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1.
J Med Biochem ; 42(3): 376-382, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37814616

RESUMO

Background: Routine screening for hereditary disorders in newborns includes screening for treatable metabolic and endocrine disorders, such as biotidinase deficiency, galactosemia, maple syrup urine disease, hypothyroidism, and cystic fibrosis. Incorrect test results may be encountered due to the use of vitamin K1. To investigate the interference effect of vitamin K1 on neonatal screening tests and to raise awareness of erroneous measurements. Methods: Heel blood samples were taken from 25 newborns born in a neonatal intensive care unit. Dry blood C0, C2, C3, C4, C4DC, C5:1, C5OH, C5DC, C6, C6DC, C8, C8:1, C8DC, C10, C10:1, C10DC, C12, C14, C14:1, C14:2, C16, C16:1, C18, C18:1, C18:2, C18:OH, methylglutaryl, valine, leucine/isoleucine, methionine, phenylalanine, argininosuccinic acid, aspartate, alanine, arginine, citrulline, glycine, ornithine, and glutamate tests were studied using the tandem mass spectrometry (MS) method. The results of the heel blood samples obtained before and after the application of vitamin K1 (Phyto menadione) were compared. Results: In two studies conducted with in vitro and in vivo tests, C0, C2, C3, C4, C4DC, C5, C5OH, C6, C8, C10, C10:1, C14, C16, C16:1, C18, C18:1, methylglutaryl, phenylalanine, argininosuccinic acid, tyrosine, aspartate, arginine, citrulline, glycine, and glutamine were all significantly elevated (p < 0.05). Conclusions: Heel blood samples may yield false results due to vitamin K1 administration. In the case of doubtful results, a new sample should be taken and the measurement should be repeated.

2.
Biotech Histochem ; 98(1): 62-68, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35930239

RESUMO

Propofol and dexmedetomidine (DEX) are widely used for anesthesia and sedation. We investigated the effects of propofol and DEX separately and in combination on the metabolic profile of carnitine in cultured normal human bronchial epithelial cells (BEAS-2B). Cells of the propofol group were cultured with 2 µg/ml propofol in RPMI-1640 medium. Cells of the DEX group were cultured with 0.2 ng/m DEX in RPMI-1640 medium. Cells of the propofol + DEX group were cultured with 2 µg/ml propofol + 0.2 ng/ml DEX in RPMI-1640 medium. The control group was untreated. Cells were incubated for 3 h following treatments. The effects of the drugs on cell viability were assessed using the MTT method and by microscopic examination following staining with acridine orange/ethidium bromide. The effects of drugs on carnitine, acetyl carnitine and 25 acylcarnitine derivative profiles were analyzed using liquid chromatography-tandem mass spectrophotometry. Neither propofol nor DEX affected cell viability. Administration of propofol, DEX or propofol + DEX to BEAS-2B cells caused no significant change in the concentrations of carnitine and acylcarnitine derivatives compared to the control group. We found that propofol and DEX exhibit no negative effects on the carnitine metabolism by BEAS-2B cells in vitro at clinically relevant concentrations. Our findings establish a baseline for clinical studies of the effects of propofol and DEX on carnitine metabolism.


Assuntos
Dexmedetomidina , Propofol , Humanos , Propofol/farmacologia , Propofol/uso terapêutico , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Carnitina/farmacologia , Células Epiteliais
3.
Arch. endocrinol. metab. (Online) ; 67(4): e000621, Mar.-Apr. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1439234

RESUMO

ABSTRACT Objective: The effects of the COVID-19 pandemic on the control of diabetes mellitus in patients are largely unknown. In this study we aimed to analyze the impact of the pandemic and the ensuing lockdown on the management of type 2 diabetes mellitus. Subjects and methods: A total of 7,321patients with type 2 diabetes mellitus (4,501 from the pre-pandemic period, 2,820 from the post-pandemic period) were studied retrospectively. Results: The admission of patients with diabetes melitus (DM) decreased significantly during the pandemic (4,501 pre-pandemic vs. 2,820 post-pandemic; p < 0.001). The mean age of patients was statistically lower (51.5 ± 14.0 vs. 49.7 ± 14.5 years; p < 0.001), and the mean glycated hemoglobin (A1c) level was significantly higher (7.9% ± 2.4% vs. 7.3% ± 1.7%; p < 0.001) in the post-pandemic period than in the pre-pandemic. The female/male ratio was similar in both periods (59.9%/40.1% for pre-pandemic, 58.6%/41.4% for post-pandemic; p = 0.304). As calculated by month the pre-pandemic rate of women was higher only in January (53.1% vs. 60.6%, p = 0.02). Mean A1c levels were higher in the postpandemic period than in the same month of the previous year, excluding July and October (p = 0.001 for November, p < 0.001 for others). Postpandemic patients admitted to the outpatient clinic were significantly younger than prepandemic visits for July (p = 0.001), August (p < 0.001) and December (p < 0.001). Conclusion: The lockdown had detrimental effects on blood sugar management in patients with DM. Hence, diet and exercise programs should be adapted to home conditions, and social and psychological support should be provided to patients with DM.

