Combination effects of herbal and western medicines on osteoporosis in rheumatoid arthritis: systematic review and meta-analysis.

Purpose: This study aimed to comprehensively review the effect of combining herbal medicine (HM) with Western Medicine (WM) compared to WM alone on bone mineral density (BMD) improvement for osteoporosis in patients with rheumatoid arthritis (RA). Methods: Randomized controlled trials (RCTs) were searched using 10 databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Nation Information by NII. We selected studies that used BMD as an evaluation index and administered HM treatment for osteoporosis in patients with RA. Subsequently, a meta-analysis was conducted using BMD as a continuous variable using RevMan version 5.4. Results: Eighteen RCTs that met the eligibility criteria of this study were selected. The total number of study participants was 1,491 (481 men and 1,010 women). The mean age of participants was 52.4 ± 7.4 years, and the mean morbidity period of RA was 6.8 ± 1.3 years. In all studies, disease-modifying anti-rheumatic drugs (DMARDs; 16 RCTs) or bisphosphonates (two RCTs) were used as WM co-intervention with HMs (17 types of HM, 18 RCTs). Overall, the combination of HM and WM improved the BMD score, producing better results than WM alone. In particular, when HM was used in combination with DMARDs, which were used in most studies, BMD improved by 0.04 g/cm2 (95% confidence interval [CI]: 0.03-0.05, p < 0.001, I2 = 19%) in the lumbar spine and 0.03 g/cm2 (95% CI: 0.02-0.03, p < 0.001, I2 = 0%) in the femoral neck compared to the DMARDs alone group after treatment. In addition to BMD, bone markers and inflammatory indicators evaluated by each RCT showed significant improvement after HM plus WM treatment. In the analysis of frequently prescribed HMs, the BMD after treatment was higher by 0.04 g/cm2 (95% CI: 0.03-0.04, p < 0.001, I2 = 45%) in the Xianlinggubao-capsule plus methotrexate (MTX) group and by 0.02 g/cm2 (95% CI: 0.00-0.03, p = 0.04, I2 = 0) in the Hanbikang-tang plus MTX group compared to the MTX alone group. Conclusion: This systematic review cautiously provides evidence for the combined therapeutic effect of HM and WM for osteoporosis in patients with RA. However, well-designed, large-scale clinical trials are necessary before recommending this combination therapy for osteoporosis in patients with RA. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=331854], identifier [CRD42022331854].

Incidence Rate of Bee Venom Acupuncture Related Anaphylaxis: A Systematic Review.

BACKGROUND: Bee venom acupuncture (BVA) is an effective treatment method for various diseases. Bee venom, however, can cause adverse effects, even rarely including life-threatening anaphylaxis, so safety-related evidence is required. In this study, we systematically estimated the incidence rate of anaphylaxis in response to BVA. METHODS: We searched eight databases (MEDLINE (Pubmed), EMBASE, Cochrane Central Register of Controlled, KISS, KMBASE, Koreamed, OASIS, and NDSL) and systematically reviewed the articles that met the inclusion/exclusion criteria. RESULTS: Among 225 potentially relevant articles, 49 were selected for this study. The overall incidence rate of anaphylaxis in response to BVA was 0.045% (95% CI 0.028-0.062). Women (0.083%, 95% CI 0.010-0.157) showed a higher incidence rate than men (0.019%, 95% CI -0.018 to 0.055), while the incidence for patients who had a skin test conducted (0.041%, 95% CI 0.011-0.072) was not significantly different compared to that obtained for patients for which there was no information about a skin test (0.047%, 95% CI 0.026-0.067). The publication year affected the incidence rate: it was highest before 1999 (1.099%, 95% CI -1.043 to 3.241), lower between 2000 and 2009 (0.049%, 95% CI 0.025-0.073), and lowest between 2010 and 2021 (0.037% 95% CI 0.014-0.060). CONCLUSIONS: In this study, we provide reference data about risk size and factors of BVA-related anaphylaxis, which is essentially required for BVA application in clinics.

Sensory electrical stimulation for suppression of postural tremor in patients with essential tremor.

Essential tremor is an involuntary trembling of body limbs in people without tremor-related disease. In previous study, suppression of tremor by sensory electrical stimulation was confirmed on the index finger. This study investigates the effect of sensory stimulation on multiple segments and joints of the upper limb. It denotes the observation regarding the effect's continuity after halting the stimulation. 18 patients with essential tremor (8 men and 10 women) participated in this study. The task, "arms stretched forward", was performed and sensory electrical stimulation was applied on four muscles of the upper limb (Flexor Carpi Radialis, Extensor Carpi Radialis, Biceps Brachii, and Triceps Brachii) for 15 seconds. Three 3-D gyro sensors were used to measure the angular velocities of segments (finger, hand, and forearm) and joints (metacarpophalangeal and wrist joints) for three phases of pre-stimulation (Pre), during-stimulation (On), and 5 minute post-stimulation (P5). Three characteristic variables of root-mean-squared angular velocity, peak power, and peak power frequency were derived from the vector sum of the sensor signals. At On phase, RMS velocity was reduced from Pre in all segments and joints while peak power was reduced from Pre in all segments and joints except for forearm segment. Sensory stimulation showed no effect on peak power frequency. All variables at P5 were similar to those at On at all segments and joints. The decrease of peak power of the index finger was noted by 90% during stimulation from that of On phase, which was maintained even after 5 min. The results indicate that sensory stimulation may be an effective clinical method to treat the essential tremor.

