Tag: mitochondria

Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome

Abstract:

OBJECTIVES: To examine the proportions of type 1 and type 2 muscle fibres and the degree of muscle fibre atrophy and hypertrophy in patients with chronic fatigue syndrome in relation to lactate responses to exercise, and to determine to what extent any abnormalities found might be due to inactivity.

METHODS: Quadriceps needle muscle biopsies were obtained from 105 patients with chronic fatigue syndrome and the proportions of type 1 and 2 fibres and fibre atrophy and hypertrophy factors were determined from histochemical preparations, using a semiautomated image analysis system. Forty one randomly selected biopsies were also examined by electron microscopy. Lactate responses to exercise were measured in the subanaerobic threshold exercise test (SATET).

RESULTS: Inactivity would be expected to result in a shift to type 2 fibre predominance and fibre atrophy, but type 1 predominance (23%) was more common than type 2 predominance (3%), and fibre atrophy was found in only 10.4% of cases. Patients with increased lactate responses to exercise did have significantly fewer type 1 muscle fibres (p<0.043 males, p<0.0003 females), but there was no evidence that this group was less active than the patients with normal lactate responses. No significant ultrastructural abnormalities were found.

CONCLUSION: Muscle histometry in patients with chronic fatigue syndrome generally did not show the changes expected as a result of inactivity. However, patients with abnormal lactate responses to exercise had a significantly lower proportion of mitochondria rich type 1 muscle fibres.

 

Source: Lane RJ, Barrett MC, Woodrow D, Moss J, Fletcher R, Archard LC. Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):362-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2169994/ (Full article)

 

Reduced oxidative muscle metabolism in chronic fatigue syndrome

Abstract:

The purpose of this study was to determine if chronic fatigue syndrome (CSF) is characterized by abnormalities in oxidative muscle metabolism. Patients with CFS according to Centers for Disease Control (CDC) criteria (n = 22) were compared to normal sedentary subjects (n = 15).

CFS patients were also tested before and 2 days after a maximal treadmill test. Muscle oxidative capacity was measured as the maximal rate of postexercise phosphocreatine (PCr) resynthesis using the ADP model (Vmax) in the calf muscles using 31P magnetic resonance spectroscopy. Vmax was significantly reduced in CFS patients (39.6 +/- 2.8 mmol/L/min, mean +/- SE) compared to controls (53.8 +/- 2.8 mmol/L/min). Two days postexercise there was no change in resting inorganic phosphate (Pi)/PCr or Vmax in the CFS patients (n = 14).

In conclusion, oxidative metabolism is reduced in CFS patients compared to sedentary controls. In addition, a single bout of strenuous exercise did not cause a further reduction in oxidative metabolism, or alter resting Pi/PCr ratios.

Comment in: Chronic fatigue syndrome and skeletal muscle mitochondrial function. [Muscle Nerve. 1997]

 

Source: McCully KK, Natelson BH, Iotti S, Sisto S, Leigh JS Jr. Reduced oxidative muscle metabolism in chronic fatigue syndrome. Muscle Nerve. 1996 May;19(5):621-5. http://www.ncbi.nlm.nih.gov/pubmed/8618560

 

Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) mainly complain of symptoms in the musculoskeletal domain (myalgias, fatigue). In 21 CFS patients the deep (muscle) versus superficial (skin, subcutis) sensitivity to pain was explored by measuring pain thresholds to electrical stimulation unilaterally in the deltoid, trapezius and quadriceps and overlying skin and subcutis in comparison with normal subjects.

Thresholds in patients were normal in skin and subcutis but significantly lower than normal (hyperalgesia) in muscles (P < 0.001) in all sites. The selective muscle hypersensitivity corresponded also to fiber abnormalities at muscle biopsy (quadriceps) performed in nine patients which were absent in normal subjects (four cases): morphostructural alterations of the sarchomere, fatty degeneration and fibrous regeneration, inversion of the cytochrome oxidase/succinate dehydrogenase ratio, pleio/polymorphism and monstruosity of mitochondria, reduction of some mitochondrial enzymatic activities and increments of common deletion of 4977 bp of mitochondrial DNA 150-3000 times the normal values.

By showing both sensory (diffuse hyperalgesia) and anatomical (degenerative picture) changes at muscle level, the results suggest a role played by peripheral mechanisms in the genesis of CFS symptoms. They would exclude the heightened perception of physiological signals from all districts hypothesized by some authors, especially as the hyperalgesia is absent in skin/subcutis.

