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Biomedical subjects

A Gross

Publications and source records attributed to A Gross.

At least 37 records · Page 2Linked to original sources

Surface strain versus substrate interaction in heteroepitaxial metal layers: Pt on Ru(0001).

By studying the adsorption of CO on up to 30 layers of Pt deposited on Ru(0001) the influence of surface strain on the adsorption energy has been disentangled from the residual chemical interaction with the substrate. While the electronic influence of the substrate has largely vanished for three Pt layers, the effect of surface strain due to the 2.5% lattice mismatch of Pt and Ru remains initially intact and is only gradually released for n>/=5 Pt layers. Electronic structure calculations confirm the experimental observations, in particular, the dramatic decrease of the CO adsorption energy on a single Pt layer which is caused by the strong Pt-Ru interlayer coupling.

Journal Article↗

Temporal and spatial distribution of paramoebae in the water column--a pilot study.

Amoebic gill disease is the main disease affecting the salmonid industry in Tasmania, but no information on the distribution of the causative pathogen, Neoparamoeba pemaquidensis, in the aquatic environment is available. This pilot study aimed to determine temporal and spatial distributions of paramoebae species in the water column, using an immuno-dot blot technique. Water samples were collected from inside fish cages at various depths (0.5, 5.5 and 11.0 m) in both summer and winter, as well as various distances (0, 0.5, 240, 280, 750 and 1100 m) away from the sea cage and farming site. Paramoebae densities were estimated using the most probable number technique (MPN). Temperature, salinity, dissolved oxygen, turbidity, nitrite and nitrates, and bacterial counts were measured for each water sample. Data were analysed using a residual maximum likelihood test and significant associations between paramoebae densities and environmental factors were analysed. Results showed that densities were significantly higher in summer (P = 0.017), at 5.5 m depth (P = 0.029), and reduced to the lowest density at 1100 m away from the cage sites (P = 0.008). Bacterial counts, turbidity and temperature were found to be significantly associated with paramoebae densities.

Amoebida↗

Limited potentiation of blood pressure response to oral tyramine by brain-selective monoamine oxidase A-B inhibitor, TV-3326 in conscious rabbits.

TV-3326 is a novel cholinesterase inhibitor that produces irreversible brain-selective inhibition of monoamine oxidase (MAO)-A and B and has antidepressant-like activity in rats after chronic oral administration. This study determined whether TV-3326 would cause less potentiation than other irreversible MAO-inhibitors of the blood pressure (BP) response to oral tyramine in conscious rabbits. Dose-response curves were established for the increase in BP induced by tyramine (5-200 mg/kg) administered orally via a naso-pharyngeal tube. From these, the dose that increased BP by 30 mmHg (ED(30)) was computed for each rabbit before and after oral administration of clorgyline, 1 mg/kg for one week, tranylcypromine 10 mg/kg, once, moclobemide, 20 mg/kg 3 times and TV-3326, 26 mg/kg for 2 weeks. Clorgyline, tranylcypromine and TV-3326 inhibited brain MAO-A by 90%; the former two inhibited intestinal MAO-A by 85-97% but TV-3326 had no effect. Tranylcypromine and clorgyline produced 6 and 20-fold increases in the pressor response to tyramine while TV-3326, like moclobemide, only potentiated it 2-fold. If TV-3326 is found to produce as little potentiation of the tyramine response in human subjects, it may be a potentially useful therapeutic agent for the treatment of Alzheimer's disease with depression.

2-Hydroxyphenethylamine↗

Reduction of jaw opening (trismus) in giant cell arteritis.

OBJECTIVE: To study the prevalence and the clinical characterisation of jaw problems in patients with giant cell arteritis (GCA). METHODS: the prevalence of such symptoms in patients with GCA was evaluated by performing a retrospective analysis of all patients with GCA and polymyalgia rheumatica who were diagnosed during admission to Hadassah University Hospital. Ten patients reported previously in the literature were also evaluated. RESULTS: Six patients out of 88 (6.8%) had complaints of reduction in jaw opening. These six patients seemed to have a much more abrupt onset of disease with shorter duration until diagnosis, higher prevalence of eye involvement (50% v 27%), and a higher rate of positive pathology (100%). CONCLUSIONS: Reduction in jaw opening in the appropriate setting may indicate the presence of GCA. This sign should not be overlooked in the presence of the claudication sign as it seems to reflect more severe GCA disease.

