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1.
Am J Emerg Med ; 56: 127-132, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35397352

RESUMEN

STUDY OBJECTIVE: To determine the analgesic efficacy of TENS treatment in patients with renal colic in the emergency department (ED). METHODS: This double-blind, randomized controlled trial was conducted in a tertiary care ED. Patients with a definitive diagnosis of renal colic were assigned (1:1) as randomized to receive the real TENS with frequency 100 Hz, pulse width 200 microseconds, voltage 2 mA, or placebo with sham TENS. Pain intensity was measured using visual analog scales (VAS) at baseline, after 15 and 30th minutes. RESULTS: A total of 100 patients were included in the final analysis: 50 patients treated with real TENS and 50 patients treated with sham TENS. VAS scores in both groups were similar at baseline. The mean reduction in VAS score at 15 min was 33.3 ± 17.6 (95% Confidence interval (CI): 28.3 to 38.3) for the real TENS group and 14.9 ± 11.6 (95% CI 11.6 to 18.2) for the sham TENS group (mean difference: 18.4 (95% CI: 12.5 to 24.4, P < 0.0001). The mean reduction in VAS score at 30 min was 63.7 ± 21.1 (95% CI: 57.7 to 69.7) for the real TENS group and 14.9 ± 16.2 (95% CI: 19.5 to 10.3) for the sham TENS group (mean difference: 48.8, 95% CI: 41.4 to 56.3, P < 0.0001). Four patients (8%) in the real TENS group and 24 patients (48%) in the sham TENS group required the rescue medication after 30th minutes. CONCLUSIONS: TENS is effective for acute pain treatment in renal colic patients in the ED. TENS therapy could be a treatment option for renal colic.


Asunto(s)
Cólico Renal , Estimulación Eléctrica Transcutánea del Nervio , Método Doble Ciego , Servicio de Urgencia en Hospital , Humanos , Dimensión del Dolor , Cólico Renal/terapia , Resultado del Tratamiento
2.
Andrologia ; 54(11): e14572, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36054500

RESUMEN

Infertility is defined as the inability of couples to have a baby without contraception after at least 1 year of regular sexual intercourse. Mechanisms to explain inflammation in male infertility of unknown causes are still being investigated. The inflammasome is a key regulator of innate immunity, which is involved in the inflammatory response to infections and various diseases through the activation of caspase-1 and the use of inflammatory cytokines. Although many factors are believed to affect the success of mTESE in infertile patients with non-obstructive azoospermia (NOA), the inflammation mechanisms in the environment have not been clearly explained in the aetiology of infertility. In this study, we aimed to investigate the effect of NLRP3 and similar inflammasome mechanisms on antioxidant mechanisms on the success of mTESE. A total of 24 NOA patients with micro-testicular sperm extraction (mTESE +) and no sperm found (mTESE -) participated in the study between January 2020 and January 2021. NLRP3, IL1-ß, TAS, TOS and OSI amounts in serum and seminal plasma parameters were compared statistically, and their effects on mTESE success were investigated. FSH, LH, estradiol and testosterone values did not differ significantly (p > 0.05) in the group with mTESE (-) and mTESE (+). Serum IL-1 Beta, NLRP3, TOS, TAS, and OSI values did not differ significantly (p > 0.05) in the group with mTESE (-) and mTESE (+). Seminal plasma TOS and OSI values were significantly lower in the group with mTESE (+) than the group with mTESE (-). Although inflammasomes such as NLRP3 and IL1-ß do not have a significant predictive value in the success of mTESE, we think the high seminal plasma values of infertile patients may be understandable with further studies. This study was conducted to determine how inflammasomes are involved in IL-1ß, pathway NLRP3, and sperm retrieval in micro testicular sperm extraction (mTESE) in infertile men.


Asunto(s)
Azoospermia , Inflamasomas , Recuperación de la Esperma , Humanos , Masculino , Inflamación , Interleucina-1beta , Proteína con Dominio Pirina 3 de la Familia NLR , Estudios Retrospectivos , Espermatozoides/fisiología , Testículo
3.
J Shoulder Elbow Surg ; 31(10): e490-e497, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35483566

RESUMEN

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.


