Vitamin D restriction enhances periovarian adipose tissue inflammation in a model of menopause.

Background: Menopause and deficiency in vitamin D (VD) are two health problems usually associated with aging women.Objective: We aimed to study inflammation in visceral adipose tissue when bilateral ovariectomy is combined with dietary restriction in VD.Methods: We studied 60 female C57BL/6 mice 3 months of age. Half of the animals had bilateral ovariectomy (Ovx group, n = 30) and half a sham procedure (Control [C] group, n = 30), and half of each Ovx or C group were fed a standard diet containing VD or a diet restricted in VD (D-) for an additional 12 weeks. Therefore, four groups were formed (n = 15 each group): C, C(D-), Ovx, and Ovx(D-). After sacrifice, the periovarian adipose tissue (PAT) was investigated.Results: In PAT, we observed different levels of hypertrophied adipocytes, enhanced proinflammatory cytokines, activation of inflammatory markers, and components of the extracellular signal-regulated kinase. The most affected PAT was seen in the Ovx(D-) group, followed by the Ovx group, the C(D-) group, and the C group (the least altered).Conclusion: The results demonstrate that ovariectomy and dietary restriction of VD are inducers of adverse effects on mouse visceral adipose tissue. When combined, these insults might enhance PAT inflammation.

Beneficial effects of maternal swimming during pregnancy on offspring metabolism when the father is obese.

We aimed to evaluate the impact of maternal exercise training on the offspring metabolism and body size caused by father obesity. C57BL/6 male 4-week-old mice were fed a high-fat diet (HF father) or control diet (C father), while equal age female mice were fed only a C diet and were separated into two groups: trained (T mother) and non-trained (NT mother), and at 12 weeks of age mice were mated. A continuous swimming protocol was applied for 10 weeks (before and during gestation), and offspring were followed since weaning until sacrifice (at 12 weeks of age). HF father, compared to C father, showed obesity, elevated total cholesterol (TC) and triglycerides (TG), and glucose intolerance. Both sexes HF/NT offspring showed hyperglycemia, glucose intolerance and high levels of TC and TG, without obesity. However, HF/T offspring showed data close to C/NT, demonstrating the beneficial effect of maternal exercise in the offspring of obese fathers.

Liver metabolism in adult male mice offspring: consequences of a maternal, paternal or both maternal and paternal high-fructose diet.

The study aimed to evaluate the consequences of the consumption of a high-fructose diet (HFR; fructose was responsible for 45% of the energy from carbohydrates) by the mother, the father, or both on C57BL/6 adult male offspring. Non-consanguineous parents received the diet (HFR or control, C) from 8 weeks before mating until weaning (n=10 fathers and n=10 mothers on each diet). After weaning, only the C diet was offered to offspring. The groups were formed by one male randomly taken from each litter. The offspring groups were identified according to the mother's diet (the first letter), then the father's diet (the second letter), that is, C/C, C/HFR, HFR/C, HFR/HFR (n=10 per group). The parents exhibited the following characteristics: compared with those of the C group, the HFR parents had higher blood pressure (BP), enlarged liver, increased hepatic triacylglycerol content, hypercholesterolemia, hypertriglyceridemia, high plasma leptin and low adiponectin. The offspring exhibited the following characteristics: compared with the C/C group, the HFR/HFR group had high BP. The C/HFR, HFR/C and HFR/HFR showed elevated uric acid and leptin levels and diminished adiponectin. The HFR/HFR group showed liver inflammation (increased NFκB, SOCS3, JNK, TNF-α, IL1-ß and IL6 levels). Likewise, SREBP-1c and FAS were upregulated. In conclusion, the consumption of a HFR by the mother and/or father is associated with adverse effects on liver metabolism in adult male offspring. When both mother and father are fed a HFR, the adverse effects on the offspring are more severe.

Assessment of Spleen Filtrate Function in Renal Transplant Recipients Using Technetium-99m Stannous Colloid Liver-Spleen Scan.

