Low-dose prasugrel versus standard-dose ticagrelor in east Asian patients with acute coronary syndrome.

Low-dose prasugrel demonstrated a similar effectiveness profile to clopidogrel in East Asian ACS patients, but its comparison with another new-generation potent P2Y12 inhibitor, ticagrelor, remains unclear. To compare the effectiveness and safety of low-dose prasugrel against those of standard-dose ticagrelor in East Asian patients with ACS. This retrospective cohort study used Taiwan's National Health and Welfare Database. This study included ACS patients who underwent percutaneous coronary intervention and, at discharge between January 1, 2018 and December 31, 2020, were prescribed with low-dose prasugrel plus aspirin or standard-dose ticagrelor plus aspirin. Stabilized inverse probability of treatment weighting was used to balance the covariates across these two groups. The primary effectiveness outcome was a composite of acute myocardial infarction, ischemic stroke, and cardiovascular death; the secondary effectiveness outcome was each of the individual components of the primary outcome, transient ischemic attack, and repeat revascularization. The primary safety outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding, and the two secondary safety outcomes were intracranial hemorrhage and gastrointestinal bleeding. A total of 24,807 patients were included in this study. Among them, 1,493 were low-dose prasugrel users and 23,314 were standard-dose ticagrelor users. No significant differences were found in primary effectiveness [HR: 0.97 (0.74-1.28)] or primary safety outcomes [HR: 1.22 (0.73-2.01)] between the two study groups. For East Asian patients with ACS, low-dose prasugrel provides comparable effectiveness without increasing bleeding risk compared to standard-dose ticagrelor. Low-dose prasugrel may be an appropriate alternative for East Asian populations.

The Effects of Pharmacist-Led Medication Therapy Management on Medication Adherence and Use of Non-Steroidal Anti-Inflammatory Drug in Patients with Pre-End Stage Renal Disease.

Purpose: Patients with chronic kidney disease (CKD) are particularly vulnerable to the risks of polypharmacy, largely owing to various comorbid conditions. This vulnerability is further compounded by an escalated risk of renal function deterioration when exposed to nephrotoxic medications. As part of the national health insurance program in Taiwan, the pre-end-stage kidney disease patient care and education plan has included pharmaceutical care since October 2021. This study aims to explore the effect of pharmacist involvement in a multidisciplinary care team for patients with kidney disease in outpatient settings. Patients and Methods: This retrospective observational study was conducted at a single center. It analyzed data from May 2022 to May 2023, focusing on patients who received medication therapy management in the kidney disease pharmacist-managed clinic. The study assessed changes in patient medication adherence, non-steroidal anti-inflammatory drugs (NSAIDs) usage, CKD stage, and urine protein-to-creatinine ratio (UPCR) after pharmacist intervention. It also documented pharmacists' medication recommendations and the rate of acceptance by physicians. Results: A total of 202 patients who had at least two clinic visits were included in the study. After pharmacist intervention, the proportion of poor medication adherence reduced significantly from 67.8% to 43.1% (p<0.001). The proportion of NSAID users also decreased significantly from 19.8% to 8.4% (p=0.001). CKD stage showed a significant reduction (p=0.007), and the average UPCR improved from 2828.4 to 2111.0 mg/g (p<0.001). The pharmacists provided a total of 56 medication recommendations, with an acceptance rate of 86%. Conclusion: The involvement of pharmacists in the multidisciplinary care team can effectively provide medication-related recommendations, ensuring the effectiveness and safety of patients' medication use, and lead to better kidney function and lower proteinuria.

Development of a social cognitive career theory scale for measuring the intention to select surgery as a career.

