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SJOGREN'S SYNDROME
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image 31. Long-term effects of Japanese herb medicine, bakumondo-to (mai-men-dong-tang), for the treatment of sicca syndrome.
image 32. The effect of bakumondo-to on salivary secretion in Sjogren syndrome.
image 33. Interferon alpha-2 (IFN alpha 2) increases lacrimal and salivary function in Sjogren's syndrome patients. Preliminary results of an open pilot trial versus OH-chloroquine.
image 34. Clinical evaluation of a commercially available oral moisturizer in relieving signs and symptoms of xerostomia in postirradiation head and neck cancer patients and patients with Sjogren's syndrome.
image 35. Treatment of primary Sjogren's syndrome with low-dose natural human interferon-alpha administered by the oral mucosal route: a phase II clinical trial. IFN Protocol Study Group.
image 36. Lung function in primary Sjogren's syndrome: a cross sectional and longitudinal study.
image 37. Oral administration of interferon-alpha induces a transient decline in oral mucosal immunoglobulins and an increase in interleukin-5.
image 38. Dietary polyunsaturated fatty acids and inflammatory mediator production.
image 39. LongoVital in the treatment of Sjogren's syndrome.
image 40. Stress-induced immunomodulation: implications for infectious diseases?
image 41. Stress and immunity in humans: a meta-analytic review.
image 42. Immunosenescence: potential causes and strategies for reversal.
image 43. Chinese herbs: a clinical review of Astragalus, Ligusticum, and Schizandrae.
image 44. Immunomodulating activity of Chinese medicinal herbs and Oldenlandia diffusa in particular.
image 45. The prostaglandin analogs, misoprostol and SC-46275, potently inhibit cytokine release from activated human monocytes.
image 46. Research on coenzyme Q10 in clinical medicine and in immunomodulation.
image 47. Anti-Ro in Sjogren's syndrome and systemic lupus erythematosus.
image 48. Antinuclear antibodies in Sjogren's syndrome.
image 49. The regulation of prostaglandin biosynthesis by the manipulation of essential fatty acid metabolism.
image 50. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group.
image 51. Autonomic cardiovascular neuropathy in Sjogren's syndrome. A controlled study.
image 52. Sjogren's syndrome: Treatment with Cyclosporin.
image 53. Thymosin administration in autoimmune disorders.
image 54. Immune complex glomerulonephritis in sicca syndrome.
image 55. Sjogren's syndrome with immune-complex tubulointerstitial renal disease.
image 56. Modification of a transplantable colon tumor and immune responses in mice fed different sources of protein, fat and carbohydrate.
image 57. Impaired function of immune reactivity to Listeria monocytogenes in diet-fed mice.
image 58. Influence of oral zinc supplementation on the lymphocyte response to mitogens of normal subjects.
image 59. Beneficial effects of oral zinc supplementation on the immune response of old people.
image 60. Interrelationships between zinc and immune function.


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31. Long-term effects of Japanese herb medicine, bakumondo-to (mai-men-dong-tang), for the treatment of sicca syndrome.

Int J Immunother (Switzerland) 1994;10(4):173-8.



32. [The effect of bakumondo-to on salivary secretion in Sjogren syndrome].

Ohno S, Suzuki T, Dohi Y
Second Department of Internal Medicine, Saitama Medical School.
Ryumachi 1990 Feb;30(1):10-6

The effect of a traditional chinese medicine 'Bakumondo to' was evaluated on salivary secretion in thirty-eight patients with Sjogren's syndrome (SjS) and the results were compared with a matchen control group of patients treated with Hochuekki-to. Hochuekki-to is also one of the traditional chinese medicine. Tsumura Bakumondo-to and Tsumura Hochuekki-to (extract granules) were used. Daily dose was 9g and 7.5g respectively. Before looking into the effects of Bakumondo-to on salivary secretion, we must define the reliability of the gum test. To avoid of learning effect, three sequential gum tests were needed. At the second gum test and the third gum test, no increase of salivary secretion was observed. So, we performed at least three gum test in each the patients studied. We have reached the following conclusion. First, in the Bakumondo-to group the salivary secretion was significantly increased from 8.2 1.1ml (m SE) to 11.4 1.4ml. (p less than 0.005) Second, in the Bakumondo-to group, the increase in salivary secretion was 3.16 0.78ml which was significantly more than the increase in control group. (p less than 0.005) Third, in the course of long-term observation, the salivary secretion in patients under Bakumondo-to treatment gradually increased. (r = 0.7290) Fourth, the improvement of salivary secretion under Bakumondo-to treatment was marked in stage I and stage II of sialographical abnormalities of the salivary gland. Finally, Bakumondo-to was very useful for managing oral manifestations in patients with SjS.



