Tissue chimerism analysis after donor lymphocyte infusion: a case of deceptive evidence

A 31-year-old female with refractory extramedullary myeloid leukemia relapse underwent peripheral blood stem-cell transplantation from her HLA-identical brother. Hematopoietic recovery followed disappearance of the lesions. Studies three-months post-transplant showed complete chimerism (CC). Fourteen months after transplantation, the patient presented with an increasing number of extramedullary sites of biopsy-proven disease relapse (as nodular skin lesions). Bone marrow was in remission with maintenance of CC. However, tissue chimerism analysis showed full recipient-cell population. After one course of conventional dose chemotherapy followed by mobilized donor-lymphocyte infusions (DLI), a complete response was achieved. DLI continued monthly but she developed new skin lesions accompanied by multiple cervical masses. Bone marrow and tissue chimerism revealed both recipient and donor cell population. We conclude that tissue chimerism analysis after DLI may not accurately document the cell origin.     

Ca(2+)-ATPase activity in streptozotocin-induced diabetic rat kidneys

Kidney Ca(2+)-ATPase activity was altered in streptozotocin (STZ)-induced diabetic rats. Male rats, 200-250 g, were rendered diabetic by injection of STZ 45 mg/kg body weight via the tail vein. Following injection, control rats and diabetic rats at 1, 4, 8 or 15 weeks were sacrificed. Kidney tissues were obtained for the isolation of Ca(2+)-ATPase. Ca(2+)-ATPase activity was determined spectrophotometrically. Total calcium was measured by atomic absorption spectrophotometry. Diabetic rats had significantly elevated blood glucose levels compared to controls. Blood glucose levels were 92.92 +/- 1.215 mg/dl (mean +/- S.E.M.) for the control group, and 362.50 +/- 9.613 mg/dl at one week and > 500 mg/dl at 4, 8 and 15 weeks of diabetes. Enzyme activities were significantly higher at 4, 8 and 15 weeks of diabetes than in the control group (p < 0.001). There was no significant increase at one week of diabetes. Ca(2+)-ATPase activity was 0.43 +/- 0.003 U/L, 0.517 +/- 0.058 U/L, 0.707 +/- 0.078 U/L, 0.730 +/- 0.006 U/L and 0.715 +/- 0.055 U/L respectively for controls and rats at 1, 4, 8 and 15 weeks of diabetes. Calcium levels in diabetic rat kidneys were also significantly higher than for controls. The increase in enzyme activity may have been caused by higher calcium levels in diabetic kidneys resulting from a compensatory response of the enzyme to high levels of the ion.     

Caffeine decreases exercise-induced myocardial flow reserve.

OBJECTIVES: We studied the acute effect of caffeine on myocardial blood flow (MBF) at rest and exercise in healthy volunteers at normoxia and during acute exposure to simulated altitude. BACKGROUND: Caffeine is a widely consumed stimulant, although its cardiovascular safety remains controversial and its effect on MBF is unknown. METHODS: 15O-labeled H2O and positron emission tomography (PET) were used to measure regional MBF at rest and immediately after supine bicycle exercise in healthy volunteers at normoxia (n = 10; mean workload, 175 W; 98% predicted; mean age, 27 +/- 6 years) as well as during hypoxia, simulating an altitude of 4,500 m by inhalation of a mixture of 12.5% oxygen (n = 8; 148 W; 78% predicted; mean age, 29 +/- 4 years). Measurements were repeated 50 min after oral ingestion of caffeine (200 mg). Myocardial flow reserve (MFR) was calculated as the ratio of hyperemic to resting MBF. RESULTS: Resting MBF was not affected by caffeine at normoxia (1.05 +/- 0.36 ml/min/g vs. 1.17 +/- 0.27 ml/min/g; p = NS), although it was significantly increased at hypoxia (1.71 +/- 0.41 ml/min/g vs. 2.22 +/- 0.49 ml/min/g; p < 0.001). By contrast, exercise-induced hyperemic MBF decreased significantly at normoxia (2.51 +/- 0.58 ml/min/g vs. 2.15 +/- 0.47 ml/min/g; p < 0.05) and hypoxia (5.15 +/- 0.79 ml/min/g vs. 3.98 +/- 0.83 ml/min/g; p < 0.005 vs. baseline; p < 0.005 vs. normoxia). The MFR decreased by 22% at normoxia (2.53 +/- 0.69 to 1.90 +/- 0.49; p < 0.01) and by 39% at hypoxia (3.13 +/- 0.60 to 1.87 +/- 0.45, p < 0.005; p < 0.05 vs. normoxia). CONCLUSIONS: In healthy volunteers, a caffeine dose corresponding to two cups of coffee (200 mg) significantly decreased exercise-induced MFR at normoxia and was even more pronounced during exposure to altitude.     

