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During two studies, effects of recombinant bovine somatotropin (rbST) on plasma and milk IGF's in cows adapted to summer (S; 12 cows) or winter (W; 12 cows) conditions were evaluated. Each study consisted of on-farm periods (30 days) followed by climatology chamber periods (CC; 30 days). Cows were given daily injections of rbST, Sometribove, USAN (25mg/day; 6 cows each study) or saline (control; 6 cows each study). During on-farm periods, blood and milk (am and pm) samples were collected once weekly. During CC periods, blood samples were collected every 2 days and milk samples (am and pm) were collected daily. Plasma IGF-I and IGF-II were increased in cows treated with rbST. A pronounced seasonal pattern in basal and rbST-stimulated plasma IGF-I but not IGF-II was detected. Higher basal and rbST-stimulated plasma IGF-I concentrations in S occurred despite large decreases in feed intake and energy balance. Milk IGF-I and IGF-II was not affected by rbST treatment or season. Although milk IGF-I and IGF-II concentrations were unaffected by rbST treatment, total IGF-output increased due to increased milk yield. The observed seasonal patterns in plasma IGF-I may be indicative of seasonal differences in the coupling of the somatotropin-IGF axis. In particular, we failed to detect an uncoupling of the somatotropin-IGF-I axis in S despite an induced negative energy balance during thermal stress.

Monoclonal antibody hepatocyte paraffin 1 (Hep Par 1) is reported to be highly specific and sensitive for hepatocellular tumours of humans and dogs. However, in a previous study we observed immunoreactivity for Hep Par 1 in an intestinal adenocarcinoma metastatic to the liver. In this paper, we examined normal intestine and 57 canine intestinal tumours including adenocarcinomas of the small and large intestine, colonorectal polyps, mucinous carcinomas, stromal tumours, leiomyosarcomas, fibrosarcoma, plasmacytomas, and osteosarcoma for immunoreactivity for Hep Par 1. Normal intestinal epithelial cells were strongly labelled, particularly at the base of crypts. However, epithelial cells in small intestinal neoplasms had variable reactivity for Hep Par 1. In contrast, normal colonic epithelium was seldom labelled, but hyperplastic or neoplastic colonic epithelium was usually reactive to Hep Par 1. Five of seven small intestinal adenocarcinomas, two of three large intestinal adenocarcinomas, two of three mucinous adenocarcinomas, and all (29) rectal polyps were positive for Hep Par 1. The staining was diffuse, granular and cytoplasmic. The only non-epithelial tumours positive for Hep Par 1 were two of four leiomyosarcomas. Hep Par 1 can be used to differentiate hepatocellular from biliary neoplasms but its value in differentiating metastatic tumours to the liver is questionable due to the reactivity of Hep Par 1 in many intestinal tumours.

A study was carried out to measure the growth and germinal tissue responses of young bull calf whose testicles were exposed to different levels of high energy, pulsed beams (X rays). Treatments (absorbed doses) were 0, 1530, 1980, 3060, or 6300 rads. Body weights were measured monthly for 10 mo; testosterone concentrations were measured in mo 2 and 5. At the end of the study, scrotal circumferences were measured, and testes were removed and weighed. Sections of testes were taken, processed, and evaluated for effects on germinal epithelium. Treatments did not affect body weights or weight gains. Testosterone concentrations at mo 5 generally decreased with increased energy dose. Testicular weights were not different among treatments; generally, scrotal circumferences decreased and germinal tissue degeneration increased as the absorbed dose was increased.

