To systematically evaluate the efficacy and safety of tripterygium glycosides (TG) combined with ACEI/ARB preparation in treating diabetic nephropathy stage IV. The computer retrievals were made in Cochrane Libarary, PubMed, Embase, SCI, Sinnomed, CNKI, Chinainfo and VIP, and hand retrievals were conducted for meeting and academic papers (updated to December 30, 2014), in order to collect randomized controlled trials and quasi-randomized control trials for TG combined with ACEI/ARB preparation in treating diabetic nephropathy stage IV and set the literature inclusion and elimination standards. Eligible literatures were included and evaluated according to standards in Cochrane Handbook. RevMan 5.3 and Stata 12.0 were used for a Meta-analysis. A total of 13 randomized controlled trials and quasi-randomized control trials involving 1119 patients with diabetic nephropathy were included. The Meta analysis result showed that compared with the control group, the combination group showed better effects in reducing the 24-hour urinary protein [MD = -0.84, 95% CI (-1.02, -0.66)], raising albumin [SMD = 0.98, 95% CI (0.81, 1.16)], the total efficiency [OR = 4.23, 95% CI (2.77, 6.46)] and the significant efficiency [OR = 5.35, 95% CI (2.70, 10.60)], with no statistical difference in Serum Creatinine between Both groups [MD = -0.82, 95% CI (-4.30, 2.66), P = 0.64]. However, the risk of adverse reactions increased by 7% [RD = 0.07, 95% CI (0.03, 0.12)]. The Egger's test showed no publication bias. Tripterygium Glycosides combined with ACEI/ARB in treating diabetic nephropathy stage IV is supper than the single administration of ACEI/ARB, with a good prospect in clinical application. Nevertheless, due to the small-size and low-quality samples in this study, more high-quality and large sample-size randomized controlled trials shall be conducted to verify the findings.
Angiotensin Receptor Antagonists ; administration & dosage ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; Diabetic Nephropathies ; drug therapy ; Drug Therapy, Combination ; Glycosides ; administration & dosage ; Humans ; Tripterygium ; chemistry

Randomized clinical trials led to the clinical recommendation that angiotensin-converting enzyme inhibitors (ACEI) should be used as standard therapy in most patients experiencing an acute myocardial infarction (AMI). However, the optimal initiation timing of treatment, as well as the exact mechanisms, have not been completely resolved, especially with the development of reperfusion strategy after AMI. Earlier initiation of ACEI might be associated with more prompt recovery of left ventricular ejection fraction due to more rapid attenuation of negative remodeling.
Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; therapeutic use ; Humans ; Myocardial Infarction ; drug therapy ; Randomized Controlled Trials as Topic ; Time Factors

4 liters of polyethylene glycol (PEG) solution is commonly used to evacuate the colon before colonoscopy. This substance, however, is known to cause electrolyte abnormalities such as hyponatremia. Seizures caused by hyponatremia associated with bowel preparation have only rarely been reported. We report the case that a 75-year-old woman with no prior history of seizures was developed severe hyponatremia (112 mEq/L) with generalized tonic-clonic seizure and mental change after ingestion of 4L of PEG solution. Past medical history was notable for thiazide diuretics. Her symptoms are improved during intravenous administration of hypertonic saline for the correction of hyponatremia. Patients with impaired ability to excrete free water those with renal insufficiency, hypothyroidism, mineralocorticoid deficiency, liver cirrhosis, or heart failure as well as those taking drugs which including thiazide diuretics, NASIDs, and ACE inhibitors have risk of hyponatremia following bowel preparation for colonoscopy. We conclude that physicians should check patient's condition and electrolyte abnormalities before colonoscopy procedures.
Administration, Intravenous ; Angiotensin-Converting Enzyme Inhibitors ; Colon ; Colonoscopy ; Eating ; Female ; Heart Failure ; Humans ; Hyponatremia ; Hypothyroidism ; Liver Cirrhosis ; Polyethylene ; Polyethylene Glycols ; Renal Insufficiency ; Seizures ; Sodium Chloride Symporter Inhibitors ; Water

OBJECTIVEThe objective of this study was to investigate arsenic induced changes in blood delta-aminolevulinic acid dehydratase (ALAD) after in vitro and in vivo exposure to this element and its response to co-administration of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) either individually or in combination.

