Prevalence, clinical features and prognosis of familial hypercholesterolemia in Chinese Han patients with acute coronary syndrome after a coronary event: a retrospective observational study.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal semi-dominant disease, characterized by markedly elevated levels of low-density lipoprotein cholesterol (LDL-c) from conception and accelerated atherosclerotic cardiovascular disease, often resulting in early death. The aim of this study was to evaluate the prevalence of clinically defined FH in Chinese Han patients with acute coronary syndrome (ACS) and compare the long-term prognosis of ACS patients with and without FH receiving lipid-lowering therapy containing statins after a coronary event. METHODS: All ACS patients were screened at the Second Affiliated Hospital of Xi'an Jiaotong University between Jan 2019 and Sep 2020, and 531 participants were enrolled. All were examined for FH under the Dutch Lipid Clinical Network (DLCN) criteria, and those patients were divided into definite/probable FH, possible FH and unlikely FH. The severity of coronary artery disease was evaluated by the Gensini scoring system. Plasma levels of total cholesterol (TC), triacylglycerol (TG), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), very low-density lipoproteins-cholesterol (VLDL-c), apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and lipoprotein (a) (Lp(a)) were determined centrally at baseline and the last follow-up visit in the fasting state. The non-high-density lipoprotein cholesterol (non-HDL-c) concentration, the TC/HDL-c and apoB/apoA1 ratios were calculated. After FH patients received lipid-lowering treatment containing statin, the target LDL-c levels recommended by the guidelines (LDL-c < 1.8 mmol/L or < 1.4 mmol/L and a reduction > 50% from baseline) were evaluated, and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) during the 12-month follow-up was recorded. RESULTS: The prevalence of clinically definite or probable FH was 4.3%, and the prevalence of possible FH was 10.6%. Compared with the unlikely FH patients with ACS, the FH patients had higher levels of TC, LDL-c, apoB, Lp(a), non-HDL-c, TC/HDL-c and apoB/apoA1 ratio, more severe coronary artery diseases and greater prevalence of left main and triple or multiple vessel lesions. After lipid-lowering therapy containing statins, a minority of FH patients reached the target LDL-c levels defined by the guidelines (χ2 = 33.527, P < 0.001). During the 12-month follow-up, a total of 72 patients experienced MACCE. The survival curve in patients in the FH group was significantly lower than that in the unlikely FH group (HR = 1.530, log-rank test: P < 0.05). Furthermore, the survival curve in patients with high LDL-c (≥ 1.8 mmol/L) was significantly lower than that in patients with low LDL-c (< 1.8 mmol/L) at the 12-month follow-up visit (HR = 1.394, log-rank test: P < 0.05). No significant difference was observed between patients with LDL-c levels ≥ 1.4 mmol/L and with < 1.4 mmol/L at the 12-month follow-up visit by using Kaplan-Meier survival analysis (HR = 1.282, log-rank test: P > 0.05). CONCLUSIONS: FH was an independent risk factor for MACCE in adult patients after a coronary event during long-term follow-up. However, there was inadequate high-intensity statins prescriptions for high-risk patients in this current study. It is important for FH patients to optimize lipid-lowering treatment strategies to reach the target LDL-c level to improve the long-term prognosis of clinical outcomes.

The synergistic effect of chemical oxidation and microbial activity on improving volatile fatty acids (VFAs) production during the animal wastewater anaerobic digestion process treated with persulfate/biochar.

Improving volatile fatty acid (VFA) production, rather than producing methane from the anaerobic digestion (AD) of waste, has become a new strategy of resource utilization. In regard to animal wastewater, the effectiveness of persulfate/biochar (potassium peroxodisulfate, PDS/BC) on the hydrolysis and acidogenesis stages and the reaction mechanisms are still unclear. In this study, the AD process on cow wastewater was controlled at the hydrolysis and acidification stages by setting the hydraulic retention time (HRT) at 25 days. The results showed that the contents of total solids (TS) and volatile solids (VS) were further reduced by PDS/BC treatment with 0.15 gPDS/gTS of PDS added. The VFAs production increased by 12.4 % from day 0 to 25 compared to the blank set. Based on our molecular analysis, the rate of increase for the dissolved organic matter with low molecular weight (0-10 kDa) was 699.5 mg/(L·d) in the first 10 days. The change rate increased nearly 2.1 times, leading to higher VFAs yield. Moreover, the activities of fermentative bacteria were enhanced and Anaerocella was determined to be the specific and critical genus. However, excessive PDS (0.3 gPDS/gTS) prolonged the acidification period and caused the inactivation of fermentative bacteria. Structural equation modeling demonstrated that PDS can directly affect VFAs yield and also had an indirect effect by influencing the decomposition of particulate matter and microbial activities. Therefore, the enhancement of VFAs production using the PDS/BC method could be due to synergistic chemical and microbial effects. Findings from this study can provide a practical strategy to enhance the VFAs production of AD technology for livestock wastewater and help reveal the reaction mechanism of PDS/BC treatment.

