Markers of endothelial dysfunction and low-grade inflammation are associated in the offspring of type 2 diabetic subjects

The offspring of type 2 diabetic patients are at elevated risk for type 2 diabetes and cardiovascular disease. The aim of our study was to characterize the role of various biomarkers of endothelial activation in a cohort of offspring of type 2 diabetic subjects and to assess the association of adhesion molecules with inflammatory markers and metabolic parameters. Cytokine and adhesion molecule levels were measured in 19 healthy subjects and in 129 offspring of patients with type 2 diabetes (109 with normal glucose tolerance and 20 with impaired glucose tolerance). Insulin sensitivity was determined with the hyperinsulinemic-euglycemic clamp, insulin secretion with the intravenous glucose tolerance test, and abdominal fat distribution with computed tomography. The levels of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-Selectin and vascular adhesion protein-1 were not increased in offspring of type 2 diabetic subjects, but they correlated with inflammatory markers (C-reactive protein, tumor necrosis-alpha, interleukin-6, interleukin-1 beta, interleukin-1 receptor antagonist, interleukin-8, interleukin-10 and interleukin-18). In conclusion, the levels of adhesion molecules were not elevated in the prediabetic state. Inflammatory markers and adhesion molecules were correlated suggesting that low-grade inflammation may precede the elevation of levels of adhesion molecules.     

Neurotrophins in chronic cough: association with asthma but not with cough severity

Background and Aims: Chronic cough is associated with an enhanced excitability of airway cough receptors, possibly due to action of neurotrophins. The present study aimed to compare the neurotrophin levels between healthy subjects and patients with chronic cough and to analyze the factors associated with these levels. Methods: Serum and sputum levels of nerve growth factor (NGF), serum levels of brain‐derived neurotrophic factor (BDNF), and neurotrophin‐3 (NT‐3) were analyzed by enzyme immunoassay in 19 healthy subjects and 47 patients with chronic cough. In addition, cough sensitivity to hypertonic saline was assessed, cough diary was kept, Leicester Cough Questionnaire was filled in, peak flow was monitored and spirometry, skin prick tests, exhaled nitric oxide measurement and histamine challenge were performed. Results: The NGF levels did not differ between the healthy subjects and the patients with chronic cough and were not associated with any index describing cough severity. However, these levels in both serum (P = 0.01) and sputum (P = 0.025) samples were associated with asthma. There was a statistically significant association between serum and sputum NGF levels (R = 0.45, P = 0.026). The serum BDNF levels did not differ between the groups and were not associated with any of the background characteristics. The serum NT‐3 levels were below the detection limit in most subjects and therefore these data were not analyzed. Conclusions: Neither chronic cough nor its severity is associated with abnormal neurotrophin levels. High NGF levels among some patients with chronic cough may indicate a presence of asthma. Please cite this paper as: Koskela HO, Purokivi MK and Romppanen J. Neurotrophins in chronic cough: association with asthma but not with cough severity. The Clinical Respiratory Journal 2009; DOI:10.1111/j.1752‐699X.2009.00143.x.     

Division of the hepatic branch of the anterior vagus nerve in fundoplication: effects on gallbladder function

Background

Cutting the hepatic branch of the anterior vagus nerve makes laparoscopic fundoplication technically easier; however, there is little data about the effect of cutting the nerve on gallbladder function.

Methods

One surgeon (MPä) preserved this nerve until March 2001 when he changed the technique. We investigated patients consecutively operated on before and after this date. A symptom questionnaire was returned by 59 patients, of whom 19 in both groups were successfully further investigated. The follow-up varied from 4 to 9 years postoperatively. The volume of the gallbladder was measured by ultrasonography before and after a fatty test meal. Alkaline phosphatase (ALP), alanine aminotransferase (ALAT), bilirubin, and amylase were determined from plasma.

Results

There was no difference in symptoms or use of antireflux medication between the groups. No difference was found in the levels of bilirubin, ALAT, or ALP. A mild elevation in plasma amylase was noted after nerve division (p = 0.041). The gallbladder ejection fraction did not differ between groups, but the fasting gallbladder volume was smaller when the nerve was cut (median 18.1 (range, 6–57.7) ml versus median 23.2 (range, 7.9–66.7) ml; p = 0.049). Both differences in plasma amylase and gallbladder fasting volume were clearer in male patients.

