JOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 6 2009
Nathan J. Cochran
Development of efficient cost-effective diets is a critical component in the refinement of production technologies for the largemouth bass, Micropterus salmoides (LMB). One of the first steps in reducing feed costs can be to decrease the amount of fish meal in the diet. The objective of this study was to evaluate reduced levels of fish meal, and a least-cost formulation diet, for second year growout of LMB under practical pond conditions. Twelve 0.04-ha ponds were stocked with juvenile LMB (210.1±3.3 g) at a stocking density of 8650 fish/ha (350 fish/pond). Each pond was randomly assigned one of the four dietary treatments with three replicate ponds per treatment. The three experimental diets contained varying levels of fish meal. Diets FM-45, FM-24, and FM-8 contained 45, 23.5, and 8% fish meal, respectively. In diets FM-24 and FM-8, fish meal was replaced by varying levels of poultry by-product meal, soybean meal, and blood meal. The fourth diet was a commercial salmonid diet widely used as a LMB growout feed (Nelson and Sons, Inc., SilvercupTM, Steelhead, Murray, UT, USA). This diet served as a commercial control (CC) and contained 46% crude protein. The experimental diets were formulated to be isonitrogenous and isocaloric with the CC diet and were fed once daily to apparent satiation for 180 d. At harvest, there were no significant differences between treatments (P > 0.05) in terms of survival, which averaged 95% overall. Mean weights of fish fed the three experimental diets FM-45, FM-24 and FM-8 were not significantly different (P > 0.05) and averaged 518, 546, and 529 g, respectively, but were all significantly greater (P, 0.05) than those fed the CC (488 g). Feed conversion ratio (FCR) of fish fed the FM-45 and FM-8 diets (1.43 and 1.46, respectively) was significantly greater (P, 0.05) than those fed the FM-24 diet (1.34). The FCR of fish fed the CC diet (1.39) was not significantly different (P > 0.05) from fish fed other diets. Feed cost per unit of weight gain ($US/kg) was significantly lower (P, 0.05) in fish fed the FM-24 and FM-8 diets ($0.73 and $0.72/kg, respectively) than in fish fed other diets. Feed cost per unit gain of fish fed the FM-45 diet ($0.83/kg) was significantly lower (P, 0.05) than those fed the CC diet ($1.04/kg). There were no significant differences (P > 0.05) in dress-out percentages or proximate composition among fish fed the four diets. This study indicates that fish meal levels in feeds used for the second year growout of LMB can be reduced to,8% of the formulation without reducing survival or growth and without negatively impacting body composition. [source]

Biological Sustainability of Live Shearing of Vicuña in Peru

CONSERVATION BIOLOGY, Issue 1 2007
CATHERINE TERESA SAHLEY
Andes; conservación basada en comunidades; Vicugna vicugna Abstract:,The vicuña's (Vicugna vicugna) fiber is highly valued as an export product that is made into luxury fabric and clothing. The price of fiber in 2004 was $566/kg, which makes the fiber a potentially important source of income for Andean agropastoral communities and serves as an incentive to allow vicuña grazing on high-elevation Andean landscapes. It is presumed that a shorn vicuña has little value for poachers, so shearing vicuñas could serve as a disincentive to poaching. Thus, the supply of vicuña fiber may be sustainable if it is procured through live shearing, which should serve as a powerful conservation tool. We evaluated the effects of capture and shearing on the demography of vicuña in one site located in the Salinas Aguada Blanca Reserve, Arequipa, Peru, where vicuñas were captured and shorn in spring and then returned to the wild. We conducted fixed-width line-transect censuses from 1997 to 2003 of this population. We compared the proportion of young born to females that were shorn versus females that were unshorn for the 3 years in which shearing occurred. We evaluated the effect of capture and shearing on proportion of young born to shorn and unshorn females at a second site, Picotani, Puno. The wild population in Arequipa that underwent capture and shearing showed a steady increase in total population and average density between 1997 and 2003. No significant difference was found between the proportion of young per female for shorn and unshorn females at either site. We conclude that in spring, capture and live shearing of vicuñas can be biologically sustainable. Further research is needed to determine whether shearing during winter months is biologically sustainable. Resumen:,La fibra de vicuña (Vicugna vicugna) tiene gran valor como un producto de exportación que es transformado en tela y ropa de lujo. El precio de la fibra en 2004 era de $566/kg, lo que hace que la fibra sea una fuente de ingreso potencialmente importante para comunidades agropastoriles Andinas y servir como un incentivo para permitir el pastoreo de vicuñas en paisajes Andinos elevados. Se presume que una vicuña trasquilada tiene poco valor para cazadores furtivos, por lo que el trasquilado de vicuñas pudiera servir como un desincentivo para la caza furtiva. Por lo tanto, el abastecimiento de fibra de vicuña puede ser sustentable si se obtiene del trasquilado de animales vivos, y el trasquilado de animales vivos debería ser una poderosa herramienta de conservación. Evaluamos los efectos de la captura y trasquilado sobre la demografía de vicuñas en un sitio localizado en la Reserva Salinas Aguada Blanca, Arequipa, Perú, donde las vicuñas fueron capturadas y trasquiladas en primavera y liberadas. Realizamos censos de esta población en transectos lineales de ancho fijo de 1997 a 2003. Comparamos la proporción de crías de hembras trasquiladas con las de hembras no trasquiladas durante los 3 años en que ocurrió el trasquilado. Evaluamos el efecto de la captura y trasquilado sobre la proporción de crías de hembras trasquiladas y no trasquiladas en un segundo sitio, Picotani, Puno. La población silvestre en Arequipa que fue capturada y trasquilada mostró un incremento constante en la población total y la densidad promedio entre 1997 y 2003. No se encontró diferencia significativa entre la proporción de crías por hembra para hembras trasquiladas y no trasquiladas en ningún sitio. Concluimos que en la primavera, la captura y trasquilado de vicuñas vivas puede ser biológicamente sostenible. Se requiere más investigación para determinar si el trasquilado durante el invierno es biológicamente sostenible. [source]

