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1.
Arq. bras. med. vet. zootec. (Online) ; 73(6): 1334-1345, Nov.-Dec. 2021. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1355678

ABSTRACT

The present work evaluated the immunomodulatory effect of thalidomide (Thal) at different doses on tumor-associated macrophages (TAMs) using a mouse model of human breast cancer. Mice were inoculated with 4T1 cells in the left flank and treated with Thal once a day at concentrations of 50, 100, and 150mg/kg body weight from the 5th day until the 28th day of tumor inoculation. The tumors were sized, proliferation index and TAMs count were evaluated in primary tumors and metastatic lungs. In addition, the metastasis rate was evaluated in the lungs. Thal at 150mg/kg significantly decreased tumor growth, proliferation index, and TAMs infiltration in primary tumors. Conversely, a higher number of TAMs and lower proliferation index were observed in metastatic lungs in mice treated with 150mg/kg of Thal. Furthermore, Thal at 150mg/kg significantly decreased the metastatic nodules in the lungs. Our findings demonstrated that Thal treatment considerably decreased the primary tumor and lung metastasis in mice associated with different TAM infiltration effects in these sites.(AU)


No presente trabalho, foi avaliado o efeito imunomodulador de diferentes doses de talidomida em macrófagos associados ao tumor (TAMs), em um modelo murino de câncer de mama. Camundongos foram inoculados com células 4T1, na região do flanco esquerdo, e tratados com talidomida, uma vez ao dia, nas doses de 50, 100 e 150mg/k, por massa corporal, do quinto dia ao 28º dia de inoculação tumoral. Os tumores foram medidos, o índice de proliferação celular e a contagem de TAMs foram avaliados nos tumores primários e nos pulmões com metástases. Além disso, a taxa de metástases pulmonares também foi avaliada. A talidomida na dose de 150mg/kg diminuiu significativamente o crescimento tumoral, o índice de proliferação celular e a infiltração de TAMs nos tumores primários. Por outro lado, maior número de TAMs e menor índice de proliferação celular foram observados nos pulmões metastáticos, em camundongos tratados com 150mg/kg de talidomida. Ademais, a talidomida na dose de 150mg/kg diminuiu significativamente os nódulos metastáticos nos pulmões. Os resultados demonstraram que o tratamento com talidomida diminuiu o crescimento tumoral e as metástases pulmonares em camundongos, associado com diferentes efeitos na infiltração de TAMs nesses locais.(AU)


Subject(s)
Animals , Mice , Thalidomide/analysis , Mammary Neoplasms, Animal/drug therapy , Macrophages/drug effects , Immunomodulation , Neoplasm Metastasis
2.
Article in Chinese | WPRIM | ID: wpr-879929

ABSTRACT

OBJECTIVE@#To investigate the effects of astragaloside Ⅳ (AS-Ⅳ) on microglia/macrophage M1/M2 polarization and inflammatory response after cerebral ischemia in rats.@*METHODS@#Forty eight male SD rats were randomly divided into sham operation control group, model control group and AS-Ⅳ group with 16 rats in each. Focal cerebral ischemia model was induced by occlusion of the right middle cerebral artery (MCAO) using the intraluminal filament. After ischemia induced, the rats in AS-Ⅳ group were intraperitoneally injected with 40 mg/kg AS-Ⅳ once a day for 3 days. The neurological functions were evaluated by the modified neurological severity score (mNSS) and the corner test on d1 and d3 after modelling. The infarct volume was measured by 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining on d3 after ischemia. The expression of M1 microglia/macrophage markers CD86, inducible nitric oxide synthase (iNOS) and pro-inflammatory factors TNF-α, IL-1β, IL-6, M2 microglia/macrophages markers CD206, arginase-1 (Arg-1), chitinase-like protein (YM1/2) and anti-inflammatory factors interleukin-10 (IL-10) and transforming growth factor beta (TGF-β) was detected by real-time RT-PCR. The expression of CD16/32/Iba1 and CD206/Iba1 was determined by double labeling immunefluorescence method in the peripheral area of cerebral ischemia.@*RESULTS@#Compared with model control group, AS-Ⅳ treatment improved neurological function recovery and reduced infarct volume after ischemia (@*CONCLUSIONS@#The findings suggest that AS-Ⅳ ameliorates brain injury after cerebral ischemia in rats, which may be related to inhibiting inflammation through promoting the polarization of the microglia/macrophage from M1 to M2 phenotype in the ischemic brain.