Daily parathyroid hormone (PTH) injections that transiently increase plasma PTH levels within the physiological range increase bone mass in osteopenic, ovariectomized (ovx) rats. This study tested the hypothesis that repeated transient decreases in plasma PTH levels from normal, induced by the daily oral administration of the calcimimetic NPS R-568, would induce an anabolic effect in bone of ovx rats with established osteopenia and/or prevent the rapid bone loss that occurs following ovx. In the reversal study, NPS R-568 was administered orally (10 or 100 micromol/kg) for 30 days to 14-month-old retired breeder rats that were ovx 5 months earlier. NPS R-568 treatment did not increase bone formation rate (BFR) or cancellous bone area (B.Ar) in the proximal tibial metaphysis, or bone mineral density (BMD), at any femoral site. In the prevention study, 3-month-old virgin rats were ovx and given NPS R-568 for the following 28 days. The 10 micromol/kg dose prevented the increase in osteoclast number and 42% of the loss of B.Ar, without affecting the elevated osteoblast populations or BFR. Surprisingly, the 100 micromol/kg dose had fewer protective effects, despite preventing the increase in BFR in both cancellous and cortical bone. Detailed analysis of cancellous bone showed that tendency for a dose-related protection of true cancellous bone occurred, but, while the 10 micromol/kg dose prevented 88% of the loss of calcified cartilage seen in control ovx rats, the 100 micromol/kg dose increased that loss by a further 31%. The mechanism underlying these disparate effects of NPS R-568 on calcified cartilage accumulation in the tibial metaphysis is unclear, but may be related to the different effects that the two doses have on plasma Ca(2+) levels. In conclusion, transient increases in PTH levels above basal, and not simple oscillations in hormone levels below normal, appear necessary for the anabolic properties of endogenous PTH to be manifested in the bones of osteopenic ovx rats.

International audience; ObjectivesInfluenza seasonality remains poorly studied in Equatorial regions. Here we assessed the seasonal characteristics and environmental drivers of influenza epidemics in French Guiana, where influenza surveillance was established in 2006.MethodsSentinel GPs monitored weekly incidence of Influenza-like illnesses (ILI) from January 2006 through December 2010 and collected nasopharyngeal specimens from patients for virological confirmation. Times series analysis was used to investigate relationship between ILI and climatic parameters (rainfall and specific humidity).ResultsBased on 1533 viruses identified during the study period, we observed marked seasonality in the circulation of influenza virus in the pre-pandemic period, followed by year-round activity in the post-pandemic period, with a peak in the rainy season. ILI incidence showed seasonal autoregressive variation based on ARIMA analysis. Multivariate dynamic regression revealed that a 1 mm increase of rainfall resulted in an increase of 0.33% in ILI incidence one week later, adjusting for specific humidity (SH). Conversely, an increase of 1 g/kg of SH resulted in a decrease of 11% in ILI incidence 3 weeks later, adjusting for rainfall.ConclusionsIncreased rainfall and low levels of specific humidity favour influenza transmission in French Guiana.

Domestic and international air-flights.To estimate the risk of tuberculosis (TB) transmission aboard aircraft.A contact investigation of passengers and crew from two flights was conducted following identification of a fellow passenger with pulmonary TB. Immediate post-exposure and follow-up tuberculin skin tests (TSTs) were obtained.Of 120 contacts, 86 (72%) had a negative TST (5 mm); 29 (24%) a positive TST (or = 5 mm), and 5 (4%) a TST conversion. Of the 29 persons with a positive TST, 27 had other identified risk factors for TB. Risk factors for positive TST included non-US birth (Relative Risk (RR) 9.7 P0.01) or history of Bacille Calmette-Guérin (BCG) vaccination (RR undefined; P0.01). Risk was not associated with specific aircraft or seat relative to the index case for US-born contacts. All five TST converters were born in countries where BCG vaccine is routinely given.The positive TST reactions and conversions suggest boosting from BCG vaccination or prior exposure in TB-endemic countries. Since two positive contacts had no other identified risk factor, TB transmission on board the aircraft could not be excluded. Contact investigation of exposed aircraft passengers should be considered on a case-by-case basis, with consideration of the infectiousness of the ill passenger and the flight circumstances.

