► Three degrees of needle rotation were examined for effects in Chinook salmon. ► Mortality, tag loss, wound extent, healing, and infection indicators were measured. ► There were no mortalities, tag ...loss, or indications of infection. ► The 90-degree needle rotation through Day 7 produced the smallest wound extent. ► Healing occurred by Day 7 and progressed by Day 14 for 90- and 180-degree rotation treatments.
Most telemetry studies require the implantation or attachment of passive transponders or active transmitters to monitor and assess fish stocks and conservation to gain an understanding of fish physiology and behavior. As new telemetry technologies become available, it is imperative to study the effect of the transmitter or implantation technique on species of interest. In this study, we investigated the effects of needle axial or bevel rotation (0-, 90-, 180-degree) on wound extent and healing, and tag loss in juvenile Chinook salmon injected with an 8-gauge needle, which is required for implantation of the injectable Juvenile Salmon Acoustic Telemetry Systems acoustic transmitter and some passive integrated transponders (PITs). Although the wounds were not closed after injection (e.g., with sutures or glue), there were no mortalities, dropped tags, or indications of fungus, ulceration, or redness around the wound. No axial rotation (0-degrees) resulted in the PIT tag frequently misloading or falling out before injection. On Day 0 and post-implantation Day 7, the 90-degree bevel rotation produced a significantly smaller wound extent than the 180-degree bevel rotation. Given the wound extent compared to size of fish, we recommend researchers should consider a 90-degree rotation over the 180-degree rotation when injecting transmitters.
The health of dairy cows given bovine somatotropin (bST) for one lactation was evaluated in 28 commercial herds located in four regions of the United States. At least six herds were in a region and ...at least one herd/ region contained fewer than 60 cows. Cows (n = 1213) were assigned randomly to control or bST groups and were treated beginning in wk 9 to 10 of lactation and every 14 d until dry-off or d 400 of lactation. Management was according to site practices. Cows were observed for health-related signs by farm personnel daily and by the herd veterinarian biweekly. Average 305-d test-day milk yields were 932kg greater for bST-treated cows. Pregnancy rates, days open, twinning, cystic ovaries, or abortions were unaffected by treatments. Supplementation of cows with bST had no effect on total mastitis cases, total days of mastitis, duration of mastitis, or the odds ratio of a cow to develop mastitis. Cows supplemented with bST used more medications for health events other than mastitis. This usage was associated primarily with treatments for disorders of the foot and hock. Supplemented cows had a slight increase in foot disorders. There was no effect of supplementation with bST on culling from the herd or removal from study. Overall, the results confirm that label directions for bST are adequate for safe use under field conditions. All clinical signs observed in this study occur normally in dairy herds and were managed in cows supplemented with bST.
The confined fluid-filled labyrinth of the human inner ear presents an opportunity for introduction of gene therapy reagents designed to treat hearing and balance dysfunction. Here we present a novel ...model system derived from the sensory epithelia of human vestibular organs and show that the tissue can survive up to 5 days in vitro. We generated organotypic cultures from 26 human sensory epithelia excised at the time of labyrinthectomy for intractable Meniere's disease or vestibular schwannoma. We applied multiply deleted adenoviral vectors at titers between 10(5) and 10(8) viral particles/ml directly to the cultures for 4-24 h and examined the tissue 12-96 h post-transfection. We noted robust expression of the exogenous transgene, green fluorescent protein (GFP), in hair cells and supporting cells suggesting both were targets of adenoviral transfection. We also transfected cultures with a vector that carried the genes for GFP and KCNQ4, a potassium channel subunit that causes dominant-progressive hearing loss when mutated. We noted a positive correlation between GFP fluorescence and KCNQ4 immunolocalization. We conclude that our in vitro model system presents a novel and effective experimental paradigm for evaluation of gene therapy reagents designed to restore cellular function in patients who suffer from inner ear disorders.
