Randomized placebo-controlled phase II trial of high-dose melatonin mucoadhesive oral gel for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing radiation therapy concurrent with systemic treatment.

PURPOSE: The objective of this trial was to evaluate the safety and efficacy of melatonin oral gel mouthwashes in the prevention and treatment of oral mucositis (OM) in patients treated with concurrent radiation and systemic treatment for head and neck cancer. METHODS: Randomized, phase II, double-blind, placebo-controlled trial (1:1 ratio) of 3% melatonin oral gel mouthwashes vs. placebo, during IMRT (total dose ≥ 66 Gy) plus concurrent Q3W cisplatin or cetuximab. Primary endpoint: grade 3-4 OM or Severe Oral Mucositis (SOM) incidence by RTOG, NCI, and a composite RTOG-NCI scales. Secondary endpoints: SOM duration and grade 2-4 OM or Ulcerative Oral Mucositis (UOM) incidence and duration. RESULTS: Eighty-four patients were included in the study. Concurrent systemic treatments were cisplatin (n = 54; 64%) or cetuximab (n = 30; 36%). Compared with the placebo arm, RTOG-defined SOM incidence was numerically lower in the 3% melatonin oral gel arm (53 vs. 64%, P = 0.36). In patients treated with cisplatin, assessed by the RTOG-NCI composite scale, both SOM incidence (44 vs. 78%; P = 0.02) and median SOM duration (0 vs. 22 days; P = 0.022) were significantly reduced in the melatonin arm. Median UOM duration assessed by the RTOG-NCI scale was also significantly shorter in the melatonin arm (49 vs. 73 days; P = 0.014). Rate of adverse events and overall response rate were similar between the two arms. CONCLUSIONS: Treatment with melatonin oral gel showed a consistent trend to lower incidence and shorter SOM duration and shorter duration of UOM. These results warrant further investigation in phase III clinical trial.

The state of the art in European research on reducing social exclusion and stigma related to mental health: a systematic mapping of the literature.

Stigma and social exclusion related to mental health are of substantial public health importance for Europe. As part of ROAMER (ROAdmap for MEntal health Research in Europe), we used systematic mapping techniques to describe the current state of research on stigma and social exclusion across Europe. Findings demonstrate growing interest in this field between 2007 and 2012. Most studies were descriptive (60%), focused on adults of working age (60%) and were performed in Northwest Europe-primarily in the UK (32%), Finland (8%), Sweden (8%) and Germany (7%). In terms of mental health characteristics, the largest proportion of studies investigated general mental health (20%), common mental disorders (16%), schizophrenia (16%) or depression (14%). There is a paucity of research looking at mechanisms to reduce stigma and promote social inclusion, or at factors that might promote resilience or protect against stigma/social exclusion across the life course. Evidence is also limited in relation to evaluations of interventions. Increasing incentives for cross-country research collaborations, especially with new EU Member States and collaboration across European professional organizations and disciplines, could improve understanding of the range of underpinning social and cultural factors which promote inclusion or contribute toward lower levels of stigma, especially during times of hardship.

Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2.

BACE2 is homologous to BACE1, a beta-secretase that is involved in the amyloidogenic pathway of amyloid precursor protein (APP), and maps to the Down syndrome critical region of chromosome 21. Alzheimer disease neuropathology is common in Down syndrome patients at relatively early ages, and it has thus been speculated that BACE2 co-overexpression with APP would promote the early neurodegenerative phenotype. However, the in vivo function of BACE2 has not yet been elucidated. The aim of the present work has been to analyse the impact of in vivo BACE2 overexpression using a transgenic mouse model. Our results suggest that BACE2 is not involved in the amyloidogenic pathway, cognitive dysfunction or cholinergic degeneration. However, TgBACE2 animals showed increased anxiety-like behaviour along with increased numbers of noradrenergic neurones in locus coeruleus, thus suggesting an unexpected role of BACE2 overexpression.

Decreased linezolid uptake in an in vitro-selected linezolid-resistant Staphylococcus epidermidis mutant.