4.
Curr HIV Res ; 20(3): 228-235, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111751

RESUMO

BACKGROUND: Increasing the sensitivity and availability of liquid chromatography tandem mass spectrometry (LC-MS/MS) devices may provide advantages in terms of revealing the changes in metabolic pathways in HIV-positive patients and elucidating the physiopathology. INTRODUCTION: The aim of this study was to determine the difference in amino acid levels between HIV-positive patients and healthy individuals by using LC-MS / MS and investigate its relationship with HIV infection. MATERIAL AND METHODS: Concentrations of 36 different amino acids and their derivatives were measured and compared in venous plasma samples from 24 HIV-positive patients and 24 healthy individuals by using the LC-MS/MS method (Shimadzu North America, Columbia, MD, USA). RESULTS: HIV-positive subjects had significantly lower alanine, 1-methyl-L-histidine, valine, aspartate, cysteine, cystine, methionine, lysine, glutamine, imino acid, tyrosine, tryptophan, threonine, sarcosine, and argininosuccinic acid and significantly higher 3-methyl-L -histidine, asparagine, glutamate, and carnosine levels as compared to healthy controls. No significant differences were detected in other amino acids. CONCLUSION: The significant differences in amino acid profile between HIV-positive and healthy subjects may represent an auxiliary biomarker of cellular damage in asymptomatic HIV-positive patients that may be examined in more detail in further studies. It may also provide guidance for symptomatic cases in terms of the association between symptoms, clinical manifestations, and deficiency or excess of certain amino acids in the context of the complete metabolomics record of HIVpositive patients.


Assuntos
Aminoácidos , Infecções por HIV , Aminoácidos/sangue , Infecções por HIV/sangue , Humanos
5.
J Shoulder Elbow Surg ; 31(10): e490-e497, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35483566

RESUMO

BACKGROUND: Oxidative stress occurs as a result of the disruption of the balance between the formations of reactive oxygen species and antioxidant defense mechanisms during the conversion of nutrients into energy. Increased body oxidative stress has been reported to be involved in the etiology of several degenerative and chronic diseases. We hypothesized that the body oxidative stress level is higher in patients with atraumatic degenerative rotator cuff tear than that in healthy individuals. METHODS: The patients who underwent arthroscopic repair for atraumatic, degenerative rotator cuff tear were prospectively evaluated. A total of 30 patients (group 1, 19 females and 11 males; mean age: 57.33 ± 6.96 years; range: 50-77 years) and 30 healthy individuals (group 2, 18 females and 12 males; mean age: 56.77 ± 6 years; range: 51-72 years) were included in the study. The Constant and American Shoulder and Elbow Surgeons scoring systems were used to evaluate the clinical outcomes. Serum oxidative stress parameters of the patients and the control group were biochemically evaluated. Accordingly, thiol/disulfide (DS) balance (DS/native thiol [NT], DS/total thiol [TT]), Total Oxidant Status (TOS), oxidative stress index, and nuclear factor erythroid-2-associated factor-2 values were used as the biochemical parameters indicating an increase in the serum oxidative stress level. Total antioxidant status and NT/TT values served as the biochemical parameters indicating a decrease in the serum oxidative stress level. RESULTS: The study follow-up duration was 12 months. A statistically significant increase was observed in American Shoulder and Elbow Surgeons and Constant scores of patients who underwent arthroscopic rotator cuff repair relative to that during the preoperative period (P = .01). The values of biochemical parameters (DS/NT, DS/TT, TOS, oxidative stress index, and nuclear factor erythroid-2-associated factor-2), which indicated an increase in the serum oxidative stress, were significantly higher in preoperative patients than those in postoperative patients, albeit the control group values were significantly lower than those of the postoperative patients. The biochemical parameters (NT/TT and total antioxidant status) indicating a decrease in the serum oxidative stress levels were significantly higher in the postoperative patients than those in the preoperative patients and significantly lower than those in the control group. CONCLUSION: High levels of markers indicating an increase in the serum oxidative stress in patients with degenerative rotator cuff rupture suggested that TOS may be involved in the etiopathogenesis of rotator cuff degeneration. Although the oxidative load decreases during the postoperative period, the fact that it is still higher than that in healthy individuals supports this claim.


Assuntos
Lesões do Manguito Rotador , Antioxidantes , Dissulfetos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxidantes , Estresse Oxidativo , Espécies Reativas de Oxigênio , Lesões do Manguito Rotador/patologia , Lesões do Manguito Rotador/cirurgia , Compostos de Sulfidrila , Resultado do Tratamento , Estados Unidos
6.
Comb Chem High Throughput Screen ; 25(1): 114-122, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33280590

RESUMO

BACKGROUND: Neurofibromatosis, also known as Von Recklinghausen disease, is a systemic and progressive genetic disease that primarily affects the skin, eyes, nervous system, and bones. The disease can occur in a variety of ways and can vary in individuals. Metabolomic-based research using blood samples has enabled new diagnostic methods to be used in the diagnosis of various diseases, especially cancer. Among the metabolites, profiling of plasma free amino acids (PFAA) is a promising approach because PFAAs bind all organ systems and play an important role in the metabolism. OBJECTIVE: This study aimed to determine the characteristics of PFAA profiles in neurofibromatosis patients and the possibility of using them for early detection and treatment of the disease. METHODS: Patients with a diagnosis of Neurofibromatosis Type I confirmed by genetic analysis and healthy individuals of the same age group without any disease were included in the study. We analysed the nineteen plasma free amino acids (phenylalanine, proline, threonine, arginine, asparagine, cystine, valine, glutamate, tyrosine, serine, glutamine, glycine, tryptophane, leucine, lysine, methionine, isoleucine, aspartate and alanine) from neurofibromatosis Type I patients and control group by liquid chromatography tandem mass spectrometry (LC-MS/MS) in Metabolism Laboratory of Harran University Research and Application Hospital. The results of the plasma free amino acid levels were divided into 3 groups as essential, semi-essential, and non-essential. The differences in amino acid levels between groups were determined. RESULTS: The levels of eight amino acids (methionine, arginine, cystine, glutamine, proline, asparagine, serine, aspartate) were significantly altered in patients with neurofibromatosis type 1. In essential amino acids, methionine levels were significantly higher in the patient group than control group. While the levels of arginine and glutamine in semi-essential amino acids were statistically significantly higher in the patient group, a significant decrease was observed in cystine and proline levels compared to the control group's amino acid levels. In the non-essential amino acids group, asparagine, serine and aspartate amino acid levels were significantly higher in the patient group compared to the control group. CONCLUSION: The current research predicates that eight amino acids, namely methionine, arginine, cystine, glutamine, proline, asparagine, serine, aspartate can be considered to be valuable biomarkers for neurofibromatosis type I. This present study is the first to build models for neurofibromatosis Type I screening using plasma free amino acids and the amino acid profile will be able to guide the prediction of the complications that may occur during the course of the disease.


