Effect of COVID-19 on cardiorenal axis: known or unknown universe?

Recent findings have confirmed relationships between coronavirus disease (COVID-19) and multiple organ dysfunction. The prevalence of cardiac and renal involvement in COVID-19 has been increasingly reported and is a marker of severe disease that not only directly or indirectly affects the organs, but may also exacerbate the underlying comorbid illness. In addition, patients affected by the new coronavirus present a systemic inflammatory condition that results in damage to several tissues, especially the heart, kidneys, and vessels. It is well known that the heart and kidneys are closely related, so that any change in one of the organs can lead to damage to the other, establishing the so-called cardiorenal syndrome. Herein, we explore some case reports of patients with COVID-19 who had heart and kidney abnormalities, consequently resulting in worse prognosis of the disease. These results highlight the importance of understanding the cause and effect between the cardiac and renal systems and the course of early SARS-CoV-2 infection.

Effect of COVID-19 on cardiorenal axis: known or unknown universe?

Recent findings have confirmed relationships between coronavirus disease (COVID-19) and multiple organ dysfunction. The prevalence of cardiac and renal involvement in COVID-19 has been increasingly reported and is a marker of severe disease that not only directly or indirectly affects the organs, but may also exacerbate the underlying comorbid illness. In addition, patients affected by the new coronavirus present a systemic inflammatory condition that results in damage to several tissues, especially the heart, kidneys, and vessels. It is well known that the heart and kidneys are closely related, so that any change in one of the organs can lead to damage to the other, establishing the so-called cardiorenal syndrome. Herein, we explore some case reports of patients with COVID-19 who had heart and kidney abnormalities, consequently resulting in worse prognosis of the disease. These results highlight the importance of understanding the cause and effect between the cardiac and renal systems and the course of early SARS-CoV-2 infection.

Occurrence of multidrug-resistant Enterococcus faecium isolated from environmental samples.

Enterococcus species are present in the microbiota of humans and animals and have also been described in the environment. Among the species, Enterococcus faecium is one of the main pathogens associated with nosocomial infections worldwide. Enterococcus faecium isolates resistant to different classes of antimicrobials have been increasingly reported, including multidrug-resistant (MDR) isolates in environmental sources, which is worrying. Therefore, this study aimed to characterize E. faecium isolates obtained from soil and water samples regarding antimicrobial resistance and virulence determinants. A total 40 E. faecium isolates were recovered from 171 environmental samples. All isolates were classified as MDR, highlighting the resistance to the fluoroquinolones class, linezolid and vancomycin. Furthermore, high-level aminoglycoside resistance and high-level ciprofloxacin resistance were detected in some isolates. Several clinically relevant antimicrobial resistance genes were found, including vanC1, ermB, ermC, mefAE, tetM, tetL, ant(6')-Ia, ant(4')-Ia, aph(3')-IIIa and aac(6')-Ie-aph(2″)-Ia. Three virulence genes were detected among the MDR E. faecium isolates, such as esp, gelE and ace. The results of this study contribute to a better understanding of MDR E. faecium isolates carrying antimicrobial resistance and virulence genes in environmental sources and report for the first time in the world the presence of vanC1-producing E. faecium isolated from soil.

Ca2+/Calmodulin-dependent kinase II delta B is essential for cardiomyocyte hypertrophy and complement gene expression after LPS and HSP60 stimulation in vitro.

Inflammation plays an important role in the development of cardiovascular diseases (CVDs), suggesting that the immune system is a target of therapeutic interventions used for treating CVDs. This study evaluated mechanisms underlying inflammatory response and cardiomyocyte hypertrophy associated with bacterial lipopolysaccharide (LPS)- or heat shock protein 60 (HSP60)-induced Toll-like receptor (TLR) stimulation and the effect of a small interfering RNA (siRNA) against Ca2+/calmodulin-dependent kinase II delta B (CaMKIIδB) on these outcomes. Our results showed that treatment with HSP60 or LPS (TLR agonists) induced cardiomyocyte hypertrophy and complement system C3 and factor B gene expression. In vitro silencing of CaMKIIδB prevented complement gene transcription and cardiomyocyte hypertrophy associated with TLR 2/4 activation but did not prevent the increase in interleukin-6 and tumor necrosis factor-alfa gene expression in primary cultured cardiomyocytes. Moreover, CaMKIIδB silencing attenuated nuclear factor-kappa B expression. These findings supported the hypothesis that CaMKIIδB acts as a link between inflammation and cardiac hypertrophy. Furthermore, the present study is the first to show that extracellular HSP60 activated complement gene expression through CaMKIIδB. Our results indicated that a stress stimulus induced by LPS or HSP60 treatment promoted cardiomyocyte hypertrophy and initiated an inflammatory response through the complement system. However, CaMKIIδB silencing prevented the cardiomyocyte hypertrophy independent of inflammatory response induced by LPS or HSP60 treatment.