OBJECTIVES: The aim of this study was to characterize the mechanism of resistance to linezolid in an in vitro-selected linezolid-resistant Staphylococcus epidermidis mutant. METHODS: A linezolid-resistant strain of S. epidermidis was selected by serial passages with increasing concentrations of linezolid. The MICs of linezolid, ciprofloxacin, tetracycline, rifampicin, vancomycin, gentamicin, tobramycin, chloramphenicol and oxacillin were determined. The 23S rRNA gene was amplified and sequenced, to search for mutations conferring linezolid resistance. The MIC of linezolid was also determined in the presence of reserpine. Finally, the accumulation of linezolid was measured and quantified by HPLC/UV. RESULTS: The obtained resistant strain had an MIC of linezolid of 64 mg/L and was stable after several passages on blood agar. The MIC measured in the presence of 25 mg/L reserpine, an efflux pump inhibitor, was not altered (MIC of 64 mg/L). The sequence of the 23S rRNA gene showed that the mutation G2576T (Escherichia coli numbering) was not present and no other mutation was found. An analysis of the accumulation of linezolid was performed, comparing the uptake of the resistant strain with that of the susceptible one. This showed that the resistant strain had significantly lower levels of linezolid accumulation than its susceptible parental strain. CONCLUSIONS: The mechanism of resistance to linezolid, in this resistant strain, may be related to a decrease in the antimicrobial uptake. This new mechanism of resistance was also related to a little loss of fitness.

Tratamiento nutricional en la enfermedad inflamatoria intestinal / Nutritional management of inflammatory bowel disease

Los pacientes con enfermedad inflamatoria intestinal presentan mayor riesgo de malnutrición. Por este motivo es muy frecuente que se precise un adecuado soporte nutricional. En estos pacientes se debe utilizar la nutrición enteral a menos que existan contraindicaciones. El soporte nutricional como tratamiento primario no está indicado en adultos (al haberse demostrado una mayor eficacia del tratamiento esteroideo) salvo en caso de intolerancia o falta de respuesta al tratamiento médico. Por el contrario, la nutrición enteral se considera el tratamiento de primera línea en niños. No existe un claro beneficio con el uso de fórmulas específicas (grasa modificada, glutamina...) por lo que no se aconseja su uso rutinario. A pesar de los grandes avances técnicos y científicos existen aún numerosos campos en los que ampliar conocimientos; algunos de los mismos se esbozan en la presente publicación (AU)

Patients with inflammatory bowel disease present higher risk for hyponutrition. For this reason, an adequate nutritional support is frequently needed. In these patients, enteral nutrition should be used unless there exist contraindications. Nutritional support as the primary therapy is no indicated in adults (since steroidal therapy has shown to be more effective) but in the case of intolerance or lack of response to medical treatment. By contrast, enteral nutrition is considered a first line therapy in children. There is no clear benefit with the use of specific formulas (modified fat, glutamine...), so that their routine use is not recommended. In spite of the great technical and scientific advances, there are still many fields in which knowledge should be broaden; some of them are pointed out in this publication (AU)

[Nutritional management of inflammatory bowel disease]. / Tratamiento nutricional en la enfermedad inflamatoria intestinal.

Patients with inflammatory bowel disease present higher risk for hyponutrition. For this reason, an adequate nutritional support is frequently needed. In these patients, enteral nutrition should be used unless there exist contraindications. Nutritional support as the primary therapy is no indicated in adults (since steroidal therapy has shown to be more effective) but in the case of intolerance or lack of response to medical treatment. By contrast, enteral nutrition is considered a first line therapy in children. There is no clear benefit with the use of specific formulas (modified fat, glutamine...), so that their routine use is not recommended. In spite of the great technical and scientific advances, there are still many fields in which knowledge should be broaden; some of them are pointed out in this publication.

In vitro activity of sertaconazole, fluconazole, ketoconazole, fenticonazole, clotrimazole and itraconazole against pathogenic vaginal yeast isolates.

