Osteoderm histology of the Pampatheriidae (Cingulata,Xenarthra, Mammalia): Implications for systematics,osteoderm growth,and biomechanical adaptation

Pampatheres are extinct, large‐bodied cingulates, which share morphological characters with both armadillos and glyptodonts but are considered to be more closely related to the latter. The osteoderm histology of six pampathere taxa was examined and compared to the histology of other cingulate osteoderms. This study investigates the development and functional adaptation of pampathere osteoderms as well as the phylogenetic relationships of the Pampatheriidae within the Cingulata. We found that pampathere osteoderms share a uniform histological organization based on a basic diploe‐like structure. After initial stages of intramembranous growth, metaplastic ossification, that is, the direct incorporation and mineralization of pre‐existing protein fibers, plays an important role in osteoderm development and provides information on various kinds of soft tissue otherwise not preserved. The latest stages of osteoderm growth are dominated by periosteal bone formation especially in the superficial cortex. Movable band osteoderms show regular arrangements of incorporated fibers that may increase the resistance of particularly weak areas against strain. The histological composition of pampathere osteoderms is plesiomorphic in its basic structure but shows a number of derived features. A unique array of Sharpey's fibers that are incorporated into the bone matrix at sutured osteoderm margins is interpreted as a synapomorphy of pampatheres. The arrangement of dermal fibers in the deep and superficial cortexes supports the close relationship between pampatheres and glyptodonts. J. Morphol., 2012. © 2011 Wiley Periodicals, Inc.     

Development of Eye Position Dependency of Slow Phase Velocity during Caloric Stimulation

The nystagmus in patients with vestibular disorders often has an eye position dependency, called Alexander’s law, where the slow phase velocity is higher with gaze in the fast phase direction compared with gaze in the slow phase direction. Alexander’s law has been hypothesized to arise either due to adaptive changes in the velocity-to-position neural integrator, or as a consequence of processing of the vestibular-ocular reflex. We tested whether Alexander’s law arises only as a consequence of non-physiologic vestibular stimulation. We measured the time course of the development of Alexander’s law in healthy humans with nystagmus caused by three types of caloric vestibular stimulation: cold (unilateral inhibition), warm (unilateral excitation), and simultaneous bilateral bithermal (one side cold, the other warm) stimulation, mimicking the normal push-pull pattern of vestibular stimulation. Alexander’s law, measured as a negative slope of the velocity versus position curve, was observed in all conditions. A reversed pattern of eye position dependency (positive slope) was found <10% of the time. The slope often changed with nystagmus velocity (cross-correlation of nystagmus speed and slope was significant in 50% of cases), and the average lag of the slope with the speed was not significantly different from zero. Our results do not support the hypothesis that Alexander’s law can only be observed with non-physiologic vestibular stimulation. Further, the rapid development of Alexander’s law, while possible for an adaptive mechanism, is nonetheless quite fast compared to most other ocular motor adaptations. These results suggest that Alexander’s law may not be a consequence of a true adaptive mechanism.     

Biochemical characterization of hepatic microsomal leukotriene B4 hydroxylases

omega-Hydroxylation of leukotriene B4 (LTB4) has been reported in human and rodent polymorphonuclear leukocytes; preliminary information indicates that this metabolism is cytochrome P-450 dependent. Therefore, these studies were initiated to characterize the cytochrome P-450-dependent metabolism of LTB4 in other tissues. LTB4 was metabolized by rat hepatic microsomes to two products, 20-hydroxy(omega)-LTB4 and 19-hydroxy(omega-1)-LTB4. The formation of these metabolites was both oxygen and NADPH dependent indicating that a monooxygenase(s) was responsible for these reactions. The apparent Km and Vmax for LTB4 omega-hydroxylase were 40.28 microM and 1202 pmol/min/mg of protein, respectively. In contrast, the apparent Km and Vmax for LTB4 (omega-1)-hydroxylase were 61.52 microM and 73.50 pmol/min/mg of protein, respectively. Both LTB4 omega- and (omega-1)-hydroxylases were inhibited by metyrapone in a concentration-dependent fashion. However, SK&F 525A inhibited LTB4 (omega-1)- but not omega-hydroxylase. In contrast, alpha-naphthoflavone decreased LTB4 omega- but not (omega-1)-hydroxylase activities. The differences in the Km apparent for substrate as well as the differential inhibition by inhibitors of cytochrome P-450 suggest that the omega- and (omega-1)-hydroxylations of LTB4 in hepatic microsomes are mediated by different isozymes of P-450. Furthermore, several additional characteristics of LTB4 hydroxylases indicate that these isozymes of P-450 may be different from those which catalyze similar reactions on medium-chain fatty acids, such as laurate and prostaglandins.     