Asunto(s)
Lesiones del Manguito de los Rotadores , Antioxidantes , Disulfuros , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxidantes , Estrés Oxidativo , Especies Reactivas de Oxígeno , Lesiones del Manguito de los Rotadores/patología , Lesiones del Manguito de los Rotadores/cirugía , Compuestos de Sulfhidrilo , Resultado del Tratamiento , Estados Unidos
4.
Int J Mol Sci ; 22(11)2021 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-34198834

RESUMEN

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.


Asunto(s)
Anhidrasa Carbónica IX/genética , Inhibidores de Anhidrasa Carbónica/farmacología , Proliferación Celular/efectos de los fármacos , Neoplasias del Cuello Uterino/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Anhidrasa Carbónica IX/antagonistas & inhibidores , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HeLa , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Compuestos de Fenilurea/farmacología , Especies Reactivas de Oxígeno/metabolismo , Sulfonamidas/farmacología , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología
5.
Eye Contact Lens ; 46 Suppl 2: S122-S128, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31425352

RESUMEN

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.


Asunto(s)
Ácidos/metabolismo , Colágeno/uso terapéutico , Reactivos de Enlaces Cruzados/uso terapéutico , Queratocono/diagnóstico por imagen , Fotoquimioterapia/métodos , Lágrimas/química , Agudeza Visual , Adolescente , Adulto , Biomarcadores/metabolismo , Niño , Femenino , Estudios de Seguimiento , Humanos , Queratocono/diagnóstico , Queratocono/metabolismo , Masculino , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Prospectivos , Rayos Ultravioleta , Adulto Joven
6.
J Enzyme Inhib Med Chem ; 34(1): 75-86, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30362386

RESUMEN

Carbonic anhydrase IX (CA IX) has recently been validated as an antitumor/antimetastatic drug target. In this study, we examined the underlying molecular mechanisms and the anticancer activity of sulfonamide CA IX inhibitors against cervical cancer cell lines. The effects of several sulfonamides on HeLa, MDA-MB-231, HT-29 cancer cell lines, and normal cell lines (HEK-293, PNT-1A) viability were determined. The compounds showed high cytotoxic and apoptotic activities, mainly against HeLa cells overexpressing CA IX. We were also examined for intracellular reactive oxygen species (ROS) production; intra-/extracellular pH changes, for inhibition of cell proliferation, cellular mitochondrial membrane potential change and for the detection of caspase 3, 8, 9, and CA IX protein levels. Of the investigated sulfonamides, one compound was found to possess high cytotoxic and anti-proliferative effects in HeLa cells. The cytotoxic effect occurred via apoptosis, being accompanied by a return of pHe/pHi towards normal values as for other CA IX inhibitors investigated earlier.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis/efectos de los fármacos , Anhidrasa Carbónica IX/antagonistas & inhibidores , Inhibidores de Anhidrasa Carbónica/farmacología , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/química , Anhidrasa Carbónica IX/genética , Anhidrasa Carbónica IX/metabolismo , Inhibidores de Anhidrasa Carbónica/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Daño del ADN , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estructura Molecular , Especies Reactivas de Oxígeno/análisis , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad
7.
Medicina (Kaunas) ; 55(7)2019 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-31311177

