Non-Hodgkin lymphoma among Brazilian agricultural workers: A death certificate case-control study

To estimate the non-Hodgkin lymphoma (NHL) mortality risk among agricultural workers in Brazil's southern states, we used death certificates to identify cases of NHL between the ages of 20 and 69 years from residents of nonurban municipalities between 1996 and 2005 (n = 1,317). Controls were randomly selected from those whose underlying cause of death did not include neoplasm or hematological diseases and paired with cases by sex, age, year of death, and state of residence (n = 2,634). Odds of being an agricultural worker among cases and controls were estimated by conditional logistic regression, stratified and adjusted by sex, state, education, and race. An increased risk of death by NHL was observed among agricultural workers 20–39 years old (OR_adj = 2.06; 95% CI 95%, 1.20–3.14). Our results suggest that the young agricultural workers from southern Brazil were more likely to die of NHL compared to nonagricultural workers.     

Making personalized medicine a reality: the challenges of a modern translational research biopsy-driven program in an academic setting: the Segal Cancer Center experience

The success of personalized medicine in the oncology clinic is very dependent on the results from a translational research effort to identify individual and host molecular biomarkers to enable proper selection of anti-cancer therapy. For this to happen, it is necessary to obtain timely access to high-quality biological samples of both host and tumor tissues and biological fluids. At the Segal Cancer Center, we have initiated several prospective sample collections based on research-driven breast biopsies in different contexts, including primary and metastatic breast lesions in patients receiving specific treatments. We here describe some of the challenges involved in such a translational research program and our experience in setting up biopsy-driven research protocols, highlighting the human aspects of conducting these complex enterprises.     

Mechanisms involved in the antinociceptive effect caused by diphenyl diselenide in the formalin test

This study investigated the mechanisms involved in the antinociceptive action induced by diphenyl diselenide ((PhSe)₂) in the formalin test. Mice were pre‐treated with (PhSe)₂ by the oral route (0.1–100 mg kg⁻¹), 30 min before formalin injection. To address some of the mechanisms by which (PhSe)₂ inhibits formalin‐induced nociception mice were treated with different drugs. The antinociceptive effect of (PhSe)₂ was shown in the first and second phases of the formalin test. The antinociceptive effect caused by (PhSe)₂ (10 mg kg⁻¹, p.o.) was prevented by intrathecal injection of K⁺ channel blockers such as apamin and charybdotoxin (small‐ and large‐conductance Ca²⁺‐activated K⁺ channel inhibitors, respectively) and tetraethylammonium (TEA, a non‐selective voltage‐dependent K⁺ channel inhibitor), but not glib‐enclamide (an ATP‐sensitive K⁺ channel inhibitor). The antinociceptive action caused by (PhSe)₂ (10 mg kg⁻¹, p.o.) was also blocked by a nitric oxide (NO) synthase inhibitor (N^ω‐nitro‐l ‐arginine, L‐NOARG) and the soluble guanylate cyclase inhibitors 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) and methylene blue. These results suggest the participation of NO/cyclic GMP/Ca²⁺ and K⁺ channel pathways in the antinociceptive effect caused by (PhSe)₂.     

Mechanisms involved in the antinociceptive and anti‐inflammatory effects of bis selenide in mice

Objectives The present study examined the mechanisms involved in the antinociceptive effects of bis selenide [(Z)‐2,3‐bis(4‐chlorophenylselanyl)prop‐2‐en‐1‐ol]. Methods The effects of oral bis selenide were tested against licking behaviour and oedema in mice induced by formalin, serotonin, histamine, glutamate, phorbol 12‐myristate 13‐acetate (PMA), 8‐bromoadenosine 3′,5′‐cyclic monophosphate (8‐BrcAMP) and pros‐taglandin E₂. The effects of a variety of receptor antagonists on the antinociceptive activity were tested to determine the likely mechanism of action of bis selenide. Key findings Bis selenide caused antinociception on the first and second phases of the formalin test, with mean ID50 values of 34.21 (29.66–39.45) and 15.86 (12.17–20.67) mg/kg and maximal inhibition of 65 ± 3% and 90 ± 1%, respectively. At 50 mg/kg bis selenide significantly inhibited (31 ± 2%) paw oedema induced by intraplantar injection of formalin. At 25 mg/kg given 5 min after the formalin injection, bis selenide caused a significant inhibition (42 ± 5%) in the second phase of the formalin test, whereas the prophylactic treatment caused more intense inhibition (64 ± 3%). Oral administration of bis selenide reduced licking and paw oedema induced by serotonin, histamine, glutamate, PGE₂, PMA and 8‐BrcAMP. The antinociceptive effect of bis selenide (25 mg/kg, p.o.) on the formalin test was reversed by i.p. administration of p‐chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis), ketanserin (a selective 5‐HT_2a receptor antagonist), ondansetron (a 5‐HT₃ receptor antagonist) and ranitidine (a histamine H₂‐receptor antagonist). Conclusions Glutamatergic, prostaglandin E₂, serotonergic (5‐HT_2a and 5‐HT₃) and histamine H₂ receptors are involved in the antinociceptive effects of bis selenide in mice. The interaction of bis selenide with protein kinase C and A signalling pathways was also demonstrated.     