Background: Surgeon shortages have emerged as a prominent global issue. Although various studies have explored the factors that influence medical students in choosing surgery as a career, addressing the need for surgeons requires a multifaceted approach. However, there is currently a lack of a theoretically grounded scale to evaluate the effectiveness of surgical career development or policy promotion. Thus, this study aimed to develop a questionnaire for assessing the preference for a surgical career by adopting the Social Cognitive Career Theory (SCCT). Materials and methods: The study aimed to develop the Social Cognitive Career Theory Scale toward Surgery (SCCTSS) by adopting the framework of SCCT. The questionnaire was created through expert consensus and the content validity index (CVI) calculation. Subsequently, a pilot version of the SCCTSS was administered to 222 medical students in their clinical clerkships, and the collected data underwent item analysis. Additionally, the validation of the SCCTSS by gender was performed. Results: The SCCTSS comprised 16 items that passed expert panel evaluation, with a CVI >0.8, mean ≥ 3.00, and an interquartile range ≤1. Item analysis demonstrated that the quality of the SCCTSS met the qualifying threshold. Furthermore, the SCCTSS questionnaire effectively validated gender differences in surgical career preference. Conclusions: We developed an internally consistent and reliable scale and validated it through an expert panel method and feedback from medical students. Further research is required to evaluate the targeted interventions that may assist in recruiting medical students into the field of surgery through the application of the SCCTSS.

The Impact of Pharmacist-Managed Service on Warfarin Therapy in Patients after Mechanical Valve Replacement.

Objective: To evaluate the impact of pharmacist interventions on international normalized ratio (INR) control during the warfarin initiation phase after mechanical valve replacement. Methods: This was a retrospective cohort study conducted in a cardiovascular surgery ward in a tertiary hospital from August 1, 2015, to July 31, 2019. Patients aged ≥20 years who were admitted for mechanical valve replacement were enrolled in this study and further classified into conventional and pharmacist-managed warfarin therapy (PMWT) groups. All participants were prospectively followed up until the first outpatient appointment after valve replacement. The effectiveness outcomes were time in therapeutic range (TTR), time to therapeutic INR, number of patients with therapeutic INR at discharge and at first outpatient appointment, and length of hospital stay. The safety outcome was the number of patients with any supratherapeutic INR during the hospital stay. Multivariate logistic regression analyses were also used to determine the predictors of a therapeutic INR at discharge or with any supratherapeutic INR during admission. Results: A total of 39 and 33 patients were enrolled in the conventional and PMWT groups, respectively. At discharge, 18 patients (46.2%) in the conventional group and 24 patients (72.7%) in the PMWT group had achieved the therapeutic INR (P=0.023). Compared to the conventional group, fewer patients in the PMWT group had supratherapeutic INR during hospital stay (35.9% vs. 9.0%, P=0.008). No significant differences were found in TTR, time to therapeutic INR, number of patients with therapeutic INR at return appointment, and length of stay between the study groups. In the multivariate regression analyses, PMWT predicted achieving therapeutic INR at discharge (odds ratio (OR) and 95% confidence interval (CI), 3.14 [1.08-9.14]) and was inversely associated with supratherapeutic INRs during admission (OR = 0.21 [0.05-0.82]). Conclusions: Among patients admitted for mechanical valve replacement, the implementation of PMWT was associated with optimal therapeutic INR at discharge and no supratherapeutic INR during admission. Therefore, pharmacist participation is essential for improving the quality of warfarin therapy.

Clinical and economic impact of clinical pharmacist intervention in a hematology unit.

BACKGROUND: Medication errors can lead to preventable adverse drug events and associated hospitalization and healthcare cost to patients. Pharmacotherapy in patients with hematologic malignancies is more complex than that in general medicine patients. This study evaluated the clinical and economic impact of clinical pharmacist intervention in a hematology unit. METHODS: This retrospective study compared the number of pharmacist interventions and the economic impact for one year before and after a clinical pharmacist was deployed in a hematology unit. The clinical pharmacist joined the ward rounds and gave patient counseling and recommendations on medication use. For pharmacist intervention analysis, we compared the number and type of interventions. For cost analysis, we calculated the cost savings, estimated the cost avoidance, and compared the benefit-cost ratio between the two periods. RESULTS: The average length of hospitalization reduced from 19.27 days to 16.69 days after clinical pharmacist deployment. The rate of pharmacist interventions in medication orders increased from 143 out of 42,501 prescriptions (0.34%) to 826 out of 44,175 prescriptions (1.87%) (P < 0.00001). The calculated cost savings (NT$37,080 and NT$252,280), cost avoidance (NT$582,100 and NT$2,304,600), and benefit-cost ratio (0.77 and 3.19) increased after clinical pharmacist deployment. CONCLUSION: This study demonstrated that the number of interventions significantly increased after clinical pharmacist deployment. This service could reduce medication errors, preventable adverse drug events, and costs of both medications and potential adverse drug events.

