Environmental pollutant sodium omadine: toxic effects in zebra fish (Danio rerio).

In recent years one of the most striking results of over-population and consumption activities in the world is the rapid increase in environmental pollutants. Environmental pollutants, one of the harmful consequences of technological and modern life, threaten the health of people and other living organisms. In this study, we aimed to determine the effects of sodium omadine (NaOM) on superoxide dismutase enzyme (SOD) activity as an antioxidant and on 8-OHdG levels as oxidative DNA damage in zebrafish. Zebrafish, obtained from the aquarium fish producer, were stocked in experimental aquariums to ensure their adaptation period to the experimental conditions 15 days before the experiment. The fish were exposed to 1 ug/L and 5 ug/L concentrations of NaOM for 24, 72, and 96 h. SOD enzyme activity (U/100 mg tissue) and 8-OHdG (pg/100 mg tissue) were measured using commercial kits. The statistically significant differences in tissue SOD levels and data for DNA damage between the groups were determined as time and dose-dependent (p < 0.05). Biocidal products are environmental pollutants that cause changes in antioxidant enzyme activities, especially in non-target organisms. Marine pollution and the degradation of ecosystems directly affect people, and the results of the study offer awareness of health problems, environmental pollution, and marine pollution.

Relationships of orexigenic and anorexigenic hormones with body fat distribution in patients with obstructive sleep apnea syndrome.

PURPOSE: We aimed to examine the relationships of disease activity and risk factors with serum levels of orexigenic and anorexigenic hormones in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Fasting blood samples were taken for hormonal analysis of all participants, abdominal/neck bioimpedance measurements were recorded, and polysomnography (PSG) analyses were performed. According to the apnea-hypopnea index (AHI), 34 patients with newly diagnosed OSAS and 34 participants without OSAS were compared. RESULTS: The median body mass index (BMI) measured in the OSAS group was 30.39 kg/m2 and AHI was 18.95 and these values were 25.40 kg/m2 and 1.55 in the control group. There was a higher level of visceral adiposity and neuropeptide Y (NPY) in the moderate-to-severe OSAS group compared to the mild OSAS and control groups, and in the mild OSAS group compared to the control group (p = 0.001, p < 0.001). A positive correlation between the level of NPY and AHI and BMI (p < 0.001, p = 0.011), and a negative correlation between NPY levels and oxygen saturation (p = 0.001) was found. Oxygen saturation and desaturation rates were correlated with body fat percentage, body fat mass, abdominal adiposity, visceral adiposity, resting metabolic rate, and NPY levels. CONCLUSIONS: The visceral adiposity ratio and increase in NPY levels are important parameters that increase the severity of OSAS. Considering the negative effects of NPY on vascular endothelium, measurement of basal NPY level before PSG in patients with OSAS is considered a parameter related to disease severity.

Does bisphenol A bioaccumulate on zebrafish? Determination of tissue bisphenol A level.

Bisphenol A (BPA) is a high-production-volume industrial chemical mainly used in the production of polycarbonates and epoxy resins utilized in the manufacture of containers, bottles, toys, and medical devices. It has systemic effects as an endocrine disruptor even at low doses. To analyze its quantity in biological materials, sensitive and reproducible methods have to be used. Different doses and duration (90 and 900 µg/L, 24 and 120 h, and 21 days) of BPA exposure to whole body zebrafish were analyzed after specific homogenization of tissue, and then a modified method HPLC was used. The mobile phase was acetonitrile and water using a gradient method of reversed-phase C18 column, and excitation = 227 nm/emission = 313 nm. The calibration curve for BPA using HPLC-fluorescence detection method was between a concentration range of 1 and 1000 ng/mL and linear, and r2 = 0.999. The mean and standard error of mean values were 4.29 ± 1.05, 2.50 ± 0.92, and 2.53 ± 0.68 for control; 10.43 ± 2.61, 11.46 ± 3.24, and 8.55 ± 3.11 for BPA-90 µg/L; and 17.78 ± 4.39, 21.55 ± 4.37, and 25.32 ± 3.25 for BPA-900 µg/L (24 h, 120 h, and 21 days, respectively). Although some statistical significance among dose/time was observed between two different dose-treated groups, statistical significance was not found in dose/time results within the group. However, the positive result of BPA in the control group can be explained by low-dose, chronic exposure or prevalence of endocrine-disrupting chemicals.

