The evidence for histamine H3 receptor-mediated endothelium-dependent relaxation in isolated rat aorta

The presence of histamine H3 receptors was evaluated on the rat aorta endothelium. In the presence of pyrilamine (1 nM, 7 nM, 10 nM) or thioperamide (1 nM, 10 nM, 30 nM) the concentration–response curve for histamine-induced (0.1 nM − 0.01 mM) endothelium-dependent rat aorta relaxation was shifted to the right without significant change of the Emax indicating competitive antagonism by pyrilamine (pA2 = 9.33 ± 0.34, slope = 1.09 ± 0.36) or thioperamide (pA2 =9.31 ± 0.16, slope=0.94 ± 0.10). Cimetidine (1 μM) did not influence histamine-induced endothelium-dependent rat aorta relaxation. In the presence of thioperamide (1 nM, 10 nM, 30 nM) the concentration–response curve for (R)α-MeHA-induced (0.1 nM − 0.01 mM) endothelium-dependent relaxation was shifted to the right without significant change of Emax indicated competitive antagonism by thioperamide (pA2 = 9.21 ± 0.4, slope = 1.03 ± 0.35). Pyrilamine (100 nM) or cimetidine (1 μM) did not influence (R)α-MeHA-induced endothelium-dependent rat aorta relaxation. These results suggest the presence of a heterogenous population of histamine receptors, H1 and H3, on rat aorta endothelium

Endothelium-dependent relaxation of rat aorta to a histamine H3 agonist is reduced by inhibitors of nitric oxide synthase, guanylate cyclase and Na+,K+-ATPase

The possible involvement of different effector systems (nitric oxide synthase, guanylate cyclase, β-adrenergic and muscarinic cholinergic receptors, cyclooxygenase and lipoxygenase, and Na+,K+-ATPase) was evaluated in a histamine H3 receptor agonist-induced ((R)α-methylhistamine, (R)α-MeHA) endothelium-dependent rat aorta relaxation assay. (R)α-MeHA (0.1 nM – 0.01 mM) relaxed endothelium-dependent rat aorta, with a pD2 value of 8.22 ± 0.06, compared with a pD2 value of 7.98 ± 0.02 caused by histamine (50% and 70% relaxation, respectively). The effect of (R)α-MeHA (0.1 nM – 0.01 mM) was competitively antagonized by thioperamide (1, 10 and 30 nM) (pA2 = 9.21 ± 0.40; slope = 1.03 ± 0.35) but it was unaffected by pyrilamine (100 nM), cimetidine (1 μM), atropine (10 μM), propranolol (1 μM), indomethacin (10 μM) or nordthydroguaiaretic acid (0.1 mM). Inhibitors of nitric oxide synthase, L-NG-monomethylarginine (L-NMMA, 10 μM) and NG-nitro-L-arginine methylester (L-NOARG, 10 μM) inhibited the relaxation effect of (R)α-MeHA, by approximately 52% and 70%, respectively). This inhibitory effect of L-NMMA was partially reversed by L-arginine (10 μM). Methylene blue (10 μM) and ouabain (10 μM) inhibited relaxation (R)α-MeHA-induced by approximately 50% and 90%, respectively. The products of cyclooxygenase and lipoxygenase are not involved in (R)α-MeHA-induced endothelium-dependent rat aorta relaxation nor are the muscarinic cholinergic and β-adrenergic receptors. The results also suggest the involvement of NO synthase, guanylate cyclase and Na+,K+-ATPase in (R)α-MeHA-induced endothelium-dependent rat aorta relaxation

A SIMPLE METHOD FOR ASSESSMENT OF MUSCLE MECHANICAL CAPACITIES FROM FUNCTIONAL MOVEMENT TASKS

The aim of the present study was to evaluate the level of agreement between the routinely used multiple-load method and a simple two-load method based on direct assessment of the F-V relationship from only 2 external loads applied. Twelve participants were tested on the maximum performance vertical jumps, cycling, bench press throws, and bench pull performed against a variety of different loads. All four tested tasks revealed both exceptionally strong relationships between the parameters of the 2 methods (median R = 0.98) and a lack of meaningful differences between their magnitudes (fixed bias below 3.4%). Therefore, addition of another load to the standard tests of various functional tasks typically conducted under a single set of mechanical conditions could allow for the assessment of the muscle mechanical properties, such as the muscle F, V, and P producing capacities

Health Coaching in Primary Care: A Pilot Study

Undergraduate Research Opportunity Program (UROP)http://deepblue.lib.umich.edu/bitstream/2027.42/116124/1/Health_Coaching_In_Primary_Care.pd

Co-overexpression of bcl-2 and c-myc in uterine cervix carcinomas and premalignant lesions

