Omega-agatoxin IVA, a P-type calcium channel antagonist, reduces nociceptive processing in spinal cord neurons with input from the inflamed but not from the normal knee joint--an electrophysiological study in the rat in vivo

High threshold voltage-dependent P- and Q-type calcium channels are involved in neurotransmitter release. In order to investigate the role of P- and Q-type calcium channels in the mechanosensory (nociceptive) processing in the spinal cord, their participation in the responses of spinal wide-dynamic-range neurons to innocuous and noxious mechanical stimulation of the knee and ankle joints was studied in 30 anaesthetized rats. The knee was either normal or acutely inflamed by kaolin/carrageenan. During the topical application of omega-agatoxin IVA (P-type channel antagonist, 0.1 microM) onto the dorsal surface of the spinal cord, the responses to innocuous and noxious pressure applied to the normal knee were increased to respectively 124 +/- 42% and 114 +/- 23% of predrug values (mean +/- SD, P < 0.05, 14 neurons). By contrast, in rats with an inflamed knee, the responses to innocuous and noxious pressure applied to the knee were reduced to respectively 72 +/- 19 and 73 +/- 22% of baseline (mean +/- SD, P < 0.01, 13 neurons). In the same neurons, omega-agatoxin IVA slightly increased the responses to pressure on the non-inflamed ankle whether the knee was normal or inflamed. Thus P-type calcium channels seem to acquire a predominant importance in the excitation of spinal cord neurons by mechanosensory input from inflamed tissue and hence in the generation of inflammatory pain. By contrast, the Q-type channel antagonist, omega-conotoxin MVIIC (1 or 100 microM), had no significant effect upon responses to innocuous or noxious pressure applied to either normal or inflamed knees (25 neurons).     

Phospholipase A2--from basic research to clinical reality]

Phospholipase A2 (PLA2) is a group of secretory as well as intracellular enzymes that release phospholipids as an early step in inflammation and play a physiologic role in digestion. In humans, the group of secretory, low-molecular-weight PLA2 (sPLA2) is differentiated from the cytosolic, high-molecular-weight PLA2 (cPLA2). The two known cPLA2 mediate the intracellular response to inflammation by releasing arachidonic acid from membrane phospholipids. Secretory pancreatic PLA2 (sPLA2-I) is a digestive zymogen secreted from pancreatic acinar cells in its inactive form. Activated by trypsin in the duodenum, it is an important digestive enzyme. In acute pancreatitis, circulating sPLA2-I indicates pancreatic injury but is mostly inactive. Synovial-type secretory PLA2 (sPLA2-II), first isolated from synovial fluid of arthritis patients, is increased in inflammation, after surgery or trauma, and in various inflammatory diseases. Unlike sPLA2-I, its catalytic activity is held responsible for mediating the systemic inflammatory reaction and its complications by regulating the synthesis of prostaglandins, leukotrienes and platelet activating factor. Clinically, sPLA2-II offers new possibilities as an early marker for severe inflammation and predicting systemic complications in severely ill patients.     

Magnetic resonance imaging of articular cartilage in the knee. An evaluation with use of fast-spin-echo imaging

The purpose of this study was to demonstrate that specialized magnetic resonance imaging provides an accurate assessment of lesions of the articular cartilage of the knee. Arthroscopy was used as the comparative standard. Eighty-eight patients who had an average age of thirty-eight years were evaluated with magnetic resonance imaging and subsequent arthroscopy because of a suspected meniscal or ligamentous injury. The magnetic resonance imaging was performed with a specialized sequence in the sagittal, coronal, and axial planes. Seven articular surfaces (the patellar facets, the trochlea, the femoral condyles, and the tibial plateaus) were graded prospectively on the magnetic resonance images by two independent readers with use of the 5-point classification system of Outerbridge, which was also used at arthroscopy. Six hundred and sixteen articular surfaces were assessed, and 248 lesions were identified at arthroscopy. Eighty-two surfaces had chondral softening; seventy-five, mild ulceration; fifty-three, deep ulceration, fibrillation, or a flap without exposure of subchondral bone; and thirty-eight, full-thickness wear. To simplify the statistical analysis, grades 0 and 1 were regarded as disease-negative status and grades 2, 3, and 4 were regarded as disease-positive status. When the grades that had been assigned by reader 1 were used for the analysis, magnetic resonance imaging had a sensitivity of 87 per cent (144 of 166), a specificity of 94 per cent (424 of 450), an accuracy of 92 per cent (568 of 616), a positive predictive value of 85 per cent (144 of 170), and a negative predictive value of 95 per cent (424 of 446) for the detection of a chondral lesion. Interobserver variability was minimum, as indicated by a weighted kappa statistic of 0.93 (almost perfect agreement). With use of this readily available modified magnetic resonance imaging sequence, it is possible to assess all articular surfaces of the knee accurately and thereby identify lesions that are amenable to arthroscopic treatment.     

Religious activity and depression among community-dwelling elderly persons with cancer: the moderating effect of race

OBJECTIVES: Research has been oriented toward elucidating the links between religion and mental health. The purpose of this article is to further our knowledge in this area by examining the effect of religious activity on depressive symptomatology among community-dwelling elderly persons with cancer. We also test whether these effects differ between Blacks and Whites. METHODS: We use two waves of data collected from a community-dwelling sample of elderly persons living in North Carolina. Depressive symptomatology is measured using four subscales from the CES-D 20 scale: somatic-retarded activity, depressed affect, positive affect, and interpersonal relations. Measures of religious activity include service attendance, religious devotion, and watching or listening to religious programs. RESULTS: The findings indicate that among Blacks with cancer, religious activity is related to lower levels of depressive symptomatology; no such relationship is found for respondent with other illnesses or no illness. Further, the effects of religious activity are stronger among Blacks than Whites. DISCUSSION: The analyses lend support to the hypothesis that religious activity is a strong predictor of depression in elderly adults with cancer. This finding, however, is not as strong as we had anticipated.     