Impact of DBP on histology and expression of HSP 70 in gill and liver tissue of Cyprinus carpio.

Di-n-butyl phthalate (DBP) widely used plasticizer in the plastic industry, affects regulation of the endocrine system and causes toxicity in animals. In the present study, the aim was to study the toxic effects/damages of DBP exposure using Hsp70 levels and histopathological changes in Carp liver and gill. Hsp70 expression levels were assessed as specific biomarker of in vivo ecotoxicological stress. Carp (Cyprinus carpio) were exposed to sub-lethal concentration of DBP (di-n-butyl phthalate, 1 mg/L) for 4, 24 and 96 h. Gill and liver tissues were evaluated histopathologically and RNA quantifications for Hsp70 expression levels were carried out using a two-step real-time RT-PCR. In liver, a rapid but non-significant increase in mRNA levels in the first 4 h was observed. mRNA levels significantly increased up to 2-3 fold after 24 and 96 h (p < 0.05). However, irregular mRNA level changes were also recorded: Gill specific and time-dependent regulation of Hsp70 expression were 4-5 fold inhibition after 4 and 24 h (p < 0.05), then increased up to 4 fold after 96 h (p < 0.05). Histopathological findings support altered transcription results as: Epithelial lifting, hyperplasia, fusion of secondary lamellae, telangiectasis, passive hyperemia and hydropic degeneration. Significant alterations of Hsp70 levels were likely due to a tissue specific response against chemical stress, cellular damage and lesions due to DBP. Carp was found to be a suitable experimental model for toxicology, and Hsp70 mRNA levels are reliable, specific biomarkers.

The importance and the differences of bone morphogenetic proteins for osteoporotic hip fractures.

Bone morphogenetic proteins (BMPs), major contributors to tissue repair, have become one of the most exciting fields in rheumatic and orthopaedic research. In our study we aimed to evaluate the relationship between osteoporotic hip fractures and the serum levels of BMPs to reveal their potential roles in the diagnosis of patients. The study group included 62 patients with osteoporotic hip fracture (Group 1; intertrochanteric fracture, Group 2; collum femoris fracture) and the control group. All fractures were due to low energy trauma, simple falls. For all subjects BMD measurements were in agreement for osteoporosis and no significant differences were observed between the two fracture groups. Biochemical markers; BMP-4 and BMP-7 (pg/mL) were determined by commercial Elisa kits from the serum samples. The mean and standard error values of serum samples for BMP-4 and BMP-7 in Group 1 (100.70 +/- 10.03, 74.41 +/- 6.31 respectively) and in Group 2 (112.34 +/- 11.52, 81.91 +/- 10.14 respectively) were not statistically different however for both groups only BMP-7 values increased statistically when compared to the control group. BMP-7 measurements may not only serve as potential biochemical markers for determining disease severity but also the increased levels, an osteogenic factor and bone stimulating agent in vivo, after trauma elevated levels are adaptive or protective and therefore may reduce the severity of the fracture.

Bovine papillomavirus type 2 infects the urinary bladder of water buffalo (Bubalus bubalis) and plays a crucial role in bubaline urothelial carcinogenesis.

Bovine papillomavirus type 2 (BPV-2) has been shown to infect and play a role in urinary bladder carcinogenesis of buffaloes grazed on pastures with ferns from the Marmara and Black Sea Regions of Turkey. BPV-2 DNA has been found in both neoplastic and non-neoplastic lesions of the urinary bladder. Furthermore, this virus may be a normal inhabitant of the urinary bladder since BPV-2 DNA has also been detected in clinically normal buffaloes. The viral activation by fern immunosuppressant or carcinogen may trigger the urothelial cell transformation. The E5 oncoprotein was solely detected in urothelial tumours and appeared to be co-localized with the overexpressed and phosphorylated platelet derived growth factor (PDGF) ß receptor in a double-colour immunofluorescence assay. Our results indicate that the E5-PDGF ß receptor interaction also occurs in spontaneous tumours of the bubaline urinary bladder, revealing an additional role of BPV-2 in bladder carcinogenesis of buffaloes.

