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[On the treatment of the osteodystrophia deformans (Paget's disease) with synthetic salmon calcitonin (author's transl)].

Sixteen patients with Paget's disease of bone aged from 51 to 80 years was treated daily with 20 micrograms (equivalent to 80 MRCU) synthetic salmon calcitonin. Fourteen patients was observed on a long time. In all cases was observed significant reductions in increased serum alkaline phosphatase. The urinary hydroxyproline excretion was also decreased. Other laboratory dates as serum calcium, serum phosphorus, serum acide phosphatase, urinary calcium and phosphorus excretion was not significantly influenced by the therapy. The treatment produced a clear remission of pain. After treatment of 6 months the dose was reduced (2 or 3 injections subcutaneously of 20 micrograms salmon calcitonin weekly). There was observed a recurrence of pain and an increase of serum alkaline phosphatase, but not until the pretreatment values. These results confirm the effectiveness of calcitonin treatment in Paget's disease of bone.

Aged

Large Haplotypes Linked to Climate and Life History Variation in Divergent Lineages of Atlantic Salmon (Salmo salar).

Advances in sequencing are revealing that linked genomic architectures, enabling the evolution of co-adapted alleles at multiple loci, often shape complex phenotypes. Several recent studies have identified such architectures (e.g., chromosomal rearrangements and supergenes) contributing to adaptation or divergence across diverse species, from plants to mammals. Specifically, within Atlantic salmon (Salmo salar ), genomic studies are revealing large haplotypes and structural variants that may underpin local adaptation in the species. Using data from > 4000 individuals from 134 locations spanning the North Atlantic Ocean, we identify a large (~3 Mbp) genomic region on Ssa18 showing patterns of differentiation and linkage disequilibrium (LD) indicative of a large haplotype block containing three divergent haplotypes (herein A, B and C haplotypes). In Europe, haplotypes A and B were common, whereas A and C were more common within North America, suggesting a shared 'ancestral' A haplotype, with different continent-specific alternative haplotypes. Data support independent origins of divergent haplotypes in each continent, as well as signals of trans-oceanic introgression of haplotypes. Haplotype frequency is strongly associated with latitude, climate and life history (smolt age); however, the strength and direction of these relationships vary across continents. Overall, our analyses were consistent with other studies that identify chromosomal rearrangements; however, long-read sequence data did not find evidence of a structural variant, and instead an ancestral fusion may explain the formation and maintenance of the observed haplotypes. Our study contributes to ongoing efforts to understand the evolutionary role of linked genomic architecture in Atlantic salmon and its significance in salmonid diversification.

Climate Change

[Renal production and excretion of AMPc after intravenous infusion of salmon calcitonin in man].

Intravenous infusion of salmon calcitonin in man produced an increase in the plasma levels and urinary excretion of cyclic AMP. This study demonstrates a net extraction of cyclic AMP from plasma by the kidneys but salmon calcitonin does not act only on the kidney and stimulates the production of cyclic AMP in extra renal tissues. The excess of cyclic AMP formed is catabolized by the kidneys.

Adult

Does salmon calcitonin influence the motility of the human gastrointestinal tract? An electromanometric and endoscopic study.

The effect of salmon calcitonin--as a relatively high dose of 25 mug by single iv. injection--upon the basal and metoclopramide-stimulated motility phenomena of the stomach and proximal duodenum as well as upon the unstimulated colon and rectosigmoid was evaluated in 12 subjects without gastrointestinal disease by quantitative electromanometric measurements performed for one hour with the aid of fluid-filled micro-balloon-catheter-systems. Additionally, in 9 subjects the reaction of the cardia, stomach, pylorus and proximal duodenum upon the same dose of the hormone was observed endoscopically for 30 minutes. Under the conditions of our study there was no evidence to be obtained for any measurable or visible effect of salmon calcitonin upon the tonus and motility of the smooth muscle organs of the human gastrointestinal tract.

Animals

Gonadotropic cells in the Atlantic salmon, Salmo salar. An experimental immunocytological, electron miscroscopical study.

The gonadotropin-producing cells (GTH-cells) in the Atlantic salmon were studied light and electron microscopically before, during and after spawning, and after injections of luteinizing hormone-releasing hormone (LH-RH). The double immunofluorescent technique was applied using rabbit anti-carp GTH as the first antibody. Numerous immunofluorescent cells were observed throughout the pars distalis, but very few in the pars intermedia. These cells are basophilic and PAS-positive, and ultrastructurally classified as globular gonadotropes. Only one gonadotropic cell type could be identified; its size, morphology and fine structure vary considerably. In the same specimen the GTH-cells can be predominantly globular or vesicular in appearance, depending on the reproductive phase of the fish. At spawning and after LH-RH injection, many GTH-cells reach a vacuolar stage; the content of the vacuoles is not immunofluorescent. Another cell type, which resembles GTH-cells in semi-thin sections, did not show gonadotropic properties; its nature and functional significance are unknown. In addition, the present study revealed an increase in the synthetic and exocytotic activity of prolactin cells after LH-RH injections. It is suggested that LH-RH mediates this effect via LH and eventually via estradiol.

