Effects of the co-carcinogen catechol on benzo[a]pyrene metabolism and DNA adduct formation in mouse skin

We have studied the effects of the co-carcinogen catechol (1,2-dihydroxybenzene)on the metabolic activation of [³H] benzo[a]pyrene (BaP) inmouse skin, in vivo and on the binding of BaP metabolites toDNA and protein at intervals from 0.5–24 h. Upon topicalapplication of 0.015 mg [³H]BaP and 0.25 or 0.5 mg catecholper mouse, catechol had little effect on the total amount of[³H]BaP metabolized in mouse skin, but it affected the relativeproportions of [³H]BaP metabolites. Catechol (0.5 mg/mouse)decreased the proportion of watersoluble [³H]BaP metabolites,ethyl acetate-soluble polar metabolites and quinones, but doubledthe levels of unconjugated 3-hydroxy-BaP at all measured intervalsafter treatment. Catechol also caused a small increase in thelevels of trans-7,8-dihydroxy-7,8-dihydroBaP and trans-9,10-dihydroxy-9,10-dihydroBaP0.5 h after treatment. Two hours after treatment, the levelsof these metabolites subsided to those of the controls. Catecholdid not affect the levels of glutathione conjugates of BaP.However, it caused a decrease in glucuronide and sulphate conjugateformation from BaP. Catechol caused an 2-fold increase in theformation of anti-7, 8-dihydroxy-9, 10-epoxy-7, 8, 9, 10-tetrahydroBaP(BPDE) DNA adducts and elevated the ratio of anti-syn-BPDE-DNAadducts 1.6 to 2.9-fold. Catechol treatment increased the radioactivityassociated with epidermal proteins after [³H]BaP application.Because catechol increased levels of 3-hydroxyBaP, we consideredthe possibility that 3-hy-droxyBaP might enhance the tumor initiatingactivities of BaP or BPDE in mouse skin; a bioassay demonstratedthat this was not the case. The results of this study indicatethat one important effect of catechol related to its co-carcinogenicityis its ability to enhance formation of anti-BPDE-DNA adductsin mouse skin.     

The Lapidus Arthrodesis: Examining the Effect of the Metatarsal Base Transfixion Screw

The modified Lapidus bunionectomy is a useful and highly powerful procedure for correcting hallux abducto valgus. Traditionally reserved for “severe” deformities, this procedure has seen a recent resurgence in the podiatric community for its unique ability to achieve tri-planar correction of this challenging deformity. Although this procedure has been extensively studied in both biomechanical labs and the clinical arenas, no clear consensus has been achieved regarding optimal fixation for this thought-provoking procedure. The current study examined the differences in strength between commercially available 5-hole locking plates with interfragmentary compression vs a crossed-screw with a third “transfixation” screw construct in a controlled setting. Ten fresh-frozen cadaveric match pair limbs (20 total limbs) were used to complete this study. Ten limbs were randomly assigned to a 3-screw construct. The other 10 contralateral limbs were assigned to a commercially available 5-hole locking plate (5 stainless steel and 5 titanium alloy) with an interfragmentary lag screw construct. The first rays were then isolated and potted into a 4-point bending device. The specimens were loaded to failure in a servohydraulic load frame at a controlled rate. Failure was defined as catastrophic or 3 mm of plantar gapping at the arthrodesis site. The mean maximal load to failure was 310.9 ± 109.4 N for the 3-screw construct. The mean maximal load to failure for the locking plate constructs was 264.1 ± 100.9 N. This difference was not statistically significant (p = .328). These results suggest that a 3-screw construct for Lapidus arthrodesis is as strong as commercially available locking plate constructs.     

Long-term rates of bladder dysfunction after decompression in patients with cauda equina syndrome

BACKGROUND CONTEXTCauda equina syndrome (CES) occurs due to compression of the lumbar and sacral nerve roots and is considered a surgical emergency. Although the condition is relatively rare, the associated morbidity can be devastating to patients. While substantial research has been conducted on the timing of treatment, the literature regarding long-term rates of bladder dysfunction in CES patients is scarce.PURPOSEThe aim of this study was to identify long-term rates of bladder dysfunction in CES patients and to compare those rates to non-CES patients who underwent similar spinal decompression.STUDY DESIGN/SETTINGRetrospective database study.PATIENT SAMPLEThe CES cohort was comprised of 2,362 patients who underwent decompression surgery following CES diagnosis with a 5-year follow-up. These patients were matched to 9,448 non-CES control patients who underwent spinal decompression without a diagnosis of CES.OUTCOME MEASURESDiagnosis of bladder dysfunction, surgical procedure to address bladder dysfunctionMETHODSUsing the national insurance claims database, PearlDiver, CES patients who underwent decompression surgery were identified and 1:4 matched to non-CES patients who underwent similar spinal decompression surgery. The 1-year, 3-year, and 5-year rates of progression to a bladder dysfunction diagnosis and surgical intervention to manage bladder dysfunction were recorded. The CES and non-CES groups were compared with univariate testing, and an analysis of risk factors for bladder dysfunction was performed with multivariate logistic regression analysis.RESULTSA total of 2,362 CES patients who underwent decompression surgery were identified and matched to 9,448 non-CES control patients. After 5 years, CES patients had a 10%–12% increased absolute risk of continued bladder dysfunction and a 0.7%–0.9% increased absolute risk of undergoing a surgical procedure for bladder dysfunction, as compared to matched non-CES patients. Multivariate analysis controlling for age, sex, obesity, tobacco use, and diabetes, identified CES as independently associated with increased 5-year risk for bladder dysfunction diagnosis (odds ratio [OR]: 1.72; 95% confidence interaval [CI] 1.56–1.89; p<.001) and procedure (OR: 1.40; 95% CI 1.07–1.81; p=.012).CONCLUSIONSUnderstanding the long-term risk for bladder dysfunction in CES patients is important for the future care and counseling of patients. Compared to non-CES patients who underwent similar spinal decompression, CES patients were observed to have a significantly higher long-term likelihood for both bladder dysfunction diagnosis and urologic surgical procedure.     

