Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer cachexia has been suggested to be mediated by various cytokines derived either from tumor or host tissue. In the murine colon-26 (C-26) adenocarcinoma model IL-1, secreted by tumor-infiltrating mononuclear phagocytes, has an important role in induction of cancer cachexia. In order to suppress production of IL-1 in peritoneal macrophages we have used liposome-mediated gene transfer of the anti-inflammatory cytokine mIL-4, known as a potent inhibitor of IL-1 production. Balb/c mice were transfected by intraperitoneal inoculation of C-26 tumor cells. The mIL-4 transfected animals showed increased survival rate, delayed symptoms of cachexia and reduced anorexia in comparison with tumor-bearing control groups. However, tumor growth inhibition was not seen in mIL-4-transfected animals. Peritoneal macrophages from surviving mIL-4-transfected mice, when stimulated with LPS ex vivo, showed decreased IL-1 alpha production, 1672 +/- 202 pg/2 x 10(6) cells in contrast to tumor-bearing control animals, 3975 +/- 89 pg/2 x 10(6) cells, mock-transfected tumor-bearing animals 4004 +/- 174 pg/2 x 10(6) cells and tumor-free animals, 3142 +/- 60 pg/2 x 10(6) cells (p < 0.004). The present study demonstrates that in vivo gene transfer of an anti-inflammatory cytokine reduces cancer-associated cachexia by inhibition of IL-1 alpha production of tumor surrounding peritoneal macrophages, without a significant effect on tumor growth.
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PMID:In vivo gene transfer of murine interleukin-4 inhibits colon-26-mediated cancer cachexia in mice. 1252 62

Recent studies have shown that acute systemic administration of the selective orexin-1 receptor antagonist SB-334867 significantly reduces food intake in rats. Although this anorectic action of orexin-1 receptor blockade is associated with an acceleration in the transition from eating to resting, it is widely recognised that the behavioural indices of satiety are not dissimilar to those of illness. In this context, Experiment 1 confirmed a significant anorectic effect of 90 (but not 60) mg/kg lithium chloride (LiCl) in male rats presented with palatable mash in the home-cage environment. Experiment 2 employed a continuous monitoring technique to contrast the effects of LiCl (90 mg/kg) and SB-334867 (10 and 30 mg/kg) on food intake and behaviour during a 1-h test with palatable mash. SB-334867 dose-dependently inhibited food intake, with the higher dose producing a comparable degree of appetite suppression (approximately 40%) to that seen with LiCl. Despite equivalent anorectic action, the two compounds produced very different effects on behaviour. LiCl reduced active behaviours (locomotion, rearing, grooming and sniffing), slowed the rate of eating and disrupted the behavioural satiety sequence (BSS). In contrast, SB-334867 (30 mg/kg) decreased the duration of feeding and grooming, and modestly accelerated the transition between eating and resting. Furthermore, whereas LiCl failed to alter posttreatment bodyweight gain, SB-334867 (30 mg/kg) produced a significant weight loss in the 24-h period immediately following injection. Overall, the divergent profiles obtained with equianorectic doses of LiCl and SB-334867 provide convincing evidence for the behavioural selectivity of SB-334867-induced anorexia.
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PMID:Differential effects of the selective orexin-1 receptor antagonist SB-334867 and lithium chloride on the behavioural satiety sequence in rats. 1505 92

Geriatric and cancer-afflicted patients often experience decreased quality of life with cachexia, anemia, anorexia, and decreased activity level. We have studied the possibility that a myogenic plasmid that expresses growth hormone releasing hormone (GHRH) can prevent and/or treat these conditions. We administered plasmid to 17 geriatric and five cancer-afflicted companion dogs with an average age of 10.5+/-1.0 and 11.3+/-0.6 years at enrollment, respectively. Effects of the treatment were documented for at least 180 days post-treatment, with 10 animals followed for more than 1 year post-treatment, on average 444+/-40 days. Treated dogs showed increased IGF-I levels, and increases in scores for weight, activity level, exercise tolerance, and appetite. No adverse effects associated with the GHRH plasmid treatment were found. Most importantly, the overall assessment of the quality of life of the treated animals increased. Hematological parameters such as red blood cell count, hematocrit, and hemoglobin concentrations were improved and maintained within their normal ranges. We conclude that intramuscular injection of a GHRH-expressing plasmid is both safe and capable of improving the quality of life in animals for an extended period of time in the context of aging and disease. The observed anabolic and hematological responses to a single dose of this plasmid treatment may also be beneficial in geriatric patients or patients with cancer-associated anemia and/or cachexia.
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PMID:Long-term effects of plasmid-mediated growth hormone releasing hormone in dogs. 1507 11

