Milk processing quality of suckled/milked goats: effects of milk accumulation interval and milking regime.

Milk with a high concentration of fat and casein is required for cheese production, and these components have a major impact for both quality and yield of the curd. Recent observations have shown that suckling can elevate milk fat concentration in goats and our aim was therefore to check the hypothesis that animal welfare and cheese-processing properties of goat milk could be optimised by appropriate management of suckled/milked goats. Twelve Swedish dairy goats were kept together with one kid each in 4 different mixed management-systems (milking combined with partial suckling) in a cross-over design. Two milk accumulation intervals were tested; Short = dams and kids were together for 16 h (T16) and Long = ; dams and kids were together for 8 h (T8 h). In addition, two milking regimes were used; Suckled Before Milking = S and Milked Before Suckling = M. Milk accumulation interval referred to how long dams and kids were separated. The milk yield available for processing (milk offtake), was weighed and analysed from each milking occasion and the suckled milk yield was estimated by a weigh-suckle-weigh method (WSW) in combination with observing the suckling behaviour during the free suckling periods. Milking managements, such as 'suckling before milking (S)', increased milk fat concentration compared to milking before suckling (M) and 'Short accumulation treatments (T16)' gave higher milk fat, casein concentration and individual curd yield (%) compared to the 'Long accumulation treatment (T8)'. The total individual curd yield (g) was the same despite treatment, but the animal welfare was most likely higher in T16 where dams and kids spent more time together.

Pharmacokinetics of meloxicam in adult goats and its analgesic effect in disbudded kids.

The pharmacokinetics and analgesic effect of the nonsteroidal anti-inflammatory drug meloxicam (0.5 mg/kg) in goats were investigated. In a randomized, cross-over design the pharmacokinetic parameters were investigated in adult goats (n = 8) after single intravenous and oral administration. The analgesic effect was evaluated in kids using a randomized, placebo controlled and blinded protocol. Kids received meloxicam (n = 6) once daily and their siblings (n = 5) got isotonic NaCl intramuscularly while still anaesthetized after cautery disbudding and injections were repeated on three consecutive days. In the adult goats after intravenous administration the terminal half-life was 10.9 ± 1.7 h, steady-state volume of distribution was 0.245 ± 0.06 L/kg, and total body clearance was 17.9 ± 4.3 mL/h/kg. After oral administration bioavailability was 79 ± 19%, C(max) was 736 ± 184 ng/mL, T(max) was 15 ±5 h, although the terminal half-life was similar to the intravenous value, 11.8 ± 1.7 h. Signs of pain using a visual analogue scale were smaller in kids treated with meloxicam compared with kids treated with placebo on the first day after disbudding, but subsequently no difference in pain was noticeable. Plasma cortisol and glucose concentrations did not differ between the two groups.

High temporal resolution tracing of photosynthate carbon from the tree canopy to forest soil microorganisms.

Half of the biological activity in forest soils is supported by recent tree photosynthate, but no study has traced in detail this flux of carbon from the canopy to soil microorganisms in the field. Using (13)CO(2), we pulse-labelled over 1.5 h a 50-m(2) patch of 4-m-tall boreal Pinus sylvestris forest in a 200-m(3) chamber. Tracer levels peaked after 24 h in soluble carbohydrates in the phloem at a height of 0.3 m, after 2-4 d in soil respiratory efflux, after 4-7 d in ectomycorrhizal roots, and after 2-4 d in soil microbial cytoplasm. Carbon in the active pool in needles, in soluble carbohydrates in phloem and in soil respiratory efflux had half-lives of 22, 17 and 35 h, respectively. Carbon in soil microbial cytoplasm had a half-life of 280 h, while the carbon in ectomycorrhizal root tips turned over much more slowly. Simultaneous labelling of the soil with (15)NH(+)(4) showed that the ectomycorrhizal roots, which were the strongest sinks for photosynthate, were also the most active sinks for soil nitrogen. These observations highlight the close temporal coupling between tree canopy photosynthesis and a significant fraction of soil activity in forests.

Large-scale forest girdling shows that current photosynthesis drives soil respiration.