33. Interferon alpha-2 (IFN alpha 2) increases lacrimal and salivary function in Sjogren's syndrome patients. Preliminary results of an open pilot trial versus OH-chloroquine.

Ferraccioli GF, Salaffi F, De Vita S, Casatta L, Avellini C, Carotti M, Beltrami
CA, Cervini C, Bartoli E
Rheumatic Disease Unit (RDU), School of Medicine of Udine, Italy.
Clin Exp Rheumatol 1996 Jul-Aug;14(4):367-71

OBJECTIVE: The effect of recombinant interferon alpha-2 (IFN alpha 2) therapy in Sjogren's syndrome (SS) was studied. METHODS: An open study was performed in which 20 SS patients were given IFN alpha 2 3.10(6) MU/3 times/week or OH-chloroquine (OH-C) 6 mg/kg/daily, for a mean period of 11 months. RESULTS: Gland assessment showed that lacrimal and salivary function improved by 67% and 61% versus 15% and 18% respectively (p < 0.01) in the patients treated with IFN alpha 2 compared to those treated with OH-C. Immunological parameters did not change over time in either group. In 3 patients a decrease in the tissue score was observed in the IFN alpha 2 group, while no changes were seen in the control group. Tolerability was acceptable. CONCLUSION: This study shows that IFN can improve tear function and dry mouth in SS, without causing significant side effects.



34. Clinical evaluation of a commercially available oral moisturizer in relieving signs and symptoms of xerostomia in postirradiation head and neck cancer patients and patients with Sjogren's syndrome.

Rhodus NL, Bereuter J
School of Dentistry, University of Minnesota, Minneapolis 55455, USA.
J Otolaryngol 2000 Feb;29(1):28-34

A major complication of irradiation therapy for head and neck cancer is salivary gland dysfunction and xerostomia. The purpose of this clinical investigation was to evaluate the effects of a commercially available oral moisturizer (Optimoist) on salivary flow rate, symptoms of xerostomia, oral pH, oral microflora, and swallowing in postirradiation head and neck cancer patients (XRT) and patients with Sjogren's syndrome (SS). Subjects who were post-XRT and subjects with SS (n = 24; mean age = 54.1) discontinued their use of any salivary substitute or moisturizer for 2 weeks prior to entering the study. Baseline whole unstimulated saliva was collected for 5 minutes using a standard sialometric technique. Candida albicans and Lactobacillus cultures were performed using kits from Orion Diagnostica, Inc., and a pH analysis was performed on the salivary sample using a Markson (model 00663) pH meter. Swallowing was assessed by clinical measures by videofluoroscopic techniques. Several subjective assessments were performed to evaluate symptoms of xerostomia. Subjects were instructed in the use of a daily diary and to use only the provided article ad libitum for a period of 2 weeks. After the 2-week period, the results indicated significant subjective and objective improvements in signs and symptoms of xerostomia. Whole unstimulated salivary flow rate improved from (mean SEM) 0.1150 0.02 to 0.2373 0.09 mL/min. Salivary pH did not change. Global subjective improvement in xerostomia improved in 58% of the subjects. Candida colonization decreased in 43% of the subjects. There was no change in Lactobacilli colonization. Swallowing objectively improved in 75% of subjects. These results indicate significant improvement in both signs of hyposalivation and symptoms of xerostomia with the use of Optimoist in postirradiation head and neck cancer patients and patients with SS.



35. Treatment of primary Sjogren's syndrome with low-dose natural human interferon-alpha administered by the oral mucosal route: a phase II clinical trial. IFN Protocol Study Group.

Ship JA, Fox PC, Michalek JE, Cummins MJ, Richards AB
Department of Oral Medicine/Pathology/Oncology, University of Michigan School of
Dentistry, Ann Arbor 48109-1078, USA. jship@umich.edu
J Interferon Cytokine Res 1999 Aug;19(8):943-51

The purpose of this investigation was to examine the safety and efficacy of four
dosages of natural human interferon-alpha (nHuIFN-alpha) delivered over a
12-week period orally in lozenges (150 IU and 450 IU, once [QD] or three times
[TID] daily) compared to placebo in subjects with primary Sjogren's syndrome.
This randomized, double-blinded clinical trial demonstrated that nHuIFN-alpha at
a dose of 150 IU administered TID by oral lozenge significantly improved
stimulated whole saliva output compared to placebo after 12 weeks of treatment.
The 150 IU TID dose also was suggestive of benefit for 5 of 7 subjective
measures of oral and ocular comfort. IFN lozenges demonstrated a good safety
profile, with no serious adverse events found in any treatment group. There were
no significant differences between the placebo and the four doses of IFN for
adverse events by total number, organ system, severity, dropouts, and number
judged to be related to treatment. In conclusion, these results demonstrated
that the use of 150 IU IFN lozenges TID for 12 weeks in subjects with primary
Sjogren's syndrome improved salivary output and decreased complaints of
xerostomia without causing significant adverse medical events.



