Metabolite Profile Characterization of Cyanobacterial Strains with Bioactivity on Lipid Metabolism Using In Vivo and In Vitro Approaches.

Cyanobacteria have demonstrated their therapeutic potential for many human diseases. In this work, cyanobacterial extracts were screened for lipid reducing activity in zebrafish larvae and in fatty-acid-overloaded human hepatocytes, as well as for glucose uptake in human hepatocytes and ucp1 mRNA induction in murine brown adipocytes. A total of 39 cyanobacteria strains were grown and their biomass fractionated, resulting in 117 chemical fractions. Reduction of neutral lipids in zebrafish larvae was observed for 12 fractions and in the human hepatocyte steatosis cell model for five fractions. The induction of ucp1 expression in murine brown adipocytes was observed in six fractions, resulting in a total of 23 bioactive non-toxic fractions. All extracts were analyzed by untargeted UPLC-Q-TOF-MS mass spectrometry followed by multivariate statistical analysis to prioritize bioactive strains. The metabolite profiling led to the identification of two markers with lipid reducing activity in zebrafish larvae. Putative compound identification using mass spectrometry databases identified them as phosphatidic acid and aromatic polyketides derivatives-two compound classes, which were previously associated with effects on metabolic disorders. In summary, we have identified cyanobacterial strains with promising lipid reducing activity, whose bioactive compounds needs to be identified in the future.

Plasma levels of oxysterols 7-ketocholesterol and cholestane-3ß, 5α, 6ß-triol in patients with allergic asthma.

The prevalence of allergic asthma is increasing on a global scale, reflecting changes in air pollution, climatic changes, and other environmental stimulants. In allergic conditions, oxidative stress occurs as a result of immune system activation. Oxidation of cholesterol leads to the formation of oxysterols. The main purpose of the study was to compare plasma levels of two oxysterols, namely 7-ketocholesterol (7-KC) and cholestane-3ß, 5α, 6ß-triol (C-triol), and a lipid peroxidation product, malondialdehyde (MDA) in allergic asthma patients with those of healthy controls, in order to provide information about the involvement of lipid peroxidation in allergic asthma.Oxysterols were quantified by LC-MS/MS in plasma samples of 120 asthma patients (90 females + 30 males) and 120 healthy controls (matched by age and sex). Plasma MDA level was analyzed by a spectrophotometric method.Plasma 7-KC (39.45 ± 20.37 ng/mL) and C-triol (25.61 ± 10.13 ng/mL) levels in patients were significantly higher than in healthy subjects (17.84 ± 4.26 ng/mL and 10.00 ± 3.90 ng/mL, respectively) (P < 0.001). Plasma MDA levels were also higher in asthmatic patients (4.98 ± 1.77 nmol/mL) than in healthy controls (1.14 ± 0.31 nmol/mL) (P < 0.001). All data support that lipid peroxidation products are involved in allergic asthma.Oxysterols were quantified for the first time in allergic asthma. Since the high plasma 7-KC and C-triol levels of allergic asthma patients correlate with high IgE levels, detection of these oxysterols by LC-MS/MS may be helpful in the clinical monitoring of allergic asthma. Current data may also lead to new approaches for the prevention, diagnosis, and treatment of the disease.Supplemental data for this article is available online at at.

Review on the ecotoxicological impacts of plastic pollution on the freshwater invertebrate Daphnia.

The environmental impacts of plastic pollution have recently attracted universal attention, especially in the aquatic environment. However, research has mostly been focused on marine ecosystems, even though freshwater ecosystems are equally if not more polluted by plastics. In addition, the mechanism and extent to which plastic pollution affects aquatic biota and the rates of transfer to organisms through food webs eventually reaching humans are poorly understood, especially considering leaching hazardous chemicals. Several studies have demonstrated extreme toxicity in freshwater organisms such Daphnia. When such keystone species are affected by ambient pollution, entire food webs are destabilized and biodiversity is threatened. The unremitting increase in plastic contaminants in freshwater environments would cause impairments in ecosystem functions and structure, leading to various kinds of negative ecological consequences. As various studies have reported the effects on daphnids, a consolidation of this literature is critical to discuss the limitations and knowledge gaps and to evaluate the risk posed to the aquatic environment. This review was undertaken due to the evident need to evaluate this threat. The aims were to provide a meaningful overview of the literature relevant to the potential impact of plastic pollution and associated contaminants on freshwater daphnids as primary consumers. A critical evaluation of research gaps and perspectives is conducted to provide a comprehensive risk assessment of microplastic as a hazard to aquatic environments. We outlined the challenges and limitations to microplastic research in hampering better-focused investigations that could support the development of new plastic materials and/or establishment of new regulations.

