Gastroparesis refers to abnormal gastric motility characterized by delayed gastric emptying in the absence of mechanical obstruction. The most common etiologies include diabetes, post-surgical and idiopathic. The most...Gastroparesis refers to abnormal gastric motility characterized by delayed gastric emptying in the absence of mechanical obstruction. The most common etiologies include diabetes, post-surgical and idiopathic. The most common symptoms are nausea, vomiting and epigastric pain. Gastroparesis is estimated to affect 4% of the population and symptomatology may range from little effect on daily activity to severe disability and frequent hospitalizations. The gold standard of diagnosis is solid meal gastric scintigraphy. Treatment is multimodal and includes dietary modification, prokinetic and anti-emetic medications, and surgical interventions. New advances in drug therapy, and gastric electrical stimulation techniques have been introduced and might provide new hope to patients with refractory gastroparesis. In this comprehensive review, we discuss gastroparesis with emphasis on the latest developments; from the perspective of the practicing clinician.展开更多
The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration,especially for the ...The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration,especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal,dynamic and static ocular barriers. Also,therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades,ocular drug delivery research acceleratedly advanced towards developing a novel,safe and patient compliant formulation and drug delivery devices/techniques,which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also,it includes development of conventional topical formulations such as suspensions,emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand,for posterior ocular delivery,research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreo-retinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topicaldrops. Also,these novel devices and/or formulations are easy to formulate,no/negligibly irritating,possess high precorneal residence time,sustain the drug release,and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also,recent developments with other ocular drug delivery strategies employing in situ gels,implants,contact lens and microneedles have been discussed.展开更多
AIM: To study the effects of chromic-P32 phosphate (32p colloids) interstitial administration in Pc-3 implanted pancreatic carcinoma, and investigate its anticancer mechanism.METHODS: Ninety-eight tumor bearing nude m...AIM: To study the effects of chromic-P32 phosphate (32p colloids) interstitial administration in Pc-3 implanted pancreatic carcinoma, and investigate its anticancer mechanism.METHODS: Ninety-eight tumor bearing nude mice werekilled at different time points after the injection of 32Pcolloids to the tumor core with observed radioactivity. The light microscopy, transmission electron microscopy (TEM) and immuno-histochemistry and flow cytometry were used to study the rates of tumor cell necrosis, proliferating cell nuclear antigen index, the micro vessel density (MVD). The changes of the biological response to the lymphatic transported 32p colloids in the inguinal lymph node (ILN) were dynamically observed, and the percentage of tumor cell apoptosis, and Apo2.7, caspase-3, Bcl-2, Baxrelated gene expression were observed too.RESULTS: The half-life of effective medication is 13 dafter injection of 32P colloids to the tumor stroma, in 1-6groups, the tumor cell necrosis rates were 20%, 45%,65%, 70%, 95% and 4%, respectively (F= 4.14-105.36, P<0.01). MVD were 38.5±4.0, 28.0±2.9, 17.0±2.9, 8.8±1.5,5.7±2.3 and 65.0±5.2 (t= 11.9-26.1, P<0.01), respectively.Under TEM fairly differentiated Pc-3 cells were found. Thirty days after medication, tumors were shrunk and dried with scabs detached, and those in control group increased in size prominently with plenty of hypodermic blood vessels. In all animals the ILN were enlarged but in medicated animals they appeared later and smaller than those in control group. The extent of irradiative injury in ILN was positively correlated to the dosage of medication. Typical tumor cell apoptosis could be found under TEM inanimals with intra-tumoral injection of low dosed 32P colloids. The peak of apoptosis occurred in 2.96 MBq group and 24 h after irradiation. In the course of irradiationinduced apoptosis, the value of Bcl-2/Bax was down regulated; Apo2.7 and caspase-3 protein expression were prominently increased dose dependently. CONCLUSION: 32p colloids intra-tumor injection having prominent anticancer effectiveness may reveal the ability of promoting cell differentiation. The low dose 32P colloids may induce human pancreatic carcinoma Pc-3 implanted tumor cell apoptosis; Apo2.7, caspase-3, Bcl-2 and Bax protein participated in regulating the process of irradiation induced cell apoptosis.展开更多
This study was aimed to develop the Chinese herbal formula with dysentery arresting and antidiarrheal effect. [Method] The Chinese herbal for-mulation was used to carry out the clinical curative effect test and pharma...This study was aimed to develop the Chinese herbal formula with dysentery arresting and antidiarrheal effect. [Method] The Chinese herbal for-mulation was used to carry out the clinical curative effect test and pharmacological test for il livestock. [Results] Curative effect test showed that the formula had good effect on abdominal pain, diarrhea and fecal changes of livestock, and the cure rate reached up to 92%. Pharmacological experiments showed that the formula had sig-nificant inhibitory effect on the gastrointestinal motility of the tested animals, and the diarrhea arresting and dysentery treating effect of the formula was also extremely significant. In addition, the formula was safe for tested animals, proving to be reli-able. [Conclusion] The formula has distinct curative effect on treating white scour of piglets, yel ow scour of piglets, livestock gastroenteritis and lienteric diarrhea, and it can also be used in veterinary clinic, as wel as be used as feed additive.展开更多
Since the calcium channel blocker (CCB) has become one of the most prescribed agents for antihypertensive monotherapy in the world, this brief review will focus on the recent research and development of the dihydrop...Since the calcium channel blocker (CCB) has become one of the most prescribed agents for antihypertensive monotherapy in the world, this brief review will focus on the recent research and development of the dihydropyridine (DHP) CCB, addressing pharmacological mecha- nisms for the clinical efficacy of the third and fourth generations of the DHP CCBs, especially on their possible central mechanisms underlying lowering blood pressure.展开更多
