Mehmet Korkmaz

Effect of Boron on Human Health

Studies on boron, its mechanism and health effects are growing although the safe limits of daily boron exposure have not been clarified. Current knowledge about the toxic levels of boron on humans is not sufficient and needs to be improved. The main toxic effect of boron in animals involves the reproductive system, including specific adverse effects in the male reproductive tract in rats, mice and dogs. Boron determination in biological matrices needs sufficiently sensitive procedures for detection at trace levels, and many techniques do exist. In this paper, we reviewed the general view of potential impact of boron on health, exposure of boron and its determination techniques.

Estimation of human daily boron exposure in a boron-rich area.

Although, the safe limits of human daily boron (B) exposure are not absolutely clear, there is a growing interest in B and its effects on human health. The aim of the present study was to estimate daily B exposure in 66 males in Turkey living in a B-rich area using water containing at least 2 mg/l boron, with an average age of 38.55 (se 1.66) years and an average number of years of residence in the B-rich area of 35.89 (se 1.73). Another group of males (n 57), living in the city centres of Balikesir and Ankara, were taken as controls; the average age and number of years of residence for this group were 29.44 (se 1.43) and 10.26 (se 1.83) years, respectively. As it is assumed that the B level in urine reflects daily B exposure, the amount of urinary B of both the study and control groups was analysed by using an inductively coupled plasma optical emission spectrometry (ICP-OES) technique. The average daily B exposure value was calculated as 6.77 (se 0.47) mg in the study group and 1.26 (se 0.1) mg in the controls. The results of this study are expected to contribute to creating a reference value for a safe daily B exposure.

The potential role of the NEK6, AURKA, AURKB, and PAK1 genes in adenomatous colorectal polyps and colorectal adenocarcinoma

Colorectal adenomatous polyp (CRAP) is a major risk factor for the development of sporadic colorectal cancer (CRC). Histone modifications are one of the epigenetic mechanisms that may have key roles in the carcinogenesis of CRC. The objective of the present study is to investigate the alternations in the defined histone modification gene expression profiles in patients with CRAP and CRC. Histone modification enzyme key gene expressions of the CRC, CRAP, and control groups were evaluated and compared using the reverse transcription PCR (RT-PCR) array method. Gene expression analysis was performed in the CRAP group after dividing the patients into subgroups according to the polyp diameter, pathological results, and morphological parameters which are risk factors for developing CRC in patients with CRAP. PAK1, NEK6, AURKA, AURKB, HDAC1, and HDAC7 were significantly more overexpressed in CRC subjects compared to the controls (p < 0.05). PAK1, NEK6, AURKA, AURKB, and HDAC1 were significantly more overexpressed in the CRAP group compared to the controls (p < 0.005). There were no significant differences between the CRAP and CRC groups with regards to PAK1, NEK6, AURKA, or AURKB gene overexpression. PAK1, NEK6, AURKA, and AURKB were significantly in correlation with the polyp diameter as they were more overexpressed in polyps with larger diameters. In conclusion, overexpressions of NEK6, AURKA, AURKB, and PAK1 genes can be used as predictive markers to decide the colonoscopic surveillance intervals after the polypectomy procedure especially in polyps with larger diameters.

Never in mitosis gene A-related kinase 6 and aurora kinase A: New gene biomarkers in the conversion from ulcerative colitis to colorectal cancer

Ulcerative colitis (UC) is an important risk factor for colorectal cancer (CRC). Histone modifications are one of the epigenetic mechanisms that may have key roles in the carcinogenesis of CRC. At present, there are no studies comparing histone modification patterns of UC and CRC in the literature. Therefore the aim of the present study was to investigate whether genes, particularly those involved in histone modification, have value in patient monitoring with regards to CRC development in UC. Key gene expressions of the histone modification enzyme were assessed and compared in CRC, UC and control groups using the RT-PCR array technique. Patients were divided into subgroups based on the extent and duration of the disease and inflammatory burden, which are considered risk factors for CRC development in UC patients. In UC and CRC groups, a significantly higher overexpression of the NEK6 and AURKA genes compared to the control group was identified. In addition, there was a significantly higher overexpression of HDAC1 and PAK1 genes in the UC group, and of HDAC1, HDAC7, PAK1 and AURKB genes in the CRC group. NEK6, AURKA, HDAC1 and PAK1 were significantly overexpressed in patients with a longer UC duration. Overexpression of AURKA and NEK6 genes was significantly more pronounced in UC patients with more extensive colon involvement. HDAC1, HDAC7, PAK1, NEK6, AURKA and AURKB are important diagnostic and prognostic markers involved in the carcinogenesis of CRC. HDAC1, PAK1, NEK6 and AURKA may be considered as diagnostic markers to be used in CRC screening for UC patients.

