Bunyamin Isik

The activities of liver adenosine deaminase, xanthine oxidase, catalase, superoxide dismutase enzymes and the levels of malondialdehyde and nitric oxide after cisplatin toxicity in rats: protective effect of caffeic acid phenethyl ester.

The aim of this experimental study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, on cisplatin-induced hepatotoxicity through adenosine deaminase (AD), xanthine oxidase (XO), catalase (CAT), superoxide dismutase (SOD) activities and malondialdehyde (MDA) and nitric oxide (NO) levels in liver tissue of rats. Wistar albino rats were divided into three groups: control group (n-6), cisplatin group (n-9) and CAPE+cisplatin group (n-8). All the chemicals used were applied intraperitoneally. Spectrophotometric methods were used to determine the activities of the above-mentioned enzymes in the liver tissue. NO level and XO activity were found to be increased in the cisplatin group compared to the control group. NO level was found to be decreased in the cisplatin+CAPE group in comparison with the cisplatin group. There was no significant change in the activity of XO between the cisplatin and cisplatin+CAPE groups. The activity of SOD was lower in the cisplatin group than both the control and cisplatin+CAPE groups. There was no significant change in the activity of CAT between the control and cisplatin groups. CAT activity was increased in the cisplatin+CAPE group compared to the cisplatin group. The AD activity and MDA level remained unchanged in all groups. The results obtained suggested that CAPE significantly attenuated the hepatotoxicity as an indirect target of cisplatin in an animal model of cisplatin-induced nephrotoxicity.

Erdosteine against acetaminophen induced Renal toxicity

Acetaminophen (APAP) induced toxicities have been a major problem in clinical practice. The aim of the present study was to demonstrate a possible protective role of erdosteine, a mucolytic agent having antioxidant properties via its active metabolites, on APAP induced renal damage in rats. Female Wistar Albino rats were divided into groups including control, erdosteine (150 mg/kg, oral), APAP (1 g/kg, oral) APAP+erdosteine (150 mg/kg, oral) and APAP+erdosteine (300 mg/kg, oral). APAP treatment caused lipid peroxidation as well as high NO level in renal tissue. Also, APAP treated rats had decreased activities of CAT and GSH-Px, but not SOD. In addition, tubular epithelial degeneration, vacuolization and cell desquamation were clearly observed in the APAP treated rats. The cellular debris in the proximal tubules and cortical interstitial congestions were prominent in the kidneys of APAP treated rats. BUN and creatinine levels were increased after APAP administration. All these pathological changes were reversed after erdosteine treatments. Erdosteine treated APAP groups showed milder tubular degeneration, epithelial vacuolization in the proximal tubules, lesser cellular desquamation and better morphology when compared with APAP groups. In conclusion, erdosteine may be a choice of preventive treatment against APAP induced nephrotoxicity.

Relation between Serum Thyroid Hormone and ‘Nondipper’ Circadian Blood Pressure Variability

Currently, the pathogenesis of nondipper hypertension remains largely unclear in patients without any renal or endocrine pathology. It is well known that overt hypothyroidism is strongly associated with diastolic hypertension. However, no study has addressed the pathogenic role of TSH, free T3 (FT3), and free T4 (FT4) in nondipper hypertension. The aim of the present investigation is to evaluate if higher TSH, low FT3 and FT4 would be associated with a nondipper hypertension profile, in patients with normal renal function and without any overt thyroid hormone disorder. 131 subjects were screened and those who met the following inclusion criteria were enrolled: (1) glomerular filtration rate (GFR) >60 ml/min; (2) no history of thyroid disorders; (3) no history of thyroid hormone medication. All subjects underwent 24-hour ambulatory blood pressure monitoring on a usual working day. Of the total population, 59 patients (45%) were classified as dippers and 72 (55%) were classified as nondippers. The only significant differences between dipper and nondipper patients appear to be related to FT3 levels and GFR. Nondipper patients had lower FT3 levels (4.5 ± 0.6 vs. 4.0 ± 0.9 pmol/l, p = 0.02) and low GFR (80.5 ± 12.2 vs. 86.9 ± 16.9 ml/min, p = 0.03), compared to dipper patients. The final regression model included serum TSH, FT3 levels, and GFR; the only independent predictor of nondipper hypertension was FT3 (p = 0.04). In conclusion, even if the mechanisms of our findings remain incompletely understood, we demonstrate a graded independent relation between lower level of FT3 and the risk of nondipping. Further studies are warranted to confirm this relationship and to elucidate the pathogenetic mechanisms of this relationship.

