Renal denervation in an animal model of diabetes and hypertension: Impact on the autonomic nervous system and nephropathy

<p>Abstract</p> <p>Background</p> <p>The effects of renal denervation on cardiovascular reflexes and markers of nephropathy in diabetic-hypertensive rats have not yet been explored.</p> <p>Methods</p> <p>Aim: To evaluate the effects of renal denervation on nephropathy development mechanisms (blood pressure, cardiovascular autonomic changes, renal GLUT2) in diabetic-hypertensive rats. Forty-one male spontaneously hypertensive rats (SHR) ~250 g were injected with STZ or not; 30 days later, surgical renal denervation (RD) or sham procedure was performed; 15 days later, glycemia and albuminuria (ELISA) were evaluated. Catheters were implanted into the femoral artery to evaluate arterial pressure (AP) and heart rate variability (spectral analysis) one day later in conscious animals. Animals were killed, kidneys removed, and cortical renal GLUT2 quantified (Western blotting).</p> <p>Results</p> <p>Higher glycemia (p < 0.05) and lower mean AP were observed in diabetics <it>vs. </it>nondiabetics (p < 0.05). Heart rate was higher in renal-denervated hypertensive and lower in diabetic-hypertensive rats (384.8 ± 37, 431.3 ± 36, 316.2 ± 5, 363.8 ± 12 bpm in SHR, RD-SHR, STZ-SHR and RD-STZ-SHR, respectively). Heart rate variability was higher in renal-denervated diabetic-hypertensive rats (55.75 ± 25.21, 73.40 ± 53.30, 148.4 ± 93 in RD-SHR, STZ-SHR- and RD-STZ-SHR, respectively, p < 0.05), as well as the LF component of AP variability (1.62 ± 0.9, 2.12 ± 0.9, 7.38 ± 6.5 in RD-SHR, STZ-SHR and RD-STZ-SHR, respectively, p < 0.05). GLUT2 renal content was higher in all groups <it>vs</it>. SHR.</p> <p>Conclusions</p> <p>Renal denervation in diabetic-hypertensive rats improved previously reduced heart rate variability. The GLUT2 equally overexpressed by diabetes and renal denervation may represent a maximal derangement effect of each condition.</p

Identifying and managing patient–ventilator asynchrony: An international survey.

Objective: To describe the main factors associated with proper recognition and management of patient ventilator asynchronies (PVA). Design: Analytical cross-sectional study. Setting: International study conducted in 20 countries through an online survey. Participants: Physicians, respiratory therapists, nurses and physiotherapists that are currently working at the Intensive Care Unit (ICU). Main variables of interest: Univariate and multivariate logistic regression models were used to establish associations between all variables (profession, training in mechanical ventilation, type of training program, years of experience and ICU characteristics) with the ability of HCPs to correctly identify and manage 6 PVA. Results: A total of 431 HCPs answered a validated survey. The main factors associated with the proper recognition of PVA were: specific training program in mechanical ventilation (MV) (OR 2.27; 95% CI 1.14-4.52; p = 0.019), courses with more than 100 hours completed (OR 2.28; 95% CI 1.29-4.03; p = 0.005) and the number of intensive care unit (ICU) beds (OR 1.037; 95% CI 1.01-1.06; p = 0.005). The main factor that influenced PVA management was recognizing 6 PVA correctly (OR 118.98; 95%CI 35.25-401.58; p < 0.001). Conclusion: Identifying and managing PVA using ventilator waveform analysis is influenced by many factors including specific training programs in MV, number of ICU beds and the recognized number of PVA.pre-print169 K

Relationships between body growth indices and environmental factors on the reproductive cycle of the Gymnodactylus geckoides Spix, 1825 (Squamata, Gymnophthalmidae) in Northeast Brazil

In this study, we analyzed the energy and reproductive cycles of female and male Gymnodactylus geckoides in the Caatinga area of northeast Brazil. We investigated whether these proxies of body condition, such as reproductive cells maturation and cellular structures changed in response to variation in abiotic and biotic factors (i.e., humidity, temperature, seasonality, body temperature, growing rate and gonad volume), using individuals stored under scientific conditions collected between September 2018 and December 2021. The condition factor showed an isometric growth pattern in the population studied. Meanwhile, the lipid, hepatic, and gonad factors correlated with body growth and showed monthly and seasonal variations, as well as reproductive cell maturation and cellular structure morphology. The cycles displayed constant replacement of energy reserves and mature reproductive cells, indicating constant and acyclic reproduction in G. geckoides. Energy reserves appear to be used for many reproductive activities, including meeting, gestation, and egg laying that occur at different frequencies during different periods in the dry and rainy seasons. Therefore, the reproductive cycle is likely to be strongly controlled by biotic factors, which are modeled using abiotic factors and environmental conditions (environmental patterns which proportionate greater resource availability). Our study is the first to investigate energy cycles and reproductive strategies in G. geckoides. It has shown that this species stores greater amounts of energy during the rainy season and then depletes these reserves during the dry period, since the rainy season correspond to the increase in energy consumption, mainly because of gestation and egg laying.Asociación Herpetológica Argentin

