The effect of New Zealand blackcurrant on sport performance and related biomarkers: a systematic review and meta-analysis.

BACKGROUND: Blackcurrants have come to be regarded as a superfood because of their high polyphenol content, namely anthocyanins. While many berry types have been studied, blackcurrant-anthocyanins may be the superior berry when it comes to athletic performance. The purpose of the review was to evaluate the effects of blackcurrant supplementation on athletic performance, oxidative markers, cognition, and side effects. METHODS: Systematic review and meta-analysis. Review manager software (version 5.3) was used for the meta-analysis. The risks of bias was independently assessed using the guidelines and criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. The data sources for the search included MEDLINE (Ovid), Google Scholar databases, additional references lists, conference proceedings and grey literature until August 2019. Eligibility Criteria included all blackcurrant (New Zealand derived) interventions, randomised control trials, human participants, placebo-controlled only. RESULTS: A total of 16 separate studies met the criteria for inclusion in the systematic review, with 9 studies contributing to this sport performance meta-analysis. There was an improvement in sport performance when supplementing with blackcurrant, 0.45 (95% CI 0.09-0.81, p = 0.01). The effective dose appears to be between 105 and 210 mg of total blackcurrant anthocyanins, prior to exercise. There were insufficient studies reporting oxidative markers, cognitive effects or biomarkers, and/or side effects to comment on the mechanism of action. CONCLUSION: Blackcurrant has a small, but significant, effect on sport performance, with no known detrimental side effects.

The protection of bovine skeletal myofibrils from proteolytic damage post mortem by small heat shock proteins.

This study aimed to determine how small heat shock proteins (sHSPs) protect myofibrillar proteins from µ-calpain degradation during ageing. Immunoprecipitation experiments with M. longissimus dorsi (LD) from Angus heifers (n = 14) examined the interaction between αß-crystallin, desmin, titin, HSP20, HSP27 and µ-calpain. Results showed that αß-crystallin associated with desmin, titin, HSP20, HSP27 and µ-calpain. Exogenous αß-crystallin reduced desmin and titin degradations in myofibrillar extracts and attenuated µ-calpain activity. In a second experiment, bull LD (n = 94) were aged at -1.5°C for up to 28 days post mortem. µ-Calpain autolysed faster in high ultimate pH (pH(u)) meat (pH(u)≥6.2) and this was concomitant with the more rapid degradation of titin and filamin in this pH(u) group. Desmin stability in intermediate pH(u) meat (pH(u) 5.8 to 6.19) may be due to the protection of myofibril-bound sHSPs combined with the competitive inhibition of µ-calpain by sHSPs.

The effect of aspirin and smoking on urinary excretion profiles of lactulose and mannitol in young women: toward a dynamic, aspirin augmented, test of gut mucosal permeability.

BACKGROUND: We explored the temporal dynamics of the lactulose mannitol test and the influence of a single dose of aspirin. METHODS: Twenty healthy female volunteers each received 600 mg aspirin or placebo in random sequence and were subsequently dosed with 10 g lactulose and 5 g mannitol, their urine collected every half hour for 6h. KEY RESULTS: The lactulose:mannitol ratios (LMR) of urine samples collected over the entire 6-h period were significantly higher than those collected in the first 3 h. Greater quantities of mannitol were excreted over the first than the subsequent 3 h. A similar pattern of temporal variation in mannitol excretion was found in smokers and non-smokers and was maintained following administration of a single 600 mg dose of aspirin. The rates at which lactulose was excreted were relatively constant over the entire 6 h period of collection, but mean levels were increased over the entire 6 h following the administration of aspirin. The effect of aspirin did not differ significantly between smokers and non-smokers. CONCLUSIONS & INFERENCES: While the LMR test is sufficiently sensitive to reproducibly detect the increase in intestinal permeability resulting from a single 600 mg oral dose of aspirin, the temporal patterns of excretion of mannitol and lactulose differ both in the presence and absence of aspirin. Hence, variation in sampling period and in method of dosage are likely to influence the result and it is preferable to examine the patterns of absorption of component sugars separately with due regard to the method of dosage.

