A pilot study of the effect of curcumin on epigenetic changes and DNA damage among patients with non-alcoholic fatty liver disease: A randomized,double-blind,placebo-controlled,clinical trial

BackgroundThe enhancement of oxidative stress in non-alcoholic fatty liver disease (NAFLD) patients may cause mutation in DNA by deamination of cytosine to 5-hydroxyuracil or uracil. This study aimed to discover the effects of curcumin on NAFLD progress, DNA damage caused by oxidative stress, and promoter methylation of mismatch repair enzymes.Material and methodsin this study, 54 NAFLD patients were randomly devided into two groups, according to a double blind parallel design either phytosomal curcumin (250 mg/day) or placebo for 8 weeks. Fasting blood samples and anthropometric measures were taken twice, once at the baseline and once at the end of the study. Promoter methylation and 8-hydroxy-2′ -deoxyguanosine (8−OHdG) concentration as DNA damage mediator were measured by restriction enzymes and enzyme-linked immunosorbent assay, respectively.ResultAnalysis was performed on 44 patients. According to our between groups analysis, curcumin significantly reduced the methylation in MutL homolog 1 (MLH1) and MutS homolog 2 (MSH2) promoter regions. The within-group comparison revealed that anthropometric variables significantly decreased. However, the result of the between groups comparison indicated no significant changes in the anthropometric variables except for BMI. Liver enzymes and 8−OHdG did not significantly change at the end of the study, neither in curcumin group nor in placebo group.ConclusionCurcumin might be able to reduce the risk of mismatch base pair in DNA among the NAFLD patients. However, it did not change the DNA damage mediator and liver enzymes. For confirming these results, more studies with longer duration, more numbers of examined genes, higher dose of curcumin, and larger sample size are required.     

匹罗卡品癫痫模型及戊四唑点燃模型的行为学、组织学对比研究

匹罗卡品癫痫持续状态(SE)模型及戊四唑点燃模型均是临床常用的癫痫动物模型,两种模型有不同特点,采用不同的模型可能会有不同的试验结果。神经元丢失及苔藓纤维出芽是癫痫产生过程中较常见的组织病理学变化,目前少见对癫痫产生过程中的续贯性研究报告。本研究同步观察两种模型     

Ultrasonographic changes of early liver cirrhosis in chronic hepatitis B: A longitudinal study

Ultrasonography of prospectively followed chronic hepatitis B patients who developed liver cirrhosis were reevaluated in order to identify the ultrasonographic changes of early cirrhosis. Ultrasonographic features of 29 patients before and after cirrhosis were as follows: portal vein diameter—1.20 cm/1.29 cm (NS); cirrhosis score—5.69/7.52 (p < 0.01); spleen size index—21.99 cm²/25.84 cm² (NS). The result suggests that ultrasonographic diagnosis of early cirrhosis is not easy on a single occasion; however, the score system method is helpful in longitudinal follow-up chronic hepatitis patients. A careful comparison of hepatic parenchymal and surface changes are mandatory. © 1993 John Wiley & Sons, Inc.     

Dose-response effect of ferulic acid against nicotine-induced tissue damage and altered lipid levels in experimental rats: a pathohistological evaluation

In the present study, ferulic acid (FA), a naturally occurring nutritional compound, was investigated for its protective effect against nicotine-induced toxicity in a dose dependent manner. The toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg body weight (b.w.) for 22 weeks in female albino Wister rats. Simultaneously, rats were treated with FA at three different doses (10, 20 and 40 mg/kg b.w.) via intragastric intubations for 22 weeks. At the end of the experiment, circulatory marker enzymes (i.e. lactate dehydrogenase and alkaline phosphatase) and tissue (lung, liver and kidney) lipid levels (i.e. cholesterol, free fatty acids, triglycerides and phospholipids) were analysed, which were significantly increased in the nicotine-treated group, whereas FA treatment positively modulated these levels. FA at a dose of 20 mg/kg b.w. was found to be more effective when compared with the other two doses. The lung, liver and kidney excised from the different groups were fixed and stained to perform histological assessments. The protective effect of FA on histological observations confirms that 20 mg/kg b.w. of FA modulates the deleterious effects of nicotine. The results suggest that FA exerts its inhibitory action against nicotine-induced tissue damage through its antioxidant and antihyperlipidemic properties.     

