RESUMO
Neonicotinoid pesticides (NNPs) and microplastics (MPs) are two emerging contaminants in agricultural environment. However, the interaction between MPs (especially biodegradable plastics) and NNPs is currently unclear. Therefore, taking thiacloprid (THI) as an example of NNPs, this study explores the adsorption-desorption process and mechanism of NNPs on MPs (traditional and biodegradable plastics), and analyzed the main factors affecting the adsorption (pH, salinity and dissolved organic matter). In addition, by using diffusive gradients in thin-films device, this study assessed the impact of MPs on the bioavailability of NNPs in soil. The results showed that the maximum adsorption capacity of polyamide 6 (96.49 µg g-1) for THI was greater than that of poly (butylene adipate co-terephthalate) (88.78 µg g-1). Aging increased the adsorption amount of THI (5.53 %-15.8 %) due to the higher specific surface area and reduced contact angle of MPs, but the adsorption mechanism remained unchanged. The desorption amount of THI from MPs in simulated intestinal fluid is 1.30-1.36 times. The MPs in soil alter the distribution of THI in the soil, increasing the bioavailability of THI while inhibiting its degradation. The results highlighted the significance of examining the combined pollution caused by MPs and NNPs.
Assuntos
Microplásticos , Neonicotinoides , Praguicidas , Poluentes do Solo , Poluentes do Solo/análise , Adsorção , Plásticos Biodegradáveis , Solo/química , Tiazinas/análiseRESUMO
Acesulfame potassium (ACK) was generally regarded as innocuous and extensively ingested. Nevertheless, ACK has recently gained attention as a burgeoning pollutant that has the potential to induce a range of health hazards, particularly to the digestive system. Herein, we uncover that ACK initiates inflammatory bowel disease (IBD) in mice and zebrafish, as indicated by the aggregation of macrophages in the intestine and the inhibition of intestinal mucus secretion. Transcriptome analysis of mice and zebrafish guts revealed that exposure to ACK typically impacts the cell cycle, focal adhesion, and PI3K-Akt signaling pathways. Using pharmacological approaches, we demonstrate that the PI3K-Akt signaling pathway and the generation of reactive oxygen species (ROS) triggered by cell division are not significant factors in the initiation of IBD caused by ACK. Remarkably, inhibition of the focal adhesion pathway is responsible for the IBD onset induced by ACK. Our results indicate the detrimental impacts and possible underlying mechanisms of ACK on the gastrointestinal system and provide insights for making informed choices about everyday dietary habits.
Assuntos
Adesões Focais , Doenças Inflamatórias Intestinais , Transdução de Sinais , Tiazinas , Peixe-Zebra , Animais , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Tiazinas/farmacologia , Adesões Focais/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , MasculinoRESUMO
The management protocol for patients with neovascular age-related macular degeneration (nAMD) involves multiple intravitreal injections (IVI) of anti-VEGF drugs. The ability to reduce the peak intraocular pressure (IOP) rise is greatly important in clinical practice. PURPOSE: This study evaluates the effect of topical hypotensive drugs on the short-term IOP rise after IVI of anti-VEGF drugs in patients with nAMD. MATERIAL AND METHODS: The prospective study included 80 patients with newly diagnosed nAMD. Before the start of treatment, the patients were divided into 4 groups of 20 people each: 1st - controls, who received no prophylactic drugs, in the 2nd, 3rd and 4th groups local instillations of one drop of hypotensive drugs brinzolamide 1%, brinzolamide-timolol, brimonidine-timolol were performed in the conjunctival sac twice: 1 day before the injection (at 20:00) and on the day of the injection 2 hours before the manipulation (at 08:00), respectively. IOP was measured in each patient using ICare Pro non-contact tonometer before injection, as well as 1 min, 30 and 60 min after injection. RESULTS: Prophylactic use of hypotensive drugs was associated with a significant decrease in IOP immediately after IVI compared to the same parameter in the 1st group (p<0.001), the maximum decrease in IOP values was observed when using a fixed combination of brimonidine-timolol by 12.1 mm Hg compared to the controls (p<0.001), the combination of brinzolamide-timolol reduced IOP by 8.5 mm Hg (p<0.001), brinzolamide 1% led to the smallest decrease in IOP - by 5.1 mm Hg (p<0.001). CONCLUSION: Study patients that received instillations of brimonidine-timolol combination of one drop into the conjunctival sac 1 day before the injection and on the day of the injection showed the maximum decrease in IOP compared to patients of the other groups.
Assuntos
Inibidores da Angiogênese , Pressão Intraocular , Injeções Intravítreas , Hipertensão Ocular , Sulfonamidas , Humanos , Masculino , Feminino , Idoso , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/prevenção & controle , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/fisiopatologia , Inibidores da Angiogênese/administração & dosagem , Estudos Prospectivos , Sulfonamidas/administração & dosagem , Resultado do Tratamento , Anti-Hipertensivos/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Tonometria Ocular/métodos , Pessoa de Meia-Idade , Timolol/administração & dosagem , Tartarato de Brimonidina/administração & dosagem , Soluções Oftálmicas/administração & dosagem , Tiazinas/administração & dosagem , Degeneração Macular/tratamento farmacológico , Degeneração Macular/diagnósticoRESUMO
Artificial sweeteners, which contain no or few calories, have been widely used in various foods and beverages, and are regarded as safe alternatives to sugar by the Food and Drug Administration. While several studies suggest that artificial sweeteners are not related to cancer development, some research has reported their potential association with the risk of cancers, including hepatocellular carcinoma (HCC). Here, we investigated whether acesulfame potassium (Ace K), a commonly used artificial sweetener, induces immune evasion of HCC cells by upregulating programmed death ligand-1 (PD-L1). Ace K elevated the protein levels of PD-L1 in HCC cells without increasing its mRNA levels. The upregulation of PD-L1 protein levels in HCC cells by Ace K was induced by attenuated autophagic degradation of PD-L1, which was mediated by the Ace K-stimulated ERK1/2-mTORC1 signaling pathway. Ace K-induced upregulation of PD-L1 attenuated T cell-mediated death of HCC cells, thereby promoting immune evasion of HCC cells. In summary, the present study suggests that Ace K promotes HCC progression by upregulating the PD-L1 protein level.
