The in vitro immunomodulatory effects of glyconutrients on peripheral blood mononuclear cells of patients with chronic fatigue syndrome

Abstract:

In humans, eight monosaccharides are required for the synthesis of glycoproteins. Dietary supplements that supply these crucial sugars are known as glyconutrients. A glyconutrient compound was added to Peripheral Blood Mononuclear Cells (PBMC) isolated from normal controls and patients with the Chronic Fatigue Syndrome (CFS), a disease associated with immune dysregulation. The in vitro immunomodulatory effects were investigated.

Cell surface expression of the glycoproteins CD5, CD8, and CD11a were significantly lower in patients with CFS compared to normal controls. Addition of glyconutrient homogenate to PBMC from patients with CFS stimulated with phytohemagglutinin significantly increased the expression of each glycoprotein.

Furthermore, natural killer (NK) cell function was reduced in CFS patients. The glyconutrient preparation significantly enhanced NK cell activity versus human herpes virus 6 (HHV-6)-infected H9 cells in an 8 h 51Cr release assay compared to placebo for PBMC from patients with CFS (p< .01).

Finally, apoptosis was significantly higher in patients with CFS. The percentage of apoptotic cells was significantly decreased in PBMC from patients with CFS that had been incubated for 48 h with glyconutrients. Thus, glyconutrients improved abnormal immune parameters in vitro in patients with CFS.

 

Source: See DM, Cimoch P, Chou S, Chang J, Tilles J. The in vitro immunomodulatory effects of glyconutrients on peripheral blood mononuclear cells of patients with chronic fatigue syndrome. Integr Physiol Behav Sci. 1998 Jul-Sep;33(3):280-7. http://www.ncbi.nlm.nih.gov/pubmed/9829439

 

Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome

Erratum in: Br J Psychiatry 1998 Jul;173:89.

 

Abstract:

BACKGROUND: The Joint Working Group of the Royal Colleges of Physicians, Psychiatrists and General Practitioners (1996) recommended graded exercise and antidepressants for patients with chronic fatigue syndrome. We assessed efficacy and acceptability of these treatments.

METHOD: Six-month prospective randomised placebo and therapist contact time controlled trial with allocation to one of four treatment cells: exercise and 20 mg fluoxetine, exercise and placebo drug, appointments only and 20 mg fluoxetine, appointments and placebo drug. Drug treatment was double blind and patients were blind to assignment to exercise or appointments.

RESULTS: Ninety-six (71%) of 136 patients completed the trial. Patients were more likely to drop out of exercise than non-exercise treatment (P = 0.05). In an intention to treat analysis, exercise resulted in fewer patients with case level fatigue than appointments only at 26 weeks (12 (18%) v. 4 (6%) respectively P = 0.025) and improvement in functional work capacity at 12 (P = 0.005) and 26 weeks (P = 0.03). Fluoxetine had a significant effect on depression at week 12 only (P = 0.04). Exercise significantly improved health perception (P = 0.012) and fatigue (P = 0.028) at 28 weeks.

CONCLUSIONS: Graded exercise produced improvements in functional work capacity and fatigue, while fluoxetine improved depression only.

Comment in:

Commentary on: randomised, double-blind, placebo-controlled trial of fluoxetine and graded exercise for chronic fatigue syndrome. [Br J Psychiatry. 1998]

Analysis of drop-out data in treatment trials. [Br J Psychiatry. 1998]

Fluoxetine and graded exercise in chronic fatigue syndrome. [Br J Psychiatry. 1998]

 

Source: Wearden AJ, Morriss RK, Mullis R, Strickland PL, Pearson DJ, Appleby L, Campbell IT, Morris JA. Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome. Br J Psychiatry. 1998 Jun;172:485-90. http://www.ncbi.nlm.nih.gov/pubmed/9828987

 

Decreased nitric oxide-mediated natural killer cell activation in chronic fatigue syndrome

Abstract:

BACKGROUND: L-Arginine (L-Arg), one of the essential amino acids, has been reported to have an immunomodulatory effect. The precise mechanism of the L-Arg-induced natural killer (NK) cell activation remains unresolved,and the effect of L-Arg on NK cells in chronic fatigue syndrome (CFS) patients has not been estimated.

