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1.
J Enzyme Inhib Med Chem ; 39(1): 2286925, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38062550

ABSTRACT

Cancer and antibiotic-resistant bacterial infections are significant global health challenges. The resistance developed in cancer treatments intensifies therapeutic difficulties. In addressing these challenges, this study synthesised a series of N,N'-dialkyl urea derivatives containing methoxy substituents on phenethylamines. Using isocyanate for the efficient synthesis yielded target products 14-18 in 73-76% returns. Subsequently, their antibacterial and anticancer potentials were assessed. Cytotoxicity tests on cancer cell lines, bacterial strains, and a healthy fibroblast line revealed promising outcomes. All derivatives demonstrated robust antibacterial activity, with MIC values ranging from 0.97 to 15.82 µM. Notably, compounds 14 and 16 were particularly effective against the HeLa cell line, while compounds 14, 15, and 17 showed significant activity against the SH-SY5Y cell line. Importantly, these compounds had reduced toxicity to healthy fibroblast cells than to cancer cells, suggesting their potential as dual-functioning agents targeting both cancer and bacterial infections.


Subject(s)
Antineoplastic Agents , Bacterial Infections , Neuroblastoma , Humans , HeLa Cells , Urea/pharmacology , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Antineoplastic Agents/pharmacology , Structure-Activity Relationship
2.
Health Info Libr J ; 41(1): 84-97, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37526131

ABSTRACT

BACKGROUND: Patients can often access the internet and social media for health information but it is not clear how much they trust and use the information retrieved. OBJECTIVE: To investigate the social media and internet use rates and preferences of orthopaedic patients, to reveal to what extent they self-treat, and to probe the affecting factors. METHODS: Two thousand fifty-eight patients admitted to an orthopaedic polyclinic were asked to fill out a survey (voluntarily) consisting of 15 items, to collect demographic data, preference for platforms and sources used, trusted sources, and the extent to which information obtained was used for self-care. RESULTS: The most preferred and most trusted sources of information were Google and other search engines, and physicians' personal websites (p < 0.001). DISCUSSION: Variables such as age, gender, educational level and occupation affect the research preferences. Reliance on social media decreases with increasing educational levels (p < 0.001). CONCLUSION: Health information and knowledge services should work with health professionals to improve aspects of health literacy among orthopaedic patients.


Subject(s)
Health Literacy , Orthopedics , Social Media , Humans , Surveys and Questionnaires , Educational Status , Internet
3.
Drug Chem Toxicol ; : 1-13, 2023 Jan 05.
Article in English | MEDLINE | ID: mdl-36606327

ABSTRACT

Nowadays, the unique features of nanoparticles (NPs) have encouraged new applications in different areas including biology, medicine, agriculture, and electronics. Their quick joining into daily life not only enhances the uses of NPs in a wide range of modern technologies but also their release into the aquatic environment causes inevitable environmental concerns. On the other hand boron exhibits key physiological effects on biological systems. This research was designed for evaluating the toxicity of magnetite nanoparticles (Fe3O4-MNPs) on aquatic organisms and obtaining data for the information gap in this area. In this study, Rainbow trout (Oncorhynchus mykiss) was considered as an aquatic indicator, and trials were designed as Ulexite (a boron mineral, UX) treatment against exposure to Fe3O4-MNPs. Synthesized and characterized Fe3O4-MNPs were exposed to rainbow trouts in wide spectrum concentrations (0.005-0.08 mL/L) to analyze its lethal dose (LC50) and cytoprotective properties by UX treatment were assessed against Fe3O4-MNPs applications for 96 h. For the initial toxicity analysis, hematological parameters (blood cell counts) were examined in experimental groups and micronucleus (MN) assay was performed to monitor nuclear abnormalities after exposure to NPs. Biochemical analyzes in both blood and liver samples were utilized to assess antioxidant/oxidative stress and inflammatory parameters. Also, 8-hydroxy-2'-deoxyguanosine (8-OHdG) assay was used to investigate oxidative DNA lesions and Caspase-3 analysis was performed on both blood and liver tissues to monitor apoptotic cell death occurrence. When antioxidant enzymes in blood and liver tissue were examined, time-dependent decreases in activity were determined in SOD, CAT, GPx, and GSH enzymes, while increased levels of MDA and MPO parameters were observed in respect to Fe3O4-MNPs exposure. It was found that TNF-α, Il-6 levels were enhanced against Fe3O4-MNPs treatment, but Nrf-2 levels were decreased at the 46th and 96th h. In the 96th application results, all parameters were statistically significant (p < 0.05) in blood and liver tissue, except for the IL-6 results. It was determined that the frequency of MN, the level of 8-OHdG and caspase-3 activity increased in respect to Fe3O4-MNPs exposure over time. Treatment with UX alleviated Fe3O4-MNPs-induced hematotoxic and hepatotoxic alterations as well as oxidative and genetic damages. Our findings offer strong evidence for the use of UX as promising, safe and natural protective agents against environmental toxicity of magnetite nanoparticles.

