Mesophyll conductance to CO2 and Rubisco as targets for improving intrinsic water use efficiency in C3 plants.

Water limitation is a major global constraint for plant productivity that is likely to be exacerbated by climate change. Hence, improving plant water use efficiency (WUE) has become a major goal for the near future. At the leaf level, WUE is the ratio between photosynthesis and transpiration. Maintaining high photosynthesis under water stress, while improving WUE requires either increasing mesophyll conductance (gm ) and/or improving the biochemical capacity for CO2 assimilation-in which Rubisco properties play a key role, especially in C3 plants at current atmospheric CO2 . The goals of the present analysis are: (1) to summarize the evidence that improving gm and/or Rubisco can result in increased WUE; (2) to review the degree of success of early attempts to genetically manipulate gm or Rubisco; (3) to analyse how gm , gsw and the Rubisco's maximum velocity (Vcmax ) co-vary across different plant species in well-watered and drought-stressed conditions; (4) to examine how these variations cause differences in WUE and what is the overall extent of variation in individual determinants of WUE; and finally, (5) to use simulation analysis to provide a theoretical framework for the possible control of WUE by gm and Rubisco catalytic constants vis-à-vis gsw under water limitations.

Diffusional limitations explain the lower photosynthetic capacity of ferns as compared with angiosperms in a common garden study.

Ferns are thought to have lower photosynthetic rates than angiosperms and they lack fine stomatal regulation. However, no study has directly compared photosynthesis in plants of both groups grown under optimal conditions in a common environment. We present a common garden comparison of seven angiosperms and seven ferns paired by habitat preference, with the aims of (1) confirming that ferns do have lower photosynthesis capacity than angiosperms and quantifying these differences; (2) determining the importance of diffusional versus biochemical limitations; and (3) analysing the potential implication of leaf anatomical traits in setting the photosynthesis capacity in both groups. On average, the photosynthetic rate of ferns was about half that of angiosperms, and they exhibited lower stomatal and mesophyll conductance to CO2 (gm ), maximum velocity of carboxylation and electron transport rate. A quantitative limitation analysis revealed that stomatal and mesophyll conductances were co-responsible for the lower photosynthesis of ferns as compared with angiosperms. However, gm alone was the most constraining factor for photosynthesis in ferns. Consistently, leaf anatomy showed important differences between angiosperms and ferns, especially in cell wall thickness and the surface of chloroplasts exposed to intercellular air spaces.

Hepatic molecular responses to Bifidobacterium pseudocatenulatum CECT 7765 in a mouse model of diet-induced obesity.

BACKGROUND AND AIMS: Bifidobacterium pseudocatenulatum CECT 7765 moderates body weight gain and metabolic parameters in high-fat diet-(HFD)-fed mice but, the mechanisms of action are not yet understood. To further understand the effects of this bacterial strain, we have investigated the molecular changes in the liver of mice fed a HFD and supplemented with the bacteria. METHODS AND RESULTS: Gene expression and protein levels were measured in the liver of C57BL/6 male mice following sub-chronic consumption of a HFD and B. pseudocatenulatum CECT 7765. Our results show that the consumption of this bacterial strain modulated the expression of key genes involved in the regulation of energy metabolism and transport of lipids that were affected by the HFD.B. pseudocatenulatum CECT 7765 significantly counteracted the effects caused by the HFD on the fatty acid transporter CD36, the transcription regulator of lipid biosynthesis EGR1 and the regulators of glucose metabolism, IGFBP2 and PPP1R3B, both at the mRNA and protein levels. The bacterial strain slightly induced the transcript levels of PNPLA2, a lipase that hydrolyses triglycerides in lipid droplets. In the standard diet (SD)-fed mice, the administration of B. pseudocatenulatum CECT 7765 donwregulated the expression of INSIG1 and HMGCR critically involved in the regulation of cholesterol levels. CONCLUSION: B. pseudocatenulatum CECT 7765 modified the expression of key regulators of fatty acid and cholesterol metabolism and transport, lipid levels and glucose levels in the liver which supports the beneficial metabolic effects of this bacterial strain.