Assuntos
Neurofibromatose 1 , Alanina , Aminoácidos/metabolismo , Arginina , Cromatografia Líquida , Histidina , Humanos , Leucina , Neurofibromatose 1/diagnóstico , Projetos Piloto , Espectrometria de Massas em Tandem , Tirosina
7.
Int Immunopharmacol ; 101(Pt B): 108358, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34782273

RESUMO

OBJECTIVES: This study investigated the effects of tocilizumab on the prevention and treatment of experimental necrotizing enterocolitis (NEC) in newborn rats. METHODS: Forty-two newborn Sprague-Dawley rats were randomly separated into three groups: NEC + placebo, NEC + tocilizumab, and the control group. NEC + placebo and NEC + tocilizumab groups were given 1 mg/kg lipopolysaccharide intraperitoneally once only on the first day, were fed with a special rodent formula every 3 h, inhaled 100% CO2 for 10 min, were exposed to cold stress at + 4 °C for 5 min, and 97% O2 for 5 min twice a day for 3 days. NEC + tocilizumab group was treated with 8 mg/kg/day tocilizumab (Actemra®) intraperitoneally, while NEC + placebo group was given intraperitoneal 0.9% saline at a dose of 2 mL/kg/day from the first day to the end of the study. All newborn rats were sacrificed on day 4. Specimens were taken for histopathologic, immunohistochemical and biochemical evaluation from the ileum and proximal colon. RESULTS: NEC + tocilizumab group had higher weight gain and survival rate compared to NEC + placebo group and clinical sickness score was reduced in NEC + tocilizumab group (p < 0.05). Lower tissue damage and apoptosis were found in the NEC + tocilizumab group compared to the NEC + placebo group (p < 0.01). Tissue Interleukin-6, Interleukin-1ß, TNF-α, myeloperoxidase and caspase-3 levels were significantly decreased in the NEC + tocilizumab group (p < 0.01). CONCLUSIONS: Tocilizumab could be a potential option in the prevention and treatment of NEC.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Enterocolite Necrosante/tratamento farmacológico , Interleucina-6/metabolismo , Receptores de Interleucina-6/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Caspases/genética , Caspases/metabolismo , Enterocolite Necrosante/induzido quimicamente , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
8.
Int J Mol Sci ; 22(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198834

RESUMO

Carbonic anhydrase IX (CAIX) is a hypoxia-related protein that plays a role in proliferation in solid tumours. However, how CAIX increases proliferation and metastasis in solid tumours is unclear. The objective of this study was to investigate how a synthetic CAIX inhibitor triggers apoptosis in the HeLa cell line. The intracellular effects of CAIX inhibition were determined with AO/EB, AnnexinV-PI, and γ-H2AX staining; measurements of intracellular pH (pHi), reactive oxygen species (ROS), and mitochondrial membrane potential (MMP); and analyses of cell cycle, apoptotic, and autophagic modulator gene expression (Bax, Bcl-2, caspase-3, caspase-8, caspase-9, caspase-12, Beclin, and LC3), caspase protein level (pro-caspase 3 and cleaved caspase-3, -8, -9), cleaved PARP activation, and CAIX protein level. Sulphonamide CAIX inhibitor E showed the lowest IC50 and the highest selectivity index in CAIX-positive HeLa cells. CAIX inhibition changed the morphology of HeLa cells and increased the ratio of apoptotic cells, dramatically disturbing the homeostasis of intracellular pHi, MMP and ROS levels. All these phenomena consequent to CA IX inhibition triggered apoptosis and autophagy in HeLa cells. Taken together, these results further endorse the previous findings that CAIX inhibitors represent an important therapeutic strategy, which is worth pursuing in different cancer types, considering that presently only one sulphonamide inhibitor, SLC-0111, has arrived in Phase Ib/II clinical trials as an antitumour/antimetastatic drug.