Perverted head-shaking and positional downbeat nystagmus in pregabalin intoxication.

Dizziness and ataxia are known adverse effects of pregabalin, but characteristic oculomotor signs in pregabalin intoxication have not been reported. Here we describe a patient who displayed perverted head-shaking and positional downbeat nystagmus after prescription of a high dosage of pregabalin. Since pregabalin reduces excitatory neurotransmitter secretion in the central nervous system, decreased excitatory inputs from the brainstem may lead to cerebellar dysfunction, causing perverted head-shaking and positional downbeat nystagmus.

Skin discolouration with acute onset parkinsonism secondary to systemic zirconium intoxication.

A 72-year-old woman presented with suspected parkinsonism and discolouration of the skin especially on sun-exposed areas. Thorough investigation revealed systemic zirconium intoxication due to intake of metallic colloids as a home remedy as a cause of the skin colour change. There may be an association between skin discolouration and her parkinsonism. This is unique in that various clinical manifestations developed following systemic ingestion of zirconium and this should serve as a warning on the risk of taking illicit dietary supplements.

Alleviation of alcoholic liver injury by betaine involves an enhancement of antioxidant defense via regulation of sulfur amino acid metabolism.

Previous studies suggested that the hepatoprotective activity of betaine is associated with its effects on sulfur amino acid metabolism. We examined the mechanism by which betaine prevents the progression of alcoholic liver injury and its therapeutic potential. Rats received a liquid ethanol diet for 6 wk. Ethanol consumption elevated serum triglyceride and TNFα levels, alanine aminotransferase and aspartate aminotransferase activities, and lipid accumulation in liver. The oxyradical scavenging capacity of liver was reduced, and expression of CD14, TNFα, COX-2, and iNOS mRNAs was induced markedly. These ethanol-induced changes were all inhibited effectively by betaine supplementation. Hepatic S-adenosylmethionine, cysteine, and glutathione levels, reduced in the ethanol-fed rats, were increased by betaine supplementation. Methionine adenosyltransferase and cystathionine γ-lyase were induced, but cysteine dioxygenase was down-regulated, which appeared to account for the increment in cysteine availability for glutathione synthesis in the rats supplemented with betaine. Betaine supplementation for the final 2 wk of ethanol intake resulted in a similar degree of hepatoprotection, revealing its potential therapeutic value in alcoholic liver. It is concluded that the protective effects of betaine against alcoholic liver injury may be attributed to the fortification of antioxidant defense via improvement of impaired sulfur amino acid metabolism.

Alterations in sulfur amino acid metabolism in mice treated with silymarin: a novel mechanism of its action involved in enhancement of the antioxidant defense in liver.

It has been known that silymarin exhibits protective activity against oxidative liver injury induced by various hepatotoxicants, but the underlying mechanism of its beneficial action remains unclear. We determined the alterations in sulfur-containing amino acid metabolism induced by silymarin in association with its effects on the antioxidant capacity of liver. Male mice were treated with silymarin (100 or 200 mg/kg, p. o.) every 12 h for a total of 3 doses, and sacrificed 6 h after the final dosing. The hepatic methionine level was increased, but the activity and protein expression of methionine adenosyltransferase were decreased by silymarin in a dose-dependent manner. S-Adenosylmethionine or homocysteine concentration was not changed, whereas the sulfur-containing metabolites generated from homocysteine in the transsulfuration pathway including cystathionine, cysteine, and glutathione were increased significantly. Cystathionine ß-synthase was induced, but cysteine dioxygenase was downregulated, both of which would contribute to the elevation of cysteine and its product, glutathione, in liver. Oxygen radical scavenging capacity of liver cytosol against peroxyl radical and peroxynitrite was increased, and also hepatic lipid peroxidation was diminished in the silymarin-treated mice. Taken together, the results demonstrate that silymarin enhances hepatic glutathione generation by elevating cysteine availability via an increment in cysteine synthesis and an inhibition of its catabolism to taurine, which may subsequently contribute to the antioxidant defense of liver.

"Visual sensory trick" in patient with cervical dystonia.

Sensory tricks are clinical maneuvers that may partially relieve dystonic contractions. Any clinical maneuver that modulates afferent sensory and efferent motor pathways could be used as a sensory trick in patients with cervical dystonia. Although various sensory tricks have been described to reduce cervical dystonia, little is known about the exact mechanisms by which they operate. We report a case of cervical dystonia that was alleviated through the use of a visual-sensory trick. Our findings suggest that visual stimulation might be an effective sensory trick in cervical dystonia by compensating for a defective sensory system, or because visual pathways might be also affected by sensory interactions in cervical dystonia.

