Nonlactating-cow therapy with a formulation of penicillin and novobiocin: therapeutic and prophylactic effects

An experimental product incorporating 500,000 IU of procaine penicillin G and 600 mg of sodium novobiocin in 2% aluminum monostearate-peanut oil gel (10-ml dose) was infused after the final milk-out at end of lactation into all 4 mammary quarters of 56 cows that were infected in at least 1 quarter. The therapeutic and prophylactic efficacies were published in the companion report. Infusion of the product in all quarters of 5 lactating cows resulted in only slight irritation. Penicillin was eliminated by the 11th milking and novobiocin by the 5th. After infusion in the dry udder, the antibiotics were no longer detectable in serous secretion after 14 days and failed to appear in urine at the earliest (7-day) sampling after administration. Neither antibiotic was detectable in the 1st postpartum milking after nonlactating periods as short as 3 weeks.     

Pharmacokinetics of heparin and its pharmacodynamic effect on plasma lipoprotein lipase activity and coagulation in healthy horses

We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity. Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination was nonlinear. Total clearance of heparin was similar after the 40 and 80 IU/kg of body weight dosages, averaging 0.45 and 0.36 IU/kg/min, respectively. However, after administration of the 120 IU/kg dose, clearance was significantly less than that after the 40 IU/kg dose. The half-life of heparin averaged 53, 70, and 136 minutes after 40, 80, and 120 IU/kg, respectively, with significant differences observed between the low and high doses. In contrast to heparin, the area under the plasma concentration vs time curve for LPL activity increased less than proportionally with dose. Maximal LPL activity observed was independent of dose, averaging 4.8 mumol of free fatty acids/ml/h. The APTT was significantly prolonged for 120 minutes after administration of the 40 IU/kg dose. Correlation coefficients for LPL activity vs either plasma heparin concentration or APTT were less than 0.7, indicating that neither laboratory measure can be used to accurately predict plasma LPL activity.     

Ischemic injury of optic nerve axons: the nuts and bolts

The disposition of enrofloxacin was measured after intravenous and oral administration to pigs. Eight clinically healthy pigs weighing 25 to 40 kg received a dose of 5 mg/kg intravenously and 10 mg/kg orally in both a fasted and a fed condition in a three-way cross-over design. Enrofloxacin was present in plasma for up to 72 hr after both intravenous and oral administration to fasted as well as fed pigs. The steady state volume of distribution was determined to 3.9 +/- 0.5 1/kg body weight which indicates that enrofloxacin was widely distributed in the body. The bioavailability was determined to 83 +/- 13% in fed and to 101 +/- 32% in fasted pigs. Based on the bioavailability and the resulting plasma concentrations it is concluded that a therapeutically active concentration for the most common porcine microbial pathogens are maintained for at least 24 hr after oral administration of 10 mg/kg body weight to fasted as well as to fed pigs. Ciprofloxacin which is an active metabolite of enrofloxacin was observed in plasma samples from all treated pigs, but the concentration never exceeded 0.1 microgram/ml. During the first 24 hr after the administration of enrofloxacin the concentration of the metabolite made up less than 10% of the corresponding concentration of the parent compound.     

Effects and interactions of dietary levels of vitamins A and E and cholecalciferol in broiler chickens