36. Lung function in primary Sjogren's syndrome: a cross sectional and longitudinal study.

Kelly C, Gardiner P, Pal B, Griffiths I
Department of Rheumatology, Royal Victoria Infirmary, Newcastle upon Tyne.
Thorax 1991 Mar;46(3):180-3

Clinical and radiological assessment of 100 patients (97 female) with primary Sjogren's syndrome was performed within six months of diagnosis in conjunction with spirometry and measurement of transfer factor for carbon monoxide (TLCO). This was repeated in an unselected subgroup of 30 patients after a mean interval of four years. On initial assessment, 43 patients had symptoms of lung disease and 10 had related physical signs; the chest radiograph was abnormal in five. There was a significant reduction (more than 2 standardised residuals) in forced expiratory volume in one second (FEV1), vital capacity (VC), and TLCO in 14, 12, and 10 patients, 24 patients overall having a significant reduction in one or more of these measures. There was a strong relation between reduction in lung function and both pulmonary symptoms and a lip biopsy specimen positive for Sjogren's syndrome. Lung function at the initial assessment in the 30 patients who were restudied was almost identical to that of the group as a whole. Seventeen now had symptoms and nine had related physical signs. The chest radiograph was abnormal in four patients. More patients had a significant reduction in FEV1, VC, and TLCO. Lung disease is sometimes an early feature of primary Sjogren's syndrome and may progress over a relatively short period.



37. Oral administration of interferon-alpha induces a transient decline in oral mucosal immunoglobulins and an increase in interleukin-5.

Naylor PH, Naylor CW, Hendrix S, Leveque FG Department of Internal Medicine, Wayne State University School of Medicine, Harper Hospital, Detroit, MI 48201, USA. pnaylor@intmed.wayne.edu
J Interferon Cytokine Res 1999 Aug;19(8):953-9

Although administration of interferon-alpha (IFN-alpha) via the oral-mucosal route has shown efficacy in a variety of human and animal diseases, the mechanism of action of orally administered IFN is not clearly understood. To assess the possibility that IFN-alpha given via a lozenge alters the local mucosal immune system, immunoglobulins (Ig) and cytokines were measured in salivary secretions. Volunteers were given low doses of IFN-alpha and saliva was collected over a 24-h period. IgA and precursor IgM were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Salivary concentrations of interleukin-5 (IL-5), the T helper cytokine primarily responsible for the switch from IgM to IgA, were also determined. After oral administration of IFN-alpha, there was an initial decline in IgM and IgA followed by a return to baseline levels by 8-24 h. This change in Ig concentration was associated with a gradual increase in IL-5, consistent with the return of Ig to baseline as a result of modulation by Ig-mediating cytokines.



38. Dietary polyunsaturated fatty acids and inflammatory mediator production.

James MJ, Gibson RA, Cleland LG
Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia, and the
Department of Pediatrics and Child Health, Flinders Medical Center, Bedford
Park, Australia.
Am J Clin Nutr 2000 Jan;71(1 Suppl):343S-8S

Many antiinflammatory pharmaceutical products inhibit the production of certain eicosanoids and cytokines and it is here that possibilities exist for therapies that incorporate n-3 and n-9 dietary fatty acids. The proinflammatory eicosanoids prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) are derived from the n-6 fatty acid arachidonic acid (AA), which is maintained at high cellular concentrations by the high n-6 and low n-3 polyunsaturated fatty acid content of the modern Western diet. Flaxseed oil contains the 18-carbon n-3 fatty acid alpha-linolenic acid, which can be converted after ingestion to the 20-carbon n-3 fatty acid eicosapentaenoic acid (EPA). Fish oils contain both 20- and 22-carbon n-3 fatty acids, EPA and docosahexaenoic acid. EPA can act as a competitive inhibitor of AA conversion to PGE(2) and LTB(4), and decreased synthesis of one or both of these eicosanoids has been observed after inclusion of flaxseed oil or fish oil in the diet. Analogous to the effect of n-3 fatty acids, inclusion of the 20-carbon n-9 fatty acid eicosatrienoic acid in the diet also results in decreased synthesis of LTB(4). Regarding the proinflammatory ctyokines, tumor necrosis factor alpha and interleukin 1beta, studies of healthy volunteers and rheumatoid arthritis patients have shown < or = 90% inhibition of cytokine production after dietary supplementation with fish oil. Use of flaxseed oil in domestic food preparation also reduced production of these cytokines. Novel antiinflammatory therapies can be developed that take advantage of positive interactions between the dietary fats and existing or newly developed pharmaceutical products.