Exercise-induced elevation in plasma oxidative generating capability augments the temporal inflammatory response stimulated by lipopolysaccharide.

Prolonged oxidative stress is detrimental to health; however, transient oxidative stress may improve immune capability. We examined whether exercise-induced increases in the plasma oxidative generating capability enhance immune responsiveness to potential pathogens. Twelve individuals underwent a 30-min row and pre and post-exercise bloods were collected for oxidative stress and immune assessment. We found that exercise induced a transient increase in plasma carbonyls (3.2-5.3 nmol/mg protein) and creatine kinase activity (0.5-1.2 absorbance/min/mg protein) and that lipopolysaccharide (LPS) stimulation (0.5-24 h) of pre- and post-exercise blood augmented temporal tumour necrosis factor-alpha (TNFalpha) secretion. Further characterisation of plasma using a modified dihydro-2',7'-dichlorohydrofluorescein (DCF) assay revealed that addition of a sub-threshold of hydrogen peroxide to post-exercise (and not pre-exercise) plasma caused a sixfold increase in the radical oxygen species (ROS) generating capability after 15 min (555 +/- 131 to 3607 +/- 488 change in fluorescent intensity [DeltaFI]), which was inhibited using 60 mM N-acetyl-L: -cysteine (920 +/- 154 DeltaFI). Furthermore, cell experiments revealed that LPS stimulation of either THP-1 cells pre-incubated with post-exercise plasma or peripheral blood mononuclear cells pre-treated with pro-oxidants, modulated the temporal secretion of key cytokines that regulate the initiation, progression and resolution of an inflammatory response. These results indicate that exercise-induced changes in plasma parameters (e.g. oxidative generating capability-dependent or independent of inflammatory mediators) augment the temporal LPS response and support the notion that repeated transient oxidative stress (such as that induced by regular exercise) is important for a "healthy" immune system.

Short-term blackcurrant extract consumption modulates exercise-induced oxidative stress and lipopolysaccharide-stimulated inflammatory responses.

Exercise-induced oxidative stress is instrumental in achieving the health benefits from regular exercise. Therefore, inappropriate use of fruit-derived products (commonly applied as prophalytic antioxidants) may counteract the positive effects of exercise. Using human exercise and cellular models we found that 1) blackcurrant supplementation suppressed exercise-induced oxidative stress, e.g., plasma carbonyls (0.9 +/- 0.1 vs. 0.6 +/- 0.1 nmol/mg protein, placebo vs. blackcurrant), and 2) preincubation of THP-1 cells with an anthocyanin-rich blackcurrant extract inhibited LPS-stimulated cytokine secretion [TNF-alpha (16,453 +/- 322 vs. 10,941 +/- 82 pg/ml, control vs. extract, P < 0.05) and IL-6 (476 +/- 14 vs. 326 +/- 32 pg/ml, control vs. extract, P < 0.05)] and NF-kappaB activation. In addition to its antioxidant and anti-inflammatory properties, we found that postexercise plasma collected after blackcurrant supplementation enhanced the differential temporal LPS-stimulated inflammatory response in THP-1 cells, resulting in an early suppression of TNF-alpha (1,741 +/- 32 vs. 1,312 +/- 42 pg/ml, placebo vs. blackcurrant, P < 0.05) and IL-6 (44 +/- 5 vs. 36 +/- 3 pg/ml, placebo vs. blackcurrant, P < 0.05) secretion after 24 h. Furthermore, by using an oxidative stress cell model, we found that preincubation of THP-1 cells with hydrogen peroxide (H(2)O(2)) prior to extract exposure caused a greater suppression of LPS-stimulated cytokine secretion after 24 h, which was not evident when cells were simultaneously incubated with H(2)O(2) and the extract. In summary, our findings support the concept that consumption of blackcurrant anthocyanins alleviate oxidative stress, and may, if given at the appropriate amount and time, complement the ability of exercise to enhance immune responsiveness to potential pathogens.

Polyphenolic phytochemicals--just antioxidants or much more?

