There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system(RAS) inhibitors and s...There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system(RAS) inhibitors and statins as reference drugs with proven efficacies in randomized clinical trials(RCTs) and examined their effectiveness in the prospective Hong Kong Diabetes Registry using adjustment methods proposed in the literature. Using time-dependent exposures to drug treatments yielded greatly inflated hazard ratios(HR) regarding the treatment effects of these drugs for cardiovascular disease(CVD) in type 2 diabetes. These errors were probably due to changing indications to use these drugs during follow up periods, especially at the time of drug commencement making time-dependent analysis extremely problematic. Using time-fixed analysis with exclusion of immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of RAS inhibitors for CVD was comparable to that in RCT. The result supported the use of the Registry for performing pharmacoepidemiological analysis which revealed an attenuated low low-density lipoprotein cholesterol related cancer risk with RAS inhibitors. On the other hand, time-fixed analysis with including immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of statins for CVD was similar to that in the RCT. Our results highlight the complexity and difficulty in removing these biases. We call for validations of the methods to cope with immortal time and drug use indications before applying them to particular research questions, so to avoid making erroneous conclusions.展开更多
Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop respondi...Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop responding properly to insulin stimulation.This condition is known as insulin resistance,which is a hallmark of two very common conditions,metabolic syndrome and type 2 diabetes（T2D）.展开更多
Background: Stroke is a worldwide health problem, the world’s second-leading cause of death and third-leading cause of disability. Currently, the majority of stroke patients are ischemic stroke patients. It is necess...Background: Stroke is a worldwide health problem, the world’s second-leading cause of death and third-leading cause of disability. Currently, the majority of stroke patients are ischemic stroke patients. It is necessary to evaluate risk factors to prevent ischemic stroke. Data and Methods: The risk factors for stroke in the previous fiscal year were analyzed. They were divided into nonmodifiable and modifiable factors. The probit and ordered probit models were used in the study, with 59341 and 50542 observations used in the estimation of the models, respectively. Results: Among the nonmodifiable factors, age, gender and cerebrovascular disease history are important risk factors. The history of cerebrovascular diseases is considered to be an especially important factor. Among the modifiable factors, taking antihypertensive drugs and recent large weight change are negative risk factors;however, sleeping well significantly reduces the probability of ischemic stroke. Conclusion: It is very important to ensure that medical personnel know a patient’s history of cerebrovascular diseases for proper treatments. Ischemic stroke might be considered an important side effect of antihypertensive drugs. Limitations: The dataset was observatory. There are various types of antihypertension drugs, and their effects are not analyzed.展开更多
Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs...Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and Pub Med.展开更多
Objective: To evaluate five drug treatment regimens in the treatment of Brucella spondylitis. Methods: Patients with clinical symptoms compatible and diagnostic test consistent with Brucella spondylitis were randomly ...Objective: To evaluate five drug treatment regimens in the treatment of Brucella spondylitis. Methods: Patients with clinical symptoms compatible and diagnostic test consistent with Brucella spondylitis were randomly assigned to five drug treatment regimens. Results: Combination therapy with doxycycline, rifampin and sulfamethoxazole for 56 consecutive days showed the highest cure rate of 20% after a single course and of 85% after a double course with affectivity rates of 55% and 95%. Cure rate and affectivity rate was significant better (P 0.05) than for patients receiving doxycycline, rifampin and streptomycin for the same period and regimens containing doxycycline were significant better than regimens without this drug. Conclusion: Combination therapy of doxycycline, rifampin and sulfamethoxazole for 8 weeks using one or two full courses should be recommended for Brucella spondylitis.展开更多
Ciprofloxacin (CFX) was loaded on Bana clay (Cameroon) and CFX loaded-clays have been evaluated as drug delivery system. Raw clays and CFX loaded compounds have been characterized by some physico-chemicals methods. &l...Ciprofloxacin (CFX) was loaded on Bana clay (Cameroon) and CFX loaded-clays have been evaluated as drug delivery system. Raw clays and CFX loaded compounds have been characterized by some physico-chemicals methods. <i>In vitro</i> release studies have been done in gastric and phosphate buffer experimental mediums;bacteriological studies have been made up on <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>. X-ray diffractometry patterns of loaded compounds show a basal spacing increasing due to CFX intercalation. On Fourier-Transformed Infrared spectrometry spectra, appearance of CFX characteristic bands and shifting of certain bands already presents on clay confirmed CFX intercalation. After 96 h of CFX released from release mediums, prolonged and continue profiles have been observed. Diffusion tests displayed an inhibition radius of ~2 cm on gelose seeded with <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> due to CFX. The overall results show a modified release of ciprofloxacin with an effective antibacterial activity, giving the way for a new ciprofloxacin drug delivery system using Bana clay as carrier.展开更多
