losartan-potassium and Weight-Gain

Hypoferremia is a marker of disease severity in cystic fibrosis (CF). The effect of systemic antibiotics on iron homeostasis during CF pulmonary exacerbation (CFPE) is unknown. Our central hypotheses were that, by the completion of treatment, serum iron would increase, serum concentrations of interleukin-6 (IL-6) and hepcidin-25, two mediators of hypoferremia, would decrease, and sputum iron would decrease.. Blood and sputum samples were collected from 12 subjects with moderate-to-severe CF (median percentage-predicted forced expiratory volume in 1 second (FEV(1) %) = 29%; median weight = 56 kg) within 24 hours of starting and completing a course of systemic antibiotics.. After treatment, subjects showed median FEV(1) % and body weight improvements of 4.5% and 2.0 kg, respectively (p < 0.05). Median serum iron rose by 2.4 μmol/L (p < 0.05), but 75% of patients remained hypoferremic. Median serum IL-6 and hepcidin-25 levels fell by 12.1 pg/mL and 37.5 ng/mL, respectively (p < 0.05). Median serum erythropoietin (EPO) and hemoglobin levels were unaffected by treatment. We observed a trend toward lower sputum iron content after treatment.. Hypoferremia is a salient characteristic of CFPE that improves with waning inflammation. Despite antibiotic treatment, many patients remain hypoferremic and anemic because of ineffective erythropoiesis.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Cystic Fibrosis; Disease Progression; Erythropoietin; Female; Forced Expiratory Volume; Hemoglobins; Hepcidins; Homeostasis; Humans; Interleukin-6; Iron; Male; Middle Aged; Sputum; Weight Gain; Young Adult

This study examined the safety, pharmacodynamic (PD), and pharmacokinetic (PK) biosimilarity of the human recombinant erythropoietin (EPO) products ior(®) EPOCIM and Eprex(®) following a 28-day repeated intravenous dose administration in male and female Sprague-Dawley rats with a 14-day recovery period. Safety profiling was based on clinical observations, clinical pathology, and pathology findings for control rats dosed with vehicle and rats dosed either with 30, 300, and 600 I.U./kg of ior(®) EPOCIM or 600 I.U. of Eprex(®) . Adverse findings for both ior(®) EPOCIM and Eprex(®) were similar and were a consequence of thrombotic events (ulcerative skin lesions, swollen hock joints/lameness, stomach ulcers) and decreased body weight gains, all known adverse reactions to this class of drug in rats. With the exception of stomach ulcers, all other adverse findings were fully reversible. Neither drug stimulated the production of antidrug antibodies. As expected, ior(®) EPOCIM and Eprex(®) both increased reticulocyte, red blood cell, hemoglobin, and hematocrit levels in rats. The PK of EPO following dosing with ior(®) EPOCIM was well behaved and consistent with the literature. The results of this study imply that ior(®) EPOCIM and Eprex(®) had safety profiles, PD responses, and toxicokinetic profiles that were biosimilar.

Topics: Administration, Intravenous; Animals; Biosimilar Pharmaceuticals; Chemistry, Pharmaceutical; Epoetin Alfa; Erythropoietin; Female; Hematinics; Male; Rats, Sprague-Dawley; Recombinant Proteins; Risk Assessment; Therapeutic Equivalency; Thrombosis; Toxicokinetics; Weight Gain

Erythropoietin (Epo) is a pleotropic cytokine with several nonhematopoietic tissue effects. High-dose Epo treatment-mediated effects on body weight, fat mass and glucose tolerance have recently been reported, thus extending its pleotropic effects to fat and glucose metabolism. However, the exact dose range of Epo treatment required for such effects remains unidentified to date. We investigated Epo dosage effect (up to 1000 U/kg) on hematocrit, body weight, body composition, glucose metabolism, food intake, and physical activity, during high-fat diet-induced obesity. We report that Epo doses (1000, 600, 300, and 150 U/kg) significantly reduced body weight gain and fat mass, while, only Epo doses of 300 U/kg and higher significantly affected glucose tolerance. None of the tested Epo doses showed any detectable effects on food intake, and only 1000 U/kg dose significantly increased physical activity, suggesting that these parameters may only be partially responsible for the metabolic effects of Epo treatment.