Optimized Deep Brain Stimulation Surgery to Avoid Vascular Damage: A Single-Center Retrospective Analysis of Path Planning for Various Deep Targets by MRI Image Fusion.

Co-registration of stereotactic and preoperative magnetic resonance imaging (MRI) images can serve as an alternative for trajectory planning. However, the role of this strategy has not yet been proven by any control studies, and the trajectories of commonly used targets have not been systematically studied. The purpose of this study was to analyze the trajectories for various targets, and to assess the role of trajectories realized on fused images in preventing intracranial hemorrhage (ICH). Data from 1019 patients who underwent electrode placement for deep brain stimulation were acquired. Electrode trajectories were not planned for 396 patients, whereas trajectories were planned for 623 patients. Preoperative various MRI sequences and frame-placed MRI images were fused for trajectory planning. The patients' clinical characteristics, the stereotactic systems, intracranial hemorrhage cases, and trajectory angles were recorded and analyzed. No statistically significant differences in the proportions of male patients, patients receiving local anesthesia, and diseases or target distributions (p > 0.05) were found between the trajectory planning group and the non-trajectory planning group, but statistically significant differences were observed in the numbers of both patients and leads associated with symptomatic ICH (p < 0.05). Regarding the ring and arc angle values, statistically significant differences were found among various target groups (p < 0.05). The anatomic structures through which leads passed were found to be diverse. Trajectory planning based on MRI fusion is a safe technique for lead placement. The electrode for each given target has its own relatively constant trajectory.

Stereotactic Surgery for Treating Intractable Tourette Syndrome: A Single-Center Pilot Study.

To evaluate the potential effect of radiofrequency ablation and deep brain stimulation in patients with treatment-refractory Tourette syndrome (TS), this study enrolled thirteen patients with TS who were admitted to our hospital between August 2002 and September 2018. Four patients received a single- or multi-target radiofrequency ablation after local, potentiated, or general anesthesia; eight patients underwent deep brain stimulation (DBS) surgery; and one patient underwent both ablation and DBS surgery. The severity of tics and obsessive compulsive disorder symptoms and the quality of life were evaluated using the Yale Global Tic Severity Scale (YGTSS), Yale−Brown Obsessive Compulsive Scale (YBOCS), and Gilles de la Tourette Syndrome Quality of Life scale (GTS-QOL), respectively, before surgery, one month after surgery, and at the final follow-up after surgery, which was conducted in December 2018. A paired-sample t test and a multiple linear regression analysis were performed to analyze the data. All patients underwent the operation successfully without any severe complications. Overall, the YGTSS total scores at one month post-surgery (44.1 ± 22.3) and at the final visit (35.1 ± 23.7) were significantly decreased compared with those at baseline (75.1 ± 6.2; both p < 0.05). Additionally, the YBOCS scores at one month post-surgery (16.5 ± 10.1) and at the final visit (12.0 ± 9.5) were significantly decreased compared with those at baseline (22.5 ± 13.1; both p < 0.05). Furthermore, the GTS-QOL scores at one month post-surgery (44.0 ± 12.8) and at the final visit (31.0 ± 17.8) were significantly decreased compared with those at baseline (58.4 ± 14.2; both p < 0.05). Results from a multiple linear regression analysis revealed that the improvement in the YGTSS total score was independently associated with the improvement in the GTS-QOL score at one month post-surgery (standardized ß = 0.716, p = 0.023) and at the final visit (standardized ß = 1.064, p = 0.000). Conversely, changes in YBOCS scores did not correlate with changes in GTS-QOL scores (p > 0.05). Our results demonstrate that tics, psychiatric symptoms, and the quality of life in patients with intractable TS may be relieved by stereotactic ablation surgery and deep brain stimulation. Furthermore, it appears that the improvement in tics contributes more to the post-operative quality of life of patients than does the improvement in obsessive compulsive symptoms.