Abstract Tetrapyrroles are multisided natural products which are of relevance in clinical medicine. Owing to their specific accumulation in tumour tissue, porphyrins, metalloporphyrins and chlorins ...have been used as in photodynamic therapy and optical imaging. Moreover, their specific uptake into inflammatory atheromatous plaques via LDL endocytosis has been reported. The present study is concerned with the synthesis of68 Ga labelled porphyrin derivatives and an in vitro assessment of the utility of radiotracers in positron emission tomography. A set of five porphyrin derivatives were labelled using68 Ga from a commercially obtained radionuclide generator. Dedicated post-processing of the generator eluate was conducted to allow for labelling in aqueous media and also under anhydrous conditions. Challenge studies and incubation in human serum confirmed the stability of the tracers. Plasma protein binding was investigated in order to confirm the presence of freely diffusible radioligand in plasma. A preliminary microPET study in a tumour-bearing rat resulted in a clear visualisation of the tumour.
Tetrapyrroles are multisided natural products which are of relevance in clinical medicine. Owing to their specific accumulation in tumour tissue, porphyrins, metalloporphyrins and chlorins have been ...used as in photodynamic therapy and optical imaging. Moreover, their specific uptake into inflammatory atheromatous plaques via LDL endocytosis has been reported. The present study is concerned with the synthesis of 68Ga labelled porphyrin derivatives and an in vitro assessment of the utility of radiotracers in positron emission tomography. A set of five porphyrin derivatives were labelled using 68Ga from a commercially obtained radionuclide generator. Dedicated post-processing of the generator eluate was conducted to allow for labelling in aqueous media and also under anhydrous conditions. Challenge studies and incubation in human serum confirmed the stability of the tracers. Plasma protein binding was investigated in order to confirm the presence of freely diffusible radioligand in plasma. A preliminary microPET study in a tumour-bearing rat resulted in a clear visualisation of the tumour.
To establish the naturally occurring range of insulin-like growth factor-I concentrations in bovine milk, samples from individual cows (n = 409) managed on five Missouri dairy herds were assayed. ...Parity, stage of lactation, and farm affected milk insulin-like growth factor-I concentration. Milk insulin-like growth factor-I concentration was higher in early lactation than mid and late lactation with concentrations in multiparous cows exceeding those in primiparous cows. Insulin-like growth factor-I concentration was negatively correlated to milk production the day of sample collection (r = –.15) and not correlated to predicted 305-d milk yields.
Unprocessed bulk tank milk samples (n = 100) from a commercial processing plant had a mean concentration of insulin-like growth factor-I in milk of 4.32ng/ml with a range of 1.27 to 8.10ng/ml. This distribution was similar to the range detected in samples from individual cows, but values were lower than those reported for human milk. Concentration of insulin-like growth factor-I in milk was not altered by pasteurization (at 79°C for 45s). However, insulin-like growth factor-I was undetectable in milk heated to temperatures (121°C for 5min) required for infant formula preparation or in commercially available infant formula. These data indicated that insulin-like growth factor-I is a normal but quantitatively variable component of bovine milk that is not destroyed by pasteurization but is undetectable in infant formula. Concentration of insulin-like growth factor-I in bovine milk is lower than concentrations reported for human milk yet similar to those reported for human saliva. Farm, stage of lactation, and parity all have large effects on variability of insulin-like growth factor-I concentration of bovine milk.
Thirty-eight dry, pregnant Jersey cows were assigned to diet and bST treatment in a 2 × 2 factorial design. During the dry period, half of the cows were fed a normal TMR (0.4% Ca; 0.3 to 0.4% P), and ...half of the cows were fed a high Ca TMR (1.5 to 1.6% Ca; 0.4 to 0.7% P). The high Ca diets were designed to induce milk fever and were relatively cationic (194 to 293 meq/kg) compared with the normal diets (–131 to 30 meq/kg). A standard dairy diet was fed to all cows postcalving. Cows received subcutaneous injections of either an oil-based excipient or 500mg of bST in an oil-based excipient every 14 d from 28 d before expected calving until approximately 14 d postcalving. Peripartal bST treatment decreased the incidence of clinical mastitis, did not affect incidence of milk fever, and increased the duration, but not the incidence, of ketosis in mature Jersey cows. Blood data confirmed the clinical responses and indicated that treated cows mobilized more bone Ca than did controls, as was evidenced by increased hydroxyproline concentrations. Treatment with bST did not affect blood concentrations of 1,25-dihydroxyvitamin D, Ca, or Mg. High Ca diets increased the incidence of milk fever and downer cow syndrome compared with normal diets. The effect of bST on mastitis and milk production must be considered as preliminary given the small size of the study. Although bST treatment increased Ca mobilization, the effect was insufficient to prevent milk fever in this model.