Subject(s)
Animals , Anti-Inflammatory Agents/therapeutic use , Brain Ischemia/drug therapy , Cell Polarity/drug effects , Inflammation/drug therapy , Macrophages/drug effects , Male , Microglia/drug effects , Random Allocation , Rats , Rats, Sprague-Dawley , Saponins/therapeutic use , Triterpenes/therapeutic use
3.
J. appl. oral sci ; 28: e20190519, 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1101254

ABSTRACT

Abstract Natural products have emerged as a rich source of bioactive compounds for adjunctive treatments of many infectious and inflammatory conditions, including periodontitis. Among the monoterpenes with significant biological properties, there is the perillyl alcohol (POH), which can be found in several essential oils and has shown immunomodulatory properties in recent studies, which may be interesting in the treatment of non-neoplastic inflammatory disorders. Objective To determine the antibacterial and immune modulatory activities of the POH. Methodology The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the POH for two significant Gram-negative periodontal pathogens were determined by macrodilution and subculture, respectively. Cell proliferation and cytotoxicity in RAW 264.7 macrophages were determined by Trypan Blue and mitochondrial enzymatic activity assay. The modulation of reactive oxygen species (ROS) was analyzed by flow cytometry and expression of TNF and arginase-1 by real-time PCR. Results The POH was effective against P. gingivalis (ATCC 33277) and F. nucleatum (ATCC 25586) with MIC= MBC=1600 μM. No cytotoxicity up to 100 µM was observed on macrophages. The cell proliferation was inhibited from 48 hours at 100 μM (p<0.05) and 250 μM (p<0.01). The POH increased ROS production at both 10 μM and 100 μM (p<0.05) in unstimulated cells. The PMA-induced ROS production was not affected by POH, whereas 100 μM significantly reduced lipopolysaccharide-induced (LPS-induced) ROS. The expression of TNF was not affected by POH in unstimulated cells or in cells polarized to M1 phenotype, whereas both concentrations of POH reduced (p<0.05) the expression of arginase-1 in M2-polarized macrophages. Conclusion The POH has antibacterial activity against periodontal pathogens and reduced proliferation of murine macrophages without significant cytotoxicity at concentrations up to 100 μM. In addition, the POH reduced the LPS-induced ROS and the expression of arginase-1 in M2-polarized macrophages.


Subject(s)
Animals , Mice , Fusobacterium nucleatum/drug effects , Reactive Oxygen Species/analysis , Porphyromonas/drug effects , Monoterpenes/pharmacology , Macrophages/drug effects , Anti-Bacterial Agents/pharmacology , Arginase/analysis , Time Factors , Biological Products/pharmacology , Microbial Sensitivity Tests , Gene Expression , Lipopolysaccharides/pharmacology , Reproducibility of Results , Tumor Necrosis Factor-alpha/analysis , Fusobacterium nucleatum/growth & development , Reactive Oxygen Species/metabolism , Porphyromonas/growth & development , Cell Proliferation/drug effects , Real-Time Polymerase Chain Reaction , Flow Cytometry , RAW 264.7 Cells , Macrophages/metabolism
4.
Int. j. morphol ; 37(4): 1527-1533, Dec. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1040165

ABSTRACT

En órganos dañados, el ácido láctico (AL) modifica la respuesta inmune innata e inflamatoria, induciendo una menor expresión de citoquinas pro-inflamatorias, que provocan, la modulación del reclutamiento de células inmunes. El daño por compresión del nervio isquiático (NI) desencadena una respuesta inflamatoria y un aumento exponencial del infiltrado inflamatorio de células inmunes, produciendo la destrucción de axones y pérdida funcional del nervio. El objetivo de este estudio es evaluar el efecto agudo de la inyección de AL, sobre la proporción de células inmunes en la fase inflamatoria temprana, en el sitio de lesión del NI post compresión. Para ello, se utilizaron 15 ratas machos Sprague Dawley adultas, en tres grupos de compresión nerviosa. Un grupo control, un grupo control negativo con placebo (100 µL PBS) y un grupo experimental con inyección de 100 µL de AL [20mM]. Al tercer día los NI se analizaron histológicamente y se estableció la proporción de células inmunes en el sitio de lesión. Los resultados muestran que la inyección intraneural de AL provoca una disminución en el porcentaje de linfocitos y un aumento en el porcentaje de macrófagos. Este es el primer trabajo de inyección intraneural de AL y demuestra el efecto modulador del AL sobre las células inmunes en el sistema nervioso periférico.


In damaged organs, lactic acid (LA) modifies the innate and inflammatory immune response, inducing a lower expression of pro-inflammatory cytokines, which provoke the modulation of immune cell recruitment. Damage by compression of the sciatic nerve (SN) triggers an inflammatory response and an exponential increase in the inflammatory infiltrate of immune cells, producing the destruction of axons and functional loss of the nerve. The objective of this study is to evaluate the acute effect of the injection of LA, on the proportion of immune cells in the early inflammatory phase, in the site of SN post-compression injury. For this, 15 adult Sprague Dawley rats were used in three groups of nervous compression. A control group, a negative control group with placebo (100 mL PBS) and an experimental group with injection of 100 mL of LA [20mM]. On the third day, the SNs were histologically analyzed and the proportion of immune cells at the injury site was established. The results show that the intraneural injection of LA causes a decrease in the percentage of lymphocytes and an increase in the percentage of macrophages. This is the first work of intraneural injection of LA and demonstrates the modulating effect of LA on immune cells in the peripheral nervous system.