RESUMEN

Background and objectives: No-reflow (NR) phenomenon is defined as insufficient myocardial perfusion in coronary circulation in the absence of angiographic evidence of mechanical obstruction. The primary mechanisms of the NR occurrence are thought to be high platelet activity and thrombus burden. Soluble CD40 ligand (sCD40L), which is released into the plasma following platelet activation, accelerates the inflammatory process and causes further platelet activation. The aim of our study is to investigate the relationship between the NR phenomenon and sCD40L level in patients with ST-elevation myocardial infarction (STEMI). Methods: A total of 81 acute STEMI patients undergoing primary percutaneous coronary intervention and 40 healthy participants were included in this study. Acute STEMI patients were classified into two groups: 41 patients with the NR phenomenon (NR group) and 40 patients without the NR phenomenon (non-NR group). The serum sCD40L level was measured for all groups. Results: The serum sCD40L level was significantly higher in the NR group than in non-NR and control groups (379 ± 20 pg/mL, 200 ± 15 pg/mL and 108 ± 6.53 pg/mL, respectively; p < 0.001). Univariate regression analysis demonstrated that male sex, age, Gensini score and sCD40L level were the possible factors affecting the occurrence of the NR phenomenon. In multivariate regression analysis, age (odds ratio [OR], 1.091; 95% confidence interval [CI], 1.023-1.163; p < 0.008) and serum sCD40L (OR, 1.016; 95% CI, 1.008-1.024; p < 0.001) remained the independent predictor of the presence of NR. Conclusions: Our study showed that serum sCD40L level was an independent predictor of the NR phenomenon occurrence.


Asunto(s)
Ligando de CD40/análisis , Fenómeno de no Reflujo/sangre , Infarto del Miocardio con Elevación del ST/sangre , Adulto , Anciano , Análisis de Varianza , Ligando de CD40/sangre , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Fenómeno de no Reflujo/epidemiología , Oportunidad Relativa , Intervención Coronaria Percutánea/métodos , Estudios Prospectivos , Curva ROC , Infarto del Miocardio con Elevación del ST/epidemiología
8.
Medicina (Kaunas) ; 55(6)2019 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-31207925

RESUMEN

Background and objectives: The aim of this study was to research oxidative stress and thiol/disulphide homeostasis in Graves' patients. Materials and Methods: The study included 33 Graves' patients (research group) and 35 healthy subjects (control group). Serum oxidative stress and thiol/disulphide homeostasis (a new and automated spectrophotometric method developed by Erel and Neselioglu) parameters were studied and compared between the groups. Results: The native and total thiol levels and the native thiol/total thiol ratio were lower in patients with Graves' disease compared to the control group (p < 0.001, p < 0.001, and p = 0.006, respectively). TOS (total antioxidant status), PC (protein carbonyl), OSI (Oxidative stress index), and disulphide/native thiol and disulphide/total thiol ratios were determined to be higher in the Graves' disease group than in the control group (p < 0.001, p = 0.001, p = 0.001, p = 0.004, and p = 0.006, respectively). In the Graves' disease group, the free triiodothyronine (FT3) and free thyroxine (FT4) levels were significantly positively correlated with impaired thiol/disulphide homeostasis and oxidative stress parameters (p < 0.05). Conclusion: The results of the current study demonstrated that oxidative stress and thiol/disulphide homeostasis increased towards disulphide formation due to thiol oxidation in Graves' disease. In addition, a positive correlation of FT3 and FT4 was observed with oxidative stress parameters and impaired thiol/disulphide homeostasis.


Asunto(s)
Disulfuros/análisis , Enfermedad de Graves/sangre , Estrés Oxidativo/fisiología , Compuestos de Sulfhidrilo/análisis , Adolescente , Adulto , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Disulfuros/sangre , Femenino , Enfermedad de Graves/fisiopatología , Homeostasis/fisiología , Humanos , Masculino , Persona de Mediana Edad , Compuestos de Sulfhidrilo/sangre , Tirotropina/análisis , Tirotropina/sangre
9.
Int Ophthalmol ; 39(10): 2325-2333, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30617855

