Arthritis Australia

By A. Thordir. Bank Street College of Education.

Oligosporidium occidentalis A new microsporidian pathogen has recently been isolated from a laboratory population of M celecoxib 200mg cheap. Two classes of uninucleate spores were produced cheap 200 mg celecoxib fast delivery, differing primarily in the length of the polar laments and the presence of a large posterior vacuole in one spore type (Becnel et al. The authors suspect that spores with long laments are involved in horizontal disease transmission, which may take place by cannibalism of infected eggs (Olsen and Hoy 2002), whereas Table 3 Protozoa recorded in phytoseiid mites Pathogen Phytoseiid host/origina Symptoms References Microsporidium phytoseiuli Phytoseiulus persimilis/c Knownb Bjrnson et al. The authors discuss this conict of morphological and molecular data and assign the new species the name Oligosporidium occidentalis. Infected female predators had a shorter life span, a lower oviposition rate and a lower number of female offspring, as infected mites have a male-biased sex ratio (Olsen and Hoy 2002). Predator colonies initiated from mites that were reared from egg to adult at 33 C showed an initial reduction in infection. Colonies initiated from progeny of the heat-treated mites remained healthy during the observation period of 10 weeks (Olsen and Hoy 2002). Microsporidium phytoseiuli and unidentied microsporidia in Phytoseiulus persimilis Three distinct species of microsporidia have been reported from P. The species assigned as Microsporidium phytoseiuli was isolated from a European population (Bjrnson et al. Early development of all three microsporidia occurred in cells of the lyrate organ. The lyrate organ occupies a signicant portion of the body and is thought to be involved in oogenesis or embryogenesis. Infection of the lyrate organ may be necessary for the efcient vertical transmission of microsporidia in P. Horizontal transmission was low (about 15%) when uninfected immatures were kept together with infected adult and immature mites (Bjrnson and Keddie 2001). Therefore, routine monitoring is necessary to detect microsporidia when disease preva- lence is low (Bjrnson and Keddie 1999). Moreover, infected females produced fewer female progeny than uninfected females, as the sex ratio of offspring of infected females is male biased (Bjrnson and Keddie 1999). Several methods to cure an infection with microsporidia were tested by Bjrnson (1998). The antimicrobial compounds albendazole, fumagillin, metronidazole and nifedipine were ineffective for control of microsporidia in P. The author doubted whether the chemical compounds were able to penetrate the egg chorion. The Pasteur method, whereby progeny of healthy mothers is selected for the rearing, was the only effective means to eliminate microsporidia from P. Predators of the commercial populations showed a low reproduction rate and unsatisfactory predation capacity. Moreover, mites were sluggish and had a swollen and whitish appearance (Beerling and van der Geest 1991a). Squash preparations of symptomatic mites revealed the presence of numerous microsporidian spores and heavily infected predators released spores after death (Beerling and van der Geest 1991a). Microsporidia were also present in the prey mites but the mechanisms of pathogen transmission have not been determined for this system. Oblong spores were detected in both predator and prey species, small and more oval spores were exclusively found in prey mites. Monoclonal antibodies were produced for one spore type that was present in both predator and prey species. Further work is needed to determine the sensitivity of this test as a suitable screening method for microsporidia in mites. Interestingly, Huger (1988) detected the microsporidium Nosema steinhausi in diseased mass-reared populations of the same phytoseiid species (N. Fungi General characteristics of fungi in insects and mites Fungi are eukaryotic heterotrophes that obtain nutrients either from dead organic matter (saprobes) or from living organisms (parasites). Some parasitic fungi are obligate patho- gens, but the majority are facultative pathogens capable of growing without their host (Tanada and Kaya 1993). Entomopathogenic fungi are characterized by their ability to attach to and penetrate host cuticle or spiracles; however, some penetrate through the gut. They replicate inside the host, usually in the hemocoel, where they compete for soluble nutrients and may release mycotoxins, which interfere with normal host development and metamorphosis and in some cases with the immune defense mechanisms (Boucias and Pendland 1998). Adhesion and germination of fungal spores on the host cuticle are highly dependent on relative humidity and temperature, but light conditions and nutritional requirements are also important factors (Tanada and Kaya 1993). Symptoms in insects may include restlessness, loss of coordination and body tremors, reproductive behaviour by castrated hosts and changes in microhabitat preference (Horton and Moore 1993; Boucias and Pendland 1998). The latter include elevation-seeking behaviour (fungal summit disease ), movement to exposed locations, change in oviposition or foraging sites and change in temperature preference (Horton and Moore 1993). Fungi in phytoseiid mites Pathogenic fungi have been recorded for only two phytoseiid species up to now (Table 4).

