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1.
An Acad Bras Cienc ; 92(4): e20191066, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33206785

RESUMO

Inflammatory dermatoses are prevalent worldwide, with impacts on the quality of life of patients and their families. The aim of this study was to determine the anti-inflammatory effects of Achyrocline satureioides oily extracts and nanocapsules on the skin using a mouse model of irritant contact dermatitis induced by croton oil, and a skin inflammation model induced by ultraviolet B (UVB) radiation. The mice were treated with 15 mg/ear oily extract (HG-OLAS) or nanocapsules (HG-NCAS) of A. satureioides incorporated into Carbopol® 940 hydrogels. We found that HG-OLAS and HG-NCAS formulations reduced ear edema in croton oil-induced lesions with maximum inhibitions of 54±7% and 74±3%, respectively. HG-OLAS and HG-NCAS formulations decreased ear edema induced by UVB radiation (0.5 J/cm2), with maximum inhibitions of 68±6% and 76±2% compared to the UVB radiation group, respectively. HG-OLAS and HG-NCAS modulated myeloperoxidase (MPO) activity after croton oil induction. Furthermore, croton oil and UVB radiation for 6 and 24 h, respectively, stimulated polymorphonuclear cells infiltration. The topical treatments reduced inflammatory processes, as shown by histological analysis. Together, the data suggest that topical application of A. satureioides oily extracts and nanocapsules produced antiedematogenic and anti-inflammatory effects. They constitute a compelling alternative for treatment of skin injuries.


Assuntos
Achyrocline , Dermatite de Contato , Nanocápsulas , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Dermatite de Contato/tratamento farmacológico , Edema/tratamento farmacológico , Humanos , Hidrogéis , Irritantes/uso terapêutico , Nanocápsulas/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Qualidade de Vida
2.
Int J Nanomedicine ; 15: 5181-5202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801685

RESUMO

Background: Combating infectious diseases caused by influenza virus is a major challenge due to its resistance to available drugs and vaccines, side effects, and cost of treatment. Nanomedicines are being developed to allow targeted delivery of drugs to attack specific cells or viruses. Materials and Methods: In this study, mesoporous silica nanoparticles (MSNs) functionalized with amino groups and loaded with natural prodrugs of shikimic acid (SH), quercetin (QR) or both were explored as a novel antiviral nanoformulations targeting the highly pathogenic avian influenza H5N1 virus. Also, the immunomodulatory effects were investigated in vitro tests and anti-inflammatory activity was determined in vivo using the acute carrageenan-induced paw edema rat model. Results: Prodrugs alone or the MSNs displayed weaker antiviral effects as evidenced by virus titers and plaque formation compared to nanoformulations. The MSNs-NH2-SH and MSNs-NH2-SH-QR2 nanoformulations displayed a strong virucidal by inactivating the H5N1 virus. They induced also strong immunomodulatory effects: they inhibited cytokines (TNF-α, IL-1ß) and nitric oxide production by approximately 50% for MSNs-NH2-SH-QR2 (containing both SH and QR). Remarkable anti-inflammatory effects were observed during in vivo tests in an acute carrageenan-induced rat model. Conclusion: Our preliminary findings show the potential of nanotechnology for the application of natural prodrug substances to produce a novel safe, effective, and affordable antiviral drug.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antivirais/farmacologia , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Nanopartículas/química , Pró-Fármacos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/imunologia , Antivirais/imunologia , Citocinas/metabolismo , Cães , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Edema/tratamento farmacológico , Edema/metabolismo , Fatores Imunológicos/imunologia , Fatores Imunológicos/farmacologia , Células Madin Darby de Rim Canino , Masculino , Camundongos , Quercetina/imunologia , Quercetina/farmacologia , Ratos , Ácido Chiquímico/imunologia , Ácido Chiquímico/farmacologia , Dióxido de Silício/química
3.
AAPS PharmSciTech ; 21(6): 211, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737606

