Tissue Hypoxia and Associated Innate Immune Factors in Experimental Autoimmune Optic Neuritis.

Visual loss in acute optic neuritis is typically attributed to axonal conduction block due to inflammatory demyelination, but the mechanisms remain unclear. Recent research has highlighted tissue hypoxia as an important cause of neurological deficits and tissue damage in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) and, here, we examine whether the optic nerves are hypoxic in experimental optic neuritis induced in Dark Agouti rats. At both the first and second peaks of disease expression, inflamed optic nerves labelled significantly for tissue hypoxia (namely, positive for hypoxia inducible factor-1α (HIF1α) and intravenously administered pimonidazole). Acutely inflamed nerves were also labelled significantly for innate markers of oxidative and nitrative stress and damage, including superoxide, nitric oxide and 3-nitrotyrosine. The density and diameter of capillaries were also increased. We conclude that in acute optic neuritis, the optic nerves are hypoxic and come under oxidative and nitrative stress and damage. Tissue hypoxia can cause mitochondrial failure and thus explains visual loss due to axonal conduction block. Tissue hypoxia can also induce a damaging oxidative and nitrative environment. The findings indicate that treatment to prevent tissue hypoxia in acute optic neuritis may help to restore vision and protect from damaging reactive oxygen and nitrogen species.

Malignant transformation of oral leukoplakia is associated with macrophage polarization.

BACKGROUND: Most oral squamous cell carcinomas (OSCC) occur on the basis of oral leukoplakias (OLP). The histologic degree of dysplasia is insufficient for the prediction of OLP malignant transformation. Immunologic parameters are gaining importance for prognostic assessment and therapy of cancer. M2 polarized macrophages were shown to be associated with OSCC progression and inferior prognosis. The current study aims to answer the question if OLP with malignant transformation into OSCC within 5 years differ from OLP without transformation regarding macrophage infiltration and polarization. METHODS: 201 specimens (50 transforming OLP, 53 non-transforming OLP, 49 corresponding OSCC and 49 healthy oral mucosa controls) were processed for immunohistochemistry. Samples were stained for CD68, CD163 and CD11c expression, completely digitalized and computer-assisted cell counting was performed. Epithelial and subepithelial compartments were differentially assessed. Groups were statistically compared using the Mann-Whitney U-test. A cut-off point for the discrimination of transforming and non-transforming OLP was determined and the association between macrophage infiltration and malignant transformation was calculated using the Chi-square test (χ2 test). RESULTS: Macrophage infiltration and M2 polarization in OLP with malignant transformation within 5 years was significantly increased compared to OLP without malignant transformation (p < 0.05). OSCC samples showed the highest macrophage infiltration and strongest M2 polarization (p < 0.05). Additionally, transforming OLP revealed a significant shift of macrophage infiltration towards the epithelial compartment (p < 0.05). χ2 test revealed a significant association of increased macrophage infiltration with malignant transformation (p < 0.05). CONCLUSION: Immunological changes precede malignant transformation of OLP. Increased macrophage infiltration and M2 polarization was associated with the development of oral cancer in OLP. Macrophage infiltration could serve as predictive marker for malignant transformation.

Evaluation of the relationship between Behcet's disease and cardiovascular disorders through metabolic function and copeptin.

