Exploring the Role of Guidelines in Contributing to Medication Errors: A Descriptive Analysis of National Patient Safety Incident Data.

INTRODUCTION: Clinical guidelines can contribute to medication errors but there is no overall understanding of how and where these occur. OBJECTIVES: We aimed to identify guideline-related medication errors reported via a national incident reporting system, and describe types of error, stages of medication use, guidelines, drugs, specialties and clinical locations most commonly associated with such errors. METHODS: Retrospective analysis of reports to the National Reporting and Learning System for England and Wales. A hierarchical task analysis (HTA) was developed, describing expected practice when using guidelines. A free-text search was conducted of medication incident reports (2016-2021) using search terms related to common guidelines. All identified reports linked to moderate-severe harm or death, and a random sample of 5100 no/low-harm reports were coded to describe deviations from the HTA. A random sample of 500 cases were independently double-coded. RESULTS: In total, 28,217 reports were identified, with 608 relating to moderate-severe harm or death. Fleiss' kappa for interrater reliability was 0.46. Of the 5708 reports coded, 642 described an HTA step discrepancy (including four linked to a death), suggesting over 3200 discrepancies in the entire dataset of 28,217 reports. Discrepancies related to finding guidelines (n = 300 reports), finding information within guidelines (n = 166) and using information (n = 176). Discrepancies were most frequently identified for guidelines produced by a local organisation (n = 405), and most occurred during prescribing (n = 277) or medication administration (n = 241). CONCLUSION: Difficulties finding and using information from clinical guidelines contribute to thousands of prescribing and medication administration incidents, some of which are associated with substantial patient harm.

Osthole Enhances Osteogenesis in Osteoblasts by Elevating Transcription Factor Osterix via cAMP/CREB Signaling In Vitro and In Vivo.

Anabolic anti-osteoporotic agents are desirable for treatment and prevention of osteoporosis and fragility fractures. Osthole is a coumarin derivative extracted from the medicinal herbs Cnidium monnieri (L.) Cusson and Angelica pubescens Maxim.f. Osthole has been reported with osteogenic and anti-osteoporotic properties, whereas the underlying mechanism of its benefit still remains unclear. The objective of the present study was to investigate the osteopromotive action of osthole on mouse osteoblastic MC3T3-E1 cells and on mouse femoral fracture repair, and to explore the interaction between osthole-induced osteopromotive effect and cyclic adenosine monophosphate (cAMP) elevating effect. Osthole treatment promoted osteogenesis in osteoblasts by enhancing alkaline phosphatase (ALP) activity and mineralization. Oral gavage of osthole enhanced fracture repair and increased bone strength. Mechanistic study showed osthole triggered the cAMP/CREB pathway through the elevation of the intracellular cAMP level and activation of the phosphorylation of the cAMP response element-binding protein (CREB). Blockage of cAMP/CREB downstream signals with protein kinase A (PKA) inhibitor KT5720 partially suppressed osthole-mediated osteogenesis by inhibiting the elevation of transcription factor, osterix. In conclusion, osthole shows osteopromotive effect on osteoblasts in vitro and in vivo. Osthole-mediated osteogenesis is related to activation of the cAMP/CREB signaling pathway and downstream osterix expression.

Immunogenicity and escape mechanisms of allogeneic tendon-derived stem cells.

The immunogenicity of tendon-derived stem cells (TDSCs) has implications for their clinical use for the promotion of tendon repair. The immunogenicity and escape mechanisms of rat patellar TDSCs were examined after allogeneic transplantation. Our results showed that TDSCs exhibited low immunogenicity as evidenced by the following: (i) the incubation of target TDSCs with immunized serum did not show antibody recognition and did not induce the complement-dependent cytotoxicity; (ii) target TDSCs elicited a very low level of lymphocyte proliferation and did not exhibit host lymphocyte-mediated cytotoxicity; and (iii) target TDSCs dose dependently suppressed the phorbol 12-myristate 13-acetate (PMA)- and ionomycin-induced host lymphocyte proliferation. For the mechanistic studies, TDSCs expressed major histocompatibility complex (MHC)-I but a very low level of MHC-II, CD86 and CD80 for the induction of T-cell response. Also, TDSCs were found to express intracellular Fas and FasL. γ-IFN pretreatment did not increase the level of MHC-II and CD86 for the upregulation of immune response. Moreover, the immunosuppressive mediators indoleamine 2,3-dioxygenase (IDO) and transforming growth factor-beta 1 (TGF-ß1) were found not to be involved in the escape mechanism of target TDSCs from host lymphocyte attack. In conclusion, allogeneic TDSCs exhibited low immunogenicity. Allogeneic TDSCs might be used for transplantation.