RESUMO

Transdermal application of analgesics allows efficient and painless delivery of medication with minimum side effect. This study was designed with the aim to formulate and characterize dexibuprofen-capsaicin emulgel for transdermal drug delivery with improved anti-inflammatory and analgesic effects. The emulgel was prepared and evaluated for physical examination, stability, spreadability, rheological behavior, viscosity, drug content determination, FTIR analysis, and ex vivo studies. Anti-inflammatory (carrageenan-induced paw edema) and analgesic (hot plate latency test) effects were determined in Sprague-Dawley rats. The dexibuprofen-capsaicin emulgel showed good physical appearance and stability having average pH 5.5 to 6.0, conductivity 73-76 s/m, spreadability (12-)17 g cm/s, drug content 102.84% ± 0.53 (for capsaicin) and 94.09% ± 0.41 (for dexibuprofen), and FTIR compatibility. It was noted that 86.956% ± 1.46 (with 100 mg menthol), 76.687% ± 1.21 (75 mg menthol), and 65.543% ± 1.71 (without menthol) of capsaicin were released. Similarly 81.342% ± 1.21 (with 100 mg menthol), 72.321% ± 1.31 (75 mg menthol), and 52.462% ± 1.23 (without menthol) of dexibuprofen were released. The cumulative amount of capsaicin permeated through rabbit skin was 9.83 ± 0.037 µg/cm2 with 100 mg menthol (as permeation enhancer), 7.23 ± 0.037 µg/cm2 with 75 mg menthol, and 2.23 ± 0.061 µg/cm2 without menthol after 6.5 h. The permeation of dexibuprofen was 19.53 ± 0.054 µg/cm2, 13.87 ± 0.032 µg/cm2, and 3.83 ± 0.074 µg/cm2. Carrageenan-induced paw edema of rat was effectively inhibited by the optimized emulgel. Similarly it was observed that DCE5 shows higher analgesic activity compared with marketed diclofenac sodium emulgel (Dicloran®). The conclusion of this research study evidently indicated a promising synergistic potential of dexibuprofen-capsaicin emulgel as an alternative to the conventional topical dosage form.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/administração & dosagem , Capsaicina/química , Géis/química , Ibuprofeno/análogos & derivados , Administração Cutânea , Analgésicos/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Carragenina/farmacologia , Edema/tratamento farmacológico , Emulsões , Ibuprofeno/química , Masculino , Coelhos , Ratos , Ratos Sprague-Dawley , Pele/metabolismo , Absorção Cutânea/efeitos dos fármacos , Viscosidade
4.
PLoS One ; 15(8): e0232302, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822373

RESUMO

Sepsis is a life-threatening condition due to a dysregulated immunological response to infection. Apart from source control and broad-spectrum antibiotics, management is based on fluid resuscitation and vasoactive drugs. Fluid resuscitation implicates the risk of volume overload, which in turn is associated with longer stay in intensive care, prolonged use of mechanical ventilation and increased mortality. Antisecretory factor (AF), an endogenous protein, is detectable in most tissues and in plasma. The biologically active site of the protein is located in an 8-peptide sequence, contained in a synthetic 16-peptide fragment, named AF-16. The protein as well as the peptide AF-16 has multiple modulatory effects on abnormal fluid transport and edema formation/resolution as well as in a variety of inflammatory conditions. Apart from its' anti-secretory and anti-inflammatory characteristics, AF is an inhibitor of capillary leakage in intestine. It is not known whether the protein AF or the peptide AF-16 can ameliorate symptoms in sepsis. We hypothesized that AF-16 decreases the degree of hemodynamic instability, the need of fluid resuscitation, vasopressor dose and tissue edema in fecal peritonitis. To test the hypothesis, we induced peritonitis and sepsis by injecting autologous fecal solution into abdominal cavity of anesthetized pigs, and randomized (in a blind manner) the animals to intervention (AF-16, n = 8) or control (saline, n = 8) group. After the onset of hemodynamic instability (defined as mean arterial pressure < 60 mmHg maintained for > 5 minutes), intervention with AF-16 (20 mg/kg (50 mg/ml) in 0.9% saline) intravenously (only the vehicle in the control group) and a protocolized resuscitation was started. We recorded respiratory and hemodynamic parameters hourly for twenty hours or until the animal died and collected post mortem tissue samples at the end of the experiment. No differences between the groups were observed regarding hemodynamics, overall fluid balance, lung mechanics, gas exchange or histology. However, liver wet-to-dry ratio remained lower in AF-16 treated animals as compared to controls, 3.1 ± 0.4, (2.7-3.5, 95% CI, n = 8) vs 4.0 ± 0.6 (3.4-4.5, 95% CI, n = 8), p = 0.006, respectively. Bearing in mind the limited sample size, this experimental pilot study suggests that AF-16 may inhibit sepsis induced liver edema in peritonitis-sepsis.


