β3-Adrenoceptors mediate smooth muscle relaxation in the rat lower oesophageal sphincter

1 The role of β₃-adrenoceptors in isoprenaline-induced relaxation of carbachol-precontracted ring segments of the rat lower oesophageal sphincter (LOS) was examined. 2 Isoprenaline (10^?8m – 10^?5m ) relaxed ring segments of the LOS in a concentration-dependent manner. Propranolol (10^?7m ) had very little antagonist effect on isoprenaline-induced relaxation. 3 Dobutamine (10^?7m – 10^?4m ), salbutamol (10^?7m – 10^?4m ) and BRL 37344 (10^?8– 10^?5m ) also all relaxed carbachol-contracted ring segments of the LOS in a concentration-dependent manner. The relaxant responses to these agonists were similarly not antagonized by propranolol (10^?7m ). 4 Cyanopindolol (10^?6m ), produced a parallel rightward displacement of isoprenaline, dobutamine, salbutamol and BRL 37344 concentration–response curves with similar potencies. The pK_B values range from 7.3 ± 0.1 to 7.7 ± 0.2. 5 The relaxant effect of isoprenaline in the rat LOS was not inhibited by N^G-nitro-l -arginine (l -NOARG; 3 × 10^?5m ), glibenclamide (10^?5m ) or tetraethylammonium (1 mm ). 6 It was concluded that β₃-adrenoceptors mediate isoprenaline-induced relaxation in rat lower oesophageal sphincter and that activation of these receptors was not linked to either ATPase-, Ca²⁺-dependent K⁺ channels or to NO release.     

Anterior eye focusing of peripheral ultraviolet and visible radiation albedo

Concern about short- and long-term ultraviolet radiation (particularly UVB) damage to the eye has led to increased research in this area. Numerous studies have confirmed the pathogenic enhancing roles of reflected ultraviolet (UV) and visible radiation in our environment. There is concern that conventional sunglasses do not protect the eye adequately from reflected rays (albedo), especially on the lateral aspect, from behind and from below. Using eye models and computer ray tracing methods, the pathways of oblique rays incident at the temporal peripheral cornea have been plotted by Maloof, Ho and Coroneo.¹ These rays are refracted and focused and theoretically can result in up to 20 times the concentration of incident irradiance at the nasal anterior chamber angle and nasal equatorial cortex of the crystalline lens. The purpose of this study was to determine the limits of angular subtense of the incident peripheral light which is refracted in this manner in human subjects and to investigate the relation between corneal shape and certain ocular parameters to the limits. A statistically significant positive correlation was found between temporal entrance angle and anterior chamber depth (r = 0.70, P< 0.0006). The entrance angle ranged from 15 degrees to 30 degrees and was located 10 degrees to 45 degrees posterior to the coronal plane. Our results support Maloof and colleagues' predictions for the implication of focused peripheral UV and high intensity visible radiation in the pathogenesis of pterygium and cortical cataract and emphasise the need for lateral eye protection in conditions of high ultraviolet albedo.     

Interaction of vascular alpha-1 adrenoceptors with multiple signal transduction pathways.

In the rat vasculature, a single alpha 1-adrenoceptor may be coupled to two distinct G proteins, one of which regulates phospholipase C activity and is insensitive to pertussis toxin, and another which regulates calcium channel function and is highly sensitive to inhibition by pertussis toxin. alpha 1-Adrenoceptor agonists may in theory activate both pathways, but the efficiency of alpha 1-adrenoceptor coupling to the pertussis-toxin-insensitive pathway is low relative to the other pathway that couples the alpha 1-adrenoceptor to calcium channels. As such, only full agonists with high intrinsic efficacy can activate both pathways, whereas partial agonists, by virtue of their lower intrinsic efficacies, are less able to activate the pertussis-toxin-insensitive pathway, thereby rendering partial alpha 1-adrenoceptor agonists more sensitive than full alpha 1-adrenoceptor agonists to inhibition by calcium channel blockers and pertussis toxin.     

Inhibitory effect of capsaicin on cholinergic transmission in ovine airways: evidence for non-cholinergic contractions

Electrical stimulation of ovine trachealis smooth muscle and bronchial ring segments induced neurogenic and monophasic atropine-sensitive contractions. Pretreatment of the tissues with capsaicin (100 microM) significantly reduced these contractions indicating a possible contribution of a peptidergic neurotransmitter to the contractions. The effect of capsaicin on electrically induced contractions was significantly inhibited by capsazepin indicating an action on vanilloid receptors. In both preparations, electrically induced contractions were not modified by tachykinin NK(1)- and NK(2)-receptor antagonists singly and in combination. It was therefore concluded that a component of the atropine-sensitive electrically induced contractions of ovine airways smooth muscles involved the release of a peptide neurotransmitter which is probably not a tachykinin. However, an action of capsaicin on prejunctional vanilloid receptors located on cholinergic nerves cannot be ruled out.     

