Inflammatory response and matrix metalloproteinases in chronic kidney failure: Modulation by adropin and spexin

Chronic kidney disease is a major global public health problem. The peptide hormones adropin and spexin modulate many physiological functions such as energy balance and glucose, lipid and protein metabolism. However, it is unclear whether these peptides may exert effects on renal damage, tissue remodeling, and inflammatory conditions. In view of the limited information, we aimed to investigate the effect of adropin and spexin on matrix metalloproteinase and inflammatory response genes a rat model of adenine-induced chronic kidney failure. Chronic kidney failure was induced in rats by administering adenine hemisulfate. Renal function was determined in an autoanalyzer. Histopathological modifications were assessed by H&E staining. mRNA expression levels of ALOX 15, COX 1, COX 2, IL-1β, IL-10, IL-17A, IL-18 IL-21, IL-33, KIM-1, MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, NGAL, TGFβ1, TIMP-1, and TNFα in kidney tissue were measured by qPCR. Our results showed an increase of 24-h urine volume, serum creatinine, BUN, and urine protein levels in group with adenine-induced CKF. Adropin and spexin treatments decreased urine protein and 24-h urine volume. Renal damage, TIMP-1, IL-33, and MMP-2 increased after CKF induction, while COX 1, MMP-9, and MMP-13 levels were significantly reduced. Furthermore, KIM-1, TIMP-1, IL-33, and MMP-2 were downregulated by spexin treatment. Renal damage, NGAL, TIMP-1 IL-17A, IL-33, MMP-2, and MMP-3 decreased after adropin treatment, while MMP-13 levels were upregulated. Treatment with adropin+spexin decreased KIM-1, NGAL, TIMP-1, IL-1β, IL-17A, IL-18, IL-33, ALOX 15, COX 1, COX 2, TGFβ1, TNFα, MMP-2, MMP-3, and MMP-7, but increased MMP-13 levels. Our findings revealed that inflammatory response and MMP genes were modulated by adropin and spexin. These peptides may have protective effects on inflammation and chronic kidney damage progression.     

Rab 5 is required for the cellular entry of dengue and West Nile viruses

The mechanisms of cellular entry of dengue and West Nile viruses are not well characterized. We show that both these viruses enter HeLa cells by clathrin-dependent endocytosis and require vacuolar acidic pH. Inhibition of the GTPase Rab 5 or 7, which regulates transport to early or late endosomes, respectively, demonstrated that Rab 5 was essential for survival of both dengue and West Nile virus. These data broaden our understanding of the pathways required for productive dengue and West Nile virus infection and may facilitate new strategies for combating disease.     

ASC/PYCARD and caspase-1 regulate the IL-18/IFN-gamma axis during Anaplasma phagocytophilum infection

Anaplasma phagocytophilum is an obligate intracellular pathogen that resides within neutrophils and can cause fever, pancytopenia, or death. IFN-gamma plays a critical role in the control of A. phagocytophilum; however, the mechanisms that regulate IFN-gamma production remain unclear. In this study, we demonstrate that apoptotic specklike protein with a caspase-activating recruiting domain (ASC)/PYCARD, a central adaptor molecule in the Nod-like receptor (NLR) pathway, regulates the IL-18/IFN-gamma axis during A. phagocytophilum infection through its effect on caspase-1. Caspase-1- and asc-null mice were more susceptible than control animals to A. phagocytophilum infection due to the absence of IL-18 secretion and reduced IFN-gamma levels in the peripheral blood. Moreover, caspase-1 and ASC deficiency reduced CD4+ T cell-mediated IFN-gamma after in vitro restimulation with A. phagocytophilum. The NLR family member IPAF/NLRC4, but not NALP3/NLRP3, was partially required for IFN-gamma production in response to A. phagocytophilum. Taken together, our data demonstrate that ASC and caspase-1 are critical for IFN-gamma-mediated control of A. phagocytophilum infection.     

Effects of Artichoke Extract Supplementation on Gonads of Cadmium-Treated Rats

The present study was designed to determine whether artichoke (Cynara scolymus) exerts a protective effect on gonads of cadmium-treated rats and if there is a relationship between artichoke supplementation and nitric oxide (NO) formation in cells. Forty Wistar albino male rats, weighing an average of 90 g each, were equally divided into four groups receiving 1 mg/100 g cadmium chloride by injection (group 1), the same dose CdCl₂ plus 3 mg/100 g artichoke extract (group 2), the same dose of artichoke extract (group 3), and male controls (group 4). Four additional groups, labeled 5–8, consisted of identically treated and control female rats. After 4 weeks of treatment, the animals were killed and their gonads were removed for histological examination. As expected, the seminiferous tubules and Leydig cells were damaged by cadmium. Ovarian tissue was not damaged to the same extent as testicular cells. Artichoke extract exerted a clear protective effect against Cd-induced testicular damage and lowered NO production to the same level of that in the control groups.     

Improvement of design of a surgical interface using an eye tracking device

Background

Surgical interfaces are used for helping surgeons in interpretation and quantification of the patient information, and for the presentation of an integrated workflow where all available data are combined to enable optimal treatments. Human factors research provides a systematic approach to design user interfaces with safety, accuracy, satisfaction and comfort. One of the human factors research called user-centered design approach is used to develop a surgical interface for kidney tumor cryoablation. An eye tracking device is used to obtain the best configuration of the developed surgical interface.

