Future opportunities in preventing ototoxicity: Caffeic acid phenethyl ester may be a candidate (Review).

Caffeic acid phenethyl ester (CAPE) is an important active component of propolis, which is derived from honeybee hives. It has received increasing attention in a variety of medical and pharmaceutical research, due to its anti­oxidant, antiproliferative, anti­inflammatory, antiviral and antifungal activity, in addition to its antineoplastic properties. Besides the use of CAPE as an antioxidant and anti­inflammatory agent in a number of in vivo studies of ear disease, its beneficial effects have been reported in the treatment of cancer, arthritis, allergies, heart disease, diabetes, kidney disease, liver disease and neurological disease. CAPE influences a number of biochemical pathways, as well as several targets involved in ear diseases, in particular, in ototoxicity. The protective effects of CAPE in ototoxicity, which may be induced by a number factors, including lipopolysaccharides, hydrogen peroxide and streptomycin, are evaluated and discussed in the present review.

Factors affecting daily instrumental activities of the elderly.

BACKGROUND/AIM: In order to determine elderly people's capabilities in daily activities, we evaluated the factors that may affect their daily instrumental activities. MATERIALS AND METHODS: We performed an observational, analytical, and cross-sectional study on 101 patients above 60 years of age in 2008 and 2009. We applied the Lawton Instrumental Activity of Daily Living (IADL) scale, the Standardized Mini-Mental State Examination (SMMSE), and the Geriatric Depression Scale (GDS) during one-on-one interviews with the patients. Demographic data and disability levels were also recorded. These data were used to evaluate the possible effects of factors on the IADL scale. RESULTS: Statistical analyses indicated that total scores of instrumental activities are affected negatively by increased age, female sex, and literacy (P < 0.001, P = 0.005, and P = 0.021), whereas scores are affected positively by educational level (P = 0.047). CONCLUSION: Our findings suggest that increased age, sex, literacy, and education levels influence elderly people's daily instrumental activities. Daily functional activities and factors influencing these activities should be determined in order to increase elderly people's quality of life and independence. It is important to evaluate elderly people's capabilities in daily activities.

Augmentation of ADAMTS9 gene expression by IL-1ß 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-1ß-induced ADAMTS9 expression. The OUMS-27 chondrosarcoma cells were exposed to IL-1ß. 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-1ß. For the effects of NF-κB and IκB inhibitors, cells were pretreated with curcumin or BAY117085 for 30 min and subsequently incubated with IL-1ß. 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. There was a significant difference between control and stimulated cells in terms of ADAMTS9/ß-actin ratio. Wortmannin and LY294002 did not have any repressive effect on the OUMS-27 whereas SB203580 and SP600125 were found to decrease the expression of ADAMTS9 gene. BAY 117085 and curcumin, which are two NF-κB inhibitors, led to a decrease in the ratio of ADAMTS9/ß-actin. As a conclusion, the pathways MAPK and NF-κB were thought to be responsible pathways for the induction of ADAMTS9 gene.

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.

Association of obesity with inflammation in occult chronic kidney disease.

BACKGROUND: There are few studies concerning the development of chronic kidney disease (CKD) in obese patients independent of its relation with other risk factors. Also, the role of inflammation in this relationship is unclear. In this study we aimed to test the hypothesis that obesity is associated with risk for CKD and whether this risk is associated with serum C-reactive protein (CRP) levels in an apparently healthy obese population. METHODS: Biochemical parameters and urinary protein excretion were determined in 110 patients with body mass index (BMI) >30.0 (calculated as kg/m2) and 50 age-matched healthy controls. Glomerular filtration rate was estimated by calculation of creatinine clearance. RESULTS: Of the patients, 17.3% had CKD. They had higher CRP levels than controls (6.52 +/- 0.58 mg/L and 4.48 +/- 1.26 mg/L, respectively, p=0.001). Furthermore, CRP levels were positively correlated with BMI, waist circumference, waist to hip ratio and proteinuria, and negatively correlated with glomerular filtration rate (GFR). When GFR was considered as the dependent variable in a multiple regression analysis, CRP maintained its significant correlation with GFR. CONCLUSION: Our study of apparently healthy obese individuals, has shown a significant association between BMI and CKD independent of other potential mediators. Furthermore, our findings suggest that inflammation may be the pathogenic mechanism of obesity-related CKD.

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 x phosphate (Ca x 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 x 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 (beta = 0.43, p = 0.001) and phosphate (beta = 0.9, p = 0.03). CONCLUSION: We demonstrate a graded independent relation between higher levels of phosphate, PTH, Ca x P product and the risk of nondipping in hypertensive patients with an estimated GFR of >60 ml/min and normal mineral metabolism.

Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearence, and proteinuria in patients with normal renal functions.

