Ivabradine treatment lowers blood pressure and promotes cardiac and renal protection in spontaneously hypertensive rats.

Hypertension is linked to hyperpolarization-activated cyclic nucleotide-gated (HCN) function, expressed in excitable and non-excitable cells. Considering that the reduction in heart rate (HR) improves coronary perfusion and cardiac performance, ivabradine (IVA) emerged as an important drug for the treatment of cardiovascular diseases. AIM: Evaluate if IVA chronic treatment effect can mitigate hypertension and reverse the cardiac and renal damage in SHR. MAIN METHODS: Rats were divided into 4 groups treated for 14 days with PBS (1 ml/kg; i.p) or IVA (1 mg/kg; i.p): 1) WKY PBS; 2) SHR PBS; 3) WKY IVA; and 4) SHR IVA. The systolic blood pressure (SBP) was measured, indirectly, before and during the treatment period with IVA (day 0, 1, 7 and 11). Rats were subjected to artery cannulation for direct blood pressure (BP) measurement. Morphofunctional and gene expression were evaluated in the heart and kidneys. KEY FINDINGS: IVA reduced SBP only in SHR on the 7th day. Direct blood pressure measurement showed that IVA chronic treatment reduced HR in the SHR. Interestingly, mean arterial pressure (MAP) was reduced in SHR IVA when compared to SHR PBS. Serum and urinary biochemical data were not altered by IVA. Moreover, IVA reduced the renal inflammatory infiltrates and increased glomerular density, besides preventing the cardiac inflammatory and hypertrophic responses. SIGNIFICANCE: IVA treatment lowered blood pressure, improved cardiac remodeling and inflammation, as well as decreasing renal damage in SHR. Further, IVA increased renal HCN2 mRNA and reduced cardiac HCN4 mRNA.

Protective Effects of Quercetin on Livers from Mice Exposed to Long-Term Cigarette Smoke.

Cigarette smoke is highly toxic, and it can promote increased production of reactive species and inflammatory response and leads to liver diseases. Quercetin is a flavonoid that displays antioxidant and anti-inflammatory activities in liver diseases. This study aimed at evaluating the protective effects of quercetin on livers from mice exposed to long-term cigarette smoke exposure. Male C57BL/6 mice were divided into five groups: control (CG), vehicle (VG), quercetin (QG), cigarette smoke (CSG), quercetin, and cigarette smoke (QCSG). CSG and QCSG were exposed to cigarette smoke for sixty consecutive days; at the end of the exposures, all animals were euthanized. Mice that received quercetin daily and were exposed to cigarette smoke showed a reduced influx of inflammatory cells, oxidative stress, inflammatory reaction, and histopathological changes in the liver, compared to CSG. These results suggest that quercetin may be an effective adjuvant for treating damage to the liver due to cigarette smoke exposure.

Applying Positive End-Expiratory Pressure During Mechanical Ventilation Causes Pulmonary Redox Imbalance and Inflammation in Rats.

BACKGROUND: Mechanical ventilation (MV) may induce or aggravate lung injury through the production of cytokines, inflammatory infiltration of neutrophils, and changes in the permeability of the alveolar-capillary barrier. The use of positive end-expiratory pressure (PEEP) helps improve gas exchanges avoiding alveolar collapse at the end of expiration. The present study aimed to analyze inflammatory response and redox imbalance in lungs of rats submitted to MV with and without PEEP. METHODS: Eighteen Wistar rats were divided into three groups: control (CG), PEEP group (PG), and zero PEEP (ZEEP) group (ZG). PG and ZG were submitted to MV for 60 min with or without PEEP, respectively. Subsequently, the animals were euthanized, and blood, bronchoalveolar lavage fluid, and lungs were collected for analyses. RESULTS: The number of neutrophils was higher in PG compared with CG. Leucocyte and neutrophil influx in bronchoalveolar lavage fluid was higher in PG compared with CG. PG showed an increase in alveolar area compared with the other groups. There were increases in the levels of chemokines, CCL3 and CCL5, in PG compared with CG. There were increases in oxidation of lipids and proteins in PG compared with other groups. There were increases in the activity of superoxide dismutase and catalase in PG compared with CG and ZG. However, there was a decrease in the ratio of glutathione to glutathione disulfide in PG compared with other groups. CONCLUSIONS: MV with PEEP caused redox imbalance and inflammation in lungs of healthy rats.

