Reviewing physical exercise in non-obese diabetic Goto-Kakizaki rats

There is a high incidence of non-obese type 2 diabetes mellitus (non-obese-T2DM) cases, particularly in Asian countries, for which the pathogenesis remains mainly unclear. Interestingly, Goto-Kakizaki (GK) rats spontaneously develop insulin resistance (IR) and non-obese-T2DM, making them a lean diabetes model. Physical exercise is a non-pharmacological therapeutic approach to reduce adipose tissue mass, improving peripheral IR, glycemic control, and quality of life in obese animals or humans with T2DM. In this narrative review, we selected and analyzed the published literature on the effects of physical exercise on the metabolic features associated with non-obese-T2DM. Only randomized controlled trials with regular physical exercise training, freely executed physical activity, or skeletal muscle stimulation protocols in GK rats published after 2008 were included. The results indicated that exercise reduces plasma insulin levels, increases skeletal muscle glycogen content, improves exercise tolerance, protects renal and myocardial function, and enhances blood oxygen flow in GK rats.

Polyphenols purified from the Brazilian aroeira plant (Schinus terebinthifolius, Raddi) induce apoptotic and autophagic cell death of DU145 cells.

Polyphenols extracted from many plants have shown antiproliferative and antitumor activities in a wide range of carcinogenesis models. The antiproliferative effects of polyphenols purified from the Brazilian aroeira plant (Schinus terebinthifolius, Raddi) were investigated on the androgen-insensitive DU145 human prostatic carcinoma cell line. A F3 fraction purified from leaf extract inhibited the DU145 cell proliferation more than 30-fold compared to the crude extract. By flow cytometric analysis, the polyphenol fraction was demonstrated to induce G0/G1 cell growth arrest and cell apoptosis. This apoptosis was evidenced by caspase 3 stimulation in F3-treated cells as compared to crude extract treated cells. The acid phosphatase activity of lysosomes was strongly activated in the lysosomal fraction of the F3-treated DU145 cells. This lysosomal activation, together with the appearance of autophagic vacuoles, suggests that "type 2 physiological cell death" was also involved in this antiproliferative effect. HPLC analysis of this F3 fraction showed 18 different subfractions. Among these subfractions, F3-3, F3-7 and F3-13 strongly inhibited DU145 cell proliferation in a dose-dependent manner. However, the nature of these polyphenols remains unknown since only one (Isoquercitrin) of the tested pure polyphenols co-migrated with F3-13. Since lysosomotropic drugs are considered as possible regulators of lysosome activity, aroeira polyphenols could target lysosomes of prostatic cancer cells to induce autophagic cell death.

Role of lysosomes on human ulcerogenic gastropathies. Effect of zinc ion on the lysosomal stability.

Numerous conditions are involved in the equilibrium between protective and aggressive factors for gastric mucosa injuring. Among them the lysosomal membrane stability plays a very important role in the inflammatory process. Zinc ion is a well-known lysosomal membrane stabilizer. When given orally to animals or even to humans it protects gastric mucosa against erosive lesions induced by a variety of experimental conditions. Compared with the control group (8.45 +/- 1.49 mU/mg) the lysosomes isolated from samples of gastric mucosa obtained from patients suffering of erosive gastropathies, showed a great liability on their membranes (18.37 +/- 4.52 mU/mg). When these patients were treated orally with zinc sulfate (100 mg of zinc element, twice a day, for two weeks) the lysosomes isolated from their gastric mucosa showed a strong reduction on enzymatic activity (5.49 +/- 1.02 mU/mg), probably due to increasing on the membrane stability. Based on these experimental findings we propose the use of zinc ion as an important adjuvant in treatment of erosive gastropathies.

Absence of zinc cytotoxicity: Effect of short-term zinc oral administration on rat gastric mucosa

Zinc ions have been reported to stabilize cellular membranes, protecting the gastric mucosa against a wide variety of ulcerative agents. The treatment with zinc sulfate intragastrically administered as one dose (20 mg/Kg body weight) daily for 30 consecutive days did not modify the normal aspect of rat gastric mucosa as observed by electron sanning microscopy. Furthermore, the X-ray microanalysis of the lysosome content performed on different gastric mucosa cells did not show the zinc element. These results suggest that zinc ion is a relatively nontoxic element for the rat gastric mucosa

[Biochemistry of schistosomiasis mansoni. VII. Lipid changes of lysosomal membranes during the initial phase of liver injury]. / Bioquímica da esquistossomose mansõnica. VII--alterações lipídicas das membranas lisossõmicas durante a fase inicial da agressão hepatica.

Aiming at investigating the changes on the lipidic constitution of hepatic lysosomal membranes at the initial phase of schistosomatic damage, mice have been infected with 30 cercarias and employed for essais in the 30th day of infection. The triacylglycerois decreased from 220 +/- 48 micrograms/mg of total proteins in the control mice, to 165 +/- 22 micrograms/mg in the infected ones. Similarly, the free cholesterol, also decreased from 539 +/- 80 to 396 +/- 54 micrograms/mg; the cholesterol esters from 270 +/- 35 to 216 +/- 36 micrograms/mg and the phosphatidylcholines from 44 +/- 5.7 to 31 +/- 4.9 micrograms/mg. The phosphatidylserines the phosphatidylethanolamines and the sphingomyelins increased, respectively from 58 +/- 9.7 to 60 +/- 8.5, from 72 +/- 7.8 to 111 +/- 15.7 and from 36 +/- 4.9 to 63 +/- 7.1 micrograms/mg. The free fatty acids showed no statistical significance on their variations. They varied from 1.7 +/- 0.25 microEq/g in the controls to 1.8 +/- 0.39 microEq/g in the infected animals. These results indicated that in the initial phase of hepatic schistosomiasis, before the formation of granulomas, important changes on the lipidic constitution of lysosomal membranes can be detected. It seems that they are provoked by the catabolic excreted by immature or adult worms of Schistosoma mansoni present in the portal vein system.

