Rheumatoid Arthritis Abstracts 6

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The effect of ginger supplementation on some immunity and inflammation intermediate genes expression in patients with active Rheumatoid Arthritis.
            (Aryaeian et al., 2019)  Download
OBJECTIVE:  Rheumatoid Arthritis (RA) is an autoimmune disease. The aim of this study was to investigate the effect of ginger supplementation on the expression of some immunity and inflammation intermediate genes in patients who suffer from RA. METHODS:  In this randomized double-blind placebo-controlled clinical trial, seventy active RA patients were allocated randomly into two groups who either received 1500 mg ginger powder or placebo daily for 12 weeks. Disease activity score and gene expression of NF-κB, PPAR-γ, FoxP3, T-bet, GATA-3, and RORγt as immunity and inflammation intermediate factors were measured using quantitative real-time PCR before and after the intervention. RESULTS:  After the intervention, FoxP3 genes expression increased significantly within ginger group and between the two groups (P-value = 0.02). Besides, T-bet and RORγt genes expression decreased significantly between the two groups (P-value < 0.05). In ginger group, PPAR-γ genes expression increased significantly (P-value = 0.047) but the difference between the two groups wasn't statistically significant (P-value = 0.12). The reduction in disease activity score was statistically significant within ginger group and between the two groups after the intervention. CONCLUSION:  It seems that ginger can improve RA by decreasing disease manifestations via increasing FoxP3 genes expression and by decreasing RORγt and T-bet genes expression.

Intravenous iron in rheumatoid arthritis
            (Clark, 1949)  Download
Early this year I gave several patients with long-standing active rheumatoid artritis a course of intravenous iron. The disease became less active as judged by changes in the E.S.R. All the patients, including these 3, said that they felt much better and had less pain in the joints while treatment with intravenous iron was being continued and for about a fortnight afterwards.


 

Pomegranate extract alleviates disease activity and some blood biomarkers of inflammation and oxidative stress in Rheumatoid Arthritis patients.
            (Ghavipour et al., 2017)  Download
BACKGROUND/OBJECTIVES:  Since the main characteristics of Rheumatoid Arthritis (RA) are joint dysfunction caused by inflammation and serious pain, anti-inflammatory agents may alleviate the clinical symptoms in RA. Pomegranate juice is rich in polyphenolic compounds that possess antioxidant and anti-inflammatory activities. This study aimed to determine the beneficial effects of pomegranate extract (POMx) in RA patients. SUBJECTS/METHODS:  A total of 55 RA patients were enrolled and randomly allocated to an intervention group (n=30) or a control group (n=25). The intervention group received 2 capsules of 250 mg POMx and the control group 2 capsules of 250 mg cellulose per day for 8 weeks. At the beginning of the study and after 8 weeks, Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS) 28 were completed and serum concentrations of C-reactive protein (CRP), matrix metalloproteinases 3 (MMP3), malondialdehyde (MDA), glutathione peroxidase (GPx) and erythrocyte sedimentation rate (ESR) were analyzed using standard methods and compared between the two groups. RESULTS:  Compared with the placebo group, POMx supplement significantly reduced the score of DAS28 (P<0.001) which could be related to the decrease in swollen (P<0.001) and tender joints (P=0.001) count, pain intensity (P=0.003) and ESR levels (P= 0.03). POMx consumption also decreased HAQ score (P=0.007) and morning stiffness (P=0.04) and increased GPx concentrations (P<0.001). There were no differences in the change in mean MMP3, CRP and MDA levels between two groups. CONCLUSIONS:  POMx alleviates disease activity and improves some blood biomarkers of inflammation and oxidative stress in RA patients.

Adenosine triphosphate; trial in the treatment of rheumatoid arthritis.
            (Godfrey, 1951)  Download
Twelve patients with severe rheumatoid arthritis were treated with adenosine triphosphate for varying periods, from five to 11 days. Adenosine triphosphate was administered intramuscularly, 20 mg. dissolved in 2 cc. of isotonic sodium chloride solution every six hours, making a total of 80 mg. every 24 hours. No local or systemic reactions were encountered. Of the 12 patients treated, 11 failed to show any symptomatic response. These results do not confirm the report by Carlström and Lövgren.