METHODS: NK cell function was evaluated in 20 subjects with CFS and compared with that in 21 healthy individuals.

RESULTS: In healthy control subjects, NK activity was significantly increased after treatment with L-Arg, an NK function enhancer, for 24 h, whereas the same treatment failed to enhance NK activity in the CFS patients. We thus focused on L-Arg metabolism, which involves nitric oxide (NO) production through NO synthase (NOS). The expression of inducible NO synthase (iNOS) transcripts in peripheral blood mononuclear cells was not significantly different between healthy control subjects and CFS patients. The L-Arg-mediated NK cell activation was abolished by addition of NG-monomethyl-L-arginine, an inhibitor for iNOS. Furthermore, incubation with S-nitroso-N-acetyl-penicillamine, an NO donor, stimulated NK activity in healthy control subjects but not in CFS patients.

CONCLUSION: These results demonstrate that the L-Arg-induced activation of NK activity is mediated by NO and that a possible dysfunction exists in the NO-mediated NK cell activation in CFS patients.

 

Source: Ogawa M, Nishiura T, Yoshimura M, Horikawa Y, Yoshida H, Okajima Y, Matsumura I, Ishikawa J, Nakao H, Tomiyama Y, Kanayama Y, Kanakura Y,Matsuzawa Y. Decreased nitric oxide-mediated natural killer cell activation in chronic fatigue syndrome. Eur J Clin Invest. 1998 Nov;28(11):937-43. http://www.ncbi.nlm.nih.gov/pubmed/9824439

 

Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin

Abstract:

Fatigue is an important symptom of a disturbed circadian rhythm. To date, no studies of circadian rhythms in patients with chronic fatigue syndrome (CFS) have been published.

The objectives of the study were to study rhythms of heart rate and systolic and diastolic blood pressure in patients with chronic fatigue syndrome compared with age-matched normotensive controls and to study the effects of melatonin and inopamil on such rhythms.

Ambulatory blood pressure (ABP) measurements (Space Lab, Inc, validated) of 18 patients with CFS were made according to the 1987 U.S. Center for Disease Control Criteria, and measurements of 12 age-matched normotensive controls were used in a cosinor analysis of the two groups. The effects of melatonin and inopamil on ABP were studied subsequently in four patients in an 8-week open-label evaluation. One patient was hypertensive (diastolic blood pressure > 90 mm Hg at least once every 4 hours), and was, therefore, excluded.

The data of the remaining 17 patients (15 women, 2 men) revealed a significant 12-hour rhythm in heart rate and 24-hour rhythm in systolic and diastolic blood pressure with 95% confidence intervals not significantly different from sinusoidal patterns. Although these rhythms were synchronous with the control group rhythms, their amplitudes were not and showed, respectively, 2.8, 2.8, and 9.0 times the size of the control group rhythms (p < 0.001, p < 0.001, and p < 0.0001, respectively). Systolic blood pressures in the patients with CFS were consistently below 100 mm Hg during the nighttime.

In a subsequent pilot study of four patients from the study population treated with melatonin 4 mg daily and inopamil 200 mg daily for 4 weeks, inopamil reduced nighttime hypotension (p < 0.05), whereas melatonin increased nighttime hypotension (p < 0.02).

Patients with CFS have increased amplitudes of circadian rhythms and systolic blood pressures consistently below 100 mm Hg during the nighttime. Positive inotropic compounds may be beneficial in such patients, but melatonin may not be.

 

Source: van de Luit L, van der Meulen J, Cleophas TJ, Zwinderman AH. Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin. Angiology. 1998 Nov;49(11):903-8. http://www.ncbi.nlm.nih.gov/pubmed/9822046

 

Yersinia enterocolitica and the chronic fatigue syndrome

Abstract:

OBJECTIVES: To investigate the potential role of Yersinia enterocolitica in patients with chronic fatigue syndrome (CFS).

METHODS: An immunoblot technique was used to detect antibodies to various Yersinia outer membrane proteins (YOPs) in serum samples from 88 patients with CFS and 77 healthy neighbourhood controls, matched for gender and age.