Pb2+ modulates the NMDA-receptor-channel complex

Summary The actions of Pb²⁺ on NMDA channel currents of acutely dissociated hippocampal CA1- and CA3-neurones from adult rats activated by aspartate plus glycine (asp/gly) were examined. A fast reversible and a slow irreversible response to Pb²⁺ were found. Pb²⁺ applied simultaneously with asp/gly decreased an inward current. The threshold concentration was below 2 M, the current was reduced > 90% at concentrations over 100 M, The decrease of the asp/gly activated current showed no voltage dependence. Opening of NMDA channels was not necessary for Pb²⁺-action, as preincubation in 50 M Pb²⁺-containing external solution for several seconds dramatically reduced the response to asp/gly/Pb²⁺. This effect was reversed within 2 to 5 s of wash. Presence of Pb²⁺ or asp/Pb²⁺ or glycine/Pb²⁺ in the external solution did not prevent recovery of the NMDA receptor/channel complex from desensitization. Prolonged perfusion of a cell with the asp/gly/Pb²⁺-containing external solution resulted in an irreversible decrease of the asp/gly current, whereas the amplitude of the asp/gly/Pb²⁺ response did not change over the duration of an experiment. We conclude that Pb²⁺ modulates NMDA channel activity via interaction with the NMDA/glycine receptor: as a result the channel current decreases.Abbreviations NMDA N-methyl-D-aspartate - LTP long-term potentiation - AP5 2-amino-5-phosphonovalerate - EGTA ethylene glycol bis(-aminoethylether)-N,N,N,N-tetraacetic acid - HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid Correspondence to H. L. Haas at the above address     

Activation of benzylic alcohols to mutagens by human hepatic sulphotransferases

Four primary and five secondary benzylic alcohols derived frompolycyclic aromatic hydrocarbons were tested for mutagenicityin Salmonella typhimurium TA98 in the presence of 3'-phosphoadenosine-5'-phosphosulphate,the cofactor for sulphotransferases, and varying amounts ofhepatic cytosol from three or four different human subjects,a 3-year-old child, an adult female, an adult male and one unknown.All compounds except one, 4H-cyclopenta[def] phenanthren-4-ol,were activated to mutagens. The interindividual variation inthe activities was at most 3-fold and the individual activitiestowards the different substrates were correlated with each other.The same compounds had previously been tested in the presenceof hepatic cytosol from rats and all compounds activated inone species were also activated in the other species. However,there were marked quantitative differences, which were furthercomplicated by the observation of a substantial sex differencein the rat. Male and female rat liver cytosol showed highersulphotransferase activities towards 1-hydroxymethylpyrene,9-hydroxymethylanthracene, 7-hydroxymethyl-12-methylbenz[a]anthraceneand 4H-cyclopenta[def]chrysen-4-ol than human liver cytosol.The largest difference in activity was seen with 7-hydroxymethyl-12-methylbenz[a]anthracene,reaching a factor of     

Karyotypic abnormalities in adenocarcinomas of the lung

Cytogenetic analysis of 114 adenocarcinomas of the lung revealed clonal abnormalities in 67 tumors. The chromosome numbers ranged from near-diploid to hypertetraploid. Clonal abnormalities seen as the sole anomaly were loss of the Y chromosome (21 tumors), trisomy 7 (2 tumors), and trisomy 12 (1 tumor). A supernumerary ring chromosome was the only clonal change in 4 tumors. The bands most often affected were 17p11-13 (13 cases), 1q10-12 and 1p22 (10 cases each), 1p11-13 and 1q21 (9 cases each), and 11p11, 11p15 and 15p11-13 (6 cases each). The chromosomes most frequently involved in structural rearrangements were chromosomes 1 (30 cases), 11 (20 cases), 3 (17 cases), 17 and 7 (16 cases each). Repeated loss of material from chromosome arms 1p, 3p, 6q, 11p, and 17p and gains of 1q were found. Recurrent structural changes were del(1)(p22) and i(5)(p10) (5 cases each) i(1)(q10), i(13)(q10), i(14)(q10) and del(17)(p11) (3 cases each). We found no abnormalities that seemed to be specifically associated with pulmonary adenocarcinomas, but isochromosomes i(1)(q10), i(5)(p10) and i(13)(q10) and changes of 6q were present in our series at frequencies higher than those generally seen in the other main types of lung cancer.