39. LongoVital in the treatment of Sjogren's syndrome.

Pedersen A, Gerner N, Palmvang I, Hoier-Madsen M
Department of Oral and Maxillofacial Surgery, Bispebjerg Hospital, Copenhagen,
Denmark. pedersen-wind@email.dk
Clin Exp Rheumatol 1999 Sep-Oct;17(5):533-8

OBJECTIVE: Sjogren's syndrome (SS) is a chronic autoimmune disease complex of unknown aetiology. There is no curative treatment for SS, however, in recent years the influence of nutrients on autoimmune processes has attracted increasing attention. LongoVital (LV) (DK. Reg. No. 5178/75) is an herbal-based tablet enriched with the recommended daily doses of vitamins. The purpose of the present study was to investigate whether 4 months' daily intake of LV as compared to placebo would affect clinical and laboratory disease parameters in patients with SS. METHODS: Forty patients with SS participated in a placebo-controlled, double-blind, randomised, clinical, 8 month cross-over study. Group A (n = 22) received LV during the first 4 months and Group B (n = 18) LV during the last 4 months. RESULTS: The unstimulated salivary flow rate increased during the LV period in Group A (p < 0.001). The stimulated salivary flow rate increased in Group B during the LV period (p < 0.05), and in Group A during the subsequent 4 months on placebo (p < 0.05). The rose bengal score decreased in Group B during (p < 0.01) and in Group A after the LV intake (p < 0.05). During the last 4 months of the study both groups showed an increase in serum levels of alpha-amylase (total: Group A, p < 0.01; Group B, p < 0.05; pancreatic fraction: Group A, p < 0.0001; Group B, p < 0.01) and in serum levels of IgM (Group A and B: p < 0.001), while levels of circulating immune complexes decreased (Group A, p < 0.05; Group B, p < 0.001). CONCLUSION: It is concluded that LV has a beneficial and prolonged effect on some of the clinical and immunoinflammatory disease markers in SS.



40. Stress-induced immunomodulation: implications for infectious diseases?

Glaser R, Rabin B, Chesney M, Cohen S, Natelson B
Department of Medical Microbiology and Immunology, Ohio State University Medical
Center, Columbus 43210-1239, USA. glaser.1@postbox.acs.ohio-state.edu
JAMA 1999 Jun 23-30;281(24):2268-70



41. Stress and immunity in humans: a meta-analytic review.

Herbert TB, Cohen S
Brain, Behavior and Immunity Center, University of Pittsburgh School of
Medicine, Pennsylvania.
Psychosom Med 1993 Jul-Aug;55(4):364-79

This article presents a meta-analysis of the literature on stress and immunity in humans. The primary analyses include all relevant studies irrespective of the measure or manipulation of stress. The results of these analyses show substantial evidence for a relation between stress and decreases in functional immune measures (proliferative response to mitogens and natural killer cell activity). Stress is also related to numbers and percent of circulating white blood cells, immunoglobulin levels, and antibody titers to herpesviruses. Subsequent analyses suggest that objective stressful events are related to larger immune changes than subjective self-reports of stress, that immune response varies with stressor duration, and that interpersonal events are related to different immune outcomes than nonsocial events. We discuss the way neuroendocrine mechanisms and health practices might explain immune alteration following stress, and outline issues that need to be investigated in this area.



42. Immunosenescence: potential causes and strategies for reversal.

Aspinall R, Andrew D
Department of Immunology, Imperial College of Medicine at Chelsea & Westminster
Hospital, London, UK.
Biochem Soc Trans 2000 Feb;28(2):250-4

Age-related deterioration in immune function has been recognized in many species. In humans the clinical manifestation of such immune dysfunction is age-related increases in the susceptibility to certain infections and in the incidence of some autoimmune disease and certain cancers. Laboratory investigations reveal age-related changes in the peripheral T cell pool, in the predominant phenotype, cytokine production profiles, signalling function and in replicative ability following stimulus with antigen, mitogens or anti-CD3 antibody. These changes in the properties of peripheral T cells are thought to be causally linked to an age-associated involution in the thymus. Our analysis reveals that thymic involution is due to a change in the thymic microenvironment linked to a reduction in the level of available interleukin 7. Treatment with interleukin 7 leads to a reversal of thymic atrophy with increased thymopoiesis. This provides the potential to reverse the immune dysfunction seen in the peripheral T cell pool by replacing old cells with new output generated in the thymus. Problems to overcome in order for such an experimental therapy to be successful require careful analysis in order to provide an optimal strategy to ensure that new T cell emigrants from the thymus have a broad range of specificities and are able to enter the peripheral T cell pool.