Screening male intracytoplasmic sperm injection candidates for mutations of the follicle stimulating hormone receptor gene

Follicle stimulating hormone (FSH) is considered to be essential for spermatogenesis. Therefore, genetic abnormalities of FSH signalling on testicular Sertoli cells would be expected to affect sperm production negatively in males. Inactivating FSH receptor mutations have been reported earlier in both males and females. All affected males had elevated FSH serum concentrations and abnormal sperm parameters. We postulated that inactivating FSH receptor mutations might be a cause of oligozoospermia or azoospermia and reviewed the clinical data of 151 male intracytoplasmic sperm injection (ICSI) candidates with special attention to FSH serum concentrations. The exclusion criteria for mutation screening of the FSH receptor gene were: a history of operative sterilization or testicular malignancy, congenital abnormality other than cryptorchidism, and a chromosomal aberration or a Y-chromosome microdeletion. The inclusion criteria were: male (ICSI candidate) with azoospermia or oligoasthenoteratozoospermia (OAT) and elevated FSH serum concentrations. In total, 23 males with OAT and five males with azoospermia were tested for mutations of the coding sequences and the intron-exon boundaries of the FSH receptor gene by polymerase chain reaction (PCR) followed by single strand conformation polymorphism analysis (SSCP). Neutral polymorphisms were readily detected using this technique in both probands and controls. None of the 28 selected patients showed a pathogenic FSH receptor mutation. Mutations in the FSH receptor gene are not a common cause of infertility in ICSI candidates.     

Sero-epidemiological analysis of the risk of virus infections for childhood leukaemia

Virus infections have been thought to be involved in the development of childhood leukaemia. In order to address this issue we determined, in a case-control study, the prevalence of antibodies to viruses infecting blood or bone-marrow cells [Epstein-Barr virsus (EBV), human herpes virus type 6 (HHV-6), parvovirus B19] as well as to the human virus known for its tumour-suppressive properties, the adeno-associated virus type 2 (AAV-2), in the sera of 121 children with leukaemia in Germany, and in 197 control individuals, hospitalized for other reasons, and matched for age and gender to the cases. In addition, we developed a questionnaire to be answered by the children's parents, in order to gain information on previous infections of the children as well as to calculate for factors which may influence serological findings. Comparative determination of the prevalence of antibodies against AAV-2, B-19 or HHV-6 revealed no significant differences in cases and controls. However, antibodies to EBV were more frequently found in children with leukaemia younger than 6 years of age (age at the time of diagnosis of leukaemia) than in controls. Apparently, infection with AAV-2 has no protective effect in childhood leukaemia, in contrast to results observed for other malignancies. Similarly, and in accordance with results on leukaemia in adults, we found no indication of a protective effect of infection with the parvovirus B-19. The data suggest that EBV, which is known to be involved in various lymphomas, may play a role in the development of childhood leukaemia in young children.     

Ant based probabilistic routing with pheromone and antipheromone mechanisms

Using the idea of probabilistic routing, calls in an ant based decentralized scheme are not routed according to the largest probabilities in the pheromone tables but randomly according to these probabilities. This principle can be particularly helpful in order to further minimize possible node congestion problems. An additional incorporation of the antipheromone mechanism in the operation of artificial ants helps in better biasing the network. This paper examines the behaviour of such a routing scheme using a proper set of suitable metrics. Copyright © 2004 John Wiley & Sons, Ltd.     

Infection by Mycobacterium tuberculosis promotes human alveolar macrophage apoptosis

The effect of Mycobacterium tuberculosis infection on the viability of healthy (control) human alveolar macrophages was evaluated by staining with ethidium homodimer and calcein to discriminate live from dead cells. Infection with M. tuberculosis H37Ra or H37Rv increased macrophage mortality at 6 days from the control level of 3.8% +/- 0.7% to 28.7% +/- 6.9% or 12.6% +/- 3.1%, respectively (P < 0.001 for comparisons of all conditions). A role for tumor necrosis factor alpha (TNF-alpha) in the M. tuberculosis-induced cytolysis of alveolar macrophages was demonstrated by increased cytotoxicity following the addition of exogenous TNF-alpha to the cultures and by enhancement of macrophage survival when M. tuberculosis-infected alveolar macrophages were treated with pentoxifylline or anti-TNF-alpha antibody. The cytolytic mechanism was determined to be apoptosis by the demonstration of a characteristic internucleosomal ladder of genomic DNA by agarose gel electrophoresis, by finding nuclear fragmentation and condensation by electron microscopy, and by in situ terminal transferase-mediated nick end labeling of fragmented DNA in alveolar macrophages infected with M. tuberculosis in vitro. The latter technique was employed to reveal extensive apoptosis within caseating granulomas from lung tissue samples from clinical tuberculosis cases. The induction of apoptosis in alveolar macrophages by M. tuberculosis may play a role in the macrophage-pathogen interaction of tuberculosis in vivo.