Escherichia coli lipopolysaccharide inhibits renin activity in human mesangial cells.

Hyperactivation of systemic renin-angiotensin system (RAS) during sepsis is well documented. However, the behavior of intrarenal RAS in the context of endotoxemia is yet to be defined. The present study evaluates the direct effect of Escherichia coli lipopolysaccharide (LPS) on immortalized human mesangial cell (HMC) RAS. Quiescent HMC were incubated with vehicle or LPS (1-100 microg/ml), and levels of angiotensin I and II (Ang I and II) and their metabolites were analyzed by high-performance liquid chromatography. In addition, angiotensin-converting enzyme (ACE) and renin activity were also investigated. Cell lysate and extracellular medium levels of Ang II were rapidly reduced (1 h) in a time- and concentration-dependent manner, reaching a significant -9 fold-change (P<0.001) after 3 h of LPS incubation. Similar results were obtained for Ang I levels (-3 fold-change, P<0.001). We ruled out Ang I and II degradation, as levels of their metabolic fragments were also significantly decreased by LPS. ACE activity was slightly increased following LPS incubation. On the other hand, renin activity was significantly inhibited, as Ang I concentration elevation following exogenous angiotensinogen administration was blunted by LPS (-60% vs vehicle, P<0.001). Renin and angiotensinogen protein levels were not affected by LPS according to Western blot analysis. Taken together, these data demonstrate for the first time that LPS significantly downregulates HMC RAS through inhibition of renin or renin-like activity. These findings are potentially related to the development of and/or recovery from acute renal failure in the context of sepsis.

Effect of an isotonic rehydration sports drink and exercise on urolithiasis in rats.

The objective of the present study was to evaluate the role of physical exercise as well as the influence of hydration with an isotonic sports drink on renal function in male Wistar rats. Four groups were studied over a period of 42 days: 1) control (N = 9); 2) physical exercise (Exe, N = 7); 3) isotonic drink (Drink, N = 8); 4) physical exercise + isotonic drink (Exe + Drink, N = 8). Physical exercise consisted of running on a motor-driven treadmill for 1 h/day, at 20 m/min, 5 days a week. The isotonic sports drink was a commercial solution used by athletes for rehydration after physical activity, 2 ml administered by gavage twice a day. Urine cultures were performed in all animals. Twenty-four-hour urine samples were collected in metabolic cages at the beginning and at the end of the protocol period. Urinary and plasma parameters (sodium, potassium, urea, creatinine, calcium) did not differ among groups. However, an amorphous material was observed in the bladders of animals in the Exe + Drink and Drink groups. Characterization of the material by Western blot revealed the presence of Tamm-Horsfall protein and angiotensin converting enzyme. Physical exercise and the isotonic drink did not change the plasma or urinary parameters measured. However, the isotonic drink induced the formation of intravesical matrix, suggesting a potential lithogenic risk.

Effect of an isotonic rehydration sports drink and exercise on urolithiasis in rats

The objective of the present study was to evaluate the role of physical exercise as well as the influence of hydration with an isotonic sports drink on renal function in male Wistar rats. Four groups were studied over a period of 42 days: 1) control (N = 9); 2) physical exercise (Exe, N = 7); 3) isotonic drink (Drink, N = 8); 4) physical exercise + isotonic drink (Exe + Drink, N = 8). Physical exercise consisted of running on a motor-driven treadmill for 1 h/day, at 20 m/min, 5 days a week. The isotonic sports drink was a commercial solution used by athletes for rehydration after physical activity, 2 ml administered by gavage twice a day. Urine cultures were performed in all animals. Twenty-four-hour urine samples were collected in metabolic cages at the beginning and at the end of the protocol period. Urinary and plasma parameters (sodium, potassium, urea, creatinine, calcium) did not differ among groups. However, an amorphous material was observed in the bladders of animals in the Exe + Drink and Drink groups. Characterization of the material by Western blot revealed the presence of Tamm-Horsfall protein and angiotensin converting enzyme. Physical exercise and the isotonic drink did not change the plasma or urinary parameters measured. However, the isotonic drink induced the formation of intravesical matrix, suggesting a potential lithogenic risk.

Purification and characterization of a neutral endopeptidase-like enzyme from human urine.

OBJECTIVE: The aims of this study were to purify and characterize a neutral endopeptidase-like enzyme (NEP-like) in human urine and propose a rapid, sensitive and specific assay for this enzyme using the fluorogenic substrate Abz-FDQ-EDDnp, where Abz = O-aminobenzoic acid and EDDnp = N-(2,4-dinitrophenyl)ethylenediamine. METHODS: Soluble urinary NEP was purified from human urine using a DEAE-cellulose Cellex D column and gel filtration on an AcA-44 column. NEP-like activity was assayed by its ability to hydrolyse bradykinin (BK) and the fluorogenic substrates Abz-BKQ-EDDnp and Abz-FDQ-EDDnp. The Km was determined using Abz-FDQ-EDDnp as a substrate. The hydrolysis products of BK and Abz-FDQ-EDDnp were analysed by high-performance liquid chromatography (HPLC). The mol. wt was estimated by polyacrylamide gel electrophoresis and the enzyme analysed by Western blot using the antibody obtained from purified recombinant NEP expressed in Pichia pastoris yeast. RESULTS: The NEP-like was purified from human urine until homogeneity and presented a mol. wt of 94000. The substrate Abz-FDQ-EDDnp was selectively hydrolysed at the F-D bond by NEP-like and by recombinant NEP. For this substrate, the NEP-like activity was maximal at pH 7.0, although a small peak of activity was observed at pH 8.0, and the determined Km was 14 microM. The enzymatic activity was inhibited by thiorphan and phosphoramidon. In Western blot analysis, NEP-like reacted strongly with a polyclonal antibody for NEP. CONCLUSION: A NEP-like enzyme was purified from human urine. Based on the mol. wt of the isolated NEP-like enzyme, it was concluded that this enzyme was produced in the kidney. In the kidney, this enzyme may cleave the kinins filtered through the glomerulus and also the kinins produced in the distal nephron. An internally quenched fluorogenic peptide, Abz-FDQ-EDDnp, was selectively hydrolysed by NEP-like and by recombinant NEP.