Evaluation of nano-technology-modified zirconia oral implants: a study in rabbits

Objective: The objective of this study was to screen candidate nano-technology-modified, micro-structured zirconia implant surfaces relative to local bone formation and osseointegration.
Materials and Methods: Proprietary nano-technology surface-modified (calcium phosphate: CaP) micro-structured zirconia implants (A and C), control micro-structured zirconia implants (ZiUnite™), and titanium porous oxide implants (TiUnite™) were implanted into the femoral condyle in 40 adult male New Zealand White rabbits. Each animal received one implant in each hind leg; thus, 20 animals received A and C implants and 20 animals received ZiUnite™ and TiUnite™ implants in contralateral hind legs. Ten animals/group were euthanized at weeks 3 and 6 when biopsies of the implant sites were processed for histometric analysis using digital photomicrographs produced using backscatter scanning electron microscopy.
Results: The TiUnite™ surface demonstrated significantly greater bone–implant contact (BIC) (77.6±2.6%) compared with the A (64.6±3.6%) and C (62.2±3.1%) surfaces at 3 weeks ( p <0.05). Numerical differences between ZiUnite™ (70.5±3.1%) and A and C surfaces did not reach statistical significance ( p >0.05). Similarly, there were non-significant differences between the TiUnite™ and the ZiUnite™ surfaces ( p >0.05). At 6 weeks, there were no significant differences in BIC between the TiUnite™ (67.1±4.2%), ZiUnite™ (69.7±5.7%), A (68.6±1.9%), and C (64.5±4.1%) surfaces ( p >0.05).
Conclusion: TiUnite™ and ZiUnite™ implant surfaces exhibit high levels of osseointegration that, in this model, confirm their advanced osteoconductive properties. Addition of CaP nano-technology to the ZiUnite™ surface does not enhance the already advanced osteoconductivity displayed by the TiUnite™ and ZiUnite™ implant surfaces.     

Efficacy and tolerability of once-monthly oral ibandronate (150 mg) and once-weekly oral alendronate (70 mg): Additional results from the monthly oral therapy with ibandronate for osteoporosis intervention (MOTION) study

Background: The MOTION (Monthly Oral Therapy with Ibandronate for Osteoporosis Intervention) study reported that once-monthly ibandronate was noninferior to once-weekly alendronate in terms of increasing bone mineral density (BMD) at the lumbar spine and total hip over 12 months. On analysis of secondary and exploratory end points in MOTION, which included trochanter and femoral neck BMD, monthly ibandronate was found to be noninferior to weekly alendronate. The coprimary, secondary, and exploratory BMD end points from MOTION have been previously reported.Objective: This report presents additional results from the MOTION study, including response rates in terms of lumbar spine and total hip BMD gains above baseline; findings from a comparison of serum concentrations of bone turnover markers; and tolerability analysis, including adverse events that led to withdrawal and gastrointestinal (GI) adverse events.Methods: MOTION was a 12-month (with 15-day follow-up), randomized, multinational, multicenter, double-blind, double-dummy, parallel-group, nonin-feriority study in postmenopausal women aged 55 to <85 years with osteoporosis. Patients were randomly assigned to receive 150-mg-monthly oral ibandronate and weekly alendronate-matched placebo, or 70-mg-weekly oral alendronate and monthly ibandronate-matched placebo, for 12 months. At baseline, day 7 of treatment, 3 and 6 months, 6 months + 7 days, and 12 months, serum concentrations of markers of bone resorption (C-telopeptide of the a chain of type 1 collagen [sCTX]) and bone formation (serum N-terminal propeptides of type 1 collagen) were measured in a subset of the total trial population. At baseline and month 12, BMD was measured using dual-energy x-ray absorptiometry. Exploratory analyses of patients whose spine, total hip, and trochanter BMD at 12 months were above baseline (responders) were also performed.Results: A total of 1760 women were enrolled (ibandronate, 887 patients; alendronate, 873). The median changes in the trough concentrations of sCTX were ?75.5% with monthly ibandronate and ?81.2% with weekly alendronate. The percentage of patients with mean lumbar spine and total hip BMD gains above baseline (responders) were 90% and 87%, respectively, for ibandronate and 92% and 90%, respectively, for alendronate. GI adverse events were reported in ≤30% of patients per group during this 1-year study.Conclusion: The data from these postmenopausal women with osteoporosis suggest that once-monthly 150-mg ibandronate therapy provided clinically comparable efficacy in terms of BMD response, reductions in bone turnover, and GI tolerability similar to that of weekly 70-mg alendronate.     

Simultaneous epicardial and endocardial substrate mapping and radiofrequency catheter ablation as first-line treatment for ventricular tachycardia and frequent ICD shocks in chronic chagasic cardiomyopathy

Background and Aims  

Slow conduction scarred areas are related with ventricular tachycardia (VT) arrhythmogenesis in nonischemic cardiomyopathy. The purpose of this study was to characterize the substrate in both epicardial and endocardial surfaces of the left ventricle and to evaluate the effectiveness of substrate mapping and ablation for VT in Chagas cardiomyopathy.