Alpha-adrenoceptors, 5-hydroxytryptamine receptors and the action of dihydroergotamine in human venous preparations obtained during saphenectomy procedures for varicose veins

Summary Changes in tension were monitored isometrically on spiral strips from human saphenous veins obtained during surgical removal of varicose veins. Concentration-response curves for noradrenaline and 5-hydroxytryptamine (5-HT) were established by cumulative administrations, curves for dihydroergotamine were constructed from the mean responses to single concentrations. The use of the antagonists prazosin, yohimbine and pizotifen provided evidence for the existence of both postjunctional ₁- and ₂-adrenoceptors and for the existence of 5-HT receptors. The venoconstrictor effects of dihydroergotamine were unchanged by prazosin. Yohimbine antagonized both dihydroergotamine and 5-HT at about 60 times higher concentrations than required against noradrenaline whereas pizotifen inhibited responses to both dihydroergotamine and 5-HT at about 100 times lower concentrations than those to noradrenaline.These new results are in contrast to conclusions drawn from animal studies and do not support the suggestion that in man the venoconstrictor activity of dihydroergotamine is mediated through stimulation of -adrenoceptors. The present results strongly suggest that in human saphenous veins the constrictor activity of dihydroergotamine is mediated at least in part through stimulation of 5-HT receptors.     

Tissue specific susceptibility of alpha-adrenoceptor mediated vasoconstriction to nifedipine

Summary The influence of the calcium antagonist nifedipine on ₁- and ₁-adrenoceptor vasoconstrictor effects was investigated in vitro. Changes in tension were monitored isometrically on helical strips of canine circumflex coronary and saphenous arteries suspended in 10 ml organ baths and of saphenous veins superfused with Krebs-Henseleit solution. Distinction between ₁- and ₂-adrenoceptor was made by using selective -adrenoceptor blocking drugs such as rauwolscine, yohimbine, corynanthine and prazosin, and the agonists noradrenaline, phenylephrine and guanfacine. In venous and both arterial vascular smooth muscles, the contractile process could be triggered by stimulation of both ₁- and ₂-like adrenoceptors. Nifedipine inhibited the venoconstrictor response to the ₂-agonist guanfacine, leaving that to the ₁-agonist phenylephrine unchanged. In saphenous arteries, nifedipine in addition to guanfacine also antagonized constrictor responses to phenylephrine, though to a significantly weaker extent. In circumflex coronary arteries, nifedipine was equally potent in antagonizing responses to both ₁- and ₂-adrenoceptor stimulation.It is suggested that the susceptibility of -adrenoceptormediated vasoconstrictor effects to blockade by calcium antagonists depends not only on the subtype of -adrenoceptor but, in addition, on the type and origin of vascular smooth muscle and may be a reflection of tissue variations in intracellular calcium stores.     

Kidney Function and Plasma Copeptin Levels in Healthy Kidney Donors and Autosomal Dominant Polycystic Kidney Disease Patients

Background and objectives

Plasma copeptin, a marker of arginine vasopressin, is elevated in patients with autosomal dominant polycystic kidney disease and predicts disease progression. It is unknown whether elevated copeptin levels result from decreased kidney clearance or as compensation for impaired concentrating capacity. Data from patients with autosomal dominant polycystic kidney disease and healthy kidney donors before and after donation were used, because after donation, overall GFR decreases with a functionally normal kidney.

Design, setting, participants, & measurements

Data were obtained between October of 2008 and January of 2012 from healthy kidney donors who visited the institution for routine measurements predonation and postdonation and patients with autosomal dominant polycystic kidney disease who visited the institution for kidney function measurement. Plasma copeptin levels were measured using a sandwich immunoassay, GFR was measured as ¹²⁵I-iothalamate clearance, and urine concentrating capacity was measured as urine-to-plasma ratio of urea. In patients with autosomal dominant polycystic kidney disease, total kidney volume was measured with magnetic resonance imaging.

