Unveiling the tartrazine binding mode with ds-DNA by UV-visible spectroscopy, electrochemical, and QM/MM methods.

Here, we studied the interaction between the food colorant tartrazine (TZ) and double stranded DNA (dsDNA), using spectroscopic, electrochemical, and computational methods such as QM/MM combined with TD-DFT. Despite the UV-vis spectroscopy is widely used to study the interaction between molecules, for the case of TZ there are discrepancies in the analyses presented in the literature available, presenting both hyperchromic and hypochromic effects and consequently different rationalizations for their results. Herein we propose the combination of UV-vis experiments with the design of high-level computational models capable of reproducing the experimental behavior to finally define the proper binding mode at the molecular scale together with the rationalization of the experimental optical response due to the complex formation. To complement the UV-vis experiments, we propose the use of electrochemical measurements, to support the results obtained through UV-vis spectroscopy, as it has been successfully used for the determination of interaction modes between small molecules and biomolecules in any condition. Our UV-vis spectroscopy experiments showed only a hypochromic effect of the absorption spectra of TZ after interaction with DNA, indicative of TZ being deeply buried in the DNA structure. The effect of ionic strength in the experimental procedures led to the dissociation of TZ, thus indicating that the interaction mode was groove binding. On the other hand, the electrochemical studies showed an irreversible reduction peak of TZ, which after the interaction with DNA exhibited a positive shift in potential that can be attributed to groove binding. The binding constant for TZ-DNA was calculated as 4.45x104M-1 (UV-vis) and 5.75x104M-1 (electrochemistry), in line with other groove binder azo dyes. Finally, through the QM/MM calculations we found that the minor-groove binding mode interacting in zones rich in adenine and thymine was the model best suited to reproduce the experimental UV-vis response.

Percutaneous plate fixation of displaced proximal humerus fractures: Do minimally invasive techniques improve outcomes and reduce complications?

OBJECTIVE: The aim of this study was to analyze the outcomes and complications of minimally invasive plate osteosynthesis (MIPO) for displaced proximal humerus fractures and elucidate if the percutaneous technique reduces the rate of avascular necrosis (AVN) without jeopardizing fracture reduction. MATERIAL AND METHODS: 118 patients with a displaced proximal humerus fracture were treated with a polyaxial locking-plate through a standardized percutaneous approach. 73 % were women and mean age was 63 years (18-89) with an average follow-up of 51 months (12-256). There were 32 two-part fractures (27 %), 57 three-part fractures (48 %) and 24 four-part fractures (25 %). Shoulder function at the last follow-up, including ROM and ability to perform daily living activities, was objectively evaluated with an adjusted Constant Score (CS). Subjective patient satisfaction was rated with an Visual Analogic Scale from 0 to 10 and the degree of residual pain with a Verbal Rating Scale (VRS). Radiographic analysis at the most recent follow-up evaluated the presence of AVN, degree of residual medial calcar displacement, and the cervicodiaphiseal angle. RESULTS: Forty patients (34 %) had a complication, 25 of them (21 %) requiring further surgery. ROM at the last follow-up was 131° of elevation (40°-180°), 38° of external rotation (SD: 17.7) and internal rotation to L3. Average adjusted Constant Score was 68 (SD: 17.76). Twenty-one patients (18 %) complained of shoulder pain (14 moderate and 7 severe) and seven were not satisfied. Radiographically, 29 patients (25 %) had varus malunion and 17 patients (14 %) showed some degree of AVN. Patients with varus malunion (CS 64.3 versus 69.8, p = 0.16) and AVN (CS 56.9 versus 70.4, p = 0.005) had lower CS. The presence of a varus malunion was directly related to the degree of initial medial calcar displacement (p = 0.001) and deficient calcar reduction at surgery (p = 0.004). AVN was statistically more prevalent when the medial calcar was inadequately reduced (p = 0.01). CONCLUSIONS: MIPO surgery for proximal humerus fractures through an anterolateral approach does not reduce the rate of mechanical complications or AVN compared with standard ORIF techniques. Moreover, percutaneous plating may preclude adequate medial calcar reduction, leading to humeral head malunion and a worse clinical outcome.

Cancer diagnosis in Catalonia (Spain) after two years of COVID-19 pandemic: an incomplete recovery.

