scholarly journals Tranilast treats cold-related hypertension by reducing the expression of NLRP3 inflammasome

2021 ◽  
Vol 1 (2) ◽  
pp. 95-101
Author(s):  
Hui Yu ◽  
Yun Zhou ◽  
Yu Duan ◽  
Yunlong Gao ◽  
Ning Fang ◽  
...  
Keyword(s):  
Cold Exposure ◽  
Nlrp3 Inflammasome ◽  
Receptor Protein ◽  
Control Group ◽  
Cold Environment ◽  
Sprague Dawley ◽  
Inhibitory Effects ◽  
Beneficial Action ◽  
To Receive

Abstract Objective Cold exposure is associated with increased prevalence of hypertension and the related severe cardiovascular events. Aberrant activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays an important role in the development of hypertension. Tranilast (TR), an inhibitor of NLRP3, provides a useful pharmacological probe for exploring the role of NLRP3 in pathogenesis associated with inflammation and its potential application as a therapeutic agent. This study was designed to examine the effects of TR on NLRP3 and hypertension in rats exposed to cold environment to simulate the frigid-zone conditions. Methods and results Sprague Dawley (SD) rats were exposed to moderate cold temperature (4±1°C), and then were randomized to receive TR or vehicle for 3 weeks, while the control group was raised under rat room temperature (RT, 23±1°C). We found that cold exposure substantially increased blood pressure, NLRP3 inflammasome level, and fibrosis in aorta, which were reversed by TR. Conclusion TR has an anti-hypertensive property in cold environment, and this beneficial action is likely conferred by its inhibitory effects on inflammation and fibrosis. These findings suggest TR as a potential drug for the treatment of cold-induced hypertension.

The Pineal Gland and Stress: Effect of Pineal Stalk Section on the Plasma Corticosteroid Response to Cold in Rabbits

1979 ◽  
Vol 44 (3) ◽  
pp. 883-890 ◽  
Author(s):  
Robert W. Rivest ◽  
Kenneth D. Roberts ◽  
Franco Leporé
Keyword(s):  
Pineal Gland ◽  
Cold Exposure ◽  
Control Group ◽  
Sham Operation ◽  
Stress Effect ◽  
Cold Environment ◽  
Corticosterone Concentration ◽  
General Adaptation ◽  
Corticosteroid Response

To investigate the role of the pineal gland on plasma corticosteroid elevation during stress, a pineal stalk section was performed in rabbits implanted with a carotid cannula, while a comparable sham operation was carried out in a control group ( n = 8) similarly implanted. Six days after the surgery, the rabbits were exposed to a cold environment for 2 hr. Blood was withdrawn periodically throughout the 2 hr. of cold stress and for an additional 2 hr. after the rabbits were returned to their cages. Results show that plasma corticosteroids (cortisol + corticosterone) concentration in both groups rose during the cold exposure and gradually declined towards resting values after removal from the cold. The lesioned rabbits, however, exhibited an earlier and higher elevation in plasma corticosteroid levels in reaction to the cold. These observations suggest that the pineal stalk in normal animals influences the corticosteroid response to a stress in such a way as to increase the latency of its onset and decrease its amplitude. This effect is interpreted in the context of the general adaptation syndrome.

Role of routine fluid replacement in children undergoing tonsillectomy

1990 ◽  
Vol 104 (10) ◽  
pp. 801-802 ◽  
Author(s):  
P. S. Wilson ◽  
D. G. Snow ◽  
J. O'Connel ◽  
D. W. Proops ◽  
M. Barrow
Keyword(s):  
Blood Loss ◽  
Prospective Study ◽  
Intravenous Infusion ◽  
Intravenous Fluid ◽  
Fluid Replacement ◽  
Control Group ◽  
A Prospective Study ◽  
To Receive

AbstractIt has been suggested that children undergoing tonsillectomy would benefit from an intravenous infusion, to counteract the period of pre-operativefasting combined with the blood loss at operation.A prospective study of 50 children undergoing tonsillectomy was undertaken. The children were randomly allocated into two groups, one to receive an infusion and a control group.There were no significant differences between the two groups, although the children with an infusion had a longer mean post-operative stay.There would seem to be no role for routine intravenous fluid replacement in children undergoing uncomplicated tonsillectomy.

