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1.
J Nanosci Nanotechnol ; 20(2): 680-691, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383063

RESUMO

BN has important roles in several physiological events, including bone growth and immune system. New infection-free cranioplasty and has an osteogenic activities material that are compatible with tissue are being developed. We aimed in our study to examine whether different combinations of Boron-nitride/Hydroxyapatite are embedded into the scaffold in the treatment of calvarial defects. 200 adult female Sprague-Dawley rats divided into 10 equal groups. Osteotomy was made by trepan drill in 8 mm diameter. The scaffolds were placed in the rats and were left to recovery for 2 months. During the experiment, CT scans were taken from the calvarial areas of the rats in the 2nd, 4th and 8th weeks. Significant healing was observed in defect diameters in 2.5% BN+10% HA, 2.5% BN and 5% BN+10% HA, respectively. After 8 weeks, it was seen that the amounts of OPN, BMP-2, RunX2 and ALP mRNA expression significantly decreased in 2.5% BN+10% HA, 2.5% BN, 5% BN+10% HA and 5% BN groups. It was shown that bone recovery was at the best grade in the groups, which contained 2.5% BN and 2.5% BN+10% HA when compared to the other groups. BN is a very promising agent that will be used in reconstructive surgery for the treatment of calvarial bone defects.

2.
Jpn J Infect Dis ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31474702

RESUMO

In addition to tube drains, pleural empyema is treated with antibiotics and anti-inflammatory drugs. We aimed to evaluate the anti-inflammatory activity of roflumilast combined with linezolid in a rat model of pleural empyema induced by Staphylococcus aureus.A total of 40 rats were separated into 7 groups: Sham (n=4), S. aureus inoculation (n=6), S. aureus + 10 mg/kg linezolid (n=6), S. aureus + 5 mg/kg roflumilast (n=6), S. aureus + 10 mg/kg linezolid+5 mg/kg roflumilast (n=6), S. aureus + 10 mg/kg roflumilast (n=6), and S. aureus + 10 mg/kg linezolid + 10 mg/kg roflumilast (n=6). Linezolid was administered 1 hour before and 12 hours after inoculation with S. aureus. Roflumilast was administered orally as a single dose 30 minutes before inoculation with S. aureus. Compared to linezolid alone, linezolid combined with 5 mg/kg roflumilast provided statistically significant improvement in TNF-alpha, IL-1 beta, vasodilation/congestion, and tissue/pleural PNM infiltration (p<0.05).Linezolid combined with 10 mg/kg roflumilast also provided statistically significant improvement TNF-alpha, IL-1 beta, IL-6, endothelin-1, vasodilation/congestion, mesothelial cell damage, lung tissue PNL, and pleural PNL compared to linezolid alone (p<0.05).Due to its anti-inflammatory effect and significant impact on recovery, roflumilast can be used in conjunction with antibiotherapy for the treatment of pleural empyema.

3.
Inflammopharmacology ; 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31309486

RESUMO

AIM: This study aimed to investigate the role of the 5-HT7 receptor in fever mechanisms and its possible effect on the antipyretic mechanism of paracetamol. MATERIALS AND METHODS: The study consisted of eight experimental groups and one control group. Group I: healthy, II: LPS, III: LPS + PARA, IV: LPS + AGO, V: LPS + ANTA, VI: LPS + AGO + ANTA, VII: LPS + AGO + PARA, VIII: LPS + ANTA + PARA, and IX: LPS + AGO + ANTA + PARA. Rectal temperatures were measured with a rectal thermometer. At the end of the experiment, tissues were examined molecularly. Real-time PCR mRNA expression analyses were performed for the 5-HT7 receptor, IL-6, and TNF-α in hypothalamus tissue. RESULTS: The mean differences in rectal temperature increased in the LPS, LPS + ANTA, and LPS + AGO + ANTA groups when compared to the healthy group and decreased in the LPS + PARA, LPS + AGO, LPS + AGO + PARA, and LPS + AGO + ANTA + PARA groups when compared to the healthy group. The IL-6 and TNF-α mRNA expression increased in the LPS, LPS + ANTA, and LPS + AGO + ANTA groups when compared to the healthy group in the 2nd and 4th hours. The IL-6 and TNF-α expression decreased in the LPS + PARA, LPS + AGO, LPS + AGO + PARA, and LPS + AGO + ANTA + PARA groups when compared to the LPS group in the 2nd and 4th hours. The 5-HT7 receptor mRNA expression increased in the LPS group when compared to the healthy group in the 2nd hour. The 5-HT7 receptor mRNA expression decreased in the LPS + AGO and LPS + AGO + PARA groups when compared to the LPS group in the 2nd hour. The 5-HT7 receptor mRNA expression increased the in LPS + ANTA and LPS + ANTA + PARA groups when compared to the LPS group in the 2nd hour. CONCLUSION: The 5-HT7 receptor is a potential defense mechanism in stopping fever and the antipyretic property of paracetamol is not due to the 5-HT7 receptor.