RESULTS: The prevalence of IgG and IgA antibodies to various Yersinia outer membrane proteins (YOPs) did not differ between patients with CFS and healthy controls. Twenty-four patients (27%) and nineteen controls (25%) had IgG antibodies to one or more YOPs. Four patients and two controls had both serum IgG and IgA antibodies to at least two different YOPs, compatible with a recent or persistent infection. Although all patients with positive IgG and IgA reactions to two or more YOPs had symptoms that could point to persistent Yersinia infection, these symptoms were also found frequently in patients without antibodies to YOPs.

CONCLUSIONS: We conclude that Y. enterocolitica is unlikely to play a major role in the aetiology of CFS.

Source: Swanink CM, Stolk-Engelaar VM, van der Meer JW, Vercoulen JH, Bleijenberg G, Fennis JF, Galama JM, Hoogkamp-Korstanje JA. Yersinia enterocolitica and the chronic fatigue syndrome. J Infect. 1998 May;36(3):269-72. http://www.ncbi.nlm.nih.gov/pubmed/9661935

Clinical and serologic follow-up in patients with neuroborreliosis

Abstract:

The authors performed a clinical and serologic follow-up study after 4.2 +/- 1.2 years in 44 patients with clinical signs of neuroborreliosis and specific intrathecal antibody production. All patients had been treated with ceftriaxone 2 g/day for 10 days. Although neurologic deficits decreased significantly, more than half the patients had unspecific complaints resembling a chronic fatigue syndrome and showed persisting positive immunoglobulin M serum titers for Borrelia in the Western blot analysis.

Comment in: Neuropsychological deficits in neuroborreliosis. [Neurology. 1999]

 

Source: Treib J, Fernandez A, Haass A, Grauer MT, Holzer G, Woessner R. Clinical and serologic follow-up in patients with neuroborreliosis. Neurology. 1998 Nov;51(5):1489-91. http://www.ncbi.nlm.nih.gov/pubmed/9818893

 

Diurnal variation of adrenocortical activity in chronic fatigue syndrome

Abstract:

Baseline morning and evening serum cortisol and ACTH concentrations, and diurnal changes in hormone levels, were measured in 30 patients with chronic fatigue syndrome (CFS) but without concurrent depressive disorder and a control group of 15 weight-, age- and sex-matched healthy volunteers.

Morning cortisol levels were non-significantly lower in CFS patients, while evening levels were non-significantly higher. ACTH concentrations were non-significantly higher in both the morning and evening. The diurnal change in cortisol levels was significantly less in CFS than in controls (p < 0.05). In CFS subjects, evening levels of cortisol correlated significantly with measures of general health and physical functioning, while diurnal change in cortisol was positively correlated with measures of functional improvement over the past year and current social functioning.

These results suggest that there is a relationship between adrenocortical function and disability in CFS, but do not reveal the causal connection.

 

Source: MacHale SM, Cavanagh JT, Bennie J, Carroll S, Goodwin GM, Lawrie SM. Diurnal variation of adrenocortical activity in chronic fatigue syndrome. Neuropsychobiology. 1998 Nov;38(4):213-7. http://www.ncbi.nlm.nih.gov/pubmed/9813459

 

Rhinitis symptoms in chronic fatigue syndrome

Abstract:

BACKGROUND: Atopy and allergic rhinitis are thought to be increased in prevalence in chronic fatigue syndrome (CFS).

METHODS: To investigate this hypothesis, 51 CFS (CFS), 34 normal (N), 27 allergic rhinitis (AR), and 17 patients with other rheumatologic diseases filled out an Airway Symptom Severity self-report questionnaire to determine the frequencies of nasal, sinus, and chest symptoms, and a Systemic Complaints self-report questionnaire to determine the frequencies of complaints referable to neurologic, rheumatologic, gastrointestinal, and other systems. All subjects received a standard set of allergy skin tests, and were subdivided into those with positive and negative results.

RESULTS: Allergy skin tests were positive in 35% of CFS and 44% of N subjects (difference not significant by Chi2). Significant rhinitis complaints were present in 83% of skin test positive CFS, 76% of skin test negative CFS, 74% of AR, and 23% of N subjects. Systemic Complaints scores were significantly elevated in skin test positive (94%) and negative (94%) CFS groups compared with AR (35%) and N (6%) groups. This score could significantly discriminate between CFS and N subjects.