4.
Medicina (Kaunas) ; 60(1)2023 Dec 30.
Article in English | MEDLINE | ID: mdl-38256343

ABSTRACT

Background and Objectives: Favipiravir (FPV) is an antiviral medication and has an inhibitory effect on Cytochrome P450 (CYP2C8) protein, which is mainly involved in drug metabolism in the liver, and the expression of this gene is known to be enhanced in neuronal cells. The metabolization of Paclitaxel (PTX), a chemotherapeutic drug used in cancer patients, was analyzed for the first time in the human SH-SY5Y neuroblastoma cell line for monitoring possible synergistic effects when administered with FPV. Materials and Methods: Further, in vitro cytotoxic and genotoxic evaluations of FPV and PTX were also performed using wide concentration ranges in a human fibroblast cell culture (HDFa). Nuclear abnormalities were examined under a fluorescent microscope using the Hoechst 33258 fluorescent staining technique. In addition, the synergistic effects of these two drugs on cultured SH-SY5Y cells were determined by MTT cell viability assay. In addition, the death mechanisms that can occur in SHSY-5Y were revealed by using the flow cytometry technique. Results: Cell viability analyses on the HDFa healthy cell culture showed that both FPV and PTX have inhibitory effects at higher concentrations. On the other hand, there were no significant differences in nuclear abnormality numbers when both of the compounds were applied together. Cell viability analyses showed that FPV and PTX applications have higher cytotoxicity, which indicated synergistic toxicity against the SHSY-5Y cell line. Also, PTX exhibited higher anticancer properties against the neuroblastoma cell line when applied with FPV, as shown in both cytotoxicity and flow cytometry analyses. Conclusions: In light of our findings, the anticancer properties of PTX can be enhanced when the drug application is coupled with FPV exposure. Moreover, these results put forth that the anticancer drug dosage should be evaluated carefully in cancer patients who take COVID-19 treatment with FPV.


Subject(s)
Amides , Neuroblastoma , Paclitaxel , Pyrazines , Humans , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Drug Synergism , COVID-19 Drug Treatment , Neuroblastoma/drug therapy
5.
Gynecol Endocrinol ; 38(3): 243-247, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34494506

ABSTRACT

AIMS: This study aims to investigate whether HRG gene C633T rs9898 and TP73 gene rs4648551 A > G polymorphisms have an effect on ovulation and response to the gonadotropin treatments. MATERIALS AND METHODS: Blood samples were received from a total of 206 individuals (116 patients from whom good quality and optimal of numbers oocytes have not been able to be obtained at the IVF Center of Ondokuz Mayis University, Faculty of Medicine and 90 controls). Genomic DNA was extracted by DNA isolation and SNP genotyping was performed by real-time qPCR method. RESULTS: According to the results, a significant difference was observed between the patient and control groups in terms of the TP73 gene variant, however there was no significant difference regarding HRG gene polymorphism. CONCLUSIONS: Our findings suggest that while AG genotype for TP73 could be a genetic marker for ovarian response, HRG gene C633T variation is not associated with ovarian response in our cohort. Further studies with larger study groups are required to investigate possible associations of these gene variants with ovarian response.


Subject(s)
Ovary , Polymorphism, Single Nucleotide , Proteins , Tumor Protein p73 , Cohort Studies , Female , Fertilization in Vitro , Genotype , Humans , Oocytes , Ovulation Induction , Proteins/genetics , Tumor Protein p73/genetics
6.
Int J Mol Sci ; 23(15)2022 Jul 26.
Article in English | MEDLINE | ID: mdl-35897815