Cortisone therapy: a challenge to academic medicine in 1949-1952.
            (Hetenyi and Karsh, 1997)  Download
On September 21, 1948, at the Mayo Clinic in Rochester, Minnesota, Charles Slocumb and Philip Hench injected 50 mg of a "new" steroid— Compound E, first isolated by their biochemist colleague Edward Kendall from adrenal glands 12 years ago—into a young woman suffering from acute rheumatoid arthritis. The injection was repeated in the afternoon and twice again on the 22nd. By the 23rd the patient conspicuously im- proved and within a week the remission was near complete. The story of Compound E illustrates the evolution of the relationship between the pharmaceutical industry and academic medicine. Collaboration between industry and academic medicine continues to be the basis for the production and evaluation of most new drugs today.

An historical review of rheumatoid arthritis treatment: 1948 to 1952.
            (Karsh and Hetenyi, 1997) Download
OBJECTIVES:  The early responses by practicing physicians to the discovery of the effect of cortisone (compound E) and adrenocorticotropic hormone (ACTH) on acute rheumatoid arthritis in 1948 and their reactions to the drugs' scarcity have been reviewed. METHODS:  Review of the relevant literature in American, British, and European medical journals and some newspapers. RESULTS:  Whereas the effect of the compound E and ACTH was stunning, their scarcity made them unavailable to most physicians. Nevertheless, practicing physicians took a lively interest in the new therapy, as witnessed by the large number of letters with comments and questions to professional journals from all over the world. As expected, most of these were about attempts to find a substitute for cortisone or a way to release it endogenously to a sufficient degree. A few alternative therapies were suggested too, some quite unorthodox. A lively interest was shown by the general public. CONCLUSIONS:  No alternative therapy recommended to treat acute rheumatoid arthritis in lieu of cortisone proved to be effective. The era of scarcity was ended by the discovery of a more efficient method to manufacture cortisone.

Effect of combined injections of deoxycortone acetate and ascorbic acid on rheumatoid arthritis.
            (Lewin and Wassen, 1949)  Download
The following is a preliminary report of an investigation on the effect of combined injections of desoxycorticosterone acetate and ascorbic acid on rheumatoid arthritis. The series comprises 9 patients (6 women and 3 men). the patients were treated with an intramuscular injection of 5 mg Deoxycortone (desoxycorticosterone) acetate in 1 ml. of oleum arachis, immediately followed by an intravenous injection of 1 g. ascorbic acid (10 ml. of 10% solution). Five minutes after the injections the articular pain began to diminish and the articular mobility began to increase. Fifteen to thirty minutes later, the pain had practically disappeared and the mobility improved as much as the anatomical changes in the joints and muscular atrophy would allow. All the patients reacted in a similar way. In some cases the improvement was astounding.

Observations on the effect of combined injections of desoxycorticosterone acetate and ascorbic acid on rheumatoid arthritis.
            (Lewin and Wassen, 1950)  Download
In a number of patients it was shown that combined injections of desoxycorticosterone acetate intramuscularly immediately followed by intra- venous injection of ascorbic acid within 30 minuta were able to produce alleviation of articular pains and improvement of the mobility.  The effect of the injections lasted between half an hour and six hours. In individual cases 24 hours and in a few other caaes with short histories for the whole observation time (2-3 weeks) after ody one injection. The dosage has generally been 5 mg desoxycorticosterone acetate intramuscularly and 1 g ascorbic acid intravenously.

Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of uncaria tomentosa for the treatment of rheumatoid arthritis.
            (Mur et al., 2002)  Download
OBJECTIVE:  To evaluate safety and clinical efficacy of a plant extract from the pentacyclic chemotype of Uncaria tomentosa (UT) in patients with active rheumatoid arthritis (RA). METHODS:  Forty patients undergoing sulfasalazine or hydroxychloroquine treatment were enrolled in a randomized 52 week, 2 phase study. During the first phase (24 weeks, double blind, placebo controlled), patients were treated with UT extract or placebo. In the second phase (28 weeks) all patients received the plant extract. RESULTS:  Twenty-four weeks of treatment with the UT extract resulted in a reduction of the number of painful joints compared to placebo (by 53.2% vs 24.1%; p = 0.044). Patients receiving the UT extract only during the second phase experienced a reduction in the number of painful (p = 0.003) and swollen joints (p = 0.007) and the Ritchie Index (p = 0.004) compared to the values after 24 weeks of placebo. Only minor side effects were observed. CONCLUSION:  This small preliminary study demonstrates relative safety and modest benefit to the tender joint count of a highly purified extract from the pentacyclic chemotype of UT in patients with active RA taking sulfasalazine or hydroxychloroquine.