Relationships between body growth indices and environmental factors on the reproductive cycle of the Gymnodactylus geckoides Spix, 1825 (Squamata, Gymnophthalmidae) in Northeast Brazil

In this study, we analyzed the energy and reproductive cycles of female and male Gymnodactylus geckoides in the Caatinga area of northeast Brazil. We investigated whether these proxies of body condition, such as reproductive cells maturation and cellular structures changed in response to variation in abiotic and biotic factors (i.e., humidity, temperature, seasonality, body temperature, growing rate and gonad volume), using individuals stored under scientific conditions collected between September 2018 and December 2021. The condition factor showed an isometric growth pattern in the population studied. Meanwhile, the lipid, hepatic, and gonad factors correlated with body growth and showed monthly and seasonal variations, as well as reproductive cell maturation and cellular structure morphology. The cycles displayed constant replacement of energy reserves and mature reproductive cells, indicating constant and acyclic reproduction in G. geckoides. Energy reserves appear to be used for many reproductive activities, including meeting, gestation, and egg laying that occur at different frequencies during different periods in the dry and rainy seasons. Therefore, the reproductive cycle is likely to be strongly controlled by biotic factors, which are modeled using abiotic factors and environmental conditions (environmental patterns which proportionate greater resource availability). Our study is the first to investigate energy cycles and reproductive strategies in G. geckoides. It has shown that this species stores greater amounts of energy during the rainy season and then depletes these reserves during the dry period, since the rainy season correspond to the increase in energy consumption, mainly because of gestation and egg laying.Asociación Herpetológica Argentin

Magnetoliposomes as nanocarriers for fluorescent potential antitumor drugs

Both aqueous magnetoliposomes (AMLs, containing magnetic nanoparticles entrapped in liposomes) and solid magnetoliposomes (SMLs, where clusters of nanoparticles are covered by a lipid bilayer) containing several different nanoparticles (magnetite, nickel ferrite, manganese ferrite or magnesium ferrite) have been developed, exhibiting a superparamagnetic behavior and diameters below 150 nm.Financial support by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding to CF-UM-UP (UID/FIS/04650/2013) and CQUM (UID/QUI/00686/2016) is acknowledged. A.R.O. Rodrigues thanks the FCT for SFRH/BD/90949/2012 PhD grant and funding to MAP-Fis Doctoral Program.info:eu-repo/semantics/publishedVersio

Lista de gêneros de Hymenoptera (Insecta) do Espírito Santo, Brasil

The first checklist of genera of Hymenoptera from Espírito Santo state, Brazil is presented. A total of 973 genera of Hymenoptera is listed, of which 555 (57%) are recorded for the first time from this state. Ichneumonoidea and Chalcidoidea are the two superfamilies with the most genera, 241 and 203 respectively. Braconidae, with 141 genera, are the richest family.The first checklist of genera of Hymenoptera from Espírito Santo state, Brazil is presented. A total of 973 genera of Hymenoptera is listed, of which 555 (57%) are recorded for the first time from this state. Ichneumonoidea and Chalcidoidea are the two superfamilies with the most genera, 241 and 203 respectively. Braconidae, with 141 genera, are the richest family.Fil: Azevedo, Celso O.. Universidade Federal do Espírito Santo; BrasilFil: Molin, Ana Dal. Texas A&M University; Estados UnidosFil: Penteado-Dias, Angelica. Universidade Federal do São Carlos; BrasilFil: Macedo, Antonio C. C.. Secretaria do Meio Ambiente do Estado de São Paulo; BrasilFil: Rodriguez-V, Beatriz. Universidad Nacional Autónoma de México; MéxicoFil: Dias, Bianca Z. K.. Universidade Federal do Espírito Santo; BrasilFil: Waichert, Cecilia. State University of Utah; Estados UnidosFil: Aquino, Daniel Alejandro. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Entomología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Smith, David. Smithsonian Institution; Estados UnidosFil: Shimbori, Eduardo M.. Universidade Federal do São Carlos; BrasilFil: Noll, Fernando B.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Gibson, Gary. Agriculture and Agri-Food Canada; CanadáFil: Onody, Helena. Universidade Federal do São Carlos; BrasilFil: Carpenter, James M.. American Museum of Natural History; Estados UnidosFil: Lattke, John. Universidad Nacional de Loja; EcuadorFil: Ramos, Kelli dos S.. Universidade de Sao Paulo; BrasilFil: Williams, Kevin. Florida State Collection of Arthropods; Estados UnidosFil: Masner, Lubomir. Agriculture and Agri-Food Canada; CanadáFil: Kimsey, Lynn. University of California; Estados UnidosFil: Tavares, Marcelo T.. Universidade Federal do Espírito Santo; BrasilFil: Olmi, Massimo. Università degli Studi della Tuscia; ItaliaFil: Buffington, Matthew L.. United States Department of Agriculture; Estados UnidosFil: Ohl, Michael. Staatliches Museum fur Naturkunde Stuttgart; AlemaniaFil: Sharkey, Michael. University of Kentucky; Estados UnidosFil: Johnson, Norman F.. Ohio State University; Estados UnidosFil: Kawada, Ricardo. Universidade Federal do Espírito Santo; BrasilFil: Gonçalves, Rodrigo B.. Universidade Federal do Paraná; BrasilFil: Feitosa, Rodrigo. Universidade Federal do Paraná; BrasilFil: Heydon, Steven. University of California; Estados UnidosFil: Guerra, Tânia M.. Universidade Federal do Espírito Santo; BrasilFil: da Silva, Thiago S. R.. Universidade Federal do Espírito Santo; BrasilFil: Costa, Valmir. Instituto Biológico; Brasi