ABSTRACT

The search for an innovative and effective drug delivery system that can carry and release targeted drugs with enhanced activity to treat Alzheimer's disease has received much attention in the last decade. In this study, we first designed a boron-based drug delivery system for effective treatment of AD by integrating the folic acid (FA) functional group into hexagonal boron nitride (hBN) nanoparticles (NPs) through an esterification reaction. The hBN-FA drug carrier system was assembled with a new drug candidate and a novel boron-based hybrid containing an antioxidant as BLA, to constitute a self-assembled AD nano transport system. We performed molecular characterization analyses by using UV-vis spectroscopy, Fourier transform infrared spectrophotometer (FTIR), scanning electron microscope (SEM), Energy-dispersive X-ray spectroscopy (EDS) and Zeta potential investigations. Second, we tested the anti-Alzheimer properties of the carrier system on a differentiated neuroblastoma (SHSY5-Y) cell line, which was exposed to beta-amyloid (1-42) peptides to stimulate an experimental in vitro AD model. Next, we performed cytotoxicity analyses of synthesized molecules on the human dermal fibroblast cell line (HDFa) and the experimental AD model. Cytotoxicity analyses showed that even higher concentrations of the carrier system did not enhance the toxicological outcome in HDFa cells. Drug loading analyses reported that uncoated hBN nano conjugate could not load the BLA, whereas the memantine loading capacity of hBN was 84.3%. On the other hand, memantine and the BLA loading capacity of the hBN-FA construct was found to be 95% and 97.5%, respectively. Finally, we investigated the neuroprotective properties of the nano carrier systems in the experimental AD model. According to the results, 25 µg/mL concentrations of hBN-FA+memantine (94% cell viability) and hBN-FA+BLA (99% cell viability) showed ameliorative properties against beta-amyloid (1-42) peptide toxicity (50% cell viability). These results were generated through the use of flow cytometry, acetylcholinesterase (AChE) and antioxidant assays. In conclusion, the developed drug carrier system for AD treatment showed promising potential for further investigations and enlightened neuroprotective capabilities of boron molecules to treat AD and other neurodegenerative diseases. On the other hand, enzyme activity, systematic toxicity analyses, and animal studies should be performed to understand neuroprotective properties of the designed carrier system comprehensively.


Subject(s)
Alzheimer Disease , Nanoparticles , Acetylcholinesterase , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/metabolism , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Boron , Boron Compounds , Drug Carriers/therapeutic use , Folic Acid/therapeutic use , Humans , Memantine/therapeutic use , Nanoparticles/chemistry
7.
J Mater Sci Mater Med ; 32(1): 6, 2021 Jan 20.
Article in English | MEDLINE | ID: mdl-33471227

ABSTRACT

In this study, borosilicate glass and 316 L stainless steel were coated with germanium (Ge) and tungsten (W) metals using the Magnetron Sputtering System. Surface structural, mechanical, and tribological properties of uncoated and coated samples were examined using SEM, X-ray diffraction (XRD), energy-dispersive spectroscopy, and tribometer. The XRD results showed that WGe2 chemical compound observed in (110) crystalline phase and exhibited a dense structure. According to the tribological analyses, the adhesion strength of the coated deposition on 316 L was obtained 32.8 N, and the mean coefficient of friction was around 0.3. Biocompatibility studies of coated metallic biomaterials were analyzed on fibroblast cell culture (Primary Dermal Fibroblast; Normal, Human, Adult (HDFa)) in vitro. Hoescht 33258 fluorescent staining was performed to investigate the cellular density and chromosomal abnormalities of the HDFa cell line on the borosilicate glasses coated with germanium-tungsten (W-Ge). Cell viabilities of HDFa cell line on each surface (W-Ge coated borosilicate glass, uncoated borosilicate glass, and cell culture plate surface) were analyzed by using (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxicity assay. The antibiofilm activity of W-Ge coated borosilicate glass showed a significant reduction effect on Staphylococcus aureus (ATCC 25923) and Pseudomonas aeruginosa (ATCC 27853) adherence compared to control groups. In the light of findings, tungsten and germanium, which are some of the most common industrial materials, were investigated as biocompatible and antimicrobial surface coatings and recommended as bio-implant materials for the first time.


Subject(s)
Biocompatible Materials/chemistry , Biofilms , Germanium/chemistry , Tungsten/chemistry , Cell Survival , Coated Materials, Biocompatible/chemistry , Corrosion , Crystallography, X-Ray/methods , Fibroblasts/metabolism , Humans , Materials Testing , Microbial Sensitivity Tests , Microscopy, Electron, Scanning , Pseudomonas aeruginosa/drug effects , Stainless Steel/chemistry , Staphylococcus aureus/drug effects , Surface Properties , Titanium/chemistry , X-Ray Diffraction
8.
Andrologia ; 53(1): e13840, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33108820