Ca2+/Calmodulin-dependent kinase II delta B is essential for cardiomyocyte hypertrophy and complement gene expression after LPS and HSP60 stimulation in vitro

Inflammation plays an important role in the development of cardiovascular diseases (CVDs), suggesting that the immune system is a target of therapeutic interventions used for treating CVDs. This study evaluated mechanisms underlying inflammatory response and cardiomyocyte hypertrophy associated with bacterial lipopolysaccharide (LPS)- or heat shock protein 60 (HSP60)-induced Toll-like receptor (TLR) stimulation and the effect of a small interfering RNA (siRNA) against Ca2+/calmodulin-dependent kinase II delta B (CaMKIIδB) on these outcomes. Our results showed that treatment with HSP60 or LPS (TLR agonists) induced cardiomyocyte hypertrophy and complement system C3 and factor B gene expression. In vitro silencing of CaMKIIδB prevented complement gene transcription and cardiomyocyte hypertrophy associated with TLR 2/4 activation but did not prevent the increase in interleukin-6 and tumor necrosis factor-alfa gene expression in primary cultured cardiomyocytes. Moreover, CaMKIIδB silencing attenuated nuclear factor-kappa B expression. These findings supported the hypothesis that CaMKIIδB acts as a link between inflammation and cardiac hypertrophy. Furthermore, the present study is the first to show that extracellular HSP60 activated complement gene expression through CaMKIIδB. Our results indicated that a stress stimulus induced by LPS or HSP60 treatment promoted cardiomyocyte hypertrophy and initiated an inflammatory response through the complement system. However, CaMKIIδB silencing prevented the cardiomyocyte hypertrophy independent of inflammatory response induced by LPS or HSP60 treatment.

Validation of photo-identification as a mark-recapture method in the spotted eagle ray Aetobatus narinari.

The spotted eagle ray Aetobatus narinari is characterized by pigmentation patterns that are retained for up to 3·5 years. These pigmentations can be used to identify individuals through photo-identification. Only one study has validated this technique, but no study has estimated the percentage of correct identification of the rays using this technique. In order to carry out demographic research, a reliable photographic identification technique is needed. To achieve this validation for A. narinari, a double-mark system was established over 11 months and photographs of the dorsal surface of 191 rays were taken. Three body parts with distinctive natural patterns were analysed (dorsal surface of the cephalic region, dorsal surface of the pectoral fins and dorsal surface of the pelvic fins) in order to determine the body part that could be used to give the highest percentage of correct identification. The dorsal surface of the pectoral fins of A. narinari provides the most accurate photo-identification to distinguish individuals (88·2%).

Reproducibility of heart rate variability parameters measured in healthy subjects at rest and after a postural change maneuver.

Heart rate variability (HRV) provides important information about cardiac autonomic modulation. Since it is a noninvasive and inexpensive method, HRV has been used to evaluate several parameters of cardiovascular health. However, the internal reproducibility of this method has been challenged in some studies. Our aim was to determine the intra-individual reproducibility of HRV parameters in short-term recordings obtained in supine and orthostatic positions. Electrocardiographic (ECG) recordings were obtained from 30 healthy subjects (20-49 years, 14 men) using a digital apparatus (sampling ratio = 250 Hz). ECG was recorded for 10 min in the supine position and for 10 min in the orthostatic position. The procedure was repeated 2-3 h later. Time and frequency domain analyses were performed. Frequency domain included low (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.4 Hz) bands. Power spectral analysis was performed by the autoregressive method and model order was set at 16. Intra-subject agreement was assessed by linear regression analysis, test of difference in variances and limits of agreement. Most HRV measures (pNN50, RMSSD, LF, HF, and LF/HF ratio) were reproducible independent of body position. Better correlation indexes (r > 0.6) were obtained in the orthostatic position. Bland-Altman plots revealed that most values were inside the agreement limits, indicating concordance between measures. Only SDNN and NNv in the supine position were not reproducible. Our results showed reproducibility of HRV parameters when recorded in the same individual with a short time between two exams. The increased sympathetic activity occurring in the orthostatic position probably facilitates reproducibility of the HRV indexes.