Subject(s)
Animals , Male , Rats , Sciatic Nerve/drug effects , Sciatic Nerve/immunology , Lactic Acid/pharmacology , Nerve Compression Syndromes/pathology , Sciatic Nerve/pathology , Lymphocytes/drug effects , Cytokines/immunology , Cytokines/metabolism , Rats, Sprague-Dawley , Lactic Acid/administration & dosage , Inflammation/immunology , Macrophages/drug effects
5.
Mem. Inst. Oswaldo Cruz ; 112(8): 561-568, Aug. 2017. graf
Article in English | LILACS | ID: biblio-894865

ABSTRACT

BACKGROUND Visceral leishmaniasis (VL) caused by Leishmania infantum is characterised by the loss of the ability of the host to generate an effective immune response. Chemokines have a direct involvement in the pathogenesis of leishmaniasis, causing a rapid change in the expression of these molecules during infection by Leishmania. OBJECTIVES Herein, it was investigated the role of CXCL10 in controlling infection by L. infantum. METHODS RAW 264.7 macrophages were infected with L. infantum in vitro and treated or not with CXCL10 (25, 50 and 100 ng/mL). Parasite load, as well as nitric oxide (NO), IL-4 and IL-10 production were assessed at 24 and 48 h after infection. In vivo, BALB/c mice were infected and treated or not with CXCL10 (5 μg/kg) at one, three and seven days of infection. Parasite load, IFN-g, IL-4, TGF-β and IL-10 were evaluated one, seven and 23 days post treatment. FINDINGS In vitro, CXCL10 reduced parasitic load, not dependent on NO, and inhibited IL-10 and IL-4 secretion. In vivo, CXCL10 was able to reduce the parasite load in both liver and spleen, four weeks after infection, representing a higher decrease in the number of parasites in these organs, also induced IFN-γ at day 23 after treatment, correlating with the decrease in parasite load, and reduced IL-10 and TGF-β. MAIN CONCLUSIONS This study suggests a partial protective role of CXCL10 against L. infantum, mediated by IFN-g, not dependent on NO, and with suppression of IL-10 and TGF-β. These data may provide information for the development of new approaches for future therapeutic interventions for VL.


Subject(s)
Animals , Male , Mice , Organ Size/physiology , Interleukin-4/biosynthesis , Interleukin-10/biosynthesis , Leishmania infantum , Chemokine CXCL10/therapeutic use , Leishmaniasis, Visceral/immunology , Leishmaniasis, Visceral/parasitology , Leishmaniasis, Visceral/drug therapy , Liver/pathology , Macrophages/drug effects , Cytokines/immunology , Interferon-gamma/analysis , Mice, Inbred BALB C
6.
An. acad. bras. ciênc ; 89(1,supl): 661-674, May. 2017. graf
Article in English | LILACS | ID: biblio-886670

ABSTRACT

ABSTRACT Mori folium, the leaf of Morus alba L. (Moraceae), has been traditionally used for various medicinal purposes from ancient times to the present. In this study, we examined the effects of water extract of Mori folium (WEMF) on the production of inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages. Our data indicated that WEMF significantly suppressed the secretion of NO and PGE2 in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects were accompanied by a marked reduction in their regulatory gene expression at the transcription level. WEMF attenuated LPS-induced intracellular ROS production in RAW 264.7 macrophages. It inhibited the nuclear translocation of the nuclear factor-kappa B p65 subunit and the activation of mitogen-activated protein kinases in LPS-treated RAW 264.7 macrophages. Furthermore, WEMF reduced LPS-induced NO production and ROS accumulation in zebrafish. Although more efforts are needed to fully understand the critical role of WEMF in the inhibition of inflammation, the findings of the present study may provide insights into the approaches for Mori folium as a potential therapeutic agent for inflammatory and antioxidant disorders.


Subject(s)
Animals , Rats , Zebrafish , Plant Extracts/pharmacology , Reactive Oxygen Species/antagonists & inhibitors , Inflammation Mediators/metabolism , Morus/chemistry , Macrophages/drug effects , Prostaglandins E/metabolism , Gene Expression , Genes, Regulator , Lipopolysaccharides , Inflammation Mediators/antagonists & inhibitors , RAW 264.7 Cells , Macrophages/metabolism , Nitric Oxide/metabolism
7.
Braz. j. infect. dis ; 21(1): 42-50, Jan.-Feb. 2017. tab, graf
Article in English | LILACS | ID: biblio-839183