Effects of Retzius sparing on robot-assisted laparoscopic prostatectomy: a systematic review with meta-analysis.

BACKGROUND: To comprehensively evaluate the efficacy and safety of Retzius sparing (RS) for men undergoing robot-assisted laparoscopic prostatectomy (RARP). METHODS: We searched four electronic databases and reference lists of relevant studies for eligible research published before March 11, 2019. After quality assessment, eligible studies were synthesized for relevant outcomes, including positive surgical margin (PSM), continence, incontinence, complication, console time, and hospital stay. RESULTS: Two randomized clinical trials and four observational studies were included in this study. Quantitative syntheses revealed significantly higher PSM rates in RS-RARP compared with conventional RARP (c-RARP) (odds ratio [OR] 1.68, p = 0.02). Furthermore, we found significantly higher PSM rates at the anterior site in RS-RARP compared with c-RARP (OR 4.34, p = 0.03) and significantly lower incontinence rates in RS-RARP in the first month (OR 0.30, p < 0.001) and 12th month (OR 0.25, p < 0.001). CONCLUSIONS: Our syntheses revealed higher PSM rates in the RS-RARP group, especially in the anterior aspect. However, RS-RARP had superior functional outcome of urinary continence and lower console time than did c-RARP with equivalent complication rates. Thus, we suggest that operators pay more attention to making clear surgical margins if the lesion is in anterior prostate when performing RS-RARP.

SLC9A3 Affects Vas Deferens Development and Associates with Taiwanese Congenital Bilateral Absence of the Vas Deferens.

BACKGROUND: The pathophysiology of Taiwanese congenital bilateral absence of the vas deferens (CBAVD) is different from that in Caucasians. In particular, major cystic fibrosis transmembrane conductance regulator (CFTR) mutations and cystic fibrosis are absent in the former. Instead, deficiency in solute carrier family 9 sodium/hydrogen exchanger isoform 3 (SLC9A3) may play a role by generating obstructive azoospermia and degraded epithelial structure in the reproductive tract. OBJECTIVES: The objective of the study was to test whether SLC9A3 variants cause Taiwanese CBAVD. MATERIALS AND METHODS: Six-month-old Slc9a3 -/-male mice were used to evaluate the effect of long-term SLC9A3 loss on the reproductive system. A case-control cohort of 29 men with CBAVD and 32 fertile men were genotyped for SLC9A3 variants. RESULTS: SLC9A3 was expressed and localized in the apical border of the epithelium of human vas deferens and glandular epithelium of the seminal vesicle. SLC9A3 deficiency specifically induces atrophy of vas deferens and unfolding of seminal vesicle mucosa in mice. Loss of SLC9A3 increased the incidence of CBAVD in humans from 3.1% to 37.9% (p < 0.001). Up to 75.9% of CBAVD patients carry at least one variant in either SLC9A3 or CFTR. DISCUSSION: Our findings build upon previous data associated with CBAVD pathogenesis. Here, we now report for the first time an association between CBAVD and loss of SLC9A3 and propose that specific defects in the reproductive duct due to SLC9A3 variants drive CBAVD development. CONCLUSION: The data implicate loss of SLC9A3 as a basis of Taiwanese CBAVD and highlight SLC9A3 function in reproduction.

Effects of transabdominal preperitoneal and totally extraperitoneal inguinal hernia repair: an update systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Compared with open herniorrhaphy, laparoscopic herniorrhaphy can yield more favorable clinical outcomes. However, previous studies failed to give definite answer for comparison between laparoscopic inguinal hernia repair approaches. This study aimed to systematically determine the differences in recurrence rate, duration of return to work, pain, surgery duration, and duration of hospital stay between transabdominal preperitoneal (TAPP) and totally extraperitoneal (TEP) approach for inguinal hernia. METHODS: PubMed, Embase, and Cochrane Library (including the Cochrane Central Register of Controlled Trials) abstracts up to September 2017 were searched for randomized controlled trials (RCTs) comparing TAPP or TEP hernia repairing. The hernia recurrence rate, time to return to work, analgesic consumption, surgery duration, hospital stay, and the pain score were recorded with subgroup analysis of the hernia type. RESULTS: Sixteen RCTs that randomized 1519 patients with hernia into TEP and TAPP repair groups were analyzed in this study. The results revealed that TEP repair resulted in shorter hospital stay of primary cases (MD - 0.87, 95% CI - 1.67 to - 0.07) but was associated with a longer operative duration in recurrent hernia group (MD 3.35, 95% CI 0.16 - 6.54). CONCLUSIONS: TEP and TAPP have their own advantages. TEP repair reduces short-term postoperative pain more effectively than TAPP repair and results in shorter hospital stay of primary cases. In contrast, TAPP repair is correlated with shorter surgery duration. These findings show that shared decision-making regarding both approaches of laparoscopic hernia repair may be needed.

