Reflexes in the shoulder muscles elicited from the human coracoacromial ligament.

Morphological studies have demonstrated mechanoreceptors in the capsuloligamentous structures of the shoulder joint, however knowledge of the role these joint receptors play in the control of shoulder stability is limited. We therefore investigated the effect of electrically induced afferent activity from mechanoreceptors in the coracoacromial ligament (CAL) on the activity of voluntary activated shoulder muscles in healthy humans. In study I, wire electrodes, for electrical stimulation, were inserted into the CAL in eight normal shoulders. In study II, a needle electrode was inserted into the CAL in seven normal shoulders. Electric activity was recorded from eight shoulder muscles by surface and intramuscular electrodes. During isometric contractions, electrical stimulation was applied to the CAL at two different stimulus intensities, a weak stimulus (stim-1) and a stronger stimulus (stim-2). In both experiments, electrical stimulation of the CAL elicited a general inhibition in the voluntary activated shoulder muscles. In study I the average latencies (mean+/-SE) of the muscular inhibition were 66+/-4 ms (stim-1) and 62+/-4 ms (stim-2) during isometric flexion and 73+/-3 ms (stim-1) and 73+/-5 ms (stim-2) during isometric extension. In study II the average latency (mean+/-SE) of the response was 66+/-4 ms (stim-1) during isometric flexion. Our results demonstrated a response, probably of reflex origin, from mechanoreceptors in the CAL to the shoulder muscles. The existence of this synaptic connection between mechanoreceptors in CAL and the shoulder muscles suggest a role of these receptors in muscle coordination and in the functional joint stability.     

Soluble serum Klotho levels in healthy subjects. Comparison of two different immunoassays

Objective

Soluble serum Klotho is a new biomarker linked to chronic kidney disease, cardiovascular disease and diabetes. This study describes the evaluation and comparison of two different immunoassays and establishment of assay specific reference intervals in adults.

Design and methods

Serum Klotho concentrations were determined in 120 healthy adults aged 19–66 years. Blood samples were collected, and stored sera were assayed for Klotho according to age and gender. In addition several other clinical and laboratory characteristics were determined in the cohort and compared to the levels of serum Klotho.

Results

Serum Klotho levels were significantly higher in time-resolved fluorescence immunoassay (TRF) compared to an ELISA (IBL) and no correlation was found between the assays. No signal was obtained in either assay when the standard curve was switched between the two different immunoassays. The median serum Klotho concentration using TRF was 61 ng/mL (2.5–97.5% reference limits; 11–181 ng/mL) for males and 99 ng/mL (2.5–97.5% reference limits; 19–316 ng/mL) for females while the ELISA gave a mean value of 472 pg/mL (2.5–97.5% reference limits; 204–741 pg/mL) with no difference between genders. Concentrations of serum Klotho were independently associated with estimated glomerular filtration rate (eGFR) and body weight using TRF whereas serum Klotho concentrations were associated with age using the ELISA.

Conclusion

Comparison of two different immunoassays for serum Klotho indicate, that the protein exists in human beings in different forms which may function as independent factors and whose role and potential value as biomarkers needs to be evaluated separately. Reference intervals specific for the different forms recognized by the different assays were calculated in this study.     

Flow‐mediated vasodilatation: variation and interrelationships with plasma lipids and lipoproteins

Objective. Endothelial dysfunction is a critical, prerequisite step in atherosclerosis, and may be evaluated by flow‐mediated vasodilatation (FMD). The objective of this study was to examine interrelationships between FMD and plasma lipids and lipoproteins, and to determine the between‐operator and within‐subject variability associated with this technique. Material and methods. FMD, plasma lipids and lipoproteins, including small dense LDL (sdLDL), were measured twice in 40 healthy volunteers, 4 weeks apart. Interrelationships between mean FMD responses and plasma lipids and lipoproteins were examined by correlation analysis. FMD measurements were taken by two independent operators, allowing determination of between‐operator variability. Within‐subject variability was determined by obtaining two measurements, 4 weeks apart, in every subject, and carried out by the same operator. Results. FMD was inversely related to plasma triglycerides (r = ?0.47, p = 0.002), total cholesterol/HDL cholesterol (r = ?0.35, p = 0.03) and apolipoprotein B (r = ?0.36, p = 0.02), but not to other plasma lipids and lipoproteins. When measuring variation in FMD, the following results were found: Between operators (SD = 4.0?FMD%) and within subjects (SD = 2.9?FMD%). Conclusions. The associations between FMD, plasma triglycerides and apoB provide evidence supporting a role for triglyceride‐rich lipoproteins in endothelial dysfunction.     

Exploring Vulnerability to Suicide in the Developmental History of Young Men: A Psychological Autopsy Study

This study explores the developmental history of ten young men who completed suicide in the transition to adulthood. The young men, aged 18–30, had no previous history of suicide attempts or treatment in mental health. In-depth interviews with four to eight informants for each suicide were analyzed using Interpretative Phenomenological Analysis. Three developmental issues from early age onwards emerged: (a) unsuccessful in becoming independent; (b) weakened competence to deal with shame; and (c) trapped in anger. The capacity to regulate emotions like shame and anger could make certain men vulnerable to suicide when facing adult challenges and defeats.     

