High ambient glucose concentration, linked to vascular complications in diabetes in vivo, modulates mRNA expression of fibronectin, collagen, tissue-type plasminogen activator, and plasminogen activator inhibitor and induces delayed replication and excess cell death in cultured vascular endothelial cells. To determine the role of high ambient glucose (30 mmol/l) in apoptosis, paired cultures of individual isolates of human umbilical vein endothelial cells (HUVECs) were exposed to both high (30 mmol/l) and low (5 mmol/l) concentrations of glucose for short-term (24, 48, and 72 h) and long-term (13 +/- 1 days) experiments. Incubation of HUVECs with high glucose for > 48 h increased DNA fragmentation (13.7 +/- 6.5% of total DNA, mean +/- SD) versus cultures kept in 5 mmol/l glucose (10.9 +/- 5.6%, P < 0.005), as measured by [3H]thymidine assays. Data were confirmed by apoptosis-specific fluorescence-activated cell sorter analysis of confluent HUVEC cultures, which displayed after long-term exposure to 30 mmol/l glucose a 1.5-fold higher prevalence of apoptosis than control cultures exposed to 5 mmol/l glucose (P < 0.005). In contrast, no increase in DNA fragmentation in response to 30 mmol/l glucose was seen for standardized cell lines (K 562, P 815, YT) and fibroblasts. Expression of clusterin mRNA, originally reported to be a molecular marker of apoptosis, was only slightly affected by short-term (24-h) high-glucose exposure but was significantly reduced after long-term incubation in 30 mmol/l glucose (82.2 +/- 13.8% of control) versus 5 mmol/l glucose, which questions the role of clusterin gene expression as a marker of apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased sclerostin serum levels in CKD patients are not due to decreased renal elimination. On the contrary, renal elimination increases with declining kidney function. Whether this has consequences on antisclerostin antibody dosing, efficacy, or safety in patients with CKD remains to be determined.
Autoimmune thyroiditis is mirrored by a hypoechoic ultrasound pattern. We determined diagnostic precision of thyroid sonography compared to that of anti-thyroid peroxidase antibody (TPOAb) concentration. Ambulatory patients with unknown thyroid status (n = 451; 407 female, ages 44 +/- 16 years; 45 male, ages 50 +/- 14 years) excluding those with suspected hyperthyroidism or on drugs known to cause hypothyroidism were recruited consecutively. Subjects were recruited from a specialized thyroid outpatient unit with higher frequencies of thyroid disorders than in the general population. Before determination of thyroid function and TPOAb concentration thyroid volume (normal values: women < 12 mL, men < 14 mL) and echogenicity (grade 1 = normal: similar to submandibular gland, hyperechoic to neck muscles; grade 2: hypoechoic to submandibular gland, hyperechoic to neck muscles, grade 3: iso-/hypoechoic to neck muscles) were determined. Positive predictive value of grade 3 pattern for detection of autoimmune thyroiditis was 94% (with overt hypothyroidism) and 96% (with any degree of hypothyroidism), that of grade 2 or 3 85% and 87%, respectively. Negative predictive value of grade 1 pattern for detection of euthyroid TPOAb negative subjects was 91%. Goiter was present in 31% and 21% of TPOAb postive and negative subjects, respectively, while 11% and 15% had an atrophic thyroid gland (p = not significant [n.s.]). Given a high intraobserver and interobserver agreement abnormal thyroid ultrasound patterns were highly indicative of autoimmune thyroiditis and allowed the detection of thyroid dysfunction with 96% probability.
Hyperthyroidism-induced vWF elevation is associated with enhanced platelet function and therefore shortened CEPI-CT values. These changes may contribute to the higher risk for cardiovascular disease in patients with hyperthyroidism. Platelet plug formation decreases during therapy with thiamazole. Furthermore, CEPI-CT appears to be sensitive to detect acquired von Willebrand disease associated with overt hypothyroidism.
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