Bradycardia during Induction Therapy with All-trans Retinoic Acid in Patients with Acute Promyelocytic Leukemia: Case Report and Literature Review.

A 41-year-old man with newly diagnosed acute promyelocytic leukemia (APL) received induction chemotherapy, containing all-trans retinoic acid (ATRA), idarubicin, and arsenic trioxide. On the 11th day of therapy, he experienced complete atrioventricular (AV) block; therefore, ATRA and arsenic trioxide were immediately postponed. His heart rate partially recovered, and ATRA was rechallenged with a half dose. However, complete AV block as well as differentiation syndrome recurred on the next day. ATRA was immediately discontinued, and a temporary pacemaker was inserted. Two days after discontinuing ATRA, AV block gradually improved, and ATRA was uneventfully rechallenged again. The Naranjo adverse drug reaction probability scale was 7 for ATRA, suggesting it was the probable cause of arrhythmia. A literature search identified 6 other cases of bradycardia during ATRA therapy, and all of them occurred during APL induction therapy, with onset ranging from 4 days to 25 days. Therefore, monitoring vital signs and performing electrocardiogram are highly recommended during the first month of induction therapy with ATRA. ATRA should be discontinued if complete AV block occurs. Rechallenging with ATRA can be considered in fully recovered and clinically stable patients.

The Effectiveness of a Simulation-Based Flipped Classroom in the Acquisition of Laparoscopic Suturing Skills in Medical Students-A Pilot Study.

OBJECTIVE: To evaluate the effectiveness of a simulation-based flipped classroom in gaining the laparoscopic skills in medical students. DESIGN: An intervention trial. SETTING: Taipei Medical University Hospital, an academic teaching hospital. PARTICIPANTS AND METHODS: Fifty-nine medical students participating in a 1-hour laparoscopic skill training session were randomly assigned to a conventional classroom (n = 29) or a flipped classroom approach (n = 30) based on their registered order. At the end of the session, instructors assessed participants' performance in laparoscopic suturing and intracorporeal knot-tying using the assessment checklist based on a modified Objective Structured Assessment of Technical Skills tool. RESULTS: Students in the flipped group completed more numbers of stitches (mean [M] = 0.47; standard deviation [SD] = 0.507) than those in the conventional group (M = 0.10; SD = 0.310) (mean difference: 0.37; 95% CI: 0.114-582; p = 0.002). Moreover, students in the flipped group also had higher stitch quality scores (M = 7.17; SD = 2.730) than those in the conventional group (M = 5.14; SD = 1.767) (mean difference = 2.03; 95% CI: 0.83-3.228; p = 0.001). Meanwhile, students in the flipped group had higher pass rates for the second throw (p < 0.001), third throw (p = 0.002), appropriate tissue reapproximation without loosening or strangulation (p < 0.001), needle cut from suture under direct visualization (p = 0.004), and needle safely removed under direct visualization (p = 0.018) than those in the conventional group. CONCLUSIONS: Comparing with traditional approach, a simulation-based flipped classroom approach may improve laparoscopic intracorporeal knot-tying skill acquisition in medical students.

Pharmacokinetics of vancomycin in adults receiving extracorporeal membrane oxygenation.

