DIEP Donor Site Satisfaction between Patients with and without History of Pregnancy.

BACKGROUND: With the success of free autologous breast reconstruction, the abdominal donor site is now an important consideration, especially in patients of childbearing age. In our institution, there are increasing patients who have successfully undergone the deep inferior epigastric artery perforator (DIEP) flap despite previous pregnancy. This study aims to answer questions on the effect of the donor site on pregnancy and vice versa. METHODS: A retrospective cohort study was conducted to identify breast cancer patients who received a free DIEP flap for breast reconstruction from January 2018 to August 2020. Patients were allocated to two groups according to whether they had prior pregnancies with successful deliveries. Demographics, flap-related parameters, surgical outcomes on breast and abdomen, and patient-reported outcome (Breast-Q questionnaire) were analyzed. Patients were excluded if follow-up time was less than 1 year, or if there was incomplete medical records or Breast-Q replies. RESULTS: Ninety-nine of 116 patients had had successful pregnancies with delivery, 17 of them remained nulliparous. No statistically significant differences existed between groups regarding demographic data, flap-related parameters, surgical outcomes on breast and abdomen. Nulliparous patients exhibited significantly lower score in physical well-being in the abdomen domain compared with delivery-experienced patients (62.1 vs. 73.4, p = 0.025). Significantly, nulliparous patients felt more tightness and pulling of the abdominal wall than the delivery-experienced patients (2.9 vs. 3.7; p = 0.05 and 3.5 vs. 4.0; p = 0.04). CONCLUSION: Free DIEP flap can be transferred safely in nulliparous patients despite a slight increase in abdominal tightness and abdominal pulling. Precise flap design and surgical approaches may help to minimize the abdominal discomfort especially on young, normal body mass index, and nonchildbearing patients.

Mediating effect of psychological capital on the relationship between mental health literacy and coping styles among newly recruited nurses.

BACKGROUND: Newly recruited nurses face multiple sources of stress and their coping styles need to be focused on to ensure good mental health. This study aimed to examine the relationship among mental health literacy, psychological capital and coping styles in newly recruited nurses. METHODS: A cross-sectional study was conducted in August and September 2022. A total of 315 newly recruited nurses were recruited in a tertiary hospital in Henan Province, central China, employing the convenience sampling method. The self-reported questionnaires were sent through a QR code, including the Mental Health Literacy Scale for Healthcare Students, Psychological Capital Questionnaire, and Simplified Coping Style Questionnaire. Pearson correlation analysis was used to evaluate the relationships among the variables. Mediation analysis was performed to identify the mediating effect of psychological capital on the relationship between mental health literacy and coping styles. RESULTS: Positive coping showed a positive relationship with psychological capital and mental health literacy, while negative coping showed a negative relationship with psychological capital and mental health literacy. For positive coping, psychological capital was a partial mediator with an effect of 0.140, accounting for 62.8%. For negative coping, a full mediating effect was shown by psychological capital between mental health literacy and negative coping, with an indirect effect of -0.048. CONCLUSION: Psychological capital plays a partial and complete mediating role between mental health literacy and different coping styles among newly recruited nurses. Diversified training and personalized guidance in improving mental health literacy and increasing psychological capital simultaneously can be provided to newly recruited nurses continuously to adjust their coping styles.

Psychological Distress and Risk Factors in Frontline Nurses Confronting COVID-19 in Less Severely Affected Areas.

The current study investigated the prevalence and risk factors of somatization, depression, and anxiety among 374 frontline nurses in less severely affected areas during the initial period of the coronavirus disease 2019 (COVID-19) outbreak. The prevalence of somatization, depression, and anxiety among frontline nurses was 41.4%, 40.1%, and 37.4%, respectively. Nurses from provincial-level hospitals were less likely to report somatization (odds ratio [OR] = 0.50; p = 0.018), depression (OR = 0.52; p = 0.024), and anxiety (OR = 0.35; p < 0.001) than those from county-level hospitals. Longer service duration was significantly associated with a higher likelihood of reporting somatization (OR = 1.06; p = 0.008) and depression (OR = 1.06; p = 0.006). Psychological distress exists in frontline nurses in less severely affected areas, and hospital levels and service duration are independent risk factors for psychological stress in these nurses. Maintaining nurses' mental health is an important issue in addressing the COVID-19 pandemic in addition to sufficient distribution of medical resources between hospitals at different levels. [Journal of Psychosocial Nursing and Mental Health Services, 61(4), 37-44.].

