Chondroitin Sulfate Enhances Proliferation and Migration via Inducing ß-Catenin and Intracellular ROS as Well as Suppressing Metalloproteinases through Akt/NF-κB Pathway Inhibition in Human Chondrocytes.

BACKGROUND: Chondroitin sulfate (CS) is found in humans' cartilage, bone, cornea, skin, and arterial wall. It consists of the foundation substance in the extracellular matrix (ECM) of connective tissue. The oral supplement form of CS is clinically used in treating osteoarthritis (OA). METHODS: Cell migration was observed by the transwell assay. The EMT, Akt/IKK/IκB pathways, TIMPs, collagen and MMPs in cell lysate were determined by Western blotting. The expression of MMP activity was determined by gelatin zymography. The production of reactive oxygen species (ROS) was determined by using a fluorescence spectrophotometer. RESULTS: In the current report, we demonstrated that CS can increase the cell proliferation and migration of chon-001 chondrocytes. Treatment with CS induced the epithelial-mesenchymal transition and increased the expression of type II collagen and TIMP-1/TIMP2 and inhibited the expressions and activities of metalloproteinase-9 (MMP-9) and metalloproteinase-2 (MMP-2). The phosphorylation of Akt, IκB kinase (IKK), IκB and p65 was decreased by CS. CS treatment resulted in ß-catenin production and XAV939, a ß-catenin inhibitor, and inhibited the cell proliferation by CS treatment. In addition, also significantly induced intracellular ROS generation. Treatment with antioxidant propyl gallate blocked cell migration induced by CS. CONCLUSION: We demonstrated that CS induced cell proliferation and migration of chondrocytes by inducing ß-catenin and enhancing ROS production. Moreover, our studies demonstrated that CS can increase the activity of chondrocytes and help patients with osteoarthritis to restore cartilage function.

Association of dietary omega-3 fatty acids with prevalence of metabolic syndrome: the National Heart, Lung, and Blood Institute Family Heart Study.

BACKGROUND & AIMS: Metabolic syndrome (MetS), characterized by abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, and insulin resistance is a major public health concern in the United States. Omega-3 fatty acids have been relatively well studied in relation to many individual cardiovascular risk factors; however, their effects on MetS are not well established. METHODS: We conducted a cross-sectional study consisting of 4941 participants from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study to assess the relation of dietary omega-3 fatty acids with the prevalence of MetS. Omega-3 intake was assessed using a food frequency questionnaire and we used generalized estimating equations to estimate adjusted odds ratios for prevalent MetS. RESULTS: Our study population had a mean age (SD) of 52.1 (13.9) years and 45.9% were men. The mean (SD) of dietary omega-3 fatty acids was 0.25 g/day (0.27). From the lowest to the highest quintile of dietary omega-3 fatty acids, multivariable adjusted ORs (95% CI) for MetS were 1.00 (ref), 0.90 (0.72-1.13), 1.03 (0.82-1.28), 0.94 (0.74-1.18), and 0.99 (0.77-1.25), respectively. In a secondary analysis, neither fish consumption nor dietary alpha-linolenic acid was associated with MetS. CONCLUSIONS: Our findings do not support an association between dietary omega-3 fatty acids and MetS in a large US population.

San-Huang-Xie-Xin-Tang attenuates inflammatory responses in lipopolysaccharide-exposed rat lungs.