Possible Effect of Chelation Treatment on Metabolomic and Lipidomic Analysis in Lead Exposure.

OBJECTIVE: This study aimed to examine patients with lead poisoning in terms of metabolomic profiles and bioactive lipids (oxysterols and sphingosine 1-phosphate [S1P]) before and after chelation therapy. METHODS: Consent was obtained from 42 individuals diagnosed with lead poisoning and blood and urine samples were collected before and after chelation therapy. The levels of 7-ketocholesterol (7-KC), cholestan-3b,5a,6b-triol (Ctriol), and S1P were measured via LC-MS/MS. Metabolomic analysis was performed via GC-MS. RESULTS: 7-KC and C-triol levels were detected higher before chelation therapy compared with after therapy (P < 0.001 for both). S1P levels were measured higher before the therapy. The results also showed that sphingolipid metabolism-related pathways were affected by lead toxicity as well as other related pathways. CONCLUSION: This preliminary study showed that lipid metabolism is affected in lead exposure and chelation therapy is effective in reversing possible damage.

Physiological and Behavioral Effects of SiO2 Nanoparticle Ingestion on Daphnia magna.

The increasingly widespread use of engineered nanoparticles in medical, industrial, and food applications has raised concerns regarding their potential toxicity to humans and the environment. Silicon dioxide nanoparticles (SiO2 NPs), which have relatively low direct toxicity, have been increasingly applied in both consumer products and biomedical applications, leading to significantly higher exposure for humans and the environment. We carried out a toxicity assessment of SiO2 NPs using the common water flea D. magna by focusing on physiological and behavioral indicators such as heart rate, swimming performance, and growth. Exposure to SiO2 NPs did not produce acute or chronic toxicity at limited concentrations (<100 µg/mL), but did have statistically significant negative effects on heart rate, swimming distance, and body size. The use of fluorescein isothiocyanate in a silica matrix allowed the tracing and visualization of clear SiO2 NP accumulation in D. magna, which was confirmed by ICP-MS. Although exposure to SiO2 NPs seemed to affect cardiac and swimming performance, such end-point experiments may be insufficient to fully understand the toxicity of these nanoparticles. However, the physiological and behavioral changes shown here suggest potential adverse effects on the aquatic environment by substances previously considered nontoxic.

Oxysterol species generated by auto-oxidation in subclinical hypothyroidism.

BACKGROUND: Auto-oxidized oxysterols are implicated in the pathogenesis of various chronic diseases. Their concentrations are indicators of oxidative stress in vivo and associated with atherosclerosis. Subclinical hypothyroidism is related with cardiac diseases and oxidative stress, but the exact mechanisms underlying these associations are not clear yet. OBJECTIVE: To investigate the auto-oxidized oxysterols, 7-ketocholesterol (7-KC) and cholestane-3ß,5α,6ß-triol (chol-triol), in patients with subclinical hypothyroidism, as well as to evaluate the impact of restoring euthyroidism on oxysterol concentrations. METHODS: In this prospective observational study, 64 patients with newly diagnosed autoimmune thyroiditis (41 with subclinical hypothyroidism and 23 euthyroidism), and 45 healthy controls were enrolled. Age, gender, and body mass index were matched among patient groups and healthy controls. Anthropometric measurements were obtained and fasting plasma 7-ketocholesterol and cholestane-3ß,5α,6ß-triol concentrations were measured by using liquid chromatography coupled with tandem mass spectrometry. Levothyroxine was then administered to all patients with subclinical-hypothyroidism. After three months, measurements of the oxysterols and serum cholesterols from the patients who have become euthyroid were repeated. RESULTS: Concentrations of 7-ketocholesterol and cholestane-3ß,5α,6ß-triol were significantly higher in patients with subclinical-hypothyroidism when compared to both euthyroid patients and healthy controls (p < 0.001 for both oxysterols). After restoration of euthyroidism, concentrations of 7-ketocholesterol and cholestane-3ß,5α,6ß-triol decreased significantly and reached similar concentrations observed in healthy controls (p < 0.001 for both oxysterols). CONCLUSIONS: Auto-oxidized oxysterol species are higher in patients with mild thyroid dysfunction, and supported the rationale for treating subclinical-hypothyroidism.