Evaluation of cerebrospinal fluid neurofilament light chain levels in multiple sclerosis and non-demyelinating diseases of the central nervous system: clinical and biochemical perspective.

The neurofilament light chain (NfL) is a promising biomarker in the diagnosis, prognosis, and treatment response evaluation of neurological diseases. The aims of this study were to compare the cerebrospinal fluid (CSF) NfL levels in multiple sclerosis (MS) and certain non-demyelinating diseases of the central nervous system (NDCNS); to determine the relationship between clinical and radiological features and CSF NfL levels in patients with MS; and to compare the enzyme-linked immunosorbent assay (ELISA) and single molecule array (SIMOA) methods for NfL measurement using paired CSF and serum samples. We retrospectively analyzed the clinical data and performed NfL measurements in CSF and serum samples of newly diagnosed and treatment-naive patients with CNS diseases evaluated between 1 January 2019 and 1 January 2020. Eligible patients were divided into three groups: MS (n=23), differential diagnosis of MS (n=19), and NDCNS (n=42). First, we compared the CSF NfL levels among the three groups using the previously validated CSF ELISA assay. Next, we evaluated the relationship between CSF NfL levels and the clinical and radiological findings in MS group. Finally, we compared CSF and serum samples from patients of the MS groups (paired serum and CSF samples, n=19) using two different methods (ELISA and SIMOA). The CSF NfL level was the highest in the NDCNS group (1169.64 [535.92-5120.11] pg/mL, p=0.025). There was a strong positive correlation between the number of T2 lesions and CSF NfL level (r=0.786, p<0.001) in the MS group. There was excellent consistency between ELISA and SIMOA for CSF samples, but not for serum samples. Our results indicated that CSF NfL levels may also be used in the management of NDCNS and that SIMOA is the most reliable method for serum NfL determination.

The Saliva Cortisol and Amylase Levels Related with Stress Response Compared by Different Analytical Methods.

Sampling of salivary cortisol and amylase is a non-invasive method and important for the evaluation of the hypothalamic-pituitary-adrenal axis function and stress levels. This study aimed to compare the values of the salivary cortisol and amylase levels which were measured by three different analytical methods to discuss the alterations of stress levels of samples. The saliva samples of young adults (n = 23) were collected between 08.00 and 09.00 a.m., noon at 12.00 (before exam) and between 14.00 and 15.00 p.m. (after unaware exam). The samples were measured within the first 48 h, and no freezing/thawing was done. Salivary cortisol and amylase levels of subjects were measured by three different analytical methods as ELISA, chemiluminescence and biosensor methods. Comparison of ELISA and biosensor methods in order to determine the salivary cortisol levels showed a good correlation y = 2.971 + 0.748x (R2 = 0.839). Salivary amylase concentrations were only detected by ELISA method. Biosensor can be offered as an alternative analytic method to the conventional determination method ELISA. It can be preferred because of the detection/information effectiveness, low cost, fast results and specificity characteristics.

The acute toxicity of fenitrothion on narrow-clawed crayfish (Astacus leptodactylus Eschscholtz, 1823) in association with biomarkers of lipid peroxidation.

The aim of this research was to evaluate the acute toxicity of fenitrothion to the crayfish (Astacus leptodactylus Eschscholtz, 1823), which is chosen as an alternative aquatic organism to fish by using the static test system and evaluate the basic lipid peroxidation parameters for the first 24 h. Crayfish of 27.3 ± 0.56 g mean weight and 10.0 ± 0.72 cm mean length were selected for the bioassay experiments. The experiments were repeated three times in 20 liters of tap water. The temperature of water was 21 ± 1°C. The data obtained were statistically evaluated by using a computer program developed by the United States Environmental Protection Agency, based on Finney's probit analysis method and the 96-h LC(50) value for crayfish was calculated to be 15.75 µg/L. The 95% lower and upper confidence limits for the LC(50) were 9.45 to 25.01 µg/L. In addition to the acute toxicity bioassay experiments, 24-h oxidative stress parameters such as malondialdehyde (MDA) levels and ferrous oxidation assay (FOX HP [hydrogen peroxide] equivalents) were also determined. Only MDA levels of hepatopancreas decreased at 5, 10, and 20 µg/L of fenitrothion doses. We can conclude that fenitrothion is highly toxic to crayfish, a nontarget organism in the ecosystem, and the lipid peroxidation indicators can be easily used for monitoring environmental effects.