Four experiments were conducted to determine the effects and interactions of feeding different levels of vitamins A, cholecalciferol (vitamin D3), and E on broiler chicks. In Experiment 1, chicks were fed marginal vitamin D3 (500 IU/kg) and increasing dietary levels of vitamin A (5,000, 10,000, 20,000, 40,000, 80,000, and 160,000 IU/kg). Bone ash was reduced by 10,000 IU/kg of vitamin A in the diet and at vitamin A levels above 20,000 IU/kg of diet body weight was reduced. In Experiment 2, two levels of vitamin A (1,500 and 15,000 IU/kg) and six levels of vitamin E (10, 500, 1,000, 2,500, 5,000, and 10,000 IU/kg) were added to the basal diet. High levels of vitamins A and E significantly (P < 0.001) reduced bone ash. The vitamin A x E interaction was significant (P < or = 0.05) for rickets. In Experiment 3, the same two levels of vitamin A as Experiment 2 and six levels of vitamin D3 (500, 1,000, 1,500, 2,000, 2,500, and 3,000 IU/kg) were added to the basal diet that contained 10,000 IU/kg of vitamin E. Body weight and bone ash were increased by increasing vitamin D3 with a corresponding reduction (P < or = 0.05) in rickets. In Experiment 4, three levels of vitamin A (1,500, 15,000, and 45,000 IU/kg), three levels of vitamin D3 (500, 1,500, and 2,500 IU/kg), and three levels of vitamin E (10, 5,000, and 10,000 IU/kg) were added to the basal diet. Significant negative responses (P < or = 0.05) to increasing dietary vitamin A were observed for bone ash, rickets, and plasma and liver vitamin E. A significant (P < 0.001) increase in bone ash and plasma calcium with a corresponding reduction in rickets was observed by increasing vitamin D3. Increasing dietary vitamin E adversely affected (P < or = 0.01) bone ash, plasma calcium, and plasma and liver vitamin A concentrations. These results indicate the need for making feed with the proper ratios of vitamins A, D3, and E.     

Evaluation of the efficacy of ciprofloxacin against Streptococcus pneumoniae by using a mouse protection model

A mouse protection model was used to investigate the association of the pharmacokinetics and pharmacodynamics with the in vivo efficacy of ciprofloxacin compared with that of penicillin G in the treatment of mice infected with Streptococcus pneumoniae ATCC 6303. Mice were inoculated intraperitoneally with 10 times the minimum lethal dose of S. pneumoniae. For determination of the 50% protective dose, subcutaneous antibiotics were begun 1 h after infection and were continued for 24 h. The 50% protective doses of ciprofloxacin and penicillin G were 25.52 +/- 1.95 and 0.307 +/- 0.006 mg/kg of body weight, respectively, an 83-fold difference in efficacy. For 100% protection with penicillin G, the time that the drug concentration needed to remain above the MIC was 51 min, a value easily achieved in most clinical situations. For 100% protection with ciprofloxacin, the peak concentration/MIC ratio must reach a value of 10.6. This ratio is rarely achieved with this drug against S. pneumoniae in clinical practice. These pharmacodynamic differences probably contribute to the reported differences in clinical success between these agents.     

Pretreatment of young pigs with vitamin E attenuates the elevation in plasma interleukin-6 and cortisol caused by a challenge dose of lipopolysaccharide

The effect of a short-term, high-dose intramuscular injection of d-alpha-tocopherol was studied in pigs given a challenge dose of lipopolysaccharide (LPS). Twenty-four pigs surgically fitted with jugular catheters were used in a 2 x 2 factorial design. Pigs received either 0 or 600 mg d-alpha-tocopherol by intramuscular injection for 3 d before receiving an intraperitoneal injection of saline containing either 0 or 5 microgram/kg body weight Escherichia coli LPS. Blood was collected from indwelling jugular catheters at 0, 1, 2, 4, 6, 8, 12 and 24 h after injection of LPS. Plasma alpha-tocopherol levels were 13-fold greater (P < 0.01) at time 0 in pigs pretreated with 600 mg d-alpha-tocopherol (9.9 +/- 1.3 mg/L) than in those not treated with d-alpha-tocopherol (0.74 +/- 0.09 mg/L). Injection of LPS increased (P < 0.05) plasma levels of interleukin-6 (IL-6) and cortisol at 2-h postinjection, regardless of vitamin E treatment. However, pigs that received alpha-tocopherol before the LPS challenge had substantially lower (P < 0.05) peak levels of IL-6 and cortisol than pigs not receiving alpha-tocopherol. These results suggest that supplementation with a surfeit level of vitamin E reduces the response of pigs to endotoxin.     

