The Waveform Fluctuation and the Clinical Factors of the Initial and Sustained Erythropoietic Response to Continuous Erythropoietin Receptor Activator in Hemodialysis Patients

Objectives. Erythropoiesis-stimulating agents (ESA) are the main treatment for anemia in hemodialysis (HD) patients. We evaluated factors determining the response after treatment of a new ESA (continuous erythropoietin erythropoietin receptor activator (CERA)). Methods. 61 HD patients were classified by their response at two different timings. First, patients whose hematocrit (Hct) increased 1.5% in the first week were defined as initial responders (IR, n = 16). We compared several parameters between IR and the rest of the study subjects (non-IR, n = 45). Second, patients whose Hct increased 2% in the 4th week were defined as sustained responders (SR, n = 12), and we did a similar comparison. Results. The Hct showed a waveform fluctuation. Compared with the rest, IR had significantly lower platelet counts and higher levels of ferritin, total protein, total bilirubin, and serum sodium, while SR had significantly lower levels of C-reactive protein and low-density lipoprotein (All P < 0.05). In comparison with the rest, higher Hct persisted for 10 weeks in SR but only for two separate weeks (the 1st and 7th week) in IR. Conclusions. The initial and sustained erythropoietic responses are independent from each other and are associated with different factors. Treatment focusing on these factors may improve the response

Acid-sensing ion channel 3 mediates peripheral anti-hyperalgesia effects of acupuncture in mice inflammatory pain

<p>Abstract</p> <p>Background</p> <p>Peripheral tissue inflammation initiates hyperalgesia accompanied by tissue acidosis, nociceptor activation, and inflammation mediators. Recent studies have suggested a significantly increased expression of acid-sensing ion channel 3 (ASIC3) in both carrageenan- and complete Freund's adjuvant (CFA)-induced inflammation. This study tested the hypothesis that acupuncture is curative for mechanical hyperalgesia induced by peripheral inflammation.</p> <p>Methods</p> <p>Here we used mechanical stimuli to assess behavioral responses in paw and muscle inflammation induced by carrageenan or CFA. We also used immunohistochemistry staining and western blot methodology to evaluate the expression of ASIC3 in dorsal root ganglion (DRG) neurons.</p> <p>Results</p> <p>In comparison with the control, the inflammation group showed significant mechanical hyperalgesia with both intraplantar carrageenan and CFA-induced inflammation. Interestingly, both carrageenan- and CFA-induced hyperalgesia were accompanied by ASIC3 up-regulation in DRG neurons. Furthermore, electroacupuncture (EA) at the ST36 rescued mechanical hyperalgesia through down-regulation of ASIC3 overexpression in both carrageenan- and CFA-induced inflammation.</p> <p>Conclusions</p> <p>In addition, electrical stimulation at the ST36 acupoint can relieve mechanical hyperalgesia by attenuating ASIC3 overexpression.</p

Hyponatremia Among the Institutionalized Elderly in 2 Long-Term Care Facilities in Taipei

Hyponatremia is common in the institutionalized elderly, and syndrome of inappropriate antidiuretic hormone secretion was deemed the most important etiologic factor. The purpose of this study was to evaluate the prevalence and etiologic factors of hyponatremia among institutionalized elderly and to explore its association with nutritional status. Methods: Subjects in 2 private long-term care facilities (LTCFs) participated in this study. Periodic nutritional evaluations, including anthropometric measurements and serial laboratory examinations, were performed every 6 months. When hyponatremia was identified, serum osmolality, serum levels of cortisol, thyrotropin, antidiuretic hormone, urine osmolality, and electrolyte profile were done instantly. Water loading tests were performed for subjects with euvolemic, hypo-osmolar hyponatremia. Nutritional status (i.e. hemoglobin, serum albumin, serum total cholesterol, body mass index [BMI], and mean body weight loss within 6 months) was compared between hyponatremic and normonatremic subjects during hyponatremic episodes and at follow-up (6 months later). Results: In total, 67 (mean age = 77.2 ± 8.8 years, M/F = 45/22) LTCF residents were enrolled. The prevalence of hyponatremia was 31.3% (21/67) during the 6-month period, and 62.5% of these cases were related to reset osmostat. In addition, BMI was similar between hyponatremic and normonatremic subjects during hyponatremic episodes (19.1 ± 3.2 vs 20.5 ± 4.0 kg/m2, p = 0.16), but became significantly lower in hyponatremic subjects 6 months later (18.5 ± 3.2 vs 20.8 ± 4.2 kg/m2, p = 0.027). However, the mean body weight loss during the 6-month follow-up was similar (3.0% vs 0.8%, p = 0.25). Furthermore, hemoglobin and serum levels of albumin were similar between groups during hyponatremic episodes and at follow-ups, but serum levels of total cholesterol were significantly lower in hyponatremic subjects on both occasions (166.9 ± 30.5 vs 190.2 ± 38.2 mg/dL, p = 0.016 during hyponatremic episodes and 153.6 ± 29.4 vs 182.8 ± 35.5 mg/dL, p = 0.003 at follow-up). Conclusion: About a third of LTC-dwelling elderly would experience hyponatremia during the 6-month period, and 62.5% of them were due to reset osmostat. The relationship between hyponatremia and undernutrition deserves further investigation

