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.

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.

The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes.

OBJECTIVE: Hypomagnesemia occurs in 25-38% of patients with type 2 diabetes. Several studies have suggested an association between magnesium (Mg) depletion and insulin resistance and/or reduction of insulin secretion in these cases. Our purpose was to evaluate if Mg supplementation (as magnesium oxide [MgO]) would improve metabolic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied 128 patients with type 2 diabetes (32 men, 96 women, aged 30-69 years), treated by diet or diet plus oral antidiabetic drugs, in the Bahia Federal University Hospital, Brazil. Patients at risk for hypomagnesemia or with reduced renal function were excluded. This study was a clinical randomized double-blind placebo-controlled trial. Patients received either placebo, 20.7 mmol MgO, or 41.4 mmol MgO daily (elementary Mg) for 30 days. Mg concentrations were measured in plasma, in mononuclear cells, and in 24-h urine samples. Fasting blood glucose, HbA1, and fructosamine were used as parameters of metabolic control. RESULTS: Of the patients, 47.7% had low plasma Mg, and 31.1% had low intramononuclear Mg levels. Intracellular Mg in patients with diabetes was significantly lower than in the normal population (62 blood donors; 1.4 +/- 0.6 vs. 1.7 +/- 0.6 micrograms/mg of total proteins). No correlation was found between plasma and intracellular Mg concentrations (r = -0.179; P = 0.15) or between Mg concentrations and glycemic control (r = -0.165; P = 0.12). Intracellular Mg levels were lower in patients with peripheral neuropathy than in those without (1.2 +/- 0.5 vs. 1.5 +/- 0.6 micrograms/mg). Similar findings were observed in patients with coronary disease (1.0 +/- 0.5 vs. 1.5 +/- 0.6 micrograms/mg). In the placebo and in the 20.7 mmol Mg groups, neither a change in plasma and intracellular levels nor an improvement in glycemic control were observed. Replacement with 41.4 mmol Mg tended to increase plasma, cellular, and urine Mg and caused a significant fall (4.1 +/- 0.8 to 3.8 +/- 0.7 mmol/l) in fructosamine (normal, 1.87-2.87 mmol/l). CONCLUSIONS: Mg depletion is common in poorly controlled patients with type 2 diabetes, especially in those with neuropathy or coronary disease. More prolonged use of Mg in doses that are higher than usual is needed to establish its routine or selective administration in patients with type 2 diabetes to improve control or prevent chronic complications.

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.

Renal artery stent placement: immediate and midterm technical and clinical results.

PURPOSE: The authors report their experience with implantation of self-expandable stents into renal arteries. PATIENTS AND METHODS: Twenty-five Wallstent endoprostheses were deployed into 18 renal arteries in 18 patients. Atheroma was the cause of the initial renal artery lesion in 15 patients (four ostial, 10 postostial, and one long occlusion). In these 15 patients, indications for stent placement were 12 immediate failures of percutaneous transluminal renal angioplasty (PTRA), two immediate PTRA complications (dissections), and one recurrent stenosis. The other renal artery lesions were three dissections (two spontaneous and one after catheterization). RESULTS: The procedure was technically successful in all patients, with residual stenosis less than 20%. However, five stents were slightly misplaced and a second stent was implanted to fully cover the lesion. Three complications occurred: one acute thrombosis 15 days after stent implantation that was successfully treated with local fibrinolysis, one asymptomatic occlusion due to early thrombosis or to delayed restenosis, and one segmental renal infarction related to extensive dissection after PTRA and not to stent placement. Following stent implantation, systolic blood pressure (P = .006) and diastolic blood pressure (P = .002) measured at 6 months decreased significantly. Angiographic follow-up was obtained in 16 patients (with intravenous technique in nine and intraarterial digital subtraction angiography in seven) at a mean of 11 months after stent placement, and ultrasonographic follow-up was obtained in the two others after 8 and 25 months, respectively. A normal patent renal artery was demonstrated in 16 patients (89%); there was one restenosis with a 75% reduction in diameter of the renal artery and the asymptomatic occlusion above mentioned. CONCLUSION: Self-expandable stent implantation is a promising technique in PTRA failures. Wallstent placement is technically feasible. Immediate results were satisfactory and the midterm restenosis rate was low in this series of patients.

[Biochemistry of schistosomiasis mansoni: involvement of siderosomes in hepatic inflammatory processes]. / Bioquímica da esquistossomose mansônica: envolvimento dos siderossomos nos processos inflamatórios hepáticos.

The inflammatory processes that develop during the advanced stages of hepatic schistosomiasis mansoni have been related in this study to: (a) accumulation of siderosomes; (b) capacity of the ferrous/ferric ions to unleash the formation of free radicals; (c) peroxidation of membrane lipids and; (d) reduction of stability of the membranes of several components of the hepatic lysosomal compartment. The lysosomes isolated from the livers of infected mice by 100 cercariae, with 80 and 100 days of infection, were respectively 2.5 and almost 4 times weaker than the control ones isolated from livers of non-infected mice. The presence of a great quantity of siderosomes has been demonstrated by transmission electronic microscopy and X-ray spectrometry microanalysis.

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 scanning 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.

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

The protective effect of zinc on gastric ulceration caused by ethanol treatment.

1. The present study was undertaken in order to demonstrate the protective action of zinc ions on the gastric mucosa of rats submitted to the ulcerogenic effect of ethanol. 2. Aqueous solutions of zinc sulfate (20 mg/kg) and/or ethanol/water (1:1, v/v) (10 ml/kg) were intragastrically administered to young adult rats. The fundus region of the stomach was submitted to scanning electron and light microscopy study. The control group received isotonic sodium sulfate by the same route. 3. The ulcerogenic action of ethanol was completely inhibited by intragastric pretreatment with zinc sulfate for 3 consecutive days. 4. The clinical use of zinc ions to protect the gastric mucosa merits consideration in the light of the present findings.

[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.

Muscle magnesium content and cardiac arrhythmias during treatment of congestive heart failure due to chronic chagasic cardiomyopathy.

Magnesium (Mg2+) plays a significant role in the electrical stability of the heart and hypomagnesemia may predispose patients to arrhythmias and digitalis toxicity. We measured the serum and skeletal muscle Mg2+ content of patients with chronic Chagasic cardiomyopathy (CCC) during treatment for congestive heart failure and compared it to 15 normal patients who were used to establish the normal values of our population. There is a high frequency of muscle Mg2+ deficiency (66%) in patients with CCC during treatment for heart failure. However, serum Mg2+ is not a sensitive index of deficiency, since hypomagnesemia occurred in only 50% of the patients whose muscle Mg2+ was low. Digitalis toxicity was observed in all muscle Mg2+-deficient patients (100%) and in 25% of patients with normal Mg2+ levels (P less than or equal to 0.05). Ventricular tachycardia (VT) occurred in 75% of muscle Mg2+-deficient patients and in none of the patients with normal magnesium levels (P less than or equal to 0.05). The frequency and severity of premature ventricular contractions (PVC) were higher in muscle Mg2+-deficient patients. We conclude that muscle Mg2+ deficiency is very common in patients with CCC being treated for congestive heart failure and that muscle Mg2+ deficiency defines a higher risk CCC group in terms of digitalis toxicity and severe ventricular arrhythmias such as ventricular tachycardia.

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.

[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.

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