Evaluation of Reduced Fish Meal Diets for Second Year Growout of the Largemouth Bass, Micropterus salmoides

Skeletal Fluorosis From Instant Tea,,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2008
Michael P Whyte MD
Abstract Introduction: Skeletal fluorosis (SF) can result from prolonged consumption of well water with >4 ppm fluoride ion (F,; i.e., >4 mg/liter). Black and green teas can contain significant amounts of F,. In 2005, SF caused by drinking 1,2 gallons of double-strength instant tea daily throughout adult life was reported in a 52-yr-old woman. Materials and Methods: A 49-yr-old woman developed widespread musculoskeletal pains, considered fibromyalgia, in her mid-30s. Additionally, she had unexplained, increasing, axial osteosclerosis. She reported drinking 2 gallons of instant tea each day since 12 yr of age. Fluoxetine had been taken intermittently for 5 yr. Ion-selective electrode methodology quantitated F, in her blood, urine, fingernail and toenail clippings, tap water, and beverage. Results: Radiographs showed marked uniform osteosclerosis involving the axial skeleton without calcification of the paraspinal, intraspinal, sacrotuberous, or iliolumbar ligaments. Minimal bone excrescences affected ligamentous attachments in her forearms and tibias. DXA Z-scores were +10.3 in the lumbar spine and +2.8 in the total hip. Her serum F, level was 120 ,g/liter (reference range, 20,80 ,g/liter), and a 24-h urine collection contained 18 mg F,/g creatinine (reference value, <3). Fingernail and toenail clippings showed 3.50 and 5.58 mg F,/kg (control means, 1.61 and 2.02, respectively; ps < 0.001). The instant tea beverage, prepared as usual extra strength using tap water with ,1.2 ppm F,, contained 5.8 ppm F,. Therefore, the tea powder contributed ,35 mg of the 44 mg daily F, exposure from her beverage. Fluoxetine provided at most 3.3 mg of F, daily. Conclusions: SF from habitual consumption of large volumes of extra strength instant tea calls for recognition and better understanding of a skeletal safety limit for this modern preparation of the world's most popular beverage. [source]

Midpoint CD34 measurement as a predictor of PBPC product yield in pediatric patients undergoing high-dose chemotherapy ,

JOURNAL OF CLINICAL APHERESIS, Issue 3 2006
Rameshwar S. Sidhu
Abstract High-dose chemo/radiotherapy of sensitive tumors requires PBPC rescue doses of >3×106 CD34/kg (range: 3,20×106 CD34/kg). Because of the diversity of stem cell treatment protocols and clinical presentation of patients at the time of peripheral blood progenitor cell (PBPC) harvest, the use of the mid-point CD34 positive cell measurement was initiated to predict the final CD34-positive cell product yield/stem cell harvest. The measurement of CD34-positive cells at the mid-point of the initial setting of 5 total blood volumes (TBV) allows for the extension, shortening, or no change in the TBV processing to achieve a maximum goal of CD34-positive cells/kg body weight required for stem cell transplantation. The estimation of mid-point CD34-positive cells guided our center to extend 22 procedures, shorten 26 procedures, and leave 20 procedures unchanged. This investigation addresses three aspects of PBPC collection in pediatric patients: (1) the processing of large blood volumes (more than the defined 3 TBV and maximum up to 13 TBV in one session) to achieve good efficiency of the procedure; (2) the use of the mid-point CD34 measurement at 2.5 of 5 TBV initially set to predict the maximum goal of CD34 cells /kg needed on the same day of PBPC collection; and (3) PBPC collection in pediatric patients <10 kg body weight (as low as 5.8 kg body weight). J. Clin. Apheresis 2006. © 2006 Wiley-Liss, Inc. [source]

The anti-diabetic effects and pharmacokinetic profiles of bis(maltolato)oxovanadium in non-diabetic and diabetic rats

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2008
Shuang-Qing Zhang
ABSTRACT The purpose of this study was to evaluate the anti-diabetic effects and pharmacokinetics of bis(maltolato)oxovanadium (BMOV) in rats. The anti-diabetic study was carried out in non-diabetic and diabetic rats by single-dose subcutaneous and intragastric administration. Pharmacokinetic investigation was performed using non-diabetic rats. Results showed that BMOV significantly decreased plasma glucose levels in diabetic rats at all given doses, and restored hyperglycaemic values to normal values after subcutaneous injections at doses of 4 and 8 mg vanadium (V)/kg or after intragastric administration at doses of 14 and 28 mgV/kg, respectively, but did not affect the plasma glucose level in non-diabetic rats. BMOV could be rapidly absorbed, slowly eliminated from plasma, widely distributed in various tissues and accumulated to a greater extent in the femur tissue. The average absolute bioavailability for intragastric administration at a single dose of 3, 6 and 12 mgV/kg was 28.1%, 33.7% and 21.4%, respectively. The presence of the peak vanadium level in the plasma was not coincident with that of the maximum effect of lowering plasma glucose levels. In conclusion, at the present dosing levels and administration routes, BMOV was effective in lowering plasma glucose levels in diabetic rats. BMOV has a promising outlook as an oral glucose-lowering drug. [source]

Clinical outcomes and graft characteristics in pediatric matched sibling donor transplants using granulocyte colony-stimulating factor-primed bone marrow and steady-state bone marrow

PEDIATRIC TRANSPLANTATION, Issue 3 2007
Kuang-Yueh Chiang
Abstract:, Matched sibling donor (MSD) transplant is a life-saving procedure for children with various hematological malignancies and non-malignancies. Traditionally, steady-state bone marrow (S-BM) has been used as the source of stem cells. More recently, peripheral blood stem cell (PBSC) after granulocyte-colony stimulating factor (G-CSF) mobilization has gained popularity. Adult studies of G-CSF-primed BM (G-BM) have shown that it produces rapid white blood cell engraftment like PBSC, but with less chronic graft-vs.-host disease. No such study has been published in pediatric patients. We conducted a pilot clinical trial of G-BM for pediatric patients. Ten patients were enrolled and were compared to a contemporaneous group of 12 patients who received S-BM. Patients in the G-BM group received a higher dose of total nucleated cells/kg (7.01 vs. 3.76 × 108, p = 0.0009), higher granulocyte,macrophage colony-forming units (CFU-GM)/kg (7.19 vs. 3.53 × 105, p = 0.01) and had shorter inpatient length of stay (28 vs. 40 days, p = 0.04). The engraftment, transfusion requirement and disease-free survival between the two groups were similar. We concluded that G-BM should be considered as an alternative graft source to S-BM, with the benefits of larger graft cell dose, higher CFU-GM dose and shorter length of stay. [source]

