scholarly journals Pre-treatment and continuous administration of simvastatin during sepsis improve metabolic parameters and prevent CNS injuries in survivor rats

Author(s):  
Carlos Henrique Rocha Catalão ◽  
Anderson de Oliveira Souza ◽  
Nilton Nascimento Santos-Júnior ◽  
Luís Henrique Angenendt da Costa ◽  
Jonathas Rodrigo dos Santos ◽  
...  

Abstract Sepsis causes overproduction of inflammatory cytokines, organ dysfunction and cognitive impairment in survivors. In addition to inflammation, metabolic changes occur according to the stage and severity of the disease. Understanding the role and place of metabolic disturbances in the pathophysiology of sepsis is essential to evaluate the framework of septic patients, predict the syndrome progress and define treatment strategies. We investigated the effect of simvastatin on the disease time course and on metabolic alterations, especially with respect to their possible consequences in the CNS of surviving rats. The animals of this study were weighed daily and followed for 10 days to determine the survival rate. In the first experiment, control or CLP-animals were randomized in 24 h, 48 h and 10 days after septic induction, for bacterial load determination and, quantification of cytokines. In the second experiment, control or CLP-animals were treated or not with simvastatin and randomized in the same three time points for cytokines quantification and assessment of their body metabolism and locomotor activity (at 48 h and 10 days), as well as the evaluation of cytoarchitecture and astrogliosis (at 10 days). The CLP-rats treated with simvastatin showed a reduction in plasma cytokines and improvement in metabolic parameters and locomotor activity, followed by minor alterations compatible with apoptosis and astrogliosis in the hippocampus and prefrontal cortex. These results suggest that the anti-inflammatory effect of simvastatin plays a crucial role in restoring energy production, maintaining a hypermetabolic state necessary for the recovery and survival of these CLP-rats.

2021 ◽  
pp. 100716
Author(s):  
Deisi Cristina Tápparo ◽  
Daniela Cândido ◽  
Ricardo Luis Radis Steinmetz ◽  
Christian Etzkorn ◽  
André Cestonaro do Amaral ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (5) ◽  
pp. 1864-1866 ◽  
Author(s):  
Erwin Kemna ◽  
Peter Pickkers ◽  
Elizabeta Nemeth ◽  
Hans van der Hoeven ◽  
Dorine Swinkels

Abstract Hepatic peptide hormone hepcidin is the key regulator of iron metabolism and the mediator of anemia of inflammation. Previous studies indicated that interleukin-6 (IL-6) mediates hepcidin increase and consequent hypoferremia during inflammation. Here we used an in vivo human endotoxemia model to analyze the effects of lipopolysaccharide (LPS) as a more upstream inflammation activator. The temporal associations between plasma cytokines, hepcidin levels, and serum iron parameters were studied in 10 healthy individuals after LPS injection. IL-6 was dramatically induced within 3 hours after injection, and urinary hepcidin peaked within 6 hours, followed by a significant decrease in serum iron. Serum prohepcidin showed no significant change within a 22-hour time frame. These in vivo human results confirm the importance of the IL-6-hepcidin axis in the development of hypoferremia in inflammation and highlight the rapid responsiveness of this iron regulatory system. (Blood. 2005;106: 1864-1866)


2001 ◽  
Vol 204 (2) ◽  
pp. 337-348 ◽  
Author(s):  
S. Coombs ◽  
C.B. Braun ◽  
B. Donovan