43. Chinese herbs: a clinical review of Astragalus, Ligusticum, and Schizandrae.

Sinclair S
Green Valley Health, 1305 Pennsylvania Ave, Hagerstown, MD 21742, USA.
Altern Med Rev 1998 Oct;3(5):338-44

Although Astragalus, Ligusticum and Schizandrae have a long history of medicinal use within the traditional Chinese system, only recently has the West begun to understand their pharmacological possibilities and clinical applications. Astragalus has demonstrated a wide range of immunopotentiating effects and has proven efficacious as an adjunct cancer therapy. Ligusticum, and its active components, have been investigated for enhancement of the immune system, treatment of ischemic disorders, and as an anti-inflammatory. Clinically, the hepato-protective and antioxidant actions of Schizandrae have proven beneficial in the treatment of chronic viral hepatitis.



44. Immunomodulating activity of Chinese medicinal herbs and Oldenlandia diffusa in particular.

Yoshida Y, Wang MQ, Liu JN, Shan BE, Yamashita U
Department of Immunology and Parasitology, Hiroshima University School of
Medicine, Japan.
Int J Immunopharmacol 1997 Jul;19(7):359-70

The effect of eight different Chinese medicinal herbs (CMHs) on lymphocytes was studied in vitro using murine spleen cells. Among the studied eight CMHs, Astragalus membranaceus and Oldenlandia diffusa markedly stimulated murine spleen cells to proliferate. The responder cells for CMHs were B cells, because the response was depleted by the treatment of spleen cells with anti-immunoglobulin (i.g.) antibody and complement and after purification by nylon wool column. This response was not due to contamination by lipopolysaccharide (LPS), because CMHs could stimulate C3H/HeJ spleen cells which are low responders to LPS. CMHs enhanced the production of Ig. CMHs also enhanced the induction of allo-antigen specific cytotoxic T lymphocytes. However, CMHs had no effect on natural killer cells. Furthermore, CMHs stimulated macrophages to produce interleukin-6 and tumor necrosis factor. The electroelution of the proteins from SDS-PAGE gel showed that the active components of Oldenlandia diffusa had an apparent molecular weight of 90-200 kD and were sensitive to pronase E and NaIO4 treatment, suggesting glycoproteins in nature. These results suggest that CMHs have immunomodulating activity in vitro and this activity could be used clinically for the modulation of immune responses.



45. The prostaglandin analogs, misoprostol and SC-46275, potently inhibit cytokine release from activated human monocytes.

Widomski D, Fretland DJ, Gasiecki AF, Collins PW
Searle Research and Development Skokie, Illinois 60077, USA.
Immunopharmacol Immunotoxicol 1997 May;19(2):165-74

Inflammatory mediator release is one of the body's responses to tissue injury and inflammation. These mediators, such as interleukin-1 beta (I1-1 beta), tumor necrosis factor (TNF-alpha), and products of arachidonic acid metabolism, are themselves proinflammatory. Purified human monocytes stimulated in vitro with E. coli-derived lipopolysaccharide (LPS) will release these key cytokines along with various other eicosanoid mediators. Monocytes incubated with LPS and the prostaglandin E-1 analog, misoprostol, released significantly lower levels of cytokines compared to monocytes incubated with LPS alone. Eicosanoid release was also affected by misoprostol. SC-46275, a more potent mucosal protective PGE1 analog, also altered the release of cytokines and eicosanoids from human monocytes. However SC-46275 inhibited I1-1 beta release with an IC50 value of 9 microM compared to 75 microM for misoprostol. SC-46275 and misoprostol both inhibited TNF-alpha release. These data suggest there is a potential immunomodulatory role for prostaglandin analogs in the therapeutic treatment of inflammatory diseases such as ulcerative colitis, Crohn's disease, and autoimmune inflammatory diseases of the central nervous system.



46. Research on coenzyme Q10 in clinical medicine and in immunomodulation.

Folkers K, Wolaniuk A
Drugs Exp Clin Res 1985;11(8):539-45

Coenzyme Q10 (CoQ10) is a redox component in the respiratory chain. CoQ10 is necessary for human life to exist; and a deficiency can be contributory to ill health and disease. A deficiency of CoQ10 in myocardial disease has been found and controlled therapeutic trials have established CoQ10 as a major advance in the therapy of resistant myocardial failure. The cardiotoxicity of adriamycin, used in treatment modalities of cancer, is significantly reduced by CoQ10, apparently because the side-effects of adriamycin include inhibition of mitochondrial CoQ10 enzymes. Models of the immune system including phagocytic rate, circulating antibody level, neoplasia, viral and parasitic infections were used to demonstrate that CoQ10 is an immunomodulating agent. It was concluded that CoQ10, at the mitochondrial level, is essential for the optimal function of the immune system.