Disseminated intravascular coagulation in Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND: Patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have high mortality rates. Disseminated intravascular coagulation has been reported in SJS/TEN patients. The influence of this lethal complication in patients with SJS/TEN is not well known. OBJECTIVE: This study aimed to investigate the risk and outcomes of disseminated intravascular coagulation in patients with SJS/TEN. METHODS: We analyzed the disseminated intravascular coagulation profiles of patients receiving a diagnosis of SJS/TEN between 2010 and 2019. RESULTS: We analyzed 150 patients with SJS/TEN (75 with SJS, 22 with overlapping SJS/TEN, and 53 with TEN) and their complete disseminated intravascular coagulation profiles. Disseminated intravascular coagulation was diagnosed in 32 patients (21.3%), primarily those with TEN. It was significantly associated with systemic complications, including gastrointestinal bleeding, respiratory failure, renal failure, liver failure, infection, and bacteremia. Additionally, SJS/TEN patients with disseminated intravascular coagulation had elevated procalcitonin levels. Among patients with SJS/TEN, disseminated intravascular coagulation was associated with a greater than 10-fold increase in mortality (78.1% vs 7%). LIMITATIONS: The study limitations include small sample size and a single hospital system. CONCLUSION: Disseminated intravascular coagulation is a potential complication of SJS/TEN and associated with higher mortality. Early recognition and appropriate management of this critical complication are important for patients with SJS/TEN.

Comparing the effectiveness of laser vs. conventional endoforehead lifting.

The objective of this study was to compare the efficacy and safety of laser versus conventional endoforehead lifting. Over a period of 12 years (January 2000-January 2012), a total of 110 patients with hyperactive muscles over the frontal region have been collected for a retrospective study. The SurgiLase 150XJ CO2 laser system, in conjunction with the flexible FIBERLASE, was used. The endoscope was 4 mm in diameter with an angle of 30°. The primary efficacy measurement was the assessment of the final outcome for using laser vs. conventional methods. Both groups were observed at three weeks, six weeks and six months after surgery. The most common complication in early convalescence (three weeks) was swelling. This was followed by local paraesthesia, ecchymosis, localized hematomas and scar with alopecia. All these problems disappeared completely after the 6-month study period. Based on a chi-square analysis, there were clinically and statistically significant differences favouring the laser endoforehead surgery in the operative time, early and late complications. All patients achieved significant improvement after both laser and conventional endoforehead surgery in the final outcome. However, the early and late complications indicated a greater difference in the laser group.

Application of Static Models to Predict Midazolam Clinical Interactions in the Presence of Single or Multiple Hepatitis C Virus Drugs.

Asunaprevir (ASV), daclatasvir (DCV), and beclabuvir (BCV) are three drugs developed for the treatment of chronic hepatitis C virus infection. Here, we evaluated the CYP3A4 induction potential of each drug, as well as BCV-M1 (the major metabolite of BCV), in human hepatocytes by measuring CYP3A4 mRNA alteration. The induction responses were quantified as induction fold (mRNA fold change) and induction increase (mRNA fold increase), and then fitted with four nonlinear regression algorithms. Reversible inhibition and time-dependent inhibition (TDI) on CYP3A4 activity were determined to predict net drug-drug interactions (DDIs). All four compounds were CYP3A4 inducers and inhibitors, with ASV demonstrating TDI. The curve-fitting results demonstrated that fold increase is a better assessment to determine kinetic parameters for compounds inducing weak responses. By summing the contribution of each inducer, the basic static model was able to correctly predict the potential for a clinically meaningful induction signal for single or multiple perpetrators, but with over prediction of the magnitude. With the same approach, the mechanistic static model improved the prediction accuracy of DCV and BCV when including both induction and inhibition effects, but incorrectly predicted the net DDI effects for ASV alone or triple combinations. The predictions of ASV or the triple combination could be improved by only including the induction and reversible inhibition but not the ASV CYP3A4 TDI component. Those results demonstrated that static models can be applied as a tool to help project the DDI risk of multiple perpetrators using in vitro data.