Acute systemic treatment with the selective orexin-1 receptor antagonist SB-334867 (30 mg/kg, i.p.) has been reported not only to inhibit food intake and to accelerate behavioural satiety in rats, but also to produce a significant loss of bodyweight over the 24 h period post-dosing. The present studies were designed to test the hypothesis that the inhibition of weight gain following acute treatment with SB-334867 is due to a persistent anorectic action of the compound. In Experiment 1, the acute effects of SB-334867 (30 mg/kg, i.p.) on food intake and behaviour in a 1 h test with palatable mash were assessed as a function of injection-test interval. Results confirmed that, when administered 30 min prior to testing, SB-334867 significantly suppressed mash intake and accelerated behavioural satiety. More importantly, significant anorexia and behavioural change were also observed when animals were tested 24 h, but not 48 h, post-dosing. As previously reported, all animals treated with the orexin-1 receptor antagonist lost bodyweight over the 24 h period following acute treatment. The generality of these findings was confirmed in Experiment 2, where acute treatment with SB-334867 (30 mg/kg, i.p.) significantly suppressed home cage chow consumption over the 24 h period post-dosing, an effect also accompanied by a significant loss of bodyweight. The results of Experiment 3 showed that, following i.p. administration of 30 mg/kg, SB-334867 has good CNS penetration, reaches peak plasma and brain concentrations at 30 min, and maintains good exposure over 4 h post-dosing. Overall, current data support the hypothesis that a persistent anorectic action contributes to the significant loss of bodyweight observed 24 h following acute dosing with SB-334867. As the compound is virtually undetectable in plasma or brain beyond 8 h post-dosing, and since nothing is known about potentially active metabolites, we consider the possibility that single dose treatment with SB-334867 results in enduring alterations to the orexin-1 receptor and/or downstream signalling pathways.
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PMID:Anorexia and weight loss in male rats 24 h following single dose treatment with orexin-1 receptor antagonist SB-334867. 1563 84

Infectious salmon anemia (ISA) is a viral disease in farmed Atlantic salmon Salmo salar, characterized by lethargy, anorexia, anemia and death. Test methods used for regulatory decisions to remove infected cages include the indirect fluorescent antibody test (IFAT), the reverse transcription-polymerase chain reaction test (RT-PCR), and virus isolation (VI). However, no thorough evaluation of these diagnostic tests has been carried out on field samples. The objective of this study was to evaluate the sensitivity and specificity of ISA diagnostic tests as individual tests and in combinations, using data collected by the provincial government surveillance program. Because a 'gold standard' reference test for ISA was not available, cage status was based on clinical disease records. A pool of fish from negative farms that had never had clinical ISA and a pool of fish from positive cages that were experiencing an outbreak of clinical ISA were obtained and assumed to be uninfected and infected respectively. A total of 1071 fish were used in this study. Depending on the test's cut-off value, the sensitivity and specificity for histopathology ranged from 30 to 73 and 72 to 99% respectively. IFAT had sensitivities and specificities in the range of 64 to 83 and 96 to 100% respectively. For the RT-PCR, sensitivity and specificity were 93 and 98% respectively. Test performances were also evaluated in series and in parallel combinations. Sensitivities are maximized when tests are evaluated in parallel, and ranged from 75 to 98%. Specificities are maximized when the tests are evaluated in series, and ranged from 99 to 100%. Current surveillance testing protocols should be reviewed to capitalize on this newly available information on test characteristics.
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PMID:Application of surveillance data in evaluation of diagnostic tests for infectious salmon anemia. 1581 27

Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa. In ABA, scheduled feeding in combination with voluntary wheel running leads to hyperactivity, reduced food intake, severe body weight loss and hypothermia. In this study it was investigated whether hyperactivity in ABA could be reduced by introducing a warm plate (which was voluntary accessible and did not influence ambient temperature) into a part of the cage. In ad libitum fed rats, the presence of the warm plate did not influence body temperature, running wheel activity (RWA), body weight or food intake. During ABA, however, rats preferred the warm plate and hypothermia was prevented, while hyperactivity and body weight loss were significantly reduced when compared to ABA rats without a plate. Correlation analysis revealed a significant association between basal body temperature and RWA during the light phase in ABA rats. However, there was no evidence that initiation of light phase RWA was a result of hypothermia. These data suggest that ABA rats prefer to prevent hypothermia passively by choosing a warm plate rather than actively regulating body temperature by hyperactivity.
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PMID:Voluntary access to a warm plate reduces hyperactivity in activity-based anorexia. 1592 12

