Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine, for patients with osteoarthritis of the knee: a multi-site, randomized, double-blind, placebo-controlled phase II clinical trial.

OBJECTIVE: To examine the efficacy and safety of Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine (TCM), in patients with knee osteoarthritis (OA). DESIGN: A multi-site, randomized, double-blind, placebo-controlled phase II dose-escalation clinical trial was conducted. Eligible patients who fulfilled American College of Rheumatology criteria were randomized to receive either HLXL or placebo. Clinical assessments included measurement of knee pain and function with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), patient global assessment (PGA), and knee pain scores every 2 weeks. A Data and Safety Monitoring Board (DSMB) was established to review the data for ensuring the quality of the trial. RESULTS: In the first stage, 28 participants were randomized to receive either low-dose HLXL-Dan (2400 mg/day) or placebo for 6 weeks. The results showed no statistical difference between the two groups. The study was then re-designed following the recommendation of DSMB. Ninety-two patients were enrolled in the second stage and were randomized to receive either high-dose HLXL-Dan (4000 mg/day for week 1-2, and 5600 mg/day for week 3-8) or placebo for 8 weeks. All outcome assessments showed significant improvements for both groups after 8 weeks but no significant between-group differences. The change (mean ± SD) of WOMAC pain and WOMAC function scores of HLXL and placebo group after 8 weeks were -1.2 ± 1.7 vs -1.4 ± 1.5, and -1.1 ± 1.6 vs -1.3 ± 1.5 respectively. No serious adverse events were reported. CONCLUSION: Although safe to use, an 8-week treatment of HLXL-Dan was not superior to placebo for reduction in pain or functional improvement in patients with knee OA. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov (NCT00755326).

Hepatoprotective and neuroprotective tocopherol analogues isolated from the peels of Citrus unshiu Marcovich.

Three tocopherol analogues methoxytocopherol (1), α-tocopherol (2) and γ-tocopherol (3) were isolated from the peels of Citrus unshiu Marcovich. The protective effects of the isolated compounds against tert-butyl hydroperoxide-induced hepatotoxicity in human liver-derived HepG2 cells and glutamate-induced oxidative stress in HT22-immortalised hippocampal cells were evaluated. Compounds 1-3 were significantly protective in HepG2 cells with EC50 values of 21.22 ± 2.01, 25.21 ± 2.11 and 25.25 ± 1.21 µM, respectively, and in HT22 cells, compounds 1-3 had EC50 values of 20.62 ± 1.36, 6.44 ± 1.65 and 9.52 ± 1.54 µM, respectively.

Radiological response predicts survival following transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma.

BACKGROUND: It remains unclear whether initial compact lipiodol uptake after transarterial chemoembolisation (TACE) is associated with improved survival in patients with hepatocellular carcinoma (HCC). AIM: To reveal the clinical relevance of compact lipiodolisation after TACE. METHODS: We studied 490 patients with unresectable HCC who had first been treated with TACE. Compact lipiodolisation was defined as the absence of an arterial enhancing lesion, reflecting complete lipiodol uptake, as assessed by dynamic computed tomography (CT) 1 month after treatment. The rate of initial compact lipiodolisation was analysed according to multiplicity and size of tumour, and survival of patients who achieved compact lipiodolisation was compared to that of patients who did not. RESULTS: Of the 490 patients, 409 (83.5%) were in Child-Pugh class A and 81 (16.5%) in class B. The rate of initial compact lipiodolisation in single HCCs was higher than that in multinodular HCCs (33.7% vs. 14.6%, P < 0.001). Among single HCCs, the rate of compact lipiodolisation in tumours ≤5, 5-10 and >10 cm was 46.6%, 13.6%, and 0% respectively. The 1-, 3- and 5-year survival rates of patients with compact uptake were 92.7%, 70.7% and 52.4% compared to 60.8%, 28.0% and 16.9% in patients with noncompact lipiodolisation. Multivariate analysis revealed that Child-Pugh class, alpha-fetoprotein level, tumour node metastasis stage, portal vein thrombosis and initial compact lipiodolisation were independent predictors of survival. CONCLUSIONS: Initial compact lipiodol uptake after transarterial chemoembolisation is associated with improved survival in patients with unresectable hepatocellular carcinoma. Accordingly, initial complete lipiodolisation should be considered a relevant therapeutic target.