[Social networks and mental disease]. / Redes sociales y enfermedad mental.

This is a three-purpose study: (a) Furthering a definition of social network analysis since such a theoretical and methodological approach is of great interest to studying social interaction, (b) Analyzing the social networks within one psychiatric case study in order to build up a network interaction model aiming at fostering future research, this interaction model being used as a concept framework, and (c) Discussing how fruitful research on social networks can prove to be in connection with the treatment of the mentally ill, as well as considering the protective and supportive functions of these networks.

Redes sociales y enfermedad mental. / [Social networks and mental disease]

This is a three-purpose study: (a) Furthering a definition of social network analysis since such a theoretical and methodological approach is of great interest to studying social interaction, (b) Analyzing the social networks within one psychiatric case study in order to build up a network interaction model aiming at fostering future research, this interaction model being used as a concept framework, and (c) Discussing how fruitful research on social networks can prove to be in connection with the treatment of the mentally ill, as well as considering the protective and supportive functions of these networks.

[Prevalence of mental disorders in the metropolitan area of the Republic of Argentina]. / Prevalencia de desórdenes mentales en el área metropolitana de la República Argentina.

The survey was carried out during 1979 (September-December). The sample covered the whole Federal District and the nineteen counties of the Greater Buenos Aires with a population of 9.908.001 persons; 18.61% in F. D. and 10,24% en G.B.A. refused to answer; 3411 were interviewed. The responses to the Present State Examination (PSE) were used for case-finding. The PSE is a semistructured interview that has been extensively tested with inpatients and outpatients. It has a technique for case-defining: the index of Definition (I.D.). A set of rules were developed to allocate the profile of symptoms present in the PSE (ninth edition) to one of the eight levels of definition. The rules were incorporated in a computer program called Catego. The prevalence of cases, as defined in the study, is 26% (ID 5-8) (30.8% in the feminine population and 20.3% in the masculine). If the threshold level (5) is excluded, the rate is 10,2%. (6,9% among males and 11,9% among females). The diagnosis derived from the Catego Program, fitted descriptively with the International Classification of Diseases (chapter 5) show the 13% of the population with neurotic perturbations, specially of depressive type, 6% with affective psychosis, 4% of schizophrenic psychosis and 1,3% of paranoic states. The major associations of prevalence rates are with sex and socioeconomic level. There is a preponderance of women with high Index of Definition. Future studies must prove the relationships between disorders and sex. We think that the interdependence of being married, children at home below 14 years, having no employment, can explain the high rates in the female population. The highest levels of the Index of Definition are associated with the lowest socioeconomic levels. The analysis of data presented here suggests more detailed studies, specially on the aetiology of depression and on the relationship between women and mental disorders.

Prevalencia de desórdenes mentales en el área metropolitana de la República Argentina. / [Prevalence of mental disorders in the metropolitan area of the Republic of Argentina]

The survey was carried out during 1979 (September-December). The sample covered the whole Federal District and the nineteen counties of the Greater Buenos Aires with a population of 9.908.001 persons; 18.61

in F. D. and 10,24

en G.B.A. refused to answer; 3411 were interviewed. The responses to the Present State Examination (PSE) were used for case-finding. The PSE is a semistructured interview that has been extensively tested with inpatients and outpatients. It has a technique for case-defining: the index of Definition (I.D.). A set of rules were developed to allocate the profile of symptoms present in the PSE (ninth edition) to one of the eight levels of definition. The rules were incorporated in a computer program called Catego. The prevalence of cases, as defined in the study, is 26

(ID 5-8) (30.8

in the feminine population and 20.3

in the masculine). If the threshold level (5) is excluded, the rate is 10,2

. (6,9

among males and 11,9

among females). The diagnosis derived from the Catego Program, fitted descriptively with the International Classification of Diseases (chapter 5) show the 13

of the population with neurotic perturbations, specially of depressive type, 6

with affective psychosis, 4

of schizophrenic psychosis and 1,3

of paranoic states. The major associations of prevalence rates are with sex and socioeconomic level. There is a preponderance of women with high Index of Definition. Future studies must prove the relationships between disorders and sex. We think that the interdependence of being married, children at home below 14 years, having no employment, can explain the high rates in the female population. The highest levels of the Index of Definition are associated with the lowest socioeconomic levels. The analysis of data presented here suggests more detailed studies, specially on the aetiology of depression and on the relationship between women and mental disorders.