Complex Variations in Branches of the Axillary Artery / Variaciones Complejas en Ramas de la Arteria Axilar

SUMMARY: The axillary artery is a continuation of the subclavian artery and transitions into the brachial artery. Variations in the axillary artery are not uncommon. During the upper-limb dissection of a 95-year-old Korean female cadaver, assorted anatomical variations of the axillary artery branches were identified. On the right side, no branches emerged from the first part of the axillary artery. The thoracoacromial artery (excluding the pectoral branch) and the common subscapular trunk arose from the second part, with the common subscapular trunk giving origins to the pectoral branch, lateral thoracic artery, and subscapular artery. The subscapular artery is divided into the thoracodorsal artery, circumflex scapular artery, and accessory posterior circumflex humeral artery. Additionally, the superior thoracic artery arose from the lateral thoracic artery. The third part of the axillary artery gave rise to the anterior and posterior circumflex humeral arteries, accessory acromial branch, and accessory thoracodorsal artery. On the left side, the thoracoacromial artery (excluding the pectoral branch) and the superior thoracic artery arose from the first part. The common subscapular trunk arose from the second part, which included the pectoral branch, lateral thoracic artery, and subscapular artery. The subscapular artery is divided into the thoracodorsal artery, circumflex scapular artery, accessory posterior circumflex humeral artery, and accessory lateral thoracic artery. The third part gave rise to the anterior and posterior circumflex humeral arteries and the accessory acromial branch. This study presents variations of the axillary artery, emphasizing their rarity, considering their embryologic basis, and highlighting their importance not only for educational purposes but also surgical and radiological applications.

La arteria axilar es una continuación de la arteria subclavia y luego esta continua como arteria braquial. Las variaciones en la arteria axilar no son infrecuentes. Durante la disección de los miembros superiores de un cadáver de una mujer coreana de 95 años, se identificaron diversas variaciones anatómicas de las ramas de la arteria axilar. En el lado derecho no se originaban ramas de la primera parte de la arteria axilar. La arteria toracoacromial (excluyendo la rama pectoral) y el tronco subescapular común surgieron de la segunda parte, y el tronco subescapular común dio origen a la rama pectoral, la arteria torácica lateral y la arteria subescapular. La arteria subescapular se dividía en arteria toracodorsal, arteria circunfleja escapular y arteria humeral circunfleja posterior accesoria. Además, la arteria torácica superior se originaba de la arteria torácica lateral. La tercera parte de la arteria axilar dio origen a las arterias circunflejas humerales anterior y posterior, la rama acromial accesoria y la arteria toracodorsal accesoria. En el lado izquierdo, de la primera parte surgían la arteria toracoacromial (excluyendo la rama pectoral) y la arteria torácica superior. De la segunda parte se originaba el tronco subescapular común, que incluía la rama pectoral, la arteria torácica lateral y la arteria subescapular. La arteria subescapular se dividía en arteria toracodorsal, arteria circunfleja escapular, arteria circunfleja humeral posterior accesoria y arteria torácica lateral accesoria. La tercera parte daba origen a las arterias circunflejas humerales anterior y posterior y a la rama acromial accesoria. Este estudio presenta variaciones de la arteria axilar, enfatizando su rareza, considerando su base embriológica y destacando su importancia no sólo para fines educativos sino también para aplicaciones quirúrgicas y radiológicas.

Impact of extent of resection and postoperative radiotherapy on survival outcomes in intracranial solitary fibrous tumors: a systematic review and meta-analysis.