ABSTRACT

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein with glutamate carboxypeptidase activity. However, its precise function in the prostate, prostasomes and seminal plasma with regard to male fertility remains unknown. This study was conducted to investigate the seminal plasma PSMA levels in fertile men and patients with oligoasthenoteratozoospermia (OAT) and to analyse its association with sperm parameters. Twenty fertile men and twenty patients admitted at the urology clinic of our institution with the diagnosis of OAT were included in the study. Following semen analysis, seminal plasma was isolated from semen ejaculates. PSMA concentrations in the seminal plasma were determined by ELISA. The correlations between seminal PSMA concentrations and semen parameters were statistically analysed. Seminal plasma PSMA concentration was significantly lower in OAT patients compared to fertile controls (p < .01). In fertile men, PSMA concentration was significantly correlated with the sperm concentration (r = -.481, p < .05), whereas in the patient group no statistically significant correlation was found between the sperm parameters and seminal PSMA level. This is the first study in the literature to investigate PSMA levels in the seminal plasma from infertile men. Decreased levels of seminal plasma PSMA might suggest a role for compromised prostasome function in the pathogenesis of OAT syndrome.


Subject(s)
Infertility, Male , Semen , Humans , Male , Prostate , Semen Analysis , Sperm Count , Sperm Motility , Spermatozoa
9.
Drug Chem Toxicol ; 44(4): 409-417, 2021 Jul.
Article in English | MEDLINE | ID: mdl-30945575

ABSTRACT

Rhus coriaria has been important in the treatment of many diseases in traditional use. In this content, the genotoxic, antigenotoxic, and oxidative stress effects of methanol extract of R. coriaria (RCE) were investigated in this study. Two hundred fifty, 500, or 750 µg/mL concentrations of RCE were not found to have DNA damaging effect on pET22-b(+) plasmid and were unable to induce micronuclei in human lymphocytes (24 or 48 h treatment period). However, it did not inhibit the genotoxic effect of mitomycin-c (0.25 µg/mL). Cytotoxic effects of RCE were investigated using mitotic index (MI) and nuclear division index (NDI). Five hundred, 1000, and 2000 mg/kg concentrations of RCE did not induce chromosome aberrations in rat bone marrow cells for 12 or 24 h treatment period. In addition, 2000 mg/kg concentration of RCE showed an antigenotoxic effect by decreasing to genotoxic effect of 400 mg/kg urethane at 12 and 24 h treatment periods. RCE showed cytotoxic effects by significantly decreasing NDI. Moreover, RCE increased cytotoxic effect of Mitomycin C (MMC). However, RCE did not induce cytotoxicity in rat bone marrow cells. The highest concentration of RCE reduced total oxidant level in 12 h treatment. Interestingly, the lowest total oxidant level was found in rats blood treated with the lowest concentration RCE and urethane together. Thousand and 2000 mg/kg concentrations of RCE decreased total antioxidant levels of rat blood at 24 h treatment period. Our results showed that RCE possess cytotoxic effect in short-term treatments in vitro. However, it does not demonstrate genotoxic or cytotoxic effects in vivo.


Subject(s)
Antioxidants/metabolism , Oxidative Stress/drug effects , Plant Extracts/administration & dosage , Rhus/chemistry , Adult , Animals , Antimutagenic Agents/pharmacology , Bone Marrow Cells/drug effects , Chromosome Aberrations/drug effects , DNA Damage/drug effects , Dose-Response Relationship, Drug , Female , Humans , In Vitro Techniques , Male , Mitomycin/toxicity , Mutagenicity Tests , Plant Extracts/pharmacology , Plant Extracts/toxicity , Rats , Rats, Sprague-Dawley , Young Adult
10.
Int J Neurosci ; 131(8): 745-754, 2021 Aug.
Article in English | MEDLINE | ID: mdl-32308094

ABSTRACT

OBJECTIVE: To investigate neuroprotective properties of the farnesene sesquiterpene on the experimental Alzheimer's disease model in vitro. METHODS: Human neuroblastoma cell line (SHSY-5Y) was differentiated into neuron-like cells by using retinoic acid to constitute the in vitro Alzheimer's Disease model. ß-amyloid 1-42 protein was applied to the transformed cells for 24 and 48 hours in a wide dose ranges (3.125-200 µM) to establish AD cytotoxicity. Then, farnesene was applied to cell cultures in a wide spectrum dose interval (1.625-100 µg/ml) to investigate neuroprotective effect against ß-amyloid for 24 and 48 hours. 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release tests were executed to determine cytotoxicity in the Alzheimer model. Nuclear DNA integrity of cells was examined under the fluorescent microscope using the Hoechst 33258 staining method. Furthermore, acetylcholinesterase (AChE) activity, total antioxidant capacity (TAC) and total oxidative status (TOS) levels were analyzed to understand the protection mechanism of the farnesene application on the cell culture model. Finally, flow cytometry analysis was used to find out the cell death mechanism after beta-amyloid and farnesene application to the cell culture. RESULTS: Cell viability tests revealed significant neuroprotection against ß-amyloid toxicity in both 24 and 48 hours and the Hoechst 33258 fluorescence staining method showed a significant decrease in necrotic deaths after farnesene application in the cell cultures. Finally, flow cytometry analysis put forth that farnesene could decrease necrotic cell death up to 3-fold resulted from beta-amyloid exposure. CONCLUSION: According to the investigations, farnesene can potentially be a safe, anti-necrotic and neuroprotective agents against Alzheimer's disease.


