Exometabolomic analysis of susceptible and multi-drug resistant Pseudomonas aeruginosa.

Multidrug resistant (MDR) Pseudomonas aeruginosa strains have recently become one of the major public health concerns worldwide leading to difficulties in selecting appropriate antibiotic treatment. Thus, it is important to elucidate the characteristics of MDR isolates. Herein, we aimed to determine the unique exometabolome profile of P. aeruginosa clinical isolates in monocultures that comprise high resistance to multiple antibiotics, and compare the differential metabolite profiles obtained from susceptible isolates by using GC/MS. Our results showed that partial least square-discriminant analysis (PLS-DA) score plot clearly discriminated the MDR and susceptible isolates indicating the altered exometabolite profiles, and highlighted the significantly enriched levels of trehalose and glutamic acid in MDR isolates. Expression of trehalose synthase (treS) was also 1·5-fold higher in MDR isolates, relatively to susceptible isolates. Overall, our study provides insights into the distinct footprints of MDR P. aeruginosa isolates in mono-culture.

Comparison of oxidative stress status and quality of life in participants with type 2 diabetes mellitus according to treatment modality.

BACKGROUND: Oxidative stress triggered by hyperglycemia in diabetic patients leads to macrovascular and microvascular complications, resulting in deterioration in the quality of life. AIMS: This study aimed to compare the oxidative stress status and quality of life in participants with type 2 diabetes mellitus according to treatment modality. PATIENTS AND METHODS: Ninety type 2 diabetes mellitus participants aged between 40 and 60 years were included in the study. Forty-five participants were receiving oral antidiabetic drugs and 45 participants were receiving insulin therapy. Total antioxidant status, total oxidant status, and paraoxonase-1 were measured and oxidative stress indices were calculated. The SF-36 quality of life questionnaire was applied to the participants. RESULTS: The total oxidant status and oxidative stress indices values were higher in the insulin-treated group than in the group treated with oral antidiabetic drugs. Paraoxonase-1 activities of the oral antidiabetic drugs-treated group were statistically significantly higher than the insulin-treated group. In the oral antidiabetic drugs-treated group, the physical function, social function, and pain subscale scores were higher than that of the insulin-treated group. In all participants, a negative correlation between total antioxidant status and fasting blood glucose and hemoglobin A1c, a positive correlation between total oxidant status and hemoglobin A1c and triglyceride, and a positive correlation was found between oxidative stress indices and fasting blood glucose and hemoglobin A1c. CONCLUSIONS: It was found that oxidative stress parameters were higher and quality of life was worse in the insulin-treated participants than participants treated with oral antidiabetic drugs. These results may be closely related to more severe chronic complications in insulin-dependent diabetes.

Brain glycogen metabolism: A possible link between sleep disturbances, headache and depression.

The functions of sleep and its links with neuropsychiatric diseases have long been questioned. Among the numerous hypotheses on sleep function, early studies proposed that sleep helps to replenish glycogen stores consumed during waking. Later studies found increased brain glycogen after sleep deprivation, leading to "glycogenetic" hypothesis, which states that there is a parallel increase in synthesis and utilization of glycogen during wakefulness, whereas decrease in the excitatory transmission creates an imbalance causing accumulation of glycogen during sleep. Glycogen is a vital energy reservoir to match the synaptic demand particularly for re-uptake of potassium and glutamate during intense glutamatergic transmission. Therefore, sleep deprivation-induced transcriptional changes may trigger migraine by reducing glycogen availability, which slows clearance of extracellular potassium and glutamate, hence, creates susceptibility to cortical spreading depolarization, the electrophysiological correlate of migraine aura. Interestingly, chronic stress accompanied by increased glucocorticoid levels and locus coeruleus activity and leading to mood disorders in which sleep disturbances are prevalent, also affects brain glycogen turnover via glucocorticoids, noradrenaline, serotonin and adenosine. These observations altogether suggest that inadequate astrocytic glycogen turnover may be one of the mechanisms linking migraine, mood disorders and sleep.

Evaluation of therapeutic potential of intraperitoneal ozone gas in combination with insulin above cranial and spinal neuropathy in rats with diabetes mellitus.