The knowledge of optimal treatments for patients with intracranial solitary fibrous tumor (SFT) is limited, with inconclusive results from previous studies. In this study, we conducted a meta-analysis of relevant studies to identify the prognostic impact of the extent of resection (EOR) and postoperative radiotherapy (PORT) on survival outcomes of patients with intracranial SFT. We searched the Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify relevant studies published till April 2022. Progression-free survival (PFS) and overall survival (OS) were the outcomes of interest. Differences between two cohorts (gross total resection [GTR] vs. subtotal resection [STR] and PORT vs. surgery only) were estimated by calculating hazard ratios. Twenty-seven studies were selected for the meta-analysis, including data of 1348 patients (GTR, n = 819 vs. STR, n = 381 and PORT, n = 723 vs. surgery only, n = 578). Pooled hazard ratios of PFS (1, 3, 5, and 10 years) and OS (3, 5, and 10 years) revealed that the GTR cohort showed sustained superiority over the STR cohort. In addition, the PORT cohort was superior to the surgery-only cohort with respect to all PFS periods. Although the 10-year OS between the two cohorts was not statistically different, PORT showed significantly better 3- and 5-year OS than surgery only. The study findings suggest that GTR and PORT provide significant benefits for PFS and OS. Aggressive surgical resection of tumors to achieve GTR followed by PORT should be implemented as optimal treatments for all patients with intracranial SFT when feasible.

Distribution of the tensor of the vastus intermedius.

The tensor of the vastus intermedius (TVI) was first described by Grob et al. in 2016. It originates from the anteroinferior greater trochanter and inserts into the upper patella and receives blood and nerves independently of other muscles. It has been overlooked, but since micro-surgery and detailed rehabilitation treatments are being developed, more research on it is warranted. Here we report on the TVI in a Korean cadaveric study. A total of 58 cadavers (41 males and 17 females) were included. Thighs were examined using a standardized dissection protocol. The quadriceps femoris muscle was identified and its components were defined by blunt dissection. A total of 116 lower limbs were dissected. In 40 of them, there was a separately innervated TVI muscle belly between the fasciae of the vastus lateralis (VL) and the vastus intermedius (VI) muscles. TVIs were classed as independent (ID), VI, and VL types according to the relative relationship between the TVI, VL, and VI, and subdivided into two parts: Part 1 was the proximal muscular portion of the TVI attached to the VL or VI, and part 2 was the distal aponeurotic area. TVIs were analyzed in detail via 58 Korean cadavers. We subdivided them on the basis of their location and association with related muscles. A larger study is needed to clarify the function and prevalence of the TVI.

Craniopharyngioma resection by endoscopic endonasal approach versus transcranial approach: A systematic review and meta-analysis of comparative studies.

Introduction: The transcranial approach (TCA) has historically been used to remove craniopharyngiomas. Although the extended endoscopic endonasal approach (EEA) to these tumors has been more commonly accepted in the recent two decades, there is debate over whether this approach leads to better outcomes. The goal of this systematic review and meta-analysis was to more comprehensively understand the benefits and limitations of these two approaches in craniopharyngioma resection based on comparative studies. Methods: We conducted a systematic literature search in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses recommendations using MEDLINE, EMBASE, and the Cochrane Library. A total of 448 articles were screened. Data were extracted and analyzed using proportional meta-analysis. Eight comparative studies satisfied the inclusion criteria. The extent of resection, visual outcomes, and postoperative complications such as endocrine dysfunction and cerebrospinal fluid (CSF) leakage were compared. Results and discussion: Eight studies, involving 376 patients, were included. Resection by EEA led to a greater rate of gross total resection (GTR) (odds ratio [OR], 2.42; p = 0.02; seven studies) with an incidence of 61.3% vs. 50.5% and a higher likelihood of visual improvement (OR, 3.22; p < 0.0001; six studies). However, TCA resulted in a higher likelihood of visual deterioration (OR, 3.68; p = 0.002; seven studies), and was related, though not significantly, to panhypopituitarism (OR, 1.39; p = 0.34; eight studies) and diabetes insipidus (OR, 1.14; p = 0.58; seven studies). Although TCA showed significantly lower likelihoods of CSF leakage (OR, 0.26; 95% confidence interval [CI], 0.10-0.71; p = 0.008; eight studies) compared to EEA, there was no significant difference in meningitis (OR, 0.92; 95% CI, 0.20-4.25; p = 0.91; six studies) between the two approaches. When both approaches can completely resect the tumor, EEA outperforms TCA in terms of GTR rate and visual outcomes, with favorable results in complications other than CSF leakage, such as panhypopituitarism and diabetes insipidus. Although knowledge of and competence in traditional microsurgery and endoscopic surgery are essential in surgical decision-making for craniopharyngioma treatment, when both approaches are feasible, EEA is associated with favorable surgical outcomes. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021234801.