Androgens are associated with the greater skeletal mass and size in men compared with women and have been used as anabolic agents promoting skeletal growth and mineral accretion in both sexes, but specific effects on growth and bone formation in the female skeleton are not well understood. The effects of 5 alpha-dihydrotestosterone (DHT) alone, and in combination with 17 beta-estradiol on bone and bone growth were studied in female ovariectomized (OVX) rats with established osteopenia. Eight weeks after OVX, rats were given 0.1 mg 17 beta-estradiol and/or 2.5 mg or 10 mg DHT administered by controlled-release pellets for 2 months. Body weights decreased with estrogen treatment but increased with DHT. Bone mineral density increased with the highest dose of DHT relative to OVX controls and the estrogen treated group. Dry and ashed bone weights and ash/dry weight ratios increased in the estrogen and DHT treated animals compared to the baseline OVX controls. Total bone calcium was greater with DHT and estrogen combined with DHT. The percent of calcium in the ash increased in all DHT treated groups. When normalized to final body weight, the total femur calcium content was significantly increased in the estrogen and estrogen with DHT groups, but not in the DHT groups compared with the baseline OVX and OVX control groups. The periosteal bone formation rates were increased with the high dose DHT alone and combined with estrogen. OVX rats had increased endochondral bone elongation rates relative to controls but this was decreased with estrogen treatment. DHT combined with estrogen increased endochondral growth rates relative to the estrogen treated group. Trabecular bone volume was decreased in all OVX groups relative to the base line group, but there were no significant effects observed with any treatments. Cancellous bone formation rates were suppressed with estrogen treatment but were partially reversed when combined with DHT. DHT treatments also increased most cancellous bone formation indices over OVX controls. While estrogen is known to preserve skeletal mass by reducing bone turnover, DHT increased skeletal mass by promoting bone growth and formation with concomitant increases in total body mass. DHT had greater effects on cortical bone and partially mitigated the suppressive effects of estrogen on bone growth and formation in the female skeleton.

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 to 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 μg/l) (e−(0·11/min)(t)) + (317·3 μg/l)(e−(0·03/min)(t)). Overall averages were: area under the curve=27·1 mg · min per 1, clearance=0·15 litres/min per 100 kg and volume of distribution of the central compartment =2·59 litres/100 kg. The t1/2 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 μg/l, 5–15 μg/l and 40–90 μg · 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. Journal of Endocrinology (1993) 139, 441–450

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 (.6 g) 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 3.0 g 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 3.0 g every 14 d.

Because cancellous bone loss occurs following ovariectomy (OVX) in rats, this has become a popular model to explore therapeutic modalities for postmenopausal bone loss in humans. The purpose of this study was to determine intestinal calcium absorption in situ and organ-, tissue-, envelope-, and site-specific changes in osseous tissues at six weeks after OVX in rats using chemical, biochemical, absorptiometric, microradiographic, and morphometric methods. There were no changes in intestinal absorption of calcium, but duodenal weight per length was significantly increased in the OVX animals compared with age-matched, sham-operated controls. There was an increase in wet bone weight, but decreases in ash/dry bone weight, total bone Ca, and Ca per ash weight in the OVX animals. There were significant decreases in the OVX animals in metaphyseal bone mineral content, as determined by photon absorptiometry and metaphyseal cancellous bone volume. The perimeter to area ratio of the metaphyseal cancellous bone in the OVX animals was increased compared with controls. Endochondral growth rates were increased in the OVX animals, attributable to an increased growth plate hypertrophic cell size and rate of chondrocyte proliferation. In the OVX animals there was an increase in modeling in the formation mode of the periosteal surface at the tibio-fibular junction. Increased periosteal modeling in the formation mode was also observed in the body of the mandible, suggesting that the changes in periosteal bone formation are not strictly coupled with changes in endochondral growth. There was an increase in modeling in the resorption mode of the endocortical surface at the tibio-fibular junction in the OVX animals. There was increased bone turnover in the OVX animals compared with controls on the endosteal surface, as indicated by increases in both formation and resorption indices, including an increase in the osteoclast population. In the long bones, OVX results in larger bones due to increases in endochondral growth and modeling in the formation mode at the periosteal surfaces, with a loss of cancellous bone and total bone calcium due to increased resorption on the endocortical surfaces and turnover (increased formation and resorption) on endosteal surfaces. This study emphasizes that osseous tissue changes following OVX in rats are tissue-specific, envelop-specific, and site-specific.

Eight pregnant Holstein cows were given weekly injections of 15 g of recombinant bST over a 2-wk period for a total dose of 30 g to determine signs of acute toxicity. Cows were monitored intensively throughout the study, and samples were taken for analyses of hormones, metabolites, chemistries, hematology, and urine analytes. Animal health throughout the study was generally excellent. Mean rectal temperatures were significantly higher in treated cows (38.7 vs. 39.2 degrees C). Least squares means for 3.5% FCM production were 15.9 and 23.0 kg/d, and net energy intakes were 29.4 and 26.9 Mcal/d for control and treated cows, respectively. Somatotropin concentrations reached more than 250 ng/ml on d 10 and remained above 200 ng/ml. Insulin and glucose concentrations were also increased but returned toward baseline values. Free fatty acid concentrations were higher in treated cows, but beta-hydroxybutyrate was not affected. Most hematological measurements were unaffected except for a reduction in erythrocyte number in treated cows and decreases in hematocrit and hemoglobin, but values were within clinically normal ranges. Although cows received in 2 wk a dose that was equivalent to the amount administered during more than 2 yr of continuous use, no signs of acute toxicity to bST were observed.