Subject(s)
Alzheimer Disease/metabolism , Neuroprotective Agents/administration & dosage , Sesquiterpenes/administration & dosage , Acetylcholinesterase/metabolism , Cell Differentiation , Cell Line, Tumor , Humans , Oxidative Stress/drug effects
11.
Metab Brain Dis ; 35(6): 947-957, 2020 08.
Article in English | MEDLINE | ID: mdl-32215836

ABSTRACT

Parkinson's disease (PD) is one of the most aggressive neurodegenerative diseases and characterized by the loss of dopamine-sensitive neurons in the substantia nigra region of the brain. There is no any definitive treatment to completely cure PD and existing treatments can only ease the symptoms of the disease. Boron nitride nanoparticles have been extensively studied in nano-biological studies and researches showed that it can be a promising candidate for PD treatment with its biologically active unique properties. In the present study, it was aimed to investigate ameliorative effects of hexagonal boron nitride nanoparticles (hBNs) against toxicity of 1-methyl-4-phenylpyridinium (MPP+) in experimental PD model. Experimental PD model was constituted by application of MPP+ to differentiated pluripotent human embryonal carcinoma cell (Ntera-2, NT-2) culture in wide range of concentrations (0.62 to 2 mM). Neuroprotective activity of hBNs against MPP+ toxicity was determined by cell viability assays including MTT and LDH release. Oxidative alterations by hBNs application in PD cell culture model were investigated using total antioxidant capacity (TAC) and total oxidant status (TOS) tests. The impacts of hBNs and MPP+ on nuclear integrity were analyzed by Hoechst 33258 fluorescent staining method. Acetylcholinesterase (AChE) enzyme activities were determined by a colorimetric assay towards to hBNs treatment. Cell death mechanisms caused by hBNs and MPP+ exposure was investigated by flow cytometry analysis. Experimental results showed that application of hBNs increased cell viability in PD model against MPP+ application. TAS and TOS analysis were determined that antioxidant capacity elevated after hBNs applications while oxidant levels were reduced. Furthermore, flow cytometric analysis executed that MPP+ induced apoptosis was prevented significantly (p < 0.05) after application with hBNs. In a conclusion, the obtained results indicated that hBNs have a huge potential against MPP+ toxicity and can be used in PD treatment as novel neuroprotective agent and drug delivery system.


Subject(s)
1-Methyl-4-phenylpyridinium/toxicity , Apoptosis/drug effects , Boron Compounds/administration & dosage , Nanoparticles/administration & dosage , Neuroprotective Agents/administration & dosage , Parkinsonian Disorders/prevention & control , Apoptosis/physiology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Humans , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/pathology
12.
Eat Weight Disord ; 25(6): 1515-1523, 2020 Dec.
Article in English | MEDLINE | ID: mdl-31576497

ABSTRACT

PURPOSE: The aim of this study was to assess depressive symptoms, self-esteem, and eating psychopathology in bariatric surgery patients at the preoperative period (t0) and at the 6-month (t1) and 12-month (t2) follow-ups after laparoscopic sleeve gastrectomy (LSG). A second aim was to investigate associations between these variables and weight loss. METHOD: The study participants were 48 bariatric surgery candidates and 50 non-obese controls. Both groups underwent assessment with the Sociodemographic Data Form, Hamilton Depression Rating Scale (HDRS), Eating Disorder Examination Questionnaire (EDE-Q), and Rosenberg Self-esteem Scale (RSES). These assessments were repeated for the patient group at t1 and t2. RESULTS: The HDRS, RSES, and EDE-Q scores were higher in the patients before LSG (t0) than in the control group. A significant progressive improvement was identified in the patient HDRS and RSES scores as well as EDE-Q weight and shape subscale scores at t1 and t2. However, the patient EDE-Q total and dietary restraint scores improved at t1 then stabilized. The patient EDE-Q eating concern subscale improved at t1, but then worsened. The patient HDRS scores at t2 were similar to the control group, but the EDE-Q and RSES scores were still higher than the control scores at t2. Regression analyses revealed no association between the preoperative scores and percent changes in postoperative scores for any scale and patient weight loss at t2. CONCLUSION: Depressive symptoms, self-esteem, and eating psychopathology showed an improving trend in patients after LSG. However, some aspects of eating psychopathology worsened despite an initial improvement. LEVEL OF EVIDENCE: III, prospective cohort and case-control study.