Reproducibility of heart rate variability parameters measured in healthy subjects at rest and after a postural change maneuver

Heart rate variability (HRV) provides important information about cardiac autonomic modulation. Since it is a noninvasive and inexpensive method, HRV has been used to evaluate several parameters of cardiovascular health. However, the internal reproducibility of this method has been challenged in some studies. Our aim was to determine the intra-individual reproducibility of HRV parameters in short-term recordings obtained in supine and orthostatic positions. Electrocardiographic (ECG) recordings were obtained from 30 healthy subjects (20-49 years, 14 men) using a digital apparatus (sampling ratio = 250 Hz). ECG was recorded for 10 min in the supine position and for 10 min in the orthostatic position. The procedure was repeated 2-3 h later. Time and frequency domain analyses were performed. Frequency domain included low (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.4 Hz) bands. Power spectral analysis was performed by the autoregressive method and model order was set at 16. Intra-subject agreement was assessed by linear regression analysis, test of difference in variances and limits of agreement. Most HRV measures (pNN50, RMSSD, LF, HF, and LF/HF ratio) were reproducible independent of body position. Better correlation indexes (r > 0.6) were obtained in the orthostatic position. Bland-Altman plots revealed that most values were inside the agreement limits, indicating concordance between measures. Only SDNN and NNv in the supine position were not reproducible. Our results showed reproducibility of HRV parameters when recorded in the same individual with a short time between two exams. The increased sympathetic activity occurring in the orthostatic position probably facilitates reproducibility of the HRV indexes.

Blockage of angiotensin II type 2 receptor prevents thyroxine-mediated cardiac hypertrophy by blocking Akt activation.

Although most of effects of Angiotensin II (Ang II) related to cardiac remodelling can be attributed to type 1 Ang II receptor (AT(1)R), the type 2 receptor (AT(2)R) has been shown to be involved in the development of some cardiac hypertrophy models. In the present study, we investigated whether the thyroid hormone (TH) action leading to cardiac hypertrophy is also mediated by increased Ang II levels or by change on AT(1)R and AT(2)R expression, which could contribute to this effect. In addition, we also evaluated the possible contribution of AT(2)R in the activation of Akt and in the development of TH-induced cardiac hypertrophy. To address these questions, Wistar rats were treated with thyroxine (T(4), 0.1 mg/kg BW/day, i.p.), with or without AT(2)R blocker (PD123319), for 14 days. Cardiac hypertrophy was identified based on heart/body weight ratio and confirmed by analysis of atrial natriuretic factor mRNA expression. Cardiomyocyte cultures were used to exclude the influence of TH-related hemodynamic effects. Our results demonstrate that the cardiac Ang II levels were significantly increased (80%, P < 0.001) as well as the AT(2)R expression (50%, P < 0.05) in TH-induced cardiac hypertrophy. The critical involvement of AT(2)R to the development of this cardiac hypertrophy in vivo was evidenced after administration of AT(2) blocker, which was able to prevent in 40% (P < 0.01) the cardiac mass gain and the Akt activation induced by TH. The role of AT(2)R to the TH-induced cardiomyocyte hypertrophy was also confirmed after using PD123319 in the in vitro studies. These findings improve understanding of the cardiac hypertrophy observed in hyperthyroidism and provide new insights into the generation of future therapeutic strategies.

Origins of the new influenza A(H1N1) virus: time to take action.