Characterization of workers or population percentage affected by low-back pain (LPB), sciatica and herniated disc due to whole-body vibrations (WBV).

Whole-body vibrations have several harmful effects on the population's health. The most suitable way to characterize the vibrations is to use the daily vibration exposure A (8) and Vibration Dose Value as specified in Directive 2002/44/EC. Therefore, based on the existing literature, we propose Probit equations that allow us to relate the population percentage affected by the vibration effects (low-back pain, sciatica, and herniated disc) with the A (8) and the Vibration Dose Value. It is worth noting that there is a good correlation between the experimental data and the expressions obtained, especially for low-back pain and herniated discs. Once the expressions have been validated, we analyze the limit values given in the aforementioned legislation, showing that the percentage of the affected population is significant for them. Therefore, this study also proposes new limits based on their own definitions, which are more in line with the results shown in the bibliography.

A prognostic model to identify short survival expectancy of medical oncology patients at the time of hospital discharge.

BACKGROUND: Hospitalization of cancer patients is associated with poor overall survival, but prognostic misclassification may lead to suboptimal therapeutic decisions and transitions of care. No model is currently available for stratifying the heterogeneous population of oncological patients after a hospital admission to a general Medical Oncology ward. We developed a multivariable prognostic model based on readily available and objective clinical data to estimate survival in oncological patients after hospital discharge. METHODS: A multivariable model and nomogram for overall survival after hospital discharge was developed in a retrospective training cohort and prospectively validated in an independent set of adult patients with solid tumors and a first admission to a unit of medical oncology. Performance of the model was assessed by C-index and Kaplan-Meier survival curves stratified by risk categories. RESULTS: From a population of 1089 patients with a first hospitalization, 757 patients were included in the training group [median survival, 43 weeks; 95% confidence interval (CI), 37-51 weeks] and 200 patients in the validation cohort (median survival, 44 weeks; 95% CI, 34 weeks-not reached). An accelerated failure time log-normal model was built, including five variables (primary tumor, stage, cause of admission, active treatment, and age). The C-index was 0.71 (95% CI, 0.69-0.73), with a good calibration, and adequate validation in the prospective cohort (C-index: 0.69; 95% CI, 0.65-0.74). Median survival in three predefined model-based risk groups was 10.7 weeks (high), 27.0 weeks (intermediate), and 3 years (low) in the training cohort, with comparable values in the validation cohort. CONCLUSIONS: In oncological patients, individualized predictions of survival after hospitalization were provided by a simple and validated model. Further evaluation of the model might determine whether its use improves shared decision making at discharge.

Lack of effect of oral administration of resveratrol in LPS-induced systemic inflammation.

PURPOSE: The high mortality index due to sepsis and the lack of an effective treatment requires the search for new compounds that can serve as therapy for this disease. Resveratrol, a well-known anti-inflammatory natural compound, might be a good candidate for the treatment of sepsis. The aim of this work was to study the effects of oral administration of resveratrol, before and after sepsis initiation, on inflammation markers in a murine model of endotoxin-induced sepsis. METHODS: Sprague-Dawley male rats were treated with resveratrol the 3 days prior to LPS administration and 45 min later. Hematological parameters, TNF-α, IL-1ß and CINC-1, FRAP and TBARS levels were determined. Resveratrol and resveratrol-derived metabolites profile in plasma was compared after oral and intraperitoneal administration. RESULTS: Oral treatment with resveratrol had no apparent systemic protective effects. However, resveratrol reduced the levels of lipid peroxidation in the small intestine and colon. Importantly, the administration of LPS caused a decrease in resveratrol absorption. When resveratrol bioavailability after i.p. administration was compared to that observed after oral administration, a different profile of resveratrol metabolites was found in plasma. CONCLUSION: These results highlight the importance of studying the bioavailability of the assayed compounds in the experimental models used to be able to choose the best route of administration depending on the target organ and to determine which compounds or derived metabolites are effective treating the studied disease.

[Objective KONTROL study: therapeutic inertia in hypertensive patients attended in primary care of Spain]. / Inercia terapéutica en pacientes hipertensos asistidos en atención primaria en España. Estudio Objetivo Kontrol.

