Inflammation- and Metastasis-Related Proteins Expression Changes in Early Stages in Tumor and Non-Tumor Adjacent Tissues of Colorectal Cancer Samples.

Chronic inflammation can induce malignant cell transformation, having an important role in all colorectal cancer (CRC) phases. Non-tumor adjacent tissue plays an important role in tumor progression, but its implication in CRC has not yet been fully elucidated. The aim was to analyze the expression of inflammatory, epithelial-mesenchymal transition (EMT), and metastasis-related proteins in both tumor and non-tumor adjacent tissues from CRC patients by western blot. Tumor tissue presented an increase in metastasis and EMT-related proteins compared to non-tumor adjacent tissue, especially in stage II. Tumor tissue stage II also presented an increase in inflammatory-related proteins compared to other stages, which was also seen in non-tumor adjacent tissue stage II. Additionally, the relapse-free survival study of Vimentin and VEGF-B expression levels in stage II patients showed that the higher the expression levels of each protein, the lower 10-year relapse-free survival. These could suggest that some metastasis-related signalling pathways may be activated in stage II in tumor tissue, accompanied by an increase in inflammation. Furthermore, non-tumor adjacent tissue presented an increase of the inflammatory status that could be the basis for future tumor progression. In conclusion, these proteins could be useful as biomarkers of diagnosis for CRC at early stages.

Mitochondrial Function Differences between Tumor Tissue of Human Metastatic and Premetastatic CRC.

Most colorectal cancer (CRC) patients die as a consequence of metastasis. Mitochondrial dysfunction could enhance cancer development and metastatic progression. We aimed to evaluate the adaptations associated with mitochondrial function in tumor tissues from stages III and IV of human CRC and whether they could ultimately be used as a therapeutic target in metastatic colorectal cancer (mCRC). We analyzed the protein levels by Western blotting and the enzymatic activities of proteins involved in mitochondrial function, as well as the amount of mitochondrial DNA (mtDNA), by real-time PCR, analyzing samples of non-tumor adjacent tissue and tumor tissue from stages III and IV CRC patients without radio- or chemotherapy treatment prior to surgery. Our data indicate that the tumor tissue of pre-metastatic stage III CRC exhibited an oxidant metabolic profile very similar to the samples of non-tumor adjacent tissue of both stages. Notable differences in the protein expression levels of ATPase, IDH2, LDHA, and SIRT1, as well as mtDNA amount, were detected between the samples of non-tumor adjacent tissue and tumor tissue from metastatic CRC patients. These findings suggest a shift in the oxidative metabolic profile that takes place in the tumor tissue once the metastatic stage has been reached. Tumor tissue oxidative metabolism contributes to promote and maintain the metastatic phenotype, with evidence of mitochondrial function impairment in stage IV tumor tissue.

Influence of pharmacokinetic/pharmacodynamic ratio on vancomycin treatment response in pediatric patients with Staphylococcus aureus bacteremia.

BACKGROUND: Staphylococcus aureus is a frequent cause of hospital-acquired bacteremia in pediatric patients. Vancomycin is the drug of choice for the treatment of methicillin-resistant strains, although treatment failure is frequently observed. Area under the curve (AUC) of plasma concentrations over the minimum inhibitory concentration (MIC) has been proposed as the best index to predict treatment response, although information about its clinical impact on pediatric patients is scarce. The objective of this study is to determine if early recovery of an AUC/MIC>400 mg*h/L for vancomycin in pediatric patients with S. aureus bacteremia is associated with clinical and microbiological treatment response. METHODS: Retrospective observational study. Pediatric patients younger than 3 years with vancomycin-treated S. aureus bacteremia were included. The pharmacokinetic parameters were calculated from the vancomycin value obtained in the first 72 hours of treatment, assuming a bicompartmental model. A multivariate analysis was performed to analyze factors associated with early clinical response, treatment failure, microbiological response and 30-day mortality. RESULTS: Fifty-one patients with S. aureus bacteremia were included in the study. In 18 patients (35.3%), strains with a MIC higher than 1.0 mg/L were isolated, being in eight (15.7%) greater than 1.5 mg/L. 22 (43.1%) patients did not reach an estimated AUC/MIC>400 during the first 72 hours. A significant association was observed between attainment of an AUC/MIC>400 and early clinical response (OR:3.23 [95% CI: 1.07-12.03]). No significant association was found between an AUC/MIC>400 and microbiological response or mortality. CONCLUSIONS: An AUC/MIC>400 is associated with early response to vancomycin in pediatric patients with S. aureus bacteremia.