Anatomical Characteristics of the Anterior Jugular Vein and Its Clinical Relevance.

INTRODUCTION: The anterior jugular vein (AJV) is part of the superficial venous drainage system of the head and neck. Recently, interest in AJV is increasing as various surgical procedures have been developed. The authors conducted a cadaveric study to determine characteristics of AJV in Koreans. METHODS: A total of 44 cadavers were dissected. Anatomical characteristics were analyzed for 34 cadavers in which AJV was well observed. RESULTS: In this study, 21 were males and 13 were females. There were 8 cadavers with only 1 AJV from both sides. There was no significant difference in anatomical characteristics according to gender or AJV variation except for a difference in the length of the neck according to gender. However, it was possible to find a safety zone at the main landmark of the neck that could avoid AJV damage. CONCLUSIONS: By using this safety zone, it is possible to prevent damage to the AJV and reduce complications during various surgical procedures on the head and neck.

A heptamethine cyanine dye serves as a potential marker for myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with inhibitory effects on T cell-mediated immune response. MDSCs accumulate under many pathological conditions, including cancers, to avoid anticancer immunity. Unlike mouse MDSCs, common specific surface markers for human MDSCs are not clearly defined, mainly due to the complexity of MDSC subsets. In this study, we investigate specific responses of the infrared dye MHI-148 to MDSCs. Mice bearing 4T1 breast cancer cells were established, and splenocytes were isolated. Flow cytometric analyses demonstrated that MHI-148 was reactive to over 80% of MDSC-specific cells manifesting CD11b+/Gr-1+ acquired from both tumor-bearing mice and naive mice. Cells sorted positive for either CD11b/Gr-1 or MHI-148 were also identical to their counterparts (99.7% and 97.7%, respectively). MHI-148, however, was not reactive to lymphocyte or monocyte populations. To determine whether MHI-148-reactive cells exert inhibitory effects on T cell proliferation, an EdU-based T cell assay was performed. MHI-148 reactive cells significantly reduced T cell proliferation with increased arginase activity and nitrite production. In an attempt to test MHI-148 as a marker for human MDSCs, MHI-148 was specifically reactive to CD11b+/CD33+/CD14- granulocytic MDSCs acquired from selected cancer patients. This study demonstrates that the near-infrared dye MHI-148 specifically reacts to mouse splenocytes with known MDSC-specific markers that have T cell suppressive functions. The dye also selectively binds to a subpopulation of immature myeloid cells acquired from cancer patients. While it is not clear how MHI-148 specifically stains MDSCs, this dye can be a novel tool to detect MDSCs and to predict the prognosis of human cancer patients.

[Latent Class Analysis for Health-Related Quality of Life in the Middle-Aged Male in South Korea].

PURPOSE: This study aimed to identify types of quality of life (QoL) based on the 5 dimensions of EQ-5D and predict factors affecting types of QoL. METHODS: This study was a secondary analysis using data from the Korean Health Panel Survey-??2012). Participants were 2,071 middle-aged men who had completed the additional survey in 2012 and the data were analyzed using SPSS 20.0 and Mplus 5.21 for latent analysis. RESULTS: Three latent classes of QoL were identified: serious (2.4% of the sample), threatened (15.5%), and stable types (82.0%). The types and characteristics of QoL among the latent classes differed. On comparing latent type 1 with latent type 2, the socioeconomic status (p<.05), employment status (p<.05), and subjective health status (p<.001) were found to be significant. On comparing latent type 1 with latent type 3, the socioeconomic status (p<.05), current smoking status (p<.001), and subjective health status (p<.001) were found to be significant. On comparing latent type 2 with latent type 3, the socioeconomic status (p<.05), subjective health status (p<.001), stress (p<.001) were found to be significant. CONCLUSION: The results showed significant heterogeneity in types of QoL and the predictors of QoL by types were different. These findings provide basic information for developing nursing interventions to improve QoL. Specific characteristics depending on the subtypes should be considered during the development of interventions.