Tob is a potential marker gene for the basal layer of the epidermis and is stably expressed in human primary keratinocytes.

BACKGROUND: Epidermis consists of multiple layers, from the proliferating basal layer to terminal differentiated cornified layers, and these layers are defined by differentiation status. Tob gene product is known to be a member of the BTG antiproliferative protein family. We investigated the expression pattern of Tob gene product to understand the possible role in differentiation of keratinocytes and epidermis. OBJECTIVES: In this study, we examined the expression of Tob gene product in the primary cultured human keratinocytes and in the in vivo epidermis. METHODS: The expression of Tob gene product was assessed by Western blotting analysis. Cellular localization of Tob was detected using the green fluorescent protein-tagged Tob cDNA expression construct. In vivo expression of Tob gene product in the epidermis was determined by immunohistochemistry with paraffin sections. RESULTS: Tob family members are degraded by the ubiquitine-proteasome system triggered by the growth signal. Tob is stably and abundantly expressed in primary cultured human keratinocytes. Furthermore, the expression of Tob in the keratinocytes persists during the differentiation induced by calcium; however, it was not detected in primary cultured fibroblasts. Also, the subcellular localization of Tob is mainly in the cellular membrane in the primary human keratinocytes. We evaluated Tob expression in normal skin, oral mucosa and different diseases, such as psoriasis, X-linked ichthyosis and squamous cell carcinoma (SCC). Using immunohistochemical analysis, we observed that Tob was selectively expressed in the basal layer of X-linked ichythyosis and the hyperproliferative basal layer of psoriasis and oral mucosa as well as in normal epidermis. In SCC, the expression of Tob gene product was relatively decreased. CONCLUSIONS: Tob is stably expressed in primary human keratinocytes and it is specifically expressed in the basal layer of in vivo epidermis.

Effects of an acetone extract of Boswellia carterii Birdw. (Burseraceae) gum resin on adjuvant-induced arthritis in lewis rats.

Ruxiang (Gummi olibanum), the dried gum resin of Boswellia carterii (BC), has been used in traditional Chinese medicine to alleviate pain and inflammation for thousands of years. In this random, blinded study, the anti-arthritic effects of a BC extract were observed and compared to vehicle control in a Lewis rat adjuvant arthritis model (n=8/group). Arthritis was induced by injecting CFA subcutaneously into the base of the tail, and the extract was administered orally (i.g.) for 10 consecutive days beginning on day 16 after the injection. Arthritic scores, paw edema, and the local tissue pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) were assessed. Toxicity and adverse effects of the extract were evaluated. At 0.90 g/kg per day, BC significantly decreased arthritic scores between days 20 and 25 (p<0.05) and reduced paw edema on days 18, 20 and 22 compared to control (p<0.05). It also significantly suppressed local tissue TNF-alpha and IL-1beta (p<0.05). No major adverse effects were observed in animals during the repeated-dose treatment profile although mild fur discoloration was noted. The data show that BC extract has significant anti-arthritic and anti-inflammation effects and suggest that these effects may be mediated via the suppression of pro-inflammatory cytokines.

Structural characterization of the 60-kDa bermuda grass pollen isoallergens, a covalent flavoprotein.

Our studies suggest a tripartite structure for the 60-kDa allergen of Bermuda grass pollen (BG60) including a short N-terminal segment, a FAD-binding domain, and a C-terminal domain. The lower molecular weight isoallergens lack the N-terminal segment. The higher protease susceptibility and the lower melting temperature of approximately 20 degrees C of the lower molecular weight isoforms suggest that the N-terminal segment is essential for a compact structure. Database screening reveals that the protease-digested peptide sequences (approximately 180 residues in total) share 40% identity with the plant berberine bridge enzymes. In particular, a 24-residue peptide sequence displays high similarity to a conserved FAD-binding motif. The spectroscopic and SDS-PAGE analyses suggest that the cofactor FAD is covalently linked to the central domain. Therefore, we conclude that BG60 is identified as the first flavinylated allergen.

Pulmonary peptide delivery: effect of taste-masking excipients on leuprolide suspension metered-dose inhalers.