A Comprehensive Review on Oxysterols and Related Diseases.

The present review aims to provide a complete and comprehensive summary of current literature relevant to oxysterols and related diseases. Oxidation of cholesterol leads to the formation of a large number of oxidized products, generally known as oxysterols. They are intermediates in the biosynthesis of bile acids, steroid hormones, and 1,25- dihydroxyvitamin D3. Although oxysterols are considered as metabolic intermediates, there is a growing body of evidence that many of them are bioactive, and their absence or excess may be part of the cause of a disease phenotype. These compounds derive from either enzymatic or non-enzymatic oxidation of cholesterol. This study provides comprehensive information about the structures, formation, and types of oxysterols even when involved in certain disease states, focusing on their effects on metabolism and linkages with these diseases. The role of specific oxysterols as mediators in various disorders, such as degenerative (age-related) and cancer-related disorders, has now become clearer. Oxysterol levels may be employed as suitable markers for the diagnosis of specific diseases or in predicting the incidence rate of diseases, such as diabetes mellitus, Alzheimer's disease, multiple sclerosis, osteoporosis, lung cancer, breast cancer, and infertility. However, further investigations may be required to confirm these mentioned possibilities.

Effects of treatment with haloperidol and clozapine on the plasma concentrations of thyroid hormones in rats.

OBJECTIVES: Psychoactive drugs are group of compounds used to treat severe mental problems, including psychosis, as well as other conditions. This study assessed clinically relevant side effects of haloperidol and clozapine on the thyroid hormones. METHODS: Haloperidol (0.05 and 2 mg/kg) or clozapine (0.5 and 20 mg/kg) was intraperitoneally injected to male Wistar rats for 28 days. The control group received 2 ml of physiological saline. A chemiluminescent immunoassay was used to measure the plasma levels of thyroid hormones. RESULTS: Plasma concentrations of thyroxine (T4) in rats treated with high-dose (2 mg/kg) of haloperidol decreased significantly compared to the control group (p=0.001). However, both low (0.5 mg/kg) and high clozapine (20 mg/kg) doses did not have a significant effect on the plasma concentrations of T4 and triiodothyronine (T3) (p>0.05). Neither of the compound had a significant effect on T3 plasma concentration levels (p>0.05). CONCLUSIONS: Haloperidol and clozapine act via different mechanisms and may have dissociable effects on thyroid hormones. Following treatment with haloperidol, significant changes in T4, but not in T3, serum levels were observed. Haloperidol and clozapine had different effects on the thyroid hormone levels. These results indicate that antipsychotic treatment can contribute to the thyroid dysfunction. Therefore, greater caution should be applied to the antipsychotics use. The thyroid function of the patients should be closely monitored, while using these drugs.

Evaluation of oxysterol levels of patients with silicosis by LC-MS/MS method.