OBJECTIVE: This study aimed to investigate the therapeutic effect of ozone in combination with insulin on cranial and spinal neuropathy in rats with diabetes mellitus (DM). MATERIALS AND METHODS: Sixty adult male Sprague Dawley rats were randomly divided into the following six groups (n = 10): control (C), ozone (O), diabetic (D), ozone-treated diabetic (DO), insulin-treated diabetic (DI), and ozone, insulin-treated diabetic (DOI). DM was induced by a single intraperitoneal (ip) streptozotocin injection (60 mg/kg), followed by 3 IU (ip) insulin administration for 60 days. Next, 1.1 mg/kg (50 µg/ml) ozone was administered to the O, DO, and DOI groups for 60 days. After inducing diabetes, the total oxidant status (TOS) and total antioxidant status (TAS) were measured; the oxidative stress index (OSI) was calculated. The brain and spinal cord tissues were obtained for histopathological evaluation. This cross sectional study was conducted in Dumlupinar University Laboratory Animals Research Center e.g 11.03.2015 ‒ 15.05.2015. RESULTS: TAS was higher in the DO, DI, and DOI groups than in the D group. TOS and OSI were lower in the DO, DI, and DOI groups than in the D group. Little pathological alterations with degenerated axons and vascular congestion were observed in the DO, DI, and DOI groups compared with the D group. CONCLUSION: Ozone with insulin can stimulate the endogenous antioxidant defense mechanism in diabetic neuropathy, thereby preventing reactive oxygen species-induced damage and protecting against cranial and spinal neuropathies (Fig. 6, Ref. 29).

Serum levels of nitrate, nitrite and advanced oxidation protein products (AOPP) in patients with nonalcoholic fatty liver disease.

BACKGROUND: Oxidative stress is increased and anti-oxidant defense mechanisms are impaired in patients with hepatosteatosis. The aim of the present study was to evaluate the serum levels of several oxidant and anti-oxidant markers in patients with nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: Thirty-four patients with NAFLD, and 19 healthy controls were included. In this study, we measured serum nitrate and advanced oxidation protein product (AOPP) as the oxidizing products and nitrite as the anti-oxidizing marker. Nitrate and nitrite levels were measured using a calorimetric method, and levels of serum AOPP were measured by a spectrophotometric method using a commercial ELISA kit. RESULTS: Serum nitrate and AOPP levels were significantly higher in the NAFLD group compared to the control group. Serum nitrite and N-N levels were similar between the two groups. Serum nitrate and N-N levels were found to be significantly higher in patients with elevated ALT levels compared to patients with normal ALT levels. Serum nitrite and AOPP levels were comparable between these groups. Mean platelet volume (MPV) was significantly lower in the NAFLD group compared to the control group. CONCLUSIONS: Serum levels of oxidizing agents including nitrate and AOPP increase in patients with NAFLD. In contrast, serum nitrite, an antioxidant agent, does not adequately increase to compensate for the oxidizing effects in these patients.

Monitoring bone morphogenetic protein-2 and -7, soluble receptor activator of nuclear factor-κB ligand and osteoprotegerin levels in the peri-implant sulcular fluid during the osseointegration of hydrophilic-modified sandblasted acid-etched and sandblasted acid-etched surface dental implants.

BACKGROUND AND OBJECTIVE: The implant surface plays a major role in the biological response to titanium dental implants. The aim of this study was to investigate levels of soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG), bone morphogenetic protein-2 (BMP-2) and -7 (BMP-7) in the peri-implant crevicular fluid (PICF) of different implants during the osseointegration period. MATERIAL AND METHODS: Forty-seven patients (22 females and 25 males, mean age 47.34 ± 10.11) were included in this study. Forty-seven implants from two implant systems (group A1 (sandblasted acid-etched [SLA]-16), group A2 (hydrophilic-modified SLA [SLActive]-16), and group B (sandblasted acid-etched [SLA]-15) were placed using standard surgical protocols. PICF samples, plaque index, gingival index and probing depth measurements were obtained at 1 and 3 mo after surgery. PICF levels of sRANKL, OPG, BMP-2/-7 were analyzed by ELISA. RESULTS: No complications were observed during the healing period. No significant differences were observed in the PICF levels of sRANKL, OPG, BMP-2 and BMP-7 for all groups at any time point (p > 0.05). A significant decrease was observed in BMP-2 levels in group A1 (p < 0.05). A significant increase in BMP-7 levels was observed only for group A2 (p < 0.05). There was a strong negative correlation between OPG and gingival index and a negative correlation between BMP-7 and plaque index (p < 0.05). CONCLUSION: Considering the correlations between clinical and biochemical parameters, the levels of these cytokines in PICF during early healing of implants reflects the degree of peri-implant inflammation, rather than differences in the implant surfaces.

Gene-directed enzyme prodrug therapy for localized chemotherapeutics in allograft and xenograft tumor models.