This study was conducted to investigate the effects of extracts of 4 Tibetan veterinary drugs on bacterial diarrhea, and to guide the clinical treatment of the disease. The inhibitory effects of the extracts of the 4 ...This study was conducted to investigate the effects of extracts of 4 Tibetan veterinary drugs on bacterial diarrhea, and to guide the clinical treatment of the disease. The inhibitory effects of the extracts of the 4 Tibetan veterinary drugs, Veronica ciliate Fisch, Usnea diffracta Vain, Sophoraflavescens var. flavescens, Lamiophlomis rotata （ Benth. ） Kudo on 14 common diarrheagenic bacteria were detected by K-B diffusion method and micro-broth dilution method. Optimization was performed on prescriptions of the 4 Tibetan veterinary drugs using orthogonal design software, and a mouse bacterial diarrhea model was established with a clinical isolate, Salmonella blegdam. According to the LD50 value of the optimal prescription of the 4 Tibetan veterinary drugs, the established mouse bacterial diarrhea model was treated in 3 dose groups, i. e. , the high, middle and low dose groups （0. 060, 0. 030 and 0. 020 g/ml, respectively）. The results showed that the 4 Tibetan veterinary drugs had very good inhibitory effects on most of the tested diarrheagenic bacteria, and among them, U. diffracta had better inhibitory effects on all the tested bacteria. The optimal prescription of the d Tibetan veterinary drugs （high dose, 0.06 g/ml） exhibited very good inhibitory effect on mouse diarrhea, indicating that the prescription has very good anti-diarrhea effect, which is beneficial to the clinical treatment of such disease and the development of Tibetan veterinary drugs.展开更多
Structure-efficacy effect of small molecular drug attracts wide attentions,but it has always been ignored in nanomedicine research.To reveal the efficacy modulation of nanomedicine,we developed a new type of paclitaxe...Structure-efficacy effect of small molecular drug attracts wide attentions,but it has always been ignored in nanomedicine research.To reveal the efficacy modulation of nanomedicine,we developed a new type of paclitaxel(PTX)-conjugated gold nanoparticles(PTX-co njugated GNPs)to investigate the influence of drug position in controlling their in vitro properties and in vivo performance.Two therapeutic ligands(TA-PEG-NH-N=PTX and TA-PTX=N-NH-PEG)were synthesized to conjugate PTX on the surface of GNPs at different positions,locating on the surface of gold conjugate and inserting between GNPs and polyethylene glycol(PEG,molecular weight 1000 Da),respectively.It was found that PEG-PTX@GNPs with PTX located between GNP and PEG exhibited higher aqueous solubility,biocompatibility,and stability.In addition,an acid sensitive hydrazone bond has been inserted between PTX and PEG in both ligands for drug release of PTX and PTX-PEG segment,respectively,at the tumor site.Further release of PTX from PTX-PEG segment is based on the esterase hydrolysis of an ester bond between PTX and PEG.This two-step drug release mechanism offers PEG-PTX@GNPs effective and sustained release behavior for desirable anticancer activity,enhanced therapeutic efficacy,and lower systematic toxicity in Hepsbearing animal models.展开更多
Chromatographic behavior of co-eluted compounds from un-extracted drug-free plasma samples was studied by LC-MS and LC-MS/MS with positive APCI.Under soft gradient,total ion chromatogram（TIC） consisted of two major ...Chromatographic behavior of co-eluted compounds from un-extracted drug-free plasma samples was studied by LC-MS and LC-MS/MS with positive APCI.Under soft gradient,total ion chromatogram（TIC） consisted of two major peaks separated by a constant lower intensity region.Early peak（0.15-0.4 min） belongs to polar plasma compounds and consisted of smaller mass ions（m/z〈 250）;late peak（3.6-4.6 min） belongs to thermally unstable phospholipids and consisted of fragments with mlz〈300.Late peak is more sensitive to variations in chromatographic and MS parameters.Screening of most targeted cardiovascular drugs at levels lower than 50 ng/mL has been possible by LC-MS for drugs with retention factors larger than three.Matrix effects and recovery,at 20 and 200 ng/mL,were evaluated for spiked plasma samples with 15 cardiovascular drugs,by MRM-LC-MS/MS.Average recoveries were above 90%and matrix effects expressed as percent matrix factor（%MF） were above 100%,indicating enhancement character for APCI.Large uncertainties were significant for drugs with smaller masses（m/z〈 250） and retention factors lower than two.展开更多
A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid （GA） and doxorubicin （DOX） conjugates at different ratios. GA （a liver-targeting ligand） and D...A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid （GA） and doxorubicin （DOX） conjugates at different ratios. GA （a liver-targeting ligand） and DOX （an antitumor drug） were both conjugated to oligomeric glycol monomethyl ether-modified sodium alginate （ALG-mOEG） for prolonged duration of action. These NP-based delivery systems exhibited active cell uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. In addition, nanoparticles with a 1：1 （W：W） ratio of GA-ALG-mOEG and DOX-ALG-mOEG （NPs-3） showed the highest cellular uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. Specifically, when mixed nanoparticles defined as NPs-3 were injected in mice, liver DOX concentration reached 61.9 μg/g 3 h after injection, and AUC0-∞ and t1/2 of DOX in liver reached 4744.9 μg·h/g and 49.5 h, respectively. In addition, mice receiving a single injection of NPs-3 exhibited much slower tumor growth （88.37% reduction in tumor weight） 16 days after injection compared with placebo. These results indicate that effective cancer treatment may be developed using mixed NP delivery systems with appropriate ratio of targeted ligand and drug.展开更多