The utility of PET and PET/CT in research and diagnosis of cancer, cardiac and neurological disorders has been widely demonstrated. Phantoms with well defined geometries that accurately model radiolabeled tracer concentrations and photon attenuation coefficients are suited for characterization of imaging systems, but not as well suited for evaluating methods sensitive to detailed anatomical structure, such as algorithms for monitoring tumor response. An ideal phantom would have the shape and activity distribution of a realistic tumor and would be useful in evaluation of automated image analysis systems. Such a phantom, imaged at sites involved in clinical trials, would be valuable for evaluating consistency and accuracy. We have developed a method of creating such phantoms by incorporating radioactive tracer as dye for a cellulose powder based rapid prototyping system. This allows us to create phantoms with spatial resolution limited only by the stereolithography printer system (slice thickness is 0.18 mm, printing resolution is 600 dpi). We have evaluated the method by printing several small phantoms with 18F and measuring activity in a gamma counter. The relative standard deviation of the activity of multiple identical phantoms was 2%. Activity in unlabeled parts was less than 2% of adjacent labeled regions. We have created and printed realistic phantoms based on the SPL human brain atlas [1,2], the Paxinos & Watson rat brain atlas [3] and from PET/CT images of human lung nodules, showing that this is a practical method for making complex radioactive phantoms that model real anatomy. We are proceeding with further development to allow us to produce phantoms with multiple activity concentrations, tunable photon attenuation coefficients and long lived isotopes.

Current anti-protrusio cages are non-porous-coated and 1 piece and they require liner cementation. These factors limit bone ingrowth, trials, and modularity. Results of a completely modular porous-coated anti-protrusio component (MAPC) are presented. Sixty-three acetabular revisions with MAPC were performed from 1998–2001 by 2 surgeons. Average follow-up was 29 months (range, 24–50). 30/63 (48%) had Paprosky type 3A or B defects. 55/63 (87%) MAPCs remain in place. Four components were removed for infection, 3 for loosening, and 1 for malposition. Eight hips dislocated, requiring 6 reoperations. Two MAPCs are radiographically loose but asymptomatic. At short-term follow-up, these results are comparable to conventional 1-piece anti-protrusio cages. Advantages include the potential for bone ingrowth and long-term fixation, surgical technique similar to large hemispherical components, ability to trial, and modularity.

Issues related to women’s health, and particularly to menopause, have been major priorities over the past decade for agencies of the U.S. Department of Health and Human Services (DHHS). In order to prevent morbidity and mortality in perimenopausal and postmenopausal women, an unprecedented concentration of resources and attention has been directed toward menopause. This has included funding of new research to elucidate the menopausal transition and to prevent morbidity, as well as support of studies of associated pharmacological, clinical, and epidemiological aspects and prevention research.

expand the quantity, quality, and relevance of nursing and midwifery professions to address population-based health needs; 2) strengthen the capacity, quality, and effectiveness of nurse and midwifery training and education programs; 3) identify innovative models to increase the number of qualified health care workers; 4) strengthen research and professional development opportunities; and 5) develop evidencebased strategies to guide future human resources for health investments Structure/Method/Design: The NEPI Coordinating Center (CC) facilitates the planning, implementation, and monitoring of this preservice nursing program in the countries of DRC, Ethiopia, Lesotho, Malawi, and Zambia. Each country receives approximately $1.2 million per year, for 5 years. There are three to six NEPI schools of nursing (SON) in each country. Under the leadership of the Ministries of Health and Education, the CC works with national nurse leaders to implement innovative interventions that respond to identified needs and have a sustainable effect on the nursing profession by increasing the number of well-prepared nursing and midwifery graduates. Results (Scientific Abstract)/Collaborative Partners (Programmatic Abstract): Envisioned by Ambassador Goosby, NEPI is supported by the Office of the U.S. Global AIDS Coordinator (OGAC) and implemented through the U.S. Department of Health and Human Services (HHS), Health Resources and Services Administration (HRSA). Ministries of Health and Education lead program implementation and assure synchronized coordination and sustainability. Other stakeholders include In-Country PEPFAR teams, USAID and its CapacityPlus Project, World Health Organization, Clinton Health Initiative, and ELMA Philanthropies. Summary/Conclusion: NEPI has strengthened the spectrum of nursing by using innovative models to invest in preservice and regulatory bodies, educators, educational practices (competency-based curricula, preceptors, clinical simulation), equipment, and support to nursing students. Concurrently, NEPI has increased the administrative and financial capacity of NEPI schools; it is expected that NEPI SONs will be able to seek and be awarded support from other funding sources.

