The influence of serum calcium concentration on total circulating parathyroid hormone (PTH) and on the relative amount of intact PTH-(1-84) and large carboxyterminal fragments was studied in the canine and bovine species and in man. Serum calcium was modified through infusions of CaCl2 or EDTA and samples obtained in time for the measurement of serum calcium and PTH concentrations. Pools of serum, corresponding to specific serum calcium concentrations, were analyzed by gel chromatography in all species. PTH was measured with a carboxyterminal radioimmunoassay. In basal conditions, total serum PTH was composed mostly of large carboxyterminal fragments, intact PTH-(1-84) representing less than 25% of the hormone in any species. With hypercalcemia, (greater than or equal to 2.0 mg/dl), total serum PTH decreased only to 40% of the original value measured in all species, despite serum calcium concentrations of over 13 mg/dl. The relative amount of intact PTH-(1-84) remained unchanged in the bovine and canine species and slightly decreased in man. Hypocalcemia (less than or equal to 2.0 mg/dl) induced a 300-450% increase in the basal PTH value measured. The relative amount of intact PTH-(1-84) became as or more important than carboxyterminal fragments in the canine species and in man, respectively, and remained slightly less in the bovine species. Despite small quantitative variations between species, these results indicate that changes in serum calcium concentration induced acute modification in PTH secretion or PTH peripheral metabolism, altering the ratio of intact hormone to carboxyterminal fragments in circulation.
Clinical mastitis is an important disease in dairies. Its treatment is mainly based on the use of antimicrobial drugs. Numerous non-antimicrobial drugs and treatment strategies have already been reported for clinical mastitis treatment, but data on their efficacy have never been collated in a systematic way. The objective of this systematic review was to identify treatments other than conventional antimicrobials for the treatment of clinical mastitis in lactating dairy cows. A systematic review was performed with studies written in English or French selected from CAB Abstracts, PubMed, and Web of Science from January 1970 to June 2014. Controlled clinical trials, observational studies, and experimental challenges were retained. Lactating dairy cows with clinical mastitis were the participant of interest. All treatments other than conventional antimicrobials for clinical mastitis during lactation were retained. Only studies comparing the treatment under investigation to a negative or positive control, or both, were included. Outcomes evaluated were clinical and bacteriological cure rates and milk production. Selection of the study, data extraction, and assessment of risk of bias was performed by 3 reviewers. Assessment of risk of bias was evaluated using the Cochrane Collaboration tool for systematic review of interventions. A total of 2,451 manuscripts were first identified and 39 manuscripts corresponding to 41 studies were included. Among these, 22 were clinical trials, 18 were experimental studies, and 1 was an observational study. The treatments evaluated were conventional anti-inflammatory drugs (n = 14), oxytocin with or without frequent milk out (n = 5), biologics (n = 9), homeopathy (n = 5), botanicals (n = 4), probiotics (n = 2), and other alternative products (n = 2). All trials had at least one unclear or high risk of bias. Most trials (n = 13) did not observe significant differences in clinical or bacteriological cure rates in comparison with negative or positive controls. Few studies evaluated the effect of treatment on milk yield. In general, the power of the different studies was very low, thus precluding conclusions on noninferiority or nonsuperiority of the treatments investigated. No evidence-based recommendations could be given for the use of an alternative or non-antimicrobial conventional treatment for clinical mastitis. However, probiotics and oxytocin with or without frequent milk out should not be recommended. We concluded that homeopathic treatments are not efficient for management of clinical mastitis.
[125I]Carboxy-terminal fragments were produced by incubating [125I]bovine PTH(1-84) with plasma membranes from the rat renal cortex. After purification by gel chromatography and characterization by sequence analysis, these fragments, mainly [125I]bovine PTH(41-84), were injected into normal and acutely nephrectomized rats during two different experiments. In each case, blood was obtained from five rats at various time points (2, 4, 6, 8, 12, 24, 48, and 96 min); tissue was taken after they had been killed (4, 8, 24, and 96 min). Plasma and weighted aliquots of tissues were counted. Plasma at each time point and the extract of various tissues at the 8-min mark were further analyzed by gel chromatography. Each radioactivity peak on each profile was identified and quantitated planimetrically. [125I]Carboxy-terminal fragments were extracted from serum biexponentially: the first exponential had a half-life of 2.3 min and the second 27.2 min in normal rats. These values increased to 3.2 min (X 1.4) and 74.0 min (X 2.7) in nephrectomized rats. In normal rats, 125I-extraction was 33.4% (kidney), 15.9% (muscle), 6.9% (bone), less than 2.7% (liver), and under 1% in other tissues. In nephrectomized rats, these values were significantly (P less than 0.005) increased to 24.6% (muscle), 10% (bone), and 6.8% (liver) with less than 1% in other tissues. Most of the 125I-radioactivity present in these tissues at the 8-min time point migrated in the same manner as injected fragments or smaller degradation products generated in situ. Tissues which play a secondary role in circulating carboxy-terminal fragment extraction in normal rats can therefore increase this activity in anephric animals. Extraction overall remains less efficient, as demonstrated by the longer half-life of fragments in nephrectomized rats.
Intramammary infection (IMI) treatment and prevention at drying-off is one of the leading causes for using antimicrobials on dairy farms. The objective of the current paper is to describe the protocol used for conducting a systematic review of the literature on non-antibiotic strategies that can be used on dairy cows at dry off to treat and prevent IMI. Relevant literature will be identified using a combination of database search strategies and iterative screening of references. To be included in the review, articles will have to: (1) be published after 1969; (2) be written in English, French, or Spanish; (3) use a study design such as a controlled trial, an observational study, or an experimental study conducted in vivo; (4) be conducted on commercial dairy cows; (5) investigate a non-antibiotic intervention used at dry off; and finally, (6) report on a relevant mastitis outcome. Titles and abstracts, then full articles will be reviewed for inclusion. Specific data will be extracted and risk of bias will be assessed for all included articles. The planned systematic review will be the first to colligate, in a coherent whole, studies investigating non-antibiotic strategies for treating and preventing IMI at drying-off.
Two antisera, C-52 and C-97, raised against bovine (b)PTH(1-84) in guinea pigs, were evaluated with 125I-[tyr53] human (h)PTH(53-84) as tracer and intact hPTH(1-84) and synthetic hPTH(39-84), representative of large carboxylterminal ("C") fragments found in circulation, as standards. In both assays, hPTH(39-84) was 5-6 times more potent than hPTH(1-84) on a molar basis in displacing the tracer. With both antisera, progressive deletion at the aminoterminal end of large "C" fragments, as in hPTH(53-84) and hPTH(65-84), lead to decreased immunoreactivity, hPTH(69-84) being non-immunoreactive. The mid-carboxylterminal fragments, hPTH(44-68) and hPTH(39-68), did not react in either assay. Each antiserum measured known quantities of pure hPTH(1-84) or hPTH(39-84) standards similarly. Serum PTH values obtained with antiserum C-97 were about 3 times higher in renal failure, 1.75 times higher in normal individuals and those with primary hyperparathyroidism, while similar to values measured with antiserum C-52 in individuals with secondary hyperparathyroidism without renal failure or with pseudohypoparathyroidism. When circulating PTH taken from patients with these disorders was fractionated by gel chromatography, both antisera recognized similar peaks of intact hPTH(1-84) and of large "C" fragments while antiserum C-97 further recognized a peak of smaller "C" fragments. This explained the different clinical behavior of the latter antiserum. Our findings demonstrate the existence of small late "C" fragments in circulation. They further suggest an influence of serum calcium and of renal function on the quantity of these fragments.
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