BACKGROUND: Functional hyposplenism (FH) is indicated by an anatomically present spleen that fails to take up radiolabeled colloid. The occurrence of FH has been reported in a small group of renal transplant recipients based on hematologic parameters. The aim of this study was to replicate this association in a larger group of renal transplant recipients with the use of technetium-99m-stannous colloid liver-spleen scan to assess the spleen function. METHODS: This survey based on single samples enrolled 101 unselected adult patients with functional kidney grafts >180 days after transplantation. All patients underwent 99mTc-stannous colloid scan to assess spleen function as well as bone marrow uptake of radiocolloid along with an anatomic and blood flow study of the spleen and kidney with the use of Doppler sonography. RESULTS: The prevalence of hyposplenism was 32.7% (33/101) for the cohort, and increased uptake of radiocolloid by the bone marrow was seen in 9.9% (10/101). According to the multivariate analysis, the frequency of hyposplenism was significantly influenced by indirect bilirubin and hemoglobin, and direct bilirubin and neutrophil count remained as independent predictors of bone marrow uptake. CONCLUSIONS: This study demonstrated that a group of renal transplant recipients has FH. In addition, bone marrow uptake might be interpreted as liver dysfunction. In this situation, the small amount of contrast (spleen compared with liver) would leave hyposplenism undiagnosed. Further prospective and longitudinal clinical studies are needed to determine the clinical impact of this condition on the management of renal transplant recipients.

High-intensity interval training (swimming) significantly improves the adverse metabolism and comorbidities in diet-induced obese mice.

AIM: Controlling obesity and other comorbidities in the population is a challenge in modern society. High-intensity interval training (HIIT) combines short periods of high-intensity exercise with long recovery periods or a low-intensity exercise. The aim was to assess the impact of HIIT in the context of diet-induced obesity in the animal model. METHODS: C57BL/6 mice were fed one of the two diets: standard chow (Lean group - LE) or a high--fat diet (Obese group - OB). After twelve weeks, the animals were divided into non-trained groups (LE--NT and OB-NT) and trained groups (LE-T and OB--T), and began an exercise protocol. For biochemical analysis of inflammatory and lipid profile, we used a colorimetric enzymatic method and an automatic spectrophotometer. One-way ANOVA was used for statistical analysis of the experimental groups with Holm-Sidak pos hoc test. Two-way ANOVA analyzed the interactions between diet and HIIT protocol. RESULTS: HIIT leads to significant reductions in body mass, blood glucose, glucose tolerance and hepatic lipid profile in T-groups compared to NT-groups. HIIT was able to reduce plasma levels of inflammatory cytokines. Additionally, HIIT improves the insulin immunodensity in the islets, reduces the adiposity and the hepatic steatosis in the T-groups. HIIT improves beta--oxidation and peroxisome proliferator--activated receptor (PPAR)-alpha and reduces lipogenesis and PPAR--gamma levels in the liver. In skeletal muscle, HIIT improves PPAR--alpha and glucose transporter-4 and reduces PPAR--gamma levels. CONCLUSION: HIIT leads to attenuate the adverse effects caused by a chronic ingestion of a high-fat diet.

Developmental origins of health and disease: experimental and human evidence of fetal programming for metabolic syndrome.

The concept of developmental origins of health and disease has been defined as the process through which the environment encountered before birth, or in infancy, shapes the long-term control of tissue physiology and homeostasis. The evidence for programming derives from a large number of experimental and epidemiological observations. Several nutritional interventions during diverse phases of pregnancy and lactation in rodents are associated with fetal and neonatal programming for metabolic syndrome. In this paper, recent experimental models and human epidemiological studies providing evidence for the fetal programming associated with the development of metabolic syndrome and related diseases are revisited.

High fat diets modulate nitric oxide biosynthesis and antioxidant defence in red blood cells from C57BL/6 mice.