The relationship between the molecular composition of dissolved organic matter and bioavailability of digestate during anaerobic digestion process: Characteristics, transformation and the key molecular interval.

In this study, swine wastewater (SW) and cow wastewater (CW) were used for anaerobic digestion (AD). We found the bioavailability of dissolved organic matter (DOM) was affected by the molecular weight ranges and molecular composition during the AD process. The organic substance in the small molecular range (0-5 kDa) accumulated due to a larger molecular fraction (>10 kDa) degradation, which enhanced the bioavailability of the DOM. Moreover, based on the excitation emission matrix-parallel factor (EEM-PARAFAC) analysis, the protein-like component in 0-5 kDa molecular size and humic-like component over 5 kDa are significantly positively correlated with DOM bioavailability. This study indicated that increasing the hydrolysis of larger organic matter and humification degree of molecular weights>5 kDa are critical solutions to improving the bioavailability of DOM. These conclusions can help explain the molecular mechanisms of DOM transformation and the AD process of livestock wastewater.

Cytoprotective Effects of Taurine on Heat-Induced Bovine Mammary Epithelial Cells In Vitro.

It is a widely known that heat stress induces a reduction in milk production in cows and impairs their overall health. Studies have shown that taurine protects tissues and organs under heat stress. However, there have yet to be studies showing the functions of taurine in mammary alveolar cells-large T antigen (MAC-T) (a bovine mammary epithelial cell line) cells under heat shock. Therefore, different concentrations of taurine (10 mM, 50 mM, and 100 mM) were tested to determine the effects on heat-induced MAC-T cells. The results showed that taurine protected the cells against heat-induced damage as shown by morphological observations in conjunction with suppressed the translocation and expression of heat shock factor 1 (HSF1). Moreover, taurine not only reversed the decline in antioxidase (superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX)) activities but also attenuated the accumulation of malondialdehyde (MDA). Meanwhile, mitochondrial damage (morphology and complex I activity) resulting from heat exposure was mitigated. Taurine also alleviated the rates of cell apoptosis and markedly depressed the mRNA expressions of BCL2 associated X, apoptosis regulator (BAX) and caspase3. Furthermore, compared with the heat stress (HS) group, the protein levels of caspase3 and cleaved caspase3 were decreased in all taurine groups. In summary, taurine improves the antioxidant and anti-apoptosis ability of MAC-T cells thereby alleviates damage of cells due to heat insults.

Bioavailability of dissolved organic matter in biogas slurry enhanced by catalytic ozonation combined with membrane separation.

Large molecular weight pig biogas slurry (L-PBS) and small molecular weight pig biogas slurry (S-PBS) were separated from original pig biogas slurry (O-PBS) using a 100 kDa membrane. The original bioavailability and biosafety of L-PBS was very low. In order to enhance the total bioavailable dissolved organic nitrogen (TB-DON) and total bioavailable dissolved organic phosphorus (TB-DOP), optimum catalytic ozonation of L-PBS conditions were determined using Box-behnken design models (P < 0.0001) and intersection tests. The optimal values for ozone concentration, pH value, active catalyst concentration and reaction time were 2.63 mg·L-1, 6.48, 1.43 g·L-1 and 40 min, respectively. Catalytic ozonation can effectively decompose and transform 68.07% of L-PBS into S-PBS to improve content organic bioavailability, with a molecular weight distribution of 0-1 kDa (13.53%), 1-5 kDa (16.62%), 5-10 kDa (11.16%), 10-30 kDa (11.73%), 30-100 kDa (15.04%). Catalytic ozonation of L-PBS can reduce protein levels from 85.28% to 47.18%, but increases the proportion of fulvic and humic components from 10.22% to 32.67% and 4.51%-20.15%, respectively. Because catalytic ozonation changes the internal components and molecular weights of L-PBS, both saw increases in TB-DON and TB-DOP from 3.33% to 41.12% and 2.43%-37.88%, respectively, with a large number of TB-DON and TB-DOP derived from hydrophilic organic components during catalytic ozonation. These important internal mechanisms changed by catalytic ozonation can effectively reduce the ecotoxicity (IR, from 76.5% to 33.1%) and phytotoxicity (GI, enhanced from 35.4% to 70.3%) of L-PBS. Therefore, catalytic ozonation combined with membrane separation is a choice technology in improving the nutrition of biogas slurry and reduce its ecological risk.