Polyphenolic phytochemicals are ubiquitous in plants, in which they function in various protective roles. A 'recommended' human diet contains significant quantities of polyphenolics, as they have long been assumed to be 'antioxidants' that scavenge excessive, damaging, free radicals arising from normal metabolic processes. There is recent evidence that polyphenolics also have 'indirect' antioxidant effects through induction of endogenous protective enzymes. There is also increasing evidence for many potential benefits through polyphenolic-mediated regulation of cellular processes such as inflammation. Inductive or signalling effects may occur at concentrations much lower than required for effective radical scavenging. Over the last 2-3 years, there have been many exciting new developments in the elucidation of the in vivo mechanisms of the health benefits of polyphenolics. We summarise the current knowledge of the intake, bio-availability and metabolism of polyphenolics, their antioxidant effects, regulatory effects on signalling pathways, neuro-protective effects and regulatory effects on energy metabolism and gut health.

Post-mortem metmyoglobin reduction in fresh venison.

The accumulation of metmyoglobin (MetMb) at the surface of meat during storage contributes significantly to its discolouration. Under appropriate conditions it may be possible to utilise residual meat MetMb reducing activity to maintain fresh colour. Venison meat colour stability is poorer compared with other species. Hence, we evaluated the capacity of completely discoloured venison (n=12 animals) to reduce MetMb under anaerobic conditions in order to decipher more clearly the role MetMb reducing activity may play. The reducing capacity of venison (1 day, 3, and 6 weeks post-mortem), electrical stimulation, surface location (top and bottom) and rigor temperature (15 and 35°C) on MetMb were evaluated. Surface MetMb decreased (P<0.001) during storage while deoxymyoglobin increased (P<0.001) demonstrating MetMb reduction. Metmyoglobin reduction was greater (P<0.001) in venison which entered rigor at 15°C, the reduction at the bottom surface of the steaks was greater (P<0.001) compared with the top surface, and electrical stimulation had no affect (P>0.05). These data demonstrate that metmyoglobin reducing activity occurs anaerobically in completely discoloured venison following storage display. The practical application for this finding needs to be determined.

In vitro models for the blood-brain barrier.

The aim of the present study was to identify a model for the blood-brain barrier based on the use of a continuous cell line, and to investigate the specificity of this model. A set of test compounds, reflecting different transport mechanisms and different degrees of permeability, as well as different physiochemical properties was selected. In vivo data for transport across the blood-brain barrier of this set of test compounds was generated as part of the study using two different in vivo models. A computational prediction model was also developed, based on 74 proprietary Pharmacia compounds, previously tested in one of the in vivo models. Molsurf descriptors were calculated and 21 descriptors were correlated with log(Brain(conc.)/Plasma(conc.)) using partial least squares projection to latent structures (PLS). However, the correlation between predicted and measured values was found to be rather low and differed between one and two log units for several of the compounds. The test compounds were analyzed in vitro using primary bovine and human brain endothelial cells co-cultured with astrocytes, and also using two different immortalized brain endothelial cell lines, one originating from rat and one from mouse. Cell models using cells not derived from the blood-brain barrier, ECV/C6, MDCK and Caco-2 cell lines, were also used. No linear correlation between in vivo and in vitro permeability was found for any of the in vitro models when all compounds were included in the analysis. The highest r2 values were seen in the bovine brain endothelial cells (r2=0.43) and MDCKwt (r2=0.46) cell models. Higher correlations were seen when only passively transported compounds were included in the analysis, bovine brain endothelial cells (r2=0.74), MDCKwt (r2=0.65) and Caco-2 (r2=0.86). By plotting in vivo Papp values against logDpH7.4 it was possible to classify compounds into four different classes: (1) compounds crossing the blood-brain barrier by passive diffusion, (2) compounds crossing the blood-brain barrier by blood-flow limited passive diffusion, (3) compounds crossing the blood-brain barrier by carrier mediated influx, and (4) compounds being actively excreted from the brain by active efflux. Papp and Pe values obtained using the different in vitro models were also plotted against logDpH7.4 and compared to the plot obtained when in vivo Papp values were used. Several of the in vitro models could distinguish between passively distributed compounds and efflux substrates. Of the cell lines included in the present study, the MDCKmdr-1 cell line gave the best separation of passively and effluxed compounds. Ratios between AUC in brain and AUC in blood were also calculated for six of the compounds and compared to ratios between Pe or Papp for transport in the apical to basolateral and basolateral to apical direction. Again the MDCKmdr-1 cell line gave the best correlation with only one compound (AZT) giving large discrepancy between in vitro and in vivo data. None of the in vitro models could identify compounds known to be substrates for carrier mediated influxed as such, and the results indicate that a tighter in vitro blood-brain barrier model probably is needed in order to facilitate studies on carrier mediated influx. The findings presented also indicate that identification of "batteries" of in vitro tests are likely to be necessary in order to improve in vitro-in vivo correlations and to make it possible to perform acceptable predictions of in vivo brain distributions from in vitro data.