BACKGROUND/PURPOSE: Extracorporeal membrane oxygenation (ECMO) alters the pharmacokinetics (PK) of vancomycin in neonates; but data on adults is limited. METHODS: This is a prospective, matched cohort, single center, pharmacokinetic study. For each adult patient who received vancomycin therapy in the ECMO group (with either centrifugal pump or roller pump), a control patient was matched by age (≥ 60 years or < 60 years), gender, and creatinine clearance (CLCr) in intensive care units. After vancomycin was administered for at least four doses, serial blood samples were drawn at 0.5 hours, 1 hour, 2 hours, 3 hours, 5 hours, 7 hours, 11 hours, 23 hours, 35 hours, and 47 hours post vancomycin infusion according to the dosing intervals. The serum concentration-time profile was fitted to a noncompartment model and a nonlinear mixed effect model to determine the PK parameters. RESULTS: Twenty-two critically ill adults without renal replacement therapy were enrolled. There were no significant differences between the ECMO group and the matched group in demographics, renal function, and PK parameters. However, vancomycin clearance in the roller pump group was significantly lower than that in the matched control (0.83 ± 0.43 mL/min/kg vs. 0.97 ± 0.43 mL/min/kg, p = 0.002). CONCLUSION: Vancomycin clearance in patients receiving ECMO with a roller pump was significantly lower than that in the matched cohort. Vancomycin PK parameters in patients on ECMO with a centrifugal pump were comparable to those in the matched control group.

Clopidogrel-Associated Neutropenia: Case Report and Review of the Literature.

Clopidogrel is a second generation of thienopyridine, which has antiplatelet effect by inhibiting P2Y12 receptor. Hematologic adverse effect is very uncommon during clopidogrel use, but some cases of clopidogrel-associated neutropenia were reported in the past decade. Until now, there was no summary data to delineate the clinical course and safe alternatives of this event. We report 2 cases of clopidogrel-associated neutropenia and review other 10 case reports from 2000 to 2014. The median onset of neutropenia was 22 days, and the recovery time was 4 days after receiving granulocyte-colony-stimulating factor. Bone marrow studies in 6 cases all showed hypocellular or toxic damage. Six cases used cilostazol, prasugrel, or ticagrelor as safe alternatives. Closely monitoring blood cell counts is highly suggested in the first month after using clopidogrel. Newer P2Y12 inhibitors, especially ticagrelor, could be effective and safe alternatives if patients had a history of clopidogrel-associated neutropenia.

Local anesthetic infusion pump for pain management following open inguinal hernia repair: a meta-analysis.

OBJECTIVES: Open inguinal hernia repair is one of the most painful procedures in day surgery. A continuous ambulatory analgesic is thought to reduce postoperative pain when it is applied to the surgical site. The aim of this study is to evaluate the efficacy of local anesthetic infusion pump following open inguinal hernia repair for the reduction of postoperative pain. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that have investigated the outcomes of using an infusion pump for delivering a local anesthetic contrasted to a control group for open inguinal hernia repair. Pain was assessed from Day 1 to Day 5 following the surgery. The secondary outcomes included analgesia use and postoperative complications. RESULTS: We reviewed 5 trials that totaled 288 patients. The analgesic effects of bupivacaine (4 trials) and ropivacaine (one trial) were compared with a placebo group. The pooled mean difference in the score measuring the degree of pain diminished significantly at Day 1 to Day 4 in the experimental group. Two studies have reported that the number of analgesics required also decreased in the experimental group. No bupivacaine-related complication was reported. CONCLUSION: Our results revealed that applying a local anesthetic infusion pump following inguinal hernia repairs was more efficacious for reducing postoperative pain than a placebo. However, the findings were based on a small body of evidence in which methodological quality was not high. The potential benefits of applying a local anesthetic infusion pump to hernia repair must still be adequately investigated using further RCTs.

Advantages of magnetic resonance imaging (MRI) of the seminal vesicles and intra-abdominal vas deferens in patients with congenital absence of the vas deferens.

