Glucuronidation and sulfation of the tea flavonoid (-)-epicatechin by the human and rat enzymes.

(-)-Epicatechin (EC) is one of the flavonoids present in green tea, suggested to have chemopreventive properties in cancer. However, its bioavailability is not clearly understood. In the present study, we determined the metabolism of EC, focusing on its glucuronic acid and sulfate conjugation using human liver and intestinal microsomes and cytosol as well as recombinant UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) isoforms in comparison with that occurring in the rat. Surprisingly, EC was not glucuronidated by the human liver and small intestinal microsomes. There was also no evidence of glucuronidation by human colon microsomes or by recombinant UGT1A7, which is not present in the liver or intestine. Interestingly, in the rat liver microsomes EC was efficiently glucuronidated with the formation of two glucuronides. In contrast, the human liver cytosol efficiently sulfated EC mainly through the SULT1A1 isoform. For the intestine, both SULT1A1 and SULT1A3 contributed. Other SULT isoforms contributed little. High-performance liquid chromatography of the sulfate conjugates showed one major sulfatase-sensitive peak with all tissues. An additional minor sulfatase-resistant peak was formed by the liver and intestinal cytosol as well as with SULT1A1 but not by the Caco-2 cytosol and SULT1A3. In the rat, EC sulfation was considerably less efficient than in the human liver. These results indicate that sulfation is the major pathway in EC metabolism in the human liver and intestine with no glucuronidation occurring. There was also a large species difference both in glucuronidation and sulfation of EC between rats and humans.     

Defects in lens fiber differentiation are linked to c-mos overexpression in transgenic mice

We describe three strains of transgenic mice derived by embryo microinjection of DNA consisting of a long terminal repeat (LTR) of Moloney murine sarcoma virus (Mo-MSV) linked to the murine c-mos coding sequences. Southern analysis of the genomic DNA of these strains suggested that in each case the transgene had integrated at a different chromosomal location. The strains were characterized by dominant changes in secondary lens fiber differentiation. Shortly after birth, insufficient elongation of differentiating lens fibers and lack of basement membrane secretion resulted in breakdown of the posterior lens capsule. This, in turn led to posterior protrusion and swelling of lens tissue. In the course of the first 3 weeks after birth, globular lens cells began to fill the entire anterior and posterior chambers of the eye. Concomitantly, there was massive overexpression of c-mos RNA in the lens. Whereas this construct has high transforming activity when transfected into NIH-3T3 cells, no hyperplasia or neoplasia have been observed in the affected lenses. Increased expression of c-mos RNA was not confined to the lens of the eye but has been detected in any of several tissues tested.     

Erythropoietin-hematocrit feedback circuit in the anemia of end-stage renal disease

Deficient erythropoietin (EP) production is thought to be a key factor in the pathogenesis of the anemia of end-stage renal disease. We describe the interrelationships between radioimmunoassayed plasma EP levels, reticulocyte counts corrected for anemia (CRC) and hematocrit (HCT) under challenge by hemorrhage, transfusions and hemodialysis in 32 chronically-hemodialyzed patients. Spontaneous hemorrhage resulted in a decrease in HCT (P = 0.001) and increases in both EP (P = 0.006) and CRC levels (P = 0.0065). Transfusions of two units of packed red cells into each of 16 patients suppressed EP (P = 0.0004) and CRC (P less than 0.0001) after about 28 and 42 hours, respectively. Repeat transfusions after one to 27 days resulted in similarly significant suppressions of both EP and CRC, except the CRC remained on higher levels for prolonged periods of times. Within a few hours after each transfusion of 2,3-diphosphoglycerate-poor red cells, both EP (P = 0.009) and CRC (P = 0.007) increased temporarily between one to 18 and three to 38 hours, respectively. Hemodialysis resulted in alkalinization (P = 0.008) of blood but not in changes of EP or CRC counts. The data show that, with the EP-HCT feedback loop persisting, increased endogenous hormone levels elicit erythropoietic responses, and that the regulation of EP levels may involve determinants such as oxy-deoxyhemoglobin interactions.     

FISH--a new noninvasive method for the diagnosis of urinary bladder carcinomas

Urinary bladder carcinoma is one of the most frequent malignant tumour diseases. The frequency increases with advancing age. The knowledge increase about genetic changes in tumour cells opens the possibility of a new noninvasive diagnosis with the help of fluorescence in situ hybridization (FISH). Comparable data are obtained by application of different diagnostic methods (fluorescence in situ hybridization, urinary bladder cancer ELISA, urinary cytology, histopathology) at different times from 6 coincidentally selected patients (preoperation, biopsy material and postoperation). The FISH test proved to be a sensitive method and correlated with the histopathological data.     

Can we assess healing of surgically treated long bone fractures on radiograph?

Purpose

To determine the frequency and causes for limitations in the radiographic evaluation of surgically treated long bone fractures.

Magnetic resonance imaging (MRI) of the knee: Identification of difficult-to-diagnose meniscal lesions

This article characterizes common meniscal pathologies, reviews magnetic resonance imaging (MRI) diagnostic criteria for meniscal tears, and identifies difficult-to-detect tears and fragments and the best MRI sequences and practices for recognizing these lesions. These difficult-to-diagnose meniscal lesions that radiologists should consider include tears, meniscocapsular separation lesions, and displaced meniscal fragments. Meniscus tears are either vertical, which are generally associated with traumatic injury, horizontal, which are associated with degenerative injury, or combinations of both. MRI has a high sensitivity for tears but not for fragments; MRI performance is also better for medial than lateral meniscal lesions. Fragment detection can be improved by recognizing signs secondary to migration, especially signs of epiphyseal irritation and mechanical impingement. Radial and peripheral tears, as well as those close to the posterior horn insertion, have been traditionally difficult to detect, but improvements in arthroscopic knowledge, identification of common lesion patterns, and selection of the proper MRI sequence and plane for each lesion type mean that, when properly used, MRI is an invaluable tool in detecting all types of meniscal tears.     

Fatal air embolism in an extremely low birth weight infant: can it be caused by intravenous injections during resuscitation?

OBJECTIVE: A preterm infant with a birth weight of 384 g who succumbed to vigorous resuscitation for sudden respiratory failure on the third day of life is presented. Postmortem examination revealed, apart from extensive pulmonary hemorrhage, a fatal amount of air mainly in the right ventricle. We believe that this air had been introduced via peripheral venous cannulas due to inadvertent and unavoidable air admixture to each injection volume administered with a syringe, and we develop an experimental model to confirm that fatal amounts of air can indeed accumulate with frequent change over of syringes within a short period of time. DESIGN: An empty 50-ml syringe was connected to a 15-cm-long connection line via a three-way tap. With a 1 ml syringe 100 doses of 0.5 ml aqua were injected into the connection line. The amount of air which had collected in the 50 ml syringe after the 100 injection cycles was measured. This process was repeated three times each by three of the authors and the average air volume introduced with 100 injections calculated for each investigator. RESULTS: The average amounts of air which had entered the closed system after 100 acts of syringe assembly and aqua administration were 1.84, 1.95, and 2.0 ml. This corresponds to an average volume of almost 0.02 ml per injection.