Effects of temperament during handling and social rank on the blood biochemical parameters of common eland (Taurotragus oryx).

Large herbivores are subject to handling and social stress in captivity. These may affect blood biochemical values, which motivated this research. Twelve healthy common eland (Taurotragus oryx) were monitored for 12 months. The animals were handled monthly, and blood samples were collected. Samples from every second month were analysed for 14 blood biochemical parameters. Temperament throughout the handling, as the summation of various behavioural responses, was calculated as a proxy of the stress generated during handling. Social behaviour was recorded each month, and the agonistic interactions were used to calculate the social rank, which was considered a proxy of social stress. Generalised Linear Mixed Models were designed to test the effects of temperament and social rank on the blood biochemical parameters while keeping sex, age, body condition, and body weight as covariates. The results show that the temperament during handling influences blood levels of albumin, alkaline phosphate, blood urea nitrogen, glucose, total bilirubin, and total protein; however, social rank has little influence, affecting just albumin. The ranges observed in the values of these biochemical parameters were still within their reference intervals, implying the absence of pathology or physiological problems during the study. The results suggest that blood biochemical values of physically restrained common eland should be carefully interpreted, even in animals already habituated to routine handling. On the contrary, social rank has low effects on the blood biochemical parameters.

Extending the interval between second vaccination and slaughter: I. Effects on growth, scrotal size and stress responses of immunocastrated ram lambs.

Immunocastration provides a less invasive means of castrating lambs. Considering increasing consumer awareness, the efficacy of this technique on commercial slaughter lambs needs to be further investigated and its effects on growth and stress responses need to be established. This study compared the growth rate, testes size and stress responses of immunocastrated lambs with that of lambs physically castrated with a Burdizzo clamp, as well as intact rams. A total of 40 Dohne Merino ram lambs (average live weight = 45.4±3.68 kg) were randomly allocated to the following four treatment groups: control (intact; R), Burdizzo-castrated (on day 2; B), immunocastrated with a 4-week (ICS4), or a 6-week (ICS6) interval between the second immunocastration vaccination and slaughter. Within the immunocastration treatments, the reaction to vaccination was assessed through injection site scoring, recording the local injection site surface temperature and assigning a walking score. The response to Burdizzo castration was assessed by scoring the reaction during the procedure, testes palpation reaction, walking gait and measuring testis temperature. Additional parameters recorded included BW, serum cortisol concentration, scrotal circumference and rectal temperature. Pain behaviours were described for the short-, medium- and long-term effects after the two methods of castration. Predominantly, tissue-hardening and bruising occurred at the injection sites of immunocastrates, but little effect was observed on walking comfort and no effect on injection site temperature or rectal temperatures. After Burdizzo castration, lambs spent more time in abnormal postures, and from day 3 (D3) to D8 of the trial, discomfort was observed during testes palpation and walking in B lambs. Serum cortisol concentrations were elevated in B lambs on D3 and D15, indicating physiological stress. Thus, immunocastration improved the welfare of castrated lambs as assessed by cortisol secretion, scrotal swelling and pain behaviours, without influencing growth rate.

Extending the interval between second vaccination and slaughter: II. Changes in the reproductive capacity of immunocastrated ram lambs.