Long-Term Insulin-Independence After Allogeneic Islet Transplantation for Type 1 Diabetes: Over the 10-Year Mark

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2009
T. Berney
Results of islet of Langerhans transplantation have markedly improved in recent years, but most patients still lose insulin independence in the long-term. We report herein the longest (over 11 years) case of insulin independence after allogeneic islet transplantation. The subject had a 27-year history of type 1 diabetes and received a single islet-after-kidney graft of 8800 islet equivalents (IEQ)/kg, pooled from 2 donors. Insulin was discontinued by 3 months posttransplant and the patient has remained off insulin ever since. Yearly follow-up studies have revealed normal metabolic control, including normal oral glucose tolerance test (OGTT). Reasons for success may involve choice of immunosuppression, low metabolic demand and low immune responsiveness as suggested by an excellent HLA matching and a high count of circulating regulatory T cells. This observation is so far an exceptional case, but clearly demonstrates the validity of the concept that long-term insulin independence after allogeneic islet transplantation is an achievable target. [source]

Effect of fat supplementation during transition period on plasma leptin and non-esterified fatty acid concentrations in Holstein cows

ANIMAL SCIENCE JOURNAL, Issue 3 2010
Ahmad AFZALZADEH
ABSTRACT The objective of this experiment was to investigate the effect of fat supplementation during the transition period on pre and postpartum body weight (BW), body condition score (BCS), non-esterified fatty acids (NEFA), glucose and leptin concentrations in Holstein cows. Holstein cows (n = 15) received a low fat diet (LF; 1.61 Mcal net energy for lactation (NEL)/kg of dry matter [DM]), moderate fat diet (MF; 1.68 Mcal NEL/kg DM) or a high fat diet (HF; 1.74 Mcal NEL/kg DM) for 4 weeks prior to calving. All cows were fed similar lactation diets ad libitum (1.74 Mcal NEL/kg DM) for 30 days after calving. Increasing diet energy density during transition period had no effect on prepartum DMI, BCS, BW, glucose and NEFA concentrations (P > 0.05); but leptin concentrations and energy balance (EB) were affected by treatments (P < 0.05). Animals fed HF had less plasma leptin prepartum. After parturition, BW, milk production, milk fat, protein, urea nitrogen and plasma glucose concentrations were affected by prepartum diets (P < 0.05). Fat supplementation prepartum did not affect postpartum NEFA. In conclusion, prepartum fat supplementation decreased leptin concentration prepartum. [source]

Pharmacokinetics and residues in milk of oxytetra-cyclines administered parenterally to dairy goats

AUSTRALIAN VETERINARY JOURNAL, Issue 7 2001
R. RULE
Objective To determine for two commercial preparations of oxytetracycline (OTC) the pharmacokinetic behaviour, the presence of detectable milk residues and the penetration in milk of OTC administered by intravenous (IV) (conventional formulation [CF]) and intramuscular (IM) routes (CF and long-acting [LA] formulations) in goats producing milk. The effects of these formulations on plasma activity values of creatine kinase (CK) and lactate dehydrogenase (LDH) were also determined as indicators of tissue damage. Procedure Five healthy lactating goats producing 1.5 ± 0.5 L/d milk and weighing 56.0 ± 4.8 kg were used. Single doses of OTC chlorhydrate (CF) were administered (20 mg OTC/kg) by IV (Trial 1 IV) and IM (Trial 1 IM) routes and OTC dehydrate (LA) by the IM route. The same goats were first given IV CF, then IM CF followed by IM LA with 3 weeks between each treatment. Blood and milk samples were taken. The quantification of OTC was performed by HPLC and the plasma activities of CK and LDH enzymes were determined by spectrophotometry. The presence of OTC residues in milk was determined by a commercial reagent. The plasma pharmacokinetic parameters were calculated using a two-compartment model. Results Estimates of kinetic variables following IV administration were: Vss= 400.0 ± 120.0 mL/kg and CL= 110.0 ± 14.0 (mL/h)/kg. The tfi for IV= 3.0 ± 0.3 h; IM, CF = 10.5 ± 2.1 h and IM, LA = 15.1 ± 3.1 h. The concentration of OTC in milk at 48 h was: IV= 0.6 ± 0.4; IM CF= 1.1 ± 0.2 and at 72 h (IM LA)= 0.6 ± 0.1 ,g/mL and the penetration in milk of OTC was: IV= 70.0 ± 18.0; IM CF= 79.0 ± 14.0 and IM LA= 66.0 ± 6.0 %. The areas under the curve of CK and LDH activities in plasma were calculated by the trapezoidal method. Values of CK and LDH IM, LA were greater (P < 0.05) than those observed for IM, CF at 2 and 3 days after administration of the antibiotic. Finally, the bioavailability of OTC CF = 92.0± 22.0 and LA= 78.0 ± 23.0 % was suitable for its usage by the IM route in lactating goats. Conclusion Plasma concentration-time values of OTC administered parenterally in production dairy goats showed similar bioavailability for the two pharmaceutical preaprations. The presence of detectable residues in milk indicates that milk should not be used for human consumption for 2 and 3 days after administration of conventional and long-acting formulations, respectively. The increments in CK and LDH activities after the IM administration of LA are consistent with the presence of tissue damage provoked by the pharmaceutical preparations at the injection site. [source]