The consumption of a high fat (HF) diet is considered a risk factor for the development of obesity. On the other hand, a monounsaturated HF diet has beneficial cardiometabolic effects. Since nitric oxide (NO) modulates vascular homeostasis, we investigate whether HF diets that vary in fatty acid composition have a different effect on theL-arginine-NO pathway and oxidative stress in C57BL/6 mice red blood cells (RBC). The olive oil diet induced an activation of L-arginine transport compared to other diets. NO synthase (NOS) activity was increased in all unsaturated HF diets (olive, sunflower and canola oils). Moreover, the expression of endothelial NOS (eNOS) and inducible NOS (iNOS) was increased in the olive oil group. In contrast, NOS activity from the lard group was decreased associated with diminished l-arginine transport. Olive oil also induced superoxide dismutase activation. Inhibition of the L-arginine-NO pathway in the lard group could contribute to cardiovascular diseases, while unsaturated HF diets may have a protector effect via enhanced NO bioavailability.

Beneficial effects of exercise training (treadmill) on insulin resistance and nonalcoholic fatty liver disease in high-fat fed C57BL/6 mice.

C57BL/6 mice develop signs and symptoms comparable, in part, to the human metabolic syndrome. The objective of the present study was to evaluate the effects of exercise training on carbohydrate metabolism, lipid profile, visceral adiposity, pancreatic islet alterations, and nonalcoholic fatty liver disease in C57BL/6 mice. Animals were fed one of two diets during an 8-week period: standard (SC, N = 12) or very high-fat (HF, N = 24) chow. An exercise training protocol (treadmill) was then established and mice were divided into SC and HF sedentary (SC-Sed, HF-Sed), exercised groups (SC-Ex, HF-Ex), or switched from HF to SC (HF/SC-Sed and HF/SC-Ex). HF/HF-Sed mice had the greatest body mass (65% more than SC/SC-Sed; P < 0.0001), and exercise reduced it by 23% (P < 0.0001). Hepatic enzymes ALP (+80%), ALT (+100%) and AST (+70%) were higher in HF/HF mice than in matched SC/SC. Plasma insulin was higher in both the HF/HF-Sed and HF/SC-Sed groups than in the matched exercised groups (+85%; P < 0.001). Pancreatic islets, adipocytes and liver structure were greatly affected by HF, ultimately resulting in islet beta-cell hypertrophy and severe liver steatosis. The HF group had larger islets than the SC/SC group (+220%; P < 0.0001), and exercise significantly reduced liver steatosis and islet size in HF. Exercise attenuated all the changes due to HF, and the effects were more pronounced in exercised mice switched from an HF to an SC diet. Exercise improved the lipid profile by reducing body weight gain, visceral adiposity, insulin resistance, islet alterations, and fatty liver, contributing to obesity and steatohepatitis control.

Beneficial effects of exercise training (treadmill) on insulin resistance and nonalcoholic fatty liver disease in high-fat fed C57BL/6 mice

C57BL/6 mice develop signs and symptoms comparable, in part, to the human metabolic syndrome. The objective of the present study was to evaluate the effects of exercise training on carbohydrate metabolism, lipid profile, visceral adiposity, pancreatic islet alterations, and nonalcoholic fatty liver disease in C57BL/6 mice. Animals were fed one of two diets during an 8-week period: standard (SC, N = 12) or very high-fat (HF, N = 24) chow. An exercise training protocol (treadmill) was then established and mice were divided into SC and HF sedentary (SC-Sed, HF-Sed), exercised groups (SC-Ex, HF-Ex), or switched from HF to SC (HF/SC-Sed and HF/SC-Ex). HF/HF-Sed mice had the greatest body mass (65 percent more than SC/SC-Sed; P < 0.0001), and exercise reduced it by 23 percent (P < 0.0001). Hepatic enzymes ALP (+80 percent), ALT (+100 percent) and AST (+70 percent) were higher in HF/HF mice than in matched SC/SC. Plasma insulin was higher in both the HF/HF-Sed and HF/SC-Sed groups than in the matched exercised groups (+85 percent; P < 0.001). Pancreatic islets, adipocytes and liver structure were greatly affected by HF, ultimately resulting in islet â-cell hypertrophy and severe liver steatosis. The HF group had larger islets than the SC/SC group (+220 percent; P < 0.0001), and exercise significantly reduced liver steatosis and islet size in HF. Exercise attenuated all the changes due to HF, and the effects were more pronounced in exercised mice switched from an HF to an SC diet. Exercise improved the lipid profile by reducing body weight gain, visceral adiposity, insulin resistance, islet alterations, and fatty liver, contributing to obesity and steatohepatitis control.