OBJECTIVE: To show the flexibility in magnetic resonance imaging (MRI) of seminal vesicle (SV) and intra-abdominal segment of vas deferens for the patients with congenital absence of the vas deferens (CAVD), including congenital bilateral absence of the vas deferens (CBAVD) and congenital unilateral absence of vas deferens (CUAVD). METHODS: Fourteen consecutive patients with CAVD had transrectal ultrasonography (TRUS) and further MRI evaluations. TRUS was performed using a 7.5-MHz transducer, and images of the SVs were obtained, calculated in the transaxial plane. MRI studies were performed with a 1.5-7 superconducting system, T1- and T2-weighted axial, coronal, and sagittal imaging of the pelvis was obtained. If the SVs were present, then their size was measured for the morphologic classification and diagnosis. All of the patients also received cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation testing. RESULTS: In a series of 12 men with CBAVD, only 4 were found to have bilateral SV agenesis using MRI. The remaining 8 men with unilateral hypoplasia still had SV remnants. MRI also detected the intra-abdominal segment of the vas deferens. Through our study of MRI, SV agenesis is not well associated with the presence of CFTR mutation in patients with CAVD. CONCLUSION: MRI provides a precise imaginal diagnosis of SV defect, which is superior to the TRUS examination for the patients with CAVD. Compared with the previous inaccurate examination method of TRUS, this study demonstrates that MRI can provide better images for the patients with CAVD for the clinical diagnosis of existing defects of internal seminal tract and internal organs.

The neuroprotective effect of platelet-rich plasma on erectile function in bilateral cavernous nerve injury rat model.

INTRODUCTION: Neurogenic erectile dysfunction resulting from cavernous nerve (CN) injury is a major complication caused by radical prostatectomy. The use of platelet-rich plasma (PRP) on the nerve-injured site has shown promising results for the nerve regeneration. However, the effects of PRP injection in corpus cavernosum after bilateral CN injury have never been investigated. AIM: To assess the neuroprotective effect of PRP injection in corpus cavernosum after bilateral CN injury. METHODS: Male Sprague-Dawley rats were randomly divided into three groups: Group I underwent sham operation, while the remaining two groups underwent bilateral CN crush. Crush injury groups were treated at the time of injury with an application of PRP or normal saline only injection in the corpus cavernosum, respectively. Four weeks later, erectile function (EF) was assessed by CN electrosimulation, and CNs as well as penile tissue were collected for histology. MAIN OUTCOME MEASURES: Intracavernous pressure (ICP) monitored during electrical stimulation of CNs; myelinated axons number of CNs and dorsal penile nerve; collagen type change, number of apoptotic cells, and mRNA expression of caspase-3 and transforming growth factor-ß1 (TGF-ß1) in the corpus cavernosum. RESULTS: Four weeks after surgery, in the vehicle-only group, the functional evaluation showed a lower mean maximal ICP than that in the sham group (P < 0.05). PRP treatments resulted in significant recovery of EF, as compared with the vehicle-only group (P < 0.05). Histologically, the PRP-treated group had a significant preservation of myelinated axons of CNs compared with the vehicle-only group (P < 0.05) and reduced the apoptotic index. The mRNA expression of TGF-ß1 in the corpus cavernosum tissue was significantly decreased in the PRP group compared with the vehicle-only group (P < 0.05). CONCLUSIONS: PRP injection in the corpus cavernosum increased the number of myelinated axons and facilitated recovery of EF in the bilateral CN injury rat model.

Using vote cards to encourage active participation and to improve critical appraisal skills in evidence-based medicine journal clubs.

RATIONALE, AIMS AND OBJECTIVES: Evidence-based medicine (EBM) journal clubs are used by health care practitioners to critique and remain updated on relevant health literature. Vote cards, in three different colours (green/yellow/red), allow participants to express their opinions (agree/doubt/reject) on the quality and possibility of clinical application regarding the article being reviewed. Our aim is to assess the efficacy of using vote cards in EBM journal clubs. METHODS: Evidence-based medicine journal club is held on a weekly basis in the Department of Surgery in Taipei Medical University Hospital, Taiwan. The participants of EBM journal clubs include medical students, resident doctors and primary care faculty members. After the presentation, participants use their vote cards to critically appraise the literature and decide if the rationales could be applied in their own practice. After a 12-week period, we evaluated the effectiveness of the vote cards based on survey findings of the participants. RESULTS: The majority of 66 respondents agreed that vote cards can improve the overall quality of EBM journal clubs, may encourage active participation and improve critical appraisal skills. They also rated the vote cards more favourably than traditional hand voting and agree that vote cards should be used in future EBM journal clubs. CONCLUSION: We suggest the regular and routine use of vote cards in EBM journal clubs.