Relation between Serum Calcium, Phosphate, Parathyroid Hormone and ‘Nondipper’ Circadian Blood Pressure Variability Profile in Patients with Normal Renal Function

Background and Aims: In patients with renal disease, an association between abnormal circadian blood pressure profile and abnormalities in bone and mineral metabolism, including vascular calcifications, is well known. However, such a link has not yet been reported in hypertensive patients with normal renal function. We aimed to evaluate if higher serum phosphate, calcium, parathyroid hormone (PTH) level and the calcium×phosphate (Ca×P) product would be associated with a nondipper hypertension, in patients with normal renal function and without any PTH disorder. Methods: 190 hypertensive subjects with the following inclusion criteria were enrolled: (1) normal phosphate and PTH levels; (2) glomerular filtration rate (GFR) >60 ml/min, and (3) no history of calcium, phosphate, vitamin D medication and hyperparathyroidism. Results: Of the total population, 76 patients (40%) were classified as dippers and 114 (60%) as nondippers. Nondipper patients had higher levels of phosphate (3.70 ± 0.61 vs. 3.35 ± 0.44 mg/dl, p = 0.001), Ca×P product (35.4 ± 6.5 vs. 31.5 ± 5.0, p = 0.001) and PTH (75.7 ± 28.8 vs. 46.6 ± 17.1 pg/ml, p = 0.000) compared to dipper patients. Independent predictors (multiple regression) for nondipper hypertension were PTH (β = 0.43, p = 0.001) and phosphate (β = 0.9, p = 0.03). Conclusion: We demonstrate a graded independent relation between higher levels of phosphate, PTH, Ca×P product and the risk of nondipping in hypertensive patients with an estimated GFR of >60 ml/min and normal mineral metabolism.

The comparison of nail and serum trace elements in patients with epilepsy and healthy subjects.

The objective of this prospective study was to determine the levels of manganese (Mn), copper (Cu), and zinc (Zn) levels in both nail and serum from patients with epilepsy. For this purpose, levels of these elements were measured in 31 patients with epilepsy and 19 healthy subjects. Element analyses were carried out by atomic absorption spectrophotometer (AAS). Increased Mn levels were detected in nail of patients with epilepsy compared to healthy controls (P<.008). The main nail Zn and Cu levels were found to be unchanged in epileptic patients compared to control subjects. There were no significant differences in serum Mn and Zn levels between epileptic patients and control subjects. However, there was a statistically significant increase in serum Cu levels in patients with epilepsy in comparison with control group (P<.009). Our results demonstrate that some trace element levels may vary in epileptic patients, and because of the more stable status, the analysis of these element levels in some tissues such as nail might be superior to serum analysis.

Platelet Parameters in Children with Upper Urinary Tract Infection: Is There a Specific Response?

Although complete blood count is routinely ordered in most upper urinary tract infections (UTI), and information regarding the patients platelet indices is made available without added cost, the relationship between platelet count and mean platelet volume (MPV) and specific platelet responses to different infectious agents has not been extensively characterized in UTI. The objectives of this study were to examine platelet counts and platelet indices in children with culture-proven upper UTI to determine if there are organism-specific platelet responses. A retrospective analysis of data from all pediatric urine samples processed at Fatih University Medical School microbiology laboratory was undertaken for a period of two years (January 1, 2005, to December 31, 2006). Of the 200 patients with positive urine cultures, 146 (73%) were infected with gram-negative bacteria and 54 (27%) grew gram-positive bacteria. The platelet count during the episode of upper UTI and the incidence of thrombocytosis was significantly higher with the gram-positive infections than with the gram-negative infections or controls (p < 0.05). A statistically significant higher MPV was detected in the subjects with upper UTI (p < 0.05). Also, our data showed a statistically significant increase in MPV with gram-positive infections compared with the other groups (p < 0.05). In conclusion, based on the importance of the hemostatic component in the pathophysiology of infections, our findings of platelet count and MPV and predictivity of the type of the organism would suggest the usefulness of the routine measurements in children with upper UTI.