Left ventricular hypertrophy induced by overnutrition early in life.

BACKGROUND AND AIMS: Human overnutrition has caused a rise in the prevalence of obesity in recent years. In addition to the deleterious effects of obesity during childhood, the long-term effects in adulthood have also been described. For instance, cardiovascular diseases, particularly left ventricular hypertrophy, and type 2 diabetes are among the diseases associated with a history of obesity. However, it remains uncertain during which period of life this association is established. Several authors have suggested that the early period of life is critical for the emergence of cardiac disorders. METHODS AND RESULTS: In this study, we examined the impact of overnutrition on the heart morphology and stereology of obese animals using an experimental model to induce an overweight phenotype. In these animals, overfeeding during lactation was able to induce a significant increase in body weight and visceral fat starting at the 10th day of life, and this increased weight persisted until 21 days of age. Impairments in triglyceride levels and cholesterol were also observed in these animals. Moreover, an increased heart weight/tibia length ratio was observed, indicating an enlarged heart. The overfed animals also had left ventricular hypertrophy with an increased area of cardiomyocytes and a decreased vessel density. CONCLUSIONS: Our findings showed that overnutrition during early life induced obesity and cardiac hypertrophy in the pups, perhaps due to a decrease in the intramyocardial vessel.

Oral isotretinoin in photoaging: clinical and histopathological evidence of efficacy of an off-label indication.

BACKGROUND: Despite evidences of the beneficial clinical effects of oral isotretinoin in the treatment of cutaneous photoaging, scientific evidences are still scarce, mainly supported by histopathological and morphometric studies. OBJECTIVES: To analyse possible clinical and morphological changes resulting from the treatment of photoaging with oral isotretinoin. METHODS: Thirty female patients, aged 40 to 55 years, phototypes II to IV, with moderate to severe photoaging were randomly assigned to two groups of 15 each. Group I (G I) patients were treated with 10 mg of isotretinoin and group II (G II) with 20 mg of oral isotretinoin thrice a week for 3 months. Skin biopsies were performed before and after the end of therapy, and the various sections were submitted to specific staining for collagen and elastic fibres. To analyse the changes, morphometric studies were performed, and the results obtained were analysed by Student's t-test (paired and non-paired). Clinical results of therapy regarding texture, colouring and aspect of the wrinkles were assessed by both physician and patient. RESULTS: The increase in the amount of collagen fibres was statistically significant with both dosage regimens (mean, 37.8%, increasing to 44.4%; P = 0.029 with the 10-mg dosage; and mean, 36.6%, increasing to 41.9%; P = 0.01 with the 20-mg dosage). A pattern pointing toward a decrease in the number of elastic fibres was found (mean, 15.3-12%; P = 0.014 with the 10-mg dosage; mean, 15.5-14%; P = 0.125 with the 20-mg dosage). Additionally, there was improvement in the general aspect of the skin, regarding texture, wrinkles depth and skin coloration. LIMITATIONS: Despite ethical considerations, a lack of a control group using placebo may render the results less accurate. CONCLUSION: Low dosages of oral isotretinoin seem to be an effective therapeutic option for cutaneous photoaging.

Allopurinol attenuates L-NAME induced cardiomyopathy comparable to blockade of angiotensin receptor.