Topics: Adiposity; Animals; Diet; Dietary Fats; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Feeding Behavior; Glucose; Hematocrit; Humans; Male; Mice; Mice, Inbred C57BL; Motor Activity; Obesity; Recombinant Proteins; Weight Gain

Anemia is a common cause of morbidity and disease and reduces the quality of life. This study examined the effect of a combination treatment (AAC) using Astragali radix (AMW) and Angelicae radix (AGW) in cyclophosphamide (CYP)-induced anemic rats on erythropoietin (EPO) expression and hematological parameters. Male 4-week-old Sprague-Dawley rats were divided into five groups with or without CYP-induced anemia and individual or the combined herbal treatments according to the experimental protocol. After treatment, reverse transcription-polymerase chain reaction was used to evaluate the effects of AAC on erythropoietin expression, and blood and serological parameters were measured. The EPO mRNA levels were lower in the CYP-treated group, compared to the normal group, and higher in the AAC-treated group. In the CYP-treated group, the serum iron concentration, total iron-binding capacity, and vitamin B(12) level were lower, but these were normal or almost normal in the AAC-treated group. The CYP-treated group gained less weight than the normal group, but weight gain was partially normalized in the AAC group. The feed efficiency ratio was lowest in the CYP group, but the differences were not significant. The numbers of red blood cells, white blood cells, and platelets, the hematocrit, and the hemoglobin level were measured. The results revealed a reduced number of blood cells in the CYP-treated group, whereas the AAC-, AMW-, and AGW-treated groups showed significantly enhanced blood cell numbers compared to the CYP-treated control group and the AAC-treated group. AAC enhanced EPO mRNA expression in the CYP-induced anemic rat and improved the hematological parameters and vitamin B(12) status.

Topics: Anemia; Angelica; Animals; Antineoplastic Agents, Alkylating; Astragalus propinquus; Blood Cell Count; Blood Cells; Cyclophosphamide; Drug Therapy, Combination; Drugs, Chinese Herbal; Energy Intake; Erythropoietin; Gene Expression; Iron; Male; Phytotherapy; Plant Roots; Rats; Rats, Sprague-Dawley; RNA, Messenger; Vitamin B 12; Weight Gain

High-dose recombinant erythropoietin (rEpo) is neuroprotective in neonatal animal models of brain injury, but the long-term consequences of neonatal exposure have not been studied.. We hypothesized that multiple injections of high-dose rEpo during the neonatal period would be safe, and would improve neurologic outcomes after exposure to neonatal hypoxia or hypoxic-ischemic injury.. Three experimental groups of Sprague-Dawley rats were assessed: (1) normoxia, (2) hypoxia and (3) hypoxia-ischemia. Groups 1 and 2 were given 0, 2,500 or 5,000 U/kg rEpo subcutaneously for the first 5 days of life (P1-P5). Group 2 animals also underwent 2 h of hypoxia (8% O(2)) daily from P1-P3. Group 3 animals underwent right carotid artery ligation followed by hypoxia (8% O(2) x 90 min) on P7, followed by either vehicle or rEpo (2,500 U/kg subcutaneously QD x3). We evaluated short- and long-term physiologic and behavioral outcomes. Major organs were evaluated grossly and histologically.. rEpo treatment transiently raised hematocrit, prevented hypoxia-induced delays in geotaxis and growth, improved forelimb strength, promoted liver growth in males, lowered the adult platelet count, but did not alter other CBC indices or histology. rEpo prevented hypoxia-ischemia-induced learning impairment and substantia nigra neuron loss.. Repeated treatment of newborn rats with high-dose rEpo was safe under all conditions tested. rEpo treatment improved the development of hypoxia-exposed newborns and prevented the learning impairment and dopamine neuron loss due to unilateral hypoxic-ischemic brain injury.