Subject(s)
Feeding and Eating Disorders , Laparoscopy , Mental Disorders , Case-Control Studies , Depression/etiology , Follow-Up Studies , Gastrectomy , Humans , Prospective Studies , Surveys and Questionnaires
13.
Andrologia ; 51(7): e13308, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31095775

ABSTRACT

The purpose of the study was to investigate whether the promoter methylation status of BRCA1 and BRCA2 DNA repair genes is associated with sperm DNA fragmentation (sDF) in infertile men with oligoasthenoteratozoospermia (OAT) which emerges due to various reasons and is effective in male infertility. Seventy-three infertile men with OAT and 20 normozoospermic volunteers participated in the study. To investigate sDF and methylation patterns of BRCA1 and BRCA2 gene promoters, TUNEL assay and methylation-specific PCR (MS-PCR) were used. The mean sDF ratio for the patients was calculated as 22.50%. The calculated cut-off value for sDF ratio was 17.0% in ROC curve analysis. Regarding sDF, a significant difference between the normozoospermic group and the OAT group with abnormal semen parameters (p < 0.001) was found. sDF demonstrated a significant effect on the semen parameters and negative correlations on sDF ratios and sperm motility, concentration and morphology. There was no statistically significant association between sDF and the methylation status of the promoter of either BRCA1 or BRCA2 genes. In routine clinical practice, sperm DNA integrity should be investigated before applying assisted reproductive techniques. To understand better the relationship between epigenetic regulation of DNA repair genes and male infertility, additional studies are required.


Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , DNA Fragmentation , DNA Methylation , Oligospermia/genetics , Adult , Epigenesis, Genetic , Humans , Male , Oligospermia/pathology , Promoter Regions, Genetic/genetics , Sperm Motility/genetics , Spermatozoa/pathology , Young Adult
14.
Cutan Ocul Toxicol ; 38(2): 196-200, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30719935

ABSTRACT

PURPOSE: To investigate the acute effects of brinzolamide, betaxolol, and latanoprost (drugs commonly used in the medical management of glaucoma) on choroidal thickness using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS: Ninety healthy volunteers were evaluated in this prospective study. Participants were randomly divided into 3 groups. Brinzolamide, betaxolol, and latanoprost were administered into the left eyes of the first group (n = 30), second group (n = 30), and third group (n = 30), respectively, and artificial tear (Sodium hyaluronate) was instilled into the right eyes of all participants. Subfoveal choroidal thickness (SFCT) was measured using EDI-OCT before and 45 minutes after administration of the antiglaucomatous drops. RESULTS: SFCT revealed a significant increase in the left eye (administered antiglaucomatous drop) in the brinzolamide (p = 0.001) and betaxolol groups (p = 0.049) and a significant increase also in the right eye (administered artificial drop) in the brinzolamide (p = 0.001) and betaxolol groups (p = 0.001). However, SFCT did not reveal a significant increase in the left eye (p = 0.213) or in the right eye (p = 0.062) in the latanoprost group. CONCLUSION: Brinzolamide and betaxolol caused an increase in SFCT, while latanoprost had no significant effect on SFCT.


Subject(s)
Antihypertensive Agents/adverse effects , Betaxolol/adverse effects , Choroid/drug effects , Latanoprost/adverse effects , Sulfonamides/adverse effects , Thiazines/adverse effects , Adult , Choroid/diagnostic imaging , Choroid/pathology , Glaucoma/diagnostic imaging , Glaucoma/drug therapy , Glaucoma/pathology , Humans , Middle Aged , Tomography, Optical Coherence , Young Adult
15.
Dig Dis ; 36(3): 244-251, 2018.
Article in English | MEDLINE | ID: mdl-29332096

ABSTRACT

AIM: Coagulation disorders may develop in association with severe acute pancreatitis (AP). Plasma thrombin-antithrombin III complex (TAT) levels are one of the principal markers of coagulation disorder. The purpose of this study was to evaluate TAT and other hemostatic parameters in patients with AP and to examine whether or not these parameters indicate the severity of AP. METHOD: Forty-six patients with AP (14 severe, 32 non-severe) and a 30-member healthy control group were recruited. The severity of AP was determined using the revised Atlanta classification. ELISA was used to measure patients' plasma TAT levels. RESULTS: The TAT levels of AP patients at presentation were higher than those of the control group (p = 0.005). The plasma TAT levels of patients with severe AP were also significantly higher than those of patients with non-severe AP (p = 0.05) and of the control group (p < 0.001). The general accuracy, sensitivity and specificity of TAT levels in predicting the severity of AP were 77.4, 77.8, and 77.3% respectively. CONCLUSION: The coagulation cascade was activated in the AP patients in our study, and this was shown to become more pronounced as severity of the disease increased. Plasma TAT levels at the time of presentation in patients with AP can be used as a marker for predicting the severity of the disease.