Bilirubin Links HO-1 and UGT1A1*28 Gene Polymorphisms to Predict Cardiovascular Outcome in Patients Receiving Maintenance Hemodialysis

Serum bilirubin levels, which are determined by a complex interplay of various enzymes, including heme oxygenase-1 (HO-1) and uridine diphosphate–glucuronosyl transferase (UGT1A1), may be protective against progression of cardiovascular disease (CVD) in hemodialysis patients. However, the combined effect of HO-1 and UGT1A1*28 gene polymorphisms on CVD outcomes among hemodialysis patients is still unknown. This retrospective study enrolled 1080 prevalent hemodialysis patients and the combined genetic polymorphisms of HO-1 and UGT1A1 on serum bilirubin were analyzed. Endpoints were CVD events and all-cause mortality. Mean serum bilirubin was highest in patients with S/S + S/L of the HO-1 promoter and UGT1A1 7/7 genotypes (Group 1), intermediate in those with S/S + S/L of the HO-1 promoter and UGT1A1 7/6 + 6/6 genotypes (Group 2), and lowest in the carriers with the L/L HO-1 promoter and UGT1A1 7/6 + 6/6 genotypes (Group 3) (p &lt; 0.001). During a median follow-up of 50 months, 433 patients developed CVD. Compared with patients in Group 3, individuals among Groups 1 and 2 had significantly lower risks for CVD events (adjusted hazard ratios (aHRs) of 0.35 for Group 1 and 0.63 for Group 2), respectively. Compared with the lower bilirubin tertile, the aHRs were 0.72 for the middle tertile and 0.40 for the upper tertile for CVD events. We summarized that serum bilirubin as well as HO-1 and UGT1A1 gene polymorphisms were associated with CVD among patients receiving chronic hemodialysis

Artificial Kidney Engineering: The Development of Dialysis Membranes for Blood Purification

The artificial kidney, one of the greatest medical inventions in the 20th century, has saved innumerable lives with end stage renal disease. Designs of artificial kidney evolved dramatically in decades of development. A hollow-fibered membrane with well controlled blood and dialysate flow became the major design of the modern artificial kidney. Although they have been well established to prolong patients&rsquo; lives, the modern blood purification system is still imperfect. Patient&rsquo;s quality of life, complications, and lack of metabolic functions are shortcomings of current blood purification treatment. The direction of future artificial kidneys is toward miniaturization, better biocompatibility, and providing metabolic functions. Studies and trials of silicon nanopore membranes, tissue engineering for renal cell bioreactors, and dialysate regeneration are all under development to overcome the shortcomings of current artificial kidneys. With all these advancements, wearable or implantable artificial kidneys will be achievable

Teaghrelin Protects SH-SY5Y Cells against MPP+-Induced Neurotoxicity through Activation of AMPK/SIRT1/PGC-1α and ERK1/2 Pathways

The prevalence and incidence of Parkinson&rsquo;s disease (PD), an age-related neurodegenerative disease, are higher among elderly people. Independent of etiology, dysfunction and loss of dopaminergic neurons are common pathophysiological changes in PD patients with impaired motor and non-motor function. Currently, preventive or therapeutic treatment for combating PD is limited. The ghrelin axis and ghrelin receptor have been implicated in the preservation of dopaminergic neurons and have potential implications in PD treatment. Teaghrelin, a compound originating from Chin-Shin Oolong tea, exhibits ghrelin agonist activity. In this study, the neuroprotective potential of teaghrelin against PD was explored in a cell model in which human neuroblastoma SH-SY5Y cells were treated with the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP+). Upon MPP+ exposure, SH-SY5Y cells exhibited decreased mitochondrial complex I activity and apoptotic cell death. Teaghrelin activated AMP-activated protein kinase (AMPK)/sirtuin 1(SIRT1)/peroxisome proliferator-activated receptor gamma (PPAR&gamma;) coactivator-1&alpha; (PGC-1&alpha;) and extracellular signal&ndash;regulated kinases 1 and 2 (ERK1/2) pathways to antagonize MPP+-induced cell death. Herein, we propose that teaghrelin is a potential candidate for the therapeutic treatment of PD

Reduction of the Plasma Uric Acid Level in Potassium Oxoate-Induced Hyperuricemic Rats by Heat-Concentrated Prunus mume Fruit Extract Containing Three Chlorogenic Acid Isomers

Gout is a common rheumatic disease, resulting from hyperuricemia. Prunus mume fruit extract, after being heat-concentrated named mei extract, was empirically found to reduce the risk of gout. While neochlorogenic acid was found as the predominant phenolic compound in the fresh juice of Prunus mume, neochlorogenic acid, chlorogenic acid, and cryptogenic acid were detected as the major phenolic compounds in the mei extract. In vitro testing showed that all the three chlorogenic acid isomers exhibited comparable inhibitory activities on xanthine oxidase. The hypouricemic effects of the mei extract were evaluated in potassium oxonate-induced hyperuricemic rats. Oral administrations of the mei extract significantly reduced the plasma uric acid level in hyperuricemic rats, but did not elevate the urinary uric acid level. The results provide in vivo evidence for the anti-hyperuricemic effects of mei extract for the first time, rationalize its therapeutic usage for the treatment of hyperuricemia and gout, and propose chlorogenic acid isomers as the active ingredients. Mei extract seems to be a potential natural functional food product