A double-blind, dose comparison study of topiramate for prophylaxis of basilar-type migraine in children: a pilot study

BACKGROUND: Basilar-type migraine (BM) is the most common migraine "variant," representing 3-19% of migraine in children.BMis characterized by attacks of dizziness, vertigo, visual disturbances, ataxia, and/or diplopia, followed by migraine headache. OBJECTIVE: The objective of this study is to assess the efficacy and safety of topiramate for prophylaxis of BM in children and adolescents (6-18 years). DESIGN: Outpatient, double-blind, parallel-group, dose comparison study with 2 phases: prerandomization (screening/washout and 4-week prospective baseline) and 12-week double blind (titration and maintenance). METHODS: Following consent and assent, subjects with BMs, as defined by the International Classification of Headache Disorders (second edition), and > or =4 migraines/month were randomized to receive either 25 mg per day or 100 mg per day of topiramate in a 1 : 1 ratio. RESULTS: Fourteen children (4 boys, 10 girls) completed the double-blind phase (7 in the 25-mg group and 7 in the 100-mg group). During the prospective baseline, the mean headache frequency of the combined group "all migraines" per month was 4.5/month (25 mg) and 4.8/month (100 mg). Average duration of migraine was 5.5 hours (25 mg) and 5.0 hours (100 mg) and average mean pain (5-point faces scale) was 3.3 for both (25 mg 100 mg). The reduction in median monthly migraine rate during the double-blind treatment phase relative to baseline was 2.9 (64.4%) and 3.6 (75.0%) for the 25-mg and 100-mg topiramate-treated groups, respectively (P < .001). The reduction in median monthly BM rate during the double-blind treatment phase relative to baseline was 2.5 (74.24%) and 2.3 (82.8%) for the 25-mg and 100-mg topiramate-treated groups, respectively. The overall reduction in BM attacks reduced from 2.84/month to 0.59/month (79.2%; P < .0042). Overall, 86% of patients responded with a greater than 50% reduction in migraine frequency (100%, 25 mg and 71%, 100 mg). Mean reduction in migraine duration was 18 minutes (25 mg) and 89 minutes (100 mg). There was no significant difference in migraine severity between the 2 groups. Parent Global Assessment was "very much" or "much improved" in 6 of 7 (25 mg) and 3 of 7 (100 mg) patients. Migraine disability as measured by PedMidas reduced from moderate to no disability (P < .001). There were no serious adverse events. CONCLUSIONS: Preventive therapy with topiramate resulted in reducing the overall migraine frequency and the frequency of attacks of BM at both 25 mg and 100 mg doses relative to the historical baseline and prospective baseline periods. The 2 treatment groups resulted in comparable outcomes.     

Short-term pain evolution in chronic low back pain with Modic type 1 changes treated by a lumbar rigid brace: A retrospective study

Background

Blocking the lumbar or lumbosacral spine with a custom-made rigid lumbar brace, based on the mechanical origin of active discopathy, is a therapeutic option for low back pain, but no study has yet defined its applicability in low back pain.

A catenary model to study transport and conjugation of baicalein, a bioactive flavonoid, in the Caco-2 cell monolayer: demonstration of substrate inhibition