AIM: To investigate the efficacy of combination treatment of IFN-α and lamivudine compared to lamivudine monotherapy, after 24 mo of administration in HBeAgnegative hepatitis B patients. METHODS: Fifty consecutive ...AIM: To investigate the efficacy of combination treatment of IFN-α and lamivudine compared to lamivudine monotherapy, after 24 mo of administration in HBeAgnegative hepatitis B patients. METHODS: Fifty consecutive patients were randomly assigned to receive IFN-α-2b (5 MU thrice per week, n = 24) plus lamivudine (100 mg daily) or lamivudine only (n = 26) for 24 mo. Patients were followed up for further 6 mo. The primary outcome was the proportion with sustained virological response (undetectable serum HBV DNA concentrations) and or sustained biochemical response (transaminase levels within normal range) at 30 mo (6 mo after the end of therapy). Secondary end-points were timed from initial virological (biochemical) response to VBR (BBR, respectively) and the emergence of YMDD mutants across the two arms. RESULTS: Five of twenty-four (21%) patients in the combination arm vs 3/26 (12%) in the lamivudine arm had sustained response (i.e., normal serum transaminase levels and undetectable HBV DNA by PCR assay) 6 mo after treatment discontinuation. A reduction in the emergence of YMDD mutants and in the development of virological breakthroughs was observed in patients receMng combination treatment (10% vs46% , P= 0.01 and 14% vs46% , P= 0.03, respectively). Time from initial virologic response to virologic breakthrough (VBR) was greater among initial responders receiving combination treatment compared to those receiving lamivudine (22.9 mo vs 15.9 mo, respectively; P = 0.005).CONCLUSION: Our results demonstrate that IFN-α plus lamivudine combination therapy does not increase the sustained response, compared to lamivudine. However, combination therapy reduces the likelihood of VBR due to YMDD mutants and prolongs the time period until the breakthrough development.展开更多
AIM: TO investigate the severity of acute pancreatitis (AP) is associated to the intensity of leukocyte activation, inflammatory up-regulation and microcirculatory disruption associated to ischernia-reperfusion inj...AIM: TO investigate the severity of acute pancreatitis (AP) is associated to the intensity of leukocyte activation, inflammatory up-regulation and microcirculatory disruption associated to ischernia-reperfusion injury. Hicrovascular integrity and inhibition of pro-inflammatory mediators are key-factors in the evolution of AP. Relaxin is an insulin-like hormone that has been attributed vasorelaxant properties via the nitric oxide pathway while behaving as a glucocorticoid receptor agonist. METHODS: AP was induced by the bilio-pancreatic duct-outlet-exclusion closed-duodenal-loops model. Treatment with relaxin was done at different timepoints. Nitric oxide synthase inhibition by L-NAME and glucocorticoid receptor (GR) blockage by mifepristone was considered. AP severity was assessed by biochemical and histopathological analyses. RESULTS: Treatment with relaxin reduced serum amylase, lipase, C-reactive protein, IL-6, IL-10, hsp72, LDH and 8-isoprostane as well as pancreatic and lung myeloperoxidase. Acinar and fat necrosis, hemorrhage and neutrophil infiltrate were also decreased. ATP depletion and ADP/ATP ratio were reduced while caspases 2-3-8 and 9 activities were increased. L-NAME and mifepristone decreased the efficiency of relaxin. CONCLUSION: Relaxin resulted beneficial in the treatment of AP combining the properties of a GR agonist while preserving the microcirculation and favoring apoptosis over necrosis.展开更多
AIM: To study the inhibitory effects of siRNAs targeting different hTERT sequences and to screen the effective siRNA sequence.METHODS: Five double-stranded siRNAs targeting coding and non-coding regions of hTERT gene ...AIM: To study the inhibitory effects of siRNAs targeting different hTERT sequences and to screen the effective siRNA sequence.METHODS: Five double-stranded siRNAs targeting coding and non-coding regions of hTERT gene were designed and synthesized by T7 transcription system in vitro. siRNA4sequence was screened by full length gene targeting technique and the rest of the siRNA sequences were selected randomly. After being purified by ethanol precipitation, the siRNAs were transfected to the human hepatocellular carcinoma cell (HepG2) by Lipofectamine 2000TM. At 48-72 h after siRNAs transfection, MTT assay,RT-PCR and Western-blot were applied to evaluate the effects of siRNAs on cell growth, mRNA and protein expression level of hTERT gene, respectively.RESULTS: Compared to the control cells, the cells treated with the five double-stranded siRNAs exhibited different degrees of inhibition of cell proliferation in a dose-dependent manner. siRNA2 and siRNA4, exhibited obvious effects of inhibiting hTERT mRNA and protein expression in HepG2cells.CONCLUSION: siRNAs targeting different hTERT sequences have significantly various inhibitory effects on hTERT gene expression. The siRNA sequence screened by full length gene targeting technique has comparable inhibitory effect with the rest siRNA sequences screened by random selection, suggesting that siRNAs and antisense oligonucleic acids may have the same effective target sites. Compared with chemical synthesis method,synthesizing double-stranded siRNA by T7 transcription system in vitro is a rapid, simple, and inexpensive method suitable for screening high-effect siRNA targeting site for specific gene.展开更多
AIM: To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to de...AIM: To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to demonstrate the colon-specific delivery of rebamipide with or without absorption enhancers using chitosan capsule as a carrier. METHODS: The permeability of rebamipide was evaluated using an in vitro diffusion chamber system, and the effects of some absorption enhancers on the permeability via colon were further investigated. The release of rebamipide from chitosan or gelatin capsule was studied by Japan Pharmacopoeia rotating basket method. The colonic and plasma concentrations were analyzed by high performance liquid chromatography (HPLC) to evaluate colon-targeting action after oral administration of various dosage forms, and rebamipide with absorption enhancers in chitosan dosage forms. RESULTS: The permeability of rebamipide across the jejunal or ileal membranes was higher than the colonic membranes. Both sodium laurate (C12) and labrasol signifi cantly increased permeability across the colon membranes. On the other hand, the release of rebamipide from chitosan capsule was less than 10%totally within 6 h. The area under concentration-time profile of drug in the colon mucosa using chitosan capsules (AUCLI, 1 6011.2 ng·h/g) was 2.5 times and 4.4 times greater than using gelatin capsules and CMC suspension, respectively. Meanwhile, the area under concentration-time profile of drug in the plasma (AUCPL) was 1016.0 ng·h/mL for chitosan capsule, 1887.9 ng·h/mL for CMC suspension p and 2163.5 ng·h/mL for gelatin capsule. Overall, both AUCLI and AUCPL were increased when C12 was co-administrated, but the increase of AUCLI was much greater; the drug delivery index (DDI) was more than 1 compared with simple chitosan capsule group. CONCLUSION: There was a regional difference in the permeability of Rabamipide across the jejunum, ileum and the colon, and passive diffusion seems to be one of the major transport mechanisms of rebamipide. Absorption enhancers can increase the permeability of rebamipide across the colon tissue signifi cantly. In addition, chitosan capsule may be a useful carrier to deliver rebamipide to the colon specifi cally and the co-administration of C12 with rebamipide may also be very useful in local treatment.展开更多
