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1.
J Biochem Mol Toxicol ; 37(3): e23263, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36419233

RESUMO

The present study investigates the effects of resveratrol (RSV) on brain and liver tissues in rats with pembrolizumab (PEMB)-induced toxicity. Obtained for the study were 28 male Sprague-Dawley rats (3-4 months old) which were divided into four groups: Group 1: Control. Group 2: Administered PEMB at 5 mg/kg/day i.p. for a week. Group 3: Administered RSV orally at the dose of 20 mg/kg/day for 30 days by gavage. Group 4: Administered PEMB and RSV at 20 and 5 mg/kg/day RSV, respectively, for 30 days. The results of this study revealed that PEMB leads to a significant increase in thiobarbituric acid reactive substance (TBARS) levels and a significant decrease in glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) activities, and glutathione (GSH) levels in the liver and brain tissues. The decreased SOD, CAT, GPx activities, and GSH levels increased significantly following RSV treatment in Group 4. The PEMB treatment showed histopathological alterations associated with strong positive cysteinyl aspartic acid-protease-3 (caspase-3) immunoreactivity, while RSV treatment reduced both the expression of caspase-3 protein and the histopathological changes. RSV administration prevents the biochemical, immunological, and histological alterations induced by PEMB. It can be suggested that the lower caspase-3 immunoreactivity in the PEMB + RSV group than in the PEMB group led to an inhibition of RSV on apoptosis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Estresse Oxidativo , Ratos , Masculino , Animais , Resveratrol/farmacologia , Caspase 3/metabolismo , Ratos Sprague-Dawley , Antioxidantes/farmacologia , Catalase/metabolismo , Glutationa/metabolismo , Fígado/metabolismo , Glutationa Peroxidase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Superóxido Dismutase/metabolismo
2.
An Acad Bras Cienc ; 95(1): e20220767, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36790273

RESUMO

Monkeypox is a zoonotic viral infection that was first identified in humans in 1970 in the Democratic Republic of Congo. The cases seen again in early May 2022 have reached 78.000 as of today. On July 23, 2022, the World Health Organization decided that the monkeypox outbreak represents a public health emergency. For the early diagnosis and effective treatment of monkeypox, inter-individual transmission routes, disease symptoms, factors affecting the course of the disease, presence of another infection, prognosis, pharmacological agents used in the prophylactic treatment, and their effects, populations at risk, waste disposal protocol should be known. For this reason, our aim is to reveal the sources of transmission of the monkeypox virus from past to present, what are the signs and symptoms in patients after infection, ways of protection from the virus, the mutation status of the virus, and treatment approaches.


Assuntos
Mpox , Humanos , Mpox/diagnóstico , Mpox/epidemiologia , Pandemias , Monkeypox virus/genética , Saúde Pública , Surtos de Doenças
3.
Drug Chem Toxicol ; : 1-9, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37424396

RESUMO

Favipiravir is a nucleoside analogue antiviral drug and inhibits the replication of many RNA viruses, especially influenza viruses. Favipiravir has also been used to treat patients with mild to moderate COVID-19 disease. However, various side effects, including neurological side effects, have been reported related to the use of favipiravir. Therefore, in this study, we aimed to investigate the possible effects of favipiravir alone or in combination with vitamin C on aged rats' brain tissue and the possible mechanisms of these effects. A total of 30 rats used in the study were randomly divided into 5 equal groups and the first group was kept as the control group. High-dose (100 mg/kg) or low-dose (20 mg/kg) favipiravir was administered alone or in combination with vitamin C (150 mg/kg) to other groups. Administration of both high and low doses of favipiravir significantly increased TBARS levels in brain tissue of aged rats. Similarly, both high and low doses of favipiravir led to significant increases in Bcl-2 and caspase-3 relative mRNA expression. However, only low dose favipiravir caused a significant increase in iNOS and IL-1ß relative mRNA expression levels. Similar results were also observed in histopathological examinations. However, co-administration of vitamin C with favipiravir attenuated some of the adverse effects of favipiravir. In conclusion, in this study, it was shown that the use of favipiravir caused some adverse effects through oxidative, inflammatory and apoptotic processes in the brain tissue of aged rats, and the potential of vitamin C to alleviate these effects.

