In vitro and in vivo effects of Enterococcus faecalis CECT7121 on Toxocara canis

The aim of the present paper was to evaluate the larvicidal effect of Enterococcus faecalis CECT7121 (Ef7121) on the Toxocara canis cycle both in vitro and in vivo. For the in vitro experiments, T. canis larvae were incubated with the supernatants of Ef7121 (EI) and mutant Ef7121 (EIm), in a pre-culture of Ef7121 (EII) and in a fresh culture with Ef7121 (EIII) and the Ef7121 mutant strain (EIIIm). The viability of the larvae was calculated after a 48 h incubation. A significant reduction of the viability of T. canis larvae was observed in EI, EII and EIII. A decrease of this inhibitory effect was observed in EIm and EIIIm (p = 0.008). In the in vivo experiments, mice were orally inoculated with three doses of Ef7121. To study the probiotic persistence in the intestine, the animals were sacrificed every four days and their intestines were dissected. The initial average bacterial levels were 9.7 x 10(4) for Ef7121 (colony forming units/g). At the end of the assay the levels were 1.46 x 10(4). No bacterial translocation was detected in mesenteric lymphatic nodules and spleen. Ef7121 interference with the biological cycle was evaluated in mice challenged with T. canis. The interference was significant when the mice were challenged with probiotic and T. canis simultaneously (p = 0.001), but it was not significant when the challenge was performed 15 days after administration of the bacterial inoculum (p = 0.06). In conclusion, Ef7121 possessed in vitro and in vivo larvicidal activity.

Combined low initial DNA damage and high radiation-induced apoptosis confers clinical resistance to long-term toxicity in breast cancer patients treated with high-dose radiotherapy

BACKGROUND. Either higher levels of initial DNA damage or lower levels of radiation-induced apoptosis in peripheral blood lymphocytes have been associated to increased risk for develop late radiation-induced toxicity. It has been recently published that these two predictive tests are inversely related. The aim of the present study was to investigate the combined role of both tests in relation to clinical radiation-induced toxicity in a set of breast cancer patients treated with high dose hyperfractionated radical radiotherapy. METHODS. Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma treated with high-dose hyperfractioned radical radiotherapy. Acute and late cutaneous and subcutaneous toxicity was evaluated using the Radiation Therapy Oncology Group morbidity scoring schema. The mean follow-up of survivors (n = 13) was 197.23 months. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radiation-induced apoptosis (RIA) at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. RESULTS. Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). Radiation-induced apoptosis increased with radiation dose (median 12.36, 17.79 and 24.83 for 1, 2, and 8 Gy respectively). We observed that those "expected resistant patients" (DSB values lower than 1.78 DSB/Gy per 200 Mbp and RIA values over 9.58, 14.40 or 24.83 for 1, 2 and 8 Gy respectively) were at low risk of suffer severe subcutaneous late toxicity (HR 0.223, 95%CI 0.073-0.678, P = 0.008; HR 0.206, 95%CI 0.063-0.677, P = 0.009; HR 0.239, 95%CI 0.062-0.929, P = 0.039, for RIA at 1, 2 and 8 Gy respectively) in multivariate analysis. CONCLUSIONS. A radiation-resistant profile is proposed, where those patients who presented lower levels of initial DNA damage and higher levels of radiation induced apoptosis were at low risk of suffer severe subcutaneous late toxicity after clinical treatment at high radiation doses in our series. However, due to the small sample size, other prospective studies with higher number of patients are needed to validate these results.

Fingermark detection based on the in situ growth of luminescent nanoparticles: towards a new generation of multimetal deposition

The in situ deposition of zinc oxide on gold nanoparticles in aqueous solution has been here successfully applied in the field of fingermark detection on various non-porous surfaces. In this article, we present the improvement of the multimetal deposition, an existing technique limited up to now to non-luminescent results, by obtaining luminescent fingermarks with very good contrast and details. This is seen as a major improvement in the field in terms of selectivity and sensitivity of detection, especially on black surfaces.

Closed rupture of the tibialis anterior tendon : a report of 2 cases

Closed rupture of the tibialis anterior tendon is a rare injury, and it usually affects individuals older than 50 years of age. This rare injury tends to occur spontaneously, and this often delays diagnosis and adequate treatment. Although direct surgical repair of the ruptured tibialis anterior tendon is generally considered the treatment of choice, nonanatomic repair, tendon lengthening, or tendon transfer might be necessary in cases where shortening of the muscle-tendon unit has taken place. In this report, we describe 2 cases that involved the surgical repair of closed ruptures of the tibialis anterior tendon. In the first case, direct repair was undertaken at approximately 6 months after the onset of symptoms, and in the second case repair of the tibialis anterior tendon required augmentation tenodesis with the extensor retinaculum. Level of Clinical Evidence: 4.

