Cryptolepis sanguinolenta: an ethnobotanical approach to drug discovery and the isolation of a potentially useful new antihyperglycaemic agent

Hypoxia induces an increase in PMN adherence to endothelial cells for which an interaction between ICAM-1 and CD18/CD11b has been demonstrated. Since PECAM-1 has been shown to be involved in PMN transmigration through the endothelium and to increase the binding capacity of leukocyte CD18/CD11b, the role of this molecule in the hypoxia-induced PMN adherence was investigated. Hypoxia did not change the total surface expression of PECAM-1 on HUVEC and did not change the cell-cell border localization of this molecule as TNF-alpha did. In addition, blocking anti-PECAM-1 antibodies could not inhibit the increased adherence of unstimulated human PMN to hypoxia-incubated HUVEC while anti-ICAM-1 partially inhibited this process. These results indicate that PECAM-1 is probably not involved in the hypoxia-induced PMN adherence to endothelial cells.     

Colour Doppler hysterosalpingosonography: a simple and potentially useful method to evaluate fallopian tubal patency

The functional state of the amacrine cells which contain enkephalin-, neurotensin- and somatostatin-like immunoreactivity of the chicken retina was monitored by measuring the rate of change in the levels of [Leu]enkephalin-like immunoreactivity in the retina. Dark-adapted birds were exposed to lights of different intensities for 12 h. At light levels of < or = 0.03 microW/cm2, the ENSLI amacrine cells were highly active but, by 0.08 microW/cm2, they reached a state of maximum inactivation. Thus, the ENSLI amacrine cells act as flip-flop devices, inactivated by critical levels of light, which correspond to those which inactivate pineal melatonin synthesis. They may, therefore, be involved in retinal pathways which signal the difference between day and night.     

Evaluation of the frictional properties of an elastomer with enhanced lipid-adsorbing ability

Wear particle production in load-bearing orthopaedic implants is one of the major factors currently limiting the service life of the implant. Most of the research carried out to date in attempting to solve this problem has used the approach of finding more wear-resistant biocompatible material pairs. In contrast, other researchers have attempted to reduce wear by encouraging elastohydrodynamic film formation through the use of elastomeric bearing surfaces. Unfortunately, these elastomeric bearing surfaces have poor tribological properties when a fluid film is not present. Boundary lubrication of an elastomeric orthopaedic bearing may alleviate some of these difficulties. The purpose of this research was to fabricate and characterize an elastomeric material that had a surface capable of specifically adsorbing a naturally occurring boundary lubricant. Dipalmitoyl phosphatidylcholine (DPPC) has been previously shown to be able to act as a boundary lubricant at stresses that occur in human load-bearing joints such as the hip and knee; therefore, DPPC was chosen for use in this study. It was expected that in an aqueous liposome suspension the static coefficient of friction microseconds of such a material would be lower, and increase less quickly over time, than a similar material without an ability to adsorb specifically DPPC when articulated against a polished chrome steel ball bearing. The lipid-adsorbing elastomer did not possess the desired tribological properties. This result was attributed to the polymer adsorbing the DPPC in the liposome phase and not in the bilayer phase, and interaction among the polymeric surface, DPPC and water. This approach to lubricating orthopaedic bearings was shown to have some merit, but a great deal of work needs to be done before such an approach can be used on a clinically available material.     

Activation of the antibacterial properties and neutrophil myeloperoxidase and acid phosphatase in patients with unstable angina pectoris

Neutrophils are very important in pathogenesis of ischemic disease. They take part in the biomorphology of thrombus and also in the damage of myocardium ischemia in a course of unstable angina pectoris. We evaluated the functional status of neutrophils in peripheral blood, by measurement of bactericidal activity and activity of granulocyte's enzymes: myeloperoxidase (MPO) and acid phosphatase in the patients with unstable angina pectoris. We studied a group of 43 people at the age from 34 to 74 years. The blood for investigation was obtained during the first five hours from the moment of hospitalization. The control group were 40 healthy people. The number of granulocytes was significantly higher in patients with unstable angina pectoris and granulocytes were metabolically activated which was shown in the bigger activity of granulocyte's enzymes like MPO and acid phosphatase than in the control group. The activation of neutrophils is developed by many factors in the course of unstable angina pectoris. They take part in the processes of thrombogenesis and thrombolysis and they are a very important origin for active oxygen metabolites, which are responsible for damage of myocardium ischemia.     

Weight control during the holidays: Highly consistent self-monitoring as a potentially useful coping mechanism.