4.
Immunopharmacol Immunotoxicol ; 45(5): 521-526, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36794622

RESUMO

Background: Favipiravir (FPV), an effective antiviral agent, is a drug used to treat influenza and COVID-19 by inhibiting the RNA-dependent RNA polymerase (RdRp) of RNA viruses. FPV has the potential to increase oxidative stress and organ damage. The purpose of this study was to demonstrate the oxidative stress and inflammation caused by FPV in the liver and kidneys of rats, as well as to investigate the curative effects of vitamin C (VitC).Methods: A total of 40 Sprague-Dawley male rats were randomly and equally divided into the following five groups: 1st; Control, 2nd; FPV = 20 mg/kg, 3rd; FPV = 100 mg/kg, 4th; FPV = 20 mg/kg + VitC (150 mg/kg), and 5th; FPV = 100 mg/kg + VitC (150 mg/kg) groups. Rats were given either FPV (orally) or FPV plus VitC (intramuscular) for 14 days. Rat blood, liver, and kidney samples were collected at 15 days to be analyzed for oxidative and histological changes.Results: FPV administration resulted in an increase in proinflammatory cytokines (TNF-α and IL-6) in the liver and kidney, as well as oxidative and histopathologic damage. FPV increased TBARS levels significantly (p < .05) and decreased GSH and CAT levels in liver and kidney tissues but had no effect on SOD activity. VitC supplementation significantly reduced TNF-a, IL-6, and TBARS levels while increasing GSH and CAT levels (p < .05). Furthermore, VitC significantly attenuated FPV-induced histopathological alterations associated with oxidative stress and inflammation in the liver and kidney tissues (p < .05).Conclusion: FPV caused liver and kidney damage in rats. In contrast, co-administration of FPV with VitC improved FPV-induced oxidative, pro-inflammatory, and histopathological changes.


Assuntos
COVID-19 , Interleucina-6 , Ratos , Masculino , Animais , Interleucina-6/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Ratos Sprague-Dawley , COVID-19/metabolismo , Estresse Oxidativo , Ácido Ascórbico/farmacologia , Ácido Ascórbico/metabolismo , Ácido Ascórbico/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Fígado , Rim , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Suplementos Nutricionais
5.
Drug Chem Toxicol ; 45(6): 2463-2470, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34308744

RESUMO

The present study aimed to investigate the protective role of capsaicin in a rat model of 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD)-induced toxicity. Exposure to TCDD which is an environmental toxicant causes severe toxic effects in the animal and human tissues. Therefore, the potential protective effect of capsaicin in TCDD-induced organ damage was investigated in rats by measuring thiobarbituric acid reactive substances (TBARS) level, superoxide dismutase (SOD) activity, and glutathione (GSH) level in the heart, liver, and kidney tissues for oxidant/antioxidant balance. Thirty-two healthy adults (250-300 g weight and 3-4 months old) male Wistar albino rats were randomly distributed into four equal groups (n = 8): Control, CAP, TCDD, TCDD + CAP. A dose of 2 µg/kg TCDD or a dose of 25 mg/kg capsaicin were dissolved in corn oil and orally administered to the rats for 30 days. The results indicated that TCDD-induced oxidative stress by increasing the level of TBARS and by decreasing the levels of GSH, and SOD activity in the tissues of rats. However, capsaicin treatment was significantly decreased TBARS levels and was significantly increased GSH level and SOD activity (p < 0.05). In addition, capsaicin (25 mg/kg) significantly attenuated TCDD-induced histopathological alteration associated with oxidative stress in the heart, liver, and kidney tissues (p < 0.05). As capsaicin regulates oxidative imbalance and attenuates histopathological alterations in the rat tissues, it may be preventing agents in TCDD toxicity.