Factor V leiden is a risk factor for myocardial infarction in young Turkish men

OBJECTIVE: Factor V Leiden is the most common known hereditary abnormality of the clotting system which leads to a reduced anticoagulant effect of activated protein C (APC resistance). FactorV Leiden has been shown to be the most frequent inherited thrombophilic disorder in patients with idiopathic venous thromboembolism. The relationship between this genetic abnormality and myocardial infarction is still unresolved. The aim of this study was to investigate whether factor V Leiden is a risk factor for myocardial infarction in young Turkish men or not. METHODS AND RESULTS: We compared 42 patients who had a diagnosis of acute MI and were younger than 40 years (35.6+/-4.8 years) with 66 healthy, age and sex-matched control subjects. Blood samples from the patients and the controls were analysed for the factor V Leiden mutation by DNA analysis, using polimerase chain reaction. Factor V Leiden mutation was found in 10 of 42 (23.8%) patients with myocardial infarction and 6 of 66 (9%) control subjects (p < 0.001).The odds ratio for MI was 3.1. (CI 95% 1.0-8.9) CONCLUSION: The results of this study suggest that the presence of factorV Leiden increases the risk of Ml in young Turkish men. ( Acta Cardiol 2004; 59(6): 594-597)     

Cannabidiol,a Major Non‐Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts

Cannabinoid ligands regulate bone mass, but skeletal effects of cannabis (marijuana and hashish) have not been reported. Bone fractures are highly prevalent, involving prolonged immobilization and discomfort. Here we report that the major non‐psychoactive cannabis constituent, cannabidiol (CBD), enhances the biomechanical properties of healing rat mid‐femoral fractures. The maximal load and work‐to‐failure, but not the stiffness, of femurs from rats given a mixture of CBD and Δ⁹‐tetrahydrocannabinol (THC) for 8 weeks were markedly increased by CBD. This effect is not shared by THC (the psychoactive component of cannabis), but THC potentiates the CBD stimulated work‐to‐failure at 6 weeks postfracture followed by attenuation of the CBD effect at 8 weeks. Using micro–computed tomography (μCT), the fracture callus size was transiently reduced by either CBD or THC 4 weeks after fracture but reached control level after 6 and 8 weeks. The callus material density was unaffected by CBD and/or THC. By contrast, CBD stimulated mRNA expression of Plod1 in primary osteoblast cultures, encoding an enzyme that catalyzes lysine hydroxylation, which is in turn involved in collagen crosslinking and stabilization. Using Fourier transform infrared (FTIR) spectroscopy we confirmed the increase in collagen crosslink ratio by CBD, which is likely to contribute to the improved biomechanical properties of the fracture callus. Taken together, these data show that CBD leads to improvement in fracture healing and demonstrate the critical mechanical role of collagen crosslinking enzymes. © 2015 American Society for Bone and Mineral Research.     

Autoimmune hepatitis induced by the prolonged hepatitis A virus infection

Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis in the world. Rarely, acute infection may persist for a long time. Autoimmune hepatitis (AIH) may provide anti-HAV IgM positivity detection for a prolonged time. On the other hand, HAV as an infectious agent may also trigger AIH. Here we presented a case which seemed like a simple acute viral hepatitis A infection at the beginning but turned out to be an AIH according to the International Autoimmune Hepatitis Group's system. A 21-year-old female was diagnosed as symptomatic acute HAV infection with anti-HAV IgM positivity and elevated aminotransferase levels. The other viral serological tests were negative. On the 6th, 12th and 18th months of the follow up, her anti-HAV IgM positivity still continued and transaminase levels were also 3 to 7 times high of the upper limit of normal. In addition, antinuclear antibody was positive. However, on the 19th month anti-HAV IgM could be detected as negative. Liver histology was prominent. The patient had a score of 16 according to the International Autoimmune Hepatitis Group's system. She was given prednisolone (10 mg/day) and azathioprine (100 mg/day). The aminotransferase levels were detected within normal ranges at the end of the first month of therapy. She was in remission during follow up for 6 years. In conclusion, prolonged HAV infection and AIH may not only trigger each other but also deteriorate the liver histology. AIH should be investigated in cases of long-lasting HAV infection in order to begin the treatment earlier. On the other hand, AIH patients should also be vaccinated for both HBV and HAV to avoid more severe diseases.     