It is widely recognized that L-NAME exposed rats develop myocardial fibrosis and hypertrophy. The aim of this study was to evaluate the contribution of xanthine oxidase (XO) to these phenomena using allopurinol, isolated or associated with olmesartan. Thirty adult male Wistar rats were divided into 5 groups (n=6) and studied for 5 weeks: L group (L-NAME, 40mg/kg/day); L+A group (L-NAME and allopurinol, 40 mg/kg/day); L+O group (L-NAME and olmesartan, 15mg/kg/day); L+A+O group (L-NAME, allopurinol, and olmesartan); and control group. L-NAME caused arterial hypertension and cardiomyocyte hypertrophy. Hypertension was prevented by olmesartan, but not by allopurinol. There was an increase of left ventricular mass index in the L-NAME group that was prevented by allopurinol, olmesartan and by the combination of both. The increase in mean cardiomyocyte transversal area caused by L-NAME was prevented by the allopurinol and olmesartan combination, or by olmesartan used as monotherapy, but not by allopurinol alone. There was a reduction in the myocardial vascularization index caused by L-NAME which was abolished by allopurinol or by olmesartan, but not by the association. L-NAME caused a reduction in the total number of cardiomyocyte nuclei. This was prevented by olmesartan alone or associated with allopurinol, but not by allopurinol alone. We conclude that XO has an important contribution to adverse cardiac remodeling in L-NAME exposed animals. Moreover, allopurinol acts without interfering with L-NAME induced hypertension. The protective action of this drug is comparable to the results obtained with olmesartan. Antioxidative mechanisms are proposed to account for the pressure independent effects of allopurinol.

Parathyroid glands: combination of sestamibi-(99m)Tc scintigraphy and ultrasonography for demonstration of hyperplasic parathyroid glands.

OBJECTIVE: To determine the frequency of the types of parathyroid gland hyperplasia and the sensitivity of sestamibi-(99m)Tc (MIBI) scintigraphy and ultrasonography (US) of patients with secondary hyperparathyroidism (SHPT) due to chronic renal failure. MATERIAL AND METHODS: We studied 43 patients with SHPT (26 females and 17 males with age range of 27-75 years). Blood tests were performed to determine intact parathyroid hormone (PTH), calcium and phosphorus concentration and parathyroid MIBI scintigraphy and US examinations were done, to evaluate each glandular function and structure. Nineteen of the 43 patients underwent total parathyroidectomy and 69 abnormal glands were removed at operation. The 69 abnormal and 4 normal glands from patients that underwent total thyroidectomy were studied by light microscopy. The results were compared and correlation was calculated to: weight, MIBI uptake and US results. RESULTS: All 43 patients had elevated serum PTH ranged from 400 to 4,075 pg/ml (1,868.0 +/- 975.9 and normal range 10-75 pg/ml). Serum calcium and phosphorus concentration were 10.13 +/- 2.02 mg/dl and 5.28 +/- 2.07 mg/dl respectively. Fifty eight of 69 glands from surgical resection were MIBI positive and 11 were negative, but their cellular composition and presentation were similar. Hyperplasic glands had increased number of all cell types considered (chief, oxyphil and clear) compared to the normal gland. Chief cell hyperplasia was the most frequent type (81 %) followed by oxyphil (9 %), clear (6 %) and adenomatous type (4 %). False negative results of 10 % to US and 4.6 % to scintigraphy were found. The correlation of gland weight and MIBI uptake were not significant (p = 0.09). The sensitivity of MIBI scintigraphy was 84 % and US was 72.5 %. CONCLUSIONS: The MIBI scintigraphy is a very sensitive tool for pre-operative localization of hyperplasic parathyroid gland and should be used as the first imaging method. The association of MIBI and US is recommended because increases the sensitivity for preoperative hyperplasic parathyroid glands identification.