Intestinal extramedullary plasmacytomas (EMPs) are rare tumours in dogs. Three cases of canine intestinal EMP with amyloid deposits are described in this report. These tumours, which were located in the rectal submucosa, had variable numbers of well-differentiated plasma cells and fewer multinucleated giant cells of plasmacytoid and histiocytic morphology, admixed with abundant amyloid. Two cases had metaplastic cartilage and bone within the amyloid deposits. Immunohistochemically, the plasma cells of all three tumours reacted for lambda-light chains of immunoglobulins but not for kappa-chains, indicating monoclonality. Plasma cells of two tumours were also positive to CD79a antiserum. Amyloid deposits were labelled with an A lambda (amyloid of immunoglobulin lambda-light chain origin) antiserum but not with antisera against its precursor protein, the immunoglobulin lambda-light chains, indicating possible conformational changes of amyloidogenic proteins during their transformation into amyloid.

The aim of this study was to compare the effect of two cytokines, IGF-I and IGF-II on skeletal development in the rat. The three medial metatarsal rudiments were dissected out from fetuses at days 19, 20 or 21 of gestation and from newborns at days 1, 3, 6 and 9 after birth, then grown in serum-free MEM medium at 37 degrees C and 5% CO2 in air. From day 19 of gestation to the end of experiment, longitudinal bone growth (mm) was significantly increased by IGF-I (2.975 +/- 0.050) and IGF-II (2.530 +/- 0.062), compared to controls (2.188 +/- 0.060). In the same way, the width (mm) at the last experimental day was 0.360 +/- 0.010 in IGF-I- and 0.327 +/- 0.008 in IGF-II-treated bones, respectively (vs 0.313 +/- 0.012 in controls). Mineralization was also stimulated under both growth factors (length of the calcified diaphysis (mm): 0.691 +/- 0.019 in IGF-I- and 0.446 +/- 0.017 in IGF-II-treated bones; vs 0.383 +/- 0.024 in controls). IGF-I and IGF-II (but to a lesser extent) stimulation was due to an increased DNA synthesis (3H-thymidine uptake) as well as protein anabolism (incorporated proline). In addition, cartilage activity (35S captation) and mineralization (45Ca fixed) were involved in the action of these cytokines. An age dependency of bone response to IGFs was pointed out, the effect being higher during the fetal period than after birth. In conclusion, our results raise the possibility that IGF-II, as well as IGF-I, is involved in the control of osteogenesis.

The effect of chronic treatment with recombinant methionyl bovine somatotropin (USAN, sometribove) on anterior pituitary secretions and its target organs was investigated in six control and six sometribove-treated British Friesian cows. Cows averaged 112 and 119 d postpartum in their fourth lactation of treatment and, except for one control, had active corpora lutea. During each lactation, treated cows received sometribove injections (500 mg) every 2 wk (injection cycle) starting 60 ± 3 d postpartum. On Day 9 of one injection cycle, blood was sampled for 390 min, starting 30 min before an intravenous injection of thyrotropin (TRH, 0.33 μg/kg), corticotropin (100 μg), and gonadotropin (GnRH, 200 μg)-releasing hormones. Baseline somatotropin (bST) and adrenocorticotropin (ACTH) were higher in sometribove-treated cows vs. controls (3.27 vs. 1.03 ng/ml and 35.24 vs. 19.28 pg/ml, respectively). Baseline total thyroxine, free thyroxine, triiodothyronine, prolactin, follicle stimulating and luteinizing hormones, estradiol, and progesterone (P4) were similar across treatments. Circulating cortisol levels did not differ between control and sometribove cows, indicating a reduced adrenal ACTH responsiveness in the latter. Releasing factors induced similar changes across treatments in hormones studied with the following exceptions: a bST spike was seen in control cows only, cortisol response to ACTH was reduced in treated cows, and a significantly higher P4 concentration was detected in the plasma of sometribove-treated cows, suggesting increased ovarian responsiveness to GnRH-stimulated P4 output. The study demonstrated reduced bST response to TRH, consistent with physiologic feedback mechanisms, whereas the release profiles of the other pituitary hormones were unaffected. Target tissue responses affected by chronic sometribove treatment appear to be adrenal cortisol and ovarian P4 output.