Peroxyl radical scavenging capacity of extracts and isolated components from selected medicinal plants.

We determined the ability of extracts and active components isolated from nine medicinal plants, Poncirus trifoliata, Astragalus membranaceus, Magnolia obovata, Salvia miltiorrhiza, Angelica dahurica, Cornus officinalis, Cnidium officinale, Pueraria lobata and Ostericum koreanum, to neutralize peroxyl radicals using the total oxyradical scavenging capacity (TOSC) assay. Peroxyl radicals were generated from thermal homolysis of 2,2'-azobis(2-methylpropionamidine) dihydrochloride, which oxidize alpha-keto-gamma-methiolbutyric acid to yield ethylene, and the TOSC of the substances tested is quantified from their ability to inhibit ethylene formation. Extracts from S. miltiorrhiza, M. obovata and P. lobata were determined to be potent peroxyl radical scavenging agents with a specific TOSC (sTOSC) being at least threefold greater than that of glutathione. Major constituents of the three plants, tanshinone, cryptotanshinone, 15,16-dihydrotanshinone, syringin, honokiol, magnolol, daidzein, puerarin and genistein, were examined for the antioxidant potential toward peroxyl radical. Puerarin and genistein were shown to have microM sTOSCs at least ten-fold greater than sTOSC of glutathione. Daidzein, syringin and honokiol demonstrated the peroxyl radical scavenging capacity comparable to that of glutathione. The implication of peroxyl radical in lipid peroxidation and other cellular damage suggests a possible protective role for the extracts and isolated components in oxidative stress caused by this reactive oxygen species.

Comparison of hydroxyl radical, peroxyl radical, and peroxynitrite scavenging capacity of extracts and active components from selected medicinal plants.

The ability of 80% ethanol extracts from five medicinal plants, Aralia continentalis, Paeonia suffruticosa, Magnolia denudata, Anemarrhena asphodeloides, and Schizonepeta tenuifolia, to neutralize hydroxyl radical, peroxyl radical and peroxynitrite was examined using the total oxyradical scavenging capacity (TOSC) assay. Peroxyl radical was generated from thermal homolysis of 2,2'-azobis (2-methylpropionamidine) dihydrochloride (ABAP) ; hydroxyl radical by an iron-ascorbate Fenton reaction; peroxynitrite by spontaneous decomposition of 3-morpholinosydnonimine N-ethylcarbamide (SIN-1) . The oxidants generated react with α-keto-γ-methiolbutyric acid (KMBA) to yield ethylene, and the TOSC of the substances tested is quantified from their ability to inhibit ethylene formation. Extracts from P. suffruticosa, M. denudata,and S. tenuifolia were determined to be potent peroxyl radical scavenging agents with a specific TOSC (sTOSC) being at least six-fold greater than that of glutathione (GSH) . These three plants also showed sTOSCs toward peroxynitrite markedly greater than sTOSC of GSH, however, only P. suffruticosa revealed a significant hydroxyl radical scavenging capacity. Seven major active constituents isolated from P. suffruticosa, quercetin, (+) -catechin, methyl gallate, gallic acid, benzoic acid, benzoyl paeoniflorin and paeoniflorin, were determined for their antioxidant potential toward peroxynitrite, peroxyl and hydroxyl radicals. Quercetin, (+) -catechin, methyl gallate, and gallic acid exhibited sTOSCs 40~85 times greater than sTOSC of GSH. These four components also showed a peroxynitrite scavenging capacity higher than at least 10-fold of GSH. For antioxidant activity against hydroxyl radical, methyl gallate was greatest followed by gallic acid and quercetin. Further studies need to be conducted to substantiate the significance of scavenging a specific oxidant in the prevention of cellular injury and disease states caused by the reactive free radical species.

Taurine depletion by beta-alanine inhibits induction of hepatotoxicity in mice treated acutely with carbon tetrachloride.

We examined the effect of taurine depletion on hepatic sulfur-containing amino acid metabolism and carbon tetrachloride-induced acute liver injury. Mice were supplemented with beta-alanine (3%) in drinking water for one week. beta-Alanine intake significantly reduced hepatic taurine levels, but did not influence S-adenosylmethionine, S-adenosylhomocysteine, glutathione levels or methionine adenosyltransferase activity in liver. However, hepatic cysteine levels were significantly elevated by beta-alanine administration. Hepatotoxicity caused by carbon tetrachloride (50 microl/kg, ip) in mice fed beta-alanine was decreased, as determined by changes in serum aspartate aminotransferase, alanine aminotransferase and sorbitol dehydrogenase activities. Hepatic glutathione and taurine levels after a carbon tetrachloride challenge were markedly increased by beta-alanine exposure. The results suggest that enhanced availability of cysteine for synthesis of glutathione and/or taurine may account for the hepatoprotective effects of beta-alanine against carbon tetrachloride-induced acute liver injury.