4.
Burns ; 45(6): 1410-1417, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31126777

RESUMO

BACKGROUND: Beeswax, Olive oil and Butter (BOB) are nutritive products that could support wound healing by adsorption to bandage. This study demonstrated the therapeutic effects of BOB on second degree burn. METHODS: Second degree burn model was created in rats. Experimental groups were assigned to Healthy, Burn, Silver Sulfadiazine (SS) and BOB. The effects of BOB were evaluated on skin regeneration, vesicles and bullae and fibroblast activity by histopathological analyses and wound contraction percent were determined. Transforming Growth Factor-Beta1 (TGF-ß1) and Vascular Endothelial Growth Factor-alpha (VEGF-α) mRNA expressions were analyzed with Real Time-Polymerase Chain Reaction. All parameters analyzed at 3rd, 7th, 14th days. RESULTS: The BOB treatment increased TGF-ß1 and VEGF-α expressions compared to Burn group. The histopathological analyses showed that epidermis and dermis layers injured due to burn. BOB treatment augmented the regeneration of these layers and increased fibroblast activity and keratinization which are play important role on the new blood vessels production. Also with the BOB treatment we showed wound contraction levels were higher than Burn and SS treatment. CONCLUSION: This study demonstrated that beeswax-olive oil-butter mixture impregnated bandage treatment in a second-degree burn rat model improved burn wound healing and encouraged skin renewal via modulating tissue TGF-ß1 and VEGF-α.

5.
Life Sci ; 221: 327-334, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30797018

RESUMO

AIMS: Sepsis is a complex pathophysiological event involving systemic inflammatory response syndrome, multiple organ dysfunction syndrome and tissue damage such as acute lung injury (ALI). Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Antioxidant, antibacterial and antiinflammatory effects of gossypin (GOS)-like flavonoids have been shown and we have hypothesized that GOS have roles in sepsis induced inflammation of lungs. MAIN METHODS: Cecal ligation and puncture (CLP) induced sepsis model was induced in rats. Effects of GOS on oxidative stress, histopathology, nuclear factor kappa B (NF-κB), IL-6 positivity and NLRP3, HMGß1, TNF-α, NF-κB, IL-1ß mRNA expression levels were evaluated in lung tissues of the septic rats. KEY FINDINGS: GOS 20 (20 mg/kg) administration to septic rats decreased oxidative stress and supported antioxidant system in lungs. GOS administration also decreased the tissue NF-κB and IL-6 immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. HMGß1, NLRP3, NF-κB, IL-1ß, and TNF-α mRNA expression significantly increased in the CLP group. Both doses of GOS significantly reduced these mRNA expression as compared with the levels in the CLP group demonstrating its anti-inflammatory potential. SIGNIFICANCE: GOS administration, may represent a novel treatment for the prevention of lung damage occurred after sepsis induction. This effect of GOS might be related to its anti-inflammatory potential that result in decreased cytokine response and improved oxidative status.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Flavonoides/farmacologia , Sepse/tratamento farmacológico , Lesão Pulmonar Aguda/prevenção & controle , Animais , Antioxidantes , Citocinas , Modelos Animais de Doenças , Feminino , Flavonoides/metabolismo , Proteínas HMGB , Inflamação , Interleucina-1beta , Interleucina-6 , Pulmão/citologia , Pulmão/fisiologia , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Estresse Oxidativo , Ratos , Ratos Wistar , Sepse/induzido quimicamente , Sepse/fisiopatologia , Fator de Necrose Tumoral alfa
6.
Neurotoxicol Teratol ; 72: 22-28, 2019 Mar - Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30685503