ABSTRACT

Abstract Objectives: Three decades after HIV recognition and its association with AIDS development, many advances have emerged – especially related to prevention and treatment. Undoubtedly, the development of Highly Active Antiretroviral Therapy (HAART) dramatically changed the future of the syndrome that we know today. In the present study, we evaluate the impact of Highly Active Antiretroviral Therapy on macrophage function and its relevance to HIV pathogenesis. Methods: PBMCs were isolated from blood samples and monocytes (CD14+ cells) were purified. Monocyte-Derived Macrophages (MDMs) were activated on classical (MGM-CSF+IFN-γ) or alternative (MIL-4+IL13) patterns using human recombinant cytokines for six days. After this period, Monocyte-Derived Macrophages were stimulated with TLR2/Dectin-1 or TLR4 agonists and we evaluated the influence of HIV-1 infection and Highly Active Antiretroviral Therapy on the release of cytokines/chemokines by macrophages. Results: The data were obtained using Monocyte-Derived Macrophages derived from HIV naïve or from patients on regular Highly Active Antiretroviral Therapy. Classically Monocyte-Derived Macrophages obtained from HIV-1 infected patients on Highly Active Antiretroviral Therapy released higher levels of IL-6 and IL-12 even without PAMPs stimuli when compared to control group. On the other hand, alternative Monocyte-Derived Macrophages derived from HIV-1 infected patients on Highly Active Antiretroviral Therapy released lower levels of IL-6, IL-10, TNF-α, IP-10 and RANTES after LPS stimuli when compared to control group. Furthermore, healthy individuals have a complex network of cytokines/chemokines released by Monocyte-Derived Macrophages after PAMP stimuli, which was deeply affected in MDMs obtained from naïve HIV-1 infected patients and only partially restored in MDMs derived from HIV-1 infected patients even on regular Highly Active Antiretroviral Therapy. Conclusion: Our therapy protocols were not effective in restoring the functional alterations induced by HIV, especially those found on macrophages. These findings indicate that we still need to develop new approaches and improve the current therapy protocols, focusing on the reestablishment of cellular functions and prevention/treatment of opportunistic infections.


Subject(s)
Humans , Adult , HIV Infections/drug therapy , HIV-1/drug effects , Antiretroviral Therapy, Highly Active , Macrophages/drug effects , CD4-Positive T-Lymphocytes/drug effects , Case-Control Studies , HIV Infections/blood , Acute Disease , Chronic Disease , Interleukins/metabolism , Tumor Necrosis Factor-alpha/metabolism , Treatment Outcome , CD4-CD8 Ratio , Statistics, Nonparametric , CD8-Positive T-Lymphocytes/drug effects , Chemokine CCL5/metabolism , Lipopolysaccharide Receptors/drug effects , Viral Load/drug effects , Chemokine CXCL10/metabolism
8.
Pakistan Journal of Pharmaceutical Sciences. 2017; 30 (1): 43-48
in English | IMEMR | ID: emr-185738

ABSTRACT

In this study we investigated the anti-inflammatory effects and mechanisms of Hizikia fusiformis [HF] extracts in lipopolysaccharide [LPS]-induced RAW 264.7 cells. We extracted HF using solvent and sub-critical water techniques. In results, HF extracts inhibited nitric oxide [NO] production in cell-free and LPS-stimulated RAW 264.7 cells. HF210 [extract prepared with sub critical water at 210[degree]C] was most effective. The HF210 extract dose-dependently inhibited inducible nitric oxide synthase expression [iNOS] and nuclear factor kappa [NF-kB] p65 translocation from cytosol to the nucleus. Furthermore, HF210 extract dose-dependently inhibited the phosphorylation of p38 mitogen-activated protein kinase [p38 MAPK], Jun N-terminal kinase [JNK], and signal transducers and activators of transcription [STAT]-1in LPS-induced RAW 264.7 cells. Thus, our results suggest that anti-inflammatory effects of HF210 extract showed a noticeable distinction by regulation of multiple signaling pathways in LPS-induced RAW 264.7 cells


Subject(s)
Phaeophyta , Plant Extracts , NF-kappa B/drug effects , Macrophages/drug effects , RAW 264.7 Cells/drug effects , Signal Transduction , Lipopolysaccharides/pharmacology
9.
Acta cir. bras ; 31(2): 119-125, Feb. 2016. graf
Article in English | LILACS | ID: lil-775562

ABSTRACT

PURPOSE: To detect whether chitin and sepia ink sponge (CS) can promote wound healing and elevate impact of CS on phagocytosis ability of macrophages. METHODS: Forty-eight rats were assigned to four groups: Normal group (Normal), negative control group (Con), chitin and sepia ink sponge group (CS) and positive control Surgicel Gauze(r) group (SG). Deep second-degree burn model was created in rats. Wound area was recorded by digital imaging and determined using Image J software. Samples were collected and kept at -80oC on 3d, 7d, 14d and 21d for cytokines detecting. Transforming growth factor (TGF)-β1, interleukin (IL)-6, matrix metalloproteinase (MMP)-1, hydroxyproline (Hyp) and macrophage activity reflected by tumor necrosis factor (TNF)-α were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Comparing to Con and SG, scabs in CS group fell off and basically healed on 21 day. TGF-β1, IL-6, MMP-1 and Hyp were significantly increased by CS and SG comparing to Con (p < 0.05), CS had more apparently adjustment on TGF-β1 and MMP-1 compared to SG; results in vitro indicated CS significantly promoted phagocytosis ability of macrophages reflected in TNF-α (p < 0.05). CONCLUSION: CS improved wound healing through exerting significant influences on secretion of kinds of cytokines and activating macrophages.