Exercise-induced regulation of phospholemman (FXYD1) in rat skeletal muscle: implications for Na+/K+-ATPase activity

Background: Na⁺/K⁺‐ATPase activity is upregulated during muscle exercise to maintain ionic homeostasis. One mechanism may involve movement of α‐subunits to the outer membrane (translocation). Aim: We investigated the existence of exercise‐induced translocation and phosphorylation of phospholemman (PLM, FXYD1) protein in rat skeletal muscle and exercise‐induced changes in V_max and K_m for Na⁺ of the Na⁺/K⁺‐ATPase. Methods: Two membrane fractionation methods and immunoprecipitation were used. Results: Both fractionation methods revealed a 200–350% increase in PLM in the sarcolemma after 30 min of treadmill running, while the phosphorylation of Ser‐68 of PLM appeared to be unchanged. Exercise did not change V_max or K_m for Na⁺ of the Na⁺/K⁺‐ATPase in muscle homogenate, but induced a 67% increase in V_max in the sarcolemmal giant vesicle preparation; K_m for Na⁺ remained constant. The main part of the increase in V_max is related to a 36–53% increase in the level of α‐subunits; the remainder may be related to increased PLM content. Similar results were obtained with another membrane purification method. In resting muscle, 29% and 32% of α₁‐ and α₂‐subunits, respectively, were co‐immunoprecipitated by PLM antibodies. In muscle homogenate prepared after exercise, immunoprecipitation of α₁‐subunits was increased to 227%, whereas the fraction of precipitated α₂ remained constant. Conclusion: Exercise translocates PLM to the muscle outer membrane and increases its association with mainly the α₁‐subunit, which may contribute to the increased V_max of the Na⁺/K⁺‐ATPase.     

Association of a dopamine beta-hydroxylase gene variant with depression in elderly women possibly reflecting noradrenergic dysfunction

BACKGROUND: Depression has a multifactorial etiology which involves genetic factors and comorbid diseases. METHODS: A cross-sectional sample of 1371 elderly women (mean age=69.2 years) was examined. Detailed information on their health was obtained. Cognitive functions were assessed by the Short Blessed Test and the Animal Naming Task. A 19 bp insertion/deletion polymorphism in the dopamine beta-hydroxylase (DBH) gene, the apolipoprotein (APOE) epsilon2/epsilon3/epsilon4 variation and 5-HTTLPR in the serotonin transporter gene were genotyped. RESULTS: Depression was univariately associated with homozygosity for the DBH gene 19 bp deletion allele (odds ratio [OR]=1.96, 95% confidence intervals [95% CI]=1.17-3.29, p=0.01), family history of depression (OR=3.86, 95% CI=1.85-8.06, p=0.0003), a composite measure of cardiovascular diseases (OR=1.96, 95% CI=1.11-3.47, p=0.02), cognitive impairment assessed by the Short Blessed Test (OR=3.88, 95% CI=1.29-11.64, p=0.02) and performance on the Animal Naming Task (OR=0.74, 95% CI=0.59-0.93, p=0.01). The strength of the association of DBH genotype with depression essentially remained unchanged after correction for other variables in a multivariate model. This association may reflect noradrenaline dysfunction in the brain.     

Hemolysin of uropathogenic Escherichia coli evokes extensive shedding of the uroepithelium and hemorrhage in bladder tissue within the first 24 hours after intraurethral inoculation of mice

Many uropathogenic Escherichia coli (UPEC) strains produce both hemolysin (Hly) and cytotoxic necrotizing factor type 1 (CNF1), and the loci for these toxins are often linked. The conclusion that Hly and CNF1 contribute to urovirulence is supported by the results of epidemiological studies associating the severity of urinary tract infections (UTIs) with toxin production by UPEC isolates. Additionally, we previously reported that mouse bladders and rat prostates infected with UPEC strain CP9 exhibit a more profound inflammatory response than the organs from animals challenged with CP9cnf(1) and that CNF1 decreases the antimicrobial activities of polymorphonuclear leukocytes. More recently, we created an Hly mutant, CP9Delta hlyA(1)::cat, and showed that it was less hemolytic and destructive for cultured bladder cells than CP9 was. Here we evaluated the relative effects of mutations in hlyA(1) or cnf(1) alone or together on the pathogenicity of CP9 in a mouse model of ascending UTI. To do this, we constructed an hlyA(1)-complemented clone of CP9Delta hlyA(1)::cat and an hlyA(1) cnf(1) CP9 double mutant. We found that Hly had no influence on bacterial colonization of the bladder or kidneys in single or mixed infections with the wild type and CP9Delta hlyA(1)::cat but that it did provoke sloughing of the uroepithelium and bladder hemorrhage within the first 24 h after challenge. Finally, we confirmed that CNF1 expression induces bladder inflammation and, in particular, as shown in this study, submucosal edema. From these data, we speculate that Hly and CNF1 may be largely responsible for the signs and symptoms of cystitis in humans infected with toxigenic UPEC.