Impact of insulin sensitivity treatment with pioglitazone on endothelial function in non-diabetic patients with arterial hypertension.

OBJECTIVE: The thiazolidindione (TDZ) pioglitazone reduces insulin resistance and blood pressure in non-diabetic patients with arterial hypertension as previously reported [Füllert et al. 2002]. The question is still not answered whether it is a direct effect on the endothelial wall or it is related with improvement of insulin sensitivity. The present investigation is the first placebo controlled study which examines the effect of TDZ induced changes of insulin sensitivity (SI) on endothelial function and blood pressure in in non-diabetic patients with high blood pressure. MATERIAL AND METHODS: Insulin sensitivity indices (SI indices) were obtained by analyzing fasting glucose and insulin concentration with homeostasis model assessment (HOMA), the glucose and insulin profiles after 75 g dextrose oral glucose tolerance tests (OGTT, Matsuda-Index) and euglycemic hyperinsulinemic clamp (m-value) in a double-blind placebo-controlled study in 60 patients with arterial hypertension before and after 4 months treatment with Pioglitazone 45 mg (PIO45). Flow-mediated dilatation of brachial artery (FMD) after reperfusion was used to determine endothelial function. Blood pressure in the morning of every visit (casual blood pressure, RRc) and 24-h ambulatory blood pressure (24RR) were measured. RESULTS: Antihypertensive treatments were equally distributed in the placebo and PIO45 group. All SI indices were closely related to with alanine-aminotransferase activities (ALAT): HOMA r = 0.1041, p < 0.05, Matsuda-Index r = 0.4242, p < 0.01, M value r = 0.1944, p < 0.01. There were no relationships of SI indices with FMD, RRc and 24RR in the study population with treated arterial hypertension. FMD was closely related to the nocturnal systolic and diastolic 24hRR (systolic r = 0.0943, p < 0.05, diastolic r = 0.0947, p < 0.05). SI indices improved after 4-month therapy with PIO45 when compared with controls: HOMA 65% (p < 0.01), Matsuda-Index 60% (p < 0.01) and M value 17.7% (p = 0.008). FMD did not change after PIO45. Casual diastolic blood pressure (p = 0.016) and systolic blood pressure were lower (p = 0.053) under PIO45. No significant changes of 24-h blood pressure were found after treatment with TDZ. CONCLUSION: 4-month treatment with PIO45 improves SI, liver function and lowers casual blood pressure (RRc. No effects on 24-h ambulatory blood pressure and on endothelial function after PIO45 therapy were observed. The higher insulin sensitivity was not related to lower blood pressure. Thus, PIO45 appears to have a direct effect on the arterial system which cannot be explained by changes of endothelial function or improved SI in non-diabetic patients with treated high blood pressure.

Pharmacodynamic effects of orally administered dexlipotam on endothelial function in type 2-diabetic patients.

OBJECTIVE: Diabetic endotheliopathy is the result of hyperglycemia and the production of oxygen-free radicals. In vitro and in vivo data have shown beneficial effects of dexlipotam (DEX), a tromethamine salt of R(+)-alpha-lipoic acid, on oxidative stress in hyperglycemic states, but no data are available on the effects of this agent on endothelial function. The purpose of this pilot study was to evaluate the impact of DEX on endothelial function in patients with type 2 diabetes (DM2) and to estimate the safety and tolerability of DEX. MATERIAL AND METHODS: DEX 960 mg and DEX 1,920 mg were investigated in DM2 patients over a period of 4 weeks using a randomized, placebo- (PLA) controlled, double-blinded study with 3 parallel groups. The marker of arterial function after 4-week therapy with DEX was the maximum percentage change versus baseline in the flow-mediated dilation of the brachial artery (FMD) after reperfusion. RESULTS: A total of 114 diabetic patients were randomized to the three study groups. DEX was safe and well tolerated. Dyspepsia appeared to be the most relevant side effect of DEX treatment. Systolic (p = 0.078) and diastolic blood pressure (p = 0.059) tended to be lower in patients treated with DEX at a dose of 1,920 mg. There were no significant differences in FMD between the placebo- and the DEX-treated groups. In patients with poorer glucose control (HbA1c > 6.5% Hb), FMD increased significantly after 4-week treatment with DEX: PLA -1.51 +/- 2.98%, DEX 960 mg +1.22 +/- 3.22, p = 0.027, DEX 1,920 mg +1.47 +/- 3.78, p= 0.012. The magnitude of the mean change compared to placebo was 2.73% (DEX 920) and 2.98% (DEX 1,920) in patients with HbAlc > 7.5% Hb (DEX 960, p = 0.007, DEX 1,920, p = 0.032). The effects of treatment were usually statistically significant in subgroups with more severe vascular stress (longer duration of disease, pretreatment history, higher LDL-C, higher blood pressure). CONCLUSION: DEX therapy appears to reduce endothelial dysfunction in DM2, especially in men with long history of DM2 and having poor glucose control. These findings will be useful in patient selection in future prospective clinical trials with drugs to treat vascular stress.

The evaluation of facial, head, neck, and temporomandibular joint pain patients.

The purposes of this paper are 1) to present an evaluation procedure for patients with signs and symptoms of temporomandibular joint (TMJ) pain dysfunction syndrome (PDS) and 2) to describe the findings of the evaluation procedure on 12 patients with TMJ PDS. The evaluation emphasizes the collection of subjective and objective data. Records from 12 patients with facial, head, and neck pain were reviewed. The most frequent symptoms were: headache (1 00%), neckache (83.3%), and ear pain (58.3%). The most frequent signs were: muscle tenderness (100%) and mandibular deviation on opening (66.7%). Subjects with lateral pterygoid muscle tenderness had digastric muscle tenderness as well. Subjects with medial pterygoid muscle tenderness had masseter and hyoid muscle tenderness. Masseter muscle tenderness was strongly related to sternocleidomastoid and mylohyoid muscle tenderness and neckache. J Orthop Sports Phys Ther 1982;3(4):193-199.