Conclusions

Cutting the hepatic branch of the anterior vagus nerve during fundoplication may reduce the size of gallbladder, but it has no effect on the ejection fraction. No clinical significance has been noted to date. Prospective trials will be necessary to confirm these findings.     

Repeatability of a computerized muscle tonometer and the effect of tissue thickness on the estimation of muscle tone

The aim of the present study was to assess the intrarater repeatability of the computerized muscle tonometer (CMT), which is a computer-driven device designed to measure and register the tone of connective tissues. The second aim was to evaluate the effect of muscle thickness on results and repeatability as well as sensitivity, which was done by comparison to a mechanical hand-held tonometer (HHT). Participants were ten healthy male volunteers. The thickness of soft tissues was measured with ultrasound and the CMT was used to evaluate the muscle tone of thigh muscles 10, 15 and 20 cm and the HHT 15 cm above the patella on both sides. Great individual variability in muscle thickness and tone was noted. Muscle thickness increased proximally on the thigh and thus the mean distance travelled by the indenter of the CMT also increased from distal to proximal from 22 to 26 mm and the work done increased from 116 to 161 mJ. Intraclass correlation (ICC) for travel and work ranged from 0.85 to 0.92 and 0.94 to 0.98, respectively. Repeatability coefficients increased somewhat at proximal measurement sites. ICC for the HHT was 0.78. The CMT also showed a considerably higher range of results, indicating greater resolution power. Despite the twofold pressure used with the HHT the distance measured was on average 60% lower compared to the CMT. In conclusion, the repeatability of the CMT was found to be good. Muscle thickness greatly affected the results and should therefore be taken into consideration when measuring muscle tone. Work was a more reliable unit of measurement than travel, which has been commonly used to describe muscle tone.     

Association of depressive symptoms with impaired glucose regulation, screen-detected, and previously known type 2 diabetes: findings from the Finnish D2D Survey

OBJECTIVE

To study the association between impaired glucose regulation (IGR), screen-detected type 2 diabetes, and previously known diabetes and depressive symptoms.

RESEARCH DESIGN AND METHODS

Altogether, 2,712 participants from three hospital districts in Finland attended a health examination. Cutoff scores ≥10 and ≥16 in the 21-item Beck Depression Inventory (BDI-21) were used for depressive symptoms. The participants were defined as having known diabetes if they reported diabetes. An oral glucose tolerance test was used to detect normal glucose regulation (NGR), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and screen-detected diabetes. The participants were defined as having IGR if they had IFG or IGT.

RESULTS

Prevalence of depressive symptoms, defined as a BDI-21 cutoff score ≥10, was 14.4% for those with NGR, 13.7% for those with IGR, 14.8% for those with screen-detected diabetes, and 26.4% for those with previously known diabetes. The corresponding prevalences for a cutoff score ≥16 were 3.4, 3.4, 4.2, and 7.5%, respectively. Compared with NGR and adjusted for demographic, lifestyle, and biological factors, the odds ratios for IGR, screen-detected diabetes, and previously known diabetes were 0.91 (95% CI 0.69–1.20), 0.70 (0.45–1.08), and 1.35 (0.84–2.15), respectively, for a cutoff score ≥10. For a cutoff score ≥16, the corresponding odds ratios were 1.05 (0.62–1.76), 0.87 (0.40–1.90), and 1.56 (0.69–3.50), respectively.