The and subunits of F form a leg-and-foot that projects from the bottom1 (membrane) side of F and stands firmly on the ring of1 c subunits celecoxib 200 mg line. The a subunit is a very hydrophobic protein that in most models is composed of five transmembrane helices buy 200 mg celecoxib otc. The b subunits are anchored within the membrane by an N-terminal -helix and extend as a peripheral stalk all the way to the head of the F domain. According to cross-linking studies, the1 b subunits contact de C-terminal part of the c subunit and the loop between helices 4 and 5 of the a subunit at the periplasmic surface. The early stage of this model postulated an alternating transition between two chemical states, assuming two catalytic sites residing on F. It was later revised to propose the cyclic1 transition of the catalytic sites based on the biochemical and electron microscopic experiments that revealed that F has the three catalytic sites [71-73]. One important feature of this model1 is that the affinity for nucleotide in each catalytic site is different from each other at any given time, and the status of the three -subunits cooperatively change in one direction accompa nying rotation. This hypothesis is strongly supported by X-ray crystallographic studies performed by Walker s group [67] that first resolved crystal structure of F, which revealed1 many essential structural features of F at atomic resolution. Another important feature found in the crystal is that while the N-terminal domains of the - and -subunits form a symmetrical smooth cavity as the bearing for rotation at the bottom of the -ring, the C-terminal domains of the -subunit show distinct3 3 asymmetric interactions with the -subunit. This prediction was confirmed in elegant experiments in the laboratories of Masasuke Yoshida and Kazuhiko Kinosita Jr. Lately the unidirectional rotation was visualized in simultaneous imaging of the conformational change of the -subunit and the rotation. This technology allows visualization of biomolecules under physiological conditions. However, it is limited by the speed at which it can successively record highly resolved images. Recent advances have improved the time resolution of the technique from minutes to tens of milliseconds, allowing single biomolecules to be watch in action in real time. This technology allows direct visualization of dynamic structural changes and dynamic processes of functioning biological molecules in physiological solutions, at high spatial-temporal resolution. Previous sin1 gle-molecule experiments on parts of this enzyme had measured rotation, but they could only be done if at least one subunit of the rotor was attached. This new approach will spread over the world and widely applied to a vast array of biological issues, leading to a number of new discoveries. Lipid rafts Cell membranes are dynamic assemblies of a variety of lipids and proteins. They form a protective layer around the cell and mediate the communication with the outside world. The 18 Oxidative Stress and Chronic Degenerative Diseases - A Role for Antioxidants original fluid mosaic model [78] of membranes suggested a homogenous distribution of proteins and lipids across the two-dimensional surface, but more recent evidence suggests that membranes themselves are not uniform and that microdomains of lipids in a more ordered state exist within the generally disorder lipid milieu of the membrane. Detergent resistant membranes, containing clusters of many rafts, can be isolated by extraction with Triton X-100 or other detergents on ice. However, this method involves breaking up the membrane and has limitations in terms of defining the size, properties, and dynamics of intact microdomains [85-88]. The raft affinity of a given protein can be modulated by intra- or extracellular stimuli. Caveolae are types of rafts that are rich in proteins of the caveolin family (caveolin-1, -2 and -3) which present a distinct signaling platform [96]. The most important role of rafts at the cell surface may be their function in signal transduction. Lipid rafts have been implicated as the sites for a great number of signaling pathways. They form concentrating platforms for individual receptors, activated by ligand binding [86]. If receptor activation takes place in a lipid raft, the signaling complex is protected from non-raft enzymes such as membrane phosphatases that otherwise could affect the signaling process. In general, raft binding recruits proteins to a new micro-environment, where the phosphory lation state can be modified by local kinases and phosphatases, resulting in downstream signalling. Individual signaling molecules within the raft are activated only for a short period of time. Immobilization of signaling molecules by cytoskeletal actin filaments and scaffold proteins may facilitate more efficient signal transmission from rafts [97]. Current evidence supports a role for lipid rafts in the initiation and regulation of The B-cell receptor signaling and antigen trafficking [98-100]. Plasma membranes typically contain higher concentrations of cholesterol and sphingomyelin than do internal membranous organelles [105-106]. Thus, along the secretion pathway, there are very low concentrations of cholesterol and sphingolipids in the endoplasmic reticulum, but the concentrations of these lipids increase from the cis-Golgi to the trans-Golgi and then to the plasma membrane [107-108].

