Metabolic Syndrome Identification in Patients Treated With Second-Generation Antipsychotic Medications.

The purpose of the current project was to assess missed opportunities to identify metabolic syndrome in patients treated with second-generation antipsychotic medication in a community hospital's inpatient psychiatric unit between January 1 and December 31, 2020. Data on demographics, metabolic syndrome risk factors, body mass index, medications, related diagnoses, and primary care providers (PCPs) were collected via retrospective chart review of 194 patients. This project used a nonexperimental design and heterogenous nonrandom convenience sample. Descriptive statistics, chi-square tests, one-tailed t tests, and binary logistic regression were used. The overall rate of metabolic syndrome was 47.4% (n = 92). A positive PCP status was significant for treatment with antihypertensives, statins, and antihyperglycemics (p < 0.05). Findings indicate the need to increase system-wide assessment of metabolic syndrome and integrate care coordination with PCPs. [Journal of Psychosocial Nursing and Mental Health Services, 60(8), 11-18.].

Mesenchymal stromal cell derived CCL2 is required for accelerated wound healing.

Mesenchymal stromal cells (MSC) have immunomodulatory effects impacting macrophages, promoting polarisation towards a reparative phenotype. CCL2 is a potent cytokine involved in the recruitment of macrophages. We hypothesised that MSC derived CCL2 may be involved in the MSC therapeutic effect by facilitating macrophage repolarisation. To further delineate this mechanism, MSC isolated from CCL2 deficient mice (MSC-KO) were applied to excisional wounds in wild-type (WT) mice. CCL2 deficiency in MSC completely abrogated the therapeutic response compared to MSC-WT. MSC-KO were unable to repolarise macrophages to the same extent as WT and this was accompanied by a reduced angiogenesis and re-epithelialisation of the wounds at day 10. This study demonstrates that MSC derived CCL2 is required for MSC induced accelerated wound healing. The role of CCL2 in the interaction between MSC and Macrophages has not been previously demonstrated in accelerated wound healing. CCL2 has a potent effect on the ability to reduce the inflammatory response through local recruitment of macrophages. This research highlights CCL2 as a possible target for augmentation of MSC therapy to enhance therapeutic potential.

Silent cerebral infarction and cognitive function following TAVI: an observational two-centre UK comparison of the first-generation CoreValve and second-generation Lotus valve.

OBJECTIVE: To compare the incidence of silent cerebral infarction and impact on cognitive function following transcatheter aortic valve implantation (TAVI) with the first-generation CoreValve (Medtronic, Minneapolis, Minnesota, USA) and second-generation Lotus valve (Boston Scientific, Natick Massachusetts, USA). DESIGN: A prospective observational study comprising a 1.5 T cerebral MRI scan, performed preoperatively and immediately following TAVI, and neurocognitive assessments performed at baseline, 30 days and 1 year follow-up. SETTING: University hospitals of Leeds and Leicester, UK. PATIENTS: 66 (80.6±8.0 years, 47% male) patients with high-risk severe symptomatic aortic stenosis recruited between April 2012 and May 2015. MAIN OUTCOME MEASURES: Incidence of new cerebral microinfarction and objective decline in neurocognitive performance. RESULTS: All underwent cerebral MRI at baseline and immediately following TAVI, and 49 (25 Lotus, 24 CoreValve) completed neurocognitive assessments at baseline, 30 days and 1 year. There was a significantly greater incidence of new cerebral microinfarction observed following the Lotus TAVI (23 (79%) vs 22 (59%), p=0.025) with a greater number of new infarcts per patient (median 3.5 (IQR 7.0) vs 2.0 (IQR 3.0), p=0.002). The mean volume of infarcted cerebral tissue per patient was equivalent following the two prostheses (p=0.166). More patients suffered new anterior (14 (48%) vs 2 (5%), p=0.001) and vertebrobasilar (15 (52%) vs 7 (19%), p=0.005) lesions following Lotus. Lotus was associated with a decline in verbal memory and psychomotor speed at 30 days. However, performance longitudinally at 1 year was preserved in all neurocognitive domains. CONCLUSIONS: There was a higher incidence of silent cerebral microinfarction and a greater number of lesions per patient following Lotus compared with CoreValve. However, there was no objective decline in neurocognitive function discernible at 1 year following TAVI with either prosthesis.