The activity of DNA topoisomerase Ⅱ prepared from either normal or tumor tissues were compared. It was found that the unknotting activity of the enzyme in malignant tumor cells was higher than that in normal cells. W...The activity of DNA topoisomerase Ⅱ prepared from either normal or tumor tissues were compared. It was found that the unknotting activity of the enzyme in malignant tumor cells was higher than that in normal cells. We selected some antitumor drugs including Chinese traditional medicine, and observed their effects on the unknotting activity of topoisomerase Ⅱ. The results showed that inhibition of the unknotting activity of the enzyme required very low concentrations of drugs, but much higher concentrations were required for other tested. Some antitumor drugs had no effect on the enzyme were also proved. It is interesting that carrageenan, an antiviral drug, strongly blocked the unknotting activity although its antitumor activity has not been reported.展开更多
An analysis of selected datasets from the FDA’s drug Adverse Event Reporting System (FAERS) leads us to hypothesize that glyphosate contamination in both food and drugs is a major contributor to chronic and acute kid...An analysis of selected datasets from the FDA’s drug Adverse Event Reporting System (FAERS) leads us to hypothesize that glyphosate contamination in both food and drugs is a major contributor to chronic and acute kidney failure respectively. In chronic kidney failure, glyphosate-induced pancreatitis results in the release of trypsin, causing a leaky vasculature. The albumin-bound glyphosate escapes into the tissues, protecting the circulatory system and kidneys but resulting in multiple symptoms related to skin, gut, brain, bones, lungs, etc. The rare and poorly understood acute kidney failure response reported for protamine sulfate and Trasylol? is strikingly similar to that associated with glyphosate poisoning. Both drugs are derived from biological tissues that are plausibly contaminated with glyphosate. These drugs protect from haemorrhage, which leads to retention of glyphosate in the vasculature, are followed by circulatory collapse and a high likelihood of death as an outcome. We support our argument by comparing symptom profiles of selected subsets of FAERS with those related to glyphosate poisoning, anomalous reactions to protamine sulfate, and conditions showing strong statistical time-trend correlations with glyphosate.展开更多
The paper was to explore the preventive effects of five drugs on mycoplasma pneumonia of swine （MPS） and to provide reference for clinical medication of pig farms in Hainan Province. A total of 444 health piglets we...The paper was to explore the preventive effects of five drugs on mycoplasma pneumonia of swine （MPS） and to provide reference for clinical medication of pig farms in Hainan Province. A total of 444 health piglets were randomly divided into 6 groups, including five medication groups （72 piglets in group A, 74 pig- lets in group B, 72 piglets in group C, 76 piglets in group D, 76 piglets in group E） and one control group （74 piglets）. The piglets in experimental groups were treated drugs once a day for successive 5 days at 30, 60, 90, 120 and 150 of age. The piglets in control group were free of medication. At 70 and 140 days of age, 15 piglets of each group were randomly selected to collect their blood sermn. The Mycoplasma hyopneumoniae （M-Hyo） antibodies in serum were measured by en- zyme-linked immunosorbent assay （ELISA）. During the experiment, the incidence rates of respiratory disease, lung lesion, feed conversion rate, average daily gain （ADG）, and mortality rate of pigs were also observed and recorded. The results showed that the five drugs had significant difference in preventative effects. Group C （Zhiyuanjing group） received the best preventive effect and the highest economic benefits. Compared with control group, the ADG and feed conversion rate in group C were increased by 7.53% and 9.09%, respectively; the incidence rate of respiratory disease was reduced by 13.44% and lung lesion was alleviated by 81.43% ; and the earnings of each pig could rise by 132.70 yuan. The preventative effect and economic benefit of the drugs was sequenced by Chansu Kechuanling and Bingchan Kechuanwang. Wante Feilin and amoxicillin had weaker preventive effects against MPS but greatly influenced growth performance of pigs, so they should be used alternatively with other drugs.展开更多
Fluphenazine (FP) treatment (50mg/kg bw, ip in saline) 30 min before or 6 or 10 h after CCl4 administration (1 ml/kg ip in olive oil) significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. FP ...Fluphenazine (FP) treatment (50mg/kg bw, ip in saline) 30 min before or 6 or 10 h after CCl4 administration (1 ml/kg ip in olive oil) significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. FP had enhancing effects on the covalent binding of CCl4 reactive metabolites to cellular constituents and on CCl4 induced lipid peroaldation.FP lowered bOdy temperature of the CCl4-poisoned animals during the 24 h observation period. The obtained results are compatible but do not prove the hypothesis that calmodulin (CaM) had participation in late occurring events preceding necrosis. FP lowering action on body temperature, however, might also play a role in the effects of this drug on the onset of CCl4 induced liver necrosis. FP levels in liver tissue as determined by gas chromatography-mass spectrometry evidenced the presence of the drug in amounts suffi cient to inhibit CaM and that suggests that not all preventive effects of FP are due to its indirect actions on the central nervous system via decreased body temperature展开更多