Insulin-like growth factor 1 (IGF-1) has roles in bone growth, and parathyroid hormone (PTH) is suspected of having effects on bone, perhaps mediated by IGF-1. The purpose of this study was to determine the individual and combined effect of PTH and IGF-1 on fetal long bone metabolism. Three medial metatarsal bones were dissected from Sprague-Dawley rat fetuses harvested at the 19th day of gestation, then grown in serum-free MEM. IGF-1 (group II) or PTH (group PP) were added at the dose of 100 ng/ml for 8 days. In a third group (PI), bones were preincubated for 4 days with PTH followed by a 4-day incubation with IGF-1. Both hormones stimulated endochondral (longitudinal) growth, the highest effect was observed with IGF-1 (II: 3.11 +/- 0.06 vs. 2.16 +/- 0.08 mm in controls). The length elicited by the PI treatment ranged between those measured with IGF-1 (II) and PTH (PP) given alone (PI: 2.80 +/- 0.04 mm; PP: 2.57 +/- 0.06 mm). In addition, both hormones enhanced periosteal growth (endomembranous ossification), as measured by the width of bones (II: 0.39 +/- 0.02 mm; PP: 0.34 +/- 0.02 mm; PI: 0.38 +/- 0.02 vs. 0.29 +/- 0.01 mm in controls). On the other hand, IGF-1 but not PTH caused a significant increase in 35S incorporation (as an indicator of sulfated proteoglycan synthesis in cartilage (percent of incorporating activity; II: 0.18 +/- 0.04%; PI: 0.09 +/- 0.01 vs. 0.03 +/- 0.01% in controls). Nevertheless, both IGF-1 and PTH enhanced osteoblastic activity as shown by increased alkaline phosphatase activity in treated bones (II: 1.18 +/- 0.00 mumol/bone; PP: 0.50 +/- 0.00 vs. 0.28 +/- 0.00 mumol/bone). In conclusion, IGF-1 had the greatest effects on growth in bone length (endochondral osteogenesis) and bone width (intramembranous osteogenesis) and appeared to stimulate both chondrogenesis and osteogenesis. It also increased growth but appeared to have greater effects on osteogenesis than on chondrogenesis. Pretreatment with IGF-1 followed by PTH produced effects that were intermediate between the groups treated with IGF-1 and PTH alone.

Eighty-two lactating Holstein cows received either one, three, or five concurrent, intramuscular injections of a unit dose (.6 g) of zinc methionyl bST (some-tribove) or five doses of the vehicle. Injections were administered at 14-d intervals from 60 d postpartum until the end of lactation or necropsy. Thirty-eight cows continued on the same treatment for a 2nd yr. Blood bST antibodies developed within the first 7 wk of treatment, and the number of cows with anti-bST binding generally declined with time. Thirteen out of 59 cows receiving bST developed binding activity25% (positives) during the 1st yr. At the .6-g dose level, no binding was detected after wk 15. Seven of the 13 positive cows were among the group randomly selected to continue on study during yr 2. In the 2nd yr, only 2 out of 24 bST-treated cows were positive. Binding activity was associated with the IgG fraction in serum. Binding capacities of antibodies ranged from .625 to 3.04 mg of bST/L, and affinities ranged from 1.14 x 10(8) to 3.14 x 10(8) L/mol. Cows considered to be clinically positive had performance similar to those of their herdmates having binding25%. No evidence of a pathologic effect of antibodies existed in treated cows, their calves, or fetuses. The presence of anti-bST antibodies did not affect milk production of the cow or growth of the calves conceived during bST treatment.