Procalcitonin as a prognostic marker for outcomes in post-cardiac arrest patients: A systematic review and meta-analysis.

AIM: This study aimed to seek evidence for the usefulness of the procalcitonin as a prognostic blood biomarker for outcomes in post-cardiac arrest patients. METHODS: We systematically searched MEDLINE, EMBASE, and the Cochrane Library (search date: 8 January, 2019). Studies on patients who experienced return of spontaneous circulation, who had out of hospital cardiac arrest and had their level of procalcitonin measured and outcomes assessed at and after hospital discharge, were included. We additionally performed subgroup analyses for confounding factors affecting patients' outcomes. To assess the risk of bias of each included study, the Quality in Prognosis Studies tool was used. RESULTS: A total of 1065 patients from 10 studies were finally included. Elevated procalcitonin level during hospital admission (at 0-24 h) was associated with in-hospital mortality (standardized mean difference (SMD) 0.64, 95% confidence interval (CI) 0.33-0.95, I2 = 26%). The elevation of procalcitonin level (at 0-48 h) was also associated with poor neurologic outcomes (at 0-24 h, SMD 0.61; 95% CI 0.44-0.79, I2 = 0%; at 24-48 h, SMD 0.58, 95% CI 0.35-0.82, I2 = 0%) as well as at 1-6 months (at 24-48 h, SMD 0.62; 95% CI 0.36-0.88, I2 = 0%). CONCLUSIONS: Overall, the findings suggested that an elevated procalcitonin level measured at 0-48 h of post-cardiac arrest syndrome was associated with poor outcomes.

Zinc Inhibits Expression of Androgen Receptor to Suppress Growth of Prostate Cancer Cells.

The prostate gland contains a high level of intracellular zinc, which is dramatically diminished during prostate cancer (PCa) development. Owing to the unclear role of zinc in this process, therapeutic applications using zinc are limited. This study aimed to clarify the role of zinc and its underlying mechanism in the growth of PCa. ZnCl2 suppressed the proliferation of androgen receptor (AR)-retaining PCa cells, whereas it did not affect AR-deficient PCa cells. In LNCaP and TRAMP-C2 cells, zinc downregulated the expression of AR in a dose- and time-dependent fashion. Zinc-mediated AR suppression accordingly inhibited the androgen-mediated transactivation and expression of the androgen target, prostate specific antigen (PSA). This phenomenon resulted from facilitated protein degradation, not transcriptional control. In studies using mice bearing TRAMP-C2 subcutaneous tumors, the intraperitoneal injection of zinc significantly reduced tumor size. Analyses of both xenograft tumors and normal prostates showed reduced expression of AR and increased cell death. Considering the significant loss of intracellular zinc and the dominant growth-modulating role of AR during PCa development, loss of zinc may be a critical step in the transformation of normal cells to cancer cells. This study provides the underlying mechanism by which zinc functions as a PCa suppressor, and forms the foundation for developing zinc-mediated therapeutics for PCa.

Targeting CD46 Enhances Anti-Tumoral Activity of Adenovirus Type 5 for Bladder Cancer.

CD46 is generally overexpressed in many human cancers, representing a prime target for CD46-binding adenoviruses (Ads). This could help to overcome low anti-tumoral activity by coxsackie-adenoviral receptor (CAR)-targeting cancer gene therapy viruses. However, because of scarce side-by-side information about CAR and CD46 expression levels in cancer cells, mixed observations of cancer therapeutic efficacy have been observed. This study evaluated Ad-mediated therapeutic efficacy using either CAR-targeting Ad5 or CD46-targeting Ad5/35 fiber chimera in bladder cancer cell lines. Compared with normal urothelia, bladder cancer tissue generally overexpressed both CAR and CD46. While CAR expression was not correlated with disease progression, CD46 expression was inversely correlated with tumor grade, stage, and risk grade. In bladder cancer cell lines, expression levels of CD46 and CAR were highly correlated with Ad5/35- and Ad5-mediated gene transduction and cytotoxicity, respectively. In a human EJ bladder cancer xenograft mouse model, with either overexpressed or suppressed CD46 expression levels, Ad5/35-tk followed by ganciclovir (GCV) treatment significantly affected tumor growth, whereas Ad5-tk/GCV had only minimal effects. Overall, our findings suggest that bladder cancer cells overexpress both CAR and CD46, and that adenoviral cancer gene therapy targeting CD46 represents a more suitable therapy option than a CAR-targeting therapy, especially in patients with low risk bladder cancers.