Effects of coenzyme Q10 supplementation on matrix metalloproteinases and DAS-28 in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled clinical trial.
            (Nachvak et al., 2019)  Download
OBJECTIVES:  This study aimed to assess the effect of CoQ10 supplementation on serum matrix metalloproteinases (MMPs) and clinical parameters in rheumatoid arthritis (RA) patients. METHOD:  In this randomized, double-blind, placebo-controlled trial, 54 RA patients who fulfilled the eligibility criteria (18-56 years, diagnosed at least 6 months ago, with DAS-28 > 3.2) were randomly assigned into two groups to receive 100 mg/day CoQ10 (n = 27) or placebo (n = 27) for 2 months. Serum MMP-1 and MMP-3 levels and clinical status using disease activity score in 28 joints (DAS-28) were assessed before and after supplementation. Data were analyzed using χ2, independent sample t test, paired t test, Wilcoxon, Mann-Whitney, and analysis of covariance. RESULTS:  A significant reduction was observed in both CoQ10 and placebo groups in the medians of serum MMP-1 (0.2 to 0.16, P < 0.001), (0.18 to 0.15, P = 0.001); swollen joint count (2 to 0, P < 0.001), (2 to 0, P = 0.009); and the means of DAS-28 (5.01 ± 1.21 to 2.34 ± 0.68, P < 0.001), (4.88 ± 0.96 to 4.04 ± 1.36, P = 0.009) respectively. Serum MMP-3 level increased significantly in placebo group (2.26 to 2.57, P = 0.020), and the MMP-3 changes between groups were significant (P = 0.027). Furthermore, significant reductions were only observed in ESR, pain score, and tender joint count in CoQ10 group compared with baseline (P = 0.001, P < 0.001, and P < 0.001, respectively). Significant differences were observed between two groups in DAS-28, pain score, and swollen and tender joint count after the intervention (P < 0.001, P < 0.001, and P = 0.012 and P < 0.001, respectively). CONCLUSIONS:  It seems that CoQ10 may provide a new complementary approach for RA patients.Key Points• CoQ10 supplementation in RA patients attenuated serum MMP-3 level.• CoQ10 supplementation in RA patients improved clinical outcomes and ameliorated disease severity.• CoQ10 may provide a new complementary approach for patients with RA.

The Treatment of Rheumatic Diseases by Lemon Juice: with Illustrative Cases from Hospital Practice
            (Rees, 1849) Download
            (1849) Book Review Download
In a recent number of the Medical Gazette I directed attention to the beneficial effects produced by the exhibition of lemon juice in rheumatic diseases. Since the publication of that notice the remedy has been used by several practitioners with very marked success; so much so, indeed, that I am inclined to believe we may now consider it quite as efficacious, if not more so, than any of the preparations of colchicum, which have for so many years enlisted the confidence of the profession in acute rheumatic affections, Lemon juice certainly …

Effects of Vitamin K on Matrix Metalloproteinase-3 and Rheumatoid Factor in Women with Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Trial.
            (Shishavan et al., 2016)  Download
OBJECTIVES:  Rheumatoid arthritis (RA) is an autoimmune disease characterized by an increase in some autoantibodies and proteolytic enzymes, leading to joint destruction. Although recent investigations have considered vitamin K as an anti-inflammatory nutrient with an important role in bone metabolism, there is currently limited information on its efficacy in RA. We aimed to examine the effects of vitamin K1 (phylloquinone) on the biomarker of joint destruction and autoantibody in patients with RA. MATERIALS AND METHODS:  This was a randomized clinical trial in which 64 women with RA who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Vitamin K1 or placebo was administered to the participants for 8 weeks. Baseline characteristics and anthropometric measures were obtained. Clinical status using disease activity score in 28 joints (DAS-28), serum levels of matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF) were assessed before and after the intervention. RESULTS:  The serum level of MMP-3 compared with the baseline values did not change significantly in the groups. However, the serum concentration of RF decreased significantly in the vitamin K1 group (p = 0.041). Intergroup comparison showed no significant change in RF serum level after adjusting for relevant confounders (p > 0.05). CONCLUSIONS:  Vitamin K1 supplementation at 10 mg/day for 8 weeks did not alter joint destruction and immune status in the patients with RA compared with the controls.