Chronic heart failure and depressive disorders have a high prevalence and incidence in the elderly. Several studies have shown how depression tends to exacerbate coexisting chronic heart failure and its clinical outco...Chronic heart failure and depressive disorders have a high prevalence and incidence in the elderly. Several studies have shown how depression tends to exacerbate coexisting chronic heart failure and its clinical outcomes and vice versa, especially in the elderly. The negative synergism between chronic heart failure and depression in the elderly may be approached only taking into account the multifaceted pathophysiological characteristics underlying both these conditions, such as behavioural factors, neurohormonal activation, inflammatory mediators, hypercoagulability and vascular damage. Nevertheless, the pathophysiological link between these two conditions is not well established yet. Despite the high prevalence of depression in chronic heart failure elderly patients and its negative prognostic value, it is often unrecognized especially because of shared symptoms. So the screening of mood disorders, using reliable questionnaires, is recommended in elderly patients with chronic heart failure, even if cannot substitute a diagnostic interview by mental health professionals. In this setting, treatment of depression requires a multidisciplinary approach including: psychotherapy, antidepressants, exercise training and electroconvulsive therapy. Pharmacological therapy with selective serotonin reuptake inhibitors, despite conflicting results, improves quality of life but does not guarantee better outcomes. Exercise training is effective in improving quality of life and prognosis but at the same time cardiac rehabilitation services are vastly underutilized.展开更多
AIM: To evaluate the therapeutic effect of Chunggan extract (CGX), a modified traditional Chinese hepatotherapeutic herbal, on the dimethylnitrosamine (DMN)-induced chronic liver injury model in rats. METHODS: L...AIM: To evaluate the therapeutic effect of Chunggan extract (CGX), a modified traditional Chinese hepatotherapeutic herbal, on the dimethylnitrosamine (DMN)-induced chronic liver injury model in rats. METHODS: Liver injuries were induced in Wistar rats by injection of DMN (ip, 10 mg/mL per kg) for 3 consecutive days per week for 4 wk. The rats were administered with CGX Coo, 100 or 200 mg/kg per day) or distilled water as a control daily for 4 wk starting from the 15^th d of the DMN treatment. Biochemical parameters (serum albumin, bilirubin, ALP, AST and ALT), lipid peroxides, hydroxyproline, as well as histological changes in liver tissues were analyzed. In addition, gene expression of TNF-α, TGF-β, TIMP-1, TIMP-2, PDGF-β, and MMP-2, all of which are known to be associated with liver fibrosis, were analyzed using real-time PCR. RESULTS: CGX administration restored the spleen weight to normal alter having been increased by DMN treatment. Biochemical analysis of the serum demonstrated that CGX significantly decreased the serum level of ALP (P 〈 0.05), ALT (P 〈 0.02), and AST (P 〈 0.02) that had been elevated by DMN treatment. CGX administration moderately lowered lipid peroxide production and markedly lowered hydroxyproline generation caused by DMN treatment in accordance with histopathological examination. DMN treatment induced a highly upregulated expression of TNF-α, TGF-β,TIMP-1, TIMP-2, PDGF-β, and MMP-2. Of these, the gene expression encoding PDGF-β and MMP-2 was still further enhanced 2 wk after secession of the 4-wk DMN treatment, and was remarkably ameliorated by CGX administration. CONCLUSION: CGX exhibits hepatotherapeutic properties against chronic hepatocellular destruction and consequential liver fibrosis.展开更多
AIM: To investigate in vitro and in vivo therapeutic effects of histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 on biliary tract cancer. METHODS: Cell growth inhibition by NVP-LAQ824 and NVP-LBH589 was stud...AIM: To investigate in vitro and in vivo therapeutic effects of histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 on biliary tract cancer. METHODS: Cell growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 7 human biliary tract cancer cell lines by MTT assay. In addition, the antitumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral drug mechanism was assessed by immunoblotting for acH4 and p21^WAFl/CIP-1, PARP assay, cell cycle analysis, TUNEL assay, and immunhistochemistry for MIB-1. RESULTS: In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines [mean IC50 (3 d) 0.11 and 0.05 μmol/L, respectively], and was associated with hyperacetylation of nucleosomal histone H4, increased expression of p21^WAF-1/CIP-1, induction of apoptosis (PARP cleavage), and cell cycle arrest at G2/M checkpoint. After 28 d, NVP- LBH589 significantly reduced tumor mass by 66% (bile duct cancer) and 87% (gallbladder cancer) in vivo in comparison to placebo, and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed increased apoptosis by TUNEL assay and reduced cell proliferation (MIB-1). CONCLUSION: Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human biliary tract cancer in vitro. In addition, NVP-LBH589 demonstrated significant in vivo activity and potentiated the efficacy of gemcitabine. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended.展开更多
Hepatocellular carcinoma (HCC) still remains a considerable challenge for surgeons.Surgery,including liver transplantation,is the most important therapeutic approach for patients with this disease.HCC is frequently di...Hepatocellular carcinoma (HCC) still remains a considerable challenge for surgeons.Surgery,including liver transplantation,is the most important therapeutic approach for patients with this disease.HCC is frequently diagnosed at advanced stages and has a poor prognosis with a high mortality rate even when surgical resection has been considered potentially curative.This brief report summarizes the current status of the management of this malignancy and includes a short description of new pharmacological approaches in HCC treatment.展开更多