The transport and metabolism of baicalein (Ba) was studied in vitro and in Caco-2 cells. Protein binding of Ba with Caco-2 lysate showed that Ba was bound to two classes of sites: a higher affinity, lower capacity site (K(A1) = 27.6 +/- 4.7 microM(-1), n(1) = 10.6 +/- 0.6 nmol/mg) and lower affinity, higher capacity site (K(A2) = 0.015 +/- 0.0013 microM(-1), n(2) = 413 +/- 21 nmol/mg). Incubation studies of Ba with Caco-2 lysate showed substrate inhibition of both glucuronidation and sulfation, with K(m) values of 0.14 +/- 0.034 and 0.015 +/- 0.0053 microM, and K(I) values of 6.75 +/- 1.70 and 0.37 +/- 0.16 microM, respectively. In the Caco-2 monolayer, Ba (8-47 microM) displayed good apparent permeabilities (P(app)) across the membrane; P(app) was found to be increased with elevated loading concentration in both the absorptive and secretory directions. However, the efflux ratio was less than unity, negating the involvement of apical efflux transporters. The concentration ratios of Ba sulfate (BS) and glucuronide (BG) decreased with increased loading Ba concentration, suggesting that BS and BG are apically excreted via transporters, likely breast cancer resistance protein and multidrug resistance-associated protein 2, respectively. Data fit to the catenary model, composed of basolateral, cellular, and apical compartments, showed a low cellular unbound fraction (0.0019 +/- 0.00018), a high passive diffusion clearance (0.012 +/- 0.00029 ml/min/mg), and substrate inhibition, with sulfation being more readily saturated and inhibited than glucuronidation, as evidenced by smaller K(m) value (0.35 +/- 0.078 versus 1.95 +/- 0.57 microM) and K(I) value (0.58 +/- 0.20 versus 7.90 +/- 1.10 microM); these patterns paralleled those observed in the lysate incubation studies. The results showed that the catenary model aptly predicts substrate inhibition kinetics and offers significant and mechanistic insight into the transport and atypical metabolism of drugs in the Caco-2 monolayer.     

Effects of chromium supplementation on blood pressure,body mass index,liver function enzymes and malondialdehyde in patients with type 2 diabetes: A systematic review and dose-response meta-analysis of randomized controlled trials

BackgroundSeveral studies reported beneficial effects of chromium supplementation for management of type 2 diabetes mellitus (T2DM). The present study aimed to provide a systematic review and meta-analysis of randomized controlled trials (RCTs) examining the effects of chromium supplementation on blood pressure, body mass index (BMI), liver function enzymes and malondialdehyde (MDA) in patients with T2DM.MethodsPubMed, Scopus, and Embase were searched up to 15 November 2020 with no language and time restriction. RCTs that reported the effects of chromium supplementation on blood pressure, BMI, liver function enzymes and MDA in patients with T2DM were included. A random-effects model was used to compute weighted mean differences (WMDs) with 95 % confidence intervals (CIs). Between-study heterogeneity was assessed by Cochran's Q test and quantified by I² statistic.ResultsOf 3586 publications, 15 RCTs were included for the meta-analysis. Pooled effect sizes indicated that chromium significantly reduced diastolic blood pressure (DBP) (WMD): -2.36 mmHg, 95 % CI: −4.14, −0.60; P = 0.008), and MDA (WMD: −0.55 umol/l, 95 % CI: −0.96, −0.14; P = 0.008). However, chromium supplementation did not significantly affect BMI, systolic blood pressure (SBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST). Meta-regression analysis did not show significant linear relationship between dose of chromium and change in BMI (p = 0.412), SBP (p = 0. 319), DBP (p = 0.102), ALT (p = 0.923), AST (p = 0.986) and MDA (p = 0.055).ConclusionThe present systematic review and meta-analysis shows that supplementation with chromium at dose of 200–1000 μg/day may reduce DBP and MDA in T2DM patients.     