Parathyroid glands: combination of sestamibi-99mTc scintigraphy and ultrasonography for demonstration of hyperplasic parathyroid glands

Objetivo. Determinar la frecuencia de los tipos de hiperplasia de glándulas paratiroides y la sensibilidad de la gammagrafía con sestamibi-99mTc (MIBI) y de la ultrasonografía (US) para evaluar pacientes con hiperparatiroidismo secundario (HPTS). Material y métodos. Fueron estudiados 43 pacientes con HPTS (26 mujeres y 17 hombres con edades entre 27 y 75 años). Fueron determinadas las concentraciones de hormona paratiroidea intacta (PTHi), calcio y fósforo y evaluada la acumulación total del MIBI en las paratiroides así como la US para evaluación de la estructura y función glandular. En 19 de los 43 pacientes fue realizada resección de 69 glándulas anormales. Las glándulas anormales y 4 normales fueron estudiadas por microscopía óptica. Los resultados fueron comparados y la correlación estimada en relación al peso y a la acumulación de MIBI. Resultados. El total de los 43 pacientes presentó niveles elevados de PTHi (400-4.075 pg/ml) y los niveles de calcio y fósforo fueron, de media, 10,13 ± 2,02 mg/dl y 5,28 ± 2,07 mg/dl, respectivamente. Cincuenta y ocho de las 69 glándulas resecadas fueron positivas para MIBI y 11 negativas. Sin embargo, la composición celular y su presentación fueron semejantes. Las glándulas con hiperplasia presentaron un número aumentado de todos los tipos celulares. Las células principales fueron el tipo celular que presentó hiperplasia más frecuentemente (81 %), seguidas por las células oxifílicas (9 %), las claras (6 %) y las adenomatosas (4 %). Se encontraron resultados falsos negativos en el 10 % de las US y en el 4,6 % de las gammagrafías. La correlación entre el peso glandular y la acumulación de MIBI no fue significativa (p = 0,09). La sensibilidad de la gammagrafía con MIBI fue del 84 % y del 72,5 % para la US. Conclusiones. La gammagrafía con MIBI es una herramienta de alta sensibilidad para la localización de las glándulas con hiperplasia y debería ser utilizada como primera opción de evaluación. Se recomienda la asociación de gammagrafía con MIBI y la US en función del aumento de sensibilidad total con el uso de ambas técnicas

Objective. To determine the frequency of the types of parathyroid gland hyperplasia and the sensitivity of sestamibi-99mTc (MIBI) scintigraphy and ultrasonography (US) of patients with secondary hyperparathyroidism (SHPT) due to chronic renal failure. Material and methods. We studied 43 patients with SHPT (26 females and 17 males with age range of 27-75 years). Blood tests were performed to determine intact parathyroid hormone (PTH), calcium and phosphorus concentration and parathyroid MIBI scintigraphy and US examinations were done, to evaluate each glandular function and structure. Nineteen of the 43 patients underwent total parathyroidectomy and 69 abnormal glands were removed at operation. The 69 abnormal and 4 normal glands from patients that underwent total thyroidectomy were studied by light microscopy. The results were compared and correlation was calculated to: weight, MIBI uptake and US results. Results. All 43 patients had elevated serum PTH ranged from 400 to 4,075 pg/ml (1,868.0 ± 975.9 and normal range 10-75 pg/ml). Serum calcium and phosphorus concentration were 10.13 ± 2.02 mg/dl and 5.28 ± 2.07 mg/dl respectively. Fifty eight of 69 glands from surgical resection were MIBI positive and 11 were negative, but their cellular composition and presentation were similar. Hyperplasic glands had increased number of all cell types considered (chief, oxyphil and clear) compared to the normal gland. Chief cell hyperplasia was the most frequent type (81 %) followed by oxyphil (9 %), clear (6 %) and adenomatous type (4 %). False negative results of 10 % to US and 4.6 % to scintigraphy were found. The correlation of gland weight and MIBI uptake were not significant (p = 0.09). The sensitivity of MIBI scintigraphy was 84 % and US was 72.5 %. Conclusions. The MIBI scintigraphy is a very sensitivity tool for pre-operative localization of hyperplasic parathyroid gland and should be used as the first imaging method. The association of MIBI and US is recommended because increases the sensitivity for preoperative hyperplasic parathyroid glands identification

Pineal gland post-natal growth in rat revisited.