A gastric carcinoid tumor concomitant with gastrointestinal stromal tumor (GIST) is rarely encountered in clinical practice. We report a 65-year-old female who had a 0.8 cm gastric carcinoid tumor on the posterior w...A gastric carcinoid tumor concomitant with gastrointestinal stromal tumor (GIST) is rarely encountered in clinical practice. We report a 65-year-old female who had a 0.8 cm gastric carcinoid tumor on the posterior wall of the upper gastric corpus detected during an esophagogastroduodenoscopy at a routine physical examination, and a concomitant 1.1 cm GIST on the anterior wall of the upper gastric corpus incidentally found during surgery of the gastric carcinoid tumor. Normal serum gastrin level and histological findings suggested that she had a type 111 gastric carcinoid tumor and a GIST which were categorized a very low risk of malignancy, based on their small size and lack of mitosis. Both tumors were treated successfully by surgical excision. The patient had an uneventful recovery. Neither recurrence nor metastasis was found after a 28-mo follow-up.展开更多
Noni juice (Morinda citrifolia) has been approved for use as a safe food within the European Union, following a review of safety. Since approval, three cases of acute hepatitis in Austrian noni juice consumers have ...Noni juice (Morinda citrifolia) has been approved for use as a safe food within the European Union, following a review of safety. Since approval, three cases of acute hepatitis in Austrian noni juice consumers have been published, where a causal link is suggested between the liver dysfunction and ingestion of anthraquinones from the plant. Measurements of liver function in a human clinical safety study of TAHITIAN NONI Juice, as well as subacute and subchronic animal toxicity tests revealed no evidence of adverse liver effects at doses many times higher than those reported in the case studies. Additionally, M. citrifolia anthraquinones occur in the fruit in quantities too small to be of any toxicological significance. Further, these do not have chemical structures capable of being reduced to reactive anthrone radicals, which were implicated in previous cases of herbal hepototoxicity. The available data reveals no evidence of liver toxicity.展开更多
AIM: Itopride is a newly developed prokinetic agent, which enhances gastric motility through both antidopaminergic and anti-acetylcholinesterasic actions. The importance of esophageal motor dysfunction in the pathoge...AIM: Itopride is a newly developed prokinetic agent, which enhances gastric motility through both antidopaminergic and anti-acetylcholinesterasic actions. The importance of esophageal motor dysfunction in the pathogenesis of gastro-esophageal reflux disease (GERD) makes it interesting to examine the effect of itopride on esophageal acid exposure.METHODS: The effect of itopride on esophageal acid reflux variables for 24 h was studied in 26 patients with GERD symptoms, pre-entry total acid exposure time (pH〈4) of more than 5% and mild esophagitis (SavaryMiller grades I, II) proven by endoscopy. Ambulatory 24hpH-metry and symptom assessment were performed after treatments with 150 or 300 mg itopride thrice a day (t.i.d.) for 30 d in random order, using an open label method.For evaluating the safety of itopride, blood biochemical laboratory test was performed and the serum prolactin level was also examined before and after treatment.RESULTS: Total symptom score was significantly decreased after treatment in 150- or 300-mg group. Itopride 300 mg was significantly effective than 150 mg on decreasing the total per cent time with pH〈4, total time with pH〈4 and DeMeester score. No serious adverse effects were observed with administration of itopride in both groups.CONCLUSION: Itopride 100 mg t.i.d, is effective on decreasing pathologic reflux in patient with GERD and therefore it has the potential to be effective in the treatment of this disease.展开更多
Accumulating evidence demonstrates that resveratrol, a natural polyphenolic compound extracted from plants, inhibit inflammation when administered. It has direct effects on suppression of platelet coagulation and cyto...Accumulating evidence demonstrates that resveratrol, a natural polyphenolic compound extracted from plants, inhibit inflammation when administered. It has direct effects on suppression of platelet coagulation and cytokines production in many experimental models. Because microcirculation occlusion and cytokines over-production is involved in many diseases such as acute pancreatitis (AP), the discovery of resveratrol as platelet and cytokines inhibitors has shed light on the treatment of AP, which still has significant mortality and morbidity. It is anticipated that this natural polyphenol could serve as a therapeutic compound in managing AP through different pathways.展开更多
AIM: To examine the effects of traditional Chinese medicine (TCM) on alcohol-induced fatty liver in rats. TCM consists of Astragalus membranaceus, Morus alba, Crataegus pinnatifida, Alisma orientale, Salvia miltior...AIM: To examine the effects of traditional Chinese medicine (TCM) on alcohol-induced fatty liver in rats. TCM consists of Astragalus membranaceus, Morus alba, Crataegus pinnatifida, Alisma orientale, Salvia miltiorrhiza, and Pueraria lobata. METHODS: The rats were separated randomly into five groups. One (the CD group) was fed a control diet for 10 wk, another (the ED group) fed an ethanol-containing isocaloric liquid diet for 10 wk, and the last three (the TCM group) were fed an ethanol-containing isocaloric liquid diet for 10 wk and dosed orally with TCM (222 mg/kg.d, TCM222; 667 mg/kg·d, TCM667; and 2 000 mg/kg.d, TCM2000, respectively) weekly during the last 4 wk. RESULTS: ED group developed fatty liver according to lipid profile and liver histological findings. Compared with the control group, liver/body weight, serum triglyceride (TG) and total cholesterol (TC), liver TG and TC, serum alanine aminotransferase (ALT) and aspartic aminotransferase (AST) significantly increased in the ED group. Whereas, in the rats administered with TCM, liver/body weight, serum TG and TC, liver TG and TC, serum ALT and AST were significantly decreased, and the degree of hepatic lipid droplets was markedly improved compared with those in the ED group. CONCLUSION: TCM treatment causes significant reduction in alcohol-induced lipid hepatic accumulation, reversing fatty liver and liver damage, and can be used as a remedy for alcoholic fatty liver.展开更多
Objective To evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA). Methods A total of 223 patients satisfying the American College of Rheumatology criteria for knee OA were chosen fo...Objective To evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA). Methods A total of 223 patients satisfying the American College of Rheumatology criteria for knee OA were chosen for this 17-week, randomized, double-dummy, diclofenac sodium-controlled trial, with diacerein dosage of 100 mg/d and diclofenac sodium of 75mg/d. Efficacy and safety of both drugs were evaluated. Results Totally 106 patients in the diacerein group and 107 patients in the diclofenac group were considered qualified for the evaluation. After 12 weeks of treatment, the total effective rates of patients/physicians’ overall assessment in diacerein and diclofenac groups were 65.4%/61.6% and 61.2%/61.2%, respectively (P>0.05). The primary efficacy parameter [visual analog scale (VAS) assessment of pain on 20 metres walking] and the secondary efficacy parameters [tenderness on palpation, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-item Short-Form (SF-36) Health Survey] significantly improved compared with baseline in both groups (P<0.05). In the follow-up period, there were no obvious changes in above parameters in diacerein group. However, in diclofenac group, pain on 20 metres walking, tenderness on palpation, and WOMAC became aggravated after withdrawing the drug for 4 weeks (P<0.05). Moreover, the consumption of paracetamol was significantly lower in diacerein group than in diclofenac group during follow-up (P<0.001). The incidences of related adverse events were 35.7% in diacerein and 45.1% in diclofenac group, respectively. Mild-to-moderate gastrointestinal disorders were the most frequent adverse events. Conclusions Diacerein is as effective as diclofenac sodium in treating patients with knee OA. Furthermore, it has better extended effect and a good safety profile. It is generally well tolerated and has no severe adverse effect.展开更多
