The relationship between nutrition screenings and nutritional status determined by malnutrition in hemodialysis patients

Objective: It is aimed to evaluate the relationship of food consumptions, biochemical blood parameters, and some anthropometrics with the screening tests using in the nutritional status of hemodialysis patients with end stage renal failure. Materials and Methods: The survey were conducted with 110 hemodialysis patients who hospitalized at the Nephrology Clinic in Akdeniz University Hospital. The routine biochemical blood parameters of the patients were analyzed and their anthropometric measurements were performed. The food consumptions were recorded by the dietician and Nutritional Risk Screening 2002 (NRS 2002), Malnutrition Universal Screening Tool (MUST) and Subjective Global Assessment (SGA)has screening tests using were performed. Results: The average age of the patients participating in the study was 55 ± 19 years. In MUST, 42.7% of the patients were at high risk, 18.2% of them at moderate risk by malnutrition. Statistically significant relationship was also negatively determined between body weight, dry weight, BMI, the waist circumference, and MUST and SGA (p<0.05). A negatively significant relationship was statistically found among albumin, creatinine, hemoglobin and calcium readouts by NRS2002, among albumin, BUN, calcium and phosphorus readouts by MUST, among albumin, hemoglobin and calcium readouts by SGA (p<0.05). Conclusion: It was observed that the dialysis patients could not get the advised nutritional quantities, thence malnutrition progressed. It is concluded that anthropometric measurements are more concordant with MUST and the biochemical symptoms with NRS2002, and therefore both must be taken into consideration in the assessment of nutritional status correctly of the end-stage renal patients undergoing hemodialysis

Evaluation of the ICT Tuberculosis test for the routine diagnosis of tuberculosis

BACKGROUND: Rapid and accurate diagnosis of tuberculosis (TB) is crucial to facilitate early treatment of infectious cases and thus to reduce its spread. To improve the diagnosis of TB, more rapid diagnostic techniques such as antibody detection methods including enzyme-linked immunosorbent assay (ELISA)-based serological tests and immunochromatographic methods were developed. This study was designed to evaluate the validity of an immunochromatographic assay, ICT Tuberculosis test for the serologic diagnosis of TB in Antalya, Turkey. METHODS: Sera from 72 patients with active pulmonary (53 smear-positive and 19 smear-negative cases) and eight extrapulmonary (6 smear-positive and 2 smear-negative cases) TB, and 54 controls from different outpatient clinics with similar demographic characteristics as patients were tested by ICT Tuberculosis test. RESULTS: The sensitivity, specificity, and negative predictive value of the ICT Tuberculosis test for pulmonary TB were 33.3%, 100%, and 52.9%, respectively. Smear-positive pulmonary TB patients showed a higher positivity rate for antibodies than smear-negative patients, but the difference was not statistically significant. Of the eight patients with extrapulmonary TB, antibody was detected in four patients. CONCLUSION: Our results suggest that ICT Tuberculosis test can be used to aid TB diagnosis in smear-positive patients until the culture results are available

Cytosolic Guanine Nucledotide Binding Deficient Form of Transglutaminase 2 (R580a) Potentiates Cell Death in Oxygen Glucose Deprivation

Transglutaminase 2 (TG2) is a hypoxia-responsive protein that is a calcium-activated transamidating enzyme, a GTPase and a scaffolding/linker protein. Upon activation TG2 undergoes a large conformational change, which likely affects not only its enzymatic activities but its non-catalytic functions as well. The focus of this study was on the role of transamidating activity, conformation and localization of TG2 in ischemic cell death. Cells expressing a GTP binding deficient form of TG2 (TG2-R580A) with high basal transamidation activity and a more extended conformation showed significantly increased cell death in response to oxygen-glucose deprivation; however, targeting TG2-R580A to the nucleus abrogated its detrimental role in oxygen-glucose deprivation. Treatment of cells expressing wild type TG2, TG2-C277S (a transamidating inactive mutant) and TG2-R580A with Cp4d, a reversible TG2 inhibitor, did not affect cell death in response to oxygen-glucose deprivation. These findings indicate that the pro-cell death effects of TG2 are dependent on its localization to the cytosol and independent of its transamidation activity. Further, the conformational state of TG2 is likely an important determinant in cell survival and the prominent function of TG2 in ischemic cell death is as a scaffold to modulate cellular processes