METHODSRat whole blood was exposed to varying concentrations (0.1, 0.2 and 0.5 mmol/L) of arsenic (III) or arsenic (V), to assess their effects on blood ALAD activity. Varying concentrations of MiADMSA and DMSA (0.1, 0.5 and 1.0 mmol/L) were also tried in combination to determine its ability to mask the effect of arsenic induced (0.5 mmol/L) inhibition of blood ALAD in vitro. In vitro and in vivo experiments were also conducted to determine the effects of DMSA and MiADMSA either individually or in combination with arsenic, on blood ALAD activity and blood arsenic concentration.

RESULTSIn vitro experiments showed significant inhibition of the enzyme activity when 0.1-0.5 mmol/L of arsenic (III and V) was used. Treatment with MiADMSA increased ALAD activity when blood was incubated at the concentration of 0.1 mmol/L arsenic (III) and 0.1 mmol/L MiADMSA. No effect of 0.1 mmol/L MiADMSA on ALAD activity was noticed when the arsenic concentration was increased to 0.2 and 0.5 mmol/L. Similarly, MiADMSA at a lower concentration (0.1 mmol/L) was partially effective in the turnover of ALAD activity against 0.5 mmol/L arsenic (III), but at two higher concentrations (0.5 and 1.0 mmol/L) a complete restoration of ALAD activity was observed. DMSA at all the three concentrations (0.1, 0.5 and 1.0 mmol/L) was effective in restoring ALAD activity to the normal value.

CONCLUSIONSThe results thus suggest that arsenic has a distinct effect on ALAD activity. Another important toxicological finding of the present study, based on in vivo experiments further suggests that combined administration of DMSA and MiADMSA could be more beneficial for reducing blood ALAD inhibition and blood arsenic concentration than the individual treatment.

Administration, Oral ; Animals ; Arsenic Poisoning ; blood ; Arsenicals ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Injections, Intraperitoneal ; Male ; Mice ; Porphobilinogen Synthase ; antagonists & inhibitors ; blood ; Rats ; Succimer ; analogs & derivatives ; pharmacology

AIMTo explore the effects of aminoguanidine (AG) inhalation on bleomycin (BLM)-induced fibrosis in lungs of rats and its possible mechanism.

METHODSSixty male Sprague-Dawley rats were randomly divided into 4 groups: BLM plus normal saline (NS) group, BLM plus 10 mmol/L AG group, BLM plus 50 mmol/L AG group, and NS plus NS group. At the same day when administrated by single intratracheal instillation of BLM (5 mg/kg) or equal volume of NS as control, the rats received NS (the same volume as AG) or AG inhalation (10 mmol/L AG, or 50 mmol/L AG, 5 min/each time, 2/day) for 30 d. The nitrite/nitrate (NO2-/NO3-) content of plasma in pulmonary artery, hydroxyproline content and the pathological changes in lungs, as well as lipid peroxide (LPO) content of plasma in pulmonary artery were examined.

RESULTSThe NO2-/NO3- content of plasma in pulmonary artery was increased in rats on day 14 after intratracheal instillation of BLM, compared with that of the control rats (P < 0.01). The hydroxyproline content in lung, the grade of pulmonary alveolitis and the content of LPO of plasma in pulmonary artery were increased in rats on day 30 after intratracheal instillation of BLM, compared with that of the control rats, respectively (P < 0.05, P < 0.01, P < 0.01). The above-mentioned changes were ameliorated by AG inhalation (10 mmol/L AG, or 50 mmol/ LAG, 5 min/each time, 2/day) for 30 d (P < 0.01, P < 0.05, P < 0.05, P < 0.01).

CONCLUSIONAG inhalation has anti-action on BLM-induced fibrosis in lung, which might be related to blockage of oxidative injury in lung.

Administration, Inhalation ; Animals ; Bleomycin ; Enzyme Inhibitors ; administration & dosage ; pharmacology ; Guanidines ; administration & dosage ; pharmacology ; Male ; Nitric Oxide Synthase ; antagonists & inhibitors ; Oxidative Stress ; drug effects ; Pulmonary Fibrosis ; chemically induced ; physiopathology ; prevention & control ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of repeated injections of L-NMMA on a goat model with osteoarthrotic temporomandibular joint (TMJ) disease.