Assuntos
Dioxinas , Dibenzodioxinas Policloradas , Animais , Masculino , Ratos , Antioxidantes/farmacologia , Capsaicina/farmacologia , Óleo de Milho/farmacologia , Dioxinas/farmacologia , Glutationa/metabolismo , Oxidantes , Estresse Oxidativo , Dibenzodioxinas Policloradas/toxicidade , Ratos Wistar , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico
6.
Turk J Med Sci ; 52(6): 1802-1813, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36945968

RESUMO

BACKGROUND: Intravesical BCG treatment fails inexplicably in 30%-45% of patients for high-grade nonmuscle-invasive bladder cancer (NMIBC). We aimed to investigate the role of PD-1/PD-L1 interaction on BCG failure of high-grade NMIBC and to identify biomarkers for predicting BCG responsive cases. METHODS: Thirty BCG responsive and 29 nonresponsive NMIBCs were included in the study. Expressions of PDL1(SP-263), MSH2, MSH6, PMS2, and MLH1 were evaluated on pre- and post-BCG transurethral resection (TUR-B) specimens by immunohistochemistry. PD-L1(SP-263) expression was categorised as negative/low, high. DNA mismatch repair protein (MMR) expressions were classified as "reduced" if ≤30% of nuclei stained, "preserved" if >30% of nuclei stained. Microsatellite instability (MSI) testing was performed by PCR using five mononucleotide markers. RESULTS: Reduced DNA MMR protein expression was found to be significantly higher in the pretreatment biopsies of BCG-responsive group than the BCG nonresponsive tumour group (p = 0.022). PD-L1 expression did not show any significant difference between the pre- and posttreatment TUR-B specimens of the BCG nonresponsive tumour group or between the pretreatment TUR-B specimens of BCG nonresponsive and the BCG responsive groups (p = 0.508, p = 0.708, respectively). DISCUSSION: Immune escape of tumour cells by PD-1/PD-L1 interaction does not seem to have any role in BCG failure of NMIBCs. Reduced MMR expression may help to determine cases that will respond well to BCG therapy. A better antitumour activity of BCG in NMIBCs with reduced MMR expression may be related to the ongoing accumulation of cancer neoantigens in correlation with increased tumour mutation load as a result of DNA repair defects.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Instabilidade de Microssatélites , Receptor de Morte Celular Programada 1/genética , Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Antígeno B7-H1 , Evasão Tumoral , Biomarcadores Tumorais/metabolismo
7.
Metab Brain Dis ; 36(2): 339-349, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33165734

RESUMO

Neurotoxicity caused by cisplatin is a major obstacle during chemotherapy. Oxidative stress and inflammation are considered the primary mechanism behind neuronal damage which affects the continuing chemotherapy regimen. Agomelatine was recently described as a neuroprotective compound against toxic insults in the nervous systems. It is an analog of the well-known antioxidant and anti-inflammatory compound melatonin and currently used for depression and sleep disturbances. In the current study, we investigated the possible neuroprotective role of agomelatine against cisplatin-induced oxidative, inflammatory, and behavioral alterations in male rats. Our results show that agomelatine prevented cisplatin-induced neurotoxicity in the HT-22 mouse hippocampal neuronal cell line. Additionally, agomelatine treatment inhibited cisplatin-induced behavioral deficits and neuronal integrity in vivo. For the evaluation of the effect of agomelatine on oxidative stress and inflammation, GSH, MDA, TNF, and IL-6 levels were analyzed in HT-22 cells and hippocampal tissues. Agomelatine significantly attenuated oxidative stress and inflammation due to the cisplatin insult in vitro and in vivo. Also, agomelatine treatment ameliorated the neuronal pathology in the hippocampus, which is strongly related to cognition and memory. Taken together, our results indicate that in males, the neuroprotective effect of agomelatine is mediated through its antioxidant and anti-inflammatory actions abrogating functional deficits.


Assuntos
Acetamidas , Antineoplásicos , Cisplatino , Hipocampo , Neuroproteção , Fármacos Neuroprotetores , Animais , Camundongos , Acetamidas/farmacologia , Antineoplásicos/toxicidade , Antioxidantes/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Linhagem Celular , Cisplatino/toxicidade , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Masculino , Ratos
8.
Stroke ; 47(11): 2776-2782, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27703089