Mid-lactation Holstein cows (n = 4) were assigned to four dietary sequences in a 4 x 4 Latin square to determine energy and protein effects on somatomedins. Diets were designed so that intakes were either high or low for net energy (NE) or crude protein (CP) with the range being representative for a lactation cycle. Each dietary treatment lasted 16 d and consisted of an adjustment period (d 1 to 7), a basal period (d 8 to 12) and a period of bovine somatotropin (bST) (40 mg/d) administration (d 13 to 16). Blood was obtained via jugular catheters every 4 h on d 11 to 16. Basal milk yield was decreased by NE or CP restriction. Milk yield was increased for cows fed all diets with bST, but response was greatest for those fed the high NE/high CP diet (31%, 7.7 kg/d). Plasma insulin-like growth factor (IGF)-I and IGF-II concentrations were not affected by diet. For all diets, bST caused an increase in plasma IGF-I (125%) and IGF-II (21%), with the increase being substantially greater for cows fed the high NE/high CP diet. Basal insulin levels differed among diets and increased with exogenous bST in cows fed the high NE/high CP diet. Results are consistent with a role of somatomedins in the mechanism by which exogenous bST increases milk yield, and variations in somatomedin response due to nutritional status may explain part of the differences in milk yield response to exogenous bST.

Highway automation technologies have been proposed in an attempt to ameliorate the urban problem of congestion and, to a lesser extent, air pollution. The methodology developed to analyze the impacts of an automated highway system in the Southern California region in 2025 is addressed in this paper. An automated highway system scenario is selected from several alternatives based on sensitivity analyses that allow for variability in network location, total network miles, and market penetration of vehicles equipped with automation features.

Six Holstein cows were used in a complete block design to examine effects of period of lactation and somatotropin (bST) administration on concentrations of insulin, insulin-like growth factors (IGF-I, IGF-II), and IGF-binding protein 2 (IGFBP-2). During late lactation, the dry period and the subsequent early lactation, cows received injections of NaHCO3 buffer for 5 d and bST for 7 d. Cows were in positive energy and protein balances during late lactation and the dry period and in slight negative balances during early lactation. Basal insulin concentrations were highest in late lactation (170 pmol/L), whereas bST concentrations were higher in early lactation (0.6 micrograms/L). Insulin was increased by bST in the dry period (255 pmol/L) and late lactation (149 pmol/L) but not in early lactation (14 pmol/L), probably because of greater availability of glucose during positive nutrient balance. Basal IGF-I was lowest in early lactation (63.6 micrograms/L) but was increased by bST during all periods. The IGF-I response to bST administration was lower during early lactation (74.1 micrograms/L) compared with late lactation (123.6 micrograms/L) and dry period (146.0 micrograms/L). The IGF-II concentrations were not affected by period of lactation of bST administration but IGF-II tended to be higher during bST administration when cows were dry. Concentration of IGFBP-2 was higher during early lactation when cows were in negative nutrient balance (479.5 micrograms/L) than during the dry period (289.2 micrograms/L) and was decreased with bST. These data support a role of insulin and IGF in regulation of milk production. Availability of nutrients may be involved in regulating these hormones, particularly during bST treatment.

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.

Changes in bone mass and cancellous bone remodeling parameters were determined during lactation in adult beagles. Bone mineral content was determined by photon absorptiometry, fraction of mineralized cancellous bone area and perimeter to area ratios by image analysis of microradiographs, and bone remodeling parameters by fluorochrome-based histomorphometry. Bone mineral content of the intact proximal humerus and fraction of mineralized tissue areas of lumbar vertebral cancellous bone were decreased during lactation when compared with controls. There were significant increases during lactation in osteoid volumes and osteoid surface, although osteoid seam thickness was not changed. There were significant increases in the fraction of fluorochrome-labeled cancellous bone surfaces in the lactating dogs when compared with controls. The mineralizing surface, bone formation rate and activation frequency were significantly increased in the lactating dogs when compared with controls. There were also significant increases in resorption parameters during lactation. These data indicate that during lactation, bone remodeling and bone turnover is increased. Increased bone remodeling during lactation in a longer-lived mammal may represent an example of a "reversible mineral deficit" which may be an important physiological mechanism in nursing mothers to ensure adequate calcium for milk production. Increased bone remodeling may also provide a physiological mechanism to enhance the capacity of the skeleton to better accommodate the greatly increased and episodic changes in mineral homeostasis during lactation.