OBJECTIVES: To determine the level of therapeutic inertia (TI), and the factors associated to the patient, doctor and the health organisation, in hypertensive patients treated in Primary Care (PC). DESIGN: Cross-sectional, multicentre study. SETTING: A sample of PC Teams from all over Spain. PARTICIPANTS: The study was conducted among PC doctors using a questionnaire and clinical records of 4 patients. MAIN MEASUREMENTS: The TI was calculated for each patient (TIp) as the proportion of visits in which there was no change in medication when this was indicated. RESULTS: A total of 543 PC doctors provided data on 2,032 patients, who fulfilled the indication of a change in requirement. There was TI In 77.8% of cases. The TIp observed was non-existent or low for 17.1% of the patients, intermediate for 42% and high for 40.8%. For the patients, the factors most associated with TIp were, age (P<.001), diabetes (P<.001), stroke (P<.01), obesity (P<.01) and a low education level (P<.001). To be female, be less than 40 years or more than 55 years, to be a family doctor with a training program other than MIR and to work in the public sector increased the probability of TIp (P<.001 for all the assumptions). CONCLUSIONS: The results of the study indicate that there is TI in 7 out every 10 visits made by hypertensive patients in Primary care. There are significant differences as regards the clinical characteristics of the patients and of the doctors.

Reasons for refusing diagnostic tests and therapeutic recommendations and associated complications in inherited heart diseases. The RELUCTANT study.

INTRODUCTION AND OBJECTIVES: Study of inherited heart diseases (IHD) involves performing diagnostic tests, which are sometimes inconvenient or stressful, in asymptomatic relatives. The aim of this study was to analyze refusal to undergo various diagnostic tests and follow therapeutic recommendations. METHODS: We assessed 1992 consecutive families with IHD to analyze refusal to undergo family screening. The study included 1539 individuals who were recommended to undergo cardiac magnetic resonance, and 837 who were recommended a drug challenge test. To study treatment refusal, we assessed 395 patients with an indication for an implantable cardioverter-defibrillator (ICD) and 402 patients with an indication for anticoagulation. RESULTS: A total of 28% of families who were recommended to undergo screening for suspected IHD did not attend, but refusal was lower if there was a family history of sudden cardiac death. In all, 23% did not undergo magnetic resonance, and the 2 main reasons were administrative problems (53%) and claustrophobia (18%). Refusal was more common in older people, women, symptomatic persons, individuals with arrhythmias, and relatives. Nearly one fifth (19%) did not take the drug challenge test, due to fear (46%) or administrative issues (25%). Refusal was more frequent in older individuals, asymptomatic persons, those with a history of arrhythmias, relatives, and those with a positive genetic study. Only a minority of patients rejected the treatments (5.1% ICD, 2.5% anticoagulation). The percentage of sudden cardiac death in persons rejecting ICD implantation was high (4.5% per year). CONCLUSIONS: One fifth of people attending screening for IHD refused to undergo more sophisticated and stressful tests. This study identified several independent predictors associated with refusal. Only a minority of high-risk patients refused treatments such as ICD implantation and anticoagulation.

[Evaluation of compliance with the antibiotic prophylaxis protocol in hysterectomy. Prospective cohort study]. / Evaluación de la adecuación al protocolo de profilaxis antibiótica en histerectomías. Estudio de cohortes prospectivo.