RESUMO

BACKGROUND AND PURPOSE: ABC/2 is still widely accepted for volume estimations in spontaneous intracerebral hemorrhage (ICH) despite known limitations, which potentially accounts for controversial outcome-study results. The aim of this study was to establish and validate an automatic segmentation algorithm, allowing for quick and accurate quantification of ICH. METHODS: A segmentation algorithm implementing first- and second-order statistics, texture, and threshold features was trained on manual segmentations with a random-forest methodology. Quantitative data of the algorithm, manual segmentations, and ABC/2 were evaluated for agreement in a study sample (n=28) and validated in an independent sample not used for algorithm training (n=30). RESULTS: ABC/2 volumes were significantly larger compared with either manual or algorithm values, whereas no significant differences were found between the latter (P<0.0001; Friedman+Dunn's multiple comparison). Algorithm agreement with the manual reference was strong (concordance correlation coefficient 0.95 [lower 95% confidence interval 0.91]) and superior to ABC/2 (concordance correlation coefficient 0.77 [95% confidence interval 0.64]). Validation confirmed agreement in an independent sample (algorithm concordance correlation coefficient 0.99 [95% confidence interval 0.98], ABC/2 concordance correlation coefficient 0.82 [95% confidence interval 0.72]). The algorithm was closer to respective manual segmentations than ABC/2 in 52/58 cases (89.7%). CONCLUSIONS: An automatic segmentation algorithm for volumetric analysis of spontaneous ICH was developed and validated in this study. Algorithm measurements showed strong agreement with manual segmentations, whereas ABC/2 exhibited its limitations, yielding inaccurate overestimations of ICH volume. The refined, yet time-efficient, quantification of ICH by the algorithm may facilitate evaluation of clot volume as an outcome predictor and trigger for surgical interventions in the clinical setting.


Assuntos
Hemorragia Cerebral/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Humanos , Processamento de Imagem Assistida por Computador/normas , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/normas
9.
Arch Pharm (Weinheim) ; 348(1): 55-61, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25581679

RESUMO

The current structure-activity relationship of profens (i.e., 2-arylpropionic acid derivatives, a class of non-steroidal anti-inflammatory drugs) discusses the importance of α-monomethyl substitution on these compounds, since the activities obtained through their corresponding arylacetic acid derivatives (i.e., α-demethylated derivatives) or α,α-dimethyl-substituted compounds are less than what is observed for the parent profens. Unfortunately, this implies a generalization in structure-activity relationships of profens in such a way that a mono-(non-methyl)alkyl group or dialkyl substituent replaced at the α-position of a profen analogue results in abolished activity. Therefore, within this study, we aimed to question this generalization employing ibuprofen, flurbiprofen, and naproxen as model compounds. A series of α-(non-methyl)alkyl-substituted ibuprofen and flurbiprofen analogues as well as α,α-dialkyl-substituted ibuprofen, flurbiprofen, and naproxen derivatives were synthesized and screened for their potential to inhibit cyclooxygenase enzymes. In addition, since profens have negligible potential to inhibit lipoxygenase enzymes, the effect of such derivatization was also questioned in lipoxygenase inhibition assays. The findings only partially agreed with the current structure-activity approach of profens and the activity results of some compounds were found as beyond ordinary.


Assuntos
Inibidores de Ciclo-Oxigenase/síntese química , Inibidores de Ciclo-Oxigenase/farmacologia , Desenho de Fármacos , Propionatos/síntese química , Propionatos/farmacologia , Araquidonato 5-Lipoxigenase/metabolismo , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Flurbiprofeno/síntese química , Flurbiprofeno/farmacologia , Ibuprofeno/análogos & derivados , Ibuprofeno/síntese química , Ibuprofeno/farmacologia , Inibidores de Lipoxigenase/síntese química , Inibidores de Lipoxigenase/farmacologia , Estrutura Molecular , Naproxeno/síntese química , Naproxeno/farmacologia , Relação Estrutura-Atividade
10.
Bioorg Med Chem ; 22(19): 5141-54, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25189690

RESUMO

Hydroxylated 6H-benzo[c]chromen-6-one derivatives (i.e., urolithins) are the main bioavailable metabolites, and biomarkers of ellagitannins present in various nutrition. Although these dietaries, the sources of urolithins, are employed in folk medicine as cognitive enhancer in the treatment of Alzheimer's Disease, urolithins have negligible potential to inhibit acetylcholinesterase and butyrylcholinesterase enzymes, the validated targets of Alzheimer's Disease. Therefore, within this research, a series of 6H-benzo[c]chromen-6-one, and 7,8,9,10-tetrahydro-benzo[c]chromen-6-one derivatives has been designed, synthesized, and their biological activities were evaluated as potential acetylcholinesterase and butyrylcholinesterase inhibitors. The compounds synthesized exerted comparable activity in comparison to rivastigmine, galantamine, and donepezil both in in vitro and in vivo studies.