Assuntos
Autofagia , Antígeno B7-H1 , Carcinoma Hepatocelular , Neoplasias Hepáticas , Tiazinas , Regulação para Cima , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Humanos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Autofagia/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Tiazinas/farmacologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Linhagem Celular Tumoral , Edulcorantes/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacosRESUMO
Furpenthiazinate is a yellow pigment formed by the Maillard reaction between cysteine and furfural under strongly acidic conditions. Here, we describe the conditions and mechanism of pigment formation in a model system and in an acid hydrolyzate of food and analyze its biological properties. A reaction solution containing 32 mM cysteine and 128 mM furfural or 64 mM cysteine and 256 mM furfural in the presence of 2-6 M hydrochloric acid that was heated to 110 °C for 1-2 h yielded approximately 3 mM furpenthiazinate. Nuclear magnetic resonance analysis of furpenthiazinate prepared using 1-13C or 5-13C d-ribose suggests that it was formed through the condensation of cysteine and two C5 chains derived from pentose with the dehydration and elimination of formic acid. Furpenthiazinate was detected in mieki, a seasoning, and some acid hydrolyzates of food, and it did not show antibacterial or mutagenic activity.
Assuntos
Furaldeído , Reação de Maillard , Tiazinas , Cisteína , Furanos , ÁcidosRESUMO
Pesticides, especially the newly developed neonicotinoids, are increasingly used in many countries around the world, including Cameroon, to control pests involved in crop destruction or disease transmission. Unfortunately, the pesticides also pose tremendous environmental problems because a predominant amount of their residues enter environmental matrices to affect other nontargeted species including humans. This therefore calls for continuous biomonitoring of these insecticides in human populations. The present study sought to assess the neonicotinoid insecticide exposures in two agrarian regions of Cameroon, the South-West region and Littoral region. The study involved 188 men, including 125 farmers and 63 nonfarmers. Spot urine samples were obtained from these subjects and subjected to liquid chromatographic-tandem mass spectrometric analysis for concentrations of neonicotinoid compounds, including acetamiprid, clothianidin, dinotefuran, imidacloprid, thiacloprid, nitenpyram, thiamethoxam, and N-dm-acetamiprid. Neonicotinoid compounds were detected in all study participants, and residues of all the screened pesticides were detected among participants. N-dm-Acetamiprid and imidacloprid were the most prevalent among the subjects (100.0% and 93.1%, respectively), whereas nitenpyram was less common (3.2%). The median values of imidacloprid and total urinary neonicotinoid concentrations were elevated among farmers (0.258 vs. 0.126 µg/L and 0.829 vs. 0.312 µg/L, respectively). Altogether the findings showed that both the farmer and nonfarmer study populations of Cameroon were exposed to multiple residues of neonicotinoids, with relatively higher levels of pesticides generally recorded among farmers. Although exposure levels of the neonicotinoids were generally lower than their respective reference doses, these results warrant further research on the health risk evaluation of multiple residues of the pesticides and reinforcement of control measures to minimize the exposure risks, especially among farmers. Environ Toxicol Chem 2024;43:952-964. © 2024 SETAC.
Assuntos
Fazendeiros , Neonicotinoides , Exposição Ocupacional , Tiazinas , Humanos , Masculino , Neonicotinoides/análise , Neonicotinoides/urina , Exposição Ocupacional/análise , Camarões , Adulto , Pessoa de Meia-Idade , Nitrocompostos/análise , Inseticidas/análise , Inseticidas/urina , Adulto Jovem , Tiazóis/análise , Tiazóis/urina , Praguicidas/análise , Praguicidas/urina , Guanidinas/análise , Guanidinas/urina , Tiametoxam , Monitoramento AmbientalRESUMO
We find that NUPR1, a stress-associated intrinsically disordered protein, induced droplet formation via liquid-liquid phase separation (LLPS). NUPR1-driven LLPS was crucial for the creation of NUPR1-dependent stress granules (SGs) in pancreatic cancer cells since genetic or pharmacological inhibition by ZZW-115 of NUPR1 activity impeded SGs formation. The KrasG12D mutation induced oncogenic stress, NUPR1 overexpression, and promoted SGs development. Notably, enforced NUPR1 expression induced SGs formation independently of mutated KrasG12D. Mechanistically, KrasG12D expression strengthened sensitivity to NUPR1 inactivation, inducing cell death, activating caspase 3 and releasing LDH. Remarkably, ZZW-115-mediated SG-formation inhibition hampered the development of pancreatic intraepithelial neoplasia (PanINs) in Pdx1-cre;LSL-KrasG12D (KC) mice. ZZW-115-treatment of KC mice triggered caspase 3 activation, DNA fragmentation, and formation of the apoptotic bodies, leading to cell death, specifically in KrasG12D-expressing cells. We further demonstrated that, in developed PanINs, short-term ZZW-115 treatment prevented NUPR1-associated SGs presence. Lastly, a four-week ZZW-115 treatment significantly reduced the number and size of PanINs in KC mice. This study proposes that targeting NUPR1-dependent SGs formation could be a therapeutic approach to induce cell death in KrasG12D-dependent tumors.
