Genetic diversity, growth and heart function of Auckland Island pigs, a potential source for organ xenotransplantation.

One of the prerequisites for successful organ xenotransplantation is a reasonable size match between the porcine organ and the recipient's organ to be replaced. Therefore, the selection of a suitable genetic background of source pigs is important. In this study, we investigated body and organ growth, cardiac function, and genetic diversity of a colony of Auckland Island pigs established at the Center for Innovative Medical Models (CiMM), LMU Munich. Male and female Auckland Island pig kidney cells (selected to be free of porcine endogenous retrovirus C) were imported from New Zealand, and founder animals were established by somatic cell nuclear transfer (SCNT). Morphologically, Auckland Island pigs have smaller body stature compared to many domestic pig breeds, rendering their organ dimensions well-suited for human transplantation. Furthermore, echocardiography assessments of Auckland Island pig hearts indicated normal structure and functioning across various age groups throughout the study. Single nucleotide polymorphism (SNP) analysis revealed higher runs of homozygosity (ROH) in Auckland Island pigs compared to other domestic pig breeds and demonstrated that the entire locus coding the swine leukocyte antigens (SLAs) was homozygous. Based on these findings, Auckland Island pigs represent a promising genetic background for organ xenotransplantation.

Can we predict inadequate response to allopurinol dose escalation? Analysis of a randomised controlled trial.

Objectives: To determine factors that predict inadequate serum urate (SU) lowering response in a randomized controlled trial of allopurinol dose escalation (DE) in gout. Methods: Participants undergoing allopurinol DE were classified as: complete response (CR)-reached target SU at month 9 and 12 of the DE phase or if still dose escalating at month 9 reached target SU by month 12; partial response (PR)-reached target at some stage but not fulfilling criteria for CR; or inadequate response (IR)-did not reach target SU at any time. Results: IR was uncommon, occurring in 13/150 (8.7%), compared with 82 (54.7%) CR, and 55 (36.6%) PR. Mean (s.e.m.) SU was higher at the end of the 12-month DE in IR compared with both CR and PR groups; 7.6 (0.31) vs 5.01 (0.06) and 5.97 (0.17) mg/dl respectively (P < 0.001). In univariate analysis, compete responders tended to be older, be receiving less allopurinol, have longer gout duration and were more likely to be New Zealand (NZ) European ethnicity, compared with IR+PR. Using multi-variate logistic regression analysis, only longer duration of gout and NZ European ethnicity remained significant independent predictors of CR. Baseline SU ⩾ 8 mg/dl had a sensitivity of 69.2% and specificity of 85.1% in predicting IR. The odds ratio for an IR if baseline SU was ⩾8 mg/dl was 11.7 (95% CI 3.3, 41.2). Conclusion: A minority of people with gout never reach target SU when allopurinol dose is increased in a treat-to-target manner. Approximately one-third of those with SU ⩾ 8mg/dl despite allopurinol ⩾300mg/d have an IR to DE. Trial registration: Australian New Zealand Clinical Trails Registry, https://www.anzctr.org.au, ACTRN12611000845932.

Lack of Evidence that Soluble Urate Directly Influences Bone Remodelling: A Laboratory and Clinical Study.

INTRODUCTION: Numerous observational studies have reported that serum urate concentration positively correlates with bone density and reduced risk of fractures. The aim of this study was to examine whether soluble urate directly influences bone remodelling. METHODS: In laboratory studies, the in vitro effects of soluble urate were examined in osteoclast, osteoblast and osteocyte assays at a range of urate concentrations consistent with those typically observed in humans (up to 0.70 mmol/L). The clinical relevance of the in vitro assay findings was assessed using serial procollagen-1 N-terminal propeptide (P1NP) and Month 12 bone density data from a randomised controlled trial of allopurinol dose escalation in people with gout. RESULTS: Addition of urate in the RAW264.7 cell osteoclastogenesis assay led to small increases in osteoclast formation (ANOVA p = 0.018), but no significant difference in bone resorption. No significant effects on osteoclast number or activity were observed in primary cell osteoclastogenesis or resorption assays. Addition of urate did not alter viability or function in MC3T3-E1 pre-osteoblast, primary human osteoblast, or MLO-Y4 osteocyte assays. In the clinical trial analysis, reducing serum urate over a 12 month period by allopurinol dose escalation did not lead to significant changes in P1NP or differences in bone mineral density. CONCLUSION: Addition of soluble urate at physiological concentrations does not influence bone remodelling in vitro. These data, together with clinical trial data showing no effect of urate-lowering on P1NP or bone density, do not support a direct role for urate in influencing bone remodelling.