 

Source: Vecchiet L, Montanari G, Pizzigallo E, Iezzi S, de Bigontina P, Dragani L, Vecchiet J, Giamberardino MA. Sensory characterization of somatic parietal tissues in humans with chronic fatigue syndrome. Neurosci Lett. 1996 Apr 19;208(2):117-20. http://www.ncbi.nlm.nih.gov/pubmed/8859904

 

Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome

Abstract:

1. Chronic fatigue syndrome is characterized by muscle fatigue and pain at rest, symptoms which are usually exacerbated with exercise. Although various studies have shown minor, non-specific morphological and biochemical changes in muscle of patients with chronic fatigue syndrome, no consistent defect has been identified. Some have suggested that an enteroviral infection in muscle may cause the chronic muscle fatigue seen in patients with chronic fatigue syndrome, with acute infection directly and irreversibly impairing mitochondrial function, and persistent infection depressing muscle protein synthesis and metabolism.

2. To clarify the involvement of enterovirus infection in chronic fatigue syndrome, muscle biopsies from a group of patients with chronic fatigue syndrome were examined for the presence of enteroviral RNA by reverse transcriptase-polymerase chain reaction techniques in relation to functional studies of muscle mitochondria and the muscle RNA/DNA ratio.

3. Fifty-eight percent of patients reported an uncharacterized ‘viral infection’ before the onset of their illness, but none of the muscle samples from 34 patients contained detectable amounts of enteroviral RNA. Muscle tissue had a general reduction in the RNA/DNA ratio and mitochondrial enzyme activities with no specific abnormality in the activity of enzymes encoded partially on the mitochondrial genome (cytochrome-c oxidase) or nuclear genome (citrate synthase, succinate reductase).

4. These data provide no evidence of an enteroviral infection in muscle of patients with chronic fatigue syndrome, although this does not exclude a role of enterovirus in initiating the disease process. The general reduction in RNA/DNA ratio and mitochondrial enzyme activities is consistent with a general reduction in habitual activity.

 

Source: McArdle A, McArdle F, Jackson MJ, Page SF, Fahal I, Edwards RH. Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome. Clin Sci (Lond). 1996 Apr;90(4):295-300. http://www.ncbi.nlm.nih.gov/pubmed/8777836

 

Electron-microscopic investigation of muscle mitochondria in chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) suffer from disabling physical and mental fatigue. Abnormalities in mitochondrial function can lead to fatigue and weakness. Ultrastructural mitochondrial abnormalities have been reported to be present in CFS patients.

We obtained percutaneous needle muscle biopsies from 15 CFS patients and 15 age- and sex-matched controls. We investigated previously reported ultrastructural abnormalites in CFS: subsarcolemmal mitochondrial aggregates, intermyofibrillar mitochondrial aggregates, mitochondrial circumference, area, pleomorphism and the presence of compartmentalization of the inner mitochondrial membrane. All of the steps of tissue processing, electron microscopy and data abstracting and analysis were performed in a totally blinded fashion. All of our data were rigorously quantified.

We found no difference in any of these studied parameters between CFS patients and controls. Although there is no ultrastructural mitochondrial abnormality in CFS patients, other lines of evidence suggest the presence of a possible functional mitochondrial abnormality.

 

Source: Plioplys AV, Plioplys S. Electron-microscopic investigation of muscle mitochondria in chronic fatigue syndrome. Neuropsychobiology. 1995;32(4):175-81. http://www.ncbi.nlm.nih.gov/pubmed/8587699

 

Serum levels of carnitine in chronic fatigue syndrome: clinical correlates

Abstract:

Carnitine is essential for mitochondrial energy production. Disturbance in mitochondrial function may contribute to or cause the fatigue seen in chronic fatigue syndrome (CFS) patients. One previous investigation has reported decreased acylcarnitine levels in 38 CFS patients.

We investigated 35 CFS patients (27 females and 8 males); our results indicate that CFS patients have statistically significantly lower serum total carnitine, free carnitine and acylcarnitine levels, not only lower acylcarnitine levels as previously reported. We also found a statistically significant correlation between serum levels of total and free carnitine and clinical symptomatology. Higher serum carnitine levels correlated with better functional capacity.

These findings may be indicative of mitochondrial dysfunction, which may contribute to or cause symptoms of fatigue in CFS patients.

 

Source: Plioplys AV, Plioplys S. Serum levels of carnitine in chronic fatigue syndrome: clinical correlates. Neuropsychobiology. 1995;32(3):132-8. http://www.ncbi.nlm.nih.gov/pubmed/8544970

 

Acylcarnitine deficiency in chronic fatigue syndrome

Abstract:

One of the characteristic complaints of patients with chronic fatigue syndrome (CFS) is the skeletal muscle-related symptom. However, the abnormalities in the skeletal muscle that explain the symptom are not clear.

Herein, we show that our patients with CFS had a deficiency of serum acylcarnitine. As carnitine has an important role in energy production and modulation of the intramitochondrial coenzyme A (CoA)/acyl-CoA ratio in the skeletal muscle, this deficiency might induce an energy deficit and/or abnormality of the intramitochondrial condition in the skeletal muscle, thus resulting in general fatigue, myalgia, muscle weakness, and postexertional malaise in patients with CFS.

