Standort in Deutschland, wo man günstige und qualitativ hochwertige Kamagra Ohne Rezept Lieferung in jedem Teil der Welt zu kaufen.

Kaufen priligy im Online-Shop. Wirkung ist gut, kommt sehr schnell, innerhalb von 5-7 Minuten. cialis was nur nicht versucht, verbrachte eine Menge Geld und Nerven, und geholfen hat mir nur dieses Tool.

Powerpoint presentation

Effects of rosiglitazone and sumatriptan on human isolated small and
large coronary arteries

Kathryn Bagot, Mozam Ali, Lee Dawson, Sandy Williams, Bob SheldrickAsterand UK Ltd, 2 Orchard Road, Royston, Hertfordshire, SG8 5HD, UK.
ƒ Species differences in receptor type, expression level or coupling can lead to marked differences in responses between laboratory animals and humans, so there is a need for testing compounds on
relevant human tissues where available.
ƒ Recently, the FDA expressed concerns over a potential increased risk for heart attacks in relation to rosiglitazone1 (PPARγ agonist used in diabetes management). Coronary vasoconstriction a known side effect of some drugs such as triptans2 (which can increase the risk of a heart attack), has been demonstrated in human isolated tissues.
ƒ In the current study, the coronary constrictor potential of rosiglitazone was compared to sumatriptan and 5-HT in human isolated small and large coronary arteries (HCA) from non-diseased hearts. Methods
Hearts from 5 donors (3 male and 2 female, age range 20-65 years) who died of non-
cardiac disorders were obtained from ethically approved organ procurement organisations. From these, left anterior descending or right coronary artery, with no visible atherosclerosis,
were dissected and cut into either small (SHCA, 0.3-0.5mm internal diameter (i.d.)) or large LHCA, 1-2mm i.d.) vessel rings. Vessels rings were suspended in organ baths containing Krebs’ physiological salt solution, gassed with 95% O / 5% CO and maintained at 37°C,
and were either normalised to 13kPa (SHCA) or stretched to a passive tension of 15mN (1.5g). After initial viability assessments with KCl (30-100mM), compounds were assessed under either endothelin (ET-1) or U-46619 pre-contraction (pre-contracted to ~20-35% of the KCl response, LHCA only) or basal conditions. Subsequently, function of the endothelium was assessed pharmacologically (see Figure 1).
Figure 1. Schematic of experimental protocol
In vessel rings from all five donors, KCl (30-100mM), PGF (1 U-46619 (0.1-3nM) caused contraction, whereas sodium nitroprusside (100µM) caused
relaxation. Substance P (1-10nM) caused relaxation in the majority of rings tested,
Sumatriptan and 5-HT but not rosiglitazone (1nM-10µM) caused concentration-dependent contractions that were similar in both SHCA and LHCA. Pre-contracting the vessels with either ET-1 or U-46619 had no effect on the magnitude of effect or potency of the three test compounds. Compared to sumatriptan, 5-HT was ~3-10-fold more potent and caused approximately double the contraction magnitude. Vehicle (DMSO, up to final concentration Figure 2. Original traces (above) of the effects of sumatriptan (green) and rosiglitazone (blue)
in SHCA. 5-HT (1µM ) and KCl (100mM) showed clear contractions at the end of the treatment
1%) caused smal but variable relaxation. See Figures 2, 3 and Table 1.
concentration-effect curves. Concentrations are log M.
concentration (logM)
concentration (logM)
concentration (logM)
concentration (logM)
Figure 3. Graphical representation (above) of concentration-effect curves to rosiglitazone (T), sumatriptan („), 5-HT (S) and vehicle ({) in SHCA-basal tone (A), LHCA-basal tone (B),
LHCA – ET-1 pre-contraction (C) and LHCA – U-46619 pre-contraction (D). Data expressed as a % of the final challenge to KCl (100mM).
Table 1. Summary table of results. Data are mean ± s.e.mean (n = 3-7 rings, 5 donors), or #range (n = 2 rings, 2 donors). E
ƒ Rosiglitazone did not contract HCA.
ƒ The magnitude of effect and potency of both sumatriptan and 5-HT were independent of the size of the HCA (<0.5mm vs. 1-2mm i.d.) or tonal level used.
ƒ Further studies are ongoing to understand the significance of these findings in relation to the reported clinical side effects of rosiglitazone.
• 2MAASSENVANDENBRINK, A et al (1998). Coronary side-effect profiling of current and prospective antimigraine drugs. Circulation, 98, 25-30
. sterand.
United Stat
United Sta es
US Toll Free
+1 (313) 263 0960
+44 (0) 1763 211600
+1 (866) 3TISSUE



The Longwood Herbal Task Force The Center for Holistic Pediatric Education and Research Devil’s Claw ( Harpagophytum procumbens ) Principal Proposed Use: Anti-inflammatory for degenerative or rheumatic joint disease and Other Proposed Uses: Analgesic for other pains (headache, menstrual pain), antipyretic, antidiabetic, appetite stimulant and bitter tonic, liver and gall bladder

Microsoft word - spray tan advice.doc

Tel: 0161 476 3301 Mobile: 07903 162 041 How to Prepare for your Spray Tan: * Please wax or shave at least 24hrs prior to your Spray Tan - this allows enough time for your pores to close again. *Exfoliate your body 24hrs pior your Spray Tan using an exfoliating mitt or brush, paying particular attention to any very dry areas such as elbows, knees, feet etc. This will remove dead

Copyright © 2010-2014 Internet pdf articles