The impact of diuretic use and ABCG2 genotype on the predictive performance of a published allopurinol dosing tool.

AIM: This research aims to evaluate the predictive performance of a published allopurinol dosing tool. METHODS: Allopurinol dose predictions were compared to the actual dose required to achieve serum urate (SU) <0.36 mmol l-1 using mean prediction error. The influence of patient factors on dose predictions was explored using multilinear regression. RESULTS: Allopurinol doses were overpredicted by the dosing tool; however, this was minimal in patients without diuretic therapy (MPE 63 mg day-1 , 95% CI 40-87) compared to those receiving diuretics (MPE 295 mg day-1 , 95% CI 260-330, P < 0.0001). ABCG2 genotype (rs2231142, G>T) had an important impact on the dose predictions (MPE 201, 107, 15 mg day-1 for GG, GT and TT, respectively, P < 0.0001). Diuretic use and ABCG2 genotype explained 53% of the variability in prediction error (R2  = 0.53, P = 0.0004). CONCLUSIONS: The dosing tool produced acceptable maintenance dose predictions for patients not taking diuretics. Inclusion of ABCG2 genotype and a revised adjustment for diuretics would further improve the performance of the dosing tool.

Allopurinol dose escalation to achieve serum urate below 6 mg/dL: an open-label extension study.

OBJECTIVES: To determine the long-term safety and efficacy of allopurinol dose escalation (DE) to achieve target serum urate (SU) in gout. METHODS: People, including those with chronic kidney disease, who completed the first 12 months of a randomised controlled trial continued into a 12-month extension study. Participants randomised to continue current dose for the first 12 months began allopurinol DE at month 12 if SU was ≥6 mg/dL (control/DE). Immediate DE participants who achieved target SU maintained allopurinol dose (DE/DE). The primary endpoints were reduction in SU and adverse events (AEs) at month 24. RESULTS: The mean (SE) change in SU from month 12 to 24 was -1.1 (0.2) mg/dL in control/DE and 0.1 (0.2) mg/dL in DE/DE group (p<0.001). There was a significant reduction in the percentage of individuals having a gout flare in the month prior to months 12 and 24 compared with baseline in both groups and in mean tophus size over 24 months, but no difference between randomised groups. There were similar numbers of AEs and serious adverse events between groups. CONCLUSIONS: The majority of people with gout tolerate higher than creatinine clearance-based allopurinol dose and achieve and maintain target SU. Slow allopurinol DE may be appropriate in clinical practice even in those with kidney impairment. TRIAL REGISTRATION NUMBER: ACTRN12611000845932.

A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout.

OBJECTIVES: To determine the efficacy and safety of allopurinol dose escalation using a treat-to-target serum urate (SU) approach. METHODS: A randomised, controlled, parallel-group, comparative clinical trial was undertaken. People with gout receiving at least creatinine clearance (CrCL)-based allopurinol dose for ≥1 month and SU ≥6 mg/dL were recruited. Participants were randomised to continue current dose (control) or allopurinol dose escalation for 12 months. In the dose escalation group, allopurinol was increased monthly until SU was <6 mg/dL. The primary endpoints were reduction in SU and adverse events (AEs). RESULTS: 183 participants (93 control, 90 dose escalation) were recruited. At baseline, mean (SD) urate was 7.15 (1.6) mg/dL and allopurinol dose 269 mg/day. 52% had CrCL<60 mL/min. Mean changes in SU at the final visit were -0.34 mg/dL in the control group and -1.5 mg/dL in the dose escalation group (p<0.001) with a mean difference of 1.2 mg/dL (95% CI 0.67 to 1.5, p<0.001). At month 12, 32% of controls and 69% in the dose escalation had SU <6 mg/dL. There were 43 serious AEs in 25 controls and 35 events in 22 dose escalation participants. Only one was considered probably related to allopurinol. Five control and five dose escalation participants died; none was considered allopurinol related. Mild elevations in LFTs were common in both groups, a few moderate increases in gamma glutamyl transferase (GGT) were noted. There was no difference in renal function changes between randomised groups. CONCLUSIONS: Higher than CrCL-based doses of allopurinol can effectively lower SU to treatment target in most people with gout. Allopurinol dose escalation is well tolerated. TRIAL REGISTRATION NUMBER: ANZCTR12611000845932; Results.