RESUMO

Serotonin exerts anti-inflammatory, antioxidant and antiapoptotic effects through 5-HT7 receptors. The present study determined the role of 5-HT7 receptors in glutamate-induced neurotoxicity by using human SH-SY5Y neuroblastoma cells. The cells were pretreated with different concentrations of 5-HT7 receptor agonist LP44 and antagonist SB269970 for 60 min, followed by treatment with glutamate. Cell proliferation was measured using xCELLigence system. Treatment with all the concentrations of LP44 significantly protected the cells from the toxic effects of glutamate after 24, 48 and 72 h. Although 5-HT7 receptor expression was significantly upregulated in glutamate-treated cells, it was downregulated in LP44-pretreated cells. Furthermore, LP44 treatment significantly decreased malondialdehyde levels and increased superoxide dismutase activities and glutathione levels. Moreover, LP44 treatment significantly decreased tumor necrosis factor alpha (TNF-α) levels and inhibited caspase 3 and caspase 9 mRNA expression. In contrast, SB269970 treatment exerted an insignificant effect on oxidative stress, inflammation and apoptosis. These findings suggest that exogenous stimulation of the 5-HT7 receptors may be protective in glutamate-induced neurotoxicity and that 5-HT7 receptor agonists can be used as therapeutic agents for preventing glutamate-induced neurological disorders.

7.
An Acad Bras Cienc ; 91(1): e20180106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30569967

RESUMO

Our aim is to investigate the potentially preventive effects of Aliskiren in a carrageenan-induced lung pleurisy model and to compare the standard anti-inflammatory agents, indomethacin and dexamethasone. The pleurisy model was induced through the injection of carrageenan (0.2 ml-%2) into the pleural cavity. After the experiment, serum and lung tissues were collected and biochemical, molecular and pathological examinations were performed. In our study, pleural inflammation decreased superoxide dismutase activity and the glutathione level and increased the malondialdehyde level in the lung of rats, while Aliskiren increased the superoxide dismutase activity and glutathione level and decreased the malondialdehyde level. In addition, carrageenan-induced pleurisy caused a significant increase in pro-inflammatory cytokines mRNA expressions (TNF-α, IL-1ß, and NF-KB), while Aliskiren administration decreased their expressions as well as the standard treatments, indomethacin and dexamethasone, did. Aliskiren administration at the 200 mg/kg dose protected the lungs in the pathological evaluation, especially against inflammatory cell infiltration and edematous lesions. It appears that Aliskiren protects the lung from carrageenan-induced pleurisy damage by regulating inflammation and antioxidant-oxidant balance via Renin Angiotensin Aldosterone System inhibition.


Assuntos
Amidas/farmacologia , Anti-Inflamatórios/farmacologia , Fumaratos/farmacologia , Pleurisia/prevenção & controle , Sistema Renina-Angiotensina/efeitos dos fármacos , Animais , Carragenina , Modelos Animais de Doenças , Glutationa/análise , Interleucina-1beta/análise , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Malondialdeído/análise , NF-kappa B/análise , Estresse Oxidativo/efeitos dos fármacos , Pleurisia/induzido quimicamente , Pleurisia/patologia , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Fator de Necrose Tumoral alfa/análise
8.
Artigo em Inglês | MEDLINE | ID: mdl-30353214

RESUMO

Sepsis is a life-threatening organ dysfunction condition response resulting in acute lung injury. Urotensin II (UII), an endogenous vasoactive peptide, is widely distributed in pulmonary, cardiovascular, central nervous, renal and metabolic systems, and especially in inflammatory regions. This study aimed to investigate whether urotensin II (UII) and UII receptor (UTR) antagonists play a role in the inflammatory response to sepsis-induced lung damage and they are possible therapeutic targets. In the study, 78 male Balb-c mice were used. A cecal ligation and puncture (CLP)-induced polymicrobial sepsis model was applied, and the effects of human urotensin II (agonist) and urantide and palosuran (antagonists) were investigated on lung tissues. Glutathione and malondialdehyde levels and SOD activity of lung tissues were investigated in addition to TNF-α, IL-1ß, IL-6, NF-κB, and UTR mRNA levels. Also, lung sections were histopathologically evaluated. Urantide and palosuran, UII receptor antagonists, decreased proinflammatory cytokines such as TNF-α, IL-1ß, IL-6, NF-κB, and also decreased oxidative stress parameters in lung tissue, which are markers of damage. UTR mRNA expression was increased in septic lungs, and both antagonists significantly decreased the elevated receptor level. Also, histopathological examination showed beneficial effects of both agonists on lung tissue. The results of this study help to understand the inflammatory and therapeutic contribution of the UII/UTR system on sepsis-induced lung damage. We can suggest that UTR receptor antagonists may be evaluated as a potential drug which reduces sepsis-induced lung damage in the future.