The purpose of this study was to evaluate the effect of taste-masking excipients on in vitro and in vivo performance of a leuprolide metered-dose inhaler (MDI) suspension formulation. Taste-masking excipients (aspartame and menthol) were added to a leuprolide suspension MDI formulation. The leuprolide MDI formulation with the taste-masking excipients was characterized in terms of milling time, particle size distribution, dose delivery and uniformity, and drug absorption in dogs. The data were compared with a formula that did not contain taste-masking excipients. It was found that the longer milling time for the leuprolide suspension with the taste-masking excipients was required to obtain a similar particle size distribution compared with the formula without taste-masking excipients using a fluid energy mill. Although measurable differences in mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were not observed between the two formulations, the percent of particles < or = 5 microns and the actuator retention for the formula with the taste-masking excipients were significantly different from the formula without taste-masking excipients using the Marple-Miller cascade impactor. Taste-masking excipients did not show a significant effect on valve delivery and through-can dose uniformity. However, the mean ex-actuator dose was 150.4 mg for the formula with the taste-masking excipients and 162.2 mg for the reference formula, respectively, indicating a significant difference. In tracheostomized dogs, both formulations showed comparable pharmacokinetic parameters including Cmax, Tmax, AUC0-12 and bioavailability (F%), indicating that the taste-masking excipients do not have an effect on lung absorption of leuprolide acetate. Therefore, inclusion of taste-masking excipients in the leuprolide MDI suspension formulation showed a significant impact on drug micronization, exactuator dose, and particle deposition pattern. Mechanistically, the unfavorable performance of leuprolide MDI in the presence of taste-masking excipients could be due to modification of the properties of the suspension itself and alteration of propellant evaporation following actuation.

A comparison of mechanical properties of all-ceramic alumina dental crowns prepared from aqueous- and non-aqueous-based tape casting.

Alumina-glass dental composites were prepared by aqueous- and non-aqueous-based tape casting and sintering at 1120 degrees C, followed by glass infiltration at 1100 degrees C. Flexural strength and fracture toughness of the composites were investigated in terms of influence of tape constituents, namely, alumina powder, binder, and plasticizer on the mechanical properties. For the alumina-glass composites prepared from the aqueous-based tapes, both strength and toughness increased with increasing alumina fraction ratio in tape constituents including organic substances, a/a+o, and binder content ratio in binder/binder + plasticizer mixture, b/b+p. For the composites prepared from the non-aqueous-based tapes, on the other hand, both strength and toughness increased with increasing the a/a+o ratio but decreased with increasing the b/b+p ratio. These observations were consistent with influence of the constituents on mean alumina particle distance in tapes, suggesting that high strength of the glass infiltrated alumina composites is related to toughening by crack bowing. The optimized strength of the aqueous and nonaqueous tape cast composites was 559 and 508 MPa, and the fracture toughness was 3.3 and 3.1 MPam(1/2), respectively.

Mechanical properties, phase stability, and biocompatibility of (Y, Nb)-TZP/Al(2)O(3) composite abutments for dental implant.

ZrO(2)/Al(2)O(3) composites were prepared by mixing a tetragonal ZrO(2), stabilized by 5.31 mol% Y(2)O(3) and 4.45 mol% Nb(2)O(5), and various amounts of Al(2)O(3). Influence of the amount of Al(2)O(3) on strength and toughness and tetragonal phase stability in the composites under autoclave conditions was investigated. In addition, in vitro and in vivo biocompatibility of the composites was examined. The composite, prepared with addition of 20 vol% Al(2)O(3), exhibited the highest strength of 700 MPa and toughness of 8.1 MPa. m(1/2) and showed no hydrothermal degradation while aging in an autoclave. The biocompatibility of the composite exhibited no cytotoxicity and no significant adverse soft-tissue response for up to 3 months implant period in guinea pigs.

Modulation of neuroendocrinological function by psychosomatic training: acute effect of ChunDoSunBup Qi-training on growth hormone, insulin-like growth factor (IGF)-I, and insulin-like growth factor binding protein (IGFBP)-3 in men.

The neuroendocrine system is regarded as the major link between the psychological state and the immune system in man. The present study was undertaken to examine the acute effect of ChunDoSunBup Qi-training, a traditional psychosomatic training, on the plasma level of growth hormone (GH), insulin-like growth factor (IGF)-I and insulin like growth factor binding protein (IGFBP)-3 in young men. To characterize the plasma level of hormones and the pattern of IGFBP-3 at pre- (-10 min), mid-time (40 min), and immediately after (post-time, +10 min) Qi-training, radioimmunoassay (RIA) and western ligand blot (WLB) analysis were used. The plasma level of GH at the mid-time was significantly increased (P<0.05) compared to the level at pre-time of Qi-training. The plasma level of IGF-I was also increased at mid-time (P<0.05) and immediately after Qi-training. There was a significant correlation between the levels of GH and IGF-I immediately after Qi-training (r=0.69, P<0.01). In this study, the change of IGFBP-3 among the several IGFBPs was determined. There was a relative shift in IGFBP-3 for the 43-kDa fraction during mid-time of Qi-training (P<0.05). These results suggest that Qi-training influences the growth hormone, IGF-I and IGFBP-3 status via brain-target organ axis in men.