Factors associated with change in radiographic damage scores in gout: a prospective observational study.

BACKGROUND/AIMS: Radiographic damage is frequently observed in patients with longstanding gout. The aim of this prospective observational study was to determine factors associated with change in radiographic damage scores in gout. METHODS: People with gout and disease duration <10 years were recruited into this prospective observational study. At the baseline visit, structured assessment was undertaken in 290 participants including detailed clinical examination and plain radiographs (XR) of the hands and feet. Participants were invited to attend a further study visit with repeat XR 3 years after the baseline visit. XR were scored for erosion and joint space narrowing according to the gout-modified Sharp/van der Heijde XR damage score. RESULTS: Age, subcutaneous tophus count and tender joint count were independently associated with XR damage score at the baseline visit. Paired serial XR were available for 140 participants. In stepwise linear regression analysis, change in total damage score over 3 years was positively associated with change in subcutaneous tophus count and baseline XR damage score, and inversely associated with baseline subcutaneous tophus count (model R2=0.39, p<0.001). Change in subcutaneous tophus count contributed most to the change in erosion score (partial R2 change=0.31, p<0.001), and baseline XR damage score contributed most to the change in narrowing score (partial R2 change=0.31, p<0.001). CONCLUSIONS: Development of new subcutaneous tophi and baseline radiographic damage are associated with progressive joint damage scores in people with gout. These data provide further evidence that the tophus plays a central role in bone erosion in gout.

Role of miR-146a in regulation of the acute inflammatory response to monosodium urate crystals.

OBJECTIVES: MicroRNAs (miRNA) are small non-coding RNAs that function as post-transcriptional repressors of gene expression. We hypothesised that miRNA regulate gene expression of proinflammatory cytokines in response to monosodium urate (MSU) crystals. METHODS: We stimulated human monocytic THP-1 cells with MSU crystals and examined miRNA and proinflammatory cytokine gene expression. The effects of miR-146a overexpression were examined by transfecting THP-1 cells with miR-146a precursor. miR-146a expression was examined in the urate peritonitis model, in peripheral blood mononuclear cells from people with gout and control participants, and in gouty tophus samples. RESULTS: MSU crystals increased miR-146a expression in THP-1 cells, but not other miRNA implicated in interleukin (IL)-1ß regulation. Overexpression of miR-146a expression reduced MSU crystal-induced IL-1ß, tumour necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1) and IL-8 gene expression. In the urate peritonitis model, reduced miR-146a expression was observed during the acute inflammatory response to MSU crystal injection. In people with intercritical gout, peripheral blood mononuclear cells expressed significantly higher levels of miR-146a, compared with normouricaemic and hyperuricaemic control participants and those with acute gout flares. Expression of miR-146a was also observed in all tophus samples. CONCLUSIONS: Collectively, these data suggest that miR-146a is a transcriptional brake that is lost during the acute inflammatory response to MSU crystals.

Urate crystal deposition in asymptomatic hyperuricaemia and symptomatic gout: a dual energy CT study.