Assuntos
Carcinoma in Situ , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Piperazinas , Tiazinas , Animais , Camundongos , Carcinoma in Situ/genética , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/genética , Caspase 3/genética , Caspase 3/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Grânulos de Estresse , Mutações Sintéticas LetaisRESUMO
BACKGROUND: CA-125 alone is widely used to diagnose progressive disease (PD) in platinum-sensitive recurrent ovarian cancer (PSROC) on chemotherapy. However, there are increasing concerns regarding its accuracy. We assessed concordance between progression defined by CA-125 and RECIST using data from the CALYPSO trial. METHODS: We computed concordance rates for PD by CA-125 and RECIST to determine the positive (PPV) and negative predictive values (NPV). RESULTS: Of 769 (79%) evaluable participants, 387 had CA-125 PD, where only 276 had concordant RECIST PD (PPV 71%, 95% CI 67-76%). For 382 without CA-125 PD, 255 had RECIST PD but 127 did not (NPV 33%, 95% CI 29-38). There were significant differences in NPV according to baseline CA-125 (≤100 vs >100: 42% vs 25%, P < 0.001); non-measurable vs measurable disease (51% vs 26%, P < 0.001); and platinum-free-interval (>12 vs 6-12 months: 41% vs 14%, P < 0.001). We observed falling CA-125 levels in 78% of patients with RECIST PD and CA-125 non-PD. CONCLUSION: Approximately 2 in 3 women with PSROC have RECIST PD but not CA-125 PD by GCIG criteria. Monitoring CA-125 levels alone is not reliable for detecting PD. Further research is required to investigate the survival impact of local therapy in radiological detected early asymptomatic PD.
Assuntos
Neonicotinoides , Neoplasias Ovarianas , Tiazinas , Humanos , Feminino , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/tratamento farmacológico , Critérios de Avaliação de Resposta em Tumores Sólidos , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma Epitelial do OvárioRESUMO
RATIONALE: The thiosuccinimide linker is widely used in the synthesis of bioconjugates. However, it is susceptible to hydrolysis and is transformed into its hydrolyzed and/or the isobaric thiazine forms, the latter of which is a fairly common product in a conjugate that contains a cysteinyl peptide. Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) and matrix-assisted laser desorption/ionization-tandem mass spectrometry (MALDI-MS/MS) are useful for differentiating these isobaric species. METHODS: Four cross-linked peptides with thiosuccinimide linkers were synthesized. Analogs with linkers that were transformed into thiazine and/or the hydrolyzed thiosuccinimide linkers were then synthesized by incubating the samples at neutral or basic pH. All the cross-linked peptides were purified using RP-HPLC (reversed-phase high-performance liquid chromatography) and differentiated using MALDI-MS, MALDI-MS/MS, and ultraviolet photodissociation. RESULTS: A cysteinyl peptide-containing conjugate, the thiosuccinimide form, was largely transformed into the hydrolyzed or thiazine forms after incubation at neutral or basic pH. MALDI-MS allowed the three forms to be differentiated: the thiosuccinimide and its hydrolysis product yielded two constituent peptides after reductive cleavage between the Cys and succinimide moieties; no fragment ions were produced from the thiazine form. In addition, MALDI-MS/MS of the thiosuccinimide form yielded two pairs of complementary fragment ions via 1,4-elimination: Cys-SH and maleimide, and dehydro-alanine and thiosuccinimide, which are different from those produced via reductive cleavage in MALDI-MS. The thiazine form yielded fragment ions resulting from the cleavage of the newly formed amide bond in the linker that resulted from thiazine formation. CONCLUSIONS: The thiosuccinimide (but not thiazine) form of the cross-linked peptide yielded individual constituent peptides using MALDI-MS and MALDI-MS/MS, showing specific 1,4-elimination for the thiosuccinimide form and cleavage at the newly formed peptide bond via transcyclization for the thiazine form.
Assuntos
Espectrometria de Massas em Tandem , Tiazinas , Espectrometria de Massas em Tandem/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Peptídeos/química , Íons , MaleimidasRESUMO
ABSTRACT Gyrate atrophy is a rare metabolic autosomal recessive disorder caused by ornithine aminotransferase enzyme deficiency that leads to characteristic progressive, degenerative chorioretinal findings. Patients complain mostly of low vision, night blindness, and peripheral vision loss. Posterior subcapsular cataract, myopia, choroid neovascularization, and intraretinal cysts may be accompanying factors related to vision loss. We encountered a patient with vision loss secondary to posterior subcapsular cataract and intraretinal cysts. After treatment with topical brinzolamide and nepafenac (and without any diet mo dification and/or supplementation), we observed 143- and 117-mm macular thickness resolutions with 2 and 1 Snellen lines of visual gain in his right and left eyes, respectively. Also, we detected a novel homozygous mutation in the ornithine aminotransferase gene: c.1253T>C (p.Leu418Pro). Carbonic anhydrase inhibitors and/or non-steroid anti-inflammatory drugs can control macular edema in patients with gyrate atrophy-associated intraretinal cysts. The genetic variants may also be a determinant in the responsiveness to the therapy type.