47. Anti-Ro in Sjogren's syndrome and systemic lupus erythematosus.

Harley JB, Scofield RH, Reichlin M
University of Oklahoma Health Sciences Center, Oklahoma City.
Rheum Dis Clin North Am 1992 May;18(2):337-58

Anti-Ro autoantibodies are frequently found in the sera of patients with Sjogren's syndrome, systemic lupus erythematosus, and subacute cutaneous lupus erythematosus as well as in the sera of mothers of infants with the neonatal lupus syndrome. Close associations have been found between anti-Ro and a number of clinical manifestations, particularly including hematologic cytopenias, heart block, and photosensitive skin rashes. Serologic and genetic associations have been found between anti-Ro and anti-La, rheumatoid factor, hypergammaglobulinemia, the histocompatibility alleles DQ1 and DQ2, and alleles of the T-cell receptor beta chain gene. The origin of anti-Ro and other autoantigens is thought to relate to the etiology of Sjogren's syndrome and systemic lupus erythematosus and remains the most fundamental unanswered question preventing a comprehensive understanding of these diseases.



48. Antinuclear antibodies in Sjogren's syndrome.

Chan EK, Andrade LE
W. M. Keck Autoimmune Disease Center, Department of Molecular and Experimental
Medicine, Scripps Research Institute, La Jolla, California.
Rheum Dis Clin North Am 1992 Aug;18(3):551-70

The definition and characterization of the reactivity of ANA in patients with SS are greatly improved with the current advances in cellular and molecular biology. Based on the characteristic autoantibody profiles in different systemic rheumatic diseases and the nature of the defined autoantigens, it has been proposed that the polyclonal autoimmune response is induced and maintained through an antigen-driven mechanism. The autoantigens are presented in the cell as components of large particles or structures composed of protein-protein or RNA-protein complexes; however, the role of these autoantibodies in the etiology and immunopathogenesis of SS remains to be determined.



49. The regulation of prostaglandin biosynthesis by the manipulation of essential fatty acid metabolism.

Horrobin DF
Rev Pure Appl Pharmacol Sci 1983 Oct-Dec;4(4):339-83

Two of the most widely used groups of drugs in medical practice are the non-steroidal anti-inflammatory agents and the steroids. Both act by modulating the conversion of essential fatty acids to prostaglandins, leukotrienes and related substances. The actions of these drugs are therefore likely to be modified by variations in the levels of substrates, notably arachidonic acid and dihomogammalinolenic acid, available for metabolism by lipoxygenase and cyclo-oxygenase enzymes. Yet most doctors who use the drugs and many scientists who carry out research on them seem unaware of the factors which determine the concentrations of the substrate essential fatty acids. This paper reviews in detail the metabolism of essential fatty acids and the interactions between nutrient intake and subsequent metabolism which determine the concentrations of the individual fatty acids. It is concluded that the efficacy of drug therapy as far as the steroids and the non-steroidal anti-inflammatory drugs are concerned could be substantially enhanced by greater knowledge of the factors which determine the availability of substrates to the key enzymes.



50. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group.

Sall K, Stevenson OD, Mundorf TK, Reis BL
Sall Eye Surgery Center, Bellflower, California, USA.
Ophthalmology 2000 Apr;107(4):631-9
Published erratum appears in Ophthalmology 2000 Jul;107(7):1220

OBJECTIVE: To compare the efficacy and safety of cyclosporin A ([CsA] 0.05% and
0.1% ophthalmic emulsions) to vehicle in patients with moderate to severe dry
eye disease. DESIGN: Multicenter, randomized, double-masked, parallel-group,
6-month, vehicle-controlled. PARTICIPANTS: A total of 877 patients with defined
moderate to severe dry eye disease (292 to 293 in each treatment group).
METHODS: Two identical clinical trials; patients were treated twice daily with
either CsA, 0.05% or 0.1%, or vehicle. The results of these two trials were
combined for analysis. MAIN OUTCOME MEASURES: Efficacy: corneal and
interpalpebral dye staining, Schirmer tear test (with and without anesthesia),
tear break-up time, Ocular Surface Disease Index (OSDI), facial expression,
patient subjective rating scale, symptoms of dry eye, investigator's evaluation
of global response to treatment, treatment success, and daily use of artificial
tears. Safety: occurrence of adverse events, best-corrected visual acuity,
intraocular pressure, biomicroscopy, and blood trough CsA concentrations.

RESULTS: Treatment with CsA, 0.05% or 0.1%, gave significantly (P < or = 0.05)
greater improvements than vehicle in two objective signs of dry eye disease
(corneal staining and categorized Schirmer values). CsA 0.05% treatment also
gave significantly greater improvements (P < 0.05) in three subjective measures
of dry eye disease (blurred vision, need for concomitant artificial tears, and
the physician's evaluation of global response to treatment). There was no
dose-response effect. Both CsA treatments exhibited an excellent safety profile,
and there were no significant topical or systemic adverse safety findings.
CONCLUSIONS: The novel ophthalmic formulations CsA 0.05% and 0.1% were safe and effective in the treatment of moderate to severe dry eye disease yielding
improvements in both objective and subjective measures. Topical CsA represents a
new pharmacologically based treatment for dry eye disease that may provide
significant patient benefits.