BACKGROUND: The aim of this study was to compare the frequency and volume of dual energy CT (DECT) urate deposits in people with asymptomatic hyperuricaemia and symptomatic gout. METHODS: We analysed DECT scans of the feet from asymptomatic individuals with serum urate ≥540 µmol/L (n=25) and those with crystal proven gout without clinically apparent tophi (n=33). RESULTS: DECT urate deposits were observed in 6/25 (24%) participants with asymptomatic hyperuricaemia, 11/14 (79%) with early gout (predefined as disease duration ≤3 years) and 16/19 (84%) with late gout (p<0.001). DECT urate deposition was observed in both joints and tendons in the asymptomatic hyperuricaemia group, but significantly less frequently than in those with gout (p≤0.001 for both joint and tendon sites). The volume of urate deposition was also significantly lower in those with asymptomatic hyperuricaemia, compared with the early and the late gout groups (p<0.01 for both comparisons). Similar urate volumes were observed in the early and late gout groups. CONCLUSIONS: Although subclinical urate deposition can occur in people with asymptomatic hyperuricaemia, these deposits occur more frequently and at higher volumes in those with symptomatic gout. These data suggest that a threshold of urate crystal volume may be required before symptomatic disease occurs.

Development of a patient-reported outcome measure of tophus burden: the Tophus Impact Questionnaire (TIQ-20).

BACKGROUND: Tophus burden is currently measured using physical examination and imaging methods. The aim of this study was to develop a patient-reported outcome (PRO) tool to assess tophus burden in people with gout. METHODS: The responses from interviews with 25 people with tophaceous gout were used to generate items for a preliminary PRO tool. Following cognitive testing of each item, a preliminary 34-item questionnaire was administered to 103 people with tophaceous gout. Rasch analysis generated a 20-item Tophus Impact Questionnaire (TIQ-20). Test-retest reproducibility and construct validity of the TIQ-20 were assessed. RESULTS: The TIQ-20 responses fit the Rasch model and demonstrated unidimensionality, adequate precision, absence of differential item functioning and adequate person separation index. The TIQ-20 included items related to pain, activity limitation, footwear modification, participation, psychological impact and healthcare use due to tophi. In the 103 patients with tophaceous gout, floor effects were observed in 4.9% and ceiling effects in 1%. The TIQ-20 test-retest intraclass correlation coefficient was 0.76 (95% CI 0.61 to 0.85). All predicted correlations for construct validity testing were observed, including weak correlation with serum urate concentrations (r<0.30), moderate correlation with subcutaneous tophus count and dual energy CT urate volume (r=0.30-0.50), and stronger correlation with Health Assessment Questionnaire scores (r>0.50). CONCLUSIONS: We have developed a tophus-specific PRO in patients with tophaceous gout. The TIQ-20 demonstrates acceptable psychometric properties. Initial results show internal, face and construct validity, reproducibility and feasibility. Further research is required to determine responsiveness to change.

Effects of the dietary replacement of maize with sun-dried cocoa pods on the performance of growing rabbits.

Twenty seven mixed-breed growing rabbits (1.2-1.3 kg body weight) aged 10-12 weeks were used to study the effects of the dietary replacement of maize with sun-dried cocoa pod husks on the performance of growing rabbits in a 6-week trial. Three treatment diets were compounded whereby sun-dried cocoa pod husks replaced maize at 0, 50, and 100 %, respectively. The animals were divided among the three treatment diets so that each diet had 3 replicates of 3 animals each. Feed intake and weight gain were recorded; faeces were also collected for digestibility trials, and cost analysis was also carried out. Results showed a significant difference (P < 0.05) in daily feed intake between the dietary treatments. However, there was no significant difference (P > 0.05) in the final metabolic weights, total metabolic weight gain, daily growth rate, and feed conversion ratio between the treatments. The digestibility study showed a decrease in the digestibility of dry matter and metabolisable energy with the increase in cocoa pod husk inclusion. Cost analysis indicate that significant net gains can be made by incorporating 200 g sundried cocoa pod husks per kg of the diet of growing rabbits compared with the same proportion of maize. These results suggest that sun-dried cocoa pod husks can totally replace maize and provide a cheap source of energy in the diets of growing rabbits.

Metabolomic profiling and bactericidal effect of Polyalthia longifolia (Sonn.) Twaites. stem bark against methicillin-resistant Staphylococcus aureus.