Topics: Animals; Animals, Newborn; Avoidance Learning; Behavior, Animal; Brain; Dopamine; Drug-Related Side Effects and Adverse Reactions; Erythropoietin; Hematocrit; Hypoxia; Hypoxia-Ischemia, Brain; Liver; Models, Animal; Neurons; Neuroprotective Agents; Organ Size; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Weight Gain

Familial Mediterranean fever (FMF) is an autosomal recessive disease seen primarily in Sephardic Jews, Turks, and Armenians. The disease manifests as recurrent attacks of fever and serositis. The most important complication of FMF is the development of renal failure due to AA type amyloidosis. There has not been extensive experience with renal replacement therapy in FMF amyloidosis. Nevertheless, there may be a concern about the possibility of higher rates of morbidity and mortality in amyloidotic patients maintained on chronic hemodialysis. Moreover, there is not enough experience regarding patients on chronic peritoneal dialysis. As a result, the best treatment modality of end-stage renal disease (ESRD) in these circumstances still remains unclear. This study aimed to compare the effect of hemodialysis and peritoneal dialysis modalities on clinical outcomes in ESRD patients associated with FMF amyloidosis.. Forty FMF patients with ESRD due to amyloidosis were retrospectively analyzed. All 40 patients were on renal replacement therapy, 20 on hemodialysis (HD), 20 on peritoneal dialysis (PD). Peritoneal solute transport rates, weekly mean creatinine clearance, and daily mean ultrafiltration (UF) of the patients on chronic peritoneal dialysis were evaluated. Weekly dialysis durations, dialysis membrane properties, Kt/V values, interdialytic weight gains, and frequency of hypotension during dialysis were evaluated on hemodialysis patients. All of the patients were examined according to their demographic characteristics, laboratory results, duration time on dialysis, erythropoietin requirements, frequencies of infectious complications requiring hospitalization, and the two renal replacement modalities mentioned above were compared in terms of these parameters.. Serum albumin levels of the patients with FMF amyloidosis who were maintained on peritoneal dialysis treatment were lower (2.87 vs 3.45) and the frequency of infections of the same group was higher (4.2 vs 0.5) than the patients with ESRD secondary to other diseases in the CAPD group.. This retrospective analysis showed that peritoneal dialysis may have some disadvantages in amyloidotic patients. Due to the high frequency of hypoalbuminemia and infectious complications seen in this group, peritoneal dialysis is widely accepted as an alternative choice of treatment when hemodialysis is not appropriate.

Topics: Adult; Amyloidosis, Familial; Biomarkers; Blood Pressure; Creatinine; Dialysis Solutions; Erythropoietin; Familial Mediterranean Fever; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis; Research Design; Retrospective Studies; Surveys and Questionnaires; Treatment Outcome; Turkey; Weight Gain

Interdialytic weight gain is an important prognostic factor in dialysis patients. Different eating patterns may affect interdialytic weight gain. The goal was to assess the effect of the Mediterranean type of diet on interdialytic weight gain of chronic hemodialysis patients.. This study had a cross-sectional design.. Four hospital-based satellite hemodialysis units in different cities in Turkey.. A total of 702 patients (279 women, 423 men; mean age, 47.8 +/- 15.5 years) were included in the study. They were grouped according to the hemodialysis centers: Alanya-Izmir (group 1, n = 194) and Ankara-Adana (group 2, n = 508).. Group 1 patients were consuming a Mediterranean type of diet, whereas group 2 patients had a diet rich in protein and carbohydrates. All of the patients were under the same dialysis and treatment protocols. The demographic data, the medications, interdialytic weight gains, and laboratory data such as serum albumin, C-reactive protein, hemoglobin, hematocrit, serum iron binding capacity, ferritin, and parathyroid hormone during the last 3 months for each patient were recorded.. The interdialytic weight gain differences between the groups were compared using the Student t-test and the Mann-Whitney U test.. When the two groups were compared according to age, sex, blood pressure, serum albumin, hematocrit, and parathyroid hormone levels, there was no statistically significant difference. Mean interdialytic weight gain for group 1 and group 2 was 2.47 +/- 0.94 kg and 3.08 +/- 0.94 kg, respectively (P < .001). When the two groups were compared according to their iron requirements, group 1 showed an increased requirement for doses of iron and erythropoietin (P < .001 and P < .001, respectively).. A Mediterranean-type diet, rich in seafood and vegetables, was associated with less interdialytic weight gain compared with a diet rich in protein and carbohydrates. Although all of our patients had the same diet education and treatment protocols, the geographic region and culture influenced their compliance to diet and their therapeutic outcomes.