Scx-transduced tendon-derived stem cells (tdscs) promoted better tendon repair compared to mock-transduced cells in a rat patellar tendon window injury model.

We hypothesized that the transplantation of Scx-transduced tendon-derived stem cells (TDSCs) promoted better tendon repair compared to the transplantation of mock-transduced cells. This study thus aimed to investigate the effect of Scx transduction on the expression of lineage markers in TDSCs and the effect of the resulting cell line in the promotion of tendon repair. Rat non-GFP or GFP-TDSCs were transduced with Scx or empty lentiviral vector (Mock) and selected by blasticidin. The mRNA expressions of Scx and different lineage markers were examined by qRT-PCR. The effect of the transplantation of GFP-TDSC-Scx on tendon repair was then tested in a rat unilateral patellar tendon window injury model. The transplantation of GFP-TDSC-Mock and scaffold-only served as controls. At week 2, 4 and 8 post-transplantation, the repaired patellar tendon was harvested for ex vivo fluorescent imaging, vivaCT imaging, histology, immunohistochemistry and biomechanical test. GFP-TDSC-Scx consistently showed higher expressions of most of tendon- and cartilage- related markers compared to the GFP-TDSC-Mock. However, the effect of Scx transduction on the expressions of bone-related markers was inconclusive. The transplanted GFP-TDSCs could be detected in the window wound at week 2 but not at week 4. Ectopic mineralization was detected in some samples at week 8 but there was no difference among different groups. The GFP-TDSC-Scx group only statistically significantly improved tendon repair histologically and biomechanically compared to the Scaffold-only group and the GFP-TDSC-Mock group at the early stage of tendon repair. There was significant higher expression of collagen type I in the window wound in the GFP-TDSC-Scx group compared to the other two groups at week 2. The transplantation of GFP-TDSC-Scx promoted healing at the early stage of tendon repair in a rat patellar tendon window injury model.

Allogeneic tendon-derived stem cells promote tendon healing and suppress immunoreactions in hosts: in vivo model.

The medium- to long-term healing effect and infiltration of inflammatory cells, after transplantation of allogeneic tendon-derived stem cell (TDSC) to the rat patellar tendon window wound, were examined. Allogeneic patellar TDSCs derived from a green fluorescent protein rat were used. The outcome of tendon healing and the infiltration of inflammatory cells were examined by histology and immunohistochemistry up to week 16 postinjury. The fate of the transplanted cells was examined by ex vivo fluorescent imaging and immunohistochemistry. Our results showed that the transplantation of allogeneic TDSCs promoted tendon healing with no increased risk of ectopic chondro-ossification up to week 16. A low infiltration of T cells, ED1 macrophages, ED2 macrophages, and mast cells in the window wound was obtained. The transplanted TDSCs were found in the window wound at week 1 and 2, but were absent after week 4 postinjury. In conclusion, allogeneic TDSCs promoted tendon repair in the medium to long term and exhibited weak immunoreactions and anti-inflammatory effects in the hosts after transplantation in a rat model. There was no increased risk of ectopic chondro-ossification after TDSC transplantation. The decrease in the number of transplanted cells with time suggested that allogeneic TDSCs did not promote tendon repair through direct differentiation.

Expression of Wnt pathway mediators in metaplasic tissue in animal model and clinical samples of tendinopathy.

OBJECTIVE: Tissue metaplasia is observed in both ossified failed healing animal model and clinical samples of tendinopathy. The Wnt signalling pathway plays a vital role in pathological calcification. We hypothesized that the Wnt signalling pathway might contribute to tissue metaplasia and failed healing in tendinopathy. This study aimed to examine the spatial-temporal expression of Wnt pathway mediators in an ossified failed tendon healing animal model and clinical samples of tendinopathy. The effect of Wnt3a on the osteogenic differentiation of tendon-derived stem cells (TDSCs) was also examined. METHODS: Ossified failed tendon healing was induced by the injection of collagenase into the patellar tendon of rats. At various times the tendons were harvested for immunohistochemical staining of Wnt3a, ß-catenin, Lrp5 and Tcf1. Patellar tendon samples were obtained from 13 patients with patellar tendinopathy (11 unossified and 2 ossified) and 10 controls. Immunohistochemical staining of Wnt3a, ß-catenin, Lrp5 and Tcf1 was similarly performed. Rat patellar TDSCs were treated with Wnt3a. The osteogenic differentiation of TDSCs was examined by ALP activity, alizarin red S staining and mRNA expression of osteogenic markers. RESULTS: There was increased expression of Wnt3a, ß-catenin, Lrp5 and Tcf1 in the healing fibroblast-like cells, chondrocyte-like cells and ossified deposits in the animal model and in some clinical samples of tendinopathy. Wnt3a increased ALP activity, calcium nodule formation and expression of osteogenic markers in TDSCs. CONCLUSION: Activation of the Wnt signalling pathway and its effect on TDSCs might contribute to tissue metaplasia and failed healing in some cases of tendinopathy.