Objective. The present study was carried out to establish the chemical profile of the methanolic extract of Polyalthia longifolia stem bark and investigate its antibacterial property against some human pathogenic bacteria. Methods. The extract was analysed using liquid and gas chromatography coupled to mass spectrometry. Antibacterial activity of P. longifolia extract against some human pathogenic bacteria was screened using the AlamarBlue method, and MIC and MBC were determined. Results and Conclusion. Liquid chromatography-mass spectrometry (LC-MS) revealed the presence of 21 compounds among which 12 were identified. Gas chromatography-mass spectrometry (GC-MS) allowed identification of 26 compounds, the three major ones being the following: cis vaccenic acid (17.79 %), 3-ethyl-3-hydroxyandrostan-17-one (13.80 %) and copaiferic acid B (12.82 %). P. longifolia extract was active against Gram-positive bacteria with MIC ranging from 1 to 2 mg ml-1 and MBC from 2 to 6 mg ml-1. This study demonstrated the bactericidal effect of the methanolic extract of Polyalthia longifolia stem bark against some human pathogenic bacteria, including methicillin-resistant S. aureus . This effect could be related to the presence in the extract of a broad diversity of well-known compounds with established pharmacological properties. These results support the ethnomedicinal use of P. longifolia stem bark in Cameroon for the management of methicillin-resistant S. aureus (MRSA)-related infections.

Chronic Gastric Ulcer Healing Actions of the Aqueous Extracts of Staple Plant Foods of the North-West, Adamawa, and West Regions of Cameroon.

Aim: This study is aimed at establishing phenolic compound profile and assessing the possible antiulcer activities of aqueous extracts of some staple plant foods from the West and North-West regions of Cameroon against chronic gastric ulcer models in rats. Materials and Methods: Phenolic constituents of extracts were evaluated using HPLC-DAD. Aqueous extracts of Corchorus olitorius, Solanum nigrum, Vigna unguiculata, Triumfetta pentandra, "nkui" spices, and "yellow soup" spices were tested at two doses (200 and 400 mg/kg). After treatments, animals were sacrificed, healing percentage and antioxidant status (catalase, superoxide dismutase, and glutathione peroxidase) were evaluated, and histological examination of gastric mucosa was realized. Results: HPLC-DAD revealed that p-hydroxybenzoic and protocatechuic acids were the phenolic compound present in all extracts. Oral administration of extracts (200 and 400 mg/kg) significantly reduced ulcer surface value and significantly increased mucus production compared to the control groups (p < 0.05). Histological study supported the observed healing activity of different extracts characterized by a reduced inflammatory response. Moreover, administration of aqueous extracts increased the activity of antioxidant enzymes. Conclusion: This study revealed that aqueous extracts of Solanum nigrum, Corchorus olitorius, Vigna unguiculata, Triumfetta pentandra, "yellow soup" spices, and "nkui" spices possess healing antiulcer effects against models of gastric ulcers. The antiulcer mechanisms involved may include increase of gastric mucus production and improvement of the antioxidant activity of gastric tissue. These activities may be due to the phenolic compounds identified in the extracts, especially p-hydroxybenzoic and protocatechuic acids present in all extracts and with known antioxidant, cytoprotective, and healing properties. However, all the diets may promote the healing process of chronic ulcers caused by excessive alcohol consumption/stress.

Antihistaminergic and Anticholinergic Properties of the Root Bark Aqueous Extract of Diospyros mespiliformis (Ebenaceae) on Hypersecretion of Gastric Acid Induced in Wistar Rats.

OBJECTIVE: The objective of this study was to elucidate the antisecretory mechanism of the root bark aqueous extract of Diospyros mespiliformis (RBAEDM) in Wistar rats. Materials and methods. RBAEDM was tested on three experimental animal models of gastric acid hypersecretion including pyloric ligation (PL), PL with histamine, and carbachol pretreatments. The ulcerated surface, mucus mass, pH, gastric acidity, and pepsin activity were determined. Some bioactive compounds revealed by qualitative phytochemistry were quantified. Some markers of oxidative stress in vivo such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and in vitro antioxidant tests (ABTS: 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid, DPPH: 2,2-diphenyl-2-picrylhydrazyl, and FRAP: ferric reducing antioxidant power) were determined. RESULTS: In the three models studied, RBAEDM resulted in increases in the percentages of inhibition ranging from 9.50 to 59.52% of gastric ulcer and mucus mass. This increase was accompanied by the reduction in acidity and pepsin activity. The administration of RBAEDM resulted in a significant decrease (p < 0.05, p < 0.01) in MDA levels correlated with a significant increase (p < 0.05, p < 0.01) in CAT and nitrite levels compared with the negative control. RBAEDM has the ability to scavenge ABTS and DPPH radicals and to reduce FRAP, and the inhibitory concentration of 50% (IC50) of the ABTS radical was 220 µg/mL compared with the butylhydroxytoluene (BHT) control (175 µg/mL). Quantitative phytochemistry revealed abundant polyphenols, flavonoids, tannins, saponins, and anthocyanin. CONCLUSION: RBAEDM protected gastric mucous membrane for gastric acid by mechanisms that would involve both anticholinergic and antihistaminergic pathways.

