Effect of the carbohydrate counting method on glycemic control in patients with type 1 diabetes

<p>Abstract</p> <p>Background</p> <p>The importance of achieving and maintaining an appropriate metabolic control in patients with type 1 diabetes mellitus (DM1) has been established in many studies aiming to prevent the development of chronic complications. The carbohydrate counting method can be recommended as an additional tool in the nutritional treatment of diabetes, allowing patients with DM1 to have more flexible food choices. This study aimed to evaluate the influence of nutrition intervention and the use of multiple short-acting insulin according to the carbohydrate counting method on clinical and metabolic control in patients with DM1.</p> <p>Methods</p> <p>Our sample consisted of 51 patients with DM1, 32 females, aged 25.3 ± 1.55 years. A protocol of nutritional status evaluation was applied and laboratory analysis was performed at baseline and after a three-month intervention. After the analysis of the food records, a balanced diet was prescribed using the carbohydrate counting method, and short-acting insulin was prescribed based on the total amount of carbohydrate per meal (1 unit per 15 g of carbohydrate).</p> <p>Results</p> <p>A significant decrease in A1c levels was observed from baseline to the three-month evaluation after the intervention (10.40 ± 0.33% and 9.52 ± 0.32%, respectively, p = 0.000). It was observed an increase in daily insulin dose after the intervention (0.99 ± 0.65 IU/Kg and 1.05 ± 0.05 IU/Kg, respectively, p = 0.003). No significant differences were found regarding anthropometric evaluation (BMI, waist, hip or abdominal circumferences and waist to hip ratio) after the intervention period.</p> <p>Conclusions</p> <p>The use of short-acting insulin based on the carbohydrate counting method after a short period of time resulted in a significant improvement of the glycemic control in patients with DM1 with no changes in body weight despite increases in the total daily insulin doses.</p

Nephroprotective Effect of Echinodorus macrophyllus Micheli on Gentamicin-Induced Nephrotoxicity in Rats

Background/Aims: Leaves of Echinodorus macrophyllus (EM), from the Alismataceae family, have been used in Brazilian folk medicine for their anti-inflammatory and diuretic properties. In this work, the diuretic and nephroprotective activities of crude extracts of EM were evaluated. Methods: Normal Wistar rats were given 0.9% NaCl containing either EM (10–300 mg/kg), furosemide (13 mg/kg) or arginine vasopressin (0.2 mg/kg). Thereafter, the rats were individually housed in metabolic cages, and urine volume was measured every 30 min for a total of 3 h. Acute kidney injury was induced by gentamicin (GM, 80 mg·kg–1·day–1, b.i.d., 5 days). Along with GM, 0.9% NaCl (control) or EM (30 mg/kg) was given to the rats by gavage. Results: EM produced a dose-dependent reduction in urine elimination. EM was effective in reversing all GM-induced alterations such as polyuria and glomerular filtration rate reduction. The GM-induced morphological alterations were not observed when EM was given concomitantly with GM. Conclusion: This study provides evidence that EM possesses nephroprotective effect which indicates that EM may have therapeutic applications in GM-induced acute kidney injury

5-Lypoxygenase products are involved in renal tubulointerstitial injury induced by albumin overload in proximal tubules in mice.

The role of albumin overload in proximal tubules (PT) in the development of tubulointerstitial injury and, consequently, in the progression of renal disease has become more relevant in recent years. Despite the importance of leukotrienes (LTs) in renal disease, little is known about their role in tubulointerstitial injury. The aim of the present work was to investigate the possible role of LTs on tubulointerstitial injury induced by albumin overload. An animal model of tubulointerstitial injury challenged by bovine serum albumin was developed in SV129 mice (wild-type) and 5-lipoxygenase-deficient mice (5-LO(-/-)). The changes in glomerular morphology and nestin expression observed in wild-type mice subjected to kidney insult were also observed in 5-LO(-/-) mice. The levels of urinary protein observed in the 5-LO(-/-) mice subjected or not to kidney insult were lower than those observed in respective wild-type mice. Furthermore, the increase in lactate dehydrogenase activity, a marker of tubule damage, observed in wild-type mice subjected to kidney insult did not occur in 5-LO(-/-) mice. LTB4 and LTD4, 5-LO products, decreased the uptake of albumin in LLC-PK1 cells, a well-characterized porcine PT cell line. This effect correlated with activation of protein kinase C and inhibition of protein kinase B. The level of proinflammatory cytokines, tumor necrosis factor-α and interleukin (IL)-6, increased in mice subjected to kidney insult but this effect was not modified in 5-LO(-/-) mice. However, 5-LO(-/-) mice subjected to kidney insult presented lower macrophage infiltration and higher levels of IL-10 than wild-type mice. Our results reveal that LTs have an important role in tubulointerstitial disease induced by albumin overload

Effect of 5-LO products on the total cortical TGF-β expression increased during kidney injury.

