Anti-Helicobacter pylori Activity of Artemisia ludoviciana subsp. mexicana and Two of Its Bioactive Components, Estafiatin and Eupatilin.

Artemisia ludoviciana subsp. mexicana has been traditionally used for the treatment of digestive ailments such as gastritis, whose main etiological agent is Helicobacter pylori. In a previous screening study, the aqueous extract exhibited a good in vitro anti-H. pylori activity. With the aim of determining the efficacy of this species as a treatment for H. pylori related diseases and finding bioactive compounds, its aqueous extract was subjected to solvent partitioning and the fractions obtained were tested for their in vitro anti-H. pylori effect, as well as for their in vivo gastroprotective and anti-inflammatory activities. The aqueous extract showed a MIC = 250 µg/mL. No acute toxicity was induced in mice. A gastroprotection of 69.8 ± 3.8%, as well as anti-inflammatory effects of 47.6 ± 12.4% and 38.8 ± 10.2% (by oral and topical administration, respectively), were attained. Estafiatin and eupatilin were isolated and exhibited anti-H. pylori activity with MBCs of 15.6 and 31.2 µg/mL, respectively. The finding that A. ludoviciana aqueous extract has significant anti-H. pylori, gastroprotective and anti-inflammatory activities is a relevant contribution to the ethnopharmacological knowledge of this species. This work is the first report about the in vivo gastroprotective activity of A. ludoviciana and the anti-H. pylori activity of eupatilin and estafiatin.

Anti-Helicobacter pylori Potential of Three Edible Plants Known as Quelites in Mexico.

"Quelites" are edible plants that are part of the traditional agro-ecosystems in Mexico. These plants, despite their already known nutritional properties, are now considered neglected and underutilized species. With the objective of promoting their reinsertion in the markets and mainly, in daily diets, efforts have been made to study them from multidisciplinary approaches to demonstrate their beneficial properties. To generate evidence of an added health-promoting value that would encourage quelites consumption, in the present work, the anti-Helicobacter pylori activity of three representative quelite species, Anoda cristata (Alache), Cnidoscolus aconitifolius (Chaya), and Crotalaria pumila (Chepil), was tested. H. pylori is considered the etiological agent of gastritis, ulcer, and gastric cancer, and represents a public health problem in Mexico and worldwide. Aqueous (AQ) and dichloromethane-methanol (DM) extracts were obtained from the three species of quelites to investigate their effect on H. pylori growth and on two of its colonization factors (adherence and urease activity). DM extracts from Chaya, Chepil, and Alache exert the best inhibitory effect on bacterial growth, with minimum inhibitory concentrations of 62.5, 125, and 250 µg/mL, respectively. AQ and DM extracts inhibit bacterial adhesion by 30% to 50%. None of them has an effect on urease activity. The two flavonoids present in A. cristata, acacetin and diosmetin, inhibit H. pylori growth by ∼90% with 3.9 µg/mL. These results provide new information about the anti-H. pylori potential of three edible quelites, and give an added value, since their routine consumption may impact on the prevention and/or control of H. pylori-associated diseases.

Gastroprotective Mechanism and Ulcer Resolution Effect of Cyrtocarpa procera Methanolic Extract on Ethanol-Induced Gastric Injury.

Gastric ulcers are a worldwide health problem and their poor healing is one of the most important causes for their recurrence. We have previously reported the remarkable gastroprotective and anti-Helicobacter pylori activities of the methanolic extract (CpMet) of Cyrtocarpa procera bark. This work investigates, in a murine model, the CpMet gastroprotective mechanism and establishes its preclinical efficacy in the resolution of ethanol-induced gastric ulcers. The results showed that the gastroprotective activity of CpMet is mainly associated with endogenous NO and prostaglandins, followed by sulfhydryl groups and KATP channels. Furthermore, CpMet (300 mg/kg, twice a day) orally administered during 20 consecutive days promoted an ulcer area reduction of 62.65% at the 20th day of the treatment. The effect was confirmed macroscopically by the alleviation of gastric mucosal erosions and microscopically by an increase in mucin content and a reduction in the inflammatory infiltration at the site of the ulcer. No clinical symptoms or signs of toxicity were observed in the treated animals. The results indicate the safety and efficacy of CpMet in promoting high quality of ulcer healing by different mechanisms, but mostly through cytoprotective and anti-inflammatory effects, making it a promising phytodrug for ulcer treatment.

