Recent advances have improved our understanding of the renin‐angiotensin system (RAS). These have included the recognition that angiotensin (Ang)‐(1‐7) is a biologically active product of the RAS ...cascade. The identification of the ACE homologue ACE2, which forms Ang‐(1‐7) from Ang II, and the GPCR Mas as an Ang‐(1‐7) receptor have provided the necessary biochemical and molecular background and tools to study the biological significance of Ang‐(1‐7). Most available evidence supports a counter‐regulatory role for Ang‐(1‐7) by opposing many actions of Ang II on AT1 receptors, especially vasoconstriction and proliferation. Many studies have now shown that Ang‐(1‐7) by acting via Mas receptor exerts inhibitory effects on inflammation and on vascular and cellular growth mechanisms. Ang‐(1‐7) has also been shown to reduce key signalling pathways and molecules thought to be relevant for fibrogenesis. Here, we review recent findings related to the function of the ACE2/Ang‐(1‐7)/Mas axis and focus on the role of this axis in modifying processes associated with acute and chronic inflammation, including leukocyte influx, fibrogenesis and proliferation of certain cell types. More attention will be given to the involvement of the ACE2/Ang‐(1‐7)/Mas axis in the context of renal disease because of the known relevance of the RAS for the function of this organ and for the regulation of kidney inflammation and fibrosis. Taken together, this knowledge may help in paving the way for the development of novel treatments for chronic inflammatory and renal diseases.
Immunoglobulin A nephropathy: a pathophysiology view Fabiano, Rafaela Cabral Gonçalves; Pinheiro, Sérgio Veloso Brant; Simões e Silva, Ana Cristina
Inflammation Research,
10/2016, Letnik:
65, Številka:
10
Journal Article, Book Review
Recenzirano
Background and aim
IgA nephropathy is one of the leading causes of primary glomerulonephritis worldwide and an important etiology of renal disease in young adults. IgA nephropathy is considered an ...immune complex-mediated disease.
Methods
This review article summarizes recent evidence on the pathophysiology of IgA nephropathy.
Results
Current studies indicate an ordered sequence of multi-hits as fundamental to disease occurrence. Altered glycan structures in the hinge region of the heavy chains of IgA1 molecules act as auto-antigens, potentially triggering the production of glycan-specific autoantibodies. Recognition of novel epitopes by IgA and IgG antibodies leads to the formation of immune complexes galactose deficient-IgA1/anti-glycan IgG or IgA. Immune complexes of IgA combined with FcαRI/CD89 have also been implicated in disease exacerbation. These nephritogenic immune complexes are formed in the circulation and deposited in renal mesangium. Deposited immune complexes ultimately induce glomerular injury, through the release of pro-inflammatory cytokines, secretion of chemokines and the resultant migration of macrophages into the kidney. The TfR1/CD71 receptor has a pivotal role in mesangial cells. New signaling intracellular mechanisms have also been described.
Conclusion
The knowledge of the whole pathophysiology of this disease could provide the rational bases for developing novel approaches for diagnosis, for monitoring disease activity, and for disease-specific treatment.
Recent advances have improved our understanding of the renin‐angiotensin system (
RAS
). These have included the recognition that angiotensin (
A
ng)‐(1‐7) is a biologically active product of the
RAS
...cascade. The identification of the
ACE
homologue
ACE2
, which forms
A
ng‐(1‐7) from
A
ng
II
, and the
GPCR M
as as an
A
ng‐(1‐7) receptor have provided the necessary biochemical and molecular background and tools to study the biological significance of
A
ng‐(1‐7). Most available evidence supports a counter‐regulatory role for
A
ng‐(1‐7) by opposing many actions of
A
ng
II
on
AT
1
receptors, especially vasoconstriction and proliferation. Many studies have now shown that
A
ng‐(1‐7) by acting via
M
as receptor exerts inhibitory effects on inflammation and on vascular and cellular growth mechanisms.
A
ng‐(1‐7) has also been shown to reduce key signalling pathways and molecules thought to be relevant for fibrogenesis. Here, we review recent findings related to the function of the
ACE2
/
A
ng‐(1‐7)/
M
as axis and focus on the role of this axis in modifying processes associated with acute and chronic inflammation, including leukocyte influx, fibrogenesis and proliferation of certain cell types. More attention will be given to the involvement of the
ACE2
/
A
ng‐(1‐7)/
M
as axis in the context of renal disease because of the known relevance of the
RAS
for the function of this organ and for the regulation of kidney inflammation and fibrosis. Taken together, this knowledge may help in paving the way for the development of novel treatments for chronic inflammatory and renal diseases.
