Association between night work and prostate cancer: a systematic review and meta-analysis.

OBJECTIVE: The aim was to conduct a systematic review and meta-analysis to study the association between night work and the development of prostate cancer. METHODS: A systematic literature search was conducted in CINAHL, Embase, MEDLINE, and Web of Science. Studies were included based on a PECOS; the population included men in/above the working age, exposure defined as night work, outcome defined as prostate cancer, and study design restricted to cohort studies. The exclusion of articles, risk-of-bias assessment, and data extraction were performed by two reviewers. A meta-analysis was conducted using a random-effects model, including a sensitivity analysis stratified based on the risk-of-bias assessment. We evaluated publication bias using a funnel plot and Egger´s test, and the level of evidence was assessed using GRADE. RESULTS: A total of 528 articles were identified, and eight cohort studies were included. Three studies had a moderate risk of bias, while five studies had a high risk of bias. The meta-analysis showed a pooled hazard ratio (HR) of 1.0 (95% CI 0.6-1.7). In the sensitivity analysis, moderate vs. high risk-of-bias studies showed a pooled HR of 1.2 (95% CI 0.3-4.1) and 0.9 (95% CI 0.6-1.3), respectively. Based on GRADE, the level of evidence was rated low. CONCLUSION: We found no association between night work and the development of prostate cancer. The evidence was assessed as limited and inconsistent. Future studies encompassing consistent definitions of night work, including objective exposure data, are highly warranted.

Ceramide and N,N,N-Trimethylphytosphingosine-Iodide (TMP-I)-Based Lipid Nanoparticles for Cancer Therapy.

PURPOSE: To evaluate the anti-tumor effect of ceramide or trimethylphytosphingosine-iodide (TMP-I) containing solid lipid nanoparticles (SLNs) prepared using trymyristin, phosphatidylcholine (PC), and Pluronic P85 (P85) for intravenous delivery of docetaxel. METHODS: Docetaxel-loaded SLNs using ceramide or TMP-I at 3.22% (w/w) with a mean diameter of 89-137 nm were successfully prepared by high pressure homogenization. The prepared nanoparticles were characterized by particle size, zeta potential, drug content, and TEM analysis. Cellular uptake and cytotoxicity were studied using adriamycin-resistant breast cancer (MCF-7/ADR) cells. The optimized formulation's dissolution profile, pharmacokinetics, and antitumor effect in mice tumor model were compared with that of control (Taxotere(®)). RESULTS: The drug release rate of docetaxel from SLNs was lower than that of control (Taxotere(®)). The prepared SLNs showed higher cellular uptake of docetaxel compared to that of Taxotere(®) in MCF-7/ADR cell lines, which was further confirmed by the confocal laser scanning microscopy (CLSM) study using coumarin 6 (C6). Prepared SLNs exhibited significantly increased antitumor efficacy, compared to Taxotere(®), in MCF-7/ADR cells. In vivo pharmacokinetic study in rats (at 10 mg/kg dose) showed that the SLNs significantly reduced in vivo clearance of drug than Taxotere(®). Interestingly, ceramide and TMP-I SLNs efficiently inhibited the tumor growth compared to Taxotere(®) in MCF-7/ADR tumor xenografted mouse model. CONCLUSION: This work showed that TMP-I and ceramide SLNs not only significantly enhanced systemic exposure of drug, but also increased antitumor efficacy compared to Taxotere(®) and control SLN.

In vitro and in vivo evaluation of N,N,N-trimethylphytosphingosine-iodide (TMP) in liposomes for the treatment of angiogenesis and metastasis.

Phytosphingosine and methyl derivatives are important mediators on cellular processes, and are associated with cell growth and death. The antitumor activity of N,N,N-trimethylphytosphingosine-iodide (TMP) as a novel potent inhibitor of angiogenesis and metastasis was evaluated in B16F10 murine melanoma cells. The results indicated that TMP itself effectively inhibited in vitro cell migration, tube formation, and the expression of angiogenic factors as well as in vivo lung metastasis. However, TMP slightly suppressed in vivo experimental tumor metastasis in its free form and induced side effects including hemolysis and local side effects. Therefore, in an attempt to reduce the toxicity and the undesirable side effects of TMP, a liposomal formulation was prepared and tested for its effectiveness. TMP liposomes retained the effectiveness of TMP in vitro while side effects were reduced, and both in vivo experimental and spontaneous tumor metastasis were significantly suppressed. These results support the conclusion that TMP effectively inhibits in vitro angiogenesis as well as in vivo metastasis, and a liposomal formulation is more efficient delivery system for TMP treatment than solution.

Intravenous nitroglycerin does not preserve gastric microcirculation during gastric tube reconstruction: a randomized controlled trial.

INTRODUCTION: Complications of oesophagectomy and gastric tube reconstruction include leakage and stenosis, which may be due to compromised microvascular blood flow (MBF) in gastric tissue. We recently demonstrated that decreased MBF could be improved perioperatively by topical administration of nitroglycerin. The aim of the present study was to investigate whether nitroglycerin, administered intravenously during gastric tube reconstruction, could preserve tissue blood flow and oxygenation in the gastric fundus, and reduce the incidence of postoperative leakage. METHODS: In this single-centre, prospective, double-blinded study, we randomized 32 patients scheduled for oesophagectomy into two groups. The intervention group received intravenous nitroglycerin during gastric tube reconstruction, and the control group received normal saline. Baseline values for MBF, microvascular haemoglobin oxygen saturation and microvascular haemoglobin concentration were determined at the gastric fundus before and after gastric tube construction and after pulling up the gastric tube to the neck. RESULTS: MBF and microvascular haemoglobin oxygen saturation decreased similarly in both groups during gastric tube reconstruction and were comparable. The oesophageal anastomosis was controlled by contrast radiography before discharge from the hospital; leakage was observed in two patients (13%) in the nitroglycerin group and five patients (31%) in the control group (not significant). CONCLUSION: Under stable systemic haemodynamic conditions, continuous intravenous administration of nitroglycerin could not prevent deterioration in gastric microvascular perfusion and microvascular haemoglobin saturation during gastric tube reconstruction.

Peripheral flow index is a reliable and early indicator of regional block success.

We investigated the usefulness of peripheral flow index (PFI) measurement using a standard pulse oximetry digit probe for early prediction of successful regional blocks. Sixty-six patients scheduled for limb surgery underwent either axillary or sciatic block using a nerve stimulator technique with mepivacaine 1.5%. PFI, which is the ratio of the pulsatile versus the nonpulsatile component of the pulse oximetry signal, was recorded from 10 min before block insertion until 30 min afterwards. PFI recordings of the unblocked limb were similarly recorded. Pinprick and cold sensation were assessed at 5-min intervals until 30 min after blockade. An increase in PFI by a factor of 1.55 at 10 min after axillary block placement (P = 0.006), and 12 min after sciatic block placement (P = 0.001) was required to predict a successful block. The sensitivity and specificity of PFI was 100% for predicting axillary block outcomes at this time. Positive predictive value was 95% and negative predictive value was 93%. For sciatic blocks, sensitivity and specificity were 90% and 100%, respectively. The calculated positive predictive value at time 12 min for sciatic blocks was 94% and negative predictive value was 92%. At 15 min after block placement, cold and pinprick sensations had the same calculated values for sensitivity and specificity at 71% and 100%, respectively, for axillary blocks. For sciatic blocks, cold sensation had a sensitivity of 77% and a specificity of 100%, whereas pinprick had a sensitivity of just 20% with a specificity of 100%. We conclude that PFI provides a simple, early, and objective assessment of the success and failure of nerve blocks.