Extensive primary cutaneous fusariosis in a patient with burns: A case report and review of the literature.

BACKGROUND: Fusarium species can cause a broad spectrum of human infections, ranging from superficial and locally invasive to disseminated, depending on the immune status of the host and portal of entry. Although several cases of cutaneous fusariosis in burn victims have been reported, molecular identification for pathogen recognition has been used only in a few cases. CASE DESCRIPTION: In this report, we describe an uncommon case of extensive primary cutaneous fusariosis caused by Fusarium keratoplasticum in a patient who sustained injuries during stubble burning. FINDINGS: A review of cases of cutaneous fusariosis in burn victims revealed that this uncommon infection could be lethal, and treatment strategies should focus on both surgical debridement and the initiation of systemic antifungal therapy. Furthermore, because skin defects can serve as a portal of entry for Fusarium species in burn victims, early and aggressive treatment is crucial to prevent serious consequences.

Revolutionizing Cancer Treatment: Unleashing the Power of Combining Oncolytic Viruses with CAR-T Cells.

Oncolytic Viruses (OVs) have emerged as a promising treatment option for cancer thanks to their significant research potential and encouraging results. These viruses exert a profound impact on the tumor microenvironment, making them effective against various types of cancer. In contrast, the efficacy of Chimeric antigen receptor (CAR)-T cell therapy in treating solid tumors is relatively low. The combination of OVs and CAR-T cell therapy, however, is a promising area of research. OVs play a crucial role in enhancing the tumor-suppressive microenvironment, which in turn enables CAR-T cells to function efficiently in the context of solid malignancies. This review aims to provide a comprehensive analysis of the benefits and drawbacks of OV therapy and CAR-T cell therapy, with a focus on the potential of combining these two treatment approaches.

Study of different pre-treatments in the comparison of the efficacy of photodynamic therapy for moderate to severe acne vulgaris.

OBJECTIVE: To evaluate the efficacy of CO2 fractional laser and microneedling pretreatment combined with ALA-PDT for moderate-to-severe acne, aiming to optimize clinical treatment. METHODS: Patients were randomly divided into three groups: Group A (CO2 fractional laser + ALA-PDT), Group B (microneedling + ALA-PDT), and Group C (ALA-PDT). Each group underwent photodynamic therapy once a week for 3 weeks. Efficacy was assessed at the end of the 4th week, and recurrence was assessed at the end of the 12th week. RESULTS: A total of 150 patients with moderate to severe acne were included in this study, with 50 patients in each group. Four weeks after the end of treatment, the effective rates were 88% for Group A, 62% for Group B, and 36% for Group C. Statistically significant differences were found between the groups (P < 0.05), with Group A showing superior efficacy compared to Group B (P < 0.05). No serious systemic or local adverse reactions were observed in any group. No recurrence was seen in any group 12 weeks after the end of treatment, and some patients continued to show improvement in skin lesions over time. CONCLUSION: Both the CO2 fractional laser group and the microneedling group improved the efficacy of photodynamic therapy for moderate to severe acne compared to the control group, with the CO2 fractional laser group demonstrating better efficacy and fewer adverse effects.

Effect of CYP3A5 expression on the inhibition of CYP3A-catalyzed drug metabolism: impact on modeling CYP3A-mediated drug-drug interactions.

The purpose of this study was to determine the impact of CYP3A5 expression on inhibitory potency (Ki or IC50 values) of CYP3A inhibitors, using recombinant CYP3A4 and CYP3A5 (rCYP3A4 and rCYP3A5) and CYP3A5 genotyped human liver microsomes (HLMs). IC50 ratios between rCYP3A4 and rCYP3A5 (rCYP3A5/rCYP3A4) of ketoconazole (KTZ) and itraconazole (ITZ) were 8.5 and 8.8 for midazolam (MDZ), 4.7 and 9.1 for testosterone (TST), 1.3 and 2.8 for terfenadine, and 0.6 and 1.7 for vincristine, respectively, suggesting substrate- and inhibitor-dependent selectivity of the two azoles. Due to the difference in the IC50 values for CYP3A4 and CYP3A5, nonconcordant expression of CYP3A4 and CYP3A5 protein can significantly affect the observed magnitude of CYP3A-mediated drug-drug interactions in humans. Indeed, the IC50 values of KTZ and ITZ for CYP3A-catalyzed MDZ and TST metabolism were significantly higher in HLMs with CYP3A5*1/*1 and CYP3A5*1/*3 genotypes than in HLMs with the CYP3A5*3/*3 genotype, showing CYP3A5 expression-dependent IC50 values. Moreover, when IC50 values of KTZ and ITZ for different HLMs were kinetically simulated based on CYP3A5 expression level and enzyme-specific IC50 values, a good correlation between the simulated and the experimentally measured IC50 values was observed. Further simulation analysis revealed that both the Ki ratio (for inhibitors) and Vmax/Km ratio (for substrates) between CYP3A4 and CYP3A5 were major factors for CYP3A5 expression-dependent IC50 values. In conclusion, the present study demonstrates that CYP3A5 genotype and expression level have a significant impact on inhibitory potency for CYP3A-catalyzed drug metabolism, but that the magnitude of its effect is inhibitor-substrate pair specific.

