Distribution of leucine-enkephalin in bone and joint tissues

The distribution and concentration of leu-enkephalin in periosteum, cortical bone, bone marrow and synovial membrane of normal rats were analysed. Periosteum, cortical bone and bone marrow of the rat femurs were collected as well as the ankles. The distribution of leu-enkephalin was analysed by immunoelectron microscopy and the concentration of leu-enkephalin was measured with radioimmunoassay. Immunoelectron microscopy showed that leu-enkephalin is abundant in monocytes of bone marrow, nerve fibers and endothelial cells in the periosteum and also in macrophage-like-cells of the synovial membrane. The concentration of leu-enkephalin measured by RIA showed highest concentration in bone marrow followed by periosteum and cortical bone. The study supports that leu-enkephalin is present and can be quantified in different compartments of bone and joint tissues suggesting that leu-enkephalin may be involved in the physiological regulation of nociception and immunoregulation.     

Epidemiological investigation of a food-borne gastroenteritis outbreak caused by Norwalk-like virus in 30 day-care centres

In March 1999, an outbreak of gastroenteritis occurred affecting 30 day-care centres served by the same caterer. A retrospective cohort study was performed in 13 randomly selected day-care centres to determine the source and mode of transmission. Electron microscopy and PCR were used to verify the diagnosis. The overall attack rate (AR) was 37% (195/524): 30% in children and 62% in adults. Modified by the age of the patient, eating pumpkin salad served on 1 March was associated with becoming an early case (odds ratio = 3.9; 95% confidence interval 1.8-8.8). No significant association was found between food consumption and becoming a late case. The primary food-borne AR was 27% and the secondary AR was 14%. The same genotype of Norwalk-like virus was found in 5 cases and in 1 ill and 1 asymptomatic food-handler. Contamination by 1 of the food-handlers seems the most likely route of spread of the virus and underlines the importance of strict hygienic routines.     

Effect of radiologic contrast media on cell volume regulatory mechanisms in human red blood cells

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate cell volume regulation in human red blood cells (RBCs) after incubation in solutions of three contrast media: iohexol (830 mOsm), ioxaglate (520 mOsm), and iodixanol (300 mOsm). MATERIALS AND METHODS: Whole blood sampled from six healthy subjects was exposed to Ringer solutions containing 25% or 5% vol/vol iohexol (final osmolality, 440 or 340 mOsm, respectively), ioxaglate (final osmolality, 395 or 335 mOsm, respectively), iodixanol (final osmolality, 330 or 315 mOsm, respectively), or NaCl (control solutions with the same osmolality as that of the contrast media). In some experiments, control RBCs were subjected to a hyposmotic solution (100 mOsm). RBC volumes were obtained with a Coulter counter. RESULTS: The RBCs showed normal regulatory cell shrinkage after hyposmotically induced swelling. All 25% vol/vol contrast material solutions and their control solutions induced RBC shrinkage (range, 6% +/- 1 [standard error] to 22% +/- 3). The same was true for cells exposed to 5% vol/vol contrast material (range, 4% +/- 1 to 7% +/- 1). The shrinkage phase was followed by cell swelling (10% +/- 2 to 20% +/- 2 for 25% contrast material and their control solutions and 8% +/- 1 to 15% +/- 2 for 5% contrast material and their control solutions). No contrast material-exposed RBCs increased their volumes to the level reached with their control solutions. CONCLUSION: RBCs exposed to hyperosmotic iohexol, ioxaglate, or iodixanol solutions shrank and then swelled. The degree of shrinkage and subsequent swelling could not be explained simply with the osmolality of the test solutions. Physicochemical properties of the contrast media must be involved, putatively affecting electrolyte fluxes over the RBC membrane. Possible targets of these effects are the K+/Cl- symporter, K+ channels, and the Na+/K+/Cl- symporter.     

Assessment of myocardium at risk with computerized vectorcardiography and technetium-99m-sestamibi-single photon emission computed tomography during coronary angioplasty

OBJECTIVE: To compare the myocardium at risk (MAR) as estimated by computerized vectorcardiography (cVCG) with MAR determined by Tc-99m-sestamibi-SPECT using coronary angioplasty as the model for transient transmural ischemia in humans. METHODS AND RESULTS: In 37 patients with stable angina pectoris, cVCG was recorded continuously during coronary angioplasty. The scintigraphic defect was quantified using an automated software program (CEqual). The ST vector magnitude (ST-VM) and the ST change vector magnitude (STC-VM) correlated well with MAR estimated by scintigraphy, ST-VM (r = 0.71, p < 0.001) and STC-VM (r = 0.84, p < 0.001). All patients with STC-VM <50 microV during occlusion had defects of less than 10% of the left ventricle. CONCLUSION: 1) ST-VM and STC-VM give a reasonable useful estimate of MAR size during transient coronary occlusion. 2) STC-VM <50 microV is a reliable limit to identify patients with MAR size less than 10%. 3) ST-VM does not add information to STC-VM with respect to detection of ischemia. 4) The existence of collateral vessels has great impact on both ST-vector changes and scintigraphic imaging of myocardial ischemia.     