The respiratory activities of plant roots, of their mycorrhizal fungi and of the free-living microbial heterotrophs (decomposers) in soils are significant components of the global carbon balance, but their relative contributions remain uncertain. To separate mycorrhizal root respiration from heterotrophic respiration in aboreal pine forest, we conducted a large-scale tree-girdling experiment, comprising 9 plots each containing about 120 trees. Tree-girdling involves stripping the stem bark to the depth of the current xylem at breast height terminating the supply of current photosynthates to roots and their mycorrhizal fungi without physically disturbing the delicate root-microbe-soil system. Here we report that girdling reduced soil respiration within 1-2 months by about 54% relative to respiration on ungirdled control plots, and that decreases of up to 37% were detected within 5 days. These values clearly show that the flux of current assimilates to roots is a key driver of soil respiration; they are conservative estimates of root respiration, however, because girdling increased the use of starch reserves in the roots. Our results indicate that models of soil respiration should incorporate measures of photosynthesis and of seasonal patterns of photosynthate allocation to roots.

Bioisosteric modification of PETT-HIV-1 RT-inhibitors: synthesis and biological evaluation.

Bioisosteric substitution of the thiourea (3, 5, 7, 9) and urea (10) moiety of PETT compounds with sulfamide (1), cyanoguanidine (2, 4) and guanidine (6, 8) functionalities, and replacement of the phenethyl group with benzoylethyl group (compounds 11-20) have been studied. Synthesis and antiviral activities are described.

Urea-PETT compounds as a new class of HIV-1 reverse transcriptase inhibitors. 3. Synthesis and further structure-activity relationship studies of PETT analogues.

The further development of allosteric HIV-1 RT inhibitors in the urea analogue series of PETT (phenylethylthiazolylthiourea) derivatives is described here. The series includes derivatives with an ethyl linker (1-5) and racemic (6-16) and enantiomeric (17-20) cis-cyclopropane compounds. The antiviral activity was determined both at the RT level and in cell culture on both wild-type and mutant forms of HIV-1. Most compounds have anti-HIV-1 activity on the wt in the nanomolar range. Resistant HIV-1 was selected in vitro for some of the compounds, and the time for resistant HIV-1 to develop was longer for urea-PETT compounds than it was for reference compounds. Preliminary pharmacokinetics in rats showed that compound 18 is orally bioavailable and penetrates well into the brain. The three-dimensional structure of complexes between HIV-1 RT and two enantiomeric compounds (17 and 18) have been determined. The structures show similar binding in the NNI binding pocket. The propionylphenyl moieties of both inhibitors show perfect stacking to tyrosine residues 181 and 188. The cyclopropyl moiety of the (+)-enantiomer 18 exhibits optimal packing distances for the interactions with leucine residue 100 and valine residue 179.

Synthesis and anti-HIV activities of urea-PETT analogs belonging to a new class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors.

A series of potent specific HIV-1 RT inhibitory compounds is described. The compounds are urea analogs of PETT (PhenylEthylThiazoleThiourea) derivatives and the series includes derivatives with an ethyl linker (1-6) and conformationally restricted analogs (7-13). The antiviral activity is determined both at the RT level and in cell culture on both native and mutant forms of HIV-1. Many compounds display activity in the nM range against wt-RT.

Evaluation of the Q16 questionnaire on neurotoxic symptoms and a review of its use.