Subject(s)
Animals , Male , Wound Healing/drug effects , Burns, Chemical/drug therapy , Chitin/pharmacology , Sepia , Macrophages/drug effects , Phagocytosis/drug effects , Random Allocation , Chitin/therapeutic use , Cytokines/drug effects , Cytokines/metabolism , Rats, Wistar , Matrix Metalloproteinase 1/drug effects , Disease Models, Animal , Hydroxyproline/metabolism , Ink , Macrophages/metabolism
10.
Yonsei Medical Journal ; : 283-290, 2016.
Article in English | WPRIM | ID: wpr-147364

ABSTRACT

Macrophages (Mphi) play a pivotal role in the protection system by recognizing and eliminating invading pathogenic bacteria. Phagocytosis and the killing of invading bacteria are major effector functions of Mphi. Although the phagocytic and bactericidal activities of Mphi have been analyzed via several methods using a light microscope, a fluorescence microscope, or a fluorescence-activated cell sorter, expensive materials and equipment are usually required, and the methods are rather complicated. Moreover, it is impossible to determine both the phagocytic and bactericidal activities of Mphi simultaneously using these methods. In this review, we describe a simple, reproducible, inexpensive, yet old-fashioned method (antibiotic protection assay) for determining the phagocytic and bactericidal activities of Mphi.


Subject(s)
Anti-Bacterial Agents/pharmacology , Gentamicins/pharmacology , Macrophages/drug effects , Phagocytosis/drug effects
11.
Braz. j. med. biol. res ; 49(12): e5826, 2016. graf
Article in English | LILACS | ID: biblio-828173

ABSTRACT

Glucagon-like peptide 1 (GLP-1), a kind of gut hormone, is used in the treatment of type 2 diabetes (T2D). Emerging evidence indicates that GLP-1 has anti-inflammatory activity. Chronic inflammation in the adipose tissue of obese individuals is a cause of insulin resistance and T2D. We hypothesized that GLP-1 analogue therapy in patients with T2D could suppress the inflammatory response of macrophages, and therefore inhibit insulin resistance. Our results showed that GLP-1 agonist (exendin-4) not only attenuated macrophage infiltration, but also inhibited the macrophage secretion of inflammatory cytokines including TNF-β, IL-6, and IL-1β. Furthermore, we observed that lipopolysaccharide (LPS)-induced macrophage conditioned media could impair insulin-stimulated glucose uptake. This effect was compensated by treatment with the conditioned media from macrophages treated with the combination of LPS and exendin-4. It was also observed that exendin-4 directly inhibited the activation of NF-κB in macrophages. In conclusion, our results indicated that GLP-1 improved inflammatory macrophage-derived insulin resistance by inhibiting NF-κB pathway and secretion of inflammatory cytokines in macrophages. Furthermore, our observations suggested that the anti-inflammatory effect of GLP-1 on macrophages can contribute to GLP-1 analogue therapy of T2D.


Subject(s)
Humans , Animals , Mice , Glucagon-Like Peptide 1/pharmacology , Inflammation Mediators/pharmacology , Inflammation/drug therapy , Insulin Resistance , Macrophages/drug effects , Peptides/pharmacology , Venoms/pharmacology , Adipose Tissue/metabolism , Cell Migration Assays , Inflammation/metabolism , Macrophages/metabolism
12.
Mem. Inst. Oswaldo Cruz ; 110(6): 809-813, Sept. 2015. graf
Article in English | LILACS | ID: lil-763096

ABSTRACT

Tuberculosis has great public health impact with high rates of mortality and the only prophylactic measure for it is the Mycobacterium bovisbacillus Calmette-Guérin (BCG) vaccine. The present study evaluated the release of cytokines [interleukin (IL)-1, tumour necrosis factor and IL-6] and chemokines [macrophage inflammatory protein (MIP)-1α and MIP-1β] by THP-1 derived macrophages infected with BCG vaccine obtained by growing mycobacteria in Viscondessa de Moraes Institute medium medium (oral) or Sauton medium (intradermic) to compare the effects of live and heat-killed (HK) mycobacteria. Because BCG has been reported to lose viability during the lyophilisation process and during storage, we examined whether exposing BCG to different temperatures also triggers differences in the expression of some important cytokines and chemokines of the immune response. Interestingly, we observed that HK mycobacteria stimulated cytokine and chemokine production in a different pattern from that observed with live mycobacteria.