15,16-Dihydrotanshinone I, a Compound of Salvia miltiorrhiza Bunge, Induces Apoptosis through Inducing Endoplasmic Reticular Stress in Human Prostate Carcinoma Cells.

5,16-dihydrotanshinone I (DHTS) is extracted from Salvia miltiorrhiza Bunge (tanshen root) and was found to be the most effective compound of tanshen extracts against breast cancer cells in our previous studies. However, whether DHTS can induce apoptosis through an endoplasmic reticular (ER) stress pathway was examined herein. In this study, we found that DHTS significantly inhibited the proliferation of human prostate DU145 carcinoma cells and induced apoptosis. DHTS was able to induce ER stress as evidenced by the upregulation of glucose regulation protein 78 (GRP78/Bip) and CAAT/enhancer binding protein homologous protein/growth arrest- and DNA damage-inducible gene 153 (CHOP/GADD153), as well as increases in phosphorylated eukaryotic initiation factor 2α (eIF2α), c-jun N-terminal kinase (JNK), and X-box-binding protein 1 (XBP1) mRNA splicing forms. DHTS treatment also caused significant accumulation of polyubiquitinated proteins and hypoxia-inducible factor (HIF)-1α, indicating that DHTS might be a proteasome inhibitor that is known to induce ER stress or enhance apoptosis caused by the classic ER stress-dependent mechanism. Moreover, DHTS-induced apoptosis was reversed by salubrinal, an ER stress inhibitor. Results suggest that DHTS can induce apoptosis of prostate carcinoma cells via induction of ER stress and/or inhibition of proteasome activity, and may have therapeutic potential for prostate cancer patients.

Gene copy number variations in Asian patients with congenital bilateral absence of the vas deferens.

BACKGROUND: Congenital bilateral absence of the vas deferens (CBAVD) is a distinct clinical entity accounting for approximately 25% of obstructive azoospermia in infertile men. The association between CBAVD and mutated CFTR (cystic fibrosis transmembrane conductance regulator) alleles is well demonstrated in Caucasians, but the identity of CBAVD-susceptibility genes remains elusive in Asians. We investigate genomic copy number variations (CNVs) in a patient cohort of Taiwan. METHODS AND RESULTS: Genome-wide screening for genetic CNVs was conducted on eight individuals with CBAVD using array-based comparative genomic hybridization. One recurrent CNV was detected on 3q26.1 in five patients, and another was detected on a reproduction-related gene PANK2 in two patients. For the former, we further characterized the breakpoints in CBAVD and assessed the incidence in healthy individuals by tiling path arrays. The deletion in each patient was confirmed, and seven out of the eight controls were also affected. Examination of the homozygous loss of PANK2 by PCR in a larger cohort showed a homozygous deletion in only one of the 26 CBAVD males, and not in any of the 20 azoospermic patients without CBAVD, nor in any of the 16 control subjects. CONCLUSIONS: Our results suggest that 3q26.1 may not be a critical region for CBAVD. Additionally no strong association was found for PANK2 in this reproduction disorder. Other reproduction-related genes, such as PBX1, BRD3, COL18A1 and HMOX1, identified by this initial study may inspire further investigation.

CFTR mutation analysis of a Caucasian father with congenital bilateral absence of vas deferens, a Taiwanese mother, and twins resulting from ICSI procedure.

Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is one of the most common autosomal recessive diseases in Caucasians. We screened for the CFTR gene mutation in a Caucasian father with congenital bilateral absence of the vas deferens (CBAVD), a Taiwanese mother, and twins resulting from an intracytoplasmic single sperm injection (ICSI) procedure. DNA fragments that showed abnormal banding patterns on temporal temperature gradient gel electrophoresis analysis followed by analysis of DNA sequence was used. The Caucasian father with CBAVD had _F508 and p.L375F mutations. The two children were heterozygous for the _F508 and p.L375F mutations, respectively. Mutation analysis of the CFTR gene should always be recommended for infertile couples seeking ICSI. The possibility of the children resulting from ICSI being a victim or carrier of CBAVD or CF, especially when the father is Caucasian with CBAVD, should be discussed during genetic counseling.