering redox-active metal ions, thereby confining the production of ROS. Host-parasite susceptibility in the Drosophila-Leptopilina system may be determined by the ability of the parasitoid to modulate hemocyte activity and prevent both effective melanotic encapsulation and the generation of cytotoxic levels of ROS.

11 beta-Hydroxysteroid dehydrogenase accounts for low prednisolone/prednisone ratios in the kidney.

The purpose of the present investigation was to establish whether the ratio of the biologically active prednisolone to its inactive metabolite prednisone is determined by the 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD). The concentration ratios of prednisolone/prednisone assessed by HPLC 60 min after ip administration of prednisolone to rats were 0.8 in kidney, 5.5 in lung, 5.7 in spleen, 6.3 in heart, 7.1 in plasma, and 43 in liver. When prednisolone was injected together with glycyrrhetinic acid, an inhibitor of the 11 beta-OHSD, the ratios of prednisolone/prednisone in plasma and all tissues increased more than 10-fold. The plasma concentrations of glycyrrhetinic acid required to exhibit apparent half-maximal inhibitory effect of the 11 beta-OHSD were more than 7-fold higher for renal than for all other tissues. Thus, the 11 beta-OHSD accounts for low prednisolone/prednisone concentration ratios in renal tissue and, therefore, has to be considered a relevant determinant for the local intrarenal immunosuppressive effect of 11 beta-hydroxysteroids such as prednisolone.

Furosemide inhibits 11 beta-hydroxysteroid dehydrogenase in vitro and in vivo.

11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) protects the non-selective renal mineralocorticoid receptor from the endogeneous glucocorticoid cortisol. Thus, drugs inhibiting 11 beta-OHSD might enhance urinary loss of potassium. In an attempt to find drugs inhibiting 11 beta-OHSD, 23 commonly used agents known to interfere with the potassium metabolism have been screened for inhibitory effect on 11 beta-OHSD. Furosemide appeared as the only inhibitor. Its inhibition constant (Ki) was 19.5 microM when kidney and 21.3 microM when liver microsomes were used as a source of 11 beta-OHSD. The type of inhibition was competitive. For confirmation that furosemide specifically inhibits 11 beta-OHSD, the complementary DNA (cDNA) of 11 beta-OHSD was transfected into COS-1 cells devoid of spontaneous expression of 11 beta-OHSD. In these cells, oxidation of corticosterone (Ki = 17.4 microM) and reduction of dehydrocorticosterone (Ki = 12.5 microM) was inhibited by furosemide. To establish whether this inhibition also occurs in vivo, the 11 beta-hydroxysteroid prednisolone was administered with and without furosemide to rats. The concentration ratio of prednisolone to its 11-ketometabolite prednisone increased in kidney and liver tissue after furosemide administration, indicating inhibition of 11 beta-OHSD. These data suggest that furosemide modulates in vivo the access of 11 beta-OH glucocorticoids to their target organs.