Obesity is a major public health problem affecting adults and children in both developed and developing countries. This condition often leads to metabolic syndrome, which increases the risk of ...cardiovascular disease. A large number of studies have been carried out to understand the pathogenesis of cardiovascular dysfunction in obese patients. Endothelial dysfunction plays a key role in the progression of atherosclerosis and the development of coronary artery disease, hypertension and congestive heart failure. Noninvasive methods in the field of cardiovascular imaging, such as measuring intima-media thickness, flow-mediated dilatation, tissue Doppler, and strain, and strain rate, constitute new tools for the early detection of cardiac and vascular dysfunction. These techniques will certainly enable a better evaluation of initial cardiovascular injury and allow the correct, timely management of obese patients. The present review summarizes the main aspects of cardiovascular dysfunction in obesity and discusses the application of recent noninvasive imaging methods for the early detection of cardiovascular alterations.
Zika virus challenges for neuropsychiatry Simões e Silva AC; Moreira JM; Romanelli RMC ...
Neuropsychiatric disease and treatment,
07/2016, Letnik:
2016, Številka:
Issue 1
Journal Article
Recenzirano
Odprti dostop
Ana Cristina Simões e Silva,1,2 Janaina Matos Moreira,1,2 Roberta Maia Castro Romanelli,2 Antonio Lucio Teixeira1,3 1Interdisciplinary Laboratory of Medical Investigation, 2Department of Pediatrics, ...Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte,Brazil; 3Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA Abstract: Before 2007, Zika virus (ZIKV) was generally considered as an arbovirus of low clinical relevance, causing a mild self-limiting febrile illness in tropical Africa and Southeast Asia. Currently, a large, ongoing outbreak of ZIKV that started in Brazil in 2015 is spreading across the Americas. Virus infection during pregnancy has been potentially linked to congenital malformations, including microcephaly. In addition to congenital malformations, a temporal association between ZIKV infection and an increase in cases of Guillain-Barré syndrome is currently being observed in several countries. The mechanisms underlying these neurological complications are still unknown. Emerging evidence, mainly from in vitro studies, suggests that ZIKV may have direct effects on neuronal cells. The aim of this study was to critically review the literature available regarding the neurobiology of ZIKV and its potential neuropsychiatric manifestations. Keywords: Zika virus, microcephaly, Guillain-Barré syndrome, neurodevelopmental disorders
This paper describes the in vitro antiviral evaluation of 27 different marine sponges (Porifera) collected off Brazilian coastline in the search for novel drug leads. With these sponges aqueous and ...organic extracts were prepared and tested for anti-herpetic (HSV-1, KOS strain), anti-adenovirus (human AdV serotype 5) and anti-rotavirus (simian RV SA11) activities. The evaluation of the cytotoxicity and potential antiviral activity of these extracts were performed by using MTT assay. Results were expressed as 50% cytotoxicity (CC50) and 50% effective (EC50) concentrations, respectively, in order to calculate the selectivity indices (SI=CC50/EC50) of each extract. From the 40 sponge extracts tested, 17 extracts showed antiviral action in different degrees. The results concerning the antiviral activity were obtained by using three different strategies: (1) simultaneous assay, when sponge extracts were added to the cells at the same time of the viruses; (2) pre treatment assay, when sponge extracts were added to the cells 15 h prior to the viruses infection; and (3) post treatment assay, when the viruses were added to the cells and remained during 2 h prior to the addition of sponge extracts. The antiviral assays with HSV-1/KOS and AdV-5 showed more promising results when the pre treatment test was employed. In relation to the RV-SA11 virus, only the simultaneous assay showed antiviral activity. The extracts presenting the most promising results were the aqueous extracts of Cliona sp., Agelas sp.2, Tethya sp., Axinella aff corrugata, Polymastia janeirensis and Protosuberites sp., and these extracts deserve special attention in further studies.