Most chemotherapy regimens rely on systemic administration of drugs leading to a wide array of toxicities. Using viral-vector-mediated gene modification of muscle tissues, we have developed a method for gene-directed enzyme prodrug therapy that allows for localized drug administration. An inactive prodrug of geldanamycin was activated locally for inhibition of tumor growth without systemic toxicities. A recombinant adeno-associated virus (rAAV) was used to deliver ß-galactosidase (LacZ) to the treatment group and green fluorescent protein to the control group. After 1 week, both groups received adenocarcinoma cells in the same location as the previous rAAV injection. The geldanamycin prodrug was administered 1 h later via intraperitoneal injection. Tumor growth was significantly suppressed in animals whose muscles were gene modified to express ß-galactosidase compared with the control. Serum assay to access hepatotoxicity resulted in no significant differences between the animals treated with the inactive or activated form of geldanamycin, indicating minimal damage to non-target organs. Using gene-directed enzyme prodrug therapy, in combination with novel recombinant AAV vectors, we have developed a method for localized activation of chemotherapeutic agents that limits the toxicities seen with traditional systemic administration of these potent drugs.

Increased H-FABP concentrations in nonalcoholic fatty liver disease. Possible marker for subclinical myocardial damage and subclinical atherosclerosis.

AIM: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder which is reported as the hepatic manifestation of metabolic syndrome with an increased risk of cardiovascular events. Patients with NAFLD are also at risk of future cardiac events independently of metabolic syndrome. The aim of this study was to examine serum concentrations of heart type fatty acid binding protein (H-FABP) in NAFLD and to investigate its correlations with metabolic parameters and subclinical atherosclerosis. PATIENTS AND METHODS: A total of 34 patients with NAFLD and 35 healthy subjects were enrolled in the study. NAFLD patients had elevated liver enzymes and steatosis graded on ultrasonography. Healthy subjects had normal liver enzymes and no steatosis on ultrasonography. H-FABP levels were measured using an enzyme linked immunosorbent assay (ELISA) method and correlations with metabolic parameters and subclinical atherosclerosis were examined. Subclinical atherosclerosis was determined with carotid artery intima-media thickness (CIMT) which was measured by high resolution B mode ultrasonography. RESULTS: H-FABP levels were elevated in patients with NAFLD (16.3 ± 4.0 ng/ml) when compared with healthy controls (13.8 ± 2.1 ng/ml; p < 0.001). NAFLD patients had significantly higher CIMT than the controls had (0.64 ± 0.17 mm vs. 0.43 ± 0.14 mm, p = 0.009). The H-FABP concentrations were significantly positively correlated with body mass index (r = 0.255, p = 0.042), fasting blood glucose level (r = 0.300, p = 0.013), CIMT (r = 0.335, p = 0.043), and homeostasis model assessment-estimated insulin resistance (HOMA-IR; r = 0.156, p = 0.306). In multiple linear regression analysis, H-FABP levels were only independently associated with CIMT (p = 0.04) CONCLUSION: Serum H-FABP concentrations increase in patients with NAFLD. Our results may not only suggest that H-FABP is a marker of subclinical myocardial damage in patients with NAFLD but also of subclinical atherosclerosis, independent of metabolic syndrome and cardiac risk factors.

Acute therapy with intravenous omeprazole on caustic esophageal injury: a prospective case series.

The ingestion of caustic substances may result in significant esophageal injury. There is no standard treatment protocol for esophageal injury and most patients are treated with a proton pump inhibitor or H2 antagonist. However, there is no clinical study evaluating the efficacy of omeprazole for caustic esophageal injury. A prospective study of 13 adult patients (>18 years of age) who were admitted to our hospital for caustic ingestion between May 2010 and June 2010 was conducted. Mucosal damage was graded using a modified endoscopic classification described by Zargar et al. Patients were treated with a proton pump inhibitor and maintained without oral intake until their condition was considered stable. Patients received omeprazole 80 mg in bolus IV, followed by continuous infusion of 8 mg/hour for 72 hours. A control endoscopy was performed 72 hours after admission. There was significant difference regarding endoscopic healing between the before and after omeprazole infusion (P = 0.004). There was no hospital mortality at the follow-up. Omeprazole may effectively be used in the acute phase treatment of caustic esophagus injuries.

Beneficial effects of Ankaferd Blood Stopper on caustic esophageal injuries: an experimental model.