Primary closure of complicated perineal wounds with myocutaneous and fasciocutaneous flaps after proctectomy for Crohn's disease.

BACKGROUND: The purpose of this study is to detail the use of advanced tissue transfer techniques to achieve primary closure of the perineal wound after proctectomy for Crohn's disease. METHODS: Between October 1984 and March 2000, we performed proctectomy with permanent intestinal stoma in 97 patients with Crohn's disease. Twelve of these patients (12.4%) required at least 1 myocutaneous flap to achieve primary closure of the perineal wound. Details of each patient's perioperative course were recorded prospectively. RESULTS: All 12 patients had fistulizing perineal Crohn's disease combined with Crohn's proctitis. Two patients had a simultaneous anal adenocarcinoma. Indications for flap closure included management of large perineal skin defects (n = 11), reconstruction of the posterior vaginal wall (n = 2), and the need to fill a large pelvic dead space (n = 3). (Three patients had a combination of the previous indications). In total, 6 rectus abdominis, 5 gluteus maximus, 1 posterior thigh, 3 chimeric posterior thigh, and 1 latissimus dorsi flaps were performed. Six patients required more than 1 flap. Three patients had complications develop related to the flaps (2 wound hematomas and 1 seroma). Complete perineal healing was achieved in all patients. CONCLUSIONS: Complex tissue flap closure of the perineal wound after proctectomy for perineal complications of Crohn's disease should be considered when simple closure is not possible or when reconstruction of the posterior wall of the vagina is necessary.

A comparison of the induction of immortalized endothelial cell impermeability by astrocytes.

The suitability of various commercially available endothelial cell lines in studies of astrocytic/endothelial cell interactions was assessed. The endothelial-like cell line ECV304 was compared with T24/83, Eahy929, and b.End5 and rat cerebral endothelial cells in their ability, when co-cultured with rat (C6) glioma cells, to form a transendothelial electrical resistance (TEER), an indicator of tight junction formation which is an important property of the blood-brain barrier. As reported previously, the basal TEER of ECV304 cell monolayers was significantly enhanced upon co-culture, an effect reproduced by human 1321N1 astrocytes and primary rat astrocytes. T24/83 cells formed a patchy, gapped monolayer, which produced a poor basal TEER with little in the way of an increase upon co-culture. Similarly, all the other cell monolayers analysed demonstrated poor TEERs that were only moderately increased upon co-culture. These data confirm that while no endothelial cell line with ideal features is available, ECV304 cells remain an appropriate choice especially for studies of astrocyte/endothelial cell interactions.

Nitric-oxide-induced inhibition of glyceraldehyde-3-phosphate dehydrogenase may mediate reduced endothelial cell monolayer integrity in an in vitro model blood-brain barrier.

The process of nitric-oxide (NO)-induced cellular toxicity may involve energy deprivation since the radical is reported to prevent both mitochondrial oxidative phosphorylation and glycolysis. In order to determine whether these processes are important in NO-induced blood-brain barrier (BBB) dysfunction, we used a cell culture model of the BBB and compared the effects of gaseous NO, potassium cyanide (KCN, a mitochondrial respiratory chain inhibitor) and iodoacetate [IA, an inhibitor of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH)] on endothelial cell ATP content, GAPDH activity and barrier integrity. NO lead to a rapid breakdown in model barrier integrity and resulted in a reduction in endothelial cell ATP content and GAPDH activity. KCN had no effect on endothelial cell ATP content or barrier integrity, while IA, at a concentration that completely blocked endothelial cell GAPDH activity, resulted in a rapid decline in ATP content but did not lead to a decline in barrier integrity until at least 2 h of exposure. These results indicate that inhibition of endothelial cell GAPDH activity rather than mitochondrial respiration causes an energy deficiency and delayed barrier dysfunction. However, the rapid detrimental effects of gaseous NO on barrier integrity cannot be fully explained by endothelial cell energy depletion and may be related to the actions of the free radical and its products on cellular lipids.