Animals

Effects of salmon calcitonin on blood glucose and insulin levels under basal conditions and after intravenous glucose load.

A study of the effects of salmon calcitonin (sCT) infusion on blood sugar and serum insulin levels under basal conditions and after intravenous glucose load in normal subjects is reported. Under basal conditions, a 30 min infusion of sCT at approximately a rate of 1 U/min produced a highly significant increase in the blood sugar (p less than 0.01) and a highly significant decrease in the serum insulin levels (p less than 0.01). After intravenous glucose load, there was a decrease of the coefficient of glucose utilization and of the insulin response both of which were highly significant (p less than 0.01).

Adult

Comparisons of Methods for Mucus Sampling and Mucin Semi-Quantification on Barramundi (Lates calcarifer) and Atlantic Salmon (Salmo salar) Epithelial Sites.

Fish epithelial surfaces are covered by a mucus layer. The highly glycosylated proteins called mucins are a main component of the mucus, which also contains a range of antibacterial enzymes, proteins, and peptides of importance for its protective properties. Here, we compared the practicality and yield of mucus harvesting from barramundi and Atlantic salmon epithelial sites using glass slide, swab, Super·SAL™ and whole tissue extract. We also compared the feasibility of using the orcinol assay, a glycan-on-membrane assay, and absorbance at 230 nm in combination with standard curves of pig gastric mucin to estimate the mucin concentration. Glycomics demonstrated that non-amine hexose content differed more between fish and tissues than terminal monosaccharides with cis-hydroxy groups, and that non-mucin molecules had a major impact on the A230-based results, making the glycan-on-membrane assay the most versatile method for estimating mucin concentration. We conclude that the most versatile tool for mucus harvesting was swabs, allowing for sufficient amounts of sample to be harvested with relative ease and low levels of contamination from the oral cavity, gill, skin, and intestine. Furthermore, the glycan-on-membrane assay was useful for measuring mucus concentration, and it was beneficial to estimate both sample concentration and purity by comparing samples at relatively similar concentrations.

Animals

Biological and immunological properties of tritiated salmon calcitonin.

Tritiated salmon calcitonin was prepared by methylation of the free amino groups using tritiated sodium borohydride as precursor. Specific radioactivity was measured in competitive inhibition studies with specific anticalcitonin antibodies or tubular membranes as binding sites for calcitonin. The value observed, approx. 4 Ci/mmol, corresponded to methylation of one third of the available N-H bonds. Tritiated calcitonin prepared in this way retained full biological activity as assessed in vitro by stimulation of adenylate cyclase and in vivo by rat bioassay. Tritiated calcitonin specifically bound to isolated renal cells and nonspecific binding did not exceed 10% of total binding. Equilibrium was obtained after 15 min incubation. The hormone-receptor complex could be dissociated in the presence of an excess of unlabelled calcitonin. This data shows that tritiated calcitonin can be used in metabolic and receptor studies.

Adenylyl Cyclases

Salmon calcitonin in the acute treatment of moderate and severe hypercalcemia in man.

The effect of i.v. infusions with salmon calcitonin was evaluated in the treatment of acute hypercalcemia in 12 patients. Clinical improvement and a less critical level of serum calcium were achieved within 24 hours for eight of the patients, for another two after treatment for 48 hours. In malignant conditions (six patients) calcitonin was less effective, which could be evaluated within 24 hours. In addition to rehydration, the rapid onset of action and the lack of side-effects make calcitonin a drug of first choice in the treatment of acute hypercalcemia.

Acute Disease

Functional significance of antibody formation after long-term salmon calcitonin therapy.

Twenty patients with Paget's disease were challenged with porcine (PCT) and salmon (SCT) calcitonin before and after 6 months SCT therapy. Acute hypocalcaemia was clearly related to the prevailing rate of bone turnover but responses to PCT showed that treatment had not disturbed this relationship. Although antibodies to SCT developed in eight patients during the period of treatment the acute hypocalcaemic response to SCT was not diminished in relation to bone turnover. It is suggested that antibodies which develop during the course of SCT therapy do not necessarily exert a functionally effective neutralizing action.

Aged

Development and significance of antibodies to salmon calcitonin in patients with Paget's disease on long-term treatment.

Sixteen consecutive patients in one unit were studied during long-term treatment of Paget's disease of bone with salmon calcitonin. Eleven patients developed detectable antibody titres at some time during treatment. In one patient with a high antibody titre evidence of resistance to treatment emerged two years after the development of antibodies, but no other patient showed evidence of resistance. The clinical and biochemical response could be maintained in the absence of an acute calcium-lowering effect of calcitonin. Although antibodies often develop during treatment with heterologous calcitonin, they are only rarely the cause of clinical resistance.

Animals

Sex chromosomes in the sockeye salmon: a Y-autosome fusion.