Topics: Acetates; Adult; Aged; Blood Pressure; Calcium Compounds; Cross-Sectional Studies; Diet, Mediterranean; Erythropoietin; Female; Ferritins; Hematocrit; Humans; Iron; Male; Middle Aged; Renal Dialysis; Seafood; Vegetables; Weight Gain

Anemia is prevalent among pregnant adolescents, but few data exist on biochemical indicators of iron status in this group. We hypothesized that among an at-risk population of African-American, pregnant adolescents, the degree of iron depletion and deficiency would be marked, and that iron deficiency anemia would comprise the majority of the observed anemia. To examine this, blood samples were collected from 80 girls (< or =18 y old) attending an inner city maternity clinic, 23 of whom were studied longitudinally in the 2nd and 3rd trimesters depending on contact at the clinic. Sample sizes for the biomarkers varied according to the blood volume available at the time the assays were completed. Descriptive statistics were applied to characterize iron status, and multivariate regression and logistic analyses were used to identify significant determinants of iron status. Depleted iron stores (ferritin < or = 15 microg/L) were indicated for 25% (n = 44) and 61% (n = 59) of adolescents during the 2nd and 3rd trimesters, respectively. Serum folate (39.3 +/- 15.4 nmol/L, n = 60), RBC folate (2378 +/- 971 nmol/L, n = 60), and serum vitamin B-12 concentrations (313 +/- 163 pmol/L, n = 60) were within normal ranges. Adolescents with serum transferrin receptor:serum ferritin ratios (R:F ratio) > 300 during the 2nd trimester were 12.5 times (95% CI 2.83, 55.25) more likely to be classified with iron deficiency anemia during the 3rd trimester (P = 0.0002) than those with lower ratios. Estimates of body iron were lower in those tested after wk 26 of gestation (P < 0.0001), and reserves were depleted in 5.0% vs. 31.3% of the 2nd (n = 40) and 3rd (n = 48) trimester cohorts, respectively. In conclusion, iron-deficiency anemia was prevalent among these pregnant minority adolescents. Targeted screening and interventions to improve diet and compliance with prenatal iron supplementation are warranted for this at-risk group.

Topics: Adolescent; Anemia, Iron-Deficiency; Birth Weight; Black or African American; Body Mass Index; Erythropoietin; Female; Ferritins; Folic Acid; Gestational Age; Hemoglobins; Humans; Iron; Iron Deficiencies; Leptin; Pregnancy; Pregnancy Complications; Pregnancy in Adolescence; Regression Analysis; Transferrin; Vitamin B 12; Weight Gain