Ankaferd Blood Stopper (ABS) is an herbal extract that enhances mucosal healing. The aim of this study was to investigate the efficacy of ABS on the healing of the esophagus and prevention of stricture development after esophageal caustic injuries in rats. The study included 50 rats. Rats were divided into five groups: group 1 (no injury, sham surgery), group 2 (injury + no ABS + study after 2 weeks of injury), group 3 (injury + ABS + study after 2 weeks of injury), group 4 (injury + no ABS + study after 4 weeks of injury), and group 5 (injury + ABS + study after 4 weeks of injury). Standard esophageal burn injury was created by applying 50% NaOH solution to distal esophagus of about 1.5 cm. To rats in the sham group, isotonic solution was given instead of NaOH. ABS (2 mL/day) was given via oral route to group 3 and 5 rats. Fourteen days (group 2 and 3) and 28 days (group 4 and 5) later, all the live rats were killed. The distal esophageal segments of all rats were removed and divided into two equal parts for biochemical and histopathological examination. Mortality rate, weight changes, inflammation, stenosis index (SI), and biochemical measurements were evaluated. The SI was found as 0.31 ± 0.03 in group 1, 0.533 ± 0.240 in group 2, 0.568 ± 0.371 in group 3, 0.523 ± 0.164 in group 4, and 0.28 ± 0.03 in group 5. The SI and inflammation in ABS-treatment group 5 was significantly lower than that in non-treatment group 4 (P= 0.005). There were no significant differences between inflammation and SI among other groups. The mortality rate was 14.2% in group 1, 37.5% in untreated group 2, 14.2% in ABS-treated group 3, 80% in untreated group 4, and 33.3% in ABS-treated group 5. The mortality rate in group 4 was significantly higher than other groups (P= 0.025). Decrease rates in mean body weights of the groups were as follows: group 1, 1%; group 2, 15%; group 3, 14%; group 4, 46%; and group 5, 15%. Biochemical tests other than albumin and creatinine were comparable among the groups. Treatment with ABS prevents inflammation, scar formation, weight loss, and mortality in esophageal caustic injuries. Additional studies to evaluate the clinical benefits of ABS in esophageal caustic injury are recommended.

Takayasu arteritis and ulcerative colitis; coexistence or misdiagnosis?

Takayasu arteritis is a chronic inflammatory disease that primarily affects large arteries such as the aorta and its proximal branches. The association between Takayasu arteritis and ulcerative colitis is an extremely rare condition. Ulcerative colitis is an inflammatory bowel disease, clinical presentation is not specific and may mimic Crohn's disease, radiation colitis, ischemic colitis, a variety of infectious processes, and colitis related to medications. Herein we report a case of Takayasu arteritis who had been misdiagnosed and treated as ulcera-

Multiple intestinal perforation in a patient with Wegener's granulomatosis: a case report and review of the literature.

Wegener's granulomatosis is a necrotizing vasculitis of unknown etiology characterized mainly by inflammation of the small- and medium-sized arteries and veins that affect any viscera. It may rarely involve the gastrointestinal tract. Only a few cases of multiple focus ileal perforation due to ulcers associated with Wegener's granulomatosis have been reported. Herein we report a case of a 32-year-old man with extensive intestinal small bowel ischaemic perforation due to Wegener's granulomatosis.

Memory and prefrontal functions in earthquake survivors: differences between current and past post-traumatic stress disorder patients.

OBJECTIVE: Many studies reported deficits in cognitive functions in post-traumatic stress disorder (PTSD). Most were, however, conducted on man-made trauma survivors. The high comorbidity of alcohol use and depression with PTSD in these studies further complicated the interpretation of their results. We compared prefrontal lobe functions and memory in three earthquake survivor groups: current PTSD, past PTSD and no PTSD. We hypothesized that prefrontal performances of the current and past PTSD groups would be worse than that of control group. METHOD: Survivors of the 1999 earthquakes in Turkey were evaluated for current and lifetime PTSD. Memory and prefrontal functions were assessed by a neuropsychological test battery. RESULTS: Current PTSD patients performed worse on attention, verbal memory, verbal fluency, and psychomotor speed. Past PTSD group was similar to the controls on most cognitive measures, except for their vulnerability to proactive interference and low performance in verbal fluency for animal names. CONCLUSION: Our findings indicate that the prefrontal organization and monitorization of verbally processed information are defective in earthquake-related PTSD patients, more so in the current PTSD group.

Spotting the signs: a case of late diagnosed painful calciphylaxis.

Although the number of cases of calciphylaxis is increasing, it is often not diagnosed until a late stage, increasing the risk of mortality. A characteristic is purple, mottled and painful lesions, which have a tendency to become necrotic.