Altered fate of tendon-derived stem cells isolated from a failed tendon-healing animal model of tendinopathy.

We hypothesized that altered fate of tendon-derived stem cells (TDSCs) might contribute to chondro-ossification and failed healing in the collagenase-induced (CI) tendon injury model. This study aimed to compare the yield, proliferative capacity, immunophenotypes, senescence, and differentiation potential of TDSCs isolated from healthy (HT) and CI tendons. TDSCs were isolated from CI and healthy Sprague-Dawley rat patellar tendons. The yield, proliferative capacity, immunophenotypes, and senescence of TDSCs (CI) and TDSCs (HT) were compared by colony-forming unit assay, BrdU assay, flow cytometry, and ß-galactosidase activity assay, respectively. Their osteogenic and chondrogenic differentiation potentials and mRNA expression of tendon-related markers were compared using standard assays. More TDSCs, which showed a lower proliferative potential and a higher cellular senescence were present in the CI patellar tendons compared to HT tendons. There was a higher alkaline phosphatase activity and mineralization in TDSCs (CI) in both basal and osteogenic media. More chondrocyte-like cells and higher proteoglycan deposition, Sox9 and collagen type II expression were observed in TDSCs (CI) pellets upon chondrogenic induction. There was a higher protein expression of Sox9, but a lower mRNA expression of Col1a1, Scx, and Tnmd in TDSCs (CI) in a basal medium. In conclusion, TDSCs (CI) showed altered fate, a higher cellular senescence, but a lower proliferative capacity compared to TDSCs (HT), which might contribute to pathological chondro-ossification and failed tendon healing in this animal model.

BMP-2 stimulated non-tenogenic differentiation and promoted proteoglycan deposition of tendon-derived stem cells (TDSCs) in vitro.

We hypothesized that BMP-2 might induce non-tenocyte differentiation and increase production of proteoglycans of tendon-derived stem cells (TDSCs). This study investigated the effects of BMP-2 on the differentiation and production of proteoglycans in TDSCs in vitro. Rat patellar TDSCs were treated without or with BMP-2. The osteogenic, adipogenic, chondrogenic, and tenogenic differentiation of TDSCs were assessed by (1) Alizarin red-S staining assay; (2) Oil Red-O staining assay; (3) haematoxylin-eosin staining, Safranin-O staining, immunohistochemical staining of Sox9, and collagen type II; and (4) qRT-PCR analysis of lineage-specific markers. The production of glycoaminoglycans (GAG) in the BMP-2-treated TDSCs was assessed by alcian blue staining. The mRNA expression of aggrecan (Acan), decorin (Dcn), biglycan (Bgn), and fibromodulin (Fmod) in TDSCs after BMP-2 treatment was assessed by qRT-PCR. BMP-2 promoted the osteogenic, adipogenic, and chondrogenic differentiation but inhibited tenogenic marker expression of TDSCs. GAG production and Acan increased while Dcn, Bgn, and Fmod decreased in TDSCs after BMP-2 stimulation. In conclusion, BMP-2 promoted GAG deposition, aggrecan expression, and enhanced non-tenocyte differentiation of TDSCs in vitro. The effect of BMP-2 on TDSCs might provide insights into the histopathological changes of tendinopathy.

Expression of chondro-osteogenic BMPs in clinical samples of patellar tendinopathy.

