Muscarinic supersensitivity in the rat urinary bladder after capsaicin pretreatment

The effects of capsaicin on urinary bladder function have been investigated in adult rats. Ten days after capsaicin treatment immunocytochemical investigations showed a nearly complete disappearance of substance P (SP) and calcitonin gene-related peptide (CGRP) in all parts of the bladder. Recordings of micturition patterns and cystometrical investigations in conscious animals revealed no functional effects of capsaicin treatment. In-vitro experiments showed that the contractile response to substance P was similar before and after capsaicin treatment and CGRP exerted no contractile effects on the urinary bladder in either group of rats. The concentration–response curve to carbachol as well as the frequency-response curve to electrical stimulation were significantly shifted to the left in bladder muscle after capsaicin treatment. However, the maximal responses were similar in control and capsaicin-treated bladders. In the presence of scopolamine the maximal response to electrical stimulation was clearly lower in bladders subjected to capsaicin treatment than in controls. In conclusion, depletion of substance P and CGRP in the rat urinary bladder by capsaicin induced no supersensitivity to these peptides. However, the increased sensitivity to carbachol and to electrical stimulation seen after capsaicin treatment indicates the development of a supersensitivity to muscarinic receptor stimulation. Despite this supersensitivity in vitro no functional effects of capsaicin treatment were found in vivo.     

Cortico-cortical mediation of short-latency (lemniscal) sensory input to the motor cortex in deeply pentobitone anaesthetized cats

In pentobarbitone-anaesthetized cats, responses were recorded as surface positive potentials in the motor cortex on forelimb and brachium conjunctivum stimulation. In such a preparation, the forelimb nerve responses are mediated via the spino-cervical tract and the dorsal column-lemniscal pathway. Lesions of the sensory cortex (sparing only the depth of the coronary sulcus) abolished or reduced short-latency peripheral responses, in the motor cortex, on both skin and muscle nerve stimulation to less than 10% of control, while brachium conjunctivum responses were unchanged. Lesions of the second somatosensory area alone reduced the motor cortex responses on peripheral nerve stimulation by 10–20%. When the sensory cortex were abolished before the spreading depression reached the recording point, as judged from the brachium conjunctivum response. The depth distribution of positive and negative field potentials, constituting the early componentsof a peripheral response in the motor cortex, closely resembled that of a cortico-cortical response evoked on stimulation in area 3. It differed from that of thalamo-cortical response evoked in brachium conjunctivum stimulation. These data suggest that most, if not all, sensory input through the dorsal column and spino-cervical tract to the motor cortex is mediatd via the sensory cortex.     

Secretion of γ-Interferon at the Cellular Level

Using a haemolytic plaque assay for gamma-interferon (IFN-gamma) secretion we found that in vitro Epstein-Barr virus (EBV) exposure of peripheral blood mononuclear cells from EBV immune individuals led to IFN-gamma secretion, which was apparent within 6 h after virus contact and peaked 12-24 h after induction. Live, ultraviolet-light-irradiated and heat-inactivated virions all caused IFN-gamma secretion. In contrast, blood mononuclear cells from EBV non-immune adults or neonates could not be activated to IFN-gamma production by EBV.     

Effects of some calcium antagonists on aggregation by adrenalin and serotonin and on α-adrenoceptor radioligand binding in human platelets