The Role of Transglutaminase 2 in Ischemic Cell Death

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Pharmacology and Physiology, 2011.Transglutaminase 2 (TG2) is an enzyme that catalyzes Ca2+ dependent transamidation reactions. TG2 plays a role in many biological functions such as growth, differentiation and inflammation. Intriguingly, TG2 can contribute to both cell survival and cell death. Increased transamidation activity of cytosolic TG2 is proposed to be detrimental, while nuclear localization of TG2 is critical for its prosurvival effects. However, it is still not clear what determines the pro-death and prosurvival roles of TG2 in the cells. Our goal in this study was to examine the role of TG2 in ischemic cell death. In the first part, we used a constitutive transamidation active (R580A) point mutant of TG2 to analyze the role of transamidation activity in ischemic cell death. R580A significantly induced cell death in response to OGD, however this effect was independent of its high transamidation activity. The detrimental affect of R580A was fully abrogated when the protein was translocated to the nucleus. These experiments also indicated that the open conformation of R580A might induce cell death in response to ischemic stress. Finally, our results show that the detrimental role of TG2 is mainly cytosolic, dependent on its conformational state and independent of its transamidation activity. In the second part of this study, we investigated the role of endogenous TG2 in ischemic cell death. Previously, we showed that neuronal selective TG2 overexpressor mice were protected against ischemic stroke. In this study, we used complete embryonic TG2 knock out (TG2-/-) mice. Interestingly, TG2-/- mice were also protected against ischemic stroke. Neurons isolated from TG2-/- mice showed diminished cell viability, however TG2-/- astrocytes were resistant to OGD-induced cell death. Further, wild type and TG2-/- neurons were both protected against OGDinduced cell death when they were co-cultured with TG2-/- astrocytes. These data suggest that the increased viability of TG2-/- astrocytes may contribute to reduction in stroke volumes in TG2-/- mice. TG2-/- astrocytes might also promote the survival of neurons after ischemic insult through neuron-astrocyte cross talk. In conclusion, our study shows that TG2 can be both detrimental and prosurvival in ischemic cell death depending on its conformational state, cellular localization and the cell type

Transglutaminase 2 facilitates or ameliorates HIF signaling and ischemic cell death depending on its conformation and localization

AbstractTransglutaminase 2 (TG2) is a widely expressed and multifunctional protein that modulates cell death/survival processes. We have previously shown that TG2 binds to hypoxia inducible factor 1β (HIF1β) and decreases the upregulation of HIF responsive genes; however, the relationship between these observations was not investigated. In this study, we investigated whether endogenous TG2 is sufficient to suppress HIF activity and whether the interaction between TG2 and HIF1β is required for this suppression. shRNA-mediated silencing of TG2 significantly enhanced HIF activation in response to hypoxia. In addition, nuclear localization of TG2 is required for its suppressive effect on HIF activity, with TG2 being recruited to HIF responsive promoters in hypoxic conditions. These observations suggest that TG2 directly regulates hypoxic transcriptional machinery; however, its interaction with HIF1β was not required for this regulation. We also examined whether TG2's effect on cell death/survival processes in ischemia is due to its effects on HIF signaling. Our results indicate that TG2 mediated HIF suppression can be separated from TG2's effect on cell survival in hypoxic/hypoglycemic conditions. Lastly, here we show that nuclear TG2 in the closed conformation and non-nuclear TG2 in the open conformation have opposing effects on hypoxic/hypoglycemic cell death, which could explain previous controversial results. Overall, our results further clarify the role of TG2 in mediating the cellular response to ischemia and suggest that manipulating the conformation of TG2 might be of pharmacological interest as a therapeutic strategy for the treatment of ischemia-related pathologies

Ferulic Acid Treats Gastric Ulcer via Suppressing Oxidative Stress and Inflammation

(1) Background: The aim of the present study was to evaluate the gastroprotective potential of ferulic acid (FA) on indomethacin-induced gastric ulcers in rats with macroscopic and microscopic examinations along with biochemical assays. (2) Methods: After 24 h starvation, the ulcer was induced in male Sprague-Dawley rats by subcutaneous indomethacin (25 mg/kg) injection. Fifteen minutes after ulcer induction, rats were treated with either tween 80 or FA. FA was given by oral gavage at 100 mg/kg, 250 mg/kg, and 500 mg/kg. In the fourth hour, rats were euthanized and collected gastric samples were evaluated macroscopically and microscopically. Antioxidant parameters including malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and inflammatory parameters comprising of myeloperoxidase (MPO), Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-1β, IL-6 and Nuclear Factor Kappa-B (NF-κB) p65 levels were also determined. (3) Results: Indomethacin injection significantly increased the macroscopic and microscopic scores. In addition, it increased the gastric MDA, MPO, TNF-α, IL-1β, IL-6, and NF-κB p65 levels but reduced SOD and GSH content. Treatment with FA significantly improved the gastric injury macroscopically and microscopically. Moreover, FA displayed a marked decrease in the gastric levels of MDA, MPO, TNF-α, IL-1β, IL-6, and NF-κB p65 and a significant increase in SOD and GSH compared to the INDO group. Ultimately, 250 mg/kg FA was determined as the most effective dose. (4) Conclusion: Our results revealed that FA has a gastroprotective effect against indomethacin-induced gastric ulcers in rats due to its antioxidant and anti-inflammatory properties. As a result, FA may be a potential treatment choice for gastric ulcers