Lidocaine as a diluent for administration of benzathine penicillin G

OBJECTIVE: Benzathine penicillin G is recommended for secondary prophylaxis of rheumatic fever. Its main disadvantage is local pain and discomfort associated with the injection. Lidocaine as a diluent may reduce this discomfort. We compared the administration of benzathine penicillin G with two diluents; sterile water and lidocaine hydrochloride 1% for penicillin concentrations and pain of injection. DESIGN: In a randomized double blind, crossover trial, 18 children ages 11 to 19 years who required prophylactic treatment for rheumatic fever were randomly divided into two groups. One received an injection of benzathine penicillin G diluted with 3.2 ml of sterile water, followed 1 month later by an injection of benzathine penicillin G diluted in lidocaine hydrochloride 1%; the second group received the same regimen in the reverse order. Serum penicillin concentrations and subjective pain sensation were determined after each injection. RESULTS: Peak serum penicillin concentrations at 24 h after injection were similar for both preparations (0.100 microg/ml for water, 0.102 microg/ml for lidocaine), as were the other serum values measured throughout the month. After 28 days detectable concentrations (> or =0.020 microg/ml) were found in 44 and 291% of the subjects, respectively (P = 0.4). Urine penicillin concentrations on Day 28 were 1.81 +/- 0.25 and 2.31 +/- 0.25 microg/ml, respectively. The pain score immediately after the injection was significantly lower with the lidocaine than with the sterile water dilution. CONCLUSION: Use of lidocaine hydrochloride as a diluent for benzathine penicillin G does not change the penicillin concentration in body fluids and significantly reduces the pain of injection. We suggest the use of lidocaine hydrochloride 1% as a diluent for benzathine penicillin G.     

Comparative surface studies of ototoxic effects of various aminoglycoside antibiotics on the organ of Corti in the guinea pig. A scanning electron microscopic study

It was the purpose of this study to establish criteria for use in comparing the toxic effects of aminoglycosid antibiotics on the organ of Corti by means of scanning electron microscopy. Amikacin, Tobramycin and Gentamicin were administered twice a day subcutaneously for 10 days to healthy guinea pigs. One group of animals was sacrificed 1 day after completion of the treatment; the other group was allowed to survive 22 days. Depending upon the dosage of the administered drug, Amikacin (150 mg per kg body weight daily, corresponding to 10 times an average recommended human dose) caused pronounced outer hair cell damage even 1 day after the treatment was stopped. At this time Gentamicin and Tobramycin (150 mg per kg body weight daily, corresponding to 50 times an average human dose) showed less damage. After 22 days' survival, late toxic effects were found mainly in Gentamicin- and Tobramycin-treated animals. After 3 weeks, nearly total outer hair cell loss was found in the basal coil, while the 2nd and 3rd coils were often less severely damaged. At this time Amikacin-treated animals showed severe damage in all coils. 300 mg per kg body weight Amikacin (i.e. 20 times the average human dose) showed about the same toxic effect on sensory cells of the guinea pig as did 150 mg Gentamicin or Tobramycin per kg body weight. We are conscious of the fact that there are problems in correlating the weight of a drug and its probable toxic effect. In comparative animal experiments we consider it useful to standardize the time of exposure, the amount of drug administered (e.g. related to the human dose) and the survival time.     

Topical retinoic acid (tretinoin) for photoaging: conceptions and misperceptions

Sinusoidal rotation and rotational stimulation tests were used to examine vestibular function in guinea pigs. The results showed that there was no statistically significant difference in the mean number of nystagmus of semi-cycle sinusoidal rotation test and the duration of nystagmus of rotational stimulation test for both the control and test groups before treatment in albinos and pigmented guinea pigs. Meantime, daily subcutaneous injection of gentamicin 125 mg/kg body weight for 12 days in albinos and pigmented guinea pigs showed no significant change in vestibular function until the 7th day of treatment. Significant impairment of vestibular function was noticed on the 10th treatment day. At 5 days after treatment vestibular impairment reached its maximum and minimal recovery was seen at 14 days after treatment. No Further improvement of vestibular function was noticed three months after treatment. The methods are feasible and reliable.     