Assuntos
Acetilcolinesterase/metabolismo , Benzopiranos/farmacologia , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Desenho de Fármacos , Benzopiranos/síntese química , Benzopiranos/química , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade
11.
J Nucl Med ; 65(6): 872-879, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38604763

RESUMO

PET using 68Ga-labeled fibroblast activation protein (FAP) inhibitors (FAPIs) holds high potential for diagnostic imaging of various malignancies, including lung cancer (LC). However, 18F-FDG PET is still the clinical gold standard for LC imaging. Several subtypes of LC, especially lepidic LC, are frequently 18F-FDG PET-negative, which markedly hampers the assessment of single pulmonary lesions suggestive of LC. Here, we evaluated the diagnostic potential of static and dynamic 68Ga-FAPI-46 PET in the 18F-FDG-negative pulmonary lesions of 19 patients who underwent surgery or biopsy for histologic diagnosis after PET imaging. For target validation, FAP expression in lepidic LC was confirmed by FAP immunohistochemistry. Methods: Hematoxylin and eosin staining and FAP immunohistochemistry of 24 tissue sections of lepidic LC from the local tissue bank were performed and analyzed visually. Clinically, 19 patients underwent static and dynamic 68Ga-FAPI-46 PET in addition to 18F-FDG PET based on individual clinical indications. Static PET data of both examinations were analyzed by determining SUVmax, SUVmean, and tumor-to-background ratio (TBR) against the blood pool, as well as relative parameters (68Ga-FAPI-46 in relation to18F-FDG), of histologically confirmed LC and benign lesions. Time-activity curves and dynamic parameters (time to peak, slope, k 1, k 2, k 3, and k 4) were extracted from dynamic 68Ga-FAPI-46 PET data. The sensitivity and specificity of all parameters were analyzed by calculating receiver-operating-characteristic curves. Results: FAP immunohistochemistry confirmed the presence of strongly FAP-positive cancer-associated fibroblasts in lepidic LC. LC showed markedly elevated 68Ga-FAPI-46 uptake, higher TBRs, and higher 68Ga-FAPI-46-to-18F-FDG ratios for all parameters than did benign pulmonary lesions. Dynamic imaging analysis revealed differential time-activity curves for LC and benign pulmonary lesions: initially increasing time-activity curves with a decent slope were typical of LC, and steadily decreasing time-activity curve indicated benign pulmonary lesions, as was reflected by a significantly increased time to peak and significantly smaller absolute values of the slope for LC. Relative 68Ga-FAPI-46-to-18F-FDG ratios regarding SUVmax and TBR showed the highest sensitivity and specificity for the discrimination of LC from benign pulmonary lesions. Conclusion: 68Ga-FAPI-46 PET is a powerful new tool for the assessment of single 18F-FDG-negative pulmonary lesions and may optimize patient stratification in this clinical setting.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares , Tomografia por Emissão de Pósitrons , Humanos , Masculino , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Pessoa de Meia-Idade , Idoso , Tomografia por Emissão de Pósitrons/métodos , Idoso de 80 Anos ou mais , Compostos Radiofarmacêuticos , Adulto , Quinolinas
12.
Nuklearmedizin ; 62(2): 55-60, 2023 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-36706783