Multiple functions of syncytiotrophoblast mitochondria.

The human placenta plays a central role in pregnancy, and the syncytiotrophoblast cells are the main components of the placenta that support the relationship between the mother and fetus, in apart through the production of progesterone. In this review, the metabolic processes performed by syncytiotrophoblast mitochondria associated with placental steroidogenesis are described. The metabolism of cholesterol, specifically how this steroid hormone precursor reaches the mitochondria, and its transformation into progesterone are reviewed. The role of nucleotides in steroidogenesis, as well as the mechanisms associated with signal transduction through protein phosphorylation and dephosphorylation of proteins is discussed. Finally, topics that require further research are identified, including the need for new techniques to study the syncytiotrophoblast in situ using non-invasive methods.

Risk for incident arterial or venous vascular events varies over the course of systemic lupus erythematosus.

OBJECTIVE: We describe the pattern of incidence of thrombovascular events after diagnosis of systemic lupus erythematosus (SLE) in a cohort of lupus patients. METHODS: Descriptive study of prospectively collected data using incidence rates of thrombovascular events and 95% confidence intervals (CI) calculated for predetermined periods of observation. Kaplan-Meier survival curves were plotted to estimate thrombovascular event-free survival. RESULTS: Among 426 individuals, person-years contributed were as follows: 399 persons and 4356.0 person-years for all events; 417 persons and 4691.9 person-years for arterial events; and 408 persons and 4846.6 person-years for venous events. The incidence of thrombovascular events was highest during the first year after SLE diagnosis (4.00, 95% CI 2.24-6.59) and after 20 years (ranging from 3.32, 95% CI 1.52-6.30, to 4.99, 95% CI 0.60-18.01), and was lowest between 1 and 5 years after SLE diagnosis (1.00, 95% CI 0.53-1.72). A similar pattern was observed for arterial events, while venous events showed a higher incidence rate only in the first 30 days after SLE diagnosis (12.06, 95% CI 3.29-30.87) and remained low afterwards. The probabilities of remaining event-free at 5, 10, and 15 years were as follows: 0.92, 0.85, and 0.78, respectively, for all thrombovascular events; 0.95, 0.88, and 0.82, respectively, for arterial events; and 0.98, 0.95, and 0.94, respectively, for venous events. CONCLUSION: Thrombovascular events occur throughout the course of lupus, with the highest risk of arterial or venous events in the first year after diagnosis, and the pattern of occurrence varying thereafter.

Antiphospholipid antibodies and thrombosis: association with acquired activated protein C resistance in venous thrombosis and with hyperhomocysteinemia in arterial thrombosis.