Three months intravenous repeated dose toxicity study of T-3762 in rats]

A three months intravenous repeated dose toxicity study of T-3762, a novel parenteral quinolone antibacterial agent, was carried out in rats at dose levels of 4, 13, 39, 130 mg/kg. Fifteen rats of each sex were used in each group. Out of these, 5 rats of each sex were used for the recovery study. The following results were obtained. 1. There were no death caused by T-3762 within the study period. In clinical signs, the squeaks during injection in 130 mg/kg group were observed, but they decreased day by day. In body weight changes, a tendency to very slight decrease of weight gain in male 130 mg/kg group were seen, but there was no significant difference from control group. In food and water consumption, there was no abnormality. 2. There were no abnormality caused by T-3762 in urinalysis, hematological examination and ophthalmological examination. 3. In blood chemistry examinations, increase of A/G ratio was seen in 13, 39 and 130 mg/kg groups, but it showed tendency of recovery after withdrawal period. 4. In macroscopic and histological findings, erosion and cavitation of the articular cartilage were seen in 3 of 20 rats in 130 mg/kg group and 1 of 20 rats in 39 mg/kg group. 5. Non-toxic dose levels is estimated to 13 mg/kg, that showed no abnormality in the articular cartilage in this study.     

Measurement of extracellular fluid volume and blood volume in sheep

Methods are described for the simultaneous measurement of extracellular fluid volume (ECFV) and plasma volume (PV) in sheep using dilution of 82Br (as sodium bromide) and 131I-labelled ovine gamma globulin. Following injection of 82Br (100 micronCi), equilibrium in blood was reached after 3 h at which time only 4% of the injected dose was in rumen water. The ECFV was measured as the mean of the 2- and 3-h bromide space after correction for the relative water content of plasma, the Gibbs-Donnan factor and the loss of 82Br into red blood cells. 131I-labelled ovine gamma globulin (20 micronCi) was injected after the 3-h 82 Br space was obtained and blood samples were taken at 10, 20, 30 and 40 min. In 16 determinations in 11 sheep (25-47 kg body weight) the mean (+/- s.e.m.) ECFV was 9112 +/- 289 ml (or 245 +/- 9 ml/kg). The mean PV for 16 observations in 11 sheep measured together with ECFV was 1597 +/- 62 ml (or 42-8 +/- 1-8 ml/kg). Although there was no relationship between body weight and PV there was a significant correlation between ECFV and body weight and also significant negative correlations between body weight and ECFV or PV when these were expressed as a function of body weight. The variation in ECFV measured on four occasions over 7-10 days in four sheep was 3-5% (range 2-6-4-6%). For PV measured in two animals on two consecutive days at the same time as ECFV the coefficient of variation was 1-5 and 2-1%. Acute sodium depletion (250-670 mmol) by parotid duct cannulation in three sheep resulted in a fall in ECFV which would account for only 15-20% of the sodium deficit. The remainder is presumably derived from ruminal sodium stores.     

Clindamycin in persisting streptococcal pharyngotonsillitis after penicillin treatment

239 patients with streptococcal pharyngotonsillitis completed treatment with phenoxymethyl penicillin 12.5 mg per kg body weight b.i.d. for 10 days. At examination after completing therapy, throat specimens from 53 patients (22%) yielded growth of group A streptococci of the same. T-type as the initial culture (bacterial treatment failure). 20 of these 53 (38%) had symptoms and signs of tonsillitis (clinical and bacterial treatment failure). 48 of the patients with bacterial failure were randomly allocated to phenoxymethyl penicillin or clindamycin in an open design; 22 of them received a second course of phenoxymethyl penicillin for 10 days and 26 were given clindamycin, 6.5 mg per kg body weight b.i.d. (children) or 300 mg t.i.d. (adults) for 10 days. After completing their treatment, 14 of 22 patients (64%) given phenoxymethyl penicillin harboured the same T-type as in the previous two cultures, while group A streptococci were not recovered from any of the 26 patients receiving clindamycin. In patients with clinical failure after phenoxymethyl penicillin treatment, a new course with this drug is not motivated. In that situation clindamycin seems to be an efficient choice.     