Methylphenidate-Induced Acute Orofacial and Extremity Dyskinesia

Methylphenidate is a short-acting stimulant. In this article, the authors report a 7-year-old male patient who presented with orofacial and limb dyskinesia after his first dose of methylphenidate treatment for a diagnosis of attention-deficit/hyperactivity disorder; he was also receiving sodium valproate treatment for epilepsy. Orofacial dyskinesia appeared 5 hours after methylphenidate administration, persisted for 10 hours, and had completely resolved within 2 days. Although limb dyskinesia after methylphenidate is a commonly reported side effect, to the authors’ knowledge this is only the second reported case to develop both orofacial and limb dyskinesia in the acute period after the first dose of methylphenidate. This case is reported to emphasize the potential side effects of methylphenidate, individual differences in drug sensitivities, and drug–receptor interactions via different mechanisms.

Relationship between Retinopathy and Cognitive Impairment among Hypertensive Subjects

Background: The relationship between hypertension and cognitive impairment has been investigated in the literature; several clinical studies suggested a relationship between hypertension and retinopathy. Methods: We examined the relationship between the retinopathy status and cognitive functions by using the Mini-Mental State Examination (MMSE) among hypertensive subjects older than 40 years who were admitted to our Family Medicine, Internal Medicine and Ophthalmology clinics. The subjects were categorized into three groups: group 1 = control subjects (n = 39), group 2 = hypertensive patients without retinopathy (n = 32), and group 3 = hypertensive patients with retinopathy (n = 25). Results: The number of patients with total MMSE scores less than 24 was distributed as follows: group 1: 3 patients (7.7%), group 2: 4 patients (12.5%), and group 3: 14 patients (56%). Hypertension was found to be related with a significant decrease in total MMSE scores in comparison with group 1 subjects (p < 0.001). Furthermore, retinopathy significantly correlated with lower MMSE scores among hypertensive patients (p = 0.001). Compared with group 1, group 3 showed a significant decrease in orientation (p = 0.001), registration (p = 0.001), attention and calculation (p = 0.004), recall (p = 0.009), and total (p < 0.001) MMSE scores. We also found a significant decrease in recall (p = 0.032) and total (p = 0.034) scores in group 3 when compared with group 2. There was a significant decrease in registration (p = 0.002) and total (p = 0.029) MMSE scores in group 2 when compared with group 1. We also observed negative correlations between duration of the disease and orientation (R = –0.597, n = 32, p = 0.001), and between duration of the disease and total (R = –0.495, n = 32, p = 0.006) scores in group 2. Conclusions: Hypertension was found to be related with a decline in MMSE scores. This relation was even more significant in the group of hypertensive patients with retinopathy. Thus, we suggest that cognitive tests be routinely used in the follow-up of hypertensive patients.

Augmentation of ADAMTS9 gene expression by IL-1β is reversed by NFκB and MAPK inhibitors, but not PI3 kinase inhibitors.

The pathways involved in the regulation of a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) expression have not yet been elucidated. Therefore, the aim of this study was to investigate the involvement of nuclear factor‐κB (NF‐κB), mitogen activated protein kinases (MAPK) and Phosphatidylinositol 3‐kinase (PI3 kinase) in ADAMTS9 gene regulation, with special focus on the involvement of NF‐κB in IL‐1β‐induced ADAMTS9 expression. The OUMS‐27 chondrosarcoma cells were exposed to IL‐1β. They were pretreated with 20 μM PD98059 (specific inhibitor of p44/42 kinase), 10 μM SB203580 (specific inhibitor of p38 kinase), 20 μM SB600125 (MAPK inhibitor), and 1 μM Wortmannin and 10 μM LY294002 (specific inhibitors of PI3 kinase) for 30 min and subsequently incubated with IL‐1β. For the effects of NF‐κB and IκB inhibitors, cells were pretreated with curcumin or BAY117085 for 30 min and subsequently incubated with IL‐1β. BAY117085 and different concentrations of curcumin were applied to the cells just after the first experiment to determine their concentration effect on ADAMTS9 gene expression. After total RNA was extracted, they were reversely transcribed with random primers and then real‐time polymerase chain reaction (PCR) was performed on cDNA samples.

Role of ING Family Genes in Head and Neck Cancer and Their Possible Applications in Cancer Diagnosis and Treatment

Esra Gunduz1, Mehmet Gunduz1,2,3,*, Levent Beder3, Ramazan Yigitoglu4, Bunyamin Isik5 and Noboru Yamanaka3 1Departments of Medical Genetics, 2Otolaryngology Head and Neck Surgery, 3Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine, Wakayama Medical University, Wakayama, 4Medical Biochemistry, 5Family Medicine, Faculty of Medicine, Fatih University, Ankara, 1,2,4,5Turkey 3Japan