Immunocastration improves the welfare of castrated commercial slaughter lambs; however, the time-point at which this technique influences semen quality and sperm production has not yet been established for various vaccination schedules. Furthermore, the effect of extended intervals between second vaccination and slaughter needs to be investigated regarding continued testosterone suppression in immunocastrated lambs. The effect of extending the interval between second immunocastration vaccination and slaughter from four to six weeks on the reproductive capacity of Dohne Merino lambs was examined. A total of 40 Dohne Merino lambs were stratified according to initial weight (45.4±3.68 kg) and randomly assigned to four treatments that included intact control rams (R), Burdizzo-castrated lambs (B) and lambs immunocastrated with either four (ICS4) or six (ICS6) weeks between second vaccination and slaughter. Blood and semen samples were collected throughout the study period to determine serum testosterone concentrations, evaluate semen quality and assess sperm viability. Semen samples from R showed improvement over the trial. Throughout the collection period, B lambs had low serum testosterone concentrations, poor sperm motility and sperm viability, as expected. However, a slight increase in the percentage of live sperm in semen samples from B lambs towards the end of the collection period indicated poor success rates of the technique in some lambs. Burdizzo-castration also caused testes tissue necrosis and abscessing, indicating physiological stress. Semen appearance scores varied for both immunocastrated treatments, but the mass motility scores decreased over time. The ICS6 lambs showed a consistent and continuous decline in serum testosterone concentrations and sperm viability, with an increased percentage of dead abnormal sperm in the semen samples at the end of the study. The ICS4 treatment was successful in interrupting serum testosterone production and reducing semen quality; however, not as consistently as the ICS6 treatment. Primary immunocastration vaccination influenced serum testosterone concentrations but consistently low levels were only realised for both treatments after secondary vaccination. Although all castration treatments influenced testes size and colour, the six-week vaccination-to-slaughter interval caused a greater decrease in testes cut surface L* (lightness) colour values and in seminiferous tubule circumference. Extending the interval between second immunocastration vaccination and slaughter resulted in a more consistent and reliable influence on reproductive capacity of immunocastrated lambs. Thus, immunocastration is a suitable alternative to Burdizzo-castration regarding the interruption of testosterone production and testis functioning.

Growth responses of entire and immunocastrated male pigs to dietary protein with and without ractopamine hydrochloride.

The interaction between dietary balanced protein, ractopamine (RAC) and Improvac (IMP) on the growth response of 120 individually penned male PIC© pigs was evaluated. The pigs entered the trial at 16 weeks of age and were assigned to 12 treatments using a 2×2×3 factorial design. Three balanced protein diets, formulated with standard illeal digestible lysine levels of 7.50 (low), 9.79 (medium) and 12.07 g/kg (high), were fed from 20 weeks. Improvac was administered at 16 and 20 weeks, the booster being given 4 weeks before slaughter. Ractopamine was supplemented at 10 mg/kg to the applicable treatments from 20 weeks. Live weight, backfat depth and food intake were measured on a weekly basis. Primary vaccination had no influence on the parameters measured. Immunocastration, RAC and higher protein diet treatments increased weight gain, but food intake was increased only with the use of IMP. Although weight gain increased in IMP-treated males, the increased feed intake resulted in their feed conversion efficiencies (FCE) being inferior to the intact controls. Feeding RAC only benefitted FCE when a high or medium protein diet was fed. Immunocastrates deposited more backfat after the booster vaccination than did entire males. Thus the cost of using RAC, IMP and of increasing dietary protein content needs to be weighed up against the additional revenue generated through the use of these interventions.

Ophthalmic drug delivery systems--recent advances.

Eye-drops are the conventional dosage forms that account for 90% of currently accessible ophthalmic formulations. Despite the excellent acceptance by patients, one of the major problems encountered is rapid precorneal drug loss. To improve ocular drug bioavailability, there is a significant effort directed towards new drug delivery systems for ophthalmic administration. This chapter will focus on three representative areas of ophthalmic drug delivery systems: polymeric gels, colloidal systems, cyclodextrins and collagen shields. Hydrogels generally offer a moderate improvement of ocular drug bioavailability with the disadvantage of blurring of vision. In situ activated gel-forming systems are preferred as they can be delivered in drop form with sustained release properties. Colloidal systems including liposomes and nanoparticles have the convenience of a drop, which is able to maintain drug activity at its site of action and is suitable for poorly water-soluble drugs. Among the new therapeutic approaches in ophthalmology, cyclodextrins represent an alternative approach to increase the solubility of the drug in solution and to increase corneal permeability. Finally, collagen shields have been developed as a new continuous-delivery system for drugs that provide high and sustained levels of drugs to the cornea, despite a problem of tolerance. It seems that new tendency of research in ophthalmic drug delivery systems is directed towards a combination of several drug delivery technologies. There is a tendency to develop systems which not only prolong the contact time of the vehicle at the ocular surface, but which at the same time slow down the elimination of the drug. Combination of drug delivery systems could open a new directive for improving results and the therapeutic response of non-efficacious systems.

