The treatment effect of rivaroxaban on clot characteristics in patients who present acutely with first time deep vein thrombosis.

BACKGROUND: The acute vascular disease deep vein thrombosis (DVT) requires oral anticoagulants to prevent progression. Monitoring therapeutic efficacy of direct oral anticoagulants (DOAC), including rivaroxaban, is problematic as no reliable test is available. Advances in rheometry have led to the development of a functional coagulation biomarker using Gel Point (GP) analysis which assesses clot structure formation. The biomarker measures incipient clot formation time (TGP) and quantifies fibrin clot structure in terms of fractal dimension (df). OBJECTIVE: This study aimed to investigate clot structure formation in first time DVT and the effect of rivaroxaban treatment. METHODS: This prospective observational cohort study measured the GP and standard laboratory markers at three sample points: pre-treatment and at 20 and 60 days following 15 mg BD and 20 mg OD rivaroxaban respectively. RESULTS: Forty DVT patients (mean age 64 years [SD±14.8]; 23 males, 17 female) were recruited. The results show that DVT vs non-DVT patients did not have a significantly different GP profile (df: 1.72±0.06 vs 1.70±0.06 and TGP: 267±68 sec vs 262±73 sec) with both within the defined healthy index. In addition, rivaroxaban therapy increased TGP to 392 s (±135 s) after 20 days, and subsequently increased to 395 s (±194 s) at 60 days but did not significantly increase df (from 1.69±0.05 to 1.71±0.06). CONCLUSIONS: The results indicate in this cohort of DVT patients there was no underlying hypercoagulable effect as determined by gel point analysis. Furthermore, the anticoagulant effect of rivaroxaban prolonged clotting, suggesting a protective effect against clot formation, without significantly reducing clot microstructural properties.

Frictional resistances of metal-lined ceramic brackets versus conventional stainless steel brackets and development of 3-D friction maps.

The frictional resistances of 2 metal-lined ceramic brackets (Luxi and Clarity) were compared with 2 conventional stainless steel brackets (Mini-Taurus and Mini-Twin) in vitro. In method 1, we varied the second-order angulation from 0 degrees to 12 degrees while maintaining the normal or ligature force constant at 0.3 kg; in method 2, we varied the ligature force from 0.1 kg to 0.9 kg while maintaining the angulation at theta = 0 degrees or theta = 11 degrees. The hardware simulated a 3-bracket system in which the interbracket distances were always 18 mm. All couples were evaluated at 34 degrees C using the same size stainless steel archwire (19 x 26 mil) and ligature wire (10 mil). In the passive region, the static and kinetic frictional forces and coefficients of friction were key parameters; in the active region, the static and kinetic binding forces and coefficients of binding were critical parameters. From outcomes of methods 1 and 2, the 4 aforementioned parameters, and a knowledge of the critical contact angle for binding, 3-dimensional friction maps were constructed in the dry and wet states from which the frictional resistances could be determined at any ligature force or second-order angulation. Those 3-dimensional maps show that metal-lined ceramic brackets can function comparably to conventional stainless steel brackets and that 18-kt gold inserts appear superior to stainless steel inserts. As the morphologies of metal inserts are improved, these metal-lined ceramic brackets will provide not only good esthetics among ceramic brackets but also minimal friction among conventionally ligated brackets.

Molecular cloning, genomic organization and selective expression of bombesin receptor subtype 3 in the sheep hypothalamus and pituitary.