文摘Gastroparesis refers to abnormal gastric motility characterized by delayed gastric emptying in the absence of mechanical obstruction. The most common etiologies include diabetes, post-surgical and idiopathic. The most common symptoms are nausea, vomiting and epigastric pain. Gastroparesis is estimated to affect 4% of the population and symptomatology may range from little effect on daily activity to severe disability and frequent hospitalizations. The gold standard of diagnosis is solid meal gastric scintigraphy. Treatment is multimodal and includes dietary modification, prokinetic and anti-emetic medications, and surgical interventions. New advances in drug therapy, and gastric electrical stimulation techniques have been introduced and might provide new hope to patients with refractory gastroparesis. In this comprehensive review, we discuss gastroparesis with emphasis on the latest developments; from the perspective of the practicing clinician.
文摘The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration,especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal,dynamic and static ocular barriers. Also,therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades,ocular drug delivery research acceleratedly advanced towards developing a novel,safe and patient compliant formulation and drug delivery devices/techniques,which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also,it includes development of conventional topical formulations such as suspensions,emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand,for posterior ocular delivery,research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreo-retinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topicaldrops. Also,these novel devices and/or formulations are easy to formulate,no/negligibly irritating,possess high precorneal residence time,sustain the drug release,and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also,recent developments with other ocular drug delivery strategies employing in situ gels,implants,contact lens and microneedles have been discussed.
基金Supported by the Jiangsu Province Public Health Bureau Foundation,No. H200117, and Jiangsu Science Technology Foundation, No.2000004
文摘AIM: To study the effects of chromic-P32 phosphate (32p colloids) interstitial administration in Pc-3 implanted pancreatic carcinoma, and investigate its anticancer mechanism.METHODS: Ninety-eight tumor bearing nude mice werekilled at different time points after the injection of 32Pcolloids to the tumor core with observed radioactivity. The light microscopy, transmission electron microscopy (TEM) and immuno-histochemistry and flow cytometry were used to study the rates of tumor cell necrosis, proliferating cell nuclear antigen index, the micro vessel density (MVD). The changes of the biological response to the lymphatic transported 32p colloids in the inguinal lymph node (ILN) were dynamically observed, and the percentage of tumor cell apoptosis, and Apo2.7, caspase-3, Bcl-2, Baxrelated gene expression were observed too.RESULTS: The half-life of effective medication is 13 dafter injection of 32P colloids to the tumor stroma, in 1-6groups, the tumor cell necrosis rates were 20%, 45%,65%, 70%, 95% and 4%, respectively (F= 4.14-105.36, P<0.01). MVD were 38.5±4.0, 28.0±2.9, 17.0±2.9, 8.8±1.5,5.7±2.3 and 65.0±5.2 (t= 11.9-26.1, P<0.01), respectively.Under TEM fairly differentiated Pc-3 cells were found. Thirty days after medication, tumors were shrunk and dried with scabs detached, and those in control group increased in size prominently with plenty of hypodermic blood vessels. In all animals the ILN were enlarged but in medicated animals they appeared later and smaller than those in control group. The extent of irradiative injury in ILN was positively correlated to the dosage of medication. Typical tumor cell apoptosis could be found under TEM inanimals with intra-tumoral injection of low dosed 32P colloids. The peak of apoptosis occurred in 2.96 MBq group and 24 h after irradiation. In the course of irradiationinduced apoptosis, the value of Bcl-2/Bax was down regulated; Apo2.7 and caspase-3 protein expression were prominently increased dose dependently. CONCLUSION: 32p colloids intra-tumor injection having prominent anticancer effectiveness may reveal the ability of promoting cell differentiation. The low dose 32P colloids may induce human pancreatic carcinoma Pc-3 implanted tumor cell apoptosis; Apo2.7, caspase-3, Bcl-2 and Bax protein participated in regulating the process of irradiation induced cell apoptosis.
基金Supported by the Science and Technology Major Project of Guizhou Province(Qiankehe Major Special Projects(2007)6013)~~
文摘This study was aimed to develop the Chinese herbal formula with dysentery arresting and antidiarrheal effect. [Method] The Chinese herbal for-mulation was used to carry out the clinical curative effect test and pharmacological test for il livestock. [Results] Curative effect test showed that the formula had good effect on abdominal pain, diarrhea and fecal changes of livestock, and the cure rate reached up to 92%. Pharmacological experiments showed that the formula had sig-nificant inhibitory effect on the gastrointestinal motility of the tested animals, and the diarrhea arresting and dysentery treating effect of the formula was also extremely significant. In addition, the formula was safe for tested animals, proving to be reli-able. [Conclusion] The formula has distinct curative effect on treating white scour of piglets, yel ow scour of piglets, livestock gastroenteritis and lienteric diarrhea, and it can also be used in veterinary clinic, as wel as be used as feed additive.
文摘Since the calcium channel blocker (CCB) has become one of the most prescribed agents for antihypertensive monotherapy in the world, this brief review will focus on the recent research and development of the dihydropyridine (DHP) CCB, addressing pharmacological mecha- nisms for the clinical efficacy of the third and fourth generations of the DHP CCBs, especially on their possible central mechanisms underlying lowering blood pressure.