OBJECTIVE: Health care-related infections are a public health problem, among them surgical site infection (SSI) are the most frequent in hospitals. The objetive of this study was to assess the effect of the compliance to antibiotic prophylaxis protocol on the incidence of surgical site infection in hysterectomized patients. METHODS: A prospective cohort study was carried out between October 2009 and December 2018. The incidence of SSI was studied after a maximum period of 30 days from the moment of surgery. The degree of adequacy of antibiotic prophylaxis in hysterectomy and the effect of its inadequacy on the incidence of infection was evaluated using relative risk (RR) adjusted with a logistic regression model. RESULTS: A total of 1,025 interventions were studied in 1,022 women. The cumulative incidence of SSI was 2,1% (n = 22). The most frequent etiology of infection was Escherichia coli (23.1%) and Proteus mirabilis (23.1%). Antibiotic prophylaxis was indicated in 1,014 interventions (98.9%) being administered in 1,009 of them (99.5%). The adherence to the protocol was 92,5%. The main cause of non-compliance was the time of onset (40.9%), followed by the choice of the antibiotic (35.2%). The effect of inadequate prophylaxis on the incidence of infection was RR = 0.9; 95% CI 0.2-3.9; p> 0.05. CONCLUSIONS: The adequacy of antibiotic prophylaxis was very high, with a low incidence of surgical site infection. No association was found between adequacy of prophylaxis and incidence of infection in hysterectomy. The continuous improvement of epidemiological surveillance in gynecology should be emphasized.

[Evaluation of compliance with the antibiotic prophylaxis protocol in breast surgery and its effect on the incidence of surgical infection]. / Evaluación de la adecuación al protocolo de profilaxis antibiótica en cirugía de mama y su efecto sobre la incidencia de infección quirúrgica.

BACKGROUND: Antibiotic prophylaxis is one of the most effective ways to avoid surgical site infection (SSI). The present study evaluates compliance with the antibiotic prophylaxis protocol and the effect of non-compliance on the incidence of SSI in breast surgery. METHODS: A prospective cohort study was carried out from July 2008 to July 2018. It assessed the degree of compliance with antibiotic prophylaxis in breast surgery and the causes of non-compliance: choice of antibiotic, route of administration, time of onset, dose and duration. The incidence of SSI was studied during the 30 days after intervention (90 in the case of implants or prostheses). Relative risk (RR) was used to assess the effect of inadequate prophylaxis. RESULTS: We studied 1,328 interventions in 1,212 women. The cumulative incidence of SSI was 1.7% (n=22) and the most common etiology was Staphylococcus aureus (47.1%). Overall antibiotic prophylaxis protocol compliance was 95.3%, (including the 568 interventions where it was not indicated). The principle causes of non-compliance were the time of onset (46.8%) and choice of antibiotic (40.3%). Non-compliance significantly increased both incidence of SSI (8.1 vs 1.3%, p=0,003) and its risk (RR=6.5, CI95% 2.3-18.1). CONCLUSIONS: The overall protocol compliance rate was very high. Non-compliance with prophylaxis protocol at least doubled the risk of SSI in breast surgery.

Systemic phenotype of sarcoidosis associated with radiological stages. Analysis of 1230 patients.

BACKGROUND: To analyze the association between Scadding radiological stages of sarcoidosis at diagnosis and the disease phenotype (epidemiology, clinical presentation and extrathoracic involvement) in one of the largest cohorts of patients with sarcoidosis reported from southern Europe. METHODS: The SARCOGEAS-Study Group includes a multicenter database of consecutive patients diagnosed with sarcoidosis according to the WASOG 1999 criteria. Extrathoracic disease at diagnosis was defined according to the 2014 instrument and the clusters proposed by Schupp et al. RESULTS: We analyzed 1230 patients (712 female, mean age 47 yrs.) who showed the following Scadding radiologic stages at diagnosis: stage 0 (n = 98), stage I (n = 395), stage II (n = 500), stage III (n = 195) and stage IV (n = 42). Women were overrepresented in patients presenting with extrathoracic/extrapulmonary disease, while the diagnosis was made at younger ages in patients presenting with BHL, and at older ages in those presenting with pulmonary fibrosis (q values <0.05). Multivariable adjusted analysis showed that patients presenting with pulmonary involvement (especially those with stages II and III) had a lower frequency of concomitant systemic involvement in some specific extrathoracic clusters (cutaneous-adenopathic/musculoskeletal, ENT and neuro-ocular/OCCC) but a higher frequency for others (hepatosplenic), in comparison with patients with extrapulmonary involvement (stages 0 and I). The presence of either BHL or fibrotic lesions did not influence the systemic phenotype of patients with pulmonary involvement. CONCLUSIONS: The key determinant associated with a differentiated systemic phenotype of sarcoidosis at diagnosis was interstitial pulmonary involvement rather than the individual Scadding radiological stage.