The bombesin receptor subtype 3 (BRS-3) is considered an orphan receptor as it has a low affinity for bombesin-like peptides and no identified natural ligand. We have reported a novel form of gastrin-releasing peptide (GRP) present in high abundance in the pregnant uterus of women and sheep. As BRS-3 was originally cloned from guinea pig uterus, we postulated that the uterine GRP-like peptide may be its natural ligand. We have therefore cloned the gene for the sheep homologue of BRS-3 and determined its distribution. The sheep BRS-3 gene spans 4 kbp and comprises three exons with intron-exon borders at positions similar to those observed for the human and mouse BRS-3 genes. The predicted amino acid sequence of ovine BRS-3 has approximately 85% identity with the human, mouse and guinea pig receptors. Highly conserved amino acids important in mediating receptor G-protein coupling to second messengers and important in ligand binding were found to be conserved in ovine BRS-3. One potentially important deviation was noted: ovine BRS-3 possesses an arginine residue at position 294 instead of a histidine residue as found in all other BRS-3. His(294) was previously identified as important in ligand-receptor interactions while Arg(294) was implicated in high ligand affinity. Thus ovine BRS-3 may have binding characteristics different from those of the human, mouse and guinea pig BRS-3 receptors. In the ewe, BRS-3 mRNA expression was detected in pituitary and hypothalamus but not in tissues of the pregnant uterus (endometrium, myometrium, chorioallantois or amnion). Nor was BRS-3 expression detected in the non-pregnant uterus or in testis. This pattern of BRS-3 expression is similar to that observed in the mouse but different from that observed in the human, rat and guinea pig. We conclude that there is no local interaction between uterine GRP-like peptide and BRS-3. However, the high expression of BRS-3 in the pituitary coupled with elevated circulating levels of this GRP-like peptide during pregnancy suggests an alternate pathway. Cloning of the ovine BRS-3 gene will permit a detailed functional analysis of this receptor in the sheep and its role in the mediation of action of uterine GRP.

Zirconia brackets: an evaluation of morphology and coefficients of friction.

The frictional characteristics of two types of zirconia (Harmony, Hudson Ltd., Sheffield, U.K., and Toray, Yamaura Corp., Tokyo, Japan) brackets were compared with those of polycrystalline alumina (Transcend 2000, Unitek Corp., Monrovia, Calif.) brackets in both dry and wet states. To compare the couples, four arch wire alloys were studied: stainless steel, cobalt-chromium, nickel titanium, and beta-titanium. Under dry conditions, the highest frictional coefficients were seen with the Harmony/beta-titanium couple (uk = 0.64); the lowest values were seen with both Transcend 2000/stainless steel (uk = 0.13) and Toray/cobalt-chromium couples (uk = 0.13). Beta-titanium arch wires produced the highest coefficients of friction against each type of ceramic bracket, except against Toray arch wires in the wet state. The presence of human saliva produced only slight changes in the frictional behavior of zirconia brackets. We conclude that currently available zirconia brackets offer no significant improvement over alumina brackets with regard to their frictional characteristics.

Frictional coefficients of ion-implanted alumina against ion-implanted beta-titanium in the low load, low velocity, single pass regime.

The frictional coefficients were measured for four wire alloys against the flats of polycrystalline alumina cylinders using a low load, low velocity, single pass device. Ion-implantations of titanium into polycrystalline alumina flats and nitrogen into beta-titanium wires reduced the static and kinetic coefficients from 0.50 and 0.44 before implantation to 0.20 and 0.25 after implantation, respectively. These results are similar in magnitude to frictional coefficients for unimplanted, control couples of stainless steel, cobalt-chromium, and nickel titanium wires against polycrystalline alumina flats. For orthodontic applications, we conclude that more efficient and reproducible appliances can be engineered for tooth movement if ion-implantation is used to reduce the abrasion of beta-titanium by polycrystalline alumina.

Comparison of the frictional coefficients for selected archwire-bracket slot combinations in the dry and wet states.

Coefficients of friction were evaluated in the dry and wet (saliva) states for stainless steel, cobalt-chromium, nickel titanium, and beta-titanium wires against either stainless steel or polycrystalline alumina brackets. For both operators' experiments, an 0.010" stainless steel ligature wire pressed each archwire into the 0.018" or 0.022" bracket slot at 34 degrees C. In the dry state and regardless of slot size, the mean kinetic coefficients of friction were smallest for the all-stainless steel combinations (0.14) and largest for the beta-titanium wire combinations (0.46). The coefficients of the polycrystalline alumina combinations were generally greater than the corresponding combinations that included stainless steel brackets. In the wet state, the kinetic coefficients of the all-stainless steel combinations increased up to 0.05 over the dry state. In contrast, all beta-titanium wire combinations in the wet state decreased to 50% of the values in the dry state. The mixed reports that saliva may promote adhesive and lubricious behaviors may have some substance.

Coefficients of friction for arch wires in stainless steel and polycrystalline alumina bracket slots. I. The dry state.