51. Autonomic cardiovascular neuropathy in Sjogren's syndrome. A controlled study.

Andonopoulos AP, Christodoulou J, Ballas C, Bounas A, Alexopoulos D
Department of Medicine, Patras University School of Medicine, Greece.
J Rheumatol 1998 Dec;25(12):2385-8

OBJECTIVE: To test patients with primary Sjogren's syndrome (SS) for evidence of autonomic neuropathy. METHODS: Thirty-two patients with primary SS and 22 age and sex matched healthy individuals were asked specific questions about symptoms suggestive of autonomic neuropathy, and were subjected to a battery of 5 cardiovascular tests: response of blood pressure to sustained hand grip, Valsalva maneuver, heart rate response to deep breathing, and heart rate and blood pressure response to standing up. The chi-squared test with Yates' correction and 95% confidence intervals were used for statistical analysis of the results. RESULTS: Sixteen patients (50%) had symptoms of autonomic neuropathy when specifically asked versus none of the controls (p < 0.0005). The frequency of abnormal responses to the tests was 68.8% in patients and 12.7% in controls (p < 0.0001). Severe autonomic cardiovascular neuropathy was found in 87.5% of the patients but in none of the healthy individuals (p < 0.0001). CONCLUSION: Our results suggest that autonomic neuropathy is a feature of a significant portion of the SS population, and such patients should have appropriate evaluation. Similarly, patients with unexplained autonomic neuropathy should be investigated for evidence of SS.



52. Sjogren's syndrome: Treatment with Cyclosporin.

Klin Monatsbl Augenheilkd (Germany, West) 1987;190(4):290-2.



53. Thymosin administration in autoimmune disorders.

Lavastida MT, Goldstein AL, Daniels JC
Thymus 1981 Feb;2(4-5):287-95

Five patients with autoimmune disorders were given thymosin, fraction 5, parenterally for periods ranging from 2 to 35 mth. Four patients had systemic lupus erythematosus and the 5th had rheumatoid arthritis and Sjogren's syndrome. Treatment with thymosin was based on the hypothesis of a T-suppressor defect in these autoimmune disorders. Circulating T lymphocytes increased and remained above pretreatment levels in all patients. Assays for cytotoxicity, using mouse thymocytes and patients' sera, were positive initially and declined during the course of the treatment. In all patients, serum cytotoxicity levels were reduced to zero. There has been clinical improvement in 3 patients, and in 1, the disease has become stable. The evaluation of the 5th patient has been inconclusive. No ill effects related to the administration of thymosin were observed.



54. Immune complex glomerulonephritis in sicca syndrome.

Moutsopoulos HM, Balow JE, Lawley TJ, Stahl NI, Antonovych TT, Chused TM
Am J Med 1978 Jun;64(6):955-60

In three patients with the sicca syndrome (Sjogren's syndrome), who were followed for one to seven years, glomerulonephritis developed. None of these patients fulfilled the diagnostic criteria for systemic lupus erythematosus. All of these patients had circulating immune complexes as detected by the Clq binding assay. Glomerular histology by light and electron microscopy revealed changes compatible with membranoproliferative glomerulonephritis in two of the patients and membranous glomerulonephritis in the third. All patients showed rapid improvement in renal function following moderate doses of corticosteroids. In addition, the treatment decreased the level of circulating immune complexes in two patients who were followed for a sufficient period of time.



55. Sjogren's syndrome with immune-complex tubulointerstitial renal disease.

Winer RL, Cohen AH, Sawhney AS, Gorman JT
Clin Immunol Immunopathol 1977 Nov;8(3):494-503



56. Modification of a transplantable colon tumor and immune responses in mice fed different sources of protein, fat and carbohydrate.

Nutter RL, Gridley DS, Kettering JD, Andres ML, Aprecio RM, Slater JM
Cancer Lett 1983 Feb;18(1):49-62

The effects of different sources of dietary protein, fat and carbohydrate on tumor development and on tests relating to cell-mediated immunity were investigated in male BALB/c mice after subcutaneous injection of 8 X 10(4) 1,2-dimethylhydrazine (DMH)-induced colon tumor (no. 51) cells. Results indicated that mice fed the milk protein source (especially at the low protein level) had smaller tumors, a higher spleen cell proliferative response to stimulation by phytohemagglutinin (PHA), and greater cytotoxic T-cell activity against the tumor cells than those fed the comparable diets containing protein from the other sources. Peripheral blood lymphocytes only from the milk-fed mice, regardless of tumor presence, exhibited a relatively low response to PHA stimulation, thereby suggesting a dietary effect on the migration pattern of PHA-responsive lymphocytes. The level of protein significantly affected both T-cell and natural killer cell cytotoxicity. The tumor-bearing mice fed the diet containing sucrose (table sugar) had a significantly lower spleen cell response to PHA stimulation than those fed the comparable diet containing dextrin. The level or source of fat did not significantly affect any of the parameters tested in this system.