CONCLUSIONS

Participants with diagnosed diabetes had a higher prevalence of depressive symptoms than participants with NGR, IGR, and previously unknown diabetes. When potential confounding factors were included in the analysis, previously known diabetes was not significantly associated with depressive symptoms.It is widely recognized that depression is more common among people with diabetes than in the general population (1). However, previous studies (2–10) that have assessed the relationship between depressive symptoms and impaired glucose tolerance (IGT) or diabetes have been inconsistent. A German study (4) that included 4,597 subjects and a Dutch study (2) that included 4,747 participants found no association between type 2 diabetes and depressive symptoms. In a general-practice setting study that included 2,849 male and 3,160 female subjects, depression was not more prevalent in people with screen-detected diabetes or impaired glucose regulation (IGR) than in people with normal glucose regulation (NGR) (5). Contrary to these studies, within the Hertfordshire Cohort Study (6) there was a relationship between depression scores and diagnosed and previously undiagnosed diabetes. A U.S. study (8) including 4,293 U.S. veterans indicated that men with undiagnosed type 2 diabetes had nearly double the odds of major depression compared with those with normal fasting glucose.In 1992, it was stated about the relationship between depression and diabetes that “the etiology is unknown but is probably complex; and biological, genetic, and psychological factors remain as potential contributors. Several neuroendocrine and neurotransmitter abnormalities common to both depression and diabetes have been identified, adding to etiological speculations” (11). It has been suggested that stress-induced activation of the hypothalamic-pituitary-adrenal axis may result in the development of metabolic abnormalities and depression (12). In addition, possible neuroendocrine abnormalities associated with both diabetes and depressive symptoms may include abnormalities in vitamin B₁₂ and sex hormone–binding globulin (SHBG) levels. Low vitamin B₁₂ levels have been found to relate to type 2 diabetes (13) and depressive symptoms (14–16). Low levels of SHBG may predict diabetes (17). SHBG binds circulating sex hormones, which have been suggested to be associated with depressive symptoms (18). In addition to these biological factors, the observed association between diabetes and depressive symptoms could be a reflection of the burden of diabetes and comorbidities.In the present study, our aim was to analyze the prevalence of depressive symptoms in people with NGR, IGR (including impaired fasting glycemia and impaired glucose tolerance), screen-detected (previously unknown) diabetes, and previously known type 2 diabetes. Furthermore, our aim was to study the association between glucose tolerance and depressive symptoms, taking into account potential confounding demographic and biological factors as well as comorbidity.     

Emotional Eating and Eating Disorder Psychopathology

The study examined to what extent emotional eating, restrained eating, and bulimic tendencies are found together in naturally occurring groups, and whether these groups differ in terms of the psychological characteristics relevant to eating disorders. One hundred twenty-seven normal-weight women filled in The Dutch Eating Behavior Questionnaire, The Eating Attitudes Test, The Eating Disorder Inventory, and five measures of psychological well-being. Cluster analysis revealed three dieter subgroups (Normal Dieters, Emotional Dieters, and Bulimic Dieters) and one nondieter group. The results showed that only some restrained eaters were emotional eaters and that only some emotional eaters had bulimic tendencies. In addition, emotional and bulimic dieters differed from nondieters more strikingly in terms of eating disorder psychopathology and low psychological well-being than normal dieters did. The results suggest that emotional eating is not responsible for overeating only but may, in concert with chronic dieting, also relate to the general psychopathology found to underlie eating disorders.     

Altered expression of collagen XVII in ameloblastomas and basal cell carcinomas

BACKGROUND: Collagen XVII (BP180) is an epithelial transmembrane protein, which presumably plays a role in cell migration and differentiation under both physiological and pathological conditions. Ameloblastoma, the most common odontogenic neoplasm, and basal cell carcinoma (BCC) of the skin exhibit similar growth patterns and share histological features. METHODS: Here, we examined the distribution and expression of collagen XVII in ameloblastomas and BCCs using immunohistochemistry and non-radioactive in situ hybridization. In both tumors, the distribution of collagen XVII varied in different parts of the lesions. RESULTS: In ameloblastomas, immunostaining for collagen XVII was usually localized in the basal and suprabasal cells of the tumor nests, although in some tumors, a diffuse intracellular staining was detected in the central cells of the neoplastic islands. In BCCs, collagen XVII was mostly seen as diffuse cytoplasmic staining in some central and peripheral cells of the tumor islands and also at the cell membranes in the basal keratinocytes of the epidermis overlying the tumor nests. Double immunostaining with antibody against gamma2 chain of laminin-5 showed that these two components of the keratinocyte adhesion complex are usually co-localized in ameloblastomas and BCCs. In both tumors, collagen XVII mRNA was found in the basal epithelial cells and in some central and peripheral cells of the tumor islands, while the stromal cells were negative. CONCLUSIONS: These findings indicate that the expression of collagen XVII may be differentially regulated in various parts of the tumor. Diffuse intracellular distribution of collagen XVII and a consequent loss of critical cellular attachments may contribute to the infiltrative and progressive growing potential of tumors.