Relationship among adiponectin, insulin resistance and atherosclerosis in non-diabetic hypertensive patients and healthy adults.

Adiponectin, which is secreted specifically by adipose tissue, has been shown to have anti-atherogenic and anti-inflammatory effects and to improve insulin resistance (IR). The aim of this study was to determine the correlations among adiponectin, IR and atherosclerosis in non-diabetic hypertensive patients and healthy volunteers. In this case control study, we collected complete demographic data from and measured several laboratory parameters in all enrolled subjects. The homeostasis model of assessment for insulin resistance (HOMA-IR) was calculated as an insulin sensitivity index. The atherogenic index of plasma (AIP), which is calculated as log (triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C)), was a significant predictor of atherosclerosis and was a better predictor of atherosclerosis than low-density lipoprotein cholesterol (LDL-C). Plasma adiponectin, interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1) and matrix metalloprotein-9 (MMP-9) concentrations were determined using enzyme-linked immunosorbent assay (ELISA). All data were analyzed using Statistical Product and Service Solutions for Windows (SPSS) 13.0 software. A total of 309 participants were enrolled in the study. Hypertensive patients with IR (n = 93) displayed significantly higher HOMA-IR values and AIPs and lower adiponectin levels than hypertensive patients without IR (n = 121) and healthy adults (n = 95) (P < 0.05). Furthermore, circulating IL-6, MCP-1 and MMP-9 concentrations differed significantly between hypertensive patients and healthy adults (P < 0.05). Additionally, adiponectin levels were found to be inversely correlated with IL-6, MCP-1, and MMP-9 levels; HOMA-IR values; and AIPs in the clinical study. HOMA-IR values and adiponectin and creatinine (Cr) concentrations remained independently associated with AIPs in all participants after adjustment for confounders via multivariate linear regression. Low adiponectin levels are positively correlated with decreased insulin sensitivity, increased pro-inflammatory cytokine production and worsening atherosclerosis in hypertensive patients and healthy adults.

Association between growth differentiation factor 15 and left ventricular hypertrophy in hypertensive patients and healthy adults.

Growth differentiation factor 15 (GDF-15) as an independent biomarker of cardiovascular diseases merits further evaluation. We studied the association between plasma GDF-15 levels and left ventricular hypertrophy (LVH) in hypertensive patients and healthy adults. Hypertensive LVH measurements were performed via echocardiography and analyzed using the cube formula, and human GDF-15 together with interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) concentrations were determined via enzyme-linked immunosorbent assay (ELISA). All data were analyzed using SPSS 13.0 software. A total of 302 participants were recruited for this clinical study. Circulating GDF-15, IL-6 and MMP-9 levels were significantly higher in LVH patients (n = 67) than in non-LVH patients (n = 172) and healthy controls (n = 63) (p < 0.001). After adjustment for confounders via multivariate logistic regression, elevated plasma GDF-15 concentrations remained independently associated with LVH in hypertensive patients. In addition, GDF-15 was positively correlated with IL-6 and MMP-9 levels in human plasma, respectively, suggesting that a link exists between GDF-15 expression and inflammation. We also calculated an optimal GDF-15 cut-off point with which LVH severity can be predicted in the current study. In conclusion, GDF-15 is associated with hypertensive LVH and may be a powerful biomarker with which LVH risk can be predicted in patients with hypertension.

Steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected Chinese patients.