The surface roughness and the coefficients of friction were measured for sixteen arch wire-bracket combinations. The sample included one rectangular arch wire product from each of the four principal alloy groups and one bracket product from among the stainless steel and polycrystalline alumina inventory. Although subsamples representing both the 0.018-inch and the 0.022-inch slot sizes were evaluated, no differences were observed in their rankings. When tested over a series of eight incident angles, the optical surface roughness of representative stainless steel and alumina brackets averaged 0.148 and 0.193 microns, respectively. After testing at a single angle (82 degree) and referencing a nomogram, the roughness of the stainless steel, cobalt-chromium, beta-titanium, and nickel-titanium arch wire surfaces averaged 0.053, 0.129, 0.137, and 0.247 microns, respectively. When the various arch wire-bracket couples were pressed against an 0.010-inch stainless steel ligature wire at 34 degrees C and otherwise prevailing atmospheric conditions, the coefficients of friction ranged from stainless steel (lowest) to cobalt-chromium, nickel-titanium, and beta-titanium (highest)--regardless of bracket product or slot size. These results corroborated earlier observations in which the same arch wire products were drawn between stainless steel or alumina contact flats. In the current research, the average coefficient of kinetic friction for the stainless steel couple (0.139) was less than that for the stainless steel arch wire against a polycrystalline alumina bracket (0.174).

Effects of surface roughness on the coefficients of friction in model orthodontic systems.

Orthodontists, like others (Engel, P.A. (1976) Impact Wear of Materials. Elsevier Scientific, New York.), often equate the smoothness of surfaces with the absence of friction. To investigate whether the surface roughness of opposing materials influence the coefficients of friction and ultimately the movement of teeth, arch wires were slid between contact flats to simulate orthodontic arch wire-bracket appliances. From laser specular reflectance measurements, the RMS surface roughness of these arch wires varied from 0.04 microns for stainless steel to 0.23 microns for nickel titanium. Using the same technique, the roughnesses of the contact flats varied from 0.03 microns for the 1 micron lapped stainless steel, to 0.26 microns for the as-received alumina. After each of the arch wire-contact flat couples was placed in a friction tester, fifteen normal forces were systemically applied at 34 degrees C. From plots of the static and kinetic frictional forces vs the normal forces, dry coefficients of friction was obtained that were greater than those reported in the dental literature. The all-stainless steel couples had lower kinetic coefficients (0.120-0.148) than the stainless steel-polycrystalline alumina couple (0.187). When pressed against the various flats, the beta-titanium arch wire (RMS = 0.14 microns) had the highest coefficients of friction (0.445-0.658), although the nickel titanium arch wire was the roughest (RMS = 0.23 microns). Scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) verified that mass transfer of the beta-titanium arch wire occurred by adhesion onto the stainless steel flats or by abrasion from the sharply faceted polycrystalline alumina flats.

Iron for the suckling.

Knowledge of the metabolism of iron by young infants is incomplete but combining practical studies based on detecting the onset of iron depletion with isotopic studies of iron economy may improve our understanding of iron metabolism in infants and our strategies for ensuring their iron supply. The iron accumulated by the fetus is enough to delay the risk of iron deficiency until four, and two months of age in term and preterm infants respectively. Breast fed term infants may not need extra iron until they are six months or older; but whereas low iron formulas are adequate for other infants until about four months of age, thereafter infants need extra iron which can be provided effectively in iron fortified formulas. Breast fed low birth weight infants need iron supplements from two months of age but those fed specific low birth weight formulas which are iron fortified should not need extra iron.

Uptake and excretion of inorganic mercury in the lobster Homarus gammarus (L.) White 1847: long-term effects of exposure to low levels of the metal.

The uptake and accumulation of inorganic mercury by lobsters, from seawater containing levels of 10 to 100 ppb, was studied over periods of up to 50 days, using radiochemical neutron activation analysis. These results were amplified by the use of radioisotope tracer experiments. It was found that the gills and the green glands accumulated the most mercury and that the metal could be excreted via the urine. Histological studies showed that long-term exposure to mercury resulted in progressive necrosis of the green glands, whereas other organs were unaffected.