Effect of the curved blade size on the outcomes of tracheal intubation performed by incoming interns: A randomized controlled manikin study.

BACKGROUND: Novice clinicians who have little or no clinical experience in tracheal intubation occasionally need a long time to perform the procedure when using a large curved blade. They also have a lower tracheal intubation success rate, especially in emergency situations, such as cardiac arrest, than experienced practitioners. This study aimed to investigate whether the size of the curved laryngoscope blade affects the outcomes of tracheal intubation performed by incoming interns on a manikin model. METHODS: After completing a pre-study survey, the participants (n = 221) were randomly assigned into the following 2 groups based on the curved blade size: size 3 (n = 111) and size 4 (n = 110) curved blade groups. This study was conducted during a 1-day boot camp for incoming interns. The participants performed tracheal intubations using Macintosh laryngoscopes with size 3 or 4 blades on a Laerdal Airway Trainer (Laerdal, Stavanger, Norway). Subsequently, the participants were asked to complete a post-study survey. The primary outcome was the time to successful intubation (TSI). Meanwhile, the secondary outcomes were the first-pass and overall success rates, self-reported proximal esophagus visualization, and esophageal intubation. All intubation attempts were recorded and assessed by a trained assistant. The data were analyzed using the Mann-Whitney U or Chi-square test. RESULTS: No significant differences in the baseline characteristics were observed between the 2 groups. The size 3 curved blade group had significantly shorter TSI than the size 4 curved blade group [25.0 (21.0-35.0) vs 36.5 (24.0-80.5) seconds, P < .001]. In addition, the size 3 curved blade group had significantly higher first-pass and overall success rates than the size 4 group (P = .001 and P = .005, respectively). Meanwhile, the size 4 curved blade group showed higher proximal esophagus visualization and esophageal intubation incidence rates than the size 3 curved blade group. CONCLUSION: The outcomes of direct orotracheal intubation performed by novice practitioners may be influenced by the blade's size. Significant emphasis should be given on key anatomical landmarks and progressive visualization for tracheal intubation during airway management training for novice clinicians.

Long-Term Prognostic Value of Late Gadolinium-Enhanced Magnetic Resonance Imaging in Patients With and Without Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Grafting.

The value of late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) for the prediction of functional recovery after surgical revascularization has been previously established. However, the impact of LGE-MRI on the long-term prognosis after coronary artery bypass grafting (CABG) remains incompletely understood. Therefore, we aimed to evaluate the long-term prognostic value of LGE-MRI, based on the presence or absence of left ventricular (LV) dysfunction, in patients with coronary artery disease undergoing CABG. One hundred forty-six consecutive patients underwent cine- and LGE-MRI before CABG. Adverse cardiac events included cardiac death, nonfatal myocardial infarction, heart failure, and unstable angina. A 3-year landmark analysis of the primary end point was also performed for patients surviving beyond 3 years after CABG. During a median follow-up of 9.4 years, 44 patients (30%) experienced adverse cardiac events. Although a LV ejection fraction <50% was associated only with adverse cardiac events at 3 years after CABG, LGE was associated with a worse outcome both at and beyond 3 years after CABG. In the overall study population, LGE presence (adjusted hazard ratio [HR] 2.58; p = 0.027), score (adjusted HR 1.06; p <0.001), and extent (adjusted HR 1.08; p <0.001) were independent predictors of adverse cardiac events. Moreover, in both the LV ejection fraction <50% and ≥50% groups, the LGE extent was an independent predictor of adverse cardiac events. In conclusion, our qualitative and quantitative analyses of LGE-MRI provide long-term prognostic information after surgical revascularization. The LGE extent was a strong predictor of adverse cardiac events, independent of the LV function.

Efficacy of CD46-targeting chimeric Ad5/35 adenoviral gene therapy for colorectal cancers.