Silicosis is one of the prolonged and irreversible occupational diseases. Crystalline silica dust, which has been linked with silicosis, occurs in different industrial areas such as constructions, ceramic, quarry, and pottery. There are significant numbers of newly diagnosed cases every year in Turkey. Patients with silicosis suffer from inflammatory respiratory disorders and silicosis-related complications such as rheumatoid arthritis, systemic sclerosis, and vasculitis. Oxysterols are defined as 27-carbon intermediates or end products of cholesterol. They are also implicated in the etiology of disease states such as atherosclerosis, neurodegenerative, and inflammatory diseases. The aim of the study is to evaluate cholesterol oxidation products in the patients with silicosis and determination of sphingosine-1-phosphate (S1P) levels which is a sphingolipid metabolite. In addition to these parameters, it is aimed to determine the possible lipid peroxidation by different parameters. For this purpose, blood samples and urine were collected from 47 patients and 30 healthy individual with their consents. In order to evaluate oxysterols, 7-ketocholesterol and cholestan 3ß,5α,6ß-triol levels were measured by LC-MS/MS method. The measured levels of 7-KC were 0.101 ± 0.005 µmol/l in patient and 0.050 ± 0.003 µmol/l in control plasma samples. Triol levels were measured as 0.038 ± 0.005 µmol/l in patient group and 0.033 ± 0.004 µmol/l in control group (p < 0.001). In addition, lipid peroxidation products were measured by human-8-isoprostane, human-4-hydroxynonenal (4-HNE), and human malondialdehyde (MDA) ELISA kits. The measured levels of HNE in the patient and control groups were 735.14 ± 288.80 pg/ml and 595.72 ± 108.62 pg/ml in plasma and 606.02 + 118.23 pg/ml and 531.84 + 107.18 pg/ml in urine, respectively (p < 0.05). F2-iP results of patients and controls were 450.0 + 101.40 pg/dl and 386.9 + 112.7 pg/ml for urine and 432.7 ± 188,8 pg/dl and 321.9 ± 69.4 pg/dl for plasma, respectively (p < 0.05). MDA levels of plasma were measured as 44.1 ± 14.6 nmol/ml in the patient and 31.9 ± 10.5 nmol/ml in the control (p < 0.05). Levels of MDA for urine samples were 30.15 + 5.06 nmol/ml and 25.15 + 6.07 nmol/ml in patients and controls, respectively (p < 0.05). S1P levels were decreased in patients compared to control group (49.05 ± 10.87 and 67.57 ± 16.25, p < 0.001). The results not only indicate a correlation between cholesterol oxidation, lipid peroxidation, and silicosis, but also provide better understanding of the role of the lipids in the mechanism of this inflammatory disease.

Apoptosis Inhibitor of Macrophage, Monocyte Chemotactic Protein-1, and C-Reactive Protein Levels Are Increased in Patients with Metabolic Syndrome: A Pilot Study.

Background: Apoptosis inhibitor of macrophage (AIM) and monocyte chemotactic protein-1 (MCP-1) are molecules that cause migration of M1 macrophages to visceral adipocytes, which is the first step in development of metabolic syndrome. The aim of this study is to evaluate the status of AIM and MCP-1 in metabolic syndrome and to investigate their use as biomarkers. Methods: Forty metabolic syndrome patients and 40 healthy individuals were enrolled in the study. Serum AIM, MCP-1, and C-reactive protein (CRP) levels were measured by enzyme-linked immunosorbent assay. Results: AIM, MCP-1, and CRP levels were significantly higher in the metabolic syndrome group (P < 0.01, P < 0.01, and P < 0.05, respectively). There was a positive correlation of serum AIM, MCP-1, and CRP levels with waist circumference (r = 0.480, r = 0.663, and r = 0.418, respectively; P < 0.01). Receiver operating characteristic (ROC) curve analyses revealed AIM, MCP-1, and CRP cutoff points as 2383.7 ng/mL, 172.8 pg/mL, and 0.366 mg/dL, which could be used in the diagnosis of metabolic syndrome with highest sensitivity and specificity. In the logistic regression model, including age, AIM, CRP, and MCP-1 as covariates, having serum AIM and CRP levels above cutoffs were significant independent predictors for metabolic syndrome (odds ratios 13.8 and 21.3), whereas the serum MCP-1 level was not a significant independent predictor, although the odds ratio was 2.6 (P = 0.193). Conclusions: These results suggest that AIM and MCP-1 may play a role in the pathogenesis of metabolic syndrome. AIM and CRP levels may be used as biomarkers in the diagnosis of metabolic syndrome. Although MCP-1 is not an independent predictor, its elevation in metabolic syndrome is noteworthy, which warrants further analyses in larger groups.

