Hemoglobin senses body temperature.

UNLABELLED: When aspirating human red blood cells (RBCs) into 1.3 mum pipettes (DeltaP = -2.3 kPa), a transition from blocking the pipette below a critical temperature T(c) = 36.3 +/- 0.3 degrees C to passing it above the T(c) occurred (micropipette passage transition). With a 1.1 mum pipette no passage was seen which enabled RBC volume measurements also above T(c). With increasing temperature RBCs lost volume significantly faster below than above a T(c) = 36.4 +/- 0.7 (volume transition). Colloid osmotic pressure (COP) measurements of RBCs in autologous plasma (25 degrees C < or = T < or = 39.5 degrees C) showed a T (c) at 37.1 +/- 0.2 degrees C above which the COP rapidly decreased (COP transition). In NMR T(1)-relaxation time measurements, the T(1) of RBCs in autologous plasma changed from a linear (r = 0.99) increment below T(c) = 37 +/- 1 degrees C at a rate of 0.023 s/K into zero slope above T(c) (RBC T(1) transition). IN CONCLUSION: An amorphous hemoglobin-water gel formed in the spherical trail, the residual partial sphere of the aspirated RBC. At T(c), a sudden fluidization of the gel occurs. All changes mentioned above happen at a distinct T(c) close to body temperature. The T(c) is moved +0.8 degrees C to higher temperatures when a D(2)O buffer is used. We suggest a mechanism similar to a "glass transition" or a "colloidal phase transition". At T(c), the stabilizing Hb bound water molecules reach a threshold number enabling a partial Hb unfolding. Thus, Hb senses body temperature which must be inscribed in the primary structure of hemoglobin and possibly other proteins.

Pleiotrophic and anti-inflammatory effects of pioglitazone precede the metabolic activity in type 2 diabetic patients with coronary artery disease.

We investigated MMP-9 levels and inflammatory markers during pioglitazone treatment in type 2 diabetic patients with cardiovascular disease. In this randomized multicenter, double blinded, placebo controlled study, 92 type 2 diabetic patients with angiographically proven CHD were randomly assigned to pioglitazone or placebo treatment. At baseline and during a 28 days observational period MMP-9, MCP1, hsCRP, IL-6, sCD40, and P-selectin were monitored. During Pioglitazone treatment, a 12% reduction in MMP-9 and a 18% reduction in hsCRP levels (p<0.05, respectively) could be observed already after 3 days. MCP-1 levels were reduced by 14% after 10 days of treatment (p<0.0001). At the end of the study, these parameters were significantly lower in the pioglitazone group as compared to the placebo group (MMP-9: 392+/-286 versus 427+/-166 ng/ml; hsCRP: 1.9+/-1.7 versus 3.1+/-2.3 ng/L; MCP-1: 413+/-115 versus 471+/-146 pg/ml; p<0.05, respectively). sCD40 levels decreased by 32.5% (p<0.05) and P-selectin decreased by 3.2% (p=0.053) in the pioglitazone group. No change could be found with regard to the other study endpoints. No changes in these parameters could be observed during placebo treatment. Even before effects on glucose metabolism could be obtained, pioglitazone exerts immediate effects on plasma markers of plaque vulnerability and inflammation.

Hemorheology and walking of peripheral arterial occlusive diseases patients during treatment with Ginkgo biloba extract.

AIM: To study the effects of Ginkgo biloba extract 761 (GbE) from the points of view of hemorheology for patients of peripheral arterial occlusive diseases (PAOD). METHODS: The treatment with GbE (240 mg.d-1, po) and the pain-free walking distance (PFWD) were carried out for 24 PAOD patients (12 nondiabetic, ND and 12 diabetic, D) over 48 wk. The parameters erythrocyte stiffness (ES) and relaxation time (RT), the blood plasma viscosity (eta), the plasma fibrinogen concentration (Cf) and the blood sedimentation rate (BSR), the PFWD, and maximal walking distance (MWD) were determined at 6 wk before treatment (-6), at the beginning of the treatment (0), and after 6, 11, 16, and 48 wk of treatment. RESULTS: At wk -6, ES and RT of both the ND- and D-group were not significantly different from a healthy control group. At wk 0, stiffness and RT were significantly higher than healthy control, and the mean PFWD was only 111 m. The eta value was significantly elevated and Cf and BSR were enhanced. Throughout 11 wk of treatment ES, RT, eta, and Cf decreased gradually and PFWD improved. Between 16 and 48 wk, ES, and RT were no longer significantly different from the controls, whereas eta and Cf decreased gradually but remained higher than normal, BSR decreased, and the PFWD improved by a factor of 3.8 times (D) and 3.3 times (ND). CONCLUSION: GbE gives therapeutic effects in PAOD patients.