INTRODUCTION: Behcet's disease (BD) is a chronic inflammatory and multisystem vasculitis. Cardiac involvement is one of the major complications of BD. Cardiac involvement is sporadic in terms of its specific relationship to mortality. How to identify and follow up on cardiac-related complications in BD patients has yet to be determined. AIM: The aim of our study is to assess cardiovascular diseases in BD patients by measuring metabolic function and copeptin levels and comparing these to a healthy control group. Knowing the specific metabolic functions that are negatively affected by BD will help doctors determine which functions need to be more closely monitored in BD patients. Our study is the first study in the available literature that evaluates copeptin in BD patients. MATERIAL AND METHODS: A control group of 58 healthy volunteers, including 32 females and 26 males (average age: 39.8 ±10.3 years, range: 18-50 years), was formed to compare with 84 BD patients (average age: 40.5 ±11 years, range: 21-63 years), including 39 females and 45 males. Diastolic and systolic blood pressure, height, weight, body mass index (BMI), and waistline were measured for both groups. All study patients were also given hemograms, and fasting blood sugar (FBS), uric acid, lipid profile, insulin, C-reactive protein (CRP), and copeptin levels were measured. An ELISA Kit was used to measure copeptin. RESULTS: FBS, CRP, and insulin levels were significantly higher in the patient group (p < 0.001, p = 0.004, and p = 0.038, respectively). Patients who had had the disease for more than 10 years had higher BMIs, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels (p = 0.034, p = 0.004, p = 0.016, and p = 0.045, respectively). Additionally, CRP levels were found to be higher in long-term patients and patients with active lesions. Diastolic blood pressure and waist circumference were also higher in the BD group. Patients who had active lesions had significantly higher diastolic blood pressure (p = 0.047). There were no statistically significant differences in copeptin levels between BD and control groups. CONCLUSIONS: Cardiovascular involvement rarely contributes to the high mortality rate of BD patients. There were meaningful elevations in metabolic markers identified when BD and cardiovascular disease risk was assessed with metabolic parameters. The cardiac disease risk should be closely followed using metabolic functions, particularly in long-term BD patients with vascular involvement.

Vascular twin nevi.

Vascular twin nevi (VTN) are characterized by the simultaneous dermatological manifestatiton of a telangiectatic naevus close to a nevus anemicus. Nevus anemicus (NA) is a vascular anomaly characterized by localized pale patches with normal melanine and melanocyte level. According to twin spotting phenomenon crossing-over in heterozygous somatic-cells during mitosis results in two different offspring homozygous cells. Consequent to this mechanism, two different vascular anomalies may occur at the same region. We present a patient with VTN and NA combination which we think serves as an example for a rare twin spotting phenomenon in the literature.

Acetone production with metabolically engineered strains of Acetobacterium woodii.

Expected depletion of oil and fossil resources urges the development of new alternative routes for the production of bulk chemicals and fuels beyond petroleum resources. In this study, the clostridial acetone pathway was used for the formation of acetone in the acetogenic bacterium Acetobacterium woodii. The acetone production operon (APO) containing the genes thlA (encoding thiolase A), ctfA/ctfB (encoding CoA transferase), and adc (encoding acetoacetate decarboxylase) from Clostridium acetobutylicum were cloned under the control of the thlA promoter into four vectors having different replicons for Gram-positives (pIP404, pBP1, pCB102, and pCD6). Stable replication was observed for all constructs. A. woodii [pJIR_actthlA] achieved the maximal acetone concentration under autotrophic conditions (15.2±3.4mM). Promoter sequences of the genes ackA from A. woodii and pta-ack from C. ljungdahlii were determined by primer extension (PEX) and cloned upstream of the APO. The highest acetone production in recombinant A. woodii cells was achieved using the promoters PthlA and Ppta-ack. Batch fermentations using A. woodii [pMTL84151_actthlA] in a bioreactor revealed that acetate concentration had an effect on the acetone production, due to the high Km value of the CoA transferase. In order to establish consistent acetate concentration within the bioreactor and to increase biomass, a continuous fermentation process for A. woodii was developed. Thus, acetone productivity of the strain A. woodii [pMTL84151_actthlA] was increased from 1.2mgL(-1)h(-1) in bottle fermentation to 26.4mgL(-1)h(-1) in continuous gas fermentation.

Detection of galanin receptors in the spinal cord in experimental autoimmune encephalomyelitis.

