Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

76 patients with the postviral fatigue syndrome (PVFS) and 30 matched controls were investigated. Virus isolation was attempted from concentrated faecal samples by direct culture and after acid dissociation of virus from antibody. Positive cultures of enteroviruses were obtained from 17 (22%) patients and 2 (7%) controls. An enterovirus-group-specific monoclonal antibody, 5-D8/1, directed against the VP1 polypeptide, was used to detect enteroviral antigen in the circulation, either free or complexed with antibody. VP1 antigen was detected in the serum of 44 (51%) of a further group of 87 PVFS patients. The number of patients positive for VP1 antigen was greater (42/44) when IgM complexes were detectable than when they were not (2/23). 1 year later, the 17 patients of the first group of 76 with positive cultures were again studied. The same virus was again isolated from 5 (29%), 13 (76%) had detectable IgM responses to enteroviruses, and 9 (53%) were positive for VP1 antigen in the serum. These results show that chronic infection with enteroviruses occurs in many PVFS patients and that detection of enterovirus antigen in the serum is a sensitive and satisfactory method for investigating infection in these patients.
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PMID:Chronic enterovirus infection in patients with postviral fatigue syndrome. 289 90

More than 100 patient-years' experience has been acquired in the treatment of 133 patients with ambulatory home total parenteral nutrition (TPN) between May 1974 and December 1983. Indications for chronic or permanent home TPN include short bowel syndrome, malabsorption, scleroderma, and vasoactive intestinal polypeptide syndrome. Indications for acute or temporary home TPN include Crohn's disease, malignancies, gastrointestinal fistulas, ulcerative colitis, anorexia nervosa, and numerous other disorders. Eighty-two patients in the acute group were treated primarily with percutaneously placed standard subclavian catheters and 51 patients in the chronic group have been treated thus far with implanted silicone rubber, Dacron-cuffed catheters for a cumulative total of 38,939 patient days. Of the 125 implanted catheters, 115 were placed in the superior vena cava and ten in the inferior vena cava for an average duration of 250 catheter-days, the longest single catheter remaining in situ for more than 8 1/2 years. Catheter-related sepsis occurred 33 times with the implanted catheters, or once every 2.6 catheter-years. One hundred and fourteen temporary catheters were placed percutaneously in the superior vena cava via a subclavian vein for an average duration of 68 days, the longest single catheter remaining in situ for 213 days. Catheter-related sepsis occurred seven times, equivalent to one episode per 3 catheter-years. Total catheter-related complications were quite infrequent and were directly related to duration of catheterization. They included venous thrombosis (12), clotted catheter (11), catheter failure or rupture (8), catheter compression (5) and inadvertent catheter removal (4). Twenty-six catheters were repaired or spliced in situ when the external segment was accidentally damaged or deteriorated secondary to long-term material fatigue. One remarkable patient has been maintained exclusively by TPN originally as an inpatient and subsequently as an outpatient for the entire 13 years of his life.
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PMID:100 patient-years of ambulatory home total parenteral nutrition. 642 31

A proline-rich polypeptide (PRP) complex, subsequently called Colostrinin, was isolated from ovine colostrum. The complex showed immunomodulatory properties in mice, rats, and chickens, inducing maturation and differentiation of thymocytes. It was recently found that Colostrinin is a cytokine-like factor that acts as an inducer of interferon gamma (IFN-gamma) and other cytokines in human peripheral blood and cord blood leukocyte cultures and has psycho-immuno-enhancing activity in volunteers. These observations prompted us to study the effect of Colostrinin on patients with Alzheimer's disease (AD). Forty six AD patients were divided into 3 groups and randomly assigned to receive orally either Colostrinin (100 microg per tablet, every second day), commercially available bioorganic selenium (100 microg selenium per tablet, every second day) or placebo tablets. One cycle of the treatment lasted 3 weeks and was separated from the next cycle by a 2 week hiatus. Each patient received 10 cycles of treatment during the year of the clinical trial. Outcomes were assessed by psychiatrists blinded to the treatment assignment. Eight of the 15 AD patients treated with Colostrinin improved and in the 7 others the disease had stabilized. In contrast, none of the 31 patients from the selenium or placebo groups with similar mild or moderate AD improved. The administration of selenium promoted stabilization in 13 of the 15 patients, whereas in the placebo group only 8 of the 16 patients were stabilized at the 12 month trials end-evaluation. Colostrinin was found to be a remarkably safe drug. Mild and transient effects were anxiety, stimulation, insomnia, and tiredness. The results obtained showed that oral administration of Colostrinin improves the outcome of AD patients with mild to moderate dementia. The results are very encouraging and deserve further research.
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PMID:Colostrinin: a proline-rich polypeptide (PRP) complex isolated from ovine colostrum for treatment of Alzheimer's disease. A double-blind, placebo-controlled study. 1060 95