Carcass traits and cutting yields of entire and immunocastrated pigs fed increasing protein levels with and without ractopamine hydrochloride supplementation.

The objective of this study was to determine the effects of increasing balanced protein, with and without ractopamine hydrochloride (RAC), in the finisher diets of immunocastrates on their carcass cutting yields and respective muscle, fat, and bone proportions. Carcass traits and yields of 120 individually housed entire male pigs and immunocastrates were evaluated following a 2 × 2 × 3 factorial design. Vaccination occurred at 16 and 20 wk of age and slaughtering at 24 wk. Up until 20 wk of age, all pigs received a commercial grower diet. Low-, medium-, and high-protein (7.50, 9.79, and 12.07 g standardized ileal digestible [SID] lysine/kg, respectively) diets were then fed for the last 28 d with RAC supplemented at 0 or 10 mg/kg. Immunocastration and RAC supplementation increased ( = 0.003 and = 0.017, respectively) the live weight at slaughter. The interaction between sex and protein ( = 0.039) for caliper backfat depths showed greater backfat depths in immunocastrates fed medium protein whereas RAC decreased ( = 0.027) the caliper backfat depth. Feeding RAC increased the trotters ( = 0.040), tenderloins (fillets; < 0.001), shoulder ( = 0.002), hindquarter ( = 0.026), loin ( = 0.028), and belly ( = 0.044) percentages. The shoulder ( < 0.001), hindquarter ( < 0.001), and loin ( = 0.005) muscle percentages were increased and the hindquarter fat percentages were decreased ( = 0.032) with RAC supplementation. Immunocastration increased the belly cut ( = 0.006), loin fat ( < 0.001), and belly fat ( < 0.001) percentages. Therefore, carcass cutting and lean yields can be improved by RAC supplementation while decreasing the backfat depth, and the increase in backfat due to immunocastration could be avoided with the correct dietary protein level.

Physical meat quality and chemical composition of the Longissimus thoracis of entire and immunocastrated pigs fed varying dietary protein levels with and without ractopamine hydrochloride.

Physical and chemical attributes of the Longissimus thoracis (LT) of 96 PIC(©) entire (E) and immunocastrated (C) pigs were evaluated. The study followed a 2 × 2 × 3 factorial design where three diets of low, medium and high proteins (7.50, 9.79 and 12.07 g digestible lysine/kg) were fed either with (10mg/kg) or without ractopamine (RAC) for the last 28 days of growth. Vaccination of C occurred at 16 and 20 weeks and slaughtering at 24 weeks of age. The LTs were analysed for moisture, protein, fat and ash contents as well as CIE L*, a*, b* colour, drip loss, cooking loss and Warner-Bratzler shear force (WBSF). Various sex and protein interactions were observed for LT protein content, L* values and WBSF. Cooking loss was decreased in C and by the medium protein diet. Feeding RAC increased WBSF values, whilst decreasing a* and b* values. However, the differences observed are minor and might be considered negligible when evaluated by a consumer.

The role of primary varicose veins in venous ulceration.

"Venous" ulceration is usually ascribed to deep venous insufficiency. We record the cases of 20 patients with 23 ulcers without a history suggestive of deep vein disease who were found to have a normal deep venous system when evaluated by Doppler ultrasound, ambulatory venous pressures, and photoplethysmography. All had gross varicose veins present for many years (mean 24 years; range 10 to 35 years), and only 14 limbs had incompetent calf perforating veins. Effective treatment is facilitated by recognition of the relationship of varicose ulcer to superficial venous disease, usually incompetence of the saphenofemoral junction, with or without the presence of incompetent calf perforating veins.