RESUMEN

PURPOSE: The aim of the study was to measure amino acid levels with the metabolomics analysis in pterygium tissue and normal conjunctiva tissue. MATERIALS AND METHODS: In this prospective, randomized, clinical study, a comparison of the amino acid profile of pterygium tissue and normal conjunctiva tissue taken during autograft pterygium surgery was made. After homogenization of the tissues, amino acid levels were measured with chromatography-mass spectrometry (LC-MS/MS) in the biochemistry laboratory. Statistical analysis was made using the Wilcoxon signed-rank test. RESULTS: Evaluation of pterygium and normal conjunctiva tissues of 29 patients, comprising 16 females and 13 males with a mean age of 54.75 ± 11.25 years (range 21-78 years) was made. While a dramatic increase was observed in all the amino acid levels in the pterygium tissue compared to the normal conjunctiva (p > 0.05), only the increases in arginine, methionine, glycine and tyrosine amino acids were determined to be statistically significant (p < 0.01), (p = 0.028), (p = 0.038), (p = 0.046). CONCLUSION: Pterygium is known to be degenerative inflammatory fibrovascular tissue. When the aetiology is examined in depth, several metabolic processes are seen to have an effect. Further studies of the amino acid profile with more extensive patient series could confirm the data obtained in the current study and contribute to the clarification of the pathogenesis of pterygium.


Asunto(s)
Aminoácidos/metabolismo , Pterigion/metabolismo , Adulto , Anciano , Conjuntiva/metabolismo , Femenino , Humanos , Masculino , Metabolómica , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
10.
Cell Mol Biol (Noisy-le-grand) ; 64(1): 75-83, 2018 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-29412798

RESUMEN

This study aimed to examine the anti-cancer and antioxidant properties and identify the phenolic content of methanolic extract obtained from the shoots of the Ornithogalum narbonense L. (OR) species, which is used for folk-medicine and food in the Sanliurfa region of Turkey. The antioxidant activity of the extract was investigated using total phenolics, flavonoids, ABTS and CUPRAC methods. Phenolic component analysis of the plant extract was performed by LC-MS/MS. The anti-cancer property of OR extract was investigated on human colon (DLD-1), endometrium (ECC-1) cancer cells and embryonic kidney (HEK-293) cells. Cytotoxic effects were defined with MTT, apoptotic activity with DNA fragmentation ELISA and AO/EB fluorescent staining, the genotoxic effect with the comet assay and the intracellular oxidative status with TAS and TOS methods. As a result of the study, it was determined that OR extract showed an antioxidant effect, and as a result of the content analysis made with LC-MS/MS, phenolic components were determined, the most abundant being cosmosiin, followed by cinnamic acid, p-coumaric acid and quinic acid. OR extract showed cytotoxic activity on DLD-1 and ECC-1 cancer cells, while the cytotoxic effect on HEK-293 cells was determined to be low. It was determined that through OR extract, by increasing the intracellular amount of free radicals on cancer cells, led to DNA damage, which consequently led to apoptosis of the cancer cells.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Ornithogalum/química , Antineoplásicos Fitogénicos/química , Antioxidantes/química , Apoptosis , Línea Celular Tumoral , Daño del ADN , Flavonoides/análisis , Células HEK293 , Humanos , Estrés Oxidativo , Fenoles/análisis , Extractos Vegetales/química , Extractos Vegetales/farmacología , Brotes de la Planta/química
11.
Cell Mol Biol (Noisy-le-grand) ; 64(13): 74-78, 2018 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-30403599

RESUMEN

Acetylcholinesterase inhibitors, including Neostigmine, have been used to reverse neuromuscular blockage for many years. Sugammadex reverses this blockage using its gamma cyclodextrin ring, a mechanism that differs from that of cholinesterases and so circumvents the side effects of Neostigmine. Although the superiority of Sugammadex to Neostigmine has been outlined in several clinical studies, to our knowledge, there is not any research into cell culture that compares the cytotoxic, genotoxic and apoptotic effects of the two drugs. Hence, this is the first study to compare the cytotoxic, genotoxic and apoptotic effects of different dosages of both drugs on human embryonic renal (HEK-293) cells. In this study, the cytotoxicity, genotoxicity and apoptotic effects of Sugammadex and Neostigmine on HEK-293 cells were analyzed with using the MTT, Comet Assay and Flow Cytometric Annexin-V methods, respectively. The results demonstrate that Neostigmine at 50, 100, 250, and 500 µg/mL is more cytotoxic than equivalent dosages of Sugammadex. Neostigmine at 500 and 1000 µg/mL was found to be more genotoxic, and Neostigmine at 500 µg/mL had a statistically higher risk of causing apoptosis and necrosis than Sugammadex (p<0.05). Neostigmine administered in-vitro in the same doses as Sugammadex had greater cytotoxic, genotoxic and apoptotic effects on HEK-293 cells.


