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Biomedical subjects

P Peter

Publications and source records attributed to P Peter.

At least 19 recordsLinked to original sources

Effect of treatment with nebivolol on parameters of oxidative stress in type 2 diabetics with mild to moderate hypertension.

AIM: The aim of this study was to examine the effect of the cadioselective B(1)-adrenoceptor blocker nebivolol on glycaemic control, lipid profile and markers of oxidative stress in patients with type 2 diabetes over a 6-month period. METHODS: Twenty-six patients with mild to moderate hypertension (140-160 mmHg systolic, 90-105 mmHg diastolic) confirmed on 24-h blood pressure monitoring, were treated with nebivolol 5 mg daily for 6 months. Total serum cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) subfractions, lipid hydroperoxides (LHPs) and total antioxidant capacity (TAC) were measured before and after 6 months of treatment. RESULTS: Nebivolol, as expected, reduced mean daytime systolic and diastolic pressures on ambulatory monitoring (149 +/- 9 to 140 +/- 13 mmHg, P = 0.02 and 84 +/- 7 to 77 +/- 9 mmHg, P < 0.001). There were no significant changes in serum cholesterol or triglycerides following treatment but a significant increase in HDL cholesterol was noted (1.12 +/- 0.19 to 1.25 +/- 0.36 mmol/L, P = 0.008). Patients showed a highly significant reduction in TAC from 501 +/- 57 to 422 +/- 29 trolox equivalent (P < 0.001). Baseline LHPs were very high and showed no significant change over the 6-month period (18.7 +/- 7.4 and 18.7 +/- 10.9 micromol/L). The LDL score increased significantly from 1.7 +/- 0.7 to 2.3 +/- 0.7 (P = 0.0002) at 6 months suggesting a change to a more atherogenic lipid profile. Neither weight nor glycaemic control changed during treatment. CONCLUSION: Nebivolol appears to be lipid neutral and may even have a positive effect on HDL cholesterol. Despite this it may promote the formation of potentially atherogenic LDL subfractions possibly as a result of reduced antioxidant defences. Further studies are needed to clarify the changes observed in parameters of oxidative stress.

Antihypertensive Agents↗

Peripheral blood and BM CD34+ CD38- cells show better resistance to cryopreservation than CD34+ CD38+ cells in autologous stem cell transplantation.

BACKGROUND: We and others have shown a critical role for CD34+ CD38- cells in hematopoietic recovery after autologous stem cell transplantation (ASCT), in particular for platelet reconstitution. Thus a routine assessment of CD34+ CD38- cells in freezing-thawing procedures for autografting could represent an important tool for predicting poor engraftment. METHODS: To compare the impact of cryopreservation on CD34+ CD38+ and CD34+ CD38- hematopoietic stem cell subsets, 193 autograft products collected in 84 patients with malignancies were assessed before controlled-rate cryopreservation in 10% DMSO and after thawing for autografting. RESULTS: Cell counts after thawing were significantly different from the pre-freezing counts for total CD34+ (P<0.0001) and CD34+ CD38+ (P<0.0001) cells, but not for CD34+ CD38- cells (P=0.252). Median losses for CD34+, CD34+ CD38+ and CD34+ CD38- cells were, respectively, 11.8%, 11.4% and 0.0%. The magnitude of fresh/post-thawing percentage cell variation was significantly different when comparing between the CD34+ CD38+ and CD34+ CD38- cell subsets (P<0.001). Moreover, CD34+ CD38- cells exhibited recovery values > or =100% in 85/160 graft products, compared with 51/193 in CD34+ CD38+ cells (P<0.0001). Also, recovery values > or =90% were significantly better in the CD34+ CD38- (98/160 grafts) than in the CD34+ CD38+ subsets (89/193 grafts) (P<0.01). DISCUSSION: In this work we have demonstrated that CD34+ cells that do not express the CD38 Ag show a significantly better resistance to cryopreservation. This could represent another example of the particular ability of less committed progenitor cells to overcome environmental injuries. Moreover, we consider routine assessment of CD34+ CD38- cells before freezing as clinically relevant, but post-thawing controls may be avoided because of their good resistance to freezing.

ADP-ribosyl Cyclase↗

Insulin resistance--the new goal!

Diabetes mellitus is a well-recognized risk-factor for coronary artery disease (CAD). Epidemiological studies have shown that the risk of CAD increases two to sixfold in patients with type 2 diabetes compared with those without the disease. Furthermore the prevalence of diabetes in the UK has increased by 30% since 1991 and the world population of people with diabetes in 2010 is expected to be twice that of 1990. In addition whilst the mortality from CAD in patients without diabetes has declined over the past 20 years the mortality in men with type 2 diabetes has not changed and in women may have increased. UKPDS and other studies have shown a significant improvement in the onset and course of microvascular complications with good diabetic control. However the same is not true for macrovascular complications for which there is no good evidence of improvement with better diabetic control. This apparent lack of benefit from improved care of diabetic patients has led to many different approaches. These include attempts to achieve even better glycaemic control, greater emphasis on other risk factors particularly hypertension and interestingly attention to the prediabetic state characterized by insulin resistance (IR). The latter is associated with a number of abnormalities which could play a causative role in the development of cardiovascular disease. This article will review the concept of IR and the possible interventions available to tackle it.

Cardiovascular Diseases↗

gamma-Hydroxybutyrate ligands possess antidopaminergic and neuroleptic-like activities.

The action of agonists or antagonists at the gamma-hydroxybutyrate (GHB) receptor represents a possibility to modulate dopaminergic activities in brain. In the present study, GHB and six structural analogs were tested for their ability to displace [3H] GHB binding from striatal membranes. All the analogs tested exhibited higher affinity for GHB as compared with GHB itself. Parallel experiments were carried out on striatal slices in order to determine IC50 values for inhibition of dopamine release in the presence of these compounds. All substances inhibited dopamine release with higher potency as compared with GHB itself. These antidopaminergic activities were confirmed in several neuropharmacological tests, usually used to predict neuroleptic activities in vivo. There appears to be a relationship between the affinity for the GHB striatal low-affinity receptor and the inhibition of dopamine release on one hand, and the antidopaminergic activity (as revealed by the in vivo tests) on the other hand. Thus, it is suggested that GHB agonists possessing antidopaminergic activities, may represent potential drugs endowed with neuroleptic properties.

Animals↗