Assuntos
Anidrase Carbônica IX/genética , Inibidores da Anidrase Carbônica/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Apoptose/efeitos dos fármacos , Anidrase Carbônica IX/antagonistas & inibidores , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HeLa , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Compostos de Fenilureia/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sulfonamidas/farmacologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
9.
Indian J Orthop ; 55(1): 169-175, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33569111

RESUMO

OBJECTIVE: Developmental dysplasia of the hip (DDH) is a complicated skeletal disease ranging from subluxation to complete dislocation of the hip as a result of insufficient development of the acetabulum and femur. To date, numerous genes such as C-X3-C motif chemokine receptor 1 (CX3CR1), ubiquinol-cytochrome c reductase complex assembly factor 1 (UQCC1) and growth/differentiation factor 5 (GDF5), have been investigated to elucidate the underlying genetic etiology. Turkish population is one of the communities where DDH patients frequently observed, but almost no study has been conducted to elucidate the genetic etiology. In our study, we aimed to investigate the polymorphism of CX3CR1 rs3732378 and UQCC1 rs6060373, which have been shown to be associated with DDH in different populations. In addition, we aimed to investigate the BMP-2 rs235768 polymorphism which has not been investigated in the etiology of DDH. METHODS: Overall, 168 subjects (68 participants in the patient group, 100 participants in the control group) were investigated. The participants with following evidence and symptoms were excluded from the two groups: any systemic syndrome, another congenital anomaly, hereditary diseases, breech presentation, history of oligohydramnios, swaddling and high birth weight (> 4000 g). 3 single-nucleotide polymorphisms (SNP) were examined by qRT-PCR method. RESULTS: For CX3CR1 rs3732378 polymorphism, significant differences were observed in genotypes and allele frequencies (p < 0.0001). This condition was associated with a 12-fold increased risk in recessive modeling and 75-fold increased risk in dominant modeling. There was no significant relationship between DDH and the other two polymorphisms. CONCLUSIONS: Our work is the first study to investigate DDH and genetic polymorphisms in Turkish population where DDH is observed quite frequently. It is also the first study to investigate the relationship between BMP-2 rs235768 polymorphism and DDH. Our study revealed a clear relationship between CX3CR1 rs3732378 polymorphism and DDH in Turkish population.

10.
Comb Chem High Throughput Screen ; 24(8): 1236-1242, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32928081

RESUMO

BACKGROUND: Various effects of Astaxanthin were shown in the studies, including its antioxidant, anti-inflammatory, anti-tumor and immunoregulatory effects. OBJECTIVE: The aim of this study was to evaluate the beneficial effects of Astaxanthin on renovascular occlusion induced renal injury and to investigate the possible mechanisms. METHODS: The rats were randomly assigned into three groups as follows: Group 1: control group (n=12), Group 2: renal ischemia-reperfusion injury group (n=12), Group 3: renal ischemia-reperfusion + asthaxantine treated group (n=12). The control group and the renal ischemia-reperfusion group were given 2cc/kg/g olive oil for 7 days before establishing ischemia to renal tissue. Astaxanthin dissolved in olive oil was given orally to the renal ischemia+astaxanthin group for 7 days before inducing renal ischemia. Caspase-(3, 8, 9), GSH, SOD, Total Thiol, TNF-α, IL-6, 8-OHdG were evaluated in each group. RESULTS: Renal IRI was verified by analysing the pathological changes of renal tissues and the renal functions after renal reperfusion. Much less renal tubular damage was determined in the IRI+ASX group in comparison to the IRI group. Caspase-8, -9 and -3 immunoreactivity was observed to be minimal in the control group. Apoptosis was observed to be significantly reduced in the IRI + ASX group with respect to the IRI group and close to the level of the control group (p <0.05). Caspase-3 levels of tissue samples were significantly increased in the IRI group compared to the other groups, but significantly lower in the IRI+ASX group with respect to the IRI group (p<0.05). The TOS and OSI levels, indicating increased oxidative stress, were significantly lower in the IRI+ASX group with respect to the IRI group (p <0.001), but still higher than the control group (p <0.001). In addition to GSH, SOD and Total Thiol levels, TAS levels were also significantly higher in the IRI + ASX group in comparison to the IRI group (p <0.05). TNF-α, IL-6, lipid hydroperoxide, AOPP and 8-OHdG levels were lower in the IRI+ASX group than the IRI group (p <0.001). MPO, IL-6, TNF-α levels, representing the parameters indicating neutrophil infiltration and inflammation of the renal tissues, significantly increased in the IRI group with respect to the other groups (p <0.005). CONCLUSION: When all the data obtained in our study were evaluated, ASX was determined to prevent renal damage due to renovascular occlusion to a great extent, through complex mechanisms involving antioxidant, anti-inflammatory and antiapoptotic effects. Biochemical, histological and oxidative stress parameters were improved due to ASX.


Assuntos
Traumatismo por Reperfusão , Animais , Rim/irrigação sanguínea , Rim/patologia , Estresse Oxidativo , Ratos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Xantofilas/farmacologia
11.
Comb Chem High Throughput Screen ; 24(8): 1243-1250, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32933455

RESUMO

BACKGROUND/AIM: This study aimed to ascertain the effects of astaxanthin on the lungs of rat pups with bronchopulmonary dysplasia (BPD) induced by hyperoxia and lipopolysaccharide (LPS). MATERIALS AND METHODS: Forty-two newborn Wistar rats, born to spontaneous pregnant rats, were divided into three groups: Hyperoxia (95% O2) + lipopolysaccharide (LPS) group, hyperoxia + LPS + astaxhantin group, and control: no treatment group (21% O2). Pups in the hyperoxia + LPS + astaxanthin group were given 100 mg/kg/day oral astaxanthin from the first day to the fifth day. Histopathologic and biochemical evaluations, including glutathione (GSH), total anti-oxidant status (TAS), total oxidant status (TOS), lipid hydroperoxide (LPO), 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), total thiol, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and caspase-3 activities, were performed. RESULTS: Better survival rates and weight gain were demonstrated in the hyperoxia + LPS + astaxanthin group (p <0.001). In the histopathologic evaluation, the severity of lung damage was significantly reduced in the hyperoxia+LPS+astaxanthin group, as well as decreased apoptosis (ELISA for caspase-3) (p <0.001). The biochemical analyses of lung tissues showed that TAS, GSH, and Total thiol levels were significantly higher in the astaxanthin treated group compared to the hyperoxia + LPS group (p <0.05) while TOS, AOPP, LPO, 8-OHdG, MPO levels were significantly lower (p <0.001). In addition, unlike the hyperoxia + LPS group, TNF-α and IL-1ß levels in lung tissue were significantly lower in the astaxanthin-treated group (p <0.001). CONCLUSION: Astaxanthin was shown to reduce lung damage caused by inflammation and hyperoxia with its anti-inflammatory, anti-oxidant, anti-apoptotic properties, and to protect the lung from severe destruction.


