Oxidative stress levels are correlated with P15 and P16 gene promoter methylation in myelodysplastic syndrome patients.

Oxidative stress and abnormal DNA methylation have been implicated in some types of cancer, namely in myelodysplastic syndromes (MDS). Since both mechanisms are observed in MDS patients, we analyzed the correlation of intracellular levels of peroxides, superoxide anion, and glutathione (GSH), as well as ratios of peroxides/GSH and superoxide/GSH, with the methylation status of P15 and P16 gene promoters in bone marrow leukocytes from MDS patients. Compared to controls, these patients had lower GSH content, higher peroxide levels, peroxides/GSH and superoxide/GSH ratios, as well as higher methylation frequency of P15 and P16 gene promoters. Moreover, patients with methylated P15 gene had higher oxidative stress levels than patients without methylation (peroxides: 460 ± 42 MIF vs 229 ± 25 MIF, p = 0.001; superoxide: 383 ± 48 MIF vs 243 ± 17 MIF, p = 0.022; peroxides/GSH: 2.50 ± 0.08 vs 1.04 ± 0.34, p < 0.001; superoxide/GSH: 1.76 ± 0.21 vs 1.31 ± 0.10, p = 0.007). Patients with methylated P16 and at least one methylated gene had higher peroxide levels as well as peroxides/GSH ratio than patients without methylation. Interestingly, oxidative stress levels allow the discrimination of patients without methylation from ones with methylated P15, methylated P16, or at least one methylated (P15 or P16) promoter. Taken together, these findings support the hypothesis that oxidative stress is correlated with P15 and P16 hypermethylation.

Acute kidney injury in an internal medicine ward in a Portuguese quaternary hospital.

BACKGROUND: The term acute kidney injury (AKI) was proposed to reflect the wide spectrum of traditional acute renal failure. RIFLE classification stratifies AKI into three classes of severity and two classes of outcome. AKIN classification proposes an improvement regarding RIFLE in the stratification of AKI, while recently published KDIGO guidelines comprise characteristics of both RIFLE and AKIN. There are no published studies on the utility and measure of agreement between classifications in patients admitted to internal medicine wards. METHODS: Prospective study undertaken in two internal medicine wards in a Portuguese hospital. Patients admitted for a minimum of 72 h, with a diagnosis of AKI or acute-on-chronic kidney disease at admission or during hospitalisation, were included. RIFLE, AKIN and KDIGO criteria were applied for identification of AKI and stratification into risk groups. RESULTS: Sixty-nine patients were included, with a mean age of 79.7±10.0 years and mean GFR of 21.7±8.8 mL/min/1.73 m2. Hypovolaemia due to dehydration was the main cause of AKI (53.6%) and, thereby, RIFLE classification identified a higher number of patients as having AKI, compared to AKIN (94.2% vs. 84.1%). Most patients (69.6%) recovered to their baseline renal function, however fifteen patients (21.7%) died, 53.3% presenting more severe kidney disease. CONCLUSIONS: Our results demonstrate good concordance and correlation between RIFLE, AKIN and KDIGO criteria for the diagnosis of AKI (p<0.001 at initial and final assessment). The authors support the need for further improvement of the classification, ultimately through the use of new biomarkers capable of earlier identification of patients at risk.

Glycogen Storage Disease type 1a - a secondary cause for hyperlipidemia: report of five cases.

BACKGROUND AND AIMS: Glycogen storage disease type Ia (GSD Ia) is a rare metabolic disorder, caused by deficient activity of glucose-6-phosphatase-α. It produces fasting induced hypoglycemia and hepatomegaly, usually manifested in the first semester of life. Besides, it is also associated with growth delay, anemia, platelet dysfunction, osteopenia and sometimes osteoporosis. Hyperlipidemia and hyperuricemia are almost always present and hepatocellular adenomas and renal dysfunction frequent late complications. METHODS: The authors present a report of five adult patients with GSD Ia followed in internal medicine appointments and subspecialties. RESULTS: Four out of five patients were diagnosed in the first 6 months of life, while the other one was diagnosed in adult life after the discovery of hepatocellular adenomas. In two cases genetic tests were performed, being identified the missense mutation R83C in one, and the mutation IVS4-3C > G in the intron 4 of glucose-6-phosphatase gene, not previously described, in the other. Growth retardation was present in 3 patients, and all of them had anemia, increased bleeding tendency and hepatocellular adenomas; osteopenia/osteoporosis was present in three cases. All but one patient had marked hyperlipidemia and hyperuricemia, with evidence of endothelial dysfunction in one case and of brain damage with refractory epilepsy in another case. Proteinuria was present in two cases and end-stage renal disease in another case. There was a great variability in the dietary measures; in one case, liver transplantation was performed, with correction of the metabolic derangements. CONCLUSIONS: Hyperlipidemia is almost always present and only partially responds to dietary and drug therapy; liver transplantation is the only definitive solution. Although its association with premature atherosclerosis is rare, there have been reports of endothelial dysfunction, raising the possibility for increased cardiovascular risk in this group of patients. Being a rare disease, no single metabolic center has experience with large numbers of patients and the recommendations are based on clinical experience more than large scale studies.