57. Impaired function of immune reactivity to Listeria monocytogenes in diet-fed mice.

Kos WL, Kos KA, Kaplan AM
Infect Immun 1984 Mar;43(3):1094-6

Mice fed a diet high in cholesterol, lard, and sucrose were shown to exhibit an impairment of specific immunity to Listeria monocytogenes. Whereas titers of L. monocytogenes in livers of normal mice decreased rapidly after 6 days of infection, L. monocytogenes persisted in livers of diet-fed mice. Adoptive transfer experiments indicated that L. monocytogenes-immune spleen cells are generated in diet-fed mice. However, the function of immune spleen cells from donors of either nutritional status was impaired in diet-fed recipients. The results indicate that the site(s) of impairment of specific immunity to L. monocytogenes in diet-fed mice occurs at a stage beyond the generation of immune T-cells.



58. Influence of oral zinc supplementation on the lymphocyte response to mitogens of normal subjects.

Duchateau J, Delespesse G, Vereecke P
Am J Clin Nutr 1981 Jan;34(1):88-93

Oral zinc sulfate was given for 1 month to 83 normal subjects distributed in four groups according to age (20 to 40; 40 to 60), sex, and oral contraception. Their in vitro lymphocyte response to phytohemagglutinin and Concanavalin A, and their serum zinc and copper levels were measured before and after treatment. They were compared in 20 untreated subjects. Zinc treatment significantly increased the lymphocyte response to phytohemagglutinin and Concanavalin A. In the group of women aged 40 to 60, this resulted in a normalisation of the response to Concanavalin A. The response to zinc was related to the starting value of lymphocyte stimulation obtained by phytohemagglutinin, i.e., in low responders this was enhanced whereas in high responders it tended to be reduced. Treatment increased serum zinc and had no effect on serum copper. There was no correlation between serum zinc or copper and the lymphocyte response. The beneficial effect of zinc supplementation on the lymphocyte response does not result from a correction of latent zinc deficiency.



59. Beneficial effects of oral zinc supplementation on the immune response of old people.

Duchateau J, Delepesse G, Vrijens R, Collet H
Am J Med 1981 May;70(5):1001-4

Zinc is known to have beneficial effects on the immune response. In an attempt to modify age-associated immune dysfunction, supplemental zinc was administered to 15 subjects over 70 years of age (220 mg zinc sulfate twice daily for a month). As compared to 15 controls, matched for age and sex, there was a significant improvement in the following immune parameters in the treated group: (1) number of circulating T lymphocytes; (2) delayed cutaneous hypersensitivity reactions to purified protein derivative, Candidin and streptokinase-streptodornase; (3) immunoglobulin G (IgG) antibody response to tetanus vaccine. Zinc treatment had no influence on the number of total circulating leukocytes or lymphocytes, or on the in vitro lymphocyte response to three mitogens: phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM). The data suggest that the addition of zinc to the diet of old persons could be an effective and simple way to improve their immune function.


60. Interrelationships between zinc and immune function.

Fraker PJ, Gershwin ME, Good RA, Prasad A
Fed Proc 1986 Apr;45(5):1474-9

Zinc deficiency is a common nutritional problem observed both in human and in animal populations that has profound effects on host defense mechanisms. Using the young adult mouse as a model, it has been demonstrated that a moderate period of suboptimal zinc causes thymic atrophy, lymphopenia, and alterations in the proportions of the various subsets of lymphocytes and mononuclear phagocytes. As a result, antibody-mediated responses to both T cell-dependent and T cell independent antigens are significantly reduced. Cytolytic T cell responses, natural killer (NK) cell activity, and delayed-type hypersensitivity (DTH) reactions are also depressed. Suboptimal zinc during in utero development of mice causes persistent states of immunodeficiency in the offspring that can even be transferred to subsequent generations. In regard to human immunological consequences of zinc deficiency, patients with the genetic disorder of zinc absorption, acrodermatitis enteropathica, also exhibit atrophic thymuses, lymphopenia, anergic DTH responses, and reduced NK cell activity. Patients suffering from sickle cell anemia or uremia with associated deficiencies in zinc exhibit similar immune deficiencies. An additional outcome of these studies has been shown to be an essential cofactor for thymulin, one of the thymic hormones. Furthermore, addition of zinc salts to culture can polyclonally activate lymphocytes as well as augment responses to mitogens in adjuvant-like manner.


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