Roles of phosphatidylinositol 3-kinase-Akt and NADPH oxidase in adenosine 5'-triphosphate-sensitive K+ channel function impaired by high glucose in the human artery

The present study was designed to examine roles of the phosphatidylinositol 3-kinase-Akt pathway and reduced nicotinamide-adenine dinucleotide phosphate oxidases in the reduced ATP-sensitive K(+) channel function via superoxide produced by high glucose in the human artery. We evaluated the activity of the phosphatidylinositol 3-kinase-Akt pathway, as well as reduced nicotinamide-adenine dinucleotide phosphate oxidases, the intracellular levels of superoxide and ATP-sensitive K(+) channel function in the human omental artery without endothelium. Levels of the p85-alpha subunit and reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits, including p47phox, p22phox, and Rac-1, increased in the membrane fraction from arteries treated with D-glucose (20 mmol/L) accompanied by increased intracellular superoxide production. High glucose simultaneously augmented Akt phosphorylation at Ser 473, as well as Thr 308 in the human vascular smooth muscle cells. A phosphatidylinositol 3-kinase inhibitor LY294002, as well as tiron and apocynin, restored vasorelaxation and hyperpolarization in response to an ATP-sensitive K(+) channel opener levcromakalim. Therefore, it can be concluded that the activation of the phosphatidylinositol 3-kinase-Akt pathway, in combination with the translocation of p47phox, p22phox, and Rac-1, contributes to the superoxide production induced by high glucose, resulting in the impairment of ATP-sensitive K(+) channel function in the human visceral artery.     

Autoimmune pancreatitis successfully treated with ursodeoxycholic acid

A 51-year-old woman with autoimmune pancreatitis is reported in whom treatment with ursodeoxycholic acid (UDCA) was beneficial. Complaining of epigastric discomfort, she presented with liver dysfunction of the cholestatic type, and diabetes mellitus. Pancreatic imaging revealed a diffuse swelling of the body, an irregular narrowing of the main pancreatic duct, and a terminal stricture of the common bile duct. Histologically, the biopsied pancreas was replaced by fibrous tissue with a small amount of mononuclear cell infiltration. She had anti-carbonic anhydrase-II antibody and anti-lactoferrin antibody. After treatment with UDCA, her liver dysfunction and diabetes mellitus improved and the pancreas size was reduced. Steroid therapy is usually indicated for this disorder, but UDCA may be given as an alternative choice.     

Chronic kidney disease categories and renal–cardiovascular outcomes in type 2 diabetes without prevalent cardiovascular disease: a prospective cohort study (JDDM25)

Aims/hypothesis

In type 2 diabetic patients at low risk for cardiovascular disease (CVD), the relationship between the clinical course of nephropathy by stage of chronic kidney disease (CKD) and onset of CVD remains unclear. Clarification of this relationship is important for clinical decision-making for both low- and high-risk diabetic patients.

Methods

This 4?year prospective study enrolled 2,954 type 2 diabetic patients with no prevalent CVD, and serum creatinine <176.8?μmol/l. The risk for CVD onset (non-fatal and fatal CVD and stroke, and peripheral arterial disease) was assessed according to CKD stage categorised by urinary albumin-to-creatinine ratio (ACR; mg/mmol) and estimated GFR (eGFR; ml?min^?1 1.73?m^?2). Association of progression from ‘no CKD’ stage (ACR <3.5?mg/mmol and eGFR ≥90?ml?min^?1 1.73?m^?2) with risk for CVD onset was also evaluated.

Results

During follow-up (median 3.8?years), 89 CVD events occurred. Compared with patients with ‘no CKD’ as reference, those with ACR?≥?35.0?mg/mmol with co-existing eGFR 60–89?ml?min^?1 1.73?m^?2 or <60?ml?min^?1 1.73?m^?2 showed increased risk for CVD onset, whereas those with eGFR ≥90?ml?min^?1 1.73?m^?2 did not. Those with ACR <3.5?mg/mmol and eGFR <60?ml?min^?1 1.73?m^?2 did not show any increased risk. Among patients with ‘no CKD’ stage at baseline, those who progressed to ACR ≥3.5?mg/mmol during follow-up showed an increased risk compared with those who did not, whereas those who progressed to eGFR <90?ml?min^?1 1.73?m^?2 did not have increased risk.

Conclusions/interpretation

The risk for CVD was associated with progression of albuminuria stage rather than eGFR stage in type 2 diabetic patients at relatively low risk for CVD.     

Fulminant candidemia diagnosed by prompt detection of pseudohyphae in a peripheral blood smear

A 77-year-old man treated with prednisolone for pemphigus developed severe sepsis by Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Several antibiotics were administered. A peripheral blood smear showed growth of a large number of yeast extending pseudohyphae which could be seen both inside and outside of leucocytes. Antifungal agents were added immediately; however, he did not recover. Several days later, blood culture showed Candida albicans septicemia. The autopsy revealed microabscesses in the lung, heart, liver and kidney. A large amount of neutrophil invasion and yeast with pseudohyphae were also detected.     

Distinct pre-attentive responses to non-scale notes: An auditory mismatch negativity (MMN) study

Objective: The aim of the present study was to examine patterns of neural activity in response to variations in scale notes and alterations from a scale note to a non-scale note.Methods: Event-related potentials (ERPs) were recorded in response to scale and non-scale violin notes using an odd-ball mismatch negativity (MMN) paradigm. Standard stimuli were set to the scale note A4 (440 Hz). Deviant stimuli included two scale notes (scale-B, B4 = 494 Hz; scale-C, C5 = 523 Hz) and a non-scale note halfway between them (non-scale, B4 + 42¢ = 506 Hz).Results: MMN amplitude elicited by the non-scale was significantly larger than that elicited by the scale-B and scale-C, which did not differ significantly from one another.Conclusion: The current results suggest that the human brain may possess pre-attentive mechanisms for extracting relational aspects among sounds of the musical scale.Significance: The results indicate that non-scale notes may be processed in a different way even in the pre-attentive stage than scale notes.