Photodecomposition of DDA

The photodecomposition of aqueous solutions of 2,2-bis (p-chlorophenyl) acetic acid (DDA) was slow in sunlight and rapid in the laboratory, producingp,p-dichlorobenzophenone (DCB),p-chlorobenzaldehyde,P-chlorophenol, and several unidentified polar products.p,p-Di-chlorobenzilic acid, andp,p-dichlorobenzhydrol gave rise to the same photoproducts, while bis-(p-chlorophenyl) methane (DDM) and chlorobenzilate were converted only to DCB. DCB andp-chlorobenzaldehyde proved to be resistant to photodegradation but gradually producedP-chlorobenzoic acid which, in turn, formedp-hydroxybenzoic and benzoic acids, probably the last environmentally detectable links in the long chain of DDT degradation to CO₂ and water.High pressure liquid chromatography (HPLC) proved to be ideal for separating and quantitating the parent compounds and their photoproducts directly from the aqueous photolysates or from methanol solutions of the isolates and standards.Contribution to Regional Project W-45, Environmental Distribution, Transformation, and Toxicological Implications of Pesticide Residues. University of Arizona Agricultural Experiment Station journal series No. 2931.     

Effects of cost sharing in health insurance on disability days

We assess how cost sharing for medical services affects restricted activity days (RADs) and work loss disability days (WLDs), using data from a controlled experiment. We grouped the experimental insurance plans into four categories, one providing free care and the other three requiring varying amounts of cost sharing. RADs per person per year decreased by one to two days with greater cost sharing, with the strongest effects among those of average or poor health status, especially the non-poor. Unlike RADs, WLDs showed no systematic differences by plan.     

Isolation and characterization of propagable cell lines (HUNC) from the androgen-sensitive Dunning R3327H rat prostatic adenocarcinoma

The Dunning H rat prostate tumor (R3327H) is a widely used experimental model of human prostatic adenocarcinoma (CaP). The Dunning H tumor has been characterized as androgen-sensitive, androgen-receptor (AR) positive, prostate-specific antigen and prostatic acid phosphatase (PAP) positive. To date, the tumor has been maintained by serial passage in vivo because of the lack of an in vitro cell line that retains the characteristics of the in vivo tumor. The objective of the present study was to establish a propagable cell line from R3327H adenocarcinoma that maintained androgen sensitivity and expression of AR, PSA and PAP. Tissue harvested from an in vivo R3327H tumor was dissociated with collagenase and placed into Richter's improved media (with supplements). A cytokeratin-positive epithelial cell line (HUNC- E) and a vimentin-positive stromal cell line (HUNC-S) were generated from the primary culture, subcultured continuously for >300 days, and passaged >50 times. Survival of the HUNC-E cell line in vitro depended on several media supplements, including nicotinamide, insulin, transferrin, selenium and epidermal growth factor (EGF). HUNC-E cells expressed AR and produced PSA and PAP throughout the culture period, as confirmed by immunocytochemistry and Western blot analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone (DHT) to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent growth and PSA production, which demonstrated the androgen-sensitive nature of the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1 ratio and introduced subcutaneously into syngeneic male hosts, tumors formed in 2/3 animals with an average latency of 7 months. RT-PCR and immunocytochemical characterization of the HUNC cell lines revealed that the cells expressed several growth factors and their cognate receptors, including HGF, TGF-alpha and the TGF-betas, indicating the establishment of potential autocrine loops in the neoplastic cells. The HUNC-E and HUNC-S CaP cell lines, which retain the characteristics of the epithelial and stromal components of the in vivo R3327H tumor, will allow a more thorough and informative molecular and biological analysis of prostatic adenocarcinoma.      

Zinc replenishment reduces esophageal cell proliferation and N- nitrosomethylbenzylamine (NMBA)-induced esophageal tumor incidence in zinc-deficient rats

Previous work has shown that sustained increased and decreased cell proliferation, induced by dietary zinc deficiency and caloric restriction respectively, influence the course of N- nitrosomethylbenzylamine (NMBA)-induced esophageal carcinogenesis in rats. The present study considered whether the increased cell proliferation and esophageal tumor incidence induced by zinc deficiency are reversed upon zinc replenishment. Weanling rats were maintained initially on a deficient diet containing 4 p.p.m. zinc. After 5 weeks, carcinogen-treated animals were given six intragastric doses of NMBA (2 mg/kg twice weekly). Controls were untreated. After the second NMBA dose, the rats were divided into three dietary groups. One group was continued on the deficient diet, while the other two groups were switched to diets containing either 75 or 200 p.p.m. zinc, with half of the members in each group fed ad libitum and half pair-fed with deficient rats. NMBA-untreated controls were similarly replenished. At various time points, esophageal cell proliferation was assessed in five animals from each group by immunohistochemical detection of cells in S phase, with in vivo 5-bromo-2'deoxyuridine labeling. At 11 weeks after the first dose, esophageal tumor incidence was greatly reduced, from 100% in the deficient group to 26 and 14% respectively in the replenished groups fed ad libitum 75 and 200 p.p.m. zinc and to 14 and 11% respectively in the replenished groups pair-fed 75 and 200 p.p.m. zinc. In addition, the number of tumors per esophagus was reduced from 9.93 +/- 4.25 in deficient rats, to a range of 0.11 +/- 0.31-0.30 +/- 0.54 in replenished animals. Following zinc replenishment, esophageal cell proliferation, as measured by labeling index (LI), the number of labeled cells and the total number of cells, was markedly decreased in NMBA-untreated and -treated esophagi as compared with those in corresponding deficient esophagi. Thus, the esophageal cell proliferation induced by zinc deficiency is reversed by zinc replenishment and replenished animals have a markedly lower incidence of esophageal tumors.      