The apparent plasticizing effect of polyethylene glycol (PEG) on the crystallinity of spray dried lactose/PEG composites.

Aqueous solutions of lactose and polyethylene glycol (PEG) were spray dried in a Büchi Model 191 spray dryer with the aim to investigate the effect of PEG on the crystallinity of the composite. A PEG concentration of 10.7% by weight of solids was studied for PEG 200, 600, 1500, 4000 and 8000. For PEG 200 and 4000 additional concentrations from 1.5-19.3% to 1.5-32.4%, respectively, were investigated. The spray dried composites were analysed with X-ray powder diffraction and modulating differential scanning calorimetry. The crystallinity of lactose in the composites varied from 0% to 60%, dependent on the molecular weight and concentration of PEG. Apparently, lactose crystallinity is promoted by low molecular weight and high concentration of the PEG. PEG did not affect the lactose glass transition temperature. It is suggested that lactose and PEG are solidified separately during spray drying and that partial crystallization of lactose is associated with effects of PEG on the rate of drying.     

Aspirin and statin medication decreases the risk of myocardial infarction associated with LTA and NFKBIL1 polymorphisms

Lymphotoxin-α (LTA) is a cytokine involved in inflammatory reactions. NFKBIL1 is a regulator of the NF-κB complex. The study investigated the associations of LTA 804 C>A and NFKBIL1-63 T>A polymorphisms with the use of statin and acetylsalicylic acid (ASA) treatment in relation to myocardial infarction (MI). The study population comprised of 600 Finnish individuals who underwent coronary angiography volunteering for the Angiography and Genes Study. Genotypes were detected by the TaqMan 5′ nuclease assay. We found a interaction between the LTA genotype (p=0.002) and the NFKBIL1 genotype (p=0.012) and statin treatment in relation to MI. Subjects with the LTA AA or the NFKBIL1 AA genotype were at a 2.77 (95% CI:1.22-6.24) and 2.85 (95% CI:1.22-6.66) times higher risk, respectively, of suffering an MI when compared to other genotypes among statin non-users. ASA treatment also modulated associations between LTA and NFKBIL1 genotypes and MI (p=0.015 and p=0.028 respectively). The NFKBIL1-A-LTA-A haplotype showed a 61% increase in the risk of MI compared to the NFKBIL1-T-LTA-C haplotype among statin non-users. Anti-inflammatory medication modifies the genotype-related risk of MI, suggesting that subjects with LTA and NFKBIL1 AA haplotype might especially benefit from the treatment.     

p53 mutations in leukemia and myelodysplastic syndrome after ovarian cancer.

PURPOSE: Although p53 mutations occur in alkylating agent-related leukemias, their frequency and spectrum in leukemias after ovarian cancer have not been addressed. The purpose of this study was to examine p53 mutations in leukemias after ovarian cancer, for which treatment with platinum analogues was widely used. EXPERIMENTAL DESIGN: Adequate leukemic or dysplastic cells were available in 17 of 82 cases of leukemia or myelodysplastic syndrome that occurred in a multicenter, population-based cohort of 23,170 women with ovarian cancer. Eleven of the 17 received platinum compounds and other alkylating agents with or without DNA topoisomerase II inhibitors and/or radiation. Six received other alkylating agents, in one case, with radiation. Genomic DNA was extracted and p53 exons 5, 6, 7, and 8 were amplified by PCR. Mutations and loss of heterozygosity were analyzed on the WAVE instrument (Transgenomic) followed by selected analysis by sequencing. RESULTS: Eleven p53 mutations involving all four exons studied and one polymorphism were identified. Genomic DNA analyses were consistent with loss of heterozygosity for four of the mutations. The 11 mutations occurred in 9 cases, such that 6 of 11 leukemias after platinum-based regimens (55%) and 3 of 6 leukemias after other treatments (50%) contained p53 mutations. Two leukemias that occurred after treatment with platinum analogues contained two mutations. Among eight mutations in leukemias after treatment with platinum analogues, there were four G-to-A transitions and one G-to-C transversion. CONCLUSIONS: p53 mutations are common in leukemia and myelodysplastic syndrome after multiagent therapy for ovarian cancer. The propensity for G-to-A transitions may reflect specific DNA damage in leukemias after treatment with platinum analogues.