<p>Mice were treated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107549#s2" target="_blank">Materials and Methods</a> section (<i>n</i> = 6 per group). (A) Representative immunohistochemical staining for total TGF-β in cortical areas of WT mice and 5-LO-deficient mice treated with saline or BSA (bars  = 40 µm). Arrows indicates markedly positive staining. (B) Quantitative analyses were expressed as means ± SE. Statistically significant in relation to *WT + SAL (<i>p</i><0.05).</p

Nestin expression is increased in subcapsular and corticomedullary glomeruli of mice subjected to kidney injury.

<p>Mice were treated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107549#pone-0107549-g001" target="_blank">Fig. 1</a> (<i>n</i> = 6 per group). (A) Representative immunohistochemical staining for nestin in the subcapsular glomerulus and (B) corticomedullary glomerulus of WT and 5-LO-deficient mice treated with saline or BSA (bars  = 20 µm). Quantitative analyses (C,D) were expressed as means ± SE. Statistically significant in relation to *WT+SAL (<i>p</i><0.05), #WT+BSA (<i>p</i><0.05), ⁺5-LO^–/–+SAL (<i>p</i><0.05).</p

Proteinuria and urinary tubular enzymes are attenuated in 5-LO-deficient mice subjected to kidney injury.

<p>The animals were given i.p. injections of saline (SAL; 0.9%) or 10 g/kg BSA for 7 days as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107549#s2" target="_blank">Materials and Methods</a> section. (A) The proteinuria was measured on days 0, 2, 4, and 6. (B) Urine samples were resolved on SDS-PAGE gels and protein analysis was based on the intensity of Coomassie Blue staining. (C) LDH was measured in urine samples as an index of cell damage. WT+SAL (<i>n</i> = 8), WT+BSA (<i>n</i> = 8), 5-LO^–/–+SAL (<i>n</i> = 8), 5-LO^–/–+BSA (<i>n</i> = 8). The results are expressed as means ± SE. Statistically significant in relation to *WT+SAL (<i>p</i><0.05), #WT+BSA (<i>p</i><0.05), ⁺5-LO^–/–+SAL (<i>p</i><0.05), and ^&5-LO^–/–+BSA (<i>p</i><0.05).</p

Basic features of BSA-induced tubulointerstitial injury model.

<p>(A) Representative Periodic-acid Schiff staining in renal cortex of WT+SAL and WT+BSA groups. Arrows, indicates epithelial cell vacuolization; *, indicates tubular shedding; &, indicates disorganization of brush-border. (B) Quantification of tubulointerstitial space area. Results were expressed as means ± SE. Statistically significant in relation to *WT + SAL (<i>p</i><0.05).</p

Macrophage infiltration is attenuated in 5-LO-deficient mice subjected to kidney injury.

<p>Mice were treated as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107549#pone-0107549-g001" target="_blank">Fig. 1</a> (<i>n</i> = 6 per group). Representative immunohistochemical staining for F4/80 in (A) cortical and (B) medullary areas of WT mice and 5-LO-deficient mice treated with saline or BSA (bars  = 40 µm). Quantitative analyses (C,D) were expressed as means ± SE. Statistically significant in relation to *WT+SAL (<i>p</i><0.05), #WT+BSA (<i>p</i><0.05), ⁺5-LO^–/–+SAL (<i>p</i><0.05).</p

LTs modulate albumin uptake and kinase activity.

<p>LLC-PK1 cells were grown on 6-well plates, kept overnight in medium depleted of serum in the presence of 10⁻⁷ M LTD₄ or 10⁻⁷ M LTB₄. After treatment, both (A) albumin uptake and (B) PKC activity were measured as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107549#s2" target="_blank">Materials and Methods</a> section. The cells were preincubated with 10⁻⁸ M calphostin C (Calph C) when indicated. (C) The effect of LTs on PKB activity measured by Ser473 phosphorylation. PKC (D) and PKB (E) activities were measured in WT and 5-LO-deficient mice treated with saline or BSA. The results are expressed as means ± SE. Statistically significant in relation to *control or WT+SAL (<i>p</i><0.05), #WT+BSA (<i>p</i><0.05).</p