Role of erythropoietin and its receptor in the development of endometriosis in rats

Objective: Besides its hematopoietic function, erythropoietin (EPO) may protect tissues from degenerative disorders. As such, EPO and its receptors were revealed in nonhematopoietic cells, including stromal and endometrial epithelial cells. However, the role of EPO in endometrial disorders is still unknown. Here, we aimed to examine the role of EPO and its receptor activation in the development of endometriosis in rats. Material and Methods: Animals were treated with EPO, darbepoietin (the synthetic form of EPO) or EPO's receptor activator, methoxy polyethylene glycol-epoetin beta (MIRCERA), after development of endometriosis. Endometriosis was induced by estrogen-administration following surgical attachment of endometrial surface on the inner abdominal wall. Treatments were started 3 weeks after induction of endometriosis and continued for the following 3 weeks. For the analysis of recurrence of endometriosis, additional analyses were conducted 3 weeks after cessation of treatments. Results: As compared with vehicle-treated animals, lesion size was reduced significantly and recurrence of endometriosis was not observed in all treatment groups. Histopathologic examination revealed that EPO and darbepoietin were more effective than MIRCERA- and vehicle-treated animals. Conclusion: Here we provide evidence that EPO is a promising candidate for the treatment of endometriosis. Our histopathologic results in particular indicate that EPO is more effective than its receptor activator MIRCERA in the development endometriosis.

Pleiotropic and Renoprotective Effects of Erythropoietin Beta on Experimental Diabetic Nephropathy Model.

BACKGROUND: This study aimed at investigating the possible protective effect of erythropoietin beta on experimental diabetic nephropathy (DN) model in rats. METHODS: Sprague Dawley rats (n = 32) were allocated into 4 equal groups of 8 each, the control (Group C), diabetes (Group D), erythropoietin beta (Group E), and erythropoietin beta treated DN (Group E + D) groups. Streptozocin (65 mg/kg) was used to induce diabetes in 10-week old rats. Erythropoietin beta was given intraperitoneally at a dose of 500 IU/kg/3 days of a week for 12 weeks. Renal function parameters, intrarenal levels and activities of oxidative stress biomarkers, serum inflammatory parameters and kidney histology were determined. RESULTS: Group E + D had lower mean albumin-to-creatinine ratio (p < 0.001) as well as higher creatinine clearance (p = 0.035) than the diabetic rats (Group D). Intrarenal malondialdehyde levels were significantly lower (p = 0.004); glutathione (GSH) levels (p = 0.003), GSH peroxidase (p = 0.004) and superoxide dismutase (p < 0.005) activities of renal tissue were significantly higher in Group E + D than in Group D. The mean serum levels of interleukin-4 (p < 0.005), interleukin 1 beta (p = 0.012), interferon gamma (p = 0.018) and tumor necrosis factor alpha (p < 0.005) were significantly lower; serum levels of monocyte chemoattractant protein 1 (p = 0.018) was significantly higher in Group E + D when compared to Group D. The mean scores of tubulointerstitial inflammation (p = 0.004), tubular injury (p = 0.013) and interstitial fibrosis (p = 0.003) were also lower in Group E + D when compared to Group D. CONCLUSION: Our data seem to suggest a potential role of erythropoietin beta for reducing the progression of DN in an experimental rat model. This protective effect is, in part, attributable to the suppression of the inflammatory response and oxidative damage.

[Saccharomyces cerevisiae fungemia in an elderly patient following probiotic treatment]. / Probiyotik tedavisinden sonra yasli bir hastada gelisen Saccharomyces cerevisiae fungemisi.