We studied the pineal gland (PG) growth separating two critical moments of the rat post-natal development: the lactation and post-weaning periods. We studied 30 Wistar rats in the post-natal day - PN day 6, 10, 21, 45, 60 and 90 using light microscopy and quantitative methods (allometry and stereology). We estimated the PG volume (using the Cavalieri's principle) and the number of pineal gland cell nuclei (PGCN, using the disector method). We analysed the correlation of the PG volume (y) versus brain weight (x) in the different age groups (the bivariate study used log-transformed data and the allometric model log y = log a + b log x). The PG growth gradually decelerated in older rats than in younger rats. The major increment of the PG growth was observed between PN day 6 and PN day 10, while the minor increment was observed after weaning between PN day 45 and PN day 60. After 60 days of age differences were no more observed. The relative growth of the PG was allometrically positive in all age groups, and growth curves separated the lactation from the after weaning periods. The number of PGCN of rat continuously increased during post-natal life and differences between the lactation and after weaning periods were significant. It is possible that the supporting cells, fibres and new synapses are responsible for that PG late post-natal increase.

Leprosy: contribution of mast cells to epineurial collagenization.

BACKGROUND: Leprosy, a disease caused by Mycobacterium leprae, is an important health problem worldwide. It is responsible for an irreversible nerve damage in which fibrosis plays an important role. The existence of an interaction between mast cells and different fibrotic conditions has long been observed. Tryptase, the most abundant protein product of human mast cells, has been shown to be mitogenic for fibroblasts and to increase type I collagen production. PATIENTS AND METHODS: In order to explore the possible relationship between tryptase-rich mast cells and nerve fibrosis in leprosy, we studied 24 sural nerve biopsies of patients with leprous neuropathy. Mast cells stained with mouse antihuman mast cell antitryptase clone AA1 as well as fibrosis, were quantitatively estimated in both epi- and endoneurial compartments. RESULTS: There was a remarkable association between collagen increase and tryptase-rich mast cell density in the epineurium but not in the endoneurium of leprous nerves. CONCLUSION: Since the epineurium in leprosy is type I collagen rich, the present findings support a tryptase-rich mast cell contribution to epineurial collagenization in leprosy through their tryptase secretion.

Amlodipine preserves the glomerular number in spontaneously hypertensive rats.

The calcium channel blockers have individual pharmacological and therapeutic properties that may vary, but as a group, they are effective antihypertensive agents in patients with renal disease. Their effects on the kidney may extend beyond BP reduction alone. Fifteen one-year-old male spontaneously hypertensive rats (SHR) were separated in three groups: Initial control group (IC), Final control group (FC, SHR received standard rat chow and fresh water ad libitum during 15 weeks), Amlodipine group (Aml, SHR) received 0.2 mg/kg/day of amlodipine in addition to food and water during 15 weeks. The glomerular number was estimated using the disector method. In the Control group, the BP level increased almost 20 per cent in the first six weeks (from 186 +/- 11 to 223 +/- 16 mmHg, p<0.01) and then BP level increased almost 15 percent until week 15 (from 223 +/- 16 to 258 +/- 20 mmHg, p<0.01). In the same period, the Aml group showed a progressively low BP, reaching a level almost 50 per cent lower in the week 15 than in the week 1 (from 190 +/- 15 to 101+/-8 mmHg, p<0.01). Amlodipine treatment significantly decreased the serum creatinine, more than 12 per cent lower than the FC group (from 70.4 +/- 6.2 to 61.4 +/- 5.2 micromol/L, p<0.05). However, proteinuria was not different when groups were compared. The FC group reached a glomerular number almost 20 percent smaller than the IC and Aml groups (from 35 x 10(3) +/- 7 x 10(3) in IC group, 34 x 10(3) +/- 4 x 10(3) in Aml group to 27 x 10(3) +/- 3 x 10(3) in FC group, p<0.05). A possible protective effect of amlodipine against the loss of glomeruli in SHR is a major additional action of amlodipine in the treatment of hypertension mainly when the renal lesion already exists.

Different edible oil beneficial effects (canola oil, fish oil, palm oil, olive oil, and soybean oil) on spontaneously hypertensive rat glomerular enlargement and glomeruli number.