Treatment of Helicobacter pylori infection in 2018.

Treatment options for the eradication of Helicobacter pylori continue to evolve. There have been many guidelines for H. pylori treatment published, which may lead to some confusion. However, most are in agreement with the most recent iteration of the Maastricht treatment guidelines. Triple therapy is still the most frequently used treatment, especially in areas of low clarithromycin resistance. Its best results are achieved when taken for a minimum of 10 days and with high-dose acid suppression. Quadruple therapy is gaining in popularity particularly in areas with increasing resistance to standard triple therapy. Whether three antibiotics, or bismuth and two antibiotics are used, excellent eradication rates are achieved, albeit with increased side effects. Levofloxacin second-line therapy is widely used; however bismuth, when available, is an increasingly successful option. Sequential therapy is challenging in terms of compliance and is no longer recommended. This past year witnessed a notable increase in the number of studies based on antimicrobial susceptibility testing and tailored eradication therapy, reflecting the role of culture-guided treatment, which may well represent the future of H. pylori treatment and prevent the inappropriate use of antibiotics.

The Use of Thromboelastography to Measure the Influence Inclusion of a Local Anesthetic Agent has on the Mechanical and Kinetic Properties of Fibrin.

CONTEXT: Delivery of slow-release local anesthesia has considerable potential for postoperative analgesia. Fibrin gel has shown huge potential for drug delivery, but has not been fully investigated for the delivery of local anesthetics nor has whether incorporation of anesthetic drugs into fibrin alters its mechanical properties. AIMS: This study aimed to evaluate the effects of bupivacaine inclusion on the mechanical and kinetic properties of fibrin as measured by thromboelastography (TEG). MATERIALS AND METHODS: Serial dilutions of fibrinogen with thrombin were tested with TEG to identify the optimal concentrations to give reproducible results. Following this, fibrinogen samples diluted with bupivacaine 0.5% in place of normal saline (also 1:20 dilution) were added to thrombin to assess what influence this had on clot strength and kinetics as measured by TEG values (with R, K, and α angle relating to clot kinetics and MA and G (or shear elastic modulus strength) relating to clot strength). RESULTS: The mean values yielded for R were higher and lower for α angle, suggesting that the inclusion of bupivacaine produced a fibrin clot at a slower rate. The values for MA and G were both lower when bupivacaine was included, suggesting inclusion of the local anaesthetic also resulted in a fibrin clot of inferior strength. These results were not statistically significant. CONCLUSION: Although TEG failed to consistently measure these properties, the results suggest that inclusion of local anesthetic affects the clotting process of fibrin, potentially interfering with its ability to function as a sealant, adhesive, or hemostat.

Acidification of Model Cheese Brines To Control Listeria monocytogenes.

Cheese brines are often used for prolonged periods, with adjustments made only to pH and salt content. Pathogens, including Salmonella enterica Typhimurium, Escherichia coli O157:H7, and Listeria monocytogenes, have been shown to survive long periods in model and commercial brines under common brining conditions. The objective of this study was to determine the survival of L. monocytogenes in model cheese brines, with and without whey added at 2%, when acidified to a pH of 2 using food-grade acids. Survival in untreated brines over a 6-month period was also assessed. Cultures of L. monocytogenes were propagated to induce salt and acid tolerance prior to inoculation at ∼6 log CFU/mL into model brines (pH 5.2, 20% NaCl). Following a week-long adaption period at 12°C, inoculated brines were acidified to pH 2.0 within 15 min using either hydrochloric, acetic, citric, or lactic acid, held at that pH for up to 24 h, and neutralized prior to enumeration and enrichment. Overall, each acid treatment was capable of achieving ≥5-log reductions in L. monocytogenes counts within 135 min at pH 2. Hydrochloric acid required the lowest volume to achieve treatment pH and was the most effective treatment in the absence of whey. However, it was the least effective in the presence of whey. Acetic acid produced rapid inactivation in both brines but required impractical volumes of acid to reach the treatment pH. Citric acid was similarly effective in both brines but was the second least effective in terms of time to achieve a ≥5-log reduction. Although only slight and insignificant differences were observed, lactic acid appears to be the more practical and promising approach for the inactivation of L. monocytogenes in cheese brines by producing the most rapid inactivation in the presence and absence of whey. Acidification as a preventive control for L. monocytogenes could increase adoption of brine treatments by small-scale cheese producers, thereby reducing food safety risks.