Methods

Surgical interface for kidney tumor cryoablation has been developed considering the four phases of user-centered design approach, which are analysis, design, implementation and deployment. Possible configurations of the surgical interface, which comprise various combinations of menu-based command controls, visual display of multi-modal medical images, 2D and 3D models of the surgical environment, graphical or tabulated information, visual alerts, etc., has been developed. Experiments of a simulated cryoablation of a tumor task have been performed with surgeons to evaluate the proposed surgical interface. Fixation durations and number of fixations at informative regions of the surgical interface have been analyzed, and these data are used to modify the surgical interface.

Results

Eye movement data has shown that participants concentrated their attention on informative regions more when the number of displayed Computer Tomography (CT) images has been reduced. Additionally, the time required to complete the kidney tumor cryoablation task by the participants had been decreased with the reduced number of CT images. Furthermore, the fixation durations obtained after the revision of the surgical interface are very close to what is observed in visual search and natural scene perception studies suggesting more efficient and comfortable interaction with the surgical interface. The National Aeronautics and Space Administration Task Load Index (NASA-TLX) and Short Post-Assessment Situational Awareness (SPASA) questionnaire results have shown that overall mental workload of surgeons related with surgical interface has been low as it has been aimed, and overall situational awareness scores of surgeons have been considerably high.

Conclusions

This preliminary study highlights the improvement of a developed surgical interface using eye tracking technology to obtain the best SI configuration. The results presented here reveal that visual surgical interface design prepared according to eye movement characteristics may lead to improved usability.

     

Enhanced biological phosphate removal by granular sludge in a sequencing batch reactor

A laboratory-scale sequencing batch reactor was started-up with flocculated biomass and operated primarily for enhanced biological phosphate removal. Ten weeks after the start-up, gradual formation of granular sludge was observed. The compact biomass structure allowed halving the settling time, the initial reactor volume, and doubling the influent COD concentration. Continued operation confirmed the possibility of maintaining a stable granular biomass with a sludge volume index less than 40 ml g^–1, while securing a removal efficiency of 95% for carbon, 99.6% for phosphate, and 71% for nitrogen. Microscopic observations revealed a morphological diversity.     

Crocus antalyensis subsp. striatus subsp. nov. (Iridaceae) from southwest Anatolia

A new subspecies Crocus antalyensis subsp. striatus subsp. nov. from western Turkey is described. It is characterized by rough papery, light brown corm tunics, leaves that exceed the flower at anthesis and are recurved, distinctly striped inner perianth segments and deeply branched pale yellow or white style. The karyotype of the new subspecies is presented.     

Effect of simultaneous nitrification and denitrification on nitrogen removal performance and filamentous microorganism diversity of a full-scale MBR plant

The nutrient removal performance of a membrane bioreactor (MBR) plant treating the wastewater of 10,000 PE was investigated with dynamic simulations. The average process performance with respect to chemical oxygen demand and total nitrogen were reported to be 97 and 81 %, respectively. The modeling study showed that low dissolved oxygen (DO) levels (0.2–0.3 mgO₂/L) due to limited aeration capacity within aeration tank that provided additional total nitrogen removal of 15–20 mgN/L. Simultaneous nitrification and denitrification process was found to be the reason of performance increase. However, low DO levels <0.3 mgO₂/L in the aeration tank triggered the proliferation of filamentous microorganisms within one month as a side effect. In this respect, the morphotypes of Type 0092 and Nocardia (Gordonia) amarae were found to be excessively abundant in the MBR system. Overflow of foam layer covering the tanks was frequently reported during bulking period. A hypochloride dosing of 4.5 gCL/kgMLSS/day was applied to get over filamentous bulking problem as a short term action.     

Functional aspects of evoked alpha and theta responses in humans and cats

A systems theoretical approach was used to compare possible functional roles of theta (4--7 Hz) and alpha (8--15 Hz) response components of brain evoked potentials. These response components were described earlier by Ba\c sar (1980). We recorded EEG and evoked potentials (EPs) from occipital scalp locations in 11 subjects. We used auditory and visual stimuli as inadequate and adequate stimuli, respectively (``cross-modality' measurements). The combined EEG-EP epochs were analysed in frequency domain with fast Fourier transform and adaptive digital filters. Alpha (8--15 Hz) response components turned out to be dependent on whether the stimulus was adequate or not (median amplitude with inadequate vs. adequate stimulation: vs. ). Theta (4--7 Hz) response components were less dependent on stimulus modality (inadequate vs. adequate stimulation: vs. ). In EP recordings the occipital alpha response almost disappeared in the first 250 ms following auditory stimulation. Comparable behaviour was observed in similar experiments with recordings from the cat visual cortex (area 17) and with occipital magnetoencephalographic recordings. Taking into account the above-mentioned previous reports on intracranial recordings in primary sensory areas of the cat brain and preliminary results of magnetoencephalographic measurements, we propose the following hypothesis: alpha responses in a time window of about 250 ms after stimulation might predominantly reflect primary sensory processing whereas the theta responses in the first 250 ms after stimulation might be more involved in supra-modality -- or cross-modality -- associative-cognitive processing. Received: 25 February 1994 / Accepted in revised form: 5 August 1994