Antioxidant enzymes change in different non-metastatic stages in tumoral and peritumoral tissues of colorectal cancer.

Antioxidant defences and oxidative stress are related to development, progression and malignancy of colorectal cancer. However, their role in early stages of cancer remains unknown. More and more recent studies have revealed that non-tumour adjacent tissue is not a normal tissue. Thus, our aim was to analyse protein levels of MnSOD (Manganese Superoxide Dismutase), acMnSOD (Acetylated Manganese superoxide Dismutase), SIRT3 (Sirtuin 3), CuZnSOD (Cupper Zinc Superoxide Dismutase), CAT (Catalase), GPx (Glutathione Peroxidase), and GRd (Glutathione Reductase) both in tumour and non-tumour adjacent tissue from colorectal cancer patients by western blot. Non-tumour adjacent tissue seemed to have higher levels of antioxidant enzymes that detoxify hydrogen peroxide compared to tumour tissue. In contrast, tumour tissue had higher levels of MnSOD and acMnSOD. Furthermore, most of the proteins analysed showed significant differences between stage I and II in both non-tumour adjacent and tumour tissue. This could indicate that antioxidant enzymes, especially MnSOD, play a crucial role in early stages of colorectal cancer in both tissues, so they could be analysed as novel biomarkers to improve colorectal cancer diagnosis.

Effectiveness and impact of the hepatitis B vaccination program in preadolescents in Catalonia 21 years after its introduction.

Hepatitis B is a viral disease of global importance. In Catalonia in the 1980s, the seroepidemiological pattern of HBV infection was low-intermediate. In 1990, the Expert Committee on Vaccinations of the Department of Health of the Generalitat of Catalonia evaluated the systematic introduction of hepatitis B vaccination in preadolescents, maintaining the vaccination of risk groups. The objective of this study was to estimate the effectiveness and impact of the systematic hepatitis B vaccination programme in preadolescents in Catalonia 21 years after its introduction. A retrospective cohort study was conducted, comparing the disease incidence in vaccinated and unvaccinated cohorts. Cases of hepatitis B were defined as those reported by the General Subdirectorate of Surveillance and Response to Public Health Emergencies between 2000 and 2014. The incidence rate was 2.5 per 100,000 persons in 1991 and 1.2 per 100,000 persons in 2014, a reduction of 52%. During the study period, 388 cases of hepatitis B infection were notified, of which three were classified as vaccine failures. Vaccine effectiveness was 99.30% (95% CI: 97.83-99.78) and the population prevented fraction in the cohorts of preadolescents studied was 64.56% (95% CI: 60.45-68.66). The effectiveness and impact of the hepatitis B vaccination program in preadolescents in Catalonia is high, with the consequent benefits for the population.

Non-tumor adjacent tissue of advanced stage from CRC shows activated antioxidant response.

Colorectal cancer (CRC) is a leading cause of malignant cancer-related morbidity and mortality, with a higher incidence in developed countries and a high mortality rate mainly attributable to metastases. The aim of the present study was to determine the metabolic adaptations related to oxidative stress in tumor tissue from advanced stages (III and IV) of CRC and whether they could be used as potential biomarkers for clinical applications. To tackle this aim, we have analyzed the protein expression levels related to oxidative stress and the enzymatic activities of MnSOD and catalase, comparing samples of non-tumor adjacent tissue and tumor tissue of CRC patients in stages III and IV. The results showed no differences between stage III and IV in tumor tissues for any of the proteins studied. However, some differences were found between samples of non-tumor adjacent tissue and tumor tissue for some of the antioxidant enzymes. Overwhelmingly, the greatest differences were detected when comparing samples of non-tumor adjacent tissue from stage III and stage IV. To the best of our knowledge, this is the first study where differences between the non-tumor adjacent tissues of CRC patients from different cancer stages were determined. This study suggests that the parameters analyzed should be evaluated as biomarkers for the evolution of CRC. Furthermore, tumor tissue status should not be of sole importance for the prognosis of CRC, as the non-tumor adjacent tissues could also merit consideration.

Impact of amikacin pharmacokinetic/pharmacodynamic index on treatment response in critically ill patients.

