Influence of oxytocin receptor single nucleotide sequence variants on contractility of human myometrium: an in vitro functional study.

BACKGROUND: Oxytocin receptor (OXTR) gene variants have been shown to affect the prevalence of preterm birth, mode of delivery and oxytocin (OXT) requirements for labor induction and augmentation. We hypothesized that this might be associated with different myometrium responses to oxytocin. Our aim was to investigate the influence of a selection of eight OXTR gene single nucleotide variants on oxytocin-induced stimulation of human myometrium contractility in vitro. METHODS: Human myometrium biopsies were collected during elective cesarean sections at term, if patients had given informed consent. Myometrial strips were submerged under tension in an organ bath and allowed to contract; the remaining material was stored at - 80 °C for further determination of relevant genetics and mRNA level. The area under the curve (AUC) of all contractions taking place in the absence of OXT and of those occurring upon OXT addition (for 30 min each) was measured. OXT stimulation, defined as the ratio between AUC measurements after OXT addition and those in the absence of OXT was calculated for each strip. TaqMan™ Assays were used to detect the allele distribution of the eight OXTR variants and to determine the relative amounts of OXTR-mRNA in the samples. For each variant, oxytocin stimulation of contractility was compared between samples homozygous for the reference allele (reference group) and samples with at least one variant allele (variant group) by linear regression. RESULTS: Sixty samples were included in the present study. For rs1042778, rs11706648, rs4686301, rs53576, rs237895, and rs237902, OXT stimulation was similar in the reference and in the variant groups. However, the values of OXT stimulation differed significantly between the reference and the variant groups for rs4686302 (3.1 vs. 4.1 times; p = 0.022) and rs237888 (3.2 vs. 5.5 times; p = 0.001). No significant differences between the levels of OXTR-mRNA in the various reference and corresponding variant groups were detected. CONCLUSIONS: Patients with variant alleles of rs237888 and/or rs4686302 may be more sensitive to oxytocin stimulation, explaining why these sequence variants have been associated with lower cesarean section prevalence and premature birth, respectively.

Whole blood, plasma viscosity, and erythrocyte aggregation as a determining factor of competitiveness in standard bred trotters.

In situations where capillary perfusion in skeletal muscles is limited, changes in blood flow play an important role. Especially alterations in intrinsic erythrocyte factors like red cell aggregation and deformability would increase blood flow resistance. In our study we investigated whether whole blood and plasma viscosity influence exercise tolerance during submaximal training and whether a difference can be realized between trained and untrained standardbred trotters. Venous blood from 42 healthy adult trotters (20 horses at the beginning of their training and 22 well trained horses) was investigated before, immediately afterwards and 30 minutes after submaximal exercise. In both groups whole blood viscosity (WBV; LS30, Contraves, Switzerland) increased significantly (p<0.001) at all shear rates (94 s-1, 2.4 s-1, 0.7 s-1) and decreased after 30 minutes to baseline, as did plasma viscosity (PV; OCR-D, Paar, Austria; p<0.001). No changes in WBV could be seen in hematocrit (40%) standardized samples. Erythrocyte aggregation (EA) indices increased (Myrenne, Germany; p<0.001). Creatin-kinase (p<0.001), lactate (p<0.001), hemoglobine (p<0.001), heart rate and oxygen saturation (p<0.05) increased, while PH (p<0.05), and BE (p<0.001) decreased during the race. In our study, submaximal exercise was related to remarkable changes in hemorheologic variables in the single animal. It was also shown that exercise resulted in a more extensive change of fluidity in well trained horses in comparison to untrained animals, at least for low shear WBV and EA (p<0.05).

Red blood cell deformability and aggregation behaviour in different animal species.

Comparative animal studies showed the wide variation of whole blood and plasma viscosity, and erythrocyte aggregation among mammalian species. Whole blood viscosity and red blood cell aggregation is influenced by red cell fluidity. To evaluate differences in erythrocyte deformability in mammals, three species were investigated, whose erythrocytes have a different aggregation property: horse, as a species with high, dog with medium, and sheep with almost unmeasurable aggregation tendency. Erythrocyte deformability was tested ektacytometrically (Elongation Index [EI], LORCA, Mechatronics, Hoorn, Netherlands) at shear stresses from 0.30 to 53.06 Pa. Equine erythrocytes showed EI-values from 0.047 at low shear stress to 0.541 at high shear stress. The EI from dog's erythrocytes ranged from 0.035 to 0.595. Sheep's erythrocytes had an EI of 0.005 at low and 0.400 at high shear stress. Although it might be presumed from the aggregation property that horse had the highest EI among the three species, the EI of canine erythrocytes exceeded the value in horses by 10% at high shear stress. Further, equine erythrocytes started to deform at higher shear stresses (1.69 Pa) than did canine and ovine cells, whose EI increased continuously with increasing shear stress. At moderate shear stress (1-5 Pa) deformability was even higher in the sheep than in the horse. However, at shear stresses higher than 5.34 Pa, equine red cell elongation clearly exceeded the values of sheep. We conclude that erythrocyte elongation is different between the animal species, not clearly linked with the aggregation property, and that the degree of deformability at various shear stresses is species-specific.

[Bone resorption at the entry of osseointegrated implants--a biomechanical phenomenon. Finite element study]. / Die Knochenresorption an der Eintrittstelle osseointegrierter Implantate--ein biomechanisches Phänomen. Eine Finite-Element-Studie.

Using finite element analysis, osseointegrated implants exposed to physiologic stresses were examined for the occurrence of stress concentrations at the site of implant entry into bone and factors affecting such stress concentrations were looked for. Qualitative and quantitative alterations of stresses around endosseous implants were computed for different implant sizes, implant materials and cortical thicknesses. The following factors were found to be important for reducing peak stresses in cortical bone: Cylindrical implants are preferable to conical implant shapes. Large implant diameters provide for more favorable stress distributions. Implant materials should have a modulus of elasticity of at least 110,000 N/mm2. Slipping between implants and cortical bone is desirable.

[Biomechanical principles of endosseous screw implants]. / Biomechanische Grundlagen enossaler Schraubenimplantate.

The present paper uses the finite element (FE) method to examine the influence exerted by the cortex layer thickness, the implant material, the implant dimensions and the thread form on the tensions developing within the bone around the implant. In the construction of an appropriate screw special attention must be paid to high rigidity of the implant, rather than to thread design, so that any kind of pointed ends are avoided. Firm incorporation of the screw by way of osseointegration should exist only in the spongiosa area and continuously decrease towards the bone surface.