文摘AIM: To investigate the efficacy of combination treatment of IFN-α and lamivudine compared to lamivudine monotherapy, after 24 mo of administration in HBeAgnegative hepatitis B patients. METHODS: Fifty consecutive patients were randomly assigned to receive IFN-α-2b (5 MU thrice per week, n = 24) plus lamivudine (100 mg daily) or lamivudine only (n = 26) for 24 mo. Patients were followed up for further 6 mo. The primary outcome was the proportion with sustained virological response (undetectable serum HBV DNA concentrations) and or sustained biochemical response (transaminase levels within normal range) at 30 mo (6 mo after the end of therapy). Secondary end-points were timed from initial virological (biochemical) response to VBR (BBR, respectively) and the emergence of YMDD mutants across the two arms. RESULTS: Five of twenty-four (21%) patients in the combination arm vs 3/26 (12%) in the lamivudine arm had sustained response (i.e., normal serum transaminase levels and undetectable HBV DNA by PCR assay) 6 mo after treatment discontinuation. A reduction in the emergence of YMDD mutants and in the development of virological breakthroughs was observed in patients receMng combination treatment (10% vs46% , P= 0.01 and 14% vs46% , P= 0.03, respectively). Time from initial virologic response to virologic breakthrough (VBR) was greater among initial responders receiving combination treatment compared to those receiving lamivudine (22.9 mo vs 15.9 mo, respectively; P = 0.005).CONCLUSION: Our results demonstrate that IFN-α plus lamivudine combination therapy does not increase the sustained response, compared to lamivudine. However, combination therapy reduces the likelihood of VBR due to YMDD mutants and prolongs the time period until the breakthrough development.
基金Supported by a research grant given to Dr Laura Iris CosenBinker by GlaxoSmithKline S.A.
文摘AIM: TO investigate the severity of acute pancreatitis (AP) is associated to the intensity of leukocyte activation, inflammatory up-regulation and microcirculatory disruption associated to ischernia-reperfusion injury. Hicrovascular integrity and inhibition of pro-inflammatory mediators are key-factors in the evolution of AP. Relaxin is an insulin-like hormone that has been attributed vasorelaxant properties via the nitric oxide pathway while behaving as a glucocorticoid receptor agonist. METHODS: AP was induced by the bilio-pancreatic duct-outlet-exclusion closed-duodenal-loops model. Treatment with relaxin was done at different timepoints. Nitric oxide synthase inhibition by L-NAME and glucocorticoid receptor (GR) blockage by mifepristone was considered. AP severity was assessed by biochemical and histopathological analyses. RESULTS: Treatment with relaxin reduced serum amylase, lipase, C-reactive protein, IL-6, IL-10, hsp72, LDH and 8-isoprostane as well as pancreatic and lung myeloperoxidase. Acinar and fat necrosis, hemorrhage and neutrophil infiltrate were also decreased. ATP depletion and ADP/ATP ratio were reduced while caspases 2-3-8 and 9 activities were increased. L-NAME and mifepristone decreased the efficiency of relaxin. CONCLUSION: Relaxin resulted beneficial in the treatment of AP combining the properties of a GR agonist while preserving the microcirculation and favoring apoptosis over necrosis.
基金Supported by the National Natural Science Foundation of China, No. 30371662
文摘AIM: To study the inhibitory effects of siRNAs targeting different hTERT sequences and to screen the effective siRNA sequence.METHODS: Five double-stranded siRNAs targeting coding and non-coding regions of hTERT gene were designed and synthesized by T7 transcription system in vitro. siRNA4sequence was screened by full length gene targeting technique and the rest of the siRNA sequences were selected randomly. After being purified by ethanol precipitation, the siRNAs were transfected to the human hepatocellular carcinoma cell (HepG2) by Lipofectamine 2000TM. At 48-72 h after siRNAs transfection, MTT assay,RT-PCR and Western-blot were applied to evaluate the effects of siRNAs on cell growth, mRNA and protein expression level of hTERT gene, respectively.RESULTS: Compared to the control cells, the cells treated with the five double-stranded siRNAs exhibited different degrees of inhibition of cell proliferation in a dose-dependent manner. siRNA2 and siRNA4, exhibited obvious effects of inhibiting hTERT mRNA and protein expression in HepG2cells.CONCLUSION: siRNAs targeting different hTERT sequences have significantly various inhibitory effects on hTERT gene expression. The siRNA sequence screened by full length gene targeting technique has comparable inhibitory effect with the rest siRNA sequences screened by random selection, suggesting that siRNAs and antisense oligonucleic acids may have the same effective target sites. Compared with chemical synthesis method,synthesizing double-stranded siRNA by T7 transcription system in vitro is a rapid, simple, and inexpensive method suitable for screening high-effect siRNA targeting site for specific gene.
基金Research Funding of Medical Association of Japanese-Chinese, Japan
文摘AIM: To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to demonstrate the colon-specific delivery of rebamipide with or without absorption enhancers using chitosan capsule as a carrier. METHODS: The permeability of rebamipide was evaluated using an in vitro diffusion chamber system, and the effects of some absorption enhancers on the permeability via colon were further investigated. The release of rebamipide from chitosan or gelatin capsule was studied by Japan Pharmacopoeia rotating basket method. The colonic and plasma concentrations were analyzed by high performance liquid chromatography (HPLC) to evaluate colon-targeting action after oral administration of various dosage forms, and rebamipide with absorption enhancers in chitosan dosage forms. RESULTS: The permeability of rebamipide across the jejunal or ileal membranes was higher than the colonic membranes. Both sodium laurate (C12) and labrasol signifi cantly increased permeability across the colon membranes. On the other hand, the release of rebamipide from chitosan capsule was less than 10%totally within 6 h. The area under concentration-time profile of drug in the colon mucosa using chitosan capsules (AUCLI, 1 6011.2 ng·h/g) was 2.5 times and 4.4 times greater than using gelatin capsules and CMC suspension, respectively. Meanwhile, the area under concentration-time profile of drug in the plasma (AUCPL) was 1016.0 ng·h/mL for chitosan capsule, 1887.9 ng·h/mL for CMC suspension p and 2163.5 ng·h/mL for gelatin capsule. Overall, both AUCLI and AUCPL were increased when C12 was co-administrated, but the increase of AUCLI was much greater; the drug delivery index (DDI) was more than 1 compared with simple chitosan capsule group. CONCLUSION: There was a regional difference in the permeability of Rabamipide across the jejunum, ileum and the colon, and passive diffusion seems to be one of the major transport mechanisms of rebamipide. Absorption enhancers can increase the permeability of rebamipide across the colon tissue signifi cantly. In addition, chitosan capsule may be a useful carrier to deliver rebamipide to the colon specifi cally and the co-administration of C12 with rebamipide may also be very useful in local treatment.