To gain insight into the possible origins of the 2009 outbreak of new influenza A(H1N1), we performed two independent analyses of genetic evolution of the new influenza A(H1N1) virus. Firstly, protein homology analyses of more than 400 sequences revealed that this virus most likely evolved from recent swine viruses. Secondly, phylogenetic analyses of 5,214 protein sequences of influenza A(H1N1) viruses (avian, swine and human) circulating in North America for the last two decades (from 1989 to 2009) indicated that the new influenza A(H1N1) virus possesses a distinctive evolutionary trait (genetic distinctness). This appears to be a particular characteristic in pig-human interspecies transmission of influenza A. Thus these analyses contribute to the evidence of the role of pig populations as "mixing vessels" for influenza A(H1N1) viruses.

Labscale anoxic stabilization ponds operated under high organic loads: long term effect of enrichment with activated sludge.

The addition of acclimatized activated sludge has been suggested as an effective enrichment procedure to increase the biological activity of waste stabilization ponds. This enrichment results in higher degradation rates compared to non enriched stabilization ponds. However, the comparison between enriched and non enriched ponds has been observed during short term experiments and it is unknown if this enrichment has long-term effect. This paper compares enriched and non enriched experimental ponds over two years of continuous operation. The enriched pond showed a degradation activity constantly twice higher. The biological indicators such as the heterotrophic and facultative plate count numbers, the chlorophyll "a" concentration and the oxygen consumption rate were also constantly higher in the enriched pond. These results suggest that an initial enrichment has a long term enhancement effect on stabilization ponds treating complex wastewaters.

Cardiac angiotensin II type I and type II receptors are increased in rats submitted to experimental hypothyroidism.

This study assessed the behaviour of angiotensin II (Ang II) receptors in an experimental hypothyroidism model in male Wistar rats. Animals were subjected to thyroidectomy and resting for 14 days. The alteration of cardiac mass was evaluated by total heart weight (HW), right ventricle weight (RVW), left ventricle weight (LVW), ratio of HW, RVW and LVW to body weight (BW) and atrial natriuretic factor (ANF) expression. Cardiac and plasma Ang II levels and serum T3 and T4 were determined. The mRNA and protein levels of Ang II receptors were investigated by RT-PCR and Western blotting, respectively. Functional analyses were performed using binding assays. T3 and T4 levels and the haemodynamic parameters confirmed the hypothyroid state. HW/BW, RVW/BW and LVW/BW ratios and the ANF expression were lower than those of control animals. No change was observed in cardiac or plasma Ang II levels. Both AT1/AT2 mRNA and protein levels were increased in the heart of hypothyroid animals due to a significant increase of these receptors in the RV. Experiments performed in cardiomyocytes showed a direct effect promoted by low thyroid hormone levels upon AT1 and AT2 receptors, discarding possible influence of haemodynamic parameters. Functional assays showed that both receptors are able to bind Ang II. Herein, we have identified, for the first time, a close and direct relation of elevated Ang II receptor levels in hypothyroidism. Whether the increase in these receptors in hypothyroidism is an alternative mechanism to compensate the atrophic state of heart or whether it may represent a potential means to the progression of heart failure remains unknown.

Angiotensin type 1 (AT1) and type 2 (AT2) receptors mediate the increase in TGF-beta1 in thyroid hormone-induced cardiac hypertrophy.

Increased thyroid hormone (TH) levels are known to induce cardiac hypertrophy. Some studies have provided evidence for a functional link between angiotensin II (ANG II) and transforming growth factor beta1 (TGF-beta1) in the heart, both being able to also induce cardiac hypertrophy. However, the contribution of this growth factor activated directly by TH or indirectly by ANG II in cardiac hypertrophy development remains unknown. To analyze the possible role of TGF-beta1 in cardiac hypertrophy induced by TH and also to evaluate if the TGF-beta1 effect is mediated by ANG II receptors, we employed Wistar rats separated into control, hypothyroid (hypo) and hyperthyroid (T4 - 10) groups combined or not with ANG II receptor blockers (losartan or PD123319). Serum levels of T3 and T4, systolic pressure and heart rate confirmed the thyroid state of the groups. The T4 - 10 group presented a significant increase in cardiac TGF-beta1 levels; however, TGF-beta1 levels in the hypo group did not change in relation to the control. Inhibition of the increase in cardiac TGF-beta1 levels was observed in the groups treated with T4 in association with losartan or PD123319 when compared to the T4 - 10 group. These results demonstrate for the first time the TH-modulated induction of cardiac TGF-beta1 in cardiac hypertrophy, and that this effect is mediated by ANG II receptors.

