Inflamação do parênquima pulmonar na asma e sua relação com as vias aéreas / Pulmonary parenchyma inflammation in asthma

A inflamação da asma não está limitada às vias aéreas e pode comprometer também o parênquima pulmonar periférico, no entanto, não há estudos na literatura que enfoquem a participação do parênquima pulmonar na asma. Objetivo: Caracterizar o infiltrado inflamatótrio do parênquima peribronquiolar e distal em vítimas de asma fatal, comparando-o ao de outras regiões de vias aéreas e a de tecido pulmonar de não asmáticos. Fragementos de tecido pulmonar obtidos de 20 pacientes com asma fatal e 10 controles, necropsiados no Serviço de verificacão de óbito da capital - São Paulo, foram submetidos a estudo de imuno-histoquímica e marcados com anticorpos anti-proteína básica principal (eosinófilos), anti-triptase (mastócitos), anti-elastase neutrofílica (neutrófilos) e anti-marcadores de superfície de linfócitos (CD3, CD$, CD* e CD20). Foram determinadas as densidades celulares no parênquima pulmonar periférico peribronquiolar e distal e nas áreas interna e externa das vias aéreas de grande e de pequeno calibre. Resultados: A densidade de eosinófilos foi significativamente maior nas duas regiões do parênquima pulmonar de asmáticos comparados aos controles, bem como as vias aéreas (p<0,02). Nos pacientes asmáticos a densidade eosinófilica se mostrou menos no parênquima distal em relação à da área interna da via aérea grande apenas (p<0,01). A densidade dos mastócitos foi maior no parênquima peribronquiolar bem como na área externa das vias aéreas de grande e de pequeno calibre de asmáticos comparados aos controles (p<0.04). Diferenças significativas quanto à densidade de linfócitos se restringiram às vias aéreas de asmáticos comparadas as de controles. Maior densidade de neutrófilos foi observada apenas no parênquima pulmonar de asmáticos (p=0.029). Conclusões: O parênquima pulmonar participa do processo inflamatório na asma fatal com aumento de células efetoras (mastócitos, neutrófilos e eosinófilos). A área externa da via aérea foi a região que melhor diferenciou o asmáticodo controle e com o maior número de diferenças significativas. A inflamação do parênquima peribronquiolar, associado ao da área externa da via áerea pequena, reforça o papel do pulmão distal na patofisiologia da asma.

Monosodium glutamate (MSG) - obese rats develop glucose intolerance and insulin resistance to peripheral glucose uptake

Different levels of insulin sensitivity have been descrebed in several animal models of obesity as well as in humans. Monosodium glutamate (MSG)-obese mice were considered not be insulin resistant from data obtained in oral glucose tolerance tests. To reevaluate insulin resistance by the intravenous glucose tolerance test (IVGTT) and by the clamp technique, newborn male Wistar rats (N = 20) were injected 5 times, every other day, with 4 g/Kg MSG (N = 10) or saline (control; N = 10) during the first 10 days of age. At 3 months, the IVGTT was performed by injecting glucose (0.75 g/Kg) through the jugular vein into freely moving rats. During euglycemic clamping plasma insulin levels were increased by infusing 3 mU. Kg(-1). min (-1) of regular insulin until a steady-state plateau was achieved. The basal blood glucose concentration did not differ between the two experimental groups. After the glucose load, increased values of glycemia (p<0.001) in MSG-obese rats occurred at minute 4 and from minute 16 to minute 32. These results indicate impaired glucose tolerance. Basal plasm insulin levels were 39.9 + 4 muU/ml in control and 66.4 + 5.3 muU/ml in MSG-obese rats. The mean post-glucose area increase of insulin was 111 percent higher in MSG-obese than in control rats. When insulinemia was clamped, at 102 or 133 muU/ml in control and MSG rats, respectively, the corresponding glucose infusion rate necessary to maintain euglycemia was 17.3 + 0.8 mg. kg (-1). min(-1) for control rats while 2.1 + 0.3 mg. kg(-1). min(-1) was sufficient for MSG-obese rats. The 2-h integrated area for total glucose metabolized, in mg. min. dl(-1), was 13.7 + 2.3 vs 3.3 + 0.5 for control and MSG rats, respectively. These data demonstrate that MSG-obese rats develop insulin resistance to peripheral glucose uptake.

Ultra-sonografia seriada do endométrio e da endocérvice durante o ciclo menstrual normal da mulher / Serial ultrasonography of the endometrium and endocervix during the normal menstrual cycle of women

Os relatos ultra-sonográficos do endométrio humano säo, em sua maior parte, obtidos de pacientes com esterilidade conjugal, nulíparas, fazendo uso de drogas indutoras da ovulaçäo. Essas pesquisas, geralmente, näo se acompanham do estudo histológico da cavidade uterina e preocupam-se, sobretudo, com o período ovulatório. Há, contudo, controvérsias na interpretaçäo das imagens. OBJETIVO. Estudas a ultra-sonografia do endométrio, no decorrer do ciclo menstrual normal. MÉTODOS. Os autores selecionaram 15 mulheres, eumenorréicas, multíparas, que näo faziam uso de drogas indutoras da ovulaçäo, DIU ou contra-conceptivos hormonais. todas foram examinadas no primeiro, no sétimo, no décimo-quarto eno vigésimo-primeiro dia do ciclo menstrual. Confrontaram-se os achados ecográficos com os resultados histológicos. RESULTADOS. Avaliaram a imagem ultra-sonográfica do endométrio em 66.66 por cento das mulheres no primeiro dia do ciclo. Em todas elas, no sétimo, décimo-quarto e vigésimo-primeiro dia essa imagem também pôde ser identificada e apreciada. Verificaram, durante o ciclo, aumento progressivo da espessura da imagem endometrial, de forma linear. O halo hipoecóico teveincidência progressiva, atingindo 93,33 por cento no vigésimo-primeiro dia do ciclo. CONCLUSÄO. As alteraçöes cíclicas do endométrio foram demonstradas pela ultra-sonografia. As modificaçöes endocervicais também foram detectadas. Todavia, säo menos exuberantes do que as observadas no endométrio

