A non-azole inhibitor of lanosterol 14 alpha-methyl demethylase in Candida albicans.

6-Hydroxy-N-methyl-N-(2-[4-phenylphenyl] ethyl)-1,2,3,4-tetrahydro-1- napthalene methanamine (A60586), a new non-azole inhibitor of ergosterol biosynthesis in Candida albicans ATCC62376 has been identified. In whole cells A60586 produced a dose related reduction of [14C]acetate incorporation into ergosterol and a concurrent increase in the radiolabelling of 4,4-dimethylated sterols. Similar observations were made with [14C]mevalonic acid lactone labelled cell free extracts. The IC50s for inhibition of ergosterol in the whole cell and cell free systems were 22 microM (10 mg/L) and 7.8 microM (3.5 mg/L), respectively. Analysis by gas chromatography of sterols from cells previously incubated at 37 degrees C for 24 h with A60586 (200 mg/L) confirmed the presence of lanosterol and 14 alpha-methyl fecosterol. These data indicate that A60586, inhibits the demethylation of the C-14 methyl group of lanosterol. The MIC of A60586 for several candida strains ranged from 12.5 to 50 mg/L, and against Cryptococcus albidus and Aspergillus niger ranged from 50 to 100 mg/L. The best in-vitro activity of A60586 was against Torulopsis glabrata (MIC range = 3.12 to 50 mg/L). The membrane permeabilizing effect of this compound (50% leakage of [14C]aminoisobutyric acid at 70 mg/L A60586) may have contributed to its in-vitro antifungal activity.     

Dissociation of behavioral inhibition within the fornix system.

Rats with transections of either the total fornix bundle, the precommissural fornix, or the postcommissural fornix columns were tested on the acquisition of a DRL-20 schedule and a modified Sidman avoidance task. Total and precommissural fornix cuts severely impaired DRL performance and facilitated avoidance acquisition. Postcommissural columns transections had no effect on DRL performance, but did facilitate performance on the avoidance task. The existing DRL data from this study and others are consistent with a hypothesized septo-hippocamposeptal inhibitory feedback loop which mediates behavioral inhibition.     

Macrolide transport in Escherichia coli strains having normal and altered OmpC and/or OmpF porins

[(14)C]Erythromycin and [(14)C]azithromycin uptake rates were studied in Escherichia coli strains containing normal OmpC and OmpF porins (strain MRC 106) and altered OmpC porins due to small insertions (strains RAM121 and OC1555) or deletions (strain RAM122) in the ompC alleles and altered OmpF porins due to small ompF deletions (strains OC1555 and PLB3255). Strains RAM121 and RAM122 also lacked OmpF porins in their outer membrane. The porin mutants demonstrated a 2- to 1224-fold increase in macrolide transport and a concurrent 3- to 530-fold decrease in MIC when compared to the parent strain, MCR106. Both strains OC1555 and PLB3255 had enhanced permeability to 1-N-phenylnaphthylamine indicating increased permeability of the outer membrane to hydrophobic molecules. The macrolides, at 2 to 1000 times MIC, failed to displace the cationic probe polymyxin; therefore, drug entry by a self-promoted mechanism was not indicated. Since >95% of macrolide is protonated and thus hydrophilic (logP(i)=-0.89) at neutral pH, the bulk of drug entry may be via the porin channels.     

Regulation of matrix metalloproteinases 2 and 9 activities by peroxynitrites in term placentas from type 2 diabetic patients

Matrix metalloproteinases (MMPs) are proteolytic enzymes related to a proinflammatory environment in several diseases, including diabetes, which can be activated by reactive nitrogen species. This work aimed to determine MMP-2 and MMP-9 activities and nitration in term placentas from type 2 diabetic patients and verify the hypothesis that peroxynitrites are positive regulators of placental MMP-2 and MMP-9 activities. For this purpose, term placentas from healthy and type 2 diabetic patients were analyzed for MMP-2 and MMP-9 levels and activities, protein nitration, and nitration of MMP-2 and MMP-9. Villous explants were cultured in the presence of peroxynitrites for further evaluation of MMP-2 and MMP-9 activities. We found that MMP-2 and MMP-9 activities were increased in term placentas from diabetic patients. These changes were found even when MMP-2 protein concentrations were diminished and MMP-9 protein concentrations were not changed in the diabetic group. Increased protein nitration and specific nitration of MMP-2 and MMP-9 were found in term placentas from diabetic patients. Peroxynitrites were able to increase the activity of placental MMP-2 and MMP-9. Taken together, this study has shown for first time that peroxynitrites can nitrate and activate MMP-2 and MMP-9 in the placenta, a nitrative pathway possibly related to MMPs overactivity in the placentas from type 2 diabetic patients.     

Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study

Journal of Neurology - To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment. This was an...     