Aged↗

Morphology of the compound eyes of Nebalia herbstii Leach, 1814 (Leptostraca, Nebaliidae).

The Nebalia compound eyes are scotopic apposition eyes that provide a roundabout view. Each ommatidium is equipped with a large, layered retinula, a flat cornea, a eucone crystalline cone made of four cone cells, and eight retinula cells arranged in three cell pairs that exhibit mirror symmetry (R1/R6, R2/R5 and R3/R4) as well as two single cells (R7 and R8). Cone cell threads run between retinula cells R1 and R2, R3 and R4, R5 and R6, R8 and R1. A plane of symmetry divides the compound eyes into anterior and posterior parts containing ommatidia arranged in mirror symmetry and having different R-cell chirality. The findings are discussed with respect to the structural features of other crustacean eyes and basic features of the arthropod compound eye.

Animals↗

Limits to buprenorphine dosing: a comparison between quintuple and sextuple the maintenance dose every 5 days.

The relative efficacy of quintuple and sextuple buprenorphine dosing in abating withdrawal symptoms for 120 h was compared in opioid-dependent outpatients. Fourteen subjects received buprenorphine in a double-blind, placebo-controlled, cross-over design. Daily sublingual maintenance doses were 4 mg/70 kg (n=4) and 8 mg/70 kg (n=10). After a stabilization period of daily maintenance administration, subjects received quintuple (5x daily maintenance dose) and sextuple (6x daily maintenance dose) doses every 120 h. Measures of opioid agonist and withdrawal effects were assessed daily. Subjective ratings of withdrawal were significantly greater than baseline ratings beyond 96-h post dosing under both regimens. There was no evidence, however, that those subjective ratings of withdrawal differed between the two regimens. Thus, these data suggest that sextuple buprenorphine dosing, administered every 5 days, does not abate opioid-withdrawal beyond 96 hours.

Adult↗

Coexistence of atomic and molecular chemisorption states: H(2)/Pd(210).

A novel H(2) molecular adsorption state on metal surfaces has been detected by temperature-programmed desorption and electron energy loss spectroscopy experiments of the H(2)/Pd(210) system. The molecular nature of this state has been verified by isotope exchange experiments. This molecular state leads to a decrease of the surface work function while atomic hydrogen on Pd(210) causes an increase. Ab initio total-energy calculations have confirmed all experimental findings. Through these calculations the microscopic nature of this novel molecular adsorption state could be identified; it turns out that this state is stabilized by the presence of atomic hydrogen on the Pd(210) surface.

Journal Article↗

Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B.

1. Rasagiline [N-propargyl-1R(+)-aminoindan], was examined for its monoamine oxidase (MAO) A and B inhibitor activities in rats together with its S(-)-enantiomer (TVP 1022) and the racemic compound (AGN-1135) and compared to selegiline (1-deprenyl). The tissues that were studied for MAO inhibition were the brain, liver and small intestine. 2. While rasagiline and AGN1135 are highly potent selective irreversible inhibitors of MAO in vitro and in vivo, the S(-) enantiomer is relatively inactive in the tissues examined. 3. The in vitro IC(50) values for inhibition of rat brain MAO activity by rasagiline are 4.43+/-0.92 nM (type B), and 412+/-123 nM (type A). The ED(50) values for ex vivo inhibition of MAO in the brain and liver by a single dose of rasagiline are 0.1+/-0.01, 0.042+/-0.0045 mg kg(-1) respectively for MAO-B, and 6.48+/-0.81, 2.38+/-0.35 mg kg(-1) respectively for MAO-A. 4. Selective MAO-B inhibition in the liver and brain was maintained on chronic (21 days) oral dosage with ED(50) values of 0.014+/-0.002 and 0.013+/-0.001 mg kg(-1) respectively. 5. The degree of selectivity of rasagiline for inhibition of MAO-B as opposed to MAO-A was similar to that of selegiline. Rasagiline was three to 15 times more potent than selegiline for inhibition of MAO-B in rat brain and liver in vivo on acute and chronic administration, but had similar potency in vitro. 6. These data together with lack of tyramine sympathomimetic potentiation by rasagiline, at selective MAO-B inhibitory dosage, indicate that this inhibitor like selegiline may be a useful agent in the treatment of Parkinson's disease in either symptomatic or L-DOPA adjunct therapy, but lack of amphetamine-like metabolites could present a therapeutic advantage for rasagiline.

