Hypoxia and its Emerging Therapeutics in Neurodegenerative, Inflammatory and Renal Diseases

Hypoxia is a common underlying condition of many disease states. Hypoxia can occur with ischemia, a lack of blood flow to tissues, or independent of ischemia as in acute lung injury, anemia, and carbon monoxide poisoning. Hypoxia may be observed in patients with diseases such as obstructive sleep apnea, cerebrovascular diseases, systemic hypertension, cardiovascular diseases, chronic obstructive pulmonary disease (COPD), pulmonary hypertension and congestive heart failure (CHF), inflammatory disease states, and acute and chronic renal diseases. In the past decade, research has shown hypoxic signaling to be involved in a range of responses from adaptation of the body to reduced oxygen to pathogenesis of disease. Hypoxic signaling intermediates orchestrate a whole host of responses from angiogenesis, glycolysis, and erythropoiesis to inflammation and remodeling, which could be beneficial or harmful to the hosting organ. The length of exposure to low oxygen pressure as well as the existing signaling pathways within different cells dictates their benefit or disadvantage from hypoxic signaling. Therefore, activation or inhibition of hypoxic intermediates could serve as novel therapeutic strategies. In this chapter, we review the role of hypoxic signaling in neurodegenerative, inflammatory, and renal disease states and the emerging therapeutic approaches involving hypoxic signaling

Hypoxia Inducible Factor 1: A Urinary Biomarker of Kidney Disease.

Identifying noninvasive biomarkers of kidney disease is valuable for diagnostic and therapeutic purposes. Hypoxia inducible factor 1 (HIF-1) expression is known to be elevated in the kidneys in several renal disease pathologies. We hypothesized that the urinary HIF-1a mRNA level may be a suitable biomarker for expression of this protein in chronic kidney disease (CKD). We compared HIF-1a mRNA levels from urine pellets of CKD and healthy subjects. To ensure that urinary HIF-1a mRNA is of kidney origin, we examined colocalization of HIF-1a mRNA with two kidney specific markers in urine cells. We found that HIF-1a mRNA is readily quantifiable in urine pellets and its expression was significantly higher in CKD patients compared with healthy adults. We also showed that the urinary HIF-1a mRNA comes primarily from cells of renal origin. Our data suggest that urinary HIF-1a mRNA is a potential biomarker in CKD and can be noninvasively assessed in patients

Assessment of glomerular filtration rate with dynamic computed tomography in normal Beagle dogs

The objective of our study was to determine individual and global glomerular filtration rates (GFRs) using dynamic renal computed tomography (CT) in Beagle dogs. Twenty-four healthy Beagle dogs were included in the experiment. Anesthesia was induced in all dogs by using propofol and isoflurane prior to CT examination. A single slice of the kidney was sequentially scanned after a bolus intravenous injection of contrast material (iohexol, 1 mL/kg, 300 mgI/mL). Time attenuation curves were created and contrast clearance per unit volume was calculated using a Patlak plot analysis. The CT-GFR was then determined based on the conversion of contrast clearance per unit volume to contrast clearance per body weight. At the renal hilum, CT-GFR values per unit renal volume (mL/min/mL) of the right and left kidneys were 0.69 ± 0.04 and 0.57 ± 0.05, respectively. No significant differences were found between the weight-adjusted CT-GFRs in either kidney at the same renal hilum (p = 0.747). The average global GFR was 4.21 ± 0.25 mL/min/kg and the whole kidney GFR was 33.43 ± 9.20 mL/min. CT-GFR techniques could be a practical way to separately measure GFR in each kidney for clinical and research purposes

Processing optimization and characterization of gelatin from catfish (Clarias gariepinus) skin

The extraction of catfish (Clarias gariepinus) skin gelatin was optimized by using response surface methodology (RSM) employing a central composite design (CCD). RSM with 3-factors, 5-levels CCD was carried out for the optimization. The independent variables were suggested which include NaOH concentration (0.07-0.23 mol/L), acetic acid concentration (0.04-0.14 mol/L) and extraction temperature (40-80°C) with the percentage of hydroxyproline recovery (Y) as dependant variable. A maximum Y of 65.32% for gelatin processing was obtained using a combination of 0.13 mol/L NaOH and 0.09 mol/L acetic acid for 1 h, followed by a hot-water extraction at 64.92°C for 3 h. The results indicated a high protein content (88.46 g/100 g) in the extracted gelatin with a viscosity of 3.45 mPa.s, 286.71 g gel strength and 173 residues per 1000 residues of imino acids (proline and hydroxyproline). Furthermore, the gelatin from catfish also showed a relatively good instrumental texture quality according to texture profile analysis (TPA)

Optimization of extraction and physicochemical properties of gelatin from pangasius catfish (Pangasius sutchi) skin

In order to optimize the extraction of gelatin from pangasius catfish skin, a response surface method (RSM) involving a Central Composite Design (CCD) was applied. Four variables, namely NaOH concentration (0-0.3 N), acetic acid concentration (0.025-0.125 N), extraction time (2-4 h) and extraction temperature (40-80°C) were selected as independent variables for the optimization using RSM. The dependent variable was calculated by hydroxyproline recovery. The optimum conditions for extraction were produced by a pre-treatment of 0.2 N NaOH and 0.1 N acetic acid along with hot water extraction at 63.7°C for 2.41 h. The results showed that the predicted response by RSM (68.53%) closely matched the experimental response of 68.16%. The results indicated that the extracted gelatin possessed high gel strength (438 g) and high content of imino acid (proline and hydroxyproline) (18.01%) with a viscosity of 4.67 mPa s. The results showed that RSM was a great optimizing tool for extraction of gelatin from pangasius catfish skin. The gelatin was also proven to have significantly (p<0.05) higher quality of physicochemical properties than those from bovine skin gelatin