Ferulic Acid Treats Gastric Ulcer via Suppressing Oxidative Stress and Inflammation

(1) Background: The aim of the present study was to evaluate the gastroprotective potential of ferulic acid (FA) on indomethacin-induced gastric ulcers in rats with macroscopic and microscopic examinations along with biochemical assays. (2) Methods: After 24 h starvation, the ulcer was induced in male Sprague-Dawley rats by subcutaneous indomethacin (25 mg/kg) injection. Fifteen minutes after ulcer induction, rats were treated with either tween 80 or FA. FA was given by oral gavage at 100 mg/kg, 250 mg/kg, and 500 mg/kg. In the fourth hour, rats were euthanized and collected gastric samples were evaluated macroscopically and microscopically. Antioxidant parameters including malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and inflammatory parameters comprising of myeloperoxidase (MPO), Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-1β, IL-6 and Nuclear Factor Kappa-B (NF-κB) p65 levels were also determined. (3) Results: Indomethacin injection significantly increased the macroscopic and microscopic scores. In addition, it increased the gastric MDA, MPO, TNF-α, IL-1β, IL-6, and NF-κB p65 levels but reduced SOD and GSH content. Treatment with FA significantly improved the gastric injury macroscopically and microscopically. Moreover, FA displayed a marked decrease in the gastric levels of MDA, MPO, TNF-α, IL-1β, IL-6, and NF-κB p65 and a significant increase in SOD and GSH compared to the INDO group. Ultimately, 250 mg/kg FA was determined as the most effective dose. (4) Conclusion: Our results revealed that FA has a gastroprotective effect against indomethacin-induced gastric ulcers in rats due to its antioxidant and anti-inflammatory properties. As a result, FA may be a potential treatment choice for gastric ulcers

OGD-induced cell death with NLS tagged R580A.

<p><b>A</b>, Immunocytochemistry of naïve striatal neurons that were infected with a control or wild type TG2 lentiviral construct. Panels a, b, c, and d represent the naïve cell transduced with control lentivirus. Panels e, f, g, and h represent naïve cells transduced with wild type TG2. Immunocytochemistry was performed with a TG2 antibody that was recognized by a FITC-conjugated mouse secondary antibody. From left to right: phase, TG2 staining labeled by FITC, Hoechst nuclear staining, merge of FITC and Hoechst staining. <b>B</b>, Immunoblots of cell lysates from naïve cells transduced with control, TG2, TG2-R580A (R580A) and NLS tagged R580A (NLS-R580A) lentiviruses. Actin blot is shown for loading controls. <b>C</b>, Fold LDH release in lentivirus infected striatal cells after 36 hr of OGD at 0.1% O₂. Both TG2 and TG2-R580A (R580A) expressing cells showed significant increases in fold LDH release after OGD treatment, while NLS-R580A showed similar fold LDH release amount as the control. (N = 8) Results are shown as mean +/− SEM, ***p<0.001.</p

OGD-induced cell death with NC9 treatment.

<p><b>A</b>, Fold <i>in situ</i> transamidation activity with ionomycin treatment in the absence (−) or presence (+) of 10 µM NC9 (Irreversible TG2 inhibitor) in comparison to basal <i>in situ</i> transamidation activity of the corresponding cell line. TG2 cells (12 fold) and TG2-R580A cells (19 fold) showed potentiation of <i>in situ</i> transamidation activity with 5µM ionomycin treatment which was inhibited 100% by NC9 treatment (N = 3). <b>B</b>, Fold LDH release after 36 h of OGD treatment at 0.1% O₂ in the absence (−) or presence (+) of 10 µM NC9 (TG2 inhibitor) in comparison to percent LDH release amount of corresponding cell line at normoxia. TG2 and TG2-C277S (C277S) cells showed significant increases in fold LDH release with NC9 treatment. (N = 4) Results are shown as mean +/− SE, *p<0.05, **p<0.01, ***p<0.001.</p