BACKGROUND: This study aimed to estimate potential undetected cancers over the first 2 years of the COVID-19 pandemic in Catalonia. METHODS: Cancer incidence was compared between pre-pandemic (2019) and pandemic (March 2020-January 2022) periods in the Catalan Pathology Registry (CPR) according to sex, age, and tumor site. The correlation between cancer diagnosis and COVID-19 health care workload was also evaluated by means of the Pearson's correlation coefficient (R). The expected incident cancers (E) during the pandemic were estimated by applying 2019 CPR cancer incidence specific rates by sex and 5-year age groups to the 2020 and 2021 Catalan population pyramids. CPR incident cancers were considered observed (O). Standardized incidence ratios (SIR) and 95% confidence intervals (CIs) were calculated using the O/E ratio. RESULTS: After two pandemic years, cancer diagnosis decreased by 12% (SIR 0.88, 95% CI 0.87-0.89), or ∼7700 undetected cancers (13 000 with nonmelanoma skin cancer). Without nonmelanoma skin cancer, 72% of the cancer underdiagnosis was generated in 2020. Diagnoses decreased more in men (whole pandemic -14%; 2020 -21%; 2021 -8%) than in women (-9%, -19%, -3%, respectively), dropping significantly overall in all pandemic waves but the fifth (first -37%, second -16%, third -8%, fourth -6%, fifth -2%, sixth -6%), and across all adult age groups. In the first wave, CPR cancer diagnosis was inversely correlated with COVID-19 caseload in primary care (R -0.91, 95% CI -0.97 to -0.75) and occupancy in conventional hospital wards (R -0.91, 95% CI -0.99 to -0.48) and intensive care (R -0.91, 95% CI 95% -0.98 to -0.70). CONCLUSIONS: Our study evaluated the overall pandemic impact on cancer diagnosis on a large scale and with minimal selection bias, showing that as of February 2022, cancer detection in Catalonia had not yet recovered to pre-pandemic levels. Pending cancer incidence data from population-based cancer registries, early CPR data could inform the development of Spanish cancer control plans.

FAIR data sharing: The roles of common data elements and harmonization.

The value of robust and responsible data sharing in clinical research and healthcare is recognized by patients, patient advocacy groups, researchers, journal editors, and the healthcare industry globally. Privacy and security concerns acknowledged, the act of exchanging data (interoperability) along with its meaning (semantic interoperability) across studies and between partners has been difficult, if not elusive. For shared data to retain its value, a recommendation has been made to follow the Findable, Accessible, Interoperable, Reusable (FAIR) principles. Without applying appropriate data exchange standards with domain-relevant content standards and accessible rich metadata that uses applicable terminologies, interoperability is burdened by the need for transformation and/or mapping. These obstacles to interoperability limit the findability, accessibility and reusability of data, thus diminishing its value and making it impossible to adhere to FAIR principles. One effort to standardize data collection has been through common data elements (CDEs). CDEs are data collection units comprising one or more questions together with a set of valid values. Some CDEs contain standardized terminology concepts that define the meaning of the data, and others include links to unique terminology concept identifiers and unique identifiers for each CDE; however, usually CDEs are defined for specific projects or collaborations and lack traceable or machine readable semantics. While the name implies that these are 'common', this has not necessarily been a requirement, and many CDEs have not been commonly used. The National Institutes of Health (NIH) CDEs are, in fact, a conglomerate of CDEs developed in silos by various NIH institutes. Therefore, CDEs have not brought the anticipated benefit to the industry through widescale interoperability, nor is there widespread reuse of CDEs. Certain institutes in the NIH recommend, albeit do not enforce, institute-specific preferred CDEs; however, at the NIH level a preponderance of choice and a lack of any overarching harmonization of CDEs or consistency in linking them to controlled terminology or common identifiers create confusion for researchers in their efforts to identify the best CDEs for their protocol. The problem of comparing data among studies is exacerbated when researchers select different CDEs for the same variable or data collection field. This manuscript explores reasons for the disappointingly low adoption of CDEs and the inability of CDEs or other clinical research standards to broadly solve the interoperability and data sharing problems. Recommendations are offered for rectifying this situation to enable responsible data sharing that will help in adherence to FAIR principles and the realization of Learning Health Systems for the sake of all of us as patients.