In the twenty first century research works, there may be a need to achieve a more reliable research result through a synergy between engineers and biological researchers. The peak absorbance data for various interacti...In the twenty first century research works, there may be a need to achieve a more reliable research result through a synergy between engineers and biological researchers. The peak absorbance data for various interacting systems were measured. These were used to show that the antiretroviral drug has the effect of increasing the peak absorbance values of both the uninfected and infected blood components, i.e., the drugs are made able to increase the light absorption capacity of the blood cells. For drug 2 that contains three components including Efavirenz, the drug effect on lymphocytes was increased by about 38% for patients that had been on antiretroviral drug treatment. Mathematical models were proposed and used in determining the coating effectiveness of antiretroviral drugs in the presence and absence of HIV. The use of the findings of this work by pharmaceutical industries may help in the search for more effective antiretroviral drugs for the treatment of HIV patients.展开更多
The development of new drugs for therapeutic purposes has become very expensive and time-consuming in American and European countries.It is estimated that on the average 50 to 100 million dollars and 10 or more years ...The development of new drugs for therapeutic purposes has become very expensive and time-consuming in American and European countries.It is estimated that on the average 50 to 100 million dollars and 10 or more years from the time of patenting are required to make a new drug available for general prescription. Every new drug needs to be charac-展开更多
Five common homoeopathic drugs viz., Belladonna, Bryonia, Colchicum, Colocynth and Lathyrus sat were selected and tested against growth and aflatoxin production of Aspergillus flavus. The result indicates that all fiv...Five common homoeopathic drugs viz., Belladonna, Bryonia, Colchicum, Colocynth and Lathyrus sat were selected and tested against growth and aflatoxin production of Aspergillus flavus. The result indicates that all five drugs suppressed the growth of A. flavus. The lower concentration of all the tested drugs induced maximum growth of fungi and maximum production of aflatoxin. However, the growth as well as aflatoxin production potentiality was considerably decreased when the concentration of the drug was increased. Out of all the five drugs, Bryonia was comparatively less effective with respect to inhibition in aflatoxin production. But Belladonna was found to be most effective drug on growth and aflatoxin production.展开更多
Objective: To evaluate the therapeutic effect of Yinchenghao decoction (YCHD, 茵陈蒿汤) and S-adenosy-L-methionine (SAM) in treating intra-hepatic cholestasis of pregnancy (TCP) and improving prognosis of perinatal ne...Objective: To evaluate the therapeutic effect of Yinchenghao decoction (YCHD, 茵陈蒿汤) and S-adenosy-L-methionine (SAM) in treating intra-hepatic cholestasis of pregnancy (TCP) and improving prognosis of perinatal newborn babies. Methods: Sixty in-patients of TCP were randomly divided into two groups, the group A treated with YCHD and the group B treated with SAM. The symptom of itching and serum biochemical indexes, including glycocholic acid, bilirubin and transaminase, were observed after 3 weeks treat-ment, and the prognosis of perinatal newborn babies between the two groups was compared after delivery. Results: After treatment, the symptom of itching, serum levels of glycocholic acid, bilirubin and transaminase improved significantly (P< 0.05) in both groups, and the prognosis of newborn in the two groups was similar (P>0. 05). Conclusion: Both YCHD and SAM could effectively treat ICP. The former is rather cheaper, so it is more feasible for spreading.Original article on CJITWM (Chin) 2004 ;24(4): 309展开更多
A large number of Chinese herbal drugs (CHDs) exhibit antibacterial activities both in vivo and in vitro, but until now little is known regarding their inhibitory mechanisms. Bacterial DNA gyrase is a proven target fo...A large number of Chinese herbal drugs (CHDs) exhibit antibacterial activities both in vivo and in vitro, but until now little is known regarding their inhibitory mechanisms. Bacterial DNA gyrase is a proven target for antibacterial agents. Aim of this study was to investigate the in-vitro inhibitory effect of methanol extracts of CHDs against supercoiling activity of bacterial DNA gyrase. Fifteen CHDs were selected and extracted with methanol, respectively. Inhibitory effect of the extracts on DNA gyrase was tested using gel-based DNA supercoiling assay. Among fifteen CHDs tested, methanol extracts of Lonicerae Japonicae Flos (S2), Taraxaci Herba (S7), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (S8) demonstrated an obvious inhibitory effect against supercoiling activity of DNA gyrase, and the others were either less active or could not be determined with the present method. Moreover, it was likely that S7 and S8 inhibit gyrase in a concentration-dependent manner. In conclusion, DNA supercoiling assay is a promising method to study the inhibitory activity of CHDs on bacterial DNA gyrase. Some CHDs do have gyrase-inhibitory activity as proposed. Further investigations are needed to elucidate the inhibition mechanism of these CHDs on supercoiling activity of gyrase.展开更多