Non-cardiac arterial disease in Catalonia: patient profiles and quality of clinical records by characteristics of the Vascular Surgery Unit.

AIM: Non-cardiac arterial disease (NCAD) is a frequent cause of hospital admission. The aim of this study was to investigate differences in patient profiles and clinical records as a function of the size of the Vascular Surgery Unit (VSU). METHODS: Retrospective observational study. Stratified cluster sampling and selection of patients hospitalized for NCAD. ANALYSIS: 1) description of patient profiles, quality of clinical records, and VSU [availability of diagnostic (DR) and therapeutic (TR) resources, and of written protocols (WP)]; 2) association between these variables and size of VSU. RESULTS: The sample consisted of 14 hospitals, 6 with a VSU of 15 or fewer beds (VSU < or = 15B) and 8 with >15 beds (VSU >15B). The mean number of DRs, TRs and WPs was 9, 2.8 and 2 in VSUs < or = 15B, and 11.5, 6.5 and 3.3 in VSUs >15B. The proportion of patients older than 70, female, with ischemic disease, or with coexisting diabetes was significantly higher in VSUs < or = 15B (67%, 31%, 95% and 57%, respectively) than in VSUs >15B (58%, 22%, 69% and 48%). Comorbid conditions and treatment during admission and at discharge were documented significantly less frequently in the clinical records in VSUs < or = 15B. Risk factors were under-reported in the clinical records of both types of VSU. CONCLUSION: Patient profiles and the quality of clinical records vary by size of VSU. Under-reporting of risk factors may hinder the implementation of prevention and treatment measures.

First clinical symptom as a prognostic factor in systemic sclerosis: results of a retrospective nationwide cohort study.

The objective of the study is to determine the importance of the mode of onset as prognostic factor in systemic sclerosis (SSc). Data were collected from the Spanish Scleroderma Registry (RESCLE), a nationwide retrospective multicenter database created in 2006. As first symptom, we included Raynaud's phenomenon (RP), cutaneous sclerosis, arthralgia/arthritis, puffy hands, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and digestive hypomotility. A total of 1625 patients were recruited. One thousand three hundred forty-two patients (83%) presented with RP as first symptom and 283 patients (17%) did not. Survival from first symptom in those patients with RP mode of onset was higher at any time than those with onset as non-Raynaud's phenomenon: 97 vs. 90% at 5 years, 93 vs. 82% at 10 years, 83 vs. 62% at 20 years, and 71 vs. 50% at 30 years (p < 0.001). In multivariate analysis, factors related to mortality were older age at onset, male gender, dcSSc subset, ILD, PAH, scleroderma renal crisis (SRC), heart involvement, and the mode of onset with non-Raynaud's phenomenon, especially in the form of puffy hands or pulmonary involvement. The mode of onset should be considered an independent prognostic factor in systemic sclerosis and, in particular, patients who initially present with non-Raynaud's phenomenon may be considered of poor prognosis.

Searching fundamental information in ordinary differential equations. Nondimensionalization technique.

Classical dimensional analysis and nondimensionalization are assumed to be two similar approaches in the search for dimensionless groups. Both techniques, simplify the study of many problems. The first approach does not need to know the mathematical model, being sufficient a deep understanding of the physical phenomenon involved, while the second one begins with the governing equations and reduces them to their dimensionless form by simple mathematical manipulations. In this work, a formal protocol is proposed for applying the nondimensionalization process to ordinary differential equations, linear or not, leading to dimensionless normalized equations from which the resulting dimensionless groups have two inherent properties: In one hand, they are physically interpreted as balances between counteracting quantities in the problem, and on the other hand, they are of the order of magnitude unity. The solutions provided by nondimensionalization are more precise in every case than those from dimensional analysis, as it is illustrated by the applications studied in this work.

[Differences in variables representative of cardiovascular disease or repercussion between subjects with high cardiovascular risk with and without any family history of early cardiovascular events]. / Diferencias en variables representativas de enfermedad o repercusión cardiovascular entre sujetos de alto riesgo cardiovascular con y sin antecedentes familiares de eventos cardiovasculares precoces.