Subject(s)
Humans , Chemokines , Macrophages/immunology , Microbial Viability/immunology , Mycobacterium bovis/classification , Cell Line , Cytokines , Interleukin-1 , Macrophages/classification , Macrophages/drug effects , Mycobacterium bovis/immunology , Tumor Necrosis Factor-alpha , Vaccines, Inactivated
13.
Einstein (Säo Paulo) ; 13(2): 196-201, Apr-Jun/2015. tab, graf
Article in English | LILACS | ID: lil-751420

ABSTRACT

ABSTRACT Objective: To evaluate the impact of traditional check-up appointment on the progression of the cardiovascular risk throughout time. Methods: This retrospective cohort study included 11,126 medical records of asymptomatic executives who were evaluated between January, 2005 and October, 2008. Variables included participants’ demographics characteristics, smoking habit, history of cardiovascular diseases, diabetes, dyslipidemia, total cholesterol, HDL, triglycerides, glucose, c-reactive protein, waist circumference, hepatic steatosis, Framingham score, metabolic syndrome, level of physical activity, stress, alcohol consumption, and body mass index. Results: A total of 3,150 patients was included in the final analysis. A worsening was observed in all risk factors, excepting in smoking habit, incidence of myocardial infarction or stroke and in the number of individuals classified as medium or high risk for cardiovascular events. In addition, a decrease in stress level and alcohol consumption was also seen. Conclusion: The adoption of consistent health policies by companies is imperative in order to reduce the risk factors and the future costs associated with illness and absenteeism. .


RESUMO Objetivo: Avaliar o impacto do modelo tradicional de check-up na progressão do risco cardiovascular ao longo do tempo. Métodos: Estudo coorte-retrospectivo com análise de 11.126 prontuários de executivos assintomáticos, atendidos entre janeiro de 2005 e outubro de 2008. Foram observados dados demográficos, tabagismo, doenças cardiovasculares, diabetes, dislipidemia prévios, valores de colesterol total e frações, triglicérides, glicemia, proteína C-reativa, circunferência de cintura, esteatose hepática, escore de Framingham, síndrome metabólica, nível de atividade física, estresse, consumo de álcool e índice de massa corporal. Resultados: Foram incluídos 3.150 pacientes. Houve piora de todos fatores de risco, com exceção do tabagismo, do aumento na incidência de doenças cardiovasculares e da população com risco médio ou alto para eventos cardiovasculares. Houve ainda redução na prevalência de pouco ativos, estresse e consumo de álcool. Conclusão: É prioritária a adoção de políticas de saúde por parte das empresas, para a melhora da condição de saúde e a redução dos custos advindos das doenças, além do absenteísmo a eles associados. .


Subject(s)
Female , Humans , Gene Expression Profiling/methods , Software , Antineoplastic Agents/pharmacology , Breast Neoplasms/genetics , Internet , Interleukins/pharmacology , Macrophages/drug effects , Macrophages/metabolism , User-Computer Interface
14.
Braz. j. med. biol. res ; 48(4): 286-291, 4/2015. tab, graf
Article in English | LILACS | ID: lil-744366

ABSTRACT

This study aimed to determine the effects of different concentrations of propofol (2,6-diisopropylphenol) on lipopolysaccharide (LPS)-induced expression and release of high-mobility group box 1 protein (HMGB1) in mouse macrophages. Mouse macrophage cell line RAW264.7 cells were randomly divided into 5 treatment groups. Expression levels of HMGB1 mRNA were detected using RT-PCR, and cell culture supernatant HMGB1 protein levels were detected using enzyme-linked immunosorbent assay (ELISA). Translocation of HMGB1 from the nucleus to the cytoplasm in macrophages was observed by Western blotting and activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the nucleus was detected using ELISA. HMGB1 mRNA expression levels increased significantly in the cell culture supernatant and in cells after 24 h of stimulating RAW264.7 cells with LPS (500 ng/mL). However, HMGB1 mRNA expression levels in the P2 and P3 groups, which received 500 ng/mL LPS with 25 or 50 μmol/mL propofol, respectively, were significantly lower than those in the group receiving LPS stimulation (P<0.05). After stimulation by LPS, HMGB1 protein levels were reduced significantly in the nucleus but were increased in the cytoplasm (P<0.05). Simultaneously, the activity of NF-κB was enhanced significantly (P<0.05). After propofol intervention, HMGB1 translocation from the nucleus to the cytoplasm and NF-κB activity were inhibited significantly (each P<0.05). Thus, propofol can inhibit the LPS-induced expression and release of HMGB1 by inhibiting HMGB1 translocation and NF-κB activity in RAW264.7 cells, suggesting propofol may be protective in patients with sepsis.


Subject(s)
Animals , Mice , Anesthetics, Intravenous/pharmacology , Cell Nucleus/drug effects , HMGB1 Protein/drug effects , Macrophages/drug effects , Propofol/pharmacology , RNA, Messenger/drug effects , Active Transport, Cell Nucleus , Anesthetics, Intravenous/administration & dosage , Blotting, Western , Cell Line , Cell Nucleus/metabolism , Enzyme-Linked Immunosorbent Assay , Gene Expression/drug effects , HMGB1 Protein/genetics , HMGB1 Protein/metabolism , Lipopolysaccharides , Macrophages/metabolism , NF-kappa B/drug effects , NF-kappa B/metabolism , Propofol/administration & dosage , Random Allocation , Real-Time Polymerase Chain Reaction , RNA, Messenger/metabolism
15.
Indian J Exp Biol ; 2015 Mar; 53(3): 158-163
Article in English | IMSEAR | ID: sea-158406