Although antiphospholipid antibodies (aPL) are associated with thrombosis, it is not known who with aPL is at higher risk for thrombosis. It was the aim of this cross-sectional study to investigate how thrombophilic factors contribute to venous or arterial thrombosis in aPL-positive individuals. In outpatient test centres at two tertiary care hospitals, two hundred and eight (208) persons requiring aPL testing were matched by age, gender and centre to 208 persons requiring a complete blood count. Persons were classified as aPL-positive (having anticardiolipin, lupus anticoagulant and/or anti-beta(2)-glycoprotein I antibodies) or aPL-negative. Several thrombophilic factors were studied using logistic regression modelling. Results showed that the aPL-positive group had three-fold more events (37%) than the aPL-negative group (12%). In unadjusted analyses, clinically important associations were observed between factor V Leiden and venous thrombosis, hyperhomocysteinemia and arterial thrombosis, and activated protein C resistance (APCR) and venous thrombosis (OR, 95% CI = 4.00, 1.35-11.91; 4.79, 2.03-11.33; and 2.03, 1.03-3.97, respectively). After adjusting for recruitment group, persons with both APCR and aPL had a three-fold greater risk (OR, 95% CI = 3.31, 1.30-8.41) for venous thrombosis than those with neither APCR nor aPL. Similarly, after adjusting for hypertension, family history of cardiovascular disease, gender and recruitment group, persons with both hyperhomocysteinemia and aPL had a five-fold increased risk (OR, 95% CI = 4.90, 1.37-17.37) for arterial thrombosis compared to those with neither risk factor. In conclusion, APCR phenotype and hyperhomocysteinemia are associated with a higher risk of venous and arterial thrombosis, respectively, in the presence of aPL.

The presence of multiple prothrombotic risk factors is associated with a higher risk of thrombosis in individuals with anticardiolipin antibodies.

OBJECTIVE: To explore the effect of multiple prothrombotic risk factors in individuals with anticardiolipin antibodies (aCL), we evaluated immunologic, coagulation, and genetic prothrombotic abnormalities in a cohort of individuals with different aCL titers. METHODS: We recruited 87 individuals into 4 categories (normal, low, intermediate, or high) based on their baseline IgG aCL (aCL-IgG) titers. We measured at followup: repeat aCL-IgG, IgM aCL (aCL-IgM), antibodies to beta2-glycoprotein I (anti-beta2-GPI), lupus anticoagulant (LAC) antibodies, protein C, protein S, activated protein C resistance, factor V506 Leiden mutation, methyl tetrahydrofolate reductase (MTHFR) C677T genotype, and prothrombin 20210A gene mutation. Thrombotic events were confirmed. RESULTS: At recruitment, 20 individuals were negative for aCL-IgG and 67 were positive (22 low, 20 intermediate, and 25 high titer). Twenty of the 87 participants had experienced a previous thrombotic event: 4 in the aCL-IgG negative group and 16 in the aCL-IgG positive group. Among the 87 individuals, the number of those with concomitant prothrombotic risk factors was as follows: 5 had no other prothrombotic risk factors, 32 had 1 risk factor, 24 had 2 risk factors, 10 had 3 risk factors, 10 had 4 risk factors, and 6 had 5 risk factors. Thrombotic events were observed in 20%, 13%, 33%, 10%, 30%, and 50% of these groups, respectively, and the odds ratio associated with a previous thrombotic event was 1.46 per each additional prothrombotic risk factor (95% confidence interval: 1.003-2.134). CONCLUSION: In individuals with positive aCL-IgG, we observed an association between the number of prothrombotic risk factors and history of thrombotic events.

Thromboembolic risk in patients with high titre anticardiolipin and multiple antiphospholipid antibodies.

Asymptomatic antiphospholipid antibody (aPL) carriers with high risk for thrombosis may benefit from preventive anticoagulation. It was our objective to test whether the risk of thrombosis increases with: 1). increasing titres of anticardiolipin antibodies (aCL) after adjustment for other cardiovascular risk factors and 2). the number of aPL detected. In a cross-sectional study, blood was collected from clinics in two teaching hospitals. The study included 208 individuals suspected of having an aPL and 208 age- and sex-matched controls having blood drawn for a complete blood count. Clinical variables included history of previous arterial (ATE) or venous (VTE) thrombotic events, traditional risk factors for cardiovascular disease, and systemic lupus erythematosus (SLE). Laboratory variables included IgG/IgM aCL, lupus anticoagulant, and IgG/IgM anti-beta2-glycoprotein I. Mean age was 46.5 years and 83% were female. Seventy-five of the 416 participants had >or= 1 aPL, and 69 had confirmed >or= 1 ATE or VTE. Family history was positive in 48% of participants, smoking in 28%, hypertension in 16%, diabetes in 6%, and SLE in 20%. A 10-unit increase in aCL IgG titre was associated with an odds ratio (OR) [95% CI] of 1.07 [1.01-1.13] for ATE and 1.06 [1.02-1.11] for VTE. The odds of a previous thrombosis increased with each additional aPL detected: 1.5 [0.93-2.3] for ATE and 1.7 [1.1-2.5] for VTE. These results indicate that increased titres of aCL and multiple aPL were associated with an increased risk of a previous thrombotic event.