In the present study we evaluated the nature of angiotensin receptors involved in the antidiuretic effect of angiotensin-(1-7) (Ang-(1-7)) in water-loaded rats. Water diuresis was induced in male ...Wistar rats weighing 280 to 320 g by water load (5 ml/100 g body weight by gavage). Immediately after water load the rats were treated subcutaneously with (doses are per 100 g body weight): 1) vehicle (0.05 ml 0.9% NaCl); 2) graded doses of 20, 40 or 80 pmol Ang-(1-7); 3) 200 nmol Losartan; 4) 200 nmol Losartan combined with 40 pmol Ang-(1-7); 5) 1.1 or 4.4 nmol A-779; 6) 1.1 nmol A-779 combined with graded doses of 20, 40 or 80 pmol Ang-(1-7); 7) 4.4 nmol A-779 combined with graded doses of 20, 40 or 80 pmol Ang-(1-7); 8) 95 nmol CGP 42112A, or 9) 95 nmol CGP 42112A combined with 40 pmol Ang-(1-7). The antidiuretic effect of Ang-(1-7) was associated with an increase in urinary Na+ concentration, an increase in urinary osmolality and a reduction in creatinine clearance (CCr: 0.65 +/- 0.04 ml/min vs 1.45 +/- 0.18 ml/min in vehicle-treated rats, P < 0.05). A-779 and Losartan completely blocked the effect of Ang-(1-7) on water diuresis (2.93 +/- 0.34 ml/60 min and 3.39 +/- 0.58 ml/60 min, respectively). CGP 42112A, at the dose used, did not modify the antidiuretic effect of Ang-(1-7). The blockade produced by Losartan was associated with an increase in CCr and with an increase in sodium and water excretion as compared with Ang-(1-7)-treated rats. When Ang-(1-7) was combined with A-779 there was an increase in CCr and natriuresis and a reduction in urine osmolality compared with rats treated with Ang-(1-7) alone. The observation that both A-779, which does not bind to AT1 receptors, and Losartan blocked the effect of Ang-(1-7) suggests that the kidney effects of Ang-(1-7) are mediated by a non-AT1 angiotensin receptor that is recognized by Losartan.
The antiviral activity of six medicinal plants from Brazilian Atlantic Tropical Forest was investigated against two viruses: Herpes simplex virus type 1 (HSV-1) and poliovirus type 2 (PV-2).
Cuphea ...carthagenensis and
Tillandsia usneoides extracts showed the best antiherpes activity.
T. usneoides dichloromethane, ethyl acetate and
n-butanol extracts, and
Lippia alba n-butanol extract showed inhibition of HSV-1, strain 29R/acyclovir resistant. In addition, only
L. alba ethyl acetate extract showed antipoliovirus activity. These results corroborate that medicinal plants can be a rich source of potential antiviral compounds.
Novel Mn(III)chlorins have been obtained and used as efficient and versatile catalysts for oxyfunctionalisation of the cyclohexane with PhIO and H
2O
2. Mn(III)chlorin/H
2O
2 should be oxidising the ...alkane by a concerted mechanism, whereas in Mn(III)chlorin/PhIO oxidations a free alkyl mechanism is operating, similarly to that observed in the oxidations catalysed by fluorinated Mn(III)porphyrins.
▪
The novel fluorinated metallochlorin 5,10,15,20-tetrakis(pentafluorophenyl)-tetrahydro-1
H-
N-methyl-pyrrolo3,4-
b-porphyrinato manganese(III),
Mn(chlor)-1, and its methylated derivative,
Mn(chlor)-2, have been studied as catalysts in the oxyfunctionalisation of cyclohexane with two oxidants, namely iodosylbenzene (PhIO) and H
2O
2. For comparison reasons two metalloporphyrins have been also used: the neutral 5,10,15,20-tetrakis(pentafluorophenyl)porphyrinato manganese(III),
Mn(porph)-1, and the cationic 5,10,15,20-tetrakis(2,3,5,6-tetrafluoro-4-trimethylammoniumphenyl)porphyrinato manganese(III),
Mn(porph)-2. It has been possible to verify a different reactivity in the H
2O
2-oxyfunctionalisation of alkanes from studies using the radical inhibitor bromotrichloromethane and competitive cyclooctane/
cis-cyclooctene oxidations. The results suggest that the formation of alcohols and ketones from the oxidation of cyclohexane occurs mainly from a free alkyl radical mechanism, which requires a Mn
V
O species to abstract a hydrogen atom from the alkane to generate the alkyl radical. On the other hand, the Mn(chlor)/H
2O
2 system possibly yields, in a first step, the Mn
III
OOH species, but this is not reactive enough to generate Mn
V
O. The Mn(chlor) hydroperoxy complex shows low efficiency in the production of the alkyl radical, leading to small amounts of alcohol and ketone. However, it seems to be an efficient species for selective epoxidation, as can be observed in the competitive cyclooctane/
cis-cyclooctene oxidation reaction.
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