Effect of insulin-glucose infusions on plasma glucagon levels in fasting diabetics and nondiabetics.

The effect of the intravenous infusion of insulin plus glucose on plasma glucagon levels was studied in hyperglycemic fasting adult-type and juvenile-type diabetics and compared with fasting nondiabetics. Adult-type diabetics were given insulin for 2 h at a rate of 0.03 U/kg-min, raising their mean insulin to between 25 and 36 muU/ml; glucagon declined from a base-line value of 71+/-2 (SEM) to 56+/-1 pg/ml at 120 min (P less than 0.001). In juvenile-type diabetics given the same insulin-glucose infusion, glucagon declined from a base-line level of 74+/-8 to 55+/-5 pg/ml at 120 min (P less than 0.05). The absolute glucagon values in the diabetic groups did not differ significantly at any point from the mean glucagon levels in nondiabetics given insulin at the same rate plus enough glucose to maintain normoglycemia. When glucagon was expressed as percent of baseline, however, the normoglycemic nondiabetics exhibited significantly lower values than adult-type diabetics at 90 and 120 min and juvenile-type diabetics at 60 min. In nondiabetics given insulin plus glucose at a rate that caused hyperglycemia averaging between 134 and 160 mg/dl, glucagon fell to 41+/-7 pg/ml at 120 min, significantly below the adult diabetics at 90 and 120 min (P less than 0.01 and less than 0.05) and the juvenile group at 60 min (P less than 0.01). The mean minimal level of 39+/-2 pg/ml was significantly below the adult (P less than 0.001) and juvenile groups (P less than 0.05). When insulin was infused in the diabetic groups at a rate of 0.4 U/kg-min together with glucose, raising mean plasma insulin to between 300 and 600 muU/ml, differences from the hyperglycemic nondiabetics were no longer statistically significant. It is concluded that, contrary to the previously reported lack of insulin effect in diabetics during carbohydrate meals, intravenous administration for 2 h of physiologic amounts of insulin plus glucose is accompanied in unfed diabetics by a substantial decline in plasma glucagon. These levels are significantly above hyperglycemic nondiabetics at certain points but differ from normoglycemic nondiabetics only when expressed as percent of the baseline. At a supraphysiologic rate of insulin infusion in diabetics, these differences disappear.     

Effects of multiple factorial intervention on ambulatory BP profile and renal function in hypertensive type 2 diabetic patients with overt nephropathy - a pilot study

Accumulating evidence has shown that diabetic patients are increasing in number, and renal and cardiovascular complications are the most common cause of death in diabetic patients. Thus, it would be of considerable value to identify the mechanisms involved in the progression of renal impairment and cardiovascular injury associated with diabetes. Recent evidence also indicated that multifactorial intervention is able to reduce the risk of cardiovascular disease and death among patients with diabetes and microalbuninuria. In this pilot study, we examined the effects of intensified multifactorial intervention, with tight glucose regulation and the use of valsartan and fluvastatin on ambulatory blood pressure (BP) profile, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio (UACR), in 20 hypertensive patients (16 male and 4 female) with type 2 diabetes mellitus and overt nephropathy. After 12 months of intensified treatment, office BP, fasting plasma glucose (FPG), and low-density lipoprotein cholesterol (LDLC) were significantly decreased compared to baseline (systolic blood pressure (SBP), 130 ± 2 vs. 150 ± 1 mmHg; diastolic blood pressure (DBP), 76 ± 1 vs. 86 ± 1 mmHg; FPG, 117 ± 5 vs. 153 ± 7 mg/dl; LDLC, 116 ± 8 vs. 162 ± 5 mg/dl, P < 0.0001). Also, compared to the baseline values, the daytime and nighttime ambulatory BP and short-term BP variability were significantly decreased after 12 months. Furthermore, while eGFR was not altered (44.3 ± 5.1 vs. 44.3 ± 6.5 ml/min/1.73 m(2), not significant (NS)), UACR showed a significant reduction after 12 months of intensified treatment (1228 ± 355 vs. 2340 ± 381 mg/g-cr, P < 0.05). These results suggest that the intensified multifactorial intervention is able to improve ambulatory BP profile, preserve renal function, and reduce urinary albumin excretion in type 2 diabetic hypertensive patients with overt nephropathy.     

Ultrasonic vocalization impairment of Foxp2 (R552H) knockin mice related to speech-language disorder and abnormality of Purkinje cells

Previous studies have demonstrated that mutation in the forkhead domain of the forkhead box P2 (FOXP2) protein (R553H) causes speech-language disorders. To further analyze FOXP2 function in speech learning, we generated a knockin (KI) mouse for Foxp2 (R552H) [Foxp2 (R552H)-KI], corresponding to the human FOXP2 (R553H) mutation, by homologous recombination. Homozygous Foxp2 (R552H)-KI mice showed reduced weight, immature development of the cerebellum with incompletely folded folia, Purkinje cells with poor dendritic arbors and less synaptophysin immunoreactivity, and achieved crisis stage for survival 3 weeks after birth. At postnatal day 10, these mice also showed severe ultrasonic vocalization (USV) and motor impairment, whereas the heterozygous Foxp2 (R552H)-KI mice exhibited modest impairments. Similar to the wild-type protein, Foxp2 (R552H) localized in the nuclei of the Purkinje cells and the thalamus, striatum, cortex, and hippocampus (CA1) neurons of the homozygous Foxp2 (R552H)-KI mice (postnatal day 10), and some of the neurons showed nuclear aggregates of Foxp2 (R552H). In addition to the immature development of the cerebellum, Foxp2 (R552H) nuclear aggregates may further compromise the function of the Purkinje cells and cerebral neurons of the homozygous mice, resulting in their death. In contrast, heterozygous Foxp2 (R552H)-KI mice, which showed modest impairment of USVs with different USV qualities and which did not exhibit nuclear aggregates, should provide insights into the common molecular mechanisms between the mouse USV and human speech learning and the relationship between the USV and motor neural systems.     

Mucosal reconstruction using an artificial dermis after KTP laser surgery

OBJECTIVE: The aim of the present study is to assess the clinical effectiveness of the artificial dermis. BACKGROUND DATA: We have previously observed prolonged postoperative pain and bleeding in patients receiving potassium titanyl phosphate (KTP) laser surgery for oral mucosal diseases. MATERIALS AND METHODS: The artificial dermis was placed on the wound and fixed to the surrounding oral mucosa by silk suturing. The silicon sheet of the artificial dermis and the sutures were removed on the seventh postoperative day. Postoperative bleeding from the oral mucosa, duration of postoperative pain, and the period required for healing were all assessed clinically. The results were compared to those in a group of similar cases which were treated without the artificial dermis. In this retrospective review, we considered 20 cases of tongue lesion treated by KTP laser (10 leukoplakias, nine squamous cell carcinomas, and one metastatic renal cell carcinoma to the tongue), nine of which were followed by application of an artificial dermis to prevent postoperative pain and bleeding, and 11 of which were not. RESULTS: No postoperative bleeding was observed in the group of cases treated with an artificial dermis, although it was observed in 45.5% in the group of cases treated without an artificial dermis. There was a statistical difference between these two groups (p < 0.03). CONCLUSION: It was concluded that use of artificial dermis prevented postoperative bleeding.