The Outpatient Developmental Services Project: integration of pediatric psychology with primary medical care for children infected with HIV.

OBJECTIVE: To present a model in which pediatric psychology services are programmatically integrated into the primary care of children seen in a special immunology program. The program centers around serial neurodevelopmental/neuropsychological evaluation of children infected with HIV. METHOD: We describe the population served and the particular services provided, with specific focus on how the program was developed. We include a discussion of the barriers to service provision that have been encountered and the strategies employed to overcome these challenges. CONCLUSIONS: This approach, while not ideal, serves as a good example of how pediatric psychology can merge with primary medical care to maximize the benefits of both specialties for a patient population that is underserved in many respects.

Crystallization and preliminary diffraction data of 60-kDa glycosylated pollen isoallergens from Bermuda grass.

Crystals grown from a 60-kDa isoallergen mixture of Bermuda grass pollen have been obtained in 30% PEG 4000 and 25% isopropanol. The crystals diffract beyond 2-A resolution and belong to a tetragonal space group with the unit cell dimensions a = b = 86 A and c = 310 A. The preferential crystal growth of the larger isoallergens with a blocked N-terminus indicates that crystallization can isolate proteins with compact conformation.

Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma.

PURPOSE: The best prognosis in hepatocellular carcinoma (HCC) can be achieved with surgical resection; however, the number of resected cases are limited due to advanced lesions or associated liver disease. The purpose of this study was to investigate the efficacy and toxicity of a prospective trial of combined transcatheter arterial chemoembolization (TACE) and local radiotherapy (RT) in unresectable HCC. METHODS AND MATERIALS: Patients with histologically proven unresectable HCC due to either advanced lesions or associated cirrhosis were eligible. From March 1992 to August 1994, 30 patients were entered into this study. TACE was performed with Lipiodol (5 ml) and doxorubicin (Adriamycin ; 50 mg), followed by gelatin sponge particle (Gelfoam) embolization. Local RT was started within 7-10 days following TACE. Mean tumor dose was 44.0+/-9.3 Gy in daily 1.8 Gy fractions. Response was assessed by computerized tomography (CT) scan 4-6 weeks following completion of the treatment and then at 1-3-month intervals. Survival was calculated from the start of TACE using the Kaplan-Meier method. RESULTS: An objective response was observed in 19 patients, giving a response rate of 63.3%. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2 in both lung and bone. Survival rates at 1, 2, and 3 years were 67%, 33.3%, and 22.2%, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Toxicity included transient elevation of liver function tests in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death. CONCLUSION: Combined TACE and local RT is feasible and tolerable. It gives a 63.3% response rate with median survival of 17 months. We feel that this regimen would be a new promising modality in unresectable HCC. Further study is required to compare the therapeutic efficacy of this regimen to TACE alone.

Isoflavonoid compounds extracted from Pueraria lobata suppress alcohol preference in a pharmacogenetic rat model of alcoholism.

The extract from an edible vine, Pueraria lobata, has long been used in China to lessen alcohol intoxication. We have previously shown that daidzin, one of the major components from this plant extract, is efficacious in lowering blood alcohol levels and shortens sleep time induced by alcohol ingestion. This study was conducted to test the antidipsotropic effect of daidzin and two other major isoflavonoids, daidzein and puerarin, from Pueraria lobata administered by the oral route. An alcohol-preferring rat model, the selectively-bred P line of rats, was used for the study. All three isoflavonoid compounds were effective in suppressing voluntary alcohol consumption by the P rats. When given orally to P rats at a dose of 100 mg/kg/day, daidzein, daidzin, and puerarin decreased ethanol intake by 75%, 50%, and 40%, respectively. The decrease in alcohol consumption was accompanied by an increase in water intake, so that the total fluid volume consumed daily remained unchanged. The effects of these isoflavonoid compounds on alcohol and water intake were reversible. Suppression of alcohol consumption was evident after 1 day of administration and became maximal after 2 days. Similarly, alcohol preference returned to baseline levels 2 days after discontinuation of the isoflavonoids. Rats receiving the herbal extracts ate the same amounts of food as control animals, and they gained weight normally during the experiments. When administered orally, none of these compounds affected the activities of liver alcohol dehydrogenase and aldehyde dehydrogenase. Therefore, the reversal of alcohol preference produced by these compounds may be mediated via the CNS. Data demonstrate that isoflavonoid compounds extracted from Pueraria lobata is effective in suppressing the appetite for alcohol when taken orally, raising the possibility that other constituents of edible plants may exert similar and more potent actions.