Assuntos
Edema/tratamento farmacológico , Peptídeos/farmacologia , Peritonite/complicações , Sepse/complicações , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Edema/complicações , Edema/patologia , Edema/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Hemoglobinas/metabolismo , Interleucina-6/sangue , Lactatos/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Peptídeos/uso terapêutico , Projetos Piloto , Troca Gasosa Pulmonar/efeitos dos fármacos , Suínos , Fator de Necrose Tumoral alfa/sangue , Resistência Vascular/efeitos dos fármacos
5.
Wilderness Environ Med ; 31(3): 332-336, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32800447

RESUMO

We report a case of a 42-y-old female patient who sustained a sting to the neck from a Trachinus draco fish. She subsequently developed complications including arytenoid membrane edema secondary to either the local anesthetic agent administered to the wound or the dracotoxin itself. The patient was examined in the emergency department after the sting. Local anesthesia with lidocaine was administered to the areas of injury at another hospital before presenting to our hospital emergency department. The patient reported that her pain partially decreased but hoarseness developed and she had difficulty breathing after the local anesthetic was administered. Laryngeal examination by our hospital's otolaryngologist revealed edema of the patient's right arytenoid membrane without evidence of vocal cord swelling. Computed tomography of the neck revealed edema in the right arytenoid membrane on the side of the neck where the local anesthetic had been injected. The patient, who was given supplementary treatment, was discharged without any complications on the seventh day of hospitalization. The principle treatment for these types of stings includes immersion in hot water, analgesic therapy, and observation for signs of local and systemic envenomation. We recommend using caution when injecting local anesthetic agents in the neck because of underlying vital structures.


Assuntos
Analgésicos/efeitos adversos , Mordeduras e Picadas/patologia , Edema/tratamento farmacológico , Venenos de Peixe/efeitos adversos , Manejo da Dor , Prega Vocal/patologia , Adulto , Analgésicos/uso terapêutico , Animais , Mordeduras e Picadas/tratamento farmacológico , Edema/induzido quimicamente , Edema/diagnóstico , Feminino , Peixes , Humanos , Injeções Subcutâneas
6.
Oral Maxillofac Surg ; 24(4): 461-468, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32638173

RESUMO

OBJECTIVE: The aim of this study was to determine if the timing of administration of systemic enzyme therapy [SET] has any effect on its efficacy in controlling postoperative sequelae of third molar surgery. STUDY DESIGN: A double blinded prospective randomized control trial was planned. The sample included patients requiring impacted mandibular third molar surgical extraction. Patients were randomly allocated to four groups (50 patients per group). Group A included administration of SET 48 h prior to surgery; Group B, started on the day of surgery; Group C started immediately after surgery and control group D included NSAIDS started 3 h after surgery. The predictor variable was timing of administration of SET. The primary outcome variables were pain and swelling measured on 1st day, 5th day, and 7th day after surgery. FINDINGS: Groups A and D reported lower mean and median VAS scores and lesser swelling than groups C and D on postop day 1. On days 5 and 7, all four groups were comparable. On overall analysis, no statistically significant difference (p > 0.05) was evident. INTERPRETATION: The results of the study showed that the differences in swelling and pain with starting the SET 2 days before, on the day of surgery, or immediately after when compared with diclofenac was not statistically significant. TRIAL REGISTRATION: CTRI Registration Number CTRI/2018/03/012502.