The inhibitory effects of verapamil, nifedipine and diltiazem, representatives of different classes of calcium antagonists, were studied on aggregation of human platelets induced by adrenalin and serotonin (5-HT). For references, the α-adrenoceptor-antagonists phentolamine (α₁ and α₂) and rauwolscine (α₂), and the s-HT₂-receptor-antagonist ketanserin were included. Verapamil in the concentration range 10^-6- 10^-4 M inhibited both adrenalin- and serotonin-induced aggregation in a concentration-dependent manner, whereas nifedipine and diltiazem had little or no effect. Phentolamine and rauwolscine were clearly weaker than verapamil as antagonists of serotonin, and ketanserin lacked effect on adrenalin-induced aggregation. Binding studies with [³H]dihydro-α-ergocryptine and [³H]rauwolscine on human platelet membranes showed equal numbers of binding sites, suggesting that only α₂-adrenoceptors were present. In the same concentration range as inhibition of aggregation was obtained, verapamil inhibited binding of either radioligand. Nifedipine, diltiazem and 5-HT were all poor inhibitors of radioligand binding. The results suggest that verapamil at high concentrations not only has α-adrenoceptor antagonistic properties but also exerts 5-HT-receptor blocking effects. This was not found with the other calcium channel blockers examined (nifedipine, diltiazem).     

Eosinophils, secretory responsiveness and glucocorticoid-induced effects on the nasal mucosa during a weak pollen season

This study examined the seasonal effects on eosinophils and secretory responsiveness of the nasal mucosa in 22 patients with allergic rhinitis due to birch pollen (11 patients received placebo and 11 budesonide, 200 micrograms once daily in each nostril). The pollen counts during the study season were too low to produce a significant symptomatology. Hence, our findings demonstrate threshold alterations of the airway mucosa in allergic rhinitis and their inhibition by anti-inflammatory drug intervention. The patients were monitored for 8 weeks with daily recordings of pollen counts and symptom scores. Once every week a series of laboratory tests was carried out: the local eosinophil influx was determined using a Rhinobrush technique; the levels of eosinophil cationic protein (ECP) were analysed in nasal lavage fluids; and the secretory response to intranasal methacholine was measured. Treatments started after a 2-week run-in period. The proportion of eosinophils increased markedly in the placebo group and was elevated also during the last two study weeks when the pollen counts were practically nil. The secretory responsiveness to methacholine increased during the pollen season and returned to baseline towards the end of the study period. The topical glucocorticoid treatment reduced the proportion of eosinophils, the ECP levels, and the secretory response to methacholine compared to placebo. We conclude that the increased traffic and activity of eosinophils and less conspicuously the increased secretory responsiveness are expressions of the mucosal inflammation that precede the development of symptoms in seasonal allergic rhinitis.     

Characterization of the prostanoid receptors and of the contractile effects of prostaglandin F2a in human pial arteries

The contractile and relaxant effects of various prostanoids were studied on isolated human pial arteries. Contractions were elicited with the following order of potency: U46619?U44069>PGB₂>PGF_2a>PGE₂?PGD₂>PGF_1a≥TXB₂, indicating that prostanoid-induced contractions probably are mediated by a thromboxane-sensitive receptor. Relaxation of PGF_2a-contracted arteries was induced with the order of potency: PGE₂> PGE₁>PGD₂?PGD₁. Vessels contrated by K⁺ were relaxed only by PGE,. Since PGI₂ was previously found to be more potent than all the prostanoids tested in the present study, relaxant responses are probably mediated via a PGI₂-sensitive receptor. The roles of free extracellular and cellularly bound calcium for the contractile effects of PGF_2a and K⁺ were estimated by incubating the arteries for various times in calcium-free medium containing 10^-5 M EGTA. Incubation for 5–10 min abolished K⁺-induced contractions, whereas after 40 min of incubation PGF_2a still induced contractions that reached 70% of control. The PGF_2a-induced contraction was biphasic in 8 out of 10 preparations. The second phase could be eliminated by increasing the EGTA-concentration to 10^-4 M, as well as by nifedipine pretreatment. In calcium-free, high K⁺ medium calcium-induced contractions were elicited at lower concentrations in the presence of PGF_2a. The results suggest that PGF_2a-induced contractions in human pial arteries are relatively independent of free extracellular calcium. PGF_2a may promote trans-membrane influx of calcium, as well as release calcium from seemingly superficially located cellular stores.     