RESUMO A atrofia girata é um distúrbio autossômico recessivo metabólico raro causado pela deficiência da enzima ornitina ami notransferase, que leva a achados degenerativos coriorretinianos progressivos característicos. Os pacientes queixam-se principalmente de baixa visão, cegueira noturna e perda de vi são periférica. A catarata subcapsular posterior, a miopia, a neovascularização da coróide e os cistos intrarretinianos podem ser fatores associados à perda da visão. Encontramos um paciente com perda de visão secundária à catarata subcapsular posterior e cistos intrarretinianos. Após o tratamento com brinzolamida tópica e nepafenaco (e sem modificação e/ou suplementação da dieta), observamos resoluções de espessura macular de 143 e 117 mm e com 2 e 1 linhas de Snellen de ganho visual nos olhos direito e esquerdo, respectivamente. Além disso, detectamos uma nova mutação homozigótica no gene da ornitina aminotransfera se: c.1253T>C (p.Leu418Pro). Inibidores da anidrase carbônica e/ou drogas anti-inflamatórias não esteróides podem controlar o edema macular em pacientes com cistos intrarretinianos associados à atrofia girata. As variantes genéticas também podem ser determinantes na responsividade ao tipo de terapia.
Assuntos
Humanos , Masculino , Adulto , Fenilacetatos/administração & dosagem , Inibidores da Anidrase Carbônica/administração & dosagem , Atrofia Girata/genética , Anti-Inflamatórios não Esteroides/administração & dosagem , Edema Macular/tratamento farmacológico , Benzenoacetamidas/administração & dosagem , Ornitina-Oxo-Ácido Transaminase/genética , Sulfonamidas/administração & dosagem , Tiazinas/administração & dosagem , Angiofluoresceinografia , Edema Macular/diagnóstico por imagem , Tomografia de Coerência Óptica , Sequenciamento de Nucleotídeos em Larga Escala , Administração Oftálmica , MutaçãoRESUMO
Abstract The effects of the non-steroidal anti-inflammatory drugs (NSAIDs) on bone quantity and quality were investigated for years. However, there is lack of information on the impact of NSAIDs on the quality of tooth-supporting alveolar bone in absence of periodontal inflammation. Thus, the aim of this study was to evaluate histometrically the influence of a selective COX-2 NSAID (Meloxicam) on the inter-radicular bone mineral density in rats. Forty-nine adult male Wistar rats were randomly divided into four experimental groups: Subcutaneous injection of 0.9% sterile saline for 15 days (G1; n=12) and 45 days (G2; n=11); and subcutaneous injection of Meloxicam for 15 days (G3; n=13) and 45 days (G4; n=13). Mineral density was histometrically determined in the inter-radicular area of the 1st mandibular molars and data analysis performed by two-way ANOVA (a=5%). Results showed no interaction between time and treatment (p>0.05) and that meloxicam did not affect the alveolar bone density. In contrast, it was found that inter-radicular alveolar bone density increased with time (91.88±3.08% and 92.86±2.38% for groups 15 and 45 days, respectively) (p<0.05). Within the limits of this study, daily administration of a selective COX-2 inhibitor (Meloxicam) did not affect the quality of the inter-radicular alveolar bone in absence of periodontal infection.
Resumo Os efeitos dos fármacos anti-inflamatórios não esteroidais (AINEs) sobre a quantidade e qualidade óssea tem sido investigados ao longo dos anos.Entretanto, há falta de informação sobre o impacto dos AINEs na qualidade do osso alveolar de suporte na ausência de inflamação periodontal. Assim, o objetivo deste estudo foi avaliar, histometricamente, a influência de um AINE seletivo para COX-2 (Meloxicam) na densidade mineral óssea inter-radicular em ratos. Quarenta e nove ratos Wistar, machos e adultos foram divididos aleatoriamente em quatro grupos experimentais: injeções subcutâneas de 0,9% de solução salina estéril por 15 dias (G1, n=12) e 45 dias (G2, n=11); e injeções subcutâneas de Meloxicam por 15 (G3, n=13) e 45 dias (G4, n=13). A densidade mineral foi determinada histometricamente na área inter-radicular dos primeiros molares mandibulares e a análise dos dados realizada por meio de ANOVA (a=5%). Os resultados mostraram nenhuma interação entre tempo e tratamento (p>0,05) e que o meloxicam não afetou a densidade óssea alveolar. Em contraste, foi encontrado que a densidade óssea alveolar inter-radicular aumentou ao longo do tempo (91,88±3,08% e 92,86±2,38% para os grupos 15 e 45 dias, respectivamente) (p<0,05). Dentro dos limites deste estudo, a administração diária de um inibidor seletivo para COX-2 (Meloxicam) não afetou a qualidade do osso alveolar inter-radicular na ausência de infecção periodontal.