OBJECTIVES: The questionnaire 16 (Q16) is commonly used to study prevalences of neurotoxic symptoms among workers exposed to organic solvents. It has also been recommended that exposed workers reporting more than six symptoms should be referred for further examination of possible chronic toxic encephalopathy. It would be useful to know whether symptoms reported in the questionnaire also reflect impairment of similar functions measured with objective or semiobjective methods in a formerly highly exposed group. METHODS: 135 painters and 71 carpenters answered the Q16, were interviewed about symptoms compatible with an organic brain damage, and took a battery of psychometric tests. A subsample of 52 painters and 45 carpenters were interviewed for psychiatric diagnosis according to Diagnostic and Statistical Manual for Mental Disorders, 3rd version (DSM III) and their vibration thresholds in hands and feet were measured. The entire group was followed up in the register of diagnoses at early retirement 1971-93. The lifetime exposure to organic solvents was assessed. Current exposure to organic solvents was found to be low or none. RESULTS: The prevalence of people with more than six symptoms in the Q16 rose with increasing cumulative exposure to solvents. The sensitivity of the questionnaire (more than six symptoms) to detect people who were assessed to exhibit symptoms compatible with an organic brain damage was only 38%. One of seven people who had retired early with a diagnosis compatible with a chronic toxic encephalopathy, and two of five people with a psychiatric diagnosis compatible with this condition, had more than six symptoms in the Q16. The agreement between Q16 replies and psychometric test results, as well as other examinations, was low. CONCLUSIONS: The notable exposure-response relation indicates that the questionnaire is useful for comparison of groups with different exposures to organic solvents. There was low agreement between the number of symptoms on the questionnaire and the assessment of symptoms compatible with organic brain damage, as well as psychiatric, or early retirement diagnoses compatible with chronic toxic encephalopathy. The questionnaire does not seem useful for screening of patients with chronic toxic encephalopathy in groups without ongoing exposure to organic solvents.

Supplemental phytases of microbial and cereal sources improve dietary phytate phosphorus utilization by pigs from weaning through finishing.

This experiment was conducted to measure the nutritional and metabolic responses of pigs fed diets with continuous supplementation of microbial and cereal phytase from weaning to finishing, and to determine the feasibility of complete replacement of inorganic P addition by supplemental phytase in swine diets. Forty-eight Landrace x Hampshire x Meishan pigs were divided into four groups. In phase 1 (10 to 50 kg BW), pigs in Groups 1, 2, 3, and 4 were fed a low-P, corn-soybean meal basal diet (BD), the BD plus microbial phytase (A. ficuum) at 1,200 units/kg, the BD plus 10% wheat bran (230 units of cereal phytase/kg), and the BD + .24% inorganic P (calcium phosphate), respectively. In phase 2 (51 to 90 kg BW), these pigs were fed a similar BD or the BD plus 1,000 microbial phytase units/kg, 20% wheat bran, or .20% inorganic P, respectively. Repeated measures included growth performance, P, Ca, and N balance, metatarsal and metacarpal bone strength, serum concentration of inorganic P, Ca, and 1,25-dihydroxycholecalciferol, and serum alkaline phosphatase activity. Pigs fed the BD supplemented with microbial phytase and pigs fed the BD supplemented with inorganic P showed almost identical responses for all variables. Pigs fed the BD supplemented with cereal phytase also had responses for various measures that were similar to those of pigs fed microbial phytase or inorganic P, except for some differences in serum inorganic P concentrations and bone strength in phase 1. Because of improvements in apparent digestibility of dietary P and N, fecal excretion of these two nutrients was reduced by 31 to 62% (P < .05) in pigs fed the BD supplemented with phytase compared with pigs fed inorganic P. It is physiologically feasible and environmentally advantageous to replace inorganic P with microbial or cereal phytase in corn-soybean meal diets for this type of pig through the entire growing-finishing period.

Phenethylthiazolylthiourea (PETT) compounds as a new class of HIV-1 reverse transcriptase inhibitors. 2. Synthesis and further structure-activity relationship studies of PETT analogs.