Increased nitric oxide production and gender-dependent changes in PPARα expression and signaling in the fetal lung from diabetic rats

The fetal lung is affected by maternal diabetes. Nuclear receptor PPARα regulates nitric oxide (NO) overproduction in different tissues. We aimed to determine whether fetal lung PPARα expression is altered by maternal diabetes, and if there are gender-dependent changes in PPARα regulation of NO production in the fetal lung. Fetal lungs from control and diabetic rats were explanted on day 21 of gestation and evaluated for PPARα expression and NO production. Fetuses were injected with the PPARα ligand LTB(4) on days 19, 20 and 21, and the fetal lung explanted on day 21 to evaluate PPARα and the inducible isoform of NO synthase (iNOS). Besides, pregnant rats were fed with olive oil- and safflower oil-supplemented diets, enriched in PPAR ligands, for evaluation of fetal lung NO production and PPARα expression. We found reduced PPARα concentrations only in the lung from male fetuses from the diabetic group when compared to controls, although maternal diabetes led to NO overproduction in both male and female fetal lungs. Fetal activation of PPARα led to changes in lung PPARα expression only in female fetuses, although this treatment increased iNOS expression in both male and female fetuses in the diabetic group. Diets supplemented with olive oil and not with safflower oil led to a reduction in NO production in male and female fetal lungs. In conclusion, there are gender-dependent changes in PPARα expression and signaling in the fetal lung from diabetic rats, although PPARα activation prevents maternal diabetes-induced lung NO overproduction in both male and female fetuses.     

Primary umbilical endometriosis. Case report and discussion on management options

INTRODUCTIONWe report a recently observed case of primary umbilical endometriosis (UE), with the main aim to discuss the management of this rare condition.PRESENTATION OF CASEA 24-year-old woman complained of a painful nodule on her umbilical region, bleeding with her menstrual cycle. Ultrasonography showed a hypoechoic superficial mass in the umbilicus and no signs of intra-abdominal endometriosis. Excision of the nodule under local anesthesia was performed. Histopathological analysis confirmed the diagnosis of umbilical endometriosis. Neither symptoms nor signs of local recurrence have been observed after 24 months.DISCUSSIONUE should be taken into account in differential diagnosis of umbilical disorders even in young nulliparous women with no typical symptoms of pelvic endometriosis. Although there is a substantial agreement about the necessity of surgery, treatment options are either local excision of the lesion or removal of the whole umbilicus with or without laparoscopic exploration of the peritoneal cavity. The decision should be tailored for the individual patient, taking into consideration the size of the lesion, the duration of symptoms and the presence of possible pelvic endometriosis.CONCLUSIONLocal excision saving the umbilicus may be the treatment of choice in patients with small UE lesions.     

A temporal model of patient disclosure in psychotherapy

Abstract

The primary aim of this study was to identify the temporal elements of patient self-disclosure in psychotherapy. Twenty-one patients in individual psychotherapy participated in a semistructured interview that explored issues related to the intrinsic decision-making process and the emotional experiences involved in disclosing intimate concerns and secrets in therapy; they also completed several Likert-type questions focused on feelings experienced after disclosures. Results indicate a general sequence of events within the disclosure process: (a) a generally positive attitude toward disclosure; (b) ambivalence before disclosure; (c) vulnerability during disclosure; (d) primarily positive emotional experiences immediately after disclosure; (e) a search for and receipt of therapist approval after disclosure; and (f) increased likelihood of future disclosures to therapists and others. The data suggest that, whereas distressful feelings (e.g., shame) often precede and accompany self-disclosure, positive feelings (e.g., relief and pride) tend to predominate during and after disclosure.

Zusammenfassung

Ein Zeitmodell von Disclosure für Patienten in Psychotherapie

Das Hauptziel dieser Untersuchung war es, die Zeitelemente von Disclosure von Patienten in Psychotherapie zu identifizieren. 21 Patienten in individueller Psychotherapie nahmen an einem halbstrukturierten Interview teil, das Fragen des intrinsischen Entscheidungsprozesses und emotionale Erfahrungen bei Disclosure von intimen Problemen und Geheimnissen in der Therapie betraf. Die Patienten füllten auch einige Antworten mithilfe Likert-skalierter Fragen zu nach Disclosure auftretenden Gefühlen aus. Die Ergebnisse zeigten eine allgemeine Abfolge von Geschehnissen beim Disclosureprozess auf: a) eine allgemein positive Einstellung zu Disclosure, b) Ambivalenz von Disclosure, c) Verletzbarkeit während Disclosure, d) überwiegend positive emotionale Erfahrungen direkt nach Disclosure, e) Suche nach Empfang von Bestätigung durch den Therapeuten nach Disclosure, und f) erhöhte Wahrscheinlichkeit von zukünftiger Disclosure dem Therapeuten und anderen gegenüber. Die Daten legen nahe, dass häufig stressvolle Erfahrungen (z. B. Scham) der Selbst-Disclosure vorhergehen bzw. sie auch begleiten, aber dass auch die Tendenz besteht, dass positive Gefühle (z. B. Erleichterung und Stolz) während und nach erfolgter Disclosure dominieren.