Prostaglandin E1 in severe Raynaud's phenomenon.

Twenty-one patients with severe Raynaud's phenomenon were treated on 29 occasions with prostaglandin E1 (PGE1), a potent vasodilator and pyrogen. A history of finger sepsis or necrosis was absent in 8 (group I) and present in 13 (group II). Three group I and eight group II patients had an associated connective tissue disease, and previously eight upper limbs had been sympathectomized in six group I patients and 14 upper limbs in eight group II patients. A total of 12 fingers had been amputated in six group II patients. Treatment comprised antibiotics for sepsis, PGE1 intravenously for 72 hours, and subsequent surgical debridement of septic and necrotic tissue in 30 fingers of eight group II patients under general anesthesia. Finger skin temperature measured half-hourly in a temperature-controlled ward cubicle (23.7 degrees +/- 0.7 degrees C), Doppler-detectable digital arterial flow, and finger/brachial systolic pressure index with local finger cooling to 10 degrees C were not improved by the administration of 0.9% saline for 72 hours, but were all significantly improved after PGE1 administration. Finger skin temperature was significantly elevated 11 weeks after treatment. The symptoms did not improve after PGE1 administration in group I patients but did improve in 12 of 13 group II patients. No finger deteriorated, and all debrided fingers healed after surgery. Nail bed removal in 11 fingers met with patient approval and prevented recurrent sepsis and necrosis. PGE1 provides a means of increasing finger blood flow during acute exacerbations of finger sepsis and necrosis; unlike sympathectomy, it is a minor procedure without prolonged side effects and is repeatable.

Significance of popliteal reflux in relation to ambulatory venous pressure and ulceration.

Fifty-one patients (55 limbs) who had had deep venous thrombosis (DVT) extending into the femoral or iliofemoral segment three to five years earlier and ten limbs of ten healthy volunteers were studied. The ambulatory venous pressure (AVP) was measured by inserting a needle in a vein on the foot; the presence of reflux in the popliteal vein was determined by a directional Doppler ultrasonic blood velocity detector. All patients had ascending venography. The results suggest that the most important factor in determining the AVP and ulceration in postthrombotic limbs is the condition of the popliteal valves. Ulceration does not occur even in the presence of occlusion if the popliteal valves are competent. The extent of DVT and recanalization or the failure of recanalization is of secondary importance.

Plasma levels of clobazam after 10-, 20-, and 40-mg tablet doses in healthy subjects.

It is evident that substantial intersubject and intrasubject varition in the bioavailability of clobazam exists following ingestion of 10, 20 and 40 mg doses in these 12 volunteers. Peak concentrations and area under the plasma level-time curve were directly proportional to the dose of clobazam and the mean plasma half-life of clobazam was about 18 hours regardless of dose administered. The t1/2 value was less than that previously reported, as the current results allow differentiation of parent drug from metabolites. This 18 hr t1/2 compares favorably with the half-life of other benzodiazepines.

Plasma levels of clobazam after three oral dosage forms in health subjects.

As can be seen from the tables, the terminal half-life of clobazam is about 50 hours, and from a solid dosage form the peak plasma level occurs approximately 1.5 hours after ingestion. Thus, there is a significant, yet relatively short, dosage form delay effect when the solid dosage forms are compared to the rapidly available solution of the drug. However, based on the areas under the curve, comparison of the solid dosage forms with the solution indicates that the fraction of clobazam absorbed is 1. Pupil diameter measurement at 2, 4, and 6 hours after ingestion of clobazam correlated well with the plasma levels at these times. Pupils were constricted to the highest degree at 2 hours and approached the initial pupillary diameter at the 6-hour measurement.