Chronic fatigue syndrome is a disorder characterised by prolonged fatigue and debility and is mostly associated with post-infection sequelae although ongoing infection is unproven. Immunological aberration is likely and this may prove to be associated with an expanding group of vasoactive neuropeptides in the context of molecular mimicry and inappropriate immunological memory. Vasoactive neuropeptides including vasoactive intestinal peptide (VIP) and pituitary adenylate activating polypeptide (PACAP) belong to the secretin/glucagon superfamily and act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to smaller peptide fragments by antibody hydrolysis. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions. Vasoactive neuropeptides are widely distributed in the body particularly in the central, autonomic and peripheral nervous systems and have been identified in the gut, adrenal gland, reproductive organs, vasculature, blood cells and other tissues. They have a vital role in maintaining vascular flow in organs, and in thermoregulation, memory and concentration. They are co-transmitters for acetylcholine, nitric oxide, endogenous opioids and insulin, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system to toxic assault, promotion of neural development and the maintenance of homeostasis. This paper describes a biologically plausible mechanism for the development of CFS based on loss of immunological tolerance to the vasoactive neuropeptides following infection, significant physical exercise or de novo. It is proposed that release of these substances is accompanied by a loss of tolerance either to them or their receptor binding sites in CFS. Such an occurrence would have predictably serious consequences resulting from compromised function of the key roles these substances perform. All documented symptoms of CFS are explained by vasoactive neuropeptide compromise, namely fatigue and nervous system dysfunction through impaired acetylcholine activity, myalgia through nitric oxide and endogenous opioid dysfunction, chemical sensitivity through peroxynitrite and adenosine dysfunction, and immunological disturbance through changes in immune modulation. Perverse immunological memory established against these substances or their receptors may be the reason for the protracted nature of this condition. The novel status of these substances together with their extremely small concentrations in blood and tissues means that clinical research into them is still in its infancy. A biologically plausible theory of CFS causation associated with vasoactive neuropeptide dysfunction would promote a coherent and systematic approach to research into this and other possibly associated disabling conditions.
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PMID:Is chronic fatigue syndrome an autoimmune disorder of endogenous neuropeptides, exogenous infection and molecular mimicry? 1508 83

Fatigue is an inevitable consequence of physical activity; yet its biological cause remains uncertain. During exercise, a polypeptide messenger molecule interleukin-6 (IL-6) is actively produced. Previously, the administration of recombinant IL-6 (rhIL-6) induced a heightened sensation of fatigue in healthy humans at rest. In contrast, anti-IL-6 receptor antibodies reduced the symptoms of chronic fatigue. In the present study, athletic performance during an exercise challenge consisting of a 10-km running time trial was significantly impaired in trained male runners following the administration of a low dose of rhIL-6 compared to the placebo trial.
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PMID:Acute interleukin-6 administration impairs athletic performance in healthy, trained male runners. 1531 82

IFN-gamma (interferon-gamma) has several applications in the treatment of IFN-gamma-related skin disorders. While systemic delivery - the major route used to administer IFN-gamma - results in significant side effects and toxicity, including fever, fatigue, nausea, vomiting and neurotoxicity, transdermal delivery has a very low transduction efficiency. In order to improve the efficiency of transdermal IFN-gamma delivery, we introduced a Pen (penetratin) peptide, a 16-amino-acid-long polypeptide corresponding to the third helix of the DNA-binding domain (homoeodomain) of Antennapedia (a Drosophila transcription factor). The human IFN-gamma gene was then fused with a gene fragment that encodes the Pen of Antennapedia in a bacterial expression vector, producing a genetic in-frame Pen-IFN-gamma. The expressed and purified Pen-IFN-gamma was then found to have a much more efficient transduction profile than native IFN-gamma. In addition, compared with native IFN-gamma, Pen-IFN-gamma exhibited similar activities when added exogenously to a culture medium: (i) induction of IRF-1 gene expression, and (ii) NF-kappaB (nuclear factor kappaB) luciferase reporter activation. These results indicate that the transdermal delivery system using Pen may be an excellent way to replenish IFN-gamma in the various disorders related to this cytokine.
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PMID:Transdermal delivery of interferon-gamma (IFN-gamma) mediated by penetratin, a cell-permeable peptide. 1580 34