Assuntos
Diclofenaco , Dente Impactado , Diclofenaco/uso terapêutico , Método Duplo-Cego , Edema/tratamento farmacológico , Terapia Enzimática , Humanos , Dente Serotino/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Peptídeo Hidrolases/uso terapêutico , Estudos Prospectivos , Extração Dentária , Dente Impactado/cirurgia
8.
BMC Infect Dis ; 20(1): 348, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414336

RESUMO

BACKGROUND: Besides the considerable role of blackflies to the transmission of many disease agents, these flies considered as annoying biting pests of wildlife, livestock, poultry, and humans. There are few literature reports of blackfly fever following Simulium spp. This study describes a case of blackfly fever and dermatitis following blackflies numerous bites in Iran. CASE PRESENTATION: The present report describes a 25-year-old man that was attacked by numerous flies while fishing and camping near Namrood river in Firuzkuh County, Tehran Province, Iran. Pruritic dermatitis with marked edema appeared mainly on the hands and legs and subsequently, the patient's condition worsened with swollen lymph nodes, joints aching, and 40 °C fever. The patient's clinical signs and symptoms were alleviated by injection of intramuscular Dexamethasone Phosphate (DEXADIC®) 8 mg/2 ml after 24 h. CONCLUSIONS: This study reported a human case with blackfly fever and dermatitis following numerous bites of Simulium kiritshenkoi, for the first time in Iran.


Assuntos
Dermatite/etiologia , Febre/etiologia , Mordeduras e Picadas de Insetos/complicações , Simuliidae , Adulto , Animais , Dermatite/tratamento farmacológico , Dexametasona/análogos & derivados , Dexametasona/uso terapêutico , Edema/tratamento farmacológico , Edema/etiologia , Feminino , Mãos , Humanos , Mordeduras e Picadas de Insetos/tratamento farmacológico , Irã (Geográfico) , Perna (Membro) , Masculino , Simuliidae/anatomia & histologia , Simuliidae/fisiologia
9.
Phytother Res ; 34(10): 2577-2585, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32314844

RESUMO

AIM: Chronic venous insufficiency (CVI) is common in adults. Some complications include skin changes, edema, heavy legs, muscle cramps, pain, and varicose veins. In traditional medicine, red vine leaf extract (AS 195) has been used to cure the symptoms of CVI. This systematic review was aimed to assess the effects of AS 195 in patients with CVI. MATERIAL AND METHODS: A systematic literature search was performed to identify trials that reported the impact of red vine leaf extract on CVI. The primary outcomes investigated were Leg (limb) volume, calf circumference, ankle circumference, tired and heavy legs, a sensation of tension, tingling sensation, and pain. RESULTS: From the 56 studies, 5 trials were selected according to our inclusion criteria. Red vine leaf extract significantly improved numbers of outcomes (lower leg volume, calf and ankle circumference, tired, heavy legs, tingling sensation, pain, the sensation of tension in the legs, cutaneous microcirculation, and transcutaneous oxygen pressure) in only some trials. The tolerability for red vine leaf extract was reported good or satisfactory. CONCLUSIONS: Red vine leaf extract had a beneficial therapeutic role in patients with CVI. Further high-quality trials are required to be carried out to provide strong evidence.


Assuntos
Extratos Vegetais/uso terapêutico , Insuficiência Venosa/tratamento farmacológico , Adulto , Doença Crônica , Ensaios Clínicos como Assunto/estatística & dados numéricos , Edema/complicações , Edema/tratamento farmacológico , Feminino , Humanos , Masculino , Dor/tratamento farmacológico , Dor/etiologia , Folhas de Planta/química , Varizes/tratamento farmacológico , Varizes/etiologia , Insuficiência Venosa/complicações
10.
AAPS PharmSciTech ; 21(3): 113, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32291553