Assuntos
Hiperóxia , Lesão Pulmonar , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Feminino , Hiperóxia/complicações , Hiperóxia/tratamento farmacológico , Hiperóxia/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Lesão Pulmonar/metabolismo , Gravidez , Ratos , Ratos Wistar , Xantofilas
12.
Anticancer Agents Med Chem ; 21(6): 725-737, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32748756

RESUMO

BACKGROUND: Pistachio is considered to be one of the fifty foods with the highest antioxidant effect. However, the anticancer effect mechanisms of this plant extracts are unknown. OBJECTIVE: The aim of this study was to investigate the anticancer effect of different extracts from the green hull of pistachio. METHODS: The cytotoxic effects of different solvent extracts on cancer and normal cells were examined by cell viability assay and flow cytometric analysis. The levels of the apoptotic gene and protein were investigated by Western Blot and ELISA, and qPCR. The intracellular free radical exchange was determined by oxidative and nitric oxide analyses. DNA damage level was measured by the 8-OHdG test. Phenolic and free fatty acid components were examined by LC-MS/MS and GC-MS, respectively. RESULTS: It was determined that the n-hexane fraction showed a higher cytotoxic effect on cancer cells. Oxidative and cell cycle analyses indicated that the n-hexane fraction arrested cell cycle of HT-29 at the sub-G1 phase by increasing DNA damage through oxidative stress. In addition, gene expression analysis of the HT-29 treated with the n-hexane fraction indicated that apoptotic and autophagic gene expressions were significantly upregulated. LC-MS/MS analysis of the n-hexane fraction revealed the presence of 15 phenolic compounds, containing mainly gallic acid and catechin hydrate, and GC-MS analysis determined the presence of the following fatty acids: 9-octadecenoic acid, 9,12-octadecadienoic acid and hexadecenoic acid. CONCLUSION: Based on these grounds, we suggest that the n-hexane fraction of pistachio green hull damages DNA, arrests the cell cycle at the G1 subphase, and induces apoptosis through oxidative pathways in colon cancer.


Assuntos
Antineoplásicos/química , Neoplasias do Colo/tratamento farmacológico , Ácidos Graxos não Esterificados/química , Fenóis/química , Pistacia/química , Extratos Vegetais/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Catequina/química , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ácidos Graxos não Esterificados/farmacologia , Ácido Gálico/química , Cromatografia Gasosa-Espectrometria de Massas , Regulação da Expressão Gênica , Células HT29 , Humanos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Transdução de Sinais , Espectrometria de Massas em Tandem
13.
Anatol J Cardiol ; 24(3): 175-182, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32870170

RESUMO

OBJECTIVE: Acute coronary syndrome (ACS) is a leading cause of death worldwide. There is great interest in defining the risk factors and underlying mechanisms of ACS among young people. The microbiota and its metabolites have recently become a popular research topic, yet there is still no study that investigated microbiota-generated metabolites as a possible risk factor in young patients with ACS. In this study, we aimed to investigate the relationship between microbiota-generated metabolites and ACS in young people. METHODS: This study included 44 young patients with ACS (<50 years of age), 39 elderly patients with ACS, and 44 patients with normal coronary arteries. Inflammatory parameters and serum trimethylamine N-oxide (TMAO) and choline levels were measured in all patients. RESULTS: Young patients with ACS had significantly higher levels of TMAO and choline compared to the control and elderly ACS groups. Also, elderly patients with ACS had a significantly higher level of TMAO than the control group. Linear regression analysis was performed to determine the independent predictors of TMAO. Two regression models were involved. The first model included young ACS and control groups, while the second model included young and elderly ACS groups. In the first model, we found that young ACS (ß=0.399, p=0.004) and smoking ACS (ß=0.211, p=0.046) were significantly associated with TMAO level. In the second model, young ACS was significantly associated with TMAO level (ß=0.230, p=0.035). CONCLUSION: In this study, we have shown that young ACS was significantly associated with increased TMAO level.


Assuntos
Síndrome Coronariana Aguda/microbiologia , Microbiota , Síndrome Coronariana Aguda/diagnóstico por imagem , Adulto , Fatores Etários , Idoso , Biomarcadores/sangue , Colina/sangue , Feminino , Humanos , Masculino , Metilaminas/sangue , Pessoa de Meia-Idade , Fatores de Risco
14.
Curr HIV Res ; 18(3): 154-164, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32539678