Phenylethylthiazolylthiourea (PETT) derivatives have been identified as a new series of non-nucleoside inhibitors of HIV-1 RT. Structure-activity relationship studies of this class of compounds resulted in the identification of N-[2-(2-pyridyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea hydrochloride (trovirdine; LY300046.HCl) as a highly potent anti-HIV-1 agent. Trovirdine is currently in phase one clinical trials for potential use in the treatment of AIDS. Extension of these structure-activity relationship studies to identify additional compounds in this series with improved properties is ongoing. A part of this work is described here. Replacement of the two aromatic moieties of the PETT compounds by various substituted or unsubstituted heteroaromatic rings was investigated. In addition, the effects of multiple substitution in the phenyl ring were also studied. The antiviral activities were determined on wild-type and constructed mutants of HIV-1 RT and on wild-type HIV-1 and mutant viruses derived thereof, Ile100 and Cys181, in cell culture assays. Some selected compounds were determined on double-mutant viruses, HIV-1 (Ile 100/Asn103) and HIV-1 (Ile100/Cys181). A number of highly potent analogs were synthesized. These compounds displayed IC50's against wild-type RT between 0.6 and 5 nM. In cell culture, these agents inhibited wild-type HIV-1 with ED50's between 1 and 5 nM in MT-4 cells. In addition, these derivatives inhibited mutant HIV-1 RT (Ile 100) with IC50's between 20 and 50 nM and mutant HIV-1 RT (Cys 181) with IC50's between 4 and 10 nM, and in cell culture they inhibited mutant HIV-1 (Ile100) with ED50's between 9 and 100 nM and mutant HIV-1 (Cys181) with ED50's between 3 and 20 nM.

Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship studies of PETT analogs.

A novel series of potent specific HIV-1 inhibitory compounds is described. The lead compound in the series, N-(2-phenethyl)-N'-(2-thiazolyl)thiourea (1), inhibits HIV-1 RT using rCdG as the template with an IC50 of 0.9 microM. In MT-4 cells, compound 1 inhibits HIV-1 with an ED50 of 1.3 microM. The 50% cytotoxic dose in cell culture is > 380 microM. The chemical structure-activity relationship (SAR) was developed by notionally dividing the lead compound in four quadrants. The SAR strategy had two phases. The first phase involved optimization of antiviral activity through independent variation of quadrants 1-4. The second phase involved the preparation of hybrid structures combining the best of these substituents. Further SAR studies and pharmacokinetic considerations led to the identification of N-(2-pyridyl)-N'-(5-bromo-2-pyridyl)-thiourea (62; LY300046.HCl) as a candidate for clinical evaluation. LY300046.HCl inhibits HIV-1 RT with an IC50 of 15 nM and in cell culture has an ED50 of 20 nM.

The PETT series, a new class of potent nonnucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase.

To identify the minimal structural elements necessary for biological activity, the rigid tricyclic nucleus of the known human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitor tetrahydroimidazobenzodiazepinthione was subjected to systematic bond disconnection to obtain simpler structures. A rational selection and testing of modeled analogs containing these potential pharmacophoric moieties led to the discovery of a new series of nonnucleoside inhibitors of RT. The lead compound of this new PETT series of nonnucleoside RT inhibitors, N-(2-phenylethyl)-N'-(2-thiazolyl)thiourea (LY73497), was found to inhibit HIV-1 but not HIV-2 or simian immunodeficiency virus in cell culture at micromolar concentrations. This derivative was also found to inhibit HIV-1 RT. Through an integrated effort involving synthesis and molecular modeling, compounds with nanomolar potency against HIV-1 in cell culture were developed. In these studies, LY300046-HCl was identified as a potent nonnucleoside inhibitor of HIV-1 RT possessing favorable pharmacokinetic properties.

Neuropsychiatric function of housepainters with previous long-term heavy exposure to organic solvents.

Neuropsychiatric effects were examined among 206 men, of whom 135 had been house painters and 71 had been house carpenters, affiliated with their respective trade unions for at least 10 years before 1970. Their lifetime organic solvent exposure was evaluated through the aid of an interview. Relevant potential confounding factors were accounted for in the statistical analysis. Neuropsychiatric symptoms compatible with chronic toxic encephalopathy were more common among the painters than among the carpenters, and these symptoms became increasingly prevalent with increasing cumulative solvent exposure. On only one of 12 psychometric tests, block design, did the painters perform worse than the carpenters, and in this test the painters' performance deteriorated with increasing cumulative exposure. For the majority of the psychometric tests, and for the coordination tests, there were no differences between the painters and carpenters, but the painters with "low" exposure tended to show better, and "heavily" exposed painters worse, results than the carpenters. The 52 painters with the heaviest cumulative exposures and 45 carpenters were examined for psychiatric diagnosis according to DSM-III, with electroencephalography and auditory evoked potential, P-300. Three painters and two carpenters had diagnoses compatible with an organic mental disorder. There were no overall differences between the painters and carpenters, either for the visually examined electroencephalograms or the P-300 latencies. The excess of neuropsychiatric symptoms among the painters was probably causally linked to solvent exposure. However, these symptoms seemed only rarely, if ever, serious enough to entail a psychiatric diagnosis. Concerning other outcomes, the investigation may not lead to a determination of whether the exposure-response relationship among the painters, with no difference between the entire group of painters and carpenters, is caused by solvent exposure or by selection factors within the group of painters.