Genotoxicity assessment of carp (Cyprinus carpio L.) fingerlings by tissue DNA damage and micronucleus test, after environmental exposure to fenitrothion.

The purpose of this study was to evaluate the adverse effects of sublethal doses of fenitrothion, an organophosphothionate insecticide on brain, gill, liver, and muscle tissues as a ratio of 8-OHdG to dG to indicate the DNA damage and erythrocyte micronucleus frequency for genotoxicity of carp (Cyprinus carpio L.) fingerlings. In our study, the mean weights and lengths of the fish (n = 4-12) were 31.13 ± 14.24 g and 12.53 ± 1.41, respectively. Before the experiment, fish were maintained in aerated dechlorinated tap water at 21.8 ± 1 °C and fed daily with commercial feed at a rate of 2% of their body weights. Experiments were conducted under static conditions in the aquaria. Technical grade (95%) fenitrothion was diluted in acetone to give a dosing solution of 10 mg/L. The increased lesions/106 DNA bases (p < 0.05) of liver tissue of exposure group (0.49 ± 0.18) was observed when compared to control group (0.28 ± 0.30). There was not any significant differences between brain tissues, no damage were detectable in gill and muscle tissues of control groups, and in exposure groups altered levels of damage were detected for gill (0.06 ± 0.05) and muscle (0.16 ± 0.21) tissues. The increased micronucleus frequencies (%) in erythrocytes of carp following the exposure to 48 h fenitrothion (6.43 ± 3.89; p<0.05) was observed when compared to control group (1.29 ± 1.03). The available data indicate that there is still lack of well-established dose-response relationships between occupational or environmental exposures and the induction of 8-OHdG. Such biomarkers may be used in assessing adverse/toxic effects of pesticides as environmental stressors.

Staying calm and teaching biochemistry to postgraduates in COVID-19 times: Pros and cons.

While we have been looking for alternative educational materials for our undergraduate students, we found ourself in Covid-19 pandemic and had to think postgraduate education. On the first day of restrictions, our major problem was to learn and find the best communication tool. The first experiences for online meetings were boring, we were not feeling our emotions but as days past we got used to it. We all understand the importance of having alternatives and have to be ready for second choices. During those challenging days, all had more time to work on our completed data, time to write, complete the proofreading of written materials. Other vital scientific activities for career development and profile building such as reading (every meeting with new articles/reviews), publishing and preparing oral presentation were fully completed during the online meetings as a part of lab meeting activities. They learned to improve communication skills, be active participants, and fight.

The evaluation of serum brain-derived neurotrophic factor and neurofilament light chain levels in patients with obstructive sleep apnea syndrome.

OBJECTIVES: This study aimed to compare serum levels of brain-derived neurotrophic factor (BDNF) and neurofilament light (NfL) chain in normal individuals and patients with mild and moderate-severe obstructive sleep apnea syndrome (OSAS). METHODS: We enrolled 81 subjects referred to Otorhinolaryngology (Ear-Nose-Throat), Gazi University Faculty of Medicine, between 2017 and 2019. Based on the severity of OSAS, patients were divided into three groups: group 1 with mild OSAS (apnea-hypopnea index [AHI] 5-15; n = 26), group 2 with moderate-severe OSAS (AHI > 15; n = 32), and group 3 with normal individuals (AHI scores < 5; n = 23). RESULTS: Serum NfL and BDNF levels were evaluated together with the clinical data for all subjects. Significant differences were seen in the oxygen desaturation index (ODI), apnea index, hypopnea index, sleep efficiency, and NfL levels (P < .05) between the three groups. In the moderate-severe group, NfL levels showed a significant positive correlation with apnea index (P < .05, r = .389), hypopnea index (P < .05, r = .455), and ODI (P = .04; r = .362). CONCLUSIONS: Our findings clarify the pathophysiology of OSAS in cases of repetitive hypoxia and chronic neuronal damage. Based on our results, we recommend that in addition to BDNF, NfL should also be evaluated in different and larger patient cohorts.