Assuntos
Animais , Masculino , Ratos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Tiazinas/farmacologia , Tiazóis/farmacologia , Dente/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Ratos WistarRESUMO
Abstract This study evaluated the action of ionizing radiation and the possible radioprotective effect of the non-steroidal anti-inflammatory drug meloxicam on the bone physiology of rat mandibles by assessing the alveolar socket healing and bone strength. Forty male Wistar rats were divided in 4 groups (n=10): control (CG), irradiated (IG), meloxicam (MG), meloxicam irradiated (MIG). A dose of 0.2 mg/kg meloxicam was administered to MG and MIG. After this, IG and MIG were irradiated with 15 Gy radiation dose in the mandible. Forty days after the above procedures, the mandibular first molars were extracted and the animals were killed after 15 or 30 days (n=5). Micro-computed tomography and bending test were used to evaluate alveolar socket healing and bone strength, respectively. At 15 days, bone volume, bone volume fraction and trabecular thickness were higher in the CG and MG than in the IG and MIG; and trabecular separation was higher in the IG compared with the others. At 30 days, there was a difference only in trabecular separation, which was higher in IG than in CG and MG, and MIG did not differ from the others. Bone strength was lower in IG compared with CG and MG, and MIG did not differ from the others. In conclusion, the ionizing radiation affected the bone physiology of rat mandibles, delaying the alveolar socket healing and reducing the bone strength. Moreover, the meloxicam had a positive effect on the trabecular separation in alveolar socket healing and on the bone strength.
Resumo Este estudo avaliou a ação da radiação ionizante e o possível efeito radioprotetor do anti-inflamatório não esteroide meloxicam na fisiologia óssea de mandíbulas de rato por meio da análise da reparação alveolar e da resistência óssea. Quarenta ratos Wistar machos foram divididos em 4 grupos (n=10): controle (GC), irradiado (GI), meloxicam (GM), meloxicam irradiado (GMI). Administrou-se uma dose única de 0,2 mg/kg de meloxicam no GM e GMI. Posteriormente, o GI e GMI foram irradiados com dose de 15 Gy na região de mandíbula. Decorridos 40 dias dos procedimentos acima, extraiu-se os primeiros molares inferiores dos animais, que foram mortos após 15 e 30 dias (n=5). Utilizou-se a microtomografia computadorizada e o teste de flexão para avaliação da reparação alveolar e da resistência óssea, respectivamente. Aos 15 dias, o volume ósseo, a fração de volume ósseo e a espessura trabecular foram maiores no GC e GM comparados ao GI e GMI; já a separação trabecular foi maior no GI em relação aos demais. Aos 30 dias, houve diferença apenas na separação trabecular, que foi maior no GI em comparação ao GC e GM, não tendo o GMI diferido dos demais. A resistência óssea no GI foi menor em relação ao GC e GM, não tendo o GMI diferido dos demais. Concluiu-se que a radiação ionizante afetou a fisiologia óssea das mandíbulas de rato, promovendo atraso na reparação alveolar e redução da resistência óssea; além disso, o meloxicam, apresentou efeito positivo na separação trabecular da reparação alveolar e na resistência óssea.
Assuntos
Animais , Ratos , Anti-Inflamatórios não Esteroides/farmacologia , Mandíbula/efeitos dos fármacos , Protetores contra Radiação/farmacologia , Tiazinas/farmacologia , Tiazóis/farmacologia , Microtomografia por Raio-XRESUMO
ABSTRACT PURPOSE : To compare ileal anastomoses in the immediate postoperative healing period after meloxicam use. METHODS: Forty two male Wistar rats were randomly divided into two groups of 21, COX and control group. To COX meloxicam in combination with morphine was given in 3 days period. Control group received only morphine during the same period. Each group was divided into three sub-groups of 7, which were euthanized at 5, 10, and 21 days postoperatively. Comparison was based in histological evaluation of collagen type I and III using sirius red, immunohistochemical through vascular endothelial growth factor and matrix metalloproteinase-9. RESULTS: Healing process in scheduled periods did not show significant differences (p>0.05) between the COX and control groups during any of the periods. CONCLUSION: The use of meloxicam in the postoperative period following ileal anastomosis did not affect healing.
Assuntos
Animais , Masculino , Tiazinas/farmacologia , Tiazóis/farmacologia , Cicatrização/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Íleo/cirurgia , Período Pós-Operatório , Fatores de Tempo , Anastomose Cirúrgica , Distribuição Aleatória , Ratos Wistar , Neovascularização Fisiológica/efeitos dos fármacos , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Modelos Animais , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Íleo/irrigação sanguíneaRESUMO
RESUMOInsuficiência cardíaca (IC) é causa frequente de internação exigindo do enfermeiro precisão na conduta clínica e adequado julgamento dos diagnósticos de enfermagem.Objetivo:verificar acurácia na determinação dos diagnósticos de enfermagem fadiga, intolerância à atividade e débito cardíaco diminuído em paciente com IC hospitalizados.Método:estudo descritivo aplicado aos enfermeiros experientes em diagnósticos de enfermagem NANDA-I e/ou IC. Avaliação da acurácia foi realizada a partir do cálculo das medidas: eficácia (E), falso negativo (FN), falso positivo (FP) e tendência (T). Foram aptos os enfermeiros com inspeção aceitável para dois diagnósticos.Resultados:o diagnóstico de enfermagem fadiga foi o mais erroneamente identificado pelos enfermeiros avaliadores.Discussão:a busca pelo aperfeiçoamento da acurácia diagnóstica reafirma a necessidade de treinamento contínuo e específico para a melhora da capacidade diagnosticadora do enfermeiro.Conclusão:o treinamento permitiu o exercício do raciocínio clínico e melhor acurácia dos enfermeiros.