In this study, the potential anti-inflammatory effect of San-Huang-Xie-Xin-Tang (SHXT) and its main component baicalin on LPS-induced lung injury were investigated and compared to the profile of dexamethasone (DEXA) in a pre-clinical animal model. Post-treatment with SHXT (75 mg/kg), baicalin (1.5 mg/kg) and DEXA (0.5 mg/kg), significantly inhibited LPS-induced hypotension, lung edema and acute survival rates. Western blotting analysis results indicated that all of them significantly inhibited LPS-induced iNOS, TGF-beta, p38MAPK, and ICAM-1 expressions in the lung tissues. Results from ELISA analysis showed that SHXT, baicalin and DEXA all decreased plasma levels of IL-1beta, TNF-alpha, and MCP-1 caused by LPS. Based on these findings, SHXT and baicalin decreased plasma concentrations of IL-1beta, TNF-alpha, MCP-1, and expressions of TGF-beta, ICAM-1, phosphorylated p38 MAPK, and iNOS, which were associated with lung injury and lethality. These evidences indicated that SHXT and baicalin showed strong anti-inflammatory activity, similar to that observed for DEXA, and therefore implicated that herbal SHXT might be therapeutically useful for the treatment of endotoxic lung injury.

Xanthones from Garcinia parvifolia.

Nine new xanthones, parvixanthones A-I (1-9), isolated from the dried bark of Garcinia parvifolia, were found to have a common 1,3,6,7-oxygenated pattern for their xanthone nucleus, but various oxygenated isoprenyl or geranyl substituent groups. The structures were determined by spectroscopic methods.

Flavonol-cinnamate cycloadducts and diamide derivatives from Aglaia laxiflora.

Leaf extracts of the Malaysian plant Aglaia laxiflora provided two cytotoxic compounds, a new rocaglaol rhamnoside (1), a known rocaglaol (2), new (but inactive) flavonol-cinnamaminopyrrolidine adducts (3-6), and their probable biosynthetic precursors (7 and trimethoxyflavonol). All structures were elucidated primarily by 2D NMR spectroscopy. The structure and stereochemistry of aglaxiflorin A (3) were confirmed by single-crystal X-ray crystallography.

Traditional Chinese medicines as immunosuppressive agents.

INTRODUCTION: Traditional Chinese Medicines (TCM) have been used for centuries in China to treat various immune-mediated disorders. METHODS: This review focuses on the clinical and experimental studies that have been performed with TCM as immunosuppressive agents for the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), atopic eczema and solid organ transplantation. RESULTS: The "thunder god" vine, Tripterygium wilfordii Hook F (TWHf), has been extensively used in China to treat SLE and RA. TWHf not only inhibited mitogen-stimulated lymphoproliferation, but its active derivatives have also been shown to inhibit production of proinflammatory cytokines by monocytes and lymphocytes, as well as prostaglandin E2 production via the cyclooxygenase, COX-2, pathway, a potential mechanism of action in patients with RA. Demethylzelasteral (TZ-93), a triterpenoid isolated from the root cortex of TWHf, the plant alkaloid berbamine, and the hydrophobic extract of a Chinese herbal decoction, CMX-13, were all shown to be active in prolonging allograft survival in experimental animal models of heart, skin and single lung transplants, respectively. There are few well-designed randomised placebo-controlled clinical trials demonstrating the efficacy of TCM in various diseases. Zemaphyte, a decoction of 10 herbs, has been shown to be efficacious in the treatment of atopic dermatitis in both children and adults in two randomised double-blind placebo-controlled trials. CONCLUSION: There is both laboratory and clinical evidence that the derivatives of many of these herbs may have significant beneficial immunosuppressive effects, however, concerns of toxicity must also be addressed, as exact dosing of the active derivatives is difficult to achieve with the current prescriptions of TCM.

Antibiotic treatment of orbital cellulitis: an analysis of pathogenic bacteria and bacterial susceptibility.

