A new species of Hoplomyzon (Siluriformes: Aspredinidae) from Maracaibo Basin, Venezuela: osteological description using high-resolution computed microtomography of a miniature species

ABSTRACT A new miniature species of banjo catfish of the genus Hoplomyzon is described from the Lake Maracaibo Basin in Venezuela. The new species is distinguished from all its congeners by the straight anterior margin of the mesethmoid (vs. a medial notch); a smooth and straight ventral surface of the premaxilla (vs. presence of bony knobs on the ventral surface of premaxilla); absence of teeth on dentary (vs. teeth present on dentary); configuration of ventral vertebral processes anterior to anal fin, which are composed of single processes anterior to anal-fin pterygiophore (vs. paired process); presence of several filamentous barbel-like structures on the ventral surface of head of adults (vs. small papillous structures in the ventral surface of head of adults); and 8 anal-fin rays (vs. 6 or 7). An extensive osteological description is made of the holotype using high-resolution x-ray computed microtomography (HRXCT)

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Development of B Cells and Erythrocytes Is Specifically Impaired by the Drug Celastrol in Mice

Background: Celastrol, an active compound extracted from the root of the Chinese medicine ‘‘Thunder of God Vine’’ (Tripterygium wilfordii), exhibits anticancer, antioxidant and anti-inflammatory activities, and interest in the therapeutic potential of celastrol is increasing. However, described side effects following treatment are significant and require investigation prior to initiating clinical trials. Here, we investigated the effects of celastrol on the adult murine hematopoietic system. Methodology/Principal Findings: Animals were treated daily with celastrol over a four-day period and peripheral blood, bone marrow, spleen, and peritoneal cavity were harvested for cell phenotyping. Treated mice showed specific impairment of the development of B cells and erythrocytes in all tested organs. In bone marrow, these alterations were accompanied by decreases in populations of common lymphoid progenitors (CLP), common myeloid progenitors (CMP) and megakaryocyte-erythrocyte progenitors (MEP). Conclusions/Significance: These results indicate that celastrol acts through regulators of adult hematopoiesis and could be used as a modulator of the hematopoietic system. These observations provide valuable information for further assessmen

Unlike for Human Monocytes after LPS Activation, Release of TNF-α by THP-1 Cells Is Produced by a TACE Catalytically Different from Constitutive TACE

Tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine today identified as a key mediator of several chronic inflammatory diseases. TNF-α, initially synthesized as a membrane-anchored precursor (pro-TNF-α), is processed by proteolytic cleavage to generate the secreted mature form. TNF-α converting enzyme (TACE) is currently the first and single protease described as responsible for the inducible release of soluble TNF-α.Here, we demonstrated the presence on THP-1 cells as on human monocytes of a constitutive proteolytical activity able to cleave pro-TNF-α. Revelation of the cell surface TACE protein expression confirmed that the observed catalytic activity is due to TACE. However, further studies using effective and innovative TNF-α inhibitors, as well as a highly selective TACE inhibitor, support the presence of a catalytically different sheddase activity on LPS activated THP-1 cells. It appears that this catalytically different TACE protease activity might have a significant contribution to TNF-α release in LPS activated THP-1 cells, by contrast to human monocytes where the TACE activity remains catalytically unchanged even after LPS activation.On the surface of LPS activated THP-1 cells we identified a releasing TNF-α activity, catalytically different from the sheddase activity observed on human monocytes from healthy donors. This catalytically-modified TACE activity is different from the constitutive shedding activity and appears only upon stimulation by LPS

The Functional Interplay between Protein Kinase CK2 and CCA1 Transcriptional Activity Is Essential for Clock Temperature Compensation in Arabidopsis

Circadian rhythms are daily biological oscillations driven by an endogenous mechanism known as circadian clock. The protein kinase CK2 is one of the few clock components that is evolutionary conserved among different taxonomic groups. CK2 regulates the stability and nuclear localization of essential clock proteins in mammals, fungi, and insects. Two CK2 regulatory subunits, CKB3 and CKB4, have been also linked with the Arabidopsis thaliana circadian system. However, the biological relevance and the precise mechanisms of CK2 function within the plant clockwork are not known. By using ChIP and Double–ChIP experiments together with in vivo luminescence assays at different temperatures, we were able to identify a temperature-dependent function for CK2 modulating circadian period length. Our study uncovers a previously unpredicted mechanism for CK2 antagonizing the key clock regulator CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1). CK2 activity does not alter protein accumulation or subcellular localization but interferes with CCA1 binding affinity to the promoters of the oscillator genes. High temperatures enhance the CCA1 binding activity, which is precisely counterbalanced by the CK2 opposing function. Altering this balance by over-expression, mutation, or pharmacological inhibition affects the temperature compensation profile, providing a mechanism by which plants regulate circadian period at changing temperatures. Therefore, our study establishes a new model demonstrating that two opposing and temperature-dependent activities (CCA1-CK2) are essential for clock temperature compensation in Arabidopsis

– Implante de Marcapasso nas Bradicardias e em Outras Situações Especiais – Estratificação de Risco de Morte Súbita na Cardiomiopatia Chagásica

A frequência cardíaca normal varia de 60 bpm a 100 bpm. Ritmos com frequência cardíaca < 60 bpm são definidos como bradicardia, que pode ser assintomática ou sintomática. As bradicardias sintomáticas têm características clínicas comuns, marcadas, sobretudo, pela síndrome do baixo fluxo cerebral e/ou sistêmico, cujos sintomas mais comuns são tontura, pré-síncope, síncope, fadiga, dispneia de esforço e bradipsiquismo, sendo comumente ocasionadas por doença do nó sinusal e bloqueio atrioventricular. As assintomáticas, geralmente, são de causas fisiológicas, representadas por bradicardia sinusal e ritmos de escape da junção atrioventricular

– Cardiodesfibrilador Implantável – Infecção em DCEI – Papel dos Fármacos Antiarrítmicos – Direção Veicular em Portadores de DCEI

Desde o primeiro implante, em 1980, até os dias atuais, ocorreram importantes avanços no cardiodesfibrilador implantável (CDI), tanto no tamanho como nas funções e programações. Atualmente esses dispositivos dispõem de terapia antitaquicardia (ATP), cardioversão com baixa energia, desfibrilação com alta energia e função antibradicardia de backup. Diversos estudos de grande porte demonstraram que o CDI trata efetivamente os eventos de taquicardia ventricular e fibrilação ventricular, reduzindo a mortalidade quando comparado com fármacos antiarrítmicos isoladamente.[...

– Terapia de Ressincronização Cardíaca

A insuficiência cardíaca é uma significante causa de morbidade e mortalidade em todo o mundo, com prevalência de 2,4% dos adultos 1 (A). Embora a sobrevivência após o diagnóstico de insuficiência cardíaca tenha melhorado nas duas últimas décadas, as taxas de morte e hospitalização por insuficiência cardíaca permanecem altas e aproximadamente 50% dos pacientes morrem dentro de 5 anos do diagnóstico 1 (A). Adicionalmente, a despeito do tratamento medicamentoso otimizado, muitos pacientes com insuficiência cardíaca permanecem sintomáticos e com redução da qualidade de vida 2 (D)