文摘There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system(RAS) inhibitors and statins as reference drugs with proven efficacies in randomized clinical trials(RCTs) and examined their effectiveness in the prospective Hong Kong Diabetes Registry using adjustment methods proposed in the literature. Using time-dependent exposures to drug treatments yielded greatly inflated hazard ratios(HR) regarding the treatment effects of these drugs for cardiovascular disease(CVD) in type 2 diabetes. These errors were probably due to changing indications to use these drugs during follow up periods, especially at the time of drug commencement making time-dependent analysis extremely problematic. Using time-fixed analysis with exclusion of immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of RAS inhibitors for CVD was comparable to that in RCT. The result supported the use of the Registry for performing pharmacoepidemiological analysis which revealed an attenuated low low-density lipoprotein cholesterol related cancer risk with RAS inhibitors. On the other hand, time-fixed analysis with including immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of statins for CVD was similar to that in the RCT. Our results highlight the complexity and difficulty in removing these biases. We call for validations of the methods to cope with immortal time and drug use indications before applying them to particular research questions, so to avoid making erroneous conclusions.
文摘Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop responding properly to insulin stimulation.This condition is known as insulin resistance,which is a hallmark of two very common conditions,metabolic syndrome and type 2 diabetes（T2D）.
文摘Background: Stroke is a worldwide health problem, the world’s second-leading cause of death and third-leading cause of disability. Currently, the majority of stroke patients are ischemic stroke patients. It is necessary to evaluate risk factors to prevent ischemic stroke. Data and Methods: The risk factors for stroke in the previous fiscal year were analyzed. They were divided into nonmodifiable and modifiable factors. The probit and ordered probit models were used in the study, with 59341 and 50542 observations used in the estimation of the models, respectively. Results: Among the nonmodifiable factors, age, gender and cerebrovascular disease history are important risk factors. The history of cerebrovascular diseases is considered to be an especially important factor. Among the modifiable factors, taking antihypertensive drugs and recent large weight change are negative risk factors;however, sleeping well significantly reduces the probability of ischemic stroke. Conclusion: It is very important to ensure that medical personnel know a patient’s history of cerebrovascular diseases for proper treatments. Ischemic stroke might be considered an important side effect of antihypertensive drugs. Limitations: The dataset was observatory. There are various types of antihypertension drugs, and their effects are not analyzed.
基金Part of this manuscript was supported by Grant from the Instituto Mexicano del Seguro Social,projects FIS/IMSS/PROT/G15/1414
文摘Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and Pub Med.
文摘Objective: To evaluate five drug treatment regimens in the treatment of Brucella spondylitis. Methods: Patients with clinical symptoms compatible and diagnostic test consistent with Brucella spondylitis were randomly assigned to five drug treatment regimens. Results: Combination therapy with doxycycline, rifampin and sulfamethoxazole for 56 consecutive days showed the highest cure rate of 20% after a single course and of 85% after a double course with affectivity rates of 55% and 95%. Cure rate and affectivity rate was significant better (P 0.05) than for patients receiving doxycycline, rifampin and streptomycin for the same period and regimens containing doxycycline were significant better than regimens without this drug. Conclusion: Combination therapy of doxycycline, rifampin and sulfamethoxazole for 8 weeks using one or two full courses should be recommended for Brucella spondylitis.
文摘Ciprofloxacin (CFX) was loaded on Bana clay (Cameroon) and CFX loaded-clays have been evaluated as drug delivery system. Raw clays and CFX loaded compounds have been characterized by some physico-chemicals methods. <i>In vitro</i> release studies have been done in gastric and phosphate buffer experimental mediums;bacteriological studies have been made up on <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>. X-ray diffractometry patterns of loaded compounds show a basal spacing increasing due to CFX intercalation. On Fourier-Transformed Infrared spectrometry spectra, appearance of CFX characteristic bands and shifting of certain bands already presents on clay confirmed CFX intercalation. After 96 h of CFX released from release mediums, prolonged and continue profiles have been observed. Diffusion tests displayed an inhibition radius of ~2 cm on gelose seeded with <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> due to CFX. The overall results show a modified release of ciprofloxacin with an effective antibacterial activity, giving the way for a new ciprofloxacin drug delivery system using Bana clay as carrier.