Selective M2 Macrophage Depletion Leads to Prolonged Inflammation in Surgical Wounds.

BACKGROUND: A prolonged inflammatory phase is seen in aberrant wound healing and in chronic wounds. Macrophages are central to wound healing. Distinct macrophage subtypes have differing roles both in initial inflammation and in later tissue repair. Broadly, these cells can be divided into M1 and M2 macrophages. M2 macrophage proliferation and differentiation is regulated by colony-stimulating factor 1 (CSF-1) signalling and can be blocked by GW2580, a competitive cFMS kinase inhibitor, thereby allowing for analysis of the effect of M2 blockade on progression of surgical wounds. MATERIALS AND METHODS: Macrophage Fas-induced apoptosis (MaFIA) transgenic mice with a macrophage-specific promoter used to express green fluorescent protein (GFP) were used to allow for cell tracking. The animals were treated by oral gavage with GW2580. Surgical wounds were created and harvested after 2 weeks for analysis. RESULTS: GW2580-treated mice had significantly more GFP+ cells in the surgical scar than vehicle-treated animals (GW2580, 68.0 ± 3.1%; vehicle, 42.8 ± 1.7%; p < 0.001), and GW2580 treatment depleted CD206+ M2 macrophages in the scar (GW2580, 1.4%; vehicle, 19.3%; p < 0.001). Treated animals showed significantly higher numbers of neutrophils (vehicle, 18.0%; GW2580, 51.3%; p < 0.01) and M1 macrophages (vehicle, 3.8%; GW2580, 12.8%; p < 0.01) in the scar compared to vehicle-treated animals. The total collagen content in the area of the scar was decreased in animals treated with GW2580 as compared to those treated with vehicle alone (GW2580, 67.1%; vehicle, 79.9%; p < 0.005). CONCLUSIONS: Depletion of M2 macrophages in surgical wounds via CSF-1 signalling blockade leads to persistent inflammation, with an increase in neutrophils and M1 macrophages and attenuated collagen deposition.

Novel methods of local anesthetic delivery in the perioperative and postoperative setting-potential for fibrin hydrogel delivery.

The benefits of high-quality postoperative analgesia are well documented and include earlier mobilization, fewer respiratory and cardiovascular complications, and shorter hospital stay. Local anesthesia-based acute pain regimens are at worst equal to and at best superior to opiate-based regimens from the perspective of analgesia. A multimodal approach limiting opioids by combining with local anesthetics has additional beneficial effect on outcomes such as nausea and vomiting, pruritus, gastrointestinal function, respiratory complications, and neutrophil function. Wound catheters providing continuous infiltration of local anesthetics offer a rational approach to effective perioperative analgesia, but their use is limited by a short duration of action. There is an identified need for further methods to optimize longer-acting delivery of these agents. This article reviews current and evolving longer-acting techniques and their limitations with particular focus on the potential advantages of a fibrin hydrogel-based system.

Preclinical evaluation of an endoscopic electroporation system.