Reference values for glucose tolerance and glucose tolerance status in cats

1. Disposition kinetics of florfenicol were studied in Pasteurella-free (control) and Pasturella-infected Muscovy ducks following intravenous and/or intramuscular injection in a single dose of 30 mg/kg body weight. In addition, the tissue distribution and residual pattern of the drug were determined in diseased ducks. 2. The maximum serum concentration of florfenicol in control healthy and infected ducks was reached 1 hour after intramuscular injection but the peak concentration in control ducks was higher than in infected birds. 3. The volume of distribution, total body clearance and systemic bioavailability were higher in infected ducks than in control birds 5.15 l/kg, 10.24 ml/kg/min and 73.03% respectively. Data relating to intravenous injection were analysed using a 2 compartment open model curve fit. 4. Florfenicol was not detected in the serum of infected ducks on the 7th day following intramuscular administration of 30 mg/kg body weight twice daily for 5 successive days but was detected in kidney, bile and liver.     

A longitudinal study of body mass index and lens opacities. The Framingham Studies

OBJECTIVES: Chlorpromazine is a known modulator of tumor necrosis factor (TNF)-alpha production. TNF-alpha is thought to be a key mediator in the development of the multiple organ dysfunction syndrome (MODS). We investigated the effect of chlorpromazine on the development of zymosan-induced MODS in mice and on plasma TNF-alpha concentrations and production capacity of TNF-alpha by peritoneal cells. DESIGN: Prospective, controlled laboratory study on zymosan-induced generalized inflammation in mice. SETTING: Animal research laboratory. SUBJECTS: C57BL/6 mice received daily doses (4 mg/kg body weight) of chlorpromazine, beginning 2 days before or 5 days after zymosan administration. In additional groups, the daily chlorpromazine dose of 4 mg/kg started 5 days after zymosan was increased 2 days later to 8 or 16 mg/kg/day. MEASUREMENTS AND MAIN RESULTS: The animals were monitored for survival, condition, body weight, and body temperature. Twelve days after zymosan was administered, all surviving animals were killed to obtain plasma, organs, and peritoneal cells. Plasma concentrations of TNF-alpha and lipopolysaccharide-stimulated production of TNF-alpha by peritoneal cells were measured. Organ weights were recorded as an indicator for organ damage. Although survival was not improved when the animals were treated with chlorpromazine, the chlorpromazine-treated survivors showed improved body weight and temperature when compared with the animals receiving zymosan only. Also, the organ weights and lung damage improved significantly in the treated group. Chlorpromazine was most effective when started before zymosan administration. When administered afterward, clinical improvement declined with the dose. In all cases, circulating TNF-alpha and production of TNF-alpha by peritoneal macrophages were lowered toward control values. CONCLUSION: Chlorpromazine mitigates the development of zymosan-induced MODS, possibly by reducing macrophage TNF-alpha production.     

Assessment of whole body L-leucine oxidation by noninvasive L-[1-13C]leucine breath tests: a reappraisal in patients with maple syrup urine disease, obligate heterozygotes, and healthy subjects