Animals↗

The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance thresholds in healthy subjects.

The aim of this study was to compare the effects of total sleep deprivation (TSD), rapid eye movement (REM) sleep and slow wave sleep (SWS) interruption and sleep recovery on mechanical and thermal pain sensitivity in healthy adults. Nine healthy male volunteers (age 26--43 years) were randomly assigned in this double blind and crossover study to undergo either REM sleep or SWS interruption. Periods of 6 consecutive laboratory nights separated by at least 2 weeks were designed as follows: N1 Adaptation night; N2 Baseline night; N3 Total sleep deprivation (40 h); N4 and N5 SWS or REM sleep interruption; N6 Recovery. Sleep was recorded and scored using standard methods. Tolerance thresholds to mechanical and thermal pain were assessed using an electronic pressure dolorimeter and a thermode operating on a Peltier principle. Relative to baseline levels, TSD decreased significantly mechanical pain thresholds (-8%). Both REM sleep and SWS interruption tended to decrease mechanical pain thresholds. Recovery sleep, after SWS interruption produced a significant increase in mechanical pain thresholds (+ 15%). Recovery sleep after REM sleep interruption did not significantly increase mechanical pain thresholds. No significant differences in thermal pain thresholds were detected between and within periods. In conclusion this experimental study in healthy adult volunteers has demonstrated an hyperalgesic effect related to 40 h TSD and an analgesic effect related to SWS recovery. The analgesic effect of SWS recovery is apparently greater than the analgesia induced by level I (World Health Organization) analgesic compounds in mechanical pain experiments in healthy volunteers.

Adult↗

Characterization of moclobemide N-oxidation in human liver microsomes.

1. Moclobemide underdergoes morpholine ring N-oxidation to form a major metabolite in plasma Rol2-5637. 2. The kinetics of moclobemide N-oxidation in human liver microsomes (HLM) (n = 6) have been investigated and the mixed-function oxidase enzymes catalysing this reaction have been identified using inhibition, enzyme correlation, altered pH and heat pretreatment experiments. 3. N-oxidation followed single enzyme Michealis-Menten kinetics (0.02-4.0 mm). Km app and Vmax ranged from 0.48 to 1.35 mM (mean +/- SD) 0.77 +/- 0.34 mM) and 0.22 to 2.15 nmol mg(-1) min(-1) (1.39 +/- 0.80 nmol mg(-1) respectively. 4. The N-oxidation of moclobemide strongly correlated with benzydamine N-oxidation a probe reaction for flavin-containing monoxygenase (FMO) activity (0.1 mM moclobemide, rs = 0.81, p < 0.005; 4 mM moclobemide, rs = 0.94, p = 0.0001). Correlations were observed between moclobemide N-oxidation and specific cytochromre P450 (CYP) activities at both moclobemide concentrations (0.1 mM moclobemide, CYP2C19 0.66, p < 0.05; 4 mM moclobemide, CYP2E1 rs = 0.56, p < 0.05). 5. The general P450 inhibitor, N-benzylimidazole, did not affect the rate of Rol2-5637 formation (0% inhibition versus control) (at 1.3 mM moclobemide. Furthermore, the rate of Ro12-5637 formation in HLM was unaffected by inhibitors Or substrates of specific P450s (< 10% inhibition versus control). 6. Heat pretreatment of HLM in the absence of NADPH (inactivating FMOs) resulted in 97% inhibition of Ro12-5637 formation. N-oxidation activity was greatest when incubated at pH 8.5. These results ilre consistent with the reaction being FMO medialtetd . 7. In conclusion, moclobemide N-oxidation activity has been observed in HLM in vitro and the reaction is predominantly catalysed by FMOs with a potentially small contribution from cytochrome P450 isoforms.

Benzamides↗

Victim's scalp on the killer's head. An unusual case of criminal postmortem mutilation.

A case of unusual postmortem mutilation of a victim's body is presented. After killing his father, the son decapitated his body and dissected the scalp free, forming a mask of the father's head and neck. The young man wore the scalp-mask over his own head to imitate the father. The motive of the murder was revenge, and the postmortem mutilation was the realization of the perpetrator's fantasies, symbolically representing a penalty for the reprehensible past life of his father.