RESUMO

BACKGROUND: Emergence of Kaposi's Sarcoma in the cases other than HIV, following the use of immunosuppressant drugs, demonstrates that it is related to weak immunity. The fact that this malignancy does not occur in every HIV-positive patient suggests that genetic predisposition may also be effective. Replacement of one of the base pairs of adenine, guanine, cytosine, and thymine that constitute the DNA sequence in the human genome with another base pair can affect susceptibility to disease, response to treatment, and immunity. OBJECTIVE: The purpose of this study is to analyze the Single Nucleotide Polymorphism that could predispose to Kaposi's sarcoma of an HIV-infected patient and to identify which nucleotides such SNPs correspond to, using the microarray technology. MATERIALS AND METHODS: The blood samples of individuals, one of whom was diagnosed with Kaposi's Sarcoma HIV (+) visiting the outpatient clinic of infectious diseases polyclinic of Harran University Research and Practice Hospital and of a healthy individual with no Kaposi's Sarcoma, were used in the study. Following the DNA isolation of the blood samples taken from the respective individuals, a SNP analysis was conducted on the microarray device. 204,000 SNPs obtained were scanned later on in the databases in an attempt to identify the SNPs related to Kaposi's Sarcoma. RESULTS: In the 204,000 SNP screenings, we scrutinized the SNPs that differ in the case of Kaposi's Sarcoma [KS (+) and HIV (+)] on the basis of Control [KS(-) and HIV(-)] and HIV+ [KS(-)], and two SNPs of the ENDRA gene, three SNPs of the ADRA1A gene, six SNPs of the STIM1 gene, four SNPs of the EFNB2 gene, and one SNP of the CD209 gene were found to be different. However, when it comes to all SNPs (all the 204.000 SNPs) screened in terms of allele, it was observed that the AA and BB alleles were lower in the patient with Kaposi's Sarcoma [KS (+) and HIV (+)] compared to other groups and AB alleles were found to be higher than others in the patient with Kaposi's sarcoma [KS] (+) and HIV (+)]. CONCLUSION: In the microarray study we have conducted, 204,000 SNPs were screened for Control (HIV-) HIV (+) and HIV (+) patient with Kaposi's Sarcoma. It was found that 32,362 of those SNPs had different alleles in the Kaposi's Sarcoma [KS + HIV (+)] patient, while they had the same ones in the control [KS (-) and HIV (-)] and HIV + [KS (-)] group. 16 of the 32,362 SNPs took place among the genes related to Kaposi's Sarcoma. In the cases of Kaposi's Sarcoma with suspected diagnosis, it can be used as a beneficial laboratory test.


Assuntos
Moléculas de Adesão Celular/genética , Efrina-B2/genética , Infecções por HIV/genética , Lectinas Tipo C/genética , Proteínas de Neoplasias/genética , Receptor de Endotelina A/genética , Receptores Adrenérgicos alfa 1/genética , Receptores de Superfície Celular/genética , Sarcoma de Kaposi/genética , Molécula 1 de Interação Estromal/genética , Adulto , Alelos , Estudos de Casos e Controles , Moléculas de Adesão Celular/imunologia , Efrina-B2/imunologia , Expressão Gênica , Predisposição Genética para Doença , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/imunologia , Infecções por HIV/virologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Lectinas Tipo C/imunologia , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Proteínas de Neoplasias/imunologia , Polimorfismo de Nucleotídeo Único , Receptor de Endotelina A/imunologia , Receptores Adrenérgicos alfa 1/imunologia , Receptores de Superfície Celular/imunologia , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/imunologia , Sarcoma de Kaposi/virologia , Molécula 1 de Interação Estromal/imunologia
15.
Comb Chem High Throughput Screen ; 23(8): 827-831, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407261

RESUMO

BACKGROUND: In blood samples taken for testing purposes during drug infusion in the intensive care unit, there is a risk of interference due to drug-reactive interaction during the analysis. CASE REPORT: A 19-year-old female patient had undergone surgery for intracranial astrocytoma, 12 years ago. Acinetobacter baumannii was found in the blood culture and deep tracheal aspiration fluid of the patient who had a fever (39.2 °C) with a body temperature during the follow-up. The patient was started on colistin 2 * 4.5 million IU. After the colistin infusion, biochemical tests were requested to control the patient's clinical situation. CK-MB mass and ProBNP values were measured in high concentrations. Cardiology consultation was requested to evaluate the increase in the CK-MB mass and ProBNP values. The patient's ECG and echocardiography showed no abnormality. The increase in cardiac markers was neither clinically acceptable nor insignificant. There was no hemolysis in the sample or analytical error in the device. Variability in the tests was thought to be due to the interference. As the bloodletting time was questioned, it was determined that it was taken during colistin treatment. In order to determine the effect of colistin-related interference on the other tests, the laboratory was contacted and additional tests (TSH, FT4, Anti- TPO, B-HCG, Estradiol, Prolactin, CA 125, CA 15-3, CA 19-9, Vitamin B12, C-Peptide, DDimer, PTH, 25 hydroxy vitamin D, PT, INR, APTT) were conducted. During colistin treatment, in many tests, bias was detected between -75 and + 268.80%. CONCLUSION: Clinicians should consider suspicious test results that are incompatible with the diagnosis for the possibility of erroneous measurements due to colistin interference and review the sampling processes.