A potential link among antioxidant enzymes, histopathology and trace elements in canine visceral leishmaniasis.

Canine visceral leishmaniasis (CVL) is a severe and fatal systemic chronic inflammatory disease. We investigated the alterations in, and potential associations among, antioxidant enzymes, trace elements and histopathology in CVL. Blood and tissue levels of Cu-Zn superoxide dismutase, catalase and glutathione peroxidase were measured in mixed-breed dogs naturally infected with Leishmania infantum chagasi, symptomatic (n = 19) and asymptomatic (n = 11). Serum levels of copper, iron, zinc, selenium and nitric oxide, and plasma lipid peroxidation were measured. Histological and morphometric analyses were conducted of lesions in liver, spleen and lymph nodes. We found lower blood catalase and glutathione peroxidase activity to be correlated with lower iron and selenium respectively. However, higher activity of Cu-Zn superoxide dismutase was not correlated with the increase in copper and decreased in zinc observed in infected animals compared to controls. Organ tissue was characterized by lower enzyme activity in infected dogs than in controls, but this was not correlated with trace elements. Lipid peroxidation was higher in symptomatic than in asymptomatic and control dogs and was associated with lesions such as chronic inflammatory reaction, congestion, haemosiderin and fibrosis. Systemic iron deposition was observed primarily in the symptomatic dogs showing a higher tissue parasite load. Dogs with symptomatic CVL displayed enhanced LPO and Fe tissue deposition associated with decreased levels of antioxidant enzymes. These results showed new points in the pathology of CVL and might open new treatment perspectives associated with antioxidants and the role of iron in the pathogenesis of CVL.

The endogenous cytokine profile and nerve fibre density in mouse ear Leishmania major-induced lesions related to nociceptive thresholds.

Several reports have shown that cutaneous leishmaniasis lesions are painless, suggesting that Leishmania infection interferes with pain perception. Comparisons of inflammation-induced hyperalgesia between BALB/c and C57BL/6 mice have been little explored in the literature, and comparative data regarding nociception in leishmaniasis are non-existent. In susceptible BALB/c mice and resistant C57BL/6 mice that were intradermally inoculated with a low dose of Leishmania major in the ear, we investigated the variation in nociception over a 12-wk period post-infection and this variation's association with the structure of nerve fibres and the presence of endogenous cytokines that are classically considered hyper- or hypo-nociceptive. Infected BALB/c mice presented susceptibility and severe lesions. Infected C57BL/6 mice exhibited resistance and healing lesions. The immune response involved pro- and anti-inflammatory cytokine secretion, respectively. The infection-induced hypoalgesia in BALB/c mice after wks 9 was accompanied by decreased levels of IL-6 and IL-10 in ear tissue with intact nerves. C57BL/6 mice showed short-lived hyperalgesia in wks 2, which was related to increased local levels of IL-6, KC/CXCL-1, TNF-α and IL-10 and a decrease in nerve density. The increase in pro-inflammatory cytokine IL-6, KC/CXCL-1 and TNF-α levels during hyperalgesia suggested a role for these mediators in afferent nerve sensitisation, which was secondary to the inflammatory damage of nerve fibres stained by PGP 9.5. In contrast, the mechanisms of hypoalgesia may include the downregulation of cytokines, the preservation of the structure of nerve endings, and as yet uninvestigated unidentified differences in neurotransmitter release or a direct role of the parasites in the context of the progressive and permissive inflammatory response of BALB/c mice.

Ethical abuses in the authorship of scientific papers

Problems regarding the order of authorship of scientific papers have become more frequent and more abusive. These problems may have heightened due to the ever increasing pressure to "publish or perish" in the academic world, given that the publication of scientific articles has become the benchmark of success in a field with few job opportunities. This article reviews the abuses in the authorship of scientific papers. Different examples are given of the most common problems and recommendations are provided for authors and journal editors.

Problemas relacionados a determinação de autoria de trabalhos científicos são freqüentes. Estes problemas vêm se agravando em decorrência da supervalorização do número de publicações no mundo acadêmico, uma vez que, a publicação de artigos científicos tornou-se uma referência de sucesso em um campo com poucas oportunidades de trabalho. Este artigo revê os abusos na autoria de artigos científicos. Diferentes exemplos são citados dos problemas mais comuns e recomendações básicas são feitas para autores e editores.