17-AAG-induced activation of the autophagic pathway in Leishmania is associated with parasite death

The heat shock protein 90 (Hsp90) is thought to be an excellent drug target against parasitic diseases. The leishmanicidal effect of an Hsp90 inhibitor, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), was previously demonstrated in both in vitro and in vivo models of cutaneous leishmaniasis. Parasite death was shown to occur in association with severe ultrastructural alterations in Leishmania, suggestive of autophagic activation. We hypothesized that 17-AAG treatment results in the abnormal activation of the autophagic pathway, leading to parasite death. To elucidate this process, experiments were performed using transgenic parasites with GFP-ATG8-labelled autophagosomes. Mutant parasites treated with 17-AAG exhibited autophagosomes that did not entrap cargo, such as glycosomes, or fuse with lysosomes. ATG5-knockout (Δatg5) parasites, which are incapable of forming autophagosomes, demonstrated lower sensitivity to 17-AAG-induced cell death when compared to wild-type (WT) Leishmania, further supporting the role of autophagy in 17-AAG-induced cell death. In addition, Hsp90 inhibition resulted in greater accumulation of ubiquitylated proteins in both WT- and Δatg5-treated parasites compared to controls, in the absence of proteasome overload. In conjunction with previously described ultrastructural alterations, herein we present evidence that treatment with 17-AAG causes abnormal activation of the autophagic pathway, resulting in the formation of immature autophagosomes and, consequently, incidental parasite death

Autophagic Induction Greatly Enhances Leishmania major Intracellular Survival Compared to Leishmania amazonensis in CBA/j-Infected Macrophages

CBA mouse macrophages control Leishmania major infection yet are permissive to Leishmania amazonensis. Few studies have been conducted to assess the role played by autophagy in Leishmania infection. Therefore, we assessed whether the autophagic response of infected macrophages may account for the differential behavior of these two parasite strains. After 24 h of infection, the LC3-II/Act ratio increased in both L. amazonensis- and L. major-infected macrophages compared to uninfected controls, but less than in chloroquine-treated cells. This suggests that L. amazonensis and L. major activate autophagy in infected macrophages, without altering the autophagic flux. Furthermore, L. major-infected cells exhibited higher percentages of DQ-BSA-labeled parasitophorous vacuoles (50%) than those infected by L. amazonensis (25%). However, L. major- and L. amazonensis-induced parasitophorous vacuoles accumulated LysoTracker similarly, indicating that the acidity in both compartment was equivalent. At as early as 30 min, endogenous LC3 was recruited to both L. amazonensis- and L. major-induced parasitophorous vacuoles, while after 24 h a greater percentage of LC3 positive vacuoles was observed in L. amazonensis-infected cells (42.36%) compared to those infected by L. major (18.10%). Noteworthy, principal component analysis (PCA) and an hierarchical cluster analysis completely discriminated L. major-infected macrophages from L. amazonensis-infected cells accordingly to infection intensity and autophagic features of parasite-induced vacuoles. Then, we evaluated whether the modulation of autophagy exerted an influence on parasite infection in macrophages. No significant changes were observed in both infection rate or parasite load in macrophages treated with the autophagic inhibitors wortmannin, chloroquine or VPS34-IN1, as well as with the autophagic inducers rapamycin or physiological starvation, in comparison to untreated control cells. Interestingly, both autophagic inducers enhanced intracellular L. amazonensis and L. major viability, while the pharmacological inhibition of autophagy exerted no effects on intracellular parasite viability. We also demonstrated that autophagy induction reduced NO production by L. amazonensis- and L. major-infected macrophages but not alters arginase activity. These findings provide evidence that although L. amazonensis-induced parasitophorous vacuoles recruit LC3 more markedly, L. amazonensis and L. major similarly activate the autophagic pathway in CBA macrophages. Interestingly, the exogenous induction of autophagy favors L. major intracellular viability to a greater extent than L. amazonensis related to a reduction in the levels of NO