De novo lipogenesis in adipose tissue is associated with course of morbid obesity after bariatric surgery.

OBJECTIVE De novo lipogenesis is involved in fatty acid biosynthesis and could be involved in the regulation of the triglyceride storage capacity of adipose tissue. However, the association between lipogenic and lipolytic genes and the evolution of morbidly obese subjects after bariatric surgery remains unknown. In this prospective study we analyze the association between the improvement in the morbidly obese patients as a result of bariatric surgery and the basal expression of lipogenic and lipolytic genes. METHODS We study 23 non diabetic morbidly obese patients who were studied before and 7 months after bariatric surgery. Also, we analyze the relative basal mRNA expression levels of lipogenic and lipolytic genes in epiploic visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT). RESULTS When the basal acetyl-CoA carboxylase 1 (ACC1), acetyl-CoA synthetase 2 (ACSS2) and ATP citrate lyase (ACL) expression in SAT was below percentile-50, there was a greater decrease in weight (P = 0.006, P = 0.034, P = 0.026), body mass index (P = 0.008, P = 0.033, P = 0.034) and hip circumference (P = 0.033, P = 0.021, P = 0.083) after bariatric surgery. In VAT, when the basal ACSS2 expression was below percentile-50, there was a greater decrease in hip circumference (P = 0.006). After adjusting for confounding variables in logistic regression models, only the morbidly obese patients with SAT or VAT ACSS2 expression ≥ P50 before bariatric surgery had a lower percentage hip circumference loss (

Bodyweight and migration-related differences in motor abilities in preschool children "Ballabeina"

Introduction: Motor abilities in schoolchildren have been decreasing in the last two decades (Bös, 2003, Tomkinson et al., 2003). This may be related to the dramatic increase in overweight and adiposity during the same time period. Children of migrant background are especially affected (Lasserre et al., 2007). But little is known about the relationship between BMI and migration background and motor abilities in preschool children. Methods/Design We carried out a cross-sectional analysis with 665 children (age 5.1 ± 0.6 years; 49.8 % female) of 40 randomly selected kindergarten classes from German and French speaking regions in Switzerland with a high migrant background. We investigated BMI, cardiorespiratory fitness (20 m shuttle run), static (displacement of center of pressure (COP)) and dynamic (balancing forward on a beam) postural control and overall fitness (obstacle course). Results: Of the children, 9.6 % were overweight, 10.5 % were obese (Swiss national percentiles) and 72.8 % were of migrant background (at least one parent born outside of Switzerland). Mean BMI from children of non-migrant background was 15.5 ± 1.1 kg/m2, while migrant children had a mean BMI of 15.8 ± 1.7 kg/m2 (p=0.08). Normal-weight children performed better in cardiorespiratory fitness (3.1 ± 1.4 vs. 2.6 ± 1.1 stages, p<0.001), overall fitness (18.9 ± 4.4 vs. 20.8 ± 4.6 sec, p<0.001) and in dynamic balance (4.9 ± 3.5 vs. 3.8 ± 2.5 steps, p<0.001) compared to overweight and obese children, while the latter had less postural sway (COP: 956 ± 302 vs. 1021 ± 212 mm, p=0.008). There was a clear inverse dose-response relationship between weight status and dynamic motor abilities. There were no significant differences in most tested motor abilities between non-migrant and migrant. The latter performed less well in only one motor test (overall fitness: 20.2 ± 5.2 vs. 18.3 ± 3.5 sec, p<0.001). These findings persisted after adjustment for BMI. Conclusion In preschool children, differences in motor abilities are already present between normal weight and overweight/obese children. However, migrant children demonstrate similar motor abilities compared to non-migrant children for almost all tests, despite their slightly higher BMI.

The bioavailability of bromazepam, omeprazole and paracetamol given by nasogastric feeding tube.