基金Supported by the Science and Technology Training Plan Project of Sichuan Province(2016KZ0007)the Fundamental Research Funds for the Central Universitiesof Southwest University for Nationalities(2017NZYQN38)
文摘This study was conducted to investigate the effects of extracts of 4 Tibetan veterinary drugs on bacterial diarrhea, and to guide the clinical treatment of the disease. The inhibitory effects of the extracts of the 4 Tibetan veterinary drugs, Veronica ciliate Fisch, Usnea diffracta Vain, Sophoraflavescens var. flavescens, Lamiophlomis rotata （ Benth. ） Kudo on 14 common diarrheagenic bacteria were detected by K-B diffusion method and micro-broth dilution method. Optimization was performed on prescriptions of the 4 Tibetan veterinary drugs using orthogonal design software, and a mouse bacterial diarrhea model was established with a clinical isolate, Salmonella blegdam. According to the LD50 value of the optimal prescription of the 4 Tibetan veterinary drugs, the established mouse bacterial diarrhea model was treated in 3 dose groups, i. e. , the high, middle and low dose groups （0. 060, 0. 030 and 0. 020 g/ml, respectively）. The results showed that the 4 Tibetan veterinary drugs had very good inhibitory effects on most of the tested diarrheagenic bacteria, and among them, U. diffracta had better inhibitory effects on all the tested bacteria. The optimal prescription of the d Tibetan veterinary drugs （high dose, 0.06 g/ml） exhibited very good inhibitory effect on mouse diarrhea, indicating that the prescription has very good anti-diarrhea effect, which is beneficial to the clinical treatment of such disease and the development of Tibetan veterinary drugs.
基金supported by grants from the National Natural Science Foundation of China(Nos.31870946,31470916,31500769 and 21705165)the Funding of Double First-rate Discipline Construction of China(No.CPU2018GF07)+1 种基金Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Fundamental Research Funds for the Central Universities(Nos.2015PT036,2016PT014,and 3011900159)。
文摘Structure-efficacy effect of small molecular drug attracts wide attentions,but it has always been ignored in nanomedicine research.To reveal the efficacy modulation of nanomedicine,we developed a new type of paclitaxel(PTX)-conjugated gold nanoparticles(PTX-co njugated GNPs)to investigate the influence of drug position in controlling their in vitro properties and in vivo performance.Two therapeutic ligands(TA-PEG-NH-N=PTX and TA-PTX=N-NH-PEG)were synthesized to conjugate PTX on the surface of GNPs at different positions,locating on the surface of gold conjugate and inserting between GNPs and polyethylene glycol(PEG,molecular weight 1000 Da),respectively.It was found that PEG-PTX@GNPs with PTX located between GNP and PEG exhibited higher aqueous solubility,biocompatibility,and stability.In addition,an acid sensitive hydrazone bond has been inserted between PTX and PEG in both ligands for drug release of PTX and PTX-PEG segment,respectively,at the tumor site.Further release of PTX from PTX-PEG segment is based on the esterase hydrolysis of an ester bond between PTX and PEG.This two-step drug release mechanism offers PEG-PTX@GNPs effective and sustained release behavior for desirable anticancer activity,enhanced therapeutic efficacy,and lower systematic toxicity in Hepsbearing animal models.
基金supported by Dean of Scientific Research at Jordan University of Science and Technology(JUST)(No.159/ 2012)
文摘Chromatographic behavior of co-eluted compounds from un-extracted drug-free plasma samples was studied by LC-MS and LC-MS/MS with positive APCI.Under soft gradient,total ion chromatogram（TIC） consisted of two major peaks separated by a constant lower intensity region.Early peak（0.15-0.4 min） belongs to polar plasma compounds and consisted of smaller mass ions（m/z〈 250）;late peak（3.6-4.6 min） belongs to thermally unstable phospholipids and consisted of fragments with mlz〈300.Late peak is more sensitive to variations in chromatographic and MS parameters.Screening of most targeted cardiovascular drugs at levels lower than 50 ng/mL has been possible by LC-MS for drugs with retention factors larger than three.Matrix effects and recovery,at 20 and 200 ng/mL,were evaluated for spiked plasma samples with 15 cardiovascular drugs,by MRM-LC-MS/MS.Average recoveries were above 90%and matrix effects expressed as percent matrix factor（%MF） were above 100%,indicating enhancement character for APCI.Large uncertainties were significant for drugs with smaller masses（m/z〈 250） and retention factors lower than two.