Labiaplasty in Asian women: Motivation, technique feasibility, and patient reported outcomes.

Labiaplasty is an increasingly popular aesthetic procedure. However, there is a lack of information regarding different surgical procedures and Asian patients' motivations and outcomes. This study aimed to understand patients' motivations for seeking labiaplasty and to examine surgical outcomes of different procedures. This retrospective study enroled patients between August 2016 and May 2021. Patient demographics, surgical procedures, complications, and revision surgeries were reviewed. Responses to questionnaires regarding patient motivations for undergoing labiaplasty, pre- and postoperative discomfort and aesthetics, Rosen's Self-Esteem Scale (RSES) scores, and Female Genital Self-Image Scale (FGSIS) scores were recorded. One hundred thirty-one patients were included, with an average age of 30.3 ± 7.78 years. Eighty-seven (66.4%) patients underwent bilateral labiaplasty, and 44 (33.6%) underwent unilateral labiaplasty. The surgical techniques included 61 (46.6%) direct resections, 50 (38.2%) wedge resections, and 20 (15.3%) "hockey stick" procedures. Wound dehiscence occurred in 37 (28.2%) patients. A significant increase in complications occurred after the hockey stick procedure and wedge resection. Patients' motivation for surgery included aesthetic reasons in 62.0%, symptom relief in 91.5%, and repeated infection in 4.2%. There was a significant difference between pre- and postoperative genital aesthetics (p 0.001) and discomfort symptoms (p 0.001). The average RSES score was 19.68 ± 4.03, and the average FGSIS score was 20.77 ± 3.20. Pain and discomfort remained the most important motivations for Asian women to seek labiaplasty, followed by aesthetic reasons. With good preoperative consultation and surgical planning, satisfaction can be achieved concerning functional and aesthetic aspects.

Evaluation of six proton pump inhibitors as inhibitors of various human cytochromes P450: focus on cytochrome P450 2C19.

Six proton pump inhibitors (PPIs), omeprazole, lansoprazole, esomeprazole, dexlansoprazole, pantoprazole, and rabeprazole, were shown to be weak inhibitors of cytochromes P450 (CYP3A4, -2B6, -2D6, -2C9, -2C8, and -1A2) in human liver microsomes. In most cases, IC50 values were greater than 40 µM, except for dexlansoprazole and lansoprazole with CYP1A2 (IC50 = ∼8 µM) and esomeprazole with CYP2C8 (IC50 = 31 µM). With the exception of CYP2C19 inhibition by omeprazole and esomeprazole (IC50 ratio, 2.5 to 5.9), there was no evidence for a marked time-dependent shift in IC50 (IC50 ratio, ≤ 2) after a 30-min preincubation with NADPH. In the absence of preincubation, lansoprazole (IC50 = 0.73 µM) and esomeprazole (IC50 = 3.7 µM) were the most potent CYP2C19 inhibitors, followed by dexlansoprazole and omeprazole (IC50 = ∼7.0 µM). Rabeprazole and pantoprazole (IC50 = ≥ 25 µM) were the weakest. A similar ranking was obtained with recombinant CYP2C19. Despite the IC50 ranking, after consideration of plasma levels (static and dynamic), protein binding, and metabolism-dependent inhibition, it is concluded that omeprazole and esomeprazole are the most potent CYP2C19 inhibitors. This was confirmed after the incubation of the individual PPIs with human primary hepatocytes (in the presence of human serum) and by monitoring their impact on diazepam N-demethylase activity at a low concentration of diazepam (2 µM). Data described herein are consistent with reports that PPIs are mostly weak inhibitors of cytochromes P450 in vivo. However, two members of the PPI class (esomeprazole and omeprazole) are more likely to serve as clinically relevant inhibitors of CYP2C19.