Saccharomyces cerevisiae, known as baker's yeast, is also used as a probiotic agent to treat gastroenteritis by modulating the endogenous flora and immune system. However, since there have been increasing reports of fungemia due to S.cerevisiae and its subspecies S.boulardii, it is recommended that probiotics should be cautiously used in immunosuppressed patients, people with underlying diseases and low-birth weight babies. To emphasize this phenomenon, in this report, a case of S.cerevisiae fungemia developed in a patient given probiotic treatment for antibiotic-associated diarrhea, was presented. An 88-year-old female patient was admitted to our hospital with left hip pain, hypotension, and confusion. Her medical history included hypertension, chronic renal failure, left knee replacement surgery, and recurrent urinary tract infections due to neurogenic bladder. She was transferred to the intensive care unit with the diagnosis of urosepsis. After obtaining blood and urine samples for culture, empirical meropenem (2 x 500 mg) and linezolid (1 x 600 mg) treatment were administered. A central venous catheter (CVC) was inserted and after one day of inotropic support, her hemodynamic parameters were stabilized. The urine culture obtained on admission yielded extended-spectrum beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli. Urine culture was repeated after three days and no bacteria were isolated. On the 4th day of admission she developed diarrhea. Toxin A/B tests for Clostridium difficile were negative. To relieve diarrhea, S.boulardii (Reflor 250 mg capsules, Sanofi Aventis, Turkey) was administered twice a day, without opening capsules. Two days later, her C-reactive protein (CRP) level increased from 23.2 mg/L to 100 mg/L without fever. Her blood culture taken from the CVC yielded S.cerevisiae. Linezolid and meropenem therapies were stopped on the 13th and 14th days, respectively, while prophylactic fluconazole therapy was replaced with caspofungin 1 x 50 mg on the fifth day. After seven days of therapy CRP and serum creatinine levels decreased to 9.1 mg/L and 1.2 mg/dl, respectively; and she was discharged from the hospital with improvement. The probiotic capsules were used unopen, thus, it was proposed that S.cerevisiae fungemia originated from translocation from the intestinal mucosa. Since it was not possible to investigate the molecular genetics of the strain isolated from the blood culture and the strain present in the probiotic, a definite conclusion about the origin of the strain could not be reached. It was thought that old age and underlying disease of the patient were the related predisposing factors for S.cerevisiae fungemia. This case emphasized that clinicians should be cautious in case of probiotic application even though in encapsulated form, even in immunocompetent patients with a history of long-term hospital stay and use of broad-spectrum antimicrobials since there may be a risk of S.cerevisiae fungemia development.

Evaluation of the effects of a high dose of erythropoietin-beta on early endotoxemia using a rat model.

BACKGROUND: Endotoxins can cause serious organ damage and death by triggering the secretion of pro-inflammatory cytokines such as TNF-alpha, IL-6 and IL-1beta in bacterial infections. OBJECTIVES: The goal of this study was to evaluate the effects of a high dose (3000 U/kg) of erythropoietin-beta (EPO) on inflammatory cytokine levels, renal function and histological changes during the early period of Lipopolysaccharide (LPS)-induced endotoxemia using a rat model. MATERIAL AND METHODS: Male Sprague Dawley (350-400 g) rats were randomized into 3 groups: Control group (n = 7); LPS group (received 20 mcg/kg LPS through intraperitoneal (i.p.) injection (n = 7); LPS+EPO group (received 3000 U/kg, ip 30 minutes before LPS administration (n = 7). Four hours after the administration of LPS, kidney tissue and serum samples were collected. Kidney function parameters, TNF-alpha, IL-6, IL-1beta, C reactive protein (CRP) and complete blood counts (CBC) were measured. The severity of renal tubular injury and caspase-9 immunoreactive cells was expressed as a percentage. RESULTS: Serum levels of urea, creatinine, TNF-alpha, IL-6 and IL-1beta were significantly increased in the LPS group (p < 0.0001 - p = 0.04) and were lower in LPS+EPO group (p < 0.0001, p = 0.01, p = 0.02, p = 01 and p < 0.0001, respectively). Pretreatment with EPO significantly increased platelet counts (p = 0.00) and decreased white blood cell counts (p = 0.02). The renal tubular injury percentage was significantly higher in the LPS group than in the control and LPS+EPO groups (p = 0.002, p = 0.003, and p = 0.005, respectively) and caspase-9 expression was lower in the LPS+EPO and control groups than in the LPS group. CONCLUSIONS: EPO might have renoprotective effects against the inflammatory process and cell apoptosis during endotoxemia.