Suitability of a recently proposed noninvasive L-[13C]leucine breath test for assessment of whole body leucine oxidation in maple syrup urine disease (MSUD) was examined. Oral L-[1-13C]leucine loads (38 micromol/kg body weight) were performed in overnight fasted MSUD patients (n = 6, classical form), obligate heterozygote parents (n = 6), and control subjects (n = 10). Three-hour 13CO2 exhalation kinetics were evaluated using curve fitting procedures. Venous blood was obtained in most cases and analyzed for 13C-labeled plasma metabolites. In control subjects, maximal 13CO2 exhalation was reached at tmax = 55 +/- 18 min. Cumulative 13CO2 output at 3 h amounted to 4.7 +/- 0.7 micromol x (kg body weight)(-1). Estimated total 3CO2 exhalation was 7.2 +/- 1.4 micromol x (kg body weight)(-1) (19.0 +/- 3.6% of the dose). Half of this amount was expired at t1/2 = 130 +/- 18 min. The data show a considerable degree of intersubject variability. Intraindividual variability was comparable, however, when checked in two volunteers. In obligate heterozygotes, 13CO2 kinetics were similar to controls (tmax = 35 +/- 8 min, t1/2 = 95 +/- 16 min). Total 13CO2 output [5.7 +/- 1.4 micromol x (kg body weight)(-1)] tended to be in the lower control range. None of the MSUD patients under study exhibited a significant increase in 13CO2 output after load. Maximal increase of label in plasma 4-methyl-2-oxopentanoate, the physiologic precursor of 13CO2, was 16.1 +/- 3.5 MPE in control subjects. In MSUD, label dilution was increased and correlated with the patients' leucine/4-methyl-2-oxopentanoate plasma levels. Considering the generally high variability of 13CO2 output and the unstable substrate pools in MSUD, we discuss the limitations of whole body leucine oxidation measurements by noninvasive approaches.     

Potential for oxytetracycline administration by three routes to cause milk residues in lactating cows, as detected by radioimmunoassay (Charm II) and high-performance liquid chromatography test methods

Milk antimicrobial residues are a serious concern for the dairy industry. Residues of the tetracycline family of antimicrobials have been reported in market milk by investigators, using radioimmunoassay and microbial receptor technology (hereafter referred to as the Charm II test). In response to these reports, an investigation was conducted to determine the potential of 3 extra-label routes of oxytetracycline (OTC) administration to cause milk residues above the Food and Drug Administration safe value of 30 parts per billion (ppb). Lactating Holstein cows were administered OTC once by use of 1 of 3 routes: IV at 16.5 mg/kg of body weight (n = 6); IM at 11 mg/kg (n = 6); and intrauterine (IU) at 2 g in 500 ml of saline solution/cow (n = 6). Duplicate milk samples were collected at the milking prior to drug administration and for the next 13 milkings at 12-hour intervals. Concentrations of OTC in milk samples were analyzed by use of the Charm II tes for tetracyclines (limit of OTC detection, approx 5 ppb) and were compared with concentrations determined by use of a high-performance liquid chromatography (HPLC) method (lower limit of OTC quantitation, approx 2 ppb). The potential for milk OTC residues above the Food and Drug Administration safe value of 30 ppb after treatment was considerably greater for the IV and IM routes, compared with the IU route.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nonspecific endothelin-receptor antagonist blunts monocrotaline-induced pulmonary hypertension in rats

Endothelin-1 (ET-1), a potent vasoactive and mitogenic peptide, has been implicated in the pathogenesis of several forms of pulmonary hypertension. We hypothesized that nonspecific blockade of ET receptors would blunt the development of monocrotaline (MCT)-induced pulmonary hypertension in rats. A single dose of the nonspecific ET blocker bosentan (100 mg/kg) given to intact rats by gavage completely blocked the pulmonary vasoconstrictor actions of Big ET-1 and partially blunted hypoxic pulmonary vasoconstriction. After 3 wk, MCT-injected (105 mg/kg sc) rats gavaged once daily with bosentan (200 mg/kg) had lower right ventricular (RV) systolic pressure (RVSP), RV-to-body weight (RV/BW) and RV-to-left ventricular (LV) plus septal (S) weight [RV/(LV+S)] ratios and less percent medial thickness of small pulmonary arteries than control MCT-injected rats. Lower dose bosentan (100 mg/kg) had no effect on these parameters after MCT or saline injection. Bosentan raised plasma ET-1 levels but had no effect on lung ET-1 levels. Bosentan (200 mg/kg) also had no effect on wet-to-dry lung weight ratios 6 days after MCT injection. When given during the last 10 days, but not the first 11 days of a 3-wk period after MCT injection, bosentan reduced RV/(LV+S) compared with MCT-injected controls. We conclude that ET-1 contributes to the pathogenesis of MCT-induced pulmonary hypertension and acts mainly during the later inflammatory rather than the acute injury phase after injection.     