Asunto(s)
Apoptosis/efectos de los fármacos , Mutágenos/toxicidad , Neostigmina/toxicidad , Sugammadex/toxicidad , Anexina A5/metabolismo , Supervivencia Celular/efectos de los fármacos , Daño del ADN , Citometría de Flujo , Células HEK293 , Humanos , Necrosis
12.
Cell Mol Biol (Noisy-le-grand) ; 64(3): 72-80, 2018 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-29506633

RESUMEN

In recent years, there is an increased research interest for plants which are natural sources of antioxidants. Lepidium sativum Subsp spinescens L., commonly found in South West Asia, is a plant known as a healthy nutritional source containing bio-molecules that carry anti-hypertensive, hypoglycemic, anti-asthmatic, antispasmodic, hepato-protective, chemoprotective, anti-inflammatory and anti-oxidant effects. In this study, we aimed to investigate the antioxidant content and activity of Lepidium sativum Subsp spinescens L. methanol extract on cancer cells. Methanol extract of dried Lepidium sativum Subsp spinescens L. was prepared. Total amount of phenolic compounds was determined by Slinkard and Singleton method using Folin-Ciocalteu reagent. Total flavonoid amount was determined according to Zhishen method. Antioxidant activity of the extract was evaluated by CUPRAC and ABTS radical scavenging activity assays. Cytotoxic effects of the plant extract on colon and endometrium cancer cells, and human peripheral lymphocyte cells were investigated in vitro by MTT and neutral red assays. Furthermore, the plant extract was investigated for necrotic effects by LDH assay; apoptotic activity by DNA ladder fragmentation, ELISA and acridine orange/ethidium bromide staining; and genotoxic effect by comet assay methods. Methanol extract of Lepidium sativum Subsp spinescens L. was found to have a high content of phenolic and flavonoid compounds. The extract showed significant antioxidant activity and also cytotoxic activity on colon and endometrium cancer cells in a concentration-dependent manner. Apoptotic activity and genotoxic effects were significantly increased, especially with 200 µg/ml concentrations at 48 hours incubation. In conclusion, it was determined that the extract evaluated in this study could be a natural source of antioxidants. Further molecular studies explaining chemo-preventive and chemotherapeutic effects on cancer cells are required to support anticancer efficacy of the plant.


Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Lepidium sativum/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Daño del ADN/efectos de los fármacos , Flavonoides/química , Flavonoides/farmacología , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fenoles/química , Fenoles/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología
13.
J Enzyme Inhib Med Chem ; 33(1): 1137-1149, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30001631