Quantum chemical investigation of nitrotyrosine (3-nitro-L-tyrosine) and 8-nitroguanine.

The structural, vibrational and electronic properties of nitrotyrosine and 8-nitroguanine have been investigated theoretically by performing the molecular mechanics (MM+ force field), the semi-empirical self-consistent-field molecular-orbital (PM3), and density functional theory calculations. The geometry of the nitrotyrosine and 8-nitroguanine molecules have been optimized, the vibrational dynamics and the electronic properties calculated in their ground states in the gas phase.

Influence of surgical trauma on neopterin concentrations in gastric carcinoma patients.

AIMS AND BACKGROUND: Impairment of immune surveillance in the immediate postoperative period may accelerate the growth of tumor cells that remain despite radical resection in advanced cases. The present study was undertaken to evaluate the impact of major surgical trauma on host cellular immunity of gastric carcinoma cases. METHODS AND STUDY DESIGN: Sixty-eight consecutive patients with gastric carcinoma were divided into three subgroups according to the classification of the American Joint Committee on Cancer Staging, and they underwent surgery with a curative intent. Thirty-eight cancer-free patients served as controls, and they underwent surgical management for benign diseases. Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) risk adjustment system was used to estimate the operative and physiological scores of patients. Plasma cortisol, serum interleukin-6 and high-sensitive C-reactive protein levels were determined in order to assess the severity of trauma-related inflammatory response. The frequency of increased neopterin concentrations of cancer patients was estimated by comparison with the average values of controls. RESULTS: Response of interleukin-6 to surgery was closely related with the postoperative cortisol of cancer patients, but not correlated with neopterin and high-sensitive C-reactive protein levels. Although the extent of tumor invasion might have gradually decreased the macrophage response to surgical trauma, the overall increase in postoperative neopterin levels of cancer cases was highly significant. However, maximal frequency of increased neopterin concentration was obtained in advanced group. CONCLUSIONS: Macrophages might recognize the traumatic challenges in every stage of gastric cancer. Increasing individual neopterin concentration was not solely specific for tumor growth, but it was partially predictive of immune competence even in advanced cases.

Determination of Tryptophan and Kynurenine by LC-MS/MS by Using Amlodipine as an Internal Standard.

Tryptophan is an essential amino acid that plays an important role in cell metabolism, and kynurenine is its main metabolic pathway. By using ultra-high-performance liquid chromatography coupled to electrospray ionization triple-quadrupole mass spectrometry, tryptophan and kynurenine were determined using amlodipine as an internal standard. The analysis was carried out on an ACE-C18 (4.6 mm × 50 mm, 5 µm) reversed-phase analytical column using the gradient elution mode. For quantitative determination, amlodipine was used as an internal standard. Detection was performed using multiple reaction monitoring in electrospray ionization mode at m/z 205.1 → 117.7 and 187.9 for tryptophan, m/z 209.1 → 146 and 93.9 for kynurenine, and m/z 409.2 → 294.1 for the internal standard. Good linearity of the analyte to internal standard peak area ratios was seen in the concentration range 1.25-4000 ng/mL for tryptophan and 0.5-1600 ng/mL for kynurenine. The method showed excellent linearity with regression coefficients of 0.99 for kynurenine and 0.996 for tryptophan. The limits of quantification were 0.55 ng/mL for tryptophan and 0.47 ng/mL for kynurenine. The % RSD for all analytes ranged from 0.3 to 3.4% for intraday and 0.4 to 8.9% for interday experiments. A simple LC-MS/MS method has been developed and validated for measuring Kyn and Trp by using an affordable and more easily available internal standard, which is amlodipine.

Neuroprotective effects of topical coenzyme Q10 + vitamin E in mechanic optic nerve injury model.