BACKGROUND: Hyperuricemia has been associated with the development of hypertension, cardiovascular, and renal disease. However, there is no data about the effect of lowering uric acid level on hypertension, renal function, and proteinuria in patients with glomerular filtration rate (GFR) >60 ml/min. We therefore conducted a prospective study to investigate the benefits of allopurinol treatment in hyperuricemic patients with normal renal function. MATERIALS AND METHODS: Forty-eight hyperuricemic and 21 normouricemic patients were included in the study. Hyperuricemic patients received 300 mg/day allopurinol for three months. All patients' serum creatinine level, 24-h urine protein level, glomerular filtration rate, and blood pressure levels were measured at baseline and after three months of treatment. RESULTS: A total of 59 patients completed the three-month follow-up period of observation. In the allopurinol group, serum uric acid levels, GFR, systolic and diastolic blood pressure, and C-reactive protein (CRP) levels significantly improved (P < 0.05). However, urine protein excretion remained unchanged (P > 0.05). No correlation was observed between changes in GFR and changes in CRP, or blood pressure in the allopurinol group. No significant changes were observed in the control group (P > 0.05). CONCLUSION: We bring indirect evidence that hyperuricemia increases blood pressure, and decreases GFR. Hence, management of hyperuricemia may prevent the progression of renal disease, even in patients with normal renal function, suggesting that early treatment with allopurinol should be an important part of the management of chronic kidney disease (CKD) patients. Long-term follow-up studies are warranted to identify the benefits of uric acid management on renal function and hypertension.

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.

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.

Relationship between retinopathy and cognitive impairment among hypertensive subjects. A case-control study in the ankara-pursaklar region.

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.

Clinical importance of gamma glutamyltransferase in the Ankara-Pursaklar region of Turkey.

OBJECTIVE: The aim of this study is to determine the etiologies of serum gamma glutamyltransferase (GGT) elevation and relations between multiple etiologies prevalent in the Pursaklar region of Ankara in Turkey. PATIENTS AND METHODS: The patients referred to the Family Medicine and Internal Medicine departments with various complaints from the Pursaklar region of Ankara between July 2000 and July 2002 were evaluated, and values for GGT, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) levels were determined. GGT elevation was classified as being associated with hepatic, biliary, and other origins. RESULTS: For GGT elevation, hepatobiliary etiologies were more prevalent. The most prevalent hepatic etiology was nonalcoholic steatohepatitis, followed by biliary etiologies. The most prevalent etiology of biliary origin was cholelithiasis. Other etiologies, in order of prevalence, were drug exposure and urinary infection. There were no gender-related differences for distribution of GGT elevation; however, the GGT values for women were higher than those for men.

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.

Hirsutism: common clinical problem or index of serious disease?

Hirsutism is a clinical condition commonly encountered in the practice of primary care medicine. The etiology and the age of the patient when it occurs vary widely. Causes range from a basic illness or condition (drug exposure, smoking, idiopathic, and obesity) to complex and serious diseases (Cushing's syndrome, neoplasms, congenital adrenal hyperplasia, insulin-resistance syndromes, hyperprolactinemia, polycystic ovary syndrome, and hyperthecosis). Hirsutism may appear in childhood as well as in older persons. Some drugs (oral contraceptives, L-thyroxine, danazol, and diazoxide), tobacco smoke, some syndromes (polycystic ovary syndrome, obesity, insulin resistance, hyperprolactinemia, hyperthecosis, congenital adrenal hyperplasia, and idiopathic), and some neoplasms (adrenal or ovarian) may lead to hirsutism. The most frequently defined "causes" of hirsutism are polycystic ovary syndrome and idiopathic hirsutism. In hirsutism of gradual onset, hyperprolactinemia, insulin-resistance syndromes, hyperthecosis, polycystic ovary syndrome, and idiopathic hirsutism may be responsible. Cushing's syndrome, neoplasms, and congenital adrenal hyperplasia should be suspected if there has been rapid onset.

Does every retroperitoneal mass associated with undescended testicle represent testicular tumor or its metastasis?

We are presenting a 36 year old male patient who was diagnosed to have a right pararenal mass on CT scan taken for evaluation of his long lasting urinary stone disease and accompanying undescended right testicle. He subsequently underwent a retroperitoneal lymph node dissection for possible testicular tumor or its metastasis in the undescended testicle or retroperitoneal primary tumor, which came out to be non malignant tissue. We confirmed that the highest possible location of the testicle when undescended is at the level of the internal inguinal ring, and paracaval masses associated with undescended testicles do not necessarily represent a testicular tumor in the retained testicle, its metastasis or an extragonadal germ cell tumor (EGT), and further work should be done to illuminate the nature of such cases.