Cost estimate for biosynfuel production via biosyncrude gasification

BIOFUELS, BIOPRODUCTS AND BIOREFINING, Issue 1 2009
Edmund Henrich
Abstract Production of synthetic fuels from lignocellulose like wood or straw involves complex technology. There-fore, a large BTL (biomass to liquid) plant for biosynfuel production is more economic than many small facilities. A reasonable BTL-plant capacity is ,1 Mt/a biosynfuel similar to the already existing commercial CTL and GTL (coal to liquid, gas to liquid) plants of SASOL and SHELL, corresponding to at least 10% of the capacity of a modern oil refinery. BTL-plant cost estimates are therefore based on reported experience with CTL and GTL plants. Direct supply of large BTL plants with low bulk density biomass by trucks is limited by high transport costs and intolerable local traffic density. Biomass densification by liquefaction in a fast pyrolysis process generates a compact bioslurry or biopaste, also denoted as biosyncrude as produced by the bioliq® process. The densified biosyncrude intermediate can now be cheaply transported from many local facilities in silo wagons by electric rail over long distances to a large and more economic central biosynfuel plant. In addition to the capital expenditure (capex) for the large and complex central biosynfuel plant, a comparable investment effort is required for the construction of several dozen regional pyrolysis plants with simpler technology. Investment costs estimated for fast pyrolysis plants reported in the literature have been complemented by own studies for plants with ca. 100 MWth biomass input. The breakdown of BTL synfuel manufacturing costs of ca. 1 , /kg in central EU shows that about half of the costs are caused by the biofeedstock, including transport. This helps to generate new income for farmers. The other half is caused by technical costs, which are about proportional to the total capital investment (TCI) for the pyrolysis and biosynfuel production plants. Labor is a minor contribution in the relatively large facilities. © 2009 Society of Chemical Industry and John Wiley & Sons, Ltd [source]

Effect of oral iron supplementation on oxidative stress and colonic inflammation in rats with induced colitis

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2001
J. Carrier
Background: Iron supplementation may increase disease activity in ulcerative colitis, possibly through the production of reactive oxygen species from the Fenton reaction. Aim: To assess the effects of two doses of oral iron on intestinal inflammation and oxidative stress in experimental colitis. Methods: Colitis was induced in rats by giving 5% dextran sulphate sodium in drinking water for 7 days. First, using a 2 × 2 factorial design, rats with or without dextran sulphate sodium received the regular diet or a diet containing iron 3%/kg diet. Second, rats with dextran sulphate sodium-induced colitis were supplemented with iron 0.3%/kg diet and compared with rats on dextran sulphate sodium and regular diet. The body weight change, histological scores, colon length, rectal bleeding, plasma and colonic lipid peroxides, colonic glutathione peroxidase and plasma vitamin E and C were measured. Faecal analysis for haem and total, free and ethylenediaminetetra-acetic acid-chelatable iron was also performed. Results: Iron 3% and iron 0.3% increased the activity of dextran sulphate sodium-induced colitis, as demonstrated by higher histological scores, heavier rectal bleeding and further shortening of the colon. This was associated with increased lipid peroxidation and decreased antioxidant vitamins. Faecal iron available to the Fenton reaction was increased in a dose-dependent manner. Conclusions: Iron supplementation taken orally enhanced the activity of dextran sulphate sodium-induced colitis and is associated with an increase in oxidative stress. [source]

A Sonic Hedgehog (SH) Fusion Protein Corrects Multifocal Defects In Experimental Diabetic Neuropathy

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000
Dr Tomlinson
Diabetic neuropathy develops from defective interactions between nerve axons and other cells in the endoneurium; such interactions are influenced in development by hedgehog proteins. This study explored the possibility that this might be maintained in the adult and form a basis for therapy in diabetic neuropathies. Streptozotocin-diabetic rats were treated (final 5 weeks of 10 weeks diabetes) with a SH-IgG fusion protein (either 0.3mg/kg or 3.0mg/kg s.c. 3 times per week); control diabetic and non-diabetic rats received vehicle. Conduction velocity (MNCV, SNCV) data and sciatic nerve levels of nerve growth factor (NGF) and neuropeptide Y (NPY) are presented below. Diabetes caused significant (p < 0.05 by ANOVA with SNK tests) reductions in all variables and treatment with SH-IgG either attenuated or prevented (p < 0.05) these reductions. Since it is well-established that the conduction deficits are unrelated to neurotrophic deficits (NGF depletion) and that NPY depletion derives from a neurotrophic defect distinct from NGF, this treatment clearly acts at multiple components of the aetiology of diabetic neuropathy. [source]

Age-dependent basal insulin patterns in children with type 1 diabetes treated with continuous subcutaneous insulin infusion

ACTA PAEDIATRICA, Issue 3 2009
Agnieszka Szypowska
Aims: Identifying age-dependent basal rates in type 1 diabetic children treated with continuous subcutaneous insulin infusion (CSII). Methods: CSII-treated children with type 1 diabetes exhibiting insulin requirement > 0.5U/kg and glycated haemoglobin (HbA1c) < 8%. The study population was composed of 198 Caucasian children (111 girls) with mean age of 9.8 ± 3.8 years, mean duration of diabetes of 4.3 ± 3.1 years and mean HbA1c value of 6.7 ± 0.7%. Data were evaluated for four age groups (0,6; 6,9; 9,12, 12,18 years). Basal rates records were downloaded from pump memory. HbA1c, weight, height were measured at scheduled visits. Results: Significant differences in the average hourly basal rate between groups were observed: I gr. 0.14 versus II gr. 0.24 versus III gr. 0.39 versus IV gr. 0.72 units/h; p < 0.0001. The average hourly basal rate correlated with age, body weight, BMI, diabetes duration and total insulin daily dose. Insulin peaks were observed for: I gr. , before midnight, II gr. , before midnight and in the early morning, gr. III and IV , in the early morning. Conclusion: Basal insulin infusion rate profiles in well-controlled paediatric patients on CSII reflect the age-dependent amount of basal insulin (20,40%) and affect circadian distribution of insulin needs. [source]

Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: Results of a twenty-four,week, multicenter, randomized, double-blind, placebo-controlled trial

ARTHRITIS & RHEUMATISM, Issue 3 2002
Stanley Cohen
Objective To evaluate the efficacy and safety of anakinra in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA). Methods Patients with moderate-to-severe active RA who were receiving MTX for 6 consecutive months, with stable doses for ,3 months (those with disease duration of >6 months but <12 years) were randomized into 6 groups: placebo or 0.04, 0.1, 0.4, 1.0, or 2.0 mg/kg of anakinra administered in a single, daily, subcutaneous injection. The primary efficacy end point was the proportion of subjects who met the American College of Rheumatology 20% improvement criteria (attained an ACR20 response) at week 12. Results A total of 419 patients were randomized in the study. Patient demographics and disease status were similar in the 6 treatment groups. The ACR20 responses at week 12 in the 5 active treatment plus MTX groups demonstrated a statistically significant (P = 0.001) dose-response relationship compared with the ACR20 response in the placebo plus MTX group. The ACR20 response rate in the anakinra 1.0-mg/kg (46%; P = 0.001) and 2.0-mg/kg (38%; P = 0.007) dose groups was significantly greater than that in the placebo group (19%). The ACR20 responses at 24 weeks were consistent with those at 12 weeks. Similar improvements in anakinra-treated subjects were noted in individual ACR components, erythrocyte sedimentation rate, onset of ACR20 response, sustainability of ACR20 response, and magnitude of ACR response. Anakinra was safe and well tolerated. Injection site reaction was the most frequently noted adverse event, and this led to premature study withdrawal in 7% (1.0-mg/kg group) to 10% (2.0-mg/kg group) of patients receiving higher doses. Conclusion In patients with persistently active RA, the combination of anakinra and MTX was safe and well tolerated and provided significantly greater clinical benefit than MTX alone. [source]

Effects of central and systemic injections of peripheral benzodiazepine receptor ligands on the anxiolytic actions of ethanol in rats

ADDICTION BIOLOGY, Issue 2 2001
G. S. Morato
The influence of peripheral benzodiazepine receptor ligands Ro5-4864 (0.05 or 1.0 mg/kg, i.p.) or PK11195 (0.05 or 1.0 mg/kg, i.p.) on the anxiolytic effect of ethanol (1.2 g/kg; 14% p/v; i.p.) was investigated in rats tested on the elevated plus-maze. Other animals were injected through intrahippocampal administrations of the ligands (0.5 or 1.0 nmol/0.5 ,l) before ethanol (1.2g/kg; 14% p/v; i.p.) and submitted to the elevated plus-maze test. The results showed that the systemic administration of either ligands 24 hours before the ethanol treatment resulted in a reduced anxiolytic effect of this drug. Only PK11195 reversed the effect of ethanol after intrahippocampal injection. These data suggest that peripheral benzodiazepine receptors play a role in ethanol anxiolysis. [source]

Effects of water deprivation on the pharmacokinetics of metformin in rats

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2007
Young H. Choi
Abstract It was reported that metformin was mainly metabolized via hepatic CYP2C11, 2D1 and 3A1/2 in rats, and in a rat model of dehydration, the expressions of hepatic CYP2C11 and 3A1/2 were not changed. Hence, it could be expected that the Clnr of metformin is comparable between two groups of rats if the contribution of CYP2D1 in the rat model of dehydration is not considerable. It was also reported that the timed-interval renal clearance of metformin was dependent on the urine flow rate in rats. In the rat model of dehydration, the 24h urine output was significantly smaller than in the controls. Hence, the urinary excretion of metformin was expected to be smaller than the controls. The above expectations were proven as follows. After intravenous administration of metformin (100mg/kg) to the rat model of dehydration, the Clnr were comparable between the two groups of rats. After both intravenous and oral administration of metformin (both 100mg/kg) to the rat model of dehydration, the 24h urinary excretion of the drug was significantly smaller than in the controls. After oral administration of metformin to the rat model of dehydration, the AUC was significantly greater (99.2% increase) than the controls. Copyright © 2007 John Wiley & Sons, Ltd. [source]

CD41+ and CD42+ hematopoietic progenitor cells may predict platelet engraftment after allogeneic peripheral blood stem cell transplantation

JOURNAL OF CLINICAL APHERESIS, Issue 2 2001
T. Demirer
Abstract The objective of this study was to quantify subpopulations of CD34+ cells such as CD41+ and CD42+ cells that might represent megakaryocyte (MK) precursors in peripheral blood stem cell (PBSC) collections of normal, recombinant human granulocyte-colony stimulating factor (rhG-CSF) primed donors and to determine whether there is a statistical association between the dose infused megakaryocytic precursors and the time course of the platelet recovery following an allogeneic PBSC transplantation. Twenty-six patients with various hematologic malignancies transplanted from their HLA identical siblings between July 1997 and December 1999 were used. All patients except one with severe aplastic anemia who had cyclophosphamide (CY) alone received busulfan-CY as preparative regimen and cyclosporine-methotrexate for GVHD prophylaxis. Normal healthy donors were given rhG-CSF 10 ,g/kg/day subcutaneously twice daily and PBSCs were collected on days 5 and 6. The median number of infused CD34+, CD41+ and CD42+ cells were 6.61 × 106/kg (range 1.47,21.41), 54.85 × 104/kg (5.38,204.19), and 49.86 × 104/kg (6.82,430.10), respectively. Median days of ANC 0.5 × 109/L and platelet 20 × 109/L were 11.5 (range 9,15) and 13 (8,33), respectively. In this study, the number of CD41+ and CD42+ cells infused much better correlated than the number of CD34+ cells infused with the time to platelet recovery of 20 × 109/L in 26 patients receiving an allogeneic match sibling PBSC transplantation (r = ,0.727 and P < 0.001 for CD41+ cells, r = ,0.806 and P < 0.001 for CD42+ cells, r = ,0.336 and P > 0.05 for CD34+ cells). There was an inverse correlation between the number of infused CD41+ and CD42+ cells and duration of platelet engraftment. Therefore, as the number of CD41+ and CD42+ cells increased, duration of platelet engraftment (time to reach platelet count of , 20 × 109/L) shortened significantly. Based on this data we may conclude that flow cytometric measurement of CD41+ and CD42+ progenitor cells may provide an accurate indication of platelet reconstitutive capacity of the allogeneic PBSC transplant. J. Clin. Apheresis. 16:67,73, 2001. © 2001 Wiley-Liss, Inc. [source]