9.
Acta Odontol Scand ; 76(2): 130-134, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29057714

RESUMO

BACKGROUND: Radiotherapy is a commonly used treatment modality in head and neck cancer; however, it also negatively affects healthy structures. Direct damage to oral soft and hard tissue frequently occurs with radiotherapy. In this study, we aimed to evaluate the effect of radiotherapy on bone surrounding titanium dental implants via biomechanical and molecular methods. MATERIALS AND METHODS: Fifty-four implants were inserted in the left tibiae of 18 adult male New Zealand rabbits (3 implants in each rabbit). After 4 weeks of the implant surgery, the left tibiae of 12 rabbits were subjected to a single dose of irradiation (15 Gy or 30 Gy). Four weeks after the irradiation, rabbits were sacrificed and removal torque test was done for the biomechanical evaluation. Bone morphogenetic protein-2 (Bmp-2) and fibroblast growth factor-2 (Fgf-2) expression analyses were performed with Real-time PCR. Statistical analysis was done using SPSS. RESULTS: The control group showed significantly higher removal torque value than the 15 and 30 Gy irradiation groups, and the 15 Gy irradiation group had higher removal torque value than the 30 Gy irradiation group (p < .001). The 15 Gy and 30 Gy irradiation groups had significantly lower Bmp-2 and Fgf-2 mRNA expressions than the control group (p < .001). In addition, the 30 Gy irradiation group had significantly lower Bmp-2 (p < .01) and Fgf-2 mRNA expressions (p < .001) than the 15 Gy group. CONCLUSION: Radiotherapy with 15 and 30 Gy doses can adversely affect osseointegration of implants by reducing the quality of bone and impairing the bone-to-implant contact. The mechanism of action seems to be related to alterations in Bmp-2 and Fgf-2 mRNA expressions.


Assuntos
Proteína Morfogenética Óssea 2/efeitos da radiação , Implantes Dentários , Materiais Dentários/efeitos da radiação , Titânio/química , Animais , Materiais Dentários/química , Relação Dose-Resposta à Radiação , Masculino , Osseointegração/efeitos da radiação , Coelhos , Propriedades de Superfície , Torque
10.
Eur J Pharmacol ; 818: 457-469, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29133126

RESUMO

This study aimed to investigate the potential role of urotensin-II receptors in sepsis-induced lung injury in diabetic mice using urotensin-II receptor agonists and antagonists. A total of 110 male CD1 mice were used in this study. Diabetes was induced by 200mg/kg streptozotocin. One month after diabetes induction, the cecal ligation and puncture-induced polymicrobial sepsis model was applied in the diabetic and non-diabetic mice. Low and high doses of human urotensin-II agonist (HU-II) and antagonist (palosuran) were administered one hour after sepsis induction. HU-II administration was repeated in two-hour intervals. Blood and tissue samples were collected at 6 and 12H after sepsis induction for biochemical, molecular, and histopathologic examinations. Regarding to the lungs mRNA expression and immunohistochemistry results of TNF-α, IL1 ß, IL6, and NF-κB, it was observed that cytokine levels significantly increased in the diabetes group and the sepsis groups compared to the healthy group; this increase was significantly higher in the diabetes-sepsis groups. Our biochemical (superoxide dismutase, glutathione, and malondialdehyde) and histopathological findings in the lungs also supported these results. All increased parameters were significantly reduced dose-dependently by the administration of palosuran, an urotensin receptor antagonist. mRNA expression of urotensin-II and its receptor were examined in the lung tissue. Palosuran administration significantly reduced the urotensin-II and urotensin-II receptor levels that increased in the damaged tissue. This study has shown that urotensin-II and urotensin-II receptors contribute to the aggravation of sepsis-induced lung injury in diabetic mice; palosuran prevents this damage by antagonizing urotensin-II receptors.