Lake Michigan mottled sculpin, Cottus bairdi, exhibit a naturally occurring and unconditioned orienting response that can be triggered by both live prey and chemically inert vibrating spheres, even in blinded animals. CoCl(2)-induced reductions of the orienting response demonstrate that the lateral line is required for this behavior in the absence of non-mechanosensory cues (such as vision), but shed no light on the relative contributions of superficial and canal neuromasts to this behavior. To determine the relative roles of these two subsystems, we measured the frequency with which mottled sculpin oriented towards a small vibrating sphere before and after two treatments: (i) immersion of fish in a solution of gentamicin, an aminoglycoside antibiotic that damages hair cells in canal, but not superficial, neuromasts; and (ii) scraping the skin of the fish, which damages the superficial, but not the canal, neuromasts. To ensure that both superficial and canal neuromasts were adequately stimulated, we tested at different vibration frequencies (10 and 50 Hz) near or at the best frequency for each type of neuromast. At both test frequencies, response rates before treatment were greater than 70 % and were significantly greater than ‘spontaneous’ response frequencies measured in the absence of sphere vibration. Response rates fell to spontaneous levels after 1 day of gentamicin treatment and did not return to pre-treatment levels for 10–15 days. In contrast, response rates stayed approximately the same after superficial neuromasts had been damaged by skin abrasion. Scanning electron microscopy confirmed hair cell damage (loss of apical cilia) in canal, but not superficial, neuromasts of gentamicin-treated animals after as little as 24 h of treatment. The sensory epithelium of canal neuromasts gradually returned to normal, following a time course similar to behavioral loss and recovery of the orienting response, whereas that of superficial neuromasts appeared normal throughout the entire period. This study shows that the orienting response of the mottled sculpin is mediated by canal neuromasts.


2018 ◽  
Vol 20 (1) ◽  
pp. 88 ◽  
Author(s):  
Mehdi Labyb ◽  
Chloé Chrétien ◽  
Aurélie Caillon ◽  
Françoise Rohner-Jeanrenaud ◽  
Jordi Altirriba

Whereas leptin administration only has a negligible effect on the treatment of obesity, it has been demonstrated that its action can be improved by co-administration of leptin and one of its sensitizers. Considering that oxytocin treatment decreases body weight in obese animals and humans, we investigated the effects of oxytocin and leptin cotreatment. First, lean and diet-induced obese (DIO) mice were treated with oxytocin for 2 weeks and we measured the acute leptin response. Second, DIO mice were treated for 2 weeks with saline, oxytocin (50 μg/day), leptin (20 or 40 µg/day) or oxytocin plus leptin. Oxytocin pre-treatment restored a normal acute leptin response, decreasing food intake and body weight gain. Chronic continuous administration of oxytocin or leptin at 40 µg/day decreased body weight in the presence (leptin) or in the absence (oxytocin) of cumulative differences in food intake. Saline or leptin treatment at 20 µg/day had no impact on body weight. Oxytocin and leptin cotreatments had no additional effects compared with single treatments. These results point to the fact that chronic oxytocin treatment improves the acute, but not the chronic leptin response, suggesting that this treatment could be used to improve the short-term satiety effect of leptin.


2011 ◽  
Vol 3 ◽  
pp. CMT.S6456
Author(s):  
Francesca Bagnato ◽  
Istvan Pirko

Multiple sclerosis (MS), a chronic inflammatory-degenerative illness of the central nervous system (CNS), remains at the moment a treatable but incurable disease. Currently available disease-modifying agents (DMA-s), the majority of which are being injected, mainly relieve the inflammatory phase of MS with little beneficial effect, if any, in halting neurodegeneration. Cladribine is an immunosuppressive agent that can be administered orally and by cycles of short-course dosing as opposed to continuous administration. Cladribine has been shown to be effective in reducing inflammatory activity of MS but much remains unknown regarding its potential beyond the control of CNS inflammation. In addition, knowledge on the safety profile of cladribine in MS is limited. Data from on going clinical studies and registries on its safety profile will shed more light on the actual benefit/risk ratio of cladribine.


2019 ◽  
Vol 21 (Supplement_M) ◽  
pp. M44-M49 ◽  
Author(s):  
Mohsen Habibian ◽  
Alexander R Lyon

Abstract A growing number of effective cancer therapies is associated with cardiovascular (CV) toxicities including myocardial injury or dysfunction, leading to reduced ventricular function, and increased risk of heart failure. As the timing of administration of cancer treatment is known, the potential for risk stratification pre-treatment, and appropriate surveillance and monitoring during treatment, and intervention with cardio-protective treatment strategies in patients exhibiting early evidence of CV toxicity is an appealing clinical strategy. The field of cardio-oncology has developed, and the application of monitoring strategies using CV biomarkers and CV imaging has been to focus of many studies and is now implemented in dedicated cardio-oncology services supporting oncology centres. In this article, we review the background and rationale for monitoring, the different options and their strengths, weaknesses and where they are helpful in specific cardiotoxic cancer therapies, and the impact in cardio-oncology care.