AIMS: To characterize and compare the pharmacokinetic profiles of bromazepam, omeprazole and paracetamol when administered by the oral and nasogastric routes to the same healthy cohort of volunteers. METHODS: In a prospective, monocentric, randomized crossover study, eight healthy volunteers received the three drugs by the oral (OR) and nasogastric routes (NT). Sequential plasma samples were analyzed by high-performance liquid chromatography-UV, pharmacokinetic parameters (Cmax, AUC(0-infinity), t(1/2), k(e), tmax) were compared statistically, and Cmax, AUC(0-infinity) and t(max) were analyzed for bioequivalence. RESULTS: A statistically significant difference was seen in the AUC(0-infinity) of bromazepam, with nasogastric administration decreasing availability by about 25%: AUC(OR) = 2501 ng mL(-1) h; AUC(NT) = 1855 ng mL(-1) h (p < 0.05); ratio (geometric mean) = 0.74 [90% confidence interval (CI) 0.64-0.87]. However, this does not appear to be clinically relevant given the usual dosage range and the drug's half-life (approx. 30 h). A large interindividual variability in omeprazole parameters prevented any statistical conclusion from being drawn in terms of both modes of administration despite their similar average profile: AUC(OR) = 579 ng mL(-1) h; AUC(NT) = 587 ng mL(-1) h (p > 0.05); ratio (geometric mean) = 1.01 (90% CI 0.64-1.61). An extended study with a larger number of subjects may possibly provide clearer answers. The narrow 90% confidence limits of paracetamol indicate bioequivalence: AUC(OR) = 37 microg mL(-1) h; AUC(NT) = 41 microg mL(-1) h(p > 0.05); ratio (geometric mean) = 1.12 (90% CI 0.98-1.28). CONCLUSION: The results of this study show that the nasogastric route of administration does not appear to cause marked, clinically unsuitable alterations in the bioavailability of the tested drugs.

Prevalence of anaemia in inflammatory bowel disease in Switzerland: a cross-sectional study in patients from private practices and university hospitals.

BACKGROUND: Anaemia represents a common complication of inflammatory bowel disease (IBD). Most studies on anaemia in IBD patients have been performed in tertiary referral centres (RC) and data from gastroenterologic practices (GP) are lacking. We investigated the frequency and severity of anaemia in IBD patients from tertiary referral centres and gastroenterologic practices compared to the general population. METHODS: Data were acquired from patients included in the Swiss IBD Cohort Study. IBD activity was evaluated by CDAI and modified Truelove and Witts severity index (MTWSI). Anaemia was defined as haemoglobin ≤120g/L in women and ≤130g/L in men. RESULTS: 125 patients from RC (66 with Crohn's disease (CD) and 59 with ulcerative colitis (UC)) and 116 patients from GP (71 CD and 45 UC) were included and compared to 6074 blood donors. Anaemia was found in 21.2% (51/241) of the IBD patients and more frequently in patients from RC as compared to GP and healthy controls (28.8% vs. 12.9% vs. 3.4%; P<0.01). IBD patients from RC suffered more frequently from active disease compared to IBD patients in GP (36% vs. 23%, P=0.032). Supplementation therapy (iron, vitamin B12, folic acid) was performed in 40% of anaemic IBD patients in GP as compared to 43% in RC. CONCLUSIONS: Anaemia is a common complication in patients with IBD and significantly more prevalent in patients from referral centres as compared to patients from gastroenterologic practices. Physicians treating IBD patients should pay attention to the presence of anaemia and ensure sufficient supplementation therapy.

Hepatitis B virus genotypes in Southeast Brazil and its relationship with histological features

Data concerning the relationship between hepatitis B virus (HBV) genotypes and liver histology are scarce. The aim of this study was to compare HBV non-B and non-C genotypes according to demographic features, clinical status, HBV-DNA levels and liver histology in Rio de Janeiro. One hundred twenty one consecutive chronic HBV-infected patients were enrolled during two-year period and data were prospectively collected. Sera were tested for HBV genotyping using restriction fragment length polymorphism. Liver biopsy was obtained from patients with either increased alanine aminotransferase (ALT) or HBV-DNA levels. Genotype A was the most common, found in 82 (68%) patients, followed by F in 19 (15%), D in 17 (14%), B in one (1%) and C in two (2%). There was no association between HBV genotypes A, D and F and gender (p = 0.37), age (p = 0.78), race (p = 0.22), mode of infection (p = 0.94), HB "e" antigen status (p = 0.37) and HBV-DNA levels (p = 0.47). The ALT levels were lower in genotype D (75%) compared with A (47%) and F (55%) (p = 0.05). Liver biopsy showed lower inflammation [histological activity index (HAI) = 4] and fibrosis (F) (= 0) scores in genotype D than in genotypes A (HAI = 5, p < 0.001; F = 2, p = 0.008) or F (HAI = 5, p = 0.009; F = 2, p = 0.01). Genotype A was the most prevalent in chronic HBV-infected patients and genotype D patients presented with less intense liver disease.