Aldosterone Blockage in Proliferative Glomerulonephritis Prevents Not Only Fibrosis,but Proliferation as Well

Studies performed recently have determined that aldosterone has not only a major role in electrolyte and water balance and K excretion, but it also modulates myofibroblast growth in the heart and blood vessels and causes fibrosis. This study investigated the effects of aldosterone blockers in rats with anti-thy 1.1 nephritis, both on proliferation and fibrosis, by comparing it to an angiotensin receptor inhibitor valsartan. Rats with anti-thy 1.1 nephritis were randomly allocated to one of the three following groups of treatment: the control group (group 1); those treated with the aldosterone receptor blocker spironolactone (group 2); and those treated with the ATRB valsartan (group 3). On day 7, the parameters of glomerular fibrosis [transforming growth factor beta, TGF staining areas %], proliferation (Ki-67), and renal damage scores were determined. The TGF-β and Ki-67 levels of control group were significantly more than the other two groups (p<0.01). The TGF staining areas percentages were significantly decreased compared to control group. The artery, glomerular, and renal injury scores evaluated between the groups were found to be significantly decreased compared to control group. In line with previous studies, this study found that in anti–thy 1.1 mesangioproliferative glomerulonephritis, aldosterone blockage affected proliferation and fibrosis.     

Effect of fabrication techniques on the optical properties of zirconia-based systems

Statement of problemHow the optical properties of zirconia restorations are affected by their differing processing techniques is unclear.PurposeThe purpose of this in vitro study was to evaluate the effects of 5 different fabrication techniques on the optical properties of zirconia-based systems, including the color difference between the corresponding shades (ΔE1_ab, ΔE₀₀), translucency parameter, opalescence parameter, and fluorescence (ΔE1_ab-FL).Material and methodsSixty zirconia disks (IPS e.max ZirCAD) were prepared (0.5 ±0.01mm thick) and veneered by using different techniques (n=15): Group L – layering with fluorapatite ceramic; Group P – pressing with fluorapatite ceramic; Group CB – veneered with pressing followed by layering technique; Group CO – digitally veneered with lithium disilicate glass-ceramic; and Group FZ – prepared from monolithic zirconia (inCoris TZI) (n=15). All the specimens were set to 1.5 ±0.02 mm in thickness. Color measurements were made with a spectrophotometer. Data were statistically analyzed with 1-way ANOVA and the Tukey honestly significant difference, Kruskal-Wallis, Bonferroni (α=.05), Pearson, and Spearman correlation tests (α=.01).ResultsSignificant differences were found among the groups for all the optical parameters (P<.05). All the groups showed color differences higher than the perceptibility and acceptability thresholds for ΔE1_ab and ΔE₀₀, except the P and FZ groups that showed values lower than the acceptability threshold (ΔE1_ab<2.7). Translucency parameter, opalescence parameter, and ΔE1_ab-FL values ranged between 5.77 and 9.95, between 4.72 and 7.07, and between 1.93 and 3.14, respectively. Strong positive correlations were found between ΔE1_ab and ΔE₀₀, as well as between translucency parameter and opalescence parameter (P<.001).ConclusionsThe optical properties of the zirconia-based systems were significantly affected by the fabrication techniques even when the same nominal shade was used. Therefore, the color reproduction, translucence, opalescence, and fluorescence of the selected materials should be considered for acceptable color matching.     

Depression in patients with euthyroid chronic autoimmune thyroiditis

Depression and chronic autoimmune thyroiditis are common diseases. The aim of this study was to determine whether the frequency of depression is elevated in patients with chronic autoimmune thyroiditis and normal thyroid function. A total of 201 subjects were included, of whom 107 and 94 participants were healthy or had euthyroid chronic autoimmune thyroiditis, respectively. Serum thyroid hormone levels and thyroid auto-antibodies were measured in all subjects. All participants were evaluated with Hamilton Depression Rating Scale (HDRS). HDRS scores of patients with euthyroid chronic autoimmune thyroiditis were higher than in healthy participants. This study suggests a possible association between depression and chronic autoimmune thyroiditis. The depression risk may be increased in patients with chronic autoimmune thyroiditis and normal thyroid function.