CONCLUSIONS: These data indicate that in this CFS population, 24% had no significant rhinitis complaints, 30% had positive skin tests suggesting the potential for allergic rhinitis complaints, and 46% had nonallergic rhinitis. The mechanism of the nonallergic component may offer insights into the pathogenesis of CFS.

 

Source: Baraniuk JN, Clauw DJ, Gaumond E. Rhinitis symptoms in chronic fatigue syndrome. Ann Allergy Asthma Immunol. 1998 Oct;81(4):359-65. http://www.ncbi.nlm.nih.gov/pubmed/9809501

 

The relationship between temporomandibular disorders and stress-associated syndromes

Abstract:

OBJECTIVES: The purpose of this study was to determine the comorbidity of temporomandibular disorders and other stress-associated conditions in patients with chronic fatigue syndrome and fibromyalgia.

STUDY DESIGN: Of 92 patients who fulfilled the criteria for chronic fatigue syndrome or fibromyalgia (or both), 39 (42%) reported a prior diagnosis of temporomandibular disorder. Further questionnaires were sent to the members of this group, and 30 patients responded.

RESULTS: Of the original 92 patients, of whom 42% reported temporomandibular disorders, 46% had histories of irritable bowel syndrome, 42% of premenstrual syndrome, and 19% of interstitial cystitis. Of the patients with temporomandibular disorders, the great majority reported an onset of generalized symptoms before the onset of facial pain. Despite this, 75% had been treated exclusively for temporomandibular disorders, usually with bite splints.

CONCLUSIONS: Patients appearing for treatment with chronic facial pain show a high comorbidity with other stress-associated syndromes. The clinical overlap between these conditions may reflect a shared underlying pathophysiologic basis involving dysregulation of the hypothalamic-pituitary-adrenal stress hormone axis in predisposed individuals. A multidisciplinary clinical approach to temporomandibular disorders would improve diagnosis and treatment outcomes for this group of patients.

 

Source: Korszun A, Papadopoulos E, Demitrack M, Engleberg C, Crofford L. The relationship between temporomandibular disorders and stress-associated syndromes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998 Oct;86(4):416-20. http://www.ncbi.nlm.nih.gov/pubmed/9798224

 

Chronic fatigue syndrome: physical and cardiovascular deconditioning

Abstract:

We investigated whether chronic fatigue syndrome (CFS) patients have physical and/or cardiovascular de-conditioning, in 273 CFS patients and 72 healthy controls.

We used laboratory tests to assess haematological, biochemical, endocrinological and immunological systems. The cardiovascular system was assessed by echocardiography and carotid echography. Body composition was determined by dual energy X-ray absorptiometry (DEXA).

CFS patients had smaller left ventricular end systolic (p < 0.001) and diastolic (p = 0.008) dimensions but thinner posterior walls (p = 0.02) than corresponding values in healthy controls. Left ventricular mass was also reduced in CFS patients (p = 0.006). Both maximum (p < 0.001) and minimum (p < 0.008) diameter of the carotid artery were smaller in CFS patients. The laboratory screening tests showed significant differences in serum albumin (p = 0.05), phosphate (p = 0.02), HDL-cholesterol (p = 0.03), HDL:total cholesterol ratio (p = 0.01), triglycerides (p = 0.02), neutrophils (p = 0.01) and thyroid-stimulating hormone (p = 0.04) between CFS patients and controls. Male CFS patients had an increased percentage of fat mass compared with healthy male subjects (p = 0.02).

This large group of CFS patients had evidence of physical and cardiovascular de-conditioning, suggesting that in these patients a graded exercise programme could lead to physical reconditioning and could increase their ability to perform physical activities.

 

Source: De Lorenzo F, Xiao H, Mukherjee M, Harcup J, Suleiman S, Kadziola Z, Kakkar VV. Chronic fatigue syndrome: physical and cardiovascular deconditioning. QJM. 1998 Jul;91(7):475-81. http://qjmed.oxfordjournals.org/content/91/7/475.long (Full article)