BACKGROUND: The pharmacokinetic (PK) profile of tenofovir disoproxil fumarate in Chinese adults infected with HIV is unknown. METHODS: A pilot, prospective, open-label study was performed to investigate the steady-state PK profile of tenofovir disoproxil fumarate in 15 Chinese HIV-infected patients among whom eight patients were treated with 300 mg tenofovir disoproxil fumarate, 300 mg lamivudine and 400/100 mg lopinavir/ritonavir, and seven with 300 mg tenofovir disoproxil fumarate, 300 mg lamivudine and 400 mg nevirapine. The plasma concentrations of tenofovir over the 24-h dosing interval were determined by HPLC. The PK parameters were calculated using the non-compartmental model in WinNonlin software. RESULTS: The PK parameters of tenofovir in the 15 patients were determined as follows (mean ± SD): AUC(0-24 h), 4074.7 ± 1551.9 ng•h/mL; Cmax,ss, 447.1 ± 217.4 ng/mL; Ctrough,ss, 98.7 ± 36.7 ng/mL; tmax,ss, 1.3 ± 0.4 h; plasma t1/2, 21.8 ± 7.6 h; and CLss/F, 45.8 ± 13.0 L/h. CONCLUSION: Tenofovir demonstrated slower elimination rate and increased plasma concentration in Chinese patients compared to previously published data from Caucasian or African subjects, which may be associated with the higher incidences of renal and bone resorption dysfunction observed in our patient population. Clinicians should be cautious of the differing PK characteristics of tenofovir among people of different races.

Relationships of Blood Pressure Circadian Rhythm and Brain Natriuretic Peptide with Left Ventricular Hypertrophy in the Patients with Primary Hypertension.

Objective To investigate the relationships of blood pressure circadian rhythm and brain natriuretic peptide (BNP) with left ventricular hypertrophy (LVH) in patients with primary hypertension. Methods Totally 349 patients (74 with LVH and 275 without LVH) with primary hypertension were enrolled in this study.Echocardiography was performed to determine left ventricular mass index (LVMI) using the Devereux formula. The nocturnal blood pressure decline rate,24-hour blood pressure (24 h PP; especially 24 h mean systolic blood pressure,24 h SBP) and blood pressure index (PPI) were determined by 24 h-ambulatory blood pressure monitoring. These 349 hypertensive patients were divided into four groups including supper-dipper group (defined as≥;20%, n=7),dipper group (defined as 10%- 20%, n=77),non-dipper group (defined as 0- 10%, n=173),and anti-dipper group (defined as<0, n=92). The baseline demographic characteristics of patients were collected. Fasting blood sugar,blood lipids,blood urea nitrogen,serum cretinine,cystatin C,uric acid,and plasma BNP level were measured. Results The patients with LVH (n=74) had significantly higher percentage of grade 3 hypertension (85.1% vs. 46.9%;χ2=34.428,P<0.001),24 h SBP (134 mmHg vs. 129 mmHg; t=3.175,P=0.002)(1 mmHg=0.133 kPa),daytime-mean SBP (134 mmHg vs. 130 mmHg; t=2.197,P=0.029),night-mean SBP(132 mmHg vs. 121 mmHg; t=4.763,P<0.001),and 24 h PP(57 mmHg vs. 52 mmHg; t=4.120,P<0.001) and PPI (0.43 vs. 0.41; t=3.335,P=0.001) and lower nocturnal blood pressure decline rate [(1.30±8.02)% vs. (5.68±7.25)%; t=-4.510,P<0.001] than the non-LVH patients (n=275). The LVH hypertensive group had significantly higher BNP level (87.8 pg/ml vs. 28.8 pg/ml; t=2.170,P=0.034) and LVMI (135.1 g/m2 vs. 88.7 g/m2; t=15.285,P<0.001) than the control group. No significant difference was observed in the BNP level among supper-dipper,dipper,non-dipper and anti-dipper groups (P=0.137).However,the difference was statistically significant in the LVMI (P=0.001). Additionally,patients in the anti-dipper group had significantly higher LVMI than those in the dipper patients (100.3 g/m2 vs. 86.3 g/m2; t=4.335,P<0.001) and non-dipper (100.3 g/m2 vs.93.7 g/m2; t=1.987,P=0.048). Patients in the non-dipper group had significantly higher LVMI than those in the dipper group (93.7 g/m2 vs. 86.3 g/m2; t=2.693,P=0.008). The multivariate linear correation analysis and logistic regressions analysis suggested a significant correlation of LVMI with BNP and the grade of hypertension. Conclusion With the increasing of plasma BNP level,the left ventricular hypertrophy is closely related to abnormal blood pressure circadian rhythm and the grade of hypertension in primary hypertensive patients.