Effects of Online Psychological Crisis Intervention for Frontline Nurses in COVID-19 Pandemic.

Objective: The psychological problems of frontline nurses in COVID-19 prevention and control are very prominent, and targeted intervention is needed to alleviate them. This study was to assess the impact of online intervention programs on psychological crisis of anxiety, depression levels and physical symptoms among frontline nurses fighting the COVID-19 pandemic. Methods: A three-stage online psychological crisis intervention program was established. The General Anxiety 7 (GAD-7) assessment, Patient Health Questionnaire-9 (PHQ-9), and the Self-rating Somatic Symptom Scale (SSS) were used to evaluate the effect of intervention on the day before entering isolation wards (Time 1), the first day after leaving the isolation ward (Time 2), and at the end of the intervention (Time 3). Results: Sixty-two nurses completed the study, including 59 female (95.2%) and three male nurses (4.8%) with an age range of 23-49 (mean 33.37 ± 6.01). A significant (P < 0.01) difference existed in the scores of GAD-7, PHQ-9, and SSS at different intervention periods. The GAD-7 score was significantly (P < 0.001) lower at the end of quarantine period (time 3) than that before entering the isolation wards (time 1) or after leaving the isolation wards (time 2), the PHQ-9 score was significantly (P = 0.016) lower at the end of quarantine period (time 3) than that after leaving the isolation wards (time 2), and the SSS score was significantly (P < 0.001) lower at the end of quarantine period (time 3) than that before entering the isolation wards (time 1) or after leaving the isolation wards (time 2). Conclusion: The three-stage online intervention program based on the psychological crisis can be effective in reducing negative emotions and somatic symptoms and improving the mental health of frontline nurses in prevention and control of the COVID-19 epidemic. It may provide an empirical basis for psychological crisis intervention of frontline medical staff when facing public health emergencies.

Predicting Emotional Valence of People Living with the Human Immunodeficiency Virus Using Daily Voice Clips: A Preliminary Study.

To detect depression in people living with the human immunodeficiency virus (PLHIV), this preliminary study developed an artificial intelligence (AI) model aimed at discriminating the emotional valence of PLHIV. Sixteen PLHIV recruited from the Taoyuan General Hospital, Ministry of Health and Welfare, participated in this study from 2019 to 2020. A self-developed mobile application (app) was installed on sixteen participants' mobile phones and recorded their daily voice clips and emotional valence values. After data preprocessing of the collected voice clips was conducted, an open-source software, openSMILE, was applied to extract 384 voice features. These features were then tested with statistical methods to screen critical modeling features. Several decision-tree models were built based on various data combinations to test the effectiveness of feature selection methods. The developed model performed very well for individuals who reported an adequate amount of data with widely distributed valence values. The effectiveness of feature selection methods, limitations of collected data, and future research were discussed.

Further assessment of 17alpha-ethinyl estradiol as an inhibitor of different human cytochrome P450 forms in vitro.