To evaluate the efficacy of darbepoetin alfa 200 microg subcutaneously every 2 weeks after therapeutic substitution for epoetin alfa.. Retrospective multicenter chart review.. Three US Oncology-affiliated outpatient sites.. Three hundred thirty anemic patients with nonmyeloid malignancies, of whom 174 had been treated previously with epoetin alfa (switched group) and 156 had not been treated recently with epoetin alfa (naive group).. Therapeutic substitution with darbepoetin alfa was started according to the US Oncology Pharmacy and Therapeutics Committee's recommended dosing guidelines: anemic patients with cancer received a starting dosage of darbepoetin alfa 200 microg every 2 weeks regardless of whether or not they had previously received epoetin alfa. Hematologic and darbepoetin alfa usage data were abstracted from consecutive medical records dated from May 2002-March 2003.. Median exposure to darbepoetin alfa was 10 weeks (25th quartile 6 wks, 75th quartile 17 wks) and 10 weeks (25th quartile 5 wks, 75th quartile 18 wks) for the naive and switched groups, respectively. The week before the switch to darbepoetin alfa, the 174 patients receiving epoetin alfa were administered the following weekly doses: less than 40,000 U (9%), 40,000 U (50%), or 45,000-90,000 U (41%). Mean hemoglobin level increased from baseline (wk 0) in both the naive and switched groups. The proportion of patients receiving a red blood cell transfusion in the darbepoetin alfa treatment phase was low (15% in each group). No variation in transfusion rates was observed across weight categories in patients who received a fixed dosage of darbepoetin alfa. Darbepoetin alfa was well tolerated. A detailed usage algorithm was validated by these results and is being used in these three US Oncology-affiliated practices.. A darbepoetin alfa starting dosage of 200 microg subcutaneously every 2 weeks administered according to US Oncology-recommended dosing guidelines is effective in treating chemotherapy-induced anemia in both epoetin alfa-naive patients and those switched from epoetin alfa.

Topics: Aged; Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hemoglobins; Humans; Injections, Subcutaneous; Male; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins; Retrospective Studies; Therapeutic Equivalency; Time Factors; Weight Gain

Congestive heart failure (CHF) and anemia were reported to affect resting energy expenditure (REE). The aim of this study was to evaluate the effect of the correction of anemia on REE in subjects with CHF.. Nine anemic patients with compensated CHF and CRF were studied before and after correction of anemia. REE was studied by an open circuit indirect calorimeter, body composition by dual-energy-X-ray absorption and total body and extracellular water by multi-frequency bioelectrical impedence. Four anemic and 5 non-anemic CHF patients who did not receive any new treatment served as controls.. After the correction of their anemia patients tended to increase weight (P<0.06), but no significant changes were observed in body composition. Daily caloric intake increased significantly (P<0.02). Ejection fraction increased (P<0.05) and pulse rate decreased significantly (P<0.001). REE and REEPP were in the normal range before correction but increased significantly afterwards (1402+/-256 vs. 1496+/-206 kcal/d, and 101+/-9 vs. 109+/-8, P<0.023 and P<0.006, respectively).. Correction of anemia in patients with CHF increases their REE. This can be related either to improved tissue oxygenation and/or to increased caloric intake.

Topics: Aged; Aged, 80 and over; Anemia; Basal Metabolism; Body Composition; Calorimetry, Indirect; Electric Impedance; Energy Intake; Erythropoietin; Female; Heart Failure; Humans; Iron; Male; Middle Aged; Oxygen Consumption; Weight Gain

Retroviral vectors encoding glucose-responsive promoters driving furin expression may provide an amplified, glucose-regulated secretion of insulin. We constructed LhI*TFSN virus to encode a glucose-regulatable transforming growth factor alpha promoter controlling furin expression with a viral LTR promoter driving constitutive expression of furin-cleavable human proinsulin. Autologous BB rat vascular smooth muscle cells transduced with LhI*TFSN virus and cultured in 1.7 and 16.7 mM glucose secreted 50.7 +/- 3.2 and 136.0 +/- 11.0 microU (mean +/- SD) of insulin per 10(6) cells per day, respectively. After the onset of diabetes spontaneously diabetic congenic DR lyp/lyp BB rats received stomach implants containing 2 x 10(6) LhI*TFSN-transduced primary rat vascular smooth muscle cells. In eight treated rats there was a major reduction in insulin requirement to as low as 25% of pretreatment level for up to 3 months and one rat became insulin free without hypoglycemia. Intraperitoneal glucose tolerance tests (IPGTTs) in diabetic rats receiving control implants did not show the characteristic decline in blood glucose of normal rats after glucose administration. In contrast, diabetic rats receiving LhI*TFSN-transduced cells showed significant clearances of blood glucose. These data suggest clinically significant levels of glucose-regulated insulin delivery from implanted vascular smooth muscle cells transduced with LhI*TFSN vector.