Plasma level studies of penbutolol after oral dose in man.

Plasma levels of penbutolol (HOE 893d) were determined in eight healthy adult male subjects after oral administration of 50-mg capsules. Fast absorpiton of the drug from the gastrointestinal tract was indicated by the rapid increase in plasma levels during the absorption phase, with a peak time at about 1 hour after dosing in all subjects. After the peak level, plasma concentrations declined biexponentially, with an average half-life of 2.5 and 27 hours for the fast and slow disposition phases, respectively. These values were in good agreement with data previously found for this drug. Cumulative excretion of intact drug in the urine of the eight subjects during 72 hours after dosing was less than 4 per cent, except for one subject who excreted 9.82 per cent of the dose. Large individual variations were found for area under the plasma level curves, disposition rates, and amounts of intact drug excreted in the urine. Significant pharmacologic effects were noted in all eight subjects at the 50-mg dose level, and mild side effects were evident in one half of these subjects. The average drop in blood pressure and pulse rate for all subjects was 26/18 mm Hg and 19 beats per minute, respectively.

Codiffusion of propylene glycol and dimethyl isosorbide in hairless mouse skin.

The in vitro percutaneous fluxes of propylene glycol (PG), cis-oleic acid (OA) and dimethyl isosorbide (DI) were determined and their effect on nifedipine (N) flux and lag time evaluated. PG, OA and DI flux through hairless mouse (HM) skin was measured in vitro by beta-scintigraphy and N permeation was measured by HPLC under finite and infinite dose conditions. Evaluation of each of the solvents separately showed that pure DI possessed the inherent ability to traverse the skin (12% in 24 h). For the tested formulation after 24 h, 57% of the PG and 40% of the DI had permeated across the skin with nearly linear permeation between 4 and 18 h and the relative order of permeation was PG > DI > N. DI permeation was further aided in the presence of PG and OA. N flux was dependent on concomitant solvent permeation. Over a 24-h test period a dose dependent response was observed for N, with 4.9-15.6 mg of N delivered from the lowest and highest doses, respectively, and the highest dose yielding zero-order flux of 146 (g/h per cm2).

Correlation of urinary excretion with in vitro dissolution using several dissolution methods for hydrochlorothiazide formulations.

Four different hydrochlorothiazide formulations were prepared, and cumulative urinary hydrochlorothiazide excretion was determined in a crossover study using six volunteers. A comparison of in vivo results showed that one formulation (Forumulation D) was significantly different from the others at 2, 3, 4, 5, 8, and 14 hr. A dissolution study was conducted on each formulation using the flask, USP basket, and magnetic basket methods at agitation speeds of 50, 100, and 150 rpm. Formulation D was significantly different from other formulations when determined using the USP basket method at 150 rpm and a sampling time of 10 min; the USP basket method at 100 rpm and a sampling time of 100 min; the flask method at 100 rpm and sampling times of 30, 40, 60, and 120 min; and the flask method at 150 rpm and sampling times of 30 and 40 min. Significant in vitro and in vivo correlations were found using a regression analysis and F test. With a correlation coefficient and 95% confidence intervals, it was established that the USP basket method at 150 rpm was the best predictor of urinary hydrochlorothiazide excretion among the dissolution methods tested.

Bioavailability and dissolution parameters of seven lithium carbonate products.

Seven commercial products and a standard powder of lithium carbonate were administered to healthy human volunteers in a crossover study. An analysis of variance of saliva levels and urinary excretion as well as an analysis of variance of peak concentration and the area under the curve from 0 to 24 hr for the saliva levels showed no significant difference between the powder and products, but a significant difference between subjects. A significant difference was found between the time of peak saliva levels, which was attributed to faster powder absorption. A dissolution study using the USP basket method at 50 and 100 rpm and the Levy beaker at 50 rpm also showed no significant difference between products after the lag time for the capsule dosage forms. With a regression analysis, a significant correlation was found between the saliva levels of the products at 2 hr and dissolution in the USP basket at 50 rpm at 4 min.