An evaluation of a supratherapeutic dose of inclisiran on cardiac repolarization in healthy volunteers: A phase I,randomized study

Inclisiran is a small interfering RNA molecule that has been shown to provide an effective and sustained reduction in low‐density lipoprotein cholesterol levels. This study aimed to determine whether a supratherapeutic dose of inclisiran affects cardiac repolarization and conduction in healthy volunteers. A phase I, randomized, double‐blind, double‐dummy, placebo‐ and positive‐controlled, three‐way crossover study was performed in 48 healthy volunteers. Volunteers were assigned to three treatments in a randomized sequence: a supratherapeutic dose of inclisiran sodium (900 mg), placebo, or moxifloxacin 400 mg as a positive control, with a minimum 7‐day washout period between treatments. Continuous electrocardiogram monitoring was performed from >60 min before dosing until 48 h after dosing. Pharmacokinetics, pharmacodynamics, and safety were also assessed. Inclisiran, at a supratherapeutic dose, did not show a clinically significant effect on the QT interval (Fridericia correction formula [QTcF]; maximal placebo‐ and baseline‐corrected change: 2.5 ms [90% confidence interval: 0.6, 4.5]) near the maximal plasma concentrations at 4 h. In addition, inclisiran did not show any effects on other electrocardiogram intervals or ST‐ and T‐wave morphology. The positive control, moxifloxacin, demonstrated the expected changes in QTcF interval, validating the adequate sensitivity of the study. A supratherapeutic dose of inclisiran sodium (900 mg) had no effect on the QTcF interval or other electrocardiogram parameters, providing additional insight and reassurance regarding the safety profile of inclisiran.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Inclisiran is a novel siRNA therapeutic agent that specifically targets the liver and has been shown to effectively, sustainably, and safely lower low‐density lipoprotein cholesterol levels, a proven risk factor for atherosclerotic cardiovascular disease. Prolongation of cardiac repolarization can result in life‐threatening arrhythmias; therefore, a thorough characterization of the effects of inclisiran on the QT/corrected QT interval is a premarketing requirement for this therapeutic agent. This is the first clinical study investigating the potential effects of an siRNA therapy on QT intervals to our best knowledge.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study addressed whether or not a supratherapeutic dose of inclisiran had any effects on cardiac repolarization based on the corrected QT interval or other electrocardiogram parameters in healthy participants.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

A supratherapeutic dose of inclisiran sodium (900 mg) was generally safe and well‐tolerated and did not show a clinically relevant effect on the QT interval. Other electrocardiogram intervals and ST‐ and T‐wave morphology were also unaltered by a supratherapeutic dose of inclisiran.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

This study demonstrated that a supratherapeutic dose of inclisiran sodium (900 mg), a novel siRNA therapeutic agent, does not affect cardiac repolarization, providing additional reassurance regarding the safety profile of inclisiran. This is the first QT clinical study investigating the effects of a novel siRNA therapeutic agent.     

纳布啡减少罗哌卡因用于硬膜外分娩镇痛的剂量:一项随机、双盲、对照研究

目的:探讨纳布啡混合罗哌卡因用于硬膜外分娩镇痛的作用.方法:选取2019年10月至2021年2月复旦大学附属妇产科医院收治的产妇104例.采用随机数字表将104例产妇随机分为纳布啡组(N组,n=52)和罗哌卡因组(L组,n=52).选择L2-3间隙进行硬膜外穿刺,穿刺成功并平卧后给予试验剂量.给药方法:N组,硬膜外注射...     

Bioequivalence study of two formulations of enalapril, at a single oral dose of 20 mg (tablets): A randomized, two-way, open-label, crossover study in healthy volunteers