Topics: Animals; Cells, Cultured; Diabetes Mellitus, Type 1; Erythropoietin; Furin; Glucose; Glucose Tolerance Test; Humans; Insulin; Male; Muscle, Smooth, Vascular; Promoter Regions, Genetic; Rats; Rats, Inbred BB; RNA, Messenger; Subtilisins; Transduction, Genetic; Transforming Growth Factor alpha; Weight Gain

The aim of this study was to compare clinical and biological results in 4 standard hemodialyzed patients originally treated by three 4-5 h sessions per week and converted within one year to daily hemodialysis sessions of 2-2.5 h each 6 times per week. The modalities and the total weekly dialysis times remained the same. With daily hemodialysis, the blood pressure and left ventricular mass index decreased significantly (p < 0.01). A significant decrease in the urea time averaged deviation (TAD) (p < 0.005) and increase in the Kt/V index (p < 0.05) were observed. A gain in dry weight was shown with a rise in caloric intake from 33+/-3.21 to 40.8+/-6.35 kcal/kg/day (p < 0.05), and the normalized protein catabolic rate (nPCR) increased significantly (p < 0.0038). One patient who was receiving erythropoietin (EPO) for anemia could stop his treatment. No arteriovenous fistula complications were observed. Daily hemodialysis seems to be the method of choice to manage hypertension and left ventricular hypertrophy in uremic patients. The increase of the urea TAD to a value closer to that of the healthy kidney due to the increase of the frequency of dialysis is probably the main explanation for clinical improvement.

Topics: Adult; Aged; Anemia; Arteriovenous Shunt, Surgical; Blood Pressure; Energy Intake; Erythropoietin; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Proteins; Renal Dialysis; Time Factors; Ultrasonography; Urea; Uremia; Weight Gain

This study investigated the hypothesis that a genetic predisposition to hypertension is involved in the etiology of the elevation in blood pressure induced by human recombinant erythropoietin (rHuEPO).. Blood pressure changes after 10 weeks of treatment with rHuEPO were compared between 26 patients with a positive family history of hypertension and 27 with a negative family history.. Mean blood pressure was significantly increased in patients with a positive family history of hypertension (+8.8 mm Hg, p < 0.001). In contrast, the change was not significant in those whose family history was negative (+1.8 mm Hg, not significant). The mean blood pressure of 14 of 26 patients with a positive family history of hypertension increased by more than 10%, whereas such an increase occurred in only 2 of 27 patients with a negative family history (p < 0.001). The two groups were similar in terms of the total dose of rHuEPO given, the degree to which their anemia improved, and their basal blood pressures.. It appears that hemodialysis patients with a positive family history of hypertension are susceptible to developing hypertension during treatment with rHuEPO.

Topics: Antihypertensive Agents; Blood Pressure; Body Weight; Causality; Confounding Factors, Epidemiologic; Erythropoietin; Female; Hematocrit; Humans; Hypertension; Incidence; Kidney Failure, Chronic; Male; Medical History Taking; Middle Aged; Renal Dialysis; Weight Gain

In this study we have examined the correlation between activity of erythropoiesis and serum concentrations of erythropoietin and insulin-like growth factor I in male and female rats during accelerated growth (day 30-90). We found that fractional incorporation of iron into newly formed red blood cells was linearily correlated with body weight gain. Total iron incorporation into newly formed red blood cells reflecting total daily red cell formation increased almost linearily between day 25 and 80 after birth in both sexes. While serum erythropoietin concentrations decreased in the time interval investigated (25-120 days), serum IGF-I levels increased in both sexes between day 25 and 55. In this period, individual values of total iron incorporation into red blood cells and serum IGF-I concentrations were linearily correlated. Our observations support the concept that IGF-I rather than erythropoietin modulates erythropoiesis during accelerated growth and thus manages a proportional increase in body mass and oxygen transport capacity.

Topics: Aging; Animals; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Growth; Insulin-Like Growth Factor I; Iron Radioisotopes; Male; Rats; Rats, Inbred Strains; Somatomedins; Weight Gain