Neonatal monosodium glutamate treatment increases epididymal adipose tissue sensitivity to insulin in three-month old rats

We determined the response of glucose transport to insulin in isolated adipocytes and the lipogenic activity of insulin in fragments of epididymal adipose tissue obtained from male MSG-obese rats. Basal glucose transport rates (pmol 3 min-1 10(5) cells-1) were 100 higher in MSG than in control cells (3-month old male Wistar rats) pre-incubated for 30 min (P < 0.01). Nevertheless, when expressed as fmol 3 min-1 microns 2 cell surface area-1, transport rates were similar for the two groups (31.2 +/- 2.6 for MSG and 26.5 +/- 3.2 for controls, N = 7). No differences were observed in maximally insulin-stimulated glucose transport rates between groups (72.6 +/- 10.6 for MSG and 101.0 +/- 12.0 for controls, N = 7). In contrast, for adipocytes pre-incubated for 2 h, the basal uptake rates were 3.7 times higher and the maximal response to insulin was 103 higher in cells from MSG rats compared to control cells. These alterations in MSG rat adipocytes were accompanied by changes in cell sensitivity to insulin (EC50, 0.13 +/- 0.02 ng/ml for MSG vs 0.46 +/- 0.10 ng/ml for controls, P < 0.01). The rates of incorporation of labelled substrates (3H2O and 14C-glucose) into total lipids showed that in vitro lipogenesis was also 79 (3H2O) and 250 (14C-glucose) higher in MSG adipose tissue fragments. The MSG animals were consistently hyperinsulinemic. These data suggest that the obesity of 3-month old MSG rats is a metabolic alteration characterized by an enhanced adipocyte capacity to transport glucose and to synthetize lipids resulting in increased insulin sensitivity.

The regulation of insulin action in isolated adipocytes. Role of the periodicity of food intake, time of day and melatonin

Isolated adipocytes from rats submitted to four weeks of ad libitum feeding (AL) or meal feeding (MF, 2 h/22 h, feeding/fasting, meal time: 8:00-10:00 a.m.) schedules or pre-incubated with or without melatonin (0, 1 nM, 10 nM, 100 nM) for 5 h were submitted to insulin-stimulated [3H]-2-deoxyglucose (0.1 mM, 0.12 microCi) uptake rate measurements and insulin binding assays. Insulin sensitivity was defined as the hormone concentration capable of producing the half-maximal transport rate. Insulin sensitivity varied depending on the previous conditions of the adipocytes. In MF animals, adipose cells were more sensitive (EC50 = 0.175 ng/ml) just at the moment of the expected meal. In AL rats, sensitivity was lower (EC50 = 0.678 ng/ml) at 8:00 a.m. and increased (EC50 = 0.398 ng/ml) at 4:00 p.m. These data clearly implicate the expectation of food and period of the day with the regulation of insulin action. All these modifications in sensitivity occurred without any change in insulin receptor number or affinity. Melatonin, a secretory product of the pineal gland, induced an increase in cell sensitivity to insulin in adipocytes incubated with the highest hormone concentration (100 nM). We conclude that factors related to feeding training and circadian rhythmicity modulate cell sensitivity to insulin.

Plasma kallikrein clearance by the liver in food-restricted rats

We measured the cleaance rate of plasma kallikrein by the liver in three groups of rats: one recently weaned, and two seven weeks old (control and food-restricted groups). The clearance rates were similar in the three groups when expressed as units/g liver. The livers of the recently weaned and food-restricted rats were, however, smaller than those of the controls and consequently their livers cleared plasma kallikrein less efficiently

Effect of fasting on monosodium glutamate-obese rats

The effect of fasting was studied in lean an monosodium glutamate (MSG)-obese rats. Daily urinary urea excretion and body weitht loss were studied before and during 21 days of fasting. MSG-obese rats showed reduced weight loss, higher total liver lipid content, and lower urea exretion during fasting, thus suggesting a higher capacity to spare body protein in comparison to controls. A significant decrease in retroperitoneal fat pad content was observed in both groups after 6 days of fasting (83% in the controls vs 35% in MSG-obese rats). These data suggest that the larger lipid stores of MSG-obese rats can explain their greater mean survival time after fasting

Inflammatory edema induced by carrageenin in monosodium glutamate-treated rats

Rats treated with monosodium glutamate (MSG) during the neonatal period show hypothalamic lesions and multiple neuroendocrine alterations manifested as a remarkable increase in levels of circulating corticosterone and obesity. Paw edema induced by local injection of carrageenin was significantly reduced in MSG-treated rats compared to normal rats. In contrast, both adrenalectomized rats and adrenalectomized, MSG-treated rats showed an increased response to carrageenin relative to controls. These results suggest that glucocorticoids are important modulators of inflammation in this phase of the process