Separate induction of human blood platelet aggregation or cytotoxicity by different concentrations of PAF-acether and thrombin

Using decreasing concentrations of PAF-acether or thrombin, it was possible to observe on human platelets, first, aggregation, classically associated to activation, then, below a threshold, cytotoxicity towardsSchistosoma mansoni larvae, proposed here as stimulation. These two activities appeared as distinct and antithetic. However, their induction might be the consequence of triggering of the same receptors with different intensity, since PAF-induced, but not thrombin-induced, cytotoxicity could be inhibited with specific PAF-antagonists BN 52021 and BN 52024 also known to inhibit PAF-induced aggregation. These results give credit to the hypothesis that haemostatic and cytotoxic properties of platelets are two distinct functions of these blood elements.     

Remote metabolic effects of cerebrovascular lesions: magnetic resonance and positron tomography imaging

Summary Combined Positron Emission Tomography (PET) and Proton Magnetic Resonance Imaging (MRI) study were performed in six patients with chronic supratentorial stroke to investigate whether remote hypometabolic regions revealed by PET showed any abnormality on MRI. Either regional oxygen consumption (n=4) or glucose utilization (n=2) were measured using PET and the ¹⁵O steady state ¹⁸FGD technique, respectively. Four patients, with deeply located brain lesions, showed a significant metabolic reduction in the overlying cerebral cortex. In the remaining two patients, affected by a large cortical infarct, there was a significant crossed cerebellar hypometabolism. The MRI weighted by the parameters spin density (), spin lattice (T₁) and spin-spin (T₂) relaxation times were obtained employing various sequences in the same subjects. In no patient did the MRI show any contrast modification in these hypometabolic remote regions, suggesting that subtle loss of tissue and/or biochemical change do not underlie the reduction in metabolic rate.     

Long-pulsed 1064-nm and 755-nm lasers for C1 leg veins on skin type IV patients: a side-by-side comparison

Lasers in Medical Science - Long-pulsed 1064-nm (LP1064) and 755-nm (LP755) lasers have been demonstrated as effective treatments for leg veins. However, few studies of these treatments on Asian...     

Outcomes of obese compared to non-obese veterans undergoing open inguinal hernia repair: a case–control study

Hernia - The optimal approach for inguinal hernia repair in the obese remains elusive. Minimally invasive techniques show equivocal results compared to the open method. None of the current analyses...     

Evaluation of Evidence for Adaptation and Special Design

Archives of Sexual Behavior -     

The effect of yohimbine on sympathetic responsiveness in essential hypertension

Summary We have studied the sympathetic response to blockade of presynaptic ₂-adrenoceptors in essential hypertension by measuring plasma concentrations of noradrenaline after a single oral dose of yohimbine, an ₂-adrenoceptor antagonist.Mean baseline plasma noradrenaline and adrenaline concentrations were similar in the hypertensive and normotensive groups. Yohimbine (0.2 mg×kg^–1 orally) caused a lesser increase in the plasma concentrations of noradrenaline in hypertensive patients (+67%) than in normotensive subjects (+178%) and a pressor response in hypertensive (but not in normotensive) patients.These results are consistent with an alteration in the balance of -adrenoceptors (for example presynaptic ₂-adrenoceptor desensitization and post-synaptic ₁-adrenoceptor hyper-responsiveness) which would help to develop and/or maintain arterial hypertension.     

Pharmacological characterization of an α1A-adrenoceptor mediating contractile responses to noradrenaline in isolated caudal artery of rat

1. The α₁-adrenoceptor population mediating contraction of caudal artery of rat has been characterized by using quantitative receptor pharmacology.
2. Cumulative concentration-effect (E/[A]) curves to noradrenaline (NA) yielded a p[A]₅₀ of 5.56±0.05 (n=16). Prazosin caused concentration-dependent, parallel, dextral shifts of E/[A] curves to NA yielding a pK_b of 8.9 (Schild regression slope=1.0). RS-17053 (N-[2-(2-cyclopropyl methoxy phenoxy) ethyl]-5-chloro-α ,α-dimethyl -1H-indole- 3-ethanamine hydrochloride; 10–100 nM), a selective α_1A-adrenoceptor antagonist, produced non-parallel, biphasic, dextral shifts of E/[A] curves to NA, suggesting the involvement of more than one α₁-adrenoceptor subtype. Analysis of the high affinity component yielded an apparent pA₂ value of 9.2±0.3.
3. A-61603, a selective agonist at α_1A adrenoceptors behaved as a full agonist relative to NA and yielded monophasic E/[A] curves with a p[A₅₀] of 7.59±0.04 (n=15). Pretreatment of tissues with chloroethylclonidine (CEC; 100 μM for 20 min, followed by 40 min washout), which preferentially alkylates α_1B- and α_1D-adrenoceptors, did not alter E/[A] curves to A-61603. Prazosin (3–300 nM) caused concentration-dependent, parallel, dextral shifts of E/[A] curves to A-61603 yielding a pA₂ estimate of 9.2±0.2.
4. Experiments with α₁-adrenoceptor antagonists of varying subtype selectivities (RS-17053, SNAP 5089, tamsulosin, 5-methylurapidil, BMY 7378, HV 723 and REC 15/2739) revealed parallel dextral shifts of E/[A] curves to A-61603. Schild regression analyses yielded pA₂ estimates of 9.2, 9.3, 11.2, 9.0, 6.3, 8.7 and 10.0 for RS-17053, SNAP 5089, tamsulosin, 5-methylurapidil, BMY 7378, HV 723 and REC 15/2739, respectively, although deviations from unit slope (possibly reflecting a secondary involvement of another α₁-adrenoceptor) hindered estimations of pK_b for some antagonists. The antagonist affinity profile obtained reflects best that described for the α_1A-adrenoceptor.
5. In conclusion, caudal artery of rat contracts in response to NA via activation of at least two α₁-adrenoceptor subtypes. One of these subtypes displays the pharmacology of the α_1A-adrenoceptor, while the other remains to be defined. Use of the novel selective agonist, A-61603, allows for limited pharmacological isolation of the α_1A-adrenoceptor permitting characterization of the properties of selective antagonists.