文摘Chronic heart failure and depressive disorders have a high prevalence and incidence in the elderly. Several studies have shown how depression tends to exacerbate coexisting chronic heart failure and its clinical outcomes and vice versa, especially in the elderly. The negative synergism between chronic heart failure and depression in the elderly may be approached only taking into account the multifaceted pathophysiological characteristics underlying both these conditions, such as behavioural factors, neurohormonal activation, inflammatory mediators, hypercoagulability and vascular damage. Nevertheless, the pathophysiological link between these two conditions is not well established yet. Despite the high prevalence of depression in chronic heart failure elderly patients and its negative prognostic value, it is often unrecognized especially because of shared symptoms. So the screening of mood disorders, using reliable questionnaires, is recommended in elderly patients with chronic heart failure, even if cannot substitute a diagnostic interview by mental health professionals. In this setting, treatment of depression requires a multidisciplinary approach including: psychotherapy, antidepressants, exercise training and electroconvulsive therapy. Pharmacological therapy with selective serotonin reuptake inhibitors, despite conflicting results, improves quality of life but does not guarantee better outcomes. Exercise training is effective in improving quality of life and prognosis but at the same time cardiac rehabilitation services are vastly underutilized.
基金Supported by the Oriental Medicine R and D Project, Ministry of Health and Welfare, Republic of Korea, No. B050018
文摘AIM: To evaluate the therapeutic effect of Chunggan extract (CGX), a modified traditional Chinese hepatotherapeutic herbal, on the dimethylnitrosamine (DMN)-induced chronic liver injury model in rats. METHODS: Liver injuries were induced in Wistar rats by injection of DMN (ip, 10 mg/mL per kg) for 3 consecutive days per week for 4 wk. The rats were administered with CGX Coo, 100 or 200 mg/kg per day) or distilled water as a control daily for 4 wk starting from the 15^th d of the DMN treatment. Biochemical parameters (serum albumin, bilirubin, ALP, AST and ALT), lipid peroxides, hydroxyproline, as well as histological changes in liver tissues were analyzed. In addition, gene expression of TNF-α, TGF-β, TIMP-1, TIMP-2, PDGF-β, and MMP-2, all of which are known to be associated with liver fibrosis, were analyzed using real-time PCR. RESULTS: CGX administration restored the spleen weight to normal alter having been increased by DMN treatment. Biochemical analysis of the serum demonstrated that CGX significantly decreased the serum level of ALP (P 〈 0.05), ALT (P 〈 0.02), and AST (P 〈 0.02) that had been elevated by DMN treatment. CGX administration moderately lowered lipid peroxide production and markedly lowered hydroxyproline generation caused by DMN treatment in accordance with histopathological examination. DMN treatment induced a highly upregulated expression of TNF-α, TGF-β,TIMP-1, TIMP-2, PDGF-β, and MMP-2. Of these, the gene expression encoding PDGF-β and MMP-2 was still further enhanced 2 wk after secession of the 4-wk DMN treatment, and was remarkably ameliorated by CGX administration. CONCLUSION: CGX exhibits hepatotherapeutic properties against chronic hepatocellular destruction and consequential liver fibrosis.
文摘AIM: To investigate in vitro and in vivo therapeutic effects of histone deacetylase inhibitors NVP-LAQ824 and NVP-LBH589 on biliary tract cancer. METHODS: Cell growth inhibition by NVP-LAQ824 and NVP-LBH589 was studied in vitro in 7 human biliary tract cancer cell lines by MTT assay. In addition, the antitumoral effect of NVP-LBH589 was studied in a chimeric mouse model. Anti-tumoral drug mechanism was assessed by immunoblotting for acH4 and p21^WAFl/CIP-1, PARP assay, cell cycle analysis, TUNEL assay, and immunhistochemistry for MIB-1. RESULTS: In vitro treatment with both compounds significantly suppressed the growth of all cancer cell lines [mean IC50 (3 d) 0.11 and 0.05 μmol/L, respectively], and was associated with hyperacetylation of nucleosomal histone H4, increased expression of p21^WAF-1/CIP-1, induction of apoptosis (PARP cleavage), and cell cycle arrest at G2/M checkpoint. After 28 d, NVP- LBH589 significantly reduced tumor mass by 66% (bile duct cancer) and 87% (gallbladder cancer) in vivo in comparison to placebo, and potentiated the efficacy of gemcitabine. Further analysis of the tumor specimens revealed increased apoptosis by TUNEL assay and reduced cell proliferation (MIB-1). CONCLUSION: Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human biliary tract cancer in vitro. In addition, NVP-LBH589 demonstrated significant in vivo activity and potentiated the efficacy of gemcitabine. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended.
基金Supported by A grant from Pineta Grande Hospital,Castel Volturno,Caserta,Italy
文摘Hepatocellular carcinoma (HCC) still remains a considerable challenge for surgeons.Surgery,including liver transplantation,is the most important therapeutic approach for patients with this disease.HCC is frequently diagnosed at advanced stages and has a poor prognosis with a high mortality rate even when surgical resection has been considered potentially curative.This brief report summarizes the current status of the management of this malignancy and includes a short description of new pharmacological approaches in HCC treatment.
文摘A gastric carcinoid tumor concomitant with gastrointestinal stromal tumor (GIST) is rarely encountered in clinical practice. We report a 65-year-old female who had a 0.8 cm gastric carcinoid tumor on the posterior wall of the upper gastric corpus detected during an esophagogastroduodenoscopy at a routine physical examination, and a concomitant 1.1 cm GIST on the anterior wall of the upper gastric corpus incidentally found during surgery of the gastric carcinoid tumor. Normal serum gastrin level and histological findings suggested that she had a type 111 gastric carcinoid tumor and a GIST which were categorized a very low risk of malignancy, based on their small size and lack of mitosis. Both tumors were treated successfully by surgical excision. The patient had an uneventful recovery. Neither recurrence nor metastasis was found after a 28-mo follow-up.