The proper choice of effective antibiotics is a mainstay for the treatment of orbital cellulitis. The lack of native data regarding the microorganism causing the infection and its antibiotic sensitivity prompted us to conduct this study. We retrospectively collected 29 cases of orbital cellulitis admitted to Chung-Ho Memorial Hospital of Kaohsiung Medical College from January 1994 to September 1998. The effectiveness of antibiotics with bacterial susceptibility was analyzed. Of the 29 cases, fifteen were male and fourteen female. The patients ranged in age from 7 months to 79 years (mean, 37.6 years). Sinusitis (9 cases, 31.0%) is the most common etiology. Fourteen cases received both medical and surgical treatments. Eighteen cases had purulent discharge from the infection areas sent for culture isolation of the microorganism. The culture positive rate was 50% (9 in 18 cases). The Staphylococcus aureus (5 cases) was the most common pathogen. The bacterial susceptibility test showed drug resistance of 100% for penicillin G (seven out of seven cases; 7/7), 100% for ampicillin (10/10), and 0% for amikacin (0/3) and vancomycin (0/7). Penicillin and ampicillin are not effective for those isolated bacteria. Oxacillin and gentamicin, frequently used in first line treatment, might encounter drug resistance in some cases. Amikacin and vancomycin, without any resistance in bacterial susceptibility tests, could be used in vision-threatening, critical, and intractable cases.

Improvement in lupus nephritis following treatment with a Chinese herbal preparation.

OBJECTIVE: To study the effect of a Chinese herbal decoction (CM), which contained 21 different herbs, on clinical remission in a patient with lupus nephritis and chronic nephrotic syndrome. DESIGN: Case report describing the clinical and laboratory markers of lupus activity in the patient before and after treatment with CM. We also studied the in vitro effect of CM and its hydrophobic extract on spontaneous IgG production by peripheral blood mononuclear cells (PBMCs) from 12 patients with systemic lupus erythematosus (SLE) compared with 9 healthy control subjects. RESULTS: Spontaneous PBMC IgG production was significantly higher in patients with SLE (mean +/- SD, 20.4+/-10.6 x 10(-5) g/L) compared with controls (4.7+/-1.9 x 10(-5) g/L) (P<.001). Addition of CM and its hydrophobic extract to PBMCs from patients with SLE resulted in significant suppression of spontaneous IgG production. CONCLUSIONS: The CM may contain some active pharmacological compound with immunosuppressive properties useful in the treatment of SLE. Further controlled studies are important to evaluate the efficacy of this medicine, potential toxic effects, and the possible immunosuppressive mechanisms of the active component(s).

Intravenous repletion of phosphorus deficiency in the chronic renal failure patients with severe hypophosphatemia.

Severe hypophosphatemia is a potentially life-threatening medical condition and might lead to a fatal outcome in critically ill patients. The situation is further complicated by the co-morbid renal failure. We evaluated the efficacy and safety of the intravenous phosphate repletion in 15 renal failure patients with severe hypophosphatemia. Six patients with advanced renal failure and nine patients under maintenance hemodialysis, 7 males and 8 females, aged between 42 and 83 years old, were found to have serum phosphate level < 1.2 mg/dL from various medical conditions and were treated with intravenous phosphate infusion. The phosphate solution prepared from sodium dihydrogen phosphate (NaH2PO4), containing 13 mg/ml phosphate and 0.5 meq/ml sodium, in the dosage 2.5-3.0 mg phosphate/Kg body weight, was administered through the central venous lins every 6-8 hours. The infusion was discontinued once serum phosphate level reached 5.0-5.5 mg/dL. Serum ionized calcium, phosphate and intact parathyroid hormone levels were serially followed at different intervals, respectively. The hemodialyzed uremic patients received their dialysis treatment as scheduled. All patients survived the hypophosphatemic period and regained normal phosphate levels after repletion. The amount of phosphate administered to reach the target level ranged between 3438 and 9150 mg and the duration of treatment varied between six and seventeen days. Hypocalcemia (< 4.2 mg/dL) was noted at eight occasions during the whole treatment period but none was symptomatic. Eleven patients recovered from the offending illness. However, four patients expired due to reasons not directly consequent to and temporally remote from hypophosphatemia. We conclude that prompt repletion of severe hypophosphatemia and phosphate deficiency with relatively slower rate of NaH2PO4 solution intravenous infusion is a safe and effective mode of treatment for renal failure and uremic patients. The longer treatment period allowed the administered minerals full equilibration. The risk of hyperkalemia is avoided and the sodium/volume load can be eliminated by dialysis.