Organ manifestations influence differently the responsiveness of 2 lupus disease activity measures, according to patients' or physicians' evaluations of recent lupus activity.

OBJECTIVE: To determine (1) which organ system manifestations contribute to the overall responsiveness of the Systemic Lupus Activity Measure (SLAM, revised 1991 with minor modifications as SLAM-R) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and (2) whether responsive items differ for physicians and patients. METHODS: Blinded data were obtained from repeated visits of 76 patients in the Study of Methotrexate in Lupus Erythematosus. At each visit, physicians and patients reported improvement, no change, or deterioration, and physicians then completed SLAM-R and SLEDAI. Items in SLAM-R and SLEDAI were grouped by organ system. The generalized estimating equations approach was used to measure associations between change in organ system activity and physician or patient perception of change in overall disease activity. The outcomes assessed, in separate analyses, were improvement and deterioration from the previous visit. RESULTS: Seventy-six patients contributed a total of 471 observations. The strongest correlates of physician-reported improvement were decreased constitutional, gastrointestinal (GI), and musculoskeletal involvement (components of SLAM-R), and decreased musculoskeletal (MSK) and central nervous system involvement (SLEDAI). Improvement reported by patients was most strongly associated with decreases in erythrocyte sedimentation rate and MSK and reticuloendothelial activity (SLAM-R), and in MSK activity (SLEDAI). Increased integument and MSK subscores (SLAM-R) and serosal and MSK subscores (SLEDAI) were associated with overall deterioration reported by physicians. Patient-reported deterioration was associated with increased GI subscores (SLAM-R) and with no changes in organ system involvement in SLEDAI. CONCLUSION: Organ systems associated with reported change in overall SLE activity differed between SLAM-R and SLEDAI, between patients and physicians, and between each direction of change.

Comparison of the responsiveness of lupus disease activity measures to changes in systemic lupus erythematosus activity relevant to patients and physicians.

Both the revised Systemic Lupus Activity Measure (SLAM-R) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) are valid and reliable measures of disease activity in systemic lupus erythematosus (SLE). However, more study of their responsiveness is needed. The purpose of this study was to compare the responsiveness of SLAM-R and SLEDAI to disease activity changes relevant to physicians and patients. Patients were evaluated monthly for up to 12 months. At each visit, the physician completed SLAM-R and SLEDAI. Patients and physicians assessed whether relevant improvement or worsening of disease activity had occurred since the previous visit. Based on repeated measurements, effect size (ES), standardized response mean (SRM), and control-standardized response mean (CSRM) were calculated for each response category, with bootstrap-based 95% confidence intervals (CIs). Seventy-six patients contributed 471 score changes. For physicians' responses, the CSRMs for SLAM-R and SLEDAI were -0.47 versus -0.42 for improvement, 0.04 versus 0.003 for no change, and 0.65 versus 0.66 for deterioration. For patients, the CSRMs for SLAM-R and SLEDAI were -0.31 versus -0.18 for improvement, -0.08 versus 0.06 for no change, and 0.48 versus 0.05 for deterioration. Only for SLAM-R did the 95% CIs exclude zero when improvement or deterioration were detected. Similar results were found for ES and SRM. Both SLAM-R and SLEDAI are responsive to changes in SLE disease activity important to physicians. Only SLAM-R is responsive to changes important to patients. These differences may result from the inclusion of subjective SLE manifestations in SLAM-R.