RESUMENInsuficiencia cardíaca (IC) es causa frecuente de ingresos hospitalarios exigindo del enfermero precisión en la conducta clínica y adecuado juzgamiento de los diagnósticos de enfermería.Objetivo:verificar la precisión en la determinación de los diagnósticos de enfermería fatiga, disminuición del gasto cardíaco e intolerancia a la actividad en pacientes con IC ingresos en hospitales.Método:estudio observacional, con enfermeros docentes y experientes en diagnósticos de enfermería NANDA-I y/o IC. Evaluación y precisión fueron realizadas por através del cálculo: eficacia (E), falso negativo (FN), falso positivo (FP) y tendecia (T). Fueron aptos los enfermeros con inspección aceptable para dos diagnósticos.Resultados:el diagnóstico de enfermería fatiga fue identificado erróneamente como por evaluadores enfermeras.Discusión:la búsqueda de la mejora de la precisión diagnóstica reafirma la necesidad de una formación continua y específica a la mejora de la capacidad del diagnosticador enfermera.Conclusión:la capacitación permitió el ejercicio del raciocínio y mejor precisión de los enfermeros.
ABSTRACTHeart failure (HF) is a common cause of hospitalization and requires accuracy in clinical judgment and appropriate nursing diagnoses.Objective:to determine the accuracy of nursing diagnoses of fatigue, intolerance to activity and decreased cardiac output in hospitalized HF patients.Method:descriptive study applied to nurses with experience in NANDA-I and/or HF nursing diagnoses. Evaluation and accuracy were determined by calculating effi cacy (E), false negative (FN), false positive (FP) and trend (T) measures. Nurses who showed acceptable inspection for two diagnoses were selected.Results:the nursing diagnosis of fatigue was the most commonly mistaken diagnosis identifi ed by the nursing evaluators.Discussion:the search for improving diagnostic accuracy reaffi rms the need for continuous and specifi c training to improve the diagnosis capability of nurses.Conclusion:the training allowed the exercise of clinical judgment and better accuracy of nurses.
Assuntos
Animais , Feminino , Anti-Inflamatórios não Esteroides/uso terapêutico , Carbazóis/uso terapêutico , Galinhas/lesões , Fraturas Ósseas/veterinária , Atividade Motora/efeitos dos fármacos , Tiazinas/uso terapêutico , Tiazóis/uso terapêutico , Fraturas Ósseas/tratamento farmacológicoRESUMO
The mandible condylar process cartilage (CP) of Wistar rats is a secondary cartilage and acts as a mandibular growth site. This phenomenon depends on adequate proteins intake and hormone actions, including insulin. Objectives The present study evaluated the morphological aspects and the expression of the insulin receptor (IR) in the cartilage of the condylar process (CP) of rats subjected to protein undernourishment. Material and Methods The nourished group received a 20% casein diet, while the undernourished group (U) received a 5% casein diet. The re-nourished groups, R and RR, were used to assess the effects of re-nutrition during puberty and adulthood, respectively. CPs were processed and stained with picro-sirius red, safranin-O and azocarmine. Scanning electron microscopy and immunohistochemistry were also performed. Results The area of the CP cartilage and the number of cells in the chondroblastic layer decreased in the U group, as did the thickness of the CP layer in the joint and hypertrophic layer. Renourishment during the pubertal stage, but not during the adult phase, restored these parameters. The cell number was restored when re-nutrition occurred in the pubertal stage, but not in the adult phase. The extracellular matrix also decreased in the U group, but was restored by re-nutrition during the pubertal stage and further increased in the adult phase. IR expression was observed in all CPs, being higher in the chondroblastic and hypertrophic cartilage layers. The lowest expression was found in the U and RR groups. Conclusions Protein malnutrition altered the cellularity, the area, and the fibrous cartilage complex, as well as the expression of the IRs. .
Assuntos
Animais , Camundongos , Anti-Inflamatórios não Esteroides/metabolismo , Ciclo-Oxigenase 1/metabolismo , /metabolismo , Inibidores de Ciclo-Oxigenase/metabolismo , Piroxicam/análogos & derivados , Tiazinas/metabolismo , Tiazóis/metabolismo , Substituição de Aminoácidos , Anti-Inflamatórios não Esteroides/química , Arginina/química , Arginina/genética , Arginina/metabolismo , Sítios de Ligação , Domínio Catalítico , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/genética , /química , /genética , Inibidores de Ciclo-Oxigenase/química , Ligação de Hidrogênio , Leucina/química , Leucina/genética , Leucina/metabolismo , Mutação , Piroxicam/química , Piroxicam/metabolismo , Estrutura Secundária de Proteína , Serina/química , Serina/genética , Serina/metabolismo , Tiazinas/química , Tiazóis/química , Tirosina/química , Tirosina/genética , Tirosina/metabolismo , ÁguaRESUMO
Background: The association between non-nutritive sweeteners and obesity is controversial. Aim: To determine whether the consumption of non-nutritive sweeteners is related to higher risk for overweight or obesity among university students in Chile, Panama, Guatemala and Peru. Material and Methods: A total of 1,224 (472 from Chile, 300 from Panama, 248 from Guatemala and 204 from Peru) male and female university students aged between 18 and 26 years participated in the study. Each student reported their food intake (frequency of weekly consumption) in a survey that contained photos of foods containing non-nutritive sweeteners adapted for each country. Anthropometry was also measured. Results: More than 80% of students consumed at least one product containing non-nutritive sweeteners. Females who ate acesulfame potassium and sucralose had a lower risk of overweight or obesity with an odds ratio (OR) of 0.5 (confidence intervals (CI) = 0.3-0.9; p = 0.003) and OR = 0.4 (IC = 0.2-0.8; p = 0.01), respectively. Conclusions: In this sample of Latinamerican university students, consumption of non-nutritive sweeteners was associated with lower risk of overweight only in females.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Comportamento Alimentar/efeitos dos fármacos , Adoçantes não Calóricos/administração & dosagem , Inquéritos Nutricionais , Obesidade/epidemiologia , Estudantes , Índice de Massa Corporal , Chile/epidemiologia , Geografia , Guatemala/epidemiologia , América Latina/epidemiologia , Obesidade/prevenção & controle , Sobrepeso/epidemiologia , Sobrepeso/prevenção & controle , Panamá/epidemiologia , Peru/epidemiologia , Fotografação , Fatores de Proteção , Risco , Fatores Sexuais , Sacarose/administração & dosagem , Sacarose/análogos & derivados , Inquéritos e Questionários , Edulcorantes/administração & dosagem , Tiazinas/administração & dosagemRESUMO