Results

Patients with autosomal dominant polycystic kidney disease (n=122, age=40 years, men=56%) had significantly higher copeptin levels (median=6.8 pmol/L; interquartile range=3.4–15.7 pmol/L) compared with donors (n=134, age=52 years, men=49%) both predonation and postdonation (median=3.8 pmol/L; interquartile range=2.8–6.3 pmol/L; P<0.001; median=4.4 pmol/L; interquartile range=3.6–6.1 pmol/L; P<0.001). In donors, copeptin levels did not change after donation, despite a significant fall in GFR (from 105±17 to 66±10; P<0.001). Copeptin and GFR were significantly associated in patients with autosomal dominant polycystic kidney disease (β=−0.45, P<0.001) but not in donors. In patients with autosomal dominant polycystic kidney disease, GFR and total kidney volume were both associated significantly with urine-to-plasma ratio of urea (β=0.84, P<0.001; β=−0.51, P<0.001, respectively).

Conclusions

On the basis of the finding in donors that kidney clearance is not a main determinant of plasma copeptin levels, it was hypothesized that, in patients with autosomal dominant polycystic kidney disease, kidney damage and associated impaired urine concentration capacity determine copeptin levels.     

Trefoil factors in inflammatory bowel disease

Inflammatory bowel disease(IBD),which comprises ulcerative colitis and Crohn’s disease,is characterized by inflammation of the gastrointestinal tract.The trefoil factors 1,2,and 3(TFF1-3)are a family of peptides that play important roles in the protection and repair of epithelial surfaces,including the gastrointestinal tract.TFFs may be involved in IBD pathogenesis and are a potential treatment option.In the present review,we describe the TFF family and their potential role in IBD by summarizing the current knowledge of their expression,possible function and pharmacological role in IBD.     

Does anxiety predict the use of urgent care by people with long term conditions? A systematic review with meta-analysis

Objective

The role of anxiety in the use of urgent care in people with long term conditions is not fully understood. A systematic review was conducted with meta-analysis to examine the relationship between anxiety and future use of urgent healthcare among individuals with one of four long term conditions: diabetes; coronary heart disease, chronic obstructive pulmonary disease and asthma.

Methods

Electronic searches of MEDLINE, EMBASE, PSYCINFO, CINAHL, the British Nursing Library and the Cochrane Library were conducted These searches were supplemented by hand-searching bibliographies, citation tracing eligible studies and asking experts within the field about relevant studies. Studies were eligible for inclusion if they: a) used a standardised measure of anxiety, b) used prospective cohort design, c) included adult patients diagnosed with coronary heart disease (CHD), asthma, diabetes or chronic obstructive pulmonary disease (COPD), d) assessed urgent healthcare use prospectively. Data regarding participants, methodology, and association between anxiety and urgent care use was extracted from studies eligible for inclusion. Odds ratios were calculated for each study and pooled using random effects models.

Results

8 independent studies were identified for inclusion in the meta-analysis, with a total of 28,823 individual patients. Pooled effects indicate that anxiety is not associated with an increase in the use of urgent care (OR = 1.078, p = 0.476), regardless of the type of service, or type of medical condition.

Conclusions

Anxiety is not associated with increased use of urgent care. This finding is in contrast to similar studies which have investigated the role of depression as a risk factor for use of urgent care.     

Drawings Reflect a New Dimension of the Psychological Impact of Long-Term Remission of Cushing's Syndrome

Context and Objective: Drawings can be used to assess perceptions of patients about their disease. We aimed to explore the utility of the drawing test and its relation to illness perceptions, quality of life (QoL), and clinical disease severity in patients after long-term remission of Cushing's syndrome. Design and Subjects: We conducted a cross-sectional study including 47 patients with long-term remission of Cushing's syndrome. Patients completed the drawing test, the Illness Perception Questionnaire-Revised, the Short-Form 36, the EuroQoL-5D, and the Cushing QoL. The Cushing's syndrome severity index was scored based on medical records. Results: Characteristics of the drawings were strongly associated with the Cushing's syndrome severity index and severity ratings of health professionals (all P < 0.02). In addition, patients perceived a dramatic change in body size during the active state of the disease compared to the healthy state before disease. Patients reported that their body does not completely return to the original size (i.e. before disease) after treatment. There were no clear associations between characteristics of the drawings and QoL or illness perceptions. This indicates that drawings and QoL or illness perceptions do not share multiple common properties and measure different aspects/dimensions of the disease process. Conclusion: Drawings reflect a new dimension of the psychological impact of long-term remission of Cushing's syndrome because drawings do not share common properties with parameters of QoL or illness perceptions, but do represent the clinical severity of the disease. The assessment of drawings may enable doctors to appreciate the perceptions of patients with long-term remission of Cushing's syndrome and will lead the way in dispelling idiosyncratic beliefs.