Biological effects of tolerable level chronic boron intake on transcription factors

The mechanism of boron effect on human transcription and translation has not been fully understood. In the current study it was aimed to reveal the role of boron on the expression of certain transcription factors that play key roles in many cellular pathways on human subjects chronically exposed to low amounts of boron. The boron concentrations in drinking water samples were 1.57±0.06mg/l for boron group while the corresponding value for the control group was 0.016±0.002mg/l. RNA isolation was performed using PAX gene RNA kit on the blood samples from the subjects. The RNA was then reverse transcribed into cDNA and analyzed using the Human Transcription Factors RT2 Profiler™ PCR Arrays. While the boron amount in urine was detected as 3.56±1.47mg/day in the boron group, it was 0.72±0.30mg/day in the control group. Daily boron intake of the boron and control groups were calculated to be 6.98±3.39 and 1.18±0.41mg/day, respectively. The expression levels of the transcription factor genes were compared between the boron and control groups and no statistically significant difference was detected (P>0.05). The data suggest that boron intake at 6.98±3.39mg/day, which is the dose at which beneficial effects might be seen, does not result in toxicity at molecular level since the expression levels of transcription factors are not changed. Although boron intake over this level will seem to increase RNA synthesis, further examination of the topic is needed using new molecular epidemiological data.

Epigallocatechin-3-gallate reduces the proliferation of benign prostatic hyperplasia cells via regulation of focal adhesions

Aims: Benign prostatic hyperplasia (BPH) is the most common urological disease that is characterized by the excessive growth of prostatic epithelial and stromal cells. Pharmacological therapy for BPH has limited use due to the many side effects so there is a need for new agents including natural compounds such as epigallocatechin‐3‐gallate (EGCG). This study was undertaken to assess the role of EGCG, suppressing the formation of BPH by reducing inflammation and oxidative stress, in cytoskeleton organization and ECM interactions via focal adhesions. Main methods: We performed MTT assay to investigate cell viability of BPH‐1 cells, wound healing assay to examine cell migration, immunofluorescence assay for F‐actin organization and paxillin distribution and finally immunoblotting to investigate focal adhesion protein levels in the presence and absence of EGCG. Key findings: We found that EGCG inhibits cell proliferation at the concentration of 89.12 &mgr;M, 21.2 &mgr;M and 2.39 &mgr;M for 24, 48 and 72 h, respectively as well as inhibitory effects of EGCG on BPH‐1 cell migration were observed in a wound healing assay. Furthermore, it was determined by immunofluorescence labeling that EGCG disrupts F‐actin organization and reduces paxillin distribution. Additionally, EGCG decreases the activation of FAK (Focal Adhesion Kinase) and the levels of paxillin, RhoA (Ras homolog gene family, member A), Cdc42 (cell division cycle 42) and PAK1 (p21 protein‐activated kinase 1) in a dose‐dependent manner. Significance: For the first time, by this study, we found evidence that BPH‐1 cell proliferation could be inhibited with EGCG through the disruption of cytoskeleton organization and ECM interactions. Consequently, EGCG might be useful in the prevention and treatment of diseases characterized by excessive cell proliferation such as BPH.

Is it Possible to Recover Cardiac Functions After Total Knee Arthroplasty

Background: Patients suffering from knee osteoarthritis lead a less active life than their healthy peers. It is well known that insufficient physical activity is the most common cause of chronic diseases. However, there is not enough research to enlighten the effect of increased functional capacity on cardiac functions after Total Knee Arthroplasty (TKA). This study aimed to investigate whether the orthopedic surgeons can predict that the patients will be healthier after TKA in terms of cardiac functions or not? Methods: 109 patients who underwent TKA were prospectively followed for one year. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and short form 36 (SF-36) surveys, BMI measures, average step count per day, the six-minute walking test (6MWT), the Five-Times-Sit-to-Stand Test (FTSST) and Doppler echocardiography were performed both in the preoperative and postoperative period. Results: After TKA, there was a substantial improvement in terms of WOMAC and SF36 survey scores. The average step count increased from 2199.6±690.8 steps/day to 4124.3±1638.8 steps/day. 6MWT and FTSST improved significantly as well. The average brisk walking time was 174.23±95.11 minutes/week. The means of early and late mitral inflow velocity ratios (E/A and Em/Am ratios) increased from 0.71±0.12 to 0.77±0.13 and from 0.66±0.13 to 0.76± 0.15 at the first year follow-up visit, respectively (p<0.001). Conclusion: In the first year, objective physical capacity measures increased together with the expected improvements in disease-specific and generic measures. After TKA, left ventricular diastolic functions may be considered to have recovered in the light of the healing signs via echocardiography.