OBJECTIVES: This study evaluated the association between the pharmacokinetic/pharmacodynamic index and treatment response to amikacin in critically ill patients. METHODS: An observational prospective study was designed. Critically ill adult patients with infection due to amikacin-sensitive Gram-negative bacteria treated with amikacin were included. Amikacin maximum (Cmax) and minimum (Cmin) plasma concentration samples were taken during the first 48-96h after the beginning of treatment. The impact of Cmax/MIC ratio and area under the concentration-time curve (AUC)/MIC ratio on early and final clinical response, microbiological eradication, development of resistant strains and renal toxicity was analysed using a multivariate model. RESULTS: A total of 85 patients received amikacin treatment, of whom 71 (83.5%) achieved a Cmax/MIC >6, 66 (77.6%) a Cmax/MIC >8, 64 (75.3%) a Cmax/MIC >10 and 72 (84.7%) an AUC/MIC >65. Clinical response at the end of treatment was significantly greater in patients with Cmax/MIC >6 [OR=5.48 (95% CI 1.28-11.40)], Cmax/MIC >8 [OR=6.01 (2.41-12.2)] and Cmax/MIC >10 [OR=8.02 (2.21-14.2)]. Cmax/MIC >10 was associated with a non-significant increase in microbiological eradication [OR=2.84 (0.76-10.61)]. Achieving Cmax/MIC >6 was associated with a lower proportion of patients with selection of resistant strains or with an increase in amikacin MIC (27.8% vs. 10.2%). Amikacin AUC was associated with development of nephrotoxicity [ROC curve 0.77 (0.66-0.87)]. CONCLUSIONS: The Cmax/MIC ratio of amikacin in critically ill patients is directly related to the response to treatment and the selection of resistant strains.

Factors influencing the spread of pertussis in households: a prospective study, Catalonia and Navarre, Spain, 2012 to 2013.

We aimed to investigate transmission rates of pertussis in household contacts of cases and factors associated with transmission. A prospective epidemiological study was conducted in 2012 and 2013 to determine the incidence of pertussis among household contacts of reported cases in Catalonia and Navarre, Spain. An epidemiological survey was completed for each case and contact, who were followed for 28 days to determine the source of infection (primary case) and detect the occurrence of secondary cases. Odds ratios (ORs) were used to estimate the effectiveness of vaccination and chemoprophylaxis in preventing new cases, using the formula (1 - OR) × 100. For the 688 primary cases, a total of 2,852 contacts were recorded. The household transmission rate was 16.1% (459/2,852) and rose according to the age (> 18 years) and lack of immunisation of the primary cases, and also the age (0-18 years), family relationship (siblings and children), lack of vaccination and chemoprophylaxis of contacts. Pertussis vaccine effectiveness in preventing new cases was 65.0% (95% confidence interval (CI): 11.6 to 86.2) for full vaccination (≥ 4 doses) and 59.7% (95% CI: -6.8 to 84.8) for incomplete vaccination (< 4 doses). The effectiveness of chemoprophylaxis was 62.1% (95% CI: 40.3 to 75.9). To reduce household transmission, contacts should be investigated to detect further cases and to administer chemoprophylaxis. The current vaccination status of cases and contacts can reduce household transmission.

Characteristics of pertussis outbreaks in Catalonia, Spain, 1997 to 2010.

In Catalonia, pertussis outbreaks must be reported to the Department of Health. This study analyzed pertussis outbreaks between 1997 and 2010 in general and according to the characteristics of the index cases. The outbreak rate, hospitalization rate and incidence of associated cases and their 95%CI were calculated. Index cases were classified in two groups according to age (<15 years and ≥15 years) and the vaccine type received: whole cell vaccine (DTwP) or acellular vaccine (DTaP). During the study period, 230 outbreaks were reported. The outbreak rate was 2.43 × 10(-6) persons-year, and outbreaks ranged from 2 to 32 cases, with a median duration of 18 days. There were 771 associated cases, with an incidence rate of 0.8 × 10(-5) persons-year.   After classifying outbreaks according to the age of the index case, 126 outbreaks (1.3 × 10(-6) persons-year) had an index case aged <15 y and 87 (0.87 × 10(-6) person-year) had an index case aged ≥15 y (RR = 1.44, 95%CI 1.10-1.90; P = 0.007). Between 2003 and 2010, after the introduction of the acellular vaccine, the index case was vaccinated with DTwP vaccine in 25 outbreaks (0.43 × 10(-6) persons-year) and with DTaP vaccine in 32 outbreaks (0.55 × 10(-6) person-year) (RR = 0.78, 95%CI 0.46-1.31; P = 0.35). Of cases, 37.2% were correctly vaccinated, suggesting waning immunity of pertussis vaccine protection and endogenous circulation of pertussis. A greater number of outbreaks had an index case aged <15 y. No changes in the disease incidence, associated cases and hospitalization rate were observed after the introduction of DTaP.