Paraoxonase 1 polymorphisms in patients with primary glomerulonephritis: a single-center study in Turkey.

INTRODUCTION: Human paraoxonase 1 (PON1) is an enzyme related with high-density lipoprotein cholesterol. The link between genetic polymorphisms of PON1 and hyperlipidemia and increased lipid oxidation may explain these complications in the course of glomerular diseases. In this study, we aimed to investigate PON1 192 and PON1 55 polymorphisms in patients with primary glomerulonephritis and healthy individuals. MATERIALS AND METHODS: Eighty-six patients with biopsy-proven primary glomerulonephritis and 50 healthy controls were included in the study. Clinical characteristics, lipid profile, paraoxonase activity, and PON1 genotypes (PON1 192 and PON1 55) of all of the participants were studied. RESULTS: Histopathological diagnoses of the patients were membranoproliferative glomerulonephritis (53.5%), focal segmental glomerulosclerosis (33.7%), and membranous nephropathy (12.8%). The patients had lower PON1 activity levels than the healthy controls. No differences were observed in PON1 192 genotypes between the two groups. However, the controls were more likely to carry PON1 55 LM genotype (odds ratio, 4.10; 95% confidence interval, 1.96 to 8.61; P < .001) and M allele (odds ratio, 3.0; 95% confidence interval, 1.45 to 6.19; P = .003) compared to the patients with primary glomerulonephritis. There was a marked elevation in the frequency of PON1 55 LL genotype in the patients compared to the controls (odds ratio, 0.33; 95% confidence interval, 0.16 to 0.68; P = .003). CONCLUSIONS: This preliminary study shows that the LL genotype might be a risk factor for the development of primary glomerulonephritis and the M allele might be a protective factor against its progression.

Risk factors for acute kidney injury after hip fracture surgery in the elderly individuals.

OBJECTIVE: We aimed to evaluate possible risk factors associated with acute kidney injury (AKI) after hip fracture surgery in the elderly individuals. DESIGN: Level II diagnostic study, evidence obtained from prospective cohort study from 1 center with level 2, and 3 patients. PATIENTS: A total of 165 patients (>65 years) with femoral neck fracture were enrolled in this prospective study between 2007 and 2010. Two patients were dropped for inadequate laboratory follow-up data. Patients with kidney failure or renal replacement therapy (RRT) history or AKI at admission were excluded. INTERVENTION: Nephrology consultation was obtained from all patients at admission. All patients had undergone bipolar cemented hip arthroplasty that was performed by the same surgical team in all patients within 24 hours of fracture and admission under the same protocol. MAIN OUTCOME MEASUREMENTS: Serum creatinine (SCr), urine output, and complete blood counts were evaluated at baseline and daily basis thereafter. The AKI was defined based on Acute Kidney Injury Network classification. Hospital charges were converted from Turkish Liras to US dollars and rounded. RESULTS: Among 163 patients, AKI occurred in 25 (15.3%) patients, all within the first 48 postoperative hours. Three (1.8%) patients required RRT. Baseline SCr levels were restored within 4.84 ± 1.34 days on average (3-8 days). No patient required RRT after discharge. The mean hospital stay was 3 days (2-6 days) longer and the hospital charge was 2500 US$ higher for the patients with AKI. After multivariable adjustment, only lower estimated glomerular filtration rate levels (odds ratio 0.945, 95%confidence interval 0.92-0.96) emerged as an independent predictor for AKI. CONCLUSION: The AKI represents a frequent complication after hip fracture surgery associated with longer hospital stay and higher treatment costs with increased morbidity. Our results show baseline renal function is an independent predictor of AKI.