Assuntos
Diabetes Mellitus Experimental/complicações , Lesão Pulmonar/etiologia , Lesão Pulmonar/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Sepse/complicações , Urotensinas/metabolismo , Animais , Peso Corporal , Jejum/sangue , Regulação da Expressão Gênica , Interleucina-6/genética , Lesão Pulmonar/genética , Masculino , Camundongos , NF-kappa B/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Receptores Acoplados a Proteínas-G/genética , Fator de Necrose Tumoral alfa/genética , Urotensinas/genética
11.
Ear Nose Throat J ; 96(12): E14-E18, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29236276

RESUMO

Nasal polyposis (NP) is an inflammatory disease of the paranasal sinuses and nasal cavity. The primary purpose of our study is to determine the expression of 5-HT7 receptors both in nasal polyps and in healthy tissue in the nasal cavity. The subsequent aim is to compare the expression of 5-HT7 receptors in patients with NP and in inferior turbinate tissue (control). The study included 60 participants (40 with NP and 20 controls) aged 35 to 62 years. Nasal polyp samples were collected from all patients and relative 5-HT7 receptor expression analyses were performed. Reverse transcription polymerase chain reaction analysis of nasal polyps and control tissue identified 5-HT7 receptor expression in the nasal cavities of controls. This expression was approximately 67 times higher in nasal polyp tissue than in healthy tissue. Our study identifies the expression of 5-HT7 receptors in the nasal cavity for the first time and the first demonstration of increased 5-HT7 receptor expression in tissue from nasal polyps, which occur in the paranasal sinuses and nasal cavity.


Assuntos
Pólipos Nasais/metabolismo , Receptores de Serotonina/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adulto , Estudos de Casos e Controles , Doença Crônica , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/metabolismo , Mucosa Nasal/metabolismo , Seios Paranasais/metabolismo , Reação em Cadeia da Polimerase
12.
Braz. j. otorhinolaryngol. (Impr.) ; 83(6): 619-626, Nov.-Dec. 2017. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-889326

RESUMO

Abstract Introduction: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. Objective: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. Methods: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined. Results: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. Conclusion: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.


Resumo Introdução: Antibióticos são frequentemente usados para o tratamento de rinossinusite. Questões têm sido levantadas sobre os efeitos adversos dos antibióticos e a resistência crescente. A falta de desenvolvimento de novos compostos antibióticos aumentou a necessidade da exploração de compostos não antibióticos que têm atividade antibacteriana. A amlodipina é um composto não antibiótico com atividade anti-inflamatória. Objetivo: O objetivo desse estudo foi investigar o papel potencial da amlodipina no tratamento da rinossinusite, avaliando seus efeitos sobre o estado oxidativo do tecido, histologia da mucosa e inflamação. Método: Quinze cobaias albinas adultas foram inoculadas com Staphylococcus aureus e tratadas com solução salina, cefazolina ou amlodipina durante sete dias. O grupo controle incluiu cinco cobaias saudáveis. Os animais foram sacrificados após o tratamento. Alterações histopatológicas foram identificadas com a coloração de hematoxilina-eosina. A inflamação foi avaliada pela densidade de infiltração de leucócitos polimorfonucleares. Foram determinados os níveis teciduais de antioxidantes (superóxido dismutase, glutationa) e um produto de oxidação (malondialdeído). Resultados: Em animais com rinossinusite induzida, a amlodipina reduziu a perda dos cílios, edema da lâmina própria e deposição de colágeno em comparação com o grupo placebo (solução salina) e embora não seja superior à cefazolina, a amlodipina diminuiu a infiltração de leucócitos polimorfonucleares. Os níveis de atividade da superóxido dismutase e glutationa foram reduzidos, enquanto os níveis de malondialdeído aumentaram significativamente nos três grupos de tratamento em comparação ao grupo controle. O grupo tratado com amlodipina apresentou aumento significante dos níveis de superóxido dismutase e glutationa e diminuição dos níveis de malondialdeído em comparação com todos os grupos de tratamento. Conclusão: O composto não antibiótico amlodipina pode ter um papel no tratamento da rinossinusite aguda através de mecanismos protetores de tecido, antioxidantes e anti-inflamatórios.