17alpha-Ethinyl estradiol (EE) was systematically evaluated as a reversible and time-dependent inhibitor of 11 human drug-metabolizing cytochromes P450 (P450s) (CYP1A1, CYP1A2, CYP1B1, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2J2, CYP3A4, and CYP3A5) in vitro. When ranked, the lowest IC(50) (concentration of inhibitor required to decrease activity by 50%) values were obtained with recombinant CYP1A1 (rCYP1A1) [IC(50(total)) = IC(50(free)) = 2.7 microM] and CYP2C19 activity in human liver microsomes (HLM) [IC(50(total)) = 4.4 microM; IC(50(free)) = 2.8 microM]. For rCYP1A1, formal inhibition studies revealed that EE was a competitive inhibitor [K(i(free)) = 1.4 microM]. All the other IC(50) values were greater than 8.0 microM, and the weakest inhibition was observed with CYP1A2 activity in HLM (IC(50(free)) > 39 microM). In agreement, the IC(50) characterizing the inhibition of melatonin (MEL) 6-hydroxylation in human intestine microsomes (CYP1A1-catalyzed) was lower than that of HLM (0.91 versus >40 microM). Because EE is known to affect the pharmacokinetics of CYP2C19 probe drugs, this result raises the possibility that the concentration of EE during first pass may exceed 1000 nM, sufficient to affect CYP1A1 and CYP2C19, with less impact on CYP3A4 and other P450s. The results implicate intestinal CYP1A1, and possibly CYP2C19, as the loci of EE drug interactions with highly extracted drugs like MEL. Overall, it is very difficult to rationalize drug interactions involving EE based on direct inhibition of CYP2B6 (e.g., selegiline) and hepatic CYP1A2 (e.g., MEL, tizanidine, caffeine, and theophylline).

Pharmacokinetics of the dipeptidyl peptidase 4 inhibitor saxagliptin in rats, dogs, and monkeys and clinical projections.

Saxagliptin is a potent, selective, reversible dipeptidyl peptidase 4 (DPP4) inhibitor specifically designed for extended inhibition of the DPP4 enzyme and is currently under development for the treatment of type-2 diabetes. The pharmacokinetics of saxagliptin were evaluated in rats, dogs, and monkeys and used to predict its human pharmacokinetics. Saxagliptin was rapidly absorbed and had good bioavailability (50-75%) in the species tested. The plasma clearance of saxagliptin was higher in rats (115 ml/min/kg) than in dogs (9.3 ml/min/kg) and monkeys (14.5 ml/min/kg) and was predicted to be low to moderate in humans. The plasma elimination half-life was between 2.1 and 4.4 h in rats, dogs, and monkeys, and both metabolism and renal excretion contributed to the overall elimination. The primary metabolic clearance pathway involved the formation of a significant circulating, pharmacologically active hydroxylated metabolite, M2. The volume of distribution values observed in rats, dogs, and monkeys (1.3-5.2 l/kg) and predicted for humans (2.7 l/kg) were greater than those for total body water, indicating extravascular distribution. The in vitro serum protein binding was low (< or =30%) in rats, dogs, monkeys, and humans. After intra-arterial administration of saxagliptin to Sprague-Dawley and Zucker diabetic fatty rats, higher levels of saxagliptin and M2 were observed in the intestine (a proposed major site of drug action) relative to that in plasma. Saxagliptin has prolonged pharmacodynamic properties relative to its plasma pharmacokinetic profile, presumably due to additional contributions from M2, distribution of saxagliptin and M2 to the intestinal tissue, and prolonged dissociation of both saxagliptin and M2 from DPP4.

Confirmation that cytochrome P450 2C8 (CYP2C8) plays a minor role in (S)-(+)- and (R)-(-)-ibuprofen hydroxylation in vitro.

Various groups have sought to determine the impact of CYP2C8 genotype (and CYP2C8 inhibition) on the pharmacokinetics (PK) of ibuprofen (IBU) enantiomers. However, the contribution of cytochrome P450 2C8 (CYP2C8) in human liver microsomes (HLMs) has not been reported. Therefore, in vitro cytochrome P450 (P450) reaction phenotyping was conducted with selective inhibitors of cytochrome P450 2C9 (CYP2C9) and CYP2C8. In the presence of HLMs, sulfaphenazole (CYP2C9 inhibitor), and anti-CYP2C9 monoclonal antibodies (mAbs) inhibited (73-100%) the 2- and 3-hydroxylation of both IBU enantiomers (1 and 20 microM). At a higher IBU concentration (500 microM), the same inhibitors were less able to inhibit the 2-hydroxylation of (S)-(+)-IBU (32-52%) and (R)-(-)-IBU (30-64%), whereas the 3-hydroxylation of (S)-(+)-IBU and (R)-(-)-IBU was inhibited 66 to 83 and 70 to 89%, respectively. In contrast, less inhibition was observed with montelukast (CYP2C8 inhibitor, < or =35%) and anti-CYP2C8 mAbs (< or =24%) at all concentrations of IBU. When (S)-(+)-IBU and (R)-(-)-IBU (1 microM) were incubated with a panel of recombinant human P450s, only CYP2C9 formed appreciable amounts of the hydroxy metabolites. At a higher IBU enantiomer concentration (500 microM), additional P450s catalyzed 2-hydroxylation (CYP3A4, CYP2C8, CYP2C19, CYP2D6, CYP2E1, and CYP2B6) and 3-hydroxylation (CYP2C19). When the P450 reaction phenotype and additional clearance pathways are considered (e.g., direct glucuronidation and chiral inversion), it is concluded that CYP2C8 plays a minor role in (R)-(-)-IBU (<10%) and (S)-(+)-IBU ( approximately 13%) clearance. By extension, one would not expect CYP2C8 inhibition (and genotype) to greatly affect the pharmacokinetic profile of either enantiomer. On the other hand, CYP2C9 inhibition and genotype are expected to have an impact on the PK of (S)-(+)-IBU.