Correlation of aspirin excretion with parameters from different dissolution methods.

The cumulative urinary excretion of four different aspirin products (two tablets, a capsule, and a timed-release tablet) was determined in a crossover study using five subjects. Comparison of in vivo results showed a significant difference in cumulative urinary excretion levels at only 1 hr. The excretion from the two regular tablets was significantly different from the timed-release tablet, but the capsule showed no significant difference from the other three products. Each product was tested in the USP, Levy beaker, and the regular and large magnetic basket dissolution apparatus. Analysis of variance of the in vitro results showed a significant difference between the aspirin products and the dissolution methods at selected times. In vitro comparison with in vivo results for the four products showed that a regression analysis can be used to determined which dissolution methods produce a significant correlation with urinary excretion.

Interaction of sulindac and metabolite with human serum albumin.

The binding of the newly developed nonsteroidal anti-inflammatory agent sulindac and its principal active metabolite, sunlindac sulfide, to human serum albumin was investigated. With the methods of dialysis, fluorescence quenching, and difference spectrophotometry, it was found that both agents were extensively bound to albumin. The binding affinity of the metabolite was considerably higher than that of sunlindac and this effect may be related to its prolonged plasma half-life versus the parent drug. Sulindac binding was albumin concentration dependent, which gave rise to an unfamilar Scatchard analysis of the dialysis data.

Glass-rubber transitions of cellulosic polymers by dynamic mechanical analysis.

The glass-rubber transition temperatures (Tg) of several cellulosic polymers [hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC)] have been examined using dynamic mechanical analysis (DMA). The melting temperatures of the above polymers were examined using a hot stage melting point apparatus. The primary Tg of three different grades of HPMC (3, 6, and 15 cps) were determined to be 160, 170, and 175 degrees C, respectively. The primary Tg of the HEC film was determined as 120 degrees C. The HPC film did not indicate a primary Tg. These cellulosic polymers also displayed secondary transitions. Hot stage melting of HPMC and HPC was observed at 225 to 254 degrees C and 190 to 195 degrees C, respectively. The HEC powder did not exhibit a melting temperature, but became darker at temperatures greater than 150 degrees C.

Transdermal drug delivery systems of albuterol: in vitro and in vivo studies.

In vitro and in vivo experiments were conducted with double- and single-layer albuterol transdermal pads designed for once-a-day application. In the in vitro experiments, dissolution of albuterol from pads and permeation of albuterol through hairless mouse skin were monitored. In the in vivo experiments, pads were applied to the chest area of four female rhesus monkeys (Macaca mulata), and an albuterol aqueous solution was injected into the saphenous vein of the same animals in a crossover design. The amount lost from pads applied to monkeys was monitored by analysis of pad residue. Blood samples were withdrawn at regular intervals and analyzed by a high-performance liquid chromatography-fluorescence method. Skin irritation due to the pad was measured by a modified Draize score test. The amounts released from the two formulations were similar. The amount released was, however, dependent on the technique used and decreased in the following manner: pad dissolution greater than in vivo amount lost from pads applied to monkeys greater than in vitro permeation through hairless mouse skin. The pharmacokinetic parameters determined after intravenous and transdermal administration were as follows: terminal half-life, 2.26 +/- 0.45 h; apparent volume of distribution, 1935 +/- 37.2 mL.kg-1; and total body clearance, 612.0 +/- 118 mL.h-1.kg-1. The average concentrations in serum after application of single- and double-layer pads were 44.60 +/- 16.40 and 62.50 +/- 8.00 ng/mL, respectively. Further, the amount lost from pads applied to monkeys correlated with the respective amount absorbed in monkeys, as calculated from the average concentration in serum and clearance.(ABSTRACT TRUNCATED AT 250 WORDS)