TGF-B3 Dependent Modification of Radiosensitivity in Reporter Cells Exposed to Serum From Whole-Body Low Dose-Rate Irradiated Mice

Prior findings in vitro of a TGF-β3 dependent mechanism induced by low dose-rate irradiation and resulting in increased radioresistance and removal of low dose hyper-radiosensitivity (HRS) was tested in an in vivo model. DBA/2 mice were given whole-body irradiation for 1 h at low dose-rates (LDR) of 0.3 or 0.03 Gy/h. Serum was harvested and added to RPMI (4% mouse serum and 6% bovine serum).This medium was transferred to reporter cells (T-47D breast cancer cells or T98G glioblastoma cells). The response to subsequent challenge irradiation of the reporter cells was measured by the colony assay. While serum from unirradiated control mice had no effect on the radiosensitivity in the reporter cells, serum from mice given 0.3 Gy/h or 0.03 Gy/h for 1 h removed HRS and also increased survival in response to doses up to 5 Gy. The effect lasted for at least 15 months after irradiation. TGF-β3 neutralizer added to the medium containing mouse serum inhibited the effect. Serum from mice given irradiation of 0.3 Gy/h for 1 h and subsequently treated with iNOS inhibitor 1400W did not affect radiosensitivity in reporter cells; neither did serum from the unirradiated progeny of mice given 1h LDR whole-body irradiation.     

Children With Chronic Pain: Response Trajectories After Intensive Pain Rehabilitation Treatment

Intensive pain rehabilitation programs for children with chronic pain are effective for many patients. However, characteristics associated with treatment response have not been well documented. In this article we report trajectories of pain and functional impairment in patients with chronic pain up to 1 year after intensive pain rehabilitation and examine baseline factors associated with treatment response. Patients (n?=?253) with chronic pain and functional disability were assessed at 5 time points (admission, discharge, 1-month, 4-month, and 12-month follow-ups). Individual trajectories were empirically grouped using SAS PROC TRAJ. For functional disability, 2 groups emerged: treatment responders (88%) and nonresponders (12%). Using a binomial logistic regression model to predict disability trajectory group, no baseline variables were significant predictors for the disability trajectory group. For pain, 3 groups emerged: early treatment responders (35%), late treatment responders (38%), and nonresponders (27%). Using multinomial regression analyses to predict pain trajectory group, older age, higher pain scores, fewer social difficulties, higher anxiety levels, and lower readiness to change were characteristics that distinguished nonresponders from responders; no significant predictors distinguished the late responders from the early responders. These results provide key information on the baseline factors that influence intensive pain rehabilitation outcomes, including risk factors that predict treatment nonresponse. Our findings have implications for developing more targeted treatment interventions.

Obstetric complications due to autoantibodies

Autoimmune diseases are most common and most active in young women; it is therefore not uncommon for obstetricians and physicians to encounter pregnant women with these conditions, and knowledge of the potential maternal, foetal and neonatal complications is essential for good clinical management. The most common maternal autoimmune endocrine conditions in pregnancy are insulin-dependent diabetes mellitus and thyroid disease. Other relatively common non-endocrine autoimmune conditions include systemic lupus erythematosus and anti-phospholipid syndrome. Much rarer autoimmune conditions include autoimmune thrombocytopenia, rheumatoid arthritis, myasthenia gravis and Addison's disease. In this chapter, we discuss autoimmune endocrine conditions and briefly mention some non-endocrine conditions of particular importance.     

Walter Whitehead

Walter Whitehead was born in 1840 at Haslem Hey, Bury, where his father's family had resided for more than 200 years. For a short time, he worked for his father in the bleaching business, but at the age of 19, he decided that he would prefer to enter the medical profession. His initial practice was in Manfield where he organized a small cottage hospital, but in 1867, he was appointed to the St. Mary's Hospital for Women and Children in Manchester. He became actively involved in many charities and organizations devoted to the protection of infants, and, in 1871, was called upon to give evidence before the Committee of the House of Commons on a Bill for the Protection of Infant Life. In 1870, he founded, and for a time served as Editor of theManchester Medical and Surgical Reports, a periodical which contained papers contributed chiefly by local members of the profession. In 1885, he was elected President of the Manchester Medical Society, and at his inaugural address attracted much attention for the first time recognizing the increased incidence of cancer. Doctor Whitehead's operative technique seemed to be characterized by originality as well as a certain simplified approach, often using scissors only. An example of these traits is seen in the two operations which to this day bear his name—his method of excising the tongue, and the other, of course, excision of hemorrhoids. His hemorrhoidectomy was severely criticized in his own day because of the characteristic “deformity”. Even today, the value of his operation continues to be debated. However, many surgeons continue to employ his technique in the primary treatment of hemorrhoidal disease. The following article is his procedure, as it was published inThe British Medical Journal in 1882.     