NO way back: nitric oxide and programmed cell death in Arabidopsis thaliana suspension cultures.

Recent research has implicated nitric oxide (NO) in the induction of the hypersensitive response (HR) during plant-pathogen interactions. Here we demonstrate that Arabidopsis suspension cultures generate elevated levels of NO in response to challenge by avirulent bacteria, and, using NO donors, show that these elevated levels of NO are sufficient to induce cell death in Arabidopsis cells independently of reactive oxygen species (ROS). We also provide evidence that NO-induced cell death is a form of programmed cell death (PCD), requiring gene expression, and has a number of characteristics of PCD of mammalian cells: NO induced chromatin condensation and caspase-like activity in Arabidopsis cells, while the caspase-1 inhibitor, Ac-YVAD-CMK, blocked NO-induced cell death. A well-established second messenger mediating NO responses in mammalian cells is cGMP, produced by the enzyme guanylate cyclase. A specific inhibitor of guanylate cyclase blocked NO-induced cell death in Arabidopsis cells, and this inhibition was reversed by the cell-permeable cGMP analogue, 8Br-cGMP, although 8Br-cGMP alone did not induce cell death or potentiate NO-induced cell death. This suggests that cGMP synthesis is required but not sufficient for NO-induced cell death in Arabidopsis. In-gel protein kinase assays showed that NO activates a potential mitogen-activated protein kinase (MAPK), although a specific inhibitor of mammalian MAPK activation, PD98059, which blocked H2O2-induced cell death, did not inhibit the effects of NO.

Surgical treatment of anorectal complications in Crohn's disease.

BACKGROUND: The purpose of our study was to elucidate features, surgical procedures, and long-term results in patients with anorectal complications of Crohn's disease. METHODS: Physical findings, surgical treatment, and long-term outcome were recorded prospectively for 224 patients who had anorectal complications of Crohn's disease between October 1984 and May 1999. RESULTS: Presenting complications included abscess (n = 36), fistula-in-ano (n = 51), rectovaginal fistula (n = 20), anal stenosis (n = 40), anal incontinence (n = 11), or a combination of features (n = 66). Twenty-four patients did not undergo surgical treatment; the remaining 200 patients underwent 284 procedures. Ultimately, 139 patients (62%) retained anorectal function; reasons for proctectomy in the remaining 85 patients included disease (n = 66), extensive fistular disease (n = 15), fecal incontinence (n = 2), and tight anal stenosis (n = 1). Patients with rectal disease had a significantly higher rate of proctectomy than patients with rectal sparing (77.6% vs. 13.6%, respectively, P<.0001). In the absence of rectal involvement, patients with multiple complications had a significantly higher rate of proctectomy than patients with single complications (23% vs. 10%, P<.05). CONCLUSIONS: A wide spectrum of surgical techniques is required for the management of the diverse anorectal complications of Crohn's disease. Complete healing and control of sepsis can be achieved in the majority of patients. Active rectal disease and multiple complications significantly increase the need for proctectomy.

Side-to-side isoperistaltic strictureplasty in extensive Crohn's disease: a prospective longitudinal study.