PURPOSE: To evaluate the effects of copaiba oil on jaw defects repair in Wistar rats treated with bioglass or adipose tissue. METHODS: A jaw defect was randomly created in forty-two rats and filled with bioglass or adipose tissue. The two groups (Gbio and Gcell) were subdivided in three subgroups with seven animals each according to gavage administration: control (distillated water), oil (copaiba oil) and melox (meloxicam). Euthanasia was performed after forty post-operative days. The bone formation was analyzed regarding the histological aspects. RESULTS: The osteoclasts activity was observed only in four subgroups (p=0.78). Regarding the osteoblasts presence, it was very similar between the subgroups, the difference was due to Gcell-melox (p=0.009) that presented less osteoblastic activity. The inflammatory cells were more evident in Gcell-melox subgroup, however, there was no difference in comparison with the other subgroups (p=0.52). Bone formation was observed in all subgroups, just two animals showed no bone formation even after 40 days. More than 50% of bone matrix mineralization was observed in 56% (23 animals) of the analyzed areas. The bone matrix mineralization was not different between subgroups (p=0.60). CONCLUSIONS: The subgroups that received copaiba oil showed bone repair, although not statistically significant in comparison to subgroups treated whit meloxicam or controls. Copaiba oil administered by gavage had no effect on bone repair in this experimental model. .
Assuntos
Animais , Masculino , Regeneração Óssea/efeitos dos fármacos , Fabaceae/química , Arcada Osseodentária/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Óleos de Plantas/farmacologia , Tecido Adiposo/transplante , Anti-Inflamatórios não Esteroides/farmacologia , Substitutos Ósseos/uso terapêutico , Cerâmica/uso terapêutico , Modelos Animais de Doenças , Anormalidades Maxilomandibulares/tratamento farmacológico , Anormalidades Maxilomandibulares/fisiopatologia , Arcada Osseodentária/fisiopatologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/fisiologia , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Tiazinas/farmacologia , Tiazóis/farmacologia , Cicatrização/efeitos dos fármacosRESUMO
Introducción. El accidente cerebrovascular es la segunda causa de muerte y la primera de discapacidad en el mundo, y más de 85 % es de origen isquémico. Objetivo. Evaluar en un modelo de infarto cerebral por embolia arterial el efecto de la atorvastatina y el meloxicam, administrados por separado y de forma conjunta, sobre la respuesta neuronal, los astrocitos y la microglia. Materiales y métodos. Se sometieron ratas Wistar a embolia de la arteria carótida y a tratamiento con meloxicam y atorvastatina, administrados por separado y conjuntamente, a las 6, 24, 48 y 72 horas. Se evaluó la reacción de las proteínas COX-2, GFAP y OX-42 en las neuronas, los astrocitos y la microglia mediante inmunohistoquímica y estudios morfológicos y de densitometría. Los datos obtenidos se evaluaron por medio de un análisis de varianza y de pruebas no paramétricas de comparación múltiple. Resultados. La isquemia cerebral por embolia arterial incrementó significativamente (p<0,001) la reacción de los astrocitos y la microglia, en tanto que la atorvastatina y el meloxicam, administrados por separado y de forma conjunta, la redujeron. La isquemia produjo acortamiento de las proyecciones de los astrocitos, engrosamiento celular, ruptura de las expansiones protoplásmicas (clasmatodendrosis) y cambios morfológicos en la microglia propios de diversas etapas de actividad. En las zonas circundantes del foco se incrementó la reacción inmunológica de la COX-2 y se redujo en el foco isquémico, en tanto que el meloxicam y la atorvastatina redujeron significativamente (p<0,001) la reacción inmunológica en la zona circundante del foco, restableciendo la marcación de la ciclooxigenasa en el foco isquémico. Conclusión. La combinación de meloxicam y atorvastatina atenúa la respuesta de los astrocitos y la microglia en el proceso inflamatorio posterior a la isquemia cerebral por embolia arterial, reduciendo la degeneración neuronal y restableciendo el equilibrio morfológico y funcional del tejido nervioso.
Introduction: Stroke is the second leading cause of death and the first cause of disability in the world, with more than 85% of the cases having ischemic origin. Objective: To evaluate in an embolism model of stroke the effect of atorvastatin and meloxicam on neurons, astrocytes and microglia. This evaluation was done administering each medication individually and in association. Materials and methods: Wistar rats were subjected to carotid arterial embolism and treatment with meloxicam and atorvastatin at 6, 24, 48 and 72 hours. Using immunohistochemistry, we evaluated the immunoreactivity of COX-2 protein, GFAP and OX-42 in neurons, astrocytes and microglia by densitometric and morphological studies. Data were evaluated by variance analysis and non-parametric multiple comparison. Results: Cerebral ischemia by arterial embolism increased significantly the reactivity of microglia and astrocytes (p<0.001), whereas it was reduced by atorvastatin, meloxicam and their association. Ischemia produced astrocytic shortening, cellular thickening, protoplasmic rupture expansions (clasmatodendrosis) and microglial morphological changes characteristic of various activity stages. In perifocal areas, immunoreactivity of COX-2 was increased and in the ischemic focus it was reduced, while meloxicam and atorvastatin significantly reduced (p<0.001) perifocal immunoreactivity, restoring the marking of cyclooxygenase in the ischemic focus. Conclusion: These results suggest that the meloxicam-atorvastatin association attenuates astrocytic and microglial response in the inflammatory process after cerebral ischemia by arterial embolism, reducing neurodegeneration and restoring the morphological and functional balance of nervous tissue .