Expression profiles of histone modification genes in gastric cancer progression

Gastric cancer (GC) development can be attributed to several risk factors including atrophic gastritis (AG), intestinal metaplasia (IM), and the presence of Helicobacter pylori (HP). Also, histone modification is an epigenetic mechanism that plays a pivotal role in GC carcinogenesis. In this preliminary study, we aimed to describe the expression profiles of histone modification in the AG, IM, and GC patient groups. A total of 80 patients with AG (n = 27), IM (n = 25), and GC (n = 28) with an additional 20 control subjects were included in the study. Expression profiles of three histone phosphorylation genes (PAK1, NEK6, and AURKA) and five histone deacetylation genes (HDACs 1, 2, 3, 5, and 7) were examined based on the results of Real Time qPCR method. It was observed that AURKA and HDAC2 genes were significantly overexpressed in all groups compared to the control (P < 0.05). In GC patients, overexpression of HDAC2 gene was detected in the absence of metastasis, and overexpression of AURKA, HDAC2, and NEK6 genes was detected in the presence of metastasis. When cancer involvements were compared, significant overexpression of the HDAC2 gene was noted in overall and corpus involvements (P < 0.05). In addition, overexpression of AURKA, NEK6, HDAC1, and HDAC2 genes and underexpression of HDAC5 gene were detected in the antrum involvement (P < 0.05). In conclusion, decreased expression of HDAC5 in GC is reported for the first time in this study, while supporting the existing literature in AURKA, NEK6, HDAC1, and HDAC2 up regulations during GC development.

Clinical features and follow-up results of the patients with methicillin-resistant Staphylococcus aureus (MRSA) in orthopedic practice -

Treatment of the infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains in orthopedic patients is a difficult and laborious process for both the patient and physician. Staphylococcus aureus(S. aureus) is one of the leading causes of community-acquired and nosocomial infections. In this study, we aimed to investigate the susceptibilityof the MRSA strainsisolated in orthopedic patients cultured for different reasons in our clinic to various antibiotics, and to evaluate clinical characteristics of the patients and factors affecting the prognosis. A total of 40 patients with MRSAisolated in our orthopedics clinic between December 2012 and November 2016 were retrospectively analyzed. Data including age, sex, comorbidities, previous surgeries, and previous antibiotic treatments were obtained from patients’ files and electronic information system. Of 40 patients, 60% were male, and 56% were over 60 years old. While 80% of the patients underwent an orthopedic surgery, 20% of them received no surgical intervention before the diagnosis. A total of 90% were in-patients, and the mean length of hospital stay was 22 days. The mean time from the date of hospitalization to the isolation of MRSA was 12 days. According to the consultation findings, in the clinical recovery process of the patients and in the treatment algorithm given to those patients, vancomycin and teicoplanin were found to be among the most important treatment options, in addition to significant debridement to be done, for MRSA strains. Our study results suggestthat, in addition to the surgical debridement, timely antibiotherapy is of utmost importance to reduce mortality and morbidity in MRSA-positive orthopedic patients.

Boron intake, osteocalcin polymorphism and serum level in postmenopausal osteoporosis

The relationship between daily boron intake and osteocalcin-mediated osteoporosis was studied in boron-exposed postmenopausal women. It is known that boron and osteocalcin are important in bone metabolism, however the effect of boron in bone metabolism has not been fully discovered. The study was performed on 53 postmenopausal women aged 55-60 living in parts of Balikesir, Turkey, where the subjects are naturally exposed to high (≥1 mg/L) or low (<1 mg/L) boron concentration in drinking water. 24-h urine samples were collected from all participants and creatinine clearance was detected. Boron intake levels of the subjects whose clearance levels were between 80-124 mL/min were measured by inductively coupled plasma-optical emission spectrometry (ICP-OES) in urine samples. Serum osteocalcin levels of the subjects were measured by osteocalcin enzyme-linked immunosorbent assay (ELISA) kit. Osteocalcin polymorphism rs1800247 was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Serum osteocalcin levels in boron-exposed postmenopausal women were significantly higher than that of control group (P ≤ 0.05) and the correlation between the serum osteocalcin level and rs1800247 polymorphism was not significant in both groups (P > 0.05). The differences in the distribution of osteocalcin genotypes and alleles in postmenopausal women were not significant between the boron exposed and the control groups (P > 0.05). Serum osteocalcin level in the CC genotype was significantly higher compared to the TC genotype in boron-exposed group (P ≤ 0.05). Our study suggests that daily boron intake of 1 mg/L may affect bone metabolism in postmenopausal women positively.