Urinary composition and postprandial blood changes in H-secoisolariciresinol diglycoside (SDG) metabolites in rats do not differ between acute and chronic SDG treatments

Although chronic exposure to secoisolariciresinol diglycoside (SDG) was shown to alter (3)H-SDG metabolite disposition in rats, the proportion of measured radioactivity attributed to known or unknown SDG metabolites was not determined. Using HPLC and GC-MS, two experiments were conducted to determine the effect of acute (1 d) vs. chronic (10 d) SDG treatment on major urinary metabolites of (3)H-SDG in female, Sprague-Dawley rats (70-72-d-old) over a 48-h period and if new urinary metabolites were detectable in rats fed nonradioactive flaxseed or SDG. A third experiment was conducted to determine changes in postprandial blood levels of (3)H-SDG metabolites over a 24-h period with acute or chronic SDG treatment. Regardless of treatment, enterodiol, enterolactone and secoisolariciresinol accounted for 75-80% of urine radioactivity. Four potential new lignan metabolites, two of which were detected in the urine of rats fed nonradioactive flaxseed or SDG, were found. Type of treatment had no effect on levels of individual urinary metabolites of (3)H-SDG. As observed for plasma lignans in women fed flaxseed, blood radioactivity peaked at 9 h and remained high until 24 h in both treatment groups, suggesting that blood lignan kinetics might be similar with flaxseed or SDG consumption and that they were comparable between humans and rats. In conclusion, the main urinary lignan metabolites were enterodiol, enterolactone and secoisolariciresinol. Urinary composition or blood levels of radioactive lignans were not affected by the duration of SDG exposure. Thus, while chronic SDG exposure alters lignan disposition in rats, it does not change the metabolite profile.     

Flaxseed and lignans increase cecal beta-glucuronidase activity in rats.

Flaxseed has been shown in previous studies to decrease some early markers of colon cancer risk in part because of its lignans. This study determined whether the intake of flaxseed and lignans is related to the activity of bacterial beta-glucuronidase, an enzyme suggested to increase colon cancer risk. Seven groups of six female rats each were fed, for four weeks, a basal high-fat (20%) diet (BD), BD supplemented with 2.5%, 5.0%, or 10.0% flaxseed, or BD with daily gavage of 0.75, 1.5, or 3.0 mg of secoisolariciresinol diglycoside (SDG), the major mammalian lignan precursor. The specific and total activities of beta-glucuronidase in the cecum were significantly related to the levels of flaxseed (r = 0.539, p < 0.008 and r = 0.599, p < 0.002, respectively) and SDG (r = 0.567, p < 0.007 and r = 0.435, p < 0.04, respectively). The urinary mammalian lignan excretion also increased with increasing flaxseed or SDG levels and thus was significantly related to the specific activity (r = 0.38, p < 0.017) and total activity (r = 0.429, p < 0.007) of beta-glucuronidase. Because flaxseed and lignans are colon cancer protective, it is concluded that, in contrast to other studies, beta-glucuronidase activity may play a beneficial role in their presence by increasing mammalian lignan absorption and enterohepatic circulation.     

Critical values for linearity tests in time‐varying smooth transition autoregressive models when data are highly persistent

Summary In this paper, we derive asymptotic distributions for linearity tests in time‐varying smooth transition autoregressive models in the presence of a unit root. The limiting distributions are non‐standard because of the unit root assumption, and it is shown that the linearity hypothesis is rejected far too often (up to 30.9% of the times at a 5% significance level) when using critical values from a chi‐square distribution.     

Burden of type 2 diabetes attributed to lower educational levels in Sweden

Background

Verbal autopsy (VA) has often been used for point estimates of cause-specific mortality, but seldom to characterize long-term changes in epidemic patterns. Monitoring emerging causes of death involves practitioners' developing perceptions of diseases and demands consistent methods and practices. Here we retrospectively analyze HIV-related mortality in South Africa, using physician and modeled interpretation.

Methods

Between 1992 and 2005, 94% of 6,153 deaths which occurred in the Agincourt subdistrict had VAs completed, and coded by two physicians and the InterVA model. The physician causes of death were consolidated into a single consensus underlying cause per case, with an additional physician arbitrating where different diagnoses persisted. HIV-related mortality rates and proportions of deaths coded as HIV-related by individual physicians, physician consensus, and the InterVA model were compared over time.

Results

Approximately 20% of deaths were HIV-related, ranging from early low levels to tenfold-higher later population rates (2.5 per 1,000 person-years). Rates were higher among children under 5 years and adults 20 to 64 years. Adult mortality shifted to older ages as the epidemic progressed, with a noticeable number of HIV-related deaths in the over-65 year age group latterly. Early InterVA results suggested slightly higher initial HIV-related mortality than physician consensus found. Overall, physician consensus and InterVA results characterized the epidemic very similarly. Individual physicians showed marked interobserver variation, with consensus findings generally reflecting slightly lower proportions of HIV-related deaths. Aggregated findings for first versus second physician did not differ appreciably.

