75 research outputs found
A Mouse Model of Metabolic Syndrome: Insulin Resistance, Fatty Liver and Non-Alcoholic Fatty Pancreas Disease (NAFPD) in C57BL/6 Mice Fed a High Fat Diet
Diet-induced obesity in C57BL/6 mice triggers common features of human metabolic syndrome (MetS). The purpose is to assess the suitability of a diet-induced obesity model for investigating non-alcoholic fatty pancreatic disease (NAFPD), fatty liver and insulin resistance. Adult C57BL/6 mice were fed either high-fat chow (HFC, 60% fat) or standard chow (SC, 10% fat) during a 16-week period. We evaluated in both groups: hepatopancreatic injuries, pancreatic islets size, alpha and beta-cell immunodensities, intraperitoneal insulin tolerance test (IPITT) and oral glucose tolerance test (OGTT). The HFC mice displayed greater mass gain (p<0.0001) and total visceral fat pads (p<0.001). OGTT showed impairment of glucose clearance in HFC mice (p<0.0001). IPITT revealed insulin resistance in HFC mice (p<0.0001). The HFC mice showed larger pancreatic islet size and significantly greater alpha and beta-cell immunodensities than SC mice. Pancreas and liver from HFC were heavier and contained higher fat concentration. In conclusion, C57BL/6 mice fed a high-fat diet develop features of NAFPD. Insulin resistance and ectopic accumulation of hepatic fat are well known to occur in MetS. Additionally, the importance of fat accumulation in the pancreas has been recently highlighted. Therefore, this model could help to elucidate target organ alterations associated with metabolic syndrome
The effect of thiamine deficiency on inflammation, oxidative stress and cellular migration in an experimental model of sepsis
Stereological tools in biomedical research
Stereological studies are more and more frequent in literature, particularly in the development/evolution, pathology, and neurosciences areas. The stereology challenge is to understand the structural inner threedimensional arrangement based on the analysis of the structure slices only showing two-dimensional information. Cavalieri and Scherle's methods to estimate volume, and Buffon's needle problem, are commented in the stereological context. A group of actions is needed to appropriately quantify morphological structures (unbiased and reproducibly), e.g. sampling, isotropic and uniform randomly sections (Delesse's principle), and updated stereological tools (disector, fractionator, nucleator, etc). Through the correct stereology use, a quantitative study with little effort could be performed: efficiency in stereology means a minimum slices sample counting (little work), low cost (slices preparation), but good accuracy. In the present text, a short review of the main stereological tools is done as a background basis to non-expert scientists
Pancreatic islet (of Langerhans) revisited
One hundred and fifty years ago, Paul
Langerhans described what would come to be known as
pancreatic ‘islet of Langerhans’. Since then, we have
accumulated knowledge about the pancreatic islet, the
cells that exist there and the hormones secreted by these
cells. The increasing prevalence of obesity, diabetes and
Alzheimer’s disease in the population (three conditions
that are linked to pancreatic islet function), the islet has
been playing a significant role in endocrinological and
metabolic studies searching how we can protect the
pancreatic islet and its cell content, or how we can
regenerate it. This review will be interested in the most
recent and relevant aspects of knowledge regarding the
pancreatic islet, always mentioning the evolution of
knowledge and future perspectives for the treatment of
diabetes and Alzheimer’s disease. The most recent
research with microRNAs and islet culture and
pseudoislet culture (organoids) allows predicting
advances in knowledge with new drugs to act on the
islet/cells (such as the hormone glucagon-like peptide
(GLP) -1) as well as induction of other islet cells like
alpha-cells and delta-cells to transform into beta-cells
Erratum to ''Stereological tools in biomedical research'': an Acad Bras Cienc 75(2003): 469-486
Effect of telmisartan on preexistent cardiac and renal lesions in spontaneously hypertensive mature rats
Fifteen adult male spontaneously
hypertensive rats (one year old) (SHR) were separated
into three groups (n=5 each) during 15 weeks as follows:
initial control group (IC); final control group (FC); and
telmisartan group (T) (1.2 mg/kg/day of telmisartan).