Résumé

Un modèle temporal de dévoilement du patient en psychothérapie

Le but premier de cette étude était d'identifier les éléments temporels du dévoilement du patient en psychothérapie. 21 patients en psychothérapie individuelle participaient à une interview semie-structurée explorant des sujets en relation avec leur processus intrinsèque de prise de décisions et les expériences émotionnelles impliquées dans le dévoilement de sujets intimes et secrets en thérapie; ils répondaient également à certaines questions de type Likert centrées sur les sentiments vécus après le dévoilement. Les résultats indiquent une séquence générale d’événements au cours du processus de dévoilement: (a) une attitude globalement positive à l’égard du dévoilement; (b) une ambivalence avant le dévoilement; (c) une vulnérabilité au moment du dévoilement; (d) des expériences émotionnelles surtout positives après le dévoilement; (e) la recherche et la réception de l'approbation par le thérapeute après le dévoilement; et (f), une probabilité élevée de futurs dévoilements à des thérapeutes et à d'autres. Les données suggèrent que des sentiments troublants (comme la honte) précèdent et accompagnent souvent le dévoilement, alors des sentiments positifs (comme le soulagement, la fierté) ont tendance à prédominer pendant et après le dévoilement.

Resumen

Un modelo temporal de develamiento del paciente en psicoterapia

El primer objetivo de este estudio fue identificar los elementos temporales del develamiento del self del paciente en psicoterapia. Veintiún pacientes en psicoterapia individual participaron en una entrevista semiestructurada que exploró temas relacionados con el proceso intrínseco de toma de decisiones y con experiencias emocionales involucradas en la confesión de preocupaciones y secretos íntimos en terapia; los entrevistados completaron también varios preguntas tipo Likert centradas en los sentimientos experimentados posteriormente a tales confesiones. Los resultados muestran una secuencia general dentro del proceso: (a) una actitud generalmente positiva hacia la confesión; (b) ambivalencia antes de la confesión; (c) vulnerabilidad durante la misma; (d) experiencias emocionales principalmente positivas inmediatamente después; (e) una búsqueda y recepción de aprobación del terapeuta luego de la confesión; y (f) aumento de la probabilidad de futuras confesiones hacia terapeutas y otros. Los datos sugieren que, si bien sentimientos tensionantes (por caso, vergüenza) preceden y acompañan frecuentemente la confesión, durante y luego de la confesión tienden a predominar los sentimientos positivos (por caso, alivio y orgullo).

Resumo

Um Modelo Temporal de Auto-Revelação do Paciente em Psicoterapia

O principal objectivo deste estudo consistiu em identificar os elementos temporais da auto-revelação (self-disclosure) do paciente em psicoterapia. Vinte e um pacientes em psicoterapia individual participaram numa entrevista semi-estruturada que explorou aspectos relacionados com o processo intrínseco de tomada de decisão e as experiências emocionais que envolvem a revelação das preocupações íntimas e segredos em terapia; também completaram várias questões do tipo Likert focadas nos sentimentos experimentados após as revelações. Os resultados indicaram uma sequência geral de acontecimentos dentro do processo de revelação: (a) uma atitude positiva generalizada face à revelação; (b) ambivalência antes da revelação; (c) vulnerabilidade durante a revelação; (d) principalmente, emoções positivas imediatamente após a revelação; (e) uma procura de e recepção de aprovação do terapeuta após a revelação; e (f) aumento da probabilidade de revelações futuras ao terapeuta e outros. Os dados sugerem que, embora, sentimentos perturbadores (e.g. vergonha) frequentemente precedam e acompanhem a auto-revelação, os sentimentos positivos (e.g. alívio e orgulho) tendem a predominar durante e após a auto-revelação.

Sommario

Un modello temporale dello svelamento dei pazienti in psicoterapia

Lo scopo principale di questo studio era identificare gli elementi temporali dell'auto-svelamento del paziente in psicoterapia.

Ventuno pazienti in psicoterapia individuale hanno partecipato ad un'intervista semistrutturata che ha esplorato questioni relative all'intrinseco processo di presa di decisioni e alle esperienze emozionali riguardanti lo svelamento di intime preoccupazioni e segreti in terapia; essi hanno anche compilato parecchie domande di tipo Likert focalizzate sulle emozioni sperimentate dopo gli svelamenti.

I risultati indicano una sequenza generale di eventi all'interno del processo di svelamento: a) un'attitudine generalmente positiva verso lo svelamento; b) ambivalenza prima dello svelamento; c) vulnerabilità durante lo svelamento; d) principalmente esperienze emozionali positive immediatamente dopo lo svelamento; e) una ricerca di ricezione dell'approvazione del terapeuta dopo lo svelamento e f) l'incremento della probabilità di futuri svelamenti ai terapeuti e agli altri.

I dati suggeriscono che, mentre le emozioni dolorose (per esempio la vergogna) spesso precedono ed accompagnano l'auto-svelamento, le emozioni positive (per esempio il sollievo e l'orgoglio) tendono a predominare durante e dopo lo svelamento.