Metallothionein induction by nonsteroidal antiinflammatory drugs

In the present study we report on the effects of commonly used nonsteroidal antiinflammatory drugs on metallothionein (MT) and MT-I mRNA levels. A single dose of chloroquine (100 mg/kg), diclofenac (100 mg/kg), indomethacin (10 mg/kg), or piroxicam (100 mg/kg) was administered ip to C57B1 mice. After 18 h, MT levels were determined with a Cd-saturation radioassay. MT-I mRNA levels were measured by Northern Blot analyses using a probe containing the mouse MT-I gene. All drugs tested caused an increase in the MT content of the liver but not of the kidneys and lung. The lowest and highest effects were observed with chloroquine (8 times the control value) and diclofenac (18 times), respectively. In accordance with the stimulation of MT synthesis, increased accumulation of hepatic MT-I mRNA could be demonstrated. These results indicate that elevated MT levels may contribute to the effectiveness of nonsteroidal antiinflammatory drugs in the treatment of rheumatoid arthritis (RA).     

Structural and functional characterization of major platelet membrane components derived by limited proteolysis of glycoprotein IIIa

The authors isolated a product of proteolytic degradation of glycoprotein IIIa (GPIIIa) which is formed on the surface of human platelets during incubation with chymotrypsin and which was previously described as the 66 kDa platelet membrane component. This component migrated with an apparent Mr 62,400 in a non-reduced system of sodium dodecyl sulfate polyacrylamide gel electrophoresis. In a reduced system it yielded two major subunits migrating with apparent Mr 14,000-17,000 and 65,000. The low-molecular weight component began with the NH2-terminal sequence of GPIIIa (GPNICTTR...) and the larger component with residue 348 of GPIIIa (GKIRSKKA...) as deduced from a cDNA clone of this glycoprotein. The two subunits appeared to be linked by one or more S-S bridges supporting the contention that GPIIIa is a highly folded molecule on the platelet membrane. In contrast to GPIIIa, the '66 kDa component' did not bind to GRGDSPK-agarose, to fibrinogen-agarose nor to insolubilized monoclonal antibody recognizing the GPIIb/IIIa complex. The exposure of fibrinogen receptors during the course of incubation of platelets with chymotrypsin preceded the formation of the '66 kDa component' characterized in this study. An intermediate product of GPIIIa proteolysis migrating with an apparent Mr 120,000 in a non-reduced system and Mr 80,000 in a reduced system was identified as a precursor of the '66 kDa component'. The '120 kDa component' was not retained on GRGDSPK-agarose or on fibrinogen-agarose but it was retained on insolubilized antibody recognizing the GPIIb/IIIa complex. Incubation of platelets with porcine pancreatic elastase or human granulocytic elastase resulted in the formation of similar proteolytic degradation fragments.     

Rate of erythropoietin formation in humans in response to acute hypobaric hypoxia

This study was carried out to investigate the early changes in erythropoietin (EPO) formation in humans in response to hypoxia. Six volunteers were exposed to simulated altitudes of 3,000 and 4,000 m in a decompression chamber for 5.5 h. EPO was measured by radioimmunoassay in serum samples withdrawn every 30 min during altitude exposure and also in two subjects after termination of hypoxia (4,000 m). EPO levels during hypoxia were significantly elevated after 114 and 84 min (3,000 and 4,000 m), rising thereafter continuously for the period investigated. Mean values increased from 16.0 to 22.5 mU/ml (3,000 m) and from 16.7 to 28.0 mU/ml (4,000 m). This rise in EPO levels corresponds to 1.8-fold (3,000 m) and 3.0-fold (4,000 m) increases in the calculated production rate of the hormone. After termination of hypoxia, EPO levels continued to rise for approximately 1.5 h and after 3 h declined exponentially with an average half-life time of 5.2 h.     

Advances in bioconversion of anthracycline antibiotics

During the last decade new anthracycline-type structures with potential usefulness in cancer treatment have been supplied both by new microbial strains and by bioconversions of precursor molecules employing cells or enzymes. We highlight recent advances in bioconversion of anthracycline structures with the main focus on late transformations such as are carried out by oxidoreductases.