RESUMO

The aim of this was to develop a well-balanced, replaceable, and patient non-infringing innovative transdermal drug delivery system "nano-vesicle transdermal gel" (NVTG) approaches for inhibiting inflammation. To consummate this objective, we developed a skin permeation nanogel system containing surface active agent along with ethanol. Carbopol 971p, hydroxypropyl methyl cellulose (HPMC K15M), and chitosan were used to fabricate the nanogels. The nanogel system was evaluated for pH, content uniformity, spreadability, rheological studies, in vitro skin permeation, and drug release. Carbapol 971p with the desired in vitro skin permeation was utilized to investigate skin irritation test and effects on inflammation using acute inflammatory paw edema models. Moreover, in vivo pharmacokinetic study was assessed. pH of this nanogels was found within the range of 6.1-7.2, whereas the viscosity was found 310.13 to 6361 cps. The ex vivo skin permeation gels showed permeation flux range, 5.9 ± 0.80 to 17.92 ± 1.13 µg/cm2 h. The highest permeation flux (17.92 ± 1.13 µg/cm2 h) was observed, which was 3.14-folds higher than that of the plain DH gel (10.72 ± 0.84 µg/cm2 h. Additionally, from toxicological study, no obvious signs of toxicity such as skin irritation (of laboratory rats) were identified. The in vivo anti-inflammatory behavior in carrageenan-induced rats showed comparatively higher inhibition of rat paw edema swelling by the prepared nanogel compared to that of the plain DH gel and marketed ibuprofen over 6 h. The amount of drug accumulated in the skin after topical application was much higher than oral application. In conclusion, developed NVTG formulation loaded with dapoxetine HCl (DH) offers new opportunities for creating novel therapeutic modality for inflammation patients with fewer adverse effects.


Assuntos
Anti-Inflamatórios/administração & dosagem , Benzilaminas/administração & dosagem , Sistemas de Liberação de Medicamentos , Edema/tratamento farmacológico , Naftalenos/administração & dosagem , Administração Cutânea , Animais , Carragenina/farmacologia , Feminino , Géis , Masculino , Ratos , Ratos Wistar
11.
Zhongguo Zhong Yao Za Zhi ; 45(5): 1167-1173, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32237461

RESUMO

To systematically evaluate the clinical efficacy and safety of Cheezheng Pain Relieving Plaster in the treatment of soft tissue injury. Four Chinese databases(namely CNKI, WanFang, VIP, CBM) and 2 English databases(namely PubMed, Cochrane Library) were retrieved from the establishment of each database to March 2019. The randomized controlled trials of Cheezheng Pain Relieving Plaster compared with routine therapy in treatment of soft tissue injury were included. The quality of the included studies was assessed using the Cochrane Risk Assessment Tool. Five studies were included, and 367 patients were enrolled. None of the included studies reported randomized concealment, blinding, follow-up and dropping off. The results showed that Cheezheng Pain Relieving Plaster may have advantages in alleviating joint pain, swelling, tenderness and dysfunction and other symptoms, with no serious adverse reaction. Compared with routine therapy, Cheezheng Pain Relieving Plaster may have advantages in the treatment of soft tissue injury. However, due to the quality of the included RCTs, the conclusions of this study were limited. In addition, to produce high-quality evidences for the clinical application of Cheezheng Pain Relieving Plaster, the conclusions of this study shall be further verified with large-sample, scientifically designed and strictly implemented clinical trials.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Dor/tratamento farmacológico , Lesões dos Tecidos Moles/tratamento farmacológico , Artralgia/tratamento farmacológico , Edema/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
13.
Chem Biol Interact ; 324: 109095, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32289289

RESUMO

Rheumatoid Arthritis (RA) affects approximately 1% of the total world population. Despite incessant research and development of new therapeutic agents, management of RA is still a troublesome affair. Histone Deacetylase 1 (HDAC1) is an epigenetic regulator which play important role in pathogenesis of RA. In present study, we hypothesized that Phenethyl isothiocyanate (PEITC), a potent inhibitor of HDAC1, may ameliorate RA. Efficacy of PEITC was evaluated in Complete Freund's Adjuvant (CFA) induced arthritis model in rats. CFA (0.1 ml) was injected subplantarly in the left hind paw on day 0 to all the groups except normal control. The administration of test drug PEITC (10, 24 & 50 mg/kg) and standard drug Ibuprofen started simultaneously and was continued for 21 days. Paw edema, total arthritic index, mobility score, stair climbing ability, behavioral parameters, and bone erosion were evaluated. Further, radiographic studies, TNF-alpha as well as HDAC1 levels in synovial tissue homogenate and histological analysis were performed. Prophylactic treatment of PEITC attenuated paw edema, total arthritic index, mobility score, stair climbing ability, behavioral parameters, and bone erosion in dose dependent manner. Furthermore, there was significant decrease in TNF-alpha as well as HDAC1 levels in synovial tissue homogenate. Histological analysis revealed no cartilage damage, bone erosion, hyperplasia at synovial lining as well as infiltration of inflammatory cells in treatment group. Results of this study suggest potent anti-rheumatoid arthritis activity of Phenethyl isothiocyanate in CFA induced RA model in rats.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Histona Desacetilase 1/metabolismo , Inibidores de Histona Desacetilases/uso terapêutico , Isotiocianatos/uso terapêutico , Analgésicos não Entorpecentes/uso terapêutico , Animais , Artrite Experimental/induzido quimicamente , Edema/tratamento farmacológico , Pé/patologia , Articulações do Pé/patologia , Adjuvante de Freund , Ibuprofeno/uso terapêutico , Locomoção/efeitos dos fármacos , Masculino , Dor/tratamento farmacológico , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
14.
Int J Mol Sci ; 21(7)2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32276463