Background: Enalapril maleate is the monoethyl ester prodrug of enalapril- at, an angiotensin-converting enzyme inhibitor indicated in the management of essential and renovascular hypertension, and in the treatment of congestive heart failure and in asymptomatic patients with left ventricular dysfunction and an ejection fraction of ≥35%. Enalapril has little pharmacologic activity until hydrolyzed in vivo to enalaprilat.Objective: The aim of the present study was to compare the bioavailability and tolerability of 2 commercial brands (test and reference formulations) of enalapril tablets (20 mg), described as the rate and extent of absorption of the active moiety, to assess their bioequivalence.Methods: This single-dose, randomized, 2-way, open-label, crossover study in healthy volunteers aged 18 to 40 years was conducted at the Clinical Pharmacology Study Unit, Hospital Clínico San Carlos (Madrid, Spain). Subjects were randomized to receive (under fasting conditions) either the test or reference formulation of enalapril (20-mg tablet) at study period 1 and the opposite formulation at study period 2. Study periods were separated by a washout period of at least 7 days. During each study period, 15 plasma extractions were made to determine enalapril and enalaprilat plasma concentrations and to calculate the pharmacokinetic (PK) properties (maximal plasma drug concentration [C_max], time to C_max [T_max], area under the plasma concentration-time curve [AUC] to the last measurable concentration [AUC_t], AUC from time 0 to infinity [AUC_0−∞], mean residence time, and elimination half-life []) of both. Physical examination, subject interview, laboratory analyses, electrocardiogram, and blood pressure (BP) were used to assess tolerability.Results: Twenty-four subjects were included in the study (12 men, 12 women; mean [SD] age, 22.8 [2.2] years [range, 19-30 years]). Of these, 1 subject (4.2%) withdrew from the study for personal reasons; thus, PK and statistical analyses included results from 23 subjects. No statistically significant sequence or period effect was found. T_max was not statistically different between the 2 formulations, and the 90% CI calculated for T_max for the difference of the medians was within the predefined range. The 90% CIs of the logarithmically transformed concentration-derived parameters (C_max AUC_t, and AUC_0−∞) also were within the predefined range; thus, the 2 formulations are considered bioequivalent. For both formulations, systolic and diastolic BPs showed significant reductions compared with baseline values (P < 0.05). Seven adverse effects were recorded, all of them transient and none of severe intensity.Conclusions: In this study of 2 commercial brands (test and reference formulations) of enalapril in healthy subjects, designed and conducted under Good Clinical Practice guidelines, a similar rate and extent of absorption for both formulations were found to be bioequivalent. Both formulations produced a significant decrease in BP values and were generally well tolerated.     

新型内冷微波天线离体肝组织凝固实验--凝固灶短轴径与时间、功率的关系初探

目的探讨新型内冷微波天线作用于离体猪肝组织，凝固灶短轴径（SD）与凝固时间和功率的关系。方法采用MTC-3型微波治疗仪和新型水循环内冷微波天线，分别以不同时间和功率组合凝固新鲜离体猪肝组织，分别分析SD与时间和功率的关系。结果①功率一定时，在一定的时间范围（18min）内，SD与作用时间有着高度的线性相关（r值0．94～0．98，P〈0．01）；功率30W时，18min后这种相关性将变差，因达一定时间点后，随着时间的延长，SD增加缓慢，甚至不再增加；但加大功率后该时间点后移；②时间一定时，功率与SD大小也存在高度近似的线性相关（r值0．94～0．98，P〈0．01）；③在18min时间段内，SD可通过其与时间和功率的二元线性回归方程（P〈0．01）求出近似值。结论①在达一定时间点后，单纯延长作用时间，SD可能不再增大，但增加功率，延长凝固时间能够继续增大SD；②在一定时间范围内，植人式微波天线对离体肝组织SD大小与作用时间、功率存在高度近似的线性相关，这种关系将有助于指导临床应用。     

Application of a six sigma model to the evaluation of the analytical performance of serum enzyme assays and the design of a quality control strategy for these assays: A multicentre study

BackgroundSix medical testing laboratories at six different sites in China participated in this study. We applied a six sigma model for (a) the evaluation of the analytical performance of serum enzyme assays at each of the laboratories, (b) the design of individualized quality control programs and (c) the development of improvement measures for each of the assays, as appropriate.MethodsInternal quality control (IQC) and external quality assessment (EQA) data for selected serum enzyme assays were collected from each of the laboratories. Sigma values for these assays were calculated using coefficients of variation, bias, and total allowable error (TEa). Normalized sigma method decision charts were generated using these parameters. IQC design and improvement measures were defined using the Westgard sigma rules. The quality goal index (QGI) was used to assist with identification of deficiencies (bias problems, precision problems, or their combination) affecting the analytical performance of assays with sigma values <6.ResultsSigma values for the selected serum enzyme assays were significantly different at different levels of enzyme activity. Differences in assay quality in different laboratories were also seen, despite the use of identical testing instruments and reagents. Based on the six sigma data, individualized quality control programs were outlined for each assay with sigma <6 at each laboratory.ConclusionsIn multi-location laboratory systems, a six sigma model can evaluate the quality of the assays being performed, allowing management to design individualized IQC programs and strategies for continuous improvement as appropriate for each laboratory. This will improve patient care, especially for patients transferred between sites within multi-hospital systems.     