RESUMEN

Selective inhibition with sulphonamides of carbonic anhydrase (CA) IX reduces cell proliferation and induces apoptosis in human cancer cells. The effect on CA IX expression of seven previously synthesised sulphonamide inhibitors, with high affinity for CA IX, as well as their effect on the proliferation/apoptosis of cancer/normal cell lines was investigated. Two normal and three human cancer cell lines were used. Treatment resulted in dose- and time-dependent inhibition of the growth of various cancer cell lines. One compound showed remarkably high toxicity towards CA IX-positive HeLa cells. The mechanisms of apoptosis induction were determined with Annexin-V and AO/EB staining, cleaved caspases (caspase-3, caspase-8, caspase-9) and cleaved PARP activation, reactive oxygen species production (ROS), mitochondrial membrane potential (MMP), intracellular pH (pHi), extracellular pH (pHe), lactate level and cell cycle analysis. The autophagy induction mechanisms were also investigated. The modulation of apoptotic and autophagic genes (Bax, Bcl-2, caspase-3, caspase-8, caspase-9, caspase-12, Beclin and LC3) was measured using real time PCR. The positive staining using γ-H2AX and AO/EB dye, showed increased cleaved caspase-3, caspase-8, caspase-9, increased ROS production, MMP and enhanced mRNA expression of apoptotic genes, suggesting that anticancer effects are also exerted through its apoptosis-inducing properties. Our results show that such sulphonamides might have the potential as new leads for detailed investigations against CA IX-positive cervical cancers.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Anhidrasa Carbónica IX/antagonistas & inhibidores , Inhibidores de Anhidrasa Carbónica/farmacología , Especies Reactivas de Oxígeno/metabolismo , Sulfonamidas/farmacología , Antígenos de Neoplasias/metabolismo , Antineoplásicos/síntesis química , Antineoplásicos/química , Anhidrasa Carbónica IX/metabolismo , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/química , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Estructura Molecular , Relación Estructura-Actividad , Sulfonamidas/síntesis química , Sulfonamidas/química
14.
Chem Biodivers ; 15(1)2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29032600

RESUMEN

The synthesis, spectroscopic properties, and in vitro cytotoxicity activity of a series of various salen-based triboron complexes have been designed and prepared from hemi-salen (L1 H3  - L4 H3 ) ligands and BF3 ·Et2 O or BPh3 under simple reaction conditions. The hemi-salen (L1 H3  - L4 H3 ) ligands and their BF2 or BPh2 chelating triboron complexes were characterized by means of NMR (1 H, 13 C, 19 F, and 11 B) spectra, FT-IR spectra, UV/VIS spectra, fluorescence spectra, mass spectra, melting point, as well as elemental analysis. The triboron [L(1 - 4) (BF2 )3 ] and [L(1 - 4) (BPh2 )3 ] complexes were investigated for their absorption and emission properties, and these complexes are also good chelates towards boron(III) fragments such as BF2 or BPh2 quantum yield in solution reaching up to 38%. The hemi-salen (L1 H3  - L4 H3 ) ligands and their BF2 or BPh2 chelating triboron complexes were tested for the in vitro anticancer activity against various cancer and normal cells (HeLa, DLD-1, ECC-1, PC-3, PNT-1A, and CRL-4010), and it was found that the cell viability of cancer cells was decreased while most of the healthy cells could still be viable. Also, the cytotoxicity studies showed that anticancer activity of hemi-salen (L1 H3  - L4 H3 ) ligands is higher than that of triboron [L(1 - 4) (BF2 )3 ] and [L(1 - 4) (BPh2 )3 ] complexes. The hemi-salen (L1 H3  - L4 H3 ) ligands showing the strongest cytotoxic effect in PC-3 cells were found to exhibit anticancer activity with apoptosis by increasing the level of ROS in the PC-3 cells.


Asunto(s)
Antineoplásicos/farmacología , Compuestos de Boro/farmacología , Etilenodiaminas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Compuestos de Boro/síntesis química , Compuestos de Boro/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Etilenodiaminas/síntesis química , Etilenodiaminas/química , Humanos , Ligandos , Estructura Molecular , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad
15.
J Obstet Gynaecol ; 38(8): 1073-1077, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29884071

RESUMEN

The pathogenesis of placenta percreta (PP) is not very well known. This study was designed to analyse the oxidative stress (OS), the thiol/disulphide balance, and ischaemia-modified albumin (IMA) the women with PP. The study included 38 pregnant women with PP and 40 similarly aged healthy pregnant women in their third trimester of gestation. We measured the IMA, native and total thiols, and disulphide concentrations in the maternal sera of all of the participating women. The IMA levels were higher and the native and total thiols were lower in the PP group than in the control group. However, there was no statistical significance with respect to the thiol/disulphide balance between the two groups. The results of this study suggest that an increase in the ischaemia and OS and a decrease in the antioxidant status may contribute to the pathogenesis of PP. Impact statement What is already known on this subject? Placenta percreta (PP) is a serious complication of pregnancy. Although there are several studies investigating the pathophysiological mechanism of PP, whether the pathology results from a lack of decidua or from the over-invasiveness of trophoblasts remains controversial. The pathology of PP is poorly understood. What do the results of this study add? This prospective study has shown an increased ischaemia modified albumin (IMA) and a decreased antioxidant capacity in the patients with placenta percreta. The results from 38 women with PP suggest that the serum concentrations of IMA and the oxidative stress parameters may be able to predict PP in cases of uncertainty. What are the implications of these findings for clinical practice and/or further research? The implication of these findings shed light on understanding the pathogenesis of PP for further research.


