Recently, IL-12 emerged as a critical player in type 2 diabetes complications. We previously reported that ischemia-induced angiogenesis is compromised in type 2 diabetic mice. In this study, we determined that IL-12 disruption rescued angiogenesis and arteriogenesis in type 2 diabetic mice. To induce type 2 diabetes, wild-type (WT), p40IL-12 (p40), and p35IL-12 (p35) mice were fed a high-fat diet (HFD) for 12 weeks. Body weight, glucose test tolerance, and insulin test tolerance were assessed. After 12 weeks of an HFD, the femoral artery was ligated and blood flow recovery was measured every week for 4 weeks. WT, p40, and p35 mice fed an HFD become obese after 12 weeks and exhibit glucose intolerance and insulin resistance. Blood flow recovery was fully restored in 2 to 3 weeks after femoral artery ligation in all groups of mice fed a normal diet. However, after 12 weeks of an HFD, blood flow recovery was compromised in WT mice, whereas it was fully recovered in p40 and p35 mice. The mechanism of blood flow recovery involves an increase in capillary/arteriole density, endothelial nitric oxide synthase/Akt/vascular endothelial growth factor receptor 2 signaling, and a reduction in oxidative stress and inflammation. The disruption of IL-12 promotes angiogenesis and increases blood flow recovery in obese type 2 diabetic mice by an endothelial nitric oxide synthase/Akt/vascular endothelial growth factor receptor 2/oxidative stress-inflammation-dependent mechanism.

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ABSTRACT. This study was conducted to evaluate the impact of antiepileptic drugs on the liver function and L-carnitine levels in children suffering from epilepsy. Sixty epileptic children aged from 1 to 15 years, together with 20 healthy controls were studied. Among them twenty-five children were treated with phenytoin (group I), 25 were treated with carbamazepine (group II) and 10 patients were treated with phenobarbital (group III). In each of the three groups, serum free carnitine levels were significantly decreased after one month of therapy compared with pretherapy levels (p<0.01, p<0.01, p<0.01 respectively). Meanwhile, the levels of L-carnitine in treated children collectively were significantly decreased in comparison with healthy children (p<0.01). Hypocarnitinemia was detected in 28% of group I, 56% of group II , and 30% of group III. Serum SGOT was significantly increased in patients treated with phenytoin and phenobarbital (p<0.01, p<0.05 respectively) compared with pretherapy levels. Whereas serum lactate and total bilirubin were significantly increased after therapy in patients treated with carbamazepine in comparison to that before significantly increased (p<0.05 for each) in comparison with controls. Moreover, a significant negative correlation was found between values of carnitine and both lactate (p<0.01) and lactate/pyruvate ratio (p<0.05) after therapy in carbamazepine treated group. It should be taken into account that carnitine rich food in the form of milk and milk products must be taken as a supplement to the antiepileptic drugs especially carbamazepine.

Background Diabetes is a metabolic disorder highly linked to several systemic complications. Diabetic patients largely suffer from hyperglycemia-induced macro- and micro-vascular abnormalities. Accumulating data have suggested a beneficial role of endothelial progenitor cells in diabetic microvascular diseases. Objective We evaluated the possible therapeutic effect of injecting transformed human umbilical cord mesenchymal stem cells on cardiovascular and renal functions in old diabetic rats. Methods Thirty old (18-14 months) male Wistar albino rats weighing 300-350g were used in the present study. Diabetes was induced by intra-peritoneal streptozotocin injection. Rats were assigned (10/group) to Naive (received no treatment), diabetic control (injected with saline), and diabetic transformed mesenchymal stem cell treated (TMSCs). Measurement of blood pressure and doppler studies were performed, and blood samples were collected. Animals were then scarified and large and small vessels were collected for immunohistopathology. Results Anti-CD31 immuno-staining has shown successful homing of the injected transformed stem cells to the vascular endothelium. TMSCs treated group featured reduced systolic blood pressure, heart rate and pulse wave velocity when compared to control group. TMSCs treated group had lower serum level of vascular endothelial growth factor (VEGF), interleukin1β (IL-1β) and tumor necrosis factor alpha (TNFα). Renal function parameters (KIM-1 and cystatin C)) were significantly lower in TMSCs treated group. Renal artery doppler study revealed improved blood flow and reduced resistance in the TMSCs treated group when compared to the control group. Conclusion We show here that transformed mesenchymal stem cells could be a potential therapeutic approach against hyperglycemia-induced macro- and micro-vascular complications in aged diabetics.