Chromosomes of 21 sockeye salmon [Oncorhynchus nerka (Walbaum)] from three locations in Washington state were examined. All males had 57 chromosomes, while all females had 58 chromosomes. Both sexes had 104 chromosome arms. It appears that in males of this species the Y chromosome and an autosome have fused to form a metacentric chromosome.

Animals

Considerations of a method of analyzing diallel crosses of atlantic salmon.

Inferences derived from a proposed mixed model analysis of a diallel cross involving four stocks of Atlantic salmon (Salmo salar) are illustrated with growth data on weight and length. Variation between stocks was more apparent when samples represented dams as opposed to sires, thus stressing the relative importance of maternal effects. However, the ranking of stocks was not altered when either the means of sire sources or the means of dam sources were considered. No heterotic effects were found for the growth traits studied.

Analysis of Variance

DNA nicking--closing activity from salmon testis.

Salmon testis is a good source of DNA nicking--closing (N--C) enzyme, as expected for rapidly proliferating cells. Partial purification was obtained but it resulted in an unstable form of N--C enzyme. Cruder fractions are useful for relaxing supercoiled DNA under conditions where other N--C enzymes are inactive. The enzyme is very tolerant of salt concentration, with activity still detectable at 0.6 M NaCl. It is also active at low temperatures with reasonable activity at 0 degrees C. However, at temperatures greater than 25 degrees C it is rapidly inactivated. Otherwise, its properties are similar to other eucaryotic N--C enzymes.

Animals

Plasma kinetics and urinary excretion of exogenous human and salmon calcitonin in man.

The metabolism and the urinary excretion of synthetic human and salmon calcitonin-(1--32) [hCT-(1--32), sCT-(1--32)] administered by constant infusions for 240 min were investigated in eight normal subjects. On gel filtration of plasma obtained during the infusions mainly intact hCT-(1--32) and sCT-(1--32) were recognized with homologous radioimmunoassay systems. During constant infusions to equilibrium of 0.04 mg hCT-(1--32) and sCT-(1--32), the metabolic clearance rates (MCR) amounted to 8.4 +/- 1.1 and 3.1 +/- 0.1 ml/kg per min, respectively (P less than 0.01). When hCT-(1--32) was infused at rates of 1 and 4 mg/240 min, the MCR were lower than with 0.04 mg hCT-(1--32), but still higher than with 0.04 mg sCT-(1--32). The half-lives of disappearance of hCT-(1--32) were faster compared to sCT-(1--32), but the difference was not statistically significant. The urinary clearance of hCT-(1--32) determined during the 1 and 4 mg/240 min infusions of hCT-(1--32), as well as of sCT-(1--32) determined during the 0.04-mg infusions of sCT-(1--32) was about 0.1% of the MCR. The half-lives of disappearance of hCT- and sCT-(1--32) incubated in vitro in plasma and urine ranged from 17 to more than 72 h, and the degradation did not affect our calculations of the metabolic breakdown of exogenous CT in vivo.

Adult

Thyrotoxicosis and hypercalcaemia: response to antithyroid drugs and salmon calcitonin.

Four patients with thyrotoxicosis, hypercalcaemia and metabolic bone disease are described. One of them had a 'hot nodule', T3 toxicosis and a parathyroid tumour and another had thin bones, subperiosteal cortical bone erosions and complete dysphagia. Hypercalcaemia persisted during treatment with antithyroid drugs in two patients, both of whom had hyperparathyroidism. The administration of salmon calcitonin to these two patients before starting antithyroid treatment produced an immediate and sustained fall in serum calcium and urinary hydroxyproline levels. Calcitonin administration should be of value in the early management of hypercalcaemic patients.

Alkaline Phosphatase

Effect of acute administration of salmon and human calcitonin on blood urate and renal excretion of uric acid in patients with Paget's disease of bone.

The sc injection of salmon calcitonin (CT) (100 MRC U) or human CT (50 MRC U) to Pagetic patients reduces the plasma urate concentration and increases the renal excretion of uric acid. This effect is independent of the natriuretic, phosphaturic, or glycosuric actions of CT and is not due to the transient increment of the glomerular filtration rate noted after CT administration. Our results suggest that the hypouricemia observed during CT treatment is related, at least in part to a direct action on the renal handling of uric acid.

Aged

Paget's disease. Radiological changes occurring in untreated patients and those on therapy with salmon calcitonin during two years' observation.

Radiological observations over two years were made in 23 patients with Paget's disease. Radiological criteria for progression and regression of disease are defined. Fourteen of the patients were treated with salmon calcitonin. Of these treated patients four showed regression of the disease and only two showed progression, both in the skull vault. Of the remaining nine untreated patients none showed regression but two showed progression. The radiological findings confirm that calcitonin will prevent the extension and sometimes induce healing of Paget's disease in long bones but that the skull appears to respond differently. Radiological changes were slow to occur and yearly or two yearly follow up is sufficient.

Aged