Effect of influenza A virus on leukocyte histamine release

Viral respiratory infections provoke asthma in many patients. In the following study we examined the effect of an in vitro incubation of influenza A on leukocyte histamine release. After incubation with a live influenza A (H3N2) virus, calcium ionophore A23187 (0.5, 1.0, and 1.5 microgram/ml)-induced leukocyte histamine release (HR) was enhanced (p less than 0.05). This effect was also found with heat- or ether-inactivated virus. Similarly, influenza A-exposed leukocytes had augmented leukocyte HR during subsequent incubation with ragweed AgE. Incubation of the leukocyte suspension with interferon (800 IU/ml) for 24 hr was also associated with enhanced HR to ragweed AgE. In contrast, interferon did not alter the calcium ionophore A23187 HR. Therefore, although interferon may mediate the enhanced leukocyte HR when ragweed AgE is the inciting stimulus, it does not change HR to the calcium ionophore.     

The radioimmunoassay of histamine release from circulating basophils in an in vitro study as support for the in vivo active systemic anaphylaxis test in the guinea pig

An in vitro anaphylaxis test is described which explores the ability of compound re-challenge to induce histamine release from polynuclear basophils in whole blood of guinea pigs that had previously been sensitised. This test is used in drug safety, in support of the in vivo active systemic anaphylaxis test, which is sometimes required by regulatory authorities, when the observed clinical signs are not conclusive. This sensitive and discriminative test is inexpensive and reduces animal utilisation.     

Allergoprints in Horse Allergic Children

In order to determine the allergenic activity of five purified horse allergens, 22 children allergic to horses according to history, skin test, and leukocyte histamine release were evaluated. Washed leukocytes from all patients were tested for allergen-induced histamine release utilizing four epidermal horse allergens (Ags 6, 9, 11 , and 15) and horse serum albumin. Crossed radioimmunoelectrophoresis was carried out with a standardized horse dander extract and serum from each patient.
The results showed considerable variation in the individual allergoprints. Ag 11 had the highest mean allergenic activity. Sensitivity to horse serum albumin was demonstrated three times. Our data show that the amount of serum IgE antibodies bound by horse allergens correlates significantly with the capacity of the allergens to induce histamine release from washed leukocytes.     

Pharmacokinetics of a novel oral slow-release form of misoprostol

BACKGROUND: The pharmacokinetics of a novel slow-release (SR) misoprostol was studied and compared to conventional misoprostol. METHODS: Thirty-one women, pregnant between 8 and 12 weeks, requesting surgical abortion were randomly allocated to receive orally 400 microg conventional misoprostol, 400 microg SR misoprostol or 800 microg SR misoprostol. Venous blood samples were taken at 0, 30, 60, 120, 240 and 360 min after the administration of misoprostol. Misoprostol acid (MPA) was determined in serum samples using liquid chromatography/tandem mass spectrometry. RESULTS: Serum peak concentration (Cmax) was highest for conventional oral misoprostol. The time to peak concentration (Tmax) was similar for all groups. The area under the curve up to 360 min was similar for conventional and for 800 microg SR misoprostol and significantly greater for these groups compared to 400 microg SR misoprostol (P = 0.013). CONCLUSION: The new SR form of misoprostol demonstrated lower peak levels but longer-lasting elevation in plasma levels compared to conventional oral misoprostol. The AUC for 800 microg SR misoprostol was similar to that of 400 microg of conventional oral misoprostol. SR misoprostol may offer an alternative to repeated administration of oral misoprostol or to vaginal administration.     

A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia

Eight mutations in the gene (the RYR1 gene) encoding the calcium release channel of sarcoplasmic reticulum (SR) in skeletal muscle are so far known to be very closely linked to malignant hyperthermia susceptibility in man and are regarded to be causative. We have examined 41 Swedish families where malignant hyperthermia had occurred in at least one member during anaesthesia, with respect to three of the known mutations. The mutations were Arg163Cys; Ile403Met and Arg614Cys (also known as the "pig mutation"). In three (i.e. 7%) of the families we detected the Arg614Cys mutation, and this was the only one of the mutations searched for that was observed. This indicates that other mutations than those searched for in this study must cause malignant hyperthermia susceptibility in most Swedish malignant hyperthermia susceptible families.     

Basophil histamine release and lymphocyte proliferation tests in latex contact urticaria

Basophil histamine release and lymphocyte proliferation tests were examined with latex allergen prepared from surgical gloves in 15 patients with latex contact urticaria. The basophil histamine release test (BHRT) yielded positive results in 13/14 (93%) patients, whereas commercial latex RAST was positive in only 9/15 (60%) patients. Lymphocyte proliferation test (LPT) was positive in 3/15 (20%) patients, suggesting that cell-mediated immune reactions may also occur in latex allergy. However, patch tests to latex were negative and neither were epidermal Langerhans cells able to present latex antigen to T lymphocytes in vitro.     