Carvacrol attenuates amikacin-induced nephrotoxicity in the rat

2021 ◽  
Author(s):  
Atta Mohammad Dost ◽  
Mehmet Gunata ◽  
Onural Ozhan ◽  
Azibe Yildiz ◽  
Nigar Vardi ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Kidney Tissue ◽  
Control Group ◽  
Histopathological Changes ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Per Oral

Abstract Amikacin (AK) is frequently used in the treatment of gram-negative and some gram-positive infections. However, its use is limited due to nephrotoxicity due to the increase in reactive oxygen radicals. The aim of this study was to investigate the role of carvacrol (CAR) against AK-induced nephrotoxicity in rats. Thirty-two Sprague Dawley rats were randomly divided into four groups as control (Vehicle), AK (400 mg/kg), CAR + AK (80 mg/kg CAR + 400 mg/kg AK), and AK + CAR (400 mg/kg AK + 80 mg/kg CAR) groups. AK and CAR were administered via intramuscular and per-oral for 7 days, respectively. Blood and kidney tissue samples were taken at the end of the experiment. Renal function and histopathological changes were compared, and the relevant parameters of oxidative stress and inflammation were detected. Histopathological findings (necrotic changes and dilatation and inflammatory cell infiltration) significantly increased in the AK group compared to the control group. Also, the rats in the AK group lost weight significantly. It was found that CAR treatment before and after AK significantly improved nephrotoxicity histopathologically (p < 0.05). However, this improvement was not detected biochemically. These results show that CAR treatment before and after AK improves nephrotoxicity in the histopathological level.

scholarly journals The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes

Blood ◽  
2019 ◽  
Vol 133 (10) ◽  
pp. 1039-1048 ◽  
Author(s):  
David A. Sallman ◽  
Alan List
Keyword(s):  
Myelodysplastic Syndromes ◽  
Immune Activation ◽  
Nlrp3 Inflammasome ◽  
Cancer Biology ◽  
Innate Immune ◽  
Cell Swelling ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Innate Immune Activation

Abstract In cancer biology, tumor-promoting inflammation and an inflammatory microenvironment play a vital role in disease pathogenesis. In the past decade, aberrant innate immune activation and proinflammatory signaling within the malignant clone and the bone marrow (BM) microenvironment were identified as key pathogenic drivers of myelodysplastic syndromes (MDS). In particular, S100A9-mediated NOD-like receptor protein 3 (NLRP3) inflammasome activation directs an inflammatory, lytic form of cell death termed pyroptosis that underlies many of the hallmark features of the disease. This circuit and accompanying release of other danger-associated molecular patterns expands BM myeloid-derived suppressor cells, creating a feed-forward process propagating inflammasome activation. Furthermore, somatic gene mutations of varied functional classes license the NLRP3 inflammasome to generate a common phenotype with excess reactive oxygen species generation, Wnt/β-catenin–induced proliferation, cation flux-induced cell swelling, and caspase-1 activation. Recent investigations have shown that activation of the NLRP3 inflammasome complex has more broad-reaching importance, particularly as a possible disease-specific biomarker for MDS, and, mechanistically, as a driver of cardiovascular morbidity/mortality in individuals with age-related, clonal hematopoiesis. Recognition of the mechanistic role of aberrant innate immune activation in MDS provides a new perspective for therapeutic development that could usher in a novel class of disease-modifying agents.

scholarly journals Tepid sponging plus dipyrone versus dipyrone alone for reducing body temperature in febrile children

2008 ◽  
Vol 126 (2) ◽  
pp. 107-111 ◽  
Author(s):  
João Guilherme Bezerra Alves ◽  
Natália Dornelas Câmara Marques de Almeida ◽  
Camila Dornelas Câmara Marques de Almeida
Keyword(s):  
Clinical Trial ◽  
Body Temperature ◽  
Randomized Clinical Trial ◽  
Primary Outcome ◽  
Control Group ◽  
Emergency Ward ◽  
Axillary Temperature ◽  
Secondary Outcomes ◽  
To Receive