RESUMO

AIM: In various medical societies, dedicated young talent sections provide an important basis for promoting young members. However, the German Society of Nuclear Medicine (DGN) had not yet implemented such a section. Therefore, the aim of this work was to assess the opinion of nuclear medicine professionals in Germany on establishing a young talent section within the DGN ("Young DGN"). METHODS: An initiative group of young DGN members developed a survey questionnaire comprising 18 questions. The questionnaire was initially sent as a PDF to the members of the DGN University Committee (Hochschulausschuss) by e-mail on 10/12/2021. As an online survey, the questionnaire was then emailed at four additional time points between 12/23/2021 and 3/18/2022 via the DGN eBrief and on 2/23/2022 to the members of the mailing list of the Berufsverband Deutscher Nuklearmediziner (BDN). RESULTS: The survey closed on 3/31/2022 with 111 responses (n=104 online surveys, n=7 PDFs). The median age of participants was 32.5 years (range, 20-80). 86% of participants indicated that they were interested in a Young DGN section, of which 67% were willing to participate. 79% indicated that nuclear medicine was an exciting field for them. 96% expressed interest in additional education offers and 60% in the establishment of a mentoring program. 75% believed that Young DGN would improve the visibility of the specialty. CONCLUSION: The survey results indicate strong support for the establishment of a young talent section within the DGN among nuclear medicine professionals in Germany. A large proportion of those who participated in the survey would envision active involvement. There was a particular consensus on the desire to expand the range of education and training activities.


Assuntos
Medicina Nuclear , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Sociedades Médicas , Cintilografia , Inquéritos e Questionários , Alemanha , Internet
13.
Turk J Pharm Sci ; 19(1): 1-8, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35227035

RESUMO

Objectives: Thioacetamide (TAA) is an organosulfur, white crystalline compound having liver injury. However, it shows toxic effects on many organs. The reverts the oxidative stress created by TAA on the heart and kidney, and decreased lipid peroxide peroxidation back with antioxidant-properties nerolidol (NRL). This study hypothesized that NRL treatment a potential ameliorate nephrotoxicity and cardiotoxicity caused by TAA. Materials and Methods: Thirty-two Wistar Albino male rats (3-4 months old and 280-300 g in weight) were divided into four groups. (a) Control, (b) TAA was administered 200 mg/kg i.p. twice a weekly (c) NRL was orally administered at the dose of 100 mg/kg per every other day by gavages. (d) TAA and NRL-treated groups were assigned 200 mg/kg TAA and 100 mg/kg NRL for three weeks. Results: As a result of these dose administration thiobarbituric acid reactive substances (TBARS) levels, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPx) levels were detected. The results were shown that TAA leads to a significant rise in TBARS level and a significant decrease in GPx, CAT, SOD, and GSH levels in the heart and kidney tissue according to the control group. The finding of this study the NRL treatment reduced TBARS levels and increased antioxidant level. Administration of NRL prevents the biochemical and histopathological alterations induced by TAA. Conclusion: The findings of this study show that the antioxidant activity of NRL can protect against biochemical and histological damage caused by TAA in heart and kidney tissue.

14.
Turk Neurosurg ; 32(5): 732-739, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35147962

RESUMO

AIM: To investigate the histological and biochemical neuroprotective effects of secukinumab (SEC) on cerebral ischemia-reperfusion (IR) injury in Sprague-Dawley male rats. MATERIAL AND METHODS: A total of 28 Sprague-Dawley male rats were randomly and equally divided into the following four groups: Sham, SEC, IR, and IR+SEC groups. Bilateral common carotid arteries were simultaneously separated and blocked for 15 minutes using two vascular mini clips in the IR and IR+SEC groups. The surgical procedure was similarly repeated in the Sham and SEC groups, but the carotid arteries were not clipped. Secukinumab was administered intraperitoneally to the SEC and IR+SEC groups once a week after the surgical procedure. Rat brain tissues were collected for biochemical analysis and histopathological examination 14 days after surgery. RESULTS: Cerebral IR caused abnormal changes in oxidative stress parameters by increasing the malondialdehyde (MDA) level and by decreasing the glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels. IR also induced histopathological alterations, such as vascular congestion, hemorrhage, and cell infiltration in the rat brain tissues. Secukinumab treatment significantly decreased the MDA levels and increased the GPx, GSH, CAT, and SOD levels. In addition, secukinumab partially prevented histopathological alterations in the brain tissues. The percentage of immunohistochemically Caspase-3-positive cells was high in the IR group; however, SEC decreased the density of cells stained with Caspase-3. CONCLUSION: IR injury was found to cause oxidative and histopathological changes in rat brain tissues, and secukinumab treatment ameliorated these pathological effects. Therefore, secukinumab may be useful to prevent and treat oxidative stressinduced brain damage in patients with ischemic stroke.