Assuntos
Infecções por Acinetobacter/diagnóstico , Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/uso terapêutico , Colistina/uso terapêutico , Antibacterianos/farmacologia , Peptídeo C/análise , Peptídeo C/metabolismo , Antígeno Ca-125/análise , Antígeno Ca-125/metabolismo , Antígeno CA-19-9/análise , Antígeno CA-19-9/metabolismo , Colistina/farmacologia , Cuidados Críticos , Estradiol/análise , Estradiol/metabolismo , Reações Falso-Positivas , Feminino , Humanos , Mucina-1/análise , Mucina-1/metabolismo , Prolactina/análise , Prolactina/metabolismo , Vitamina B 12/análise , Vitamina B 12/metabolismo , Adulto Jovem
16.
Arq. bras. oftalmol ; 83(1): 5-10, Jan.-Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1088955

RESUMO

ABSTRACT Purpose: The aim of the present study was to measure the free carnitine and acylcarnitine levels in pterygium tissue and normal conjunctival tissue at the metabolomics level using tandem mass spectrometry. Methods: In this prospective, clinical randomized study, pterygium tissues and normal conjunctival tissues taken during pterygium excision with autograft were compared regarding their free carnitine and acylcarnitine profiles. After tissue homogenization, carnitine levels were measured using tandem mass spectrometry. The data were statistically analyzed with the Wilcoxon signed-rank test. Results: Pterygium and normal conjunctival tissue samples from a single eye of 29 patients (16 females, 13 males; mean age, 54.75 ± 11.25 years [range, 21-78 years]) were evaluated. While the free carnitine (C0) level was significantly high in the pterygium tissue (p<0.001), acylcarnitine levels were significantly high in some esterized derivatives (C2, C5, C5:1, C5DC, C16:1, C18, methylglutarylcarnitine) (p<0.05). No statistically significant difference was determined for the other esterized derivatives (p>0.05). Conclusion: That the carnitine levels in pterygium tissue were higher suggests that acceleration of cell metabolism developed secondary to chronic inflammation and the premalignant characteristics of pterygium tissue. High carnitine levels may also effectively suppress the apoptosis process. The data reported in our study indicate that further, more extensive studies of the carnitine profile could help clarify the pathogenesis of pterygium.


RESUMO Objetivo: O objetivo deste estudo foi medir os níveis de carnitina livre e acil-carnitina a nível metabolómico com espectrometria de massa em tandem no tecido do pterígio e no tecido conjuntivo normal. Método: Neste estudo prospetivo, clínico e aleatório, os tecidos de pterígio e os tecidos normais de conjuntiva, retirados durante a cirurgia de pterígio com autoenxerto, foram comparados em relação ao perfil de carnitina livre e de acil-carnitina. Após a homogeneização dos tecidos, os níveis de carnitina foram medidos por espectrometria de massa em tandem. A análise estatística dos dados foi realizada com o teste dos postos sinalizados de Wilcoxon. Resultados: A avaliação foi feita através de amostras de tecido pterígio e de conjuntiva normal de um único olho de 29 pacientes (16 mulheres, 13 homens). A média de idade dos pacientes foi de 54,75 ± 11,25 anos (faixa dos 21 aos 78 anos). Enquanto o nível de carnitina livre (C0) foi significativamente elevado no tecido pterígio (p<0,001), os níveis de acil-carnitina foram significativamente elevados em alguns derivados esterificados (C2, C5, C5: 1, C5DC, C16:1, C18, metilglutaril carnitina) (p<0,05). Não foi determinada uma diferença estatisticamen te significante noutros derivados esterificados (p>0,05). Conclusão: Os níveis mais elevados de carnitina no tecido do pterígio sugerem que a aceleração do metabolismo celular se tenha tornado secundária com o efeito da inflamação crónica e o caráter pré-maligno do tecido do pterígio. Os níveis elevados de carnitina também podem ser eficazes na supressão do processo de apoptose. Os dados obtidos no estudo indicam que estudos mais extensivos do perfil da carnitina contribuiriam para o esclarecimento da patogénese do pterígio.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Pterígio/metabolismo , Carnitina/análise , Carnitina/análogos & derivados , Túnica Conjuntiva/anormalidades , Pterígio/cirurgia , Carnitina/metabolismo , Estudos Prospectivos , Túnica Conjuntiva/cirurgia , Túnica Conjuntiva/metabolismo , Espectrometria de Massas em Tandem , Metabolômica
17.
Artigo em Inglês | MEDLINE | ID: mdl-31889481

RESUMO

OBJECTIVE: The primary objective of this study was to compare oxidative DNA damage markers, apoptosis markers and changes in miRNA levels in patients diagnosed with cancer and treated through chemotherapy. Our secondary objective was also to evaluate tumor responses that can be determined after post-chemotherapy clinical evaluations by physical examinations, laboratory results and radiological imagings, and to compare the clinical results to oxidative stress and apoptosis markers and micro RNA levels. MATERIALS AND METHODS: To do that we designed a prospective observational cross-sectional study. A total of 34 cancer patients and 27 healthy controls were included in the study from the Harran University School of Medicine Department of Oncology. Newly diagnosed chemotherapy or radiotherapy naive patients without any chronic diseases were included into the study. Patients with a poor performance status (ECOG 2 and 3) and patients who did not meet the inclusion criteria were excluded. The cancer patients received chemotherapy according to their scheduled periods. Blood samples were taken from the patients before the first chemotherapy course and before the second chemotherapy round. Patients were called for toxicity control on the 10th day after the chemotherapy. Pre-chemotherapy, post-chemotherapy and control group miR-29a expression levels, change in apoptosis markers and oxidative DNA damage markers were obtained and compared. We studied 8-hydroxy 2-deoxyguanosine, total oxidant status, total anti-oxidant status, and oxidative status index for oxidative stress markers. We studied M30 and M65 as apoptosis markers. Clinical results of efficiency of the chemotherapy was acquired and compared to biochemical markers based on chemotherapy results. Chemotherapy toxicities were recorded. RESULTS: As a result, we found oxidative DNA damage markers and apoptosis markers were high in the cancer group, demonstrating that oxidative DNA damage and apoptosis might play a direct or indirect role in cancer etiology. However, there were subtle differences between pre-chemotherapy and post-chemotherapy levels. Mir-29a expressions were lower in cancer patients as compared to controls. However, the expression levels were not significantly change in pre- and postchemotherapy status. Moreover, we found no relationship between clinical status of patients (progression and regression) and studied biochemical markers. CONCLUSION: Thus, checking for DNA damage markers and taking precautions to lower the levels of these markers in individuals with cancer risk may be helpful in preventing cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/análise , MicroRNAs/análise , Neoplasias/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Biomarcadores Tumorais/genética , Estudos Transversais , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Estudos Prospectivos
18.
Arq Bras Oftalmol ; 83(1): 5-10, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31531547