Detection of incident breast and colorectal cancer cases from an administrative healthcare database in Catalonia, Spain.

OBJECTIVE: To validate the Catalan minimum basic data set (MBDS) of hospital discharges as an information source for detecting incident breast (BC) and colorectal cancer (CRC), against the Hospital del Mar Cancer Registry (RTHMar) in Barcelona (Spain) as the gold standard. METHODS: Using ASEDAT software (Analysis, Selection and Extraction of Tumour Data), we identified Catalan public hospital discharge abstracts in patients with a first-time diagnosis of BC and CRC in the years 2005, 2008, and 2011, aggregated by unique patient identifiers and sorted by date. Once merged with the RTHMar database and anonymized, tumour-specific algorithms were validated to extract data on incident cases, tumour stage, surgical treatment, and date of incidence. RESULTS: MBDS had a respective sensitivity and positive predictive value (PPV) of 78.0% (564/723) and 90.5% (564/623) for BC case detection; and 83.9% (387/461) and 94.9% (387/408) for CRC case detection. The staging algorithms overestimated the proportion of local-stage cases and underestimated the regional-stage cases in both cancers. When loco-regional stage and surgery were combined, sensitivity and PPV reached 98.3% and 99.8%, respectively, for BC and 96.4% and 98.4% for CRC. The differences between dates of incidence between RTHMar and MBDS were greater for BC cases without initial surgery, whereas they were generally smaller and homogeneous for CRC cases. CONCLUSIONS: The MBDS is a valid and efficient instrument to improve the completeness of a hospital-based cancer registry (HBCR), particularly in BC and CRC, which require hospitalization and are predominantly surgical.

Immunomodulatory tetracyclines shape the intestinal inflammatory response inducing mucosal healing and resolution.

BACKGROUND AND PURPOSE: Immunomodulatory tetracyclines are well-characterized drugs with a pharmacological potential beyond their antibiotic properties. Specifically, minocycline and doxycycline have shown beneficial effects in experimental colitis, although pro-inflammatory actions have also been described in macrophages. Therefore, we aimed to characterize the mechanism behind their effect in acute intestinal inflammation. EXPERIMENTAL APPROACH: A comparative pharmacological study was initially used to elucidate the most relevant actions of immunomodulatory tetracyclines: doxycycline, minocycline and tigecycline; other antibiotic or immunomodulatory drugs were assessed in bone marrow-derived macrophages and in dextran sodium sulfate (DSS)-induced mouse colitis, where different barrier markers, inflammatory mediators, microRNAs, TLRs, and the gut microbiota composition were evaluated. The sequential immune events that mediate the intestinal anti-inflammatory effect of minocycline in DSS-colitis were then characterized. KEY RESULTS: Novel immunomodulatory activity of tetracyclines was identifed; they potentiated the innate immune response and enhanced resolution of inflammation. This is also the first report describing the intestinal anti-inflammatory effect of tigecycline. A minor therapeutic benefit seems to derive from their antibiotic properties. Conversely, immunomodulatory tetracyclines potentiated macrophage cytokine release in vitro, and while improving mucosal recovery in colitic mice, they up-regulated Ccl2, miR-142, miR-375 and Tlr4. In particular, minocycline initially enhanced IL-1ß, IL-6, IL-22, GM-CSF and IL-4 colonic production and monocyte recruitment to the intestine, subsequently increasing Ly6C- MHCII+ macrophages, Tregs and type 2 intestinal immune responses. CONCLUSIONS AND IMPLICATIONS: Immunomodulatory tetracyclines potentiate protective immune pathways leading to mucosal healing and resolution, representing a promising drug reposition strategy for the treatment of intestinal inflammation.

Immunomodulatory tetracyclines ameliorate DNBS-colitis: Impact on microRNA expression and microbiota composition.