Zinc, copper, and oxysterol levels in patients with type 1 and type 2 diabetes mellitus.

BACKGROUND: The present study has the objective to assess the zinc (Zn), copper (Cu), and oxysterols plasma levels in type 1 (DM1) (n = 26) and type 2 (DM2) (n = 80) diabetes patients, as compared to healthy controls (n = 71), in order to testify whether metal levels may have a significant impact on the association between oxysterols and diabetes. METHODS: Plasma trace elements and plasma oxysterols were assessed using atomic absorption spectrometry and LC-MS/MS, respectively. Lifestyle, smoking status, alcohol intake, and drug usage, as well as microvascular complications, were also monitored and reported. RESULTS: The obtained data demonstrated that both DM1 and DM2 patients were characterized by significantly elevated HbA1c, FBG, TC, LDL-C, VLDL-C, and TG levels as compared to controls. Plasma Zn levels and Zn/Cu ratio in DM1 and DM2 patients were about 3- and 2-fold lower than controls. No significant differences in plasma Cu levels were reported. The 7-ketocholesterol (7-kchol) levels in DM1 and DM2 patients exceeded these values in healthy individuals by 2.5 and 5-fold, respectively. Similarly, cholestan-3ß, 5α, 6ß-triol (chol-triol) levels were more than 3- and 6-fold higher when compared to the respective values in non-diabetic controls. In regression models decreased plasma Zn and elevated oxysterol levels were significantly associated with HbA1c and fasting plasma glucose levels, after adjustment for anthropometric and clinical variables, as well as routine biochemical markers. CONCLUSIONS: Plasma Zn concentration is inversely associated with both 7-kchol and chol-triol levels. Assessment of Zn and oxysterol levels may be used both for risk assessment and as targets for the treatment of diabetes mellitus.

Effects of clozapine and haloperidol treatment on plasma concentrations of androgen hormones and androgendependent organ changes in rats.

OBJECTIVES: Metabolic and endocrine adverse effects are among the most concerning unfavorable consequences of commonly used psychotropic drugs. The present research was planned to assess and determine the effects of haloperidol and clozapine on testosterone, cortisol, and corticosterone levels and also their influence on androgen-dependent organs in adult male Wistar rats. MATERIALS AND METHODS: Animals were casually distributed into three groups (n = 10 in each group). Drugs were administered intraperitoneally for 28 days. The control group received 2 mL of physiological saline, the second group received haloperidol (0.5 mg/kg), and the third group received clozapine (0.5 mg/kg). The subsequent testosterone, cortisol, and corticosterone plasma concentration levels were analyzed with chemiluminescent immunoassay. RESULTS: Clozapine and haloperidol treatments altered testosterone hormone levels. Testosterone mean values in both the clozapine (1.00-0.58) and haloperidol (0.65-0.62) groups were found to be lower than compared to controls (P = 0.003, P < 0.001). Histomorphometric analysis results also showed reduced testes size and reduced weight of androgen-dependent organs in drug-treated rats. CONCLUSION: It can be suggested that clozapine and haloperidol are effective in reducing the testosterone plasma concentration level and androgen-dependent organ sizes; therefore, clinicians should be aware of these effects when considering the use of antipsychotic drugs.

The Effect of Effort Test on the Levels of Ischemia Modified Albumin, 7-ketocholesterol and Cholestan-3ß , 5α , 6ß -triol and their Role in the Diagnosis of Coronary Artery Disease.