Conclusions

VA effectively detected a very significant epidemic of HIV-related mortality. Using either physicians or InterVA gave closely comparable findings regarding the epidemic. The consistency between two physician coders per case (from a pool of 14) suggests that double coding may be unnecessary, although the consensus rate of HIV-related mortality was approximately 8% lower than by individual physicians. Consistency within and between individual physicians, individual perceptions of epidemic dynamics, and the inherent consistency of models are important considerations here. The ability of the InterVA model to track a more than tenfold increase in HIV-related mortality over time suggests that finely tuned "local" versions of models for VA interpretation are not necessary.     

Phorbol ester induces rapid actin assembly in neutrophil leucocytes independently of changes in [Ca2+]i and pHi

Summary The phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA), at nanomolar concentrations, induces rapid (t _1/2 approximately 30 s) protrusion of multiple petal-shaped lamellae by neutrophil leucocytes. Lamellae are richly endowed with actin filaments as determined by the localization of rhodamine-phalloidin, suggesting extensive assembly at the cell cortex. Direct measurement of the proportion of total cell actin which is polymerized, by using a deoxyribonuclease I inhibition assay, indicates that the proportion of polymerized actin approximately doubles, and that assembly initiated by 30nm TPA occurs with no obvious lag phase and with a t_1/2 of about 30 s. A half-maximal response was induced at 2nm TPA. Since both actin assembly and protrusion of lamellae are completely inhibited by 10^–6 m cytochalasin D, protrusion of lamellae is presumably dependent on actin filament assembly.To examine whether TPA induces actin assembly via changes in [Ca²⁺]_i or pH_i, these parameters were monitored in cells loaded with the fluorescent indicators quin2 and quene1 respectively. Addition of TPA caused no change in [Ca²⁺]_i but a biphasic change in pH_i. To examine further the potential role of ionic changes in regulation of actin assembly, the morphological responses of cells to TPA were monitored in severely Ca²⁺-depleted cells, or cells in which pH_i had been experimentally raised or lowered by simultaneous additions of a weak base (NH₄Cl) or weak acid (CH₃COONa) respectively. The protrusion of lamellae induced by TPA was completely unaffected by these experimental manipulations indicating that TPA can directly regulate actin assembly, and hence morphology, by mechanisms essentially independent of [Ca²⁺]_i and pH_i. Since TPA is believed to mimic diacylglycerol, which is putatively generated by cleavage of phosphatidylinositol-4, 5-bisphosphate in a number of cellular responses involving actin filament assembly, these results implicate diacylglycerol, either acting directly, or via protein kinase C-mediated phosphorylation, as a common step in the receptor-mediated regulation of cortical actin filament assembly in cells.     

Schwannoma of the appendix: A case report and review of the literature

Appendiceal neoplasms are uncommon and found in 1.6 per cent of appendicectomy specimens. Schwannomas arising from the appendix are of significant rarity, with only a few previously‐reported cases. In this study, we present the case of a 31‐year‐old man who underwent a laparoscopic appendicectomy and was found to have an appendiceal schwannoma. In the present study, we review the literature of this rare condition, which serves to highlight the potential for appendiceal neoplasia to occur in a macroscopically‐normal appendix. Furthermore, it emphasizes the potential risk of missed appendiceal neoplasia as a sequelae of nonoperative management of suspected appendicitis.     

A retrospective explanatory case study of the implementation of a bleeding management quality initiative,in an Australian cardiac surgery unit

Background

Bleeding management in cardiac surgery is challenging. Many guidelines exist to support bleeding management; however, literature demonstrates wide variation in practice. In 2012, a quality initiative was undertaken at The Prince Charles Hospital, Australia to improve bleeding management for cardiac surgery patients. The implementation of the quality initiative resulted in significant reductions in the incidence of blood transfusion, re-exploration for bleeding; superficial leg and chest wound infections; length of hospital stay, and cost. Given the success of the initiative, we sought to answer the question; “How and why was the process of implementing a bleeding management quality initiative in the cardiac surgery unit successful, and sustainable?”

Transradial simultaneous kissing stenting (SKS) with SheathLess access

Transradial coronary intervention is usually performed via a 5 or 6 Fr sheath due to the small calibre of radial arteries. Simultaneous kissing stenting (SKS) technique requires a guiding catheter 7 Fr or larger and is therefore difficult to perform via transradial approach. Conversion to femoral approach or additional arterial access is usually required to achieve this goal. To overcome this limitation, a hydrophilic 7.5 Fr SheathLess guiding catheter can be exploited. This catheter possesses approximately the same size outer diameter as a 6 Fr sheath and an internal diameter of a 7.5 Fr catheter. A smooth and successful performance of SKS through transradial approach is described using this catheter. © 2009 Wiley‐Liss, Inc.