Adenosine receptors participate in anabolic-androgenic steroid-induced changes on risk assessment/anxiety-like behaviors in male and female rats.

Anabolic-androgenic steroids (AAS) and caffeine can induce several behavioral alterations in humans and rodents. Administration of nandrolone decanoate is known to affect defensive responses to aversive stimuli, generally decreasing inhibitory control and increasing aggressivity but whether caffeine intake influences behavioral changes induced by AAS is unknown. The present study aimed to investigate behavioral effects of caffeine (a non-selective antagonist of adenosine receptors) alone or combined with nandrolone decanoate (one of the most commonly AAS abused) in female and male Lister Hooded rats. Our results indicated that chronic administration of nandrolone decanoate (10 mg/kg, i.m., once a week for 8 weeks) decreased risk assessment/anxiety-like behaviors (in the elevated plus maze test), regardless of sex. These effects were prevented by combined caffeine intake (0.1 g/L, p.o., ad libitum). Overall, the present study heralds a key role for caffeine intake in the modulation of nandrolone decanoate-induced behavioral changes in rats, suggesting adenosine receptors as candidate targets to manage impact of AAS on brain function and behavior.

Primary glomerular diseases in Brazil (1979-1999): is the frequency of focal and segmental glomerulosclerosis increasing?

AIMS: Different patterns of glomerulonephritis (GN) are reported from all over the world and the occurrence of primary GN is changing in the course of time. We report the frequencies of primary GN in a major teaching hospital in Brazil, from 1979-1999. METHODS: The case files of renal biopsies of primary GN were reviewed. The included patients were > 14 years of age, with native kidneys, and the specimens were examined with at least light and immunofluorescence microscopy. We excluded biopsy results of patients with any kind of known secondary glomerular involvement. Differences in proportions of diagnoses between the periods over time were evaluated using Chi-square test for trend. RESULTS: We considered 943 patients for the analysis. Focal and segmental glomerulosclerosis (FSGS) was the most common lesion (n = 279), followed by membranous GN (n = 140), membranoproliferative type I GN (n = 109) and IgA nephropathy (n = 109). FSGS (32.1%) was the most frequent diagnosis among nephrotic patients whereas IgAN (29.4%) predominated in non-nephrotic ones. The occurrence of FSGS increased from the earlier to the later periods: 22.3% (1979-1983), 23.7% (1984-1988), 35.7% (1989-1993), 33.9% (1994-1999), p < 0.05. The increase in frequency of FSGS was proportionally higher in non-nephrotic patients and FSGS became as common as IgA nephropathy in this group (31.6% and 28.0%, respectively) from 1994-1999. CONCLUSIONS: FSGS was the most common pattern of primary glomerulonephritis and its relative frequency seems to be increasing in biopsied patients over time. The reasons for this behavior are unclear and warrant further investigations.

[Hematuria in children: retrospective study of 128 pediatric patients] / Hematúria na criança: estudo retrospectivo de 128 casos.

OBJECTIVE: To evaluate the diagnostic frequency of the various diseases associated with the development of hematuria in children, in a pediatric nephrology unit pertaining to a university hospital. METHODS: The clinical records of 128 children (70 male, 50 female) who presented intermittent/persistent macroscopic hematuria or persistent microscopic hematuria as the chief clinical complaint/finding, in the period of 1978-1995, were retrospectively analyzed. This evaluation was performed with special attention to the patientacute;s clinical history, physical examination, personal and family morbid history information. Patients whose investigation was not complete were not considered for analysis. The mean age on presentation was 8.2 years (5 months - 16 years) and the mean period of observation was 3.2 years (1 month-15 years). RESULTS: Macroscopic hematuria occurred in 104 patients and persistent microscopic hematuria was present in 24 patients. Urinary metabolic disturbances and urinary lithiasis, alone or in association, were diagnosed in the majority of the patients (65.5%). Hypercalciuria was the urinary metabolic disturbance (90.1%) mostly detected, either alone (73.2%) or in association with hyperuricosuria (16.9%). A positive family history of lithiasis was reported in 32.1% of the patients in which the diagnosis of lithiasis/urinary metabolic disturbance was confirmed. Glomerulopathies were diagnosed in 25% of the patients, with the predominance of post-infectious acute glomerulonephritis (11 patients, 34%). In 6 children, the etiology of hematuria was not elucidated, despite extensive investigation, including renal biopsy.CONCLUSION: The authors present an algorithm for the diagnosis of hematuria in children and suggest that in cases of isolated hematuria, presenting without clinical clues to the possible etiology, laboratory investigation should be started with the evaluation of urinary metabolic disturbances / lithiasis.