PURPOSE: The pathogenesis of patellar tendinopathy remains unclear. Expression of BMP-2/-4/-7 was reported in an ossified failed tendon healing animal model of patellar tendinopathy. This study aimed to investigate the expression of these chondro-osteogenic BMPs in clinical samples of patellar tendinopathy. METHODS: Patellar tendon samples were collected from 16 consecutive patients with patellar tendinopathy and 16 consecutive controls undergoing anterior cruciate ligament reconstruction with bone-patellar tendon-bone autograft in the authors' hospital after getting their consent. The expression of BMP-2/-4/-7 was examined in all samples using immunohistochemistry. Ossification observed in two tendinopathy samples was characterized by histology, alizarin red S staining, alcian blue staining, TRAP staining and immunohistochemical staining of Sox9, osteopontin (OPN) and osteocalcin (OCN). RESULTS: Regions of hypo- and hyper-cellularity and vascularity, with loss of crimp structure of collagen matrix, were observed in patellar tendinopathy samples. Round cells and in some cases, cells with typical chondrocyte phenotype were observed. For the ossified tendinopathy samples with positive alizarin red S staining, OPN-positive and Sox9-positive chondrocyte-like cells in alcian blue-stained extracellular matrix, OCN-positive osteoblast-like cells and TRAP-positive multi-nucleated cells were observed around the ossified deposits. No expression of BMP-2/-4/-7 was observed in healthy patellar tendons. However, the expression of BMP-2/-4/-7 was observed in all patellar tendinopathy samples with or without ossification. CONCLUSIONS: Clinical samples of patellar tendinopathy showed ectopic expression of BMP-2/-4/-7. This was not evident in control samples from healthy patellar tendons. LEVEL OF EVIDENCE: Prognostic studies, Level III.

Comparison of potentials of stem cells isolated from tendon and bone marrow for musculoskeletal tissue engineering.

The use of tendon-derived stem cells (TDSCs) as a cell source for musculoskeletal tissue engineering has not been compared with that of bone marrow stromal cells (BMSC). This study compared the mesenchymal stem cell (MSC) and embryonic stem cells (ESC) markers, clonogenicity, proliferative capacity, and multilineage differentiation potential of rat TDSC and BMSC in vitro. The MSC and ESC marker profiles of paired TDSC and BMSC were compared using flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Their clonogenicity and proliferative capacity were compared using colony-forming and 5-bromo-2'-deoxyuridine assays, respectively. The expression of tenogenic, osteogenic, and chondrogenic markers at basal state were examined using qRT-PCR. Their osteogenic, chondrogenic, and adipogenic differentiation potentials were compared using standard assays. TDSC and BMSC showed similar expression of CD90 and CD73. TDSC expressed higher levels of Oct4 than BMSC. TDSC exhibited higher clonogenicity, proliferated faster, and expressed higher tenomodulin, scleraxis, collagen 1 α 1 (Col1A1), decorin, alkaline phosphatase, Col2A1, and biglycan messenger RNA levels than BMSC. There was higher calcium nodule formation and osteogenic marker expression in TDSC than BMSC upon osteogenic induction. More chondrocyte-like cells and higher glycosaminoglycan deposition and chondrogenic marker expression were observed in TDSC than BMSC upon chondrogenic induction. There were more oil droplets and expression of an adipogenic marker in TDSC than BMSC upon adipogenic induction. TDSC expressed higher Oct4 levels, which was reported to positively regulate mesendodermal lineage differentiation, showed higher clonogenicity and proliferative capacity, and had greater tenogenic, osteogenic, chondrogenic, and adipogenic markers and differentiation potential than BMSC. TDSC might be a better cell source than BMSC for musculoskeletal tissue regeneration.

Tendon-derived stem cells (TDSCs) promote tendon repair in a rat patellar tendon window defect model.

Injured tendons heal slowly and often result in the formation of mechanically and functionally inferior fibrotic scar tissue or fibrous adhesions. This study investigated the use of tendon-derived stem cells (TDSCs) for tendon repair in a rat patellar tendon window defect model. Fibrin glue constructs with or without GFP-TDSCs were transplanted into the window defect. The patellar tendons were harvested for histology, ex vivo fluorescent imaging and biomechanical test at various time points up to week 4. Our results showed that TDSCs significantly enhanced tendon healing as indicated by the increase in collagen production as shown by hematolxylin stain-ability of the tissue, improvement of cell alignment, collagen fiber alignment and collagen birefringence typical of tendon. The labeled cells were observed at weeks 1 and 2 and became almost undetectable at week 4. Both the ultimate stress and Young's modulus were significantly higher in the TDSCs group compared to those in the fibrin glue group at week 4. In conclusion, TDSCs promoted earlier and better repair in a rat patellar tendon window defect model.

Expression of chondro-osteogenic BMPs in ossified failed tendon healing model of tendinopathy.