Collection of peripheral blood stem cells with granulocyte-colony-stimulating factor alone in testicular cancer patients

INTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2000
KISABURO HANAZAWA
Abstract Background: High-dose chemotherapy with the transplantation of peripheral blood stem cells (PBSC) has been performed for the treatment of advanced testicular cancer patients. Recently, it has been reported that, in healthy donors, a large quantity of stem cells can be transferred to peripheral blood using granulocyte-colony-stimulating factor (G-CSF) alone. Therefore, it was decided to try to harvest PBSC from three patients having testicular cancers with G-CSF alone. Methods: The three patients with testicular cancer were 26, 56 and 62-years-old. They had undergone five, two and three cycles of chemotherapy, respectively, but no radiation therapy. Granulocyte colony-stimulating factor was subcutaneously injected (250 ,g) into each patient twice per day for 6 days. Peripheral blood stem cells were harvested for 3 days (days 4,6) and mononuclear cells (MNC), CD34-positive cells and colony-forming units of granulocyte-macrophage (CFU-GM) in PBSC collected by apheresis were measured. Results: Apheresis showed that the total MNC count was 20.2 × 108/kg (range, 10.6,25.9 × 108/kg), the CD34-positive cell count was 0.98 × 106/kg (range, 0.75,1.4 × 106/kg) and the total CFU-GM count was 1.36 × 105/kg (range, 0.25,3.0 × 105/kg). Conclusion: After mobilization of peripheral blood stem cells with G-CSF alone, sufficient amounts of MNC were obtained from testicular cancer patients who had undergone chemotherapy several times. However, sufficient amounts of CD34-positive cells and CFU-GM could not be obtained. These results suggested that the G-CSF dose was not adequate for harvesting sufficient amounts of CD34-positive cells and CFU-GM. [source]

Unrelated cord blood transplantation in children with severe congenital neutropenia

PEDIATRIC TRANSPLANTATION, Issue 6 2009
M. Akif Yesilipek
Abstract:, SCN is an inherited hematological disorder with severe neutropenia and recurrent infections. Although there are some reports that recombinant rhG-CSF improves clinical outcome, allogeneic HSCT appears to be the only curative treatment for these patients. We report here two children with SCN successfully treated by CBT from unrelated donors. They were refractory to rhG-CSF treatment and have no identical family donor. Bu + CY were given as conditioning. Case 1 and Case 2 received 6/6 and 5/6 HLA-matched unrelated umbilical cord blood, respectively. The number of infused nucleated cells was 6, 18 × 107/kg and CD34+ cell number was 3, 74 × 105/kg in Case 1. Those cell numbers were 8, 8 × 107/kg and 5, 34 × 105/kg for Case 2, respectively. Neutrophil/platelet engraftments were 45/49 days in Case 1 and 24/36 days in Case 2. Grade II cutaneous acute GVHD was seen in Case 2 that was treated successfully with prednisolone. Both patients are well with normal hematological findings and full donor chimerism for post-transplant 20 and 24 months, respectively. We conclude that UCB can be considered as a safe source of stem cell in patients with SCN who need urgent HSCT. [source]

Feasibility and long-term results of autologous PBSC transplantation in recurrent undifferentiated nasopharyngeal carcinoma

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2001
Mario Airoldi MD
Abstract Background Recurrent undifferentiated nasopharyngeal carcinoma (UNPC) is a chemosensitive illness. Here we report long-term results of high-dose chemotherapy (HDC) as late intensification, with autologous peripheral blood stem cell (PBSC) support. Methods Six patients (5 men, 1 woman; median age 41years; median ECOG PS = 0) with recurrent UNPC (local, 2; local + nodal, 2; bone metastasis, 2) have been enrolled. All patients had been previously treated with neoadjuvant chemotherapy and radiotherapy; 3 of 4 local relapses had received a re-irradiation. Every patient received three courses of cisplatin + epirubicin and 1 cycle of epirubicin followed by PBSC collection. A median of 7.2 × 106/kg (range, 4.5,18) CD34+ cells were reinfused. HDC was according ICE scheme: ifosfamide, 2.5 g/m2/d, + carboplatin, 300 mg/m2/d, + VP-16, 300 mg/m2/d days 1 through 4. Results After conventional chemotherapy, we had 1 CR (16%), 3 PR (50%), and 2 NC (34%). After HDC, we had 4 CR (66%) ,1 PR (17%), and 1 MR (17%). Toxicity was manageable. After a median follow-up of 30 months (range, 14,50), two patients are alive without disease (34%), one is alive with bone disease (16%), and three (50%) died of disease at 16, 18, and 24 months. Conclusions HDC has an acceptable toxicity, can convert PR in CR, and seems effective, with long-lasting CRs. © 2001 John Wiley & Sons, Inc. Head Neck 23: 799,803, 2001. [source]

Collection of peripheral blood stem cells with granulocyte-colony-stimulating factor alone in testicular cancer patients

Multiple myeloma patients receiving large volume leukapheresis efficiently yield enough CD34+ cells to allow double transplants