Platelet-binding immunoglobulins in pregnancy-induced hypertension I. Platelet-associated IgM on fetal platelets: evidence of a fetal autoimmune reaction?

Pregnancy-induced hypertension (PIH) can be complicated by maternal or fetal thrombocytopenia, or both. In order to investigate possible immunologic causes of these thrombocytopenias, platelet-associated IgG (PAIgG) and IgM (PAIgM) were measured in mothers with PIH and in their infants and compared with those from patients with autoimmune thrombocytopenic purpura (ATP), a known immunodestructive platelet disorder. Many PIH patients (33.3%) and most ATP patients (68.1%) had elevated levels of maternal PAIgG. In both diseases, the amount of PAIgG was directly proportional with the degree of thrombocytopenia (r = 0.446 in PIH and R = 0.668 for ATP). But in neither disease did the degree of maternal thrombocytopenia correlate with the degree of neonatal thrombocytopenia (r = 0.153 for PIH and R = 0.175 for ATP). Umbilical cord samples from PIH patients contained PAIgG (53.3%) and PAIgM (53.8%), whereas the umbilical cord samples from ATP patients had elevated amounts of PAIgG but not PAIgM. PAIgM in the umbilical cord blood could not be accounted for by IgM rheumatoid factors, IgM-containing immune complexes, or non-specific adsorption because of elevated total IgM levels. The umbilical cord blood PAIgM was probably not of maternal origin because it was observed even when the maternal blood contained no PAIgM and maternal IgM is not normally transported transplacentally. Therefore, the PAIgM appears to be of fetal origin. These results suggest that both maternal and fetal immunologic mechanisms may be involved in PIH-induced thrombocytopenia; if so, this is one of the first reported examples of a possible fetal autoimmune response.     

Posttraumatic Stress Disorder and One‐Year Outcome in Methadone Maintenance Treatment

Background: Although opiate use may be associated with posttraumatic stress disorder (PTSD), it is not clear whether PTSD is associated with retention in methadone maintenance. Objectives: To evaluate among those receiving methadone maintenance at an urban methadone maintenance clinic the frequency of life‐time traumatic experiences, the predictors and prevalence of current PTSD, and whether PTSD affects retention at 1 year. Methods: Eighty‐nine people participated in the study. The Post Traumatic Diagnostic Scale was used to determine the prevalence of PTSD. The Life Stressor Checklist Revised was used to evaluate trauma history. Logistic regression analyses examined associations between demographic characteristics, substance use, trauma‐related variables, and PTSD. Similar logistic regression analyses were used to examine retention in methadone maintenance at 1 year. Results: The mean number of reported lifetime stressful events was 8.0 (SD = 3.7). Twenty‐seven percent were diagnosed with PTSD. Nearly 92% of those with PTSD had co‐occurring depressive symptoms. Female gender (adjusted odds ratio [AOR][95% CI]; 3.89 [1.07–14.01]), number of traumatic events (AOR [95% CI]; 1.34 [1.13–1.61]), and less education (AOR [95% CI]; 4.13 [1.14–14.98]) were significantly associated with PTSD. Those with a toxicology positive screen were 80% less likely to remaine in methadone maintenance at 1 year (OR [95% CI]; 0.20 [0.07–0.52]). PTSD diagnosis was not significantly associated with treatment retention at 1 year (OR [95% CI]; 0.61 [0.23–1.64]). Conclusions and Scientific Significance: Future studies are needed to determine if treatment of PTSD that is integrated into methadone maintenance programs may impact continued substance abuse use and thereby improve retention in care. (Am J Addict 2012;21:524–530)     

Hydroxyurea treatment decreases glomerular hyperfiltration in children with sickle cell anemia

Glomerular hyperfiltration and microalbuminuria/proteinuria are early manifestations of sickle nephropathy. The effects of hydroxyurea therapy on these renal manifestations of sickle cell anemia (SCA) are not well defined. Our objective was to investigate the effects of hydroxyurea on glomerular filtration rate (GFR) measured by ^99mTc‐DTPA clearance, and on microalbuminuria/proteinuria in children with SCA. Hydroxyurea study of long‐term effects (HUSTLE) is a prospective study (NCT00305175) with the goal of describing the long‐term cellular, molecular, and clinical effects of hydroxyurea therapy in SCA. Glomerular filtration rate, urine microalbumin, and serum cystatin C were measured before initiating hydroxyurea therapy and then repeated after 3 years. Baseline and Year 3 values for HUSTLE subjects were compared using the Wilcoxon Signed Rank test. Associations between continuous variables were evaluated using Spearman correlation coefficient. Twenty‐three children with SCA (median age 7.5 years, range, 2.5–14.0 years) received hydroxyurea at maximum tolerated dose (MTD, 24.4 ± 4.5 mg/kg/day, range, 15.3–30.6 mg/kg/day). After 3 years of treatment, GFR measured by ^99mTc‐DTPA decreased significantly from 167 ± 46 mL/min/1.73 m² to 145 ± 27 mL/min/1.73 m² (P = 0.016). This decrease in GFR was significantly associated with increase in fetal hemoglobin (P = 0.042) and decrease in lactate dehydrogenase levels (P = 0.035). Urine microalbumin and cystatin C levels did not change significantly. Hydroxyurea at MTD is associated with a decrease in hyperfiltration in young children with SCA. Am. J. Hematol., 88:116–119, 2013. © 2012 Wiley Periodicals, Inc.