An inherited radic cases of meningitis in adult cows have been caused hypomyelinogenesis has been reported in Jersey calves generic celecoxib 100 mg on line. The foci of chronic infection such as traumatic reticuloperito- more excited the calf becomes and struggles to move discount celecoxib 100 mg on line, nitis abscesses. It disappears when the calf is mon predisposing cause of sporadic bacterial meningitis completely relaxed. When multiple cases of Axonopathy acute meningitis occur within a herd of adult cattle, His- We recently studied a group of related Holstein calves tophilus (Haemophilus) somni infection should be sus- that at birth were usually able to stand and walk but had pected. When Etiology meningitis precedes other major organ infection, signs of Gram-negative septicemia in neonates is the most com- fever, depression, head pressing or headache appear- mon cause of meningitis in dairy cattle. The gait is stiff, and the head is often held cient levels of passively acquired immunoglobulins to straight, with the muzzle extended. Septicemia may origi- ful, and the animal may appear to have a headache with nate in umbilical infections or more commonly by oral the eyelids partially closed and the head and neck ex- inoculation of pathogens. The heifer was treated with ampicillin and supportive treatment and recovered in 1 month. A 10-day-old Holstein calf with bacterial meningitis caus- ing severe opisthotonos. Depression Adult cattle affected with meningitis usually have fe- is so severe that presence or absence of vision may be ver and profound depression. A stiff, stilted gait and difcult to determine, and occasional seizures are ob- headache appearance (stargazing or continually press- served in some patients. Affected cows die within 24 to ing head or muzzle against an object) are common 48 hours of onset unless treated specically for H. Inammation of the visual cortex can result in tiple cases over a period of several months, until appro- blindness with normal pupillary function. Treatment Broad-spectrum antibiotics constitute the primary treat- ment for meningitis in calves and adult cattle. For example, in neonatal calves, the antici- pated cause would be a gram-negative organism such as E. Although not permitted in North Focal chorioretinitis with hemorrhage dorsal to the optic America, enrooxacin would be an excellent antimicro- disc in a Holstein yearling with thrombotic meningoen- bial selection for gram-negative meningitis. In subacute cases, calves that are aggressively treated too late with proper macrophages may predominate. The uid can appear antibiotics may live for several days but never regain normal on visual examination, or it can be grossly discol- reasonable mentation and have necrotic lesions in the ored (red to orange). Serum pro- life-threatening inammation and cerebral edema associ- tein and immunoglobulin levels should be evaluated in ated with meningitis. Seizures may be controlled with meningitis secondary to acute or chronic infections 5 to 10 mg of diazepam in neonatal meningitis patients. These cattle have been ill for variable lengths of time, and the developing signs of Prevention meningitis may be mistakenly assumed to be progres- Adequate passive transfer of immunoglobulins through sive systemic illness associated with failure to respond well-managed colostrum feeding of each newborn calf to therapy for the primary condition. In addition, direct extension from chronic frontal sinusitis and bacterial seeding as- sociated with nose rings in bulls are other potential causes of brain abscesses in adult cattle. Although the relationship with frontal sinusitis is obvious, the in- ferred higher risk of cattle or bulls with nose rings for brain or pituitary abscesses is very interesting. Theories to explain this phenomenon center around the complex rete mirabile circulation that encircles the pituitary re- gion and is suspended in the cavernous sinuses, which drain the nasal cavity. Arcanobacterium pyogenes is the most common organism isolated from brain abscesses in cattle. As the abscess enlarges, varying degrees of visual when walked in a tight circle or over rough ground. If the abscess fected cattle continue to eat despite extensive space- becomes sufciently large, it will interfere with venous occupying abscesses. Antiinamma- Depression and a stargazing attitude have been observed tory or antibiotic therapy may stabilize or transiently in cattle with cerebral abscesses. Bradycardia coupled improve the animal s signs, but regression coincides with depression and a stargazing attitude has been de- with stoppage of medications. The bradycardia may result from involvement of hypothalamus or may be caused by the anorexia. Diagnosis Abscesses localized to one cerebral hemisphere usu- Antemortem conrmation of brain or pituitary ab- ally cause blindness with intact pupillary function in the scesses may be difcult. Treatment Other than long-term antibiotic therapy and potential drainage, therapy is limited and prognosis grave. We are unaware of successful surgery for brain abscesses in cat- tle, although this is occasionally possible in some other species. Symptomatic therapy with antibiotics and anti- inammatories may cause a slight improvement in the animal s neurologic signs but is short-lived, and death is inevitable for most cattle affected with brain abscesses. A left cerebral abscess was identi- from humans and animals, is the cause of the most com- ed at necropsy. Although this facultative intracellular organism occasionally causes septicemia in young calves and abortion in adult cows, it is best known for the neurologic infection of the brain- stem that is labeled listeriosis or circling disease in adult cattle and other ruminants. Use gloves when exam- ining these animals because humans are susceptible to this infectious agent.