Tissue-specific modulation of angiotensin-converting enzyme (ACE) in hyperthyroidism.

We have previously demonstrated the interaction between the RAS and thyroid hormones (TH). The present study was designed to determine the role of TH in the local regulation of ACE activity and expression in different tissues. Adult male Wistar rats were randomized into three groups: T4-25 and T4-100 (0.025 and 0.100mg/kg of body weight/day of l-thyroxine for 14 days, respectively) and control. Hemodynamic parameters as well as cardiac and renal hypertrophy were evaluated. ACE activity and mRNA levels were determined by Fluorimetric and Northern blot assays, respectively. Both doses increased SBP and HR, as well as inducing cardiac and renal hypertrophy. Pulmonary and serum ACE levels were comparable among the groups. Both doses promoted increased renal ACE activity and expression but surprisingly ACE was diminished in the heart in both hyperthyroid groups. This change was mediated by a tissue-specific transcription mechanism.

Treatment of wastewater containing high phenol concentrations using stabilisation ponds enriched with activated sludge.

Treatment of wastewater containing high phenol concentrations (up to 4,000 mg/l, 1,600 kg/ha.d) in laboratory-scale stabilisation ponds enriched with activated sludge was studied. Phenol was biodegraded efficiently, even when fed as the sole carbon source. At influent concentrations of 1,000, 1,300, 1,600, 1,900, 2,500, 3,000 and 4,000 mg/l of phenol (loading rates of 400, 520, 640, 760, 1,000, 1,200 and 1,600 kg phenol/ha.d), the phenol removal efficiencies were 92, 89, 81, 81, 76, 65 and 22%, respectively. At 4,000 mg/l of phenol, the enriched ponds were significantly inhibited. The maximum phenol removal rate observed was 780 kg/ha.d, which is 7.7 times higher than the maximum value reported for attached-growth waste stabilisation ponds. All along the experiments, the enriched ponds showed removal rates 1.8-20.5 times higher than the values observed in control pond (not enriched). The results suggest that enrichment is an effective method to increase xenobiotic removal rates of stabilisation ponds.

Thyroxine-induced cardiac hypertrophy: influence of adrenergic nervous system versus renin-angiotensin system on myocyte remodeling.

The present study assessed the possible involvement of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) in thyroxine (T4)-induced cardiac hypertrophy. Hemodynamic parameters, heart weight (HW), ratio of HW to body weight (HW/BW), and myocyte width were evaluated in absence of thyroid hormone (hypothyroidism) and after T4 administration. Male Wistar rats were used. Some were subjected to thyroidectomies, whereas hyperthyroidism was induced in others via daily intraperitoneal injection of T4 (25 or 100 microg x 100 g BW(-1) x day(-1)) for 7 days. In some cases, T4 administration was combined with the angiotensin I-converting enzyme inhibitor enalapril (Ena), with the angiotensin type 1 (AT1) receptor blocker losartan (Los) or with the beta-adrenergic blocker propanolol (Prop). Hemodynamics and morphology were then evaluated. Systolic blood pressure (SBP) was not altered by administration of either T4 alone or T4 in combination with the specific inhibitors. However, SBP decreased significantly in hypothyroid rats. An increased heart rate was seen after administration of either T4 alone or T4 in combination with either Los or Ena. Although the higher dose of T4 significantly increased HW, HW/BW increased in both T4-treated groups. Ena and Prop inhibited the increase in HW or HW/BW in hyperthyroid rats. Morphologically, both T4 dose levels significantly increased myocyte width, an occurrence prevented by RAS or SNS blockers. There was a good correlation between changes in HW/BW and myocyte width. These results indicate that T4-induced cardiac hypertrophy is associated with both the SNS and the RAS.

Effect of transgenic overexpression of NR2B on NMDA receptor function and synaptic plasticity in visual cortex.

