Menthol stimulates calcium absorption in the rumen but not in the jejunum of sheep.

Stimulation of Ca2+ absorption can counteract hypocalcemia at the onset of lactation. The plant bioactive lipid compound (PBLC) menthol is an agonist for nonselective cation channels of the transient receptor potential (TRP) family. It acutely stimulated Ca2+ absorption in ruminal epithelia of nonadapted animals ex vivo and caused higher plasma Ca2+ concentrations in cows and sheep in vivo. To elucidate the pathway by which menthol feeding increases plasma Ca2+ level, the present study aimed to investigate the long-term dose-dependent effects of dietary menthol-rich PBLC on Ca2+ absorption and mRNA abundances of TRP channels in both rumen and jejunum. Twenty-four growing Suffolk sheep were equally distributed to a Con, PBLC-L, and PBLC-H group, which received 0, 80, and 160 mg/d of a menthol-rich PBLC. After 4 wk, ruminal and jejunal epithelia were analyzed for mRNA abundances of TRPA1, TRPV3, TRPV5-6, and TRPM6-8 genes. The Ca2+ flux rates and electrophysiological properties of epithelia from rumen and mid-jejunum were measured in Ussing chambers in the presence and absence of mucosal Na+. Acute changes in Ca2+ flux rates were measured after mucosal application of 50 µM menthol. Ruminal epithelia had quantifiable transcripts of TRPV3 = TRPM6 >TRPM7 >TRPA1 with no difference among feeding groups. Jejunum had quantifiable transcripts of TRPM7 >TRPA1 ≥ TRPM6 ≥ TRPV6 >TRPV5, where TRPA1, TRPV5, and TRPV6 tended to decrease linearly with increasing PBLC dose. Absorptive net flux of Ca2+ was detected only in the rumen, whereas jejunum showed a high passive permeability to Ca2+. Net flux rates of Ca2+ in the rumen increased in a quadratic manner (highest in PBLC-L animals) and were systematically decreased with the omission of mucosal Na+. Short-circuit current increased in both PBLC feeding groups compared with Con only in the rumen. Acute application of menthol-stimulated mucosal-to-serosal and net Ca2+ flux rates only in ruminal epithelia with higher stimulation in PBLC-fed animals. We conclude that Ca2+ transport is mainly active and transcellular in the rumen. It most likely involves TRPV3 that can be stimulated by menthol. Pre-feeding of menthol-rich PBLC enhances ruminal Ca2+ absorption and sensitizes it to acute stimulation by menthol. By contrast, intestinal Ca2+ absorption is not sensitive to menthol stimulation. Menthol could be used as a tool to enhance ruminal Ca2+ absorption and to prevent hypocalcemia in dairy cows.

Dietary supplementation of essential oils in dairy cows: evidence for stimulatory effects on nutrient absorption.

Results of recent in vitro experiments suggest that essential oils (EO) may not only influence ruminal fermentation but also modulate the absorption of cations like Na+, Ca2+ and NH4 + across ruminal epithelia of cattle and sheep through direct interaction with epithelial transport proteins, such as those of the transient receptor potential family. The aim of the current study was to examine this hypothesis by testing the effect of a blend of essential oils (BEO) on cation status and feed efficiency in lactating dairy cows. In the experiment, 72 dairy cows in mid-to-end lactation were divided into two groups of 36 animals each and fed the same mixed ration with or without addition of BEO in a 2×2 cross-over design. Feed intake, milk yield and composition, plasma and urine samples were monitored. Feeding BEO elevated milk yield, milk fat and protein yield as well as feed efficiency, whereas urea levels in plasma and milk decreased. In addition, plasma calcium levels increased significantly upon BEO supplementation, supporting the hypothesis that enhanced cation absorption might contribute to the beneficial effects of these EO.

Refinement of the chromosome 5p locus for craniometaphyseal dysplasia.

Craniometaphyseal dysplasia--Jackson type (CMDJ) is an autosomal dominant bone dysplasia with hyperostosis and sclerosis of the skull and abnormal modelling of the metaphyses. In a large German pedigree, a locus for CMDJ has been mapped previously to the short arm of chromosome 5 (5p15.2-p14.1), defining a 19-cM disease interval between markers D5S2004 and D5S502. Analysis of a large Australian pedigree together with a second German family confirms linkage to the same region. Obligate recombinations in the new families and confirmation of a supposed recombination in the previously reported German kindred have enabled us to narrow the critical region down to approximately 4 cM between markers D5S1987 and D5S1991.

Metaphyseal dysplasia: a new autosomal dominant type in a large German kindred.

We describe a new autosomal dominant type of metaphyseal dysplasia (MD) in five generations of a German kindred. The main characteristics are metaphyseal widening and undermodeling of the tubular bones with Erlenmeyer flask-like appearance of the distal femora (typical of MD), with unusually severe varus deformity of the radii and flat exostoses of the long bones localized in the metaphyses. The skull is unaffected. Allelism with craniometaphyseal dysplasia (CMD) was excluded by linkage analysis.

Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia.

Craniometaphyseal dysplasia (CMD) is a bone dysplasia characterized by overgrowth and sclerosis of the craniofacial bones and abnormal modeling of the metaphyses of the tubular bones. Hyperostosis and sclerosis of the skull may lead to cranial nerve compressions resulting in hearing loss and facial palsy. An autosomal dominant form of the disorder (MIM 123000) was linked to chromosome 5p15.2-p14.1 (ref. 3) within a region harboring the human homolog (ANKH) of the mouse progressive ankylosis (ank) gene. The ANK protein spans the outer cell membrane and shuttles inorganic pyrophosphate (PPi), a major inhibitor of physiologic and pathologic calcification, bone mineralization and bone resorption. Here we carry out mutation analysis of ANKH, revealing six different mutations in eight of nine families. The mutations predict single amino acid substitutions, deletions or insertions. Using a helix prediction program, we propose for the ANK molecule 12 membrane-spanning helices with an alternate inside/out orientation and a central channel permitting the passage of PPi. The mutations occur at highly conserved amino acid residues presumed to be located in the cytosolic portion of the protein. Our results link the PPi channel ANK with bone formation and remodeling.

Craniometaphyseal dysplasia in six generations of a German kindred.

Craniometaphyseal dysplasia (CMD) was found in 6 generations of a large German kindred; 24 affected individuals were identified. The clinical diagnosis was confirmed by further examinations in 15 individuals, including 2 exhumed skeletons. Five deceased individuals were considered to be undoubtedly affected by reviewing photographs, and 4 must have had CMD from genealogical considerations. Pedigree analysis was performed over 8 generations back to persons born at the beginning of the 18th century in a central area of Germany. The trait could be traced back to a common male ancestor, born in 1790. Molecular genetic investigations on 3 generations of this kindred are in progress. In the present study we describe the clinical characteristics of the family.

The gene for autosomal dominant craniometaphyseal dysplasia maps to chromosome 5p and is distinct from the growth hormone-receptor gene.

Craniometaphyseal dysplasia (CMD) is an osteochondrodysplasia of unknown etiology characterized by hyperostosis and sclerosis of the craniofacial bones associated with abnormal modeling of the metaphyses. Sclerosis of the skull may lead to asymmetry of the mandible, as well as to cranial nerve compression, that finally may result in hearing loss and facial palsy. We have analyzed a large German kindred with autosomal dominant (AD) CMD and found tight linkage between the disorder and microsatellite markers on chromosome 5p (maximum two-point LOD score 4.82; theta = 0). Our results clearly establish the existence of a locus for AD CMD on central chromosome 5p (5p15.2-p14.1). This region overlaps with the mapping interval of the growth hormone-receptor (GHR) gene (5p14-p12), which is known to be involved in the mitogenic activation of osteoblasts. Therefore, we tested the GHR gene as a candidate gene. However, recombination events between the CMD locus and the GHR gene identified in two members of this family clearly exclude this candidate.

[Radius-femoral dysplasia. A new form of hereditary metaphyseal dysplasia]. / Radio-femorální dysplazie. Nová forma hereditárních metafyzárních dysplazií.

Höhle and Braun described a new form of hereditary metaphyseal dysplasia. It is characterized by changes in distal metaphyses of femoral bones which are formed as Erlenmeyer flasks, further by club-shaped dysplasias of the metaphyses of the other long bones, absence of skeletal hyperostosis and by characteristic varus-deformations of radial bones. An extensive family history research showed that the oldest carriers of these anomalies came from a small town in northern Bohemia. Completely identical case reports were published describing the carriers of metaphyseal dysplasia characters whose origin was also traced to the same region. The authors aim at drawing attention to this new disease, finding more carriers of metaphyseal dysplasia characters and at giving an impulse to an extensive research into this extremely systemic rare bone disease.

[Diaphyseal dysplasia (Camurati-Engelmann)]. / Diaphsäre Dysplasie (Camurati-Engelmann).

Nine cases in three families with diaphyseal dysplasia are reported. In one family diaphyseal dysplasia and neurofibromatosis are combined. A lymphatic leucosis was found in one case. The possible autosomal recessive mode of inheritance in one family refer to heterogeneity in diaphyseal dysplasia.

[A new form of familial metaphyseal dysplasia. Preliminary report]. / Eine neue Form der familiären metaphysären Dysplasie. Vorläufige Mitteilung.

A new hereditary form of metaphyseal dysplasia is described. A clear distinction from other forms of metaphyseal dysplasias is evident by the lack of hyperostosis of the skull, an autosomal dominant inheritance, Erlenmeyer flask deformity of the distal femoral metaphyses, and characteristic deformations of the radius. The observation is discussed, and reference is given to an identical observation published earlier.