Cyclooxygenase-2 is Upregulated in Copper-Deficient Rats

Copper deficiency inactivates Cu/Zn-SOD and promotes accumulation of reactive oxygen species. This process likely impairs nitric oxide (NO)-mediated relaxation as well as triggers vascular inflammation. The current study was designed to determine whether COX-2, a proinflammatory protein, expression and activity are upregulated in the oxidative environment associated with inadequate Cu. Weanling male Sprague Dawley rats were fed purified diets which were either Cu-adequate (Cu-A); Cu-marginal (Cu-M), Cu-deficient (Cu-D), or the Cu-D diet combined with the SOD mimetic Tempol (Cu-D/T; 1 mM in drinking water) for 4 weeks. COX-2 protein, PGE₂ (COX-2 metabolite) and isoprostanes (index of oxidative stress) were all higher in the Cu-D group vs Cu-A group, but no significant differences occurred between the Cu-M and Cu-A groups. Tempol protected against an attenuation of NO-mediated vasodilation in the Cu-D rats but did not prevent the elevation of PGE₂ or isoprostanes. Our data suggest a role for copper as a modulator of oxidative stress and inflammation independent of SOD activity or NO-derived oxidants.     

Lithium protects against toxic effects of cadmium in the rat testes

Purpose  

To investigate the protective effect of Lithium against the toxic effect of Cadmium in the rat testes.     

Endothelium-dependent relaxation in isolated renal arteries of diabetic rabbits

1 In this study, we have investigated the vasodilator response to acetylcholine under diabetes conditions in isolated renal arteries of rabbits. We have also examined the contribution of endothelium-derived nitric oxide (EDNO) and endothelium-derived hyperpolarizing factor (EDHF) to the endothelium-dependent relaxation caused by acetylcholine in the renal arteries of alloxan-induced diabetic rabbits. 2 Acetylcholine (10(-10) - 10(-4) M) produced cumulative concentration-response curve in the renal arteries of both control and diabetic rabbits. The EC50 values and maximal responses to acetylcholine were not significantly different relative to diabetic conditions. In order to isolate the EDHF component of acetylcholine-induced vasodilator response, L-nitro-methyl arginine ester (L-NAME, 10(-4) M) and indomethacin (10(-6) M) were added to the Krebs' solution throughout the experiment. Under these conditions, acetylcholine induced vasodilatation in the isolated renal arteries from both control and diabetic rabbits. The vasodilator response to acetylcholine was not affected under diabetic conditions. 3 Sodium nitroprusside (SNP)-induced relaxation was increased in the diabetic rabbits compared with the control animals. 4 Tetrabutyl ammonium (TBA, 0.5 mM) produced a significant reduction in acetylcholine-induced vasodilatation in both preparations from control and diabetic animals, consistent with involvement of K+ channels in mediating this response. Glibenclamide (1 microM) attenuated acetylcholine-induced vasodilatation in preparations from control animals only, while iberiotoxin (0.05 microM) significantly reduced the vasodilator response to acetylcholine in preparations from both control and diabetic animals. 5 The role of EDNO in mediating acetylcholine-induced vasodilatation was examined. The vascular preparations were incubated with 20 mM K(+)-Krebs' solution to inhibit the EDHF contribution to acetylcholine-induced vasodilatation. Under this condition, acetylcholine induced a vasodilator response in both preparations from control and diabetic rats. Pretreatment with L-NAME (10(-4) M) attenuated acetylcholine-induced vasodilatation in both preparations, indicating an nitric oxide-mediated vasodilator response. 6 Our results indicated that acetylcholine-induced vasodilatation in the isolated renal arteries of alloxan-induced diabetic rabbits was not affected under diabetic conditions. Acetylcholine-induced vasodilatation is mediated by two vasodilator components; namely, EDHF and EDNO. The contribution of EDHF and EDNO to acetylcholine-induced vasodilatation was not affected under diabetic conditions and there was no indication of endothelial dysfunction associated with diabetes. EDHF component was found to act mainly through high conductance Ca(2+)-activated K+ channels under normal and diabetic conditions, while the adenosine triphosphate-dependent K+ channels were involved in mediating acetylcholine vasodilator response in the control preparations only.     

Vernal keratoconjunctivitis and intestinal parasitic infestations in black children

The study aimed at finding out any association between vernal keratoconjunctivitis (VKC) and intestinal worm infestations in black children in Nigeria. This is a report of a case-control study of a total of 117 cases of VKC and 198 controls, who were newly presenting to two hospitals in Ibadan. The controls were comparable to the cases in many respects. While 67 (57%) of cases admitted to previous passage of worms, 59 (50.5%) children actually had parasitic infestations. Of these 59 children, 30 (51%) were due to roundworm, 12 (20%) to hookworm, 14 (24%) to protozoal infestation and others, e.g., tapeworms, 13 (5%). Among controls, 36.8% had parasitic infestation, out of which roundworms were responsible for 11.6%, hookworms 7.6%, protozoa 14.1% and others 3.5%. Children with VKC have almost twice (odds ratio = 1.68) the risk of having been infested by worms. Both older age in children and roundworm infestation were not independent risk factors for VKC. There was no significant association among all ages, sex, hookworm and other worms with VKC. Deworming may prove beneficial for children with VKC; however, more studies with appropriate design are required to prove this.