13.
Eurasian J Med ; 49(1): 53-58, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28416934

RESUMO

Sepsis is a complex condition characterized by the simultaneous activation of inflammation and coagulation in response to microbial insult. These events manifest as systemic inflammatory response syndrome or sepsis symptoms through the release of proinflammatory cytokines, procoagulants, and adhesion molecules from immune cells and/or damaged endothelium. Today, sepsis is a severe multisystem disease with difficult treatments for its manifestations and high mortality rates. In the last two decades in particular, many studies have been conducted on sepsis that cause shock, multiorgan dysfunction, and organ failure by especially leading to hemodynamic changes. In sepsis, increasing antibiotic resistance and medicine-resistant hemodynamic changes have resulted in further research on new treatment modalities in addition to classical treatments. In the last decade, the sepsis physiopathology has been elucidated. Various therapeutic agents have been used in addition to antibiotherapy, but no satisfactory results have been obtained. This review summarizes the sepsis pathophysiology, current treatment protocols, and new approaches.

14.
Int Immunopharmacol ; 43: 227-235, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28043031

RESUMO

BACKGROUND AND AIM: Hepatocellular cancer (HCC) is the sixth most common cancer and liver fibrosis is strongly associated with HCC. Treatment options are limited, and preventive strategies should be developed. An important step in the beginning of liver fibrosis is a strong inflammatory response. 5-HT7 is the last recognized member of the serotonin receptor family and is expressed in both central nerve system and peripheral system and have a lot of functions like learning, memory, smooth muscular relaxation, in the control of circadian rhythms and thermoregulation, pain and migraine, schizophrenia, anxiety, cognitive disturbances, and even inflammation. METHODS: We therefore examined the biochemical, histopathological and molecular effects of the 5-HT7 receptor agonist and antagonist on inflammatory liver fibrogenesis in animal models of progressive cirrhosis: a mouse model induced by carbon tetrachloride (CCl4) and in Hep3b cells. RESULTS: 5-HT7 expression was observed in the liver in vivo and in vitro in CCl4-induced damage. 5-HT7 receptor agonist but not the antagonist reduced liver markers in mice and in Hep3b cells in carbon tetrachloride (CCl4) induced damage. 5-HT7 agonist, but not antagonist, protected liver tissue from oxidative stress in fibrosis. 5-HT7 agonist but not antagonist induces anti-inflammatory, anti-fibrinotic and anti-cytokine features in liver fibrosis in vivo and in vitro. CONCLUSIONS: 5-HT7 receptors have modulatory function and are an up-and-coming pharmacological target in the inflammatory fibrotic process. 5-HT7 receptor agonist LP-44 showed significant hepatoprotective effects against liver fibrosis, and LP-44 might become a useful therapeutic target for chronic liver inflammation and fibrosis.


Assuntos
Carcinoma Hepatocelular/imunologia , Inflamação , Neoplasias Hepáticas/imunologia , Fígado/metabolismo , Lesão Pulmonar/imunologia , Receptores de Serotonina/metabolismo , Animais , Tetracloreto de Carbono , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular , Fibrose , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Receptores de Serotonina/genética , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Sulfonamidas/farmacologia
15.
Ren Fail ; 39(1): 314-322, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28100100

RESUMO

Contrast media (CM) is known to have nephrotoxic adverse effects. Epigallocatechin-3-gallate (EGCG) is the most abundant and active catechin in green tea, and has strong antioxidant and anti-inflammatory properties. This study investigated whether EGCG can reduce contrast-induced nephrotoxicity (CIN), alone or with glycerol (GLY)-induced renal damage, and to understand its mechanisms of protection against toxicity, using models of GLY and CIN in rats. The rats were separated into eight groups (n = 6 in each), as follows: Healthy, GLY, CM, GLY + CM, CM + EGCG 50 mg/kg (po), GLY + CM + EGCG 50 mg/kg (po), CM + EGCG 100 mg/kg (po), and GLY + CM + EGCG 100 mg/kg (po). Both doses of EGCG protected against CM-induced renal dysfunction, as measured by serum creatinine and blood urea nitrogen (BUN). In addition, EGCG treatment markedly improved CIN-induced oxidative stress, and resulted in a significant down-regulatory effect on tumor necrosis factor (TNF)-α and nuclear factor (NF)-κB mRNA expression. Moreover, histopathological analysis showed that EGCG also attenuated CM-induced kidney damage. Considering the potential clinical use of CM and the numerous health benefits of EGCG, this study showed the protective role of multi-dose EGCG treatment on CIN and GLY-aggravated CIN through different mechanisms.