[Mechanism and prevention of hemolysis in jaundiced infants in phototherapy].

It has been reported that the prolonged phototherapy results in decreased glutathione reductase (GR) activity in red blood cells. We found short-term phototherapy had the same side-effect. Besides it aggravates hemolysis of newborns during the therapy. This side-effect can be prevented by oral administration of Vit B2. Eighteen jaundiced infants who were given Vit B2 5mg three times a day during the phototherapy, and the control group of 16 patients were not given Vit B2. The results showed that the decrease of hemoglobin and the time of jaundice disappearance during the phototherapy were more favourable in the oral Vit B2 group than those of the control. These results indicated that the short-term phototherapy not only results in decreased GR activity in red blood cell, but also results in hemolysis of the newborn. This side-effect can be prevented by oral administration of Vit B2.

Effects of manidipine hydrochloride on blood pressure in hypertensive patients--a comparison with nifedipine retard.

Manidipine hydrochloride (MH) is a new calcium channel antagonist which is not yet available in Taiwan. Thus, a clinical trial was performed. The clinical effects and adverse effects of MH were compared with those of nifedipine hydrochloride retard monotherapies. Sixty-three out-patients with mild to moderate hypertension and no advanced systemic diseases were randomly divided into 2 groups. Twenty patients remained in each group after some patients withdrew from the study. Blood pressure decreased significantly after treatment in both groups (p < 0.01). In the manidipine group, systolic blood pressure (SBP) decreased from 164 +/- 14 to 140 +/- 18 mmHg and diastolic BP (DBP) decreased from 99 +/- 6 to 87 +/- 7 mmHg by the 8th week. In the nifedipine group, SBP decreased from 163 +/- 11 to 134 +/- 17 mmHg and DBP decreased from 101 +/- 10 to 88 +/- 9 mmHg by the 8th week. Pulse rates did not change significantly. Antihypertensive efficacy was 18/20 (90%) and 19/22 (86.4%) in the manidipine and nifedipine groups, respectively. There were a few adverse effects in both groups, the reaction was severe as to lead to the discontinuation of medication in two patients in the nifedipine group. No significant changes in laboratory tests were identified in either group, except for minimal decreases of lactate dehydrogenase and creatine kinase in the nifedipine group. We conclude that MH was equally safe and effective as nifedipine and it may have less severe side effects compared to nifedipine.

[New method for selectivity optimization in thin layer chromatography and its application in pharmaceutical analysis].

A new experimental design method named the step climbing method (SCM), as well as a new global criterion (NRC), are proposed for the selectivity optimization of thin layer chromatography. The method offers chromatographers a convenient means to decide the optimum developer composition for thin layer chromatography. The principle of the method is described, and examples of applications in pharmaceutical analysis are given to certify the feasibility of the method. Clearly, it may also be used for the selectivity optimization in high performance liquid chromatography.

History of epilepsy in Chinese traditional medicine.

The first known document on epilepsy in China appeared in The Yellow Emperor's Classic of Internal Medicine, Huang Di Nei Ching, written by a group of physicians around 770-221 B.C. The description of epilepsy in this book and in many others later published was confined to generalized convulsive seizures. No documentation of absence or simple partial seizures was provided. The first classification of epilepsy, probably by Cao Yuan Fang in A.D. 610, listed five types of epilepsy: "Yang Dian," "Yin Dian," "Feng (Wind) Dian," "Shih (Wet) Dian," and "Lao (Labor) Dian." Later, other classifications named seizures after the cry of animals whose cry the "epileptic cry" resembled, or after "visceral organs" believed to be responsible for the seizures. The concept of partial versus generalized seizures, however, was not observed in any of these classifications. The treatment of epilepsy, based on principles of "Yin Yang Wu Xing," consisted of herbs, acupuncture, and massage.