基金financially supported by the National Natural Science Foundation of China(Nos.51073080 and 51273095)Natural Science Foundation of Tianjin(No.13JCYBJC25100)and PCSIRT(No.IRT1257)
文摘A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid （GA） and doxorubicin （DOX） conjugates at different ratios. GA （a liver-targeting ligand） and DOX （an antitumor drug） were both conjugated to oligomeric glycol monomethyl ether-modified sodium alginate （ALG-mOEG） for prolonged duration of action. These NP-based delivery systems exhibited active cell uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. In addition, nanoparticles with a 1：1 （W：W） ratio of GA-ALG-mOEG and DOX-ALG-mOEG （NPs-3） showed the highest cellular uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. Specifically, when mixed nanoparticles defined as NPs-3 were injected in mice, liver DOX concentration reached 61.9 μg/g 3 h after injection, and AUC0-∞ and t1/2 of DOX in liver reached 4744.9 μg·h/g and 49.5 h, respectively. In addition, mice receiving a single injection of NPs-3 exhibited much slower tumor growth （88.37% reduction in tumor weight） 16 days after injection compared with placebo. These results indicate that effective cancer treatment may be developed using mixed NP delivery systems with appropriate ratio of targeted ligand and drug.
文摘The activity of DNA topoisomerase Ⅱ prepared from either normal or tumor tissues were compared. It was found that the unknotting activity of the enzyme in malignant tumor cells was higher than that in normal cells. We selected some antitumor drugs including Chinese traditional medicine, and observed their effects on the unknotting activity of topoisomerase Ⅱ. The results showed that inhibition of the unknotting activity of the enzyme required very low concentrations of drugs, but much higher concentrations were required for other tested. Some antitumor drugs had no effect on the enzyme were also proved. It is interesting that carrageenan, an antiviral drug, strongly blocked the unknotting activity although its antitumor activity has not been reported.
文摘An analysis of selected datasets from the FDA’s drug Adverse Event Reporting System (FAERS) leads us to hypothesize that glyphosate contamination in both food and drugs is a major contributor to chronic and acute kidney failure respectively. In chronic kidney failure, glyphosate-induced pancreatitis results in the release of trypsin, causing a leaky vasculature. The albumin-bound glyphosate escapes into the tissues, protecting the circulatory system and kidneys but resulting in multiple symptoms related to skin, gut, brain, bones, lungs, etc. The rare and poorly understood acute kidney failure response reported for protamine sulfate and Trasylol? is strikingly similar to that associated with glyphosate poisoning. Both drugs are derived from biological tissues that are plausibly contaminated with glyphosate. These drugs protect from haemorrhage, which leads to retention of glyphosate in the vasculature, are followed by circulatory collapse and a high likelihood of death as an outcome. We support our argument by comparing symptom profiles of selected subsets of FAERS with those related to glyphosate poisoning, anomalous reactions to protamine sulfate, and conditions showing strong statistical time-trend correlations with glyphosate.
基金National Natural Science Foundation of China(31560696)Special Project of Enterprises-Universities-Researches Integration of Hainan Province(cxy20150008)Special Project of Technology Development in Scientific Research Institutes of Hainan Province(KYYS-2014-32)
文摘The paper was to explore the preventive effects of five drugs on mycoplasma pneumonia of swine （MPS） and to provide reference for clinical medication of pig farms in Hainan Province. A total of 444 health piglets were randomly divided into 6 groups, including five medication groups （72 piglets in group A, 74 pig- lets in group B, 72 piglets in group C, 76 piglets in group D, 76 piglets in group E） and one control group （74 piglets）. The piglets in experimental groups were treated drugs once a day for successive 5 days at 30, 60, 90, 120 and 150 of age. The piglets in control group were free of medication. At 70 and 140 days of age, 15 piglets of each group were randomly selected to collect their blood sermn. The Mycoplasma hyopneumoniae （M-Hyo） antibodies in serum were measured by en- zyme-linked immunosorbent assay （ELISA）. During the experiment, the incidence rates of respiratory disease, lung lesion, feed conversion rate, average daily gain （ADG）, and mortality rate of pigs were also observed and recorded. The results showed that the five drugs had significant difference in preventative effects. Group C （Zhiyuanjing group） received the best preventive effect and the highest economic benefits. Compared with control group, the ADG and feed conversion rate in group C were increased by 7.53% and 9.09%, respectively; the incidence rate of respiratory disease was reduced by 13.44% and lung lesion was alleviated by 81.43% ; and the earnings of each pig could rise by 132.70 yuan. The preventative effect and economic benefit of the drugs was sequenced by Chansu Kechuanling and Bingchan Kechuanwang. Wante Feilin and amoxicillin had weaker preventive effects against MPS but greatly influenced growth performance of pigs, so they should be used alternatively with other drugs.