Assuntos
Antioxidantes/farmacologia , Catequina/análogos & derivados , Meios de Contraste/efeitos adversos , Glicerol/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Animais , Nitrogênio da Ureia Sanguínea , Catequina/farmacologia , Citocinas/sangue , Rim/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Chá
16.
Braz J Otorhinolaryngol ; 83(6): 619-626, 2017 Nov - Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27769794

RESUMO

INTRODUCTION: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. OBJECTIVE: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. METHODS: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined. RESULTS: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. CONCLUSION: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.


Assuntos
Anlodipino/farmacologia , Anti-Inflamatórios/farmacologia , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Anlodipino/uso terapêutico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Cefazolina/farmacologia , Cefazolina/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Glutationa/análise , Glutationa/efeitos dos fármacos , Cobaias , Malondialdeído/análise , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Distribuição Aleatória , Valores de Referência , Reprodutibilidade dos Testes , Rinite/microbiologia , Rinite/patologia , Sinusite/microbiologia , Sinusite/patologia , Staphylococcus aureus , Superóxido Dismutase/análise , Superóxido Dismutase/efeitos dos fármacos , Resultado do Tratamento
17.
Vascular ; 25(2): 163-169, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27278523

RESUMO

Background The diagnosis of acute mesenteric ischemia is variable. Early diagnosis is important for reducing the mortality and morbidity rates. Aim This experimental study aims to investigate the diagnostic utility of D-dimer and neopterin as a marker for the early stage of acute mesenteric ischemia caused by occlusion of superior mesenteric artery. Methods The levels of D-dimer and neopterin were measured using an animal acute mesenteric ischemia model in 21 male rabbits. Superior mesenteric artery occlusion (Group 1, n = 14) and control (Group 2, n = 7) groups were identified. Blood samples at different times are collected from each rabbits. Blood samples from superior mesenteric artery occlusion group were taken 30 min after anesthesia but before laparotomy, 1, 2, and 3 h after superior mesenteric artery ligation. Blood samples from control group were taken 1 h before, 1 and 3 h after anesthesia and laparotomy. The D-dimer and neopterin levels of each blood sample were measured. Results The probability of acute mesenteric ischemia was found to be 36 times higher when the D-dimer level was over 0.125 ng/L, whereas the probability was 19.2 times higher when the neopterin level was over 1.25 nmol/L. Conclusions In this experimental study, the combined elevation of two significant markers, D-dimer and neopterin, may be helpful for the early diagnosis of acute mesenteric ischemia.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Isquemia Mesentérica/sangue , Isquemia Mesentérica/diagnóstico , Oclusão Vascular Mesentérica/sangue , Oclusão Vascular Mesentérica/diagnóstico , Neopterina/sangue , Doença Aguda , Animais , Área Sob a Curva , Biomarcadores/sangue , Modelos Animais de Doenças , Diagnóstico Precoce , Ligadura , Masculino , Artéria Mesentérica Superior/cirurgia , Isquemia Mesentérica/etiologia , Oclusão Vascular Mesentérica/etiologia , Valor Preditivo dos Testes , Curva ROC , Coelhos , Fatores de Tempo , Regulação para Cima
18.
Biochem Genet ; 55(1): 34-47, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27586707

RESUMO

This study aimed to investigate the effects of the 5-HT7 receptor agonist (LP44) and antagonist (SB269970) on LPS-induced in vivo tissue damage and cell culture by molecular methods. This study was conducted in two steps. For in vivo studies, 24 female rats were divided into four groups. Group I: healthy; II (2nd h): LPS 5 mg/kg administered intraperitoneally (i.p.); III (4th h): LPS 5 mg/kg administered i.p.; IV (8th h): LPS 5 mg/kg administered i.p. For in vitro studies, we used the A549 cell line. Groups: I control (healthy) (2-4 h); II LPS: 1 µg/ml E. Coli O55:B5 strain (2-4 h); III agonist (LP44) 10-9 M (2-4 h); IV antagonist (SB269970) 10-9 M (2-4 h); V LPS+agonist 10-9 M (LP44 1 µg/ml) (2-4 h); VI LPS+antagonist 10-9 M (2-4 h). In molecular analyses, we determined increased TNF-α, IL-1ß, NF-κB, and 5-HT7 mRNA expressions in rat lung tissues and increased TNF-α, iNOS, and 5-HT7 mRNA expressions in the A549 cell line. In in vitro parameters, LP44 agonist administration-related decrease was observed. Our study showed that lung 5-HT7 receptor expression is increased in LPS-induced endotoxemia. All this data suggest that 5-HT7 receptor overexpression is an important protective mechanism during LPS-induced sepsis-related cell damage.