Eighty-two lactating Holstein cows in their first, second, or third lactation received either one, three, or five concurrent i.m. injections of a unit dose (.6g) of zinc methionyl bST (sometribove) ...or five doses of the vehicle. Injections were given at 14-d intervals from 60±3 d postpartum until the end of lactation or necropsy. Thirty-eight animals were continued on treatment for a 2nd yr Sometribove did not affect the incidence of ketosis, milk fever, tetany, or pneumonia. Digestive disorders, primarily cows going off feed, were increased by bST during yr 1 only. The incidence of lameness was increased by bST in some time frames because of an increase in the 3.0-g bST group. Lameness was not associated with treatment-specific histopathologic changes or with abnormalities in cartilage or bone. Reproductive health generally was unaffected by treatment, but delayed conception and increased incidence of abortion were noted, Incidence of cystic ovaries was unaffected by bST. Pregnancy rates were decreased during the 100-d breeding interval of yr 1 but not during the 215-d interval of yr 2. The incidence of clinical mastitis was increased by bST, primarily at the 3.0-g dose. During the 2-yr study, 0, 3, 3, and 2 cows died or became moribund on 0, .6, 1.8, and 3.0g of bST, respectively. Health issues identified for further evaluation included lameness and clinical mastitis for the 3.0-g group and early removal from the herd and decreased reproductive performance for all bST groups. Bovine somatotropin caused no treatment-specific toxic effects in dairy cows even at 3.0g every 14 d.
Two studies were designed to examine the pharmacokinetic and galactopoietic potency of three molecular variants of recombinant-derived bovine GH (rbGH): Met1, Leu127-bGH, Ala1, Val127-bGH and Ala1, ...Val127, His133-bGH. Histidine substitution for arginine at residue 133 of rbGH was shown to impart thrombin resistance. In a Latin square design, nine lactating Holstein cows received a 25 mg rbGH bolus infusion via the jugular vein followed by frequent blood sampling over the next 12 h. The serum GH concentration data were found to fit a two-compartment open model. Neither primary nor secondary kinetic parameter estimates differed significantly (P > 0.05) among the three rbGH variants. Thus, the disposition of GH concentration at time t was described by the equation C(t) = (1295.5 micrograms/l) (e-(0.11/min)(t)) + (317.3 micrograms/l)(e-(0.03/min)(t)). Overall averages were: area under the curve = 27.1 mg.min per l, clearance = 0.15 litres/min per 100 kg and volume of distribution of the central compartment = 2.59 litres/100 kg. The t 1/2 for the two compartments averaged 8.2 and 29.1 min. In the second study, 36 lactating Holstein cows received i.m. injections of one of four oil-based formulation treatments: control vehicle or 500 mg of one of the three rbGH variants every 14 days for 42 days. Average and maximum serum GH concentrations and area under the curve estimates were increased by approximately 3-6 micrograms/l, 5-15 micrograms/l and 40-90 micrograms.day per 1 respectively. Ala1, Val127 rbGH treatments elicited greater blood GH concentrations than Met1, Leu127-bGH when administered in an oil-based formulation. Blood GH responses did not directly translate into milk response differences, possibly due to differences in biopotency or receptor availability. Thrombin resistance resulting from substitution of histidine at position 127 of rbGH did not affect blood GH pharmacokinetic parameters or milk response over other rbGH variants.
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