Single dose dexamethasone prophylaxis of postembolisation syndrome after chemoembolisation in hepatocellular carcinoma patient: A randomised,double-blind,placebo-controlled study

BACKGROUNDEven in the immuno-oncology era, transcatheter arterial chemoembolisation (TACE) is the most effective way to treat intermediate stage hepatocellular carcinoma (HCC). Postembolisation syndrome (PES) is the most common side effect from TACE and there is still no standard prevention guideline.AIMTo evaluate the efficacy of single dose intravenous dexamethasone regimen to prevent PES after TACE among patients with HCC. METHODSThis study enrolled patients with HCC who had eligible indication for TACE without macrovascular invasion/extrahepatic metastasis. Patients were randomly assigned to either an intravenous single dose of dexamethasone 8 mg or placebo one hour before TACE. The primary outcome was a negative result of PES at 48 h after TACE, which was defined as score < 2 of Southwest Oncology Group toxicity coding criteria using fever, nausea, vomiting and pain to calculated. And the secondary end point was duration of admission between two groups.RESULTSOne hundred patients were randomly assigned 1:1. Under intention-to-treat analysis, 49 patients were randomly assigned to the dexamethasone and 51 to the placebo groups. Both groups were similar for baseline characteristics. The negative PES rate was significantly higher in the dexamethasone group than in the placebo group (63.3% vs 29.4%; P = 0.005). Mean Southwest Oncology Group toxicity coding PES was 2.14 (95%CI: 1.41-2.8) vs 3.71 (95%CI: 2.97-4.45) between the dexamethasone and placebo groups, respectively. Cumulative incidence of fever was significantly lower in dexamethasone group with P < 0.001, pain, nausea and vomiting were also lower in the dexamethasone group compared with the placebo group (P = 0.16, P = 0.11, and P = 0.49). The dexamethasone regimen was generally well tolerated by patients with HCC patients including those with hepatitis B virus infection and well-controlled diabetes mellitus.CONCLUSIONSingle dose dexamethasone was effective at preventing PES among patients with HCC treated with TACE. The study showed no adverse events of special interest related to dexamethasone.     

Effects of barnidipine hydrochloride, a calcium channel blocker, on renal microcirculation in rats: a pilot study

Barnidipine hydrochloride, a dihydropyridine calcium channel blocker, increases both renal blood flow and glomerular filtration while effectively reducing blood pressure. The goal of the present study was to determine the effects of barnidipine on renal microcirculation. We used the rat in vivo split hydronephrotic kidney model to directly observe renal arterioles by light microscopy. When administered into the organ bath (ie, administered from outside of the blood vessels), 10⁻⁷ M of barnidipine significantly dilated both afferent and efferent arterioles and increased glomerular blood flow in both normotensive and hypertensive rats. Systolic blood pressure remained unchanged. Intravenous injection of barnidipine 600 μg/kg body weight dilated afferent arterioles and increased glomerular blood flow in normotensive rats. In contrast, the same treatment in hypertensive rats caused significant sustained dilatation of both afferent and afferent arterioles and gradually reduced systolic blood pressure. Future studies are needed to determine the clinical relevance of these effects of barnidipine     

Effects of gliclazide dose escalation on postprandial hyperglycemia in type 2 diabetes mellitus: A prospective, open-label, case-controlled, dose-escalation study

