Glutamine dipeptide supplementation improves clinical responses in patients with diabetic foot syndrome

ABSTRACT The effect of glutamine dipeptide (GDP) supplementation in patients with diabetic foot syndrome was evaluated. A total of 22 patients took part in the study. GDP was supplied in 10 g sachets, and was dissolved in water immediately before use, with ingestion once a day, after lunch or after dinner (20 g/day) over a period of 30 days. Quantification of foot insensitive areas, oxidative stress, blood cytokines, and biochemical, hematological and toxicological parameters was performed before and after GDP supplementation. We observed an increase in blood levels of interferon-&#945; (P=0.023), interferon-&#947; (P=0.038), interleukin-4 (P=0.003), interleukin-6 (P=0.0025), interleukin-7 (P=0.028), interleukin-12 p40 (P=0.017), interleukin-13 (P=0.001), leukocytes (P=0.037), eosinophils (P=0.049), and typical lymphocytes (P<0.001) due to GDP administration. In addition, we observed a reduced number (P=0.048) of insensitive areas on the foot, and reduction (P=0.047) of fasting hyperglycemia. Patients also showed increased blood high density lipoprotein (P<0.01) and protein thiol groups (P=0.004). These favorable results were associated with the absence of renal and hepatic toxicity. These results are of clinical relevance, since supplementation with GDP over 30 days improved clinical responses in patients with diabetic foot syndrome

Linseed oil attenuates fatty liver disease in mice fed a high-carbohydrate diet

The impact of linseed oil as a lipid source on liver disease induced by a high-carbohydrate diet (HCD) was evaluated. Adult male Swiss mice received an HCD containing carbohydrates (72.1%), proteins (14.2%), and lipids (4.0%). The Control HCD group (HCD-C) received an HCD containing lard (3.6%) and soybean oil (0.4%) as lipid sources. The L10 and L100 groups received an HCD with 10 and 100% linseed oil as lipid sources, respectively. A group of mice were euthanized before receiving the diets (day 0) and the remaining groups after 56 days of receiving the diets (HCD-C, L10, and L-100 groups). Morphological and histopathological analyses, as well as collagen deposition were evaluated. Perivenous hepatocytes (PVH) of the HCD-C group were larger (P<0.05) than periportal hepatocytes (PPH) in the median lobe (ML) and left lobe (LL). There was a greater (P<0.05) deposition of type I collagen in PPH (vs PVH) and in the ML (vs LL). The ML exhibited a higher proportion of apoptotic bodies, inflammatory infiltrate, and hepatocellular ballooning. All these alterations (hepatocyte size, deposition of type I collagen, apoptotic bodies, inflammatory infiltrate, and hepatocellular ballooning) induced by HCD were prevented or attenuated in L10 and L100 groups. Another indicator of the beneficial effects of linseed oil was the lower (P<0.05) number of binucleated hepatocytes (HCD-C vs L10 or L100 group). In general, the L100 group had greater effects than the L10 group. In conclusion, linseed oil impedes or reduces the liver injury progression induced by an HCD

Assessment of NADPH-diaphorase stained myenteric neurons of the jejunum of diabetic rats supplemented with ascorbic acid Avaliação dos neurônios NADPH-diaforase reativos do jejuno de raots diabéticos suplementados com ácido ascórbico