Chondrocytes phenotype/markers were expressed in clinical samples of tendinopathy and calcifying tendinopathy. This study examined the spatial-temporal expression of chondro-osteogenic Bone Morphogenetic Proteins (BMPs), which might contribute to ectopic chondro-osteogenesis and failed healing process in tendinopathy. Collagenase was injected into patellar tendon of rats to induce ossified failed tendon healing. At week 2, 4, 8, 12, and 16, the patella tendon was harvested for immunohistochemical staining and analysis of BMP-2/4/7. BMP-4/7 showed similar expression patterns, which was different from BMP-2. The expression of BMP-2 in the tendon matrix increased at week 2 and was reduced to nearly undetectable level afterwards except at the chondro-ossification sites. However, the expression of BMP-4/7 in the healing tendon fibroblast-like cells and matrix increased at week 2, reduced at week 4 and 8 and increased again at week 12 and 16, consistent with transient healing at week 8 in this animal model. There was increasing strong expression of BMP-4/7 in the chondrocyte-like cells in the un-ossified and ossified areas from week 8-16. BMP-4/7, besides BMP-2, might also contribute to ectopic chondro-osteogenesis and failed healing in tendon injuries. BMP-4/7, but not BMP-2, might be involved in regulating late events in ossified failed tendon healing.

Red yeast rice increases excretion of bile acids in hamsters.

OBJECTIVE: To investigate the hypocholesterolemic activity of red yeast rice (RYR) and its underlying mechanism. METHODS: Three groups of hamsters were fed either the control diet or one of the two experimental diets containing by weight 0.1% RYR (0.1RYR) or 0.3% RYR (0.3RYR). Blood (0.5 mL) was collected from the retro-orbital sinus into a heparinized capillary tube at the end of week 0, 3, and 6. Plasma lipoproteins were measured using enzymatic kits, while fecal neutral and acidic sterols were quantified using a gas-liquid chromatography. RESULTS: Plasma total cholesterol was reduced by 12% in 0.1RYR group and by 18% in 0.3RYR group compared with the control value. Similarly, plasma triacylglycerol was decreased by 11% in 0.1RYR group and by 24% in 0.3RYR group. Western blotting analysis demonstrated that RYR had no effect on sterol regulatory element binding protein 2, liver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7alpha-hydroxylase. HPLC analysis confirmed that RYR contained 0.88% monacolin K. It was recently found that RYR supplementation increased excretion of fecal acidic sterols by 3-4 folds compared with the control value. CONCLUSION: Hypocholesterolemic activity of RYR is mediated at least partially by enhancement of acidic sterol excretion.

Choosing hamsters but not rats as a model for studying plasma cholesterol-lowering activity of functional foods.

Rats and hamsters are commonly used rodents to test the efficacy of cholesterol-lowering functional foods. In general, a diet containing 1% cholesterol for rats whereas a diet containing 0.1% cholesterol for hamsters is used to induce the hypercholesterolemia. The present study was carried out to compare hamsters with rats as a hypercholesterolemia model. Golden Syrian hamsters and Sprague Dawley rats were randomly divided into four groups and fed one of the four diets containing 0-0.9% cholesterol. Results demonstrated that serum total cholesterol (TC) in hamsters was raised 73-81% higher than that in rats fed the same cholesterol diets. Unlike rats in which HDL-C accounted very little for serum TC, the lipoprotein profile in hamsters was closer to that in humans. We investigated interaction of higher cholesterol diets with 3-hydroxy-3-methylglutary-CoA (HMG-CoA) reductase, low-density lipoprotein receptor (LDL-R) and cholesterol-7alpha-hydroxylase (CYP7A1), sterol regulatory element binding protein-2 (SREBP-2), and liver X receptor (LXR-alpha). Results showed hamsters and rats metabolized cholesterol differently. In view that hamsters synthesize and excrete cholesterol and bile acids in a manner similar to that in humans, it is concluded that hamsters but not rats shall be chosen as a model to study efficacy of cholesterol-lowering functional foods.

Anti-hypertensive nutraceuticals and functional foods.