RESUMO

The compound (E)-2-cyano-3-(1H-indol-3-yl)-N-phenylacrylamide (ICMD-01) was designed and developed based on the structures of clinically relevant drugs indomethacin and paracetamol through the molecular hybridization strategy. This derivative was obtained by an amidation reaction between substituted anilines and ethyl 2-cyanoacetate followed by a Knoevenagel-type condensation reaction with indole aldehyde that resulted in both a viable synthesis and satisfactory yield. In order to assess the immunomodulatory and anti-inflammatory activity, in vitro assays were performed in J774 macrophages, and significant inhibitions (p < 0.05) of the production of nitrite and the production of cytokines (IL-1ß and TNFα) in noncytotoxic concentrations were observed. The anti-inflammatory effect was also studied via CFA-induced paw edema in vivo tests and zymosan-induced peritonitis. In the paw edema assay, ICMD01 (50 mg kg-1) showed satisfactory activity, as did the group treated with dexamethasone, reducing edema in 2-6 h. In addition, there was no significant inhibition of PGE2, IL-1ß or TNFα in vivo. Moreover, in the peritonitis assay that assesses leukocyte migration, ICMD-01 exhibited promising results. Therefore, these preliminary studies demonstrate this compound to be a strong candidate for an anti-inflammatory drug together with an improved gastrointestinal safety profile when compared to the conventional anti-inflammatory drugs.


Assuntos
Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Peritonite/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Linhagem Celular , Citocinas , Masculino , Camundongos , Peritonite/induzido quimicamente , Zimosan/toxicidade
15.
Phytomedicine ; 69: 153194, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32146299

RESUMO

BACKGROUND: The frequency of allergic diseases is constantly rising. Dysregulated production of isotype E immunoglobulins is one of the key factors behind allergic reactions and its modulation is therefore an important target for pharmacological intervention. Natural products of the pseurotin family were reported to be inhibitors of IgE production in B-cells. Mechanistic details underlying these effects are however not well understood. PURPOSE: In the present study, we synthesized new analogs of natural pseurotins and extensively investigated their inhibitory effects on activation, proliferation and differentiation of B-cells, as well as on the production of IgE. STUDY DESIGN: Effects of two natural pseurotins (pseurotins A and D) and a collection of fully synthetic pseurotin analogs were studied on mouse B-cells stimulated by the combination of IL-4 and E. coli lipopolysaccharide. The IgE production was determined along with cell viability and cell proliferation. The phosphorylation of selected members of the STAT transcription factor family was subsequently investigated. Finally, the in vivo effect of pseurotin D on the ovalbumin-induced delayed type hypersensitivity response was tested in mice. RESULTS: We discovered that several fully synthetic pseurotin analogs were able to decrease the production of IgE in stimulated B-cells with potency comparable to that of pseurotins A and D. We found that the two natural pseurotins and the active synthetic analogs inhibited the phosphorylation of STAT3, STAT5 and STAT6 proteins in stimulated B-cells, resulting in the inhibition of B-cell proliferation and differentiation into the plasma cells. In vivo, pseurotin D decreased ovalbumin-induced foot pad edema. CONCLUSION: Our results advance the current mechanistic understanding of the pseurotin-induced inhibition of IgE production in B-cells by linking the effect to STAT signaling, and associated modulation of B-cell proliferation and differentiation. Together with our finding that structurally simpler pseurotin analogs were able to reproduce the effects of natural pseurotins, the presented work has implications for the future research on these secondary metabolites in the context of allergic diseases.