BACKGROUND AND STUDY AIMS: Targeted delivery of specific chemotherapeutic drugs into tumors can be achieved by delivering electrical pulses directly to the tumor tissue. This causes a transient formation of pores in the cell membrane that enables passive diffusion of normally impermeant drugs. A novel device has been developed to enable the endoscopic delivery of this tumor permeabilizing treatment. The aim of the preclinical studies described here was to investigate the efficacy and safety of this nonthermal ablation system in the treatment of gastrointestinal cancer models. METHODS: Murine, porcine, and canine gastrointestinal tumors and tissues were used to assess the efficacy and safety of electroporation delivered through the special device in combination with bleomycin. Tumor cell death, volume, and overall survival were recorded. RESULTS: Murine tumors treated with electrochemotherapy showed excellent responses, with cell death being induced rapidly, mainly via an apoptotic-type mechanism. Use of the system in canine gastrointestinal cancers demonstrated successful local endoluminal tumor resolution, with no safety or adverse effects noted. CONCLUSIONS: Electroporation via the new device in combination with bleomycin offers a nonthermal tumor ablative approach, and presents clinicians with a new option for the management of gastrointestinal cancers.

A Novel Selectable Islet 1 Positive Progenitor Cell Reprogrammed to Expandable and Functional Smooth Muscle Cells.

Disorders affecting smooth muscle structure/function may require technologies that can generate large scale, differentiated and contractile smooth muscle cells (SMC) suitable for cell therapy. To date no clonal precursor population that provides large numbers of differentiated SMC in culture has been identified in a rodent. Identification of such cells may also enhance insight into progenitor cell fate decisions and the relationship between smooth muscle precursors and disease states that implicate differentiated SMC. In this study, we used classic clonal expansion techniques to identify novel self-renewing Islet 1 (Isl-1) positive primitive progenitor cells (PPC) within rat bone marrow that exhibited canonical stem cell markers and preferential differentiation towards a smooth muscle-like fate. We subsequently used molecular tagging to select Isl-1 positive clonal populations from expanded and de novo marrow cell populations. We refer to these previously undescribed cells as the PPC given its stem cell marker profile, and robust self-renewal capacity. PPC could be directly converted into induced smooth muscle cells (iSMC) using single transcription factor (Kruppel-like factor 4) knockdown or transactivator (myocardin) overexpression in contrast to three control cells (HEK 293, endothelial cells and mesenchymal stem cells) where such induction was not possible. iSMC exhibited immuno- and cytoskeletal-phenotype, calcium signaling profile and contractile responses similar to bona fide SMC. Passaged iSMC could be expanded to a scale sufficient for large scale tissue replacement. PPC and reprogramed iSMC so derived may offer future opportunities to investigate molecular, structure/function and cell-based replacement therapy approaches to diverse cardiovascular, respiratory, gastrointestinal, and genitourinary diseases that have as their basis smooth muscle cell functional aberrancy or numerical loss. Stem Cells 2016;34:1354-1368.

Consequence of cerebral embolism after transcatheter aortic valve implantation compared with contemporary surgical aortic valve replacement: effect on health-related quality of life.

BACKGROUND: Incidence of cerebral microinfarcts is higher after transcatheter aortic valve implantation (TAVI) compared with surgical aortic valve replacement (SAVR). It is unknown whether these lesions persist and what direct impact they have on health-related quality of life. The objective was to identify predictors of cerebral microinfarction and measure their effect on health-related quality of life during 6 months after TAVI when compared with SAVR. METHODS AND RESULTS: Cerebral MRI was conducted at baseline, post procedure, and 6 months using diffusion-weighted imaging. Health-related quality of life was measured at baseline, 30 days, and 6 months with short form-12 health outcomes and EuroQol 5 dimensions questionnaires. One hundred eleven patients (TAVI, n=71; SAVR, n=40) were studied. The incidence (54 [77%] versus 17 [43%]; P=0.001) and number (3.4±4.9 versus 1.2±1.8; P=0.001) of new microinfarcts were greater after TAVI than after SAVR. The total volume per microinfarct was smaller in TAVI than in SAVR (0.23±0.24 versus 0.76±1.8 mL; P=0.04). The strongest associations for microinfarction were: TAVI (arch atheroma grade: r=0.46; P=0.0001) and SAVR (concomitant coronary artery bypass grafting: r=-0.33; P=0.03). Physical component score in TAVI increased after 30 days (32.1±6.6 versus 38.9±7.0; P<0.0001) and 6 months (40.4±9.3; P<0.0001); the improvement occurred later in SAVR (baseline: 34.9±10.6; 30 days: 35.9±10.2; 6 months: 42.8±11.2; P<0.001). After TAVI, there were no differences in the short form-12 health outcome scores according to the presence or size of new cerebral infarction. CONCLUSIONS: Cerebral microinfarctions are more common after TAVI compared with SAVR but seem to have no negative effect on early (30 days) or medium term (6 months) health-related quality of life. Aortic atheroma (TAVI) and concomitant coronary artery bypass grafting (SAVR) are independent risk factors for cerebral microinfarction.