Liver function tests and urinary albumin in house painters with previous heavy exposure to organic solvents.

The serum activities or concentrations of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), albumin, gamma-glutamyl transpeptidase (GGT), bilirubin (BIL), cholic acid (CHOL), chenodeoxycholic acid (CHENO), and transferrin with isoelectric point 5.7, and the urinary excretion of albumin were determined among male current or former house painters (n = 135) and house carpenters (n = 71) who had worked in their trades for at least 10 years before 1970. Workers who showed a value above the 90th percentile among the carpenters in at least one of the tests ASAT, ALAT, GGT, BIL, CHOL, or CHENO were regarded as showing "possible signs of liver dysfunction". Each participant's lifetime solvent exposure was evaluated by interview. The painters were divided into categories with low, intermediate, and heavy cumulative exposure during life (LTSE) or during the most exposed year (MEYSE). All participants stated none or slight recent exposure. The prevalence of possible signs of liver dysfunction increased with solvent exposure category according to LTSE as well as MEYSE with a numerically higher risk estimate in the heavy exposure category for MEYSE than for LTSE. ALP activity increased with exposure category according to both exposure estimates. This increase seemed to be due to an interaction between exposure to solvents and current or previous long term intake of medicines potentially toxic to the liver. None of these results was affected by whether or not the subjects had been exposed to solvents during the year before the investigation. The exposure to solvents was not significantly related to any other outcome variable. It is concluded that long term heavy exposure to solvents may elicit changes in conventional liver function tests indicative of a mild chronic effect on the liver. The findings also suggest that heavy solvent exposure during short time periods is a more likely cause of the findings than lifetime cumulative solvent exposure and that an interaction between solvent exposure and medicines potentially harmful to the liver may be important in the causation of the effects.

Diagnoses of alcohol abuse and other neuropsychiatric disorders among house painters compared with house carpenters.

The incidence of alcoholism and the incidence of other neuropsychiatric diagnoses were compared between the 767 house painters and the 1212 house carpenters, born in 1925 or later, who were members of the Stockholm branches of their respective trade unions in 1965 and who had been members for at least 10 years before 1970. Four different outcome registers were used: (1) the alcohol crime register, which contained all persons who had broken any law regulating the handling and consumption of alcohol (follow up period 1972-6). (2) The register of diagnoses at early retirement (follow up period 1971-84). (3) The register of diagnoses at discharge from inpatient psychiatric care (follow up period 1968-83). (4) The register of causes of death (follow up period 1965-86). Exposures to solvents and consumption of alcohol were evaluated by interviews with samples of the cohorts. A high average cumulative exposure to solvents was found among the painters. The mean consumption of alcohol was similar in the two cohorts. The incidence of diagnoses of neuropsychiatric disorders was higher in painters than in carpenters in all registers. Alcoholism was the most common neuropsychiatric disorder diagnosed and showed the highest relative risk. The excess of alcoholism among the painters was, however, due singularly to painters who had several registrations in the alcohol crime register or diagnoses of alcoholism in multiple registers. Thus the study implies that excessive alcohol consumption or severe damage due to alcohol, or both, but not less severe problems, were more common in painters than in carpenters. This suggests an interaction between exposure to solvents and intake of alcohol causing an increase in diagnosis of alcoholism among painters.

Gastric cannulation of pregnant sows.