Influence of exogenous porcine growth hormone on vitamin D metabolism and calcium and phosphorus absorption in intact pigs

The influence of growth hormone (GH) on vitamin D metabolism and calcium and phosphorus absorption in vivo is not clear. We, therefore, measured calcium and phosphorus balance, plasma 1,25-dihydroxyvitamin D (1,25(OH)2D), and intestinal vitamin D-dependent calcium-binding protein (CaBP 9k) in intact growing pigs given exogenous GH. Six 10-week-old pigs were given two daily subcutaneous injections of 50 micrograms porcine GH/kg body weight for 2 months; six control pigs were given vehicle. They were all fed a diet containing 1.1% Ca, 0.6% P, and 1000 IU vitamin D3/kg. Apparent Ca and P absorption and retention were measured in a 10-day balance trial at the end of the 2 months. The plasma levels of Ca, P, 1,25(OH)2D, IGF-I, and GH were determined, and the duodenal and jejunal mucosal CaBP 9k content was measured at slaughter. The plasma Ca and P of GH-treated pigs were unchanged, but all aspects of mineral metabolism, including the plasma 1,25(OH)2D concentration (40%), Ca absorption and retention (70%), P absorption (33%) and retention (45%), and jejunal CaBP 9k (40%), were stimulated, in addition to an increase in the circulating IGF-I concentration.     

The effect of fenfluramine dosage regimen and reduced food intake on levels of 5-HT in rat brain

Male Wistar rats received fenfluramine in subacute (5 mg/kg b.i.d. i.p. for 4 days) or escalating (0.5, 1, 1.5, 2, 3, 4 and 5 mg/kg b.i.d. i.p., each dose given for 4 days) doses. Saline-treated controls received food ad libitum, or were pair-fed with the fenfluramine-treated animals. Rats were killed 1, 15 and 30 days after drug withdrawal. On day 1, plasma and brain fenfluramine levels were higher, and hypothalamus norfenfluramine levels were lower following escalating compared to subacute dosing, although total active drug levels were unaltered. Both treatment regimes, and pair-feeding reduced food intake and body weight. Subacute fenfluramine reduced brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels for up to 30 days. Brain 5-HT and 5-HIAA levels were unaltered following escalating-doses of fenfluramine. Additionally, pair-feeding transiently decreased hippocampal 5-HT levels. These data suggest that escalating-doses of fenfluramine prevent the 5-HT-depleting effect of a sub-cute challenge without altering the anorexic action of the drug.     

Activity of 72-kDa and 92-kDa matrix metalloproteinases in placental tissues of cows with and without retained fetal membranes

We produced hypertrophic and metaplastic changes of goblet cells in rat nasal respiratory epithelium by the intranasal instillation of endotoxin (ETN). In the present study, we examined in vivo effects of indomethacin (IND), dexamethasone (DEX), and erythromycin (EM) on intraepithelial mucus production using this animal model. Intraperitoneal injection of IND (2 to 4 mg/kg body weight x 4 days) or DEX (4 to 8 mg/kg body weight x 4 days) significantly inhibited intraepithelial mucus production induced after 3 days of ETN instillations. Intraperitoneal injection of EM (100 mg/kg body weight x 8 days), aminobenzylpenicillin (ABPC, 200 mg/kg body weight x 8 days), and cephalothin (CET, 200 mg/kg body weight x 8 days) also inhibited intraepithelial mucus production induced after 7 days of ETN instillations. When compared with ABPC and CET, EM had a greater inhibitory effect. These results indicate that ETN-induced intraepithelial mucus production can be inhibited by treatment with the anti-inflammatory drugs IND and DEX. Antibiotics such as EM, ABPC, and CET will also be effective, probably by preventing secondary bacterial infection, and EM has an additional inhibitory effect on intraepithelial mucus production.