CD46 is a complement inhibitor membrane cofactor which also acts as a receptor for various microbes, including species B adenoviruses (Ads). While most Ad gene therapy vectors are derived from species C and infect cells through coxsackie-adenovirus receptor (CAR), CAR expression is downregulated in many cancer cells, resulting inefficient Ad-based therapeutics. Despite a limited knowledge on the expression status of many cancer cells, an increasing number of cancer gene therapy studies include fiber-modified Ad vectors redirected to the more ubiquitously expressed CD46. Since our finding from tumor microarray indicate that CD46 was overexpressed in cancers of the prostate and colon, fiber chimeric Ad5/35 vectors that have infection tropism for CD46 were employed to demonstrate its efficacy in colorectal cancers (CRC). CD46-overexpressed cells showed a significantly higher response to Ad5/35-GFP and to Ad5/35-tk/GCV. While CRC cells express variable levels of CD46, CD46 expression was positively correlated with Ad5/35-mediated GFP fluorescence and accordingly its cell killing. Injection of Ad5/35-tk/GCV caused much greater tumor-suppression in mice bearing CD46-overexpressed cancer xenograft compared to mock group. Analysis of CRC samples revealed that patients with positive CD46 expression had a higher survival rate (p=0.031), carried tumors that were well-differentiated, but less invasive and metastatic, and with a low T stage (all p<0.05). Taken together, our study demonstrated that species B-based adenoviral gene therapy is a suitable approach for generally CD46-overexpressed CRC but would require careful consideration preceding CD46 analysis and categorizing CRC patients.

VEGF-A regulated by progesterone governs uterine angiogenesis and vascular remodelling during pregnancy.

The features and regulation of uterine angiogenesis and vascular remodelling during pregnancy are poorly defined. Here we show that dynamic and variable decidual angiogenesis (sprouting, intussusception and networking), and active vigorous vascular remodelling such as enlargement and elongation of 'vascular sinus folding' (VSF) and mural cell drop-out occur distinctly in a spatiotemporal manner in the rapidly growing mouse uterus during early pregnancy - just after implantation but before placentation. Decidual angiogenesis is mainly regulated through VEGF-A secreted from the progesterone receptor (PR)-expressing decidual stromal cells which are largely distributed in the anti-mesometrial region (AMR). In comparison, P4 -PR-regulated VEGF-A-VEGFR2 signalling, ligand-independent VEGFR3 signalling and uterine natural killer (uNK) cells positively and coordinately regulate enlargement and elongation of VSF. During the postpartum period, Tie2 signalling could be involved in vascular maturation at the endometrium in a ligand-independent manner, with marked reduction of VEGF-A, VEGFR2 and PR expressions. Overall, we show that two key vascular growth factor receptors - VEGFR2 and Tie2 - strikingly but differentially regulate decidual angiogenesis and vascular remodelling in rapidly growing and regressing uteri in an organotypic manner.

Videographic analysis of glottic view with increasing cricoid pressure force.

STUDY OBJECTIVE: Cricoid pressure may negatively affect laryngeal view and compromise airway patency, according to previous studies of direct laryngoscopy, endoscopy, and radiologic imaging. In this study, we assess the effect of cricoid pressure on laryngeal view with a video laryngoscope, the Pentax-AWS. METHODS: This cross-sectional survey involved 50 American Society of Anesthesiologists status I and II patients who were scheduled to undergo elective surgery. The force measurement sensor for cricoid pressure and the video recording system using a Pentax-AWS video laryngoscope were newly developed by the authors. After force and video were recorded simultaneously, 11 still images were selected per 5-N (Newton; 1 N = 1 kg·m·s(-2)) increments, from 0 N to 50 N for each patient. The effect of cricoid pressure was assessed by relative percentage compared with the number of pixels on an image at 0 N. RESULTS: Compared with zero cricoid pressure, the median percentage of glottic view visible was 89.5% (interquartile range [IQR] 64.2% to 117.1%) at 10 N, 83.2% (IQR 44.2% to 113.7%) at 20 N, 76.4% (IQR 34.1% to 109.1%) at 30 N, 51.0% (IQR 21.8% to 104.2%) at 40 N, and 47.6% (IQR 15.2% to 107.4%) at 50 N. The number of subjects who showed unworsened views was 20 (40%) at 10 N, 17 (34%) at 20 and 30 N, and 13 (26%) at 40 and 50 N. CONCLUSION: Cricoid pressure application with increasing force resulted in a worse glottic view, as examined with the Pentax-AWS Video laryngoscope. There is much individual difference in the degree of change, even with the same force. Clinicians should be aware that cricoid pressure affects laryngeal view with the Pentax-AWS and likely other video laryngoscopes.