Adult↗

Local anesthetics attenuate lysophosphatidic acid-induced priming in human neutrophils.

UNLABELLED: Lysophosphatidic acid (LPA) is an intercellular phospholipid mediator with a variety of actions that suggest a role in stimulating inflammatory responses. We therefore studied its actions on neutrophil (PMN) motility and respiratory burst. Because local anesthetics (LA) inhibit LPA signaling and attenuate PMN responses, we also investigated the effects of LA on these actions. Chemotaxis of human PMNs under agarose toward LPA (10(-10)-10(-3) M) was studied, with and without 1 h prior incubation in lidocaine (10(-9)-10(-4) M). Priming as well as activating effects of LPA on PMNs were measured using a cytochrome-c assay of superoxide anion (O2-) production. PMNs were incubated with lidocaine, tetracaine, or S-(-) ropivacaine (all at 10(-6)-10(-4) M) for 10 min or 1 h to assess interference with LPA signaling. LPA demonstrated chemoattractive effects towards human PMNs; this effect was concentration-dependently attenuated by lidocaine. LPA alone did not activate PMNs. However, it acted as a priming agent. LA in clinically relevant concentrations decreased (O2-) production induced by LPA/N-formylmethionine-leucyl-phenylanaline. LPA acts as a chemoattractant and priming agent; however, it does not activate PMNs. LA, in clinically relevant concentrations, attenuate chemotactic and metabolic responses as a result of LPA. These results may explain the antiinflammatory effect of local anesthestics. IMPLICATIONS: Lysophosphatidic acid (LPA) influences two functions of human neutrophils, migration and metabolic activity. It acted as a chemoattractant and a priming-but not activating-agent. Responses to LPA were attenuated by local anesthetics in clinically relevant concentrations.

Anesthetics, Local↗

Local anesthetic effects on priming and activation of human neutrophils.

BACKGROUND: Local anesthetics (LAs) have been shown to inhibit human polymorphonuclear neutrophil (hPMN) functions in vitro, but mechanisms are poorly understood. In this study the authors determined how LAs affect superoxide anion production of hPMNs primed with platelet-activating factor (PAF). The authors studied which pharmacologic properties of LAs are important for this action and assessed the LA site of action within the PAF signaling pathway. METHODS: Metabolic activity of primed and/or activated hPMNs were measured using the cytochrome-c assay. hPMNs were incubated with several LAs for 1 h to assess interference with PAF signaling. Using protein kinase C (PKC) inhibitors, the PKC activator phorbol myristate acetate (PMA), and the phospholipase C (PLC) antagonist U-73122, we studied involvement of PKC and PLC in the priming process. Pertussis toxin (PTX) was used to characterize the G proteins mediating this pathway. Combined administration of lidocaine with PMA or PTX was used to determine the LA site of action within the priming pathway. RESULTS: Platelet-activating factor effectively primed hPMNs. Ester LAs (tetracaine and benzocaine) exerted the most profound inhibitory effect on PAF-primed hPMNs, whereas inhibitory potency of amide LAs increased with decreased charged fraction. The major PAF-induced priming pathway is PLC- and PKC-dependent and mainly Gq-mediated. The main target site for LA in this pathway is located upstream of PKC. CONCLUSIONS: Local anesthetics in clinically relevant concentrations inhibit superoxide anion production of PAF-primed hPMNs. Effects on priming by these compounds might explain, at least in part, the previously unexplained difference between concentrations of LAs required for their antiinflammatory action in vitro and in vivo. This study suggests a target site for LAs within a Gq-coupled signaling pathway.

Anesthetics, Local↗

The Knee Society Index of Severity for failed total knee arthroplasty: development and validation.