ABSTRACT

Chyawanprash is an ayurvedic formulation used in Indian traditional medicinal system for its beneficial effect on human health. We investigated the immunostimulatory effects of Chyawanprash (CHY) using in vitro assays evaluating the secretion of cytokines such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1beta (IL-1β) and Macrophage Inflammatory Protein-1-alpha (MIP-1-α) from murine bone marrow derived Dendritic Cells (DC) which play pivotal role in immunostimulation. The effects of CHY on phagocytosis in murine macrophages (RAW264.7) and Natural Killer (NK) cell activity were also investigated. At non-cytotoxic concentrations (20–500 µg/ml), CHY enhanced the secretion of all the three cytokines from DC. CHY also stimulated both, macrophage (RAW264.7) as well as NK cell activity, in vitro. In conclusion, the data substantiates the immunoprotective role of CHY at cellular level mediated by immunostimulation in key immune cells viz. dendritic Cells, macrophages and NK cells.


Subject(s)
Adjuvants, Immunologic/pharmacology , Animals , Cell Line , Cytokines/analysis , Cytotoxicity, Immunologic/drug effects , Dendritic Cells/drug effects , Drug Evaluation, Preclinical , In Vitro Techniques , Killer Cells, Natural/drug effects , Macrophages/drug effects , Male , Medicine, Ayurvedic , Mice , Mice, Inbred C57BL , Phagocytosis/drug effects , Plant Preparations/pharmacology , Specific Pathogen-Free Organisms , Spleen/cytology , Zymosan
16.
Arch. endocrinol. metab. (Online) ; 59(1): 47-53, 02/2015. tab, graf
Article in English | LILACS | ID: lil-746451

ABSTRACT

Objective The diabetic state induced by streptozotocin injection is known to impair oligodendroglial remyelination in the rat brainstem following intracisternal injection with the gliotoxic agent ethidium bromide (EB). In such experimental model, propentofylline (PPF) recently showed to improve myelin repair, probably due to its neuroprotective, antiinflammatory and antioxidant effects. The aim of this study was to evaluate the effect of PPF administration in diabetic rats submitted to the EB-demyelinating model. Materials and methods Adult male rats, diabetic or not, received a single injection of 10 microlitres of 0.1% EB solution into the cisterna pontis. For induction of diabetes mellitus the streptozotocin-diabetogenic model was used (50 mg/kg, intraperitoneal route – IP). Some diabetic rats were treated with PPF (12.5 mg/kg/day, IP route) during the experimental period. The animals were anesthetized and perfused from 7 to 31 days after EB injection and brainstem sections were collected for analysis of the lesions by light and transmission electron microscopy. Results Diabetic rats injected with EB showed larger amounts of myelin-derived membranes in the central areas of the lesions and considerable delay in the remyelinating process played by surviving oligodendrocytes and invading Schwann cells after the 15th day. On the other hand, diabetic rats that received PPF presented lesions similar to those of non-diabetic animals, with rapid remyelination at the edges of the lesion site and fast clearance of myelin debris from the central area. Conclusion The administration of PPF apparently reversed the impairment in remyelination induced by the diabetic state. Arch Endocrinol Metab. 2015;59(1):47-53 .


Subject(s)
Animals , Male , Astrocytes/drug effects , Demyelinating Diseases/drug therapy , Diabetes Mellitus, Experimental/drug therapy , Myelin Sheath/physiology , Neuroprotective Agents/pharmacology , Xanthines/pharmacology , Disease Models, Animal , Demyelinating Diseases/pathology , Diabetes Mellitus, Experimental/chemically induced , Ethidium/toxicity , Microscopy, Electron, Transmission , Macrophages/drug effects , Mesencephalon/pathology , Nerve Regeneration/drug effects , Neuroprotective Agents/administration & dosage , Pons/pathology , Rats, Wistar , Streptozocin , Schwann Cells/drug effects , Xanthines/administration & dosage
17.
Mem. Inst. Oswaldo Cruz ; 110(1): 56-64, 03/02/2015. tab, graf
Article in English | LILACS | ID: lil-741619

ABSTRACT

Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV) RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+), HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+), acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-). All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection.


Subject(s)
Animals , Humans , Mice , Annexin A1/pharmacology , Macrophages/drug effects , Macrophages/immunology , Neutrophils/cytology , Neutrophils/immunology , Apoptosis , Actins/metabolism , Annexin A1/deficiency , Annexin A1/genetics , Annexin A1/immunology , Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic AMP/metabolism , Dexamethasone/pharmacology , In Vitro Techniques , /biosynthesis , Mice, Knockout , Macrophages/metabolism , Peptides , Phagocytosis/drug effects , Transforming Growth Factor beta/biosynthesis
18.
Rev. méd. Chile ; 143(1): 120-123, ene. 2015. ilus
Article in Spanish | LILACS | ID: lil-742561

ABSTRACT

We report a 37 years old male with a dermatomyositis treated with oral cyclophosphamide. He was admitted to the hospital due to a zone of skin necrosis with purulent exudate, located in the second left toe. A complete blood count showed a leukocyte count of 2,600 cells/mm³. A Chest CAT scan showed a pneumomediastinum with emphysema of adjacent soft tissue. Cyclophosphamide was discontinued and leukocyte count improved. The affected toe was amputated and a chest CAT scan showed a partial resolution of the pneumomediastinum. We discuss and review the pathogenesis, clinical presentation and management of pneumomediastinum and cutaneous necrosis in association with dermatomyositis.