Assuntos
Animais , Feminino , Ratos , Isquemia Encefálica/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Embolia Intracraniana/complicações , Degeneração Neural/prevenção & controle , Pirróis/uso terapêutico , Tiazinas/uso terapêutico , Tiazóis/uso terapêutico , Atorvastatina , /análise , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Biomarcadores , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Estenose das Carótidas/complicações , Estenose das Carótidas/patologia , Inibidores de Ciclo-Oxigenase/administração & dosagem , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Proteína Glial Fibrilar Ácida/análise , Ácidos Heptanoicos/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inflamação , Embolia Intracraniana/patologia , Microglia/efeitos dos fármacos , Microglia/patologia , Proteínas do Tecido Nervoso/análise , Pirróis/administração & dosagem , Distribuição Aleatória , Ratos Wistar , Tiazinas/administração & dosagem , Tiazóis/administração & dosagemRESUMO
PURPOSE: To evaluate the renal function in healthy dogs submitted to nonselective and preferential COX-2 nonsteroidal anti-inflammatory drug (NSAID) therapy. METHODS: Twenty four healthy dogs were distributed into four groups (G) (n=6): ketoprofenG - treated with ketoprofen; nimesulideG - treated with nimesulid; meloxicanG - treated with meloxican; and etodolacG - treated with etodolaco. All the dogs received the NSAIDs for 10 days by oral route. Physical examination and renal function (urinalysis, urinary sodium and gamma-glutamyl transpeptidase (GGT), serum urea, creatinine, potassium and sodium, and endogenous creatinine clearance) were evaluated before, after five and ten days (T0, T5 and T10) of the treatment in all groups. RESULTS: Changes were observed in urinalysis, with a significant increase in renal cells in the urine at T5 and T10 in nimesulideG. Significant reduction in urinary sodium in nimesulideG at T5 was observed. The clearance values were lower in ketoprofenG at T10. CONCLUSIONS: Meloxicam and etodolac were the drugs that have proven to be safer for short-term therapy in healthy dogs in relation to renal function. NSAIDs ketoprofen and nimesulide should be used judiciously in dogs with renal dysfunction, since there are promoted changes in renal function.
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Animais , Cães , Feminino , Anti-Inflamatórios não Esteroides/uso terapêutico , Etodolac/uso terapêutico , Cetoprofeno/uso terapêutico , Rim/efeitos dos fármacos , Sulfonamidas/uso terapêutico , Tiazinas/uso terapêutico , Tiazóis/uso terapêutico , Administração Oral , Creatinina/urina , Inibidores de Ciclo-Oxigenase/uso terapêutico , Rim/fisiologia , Potássio/urina , Sódio/urina , Fatores de Tempo , Resultado do Tratamento , gama-Glutamiltransferase/urinaRESUMO
Purpose We aimed to compare the effect and feasibility of a combined therapy with tamsulosin hydrochloride plus meloxicam, and tamsulosin hydrochloride alone in patients with benign prostate hyperplasia symptoms and impact on nocturia and sleep quality. Materials and Methods Four hundred male patients were included in this study between 2008 and 2011. Patients were randomly divided into two groups: one received tamsulosin hydrochloride 0.4 mg (Group 1, 200 patients) and the other tamsulosin hydrochloride 0.4 mg plus meloxicam 15 mg (Group 2, 200 patients) prospectively. Patients were evaluated for benign prostate hyperplasia (BPH) symptoms according to the American Urological Association clinical guidelines and sleep quality according to Pittsburgh Sleep Quality Index (PSQI). Patients were reevaluated after three months of treatment. The International Prostatic Symptom Score (IPSS), IPSS-Quality of Life (IPSS-QoL), maximal urinary flow rates (Qmax), average urinary flow rates (AFR), post void residual urine volumes (PVR), nocturia and Pittsburgh Sleep Quality Score (PSQS) were recorded at baseline and after three months. Results Mean age was 63.3 ± 6.6 and 61.4 ± 7.5 years in groups 1 and 2, respectively (p = 0.245). There were no statistically significant differences between both groups. Also, baseline prostate specific antigen (PSA), prostate volume, creatinine, International Prostatic Symptom Score (IPSS), IPSS-Quality of Life (IPSS-QoL), maximal urinary flow rates (Qmax), average urinary flow rates (AFR), post void residual urine volumes (PVR), nocturia and Pittsburgh Sleep Quality Score (PSQS) were similar in both groups. In addition, the total IPSS, IPSS-QoL, PVR, nocturia, and PSQS were significantly lower in Group 2 compared with Group 1 after treatment (p < 0.05). Qmax and AFR were higher significantly in Group 2 compared with Group 1 after treatment (p < 0.05). Conclusions Cyclooxygenase (COX)-2 inhibitors ...