The study examined the extent to which trait self-monitoring (the systematic observation and recording of target behaviors) was related to weight control during the high-risk holiday season. The participants (32 women, 6 men) averaged 223.1 lbs (101.41 kg), 57.2% overweight, 50.2 weeks of participation, and 21.3 lbs (9.68 kg) lost at the beginning of the study. Consistency of self-monitoring and weight changes were assessed for 3 holiday versus 7 nonholiday weeks. Analyses of variance (Consistency of Self-Monitoring Groups?×?Holiday/Nonholiday Weeks) revealed that participants gained 500% more weight per week during holiday compared with nonholiday weeks. Only participants in the most consistent self-monitoring quartile averaged any weight loss over the 10 weeks of the study and during the holiday weeks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Anatomical M-mode": a new echocardiographic technique potentially useful in the quantitative study of the left ventricle

According to the data collected at the Rome-based National Reference Centre for Enterobacteria, 266,547 Salmonella strains isolated from human sources (226,513) and from non human sources (40,034) were characterised in Italy during the period 1973-1995. The serotype of all isolates, and the antibiotype and phage type of selected isolates were determined. Human-source isolations grew from 4372 in 1973 to 12,310 in 1995: non-human source isolations, from 339 in 1973 to 3459 in 1995. Salm. Typhimurium ranked first in the list of the most common serotypes isolated from both sources in the period 1973-1988 except in the years 1975 and 1976 when it was overtaken by Salm. Wien. Since 1983 Salm. Enteritidis has been among the top ten isolates from animals, and ranked first in the list of isolates from humans in 1988 and from non human sources in 1991. During the last years the number of multidrug-resistant strains, mostly belonging to phage types 104 and 193 of Salm. Typhimurium has been rising. Salmonella strains have also been isolated from numerous extraintestinal infections, almost exclusively caused by Salm. Enteritidis and Typhimurium.     

Amino acid variation in the GyrA subunit of bacteria potentially associated with natural resistance to fluoroquinolone antibiotics

In studies of genetic diversity in natural microbial populations, we have analyzed nucleotide sequences in the quinolone resistance-determining region of the bacterial gyrA gene in ciprofloxacin-resistant and nonselected soil bacteria obtained from the environment. It is apparent that this sequence is highly variable, and resistance to fluoroquinolone antibiotics occurring in environmental populations of bacteria is due at least in part to natural sequence variation in this domain. We suggest that the development of new antimicrobial agents, including completely synthetic antimicrobials such as the fluoroquinolones, should incorporate the analysis of resistance mechanisms among microbes in natural environments; these studies could predict potential mechanisms of resistance to be encountered in subsequent clinical use of the agents and would guide chemical modification designed to evade resistance development.     

Oxidative stress in Staphylococcus aureus associated to the cleavage of an isoxazolylnaphthoquinoneimine with antibacterial capacity

Staphylococcus aureus was inhibited by exposure to 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4-imine (Q1). This compound was cleavaged in the presence of bacteria and an efflux of isoxazolamine was detected whereas in the S. aureus membrane and cytoplasm was observed an absorption band similar to that of the bencenoid ring. Non-viable bacteria showed intact Q1 intracellularly and in the membrane. Antistaphylococcus effect was associated to Q1 interaction with the respiratory chain, the oxidative metabolites were stimulated; there was cellular injury simultaneous to reduction of antibiotic molecule and efflux of isoxazolamine. The bacteria treated with Q1 increased its oxygen consumption and superoxide anion generation. Superoxide dismutase (SOD) production was stimulated, but it was principally extracellular in S. aureus. Escherichia coli, a species resistant to the antibiotic, did not reduce Q1 and showed lower superoxide anion generation; besides, there was an increase of intracellular SOD with extracellular decrease.     

Fatty acid ethyl esters: potentially toxic products of myocardial ethanol metabolism

The chronic consumption of alcohol has proven detrimental to heart tissue and can lead to alcohol-induced heart muscle disease, a condition which may result in arrhythmias, cardiomegaly, and congestive heart failure. A search for the molecular mechanism underlying observed alcohol-induced end-organ damage, such as that seen in heart, has lead to the discovery of a nonoxidative pathway for the metabolism of alcohol in several human tissues including heart, brain, pancreas, and liver. It has been revealed that nonesterified fatty acids are esterified with ethanol to produce fatty acid ethyl esters (FAEE), neutral molecules which can accumulate in mitochondria and impair cell function. The observation that FAEEs are synthesized at high rates in the heart, and other organs that lack oxidative ethanol metabolism, provides a plausible link between the observed tissue damage, the ingestion of alcohol, and the subsequent development of alcohol-induced heart muscle disease. The synthesis of FAEEs are catalyzed by FAEE synthase enzyme, four of which have been characterized and purified to homogeneity from the human myocardium. Further analysis of these FAEE synthase enzymes opens up a new possibility to characterize and map a gene for alcohol-induced end-organ damage, such as that observed in heart and other organs. FAEEs have been found to be important metabolites of alcohol and are most commonly accumulated in those organs which are damaged by alcohol abuse, i.e. heart. It may now be important to establish a genetic link between alcohol abuse and alcohol-induced heart muscle disease in order to understand the mechanism of alcohol-induced cardiomyopathy.     