We have tested the different edible oil effects on the blood pressure (BP) control and the following glomerular protection. Six groups of 12-week-old male spontaneously hypertensive rats (SHR) (n = 5), have received different edible oils (fish, canola, palm, olive, and soybean) or a placebo by gavage for 13 weeks. Renal cortex was analyzed through light microscopy and stereology. Usual BP increase, glomerulosclerosis, glomerular enlargement, and glomeruli loss in SHR has been prevented (fish, canola and palm oils) or attenuated (olive and soybean oils) by these oil long-term administration. The most favorable effect has been seen in the fish oil administration (source of n-3 polyunsaturated fatty acids, PUFA, eicosapentaenoic and docosahexaenoic acids), followed by both canola and palm oils (source of n-3 PUFA plus n-9 monounsaturated, MUFA, and saturated fatty acid, respectively), and finally both olive and soybean oils (source of n-9 MUFA and n-6 PUFA, respectively).

Malnutrition during lactation in rats is associated with higher expression of leptin receptor in the pituitary of adult offspring.

OBJECTIVE: Recent studies have shown that leptin receptor is expressed in human and rat pituitary glands. The expression of leptin receptor in rats whose dams were malnourished during lactation has not been previously reported. METHODS: We examined leptin receptor expression in the pituitary gland of adult rats whose dams were assigned to one of the following groups during lactation: control diet, protein-restricted diet (8% protein), or energy-restricted diet (the control diet fed in restricted quantities that were calculated according to the mean ingestion of the protein-restricted group). After weaning, all pups had free access to the control diet until they reached adult age, at which time leptin receptor expression in the pituitary was analyzed by immunohistochemistry. RESULTS: Adult animals from protein- and energy-restricted dams had a higher expression of leptin receptor in pituitary tissue, normal serum leptin concentrations, higher serum tri-iodothyronine concentrations, and lower thyroid-stimulating hormone concentrations than did the control rats. CONCLUSIONS: In the fed state, leptin has a stimulatory effect on release of thyroid-stimulating hormone. The higher expression of leptin receptor in the pituitary of animals from protein- and energy-restricted dams may suggest a postreceptor failure in leptin action. This higher receptor expression may have allowed a greater inhibition of release of thyroid-stimulating hormone.

Effect of unilateral nephrectomy on renal function of diabetic rats.

Glomerular alterations of experimental diabetes mellitus are observed in animals submitted to a reduction in renal mass, suggesting that some mechanisms responsible for the progression of renal disease are common. The aim of this study was to investigate the effect of nephrectomy on the renal function and morphology of diabetic rats. Male Wistar rats were divided into 4 groups: control (C), n=8; diabetic (DM), n=8; non-diabetic nephrectomized (Nx), n=8; (DMNx), n=9. DM was induced by streptozotocin (65 mg/Kg), and animals were treated with insulin. After 12 weeks, the glomerular filtration rate (GFR), renal plasma flow (RPF) and mean arterial pressure (MAP) were evaluated in unanaesthetized animals. Glomerular volume (GV), glomerular sclerosis index (GSI), mesangial volume density (Vvmes) and glomerular capillary surface density (Svcap) were also evaluated. Results show that kidney weight increased in Nx groups, being higher in DMNx. GFR was higher in Nx groups as was RPF, being higher in DMNx. RVR was lower in Nx groups, especially in DMNx. MAP was not different among the groups. RPF and GFR showed a high correlation for the DMNx group (r=0.95, p=0.02). The DMNx group showed a correlation between RVR and GFR (r=-0.96, p=0.005). The GV increased in Nx groups, and the GSI was higher in DMNx. Vvmes and Svcap increased in DMNx group. In summary, Nx groups developed similar degrees of glomerular hypertrophy, but only DMNx showed an increased value for GSI. The present data suggest that the acceleration of glomerular lesions in DMNx animals was more closely associated to hemodynamic adaptations than to glomerular hypertrophy.