AIMS: The neuropeptide galanin is a widely distributed neurotransmitter/neuromodulator that regulates a variety of physiological processes and also participates in the regulation of stress responses. The aims of the present study were to investigate the expression of galanin receptors (GalR1, GalR2, GalR3) in the spinal cords in a murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) using qPCR analysis and to determine GalR1 cellular localization (oligodendrocytes, microglia, astrocytes, ependymal cells, and endothelial cells in the capillaries) by immunohistochemistry. METHODS: Twelve samples from the EAE group and 14 samples from the control group were analyzed. Spinal cords samples were obtained at the peak of the EAE disease. RESULTS: The GalR1 mRNA level was significantly decreased in the EAE mice compared with the controls (P=0.016), whereas the mRNA levels of GalR2 and GalR3 were not significantly different for the EAE and the control mice. No significant correlations were found between the severity of the EAE disease and the mRNA levels of GalR1, GalR2 and GalR3. Immunochemical detection of the GalR1 revealed its expression in the ependymal and endothelial cells. Additionally, a weak GalR1 immunoreactivity was occasionally detected in the oligodendrocytes. CONCLUSION: This study provides additional evidence of galanin involvement in EAE pathophysiology, but this has to be further investigated.

Edaravone attenuates disease severity of experimental auto-immune encephalomyelitis and increases gene expression of Nrf2 and HO-1.

The aim of this study was to evaluate therapeutic potential of edaravone in the murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) and to expand the knowledge of its mechanism of action. Edaravone (6 mg/kg/day) was administered intraperitoneally from the onset of clinical symptoms until the end of the experiment (28 days). Disease progression was assessed daily using severity scores. At the peak of the disease, histological analyses, markers of oxidative stress (OS) and parameters of mitochondrial function in the brains and spinal cords (SC) of mice were determined. Gene expression of inducible nitric oxide synthase (iNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha was determined at the end of the experiment. Edaravone treatment ameliorated EAE severity and attenuated inflammation in the SC of the EAE mice, as verified by histological analysis. Moreover, edaravone treatment decreased OS, increased the gene expression of the Nrf2 and HO-1, increased the activity of the mitochondrial complex II/III, reduced the activity of the mitochondrial complex IV and preserved ATP production in the SC of the EAE mice. In conclusion, findings in this study provide additional evidence of edaravone potential for the treatment of multiple sclerosis and expand our knowledge of the mechanism of action of edaravone in the EAE model.

Correlation between the Diagnostic Yield from the Bronchoalveolar Lavage Fluid Analysis and Clinicoradiological Findings in Sarcoidosis.

OBJECTIVES: The diagnosis of sarcoidosis is frequently challenging, requiring a search for less invasive, more reliable diagnostic methods. The bronchoalveolar lavage fluid (BALF) analysis has been used in the differential diagnosis of sarcoidosis for many years with a wide sensitivity and specificity rates. The objective of the study is to investigate whether diagnostic performance of the BALF analysis is altered by clinicoradiological findings of patients with sarcoidosis. MATERIALS AND METHODS: The present study is a retrospective, single-center, observational study, designed in a sarcoidosis outpatient clinic in a training hospital. Patients who had undergone the bronchoalveolar lavage BAL procedure at diagnosis were included in the study. Demographics, clinical and detailed chest X-ray, and high-resolution computed tomography (HRCT) findings at diagnosis were recorded. According to the diagnostic performance, the BALF results were grouped as "diagnostic" and "non-diagnostic," and recorded parameters were compared between the groups. RESULTS: Considering the BALF analysis of all the 257 patients, the mean lymphocyte ratio was 41±17.5 (5-80), and the mean CD4/CD8 was 5.5±4.7 (0.1-24.7). The BALF analysis was diagnostic in 56% (n=145) of patients. Diagnostic performance of the procedure did not correlate with any of the demographic data, smoking status, spirometric findings, chest X-ray staging, HRCT findings, and tomography scoring. Extrapulmonary involvement was significantly more frequent in the diagnostic group (66% vs. 34%, p=0.006). CONCLUSION: BALF results signal sarcoidosis in more than half of the patients. The diagnostic role of BALF is greater in patients with extrapulmonary involvement.