Pathogenic role of HIF-1α in prostate hyperplasia in the presence of chronic inflammation.

Benign prostatic hyperplasia (BPH) commonly occurs in older men with chronic prostatitis. Although BPH is frequently accompanied by inflammation, it is unclear whether inflammation underlies prostate enlargement. Recently, we reported that hypoxia-inducible factor 1α (HIF-1α), which is known to be induced by proinflammatory cytokines, is involved in testosterone-induced prostate hyperplasia. Therefore, we hypothesized that cytokines secreted from infiltrated macrophages under inflammatory conditions stimulate prostate enlargement by up-regulating HIF-1α. In the present study, we injected lipopolysaccharide (LPS) into rat prostates to mimic prostatitis and evaluated prostate hyperplasia 14days later. Epithelial cells of LPS-treated prostates were found to be highly proliferative and HIF-1α levels in prostate tissues to be elevated. When prostate epithelial cells were incubated in conditioned medium from macrophages activated with LPS, they robustly expressed HIF-1α, and under these conditions IL-1ß, IL-6, and TNF-α cytokines were found to mediate HIF-1α induction. In addition, HIF-1α was found to enhance the expression of Twist, which initiates epithelial-mesenchymal transition (EMT). Furthermore, profound EMT features were observed in LPS-treated rat prostates, and the natural HIF-1α inhibitors ascorbate and curcumin were found to attenuate EMT and prostate hyperplasia both in vivo and in vitro. Based on these results, we propose that HIF-1α mediates prostate enlargement under inflammatory conditions, and we suggest that HIF-1α be viewed as a promising target for blocking the transition from prostatitis to BPH.

Survivin mediates prostate cell protection by HIF-1alpha against zinc toxicity.

BACKGROUND: The prostate contains extremely high concentrations of zinc, but survives and grows without apparent injury. This begs the question as to how prostate cells avoid the toxic effects of zinc. In a previous study, the authors found that; HIF-1alpha is expressed concomitantly with the accumulation of zinc in the epithelial cells of normal rat prostates, the zinc ion stabilizes HIF-1alpha in prostate cells, and that HIF-1alpha protects prostate cells from zinc toxicity. In the present study, the authors addressed the mechanism responsible for the protective effect of HIF-1alpha in a high zinc environment. METHODS: Immunofluorescent staining, immunoblotting, reverse transcription-polymerase chain reaction, reporter assay, and cell cycle analysis. RESULTS: Survivin was induced by ZnCl(2) in a HIF-1 dependent manner in both DU-145 and PNT2 prostate cells. Furthermore, HIF-1 induced survivin expression at the transcriptional level and the induction of survivin was abolished by HIF-1alpha knock-down. In addition, HIF-1-dependent survivin overexpression promoted prostrate cell survival and prevented cell arrest in the presence of high zinc concentrations, and si-survivin transfected cells under zinc rich conditions contained markedly higher levels of cleaved caspase-9 and PARP than si-con transfected cells. Finally, survivin expression patterns well matched rat prostate proliferation statuses. CONCLUSION: Under zinc rich conditions, prostate epithelial cells HIF-1-dependently express survivin, which promotes prostate cell proliferation, and prevents apoptosis and cell cycle arrest. Accordingly, the HIF-1alpha-survivin pathway appears to facilitate prostate cell survival and growth in zinc rich environments, and this pathway could be a therapeutic target for the treatment of prostate hyperplasia.

Pyrithione-zinc Prevents UVB-induced Epidermal Hyperplasia by Inducing HIF-1alpha.