Subject(s)
Antithrombin III/metabolism , Pancreatitis/blood , Peptide Hydrolases/metabolism , Acute Disease , Biomarkers/blood , C-Reactive Protein/metabolism , Carboxypeptidase B2/metabolism , Case-Control Studies , Female , Humans , Male , Middle Aged , ROC Curve
16.
Andrologia ; 50(9): e13124, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30132931

ABSTRACT

Male fertility rates have shown a progressive decrease in both developing and industrialised countries in the past 50 years. Clinical and epidemiological studies have demonstrated controversial results about the harmful effects of cigarette smoking on seminal parameters. Some studies could not establish a negative effect by tobacco smoking on sperm quality and function, whereas others have found a significant reduction in sperm quality and function. This study reviews the components in cigarette smoke and discusses the effects of smoking on male fertility by focusing extensively on smoking-induced genetic and epigenetic alterations in infertile men. Chromosomal aneuploidies, sperm DNA fragmentation and gene mutations are discussed in the first section, while changes in DNA methylation, chromatin remodelling and noncoding RNAs are discussed in the second section as part of epigenetic alterations.


Subject(s)
Epigenesis, Genetic , Infertility, Male/genetics , Smoke/adverse effects , Smoking/adverse effects , Animals , Humans , Male
17.
J Pak Med Assoc ; 68(1): 38-41, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29371715

ABSTRACT

OBJECTIVE: The purpose of this retrospective study was to clarify the relationship of shunt infection to childhood hydrocephalus etiology. METHODS: We analyzed 1021 patients with childhood hydrocephalus who underwent V-P shunting over a period of approximately 15 years. The etiology of 1021 patients include myelomeningocele (794 patient), congenital (165 patient) and intraventricular haemorrhage (62 patient). RESULTS: Of the 1021 patients who underwent V-P shunting, 19.32% exhibited shunt infection. Shunt infection developed in 180 (22.67%) of 794 patients with myelomeningocele, 9 (5.45%) of 165 patients with congenital obstructive hydrocephalus, and 9 (14.51%) of 62 patients with intraventricular haemorrhage. Recurrent shunt infection was detected in 54 (27.27%) of 198 patients with a previous shunt infection. CONCLUSIONS: Patients with previous shunt infection as well as those with shunts associated with myelomeningocele were observed to be at a greater risk for shunt infection. Results indicated that patients with congenital obstructive hydrocephalus may be less prone to shunt infections.


Subject(s)
Hydrocephalus/epidemiology , Postoperative Complications/epidemiology , Ventriculoperitoneal Shunt/adverse effects , Child , Humans , Hydrocephalus/etiology , Hydrocephalus/surgery , Retrospective Studies
18.
Bioconjug Chem ; 28(5): 1443-1451, 2017 05 17.
Article in English | MEDLINE | ID: mdl-28441501

ABSTRACT

Poly(ethylene glycol) (PEG) based bulk hydrogels and cryogels containing activated carbonate groups as amine reactive handles to facilitate drug conjugations through carbamate linkages were fabricated and evaluated as slow releasing drug reservoirs. As an initial approach, photopolymerization of N-hydroxysuccinimide (NHS)-activated carbonate functional group containing monomer and PEG-methacrylate in the presence of a cross-linker was utilized to obtain bulk hydrogels with high gel conversions. The resultant hydrogels possessed moderate water uptake (170-340%) which was dependent on the monomer ratios. These hydrogels were functionalized with an anticancer drug, namely, doxorubicin. Surprisingly, while negligible drug release was observed from the bulk hydrogels under normal pH, only about 6% drug release was observed under acidic condition. Limited swelling of these hydrogels as well as lack of porous structure as deduced from scanning electron microscopy analysis might explain the poor drug release. To enhance the drug releasing capacity of these hydrogels that might stem from the increased porosity, reactive carbonate group bearing cryogels were synthesized. Compared to the bulk hydrogels, cryogels were highly porous in structure and also possessed much higher swelling capacity (1150-1500%). As a result of these distinctions, a 7-fold enhancement in drug release was observed for the cryogel system compared to the relating hydrogel. In vitro studies demonstrated that the anticancer drug doxorubicin conjugated through carbamate linkers to the cryogels was released and proved effective against MDA-MB-231 human breast cancer cells. Overall, a novel class of slow releasing nontoxic hydrogel and cryogel scaffolds with potential applications as anticancer drug reservoirs was realized.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Breast Neoplasms/drug therapy , Carbamates/chemistry , Cryogels/chemistry , Doxorubicin/pharmacology , Drug Liberation , Hydrogels/chemistry , Antibiotics, Antineoplastic/chemistry , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Doxorubicin/chemistry , Drug Carriers , Female , Humans , Tumor Cells, Cultured
19.
Drug Chem Toxicol ; 40(4): 463-469, 2017 Oct.
Article in English | MEDLINE | ID: mdl-27998191