HLA Alleles Influence the Clinical Signature of Amoxicillin-Clavulanate Hepatotoxicity.

BACKGROUND AND AIM The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases. METHODS High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls. RESULTS The distributions of class I alleles A*3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B*1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB1*1501-DQB1*0602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A*3002 and/or B*1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB1*1501-DQB1*0602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy's Law criteria. The phenotype frequencies of B*1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB1*0301-DQB1*0201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB1*1302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07). CONCLUSIONS HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients.

R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study.

BACKGROUND The role of re-treatment with rituximab in aggressive B-cell lymphomas still needs to be defined. This study evaluated the influence of prior exposure to rituximab on response rates and survival in patients with diffuse large B-cell lymphoma treated with rituximab plus etoposide, cytarabine, cisplatinum and methylprednisolone (R-ESHAP). DESIGN AND METHODS We retrospectively analyzed 163 patients with relapsed or refractory diffuse large B-cell lymphoma who received R-ESHAP as salvage therapy with a curative purpose. Patients were divided into two groups according to whether rituximab had been administered (n=94, "R+" group) or not (n=69, "R-" group) prior to R-ESHAP. RESULTS Response rates were significantly higher in the R- group in the univariate but not in the multivariate analysis. In the analysis restricted to the R+ group, we observed very low complete remission and overall response rates in patients with primary refractory disease (8% and 33%, respectively), as compared to those in patients who were in first partial remission (41% and 86%) or who had relapsed disease (50% and 75%) (p<0.01 in both cases). Overall, 60% and 65% of patients in the R+ and R- groups, respectively, underwent stem-cell transplantation after the salvage therapy. With a median follow-up of 29 months (range, 6-84), patients in the R+ group had significantly worse progression-free survival (17% vs. 57% at 3 years, p<0.0001) and overall survival (38% v 67% at 3 years, p=0.0005) than patients in the R- group. Prior exposure to rituximab was also an independent adverse prognostic factor for both progression-free survival (RR: 2.0; 95% CI: 1.2-3.3, p=0.008) and overall survival (RR: 2.2; 95% CI: 1.3-3.9, p=0.004). CONCLUSIONS R-ESHAP was associated with a high response rate in patients who were not refractory to upfront rituximab-based chemotherapy. However, the survival outcome was poor for patients previously exposed to rituximab, as compared to in those who had not previously been treated with rituximab.

The diamine oxidase gene is associated with hypersensitivity response to non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity drug reactions. Histamine is released in the allergic response to NSAIDs and is responsible for some of the clinical symptoms. The aim of this study is to analyze clinical association of functional polymorphisms in the genes coding for enzymes involved in histamine homeostasis with hypersensitivity response to NSAIDs. We studied a cohort of 442 unrelated Caucasian patients with hypersensitivity to NSAIDs. Patients who experienced three or more episodes with two or more different NSAIDs were included. If this requirement was not met diagnosis was established by challenge. A total of 414 healthy unrelated controls ethnically matched with patients and from the same geographic area were recruited. Analyses of the SNPs rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and DAO genes were carried out by means of TaqMan assays. The detrimental DAO 16 Met allele (rs10156191), which causes decreased metabolic capacity, is overrepresented among patients with crossed-hypersensitivity to NSAIDs with an OR  = 1.7 (95% CI  = 1.3-2.1; Pc  = 0.0003) with a gene-dose effect (P = 0.0001). The association was replicated in two populations from different geographic areas (Pc  = 0.008 and Pc  = 0.004, respectively). CONCLUSIONS AND IMPLICATIONS: The DAO polymorphism rs10156191 which causes impaired metabolism of circulating histamine is associated with the clinical response in crossed-hypersensitivity to NSAIDs and could be used as a biomarker of response.