OBJECTIVE: The use of immunomodulatory antibiotics to simultaneously target different factors involved in intestinal inflammatory conditions is an interesting but understudied pharmacological strategy. A great therapeutic potential has been obtained with minocycline and doxycycline in experimental colitis. Therefore, understanding the contribution of the different activities of immunomodulatory tetracyclines is crucial for the improvement and translation of their use into clinic. DESIGN: A comparative pharmacological study including tetracyclines and other antibiotic or immunomodulatory drugs was performed in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice. The correlation between the therapeutic efficacy of each drug and changes in the gut microbiota composition, markers of barrier integrity, inflammatory mediators, microRNAs and TLRs was analysed to identify the main mechanisms of action. RESULTS: Tetracyclines counteracted most of the markers found altered in DNBS-colitis, which differed from effects of corticosteroid treatment. Of note, administration of tetracyclines led to increased mucosal protection, associated with up-regulated expression of CCL2, miR-142 and miR-375. All drugs with antibiotic activity ameliorated the progression of inflammation and reduced neutrophil-related genes, such as miR-223, despite their effects were not associated with restored intestinal dysbiosis. However, reduced bacterial richness was correlated with increased expression of TLR2 and TLR9 in antibiotic-treated groups and TLR6 was also up-regulated by the immunomodulatory tetracyclines with higher efficacy (doxycycline, minocycline and tigecycline). CONCLUSION: The anti-inflammatory effect of tetracyclines involves specific modifications in TLR and microRNA expression leading to an improved microbial-derived signalling and mucosal protection. These results support the potential of immunomodulatory tetracyclines to prevent inflammation-associated tissue damage in acute intestinal inflammation.

Endoscopic Treatment for Vesicoureteral Reflux in Recurrent Urinary Tract Infections in Kidney Transplant: Experience of One Center.

Vesicoureteral reflux (VUR) after renal transplantation in adult patients has been reported. In renal transplant recipients, symptomatic urinary tract infection can cause high morbidity despite improved immunosuppressive and antibiotic treatment. In our country there have been few reported cases about use of copolymer of dextranomer and hyaluronic acid (DX-HA) injection in a renal transplant. We present 3 cases of recurrent or complicated infections with evidence of high-grade VUR, which were treated with DX-HA. Only 1 case had a partial remission; however, there were no episodes of urinary tract infection in 12 months of follow-up. Suburethral injection is an endoscopic treatment modality with low morbidity in our country.

Michael addition of carbonyl compounds to nitroolefins under the catalysis of new pyrrolidine-based bifunctional organocatalysts.

Novel bifunctional pyrrolidine-based organocatalysts for the asymmetric Michael addition of carbonyl compounds to nitroolefins have been synthesised from homoallylamines, which are easily obtained from (R)-glyceraldehyde as a chiral precursor. Under optimal reaction conditions, these bifunctional organocatalysts showed a high catalytic efficiency (almost quantitative yield in most cases) and stereoselectivity in the Michael addition reactions of a variety of aldehydes (up to 98 : 2 dr and 97% ee) and ketones (up to 98 : 2 dr and 99% ee) to nitroolefins.

Menos no es más, pero puede ser el principio del cambio / Less is not more, but it can be the beginning of the change

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Reoperations after primary breast conserving surgery in women with invasive breast cancer in Catalonia, Spain: a retrospective study

Background. Although complete tumor resection is accepted as the best means to reduce recurrence, reoperations after lumpectomy are a common problem in breast cancer. The aim of this study was to assess the reoperation rates after primary breast conserving surgery in invasive breast cancer cases diagnosed in Catalonia, Spain, between 2005 and 2011 and to identify variations based on patient and tumour characteristics. Methods. Women with invasive incident breast cancer identified from the Patient’s Hospital Discharge Database [174.0-174.9 codes of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) as the primary diagnosis] and receiving primary breast conserving surgery were included in the study and were followed up to 3 and 12 months by collecting information about repeat breast cancer surgery. Results. Reoperation rates after primary breast conserving surgery decreased from 13.0 % in 2005 to 11.7 % in 2011 at 3 months and from 14.2 % in 2005 to 12.9 % in 2011 at 12 months’ follow-up. While breast conservation reoperations saw a slight, non-significant increase in the same period (from 5.7 to 7.3 % at 3 months, and from 6.0 to 7.5 % at 12 months), there was a significant decrease in radical reoperation (from 7.3 to 4.4 % at 3 months and from 8.2 to 5.4 % at 12 months). Overall, additional breast surgeries decreased among younger women. Conclusions. Despite the rise of breast conserving surgery, reoperation rates following initial lumpectomy in Catalonia decreased by 10 % at 3 and 12 months’ follow-up, remaining low and almost unchanged. Ultimately, there was also a significant decrease in mastectomies (AU)

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Lack of adherence to SHEA-IDSA treatment guidelines for Clostridium difficile infection is associated with increased mortality.