Assuntos
Linfócitos B/efeitos dos fármacos , Imunoglobulina E/metabolismo , Plasmócitos/citologia , Pirrolidinonas/química , Pirrolidinonas/farmacologia , Animais , Linfócitos B/citologia , Linfócitos B/fisiologia , Diferenciação Celular/efeitos dos fármacos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Escherichia coli/química , Imunoglobulina E/sangue , Imunoglobulina M/sangue , Imunoglobulina M/metabolismo , Lipopolissacarídeos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Ovalbumina/toxicidade , Fosforilação/efeitos dos fármacos , Plasmócitos/fisiologia , Fatores de Transcrição STAT/metabolismo
16.
PLoS One ; 15(3): e0230645, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210452

RESUMO

Houttuynia cordata Thunb. has been used as a traditional medicine to treat a variety of ailments in Asian countries such as China, Japan, South Korea, and Thailand. In Thailand, H. cordata fermentation products (HCFPs) are commercially produced and popularly consumed throughout the country without experimental validation. Anti-inflammatory activity of H. cordata fresh leaves or aerial parts has previously been reported, however, the anti-inflammatory activity of the commercially available HCFPs produced by the industrialized process has not yet been investigated. The aim of this study was to evaluate in vitro and in vivo anti-inflammatory potential of the selected industrialized HCFP. LPS-induced RAW264.7 and carrageenan-induced paw edema models were used to evaluate the anti-inflammatory activity of HCFP. The phenolic acid components of HCFP aqueous and methanolic extracts were investigated using HPLC analysis. In RAW264.7 cells, the HCFP aqueous and methanolic extracts reduced NO production and suppressed LPS-stimulated expression of PGE2, iNOS, IL-1ß, TNF-α and IL-6 levels in a concentration-dependent manner, however, less effect on COX-2 level was observed. In Wistar rats, 3.08 and 6.16 mL/kg HCFP reduced paw edema after 2 h carrageenan stimulation, suggesting the second phase anti-edematous effect similar to diclofenac (150 mg/kg). Whereas, 6.16 mL/kg HCFP also reduced paw edema after 1 h carrageenan stimulation, suggesting the first phase anti-edematous effect. Quantitative HPLC revealed the active phenolic compounds including syringic, vanillic, p-hydroxybenzoic and ferulic acids, which possess anti-inflammatory activity. Our results demonstrated for the first time the anti-inflammatory activity of the industrialized HCFP both in vitro and in vivo, thus validating its promising anti-inflammation potential.


Assuntos
Anti-Inflamatórios/farmacologia , Suplementos Nutricionais/análise , Houttuynia/metabolismo , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Houttuynia/química , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fenóis/análise , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Células RAW 264.7 , Ratos , Ratos Wistar
17.
Intern Med ; 59(11): 1387-1393, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32132333

RESUMO

We herein report a rare case of cutaneous and lymph node metastases that recurred 12 years after radical total gastrectomy for stage IIA gastric cancer. A 62-year-old man had undergone total gastrectomy for stage IIA gastric cancer 12 years earlier without postoperative adjuvant chemotherapy. At 12 years after the surgery, he was admitted for left jugular swelling. Computed tomography revealed supraclavicular lymph node swelling and precordial subcutaneous edema. The lymph node specimens and cutaneous biopsies indicated late recurrence of the gastric cancer. Concurrent chemoradiotherapy was administered effectively, but after eight months, the patient died due to deterioration in his general condition.