Intensive Serum Urate Lowering With Oral Urate-Lowering Therapy for Erosive Gout: A Randomized Double-Blind Controlled Trial.

OBJECTIVE: To determine whether a therapeutic approach of intensive serum urate lowering results in improved bone erosion scores in patients with erosive gout. METHODS: We undertook a 2-year, double-blind randomized controlled trial of 104 participants with erosive gout who were receiving serum urate-lowering therapy orally and who had serum urate levels of ≥0.30 mmoles/liter at baseline. Participants were randomly assigned to either an intensive serum urate target of <0.20 mmoles/liter or a standard target of <0.30 mmoles/liter (considered the standard according to rheumatology guidelines). Oral serum urate-lowering therapy was titrated to target using a standardized protocol (with the maximum approved doses of allopurinol, probenecid, febuxostat, and benzbromarone). The primary end point was the total computed tomography (CT) bone erosion score. Outcome Measures in Rheumatology (OMERACT) gout core outcome domains were secondary end points. RESULTS: Although the serum urate levels were significantly lower in the intensive target group compared to the standard target group over the study period (P = 0.002), fewer participants in the intensive target group achieved the randomized serum urate target level by year 2 (62% versus 83% of patients in the standard target group; P < 0.05). The intensive target group required higher doses of allopurinol (mean ± SD 746 ± 210 mg/day versus 497 ± 186 mg/day; P < 0.001) and received more combination therapy (P = 0.0004) compared to the standard target group. We observed small increases in CT bone erosion scores in both serum urate target groups over 2 years, with no between-group difference (P = 0.20). OMERACT core outcome domains (gout flares, tophi, pain, patient's global assessment of disease activity, health-related quality of life, and activity limitation) improved in both groups over 2 years, with no between-group differences. Adverse event and serious adverse event rates were similar between the groups. CONCLUSION: Compared to a serum urate target of <0.30 mmoles/liter, more intensive serum urate lowering is difficult to achieve with an oral urate-lowering therapy. Intensive serum urate lowering leads to a high medication burden and does not improve bone erosion scores in patients with erosive gout.

Highly conserved influenza A sequences as T cell epitopes-based vaccine targets to address the viral variability.

Vaccines are the only proven effective method for prevention of human infectious diseases. Almost all traditional vaccines require activating immunological memory B cells to secrete neutralizing antibodies against invading pathogens. The complication with influenza viruses is the high viral mutation rate that results in immune escape through modification of the B cell epitopes. Studies of T-cell immunity to influenza infection provide an alternative vaccine strategy based on highly conserved T-cell epitopes. In this review, we discuss the importance of T cell-mediated immunity in influenza infection and the need for a targeted vaccine approach focused on highly conserved T-cell epitopes to mitigate immune escape. We propose 15 highly conserved pan-influenza sequences as possible T cell epitopes-based vaccine targets for broad protection and lasting immunity against variant influenza strains.

Eremomastax speciosa (Hochst.) Cufod. counteracts the delaying effect of indomethacin on Helicobacter pylori-associated chronic gastric ulcers healing.