BACKGROUND: Oxysterols have been shown to play a role in plaque formation while ischemia modified albumin (IMA) is widely accepted as an acute marker for ischemia. The effort test is one of the methods used to identify the presence of coronary artery disease. Thus, there may be a relationship between effort test result and the levels of IMA, 7-ketocholesterol (7-KC) and cholestane-3ß,5α,6ß-triol (C-triol). METHODS: Thirty patients who underwent effort test and 30 healthy subjects were included in the study. IMA levels were determined with the albumin-cobalt binding test, 7-KC and C-triol levels were determined with LC-MS/MS. Among the patients, two subgroups were identified according to the results of the effort test, group 1 consisted of patients with a positive effort test (n = 12), and group 2 consisted of patients who had a negative effort test (n = 18). RESULTS: 7-KC levels of patients were significantly higher compared to healthy subjects (39.87 ± 2.13 ng/mL, 20.26 ± 1.35 ng/mL; p=0.001). In patients, post-test 7-KC levels were significantly lower than pre-test levels (post-test vs. pre-test: 37.73 ± 2.44 ng/mL vs. 41.07 ± 2.18 ng/mL; p<0.001). There was a significant difference in post-test 7-KC levels among all study groups (negative, positive and healthy: 37.73 ± 2.44 ng/mL, 39.87 ± 2.13 ng/mL, 20.26 ± 1.35 ng/mL, respectively). There was no significant difference in IMA levels. CONCLUSIONS: Patients with positive effort test had significantly higher levels of 7-KC. Additionally, after the effort test, the 7-KC value was reduced. 7-KC is a biomarker of oxidative damage and its value or changes before and after the effort test may be used as a biomarker in the diagnosis and follow-up of coronary artery disease.

Oxysterol concentrations are associated with cholesterol concentrations and anemia in pediatric patients with sickle cell disease.

Sickle cell disease (SCD) causes anemia, oxidative stress, chronic inflammation, and lipid abnormalities. Oxysterols are oxidized derivatives of cholesterol and affect cholesterol metabolism and eryptosis. Our aim was to determine whether the plasma concentrations of 7-ketocholesterol (7-KC) and cholestane-3ß,5α,6ß-triol (C-triol) were associated with hemolysis and lipid profile in patients with SCD. A total of 32 steady-state pediatric patients with SCD (22 HbSS and 10 HbSß+) and 25 healthy controls were included in the study. Hemolysis parameters, ferritin, serum iron, lipids, 7-KC and C-triol concentrations of all subjects were measured. Oxysterols were quantified with N,N-dimethylglycine derivatization via LC-MS/MS. 7-KC and C-triol concentrations were found to be increased in SCD patients, while there was no difference between the HbSS and HbSß+ subgroups. 7-KC concentrations s were correlated negatively with hemoglobin and positively with lactate dehydrogenase concentrations, while C-triol concentrations were negatively correlated with HDL cholesterol. Furthermore, while 7-KC and C-triol concentrations were highly correlated among controls, there was no correlation in patients. The findings of our study suggest that 7-KC and C-triol may have a role in SCD pathophysiology. The lack of correlation in patients' 7-KC and C-triol concentrations suggest alterations in oxysterol production in patients with SCD.

A reappraisal on metformin.

This review investigates the different biological effect of Metformin (MET) in different conditions. MET is an oral antidiabetic drug used for the treatment of type 2 diabetes mellitus (T2DM) particularly in overweight people. The main mechanism of action of the MET is inhibition of hepatic glucose production and reduction of insulin resistance. In addition to its antidiabetic effects, MET is also found to be related with the risk for development of several human solid cancers types such as colorectal, breast and pancreas cancer in the diabetic patients. Nowadays according to some researches, MET is believed to decrease or prevent aging and mortality. Moreover, clinical and experimental evidence has shown that MET has beneficial effects in patient with obesity, polycystic ovarian syndrome and Alzheimer's disease. Recent studies have shown that activation of adenosine monophosphate-activated protein kinase (AMPK) by MET can explain its beneficial metabolic effects. In this manuscript, a reevaluation of mechanisms as well as pharmacokinetic properties, genetic variants of transporters, drug-drug interactions, side effects and potential clinical benefits of MET have been reviewed.

Modic changes in the adjacent vertebrae due to disc material infection with Propionibacterium acnes in patients with lumbar disc herniation.