Carotid intima media thickness in obese children: is there an association with hyperlipidemia?

BACKGROUND: We aimed to evaluate the association between hyperlipidemia and carotid intima media thickness in obese children, compared to non-obese ones. METHODS: Two hundred (110 girls, 90 boys) children aged between 6 and 15 years participated in this study. The obese group included 53 girls, 47 boys whose body mass indices (BMI) above 95th percentile, the control group included 57 girls, 43 boys who had normal weight. Fasting total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels were measured. Carotid intima media thickness (cIMT) was performed with neck ultrasound. RESULTS: The median thickness of right, left and mean carotis intima media were statistically higher in the study group, compared to the control group. The mean cholesterol, triglyceride, HDL-C, LDL-C levels of the study group were statistically higher, compared to the control group. There was no relationship between BMI and left carotis intima media thickness, but there was statistically significant relationship between BMI and right, mean cIMTs in the study group. There was no correlation between serum lipid levels and cIMTs in the study group. The mean atherogenic index of the study group was statistically higher, compared to the control group. There was no statistical correlation between atherogenic index and cIMTs in both of the groups. CONCLUSIONS: We observed that obese children had higher carotis intima media thicknesses. Carotis intima media thickness related to obesity can play an important role in future pre-atherosclerotic changes. Large population based studies are required to confirm this associaton.

Nurses' knowledge and educational needs regarding genetics.

BACKGROUND: Nurses now require a basic knowledge of genetics to provide patient care in a range of settings. OBJECTIVES: To determine Turkish registered nurses' current knowledge and educational needs in relation to genetics. DESIGN: A descriptive, cross-sectional study. SETTINGS: Turkish registered nurses working in a university hospital in Turkey were recruited. PARTICIPANTS: All registered nurses were invited to participate and 175 completed the study. METHODS: The survey instrument, basic knowledge of health genetics, confidence in knowledge and the nurses' need for genetics education were used to collect data. RESULTS: The majority (81.1%, n=142) of participants indicated that genetics was not taught during their degree program, although 53.1% to 96% of respondents felt confident in defining different genetic concepts. The average genetics knowledge score was 6.89±1.99 of a possible 11 (range 0-11). The majority (70.3%) expressed a strong wish to attend a continuing nursing education program in genetics. CONCLUSIONS: The study shows that although Turkish nurses are not sufficiently knowledgeable to apply genetics in practice, they are willing to have more education to support their care of patients. Nurses need to have more education related to genetics in accordance with advances in human genetics to optimize health care.

Relationship between depression and loneliness in elderly and examination of influential factors.

This study was planned and conducted for the purpose of examining the relationship between depression and loneliness in elderly people and the influencing factors. The study was a descriptive and correlational study and its population consisted of 17,080 older individuals aged sixty and over who were registered at six Family Healthcare Centers (FHCs) located in the provisional center of Malatya. The sample of the study comprised of 913 elderly people who were chosen from the elderly people registered at the FHCs first by cluster sampling and then by simple random sampling from the clusters in proportion to the population. The data was collected between April and June 2011 using a questionnaire developed by the investigators in line with the literature, the Geriatric Depression Scale (GDS) and the UCLA Loneliness Scale (ULS). They had a mean score of 13.83 ± 7.4 from the GDS and 40.50 ± 12.1 from the ULS. A positive correlation was found between Geriatric Depression and loneliness (r=0.608, p<0.001). It was observed that there was a significant correlation between loneliness and depression in the elderly people living in a community, presence of social security and higher income, on the other hand, led to lower mean scores. In view of these results, it can be advised that a minimum income should be secured for elderly people whether they have social security or not, their families and the society should be trained not to leave elderly people alone.