Epidemiological studies have demonstrated that elevated blood pressure is one of the major risk factors for stroke and coronary heart disease (CHD). A close association between blood pressure and the incidence of cardiovascular diseases is well established if systolic/diastolic blood pressure is above 140/90 mmHg. In recent years, nutraceuticals and functional foods have attracted considerable interest as potential alternative therapies for treatment of hypertension, especially for prehypertensive patients, whose blood pressure is marginally or mildly high but not high enough to warrant the prescription of blood pressure-lowering medications. This review summarizes the findings of recent studies on the chemistry, production, application, efficacy, and mechanisms of popular blood pressure-lowering nutraceuticals and functional foods including the Dietary Approaches to Stop Hypertension (DASH) diet plan, L-arginine, chlorogenic acid, fermented milk, garlic, onion, tea, soybean, ginger, hawthorn, and fish oil.

Dysregulated microRNAs and their predicted targets associated with endometrioid endometrial adenocarcinoma in Hong Kong women.

The objective of this study, a parallel study to global gene expression profiling, was to identify dysregulated microRNAs (miRNAs) associated with endometrioid endometrial adenocarcinoma (EEC), examine their correlation with clinico-pathological characteristics and identify predicted target genes of the dysregulated miRNAs. Using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), profiling of miRNA expression was performed in 30 EECs and 22 normal counterparts in which genome-wide gene expression had been previously profiled and reported. Clustering analysis identified 30 miRNAs which were significantly dysregulated in EEC. The expression of a sub-group of miRNAs was significantly correlated with clinico-pathological characteristics including stage, myometrial invasion, recurrence and lymph node involvement. By searching for predicted miRNA targets that were linked to the dysregulated genes previously identified, 68 genes were predicted as candidate targets of these 30 dysregulated miRNAs. miR-205 was significantly overexpressed in EECs compared with normal controls. After transfection of a miR-205 inhibitor, the expression of miR-205 in endometrial cancer cell line RL95-2 cells decreased whereas its predicted target gene, JPH4, showed increased protein expression. JPH4 seems to be a real miR-205 target in vitro and in vivo, and a candidate tumor suppressor gene in EEC. Based on this study in EEC, miRNAs predicted to be involved in tumorigenesis and tumor progression have been identified and placed in the context of the transcriptome of EEC. This work provides a framework on which further research into novel diagnosis and treatment of EEC can be focused.

Conjugated and non-conjugated octadecaenoic acids affect differently intestinal acyl coenzyme A: cholesterol acyltransferase activity.

We investigated the relative hypocholesterolemic activity of linoleic acid (LA), conjugated linoleic acid (CLA), alpha-linolenic acid (LN) and conjugated linolenic acid (CLN) in hamsters. Five groups of hamsters (n=10 each) were fed either the control diet or one of the four fatty acids-supplemented diets for 6 weeks. Results demonstrated that the four octadecaenoic acids decreased plasma cholesterol differently, with CLA being the most effective. Western blotting and RT-PCR analysis demonstrated that the four octadecaenoic acids had no effect on sterol regulatory element binding protein-2 (SREBP-2), liver X receptor (LXR), 3-hydroxy-3-methylglutary-CoA reductase (HMGR), LDL receptor (LDLR), and cholesterol-7alpha-hydroxylase (CYP7A1). However, the four octadecaenoic acids increased the excretion of fecal neutral sterols with CLA being most effective followed by LN, LA and CLN, suggesting they all differentially affect cholesterol absorption. Dietary CLA was associated with the least intestinal acyl coenzyme A: cholesterol acyltransferase (ACAT) activity followed by LN, LA and CLN in a decreasing trend. Since esterification of cholesterol is catalyzed by intestinal ACAT, and is a rate-limiting step in cholesterol absorption, it was concluded that the varying effects of CLA, LN, LA and CLN on blood cholesterol were mediated, at least in part, by their inhibition on intestinal ACAT activity.

Dosing effects of an antiosteoporosis herbal formula--a preclinical investigation using a rat model.

Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psoraleae are three frequently used Chinese herbs traditionally used for tonifying the 'kidney system'. They were selected for the present study to formulate an herbal preparation with a weight ratio of 5:4:1 based on their phytochemical, nature, documented treatment efficacy and toxicity. The dosing effects (1 g/day, 0.5 g/day and 0.175 g/day) of the antiosteoporosis function of the water extract of this formula were tested in ovariectomy- and calcium deficiency-induced osteoporotic rats. Eleven weeks of herbal treatment demonstrated a beneficial effect on the preservation of bone mineral density (BMD) at the femur neck in a dose-dependent manner with the preference for higher dosage. No significant increase in uterus weight was observed in the herbal formula treated rats. In addition, microarray data of kidney tissue revealed that this herbal formula was able to down-regulate the expression of phase II drug metabolizing enzymes, similar to the effects of estrogens.