OBJECTIVES: The objective of this study was to determine our institution's compliance with 2010 Society for Healthcare Epidemiology of America and IDSA Clostridium difficile infection (CDI) treatment guidelines and their respective outcomes. METHODS: We collected clinical parameters, laboratory values, antibiotic therapy and clinical outcomes from the electronic medical records for all patients hospitalized at our institution with a diagnosis of CDI from December 2012 to November 2013. We specifically evaluated whether SHEA-IDSA treatment guidelines were followed and evaluated the associations between guideline adherence and severe outcomes including mortality. RESULTS: We identified 230 patients with CDI meeting inclusion criteria during the study period. Of these, 124 (54%) were appropriately treated, 46 (20%) were under-treated and 60 (26%) were over-treated. All-cause 90 day mortality was 17.4% overall; 43.5% in the under-treated group versus 12.9% in those appropriately treated (P < 0.0001) and 10.9% in those appropriately treated plus over-treated (P < 0.0001). Similarly, 90 day mortality attributed to CDI was 21.7% in those under-treated versus 8.9% in those appropriately treated (P = 0.03) and 8.2% in those either appropriately treated or over-treated (P = 0.015). Severe-complicated CDI occurred in 46 patients. In this subgroup, there was a non-significant trend towards increased mortality in under-treated patients (56.7%) compared with appropriately treated patients (37.5%, P = 0.35). Under-treatment was also associated with a higher rate of CDI-related ICU transfer (17.4% versus 4.8% in those appropriately treated, P = 0.023). CONCLUSIONS: Adherence to CDI treatment guidelines is associated with improved outcomes especially in those with severe disease. Increased emphasis on provision of appropriate, guideline-based CDI treatment appears warranted.

Reoperations after primary breast conserving surgery in women with invasive breast cancer in Catalonia, Spain: a retrospective study.

BACKGROUND: Although complete tumor resection is accepted as the best means to reduce recurrence, reoperations after lumpectomy are a common problem in breast cancer. The aim of this study was to assess the reoperation rates after primary breast conserving surgery in invasive breast cancer cases diagnosed in Catalonia, Spain, between 2005 and 2011 and to identify variations based on patient and tumour characteristics. METHODS: Women with invasive incident breast cancer identified from the Patient's Hospital Discharge Database [174.0-174.9 codes of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) as the primary diagnosis] and receiving primary breast conserving surgery were included in the study and were followed up to 3 and 12 months by collecting information about repeat breast cancer surgery. RESULTS: Reoperation rates after primary breast conserving surgery decreased from 13.0 % in 2005 to 11.7 % in 2011 at 3 months and from 14.2 % in 2005 to 12.9 % in 2011 at 12 months' follow-up. While breast conservation reoperations saw a slight, non-significant increase in the same period (from 5.7 to 7.3 % at 3 months, and from 6.0 to 7.5 % at 12 months), there was a significant decrease in radical reoperation (from 7.3 to 4.4 % at 3 months and from 8.2 to 5.4 % at 12 months). Overall, additional breast surgeries decreased among younger women. CONCLUSIONS: Despite the rise of breast conserving surgery, reoperation rates following initial lumpectomy in Catalonia decreased by 10 % at 3 and 12 months' follow-up, remaining low and almost unchanged. Ultimately, there was also a significant decrease in mastectomies.

2016 Expert consensus document on prevention, diagnosis and treatment of short-term peripheral venous catheter-related infections in adult.

The use of endovascular catheters is a routine practice in secondary and tertiary care level hospitals. Short peripheral catheters have been found to be associated with the risk of nosocomial bacteremia resulting in morbidity and mortality. Staphyloccus aureus is mostly associated with peripheral catheter insertion. This Consensus Document has been elaborated by a panel of experts of the Spanish Society of Cardiovascular Infections in cooperation with experts from the Spanish Society of Internal Medicine, Spanish Society of Chemotherapy and Spanish Society of Thoracic-Cardiovascular Surgery and aims at define and establish the norm for management of short duration peripheral vascular catheters. The document addresses the indications for insertion, catheter maintenance and registry, diagnosis and treatment of infection, indications for removal and stresses on continuous education as a driver for quality. Implementation of this norm will allow uniformity in usage thus minimizing the risk of infection and its complications.