Prevalence of adult primary glomerular diseases: retrospective analysis of 206 kidney biopsies (1990-1993).

The prevalences of the various histopathologic forms of primary glomerular disease (PGD) were evaluated by the retrospective analysis of 206 kidney biopsies performed in a three-year period (september 1990-september 1993) in patients between 14 and 73 years of age (107 men and 99 women). Data were compared with those of a study conducted in 1985-1987, on patients of the same age group. In the present study, primary glomerular diseases showed the following prevalences: focal glomerulosclerosis, 43.2%; membranous GN, 20.4%; membranoproliferative GN, 14.1%; IgA nephropathy, 10.2%; minimal-change disease, 5.3%; mesangioproliferative GN, 2.9%; acute diffuse GN, 1.9%; rapidly progressive GN and proliferative focal segmental GN, 1% each one. Prevalences were similar in both sexes. Primary glomerular diseases were significantly more prevalent in patients with 35 years or less than in those up this age (64.6% vs 34.4%). Nonproliferative primary glomerular diseases were significantly more prevalent than the proliferative forms (68.9% vs 31.1%). The prevalences of the various histopathologic of PGD, with few exceptions, were about similar in the periods 1985-1987 and 1990-1993: the prevalences of focal glomerulosclerosis, membranous GN, IgA nephropathy and mesangioproliferative GN showed no significant differences; the prevalence of membranoproliferative GN increased (6.8% vs 14.1%), but that of type II remained very low (0.5%). Focal glomerulosclerosis was the most prevalent PGD. The prevalence of IgA nephropathy remained low, comparable with the smallest prevalences found in some of the Western countries.

IgA nephropathy: acute renal failure, acute tubular necrosis, and features of postinfectious acute glomerulonephritis.

From 1976 to 1987 on our Nephrological Unit, 57 patients with IgA nephropathy (IgAN) proven by renal biopsies were found. Three of those presented with acute tubular necrosis (ATN) and glomerulitis, without extrarenal predisposing cause in two; and showed, as prominent manifestation, a severe acute renal failure syndrome (ARFS), needing dialytic treatment. All three had hematuria, which was macroscopic in two and microscopic in one. Thus the prevalence of the association of glomerulitis and ATN was about 5.2%. There was complete recovery of renal functions in all three patients, but the usual symptomatology of IgAN. Two patients presented polymorphonuclear neutrophils infiltration of glomerular capillaries and in one of them, electron-dense deposits on the epithelial side of glomerular basement membrane ("humps") were observed, as well as those identified in the mesangial area. The glomerular polymorphonuclear neutrophils infiltration and endothelial cells proliferation (cases 1 and 3), the presence of "humps" (case 1), high antistreptolysin O (ASO) titers (cases 1 and 2), and low serum complement levels (case 1), suggest the possibility that antigens able to cause postinfectious glomerulonephritis (streptococcal or not) could induce in some individuals, by another immunopathogenetic route, mixed histopathological and clinical features of IgAN and postinfectious glomerulonephritis.

[Histopathologic study of primary glomerulopathies: retrospective analysis of 197 renal biopsies (1985-1987)]. / Estudo histopatológico das glomerulopatias primárias: análise retrospectiva de 197 biopsias renais (1985-1987).

The histopathological prevalence of primary glomerular diseases in patients aged 14 to 70 years (105 males, 92 females) was analysed: 140 (71%) were aged from 14 to 35 years and 57 (29%) were older than 35 years, the difference being significant (p less than 0.001). The following data were found at our Nephrological Unit: the prevalence of focal glomerular sclerosis was 37.1%; of the membranous glomerulonephritis 16.2%; of the IgA nephropathy 8.6%; of the membranoproliferative glomerulonephritis 6.1%; of the minimal change disease 5.1%. The acute diffuse glomerulonephritis, the rapidly progressive glomerulonephritis and the chronic glomerulonephritis showed the same prevalence of 4.6%, and the mesangial proliferative glomerulonephritis and the kidney in Alport's syndrome that of 3.6%. Diagnosis was not defined by renal biopsy in 6.1% of the patients. Failures to achieve diagnosis were due to biopsies with less than 5 glomeruli on optic microscopy or losses affecting the immunofluorescence procedures. It was concluded that the highest prevalence was that of the focal glomerular sclerosis, found in more than one third of the patients. It was followed by the prevalence of the membranous glomerulonephritis which occurred in about one sixth of our cases. The prevalence of IgA nephropathy, minimal change disease, membranoproliferative glomerulonephritis and of other primary glomerulopathies were low. The prevalence of focal glomerular sclerosis was significantly higher (p less than 0.001) in the younger group of patients (14-35 years) than in the older one; the same fact was seen in the prevalence of the proliferative histopathological forms of glomerulonephritis (p less than 0.025), grouping IgA nephropathy, membranoproliferative glomerulonephritis, rapidly progressive glomerulonephritis and mesangial proliferative glomerulonephritis.