The NMDA receptor (NMDAR) is a heteromer comprised of NR1 and NR2 subunits. Mice that overexpress the NR2B subunit exhibit enhanced hippocampal LTP, prolonged NMDAR currents, and improved memory ( Tang et al., 1999). In the current study, we explored visual cortex plasticity and NMDAR function in NR2B overexpressing transgenic mice. Unlike the hippocampus, in vitro synaptic plasticity of the visual cortex was unaltered by NR2B overexpression. Consistent with the plasticity findings, NMDAR excitatory postsynaptic current (EPSC) durations from layer 2/3 pyramidal cells were similar in wild-type (wt) and transgenic (tg) mice. Furthermore, temporal summation of NMDAR EPSCs to 10, 20, and 40 Hz stimulation did not differ between cells from wt and tg mice. Finally, although in situ studies clearly demonstrate overexpression of NR2B mRNA in visual cortex, we failed to observe a significant elevation in the synaptic expression of NR2B protein. We conclude that the synaptic ratio of NR2B over NR2A in the NMDA receptor complex in the visual cortex is not significantly influenced by the transgene overexpression. These data suggest that mRNA availability is not a limiting factor for the synthesis of NR2B protein in the visual cortex, and support the hypothesis that levels of NR2A, rather than NR2B, normally determine the subunit composition of NMDARs in visual cortex.

Endocarditis infecciosa en la República Argentina (Estudio E.I.R.A.): resultados generales / Infective endocarditis in Argentina: general results

Se describen 294 episodios de endocarditis infecciosa en 285 pacientes con predominio del sexo masculino y edad promedio de 54,1 años. El 55,5 por ciento tenía cardiopatía subyacente y en el 63,3 por ciento se encontró un evento predisponente. La signosintomatología resultó inespecífica y el tiempo promedio previo al diagnóstico fue de 33 ñ 34 días. En el 83 por ciento de los casos se visualizaron vegetaciones por eco. El 30 por ciento de los pacientes presentó insuficiencia cardíaca severa. El compromiso izquierdo se observó en 232 casos (39 por ciento aórticos, 29 por ciento mitrales y 11 por ciento mitroaórticos); la tricúspide estuvo comprometida en 40 oportunidades y la pulmonar en 3 (14,8 por ciento). La clasificación de Duke presentó mayor sensibilidad diagnóstica (AU)

Endocarditis infecciosa en pacientes drogadictos endovenosos: presentación clínica y evolución intrahospitalaria / Infective endocarditis in intravenous drug users

Este estudio analizó las características de cuarenta episodios de endocarditis infecciosa en 38 pacientes con drogadicción intravenosa como factor predisponente. Tenían una edad promedio de 28,9 años; 90 por ciento eran de sexo masculino, con compromiso de válvula sana en 82,5 por ciento de los casos; 20 por ciento de los pacientes habían tenido un episodio o más de endocarditis previa; 77,5 por ciento tuvieron afectación derecha; el agente causal más frecuente fue el Staphylococcus aureus, con 70 por ciento de hemocultivos positivos y 90 por ciento de incidencia de HIV. Las complicaciones más frecuentes fueron la insuficiencia cardíaca y el tromboembolismo de pulmón.La mortalidad hospitalaria fue más elevada que la descripta habitualmente en esta población (AU)

Endocarditis infecciosa en la República Argentina: complicaciones y mortalidad / Infective endocarditis in Argentina: complications and mortality

En 294 episodios de endocarditis infecciosa se observaron 208 (70,8 por ciento) complicaciones. El 55 por ciento fueron cardíacas, principalmente insuficiencia cardíaca por compromiso aórtico o mitroaórtico. En 9 por ciento de los casos se observaron abscesos anulares, más frecuentemente en las endocarditis infecciosas protésicas. Se observaron 76 embolias, de las cuales 35 fueron en el sistema nervioso central, 21 pulmonares y 10 en miembros. Se diagnosticaron 10 aneurismas micóticos cerebrales con 80 por ciento de mortalidad. La mortalidad hospitalaria fue del 23,5 por ciento y se correlacionó con cuadro séptico severo, insuficiencia cardíaca y embolismo sistémico (AU)