Effect of aqueous and particulate silk fibroin in a rat model of experimental colitis.

Silk fibroin (SF) has anti-inflammatory properties and promotes wound healing. Moreover, SF particles act as carriers of active drugs against intestinal inflammation due to their capacity to deliver the compound to the damaged colonic tissue. The present work assesses the effect of SF in the trinitrobenzenesulfonic acid model of rat colitis that resembles human intestinal inflammation. SF (8mg/kg) was administered in aqueous solution orally and in two particulate formats by intrarectal route, following two technologies: spray drying to make microparticles and desolvation in organic solvent to produce nanoparticles. SF treatments ameliorated the colonic damage, reduced neutrophil infiltration and improved the compromised oxidative status of the colon. They also reduced the gene expression of pro-inflammatory cytokines like IL-1ß and the anti-inflammatory cytokine IL-10. Moreover, they improved the intestinal wall integrity by increasing the gene expression of some of its markers (villin, trefoil factor-3 and mucins), thus accelerating the healing. The immunomodulatory properties of SF particles were also tested in vitro in macrophages: they activated the immune response in basal conditions without increasing it after a pro-inflammatory insult. In conclusion, SF particles could be useful as carriers to deliver active drugs to the damaged intestinal colon with additional anti-inflammatory and healing properties.

Long-term results after treatment of pertrochanteric femoral fractures with percutaneous compression plate (PCCP).

OBJECTIVE: This study sought to evaluate the long-term osteosynthesis results for AO/OTA 31.A1-A2 pertrochanteric fractures treated with the percutaneous compression plate (PCCP). MATERIALS AND METHODS: This investigation was a retrospective observational descriptive study of 335 patients, with a minimum follow-up of 2 years and a maximum follow-up of 8 years (2004-2011). RESULTS: The average post-operative hospital stay was 6.2 days, and the average decrease in haemoglobin levels after the intervention was 2.7 mg/dL, with transfusion required for one-third of the patients. Complications related to the implant were observed in 4.2 % of patients; the most notable complication was cut-out (2.4 % of patients), and 3 cases involved pseudarthrosis with breakage of the implant (0.9 % of patients). CONCLUSIONS: From the results obtained in this study and an analysis of previously published work, we believe that the PCCP may be the implant of choice for AO/OTA 31.A1-A2 fractures.

Intestinal anti-inflammatory activity of calcium pyruvate in the TNBS model of rat colitis: Comparison with ethyl pyruvate.

Pyruvate is a key intermediate of the carbohydrate metabolism with endogenous scavenger properties. However, it cannot be used in clinics due to its instability. Ethyl pyruvate (EP) has shown better stability as well as an antioxidant and anti-inflammatory activity. Calcium pyruvate monohydrate (CPM) is another stable pyruvate derivative that could also provide the benefits from calcium, fundamental for bone health. Considering everything, we propose CPM as a therapeutic strategy to treat diseases with an immune component in which there is also a significant dysregulation of the skeletal homeostasis. This could be applicable to inflammatory bowel disease, which is characterized by over-production of pro-inflammatory mediators, including cytokines and reactive oxygen and nitrogen metabolites that induces intestinal mucosal damage and chronic inflammation, and extra-intestinal symptoms like osteopenia and osteoporosis. The effects of CPM and EP (20, 40 and 100mg/kg) were evaluated on the trinitrobenzenesulfonic acid (TNBS) model of colitis in rats, after a 7-day oral treatment, with main focus on colonic histology and inflammatory mediators. Both pyruvates showed intestinal anti-inflammatory effects in the TNBS-induced colitis. They were evident both histologically, with a recovery of the mucosal cytoarchitecture and a reduction of the neutrophil infiltration, and through the profile of inflammatory mediators (IL-1, IL-6, IL-17, IL-23, iNOS). However, CPM appeared to be more effective than ethyl pyruvate. In conclusion, CPM exerts intestinal anti-inflammatory effect on the TNBS-induced colitis in rats, although further experiments are needed to explore its beneficial effects on bone health and osteoporosis.