PURPOSE: We aimed to create mechanic optic nerve injury model in rats and investigate the neuroprotective effects of topical Coenzyme Q10 + Vitamin E (CoQ + Vit.E) molecules on retinal ganglion cells. METHODS: Mechanic optic nerve injury model was created in the right eyes of rats (n = 12). Rats were divided into two groups: glaucoma model with sham treatment and topical CoQ + Vit.E treatment. Treatment was applied for 4 weeks. Glial fibrillary acidic protein, Brn-3a antibody, and anti-Iba1 were examined by immunohistochemistry. Glial fibrillary acidic protein, Bax, Bcl-xL, and Tfam protein expression were measured by Western blot analysis. RESULTS: The number of Brn-3a-positive retinal ganglion cell was 15.0 ± 1.0 (min: 14, max: 16) in sham treatment group and 22.2 ± 4.8 (min: 18, max: 29) in topical CoQ10 + Vit.E treatment group. The protection of Brn-3a in CoQ10 + Vit.E was statistically significant (p < 0.05). Glial fibrillary acidic protein-positive astroglial counts were recorded as 11.7 ± 2.1 (min: 10, max: 14) in sham treatment and 2.5 ± 1.5 (min: 1, max: 4) in topical CoQ10 + Vit.E treatment group (p < 0.05). Topical CoQ10 + Vit.E treatment also decreased Iba1 expression in the retina of mechanic optic nerve injury groups. CoQ10 + Vit.E treatment prevented apoptotic cell death by increasing Bcl-xL protein expression. Also, CoQ10 + Vit.E preserved Tfam protein expression in the retina. CONCLUSION: This study has shown that in glaucoma treatment the neuron protecting effect of topical CoQ10 + Vit.E molecules can be valuable.

Sublethal cyfluthrin toxicity to carp (Cyprinus carpio L.) fingerlings: biochemical, hematological, histopathological alterations.

This study measures a whole series of biological endpoints, and histopathological and behavioral changes of carp (Cyprinus carpio L.) fingerlings in order to investigate the adverse effects of a sublethal concentration of 10 microg/L cyfluthrin for 48h and one week using the semi-static test system. The most significantly altered findings of this study was that total antioxidant status levels decreased in 48h, chloride levels decreased in one week, and sodium and phosphorous levels increased in the 48h-exposed group. Plasma cortisol increased in both the 48h-exposed and the one-week-exposed groups. The unique tissue was the brain that had an increased level of malondialdehyde after one week of exposure. Such biomarkers may be used in assessing adverse/toxic effects of pesticides as environmental stressors. Potential oxidative-stress-inducing effect of synthetic pyrethroid cyfluthrin, as lipid peroxidation, in addition to its sodium channel blocking, is reported for the first time as an additional mechanism of action.

Usefullnes of atherogenic indices and Ca-LDL level to predict subclinical atherosclerosis in patients with psoriatic arthritis?

BACKGROUND: To investigate the link between carbamylated low-density lipoprotein (ca-LDL), atherogenic index of plasma (AIP), atherogenic coefficient (AC), Castelli's risk indices I and II (CRI I and II) and subclinic atherosclerosis in psoriatic arthritis (PsA). METHODS: Thirty-ninepatients and 19 age, sex, body mass index matched healthy controls were included. Insulin resistance (IR) was assessed with homeostasis of model assessment-IR (HOMA-IR). Carotid intima-media thickness (CIMT) was measured at both common carotid arteries and mean CIMT was calculated. RESULTS: The mean age was 49.50 ± 11.86 years and 64.1% were females in PsA group. In the PsA group, CIMT and HOMA-IR were significantly higher (p = 0.003, p = 0.043, respectively). AIP, AC, TG/HDL, CRI-1, CRI-2 and ca-LDL levels were similar between groups. In PsA group, CIMT was positively correlated with HOMA-IR, TG/HDL and AIP. Although ca-LDL was positively correlated with serum amyloid A (r = 0.744, p < 0.001), no correlation was detected between ca-LDL and CIMT (r = 0.215, p = 0.195). PsA patients with IR tended to have higher ca-LDL levels than patients without IR, but this difference lacked statistical significance (33.65 ± 26.94, 28.63 ± 28.06, respectively, p = 0.237). CONCLUSIONS: A significant increase in CIMT was seen in PsA patients without clinically evident cardiovascular disease or any traditional atherosclerosis risk factors. CIMT was correlated with HOMA-IR, TG/HDL and AIP.