Epidermal keratinocytes overgrow in response to ultraviolet-B (UVB), which may be associated with skin photoaging and cancer development. Recently, we found that HIF-1alpha controls the keratinocyte cell cycle and thereby contributes to epidermal homeostasis. A further study demonstrated that HIF-1alpha is down-regulated by UVB and that this process is involved in UVB-induced skin hyperplasia. Therefore, we hypothesized that the forced expression of HIF-1alpha in keratinocytes would prevent UVB-induced keratinocyte overgrowth. Among several agents known to induce HIF-1alpha, pyrithione-zinc (Py-Zn) overcame the UVB suppression of HIF-1alpha in cultured keratinocytes. Mechanistically, Py-Zn blocked the degradation of HIF-1alpha protein in keratinocytes, while it did not affect the synthesis of HIF-1alpha. Moreover, the p21 cell cycle inhibitor was down-regulated after UVB exposure, but was robustly induced by Py-Zn. In mice repeatedly irradiated with UVB, the epidermis became hyperplastic and HIF-1alpha disappeared from nuclei of epidermal keratinocytes. However, a cream containing Py-Zn effectively prevented the skin thickening and up-regulated HIF-1alpha to the normal level. These results suggest that Py-Zn is a potential agent to prevent UVB-induced photoaging and skin cancer development. This work also provides insight into a molecular target for treatment of UVB-induced skin diseases.

Vitamin C supplementation prevents testosterone-induced hyperplasia of rat prostate by down-regulating HIF-1alpha.

Benign prostatic hyperplasia (BPH) is a disease that impairs the well-being of many aged men. To alleviate BPH symptoms or to find a cure for this disease, key molecules should be identified that control prostate cell proliferation. Recently, HIF-1alpha has attracted attention in this context, because it is highly expressed in hyperplasic prostates and prevents prostate cell death. Thus, given that vitamin C inhibits HIF-1alpha expression in several malignant tumors, we examined its therapeutic potential in BPH. HIF-1alpha was noticeably induced by testosterone in prostate cells, and this HIF-1alpha induction was abolished by vitamin C. Vascular endothelial growth factor (VEGF) promoter activity reporter assays and semi-quantitative RT-PCR revealed that vitamin C inhibited HIF-1-dependent VEGF expression. Furthermore, HIF-1alpha suppression by vitamin C was rescued by knocking down HIF-prolyl hydroxylase-2, suggesting that vitamin C destabilizes HIF-1alpha via prolyl hydroxylation. Moreover, vitamin C treatment abolished cell proliferation induced by testosterone treatment to the control level. These results suggest that vitamin C inhibits testosterone-induced HIF-1alpha expression and by so doing effectively prevents prostate hyperplasia. In male rats, testosterone treatment for 4 weeks induced prostate hyperplasia. Furthermore, HIF-1alpha and VEGF levels were significantly elevated in hyperplasic prostates. In vitamin C-treated rats, however, most prostate hyperplasia parameters and prostrate HIF-1alpha/VEGF levels were markedly reduced. Accordingly, our findings indicate that vitamin C could be further developed clinically for use as an anti-BPH agent.

Involvement of HIF-1alpha in UVB-induced epidermal hyperplasia.

Keratinocyte overgrowth after UVB exposure is believed to contribute to skin photoageing and cancer development. However, little is known about the transcription factors that epigenetically regulate keratinocyte response to UVB. Recently, HIF-1alpha was found to play a role in epidermal homeostasis by controlling the keratinocyte cell cycle, and thus, we hypothesized that HIF-1alpha is involved in UVB-induced keratinocyte growth. In cultured keratinocytes, HIF-1alpha was found to be down-regulated shortly after UVB exposure and to be involved in UVB-induced proliferation. In mice repeatedly treated with UVB, the epidermis became hyperplasic and keratinocytes lacked HIF-1alpha in nuclei. Based on these results, we suggest that the deregulation of HIF-1alpha is associated with UVB-induced hyperplasia of the epidermis. This work provides insight of the molecular mechanism underlying UV-induced photoageing and skin cancer development.