On the other hand order celecoxib 100 mg free shipping, diffuse damage at smaller size scales discount celecoxib 200mg visa, around 1 m and less, may be repaired by a different mechanism and may not be an inevitable precursor of microcracks. With an in vivo rat ulnar model that introduces diffuse damage in tensile cortices without linear microcracks, Seref-Ferlenguez et al. This may occur by physico-chemical bridging with calcium deposition within the small gaps or with products of nearby osteocytes. The relative importance of remodeling and direct repair mechanisms in humans is uncertain in light of the fact that cortical remodeling occurs constitutively throughout the human skeleton. This remodeling process occurs in foci and ensures the overall mechanical integrity of the skeleton while renewing the tis- sue, adjusting the bone architecture to mechanical forces, and repairing microdam- age. By replacing mature mineralized matrix, remodeling pro- vides new mineral that is less crystalline and more readily soluble to contribute to calcium homeostasis. Histomorphometric evidence shows that the balance between bone resorption and formation is inadequate to conserve skeletal mass throughout the lifespan. One of the best established age-related changes in cancellous bone is the reduction in wall width [119]. The reduction is approximately one-third from young adulthood Osteoporosis and Mechanisms of Skeletal Aging 291 to seniority and is the result of a reduction in bone formation rate. In addition, those confounders challenge clinical decision-making; a better biomarker for status of bone metabolism is needed. In one study, dynamic parameters of bone formation and static parameters of bone resorption were determined for osteoporotic and control women and men. Distinctions can be made between those age-related changes that are caused by intrinsic cellular factors and those induced by the extrinsic somatic environment, e. These are examples of extrinsic fac- tors that change with age and affect skeletal cells. The unfavorable skeletal effects of the menopause and of male hypogonadism are well known, but the effects of age-related declines in serum T on bone mass are unclear and may be related to conversion of T to E2. A unifying hypothesis on the pos- sible mechanisms of bone loss associated with age-related declines in sex steroids (Fig. Vokes The themes also draw attention to mechanistic relationships between aging and cer- tain chronic diseases. A common theme emerges from examining these pro- cesses; they may be benecial mechanisms that optimize normal tissue homeosta- sis, but under chronic circumstances may become harmful to the cells or environment. Understanding the relative roles of these mechanisms in skeletal aging may point to potential therapeutic targets [139 ]. Because the premature osteoporosis in Werner syndrome has features that are different from osteoporosis in the general population, such as higher incidence of fractures in men than women, and earlier loss of cortical than trabecular bone [140], it may not provide a relevant model for natural skeletal aging. It was sug- gested that intermittent or transient telomerase activation may be a feasible clinical intervention. Methylation generally inactivates respective promoter regions and is maintained upon replication. Both hyper- methylation and hypomethylation sites were detected, ndings that may explain why demethylating agents do not categorically control replicative senescence [142]. Proteasome inhibitors have been shown to increase osteogenesis in mouse models [145]. The relationship between senescence and autophagy is complex, with dif- ferent models showing that autophagy either protects from senescence or triggers senescence. In those cells, low dose irradiation led to only a transient rise in apoptosis, followed by senescence of the surviving cells. A growing body of information about the func- tions of autophagy in various mouse bone cells provides a basis for future aging research [148]. Those mediators also interact in com- plex ways and have different effects at different set points, but are likely to contrib- ute to skeletal aging [149, 150]. The growing understanding of cross-talk between bone and fat [151] and between bone and muscle [152] may provide new approaches to improve health of the aging population. In contrast, common antioxidants have not been shown to have enduring benecial effects on aging bones, but newer agents such as mitochondria-targeting compounds may have potential [155, 156]. Thus, when present chronically, the damage response networks that normally facilitate repair and survival can compromise tissue homeostasis and lead to cellular apoptosis and senescence. With aging, the relative activities of pro-inammatory M1 macrophages and anti-inammatory M2 macrophages favor M1 and subsequent decrease in osteoblast differentiation and increased osteoclast differentiation [160]. This information helps to explain Osteoporosis and Mechanisms of Skeletal Aging 297 how age-associated bone loss is linked to uncoupling of osteoblastic and osteoclas- tic activities in favor of bone resorption. Cellular senescence is a benecial response to damage and stress and prevents dysplasia and cancer by suppressing proliferation of compromised cells. Some of the research with those cells is motivated by their possible therapeu- tic use for age-related and other disorders [65]. To that end, ways to increase ex vivo proliferative and differentiation capacity of cells derived from the elderly become a paramount challenge. Although these are convenient ways to study cellular senescence, their ndings need to be conrmed with cells from subjects across the lifespan.