Assuntos
Lesão Pulmonar , Receptores de Serotonina/metabolismo , Células A549 , Animais , Sobrevivência Celular/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Inflamação/induzido quimicamente , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Transporte Proteico/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
19.
Chem Biol Interact ; 258: 266-75, 2016 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-27645307

RESUMO

PURPOSE: Previously blocking the renin angiotensin system (RAAS) has been effective in the prevention of gastric damage. Therefore, the aim of this study was to investigate the effects of aliskiren, and thus, direct renin blockage, in indomethacin-induced gastric damage model. METHODS: Effects of aliskiren were evaluated in indomethacin-induced gastric damage model on Albino Wistar rats. Effects of famotidine has been investigated as standard antiulcer agent. Stereological analyses for ulcer area determination, biochemical analyses for oxidative status determination and molecular analyses for tissue cytokine and cyclooxygenase determination were performed on stomach tissues. In addition, to clarify antiulcer effect mechanism of aliskiren pylorus ligation-induced gastric acid secretion model was applied on rats. RESULTS: Aliskiren was able to inhibit indomethacin-induced ulcer formation. It also inhibited renin, and thus, decreased over-produced Angiotensin-II during ulcer formation. Aliskiren improved the oxidative status and cytokine profile of the stomach, which was most probably impaired by increased Angiotensin II concentration. Aliskiren also increased gastroprotective prostaglandin E2 concentration. Finally, aliskiren did not change the gastric acidity in pylorus ligation model. CONCLUSION: Aliskiren exerted its protective effects on stomach tissue by decreasing inflammatory cytokines and oxidative stress as a result of inhibiting the RAAS, at a rate-limiting step, as well as its end product, angiotensin II. Aliskiren also significantly increased protective factors such as PGE2, but not affect aggressive factors such as gastric acidity.


Assuntos
Amidas/farmacologia , Amidas/uso terapêutico , Fumaratos/farmacologia , Fumaratos/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Animais , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Dinoprostona/metabolismo , Glutationa/metabolismo , Concentração de Íons de Hidrogênio , Indometacina , Cinética , Masculino , Malondialdeído/metabolismo , Modelos Biológicos , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Estômago/efeitos dos fármacos , Estômago/enzimologia , Estômago/patologia , Úlcera Gástrica/genética , Superóxido Dismutase/metabolismo
20.
Eurasian J Med ; 48(2): 135-41, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27551178

RESUMO

After a Turkish scientist took Nobel Prize due to his contributions to understand clock genes, melatonin, closely related to these genes, may begin to shine. Melatonin, a hormone secreted from the pineal gland at night, plays roles in regulating sleep-wake cycle, pubertal development and seasonal adaptation. Melatonin has antinociceptive, antidepressant, anxiolytic, antineophobic, locomotor activity-regulating, neuroprotective, anti-inflammatory, pain-modulating, blood pressure-reducing, retinal, vascular, anti-tumor and antioxidant effects. It is related with memory, ovarian physiology, and osteoblast differentiation. Pathologies associated with an increase or decrease in melatonin levels are summarized in the review. Melatonin affects by four mechanisms: 1) Binding to melatonin receptors in plasma membrane, 2) Binding to intracellular proteins such as calmoduline, 3) Binding to Orphan nuclear receptors, and 4) Antioxidant effect. Receptors associated with melatonin are as follows: 1) Melatonin receptor type 1a: MT1 (on cell membrane), 2) Melatonin receptor type 1b: MT2 (on cell membrane), 3) Melatonin receptor type 1c (found in fish, amphibians and birds), 4) Quinone reductase 2 enzyme (MT3 receptor, a detoxification enzyme), 5) RZR/RORα: Retinoid-related Orphan nuclear hormone receptor (with this receptor, melatonin binds to the transcription factors in nucleus), and 6) GPR50: X-linked Melatonin-related Orphan receptor (it is effective in binding of melatonin to MT1). Melatonin agonists such as ramelteon, agomelatine, circadin, TIK-301 and tasimelteon are introduced and side effects will be discussed. In conclusion, melatonin and related drugs is a new and promising era for medicine. Melatonin receptors and melatonin drugs will take attention with greater interest day by day in the future.

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