 

Rheumatoid arthritis treated with anterior pituitary growth hormone.
            (Wheatley, 1950)  Download
After reading the leading article (1949) on recent discoveries of the effects of cortical hormones on rheumatoid arthritis I am prompted to describe a case unsuccessfully treated with anterior pituitary growth hormone. Thyroid and hexoestrol were discontinued and 1 ml. of antuitrin G was given by subcutaneous injection. No further antuitrin G was given, and one month later chrysotherapy (injection of gold salts) was instituted. From this she has benefited greatly. The administration of anterior pituitary growth hormone in small doses over a period of three months produced no improvement. In view of the fact that very large doses of "cortisone" are required to effect improvement in this disease, and the complete failure of smaller ones, it would be interesting to observe whether much larger doses of anterior pituitary growth hormone might have any effect.

The synergistic action of paraaminobenzoic acid and cortisone in the treatment of rheumatoid arthritis.
            (Wiesel et al., 1951)  Download
An additive or synergistic effect of paraaminobenzoic acid and cortisone in the treatment of rheumatoid arthritis has been shown.

 


References

Aryaeian, N, et al. (2019), ‘The effect of ginger supplementation on some immunity and inflammation intermediate genes expression in patients with active Rheumatoid Arthritis.’, Gene, 698 179-85. PubMed: 30844477
Clark, AM (1949), ‘Intravenous iron in rheumatoid arthritis’, The Lancet, 254 (6584), 860-61. PubMed:
Ghavipour, M, et al. (2017), ‘Pomegranate extract alleviates disease activity and some blood biomarkers of inflammation and oxidative stress in Rheumatoid Arthritis patients.’, Eur J Clin Nutr, 71 (1), 92-96. PubMed: 27577177
Godfrey, L (1951), ‘Adenosine triphosphate; trial in the treatment of rheumatoid arthritis.’, J Am Med Assoc, 145 (5), 318-19. PubMed: 14794445
Hetenyi, G and J Karsh (1997), ‘Cortisone therapy: a challenge to academic medicine in 1949-1952.’, Perspect Biol Med, 40 (3), 426-39. PubMed: 9167262
Karsh, J and G Hetenyi (1997), ‘An historical review of rheumatoid arthritis treatment: 1948 to 1952.’, Semin Arthritis Rheum, 27 (1), 57-65. PubMed: 9287391
Lewin, E and E Wassen (1949), ‘Effect of combined injections of deoxycortone acetate and ascorbic acid on rheumatoid arthritis.’, Lancet, 2 (6587), 993. PubMed: 15396186
——— (1950), ‘Observations on the effect of combined injections of desoxycorticosterone acetate and ascorbic acid on rheumatoid arthritis.’, Acta Med Scand Suppl, 246 99-109. PubMed: 14789497
Mur, E, et al. (2002), ‘Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of uncaria tomentosa for the treatment of rheumatoid arthritis.’, J Rheumatol, 29 (4), 678-81. PubMed: 11950006
Nachvak, SM, et al. (2019), ‘Effects of coenzyme Q10 supplementation on matrix metalloproteinases and DAS-28 in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled clinical trial.’, Clin Rheumatol, 38 (12), 3367-74. PubMed: 31392559
Rees, G O (1849), The Treatment of Rheumatic Diseases by Lemon Juice: with Illustrative Cases from Hospital Practice, (Longman, Brown, Green and Longmans).
Shishavan, NG, et al. (2016), ‘Effects of Vitamin K on Matrix Metalloproteinase-3 and Rheumatoid Factor in Women with Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Trial.’, J Am Coll Nutr, 35 (5), 392-98. PubMed: 26156560
(1849), ‘The Treatment of Rheumatic Diseases by Lemon-Juice; with Illustrative Cases from Hospital Practice.’, Br Foreign Med Chir Rev, 4 (8), 529-30. PubMed: 30164951
Wheatley, D (1950), ‘Rheumatoid arthritis treated with anterior pituitary growth hormone.’, Br Med J, 1 (4668), 1472. PubMed: 15426781
Wiesel, LL, AS Barritt, and WM Stumpe (1951), ‘The synergistic action of paraaminobenzoic acid and cortisone in the treatment of rheumatoid arthritis.’, Am J Med Sci, 222 (3), 243-48. PubMed: 14877810