Prognostic Role of Hypothyroidism in Heart Failure: A Meta-Analysis.

Hypothyroidism is a risk factor of heart failure (HF) in the general population. However, the relationship between hypothyroidism and clinical outcomes in patients with established HF is still inconclusive.We conducted a systematic review and meta-analysis to clarify the association of hypothyroidism and all-cause mortality as well as cardiac death and/or hospitalization in patients with HF. We searched MEDLINE via PubMed, EMBASE, and Scopus databases for studies of hypothyroidism and clinical outcomes in patients with HF published up to the end of January 2015. Random-effects models were used to estimate summary relative risk (RR) statistics. We included 13 articles that reported RR estimates and 95% confidence intervals (95% CIs) for hypothyroidism with outcomes in patients with HF. For the association of hypothyroidism with all-cause mortality and with cardiac death and/or hospitalization, the pooled RR was 1.44 (95% CI: 1.29-1.61) and 1.37 (95% CI: 1.22-1.55), respectively. However, the association disappeared on adjustment for B-type natriuretic protein level (RR 1.17, 95% CI: 0.90-1.52) and in studies of patients with mean age <65 years (RR 1.23, 95% CI: 0.88-1.76).We found hypothyroidism associated with increased all-cause mortality as well as cardiac death and/or hospitalization in patients with HF. Further diagnostic and therapeutic procedures for hypothyroidism may be needed for patients with HF.

Comparison of nevirapine plasma concentrations between lead-in and steady-state periods in Chinese HIV-infected patients.

OBJECTIVES: To investigate the potential of nevirapine 200 mg once-daily regimen and evaluate the influence of patient characteristics on nevirapine concentrations. METHODS: This was a prospective, multicentre cohort study with 532 HIV-infected patients receiving nevirapine as a part of their initial antiretroviral therapy. Plasma samples were collected at trough or peak time at the end of week 2 (lead-in period) and week 4, 12, 24, 36, and 48 (steady-state period), and nevirapine concentrations were determined using a validated HPLC method. Potential influencing factors associated with nevirapine concentrations were evaluated using univariate and multivariate logistic regression. RESULTS: A total of 2348 nevirapine plasma concentrations were collected, including 1510 trough and 838 peak values. The median nevirapine trough and peak concentration during the lead-in period were 4.26 µg/mL (IQR 3.05-5.61) and 5.07 µg/mL (IQR 3.92-6.44) respectively, which both exceeded the recommended thresholds of nevirapine plasma concentrations. Baseline hepatic function had a moderate effect on median nevirapine trough concentrations at week 2 (4.25 µg/mL v.s. 4.86 µg/mL, for ALT <1.5 × ULN and ≥ 1.5 × ULN, respectively, P = 0.045). No significant difference was observed in median nevirapine trough concentration between lead-in and steady-state periods in patients with baseline ALT and AST level ≥ 1.5 × ULN (P = 0.171, P = 0.769), which was different from the patients with ALT/AST level <1.5ULN. The median trough concentrations were significantly higher in HIV/HCV co-infected patients than those without HCV at week 48 (8.16 µg/mL v.s. 6.15 µg/mL, P = 0.004). CONCLUSIONS: The 200 mg once-daily regimen of nevirapine might be comparable to twice-daily in plasma pharmacokinetics in Chinese population. Hepatic function prior to nevirapine treatment and HIV/HCV coinfection were significantly associated with nevirapine concentrations.

Quantification of tenofovir in human plasma by solid-phase extraction and high-performance liquid chromatography coupled with UV detection.