Serum and urinary creatinine and proteinuria were not
different comparing untreated and telmisartan-treated
SHRs. FC rats showed a continuous BP increase during
the study while T rats reached the 15th week with a
significantly low BP. The LV mass index was
significantly smaller in the T group than in the FC
group, as was the glomerular hypertrophy. The
cardiomyocyte nuclei density per area and the
cardiomyocyte mean cross-sectional area were smaller in
the T group than in both the IC and FC groups.
Intramyocardial artery densities (per area and per
volume) were greater in the T group than in untreated
SHRs, but myocardial fibrosis was reduced. In
conclusion, telmisartan monotherapy effects on BP and
also on the hypertension target organs, heart and kidney,
are favorable. Telmisartan is able to attenuate SHR
cardiomyocyte and glomerular hypertrophies, and
myocardial reactive fibrosis as well. It also is favorable
to the intramyocardial microcirculation
Glomerular profile numerical density per area and mean glomerular volume in rats submitted to nitric oxide synthase blockade
Rats submitted to chronic inhibition of nitric
oxide synthase (NOS) have developed systemic
hypertension and consequent renal injury. The present
study aims to determine glomerular quantitative changes
due to NOS inhibition in rats. Adults and normotensive
Wistar rats were separated into control and L-NAME
groups (each group n=10). The animals received water
and food ad libitum, while L-NAME rats received N ~ -
Nitro-L-Arginine methyl Ester hydrochloride to inhibit
NOS (50mg/kg/day) in drinking water during 40 days.
After that period the rats were sacrificed, the kidneys
were removed, measured, and prepared for histological
and stereological analyses. The glomerular density per
area [NA(giom)] and the mean glomerular volume [Y]
were determined per animal in 15 random fields. In LNAME
rat the blood pressure was 76% higher than the
respective control group with the same age. Glomeruli
had global or segmental glomerular sclerosis; some
glomeruli only presented an atrophic structure. The renal
volume was not different between control and L-NAME
rats (p>0.05). However, L-NAME rats had the NA(giom)
33% smaller than the control rats (p=0.0001) and,
concomitantly, L-NAME rats had the Y (glom) 33%
higher than the control ones (p=0.004). These results
demonstrate morphological renal alterations caused by
NOS inhibition and hypertension
Papel da óxido nítrico sintase na etiopatogenia da estenose hipertrófica do piloro na infância
OBJETIVOS: reproduzir, experimentalmente, em ratos, por meio do inibidor da enzima óxido nítrico sintase (ONS - L-NAME), os achados histopatológicos correspondentes a estenose hipertrófica do piloro da infância (EHPI). MÉTODOS: para reproduzir o modelo de inibição de ONS na produção de EHPI, administrou-se L-NAME em ratas grávidas, a partir do 14º dia gestacional (grupo L-NAME), comparando-se com uma gestação de controle. Após o nascimento, todos os ratos do grupo L-NAME foram mantidos sob inibição da ONS até o 42º dia de vida, quando foram sacrificados. Os filhotes da gestação de controle, em que nenhuma droga foi administrada, foram também sacrificados com 42 dias de vida. Os animais e as vísceras foram analisados e pesados. A região pilórica foi preparada tecnicamente e observada em microscopia de luz. RESULTADOS: em comparação com os animais de controle, os L-NAME tiveram peso corporal e intestinal menor e peso gástrico maior. Nos animais L-NAME a microscopia de luz evidenciou hipertrofia da camada circular do músculo liso do piloro. CONCLUSÃO: este trabalho reproduziu um modelo experimental de estudo da estenose hipertrófica do piloro e comprovou, neste modelo, a associação da ausência da ON sintase na musculatura do piloro
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 (65mg/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
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