Evaluación farmacocinética y clínica de una formulación en cápsulas de carbonato de litio: I Parte / Pharmacokinetic and clinic evaluation of a pharmaceutical form (capsule) of lithium carbonate: part I

El carbonato de litio es un fármaco de amplio uso en psiquiatría en el tratamiento de las enfermedades afectivas. Su eficacia indiscutible ha significado un considerable aumento de su consumo. Por tal razón nació la idea de incorporar una nueva farmacéutica con un criterio técnico que nos llevara a disminuir costos y/o ampliar cobertura. Nuestro estudio se basó en comparar los parámetros farmacocinéticos y biodisponibilidad del comprimido convencional con la cápsula de carbonato de litio. Se realizó un estudio farmacocinético para ambas formas farmacéuticas de carbonato de litio de 300 mg. cada una, sometiendo a tres voluntarios sanos a una dosis oral de 600 mg. con un intervalo de depuración de un mes entre una forma farmacéutica y otra. Se tomó muestras de sangre a las 1,2,3,4,6,8,12 y 24 hrs., determinándose la concentración plasmática de Litio por Fotometría de Llama. Los parámetros farmacocinéticos encontrados en voluntarios sanos para una dosis de 600 mg. de carbonato de litio son: comprimidos t Máx. -3,0 hrs., c Máx. 0.51 Meq/Lt, Cápsula t Máx 2,0 hrs. c Max. 0,67 Meq/Lt. La vida media (t 1/2) obtenida concuerda con la literatura t 1/2 - (comp) = 13,8 hrs. t 1/2 (cápsula) = 14,6 hrs. El área bajo la curva ABC, equivale en términos prácticos a la biodisponibilidad, demuestra que ambas formas farmacéuticas, cápsulas y comprimidos no presentan diferencias significativas (t = 0,1821; p < 0.45), resultado importante, pues permite respaldar el uso clínico de la cápsula de carbonato de litio y considerarlo como una alternativa viable para nuestros pacientes

Evaluación farmacocinética y clínica de una formulación en cápsulas de carbonato de litio: II Parte / Pharmacokinetic and clinic evaluation of pharmaceutical form (capsule) of lithium carbonate: Part II

En relación al aumento mantenido del consumo de carbonato de litio en el Hospital Psiquiátrico de Santiago observado desde el año 1986, se realizó un estudio farmacocinético de una formulación en cápsulas de carbonato de litio de 300 mg. en tres voluntarios sanos. Este estudio concluyó que la formulación en cápsulas presenta un comportamiento farmacocinético similar al de los comprimidos de 300 mg. elaborados por un laboratorio nacional. Basados en el estudio antes mencionado, se realizó un estudio clínico de 28 días de duración, en el que 13 pacientes (12 con el diagnóstico de Enfermedad Afectiva Bipolar y uno con el diagnóstico de Esquizofrenia) fueron tratados con carbonato de litio en cápsulas, en dosis entre 900 y 1800 mgrs./día y litemias promedio entre 0.6 y 0.9 m.Eq Lt. Un paciente bipolar fue tratado con comprimidos de carbonato de litio. de acuerdo a la evaluación con la escala de manía y depresión de Bech-Rafaelsen realizado los días 0 y 28 del estudio, los pacientes en fase maníaca mejoraron de manera estadísticamente significativa (P<0.0005), y los pacientes depresivos de la misma manera con un (P<0.025). Dos pacientes fueron marginados del estudio por no cumplir con el calendario de litemias. Doce pacientes han completado un período de observación de un año en el policlínico de Enfermedades Afectivas del Hospital Psiquiátrico sin que hayan presentado recaídas, siendo tratados en forma profiláctica con la formulación en cápsulas. En consecuencia, los resultados obtenidos del estudio farmacocinético y clínico nos permiten recomendar el uso de carbonato de litio en cápsulas de 300 mg