Acute infection is known to perturb psycho-neuroendocrine-immune (PNI) gene expression. Oligonucleotide microarrays were used to examine PNI gene expression in the peripheral blood of 13 subjects with infectious mononucleosis (IM). Novel peripheral blood gene expression activity was correlated with central-nervous-system-mediated symptoms including fatigue and sleep disturbance. Of note, expression of the MADS box transcription enhancer factor 2 polypeptide C (MEF2C) gene, previously implicated in skeletal muscle myogenesis, correlated with symptoms of musculo-skeletal pain and fatigue. Expression of the hypocretin/orexin receptor HCRTR2, which has been implicated in narcolepsy, correlated with sleep disturbance. And, VACHT, the vesicular acetylcholine transporter, was highly correlated with neurocognitive disturbance. The expression of both HCRTR2 and MEF2C in the peripheral blood was validated by reverse transcription PCR. Thus, investigation of the PNI response in peripheral blood may provide novel insights into the complex pathophysiology of centrally mediated disease states.
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PMID:Correlation of psycho-neuroendocrine-immune (PNI) gene expression with symptoms of acute infectious mononucleosis. 1637 18

Parkinson's disease (PD) is a motor disease including disorders of mobility, fine tremor, rigidity and posture caused by a relentless deterioration of dopaminergic cells in the substantia nigra (SN). Disorders of affect and a range of other symptoms including fatigue, cognitive dysfunction and mental confusion, sleep disorder and addictions are also seen as other CNS sites are also affected. Idiopathic and genetic causes together with inflammatory and degenerative disorders of ageing have been postulated as contributing to PD. Autoimmunity affecting certain vasoactive neuropeptides (VNs) has been postulated as contributing to certain fatigue-related conditions in humans and may be consistent with compromise of receptors associated with VNs and including receptors for vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP). Pro-inflammatory responses are seen in PD patients consistent with apoptotic neurodegeneration. Involvement of the Th1 directed cytokine interferon-gamma has been demonstrated and Th2 directed cytokines such as IL-10 protect against inflammation-mediated degeneration of dopaminergic neurons in the SN. Nitric-oxide dysregulation is also postulated in PD by fostering dopamine depletion via nitric-oxide synthase (iNOS). Both PACAP and VIP have neuroprotective effects in PD models by inhibiting the production of inflammatory mediators. PACAP specifically protects against the neurotoxicity induced by rotenone as well as protecting against oxidative stress-induced apoptosis. These findings suggest that a defect in VN function may act adversely on SN cells and hence contribute to a clinical presentation consistent with PD. The conclusion drawn from these findings is that PD may be an autoimmune disorder of VNs, specifically PACAP and VIP. Possibly unusual or anatomically specific receptors for these VNs may be involved. If proven, this hypothesis would have significant implications for immunological and pharmacological treatment and prevention of PD.
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PMID:Is Parkinson's disease an autoimmune disorder of endogenous vasoactive neuropeptides? 1756 59

A case of a 71-year-old male with ectopic adrenocorticotropic polypeptide (ACTH)-producing thymic carcinoid tumor presenting Cushing's syndrome was reported. This patient had symptoms of fatigue and a polyposia for 2 years before a mediastinal tumor was detected. Chest computed tomography (CT) scan demonstrated an anterior mediastinal mass, and serum ACTH and cortisol level revealed very high. Secretion of cortisol was not inhibited in an 8-mg dexamethazone suppression test. We diagnosed ectopic ACTH-producing tumor, and performed complete excision of the thymus including thymic tumor. Histologically, the tumor demonstrated typical carcinoid with the positivity of ACTH immunostaining. After the operation, ACTH and cortisol levels were reduced and the clinical symptoms were improved rapidly. We have concluded that it is important to control serum perioperative cortisol level for the prevension of morbidity.
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PMID:[Thymic carcinoid tumor with Cushing syndrome]. 1826 53

Fatigue is a predictable outcome of prolonged physical activity; yet its biological cause remains uncertain. During exercise, a polypeptide messenger molecule interleukin- 6 (IL-6) is actively produced. Previously, it has been demonstrated that administration of recombinant IL-6 (rhIL-6) impairs 10-km run performance and heightened sensation of fatigue in trained runners. Both high carbohydrate diets and carbohydrate ingestion during prolonged exercise have a blunting effect on IL-6 levels postendurance exercise. We hypothesized that carbohydrate ingestion may improve performance during a prolonged bout of exercise as a consequence of a blunted IL-6 response. Seven recreationally trained fasted runners completed two 90-min time trials under CHO supplemented and placebo conditions in a randomized order. The study was of a double-blinded, placebo-controlled, cross-over study design. Distance covered in 90 min was significantly greater following exogenous carbohydrate ingestion compared with the placebo trial (19.13+/-1.7 km and 18.29+/-1.9 km, respectively, p=.0022). While postexercise IL-6 levels were significantly lower in the CHO trial compared with the placebo trial (5.3+/-1.9 pg.mL(-1) and 6.6+/-3.0 pg.mL(-1), respectively; p=.0313), this difference was considered physiologically too small to mediate the improvement in time trial performance.
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PMID:The effect of carbohydrate ingestion on the interleukin-6 response to a 90-minute run time trial. 1956 22


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