Heliyon ◽  
2019 ◽  
Vol 5 (8) ◽  
pp. e02351
Author(s):  
Rosana Krauss Niedzialkoski ◽  
Monica Sarolli Silva de Mendonça Costa ◽  
Luiz Antonio de Mendonça Costa ◽  
Larissa Macedo dos Santos Tonial ◽  
Felippe Martins Damaceno ◽  
...  

Author(s):  
Timothy Crook ◽  
Andrew Gaya ◽  
Raymond Page ◽  
Sewanti Limaye ◽  
Anantbhushan Ranade ◽  
...  

Abstract Purpose Selection of cytotoxic chemotherapy agents (CCA) based on pre-treatment evaluation of drug sensitivities is a desirable but unmet goal for personalized anticancer treatment strategies. Prior attempts to correlate in vitro Chemo-Response Profiles (CRP) of tumor explants or Circulating Tumor Cells (CTCs) with clinical outcomes have been largely unsuccessful. Methods We present results from a large cohort (n = 5090, three Arms) of patients with various solid organ tumors, where CRP of Circulating Tumor-Associated Cells (C-TACs) was determined against cancer-specific CCA panels to generate a database of 56,466 unique CRP. Results In Arm 1 (n = 230), 93.7% concordance was observed between CRP of C-TACs and concurrently obtained Tumor tissue Derived Cells (TDCs). In arm 2 (n = 2201, pretreated), resistance of C-TACs to ≥ 1 CCA was observed in 79% of cases. In a blinded subset analysis of 143 pretreated patients with radiologically ascertained disease progression, CRP of C-TACs was 87% concordant with in vivo treatment failure. In Arm 3 (n = 2734, therapy naïve), innate resistance of C-TACs to ≥ 1 CCA was observed in 61% of cases. In a blinded subset analysis of 77 therapy naïve patients, in vitro chemo-sensitivity of C-TACs was concordant with radiologically ascertained treatment response to first line CCA in 97% of cases. Conclusion To our knowledge, this is the first expansive and in-depth study demonstrating that real-time CRP of C-TACs is a viable approach for non-invasive assessment of response to CCA in solid organ cancers.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 555-555
Author(s):  
Ji Hyung Hong ◽  
Jae Ho Byun ◽  
Eun Kyoung Choi ◽  
Jin Kyoung Oh ◽  
Ji-Hun Kim ◽  
...  

555 Background: Recently, novel metabolic parameters in 18F-FDG PET/CT such as total lesion glycolysis (TLG) and metabolic tumor volume (MTV) as well as maximum standardized uptake value (SUVmax) have been reported to be prognostic and be related with genomic aberration. We evaluated the prognostic role of these metabolic parameters and the correlation with clinical features in resected colon cancer. Methods: This study included 212 colon cancer patients who underwent surgical resection of stage II and III disease and conducted pre-treatment 18F-FDG PET/CT between February 2009 and December 2013. TLG, MTV of the primary tumors as well as SUVmax were analyzed according to clinical features including KRAS mutation, pre-treatment carcinoembryonic antigen (CEA) and recurrence free survival (RFS). Results: TLG was significantly higher in patients with right colon cancer than those with left colon cancer ( P = 0.015) and in patients with elevated CEA than those with normal range of CEA ( P = 0.034), while MTV and SUVmax were not correlated with cancer location and CEA level. KRAS mutation analysis using peptide nucleic acid-mediated real-time polymerase chain reaction clamping was conducted in 94 patients and forty-one (43.6%) patients showed KRAS mutation in tumor tissues. TLG was significantly higher in patients with mutated KRAS compared with in those with wild KRAS ( P = 0.021). CEA was significantly higher in patients with mutated KRAS than those with wild KRAS ( P-value = 0.024). CEA and TLG could predict KRAS mutation showing odds ratio 1.07 and 1.02 in the multivariate logistic analysis ( P-value = 0.024, 0.048). There was no difference of RFS between in patients with high TLG and in those with low TLG. Conclusions: Based on the result that TLG had a predictive role for KRAS mutation and was related with tumor location and CEA value, we suggested that TLG might reflect genomic alteration and other clinical features as well as tumor burden. It could be useful for differentiating different population of colon cancer and further study is clinically warranted.


Sign in / Sign up

Export Citation Format

Share Document