Eicosapentaenoic acid is an omega-3 fatty acid, a group of fatty acids characterized by a double bond that sits three carbons down from the n terminal of the molecule. Derived from dark, rich fish, eicosapentaenoic acid has received increasing attention as a therapy for the cancer anorexia/weight loss syndrome. Multiple studies, including laboratory and preliminary clinical studies suggest this fish oil derivative may benefit cancer patients. Recently, however, three large comparative studies suggest that eicosapentaenoic acid is relatively ineffective for treating this syndrome. In view of these recent results, the goals of this review are as follows: (1) to provide background on the mandate for further study of the cancer-associated anorexia/weight loss syndrome; (2) to review the preliminary data that have suggested that eicosapentaenoic acid is a promising agent for treating this syndrome; (3) to review the methodology and findings of the more recent, definitive clinical trials; (4) to discuss and speculate on why the earlier positive findings drew conclusions that are discrepant from the results of more recent comparative clinical studies.
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PMID:Fish oil, lean tissue, and cancer: is there a role for eicosapentaenoic acid in treating the cancer anorexia/weight loss syndrome? 1592 42

Infectious salmon anemia (ISA) is a viral disease occurring in farmed Atlantic salmon (Salmo salar) that is characterized by lethargy, anorexia, anemia and death. To control the disease in New Brunswick, Canada, 7.5 million fish from outbreak cages have been destroyed since 1997. Despite changes made by farmers, 2002 was the worst year ever for ISA losses in the region. We evaluated the associations between potential risk factors and ISA outbreaks in the Atlantic-salmon sites in New Brunswick. This was a multilevel study in which the site-level design was a retrospective cohort study while the cage-level design was a modified case-cohort study. The questionnaire was divided into site-level questions, cage-level questions and hatchery information. The important factors identified by this study can be categorized as environmental, farmer controlled or industry controlled according to the capacity to change or eliminate them. Environmental risk factors such as increasing the depth of the net (if nets were <or=9 m, odds ratio (OR)=3.34) and decreasing the depth of water underneath the net (if depth of water underneath the net >3m, OR=3.34) are for the most part dictated by site location. Wild pollock (Pollachius virens) in the cage reflects the number of wild pollock that live in the site location. If there were >or=1000 pollock in the cage, the odds of disease in the cage increased 4.43-fold. Risk factors that are under farm control include increasing the number of times that the salmon are treated for sea lice (OR=3.31 if lice treatments are <or=2 times), transferring small smolts into seawater (OR=2.40 if smolts weighed >99 g) and improving on the adaptation of smolts to seawater to reduce post-transfer mortalities (OR=4.52 if there was at least one cage with post-transfer mortalities >5%). The industry-controlled factors need to be addressed by the industry as a whole. Organizing boat travel to minimize the time and frequency of boats travelling to or by sites currently is being reviewed. This will be extremely important because the OR=9.43 if processing boats travel within 1 km of the site and the OR=4.03 if the site has dry feed delivered by the feed company. Because the hazard ratio increased stepwise from 1 if the nearest neighbor with ISA was >or=5 km up to 5.5 if the nearest site with ISA was within 0.5 km, increasing the distance between sites might be necessary for effective control.
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PMID:Risk factors for outbreaks of infectious salmon anemia in farmed Atlantic salmon, Salmo salar. 1618 35

Toxoplasmosis is a common cause of death in wild and captive Australian marsupials, yet descriptions of clinical disease, diagnosis and pathological lesions are limited and incomplete. Infection with Toxoplasma gondii was diagnosed, using immunohistochemical techniques, following the acute death of a juvenile common wombat, Vombatus ursinus, that was being bottle raised by wildlife carers. This animal's cage mate developed dyspnoea, tachycardia and anorexia 3 weeks later. Serum was collected prior to euthanasia and necropsy examination. Pathological lesions in both animals were similar and toxoplasma cysts were seen in most organs examined but particularly in the neurological and respiratory systems. Serological testing of the second wombat supported the histological diagnosis and indicated that the tests have valuable roles in both diagnosing infections ante-mortem and in distinguishing between acute and chronic infections.
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PMID:Toxoplasma gondii infection in two common wombats (Vombatus ursinus). 1655 59

Cancer metastases (spread to distant organs from the primary tumor site) signify systemic, progressive, and essentially incurable malignant disease. Anorexia and wasting develop continuously throughout the course of incurable cancer. Overall, in Westernized countries nearly exactly half of current cancer diagnoses end in cure and the other half end in death; thus, cancer-associated cachexia has a high prevalence. The pathophysiology of cancer-associated cachexia has two principal components: a failure of food intake and a systemic hypermetabolism/hypercatabolism syndrome. The superimposed metabolic changes result in a rate of depletion of physiological reserves of energy and protein that is greater than would be expected based on the prevailing level of food intake. These features indicate a need for nutritional support, metabolic management, and a clear appreciation of the context of life-limiting illness.
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PMID:Cancer-associated cachexia and underlying biological mechanisms. 1660 32


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