The ability of quantitative ultrasound to predict the mechanical properties of trabecular bone under different strain rates

The ability of quantitative ultrasound to predict the mechanical properties of trabecular bone under different strain rates was investigated. Ultrasound velocity (UV) and broadband attenuation (BUA) were measured for 60 specimens of human trabecular bone. Samples were divided into two equal groups and loaded in compression at the strain rates of 0.0004 and 0.08 s-1. The ultimate strength, elastic modulus, and energy absorption capacity were determined for each specimen. Specimens tested at 0.08 s-1 had a mean value of strength 63% higher than the specimens tested at 0.0004 s-1. The elastic modulus and energy absorption capacity were 82% and 42% higher, respectively, for the higher strain rate. UV and BUA were significantly associated with most mechanical properties at both strain rates. All mechanical properties were also correlated strongly with a linear combination of UV and BUA for both the low and high loading rates. The use of ultrasound parameters may provide good clinical means for assessing the resistance of trabecular bone to both low and high energy trauma.     

The ability of human Schwann cell grafts to promote regeneration in the transected nude rat spinal cord

Advances in the purification and expansion of Schwann cells (SCs) from adult human peripheral nerve, together with biomaterials development, have made the construction of unique grafts with defined properties possible. We have utilized PAN/PVC guidance channels to form solid human SC grafts which can be transplanted either with or without the channel. We studied the ability of grafts placed with and without channels to support regeneration and to influence functional recovery; characteristics of the graft and host/graft interface were also compared. The T9-T10 spinal cord of nude rats was resected and a graft was placed across the gap; methylprednisolone was delivered acutely to decrease secondary injury. Channels minimized the immigration of connective tissue into grafts but contributed to some necrotic tissue loss, especially in the distal spinal cord. Grafts without channels contained more myelinated axons (x = 2129 +/- 785) vs (x = 1442 +/- 514) and were larger in cross-sectional area ( x = 1.53 +/- 0.24 mm2) vs (x = 0.95 +/- 0.86 mm2). The interfaces formed between the host spinal cord and the grafts placed without channels were highly interdigitated and resembled CNS-PNS transition zones; chondroitin sulfate proteoglycans was deposited there. Whereas several neuronal populations including propriospinal, sensory, motoneuronal, and brainstem neurons regenerated into human SC grafts, only propriospinal and sensory neurons were observed to reenter the host spinal cord. Using combinations of anterograde and retrograde tracers, we observed regeneration of propriospinal neurons up to 2.6 mm beyond grafts. We estimate that 1% of the fibers that enter grafts reenter the host spinal cord by 45 days after grafting. Following retrograde tracing from the distal spinal cord, more labeled neurons were unexpectedly found in the region of the dextran amine anterograde tracer injection site where a marked inflammatory reaction had occurred. Animals with bridging grafts obtained modestly higher scores during open field [(x = 8.2 +/- 0.35) vs (x = 6.8 +/- 0.42), P = 0.02] and inclined plane testing (x = 38.6 +/- 0. 542) vs (x = 36.3 +/- 0.53), P = 0.006] than animals with similar grafts in distally capped channels. In summary, this study showed that in the nude rat given methylprednisolone in combination with human SC grafts, some regenerative growth occurred beyond the graft and a modest improvement in function was observed.     

Antioxidant properties of the decarboxylated dimer of aminoethylcysteine ketimine: assessment of its ability to scavenge peroxynitrite

In the present study we used an in-vitro technique to examine initiation and propagation of blood coagulation at the surface of tantalum coronary stents exposed to flowing platelet-rich and platelet-free plasma. The time course of factor IXa production at the surface of the stent was not influenced by platelets. In spite of a significant factor IXa production, no thrombin activity was detected when the tantalum stent was exposed to platelet-free plasma; only when the stent was exposed to platelet-rich plasma was extensive thrombin production observed. These findings indicate that tantalum triggers blood coagulation, but that (adherent) platelets are essential for thrombin generation. Heparin-coated tantalum stents exposed to flowing platelet-rich plasma showed that factor IXa generation was slightly reduced compared with the bare stent. However, the heparin coating drastically delayed the onset of thrombin generation and largely reduced the steady-state production of thrombin. We found a clear relationship between the antithrombin binding capacity and the antithrombogenic potential of the heparin-coated stents. The mode of action of immobilized heparin is thought to abrogate thrombin generation by inhibiting thrombin-dependent positive feedback reactions at the surface of the coronary stent.     