The role of adipose protein derived hydrogels in adipogenesis.

Biomaterials that induce adipogenesis may ultimately serve as alternatives to traditional tissue reconstruction and regeneration techniques. In addition, these materials can provide environments for studying factors that regulate adipogenesis. The present study investigates the potential of adipose-derived matrices to induce adipogenesis in vitro and in vivo. Solutions containing basement membrane proteins and growth factors were extracted from subcutaneous adipose tissue. These extracts could be induced to form gels by either incubating the solutions at 37 degrees C or adjusting the pH to 4.0. The adipose extracts promoted rapid preadipocyte aggregation and formation of lipid-loaded colonies in vitro. Differentiation on adipose-derived gels was greater than tissue culture dishes and the tumor-derived product Matrigel (p < 0.05). Significant adipose formation was observed when adipose-derived gels were implanted around a rat epigastric pedicle bundle. Adipose levels in these gels were significantly greater than Matrigel (p < 0.05). The duration of adipose formation depended on the mechanism for gelling the solutions, with acid gelled matrices having greater adipose levels at 6 weeks than temperature gelled matrices. These adipose-derived hydrogels promote rapid adipogenesis in vitro and in vivo. They may lead to new materials for adipose tissue engineering, and provide an environment for studying cell-matrix interactions in adipogenesis.

Measures of bioavailable serum sex hormone levels in aging Chinese by protein chip.

The purpose of this study was to develop a protein chip technique based on receptor binding assays to measure bioavailable serum sex hormone levels (BSSHL). 224 aging healthy Chinese were investigated to get the referenced values of BSSHL for the first time. In the assays recombined sex hormone receptor proteins were jointed to polysaccharide coated slides to make protein chip, and the dose-dependence curves of sex hormone on chip were prepared. The data showed that this method had good precision (CV < 16%) and accuracy (Bias < 10%), and the sensitivity could reach 1 pmol/L. From the results, BSSHL of men and women declined with aging, but no significant differences were observed. The BSSHL of aging men were higher than those of women. The bioavailable serum androgen level of men was 52-112 pmol/L, women's was 3-70 pmol/L and the whole group was 41.9-81.4 pmol/L. The bioavailable serum estrogen level of men was 0.8-3.0 pmol/L, women's was 1.2-2.5 pmol/L and the whole group was 0.6-2.64 pmol/L. Based on the assays, BSSHL measurement by protein chip can meet the needs of epidemiological studies in terms of speed, accuracy and sample volume required, and was helpful in quantitative assessment of aging people's health.

Automated on-line SPE LC-MS/MS method to quantitate 6beta-hydroxycortisol and cortisol in human urine: use of the 6beta-hydroxycortisol to cortisol ratio as an indicator of CYP3A4 activity.

A sensitive method for quantitation of urinary 6beta-hydroxycortisol (6beta-HC) and cortisol using on-line SPE and LC-MS/MS was developed and validated. Human urine samples were injected directly onto an on-line solid phase extraction apparatus, Prospekt-2, followed by HPLC separation and electrospray triple quadrupole LC-MS/MS detection. The inter-day precision for the 6beta-HC:cortisol ratio was 7-9%. The lower limit of quantitation was 1 and 0.2 ng/mL for 6beta-HC and cortisol, respectively. Using the method we observed a diurnal variation on the 6beta-HC:cortisol ratio in healthy volunteers with the maximal ratio observed in the 2-10 pm urine collection period.