Does preemptive gabapentin modulate cytokine response in total knee arthroplasty? A placebo controlled study.

BACKGROUND: Gabapentin, as a structural analogue of γ-aminobutyric acid, has been investigated to provide pain relief in the early postoperative period following various surgical interventions. OBJECTIVES: The objective of this study was to investigate whether preemptive oral administration of gabapentin 800 mg can reduce postoperative pain and modulate the inflammatory cytokine response in comparison to placebo in patients undergoing total knee arthroplasty under general anesthesia. MATERIAL AND METHODS: Fifty-two patients were randomly divided into 2 groups before surgery, either to receive peroral gabapentin 800 mg or placebo drug, 1 h before surgery. All patients had general anesthesia with endotracheal intubation, in a standardized fashion, by the same anesthetist. Thirty min before completion of surgery, intramuscular diclofenac sodium 75 mg was administered. Following extubation, visual analogue pain scale (VAS) scores and additional analgesic requirements were recorded at 15 min at post-anesthesia care unit (PACU), and at 4th and 24th h postoperatively. Plasma levels of interleukin 6 (IL-6), and tumor necrosis factor R (TNF-R) were measured at predetermined time points (T0 1 h before administration of gabapentin, T1 at postoperative the 4th h mark, and T2 at postoperative at the 24th h mark). RESULTS: The VAS scores at postoperative 4th h were significantly higher in placebo and gabapentin groups compared with VAS scores at PACU and at 24th h. The groups did not differ in terms of additional analgesic requirements. In gabapentin group, IL-6 levels at T1 and T2 were significantly lower in comparison to values measured in placebo group at the same time points. This difference was not significant in TNF-R levels between the groups. CONCLUSIONS: Though preemptive oral gabapentin administration did not reduce postoperative pain and analgesic requirements in total knee arthroplasty surgery, it attenuated IL-6 production on the first postoperative day.

Uncomplicated type 1 diabetes is associated with increased asymmetric dimethylarginine concentrations.

CONTEXT: Asymmetric dimethylarginine (ADMA) has recently emerged as an independent risk marker for cardiovascular disease, but studies investigating the ADMA levels in type 1 diabetes mellitus (DM) are scarce. OBJECTIVE: We aimed to evaluate plasma ADMA, L-arginine concentrations, and L-arginine to ADMA ratio in uncomplicated type 1 diabetic patients and controls. DESIGN AND SUBJECTS: Forty patients with type 1 DM who did not have clinical evidence of vascular complications and 35 healthy controls were included in the study. RESULTS: Plasma ADMA concentrations were higher (2.6 +/- 1.9 vs. 1.7 +/- 0.7 micromol/liter, P < 0.01), and L-arginine levels were lower (79.3 +/- 22.6 vs. 89.6 +/- 19.4 micromol/liter, P < 0.05) in the diabetic group, compared with controls. The L-arginine to ADMA ratio was also lower in the diabetic group (38.7 +/- 17.1 vs. 62.0 +/- 27.9, P < 0.0001). In diabetic patients, logADMA correlated positively with body mass index (BMI) (P = 0.01), fasting blood glucose (P = 0.006), and low-density lipoprotein cholesterol (LDL-c) (P = 0.01) and negatively with high-density lipoprotein cholesterol (P = 0.03). L-arginine to ADMA ratio correlated negatively with BMI (P = 0.004), fasting blood glucose (P = 0.02), and LDL-c (P = 0.01) and positively with high-density lipoprotein cholesterol (P = 0.04). In controls, logADMA and L-arginine to ADMA ratio correlated with BMI and LDL-c (P < 0.05). In regression analysis, BMI predicted 15% variance of ADMA levels (P = 0.02). CONCLUSIONS: We demonstrated that ADMA increases and L-arginine to ADMA ratio decreases, even before the development of vascular complications in type 1 DM.