The Moxus Modular metabolic system evaluated with two sensors for ventilation against the Douglas bag method

This study evaluated the Moxus metabolic system with the Douglas bag method (DBM) as criterion. Reliability and validity were investigated in a wide range of ventilation and oxygen uptake and two sensors for determining ventilation were included. Thirteen well-trained athletes participated in one pre-test and four tests for data collection, exercising on a cycle ergometer at five submaximal powers (50–263 W) and at $ V{\text{O}}_{{2{ \hbox{max} }}} $ . Gas exchange variables were measured simultaneously using a serial setup with data collected on different days in an order randomized between Moxus with pneumotachometer (MP) and turbine flowmeter (MT) sensors for ventilation. Reliability with both sensors was comparable to the DBM. Average CV (%) of all exercise intensities were with MP: 3.0 ± 1.3 for VO₂, 3.8 ± 1.5 for VCO₂, 3.1 ± 1.2 for the respiratory exchange ratio (RER) and 4.2 ± 0.8 for V _E. The corresponding values with MT were: 2.7 ± 0.3 for VO₂, 4.7 ± 0.4 for VCO₂, 3.3 ± 0.9 for RER and 4.8 ± 1.4 for V _E. Validity was acceptable except for small differences related to the determination of ventilation. The relative differences in relation to DBM at the powers including $ V{\text{O}}_{2\hbox{max} } $ were similar for both sensors with the ranges being: +4 to ?2 % for V _E, +5 to ?3 % for VO₂ and +5 to ?4 % for VCO₂ while RER did not differ at any power. The Moxus metabolic system shows high and adequate reliability and reasonable validity over a wide measurement range. At a few exercise levels, V _E differed slightly from DBM, resulting in concomitant changes in VO₂ and VCO₂.     

One-pot synthesis of enantiopure syn-1,3-diacetates from racemic syn/anti mixtures of 1,3-diols by dynamic kinetic asymmetric transformation

A one-pot synthesis of enantiomerically pure syn-1,3-diacetates starting from readily accessible racemic diastereomeric mixtures of 1,3-diols has been realized by combining (i) enzymatic transesterification, (ii) ruthenium-catalyzed epimerization of a secondary alcohol in a diol or diol monoacetate, and (iii) intramolecular acyl migration in a syn-1,3-diol monoacetate. The in situ coupling of these three processes results in an efficient enantioselective synthesis of acyclic syn-1,3-diacetates via combined deracemization-deepimerization and constitutes a dynamic kinetic asymmetric transformation concept. Several differently substituted unsymmetrical, acyclic syn-1,3-diacetates were obtained in yields up to 73% with excellent enantioselectivities (>99%) and good diastereomeric ratios (>90% syn).     

Evaluation of cytochrome P450-derived eicosanoids in humans with stable atherosclerotic cardiovascular disease

ObjectivePreclinical and genetic epidemiologic studies suggest that modulating cytochrome P450 (CYP)-mediated arachidonic acid metabolism may have therapeutic utility in the management of coronary artery disease (CAD). However, predictors of inter-individual variation in CYP-derived eicosanoid metabolites in CAD patients have not been evaluated to date. Therefore, the primary objective was to identify clinical factors that influence CYP epoxygenase, soluble epoxide hydrolase (sEH), and CYP ω-hydroxylase metabolism in patients with established CAD.MethodsPlasma levels of epoxyeicosatrienoic acids (EETs), dihydroxyeicosatrienoic acids (DHETs), and 20-hydroxyeicosatetraenoic acid (20-HETE) were quantified by HPLC–MS/MS in a population of patients with stable, angiographically confirmed CAD (N = 82) and healthy volunteers from the local community (N = 36). Predictors of CYP epoxygenase, sEH, and CYP ω-hydroxylase metabolic function were evaluated by regression.ResultsObesity was significantly associated with low plasma EET levels and 14,15-EET:14,15-DHET ratios. Age, diabetes, and cigarette smoking also were significantly associated with CYP epoxygenase and sEH metabolic activity, while only renin-angiotensin system inhibitor use was associated with CYP ω-hydroxylase metabolic activity. Compared to healthy volunteers, both obese and non-obese CAD patients had significantly higher plasma EETs (P < 0.01) and epoxide:diol ratios (P < 0.01), whereas no difference in 20-HETE levels was observed (P = NS).ConclusionsCollectively, these findings suggest that CYP-mediated eicosanoid metabolism is dysregulated in certain subsets of CAD patients, and demonstrate that biomarkers of CYP epoxygenase and sEH, but not CYP ω-hydroxylase, metabolism are altered in stable CAD patients relative to healthy individuals. Future studies are necessary to determine the therapeutic utility of modulating these pathways in patients with CAD.