Intraperitoneal co-administration of low dose urethane with xylazine and ketamine for extended duration of surgical anesthesia in rats.

Procedures involving complex surgical techniques in rats, such as placement of abdominal aortic graft require extended duration of surgical anesthesia, which often can be achieved by repeated administrations of xylazine-ketamine combination. However such repeated anesthetic administration, in addition to being technically challenging, may be associated with potential adverse events due to cumulative effects of anesthesia. We report here the feasibility of using urethane at low dose (~1/10 the recommended anesthetic dose) in combination with a xylazine-ketamine mix to achieve an extended duration of surgical anesthesia in rats. The anesthesia induction phase was quick and smooth with an optimal phase of surgical anesthesia achieved for up to 90 minutes, which was significantly higher compared to that achieved with use of only xylazine-ketamine combination. The rectal temperature, heart rate and respiratory rate were within the physiological range with an uneventful recovery phase. Post surgery the rats were followed up to 3 months without any evidence of tumor or any other adverse effects related to the use of the urethane anesthetic combination. We conclude that low dose urethane can be effectively used in combination with xylazine and ketamine to achieve extended duration of surgical anesthesia up to 90 minutes in rats.

Allogeneic mesenchymal stem cells, but not culture modified monocytes, improve burn wound healing.

The use of cell therapy to improve burn wound healing is limited as a validated cell source is not rapidly available after injury. Progenitor cells have shown potential to drive the intrinsic wound regeneration. Two sources of cells, allogeneic mesenchymal stem cells (MSC) and autologous culture modified monocytes (CMM), were assessed for their ability to influence burn wound healing. Both could be widely available shortly after injury. Cells were delivered in a fibrin matrix following contact burns in a porcine burns model. Application of MSC significantly decreased the area of unhealed burn compared to CMM or delivery matrix alone (6% MSC, 27% CMM, 24% Matrix, p<0.001). MSC treated wounds showed histological evidence of improved wound healing with increased collagen content (MSC 49%, CMM 42%, p<0.01), increased epidermal area (MSC 8.8%, CMM 6.1%, p<0.01) and dermal thickness (MSC 1108 µm, CMM 1007 µm, p<0.01) compared to CMM treated wounds. Labelled MSC and CMM were identified in the wounds after 2 weeks by immunohistochemistry and FACS. A single application of allogeneic MSC improves the rate of burn wound healing and improves the histological appearance of the burn wound. These cells show potential as a cell therapy that is rapidly available following burn.

Analysis of attitudes toward the source of progenitor cells in tissue-engineered products for use in burns compared with other disease states.

The first trials using progenitor cells to improve burn wound healing are beginning. However, there remains a paucity of data on patients' opinions of the source of stem cells. In this study, 279 patients attending plastic surgery/burns outpatient and medical outpatient clinics were questioned to assess willingness to accept a tissue-engineered skin product derived from a variety of sources. Levels of acceptance for the use of progenitor cells derived from these sources for treatment across a range of disease states (burns, Parkinson's disease, diabetes, and for cosmetic use) were also assessed. Overall, 80% of those questioned would accept a tissue-engineered product. Autologous cells were the preferred choice of cells (acute burns 94%, diabetes 95%, Parkinson's 93.9%). Allogeneic cells were still widely accepted (acute burns 67%, diabetes 66.7%, Parkinson's 69.2%). There was no difference observed between plastic surgical patients and medical patients in acceptance of cell therapy for burns, Parkinson's disease, or diabetes. There is good potential acceptance for the use of both autologous and allogeneic cells for the treatment of acute burns and burns' scarring as well as in diabetes and Parkinson's disease. Disease state does not appear to influence overall acceptability and choice of cells.

Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage: a prospective, randomized, controlled trial (LUMAS).

BACKGROUND AND PURPOSE: A single-center prospective randomized controlled trial has been conducted to determine if lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage reduces the prevalence of delayed ischemic neurological deficit and improves clinical outcome. METHODS: Patients with World Federation of Neurological Surgeons Grade 1 to 3 aneurysmal subarachnoid hemorrhage and modified Fisher Grades 2, 3, 4, and 3+4 were randomized to either the study group of standard therapy plus insertion of a lumbar drain or the control group of standard therapy alone. The primary outcome measure was the prevalence of delayed ischemic neurological deficit. RESULTS: Two hundred ten patients with aneurysmal subarachnoid hemorrhage (166 female, 44 male; median age, 54 years; interquartile range, 45-62 years) were recruited into the control (n=105) and study (n=105) groups of the trial. World Federation of Neurological Surgeons grade was: 1 (n=139), 2 (n=60), and 3 (n=11); Fisher grade was: 2 (n=87), 3 (n=85), and 4 (n=38). The prevalence of delayed ischemic neurological deficit was 35.2% and 21.0% in the control and study groups, respectively (P=0.021). The prevalence of a modified Rankin Scale score of 4, 5, or 6 at Day 10 and 6 months, respectively, was 62.5% and 18.6% in the control group and 44.8% and 19.8% in the study group (P=0.009 and 0.83, respectively). CONCLUSIONS: Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage has been shown to reduce the prevalence of delayed ischemic neurological deficit and improve early clinical outcome but failed to improve outcome at 6 months after aneurysmal subarachnoid hemorrhage. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00842049.

Diffusion-weighted MRI determined cerebral embolic infarction following transcatheter aortic valve implantation: assessment of predictive risk factors and the relationship to subsequent health status.

BACKGROUND: 'Silent' cerebral infarction and stroke are complications of transcatheter aortic valve implantation (TAVI). OBJECTIVE: To assess the occurrence of cerebral infarction, identify predictive risk factors and examine the impact on patient health-related quality of life (HRQoL). METHODS: Cerebral diffusion weighted MRI of 31 patients with aortic stenosis undergoing CoreValve TAVI was carried out. HRQoL was assessed at baseline and at 30 days by SF-12v2 and EQ5D questionnaires. RESULTS: New cerebral infarcts occurred in 24/31 patients (77%) and stroke in 2 (6%). Stroke was associated with a greater number and volume of cerebral infarcts. Age (r=0.37, p=0.042), severity of atheroma (arch and descending aorta; r=0.91, p<0.001, r=0.69, p=0.001, respectively) and catheterisation time (r=0.45, p=0.02) were predictors of the number of new cerebral infarcts. HRQoL improved overall: SF-12v2 physical component summary increased significantly (32.4±6.2 vs 36.5±7.2; p=0.03) with no significant change in mental component summary (43.5±11.7 vs. 43.1±14.3; p=0.85). The EQ5D score and Visual Analogue Scale showed no significant change (0.56±0.26 vs. 0.59±0.31; p=0.70, and 54.2±19 vs. 58.2±24; p=0.43). CONCLUSION: Multiple small cerebral infarcts occurred in 77% of patients with TAVI. The majority of infarcts were 'silent' with clinical stroke being associated with a both higher infarct number and volume. Increased age and the severity of aortic arch atheroma were independent risk factors for the development of new cerebral infarcts. Overall HRQoL improved and there was no association between the number of new cerebral infarcts and altered health status.

Deficiency of CX3CR1 delays burn wound healing and is associated with reduced myeloid cell recruitment and decreased sub-dermal angiogenesis.

