Pinealectomy interferes with the circadian clock genes expression in white adipose tissue

Melatonin, the main hormone produced by the pineal gland, is secreted in a circadian manner (24‐hr period), and its oscillation influences several circadian biological rhythms, such as the regulation of clock genes expression (chronobiotic effect) and the modulation of several endocrine functions in peripheral tissues. Assuming that the circadian synchronization of clock genes can play a role in the regulation of energy metabolism and it is influenced by melatonin, our study was designed to assess possible alterations as a consequence of melatonin absence on the circadian expression of clock genes in the epididymal adipose tissue of male Wistar rats and the possible metabolic repercussions to this tissue. Our data show that pinealectomy indeed has impacts on molecular events: it abolishes the daily pattern of the expression of Clock, Per2, and Cry1 clock genes and Pparγ expression, significantly increases the amplitude of daily expression of Rev‐erbα, and affects the pattern of and impairs adipokine production, leading to a decrease in leptin levels. However, regarding some metabolic aspects of adipocyte functions, such as its ability to synthesize triacylglycerols from glucose along 24 hr, was not compromised by pinealectomy, although the daily profile of the lipogenic enzymes expression (ATP‐citrate lyase, malic enzyme, fatty acid synthase, and glucose‐6‐phosphate dehydrogenase) was abolished in pinealectomized animals.     

A clinically applicable method to preserve urine and bladder washing cells for flow cytometric monitoring of bladder cancer patients

We describe a method to fix exfoliated bladder cells that is suitable for followup of bladder cancer patients by deoxyribonucleic acid flow cytometry. After fixation with room temperature methanol plus acetic acid (20:1, volume:volume) urine and bladder washing samples from these patients can be stored at room temperature for 3 to 7 days and then assessed reliably for the presence of aneuploidy and the percentage of hyperdiploid cells. For those with active transitional cell carcinoma diagnostic accuracy comparing fresh to fixed specimens was improved from 58 to 92% with urine and from 50 to 100% with washing samples. For patients with a history of transitional cell carcinoma who currently are free of disease the false positive rate remains unchanged after fixation. The procedure described is suitable for use in the outpatient clinic and should permit shipping of samples without refrigeration to a central flow cytometry facility for analysis.     

Heterogeneity ofin vitro chemosensitivity in perioperative breast cancer cells to mitoxantroneversus doxorubicin evaluated by a microplate ATP bioluminescence assay

Summary Apart from clinical trials, mitoxantrone (MX) is rarely used in breast cancer (BC) due to the anticipated anthracycline cross-resistance. We have examined this drug versus doxorubicin (DOX) using data obtained fromin vitro microplate ATP tumor chemosensitivity assays (ATP-TCA) of BC cells which were derived from 55 chemotherapy-naive patients at time of primary surgery. Both drugs were tested at 6 different concentrations ranging from 6.25% to 200% peak plasma concentrationin vivo (PPC). Differences between DOX and MX observed for mean IC₅₀, IC₉₀, and a sensitivity index (SI) were not statistically significant.In vitro response rates were 44% for DOX and 52% for MX. 34 of 52 eligible assays (65%) showed comparable activity of both drugs whereas a lack of cross-resistance was observed in the remaining 18 (35%) tumors as indicated by differences for SI. Cumulative concentration-response plots of tumors respondingin vitro with a 50 percent or 90 percent tumor cell inhibition showed a strong dose-dependence for both DOX and MX at concentrations which normally can be achieved within clinical tumors (i.e. 6.25%-50% PPC). At higher concentrations, however, cytotoxicity of DOX and MX could not be improved by furtherin vitro dose escalation. Moreover, a substantial proportion of BC specimens (DOX: 48.1%; MX: 40.4%) did not experience a 90 tumor cell inhibition at 200% PPC. In conclusion,in vitro results obtained by ATP-TCA indicate that there is no cross-resistance between MX and DOX in a substantial proportion of BC patients. This may be clinically useful and suggests that combinations including MX should be tested in patients clinically resistant to DOX containing regimens. Since both drugs produced sigmoidal concentration-response curves, dose escalation beyond a certain point may not produce increased sensitivity.     

Clinical Perspectives and Pearls from the 2015 ESC NSTE-ACS Guidelines

Four years after the latest edition, the 2015 non-ST-segment elevation acute coronary syndromes guidelines of the European Society of Cardiology have been published. Novel aspects include a new diagnostic algorithm for non-ST-segment elevation myocardial infarction using high-sensitivity cardiac troponins as well as guidance on cardiac rhythm monitoring duration. A large section is dedicated to antiplatelet therapy including initiation and duration of dual-antiplatelet therapy as well as the management of patients requiring, at the same time, long-term oral anticoagulation. New sections include the management of antiplatelet agent in patients requiring coronary artery bypass surgery and of acute bleeding events related to antiplatelet agents, vitamin K antagonist (VKA), and non-VKA oral anticoagulant drugs. Current evidence supports the radial access over the femoral one for coronary angiography and percutaneous revascularization.     

Phlebotomine fauna in the Ponta Porã city: epidemiological importance in border line between Brazil and Paraguay

ObjectiveTo identify the urban phlebotomine sandfly fauna in Ponta Porã, Mato Grosso do Sul State, Brazil.MethodsThe captures were undertaken from April 2009 to March 2010 with CDC light traps in 14 ecotopes (intra and peridomicile) in different areas of the city, Shannon traps being used in areas with abundant vegetation.ResultsA total of 707 specimens were captured with CDC light traps (565 males and 142 females) and 155 specimens (112 males and 43 females) with Shannon traps, a total of 862 phlebotomines. The specimens captured belonged to eight species: Lutzomyia longipalpis (Lutz & Neiva, 1912), Evandromyia cortelezzii (Brethes, 1923), Sciopemyia sordelli (Shannon & Del Ponte, 1927), Pintomyia pessoai (Coutinho & Barretto, 1940); Pintomyia monticola (Costa Lima, 1932); Brumptomyia brumpti (Larousse, 1920); Nyssomyia whitmani (Antunes & Coutinho, 1939) and Psathyromyia shannoni (Dyar, 1929). Lutzomyia longipalpis, the main vector of Leishmania (Leishmania) chagasi, was the species most frequently captured (97.03%) and also the most abundant according to the standardized abundance index (SAI)=0.86.ConclusionsThe highest species richness was captured, with CDC light traps, inside the domiciles and the species diversity and evenness in the peridomicile, clearly indicating a preference for anthropic environments.