Objectives: The aims of this study were to determine the effects of increasing doses of gliclazide on postprandial glucose excursions after a standardized breakfast and lunch, and to clarify the relationship between gliclazide dose and glucose response.Methods: This prospective, open-label, case-controlled, dose-escalation study was conducted at the Addington Hospital Diabetes Clinic, eThekwini/Durban, KwaZulu-Natal, South Africa. Male and female patients aged ≥18 years with type 2 diabetes mellitus (DM) and postprandial hyperglycemia (2-hour postprandial blood glucose [PPBG_{2 h}] level, ≥11.1 mmol/L [≥200 mg/dL]) and receiving an oral hypoglycemic agent were eligible. After a 1-week washout period during which patients were asked to discontinue treatment with all oral hypoglycemic agents, baseline glycemic measurements were performed (fasting blood glucose, PPBG_{2 h}, 6-hour postprandial blood glucose [PPBG_{6 h}], mean blood glucose [MBG], plasma insulin, fasting serum fructosamine, and glycosylated hemoglobin). All patients subsequently received 2 weeks of oral treatment with each of 3 doses of gliclazide: 40, 80, and 160 mg/d. Glycemic parameters were measured at the end of each dosing interval. Adverse-effect monitoring included direct reporting of untoward effects to the resident medical practitioner, clinical examination, monitoring of home blood glucose records, hematology, and liver and kidney function tests. Compliance was assessed using pill counts, examination of diary entries, and patient interview.Results: Thirty-three patients were screened; 14 entered the dose-escalation phase. Thirteen patients completed the study (7 women, 6 men; mean [SD] age, 52.0 [11.1] years); 1 was withdrawn because of poor compliance. Dose escalation from 40 to 80 mg/d was associated with a significant change only in MBG (mean [SD], 11.3 [4.2] vs 10.0 [3.9] mmol/L [203.6 (75.7) vs 180.1 (70.3) mg/dL]; P<0.001). Dose escalation from 80 to 160 mg/d was associated with a significant change only in PPBG_{6 h} (9.5 [4.2] vs 10.3 [4.1] mmol/L [171.1 (75.7) vs 185.6 (73.9) mg/dL]; P=0.018). No other significant changes in glycemic parameters between doses were found throughout the treatment period. No adverse effects were reported.Conclusions: In this small study of gliclazide dose escalation in patients with type 2 DM and postprandial hyperglycemia, gliclazide 80 mg/d was associated with a reduction in postprandial hyperglycemia. Dose escalation from 80 to 160 mg/d was not found to be associated with additional clinical benefit. Based on these results, we recommend that gliclazide dose escalation to the maximum dose recommended by the manufacturer be guided by measures of glycemia. All doses were well tolerated.     

New indicators in evaluation of hemolysis,elevated liver enzymes,and low platelet syndrome: A case-control study