JOURNAL OF CLINICAL APHERESIS, Issue 1 2009
A.C. Zubair
Abstract Current protocols for myeloma patients require more than one autologous transplant. We performed a retrospective study to determine the cost-effectiveness of large volume leukapheresis (LVL) compared with standard volume leukapheresis (SVL) collection when two transplants are required. We evaluated 87 patients who underwent a cumulative total of 260 LVL and SVL collections. The median product volume per collection was 356 ml for LVL, and this was significantly higher than the median product volume per collection for SVL (median 149.5 ml, P < 0.001). The median total CD34+ cell yield/kg was 6.4 × 106 for LVL and 5.2 × 106 for SVL. This difference was statistically significant (P = 0.005). Because the target CD34+ cell dose for a single transplant was 3 × 106/kg at our institution, overall the LVL yields enough CD34+ cells that could allow for two transplants. Therefore, more patients in the LVL group were able to undergo a potential second transplant. Because of the reserved cells for a second transplant, LVL patients received significantly less CD34+ cell/kg per transplant than the patients in SVL group (P = <0.001). As a result, LVL group had statistically significant but clinically insignificant delay in neutrophil (P = <0.001) and platelet (P = 0.02) engraftments. Additionally, using LVL instead of SVL to collect ,6 × 106/kg CD34+ cells may potentially save $7,497 per patient. We therefore conclude that LVL is the method of choice for collection of multiple myeloma patients when two transplants are anticipated. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc. [source]

The number of CD34+ cells in peripheral blood as a predictor of the CD34+ yield in patients going to autologous stem cell transplantation

JOURNAL OF CLINICAL APHERESIS, Issue 2 2006
A.L. Basquiera
Abstract The number of CD34+ cells in peripheral blood (PB) is a guide to the optimal timing to harvest peripheral blood progenitor cells (PBPC). The objective was to determine the number of CD34+ cells in PB that allows achieving a final apheresis product containing ,1.5 × 106 CD34+ cells/kg, performing up to three aphereses. Between March 1999 and August 2003, patients with hematological and solid malignancies who underwent leukapheresis for autologous bone marrow transplantation were prospectively evaluated. Seventy-two aphereses in 48 patients were performed (mean 1.45 per patient; range 1,3). PBPC were mobilized with cyclophosphamide plus recombinant human granulocyte-colony stimulating factor (G-CSF) (n = 40), other chemotherapy drugs plus G-CSF (n = 7), or G-CSF alone (n = 1). We found a strong correlation between the CD34+ cells count in peripheral blood and the CD34+ cells yielded (r = 0.903; P < 0.0001). Using receiver-operating characteristic (ROC) curves, the minimum number of CD34+ cells in PB to obtain ,1.5 × 106/kg in the first apheresis was 16.48 cells/,L (sensitivity 100%; specificity 95%). The best cut-off point necessary to obtain the same target in the final harvest was 15.48 cells/,L, performing up to three aphereses (sensitivity 89%; specificity 100%). In our experience, ,15 CD34+ cells/,L is the best predictor to begin the apheresis procedure. Based on this threshold level, it is possible to achieve at least 1.5 × 106/kg CD34+ cells in the graft with ,3 collections. J. Clin. Apheresis 2005. © 2005 Wiley-Liss, Inc. [source]

Large-volume leukapheresis using femoral venous access for harvesting peripheral blood stem cells with the Fenwal CS 3000 Plus from normal healthy donors: Predictors of CD34+ cell yield and collection efficiency

JOURNAL OF CLINICAL APHERESIS, Issue 1 2003
Sang Kyun Sohn
Abstract The current paper reports on the predicting factors associated with satisfactory peripheral blood stem cell collection and the efficacy of large-volume leukapheresis (LVL) using femoral vein catheterization to harvest PBSCs with Fenwal CS 3000 Plus from normal healthy donors for allogeneic transplantation. A total of 113 apheresis procedures in 57 patients were performed. The median number of MNCs, CD3+ cells, and CD34+ cells harvested per apheresis was 5.3 × 108/kg (range, 0.3,11.0 × 108/kg), 3.0 × 108/kg (range, 0.2,6.6 × 108/kg), and 7.9 × 106/kg (range, 0.1,188.9 × 106/kg), respectively. The median collection efficiency of MNCs and CD34+ cells was 49.8% and 49.7%, respectively. A highly significant correlation was found between the collected CD34+ cell counts and the pre-apheresis WBC counts in the donors (P = 0.013), and between the collected CD34+ cell counts and the pre-apheresis peripheral blood (PB) CD34+ cell counts (P<0.001). Harvesting at least >4 × 106/kg CD34+ cells from the 1st LVL was achieved in 44 (77.2%) out of 57 donors and in 19 (90.5%) out of 21 donors with a PB-CD34+ cell count of >40/,l. There was no significant difference in the harvested MNC and CD34+ cell counts between the 1st and 2nd apheresis. The catheter-related complications included catheter obstruction (n = 2) and hematoma at the insertion site (n = 3). Accordingly, LVL using femoral venous access for allogeneic PBSC collection from normal healthy donors would appear to be safe and effective. J. Clin. Apheresis 18:10,15, 2003. © 2003 Wiley-Liss, Inc. [source]

CD41+ and CD42+ hematopoietic progenitor cells may predict platelet engraftment after allogeneic peripheral blood stem cell transplantation

Retrospective comparison of mobilization methods for autologous stem cell transplantation in multiple myeloma,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2009
Hideki Nakasone
The combination of cyclophosphamide and granulocyte-colony stimulating factor (G-CSF) has widely been used to mobilize hematopoietic stem cells (HSCs) for autologous stem cell transplantation (ASCT) for multiple myeloma (MM). Recently, however, alternative approaches such as G-CSF alone or etoposide followed by G-CSF have been investigated. We, therefore, retrospectively analyzed the effects of these mobilization methods on collection yield and disease outcome in ASCT for MM. We reviewed 146 MM patients from whom we intended to collect stem cells. For mobilization, 67, 58, and 21 patients received cyclophosphamide and G-CSF, etoposide and G-CSF, and G-CSF alone (including nonmyelosuppressive chemotherapy followed by G-CSF), respectively. Among them, 136 achieved the target number of HSCs (at least 2 × 106/kg). Lower creatinine and higher albumin levels at diagnosis were significantly associated with successful yield. A lower number of infused HSCs, use of the etoposide for mobilization and high ISS were associated with delayed hematopoietic recovery. The mobilization methods did not significantly affect either the successful collection of more than 2 × 106 CD34-positive cells/kg or PFS after ASCT. G-CSF alone was sufficient for stem cell mobilization for a single ASCT. The optimal approach to collect HSCs in MM remains to be elucidated. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source]