BACKGROUND: Tenofovir is used in the treatment of HIV and hepatitis virus infections. The aim of this work was to develop and validate an high-performance liquid chromatography coupled with ultraviolet detection assay that can be implemented in most laboratories for the purposes of therapeutic drug monitoring and pharmacokinetic studies. METHODS: Two hundred microliters of plasma sample was used for the assay. Sample processing was carried out with solid-phase extraction. Tegafur was used as the internal standard. The chromatographic separation was achieved on a C18 reverse-phase analytic column with a mobile phase consisting of sodium phosphate buffer (pH: 6.12; 20.0 mM)-acetonitrile-tetrabutylammonium hydroxide solution (pH: 13.64; 1.14 mM) (90.0:10.0:0.3, v/v/v). The detection was at 262 nm, and the column oven was set at 35°C. RESULTS: The linear range of the calibration curve was 20-2000 ng/mL (r > 0.999, n = 6). The absolute extraction recoveries were 97.4% ± 2.5% and 81.6% ± 0.8% for tenofovir and tegafur, respectively. The relative standard deviations were 2.3%-3.3% for the intraday and 2.8%-5.3% for the interday analyses. The accuracy was within 100% ± 7%. The successful application of this method in a pharmacokinetic study in Chinese HIV-infected patients confirmed its robustness and reliability. CONCLUSIONS: A validated and reproducible method has been established to quantify the concentration of tenofovir in human plasma by high-performance liquid chromatography coupled with ultraviolet detection.

Simultaneous quantification of lopinavir and ritonavir in human plasma by high performance liquid chromatography coupled with UV detection.

High performance liquid chromatography was coupled with UV detection for simultaneous quantification of lopinavir (LPV) and ritonavir (RTV) in human plasma. This assay was sensitive, accurate and simple, and only used 200 µL of plasma sample. Samples were liquid-liquid extracted, and diazepam was used as an internal standard. The chromatographic separation was achieved on a C18 reversed-phase analytic column with a mobile phase of acetonitrile-sodium dihydrogen phosphate buffer (10 mmol L(-1), pH 4.80) (60:40, v/v). UV detection was conducted at 205 nm and the column oven was set at 40°C. Calibration curves were constructed between 0.5-20 µg mL(-1) for LPV and 0.05-5 µg mL(-1) for RTV. The relative standard deviations were 2.16%-3.20% for LPV and 2.12%-2.60% for RTV for intra-day analysis, and 2.34%-4.04% for LPV and 0.31%-4.94% for RTV for inter-day analysis. The accuracy was within 100%±10%. The mean extraction recoveries were 79.17%, 52.26% and 91.35% for RTV, LPV and diazepam, respectively. This method was successfully applied to human plasma samples from patients orally administered a salvage regimen of lopinavir-ritonavir tablets.

Nevirapine plasma concentrations are associated with virologic response and hepatotoxicity in Chinese patients with HIV infection.

BACKGROUND: Limited information is available on the relationship between nevirapine plasma concentrations and virologic response or liver toxicity in Chinese patients with HIV infection. The objective of this prospective study was to test this relationship and to determine the minimal therapeutic trough concentration of nevirapine for Chinese patients. METHODS: A total of 227 HIV-infected, treatment naïve patients were enrolled into this study. Blood samples were taken at C(trough) (12 hr postdose) and C(2) (2 hr postdose) for measurement of nevirapine concentrations 6 months after treatment initiation. Therapeutic outcomes, viral load and CD4 cell count, were assessed at 3 and 6 months after starting therapy, while the evaluation of hepatotoxicity was undertaken 12 months after nevirapine treatment. RESULTS: A significant correlation between nevirapine trough concentrations and viral load was noticed after 6 months of treatment, particularly in patients with partial response and viral failure (p<0.01). The therapeutic C(trough) of nevirapine for Chinese patients was determined to be 3.9 µg/ml using the receiver operating characteristic curve. Virologic failure was observed in 21% (6/29) of patients with low nevirapine concentrations (<3.9 µg/ml) versus 5% (4/87) in patients with concentrations higher than 3.9 µg/ml (p = 0.015). Hepatotoxicity was significantly associated with the median nevirapine trough concentrations among male patients (8.20 vs. 5.48 µg/ml, p = 0.015) and hepatitis C virus co-infection (p = 0.039). CONCLUSIONS: Among Chinese patients with HIV infection, the therapeutic C(trough) of nevirapine was 3.9 µg/ml, higher than the recommended 3.0 µg/ml. The correlation between nevirapine concentrations, efficacy and hepatotoxicity suggests the benefit of dosage adjustment based on therapeutic drug monitoring among Chinese HIV-infected patients to optimize nevirapine containing antiretroviral therapy.