In vitro antibacterial activities of ampicillin and amoxycillin were compared against pigmented and non-pigmented strains of Serratia marcescens. Ampicillin appeared more effective than amoxycillin; three-fourths of all strains consistently exhibited an ampicillin minimum inhibitory concentration (MIC) of at least one tube less than that recorded for amoxycillin. Complete cross resistance was not observed as has previously been inferred. Further, greater bactericidal activity was demonstrated with ampicillin; minimum bactericidal concentrations (MBC) were either the same as or one tube greater than the MIC. MBC's for amoxycillin, however, were significantly higher; often four to five times greater than the MIC. Ampicillin exhibited greater bactericidal activity as inferred from differences observed in the biological lesions induced, as recorded through observations by scanning electron microscopy (SEM). Spheroplasts were the predominant morphological alteration induced by ampicillin. In contrast, only filament formation, which demonstrated a degree of reversibility, was induced by amoxycillin.

Changes in bone chemistry, cortical bone morphometry, and periosteal and trabecular bone formation rates were determined during pregnancy and lactation in rats. Data were obtained using chemical, static morphometric, and fluorochrome-based histomorphometric methods in pregnant or lactating animals and compared with age-matched, unmated controls. There were significant increases in bone weight, ash weight, calcium content, and femoral cross-sectional area by late pregnancy and decreases in these same parameters during lactation. There were also decreases in bone mass and increases in surface:volume ratios of trabecular bone during lactation. There were increases in femoral periosteal and endosteal perimeters associated with the reproductive cycle. Bone formation and appositional rates at the periosteal and endosteal surfaces were elevated during pregnancy, particularly evident at midpregnancy. Periosteal bone formation rates declined during lactation, but trabecular bone formation rates increased. These results indicate that during pregnancy there are increases in bone formation rates contributing to the increases in skeletal mass. During lactation in rats, reductions in skeletal mass are accompanied by increases in bone turnover, particularly evident in trabecular bone.

Lactose promotes the intestinal absorption of calcium independent of the vitamin D endocrine system. The purpose of this study was to determine the effect of lactose supplementation on endochondral bone growth, bone development and mineralization in weanling rats fed a vitamin D-deficient diet. Rat pups were weaned from vitamin D-deficient dams and fed a vitamin D-deficient diet containing sucrose as the primary carbohydrate source or a similar diet but containing 20% lactose. After 4 wk, body weights, serum calcium levels and endochondral bone elongation rates in the lactose-fed animals were higher than in rats fed the sucrose diet. In addition, bone weights, bone calcium content, percent bone ash of bone dry weight, percent metaphyseal osseous tissues and bone osteoid content in the lactose-fed rats were different from those in the rats fed the sucrose diet. In all cases the changes in osseous tissues that were observed in the animals fed the lactose-supplemented diet were toward normal values as observed in age-matched animals fed a vitamin D-replete diet. The improvements in bone growth and development due to lactose supplementation occurred independent of the vitamin D endocrine system and are likely the result of improved calcium absorption in the intestine.

G. A. Sansing , E. B. Lillehoj , R. W. Detroy and M. A. Miller . Synergistic toxic effects of citrinin, ochratoxin A and penicillic acid in mice. Toxicon14, 213–220, 1976.—The ld 50's in mice of citrinin, ochratoxin A, and penicillic acid injected intraperitoneally were 89, 22, and 100 mg per kg of body weight, respectively. Paired combinations of the mycotoxins, citrinin: ochratoxin A (CI:OA), ochratoxin A:penicillic acid (OA:PA), and penicillic acid:citrinin (PA:CI) elicited synergistic lethal responses. After administration of citrinin, 14C-orotic acid incorporation into both liver and kidney increased significantly by 27 hr with a return to control levels at 51 hr. Treatment with penicillic acid also increased orotic acid incorporation into liver ribonucleic acid (RNA) at 27 hr and at 4 hr in the kidney. Ochratoxin A inhibited orotic acid incorporation into both liver and kidney RNA 6 hr after toxin injection with a subsequent return to control levels at 27 hr. Orotic acid incorporation was inhibited in both kidney and liver 6 hr after treatment with the toxin combination CI:OA, PA:CI stimulated precursor incorporation into kidney RNA at 27 hr and inhibited the function in liver. The OA:PA combination inhibited orotic acid incorporation in both organs 15–27 hr after toxin treatment.