The in vitro activity of sertaconazole was compared with those of the most commonly used vaginal antimycotic agents--fluconazole, ketoconazole, fenticonazole, clotrimazole and itraconazole--against 94 strains of clinical isolates of Candida spp. using a macrodilution method in Casitone agar medium. The sertaconazole concentration (microgram/ml), at which 90% of the strains were inhibited, was 0.06 for C. albicans, 0.25 for C. glabrata and C. parapsilosis, 1 for C. krusei and 2 for C. tropicalis. These values show that sertaconazole is one of the most active products against yeasts causing vulvovaginal candidiasis, its activity against C. glabrata being particularly relevant.

Sertaconazole: pharmacology of a gynecological antifungal agent.

Sertaconazole is a broad spectrum antifungal agent with excellent activity against yeasts, dermatophytes and opportunistic fungi. In addition to this antifungal efficacy, it has a good safety profile, sustained cutaneous retention, and low systemic absorption, all of which make it ideal for topical applications. In this study, the pharmacological properties of sertaconazole related to the treatment of vaginal fungi, in particular vulvovaginal candidiasis, are reviewed. As with all other infectious processes, the interacting components are infectious microorganism, host and drug. The following properties of sertaconazole have been investigated in pre-clinical studies: its in vitro spectrum of activity and potency against causative agents and accompanying factors in vaginal infection; its mechanism of action, whether it acts on the pathogenic properties of the microorganism; if it affects host defense mechanisms and how its antifungal activity is manifested in vivo in experimental candidiasis in the mouse.

In vitro activity of sertaconazole against Malassezia furfur and pachydermatis in different culture media.

The activity of sertaconazole against Malassezia furfur and pachydermatis was tested in different culture media in order to elucidate the factors that can influence its activity. The addition to the culture media of lipids, which are necessary for M. furfur to grow, was found to decrease the activity of this antifungal to a great extent. Since the aim of in vitro drug testing is to provide representative data of its activity which must be indicative for its clinical efficacy, and in view of the good clinical response of M. furfur infection to sertaconazole, it is concluded that the activity of this antifungal against M. furfur cannot be determined by the in vitro data provided by conventional methods due to such influential factors.

In vitro anti-Helicobacter pylori activity of ebrotidine.

The in vitro anti-Helicobacter pylori (H. pylori) activity of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene) amino]-4-thiazolyl]methyl]thio]ethyl]amino]methylene]-4-bromo- benzenesulfonamide, CAS 100981-43-9, FI-3542) versus ranitidine, and their effect on the susceptibility to the antimicrobial agents used in H. pylori eradication were investigated. Assessment was performed by determining the minimum inhibitory concentrations (MIC) against 9 strains of H. pylori, 8 from clinical source and 1 from the American Type Culture Collection (ATCC 43504), in Mueller-Hinton solid media plus 7% blood. The concentration of inocula was 10(7) CFU/ml, incubation was performed at 37 degrees C in microaerophilic atmosphere, and results were read after 5 days of growth. Ebrotidine gave a mean MIC value of 75 micrograms/ml, while that for ranitidine was > 1000 micrograms/ml. Ebrotidine at 100 micrograms/ml enhanced the activity of the antimicrobials studied as follows: erythromycin 3 times, tetracycline 1.1 times, amoxicillin 3 times, metronidazole-sensitive strains 9 times and clarithromycin 5 times. Ranitidine had no effect on the MIC of the antibiotics even at 500 micrograms/ml.

Incidence of Listeria monocytogenes in fresh foods in Barcelona (Spain).

From September 1989 to March 1990, a study of Listeria spp. was carried out on 311 samples of raw foodstuffs from markets and other establishments in the city of Barcelona. These foodstuffs included vegetables (103 samples), minced meats from pork, beef and poultry (168 samples) and bivalve molluscs (40 samples). L. monocytogenes was isolated in 7.8% of the vegetable samples, 17.3% of the minced meats and in 7.5% of bivalve molluscs. The most frequent serovars were 1/2 and 4. Other species isolated were L. innocua, L. welschimeri and L. seeligeri.