Asunto(s)
Disulfuros/sangre , Placenta Accreta/sangre , Compuestos de Sulfhidrilo/sangre , Adulto , Biomarcadores/sangre , Femenino , Humanos , Embarazo , Tercer Trimestre del Embarazo , Estudios Prospectivos , Albúmina Sérica Humana
17.
J Coll Physicians Surg Pak ; 33(6): 616-619, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37300254

RESUMEN

OBJECTIVE: To investigate the relationship between the coma scores-Glasgow coma scale (GCS), Sequential Organ Failure Assessment (SOFA), and Acute Physiological and Chronic Health Assessment (APACHE-II)-in intensive care unit (ICU) patients and the percentage of macrocytosis (%MAC), immature granulocyte (IG), cellular haemoglobin concentration (cHGB), nucleated red blood cell (NRBC), nucleated red cell/ white cell ratio (NR/W), hyperchromic ratio (%HPR), and platelet distribution width (PDW) values. STUDY DESIGN: A descriptive comparative study. Place and Duration of the Study: Medicine Faculty, University of Harran, Turkiye, from December 2020 to May 2022. METHODOLOGY: The hemogram parameters of the patient groups with a GCS of 3-8 (n=51) and a GCS of 9-15 (n=43) and a control group of 55 healthy volunteers were measured using the new-generation hemogram autoanalyzer AlinityHQ (Abbott, USA). These parameters were compared with the coma scores (GCS, SOFA, and APACHE-II) of the patients. RESULTS: There was a statistically significant difference in IG, %MAC and PDW values (p-values were 0.025, 0.011, and 0.004, respectively) and an inverse correlation with GCS scores (correlation coefficients were -0.247, -0.264, and -0.297, respectively) was observed. There was also a significant correlation between the SOFA scores and %HPR and cHGB (correlation coefficients were 0.234, -0.358, p-values were 0.025, 0.001, respectively), and the APACHE-II scores and NRBC and NR/W values (correlation coefficients were -0.270, -0.247, p values were 0.009, 0.017, respectively). CONCLUSION: While other haematological parameters other than PDW were not associated with coma scores, parameters measured using new-generation haematological devices (%MAC, IG, cHGB, NRBC, NR/W, and %HPR) were found to be associated with estimated coma scores. These parameters can therefore be used as simple, rapid prognostic biomarkers and assist researchers in the development of new scoring models. KEY WORDS: ICU, Hyper, Coma, Sofa, Apache.


Asunto(s)
Coma , Unidades de Cuidados Intensivos , Humanos , Coma/diagnóstico , Estudios Retrospectivos , Cuidados Críticos , APACHE , Escala de Coma de Glasgow , Pronóstico , Curva ROC
18.
Biotech Histochem ; 98(1): 62-68, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35930239

RESUMEN

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.


Asunto(s)
Dexmedetomidina , Propofol , Humanos , Propofol/farmacología , Propofol/uso terapéutico , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Carnitina/farmacología , Células Epiteliales
19.
Arch Endocrinol Metab ; 67(4): e000621, 2023 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-37252703

RESUMEN

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.


Asunto(s)
COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , Femenino , Masculino , Pandemias , Hemoglobina Glucada , Estudios Retrospectivos , Control de Enfermedades Transmisibles
20.
J Med Biochem ; 42(3): 376-382, 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37814616

RESUMEN

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.

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