Estrogen down-regulates uncoupling proteins and increases oxidative stress in breast cancer.

Oxidative stress has been postulated as one of the mechanisms underlying the estrogen carcinogenic effect in breast cancer. Estrogens are known to increase mitochondrial-derived reactive oxygen species (ROS) by an unknown mechanism. Given that uncoupling proteins (UCPs) are key regulators of mitochondrial energy efficiency and ROS production, our aim was to check the presence and activity of UCPs in estrogen receptor (ER)-positive and ER-negative breast cancer cells and tumors, as well as their relation to oxidative stress. Estrogen (1 nM) induced higher oxidative stress in the ER-positive MCF-7 cell line, showing increased mitochondrial membrane potential, H(2)O(2) levels, and DNA and protein damage compared to ER-negative MDA-MB-231 cells. All isoforms of uncoupling proteins were highly expressed in ER-positive breast cancer cells and tumors compared to negative ones. ROS production in mitochondria isolated from MCF-7 was increased by inhibition of UCPs with GDP, but not in mitochondria from MDA-MB-231. Estrogen treatment decreased uncoupling protein and catalase levels in MCF-7 and decreased GDP-dependent ROS production in isolated mitochondria. On the whole, these results suggest that estrogens, through an ER-dependent mechanism, may increase mitochondrial ROS production by repressing uncoupling proteins, which offers a new perspective on the understanding of why estrogens are a risk factor for breast cancer.

Trombosis del tronco celíaco en paciente con situs inversus totalis / Celiac trunk thrombosis in a patient with situs inversus totalis

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[Reporting of newly diagnosed HIV infections in Catalonia, Barcelona, Spain. Implementation and results]. / Declaración de los nuevos diagnósticos de infección por el VIH en Cataluña. Implementación y resultados.

OBJECTIVES: To describe newly diagnosed HIV infections from the HIV Reporting System in Catalonia (2001-2003), and to compare the characteristics of the epidemic based on the use of the HIV Reporting System and the Catalonian AIDS Registry versus those based on the Catalonian AIDS Registry alone. METHODS: Data were collected from newly diagnosed HIV infections and AIDS cases between 2001 and 2003 in Catalonia. RESULTS: Among the newly diagnosed HIV infections (1,765) the most frequent route of HIV infection was heterosexual transmission (46.8%), followed by men who had sex with men (26.7%), and injecting drug use (19.9%). Out of the 1,210 AIDS cases, the most common route of HIV transmission was injecting drug used (42.2%), followed by (heterosexual transmission 34.5%) and MSM (18.0%). Comparison of routes of HIV transmission in the two reporting systems (HIV/AIDS versus AIDS) revealed statistically significant differences. CONCLUSIONS: The HIV/AIDS Reporting System based on reporting of newly diagnosed HIV infections is feasible, since it has been useful in achieving the objectives of epidemiological HIV infection surveillance. It also provides more accurate information than does the AIDS Registry, which can be used to describe recent patterns of HIV transmission. The completeness of the new reporting system may be enhanced by including the diagnosis of HIV infection among the diseases of mandatory notification.