UNLABELLED: INTRODUCTION, BASES AND AIMS: Study the possible associations between any family history of early heart disease and variables expressive of heart disease, lesion or repercussion in subjects of high cardiovascular risk. MATERIAL AND METHODS: Nationwide cross-sectional study with 2264 consecutive patients in the Outpatient Clinic of Internal Medicine 18 years of age or older and with high or extremely high cardiovascular risk taken from the CIFARC (Integral Control of High Risk Cardiovascular Factors) study run by the SEMI (Spanish Internal Medicine Association) cardiovascular Risk Group. We have studied the relationship between the presence or lack of same in family histories of early heart disease (AFP-Family History of early heart disease, hereafter FH) and different variables in the factors concerning cardiovascular risk and target organ lesion. The statistical treatment (Chi-2, ANOVA and Pearson s linear regression) was performed using the STATISTIX programme. RESULTS AND DISCUSSION: We observed a significative increase (p<0.05) in the group with FH with a percentage of the following variables: Total cholesterol>250 mg/dl, HDL<40 mg/dl, LDL>130 mg/dl, LVH (left ventricular hypertrophy), creatinine 1.2-2mg/dl, retinopathy I-II, serious retinopathy, smoking, proteinuria>300 mg/dl, kidney insufficiency and peripheral vascular disease. This significative increase in the variables under study appeared in males of over 55 years of age and in females of over 65 years of age; nevertheless, this increase in the incidence rate is becoming more common as of age 50 in males, with a maximum in both sexes after the age of 70. No significative differences were noted with regard to sex, BMI (Body Mass Index), atheromatosis, ischemic cardiopathy and cerebrovascular disease. On the whole, subjects of both sexes of the FH group have come to the clinic 3 years earlier than those of the group without FH. CONCLUSIONS: Patients with FH show a greater incidence of certain factors concerning heart risk and target organ lesion.

First month prednisone dose predicts prednisone burden during the following 11†months: an observational study from the RELES cohort.

AIM: To study the influence of prednisone dose during the first month after systemic lupus erythematosus (SLE) diagnosis (prednisone-1) on glucocorticoid burden during the subsequent 11 months (prednisone-2-12). METHODS: 223 patients from the Registro Español de Lupus Eritematoso Sistémico inception cohort were studied. The cumulative dose of prednisone-1 and prednisone-2-12 were calculated and recoded into a four-level categorical variable: no prednisone, low dose (up to 7.5 mg/day), medium dose (up to 30 mg/day) and high dose (over 30 mg/day). The association between the cumulative prednisone-1 and prednisone-2-12 doses was tested. We analysed whether the four-level prednisone-1 categorical variable was an independent predictor of an average dose >7.5 mg/day of prednisone-2-12. Adjusting variables included age, immunosuppressives, antimalarials, methyl-prednisolone pulses, lupus nephritis and baseline SLE Disease Activity Index (SLEDAI). RESULTS: Within the first month, 113 patients (51%) did not receive any prednisone, 24 patients (11%) received average low doses, 46 patients (21%) received medium doses and 40 patients (18%) received high doses. There was a strong association between prednisone-1 and prednisone-2-12 dose categories (p<0.001). The cumulative prednisone-1 dose was directly associated with the cumulative prednisone-2-12 dose (p<0.001). Compared with patients on no prednisone, patients taking medium (adjusted OR 5.27, 95% CI 2.18 to 12.73) or high-dose prednisone-1 (adjusted OR 10.5, 95% CI 3.8 to 29.17) were more likely to receive prednisone-2-12 doses of >7.5 mg/day, while patients receiving low-dose prednisone-1 were not (adjusted OR 1.4, 95% CI 0. 0.38 to 5.2). If the analysis was restricted to the 158 patients with a baseline SLEDAI of ≥6, the model did not change. CONCLUSION: The dose of prednisone during the first month after the diagnosis of SLE is an independent predictor of prednisone burden during the following 11 months.

Linear mixed irreversible inhibition of the autocatalytic activation of zymogens. Kinetic analysis checked by simulated progress curves.