MDL 72222: a potent and highly selective antagonist at neuronal 5-hydroxytryptamine receptors

Summary The properties of MDL 72222 (1H,3,5H-tropan-3-yl-3,5-dichlorobenzoate), a novel compound with potent and selective blocking actions at certain excitatory 5-hydroxytryptamine (5-HT) receptors on mammalian peripheral neurones, are described.On the rabbit isolated heart, MDL 72222 was a potent antagonist of responses mediated through the receptors for 5-HT present on the terminal sympathetic fibres. The threshold for antagonism was approximately 0.1 nM and the negative logarithm of the molar concentration of MDL 72222 which reduced the chronotropic response of the isolated rabbit heart to twice an ED₅₀ of 5-HT to that of the ED₅₀ was 9.27. MDL 72222 was also highly selective since responses to the nicotine receptor agonist, dimethylphenylpiperazinum iodine (DMPP), were inhibited only at concentrations more than 1000 times those necessary to inhibit 5-HT.In the anaesthetised rat, MDL 72222 produced marked blockade of the Bezold-Jarisch effect of 5-HT. Again, inhibition was selective since much higher doses of MDL 72222 failed to alter the response to electrical stimulation of the efferent vagus nerves. In contrast, MDL 72222 proved only a weak and essentially non-selective antagonist of responses mediated by the 5-HT M-receptor present on the cholinergic nerves of the guinea-pig ileum.MDL 72222 does not block smooth muscle contractile responses elicited by oxytocin or mediated through 5-HT D-receptors, muscarinic or nicotinic cholinoceptors or histamine H₁-receptors except at relatively high concentrations. Similarly, in a number of radioligand binding assays carried out using brain tissue membranes, the displacing effects of MDL 72222 were absent or weak at sites identifying compounds with activity at ₁, ₂ or -adrenoceptors, 5-HT₁ or 5-HT₂ receptors, benzodiazepine receptors or histamine H₁-receptors.MDL 72222 is the first reported selective and potent antagonist of responses mediated through the 5-HT receptors present on the terminal sympathetic neurones of the rabbit heart and on the neurones subserving the afferent limb of the Bezold-Jarisch reflex. The compound should provide a useful means by which responses mediated through such sites can be distinguished.     

Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials

The meta-analysis was performed to assess the efficacy and safety of daily oral L-arginine and phosphodiesterase type 5 inhibitors (PDE5Is) alone or combination in treating patients with erectile dysfunction (ED). We performed a search of randomised controlled trials in the following databases: PubMed, EMBASE and Cochrane Library databases. Four articles including 373 patients were studied. Erectile functions were significantly improved in three therapy groups compared with baseline. Patients who received the combination of L-arginine and PDE5Is showed significant improvement compared to those treated with L-arginine and PDE5Is alone, as assessed by sexual function index (p <0.00001 and p =0.005, respectively) and total testosterone (p <0.00001 and p =0.0007, respectively). Furthermore, patients who treated with PDE5Is alone exhibited the better efficacy than those treated with L-arginine alone in respects of sexual function index (p <0.00001) and total testosterone (p =0.0001). However, the combination of L-arginine and PDE5Is had no obvious difference relative to PDE5Is alone in terms of various adverse events (AEs). Conclusively, compared with monotherapy, the combination of L-arginine and PDE5Is showed a greater improvement of sexual function and total testosterone, and did not significantly increase the AEs. Besides, PDE5Is alone revealed a better effect than those treated with L-arginine alone for patients with ED.     

A systematic review of reporting quality for anaesthetic interventions in randomised controlled trials

Interventions from randomised controlled trials can only be replicated if they are reported in sufficient detail. The results of trials can only be confidently interpreted if the delivery of the intervention was systematic and the protocol adhered to. We systematically reviewed trials of anaesthetic interventions published in 12 journals from January 2016 to September 2019. We assessed the detail with which interventions were reported, using the Consolidated Standards of Reporting Trials statement for non-pharmacological treatments. We analysed 162 interventions reported by 78 trials in 18,675 participants. Detail sufficiently precise to replicate the intervention was reported for 111 (69%) interventions. Intervention standardisation was reported for 135 (83%) out of the 162 interventions, and protocol adherence was reported for 20 (12%) interventions. Sixty (77%) out of the 78 trials reported the administrative context in which interventions were delivered and 36 (46%) trials detailed the expertise of the practitioners. We conclude that bespoke reporting tools should be developed for anaesthetic interventions and interventions in other areas such as critical care.