[Lysosomotropism and anti-inflammatory action of gold salts]. / Lysosomotropisme et action anti-inflammatoire des sels d'or.

Gold salts have been widely used in the past 70 years in the treatment of various connective tissue diseases and more particularly in rheumatoid arthritis. However their mechanism of action remains poorly understood. Gold salts are transported in the blood linked with several serum proteins including immunoglobulins. Methods of analytical electron microscopy (Castaing probe) have shown that gold is actively concentrated in the lysosomes of various cell types, including the proximal tubular cells of the kidney and certain bone marrow cells. These data, together with those provided by biochemical techniques, suggest that sodium aurothiopropanol sulfonate modifies the stability of lysosome membranes. In the present study it is shown that the stability of kidney lysosomes of treated rats was increased by 42.4 per cent after treatment for 3 days. This protective action was also seen when lysosomes were subjected to lysis by digitonin. The protective effect of gold salts on the lysosomal membrane may be explained by the formation of chemical complexes between gold and sulfhydryl groups present in the membrane, resulting in stable mercaptic bonds. These findings suggest that the increase in stability of lysosomal membranes plays a significant role in the anti-inflammatory action of gold salts.

Renal involvement in visceral leishmaniasis.

In a prospective study of 50 patients with visceral leishmaniasis, laboratory abnormalities suggestive of renal involvement were not infrequent. Proteinuria and/or microscopic hematuria or pyuria were observed in 51% of such cases. Twenty-four hour urinary protein excretion was elevated in 57% of patients in all cases below 1g/24 hours. An abnormal acid-load test was demonstrated in 12 of 18 patients studied before therapy of the parasitic infection with N-methyl-glucamine. Of interest was the demonstration of tubulo-interstitial involvement in the renal histology of all seven patients studied; also, in five of seven patients there was a proliferative glomerulonephritis, usually mild, on histologic examination. In general, there was a tendency to subsidence of abnormal laboratory findings within one month after specific therapy. Renal involvement in visceral leishmaniasis was mild and seemed to revert with the cure of the leishmanial infection.

Analises de amostras biologicas por microscopia ionica. / Analysis of biological samples by ionic microscopy

Os autores avaliaram detalhadamente o metodo de microanalise de amostras biologicas por microcospia ionica, proposto por Castaing e Slodzian, alem de compara-lo com outros metodos analiticos para volumes extremamente pequenos. Com a microscopia ionica analitica, podem-se obter imagens de distribuicao de determinados elementos estaveis ou radioativos, constitutivos de diferentes amostras biologicas como esfregaco celulares, cortes de tecido por congelacao ou apos inclusao em parafina etc.Comparando-se a microscopia analitica ionica com a microautoradiografia, a primeira tem a grande vantagem de detectar a maioria dos nuclideos presentes numa amostra biologica, mesmo em concentracoes tao baixas quanto 0,1 ppm e com uma resolucao espacial de 0,5 micro m num volume de 1micro m3

Biochemistry of schistosomiasis mansoni. IV - Effects of oxamniquine on the hepatic lysosomal activity.

Uma das caracteristicas mais importantes e que sempre acompanha a lesao hepatica causada pela esquistossomose mansonica, e o processo inflamatorio que se desenvolve em torno do verme vivo ou morto, assim como do ovo deste parasita. Este processo inflamatorio esta intimamente ligado a uma maior labilidade das membranas lisossomiais. A oxamniquine, droga extensivamente usada no tratamento desta doenca, foi testada in vitro e in vivo para investigacao de possivel efeito fisico-quimico sobre as membranas dos lisossomas. Os resultados in vitro, indicaram que esta droga, possui efeito estabilizador sobre 27,1% destas particulas intracelulares. As observacoes in vivo, foram levadas a efeito, apos a injecao intraperitonial da droga, na dose de 7,5 mg/kg de peso, em camundongos. Estes animais, assim tratados, foram utilizados, 1,3,6,9 e 12 dias apos o tratamento. Os resultados, mostraram uma labilizacao de 22,7% das membranas lisossomiais, apos o primeiro dia, aumentando para 60,1% em torno do terceiro dia. No sexto dia o tratamento, o efeito labilizador decresceu para 37,2%. Ja no nono dia, observou-se o oposto, um efeito estabilizador na ordem de 35,7% dos lisossomas. Apos o decimo segundo dia, estas organelas vortaram a normalidade fisico quimico de suas membranas

Variacoes na atividade da ceruloplasmina serica humana. / Variations on the activity of human serum ceruloplasmin

Soros sanguineos de 100 individuos sadios foram utilizados na determinacao polarografica da atividade ceruloplasminica, com a finalidade de serem detectadas variacoes nas taxas basais desta enzima, ligadas com o sexo, cor e gravidez. Os resultados obtidos mostram variacoes bastante importantes na dependencia destes parametros, as quais deverao ser levadas em conta na utilizacao correta desta enzima como meio de diagnostico e de acompanhamento terapeutico de varias doencas