Declaración de los nuevos diagnósticos de infección por el VIH en Cataluña. Implementación y resultados / Reporting of newly diagnosed HIV infections in Catalonia. Barcelona. Spain. Implementation and results

Objetivos: Describir los resultados de la notificación de nuevos diagnósticos de infección por el virus de la inmunodeficiencia humana (NDIVIH) en Cataluña (2001-2003), y comparar las características de la epidemia como resultado de la utilización de este nuevo sistema de información junto con el Registro de casos de sida de Cataluña, con las halladas únicamente en el Registro de casos de sida. Métodos: Datos de las notificaciones de NDIVIH y de casos de sida entre 2001 y 2003 en Cataluña. Resultados: Entre los NDIVIH (n = 1.765), la vía de transmisión más frecuente fue las relaciones heterosexuales (46,8%), seguida de las relaciones homosexuales entre varones (26,7%) y el uso de drogas por vía parenteral (19,9%). Entre los 1.210 casos de sida, la forma de transmisión más frecuente fue el uso de drogas por vía parenteral (42,2%), seguida de relaciones heterosexuales (34,5%) y de las relaciones homosexuales entre varones (18,0%). La diferencia de utilizar una o 2 fuentes de información respecto a la variable vía de transmisión de la infección fue estadísticamente significativa. Conclusiones: El sistema de información basado en los datos sobre NDIVIH es viable, ha sido útil para conseguir los objetivos previstos en el sistema de vigilancia epidemiológica del VIH y proporciona información más precisa que el Registro de sida para describir los actuales patrones de transmisión del virus. La exhaustividad del nuevo sistema de información podría mejorar mediante la incorporación del diagnóstico de infección al sistema de enfermedades de declaración obligatoria

Objectives: To describe newly diagnosed HIV infections from the HIV Reporting System in Catalonia (2001-2003), and to compare the characteristics of the epidemic based on the use of the HIV Reporting System and the Catalonian AIDS Registry versus those based on the Catalonian AIDS Registry alone. Methods: Data were collected from newly diagnosed HIV infections and AIDS cases between 2001 and 2003 in Catalonia. Results: Among the newly diagnosed HIV infections (1,765) the most frequent route of HIV infection was heterosexual transmission (46.8%), followed by men who had sex with men (26.7%), and injecting drug use (19.9%). Out of the 1,210 AIDS cases, the most common route of HIV transmission was injecting drug used (42.2%), followed by (heterosexual transmission 34.5%) and MSM (18.0%). Comparison of routes of HIV transmission in the two reporting systems (HIV/AIDS versus AIDS) revealed statistically significant differences. Conclusions: The HIV/AIDS Reporting System based on reporting of newly diagnosed HIV infections is feasible, since it has been useful in achieving the objectives of epidemiological HIV infection surveillance. It also provides more accurate information than does the AIDS Registry, which can be used to describe recent patterns of HIV transmission. The completeness of the new reporting system may be enhanced by including the diagnosis of HIV infection among the diseases of mandatory notification

Synthesis of 2,3:4,6-di-O-isopropylidene-D-allopyranose from D-glucose.

2,3:4,6-Di-O-isopropylidene-d-allopyranose can be conveniently prepared from d-glucose via a synthetic sequence, which includes Mitsunobu inversion at O-3, di-O-isopropylidenation of phenyl-1-thio-d-alloside and anomeric deprotection on treatment with NBS/CaCO3.

[Meningococcal disease in Catalonia, Spain (1990-1997)]. / Enfermedad meningocócica en Cataluña (1990-1997).

BACKGROUND AND OBJECTIVE: We aimed to study the behavior of meningococcal disease in Catalonia during the period 1990-1997, identifying the possible epidemic periods. MATERIAL AND METHOD: All cases reported to the notifiable disease system which fulfilled the criteria of confirmed or suspected cases during this period were analyzed. RESULTS: The global incidence rate was 4.8/100,000. The incidence rate for serogroup B was 1.9/100,000 and for serogroup C 0.8/100,000. The disease incidence tended to diminish slightly during the study period, with a constant annual growth of 0.11/100,000. The increased incidence of serogroup C cases in 1996-1997 was associated with an increased incidence in the 10-19 years age group. CONCLUSIONS: Globally, in the 1990-1997 period, the disease incidence tended to diminish slightly. During the last two years, an increased incidence was observed, mostly due to the increase in the number of serogroup C cases. This fact was associated with a change in the age pattern of cases, which increased in the 10-19 years age group, as observed in other countries and coinciding with epidemic periods or greater meningococcal activity.

Unexpected remarkable stability of primary ozonides derived from alkenyl stannanes. One-pot synthesis of 1,2-diols from alkynes.

Primary ozonides derived from alkenyl stannanes display an unusual stability and can be transformed into 1,2-diols by treatment with dimethyl sulfide and borane-methyl sulfide complex. This observation has been incorporated into the development of a novel one-pot strategy for the conversion of alkynes into 1,2-diols.