Subject(s)
Animals , Female , Rats , Benzoxazines/therapeutic use , Cannabinoids/agonists , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/pathology , Morpholines/therapeutic use , Naphthalenes/therapeutic use , Neurons/drug effects , Oligodendroglia/drug effects , Analysis of Variance , Amyloid beta-Protein Precursor/metabolism , Caspase 9/metabolism , /metabolism , Cell Count/methods , Central Nervous System/pathology , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Encephalomyelitis, Autoimmune, Experimental/complications , Macrophages/drug effects , Neurologic Examination , Nerve Degeneration/etiology , Nerve Degeneration/prevention & control , Poly(ADP-ribose) Polymerases/metabolism , Spinal Cord/drug effects , Spinal Cord/pathology , T-Lymphocytes/drug effects , Time Factors
19.
Article in English | WPRIM | ID: wpr-130576

ABSTRACT

Plants used for traditional medicine contain a wide range of substances that can be used to treat various diseases such as infectious diseases. The present study was designed to evaluate the antileishmanial effects of the essential oil and methanolic extract of Myrtus communis against Leishmania tropica on an in vitro model. Antileishmanial effects of essential oil and methanolic extract of M. communis on promastigote forms and their cytotoxic activities against J774 cells were evaluated using MTT assay for 72 hr. In addition, their leishmanicidal activity against amastigote forms was determined in a macrophage model, for 72 hr. Findings showed that the main components of essential oil were alpha-pinene (24.7%), 1,8-cineole (19.6%), and linalool (12.6%). Findings demonstrated that M. communis, particularly its essential oil, significantly (P<0.05) inhibited the growth rate of promastigote and amastigote forms of L. tropica based on a dose-dependent response. The IC50 values for essential oil and methanolic extract was 8.4 and 28.9 mug/ml against promastigotes, respectively. These values were 11.6 and 40.8 mug/ml against amastigote forms, respectively. Glucantime as control drug also revealed IC50 values of 88.3 and 44.6 mug/ml for promastigotes and amastigotes of L. tropica, respectively. The in vitro assay demonstrated no significant cytotoxicity in J774 cells. However, essential oil indicated a more cytotoxic effect as compared with the methanolic extract of M. communis. The findings of the present study demonstrated that M. communis might be a natural source for production of a new leishmanicidal agent.


Subject(s)
Animals , Antiprotozoal Agents/isolation & purification , Cell Line , Cell Survival/drug effects , Cyclohexanols/isolation & purification , Inhibitory Concentration 50 , Leishmania tropica/drug effects , Macrophages/drug effects , Mice , Monoterpenes/isolation & purification , Myrtus/chemistry , Oils, Volatile/isolation & purification , Plant Extracts/isolation & purification
20.
Article in English | WPRIM | ID: wpr-130569

ABSTRACT

Plants used for traditional medicine contain a wide range of substances that can be used to treat various diseases such as infectious diseases. The present study was designed to evaluate the antileishmanial effects of the essential oil and methanolic extract of Myrtus communis against Leishmania tropica on an in vitro model. Antileishmanial effects of essential oil and methanolic extract of M. communis on promastigote forms and their cytotoxic activities against J774 cells were evaluated using MTT assay for 72 hr. In addition, their leishmanicidal activity against amastigote forms was determined in a macrophage model, for 72 hr. Findings showed that the main components of essential oil were alpha-pinene (24.7%), 1,8-cineole (19.6%), and linalool (12.6%). Findings demonstrated that M. communis, particularly its essential oil, significantly (P<0.05) inhibited the growth rate of promastigote and amastigote forms of L. tropica based on a dose-dependent response. The IC50 values for essential oil and methanolic extract was 8.4 and 28.9 mug/ml against promastigotes, respectively. These values were 11.6 and 40.8 mug/ml against amastigote forms, respectively. Glucantime as control drug also revealed IC50 values of 88.3 and 44.6 mug/ml for promastigotes and amastigotes of L. tropica, respectively. The in vitro assay demonstrated no significant cytotoxicity in J774 cells. However, essential oil indicated a more cytotoxic effect as compared with the methanolic extract of M. communis. The findings of the present study demonstrated that M. communis might be a natural source for production of a new leishmanicidal agent.


Subject(s)
Animals , Antiprotozoal Agents/isolation & purification , Cell Line , Cell Survival/drug effects , Cyclohexanols/isolation & purification , Inhibitory Concentration 50 , Leishmania tropica/drug effects , Macrophages/drug effects , Mice , Monoterpenes/isolation & purification , Myrtus/chemistry , Oils, Volatile/isolation & purification , Plant Extracts/isolation & purification
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