Diabetic ketoacidosis in patients with soft-tissue necrotizing infections

Necrotizing soft tissue infection is an uncommon and severe infection of the skin, subcutaneous tissue and superficial fascia which is usually accompanied by severe systemic toxicity. These infections occur more frequently in diabetics and are associated with higher morbidity and mortality rate. The prognosis of necrotizing fasciitis is known to be dependent on early recognition and treatment. Therefore, clinical awareness is important to avoid fatal outcome in patients with diabetes mellffus. We present three patients with undiagnosed type 2 diabetes in whom hyperglycaemia may have facilffated me development of necrotizing tissue infection, which in tum may have precipitated diabetic ketoacidosis in patients who rarely develop this metabolic complication.     

Oxidative stress in hemodialysis patients: is NADPH oxidase complex the culprit?

Oxidative stress results from an imbalance between oxidant production, including reactive oxygen species (ROS), reactive nitrogen species (RNS), chlorinated compounds, and antioxidant defense mechanisms. Most reports prove that oxidative stress is present in ESRD patients. Several studies tend to accreditate the hypothesis by which oxidative stress is a strong co-factor for the development of complications related to long-term HD such as atherosclerosis, amyloidosis, malnutrition, anemia, and infection. In order to evaluate the rationale for curative action against oxidative damage in chronic renal failure patients, we reviewed the putative factors involved in this process. Antioxidant systems are severely impaired in uremic patients and gradually altered with the degree of renal failure. Moreover, the inflammatory state caused by the hemoincompatibility of the dialysis system plays a critical role in the activation of NADPH oxidase, aggravating the pro-oxidant status of uremic patients. Prevention of ROS overproduction by improvement of dialysis biocompatibility, an important component of adequate dialysis, might be completed by antioxidant supplementation.     

Renal injuries: diagnosis and current management

Abdominal trauma is relatively frequent and around 5% of the cases correspond to renal trauma. At present, a large percentage of cases can be managed conservatively. Generalised use of CT and cumulative experience have defined the cases that can be treated with good prospects. The currently accepted indications for imaging techniques and the most frequent ratings used are described. Similarly, the indications for surgical renal examination are listed and the principles for renal reconstruction described in the most recent publications of the most experienced medical centres.     

Endogenous histamine in the medial septum-diagonal band complex increases the release of acetylcholine from the hippocampus: a dual-probe microdialysis study in the freely moving rat

The effects of histaminergic ligands on both ACh spontaneous release from the hippocampus and the expression of c-fos in the medial septum-diagonal band (MSA-DB) of freely moving rats were investigated. Because the majority of cholinergic innervation to the hippocampus is provided by MSA-DB neurons, we used the dual-probe microdialysis technique to apply drugs to the MSA-DB and record the induced effects in the projection area. Perfusion of MSA-DB with high-KCl medium strongly stimulated hippocampal ACh release which, conversely, was significantly reduced by intra-MSA-DB administration of tetrodotoxin. Histamine or the H2 receptor agonist dimaprit, applied directly to the hippocampus, failed to alter ACh release. Conversely, perfusion of MSA-DB with these two compounds increased ACh release from the hippocampus. Also, thioperamide and ciproxifan, two H3 receptor antagonists, administered into MSA-DB, increased the release of hippocampal ACh, whereas R-alpha-methylhistamine, an H3 receptor agonist, produced the opposite effect. The blockade of MSA-DB H2 receptors, caused by local perfusion with the H2 receptor antagonist cimetidine, moderated the spontaneous release of hippocampal ACh and antagonized the facilitation produced by H3 receptor antagonists. Triprolidine, an H1 receptor antagonist, was without effect. Moreover, cells expressing c-fos immunoreactivity were significantly more numerous in ciproxifan- or thioperamide-treated rats than in controls, although no colocalization of anti-c-fos and anti-ChAT immunoreactivity was observed. These results indicate a role for endogenous histamine in modulating the cholinergic tone in the hippocampus.     

Nutritional and lifestyle determinants of DNA oxidative damage: a study in a Mediterranean population

In order to evaluate dietary and lifestyle determinants of oxidative DNA damage we used a modification of the 'comet assay' (single cell alkaline gel electrophoresis), with the fpg enzyme (formamidopyrimidine DNA glycosilase), to measure the basal level of DNA oxidation in peripheral lymphocytes donated by 71 healthy adults living in Florence, Italy. Detailed information about dietary and lifestyle habits was collected by two validated and standardized questionnaires; we also measured plasma concentrations of selected micro-nutrients (six carotenoids, retinol, alpha- and gamma-tocopherol). DNA damage, measured as percent DNA migrated in the comet tail (mean 4.67%, interquartile range 2.36-6.62%), was not associated with gender, age, weight, body mass index, physical activity or smoking history. A positive correlation with height and period of blood sampling emerged: DNA damage tended to be higher among taller subjects (P = 0.02) and in samples obtained in summer months (P = 0.02). Multivariate analyses showed a positive association with coffee (P = 0.01) and tomato consumption (P = 0.05). Instead, the consumption of cruciferous vegetables tended to be negatively associated with oxidative damage (P = 0.09). Furthermore, a positive non-significant association between the consumption of total vegetables and fresh fruit and DNA damage emerged (P = 0.08 and P = 0.10, respectively). The estimated intake of simple sugars showed a strong positive association with oxidative DNA damage (P = 0.01), while vitamin E showed a borderline positive association (P = 0.06). The plasma levels of several micro-nutrients did not appear to influence DNA damage. Our results, although based on a relatively small group of subjects, indicate that individual dietary and lifestyle habits only modestly affect the levels of lymphocyte DNA oxidation and suggest that specific dietary patterns, rich in fresh fruit and vegetables, are not clearly related to decreased oxidative damage in peripheral lymphocytes in a Mediterranean population.     

Cooperative transformation of 32D cells by the combined expression of IRS-1 and V-Ha-Ras

32D cells expressing v-Ha-Ras fail to show a transformed phenotype. Since Ras requires an active IGF-1R for transformation of fibroblasts, we asked whether expression of IRS-1 or Shc (two of the major substrates of the IGF-1R) could co-operate with oncogenic Ras in transforming 32D cells. We find that IRS-1, but not Shc, in combination with v-Ha-Ras generates a fully transformed phenotype in 32D cells. 32D cells expressing both IRS-1 and v-Ha-Ras (32D/IRS1/Ras) survive and proliferate in the absence of IL-3, do not undergo granulocytic differentiation in the presence of G-CSF and form tumors in nu/nu and syngeneic mice. In contrast, 32D cells expressing singly IRS-1 or v-Ha-Ras exhibit only a block in differentiation capacity. Over-expression of Shc proteins, by itself, promotes differentiation of 32D cells. Concomitant expression of IRS-1 and v-Ha-Ras synergistically phosphorylates ERK-1 and ERK-2 whereas a MEK inhibitor rapidly induces death of 32D/IRS1/Ras transformed cells. Furthermore, transformed 32D/IRS1/Ras cells display high levels of PI3-K activation and undergo rapid apoptosis when exposed to PI3-K inhibitors. The data indicate that: (1) a fully transformed phenotype in 32D cells is generated when a block in differentiation (v-Ha-Ras) is coupled with another differentiation block (IRS-1); (2) PI3-K and MAPK activity are required for the survival of transformed cells; (3) the signals generated by IRS-1 and oncogenic Ras converge on ERK and PI3-K resulting in high levels of activation.