Autocatalytic zymogen activation is a phenomenon of great importance for understanding some fundamental physiological processes involved in the enzyme regulation of gastrointestinal-tract enzymes, blood coagulation, fibrinolysis and the complement system. Examples of such processes are the activation of prekallikrein, trypsinogen and pepsinogen, all of which are controlled by natural proteinase inhibitors. This work studies the kinetics of a general autocatalytic zymogen activation process overlapped by two two-step irreversible inhibitions, i.e. a linear mixed irreversible inhibition. The kinetic equations for the whole course of the reaction are derived for this mechanism. In addition, we determine the corresponding kinetics for a number of particular cases of the general model analyzed, i.e. for reversible and irreversible non-competitive, competitive and uncompetitive inhibition systems which are considered particular cases of the general mechanism studied. The kinetic behavior of the system is related to a parameter, a dimensionless quantity, which shows whether the inhibition or the activation route prevails, in a similar way to that which we have previously carried out for other mechanisms. Finally, based on the kinetic equations obtained, a procedure for discriminating between the different mechanisms considered is suggested. The results of this contribution can be directly applied to most physiological autocatalytic zymogen activations in the presence of an inhibitor, allowing their complete kinetic characterization and suggesting procedures for varying the relative weight of the catalytic and inhibition routes or for changing the predominant route.

Intestinal release and uptake of phenolic antioxidant diferulic acids.

Diferulic acids are potent antioxidants and are abundant structural components of plant cell walls, especially in cereal brans. As such, they are part of many human and animal diets and may contribute to the beneficial effect of cereal brans on health. However, these phenolics are ester-linked to cell wall polysaccharides and cannot be absorbed in this form. This study provides the first evidence that diferulic acids can be absorbed via the gastrointestinal tract. The 5-5-, 8-O-4-, and 8-5-diferulic acids were identified in the plasma of rats after oral dosing with a mixture of the three acids in oil. Our study also reveals that human and rat colonic microflora contain esterase activity able to release 5-5-, 8-O-4-, and 8-5-diferulic acids from model compounds and dietary cereal brans, hence providing a mechanism for release of dietary diferulates prior to absorption of the free acids. In addition, cell-free extracts from human and rat small intestine mucosa exhibited esterase activity towards diferulate esters. Hence, we have shown that esterified diferulates can be released from cereal brans by intestinal enzymes, and that free diferulic acids can be absorbed and enter the circulatory system. Our results suggest that the phenolic antioxidant diferulic acids are bioavailable.

Superoxide scavenging by polyphenols: effect of conjugation and dimerization.

The superoxide anion scavenging capacity of two flavonols (quercetin and kaempferol) and some of their conjugates (quercetin-3-rhamnoglucoside, quercetin-3-sophoroside, quercetin-3-sulphate, quercetin-3-glucuronide, kaempferol-3-sophoroside, kaempferol-3-glucuronide) and of several hydroxycinnamic acids (caffeic acid, ferulic acid, 5-5 diferulic acid, 8-O-4 diferulic acid and 8-8 diferulic acid) were studied. Superoxide anions were generated non-enzymatically in a phenazine methosulphate-NADH system and assayed by reduction of nitro-blue tetrazolium. Among the flavonols examined, the most effective scavengers of superoxide anions were the sophoroside, glucuronide and rhamnoglucoside conjugates. Conversely, quercetin-3-sulphate and the flavonol aglycones, exhibited some pro-oxidant activity at the range of concentrations tested (0.5-10 microM). These results show that conjugation has a marked effect on the scavenging capacity of flavonols and that the type of conjugate at the 3-position determines the final superoxide scavenging capacity. Caffeic acid and ferulic acid showed no effect on the generation of superoxide anions by phenazine methosulphate-NADH. However, dimerization of ferulic acid enhanced the superoxide scavenging capacity of this hydroxycinnamic acid, but this depended on the type of linkage between the monomers. The order, from highest to lowest, of superoxide radical scavenging capacity for the dimers of ferulic acid was: 5-5-diferulic acid > 8-O-4-diferulic acid > 8-8-diferulic acid.