Genetic compatibility between Anopheles lesteri from Korea and Anopheles paraliae from Thailand

To assess differentiation and relationships between Anopheles lesteri and Anopheles paraliae we established three and five iso-female lines of An. lesteri from Korea and An. paraliae from Thailand, respectively. These isolines were used to investigate the genetic relationships between the two taxa by crossing experiments and by comparing DNA sequences of ribosomal DNA second internal transcribed spacer (ITS2) and mitochondrial DNA cytochrome c oxidase subunit I (COI) and subunit II (COII). Results of reciprocal and F1-hybrid crosses between An. lesteri and An. paraliae indicated that they were compatible genetically producing viable progenies and complete synaptic salivary gland polytene chromosomes without inversion loops in all chromosome arms. The pairwise genetic distances of ITS2, COI and COII between these morphological species were 0.040, 0.007-0.017 and 0.008-0.011, respectively. The specific species status of An. paraliae in Thailand and/or other parts of the continent are discussed.

Nevirapine vs efavirenz in virologically supressed patients: Differences in lipoprotein subclasses and inflammatory biomarkers.

Background: The interaction between lipid disturbances and inflammatory markers is not well known in patients on antiretroviral therapy (ART). As nevirapine (NVP) is associated with a better lipid profile than efavirenz (EFV), we investigated the relationships between lipid profiles, lipoprotein subclasses and inflammatory biomarkers in patients with prolonged viral suppression with either NVP or EFV and no obvious clinical inflammation. Methods: 122 clinically stable HIV-infected patients with HIV-1 RNA <20 copies longer than 6 months on NNRTI therapy were studied. 72 (59%) were on EFV and 50 (41%) on NVP. Any potentially inflammatory co-morbid diseases (concurrent viral hepatitis, diabetes, hypertension, chronic liver or renal diseases), or statin treatment, were exclusion criteria. Inflammatory biomarkers included hsCRP, LpPLA2, sCD40L, IL-6, IL-8, t-PA, MCP-1, p-selectin and VCAM-1. Lipoprotein subclass measures (VLDL, LDL, IDL and HDL particle number and size) were obtained by the use of proton nuclear magnetic resonance spectroscopy. Results: 82% were male; median age 45 years. Median CD4 count 550/μL (IQR 324). Median time since HIV diagnosis 96 months (IQR 102) and accumulated time on ART 50 months (IQR 101). Patients on NVP had higher time since HIV diagnosis (126.9 [66.7] vs 91.3 [6.6] months, p=0.008) a prolonged time on ART (89.6 [54.6] vs 62.3 [52.2] months, p=0.01) and were older (47.7 vs 40.7 years, p=0.001) than those on EFV. NVP-treated patients presented increased HDL-c (55.8 [16] vs 48.8 [10.7] mg/dL, p=0.007) and apoA1 levels (153.4 [31.9] vs 141.5 [20.5] mg/dL, p=0.02), and reduced apoB/apoA1 ratio (0.68 [0.1] vs 0.61 [0.1], p=0.003) than EFV-treated patients. No differences in inflammatory markers or lipoprotein subclasses were found between NVP and EFV. In patients with extreme lipid values (less favorable: 75th percentiles of LDL, small/dense LDLp and small HDLp, or more favorable: HDL p75 and apoB/apoA1 ratio p25), no consistent differences in inflammatory biomarkers were found. Conclusions: Patients with prolonged viral suppression on NVP present significantly higher HDL and apoA1 levels and reduced apoB/apoA1 ratios than those on EFV, but no differences were found in lipoprotein particles nor inflammatory biomarkers. Relationships between lipid parameters and inflammatory biomarkers in NNRTItreated patients are complex and do not show a linear relationship in this study.

False phylogenies on wood mice due to cryptic cytochrome-b pseudogene.

The phylogeny and phylogeography of the Old World wood mice (subgenus Sylvaemus, genus Apodemus, Muridae) are well-documented. Nevertheless, the distributions of species, such as A. fulvipectus and A. ponticus remain dubious, as well as their phylogenetic relationships with A. sylvaticus. We analysed samples of Apodemus spp. across Europe using the mitochondrial cytochrome-b gene (cyt-b) and compared the DNA and amino-acid compositions of previously published sequences. The main result stemming from this study is the presence of a well-differentiated lineage of Sylvaemus including samples of various species (A. sylvaticus, A. fulvipectus, A. ponticus) from distant locations, which were revealed to be nuclear copies of the mitochondrial cyt-b. The presence of this cryptic pseudogene in published sequences is supported by different pathways. This has led to important errors in previous molecular trees and hence to partial misinterpretations in the phylogeny of Apodemus.