ABSTRACT

Macrolide antibiotic roxithromycin was evaluated in terms of its genotoxic, cytotoxic and oxidative stress effects. For this purpose; 25, 50, 100 and 200 µg/mL concentrations of roxithromycin were dissolved in dimethyl sulfoxide and treated to human peripheral blood lymphocytes for two different treatment periods (24 and 48 h). In chromosome aberration (CA) and micronucleus (MN) tests, roxithromycin did not show genotoxic effect. But it induced sister chromatid exchange (SCE) at the highest concentration (200 µg/mL) for the 24-h treatment period and at all concentrations (except 25 µg/mL) for the 48-h treatment period. Looking at cytotoxic effect of roxithromycin, statistically insignificant decreases on mitotic index and proliferation index were observed. Roxithromycin decreased nuclear division index (NDI) at highest two concentrations (100 and 200 µg/mL) for the 24-h treatment period and at all concentrations (expect 25 µg/mL) for the 48-h treatment period. Total oxidant values, total antioxidant values and oxidative stress index did not change with roxithromycin treatment. Eventually, roxithromycin did not have genotoxic and oxidative stress effects in human-cultured lymphocytes.


Subject(s)
Anti-Bacterial Agents/adverse effects , Cell Nucleus Division/drug effects , Lymphocytes/drug effects , Mutagens/adverse effects , Roxithromycin/adverse effects , Sister Chromatid Exchange/drug effects , Adult , Cell Proliferation/drug effects , Cells, Cultured , DNA Repair/drug effects , DNA Replication/drug effects , Female , Humans , Lymphocytes/cytology , Lymphocytes/immunology , Lymphocytes/metabolism , Male , Micronucleus Tests , Mitotic Index , Mutagenicity Tests , Osmolar Concentration , Oxidative Stress/drug effects , Young Adult
20.
Surg Radiol Anat ; 39(12): 1377-1383, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28725916

ABSTRACT

PURPOSE: The purpose of this study was to elucidate the anatomy and clinical importance of extraforaminal ligaments in the cervical region. METHODS: This study was performed on eight embalmed cadavers. The existence and types of extraforaminal ligaments were identified. The morphology, quantity, origin, insertion, and orientation of the extraforaminal ligaments in the cervical region were observed. RESULTS: Extraforaminal ligaments could be divided into two types: transforaminal ligaments and radiating ligaments. It was observed that during their course, transforaminal ligaments cross the intervertebral foramen ventrally. They usually originate from the anteroinferior margin of the anterior tubercle of the cranial transverse process and insert into the superior margin of the anterior tubercle of the caudal transverse process. The dorsal aspect of the transforaminal ligaments adhere loosely to the spinal nerve sheath. The length, width and thickness of these ligaments increased from the cranial to the caudal direction. A single intervertebral foramen contained at least one transforaminal ligament. A total of 98 ligaments in 96 intervertebral foramina were found. The spinal nerves were extraforaminally attached to neighboring anterior and posterior tubercle of the cervical transverse process by the radiating ligaments. The radiating ligaments consisted of the ventral superior, ventral, ventral inferior, dorsal superior and dorsal inferior radiating ligaments. Radiating ligaments originated from the adjacent transverse processes and inserted into the nerve root sheath. The spinal nerve was held like the hub of a wheel by a series of radiating ligaments. The dorsal ligaments were the thickest. From C2-3 to C6-7 at the cervical spine, radiating ligaments were observed. They developed particularly at the level of the C5-C6 intervertebral foramen. CONCLUSIONS: This anatomic study may provide a better understanding of the relationship of the extraforaminal ligaments to the cervical nerve root.


Subject(s)
Cervical Vertebrae/anatomy & histology , Ligaments/anatomy & histology , Spinal Nerve Roots/anatomy & histology , Aged , Cadaver , Humans , Male , Middle Aged
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