CONTEXT AND OBJECTIVE: The role of tepid sponging to promote fever control in children is controversial. We did not find any studies reporting on the effectiveness of tepid sponging in addition to dipyrone. The aim of this study was to compare the effects of tepid sponging plus dipyrone with dipyrone alone for reducing fever. DESIGN AND SETTING: A randomized clinical trial was undertaken at Instituto Materno-Infantil Professor Fernando Figueira, Recife, Pernambuco. METHODS: Children from six months to five years old with axillary temperature greater than 38 ºC in the emergency ward between January and July 2006 were eligible. One hundred and twenty children were randomly assigned to receive oral dipyrone (20 mg/kg) or oral dipyrone and tepid sponging for 15 minutes. The primary outcome was mean temperature reduction after 15, 30, 60, 90 and 120 minutes. Secondary outcomes were crying and irritability. RESULTS: 106 children finished the study. After the first 15 minutes, the fall in axillary temperature was significantly greater in the sponged group than in the control group (p < 0.001). From 30 to 120 minutes, better fever control was observed in the control group. Crying and irritability were observed respectively in 52% and 36% of the sponged children and in none and only two of the controls. CONCLUSIONS: Tepid sponging plus dipyrone cooled faster during the first 15 minutes, but dipyrone alone presented better fever control over the two-hour period. Tepid sponging caused mild discomfort, crying and irritability for most of the children.

scholarly journals The Role of the Effects of Autophagy on NLRP3 Inflammasome in Inflammatory Nervous System Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Shizhen Zhao ◽  
Xiaotian Li ◽  
jie Wang ◽  
Honggang Wang
Keyword(s):  
Nervous System ◽  
Nlrp3 Inflammasome ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cerebral Hypoperfusion ◽  
Receptor Protein ◽  
Future Research ◽  
Nervous System Diseases ◽  
Caspase 1

Autophagy is a stable self-sustaining process in eukaryotic cells. In this process, pathogens, abnormal proteins, and organelles are encapsulated by a bilayer membrane to form autophagosomes, which are then transferred to lysosomes for degradation. Autophagy is involved in many physiological and pathological processes. Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, containing NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and pro-caspase-1, can activate caspase-1 to induce pyroptosis and lead to the maturation and secretion of interleukin-1 β (IL-1 β) and IL-18. NLRP3 inflammasome is related to many diseases. In recent years, autophagy has been reported to play a vital role by regulating the NLRP3 inflammasome in inflammatory nervous system diseases. However, the related mechanisms are not completely clarified. In this review, we sum up recent research about the role of the effects of autophagy on NLRP3 inflammasome in Alzheimer’s disease, chronic cerebral hypoperfusion, Parkinson’s disease, depression, cerebral ischemia/reperfusion injury, early brain injury after subarachnoid hemorrhage, and experimental autoimmune encephalomyelitis and analyzed the related mechanism to provide theoretical reference for the future research of inflammatory neurological diseases.

Abstract P141: Immunosuppressant Treatment Attenuates Augmentation Of Intrarenal NLRP-3 Inflammasome In Angiotensin II-dependent Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Ryousuke Satou ◽  
Martha G Franco ◽  
Akemi Katsurada ◽  
Courtney M Dugas ◽  
L G NAVAR
Keyword(s):  
Angiotensin Ii ◽  
Nlrp3 Inflammasome ◽  
Bacterial Infections ◽  
Kidney Injury ◽  
Control Group ◽  
Inflammasome Activation ◽  
Mrna Levels ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Normotensive Control