The purpose of this project was to study the effect of superalimentation in lactating sows through permanent, surgically placed, gastric cannulas. A surgical technique was developed to install gastric cannulas into pregnant sows to allow superalimentation by introducing feed through the cannula. After induction of general anesthesia, a flexible, T-shaped cannula (22 mm outside diameter) was surgically placed in the dorsal portion of the greater curvature of the stomach and exteriorized through the tenth intercostal space approximately 30 cm left of the dorsal midline. Cannulas were installed on day 85 +/- 5 days of gestation. Anesthesia, surgical procedures, and the subsequent presence of the cannula did not affect the size or number of live pigs at birth. In addition, the prevalence of stillbirths and mummified fetuses was not significantly different than that of noncannulated sows. The gastric cannulas did not affect lactation performance, as litter size and weight were unaffected when compared with that in noncannulated controls. Postmortem examination of euthanatized sows revealed adhesions of the gastric wall to the abdominal wall, thus eliminating the possibility of leakage of the gastric contents into the peritoneum. Detrimental effects of the cannulas on gastric function or capacity were not detected, and cannulas could be maintained through multiple parities.

Effects of adding fat to the sow lactation diet on lactation and rebreeding performance.

One-hundred-three multiparous sows were randomly assigned to one of two lactation diets containing either no supplemental animal fat (C) or 10% added fat (F) during two seasons, summer (S) and winter (W), in a 2 X 2 factorial arrangement of treatments. Sows were placed on their respective dietary treatments 1 wk prior to farrowing and were fed these diets ad libitum throughout the 28-d lactation period. Weekly feed intake and total feed intake were not affected by diet or season, while weekly metabolizable energy (ME) intake tended to be higher during week 1 and 3, and was higher (P less than .04) during wk 2 for sows fed diet F. Sow weight loss from farrowing to 21 d of lactation and to weaning (28 d) were unaffected by diet or season. Average pig birth weight was .15 kg higher (P less than .01) for pigs born during S compared with those born in W. Sows receiving diet F had heavier litters at 21 d (P less than .01) and heavier average pig 21-d weights (P less than .01). This was primarily due to the 13.1% increase (P less than .04) in estimated milk yield and the higher fat concentration (P less than .001) of milk consumed by the pigs nursing sows fed diet F. Interval between weaning and rebreeding was shortened by 5.9 d (P less than .01) for sows during W than during S, and tended to be lower for sows fed diet F (7.3 d) compared with that of sows fed diet C (9.7 d).(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental comparisons of boars and barrows: I. Growth rate, carcass and muscle characteristics.

The rate of gain, carcass measurements and three muscles were evaluated in 65 crossbred boars representing 13 litters that were allotted at 4 wk of age to slaughter weight and treatment groups as follows: 1) 105 kg, castrated; 2) 105 kg, intact; 3) 118 kg, intact; 4) 132 kg, intact and 5) 145 kg, intact. One barrow and four boars within a litter constituted a replicate and each replicate was penned separately. The growth rate of all boars to 105 kg constituted one group and was compared with the growth rate of barrows to 105 kg live body weight. Average daily gain from 4 wk until 105 kg did not differ significantly between boars and barrows. Growth rate of the boars continued at an increasing rate until they reached 87.3 kg live weight, while maximum daily gain of barrows occurred at 76.3 kg live weight or 11 kg less than that of boars. At 105 kg, boars had 31.3% less 10th rib backfat thickness and 2.9% greater carcass length than barrows, but longissimus muscle area did not differ. Barrows had greater backfat thickness at 105 kg than 145-kg boars. As live weight increased from 105 to 145 kg, carcass length, 10th rib backfat thickness and longissimus area of boars increased (P less than .01) linearly. Fat-free muscle weights of the brachialis (BR), semitendinosus (ST) and longissimus (L) did not differ between boars and barrows at 105 kg. Boars at 105 kg had 1.3 and 1.7% more moisture in the BR and ST, respectively, than barrows. Percentage protein, total intramuscular fat and fiber diameter in the BR, ST and L muscles did not differ between boars and barrows at 105 kg or with increasing live weight in boars. Total RNA increased linearly (P less than .05) in the BR and ST as boars increased in live weight from 105 to 145 kg.