OBJECTIVE: To report on the results of a prospective longitudinal study of a new bowel-sparing procedure (side-to-side isoperistaltic strictureplasty [SSIS]) in patients with extensive Crohn's disease. METHODS: Between January 1992 and April 1999, the authors operated on 469 consecutive patients for Crohn's disease of the small bowel. Seventy-one patients (15.1%) underwent at least one strictureplasty; of these, 21 (4.5%; 12 men, 9 women; mean age 39) underwent an SSIS. The long-term changes occurring in the SSIS were studied radiographically, endoscopically, and histopathologically. RESULTS: The indication for surgical intervention was symptomatic partial intestinal obstruction in each of the 21 patients. Fourteen SSISs were constructed in the jejunum, four in the ileum, and three with ileum overlapping colon. The average length of the SSIS was 24 cm. Performance of an SSIS instead of a resection resulted in preservation of an average of 17% of small bowel length. One patient suffered a postoperative gastrointestinal hemorrhage. All patients were discharged on oral feedings after a mean of 8 days. In all cases, SSIS resulted in resolution of the preoperative symptoms. With follow-up extending to 7.5 years in 20 patients (one patient died of unrelated causes), radiographic, endoscopic, and histopathologic examination of the SSIS suggests regression of previously active Crohn's disease. CONCLUSIONS: SSIS is a safe and effective procedure in patients with extensive Crohn's disease. The authors' results provide radiographic, endoscopic, and histopathologic evidence that active Crohn's disease regresses at the site of the SSIS.

The role of laparoscopy and strictureplasty in the management of inflammatory bowel disease.

The surgical management of Crohn's disease has always been a challenging issue for physicians because of concerns of the historical need for repeated surgeries over time, the physiological limitations of a shortened small bowel, and the transmural, fistulizing, and/or skip-lesion nature of the disease. Patients are fearful of the potentially disfiguring results, especially the need for a permanent ostomy. The challenge has been to develop surgical approaches that are bowel sparing and/or minimally invasive. Stricutureplasty has been used with relatively good results as a bowel-sparing procedure for patients with small-bowel Crohn's disease, potentially sparing patients of a short-bowel syndrome. Laparoscopic approaches to Crohn's disease have thus far been mostly limited to ileocecal resections in selected patients, but as more expertise is developed, will hopefully be extended to other surgical procedures in patients with Crohn's disease in the future. Patient criteria, success rates, complications, and economic implications are discussed for each procedure.

Butyric acid mediated induction of enhanced transendothelial resistance in an in vitro model blood-brain barrier system.

Previously we reported that the co-culture of non-brain vascular endothelial cells with glioma cells leads to the induction of a more differentiated endothelial cell phenotype which exhibits important properties of the blood-brain barrier (BBB). Recognising the potential for improving the model barrier system with agents known to modify the growth and differentiation of cells in culture we examined the effects of four differentiating agents (butyric acid, dexamethasone, retinoic acid, and dimethyl sulfoxide) on barrier function. Of these agents only butyric acid and dexamethasone resulted in an enhancement (depending on the dose used) of transendothelial electrical resistance (barrier function). The greatest effect was observed with butyric acid in a dose-dependent manner and was slow in onset and only occurred in the endothelial/glial cell co-cultures. These data indicate that butyric acid may be a beneficial agent in optimising conditions necessary for induction of BBB properties in in vitro barrier systems.

Upregulation of intercellular adhesion molecule-1 expression on human endothelial cells by tumour necrosis factor-alpha in an in vitro model of the blood-brain barrier.

Adhesion molecules on the endothelial surface of the blood-brain barrier (BBB) play an important role in the pathogenesis of many encephalopathies, including multiple sclerosis (MS) and cerebral malaria (CM). The expression of four surface molecules of relevance to MS and CM on the immortalized human umbilical vein endothelial cell line, ECV304, was investigated using immunofluorescence flow cytometry. We found that ECV304 cells express intercellular adhesion molecule-1 (ICAM-1) and low levels of CD36, but not vascular cell adhesion molecule-1 (VCAM-1) or E-selectin. This expression pattern was unaltered on ECV304 cells which were co-cultured with C6 glioma cells; conditions under which the endothelial cells display enhanced barrier formation. Tumour necrosis factor-alpha (TNF-alpha), which is elevated in MS and CM, decreased the integrity of the barrier in co-cultured endothelial cells and upregulated the expression of ICAM-1 nine-fold. The significance of elevated ICAM-1 expression in relation to the binding of parasitised erythrocytes at the BBB in CM is discussed.