Antihypertensive effects of oleuropein-enriched olive leaf extract in spontaneously hypertensive rats.

The effects of chronic consumption of oleuropein-enriched (15% w/w) olive leaf extract (OLE) on blood pressure, endothelial function, and vascular oxidative and inflammatory status in spontaneously hypertensive rats (SHR) were evaluated. Ten Wistar Kyoto rats (WKY) and twenty SHR were randomly assigned to three groups: a control WKY group, a control SHR group and a SHR group treated with OLE (30 mg kg(-1)) for 5 weeks. Long-term administration of OLE reduced systolic blood pressure, heart rate, and cardiac and renal hypertrophy. OLE treatment reversed the impaired aortic endothelium-dependent relaxation to acetylcholine observed in SHR. OLE restored aortic eNOS phosphorylation at Ser-1177 and Thr-495 and increased eNOS activity. OLE eliminated the increased aortic superoxide levels, and reduced the elevated NADPH oxidase activity, as a result of reduced NOX-1 and NOX-2 mRNA levels in SHR. OLE reduced the enhanced vascular TLR4 expression by inhibition of mitogen-activated protein kinase (MAPK) signaling with the subsequent reduction of proinflammatory cytokines. In conclusion, OLE exerts antihypertensive effects on genetic hypertension related to the improvement of vascular function as a result of reduced pro-oxidative and pro-inflammatory status.

Mejorando la respuesta patológica completa con tres esquemas diferentes de antraciclinas en densidad de dosis como primera línea en el tratamiento preoperatorio del cáncer de mama localmente avanzado / Improving the complete pathological response with three different schemes anthracyclines dose density as the first line in the preoperative treatment locally advanced breast cancer

Es un estudio prospectivo multiinstitucional que conlleva, a su vez, tres subestudios y luego se hace el metaanalisis de estos estudios piloto en pacientes con cáncer de mama localmente avanzado que reciben quimioterapia preoperatoria con antraciclinas en densidad de dosis seguido de tres esquemas diferentes, teniendo como objetivo llegar a la respuesta patológica completa (pCR). MATERIAL Y METODOS. Participaron 150 pacientes, 28 pacientes en el primer grupo (4AC+4AT), 57 pacientes en el segundo grupo (4AC+4CptT) y 65 pacientes en el tercer grupo (4AC+ 12 TXe), todos de inicio cánceres inoperables no metastásicos. RESULTADOS. En el primer grupo la RPC fue de 28 %, en el segundo grupo 20 % y en el tercer grupo 24 %, que se incrementó a 35 %, 19 %y 30 %, respectivamente, cuando solo se tabulo los datos de las pacientes que culminaron todo el tratamiento y que no presentaron progresión de enfermedad. CONCLUSIONES. En pacientes con tumores gigantes y en mds de 90 % EC III, las respuestas obtenidas son muy significativas solo con uso de quimioterapia, además de un ahorro económico importante al no usar biológicos. Con esto no se pretende ignorar la gran ayuda de los biológicos, simplemente que, para la realidad peruana, se proponen nuevas alternativas...

Is a prospective multi-institutional study involved three substudies in turn and then the meta-analysis of these pilot studies in patients with breast cancer with locally advanced receiving preoperative chemotherapy with anthracycline dose density followed by 3 different schemes, taking aim to reach the pCR. MATERIAL AND PATIENTS METHODS. 150 patients, 28 patients in the first group (4AC + 4AT), 57 patients in the second group (4CptT 4AC +) and 65 patients in the third group (4AC + I2TXe), all of them with inoperable cancers with nonmetastatic disease. RESULTS. The pCR In the first group was 28 %, in the second group 20% and in the third group 24 %, which increased to 35 %, 19 % and 30 % respectively when only the data of the patients culminating all treatment and no progression of disease was tabulated. CONCLUSIONS. Whereas these patients with giant tumors and in 90 % EC III responses obtained are significant only with use of chemotherapy, in addition to significant cost savings by not using biological agents. We not pretended ignore the evidence that the biological products help in excellent manner, but for our country this is an alternative good way...