To establish the role of co-overexpression of bcl-2 and c-myc protooncogenes in uterine cervix carcinogenesis, we examined 138 tissue samples of low grade cervical squamous intraepithelial lesions (SIL), high grade SIL, portio vaginalis uteri (PVU) carcinoma in situ and PVU invasive carcinoma, stage IA-IIA (study group) and 36 samples without SIL or malignancy (control group). The expression of bcl-2 and c-myc was detected immunohistochemically using a monoclonal antibody. Fisher's exact test (P<0.05) was used to assess statistical significance. Overexpression of bcl-2 was found to increase in direct relation to the grade of the cervical lesions. High sensitivity was of great diagnostic significance for the detection of these types of changes in the uterine cervix. On the basis of high predictive values it can be said that in patients with bcl-2 overexpression there is a great possibility that they have premalignant or malignant changes in the uterine cervix. Co-overexpression of bcl-2 and c-myc oncogenes was found only in patients with PVU invasive carcinoma (6/26-23.0%). Statistically significant difference was not found in the frequency of co-overexpression in patients with PVU invasive carcinoma in relation to the control group (Fisher's test; P=0.064). The method's sensitivity of determining these oncogenes with the aim of detecting PVU invasive carcinoma was 23%, while specificity was 72.2%. On the basis of high predictive values (100%), speaking in statistical terms, it can be concluded that all patients with co-overexpression of bcl-2 and c-myc oncogenes will have PVU invasive carcinoma. We confirmed in our research that co-overexpression of bcl-2 and c-myc oncogenes was increased only in PVU invasive carcinoma. However, a more extensive series of samples and additional tests are required to establish the prognostic significance of bcl-2 and c-myc co-overexpression in cervical carcinogenesis

Development of exchange lists for M editerranean and H ealthy E ating D iets: implementation in an intervention trial

Background There has been little research published on the adaptation of diabetic exchange list diet approaches for the design of intervention diets in health research despite their clinical utility. The exchange list approach can provide clear and precise guidance on multiple dietary changes simultaneously. The present study aimed to develop exchange list diets for M editerranean and H ealthy E ating, and to evaluate adherence, dietary intakes and markers of health risks with each counselling approach in 120 subjects at increased risk for developing colon cancer. Methods A randomised clinical trial was implemented in the USA involving telephone counselling. The M editerranean diet had 10 dietary goals targeting increases in mono‐unsaturated fats, n ‐3 fats, whole grains and the amount and variety of fruits and vegetables. The Healthy Eating diet had five dietary goals that were based on the US H ealthy P eople 2010 recommendations. Results Dietary compliance was similar in both diet arms, with 82–88% of goals being met at 6 months, although subjects took more time to achieve the M editerranean goals than the H ealthy E ating goals. The relatively modest fruit and vegetable goals in the Healthy Eating arm were exceeded, resulting in fruit and vegetable intakes of approximately eight servings per day in each arm after 6 months. A significant ( P  < 0.05) weight loss and a decrease in serum C ‐reactive protein concentrations were observed in the overweight/obese subgroup of subjects in the M editerranean arm in the absence of weight loss goals. Conclusions Counselling for the M editerranean diet may be useful for both improving diet quality and for achieving a modest weight loss in overweight or obese individuals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108685/1/jhn12158.pd

Non-steroidal anti-inflammatory drug (NSAID) use and levels of a lipid oxidation marker in plasma and nipple aspirate fluids

Non-steroidal anti-inflammatory drugs (NSAIDs) are thought to reduce cancer risk by inhibiting cyclo-oxygenases, resulting in deceased formation of inflammatory mediators and oxidative stress. We examined whether the level of one oxidative stress marker, 15-F 2t -isoprostane, was affected by NSAID use in plasma and breast nipple aspirate fluids (NAF) of pre-menopausal women who were participating in a dietary intervention trial ( n =121). Baseline levels of 15-F 2t -isoprostane were lower in NSAID users than non-users in both NAF and plasma, although the differences did not persist after intervention. Over the duration of the study, information on NSAID use was collected five times, and average 15-F 2t -isoprostane levels in both NAF and plasma exhibited a statistically significant trend for decreases with increased frequency of NSAID use. These results indicate that NSAID use can result in lower levels of 15-F 2t -isoprostane, which may have implications for the effects of NSAID use on breast cancer risk.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44237/1/10549_2005_Article_9102.pd

Twin-screw granulation – a systematic analysis of process parameters

Twin-screw granulation has a significant advantage over traditional granulation methods leading to the possibility of continuous manufacturing. Although this technology has drawn attention in recent years, the general understanding of the process is limited. This study gives a brief overview of the most important process parameters and their influence on product quality. Experimental results from a benchtop granulator and an in-line particle size measurement have been analysed. From this basic study conclusions can be drawn how to tailor the particle size distribution in twin-screw granulation. The most crucial parameters are the liquid-to-solid ratio and the filling level of the screws