The development of a good blood supply is a key step in burn wound healing and appears to be regulated in part by myeloid cells. CX3CR1 positive cells have recently been identified as myeloid cells with a potential role in angiogenesis. The role of functional CX3CR1 system in burn wound healing is not previously investigated. A 2% contact burn was induced in CX3CR1(+/gfp) and CX3CR1(gfp/gfp) mice. These transgenic mice facilitate the tracking of CX3CR1 cells (CX3CR1(+/gfp)) and allow evaluation of the consequence of CX3CR1 functional knockout (CX3CR1(gfp/gfp)) on burn wound healing. The progression of wound healing was monitored before tissue was harvested and analyzed at day 6 and day 12 for migration of CX3CR1 cells into burn wound. Deficiency of a functional CX3CR1 system resulted in decreased recruitment of CX3CR1 positive cells into the burn wound associated with decreased myeloid cell recruitment (p<0.001) and reduced maintenance of new vessels (p<0.001). Burn wound healing was prolonged (p<0.05). Our study is the first to establish a role for CX3CR1 in burn wound healing which is associated with sub-dermal angiogenesis. This chemokine receptor pathway may be attractive for therapeutic manipulation as it could increase sub dermal angiogenesis and thereby improve time to healing.

Differential effectiveness of berry polyphenols as anti-giardial agents.

Following previous work on the anti-giardial effect of blueberry polyphenols, a range of polyphenol-rich extracts from berries and other fruits was screened for their ability to kill Giardia duodenalis, an intestinal parasite of humans. Polyphenol-rich extracts were prepared from berries using solid-phase extraction and applied to trophozoites of Giardia duodenalis grown in vitro. All berry extracts caused inhibition at 166 µg gallic acid equivalents (GAE)/ml phenol content but extracts from strawberry, arctic bramble, blackberry and cloudberry were as effective as the currently used drug, metronidazole, causing complete trophozoite mortality in vitro. Cloudberry extracts were found to be the most effective causing effectively complete trophozoite mortality at 66 µg GAE/ml. The polyphenol composition of the more effective berry extracts suggested that the presence of ellagitannins could be an important factor. However, the potency of cloudberry could be related to high ellagitannin content but also to the presence of substantial amounts of unconjugated p-coumaric acid and benzoic acid. These in vitro effects occur at concentrations easily achievable in the gut after berry ingestion and we discuss the likelihood that berry extracts could be effective anti-giardial agents in vivo.

The effect of blueberry extracts on Giardia duodenalis viability and spontaneous excystation of Cryptosporidium parvum oocysts, in vitro.

The protozoan parasites Giardia duodenalis and Cryptosporidium parvum are common causes of diarrhoea, worldwide. Effective drug treatment is available for G. duodenalis, but with anecdotal evidence of resistance or reduced compliance. There is no effective specific chemotherapeutic intervention for Cryptosporidium. Recently, there has been renewed interest in the antimicrobial properties of berries and their phenolic compounds but little work has been done on their antiparasitic actions. The effect of various preparations of blueberry (Vaccinium myrtillus) extract on G. duodenalis trophozoites and C. parvum oocysts were investigated. Pressed blueberry extract, a polyphenolic-rich blueberry extract, and a commercially produced blueberry drink (Bouvrage) all demonstrated antigiardial activity. The polyphenol-rich blueberry extract reduced trophozoite viability in a dose dependent manner. At 167 microgml(-1), this extract performed as well as all dilutions of pressed blueberry extract and the Bouvrage beverage (9.6+/-2.8% live trophozoites remaining after 24h incubation). The lowest dilution of blueberry extract tested (12.5% v/v) contained >167 microgml(-1) of polyphenolic compounds suggesting that polyphenols are responsible for the reduced survival of G. duodenalis trophozoites. The pressed blueberry extract, Bouvrage beverage and the polyphenolic-rich blueberry extract increased the spontaneous excystation of C. parvum oocysts at 37 degrees C, compared to controls, but only at a dilution of 50% Bouvrage beverage, equivalent to 213 microgml(-1) gallic acid equivalents in the polyphenolic-rich blueberry extract. Above this level, spontaneous excystation is decreased. We conclude that water soluble extracts of blueberries can kill G. duodenalis trophozoites and modify the morphology of G. duodenalis and C. parvum.