The relation between hyperglycemia and diabetic neuropathy has already been demonstrated in some studies. Among the theories proposed for its etiology the oxidative stress stands out. The performance of nitric oxide as a link between the metabolic and vascular neuropathogenic factors that triggers the diabetic neuropathy has already been put forward. This study aimed to assess the quantification and measurements of the cell body profile area (CBPA) of NADPH-diaphorase reactive (NADPH-dp) myenteric neurons of the jejunum of diabetic rats (induced by streptozotocin) supplemented with Ascorbic Acid (AA). These changes in the myenteric neurons seem to be related to the gastrointestinal disturbances observed in diabetes mellitus (DM). Twenty male Wistar rats (Rattus norvegicus) were distributed in 4 groups (n=5): controls (C), control supplemented (CS), diabetic (D), and diabetic suplemented (DS). DM was induced by estreptozotocin (50mg/kg body wt). One week after the induction and confirmation of the DM (glycemia exam), animals of the groups CS and DS received 50mg of AA three times a week by gavage. After 90 days of experiment, the animals were anesthetized with lethal thiopental dose (40mg/kg) and the collected jejunum processed for the histochemistry NADPH-diaphorase technique. Whole-mount preparations were obtained for quantitative and morphometric analysis of the myenteric neurons. A quantity of jejunum neurons in the Group D (96&plusmn;7.5) was not different (P>0.05) from Group DS (116&plusmn;8.08), C (92&plusmn;9.7), and CS (81&plusmn;5.4), but in Group DS the quantity was higher (P<0.05) than in Group C and CS. The CBPA of neurons from Group D (189.50&plusmn;2.68µm²) and DS (195.92&plusmn;3.75µm²) were lower (P<0.05) than from Group C (225.13&plusmn;4.37µm²) and CS (210.23&plusmn;3.15µm²). The streptozotocin-induced DM did not change the jejunum-ileum area, the jejunum myenteric plexus space organization and the density of NADPH-dp neurons. The 50g AA-supplementation, three times a week, during 90 days, did not decrease hyperglycemia; however, it had a neuroprotective effect on the myenteric neurons, minimizing the increase on the CBPA of NADPH-dp neurons and increasing the amount of NADPD-dp neurons.<br>A relação entre hiperglicemia e neuropatia diabética foi demonstrada em várias pesquisas. Entre as teorias propostas para sua etiologia destaca-se o estresse oxidativo. O papel do óxido nítrico como elo entre os fatores neuropatogênicos metabólico e vascular que ativam a neuropatia diabética tem sido ressaltado. Este estudo objetivou avaliar a quantificação e a morfometria da área do perfil do corpo celular (CBPA) de neurônios mioentéricos NADPH-diaforase reativos (NADPH-dp) do jejuno de ratos diabéticos e suplementados com Ácido Ascórbico (AA), uma vez que alterações nos neurônios mioentéricos parecem estar relacionadas aos distúrbios gastrointestinais observados no diabetes mellitus (DM). Vinte ratos machos da linhagem Wistar (Rattus norvergicus) foram distribuídos em 4 grupos (n=5): controle (C), controle suplementado (CS), diabético (D) e diabético suplementado (DS). O DM foi induzido através de injeção de estreptozootocina (50mg/kg de peso corporal). Uma semana depois da indução e confirmação do DM (glicemia), animais dos grupos CS e DS receberam, via gavagem, 50mg de AA três vezes por semana. Após 90 dias de período experimental, os animais foram anestesiados com dose letal de thiopental intravenosa (40mg/kg) e o jejuno foi retirado e processado para a técnica histoquímica da NADPH-diaforase. Preparados de membrana foram obtidos para análises quantitativa e morfométrica dos neurônios mioentéricos. A quantidade de neurônios do jejuno do Grupo D (96&plusmn;7,5) não diferiu (P>0,05) dos Grupos DS (116&plusmn;8,08), C (92&plusmn;9,7) e CS (81&plusmn;5,4), mas no Grupo DS o número de neurônios foi superior (P<0,05) aos Grupos C e CS. A CBPA de neurônios do Grupo D (189,50&plusmn;2,68µm²) e DS (195,92&plusmn;3,75µm²) foi menor (P<0,05) do que a dos Grupos C (225,13&plusmn;4,37µm²) e CS (210,23&plusmn;3,15µm²). O DM induzido por estreptozootocina não alterou a área do jejuno-íleo, a organização espacial do plexo mioentérico e a densidade de neurônios de NADPH-dp do jejuno. A suplementação de 50mg de AA, três vezes por semana, durante 90 dias, não diminuiu a hiperglicemia, porém teve efeito neuroprotetor nos neurônios mioentéricos, minimizando o aumento na CBPA dos neurônios NADPH-dp e aumentando a quantidade de neurônios reativos a NADPD-diaforase

Oxidative stress action in cellular aging

Various theories try to explain the biological aging by changing the functions and structure of organic systems and cells. During lifetime, free radicals in the oxidative stress lead to lipid peroxidation of cellular membranes, homeostasis imbalance, chemical residues formation, gene mutations in DNA, dysfunction of certain organelles, and the arise of diseases due to cell death and/or injury. This review describes the action of oxidative stress in the cells aging process, emphasizing the factors such as cellular oxidative damage, its consequences and the main protective measures taken to prevent or delay this process. Tests with antioxidants: vitamins A, E and C, flavonoids, carotenoids and minerals, the practice of caloric restriction and physical exercise, seeking the beneficial effects on human health, increasing longevity, reducing the level of oxidative stress, slowing the cellular senescence and origin of certain diseases, are discussed.<br>Diferentes teorias tentam explicar o envelhecimento biológico através da alteração das funções e estrutura dos sistemas orgânicos e células. Ao longo da vida, os radicais livres presentes no estresse oxidativo conduzem à peroxidação dos lipídios das membranas celulares, desequilíbrio da homeostase, formação de resíduos químicos, mutações gênicas no DNA, disfunção de certas organelas, bem como ao surgimento de doenças devido à lesão e/ou morte celular. Nesta revisão descreve-se a ação do estresse oxidativo no processo de envelhecimento das células, enfatizando fatores como os danos oxidativos celulares, suas conseqüências e as principais medidas protetoras adotadas para se prevenir ou retardar este processo. Testes com antioxidantes: vitaminas A, E e C, flavonóides, carotenóides e minerais; a prática de restrição calórica e exercícios físicos, que buscam efeitos benéficos sobre a saúde humana, aumentando a longevidade, reduzindo o nível de estresse oxidativo, retardando a senescência celular e a origem de certas doenças, são discutidos