BACKGROUNDIndices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), platelet distribution width (PDW), and red cell distribution width (RDW) are considered new markers of the systemic inflammatory response (SIR), and have been widely implemented for the diagnosis of patients with inflammatory diseases. These new indicators have also been widely investigated in preeclampsia (PE) but less analyzed in hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome.AIMTo compare SIR markers among HELLP patients, PE only patients, and healthy gravidae.METHODSThis retrospective case-control study enrolled 630 cases, including 210 patients with HELLP syndrome (HELLP group), 210 patients with only PE (PE group) and 210 healthy gravidae (control group). The three groups were matched by age, parity, status of assisted reproduction, and multiple pregnancies. Birthweight, gestational age at complete blood count collection, gestational age at delivery, mode of delivery, etc. were recorded. The main indices as NLR, PLR, MPV, PDW, and RDW among the groups were compared, as well as some secondary outcomes including neutrophil, platelets, and hemoglobin.RESULTSThe NLR (6.4 vs 4.3 vs 3.5), MPV (11.9 vs 11.2 vs 10.7), PDW (16.4 vs 13.3 vs 14.2), leukocyte (12.4 × 10⁹/L vs 9.7 × 10⁹/L vs 8.7 × 10⁹/L) and neutrophil count (9.9 × 10⁹/L vs 7.3 × 10⁹/L vs 6.1 × 10⁹/L) were highest in the HELLP group, lower in the PE group, and lowest in the control group. Both the overall comparisons between the three groups (all ^bP < 0.01) and pairwise comparisons between every two groups elicited statistically significant differences (all ^dP < 0.01, except control vs PE: ^cP < 0.05 in PDW). The average lymphocyte counts were 1.4 (1.1, 2.0) × 10⁹/L in the HELLP group, 1.6 (1.3, 2.0) × 10⁹/L in the PE group and 1.7 (1.4, 2.0) × 10⁹/L in the control group. The overall comparison of lymphocyte count within the three groups had statistically significant differences (P = 0.000). The pairwise comparisons between every two groups demonstrated that the HELLP group had a lower lymphocyte count than both the PE (P = 0.019) and control groups (P = 0.000), but the difference between the PE and control groups was not statistically significant (P = 0.432). The overall comparisons on platelet counts and the PLR among these three groups also showed statistically significant differences (both P = 0.000), from low to high being those in the HELLP group (43.4 × 10⁹/L, 64.0), control group (180.5 × 10⁹/L, 103.6) and PE group (181.5 × 10⁹/L, 112.8). Pairwise comparisons of neither index displayed statistically significant differences between the PE and control groups (both P > 0.05), while the differences in the two indices between the HELLP group and the two other groups were still statistically significant (all P = 0.000). RDW values were highest in the HELLP group (14.5% [13.6, 15.3]), lower in the control group (14.1% [13.5, 14.8]) and lowest in the PE group (13.9% [13.4, 14.9]). The difference between the PE and control group did not show statistical significance (P = 1.000), while RDW values in the HELLP group were higher than those in the other two groups (^cP < 0.05 vs control, ^dP < 0.01 vs PE).CONCLUSIONSIR markers such as NLR, RDW, MPV, and PDW were increased and PLR was decreased in HELLP. These SIR markers may become new indicators in the evaluation of HELLP syndrome.     

The effects of oral zinc sulphate during radiotherapy on anti-oxidant enzyme activities in patients with head and neck cancer: a prospective, randomised, placebo-controlled study

The purpose was to determine the effects of oral zinc sulphate along with radiotherapy on anti-oxidant enzyme activities in patients with head and neck cancer. Thirty patients with head and neck cancer were randomly assigned to receive either zinc sulphate capsules (including 50 mg zinc) (n = 15) or placebo (n = 15) three times a day, starting on the day of the first radiotherapy fraction and continuing throughout the scheduled radiotherapy course including weekends and 6 weeks after radiotherapy. The patients were treated with telecobalt radiation at conventional fractionation of 2 Gy/fraction and five fractions/ week in 20-35 fractions for a period of 4-7 weeks. Blood samples for biochemical parameters were collected after an overnight fast (12 h) before radiotherapy, the first day and 6 weeks after radiotherapy. In the placebo group, three patients were excluded. No difference was detected in any final measurement activities of erythrocyte anti-oxidant enzyme such as copper-zinc superoxide dismutase (Cu-Zn SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in the direct comparison between the zinc sulphate and the placebo group, except erythrocyte SOD activities measured the first day after radiotherapy (p < 0.03). In the respective measurement analysis of the groups in themselves, in the zinc sulphate group, while the statistical analysis for the activities of erythrocyte CAT and GSH-Px were significantly different (chi2 = 12.4, p < 0.05; chi2 = 8.9, p < 0.05, respectively) before radiotherapy, the first day and 6 weeks after radiotherapy, the activities of SOD did not differ (chi2 = 4.2, p > 0.05). In these three measurements, there was no statistical significance in the activities of enzymes in erythrocyte Cu-Zn SOD, CAT and GSH-Px in the placebo group. Before radiotherapy, plasma zinc levels were normal in 16 patients (59.2%) and were lower in 11 patients (40.8%) compared with laboratory levels. It would be worthwhile studying the effect of oral zinc sulphate supplements to improve the anti-oxidant enzyme activity in radiation-treated cancer patients, in the hope of reducing radiation-induced toxicity.