METHODSEight goats were selected in this study. Bilateral TMJ osteoarthrosis (OA) was induced by injecting 0.5% collagenase. L-NMMA was injected into one side of TMJs at 4 weeks after collagenase injection (one time every three days). Another joint as control was simultaneously injected using 0.9% saline solution. All goats were killed at 12 weeks after collagenase injection. The TMJ specimens were harvested and processed for histological examination. Modified Mankin's grading score system was used for evaluating changes in the TMJ.

RESULTSThe control side of TMJs showed severe osteoarhrotic changes in the condyle whereas the L-NMMA-treated TMJs showed less degenerative alterations. The histologic score was 3.83 in the L-NMMA treated side, and 6.33 in the control. There was a significant difference in osteoarthrotic changes between the L-NMMA-treated and control TMJs (P < 0.01).

CONCLUSIONSRepeated intra-articular injection of L-NMMA into TMJ may play a role in inhibiting TMJOA progression.

Animals ; Enzyme Inhibitors ; administration & dosage ; therapeutic use ; Female ; Goats ; Injections, Intra-Articular ; Male ; Osteoarthritis ; drug therapy ; Temporomandibular Joint Disorders ; drug therapy ; omega-N-Methylarginine ; administration & dosage ; therapeutic use

OBJECTIVETo compare the effects of high, middle and low doses of enalapril in preventing left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats, especially evaluating the efficacy of low dose enalapril.

METHODSAMI was induced by ligating the left coronary artery in 149 female SD rats. 48 hours after the procedure, the 97 surviving rats were randomized to one of the following four groups: (1) AMI controls (n = 24), (2) high-dose (10 mg x kg(-1) x d(-1), n = 25), (3) middle-dose (1 mg x kg(-1) x d(-1), n = 23), and (4) low-dose (0.1 mg x kg(-1) x d(-1), n = 25) enalapril groups. In addition, sham-operated (n = 13) and normal rats (n = 10) were randomly selected to serve as non-infarction controls. Enalapril was delivered by direct gastric gavage. After 4 weeks of therapy, hemodynamic studies were performed, then the rat hearts were fixed with 10% formalin and pathology analysis was performed. Exclusive of the dead rats and those with MI size < 35% or > 55%, complete experimental data were obtained from 67 rats, which were comprised of (1) AMI controls (n = 13), (2) high-dose enalapril (n = 13), (3) middle-dose enalapril (n = 12), (4) low-dose enalapril (n = 12), (5) sham-operated (n = 8) and (6) normal (n = 9) groups.

RESULTSThere were no significant differences among the four AMI groups in infarction size (all P > 0.05). Compared with the sham-operated group, the left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), absolute and relative weight (LVAW, LVRW) in AMI group were all significantly increased (all P < 0.001), while maximum LV pressure rising and dropping rates (+/- dp/dt) and their corrected values by LV systolic pressure (+/- dp/dt/LVSP) were all significantly reduced in the AMI control group (P < 0.01 - 0.001), indicating LVRM occurred and LV systolic and diastolic functions were impaired. Compared with the AMI group, LVEDP, LVV, LVAW and LVRW were all significantly decreased in the three enalapril groups (control P < 0.001), with the reduction of LVEDP, LVV and LVAW being more significant in high-dose than in low-dose enalapril groups (all P < 0.05), and the +/- dp/dt/LVSP were significantly increased only in the high and middle-dose enalapril groups (P < 0.01).

CONCLUSIONSHigh, middle and low doses of enalapril were all effective in preventing LVRM after AMI in the rat, with low dose enalapril being effective and high dose superior. As for LV functional improvement, only high and middle-dose enalapril were effective.

Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; pharmacology ; Animals ; Dose-Response Relationship, Drug ; Enalapril ; administration & dosage ; pharmacology ; Female ; Myocardial Infarction ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Ventricular Remodeling ; drug effects

OBJECTIVE: To determine the relation between plasma tissue factor (TF) and serum angiotensin II(AngII) and the effect of different dosages of fosinopril on chronic heart failure(CHF). METHODS: Thirty healthy controls and 35 CHF patients were recruited to observe AngII,TF, left ventricular ejection fractions(LVEF) and left ventricular end-systolic volume index (LVESVI) at baseline and 10 weeks after the treatment. The 35 patients were randomly assigned into 2 groups: A routine dosage fosinopril group received 10 mg once daily and a middle dosage group received 10 mg twice a day for 10 weeks. RESULTS: Compared with the healthy controls, AngII,TF,and LVESVI significantly increased (P<0.01) and LVEF significantly decreased (P<0.01) in CHF patients. The TF was positively correlated with AngII(r=0.2491, P<0.01) in the patients. After the 10-week treatment with different dosages of fosinopril, AngII,TF,and LVESVI obviously decreased(P<0.05 or P<0.01) and LVEF significantly increased in the 2 groups (P<0.05 or P<0.01). The middle dosage group changed more than the routine dosage group (P<0.01). CONCLUSION TF is positively correlated with AngII in CHF patients. Fosinopril can greatly improve cardiac function and antagonize prethrobotic state,and the therapeutic effect improves with the dosage increase.
Aged ; Angiotensin II ; blood ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; Chronic Disease ; Female ; Fosinopril ; administration & dosage ; Heart Failure ; blood ; drug therapy ; Humans ; Male ; Middle Aged ; Thromboplastin ; metabolism

To evaluate the effects of cyclosporin A (CyA) on clinical outcome and pathologic changes in children with IgA nephropathy (IgAN), we retrospectively evaluated 14 children (mean age 8.9+/-2.9 yr; eight males, six females) who were treated with CyA and steroids. The starting dose of CyA was 5 mg/kg per day, and the drug level was maintained at 100-200 ng/mL. The mean CyA level was 183.8+/-48.3 ng/mL (range 120.7-276.0 ng/mL) and the mean duration of CyA therapy was 10.9+/-1.9 months (range 8-12 months). After CyA therapy the mean 24 hr urinary protein excretion declined from 107.1+/-35.1 mg/m2/hr to 7.4+/-2.4 mg/m2/hr (P<0.001) and serum albumin increased from 3.3+/-0.6 g/dL to 4.3+/-0.3 g/dL (P<0.001). At a follow-up biopsy the histological grade of IgAN was improved in seven (50%) of the 14 patients, remained the same in three (21%), and was aggravated in four (29%). Serum creatinine, creatinine clearance, and blood pressure did not differ before and after CyA therapy. Two patients (14%) showed CyA-induced nephrotoxicity at the second biopsy. Our findings indicate that CyA therapy may be effective in reducing proteinuria and regressing renal pathology in a subset of children with IgAN.
Angiotensin-Converting Enzyme Inhibitors/*administration & dosage ; Child ; Cyclosporine/*administration & dosage ; Drug Combinations ; Female ; Glomerulonephritis, IGA/*diagnosis/*drug therapy ; Humans ; Immunosuppressive Agents/administration & dosage ; Male ; Steroids/*administration & dosage ; Treatment Outcome

This study is to investigate the effects of cisplatin combined with heparanase inhibitor OGT2115 on proliferation, invasion and migration of human nasopharyngeal carcinoma cells CNE-2 and to provide a new target for the treatment of metastasis of nasopharyngeal carcinoma. MTT assay was used to detect the cell viability of CNE-2 after exposure to different concentrations of DDP (2, 4, 8, 16 and 32 micromol x L(-1)), different concentrations of OGT2115 (0.4, 0.8, 1.6, 3.2 and 6.4 micromol x L(-1)), and DDP combined with OGT2115. Transwell assay was applied to analyze the effects of drugs on invasion and migration of human nasopharyngeal carcinoma cells. Wound healing assay was performed to detect cell migration and heparanase activity was analyzed by ELISA. MTT results showed that DDP can inhibit the proliferation of CNE-2 cells in a time and concentration-dependent manner, with an IC50 of 24.03 micromol x L(-1) at 24 h (P < 0.05), low concentration of DDP has almost no inhibitory effect on cell invasion and migration. DDP combined with OGT2115 can significantly inhibit cell invasion and migration. Inhibition of heparanase can significantly enhance anti-invasion and anti-proliferation of DDP.
Antineoplastic Agents ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cisplatin ; administration & dosage ; pharmacology ; Drug Combinations ; Enzyme Inhibitors ; metabolism ; pharmacology ; Glucuronidase ; antagonists & inhibitors ; metabolism ; Humans ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Invasiveness