The impact of CD34+ cell dose on platelet engraftment in pediatric patients following unmanipulated haploidentical blood and marrow transplantation,

PEDIATRIC BLOOD & CANCER, Issue 6 2009
Ying-Jun Chang PhD
Abstract Objective Unmanipulated haploidentical blood and marrow transplantation has been developed as an alternative transplant strategy for pediatric patients with hematological diseases. The aim of this study was to investigate the effects of donor and recipient characteristics on hematopoietic recovery in pediatric patients following unmanipulated haploidentical transplantation. Methods Factors correlating with hematopoietic recovery in 133 pediatric patients after unmanipulated haploidentical transplantation were analyzed retrospectively. Results All patients reached an absolute neutrophil count of 500/µl in a median of 12 days (range, 9,49 days). One hundred thirty-three patients reached an untransfused platelet count of more than 20,000/µl in a median of 15 days (range, 7,180 days). Univariate analysis showed five factors associated with platelet engraftment. These were time to transplantation after diagnosis (P,=,0.072), infused nuclear cells/kg of recipient weight (P,=,0.028), CD3+ cells/kg of recipient weight (P,=,0.082), CD4+ cells/kg of recipient weight (P,=,0.083), and CD34+ cells/kg of recipient weight (P,=,0.012). Multivariate analysis showed that infused CD34+ cells/kg of recipient weight (CD34+ cells more than 2.42,×,106/kg vs. less than or equal to 2.42,×,106/kg, HR,=,1.733; 95% CI 1.222,2.549; P,=,0.002) were significantly associated with an increased risk of platelet engraftment. Patients receiving a CD34+ cell dose more than 2.42,×,106/kg had a short time [12 days (range, 7,176 days)] to achieve an untransfused platelet engraftment, compared to 18 days (range, 7,180 days) in patients receiving a lower dose (P,<,0.001). Conclusions Our results suggest that low number of CD34+ cells in allografts is a critical factor associated with delayed platelet engraftment after unmanipulated haploidentical transplantation in pediatric patients. Pediatr Blood Cancer 2009;53:1100,1106. © 2009 Wiley-Liss, Inc. [source]

Hematopoietic and immune recovery after allogeneic peripheral blood stem cell transplantation and bone marrow transplantation in a pediatric population

PEDIATRIC TRANSPLANTATION, Issue 4 2002
Yoshihisa Nagatoshi
Abstract: To compare the hematopoietic and immune recoveries after allogeneic transplantation with different cell sources, we analyzed the recovery patterns of blood components after allogeneic peripheral blood stem cell transplantation (PBSCT) in comparison with that after allogeneic bone marrow transplantation (BMT) in a pediatric population. Sixteen patients received PBSCT, and 24 received BMT between January, 1995 and March, 2000. The patients had acute lymphoblastic leukemia (ALL; n = 22), acute myelogenous leukemia (AML; n = 8), myelodysplastic syndrome (MDS; n = 3), or other diseases (n = 7). The median ages of patients in the PBSCT and BMT groups were 9 yr and 6 yr, respectively. Cyclosporin A (CsA) plus methotrexate or methylprednisolone was used as a graft-vs.-host disease (GvHD) prophylaxis regimen in the PBSCT group, whereas CsA alone or methotrexate alone was used in the BMT group. Circulating lymphocyte numbers and subpopulations determined by flow cytometric analysis were used as markers of immune recovery. In the PBSCT group, the median number of harvested CD34+ cells was 7.25 (range: 1.3,27.6) × 106/kg of the recipient's body weight, while the median number of harvested nucleated cells was 4.7 (range: 3.7,10.5) × 108/kg. All of the patients were engrafted. Myeloid engraftment occurred sooner after PBSCT than after BMT (median number of days to achieve absolute neutrophil counts (ANC) > 0.5 × 109/L; 11 and 15, respectively; p < 0.0001) and similar results were found for platelet engraftment (median number of days to achieve a platelet count of > 20 × 109/L; 12 and 21, respectively; p = 0.004). On the other hand, after PBSCT the absolute numbers of total circulating lymphocytes and lymphocyte subpopulations were not significantly different from those after BMT. The incidence of acute GvHD after PBSCT was the same as that after BMT, while chronic GvHD developed more frequently after PBSCT than after BMT (p = 0.005). In a pediatric population, the indications for PBSCT and BMT should be based on these findings in addition to regard for the donor's safety. [source]

Ifosphamide, etoposide and epirubicin is an effective combined salvage and peripheral blood stem cell mobilisation regimen for transplant-eligible patients with non-Hodgkin lymphoma and Hodgkin disease

BRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2007
Mark J. Bishton
Summary A total of 143 patients with relapsed (n = 90), primary refractory (n = 32) and first line chemotherapy responsive (n = 21) non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD) were treated with IVE (ifosphamide, etoposide and epirubicin) chemotherapy with the intent to proceed to high-dose therapy with either autologous or allogeneic transplantation, following peripheral blood stem cell mobilisation. A major response (complete/partial response) to IVE was seen in 115 patients (80·4%) with 5-year overall survival (OS) and event free survival (EFS) of 53% and 43%, respectively. Subgroup analysis showed overall response rates of 93·1% for HD with a 5-year OS and EFS of 62% and 52% respectively, while NHL showed response rates of 78·0% with 5-year OS and EFS of 50% and 39% respectively. The median number of CD34 +ve cells mobilised following IVE was 7·86 × 106 (range 1·72,42·91 × 106), with 60% mobilising >2 × 106/kg in a single collection. Grade IV neutropenia was seen in 79·6% patients and 77/270 cycles required intravenous antibiotic treatment. We conclude that IVE has a high response rate across a range of refractory and relapsed lymphoma with acceptable toxicity and excellent PBSC mobilising characteristics. [source]