文摘Noni juice (Morinda citrifolia) has been approved for use as a safe food within the European Union, following a review of safety. Since approval, three cases of acute hepatitis in Austrian noni juice consumers have been published, where a causal link is suggested between the liver dysfunction and ingestion of anthraquinones from the plant. Measurements of liver function in a human clinical safety study of TAHITIAN NONI Juice, as well as subacute and subchronic animal toxicity tests revealed no evidence of adverse liver effects at doses many times higher than those reported in the case studies. Additionally, M. citrifolia anthraquinones occur in the fruit in quantities too small to be of any toxicological significance. Further, these do not have chemical structures capable of being reduced to reactive anthrone radicals, which were implicated in previous cases of herbal hepototoxicity. The available data reveals no evidence of liver toxicity.
基金Supported by the 2004 Research Fund of Wonkwang University
文摘AIM: Itopride is a newly developed prokinetic agent, which enhances gastric motility through both antidopaminergic and anti-acetylcholinesterasic actions. The importance of esophageal motor dysfunction in the pathogenesis of gastro-esophageal reflux disease (GERD) makes it interesting to examine the effect of itopride on esophageal acid exposure.METHODS: The effect of itopride on esophageal acid reflux variables for 24 h was studied in 26 patients with GERD symptoms, pre-entry total acid exposure time (pH〈4) of more than 5% and mild esophagitis (SavaryMiller grades I, II) proven by endoscopy. Ambulatory 24hpH-metry and symptom assessment were performed after treatments with 150 or 300 mg itopride thrice a day (t.i.d.) for 30 d in random order, using an open label method.For evaluating the safety of itopride, blood biochemical laboratory test was performed and the serum prolactin level was also examined before and after treatment.RESULTS: Total symptom score was significantly decreased after treatment in 150- or 300-mg group. Itopride 300 mg was significantly effective than 150 mg on decreasing the total per cent time with pH〈4, total time with pH〈4 and DeMeester score. No serious adverse effects were observed with administration of itopride in both groups.CONCLUSION: Itopride 100 mg t.i.d, is effective on decreasing pathologic reflux in patient with GERD and therefore it has the potential to be effective in the treatment of this disease.
文摘Accumulating evidence demonstrates that resveratrol, a natural polyphenolic compound extracted from plants, inhibit inflammation when administered. It has direct effects on suppression of platelet coagulation and cytokines production in many experimental models. Because microcirculation occlusion and cytokines over-production is involved in many diseases such as acute pancreatitis (AP), the discovery of resveratrol as platelet and cytokines inhibitors has shed light on the treatment of AP, which still has significant mortality and morbidity. It is anticipated that this natural polyphenol could serve as a therapeutic compound in managing AP through different pathways.
文摘AIM: To examine the effects of traditional Chinese medicine (TCM) on alcohol-induced fatty liver in rats. TCM consists of Astragalus membranaceus, Morus alba, Crataegus pinnatifida, Alisma orientale, Salvia miltiorrhiza, and Pueraria lobata. METHODS: The rats were separated randomly into five groups. One (the CD group) was fed a control diet for 10 wk, another (the ED group) fed an ethanol-containing isocaloric liquid diet for 10 wk, and the last three (the TCM group) were fed an ethanol-containing isocaloric liquid diet for 10 wk and dosed orally with TCM (222 mg/kg.d, TCM222; 667 mg/kg·d, TCM667; and 2 000 mg/kg.d, TCM2000, respectively) weekly during the last 4 wk. RESULTS: ED group developed fatty liver according to lipid profile and liver histological findings. Compared with the control group, liver/body weight, serum triglyceride (TG) and total cholesterol (TC), liver TG and TC, serum alanine aminotransferase (ALT) and aspartic aminotransferase (AST) significantly increased in the ED group. Whereas, in the rats administered with TCM, liver/body weight, serum TG and TC, liver TG and TC, serum ALT and AST were significantly decreased, and the degree of hepatic lipid droplets was markedly improved compared with those in the ED group. CONCLUSION: TCM treatment causes significant reduction in alcohol-induced lipid hepatic accumulation, reversing fatty liver and liver damage, and can be used as a remedy for alcoholic fatty liver.
文摘Objective To evaluate the efficacy and safety of diacerein in patients with knee osteoarthritis (OA). Methods A total of 223 patients satisfying the American College of Rheumatology criteria for knee OA were chosen for this 17-week, randomized, double-dummy, diclofenac sodium-controlled trial, with diacerein dosage of 100 mg/d and diclofenac sodium of 75mg/d. Efficacy and safety of both drugs were evaluated. Results Totally 106 patients in the diacerein group and 107 patients in the diclofenac group were considered qualified for the evaluation. After 12 weeks of treatment, the total effective rates of patients/physicians’ overall assessment in diacerein and diclofenac groups were 65.4%/61.6% and 61.2%/61.2%, respectively (P>0.05). The primary efficacy parameter [visual analog scale (VAS) assessment of pain on 20 metres walking] and the secondary efficacy parameters [tenderness on palpation, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-item Short-Form (SF-36) Health Survey] significantly improved compared with baseline in both groups (P<0.05). In the follow-up period, there were no obvious changes in above parameters in diacerein group. However, in diclofenac group, pain on 20 metres walking, tenderness on palpation, and WOMAC became aggravated after withdrawing the drug for 4 weeks (P<0.05). Moreover, the consumption of paracetamol was significantly lower in diacerein group than in diclofenac group during follow-up (P<0.001). The incidences of related adverse events were 35.7% in diacerein and 45.1% in diclofenac group, respectively. Mild-to-moderate gastrointestinal disorders were the most frequent adverse events. Conclusions Diacerein is as effective as diclofenac sodium in treating patients with knee OA. Furthermore, it has better extended effect and a good safety profile. It is generally well tolerated and has no severe adverse effect.