Association of serum podocalyxin levels with peripheral arterial disease in patients with type 2 diabetes.

OBJECTIVE: Renal podocalyxin is a marker for kidney diseases. Previous studies have shown the expression of serum podocalyxin (s-Podxl) in the endothelial cells of blood vessels. We aimed to investigate the association between s-podxl levels and peripheral arterial disease (PAD) in subjects with type 2 diabetes (T2DM). SUBJECTS AND METHODS: Serum Podxl levels were analyzed in 69 subjects with normal glucose tolerance and PAD (NGT-PAD), 120 subjects with T2DM and PAD (D-PAD) and 36 subjects with T2DM without PAD (D-NPAD). RESULTS: In D-PAD Patients, s-Podxl was significantly higher (17.67 ±â€¯20.7 ng/mL) than in D-NPAD subjects (9.97 ±â€¯5.34 ng/mL; P < 0.001). Subjects with NGT-PAD had significantly higher s-Podxl levels (15.34 ±â€¯18.21 ng/mL), than D-NPAD patients (P < 0.001). Subjects with D-PAD and medial calcific sclerosis (MCS) had significantly higher s-Podxl levels compared to the same group but without MCS (P < 0.02). In D-PAD patients, MCS (P = 0.003) and glycosylated hemoglobin (P < 0.001) were the two variables that had the strongest prediction for s-Podxl as revealed by regression analysis. Multivariate regression showed that an increase of one standard deviation in s-Podxl was associated with an odds ratio of 3.4 (95% confidence interval = 2.2-4.6, P < 0.001) for the prevalence of PAD. CONCLUSIONS: This is the first study showing an association between s-Podxl and PAD in patients with T2DM. S-Podxl was higher in D-PAD patients than in D-NPAD subjects. In NGT-PAD patients, s-Podxl was also higher than in D-NPAD patients. In patients with D-PAD, s-Podxl was positively associated with MCS.

Association of low serum Meteorin like (Metrnl) concentrations with worsening of glucose tolerance, impaired endothelial function and atherosclerosis.

OBJECTIVE: Meteorin-like (Metrnl) is a novel secreted protein that has a beneficial effect on glucose homeostasis with anti-inflammatory properties. Our goal is to determine whether low serum Metrnl levels are associated with worsening of glucose tolerance, impaired endothelial function, and atherosclerosis. METHODS: This study included 260 adults, 89 of whom had normal oral glucose tolerance (nOGT), 77 with glucose tolerance impairment (GTI) and 94 with type 2 diabetes (T2DM). Insulin resistance was assessed by evaluating the homeostasis model assessment of insulin resistance (HOMA-IR). Serum Metrnl level, proinflammatory, biochemical, endothelial and atherosclerosis parameters were measured. RESULTS: Serum Metrnl levels decreased significantly in patients with T2DM versus subjects with nOGT (P < 0.001). Metrnl levels were negatively correlated with fasting blood glucose, 2-h postload glucose (2 h-PLG), fasting insulin, HOMA-IR, HbA1c, high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), Carotid intima media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. High serum Metrnl level was significantly correlated with reduced risk of T2DM as revealed by multivariate logistic regression analysis after control of potential risk factors for diabetes. Furthermore, the association remains significant after further adjustment for IL-6, TNF-α, hs-CRP, CIMT, baPWV, ICAM-1, VCAM-1 and E-selectin. CONCLUSIONS: Low Serum Metrnl may be associated with worsening of glucose tolerance, impaired endothelial function and atherosclerosis. It may also be considered a possible surrogate marker of endothelial dysfunction, and atherosclerosis and an independent risk factor of T2DM.

Recurrent variceal haemorrhage managed with splenic vein stenting.

INTRODUCTION: Extrahepatic Portal Hypertension (EPH) is defined as extrahepatic hypertension of the portal venous system in the absence of liver cirrhosis. Isolated splenic vein stenosis/occlusion as one of the causes of extrahepatic portal hypertension is uncommon, comprising less than 5 % of all cases of portal hypertension. However, it is an increasingly recognised complication of both acute and chronic pancreatitis, and with the advent of more effective diagnostic methods, interventional radiological methods for its management are also becoming more effective. Often these would negate the need for invasive splenectomy surgery for the treatment of symptomatic hypersplenism and varices. METHODS: A case of a 38 year old gentleman, known to have Crohn's disease, presented with severe acute gallstone pancreatitis with necrosis of the pancreatic neck and body. His course was very complicated, requiring two laparotomies and various interventional drainages of variceal bleeds. As a result of non resolving recurrent variceal haemorrhage, it was decided to proceed with splenic vein stenting to relieve the consequences of splenic vein stenosis. A percutaneous transhepatic splenic vein stent was deployed. RESULTS: Immediate decompression of the varices was noted with no further haemmorrhage. CONCLUSION: There are little data to date on splenic vein stenting in the setting of EPH secondary to non-malignant pancreatic disease. We report a case managed successfully with splenic vein stenting and review the existing literature.

Place cell rate remapping by CA3 recurrent collaterals.

Episodic-like memory is thought to be supported by attractor dynamics in the hippocampus. A possible neural substrate for this memory mechanism is rate remapping, in which the spatial map of place cells encodes contextual information through firing rate variability. To test whether memories are stored as multimodal attractors in populations of place cells, recent experiments morphed one familiar context into another while observing the responses of CA3 cell ensembles. Average population activity in CA3 was reported to transition gradually rather than abruptly from one familiar context to the next, suggesting a lack of attractive forces associated with the two stored representations. On the other hand, individual CA3 cells showed a mix of gradual and abrupt transitions at different points along the morph sequence, and some displayed hysteresis which is a signature of attractor dynamics. To understand whether these seemingly conflicting results are commensurate with attractor network theory, we developed a neural network model of the CA3 with attractors for both position and discrete contexts. We found that for memories stored in overlapping neural ensembles within a single spatial map, position-dependent context attractors made transitions at different points along the morph sequence. Smooth transition curves arose from averaging across the population, while a heterogeneous set of responses was observed on the single unit level. In contrast, orthogonal memories led to abrupt and coherent transitions on both population and single unit levels as experimentally observed when remapping between two independent spatial maps. Strong recurrent feedback entailed a hysteretic effect on the network which diminished with the amount of overlap in the stored memories. These results suggest that context-dependent memory can be supported by overlapping local attractors within a spatial map of CA3 place cells. Similar mechanisms for context-dependent memory may also be found in other regions of the cerebral cortex.