文摘Fluphenazine (FP) treatment (50mg/kg bw, ip in saline) 30 min before or 6 or 10 h after CCl4 administration (1 ml/kg ip in olive oil) significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. FP had enhancing effects on the covalent binding of CCl4 reactive metabolites to cellular constituents and on CCl4 induced lipid peroaldation.FP lowered bOdy temperature of the CCl4-poisoned animals during the 24 h observation period. The obtained results are compatible but do not prove the hypothesis that calmodulin (CaM) had participation in late occurring events preceding necrosis. FP lowering action on body temperature, however, might also play a role in the effects of this drug on the onset of CCl4 induced liver necrosis. FP levels in liver tissue as determined by gas chromatography-mass spectrometry evidenced the presence of the drug in amounts suffi cient to inhibit CaM and that suggests that not all preventive effects of FP are due to its indirect actions on the central nervous system via decreased body temperature
文摘In the twenty first century research works, there may be a need to achieve a more reliable research result through a synergy between engineers and biological researchers. The peak absorbance data for various interacting systems were measured. These were used to show that the antiretroviral drug has the effect of increasing the peak absorbance values of both the uninfected and infected blood components, i.e., the drugs are made able to increase the light absorption capacity of the blood cells. For drug 2 that contains three components including Efavirenz, the drug effect on lymphocytes was increased by about 38% for patients that had been on antiretroviral drug treatment. Mathematical models were proposed and used in determining the coating effectiveness of antiretroviral drugs in the presence and absence of HIV. The use of the findings of this work by pharmaceutical industries may help in the search for more effective antiretroviral drugs for the treatment of HIV patients.
文摘The development of new drugs for therapeutic purposes has become very expensive and time-consuming in American and European countries.It is estimated that on the average 50 to 100 million dollars and 10 or more years from the time of patenting are required to make a new drug available for general prescription. Every new drug needs to be charac-
文摘Five common homoeopathic drugs viz., Belladonna, Bryonia, Colchicum, Colocynth and Lathyrus sat were selected and tested against growth and aflatoxin production of Aspergillus flavus. The result indicates that all five drugs suppressed the growth of A. flavus. The lower concentration of all the tested drugs induced maximum growth of fungi and maximum production of aflatoxin. However, the growth as well as aflatoxin production potentiality was considerably decreased when the concentration of the drug was increased. Out of all the five drugs, Bryonia was comparatively less effective with respect to inhibition in aflatoxin production. But Belladonna was found to be most effective drug on growth and aflatoxin production.
文摘Objective: To evaluate the therapeutic effect of Yinchenghao decoction (YCHD, 茵陈蒿汤) and S-adenosy-L-methionine (SAM) in treating intra-hepatic cholestasis of pregnancy (TCP) and improving prognosis of perinatal newborn babies. Methods: Sixty in-patients of TCP were randomly divided into two groups, the group A treated with YCHD and the group B treated with SAM. The symptom of itching and serum biochemical indexes, including glycocholic acid, bilirubin and transaminase, were observed after 3 weeks treat-ment, and the prognosis of perinatal newborn babies between the two groups was compared after delivery. Results: After treatment, the symptom of itching, serum levels of glycocholic acid, bilirubin and transaminase improved significantly (P< 0.05) in both groups, and the prognosis of newborn in the two groups was similar (P>0. 05). Conclusion: Both YCHD and SAM could effectively treat ICP. The former is rather cheaper, so it is more feasible for spreading.Original article on CJITWM (Chin) 2004 ;24(4): 309
文摘A large number of Chinese herbal drugs (CHDs) exhibit antibacterial activities both in vivo and in vitro, but until now little is known regarding their inhibitory mechanisms. Bacterial DNA gyrase is a proven target for antibacterial agents. Aim of this study was to investigate the in-vitro inhibitory effect of methanol extracts of CHDs against supercoiling activity of bacterial DNA gyrase. Fifteen CHDs were selected and extracted with methanol, respectively. Inhibitory effect of the extracts on DNA gyrase was tested using gel-based DNA supercoiling assay. Among fifteen CHDs tested, methanol extracts of Lonicerae Japonicae Flos (S2), Taraxaci Herba (S7), Glycyrrhizae Radix et Rhizoma Praeparata cum Melle (S8) demonstrated an obvious inhibitory effect against supercoiling activity of DNA gyrase, and the others were either less active or could not be determined with the present method. Moreover, it was likely that S7 and S8 inhibit gyrase in a concentration-dependent manner. In conclusion, DNA supercoiling assay is a promising method to study the inhibitory activity of CHDs on bacterial DNA gyrase. Some CHDs do have gyrase-inhibitory activity as proposed. Further investigations are needed to elucidate the inhibition mechanism of these CHDs on supercoiling activity of gyrase.