Assuntos
Anticorpos Monoclonais Humanizados , Isquemia Encefálica , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Animais , Masculino , Ratos , Isquemia Encefálica/tratamento farmacológico , Caspase 3 , Catalase/metabolismo , Infarto Cerebral , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Malondialdeído , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo , Ratos Sprague-Dawley , Reperfusão , Traumatismo por Reperfusão/patologia , Superóxido Dismutase/metabolismo
15.
Turk Patoloji Derg ; 37(2): 93-105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33973640

RESUMO

Aziz Sancar, Nobel Prize winning Turkish scientist, made several discoveries which had a major impact on molecular sciences, particularly disciplines that focus on carcinogenesis and cancer treatment, including molecular pathology. Cloning the photolyase gene, which was the initial step of his work on DNA repair mechanisms, discovery of the "Maxicell" method, explanation of the mechanism of nucleotide excision repair and transcription-coupled repair, discovery of "molecular matchmakers", and mapping human excision repair genes at single nucleotide resolution constitute his major research topics. Moreover, Sancar discovered the cryptochromes, the clock genes in humans, in 1998, and this discovery led to substantial progress in the understanding of the circadian clock and the introduction of the concept of "chrono-chemoterapy" for more effective therapy in cancer patients. This review focuses on Aziz Sancar's scientific studies and their reflections on molecular pathology of neoplastic diseases. While providing a new perspective for researchers working in the field of pathology and molecular pathology, this review is also an evidence of how basic sciences and clinical sciences complete each other.


Assuntos
Pesquisa Biomédica/história , Neoplasias/história , Prêmio Nobel , Patologia Molecular/história , Clonagem Molecular , Criptocromos/genética , Criptocromos/metabolismo , Reparo do DNA , Desoxirribodipirimidina Fotoliase/genética , Desoxirribodipirimidina Fotoliase/metabolismo , Regulação Neoplásica da Expressão Gênica , História do Século XX , História do Século XXI , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia
16.
Eur J Radiol ; 133: 109390, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33181485

RESUMO

PURPOSE: This study aims to compare three guidelines according to their diagnostic accuracy in the management of thyroid nodules. METHODS: A total of 540 patients with 597 thyroid nodules were enrolled in this study. Sonographic images were classified and scored with the American Thyroid Association (ATA-2015), American College of Radiology (ACR), and European Thyroid Association (EU) Thyroid Imaging, Reporting, and Data Systems (ACR-TIRADS and EU-TIRADS) guidelines. Fine-needle aspiration biopsy (FNAB) was performed, and cytopathological results were reported with the Bethesda system. Outcomes of these three classification systems were then correlated with Bethesda results. RESULTS: FNAB procedures revealed a total of 447 benign and 45 malignant nodules. With guideline dedicated FNAB criteria; 38 malignant nodules could have been diagnosed with ATA-2015, which is followed by 34 nodules with ACR-TIRADS, and 31 nodules with EU-TIRADS. Nonetheless, 301 benign nodules would have been biopsied with ATA-2015, 143 benign nodules with ACR-TIRADS, 222 benign nodules with EU-TIRADS. The accuracy rate was found to be highest with ACR-TIRADS (59.93 %); while 55.20 % with ATA-2015 and 51.25 % with EU-TIRADS. The sensitivity and specificity ratios of these guidelines were as follows; ATA-2015 (82.22, 53.47), ACR-TIRADS (48.89, 60.63), and EU-TIRADS (86.67, 48.99). A total of 23 nodules (3.8 %) could not be classified with ATA-2015. CONCLUSION: Diagnostic strengths, unnecessary recommended FNAB rates, and categorization capabilities differ among various guidelines. Clinicians and interventional radiologists should keep in mind these features in the management of thyroid nodules.


Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Biópsia por Agulha Fina , Humanos , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia , Estados Unidos
17.
Turk Patoloji Derg ; 36(2): 93-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189322

RESUMO

Biobanks are units where high quality and long-term protection of biomaterials is maintained. This system, in which biological materials and data are systematically recorded and stored, is a unique resource for the study of the pathophysiology of disease, the development of diagnostic biomarkers, and working with human tissues for the potential discovery of targeted therapeutic agents. At this point, the pathology unit plays a unifying and complementary role between the clinical and core disciplines and offers optimal management of the patients' biomaterials for diagnostic and research projects. The aim of this article is to present general information with regard to a biobank constructed for the storage of tumor tissue and blood biospecimens. Ethical issues (informed consent, protection of confidentiality and privacy, and secondary use of biospecimens) and the information technology system (collection, systematic recording, backup and protection of clinical information) are important issues in biobanking. The selection of freezers to be used in storage (mechanical freezers, liquid-vapor nitrogen tanks), and if mechanical freezers are preferred the establishment of the relevant infrastructure and support team (such as additional power units for protection from power outages), the preservation of materials by aliquoting in different freezers, ensuring financing so as to afford the cost of the infrastructure, and implementation of all these dynamics while adhering to international guidelines are of the utmost importance.


Assuntos
Bancos de Espécimes Biológicos , Patologia , Humanos
18.
Braz. J. Pharm. Sci. (Online) ; 58: e21219, 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1420483

RESUMO

Abstract The aim of the present study is to investigate the cardioprotective effects of 18ß-glycyrrhetinic acid (18ß -GA) against oxidative and histological damage caused by global cerebral ischemia/ reperfusion (I/R) in C57BL/J6 mice. All male mice (n:40) were randomly divided into four groups: (1) sham-operated (Sham), (2) I/R, (3) 18ß-GA, and (4) 18ß -GA+I/R. Ischemia was not applied to the sham and 18ß-GA groups. In the I/R group, the bilateral carotid arteries were clipped for 15 min to induce ischemia, and the mice were treated with the vehicle for 10 days. In the 18ß-GA group, the mice were given 18ß-GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the 18ß-GA+I/R group, the ischemic procedure performed to the I/R model was applied to the animals and afterwards they were intraperitoneally (i.p.) treated with 18ß-GA (100 mg/kg) for 10 days. It was found that global cerebral I/R increased TBARS levels and decreased antioxidant parameters. The 18ß-GA treatment decreased the level of TBARS and increased GSH, GPx, CAT, SOD activities. Also, the control group cardiac tissue samples were observed to have a normal histological appearance with the Hematoxylin-Eosin staining method. Histopathological damage was observed in the heart tissue samples belonging to the I/R group. The 18ß-GA treatment ameliorates oxidative and histological injury in the heart tissue after global ischemia reperfusion, and may be a beneficial alternative treatment


Assuntos
Animais , Masculino , Camundongos , Cardiotônicos/efeitos adversos , Reperfusão/efeitos adversos , Isquemia Encefálica/patologia , Coloração e Rotulagem/instrumentação , Estresse Oxidativo , Antioxidantes/farmacologia
20.
Head Neck Pathol ; 10(2): 252-5, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26292650

RESUMO

Pagetoid spread, is used to define intraepithelial spread of cancer cells, when a massive carcinoma is identified beneath the basal membrane. There are only few reports of pagetoid spread at the head and neck region. Herein a 74 year old male patient with bilateral transglottic laryngeal high grade malignant epithelial tumor with pagetoid spread is presented. The tumor was located at the submucosa and there was spread of the CK7 and CK19 positive tumor cells into the non neoplastic mucosa, which was CK5/6 positive, sparing the basement membrane, creating a typical pagetoid pattern. Radiographic and positron emission tomography scan examination of the patient was unremarkable at presentation other than the laryngeal and neck lesions; but extensive systemic metastasis developed at 6 months following operation. To the best of our knowledge no epithelial malignancy with pagetoid spread was described at the larynx. Pagetoid spread may be a hallmark of very aggressive behavior in laryngeal carcinoma.


Assuntos
Carcinoma/patologia , Neoplasias Laríngeas/patologia , Metástase Neoplásica/patologia , Idoso , Biomarcadores Tumorais/análise , Humanos , Imuno-Histoquímica , Masculino
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