The effects of exogenous sphingosine on Neuro2a cells are strictly related to the overall capacity of cells to metabolize sphingosine

Neuro2a cells were exposed to different doses (1-40 nmol/10(6) cells) of [C3-3H]sphingosine and the relationship between metabolism and biological effects of sphingosine was investigated. Sphingosine appeared to be rapidly taken up and metabolized. The incorporation of sphingosine was not merely dependent on its concentration but primarily on the dose per cell of administered sphingosine. At low doses, [3H]sphingosine represented a minor portion of the cellular radioactivity, and N-acylated metabolites, particularly ceramide, largely prevailed over degradation products. Concomitantly with ceramide increase, Neuro2a differentiation took place. With increasing exogenous sphingosine/doses, the acylation process reached saturation. From this point on, [3H]sphingosine started accumulating and eventually cell toxicity occurred. In conclusion, the biological effects exerted by exogenous sphingosine on Neuro2a cells are not merely dependent on the long-chain base concentration in the culture medium, but are strictly related to the cellular dose of exogenous sphingosine and to the capacity of cells to metabolize sphingosine.     

The police officer's dilemma: Using ethnicity to disambiguate potentially threatening individuals.

Using a simple videogame, the effect of ethnicity on shoot/don't shoot decisions was examined. African American or White targets, holding guns or other objects, appeared in complex backgrounds. Participants were told to "shoot" armed targets and to "not shoot" unarmed targets. In Study 1, participants made the correct decision to shoot an armed target more quickly if the target was African American than if he was White, but decided to "not shoot" an unarmed target more quickly if he was White. Study 2 used a shorter time window, forcing this effect into error rates. Study 3 replicated Study 1's effects and showed that the magnitude of bias varied with perceptions of the cultural stereotype of African Americans as dangerous, and with levels of contact. Study 4 revealed equivalent levels of bias among White and African American participants in a community sample. Implications and potential underlying mechanisms are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Targeting of nucleic acid junctions: addressing to a branch point an oligodeoxynucleotide conjugated with an intercalator

It is possible to enhance targeting of a DNA stem flank domain with a complementary DNA when it is conjugated with diphenyl ether at the branch point. The nucleoside 2'-deoxy-5-methyl- N 4-(4-phenoxyphenyl)cytidine (5) was synthesized from thymidineby tritylation, acetylation, amination via 2,4, 6-trimethylbenzenesulfonyl activation and subsequent de-protection. When a three-way junction is formed with a bulged nucleoside 5 at the branch point, the thermal melting temperature was increased by 9 degreesC when compared with wild-type DNA. When hybridizing to one of the flanks at a stem allowing coaxial stacking to the stem, modification at the branch point resulted in DeltaTm= 5.8 degreesC. For targeting to RNA the results were more ambiguous. RNase H activity was observed in some cases when an intercalating aromatic ring was addressed at the branch point. RNase H activity was observed even for a short 7mer ODN.     

Landmark discrimination in the rat: A measure of allocentric spatial ability.

A landmark discrimination task similar to that previously used with monkeys (W. Pohl, 1973) was adapted to measure allocentric spatial ability in rats. Rats were trained to approach 1 of 2 food wells, placed 36 cm apart, based on the proximity of the landmark. During initial training, the landmark was adjacent to the baited food well (0 cm). As training progressed, the distance of the landmark from the baited food well was increased in 1.25-cm increments. Results show that rats were able to successfully use a landmark as an external referent up to a distance of 11 cm (when the midpoint between food wells was 18 cm). Following the stepwise training phase, a 64-trial test of mixed distances was administered, and performance was above 80% up to and including 12.5 cm from the near landmark. Results suggest that this landmark discrimination task provides a means to assess allocentric spatial ability in rats and to explore underlying neural mechanisms across species. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The amino acid composition of rat bile

The pattern of amino acids in the bile of rats differs from the pattern in the serum of these animals, since bile contains significantly greater amounts of acidic and sulphur-containing amino acids and glycine than serum, while the serum contained more basic amino acids than bile, indicating that secretion of amino acids into bile may involve specific transport processes.