ETHNOPHARMACOLOGICAL RELEVANCE: Information collected from local traditional healers reported that Eremomastax speciosa (Hochst.) Cufod. has for a long time been used to manage gastric ulcers in many regions of Cameroon and beyond. This traditional use is supported by numerous studies. However, efficacy of this plant has never been tested in case of chronic gastric ulcers associating Helicobacter pylori infection. AIM OF THE STUDY: This study was designed to investigate curative effects of the aqueous extract of E. speciosa leaves (AEESL) against chronic gastric ulcers associated to Helicobacter pylori infection. MATERIALS AND METHODS: Two experimental methods of chronic gastric ulcers, involving H. pylori infection, were performed using Wistar rats, namely: acetic acid-induced ulcers and "unhealed ulcers". E. speciosa extract was tested at three doses (100; 200; 400 mg/kg) and at the end of experiments, some in vivo antioxidant parameters were measured, bacterial load in stomach tissue calculated and histopathological examinations performed. RESULTS: E. speciosa reduced ulcer index at all the doses and significantly increased mucus production as well as antioxidant (mainly SOD and GSH) level. Bacterial load in stomach significantly decreased (p < 0.05) in extract-treated groups (200 and 400 mg/kg) as confirmed by histopathological observations. The extract was found to be non toxic to healthy and cancerous cells (IC50 > 1000 µg/mL). CONCLUSIONS: E. speciosa accelerated healing of gastric ulcers even in presence of indomethacin, while decreasing bacterial loads in rats' stomachs. These results provide supplementary support to the use of E. speciosa in ethnomedicine and open new perspectives regarding development of a herbal-based monotherapy able to efficiently replace/supplement standard antiulcer tri/quadritherapy.

Flare Rate Thresholds for Patient Assessment of Disease Activity States in Gout.

OBJECTIVE: To determine the relationship between gout flare rate and self-categorization into remission, low disease activity (LDA), and patient acceptable symptom state (PASS). METHODS: Patients with gout self-categorized as remission, LDA, and PASS, and reported number of flares over the preceding 6 and 12 months. Multinomial logistic regression was used to determine the association between being in each disease state (LDA and PASS were combined) and flare count, and self-reported current flare. A distribution-based approach and extended Youden index identified possible flare count thresholds for each state. RESULTS: Investigators from 17 countries recruited 512 participants. Remission was associated with a median recalled flare count of zero over both 6 and 12 months. Each recalled flare reduced the likelihood of self-perceived remission compared with being in higher disease activity than LDA/PASS, by 52% for 6 months and 23% for 12 months, and the likelihood of self-perceived LDA/PASS by 15% and 5% for 6 and 12 months, respectively. A threshold of 0 flares in preceding 6 and 12 months was associated with correct classification of self-perceived remission in 58% and 56% of cases, respectively. CONCLUSION: Flares are significantly associated with perceptions of disease activity in gout, and no flares over the prior 6 or 12 months is necessary for most people to self-categorize as being in remission. However, recalled flare counts alone do not correctly classify all patients into self-categorized disease activity states, suggesting that other factors may also contribute to self-perceived gout disease activity.

In vitro and in vivo anti-Helicobacter/Campylobacter activity of the aqueous extract of Enantia chlorantha.

The aqueous extract of Enantia chlorantha Oliver (Annonaceae) stem bark, a plant widely used in Cameroon for the traditional treatment of gastritis and stomach problems, was assessed for in vitro and in vivo anti-Helicobacter/Campylobacter properties using the well diffusion assay, agar dilution assay, and killing rate determination. The in vitro activity was dose-dependent, and the same antimicrobial parameters (MAQ = 0.63 mg; MIC = 0.39 mg/mL; MBC = 1.56 mg/mL; ET(100) = 8 h) were obtained for both H. pylori and C. jejuni/coli. When the plasma active principle concentration equivalence was determined in vitro using plasma from rats exposed to a single dose (3000 mg/kg) of the extract, the peak absorption of E. chlorantha active principle against H. pylori occurred at 2 h. Plasma activity was nil 8 h after extract administration. The in vivo H. pylori eradication potency of the extract was assessed using mice infected with H. pylori. Antral mucus sample cultures from mice treated with E. chlorantha extract (500 and 1000 mg/kg for 3 days) did not yield any growth. The results suggest that in addition to its in vitro activity, E. chlorantha water extract also possesses in vivo antibiotic effects against H. pylori.