Compared with primary knee replacement, total knee arthroplasty revision surgery is a more complex procedure and accounts for greater expenditures of healthcare resources at each clinical stage. Overall, patients having revision procedures have poorer functional outcomes and higher complication rates than patients having primary arthroplasty. Despite the expanded scope of revision problems and the rapidly emerging technology in revision surgery, the long-term success of any method remains in question. Because there is little consensus on the timing of revision surgery, optimal surgical reconstruction, and the type of prosthesis to be implanted, the Knee Society began development of an Index of Severity for Failed Total Knee Arthroplasty. Fifty-four percent of Knee Society members completed an 82-item questionnaire that determined their clinical impression about potential risk factors for the outcomes of revision surgery for failed total knee replacements. Using these results, a consensus group developed the final version of the index. The result of the nominal group process was the Knee Society Index of Severity, which was based on eight distinct domains. Each domain was divided into attributes and weights based on the questionnaire responses and consensus meeting. Actual case scenarios from five institutions were used to test interrater reliability and validity. The interrater reliability of the average score of all ratings was 0.95; the correlation of the criterion rating with the mean rating was 0.77. When three outliers were not included, the Pearson product correlation increased to 0.92. These data support the application of the Knee Society Index of Severity as a critical component of risk factor studies, effectiveness research, and cost-effectiveness analysis involving revisions of total knee replacements.

Arthroplasty, Replacement, Knee↗

The Knee Society Index of Severity for failed total knee arthroplasty: practical application.

Previous classifications of severity for total knee arthroplasty revisions have been based largely on bone loss of the femur and tibia. These approaches failed to address the more technically difficult issues in revision surgery such as surgical exposure, contractures, extremity alignment, implant removal, soft tissue stability (in the anteroposterior and in the sagittal planes), extensor mechanism integrity, and patellar revisability. Through the Knee Society, the authors developed a severity index that incorporated these latter factors into one measure. The current authors describe the application of the Knee Society Index of Severity for failed total knee arthroplasty and its method of scoring.

Arthroplasty, Replacement, Knee↗

Marked clozapine-induced slowing of EEG background over frontal, central, and parietal scalp areas in schizophrenic patients.

The authors studied how clozapine treatment of patients with chronic schizophrenia affects the scalp topographic distribution of different frequency bands on EEG. Twenty-one patients treated with clozapine, in addition to zero to two typical neuroleptics (13 patients were treated with clozapine as the only neuroleptic), were compared with two control groups: one of healthy subjects and another of patients with schizophrenia receiving one to three typical neuroleptics and no clozapine. Significant differences in the EEG topography were seen between the groups: The theta and delta powers and were increased in the clozapine group compared with the two other groups (P < 0.001). Changes were observed over all electrodes, and were most prominent at the frontal, central, and parietal electrode locations. The nonclozapine-treated group of patients and the healthy control group did not differ significantly from each other. These results suggest that the topographic EEG features caused by clozapine are quite specific to it and can be differentiated from those of other neuroleptics.

Adult↗

Major outer membrane protein Omp25 of Brucella suis is involved in inhibition of tumor necrosis factor alpha production during infection of human macrophages.

Brucella spp. can establish themselves and cause disease in humans and animals. The mechanisms by which Brucella spp. evade the antibacterial defenses of their host, however, remain largely unknown. We have previously reported that live brucellae failed to induce tumor necrosis factor alpha (TNF-alpha) production upon human macrophage infection. This inhibition is associated with a nonidentified protein that is released into culture medium. Outer membrane proteins (OMPs) of gram-negative bacteria have been shown to modulate macrophage functions, including cytokine production. Thus, we have analyzed the effects of two major OMPs (Omp25 and Omp31) of Brucella suis 1330 (wild-type [WT] B. suis) on TNF-alpha production. For this purpose, omp25 and omp31 null mutants of B. suis (Deltaomp25 B. suis and Deltaomp31 B. suis, respectively) were constructed and analyzed for the ability to activate human macrophages to secrete TNF-alpha. We showed that, in contrast to WT B. suis or Deltaomp31 B. suis, Deltaomp25 B. suis induced TNF-alpha production when phagocytosed by human macrophages. The complementation of Deltaomp25 B. suis with WT omp25 (Deltaomp25-omp25 B. suis mutant) significantly reversed this effect: Deltaomp25-omp25 B. suis-infected macrophages secreted significantly less TNF-alpha than did macrophages infected with the Deltaomp25 B. suis mutant. Furthermore, pretreatment of WT B. suis with an anti-Omp25 monoclonal antibody directed against an epitope exposed at the surface of the bacteria resulted in substancial TNF-alpha production during macrophage infection. These observations demonstrated that Omp25 of B. suis is involved in the negative regulation of TNF-alpha production upon infection of human macrophages.

Antibodies, Bacterial↗