Assuntos
Quimiorradioterapia , Edema/tratamento farmacológico , Gastrectomia , Metástase Linfática/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Edema/etiologia , Evolução Fatal , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia
18.
J Infect Public Health ; 13(4): 472-479, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32139293

RESUMO

BACKGROUND: The present work is an extension of ongoing efforts toward the development and identification of new molecules as monotherapy displaying anti-inflammatory and anti-infective activities and a wide-range of gastrointestinal selectivity. A series of novel set of trisubstituted thiazole compounds (AR-17a to AR-27a) have synthesized and evaluated for their in-vitro and in-vivo anti-inflammatory activities. Synthesized trisubstituted thiazole compounds were also evaluated for their potential antibacterial activity against clinical pathogens causing infectious disease. MATERIAL AND METHOD: The structures of synthesized compounds were characterized by FTIR, 1H NMR, Mass spectroscopic techniques and evaluated for their in-vitro and in-vivo anti-inflammatory effects using the human red blood cell (HRBC) membrane stabilization method and a carrageenan-induced rat paw oedema model, respectively, Diclofenac sodium and Ibuprofen were used as standard drugs. The synthesized compounds AR-17atoAR-27a screened for their in-vitro antibacterial activity against the gram-positive bacteria Staphylococcus aureus (ATCC25923) and Enterococcus faecalis (ATCC29212) and the gram-negative bacteria Escherichia coli (ATCC8739) and Pseudomonas aeruginosa (ATCC9027) using ciprofloxacin and cefdinir as standard drugs. RESULT: Compounds AR-17a and AR-27a elicited maximum anti-inflammatory activity, providing 59% and 61% protection at 20mg/kg, respectively, in the inflamed paw model. Among the tested compounds, AR-17a (6.25), (54) and AR-27a (1.56), (52) had the least minimum inhibitory concentration values and the highest zone of inhibition, indicating their marked antibacterial activities. The lowest conc. were observed at 1.56, 6.25µg/mL for inhibition of bacteria by most of the compounds. CONCLUSION: Novel set of trisubstituted thiazole compounds (AR-17a to AR-27a) have synthesized and characterized successfully. The preliminary screening revealed that these compounds possess promising anti-inflammatory and antibacterial activities. In addition, the objective of the study was achieved with few of the promising structures like AR-17a to AR-27a, which are prove to be potential monotherapy candidates for the treatment of chronic inflammatory diseases and bacterial infections.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Tiazóis/farmacologia , Animais , Antibacterianos/síntese química , Anti-Inflamatórios/síntese química , Edema/tratamento farmacológico , Feminino , Fluoroquinolonas/síntese química , Fluoroquinolonas/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Ratos , Relação Estrutura-Atividade , Tiazóis/síntese química
20.
Pharmacol Rep ; 72(1): 36-46, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32016854

RESUMO

BACKGROUND/OBJECTIVES: 4-(Arylchalcogenyl)-1H-pyrazoles containing selenium or sulfur (0.001-50 mg/kg) were investigated regarding the intragastric route effect (ig) administration on nociception in mice. In this study, nociception and inflammation were induced by chemical agents such as formalin (0.92%), sodium L-glutamate 1-hydrate (20 µmol), croton oil (2.5%), acetic acid (1.6%) and thermic model with a hot plate test. RESULTS: Compounds 1a-c had the ability to reduce licking time in both phases (neurogenic and inflammatory) of the formalin test and glutamate. Only compounds 1a and 1b had the ability to reduce the number of abdominal writhes caused by acetic acid. The same was observed with the positive control celecoxib. To evaluate the possible anti-inflammatory activity of compounds 1a-c, the induction of paw edema by formalin and ear edema by croton oil was performed. For the inflammation induced by formalin, significant effects were observed from the dose of 0.1 mg/kg (1a-b) and 10 mg/kg (1c). In the ear edema test, it can be observed that only compound 1a had a significant effect. In the hotplate test, all the compounds had the ability to reduce the latency time. CONCLUSION: The results demonstrated that acute antinociceptive and anti-inflammatory effects of 4-(arylchalcogenyl)-1H-pyrazoles 1a is better than compared with the compound 1b and 1c in mice. This resulted in these molecules attracting the interest of researchers to perform future studies to develop new drugs to treat pain and inflammatory clinical conditions.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Pirazóis/farmacologia , Analgésicos/administração & dosagem , Analgésicos/química , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Celecoxib/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Inflamação/tratamento farmacológico , Masculino , Camundongos , Nociceptividade/efeitos dos fármacos , Dor/tratamento farmacológico , Pirazóis/administração & dosagem , Pirazóis/química , Selênio/química , Enxofre/química
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