RESUMO

PURPOSE: The aim of the present study was to measure the free carnitine and acylcarnitine levels in pterygium tissue and normal conjunctival tissue at the metabolomics level using tandem mass spectrometry. METHODS: In this prospective, clinical randomized study, pterygium tissues and normal conjunctival tissues taken during pterygium excision with autograft were compared regarding their free carnitine and acylcarnitine profiles. After tissue homogenization, carnitine levels were measured using tandem mass spectrometry. The data were statistically analyzed with the Wilcoxon signed-rank test. RESULTS: Pterygium and normal conjunctival tissue samples from a single eye of 29 patients (16 females, 13 males; mean age, 54.75 ± 11.25 years [range, 21-78 years]) were evaluated. While the free carnitine (C0) level was significantly high in the pterygium tissue (p<0.001), acylcarnitine levels were significantly high in some esterized derivatives (C2, C5, C5:1, C5DC, C16:1, C18, methylglutarylcarnitine) (p<0.05). No statistically significant difference was determined for the other esterized derivatives (p>0.05). CONCLUSION: That the carnitine levels in pterygium tissue were higher suggests that acceleration of cell metabolism developed secondary to chronic inflammation and the premalignant characteristics of pterygium tissue. High carnitine levels may also effectively suppress the apoptosis process. The data reported in our study indicate that further, more extensive studies of the carnitine profile could help clarify the pathogenesis of pterygium.


Assuntos
Carnitina/análogos & derivados , Carnitina/análise , Túnica Conjuntiva/anormalidades , Pterígio/metabolismo , Adulto , Idoso , Carnitina/metabolismo , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/cirurgia , Feminino , Humanos , Masculino , Metabolômica , Pessoa de Meia-Idade , Estudos Prospectivos , Pterígio/cirurgia , Espectrometria de Massas em Tandem , Adulto Jovem
19.
Acta Clin Belg ; 75(2): 123-127, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30585134

RESUMO

Objectives: The purpose of this study is to investigate the elimination ratios of requested unnecessary tests and the cost-effectiveness to be achieved by means of 5 different algorithms with clinical validity defined in an artificial intelligence program.Methods: The clinician orders received from the hospital information management system were adapted to eliminate AST, direct bilirubin, chlorine, fPSA and fT3 tests using five different algorithms defined in the ALIN IQ software.Results: In this study, 18387 AST, 9500 direct bilirubin, 61 free PSA, 1127 FT3 and 11172 chlorine tests that were ordered within 45 days were eliminated using 5 different algorithms defined in the ALIN IQ software in the Laboratory of Harran University Faculty of Medicine. USD 5592.76 was saved in 45 days. The annual saving is expected to be 363710 tests and USD 45363.49.Conclusion: Five different tests were successfully eliminated with this study. Open-code smart softwares, which can create indefinite algorithms may be utilized as test eliminators in diagnostic clinical laboratories. Millions of dollars may be saved by means of such artificial intelligence softwares that can be adapted to any analyzer across the world.


Assuntos
Algoritmos , Testes de Química Clínica , Análise Custo-Benefício , Inteligência Artificial , Testes de Química Clínica/economia , Testes de Química Clínica/estatística & dados numéricos , Humanos , Resultado do Tratamento
20.
Eye Contact Lens ; 46 Suppl 2: S122-S128, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31425352

RESUMO

OBJECTIVES: This study examined changes in the levels of organic acids, which are important tear metabolites, after corneal collagen crosslinking (CXL) treatment for keratoconus. METHODS: This prospective, nonrandomized, interventional case series included a single eye from 24 patients who were scheduled to receive CXL treatment (Dresden protocol) for progressive keratoconus. Before CXL treatment and at 6 months after treatment, tears were collected in capillary tubes. The patients were separated into four groups as males, females, and ages 18 years younger and >18 older. The organic acid profiles of the tear samples were analyzed using mass spectrometry. RESULTS: An evaluation was made of 12 females and 12 males with a mean age of 19.20±4.06 years (range: 12[FIGURE DASH]27 years). The greatest percentage increase in organic acids after CXL treatment was observed for N-acetyl-L-aspartic acid (66% increase). The organic acid showing the greatest decrease was 3-OH butyric acid (61% decrease). A decrease of 46% was found (P=0.263) in the lactic acid/malic acid ratio. CONCLUSION: Metabolomic studies of tears could facilitate a new and objective process in the follow-up period or in the determination of prognosis after CXL treatment for diseases such as keratoconus, which has a multifactorial etiology.


Assuntos
Ácidos/metabolismo , Colágeno/uso terapêutico , Reagentes de Ligações Cruzadas/uso terapêutico , Ceratocone/diagnóstico por imagem , Fotoquimioterapia/métodos , Lágrimas/química , Acuidade Visual , Adolescente , Adulto , Biomarcadores/metabolismo , Criança , Feminino , Seguimentos , Humanos , Ceratocone/diagnóstico , Ceratocone/metabolismo , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Prospectivos , Raios Ultravioleta , Adulto Jovem
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