INTRODUCTION: Modic changes (MCs) in vertebral bones are induced by two mechanisms of mechanical factors and infection. As Propionibacterium acnes (P. acnes) have been reported to be associated with LBP. The aim of this study is to evaluate the MCs in patients with disc herniation and positive for P. acnes. METHODS AND MATERIAL: A total of 120 patients with disc herniation surgery were enrolled into the study. The samples were excised during discectomy and then cultured in both anaerobic and aerobic incubations. Gram staining was employed for investigation of all colonies. The cultured P. acnes were detected by 16S rRNA-based polymerase chain reaction (PCR). MCs of baseline MRI were evaluated. RESULTS: In this study, 120 subjects (69 male and 51 female) with mean age of 43.15 ± 12.62 years were investigated. Sixty disc samples and eight muscle samples were positive for microorganisms. Moreover, 16S rDNA gene was identified in 46 (38.3%) disc samples. Moreover, 36/46 patients with P. acnes in their sample had MCs. CONCLUSION: According to the results and presence of 36/46 MCs in patients with lumbar disc herniation, positive for P. acnes suggests that P. acnes can lead to edema on the vertebrae endplates near to infected area.

The effect of transdermal nitroglycerin on pain control in diabetic patients with peripheral neuropathy.

BACKGROUND: Despite high prevalence of diabetic peripheral neuropathy there is no definite treatment for the condition. The present study was conducted to assess the efficacy of transdermal nitroglycerin patch in pain control of patients with DPN. METHODS: This randomized, double-blind, crossover study was conducted on 30 patients with symmetric distal peripheral neuropathy and good glycemic control. The patients were randomly assigned to receive nitroglycerin transdermal and placebo patches in two 4-week stages. The severity of pain and other neuropathic sensory symptoms were assessed at the end of each course. RESULTS: Mean reduction of pain severity was more prominent in the NTG group compared to placebo group of the study (p = 0.048) at least during the first phase of the study. Except for mood and sleep, a significant reduction in all Brief Pain Inventory scores was noted in the drug group (all corrected p < 0.05). SF-MPQ also showed the drug patch to be effective in improving different aspects of pain measured using McGill Pain Questionnaire, except for Role-emotional. CONCLUSIONS: It could be concluded that nitroglycerin plasters can effectively help alleviate pain in patients with diabetic neuropathy. TRIAL REGISTRATION: IRCT201308223213N1.

The Effect of Epidural Bupivacaine on BIS Levels in the Awake Phase and on the Maintenance Doses of Propofol and Fentanyl During General Anesthesia.

BACKGROUND: Simultaneous administration of epidural local anesthetic agents (LA) and general anesthetics (intravenous or inhaled) is a common procedure in patients undergoing major operations. The effects of epidural anesthesia during combined general-epidural anesthesia on the alertness level (CGEA) in the awake phase and the doses of anesthetics have been reported. OBJECTIVES: The present study was designed to determine the effects of epidural bupivacaine on the alertness level measured by bispectral index (BIS) in the awake phase and the maintenance doses of propofol and fentanyl during general anesthesia for vascular operation on the lower limb. PATIENTS AND METHODS: A double-blinded randomized clinical trial was conducted on patients awaiting vascular surgery on lower extremities in a teaching hospital from October 2007 to October 2008. During the epidural anesthesia, the control group received 0.9% NS while 0.125% bupivacaine was injected in the case group via the epidural route. No sedative drug was utilized for epidural catheter placement. The BIS measurement was performed in both groups during the awake phase, before performing epidural anesthesia, and 10 minutes after epidural injection at 1-min intervals for 15 min. After induction of general anesthesia in both groups, anesthesia maintenance was established using the infusion of propofol with the aim of keeping the BIS level between 40 and 50 throughout the anesthesia. At the end of the study period, maintenance dose requirements of propofol and fentanyl were measured. RESULTS: Thirty-two patients were enrolled in the study. There was no difference in BIS levels of the two groups in the awake phase. There was a significant difference between the propofol and fentanyl requirements of the two groups. CONCLUSIONS: Performing CGEA using bupivacaine was reported to reduce propofol and fentanyl doses required to maintain BIS levels between 40 and 50 considerably.