Specialist paediatric dentistry in Sweden 2008 – a 25‐year perspective

International Journal of Paediatric Dentistry 2010; 20: 313–321 Background. Paediatric dentistry in Sweden has been surveyed four times over the past 25 years. During this period postgraduate training, dental health, and the organization of child dental care have changed considerably. Aim. To investigate services provided by specialists in paediatric dentistry in Sweden in 2008, and to compare with data from previous surveys. Design. The same questionnaire was sent to all 30 specialist paediatric dental clinics in Sweden that had been used in previous surveys. Comparisons were made with data from 1983, 1989, 1996 and 2003. Results. Despite an unchanged number of specialists (N = 81 in 2008), the number of referrals had increased by 16% since 2003 and by almost 50% since 1983. There was greater variation in reasons for referrals. The main reason was still dental anxiety/behaviour management problems in combination with dental treatment needs (27%), followed by medical conditions/disability (18%), and high caries activity (15%). The use of different techniques for conscious sedation as well as general anaesthesia had also increased. Conclusions. The referrals to paediatric dentistry continue to increase, leading to a heavy work load for the same number of specialists. Thus, the need for more paediatric dentists remains.     

Bleeding risk in ‘real world’ patients with atrial fibrillation: comparison of two established bleeding prediction schemes in a nationwide cohort

Summary. Background: Oral anticoagulation (OAC) in patients with atrial fibrillation (AF) is a double‐edged sword, because it decreases the risk of stroke at the cost of an increased risk of bleeding. We compared the performance of a new bleeding prediction scheme, HAS‐BLED, with an older bleeding prediction scheme, HEMORR₂HAGES, in a cohort of ‘real‐world’ AF patients. Methods: By individual‐level‐linkage of nationwide registers, we identified all patients (n = 118 584) discharged with non‐valvular AF in Denmark during the period 1997–2006, with and without OAC. Major bleeding rates during 1 year of follow‐up were determined, and the predictive capabilities of the two schemes were compared by c‐statistics. The risk of bleeding associated with individual risk factors composing HAS‐BLED was estimated using Cox proportional‐hazard analyses. Results: Of AF patients receiving OAC (n = 44 771), 34.8% and 47.3% were categorized as ‘low bleeding risk’ by HAS‐BLED and HEMORR₂HAGES, respectively, and the bleeding rates per 100 person‐years were 2.66 (95% confidence interval [CI], 2.40–2.94) and 3.06 (2.83–3.32), respectively. C‐statistics for the two schemes were 0.795 (0.759–0.829) and 0.771 (0.733–0.806), respectively. The risk factors composing HAS‐BLED were associated with varying risks, with a history of bleeding (hazard ratio [HR] 2.98; 95% CI 2.68–3.31) and being elderly (HR 1.93; 95% CI 1.71–2.18) being associated with the highest risks. Comparable results were found in AF patients not receiving OAC (n = 77 813). Conclusions: In an unselected nationwide cohort of hospitalized patients with atrial fibrillation, the HAS‐BLED score performs similarly to HEMORR₂HAGES in predicting bleeding risk but HAS‐BLED is much simpler and easier to use in everyday clinical practise.     

Heparin Cofactor II, Antithrombin and Protein C in Plasma from Term and Preterm Infants

ABSTRACT. The coagulation inhibitors heparin cofactor II (HCII), antithrombin (AT) and protein C (PC) were measured in healthy term and preterm infants in order to establish reference standards. The mean value for HCII in term infants was found to be about half of the adult values. Values below 25% in healthy infants may suggest hereditary deficiency states. One girl with congenital HC II deficiency was detected. Mean AT and PC levels were somewhat higher than HC II. Healthy preterm infants have significantly lower HC II and AT values than healthy term infants. Serial AT measurements have been used in monitoring seriously ill infants and used as a prognostic indicator. In a small number of unhealthy neonates HC II was reduced to an even greater extent than AT, and on recovery normalized more rapidly than AT.