Activated inflammasomes enhance maturation of pro-inflammatory cytokines, which facilitates the development of kidney injury. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), one of major subunits in the inflammasome complex, plays a crucial role in innate immunity and inflammation. Although NLRP3 inflammasome is activated by ATP-P2Y7 axis and reactive oxygen species, the expression of pro-NLRP3 is promoted by NF-κB activated by cytokines or PAMPs/DAMPs. Thus, we hypothesized that mycophenolate mofetil (MMF), an immunosuppressant, attenuates augmentation of intrarenal NLRP3 and consequent progression of kidney injury in angiotensin II (Ang II)-dependent hypertension. Ang II (80 ng/min) was infused with/without daily MMF administration (50 ng/kg) to Sprague-Dawley rats for 2 weeks. mRNA levels of intrarenal NLRP3 and AIM2, which forms another type of inflammasome complex by viral or bacterial infections, were measured by droplet digital PCR. Furthermore, kidney injury was evaluated. MMF treatment mitigated Ang II-induced macrophage infiltration into kidneys, suggesting immunosuppression by the drug. Ang II infusion significantly increased intrarenal NLRP3 mRNA levels (normotensive control group: 4.12±1.1 copies/ng RNA vs. Ang II-infused group: 9.96±1.8 copies, N=5). The elevated NLRP3 expression in kidneys of Ang II-infused rats was attenuated by MMF treatment (6.24±1.4 copies). In contrast, intrarenal AIM2 levels were lower than NLRP3 in the control group and the levels were not altered by Ang II infusion or MMF treatment (normotensive control group: 0.42±0.1 copies, Ang II-infused group: 0.35±0.06 copies and Ang II+MMF group: 0.35±0.08 copies). Urinary protein and angiotensinogen levels were elevated in Ang II-infused rats and MMF treatment suppressed the augmentations. Histological analyses also showed the development of kidney injury including mesangial expansion and tubulointerstitial fibrosis observed in the hypertensive rats, but these injury markers were mitigated by MMF. These results demonstrate activation of the NLRP3 inflammasome in Ang II dependent hypertension and indicate that immunosuppression by MMF mitigates the inflammasome activation, which contributes to attenuation of the kidney injury.

scholarly journals Effects of Shizhifang on NLRP3 Inflammasome Activation and Renal Tubular Injury in Hyperuricemic Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-19 ◽  
Author(s):  
Yansheng Wu ◽  
Fei He ◽  
Yingqiao Li ◽  
Huiling Wang ◽  
Liqiang Shi ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Factors ◽  
Control Group ◽  
Inflammasome Activation ◽  
Tubular Injury ◽  
Sprague Dawley ◽  
Positive Effects ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation ◽  
Renal Tubular

Objective. Uric acid (UA) activates the NLRP3-ASC-caspase-1 axis and triggers cascade inflammatory that leads to hyperuricemic nephropathy and hyperuricemia-induced renal tubular injury. The original study aims to verify the positive effects of the traditional Chinese medicinal formula Shizhifang (SZF) on ameliorating the hyperuricemia, tubular injury, and inflammasome infiltration in the kidneys of hyperuricemic lab rats. Method. Twenty-eight male Sprague-Dawley rats were divided into four groups: control group, oxonic acid potassium (OA) model group, OA + SZF group, and OA + Allopurinol group. We evaluated the mediating effects of SZF on renal mitochondrial reactive oxygen species (ROS) and oxidative stress (OS) products, protein expression of NLRP3-ASC-caspase-1 axis, and downstream inflammatory factors IL-1β and IL-18 after 7 weeks of animals feeding. Result. SZF alleviated OA-induced hyperuricemia and inhibited OS in hyperuricemic rats (P<0.05). SZF effectively suppressed the expression of gene and protein of the NLRP3-ASC-caspase-1 axis through accommodating the ROS-TXNIP pathway (P<0.05). Conclusion. Our data suggest that SZF alleviates renal tubular injury and inflammation infiltration by inhibiting NLRP3 inflammasome activation triggered by mitochondrial ROS in the kidneys of hyperuricemic lab rats.

Randomized phase III trial evaluating the role of erythropoietin in the prevention of chemotherapy-induced anemia.