Furthermore, the concentration of serum acylcarnitine in patients with CFS tended to increase to the normal level with the recovery of general fatigue. Therefore, the measurement of acylcarnitine would be a useful tool for the diagnosis and assessment of the degree of clinical manifestation in patients with CFS.

 

Source: Kuratsune H, Yamaguti K, Takahashi M, Misaki H, Tagawa S, Kitani T. Acylcarnitine deficiency in chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S62-7. http://www.ncbi.nlm.nih.gov/pubmed/8148455

 

Enteroviruses and postviral fatigue syndrome

Abstract:

Postviral fatigue syndrome (PFS) occurs both in epidemics and sporadically. Many of the original epidemics were related to poliomyelitis outbreaks which either preceded or followed them.

The core clinical symptoms are always the same: severe fatigue made worse by exercise, myalgia, night sweats, atypical depression and excessive sleep. The other common symptoms include dysequilibrium disorders and irritable bowel syndrome.

We have detected enteroviral genome sequences in muscle biopsies from cases of PFS, using specific enteroviral oligonucleotide primers in the polymerase chain reaction (PCR). In addition, whole virus particles can be demonstrated in PCR-positive muscle, using solid-phase immuno-electron microscopy.

An increase in the number and size of muscle mitochondria was found in 70% of PFS cases, suggesting an abnormality in metabolic function. Evidence of hypothalamic dysfunction was present, particularly involving 5-hydroxytryptamine metabolism.

A putative model of PFS, based on persistent enteroviral infection in laboratory mice, revealed resolving inflammatory lesions in muscle with, however, a marked increase in the production of certain cytokines in the brain. This model may help to explain the pathogenesis of PFS.

 

Source: Behan PO, Behan WM, Gow JW, Cavanagh H, Gillespie S. Ciba Found Symp. 1993;173:146-54; discussion 154-9. http://www.ncbi.nlm.nih.gov/pubmed/8387908

 

Chronic fatigue syndrome: a joint paediatric-psychiatric approach

Comment on: Chronic fatigue syndrome: a joint paediatric-psychiatric approach. [Arch Dis Child. 1992]

 

SIR,-While agreeing that physical, psychological, and social factors must all be taken into account in the management of this complex and controversial syndrome I would disagree with Dr Margaret Vereker’s statement that no organic pathology can be detected to account for any of the symptoms. This conclusion has been made without reference to a number of research papers describing persisting viral infection, neuromuscular abnormalities in both structure and function, and immune system dysfunction.

Gow et al using polymerase chain reaction techniques, have been able to demonstrate the presence of enteroviral genome in muscle biopsies from a significant number of patients (53%) compared with controls (15%). None of the healthy control group in this study had evidence of viral particles in their muscle, this was only found in those with colonic or breast malignancies. Precisely what cytopathological effect this intracellular virus is having within muscle remains open to debate. However, Behan et al have published electron microscopic evidence of structural damage to the muscle mitochondria along with type II fibre atrophy; this is a finding which is not normally considered to be consistent with simple disuse.

You can read the rest of this letter here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1793782/pdf/archdisch00632-0102a.pdf

 

Source: Shepherd C. Chronic fatigue syndrome: a joint paediatric-psychiatric approach. Arch Dis Child. 1992 Nov;67(11):1410. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1793782/

 

Amplification and identification of enteroviral sequences in the postviral fatigue syndrome

Abstract:

Evidence from several sources has long suggested that enteroviruses might play a role in the postviral fatigue syndrome (PVFS).

We used the most sensitive molecular virological method available at present, the polymerase chain reaction (PCR) amplification technique, to look for enteroviral copies in peripheral blood leucocytes and muscle from a well-defined group of patients. We demonstrated that our PCR method amplified a sequence common to a wide range of enteroviral serotypes. A highly significant number of the muscle biopsies (53%: P = less than 0.001) from the patients were positive for enteroviral sequences. With regard to the leucocyte samples, 16% in both patient and control were positive.

The PCR results on the peripheral blood leucocytes were in keeping with serological findings, in showing that the level of exposure to enteroviruses seemed to be the same in patients and controls: it was therefore of the greatest interest that patients were 6.7 times more likely to have enteroviral genome in their muscle.

We conclude that persistent enteroviral infection plays a role in the pathogenesis of PVFS, also providing preliminary evidence that severe mitochondrial injury is one of the mechanisms involved.

 

Source: Gow JW, Behan WM. Amplification and identification of enteroviral sequences in the postviral fatigue syndrome. Br Med Bull. 1991 Oct;47(4):872-85. http://www.ncbi.nlm.nih.gov/pubmed/1665380