Effects of preinterview suggestion on counselor memory, clinical impression, and confidence in judgments.

This study examined the effects of schematic preinterview suggestion on counselors' (a) recognition memory of the information presented by the client; (b) clinical impression rating of the client; and (c) confidence in rating clinical impression. Fifty-two Master's-level counselor-trainees were assigned randomly to two conditions of preinterview suggestion about the status of the client (i.e., depression and no depression). After subjects had received appropriate preinterview information (i.e., depression or no-depression content) and had viewed a videotaped counseling interview, information was gathered from them. The results indicated that the preinterview suggestion (a) did not affect counselor-trainees' clinical impression rating of the client; (b) did not affect confidence of rating; and (c) yielded a weak, but significant, confirmatory memory. Implications for the interview setting are discussed.

Surgical treatment of stage III lung cancer after chemotherapy and radiotherapy.

We have experienced eight patients with advanced bronchogenic carcinomas who underwent resectional surgery after receiving preoperative adjuvant chemotherapy and radiotherapy during the period March, 1990, to February, 1992. Four patients were in stage IIIA and four in stage IIIB, of which six had epidermoid carcinomas and two small cell carcinomas. All patients were male with ages ranging from 48 to 73 (mean 56.7) years. The induction chemotherapy for six patients consisted of cisplatin and VP-16 (Etoposide) only, and two patients were given fluorouracil/cyclophosphamide and cyclophosphamide/adriamycin/cisplatin in addition to cisplatin/VP-16, respectively. All patients also received four to six weeks of radiotherapy following chemotherapy and were re-evaluated for the possibility of surgery after four weeks of observation. All patients underwent pneumonectomies. Postoperative histological staging revealed complete responses in two patients, partial responses in three and no response in three. Patients were followed-up for seven to 33 (mean 21.5) months after the diagnosis of lung cancer. Six patients died 1, 2, 3, 10, 14 and 26 months postoperatively and two patients are alive, revealing no evidence of tumor recurrence 24 months postoperatively. Induction therapy may induce a better resectability by the conversion of the lung cancer to a lower clinical stage by the time of surgery.

Dietary fibers and fats alter rat colon protein kinase C activity: correlation to cell proliferation.

Protein kinase C activity and cell proliferation in rat proximal colonic mucosa were determined following diet modification with select fibers and fats for 3 wk. Rats were assigned to one of nine dietary groups: three fibers (cellulose or pectin at 6 g/100 g diet or fiber free) x three fats (beef tallow, corn oil, fish oil at 15 g/100 g diet). Protein kinase C activity was determined by measuring the phosphorylation of a highly selective synthetic peptide derived from myelin basic protein. In vivo cell proliferation was measured by bromodeoxyuridine incorporation into DNA. There was a significant main effect of fat (P = 0.0008) but not fiber (P = 0.375) on the ratio of membrane to cytosolic protein kinase C with diets containing fish oils resulting in the highest ratios, corn oils in the lowest ratios and beef tallow producing an intermediate ratio. There was an interactive effect of fat and fiber on the proliferative zone (P = 0.04). Pectin resulted in a significantly greater proliferative zone than did cellulose and the fiber-free diet but only when the fat source was corn oil. There was a positive correlation between proliferative zone and both membrane protein kinase C activity (r = 0.76, P = 0.02) and protein kinase C membrane:cytosol ratio (r = 0.64, P = 0.06). Although the positive relationship between proliferative zone and protein kinase C activity has been reported previously, the high membrane protein kinase C activity found with fish oil supplementation compared to the low activity found with corn oil supplementation was unexpected.(ABSTRACT TRUNCATED AT 250 WORDS)