1997 ◽  
Vol 15 (7) ◽  
pp. 2715-2721 ◽  
Author(s):  
L Del Mastro ◽  
M Venturini ◽  
R Lionetto ◽  
O Garrone ◽  
G Melioli ◽  
...  
Keyword(s):  
Early Stage ◽  
Cost Effective ◽  
Additional Treatment ◽  
Phase Iii ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Clinically Significant ◽  
Few Data ◽  
To Receive

PURPOSE Although erythropoietin (EPO) is known to be useful in treating chemotherapy-induced anemia, few data are available on its potential preventive role. The aim of this study was to evaluate the ability of EPO in preventing the development of clinically significant anemia in patients treated with chemotherapy. PATIENTS AND METHODS Sixty-two early-stage breast cancer patients undergoing accelerated adjuvant chemotherapy were randomized to receive EPO 150 U/kg three times a week or no additional treatment. Chemotherapy consisted of six cycles of cyclophosphamide 600 mg/m2, epirubicin 60 mg/m2, and fluorouracil 600 mg/m2 (CEF) intravenously on day 1, every 2 weeks with the support of granulocyte colony-stimulating factor (G-CSF), 5 microg/kg subcutaneously from day 4 to day 11. RESULTS Throughout the six cycles of chemotherapy, EPO-treated patients maintained stable values of hemoglobin, whereas control patients developed a progressive anemia. At the end of chemotherapy, the mean (+/- SD) hemoglobin decrease in the control group was 3.05 g/dL (+/- 1.0; 95% confidence interval [CI], 2.6 to 3.5), whereas in the EPO group it was 0.8 (+/- 1.4; 95% CI, 0.3 to 1.4). Clinically significant anemia (hemoglobin < or = 10 g/dL) occurred in 16 patients (52%; 95% CI, 33 to 69) in the control arm and in no patient (0%; 95% CI, 0 to 14) in the EPO arm (P = .00001). CONCLUSION EPO prevents anemia in patients undergoing chemotherapy. Further trials are required to identify subsets of patients in which the preventive use of this drug could be cost-effective.

scholarly journals Potential role of BAY11-7082, a NF-κB blocker inhibiting experimental autoimmune encephalomyelitis in C57BL/6J mice via declining NLRP3 inflammasomes

2021 ◽  
Author(s):  
Yue Lang ◽  
Fengna Chu ◽  
Lingling Liu ◽  
Chao Zheng ◽  
Chunrong Li ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Nlrp3 Inflammasome ◽  
Demyelinating Disease ◽  
Control Group ◽  
Autoimmune Encephalomyelitis ◽  
Treatment Groups ◽  
Prevention And Treatment ◽  
Nlrp3 Inflammasomes ◽  
Experimental Autoimmune

Abstract Multiple sclerosis (MS) is an inflammatory autoimmune demyelinating disease of the central nervous system. NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, is implicated in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which NLRP3 inflammasome is involved in the development of MS and EAE is not clear. NF-kappaB (NF-κB) is associated with the activity of NLRP3 inflammasomes, but the role of NF-κB is controversial. We sought to demonstrate that both NF-κB and NLRP3 contribute to development of MS and EAE, and NF-κB pathway is positively correlated with NLRP3 activation in EAE. The inhibitor of NF-κB and NLRP3, BAY11-7082, can prevent and treat EAE. BAY11-7082 (5mg/kg/i.p and 20 mg/kg/i.p) was intraperitoneally administered to EAE mice at the time of second injection of pertussis toxin (BAY11-7082 prevention group) or at the onset of symptoms (BAY11-7082 treatment group). mRNA expressions of NLRP3 were determined by qPCR. Protein expressions of NLRP3, NF-κBp65, and phosphorylated-p65 were determined by Western blotting. Serum levels of inflammatory cytokines were measured by Cytometric Bead Array. Mice treated with BAY11-7082 (both prevention and treatment groups) showed lower clinical scores and attenuated pathological changes. NLRP3 inflammasome and activity of NF-κB in spinal cord of EAE mice was higher than that in control group. However, the level of NLRP3 inflammasome decreased in BAY11-7082 prevention and treatment groups. BAY11-7082 is a promising therapeutic agent for MS. NLRP3 activation in EAE maybe related with NF-κB pathway.

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