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Traditional local image descriptors such as SIFT and SURF are based on processings similar to those that take place in the early visual cortex. Nowadays, convolutional neural networks still draw inspiration from the human vision system, integrating computational elements typical of higher visual cortical areas. Deep CNN’s architectures are intrinsically hard to interpret, so much effort has been made to dissect them in order to understand which type of features they learn. However, considering the resemblance to the human vision system, no enough attention has been devoted to understand if the image features learned by deep CNNs and used for classification correlate with features that humans select when viewing images, the so-called human fixations, nor if they correlate with earlier developed handcrafted features such as SIFT and SURF. Exploring these correlations is highly meaningful since what we require from CNNs, and features in general, is to recognize and correctly classify objects or subjects relevant to humans. In this paper, we establish the correlation between three families of image interest points: human fixations, handcrafted and CNN features. We extract features from the feature maps of selected layers of several deep CNN’s architectures, from the shallowest to the deepest. All features and fixations are then compared with two types of measures, global and local, which unveil the degree of similarity of the areas of interest of the three families. From the experiments carried out on ETD human fixations database, it turns out that human fixations are positively correlated with handcrafted features and even more with deep layers of CNNs and that handcrafted features highly correlate between themselves as some CNNs do.

Objectif - Dans le contexte de la leucémie myéloïde chronique (LMC), la recherche du transcrit de fusion BCR-ABL1 est devenue indispensable pour confirmer le diagnostic moléculaire. Dans cette étude, nous décrivons les différents types de transcrits de fusion BCR-ABL1 retrouvés chez des patients de l’Ouest algérien atteints de leucémie muéloïde chronique (LMC). Méthodes - Au total 167 patients suspects de LMC ont été inclus dans cette étude. La recherche qualitative des transcrits de fusion a été réalisée au service de biochimie de l’Etablissement hospitalier et universitaire d’Oran, par la technique d’amplification en chaine par polymérase après rétro-transcription (RT-PCR). Résultats - Les deux types de transcrits de fusion BCR-ABL1de type majeur Mb3a2 et Mb2a2 étaient présents respectivement dans 59,8 et 36.4 % des cas. Deux patients (1,8%) avaient un transcrit atypique rare de type e19a2 et deux autres (1,8%), ont co-exprimé les deux types b3a2 et b2a2. Conclusion - Notre étude a confirmé les données de la littérature en montrant une incidence plus élevée du transcrit majeur.

Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease caused by Protozoa of the genus Leishmania. Clinical manifestations of this disease are the result of a complex interplay of diverse factors, including the genetic background and the immune status of the host. Understanding the impact of these factors on the CL pathology may provide new targets to manage the infection and improve clinical outcome. The NLRP3 inflammasome, an innate immune complex of several cell types, seems to be involved in the CL physiopathology. Current studies of its role show contradictory effects of this complex on the evolution of Leishmania infection in mice and humans. In this review, we discuss the data regarding different roles of the NLRP3 inflammasome in murine and human CL.

Aim In chronic myeloid leukemia (CML), the impact of MBCR-ABL1 major transcript type on disease phenotype and response to treatment still controversial to date. This work aims to study the influence of Mb3a2 and Mb2a2 transcripts on clinico-biological parameters and the molecular response in patients with chronic phase chronic myeloid leukemia (CP-CML) treated with Imatinib as frontline therapy. Methods This is six years prospective study started in March 1 st, 2013. 67 patients with newly CP-CML were treated by Imatinib as frontline therapy. Clinical and biological characteristics disease were collected for all patients. Molecular typing was performed by multiplex RT-PCR and quantification of transcripts by real-time quantitative PCR (qRT-PCR). The cumulative incidence of deep molecular response (DMR) was estimated by the Kaplan-Meier method. The comparison was made using the parametric Log-Rank test. A value of P ≤ 0.05 is considered significant. Results 61% of patients expressed b3a2, 35.82% b2a2 and 2.98% expressed a rare transcript of type e19a2. At diagnosis, the b2a2 type had a higher level of expression than that of b3a2 (67.92 vs 53.79%; P = 0.03). This insignificant difference between the two transcript subgroups was also observed for rates below 1% at 6 months (54 vs 39; P = 0.26) and below 0.1% (54 vs 44 %; P = 0.50), (77 vs 50%; P = 0.09) and (81 vs 78 %; P = 0.52) at 12, 18 and 24 months respectively. The two types of transcript had almost the same kinetics. Nevertheless, the absolute value of the BCR-ABL1/ABL ratio decrease was faster in the group of patients expressing b3a2, than in those expressing b2a2. At 18 months post IM therapy, patients with a b3a2 transcript have a trend of better MMR that those with b2a2 (77 vs 50%; P = 0.09). The DMR was not significantly different between two groups at 24 months (50 vs 32%; P = 0.20) and 36 months (75 vs 70%; P = 0.54) respectively. The cumulative probability of achieving MRD at 5 years was higher in patients with b3a2 type but not statistically significant; (85 vs. 68%; P = 0.17). Conclusion Patients with b3a2 transcript may be associated with a better response to Imatinib therapy.

The outbreak of coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has emerged in China in December 2019 and rapidly spread to more than 196 countries worldwide. The physiopathology of human SARS-CoV-2 has not been completely understood, but its pathogenesis has been linked to a disproportionate response of the immune system. Just as described for SARS and MERS, an uncontrolled systemic inflammatory response, known as cytokine release syndrome (CRS) was observed in severe COVID-19 patients. It results from the release by immune and non-immune effector cells of substantial amounts of pro-inflammatory cytokines and appears to contribute to SARS-CoV-2 pulmonary inflammation and extensive lung damage. In addition, hyper-coagulation and thrombosis resulted from the important release of pro-inflammatory cytokines contribute to the lethality of subjects severely infected with SARS-CoV-2. It is therefore essential to have a deep understanding of the various cytokines involved in this exacerbated immune response, and that could be targeted by potential immunological treatments. The aim of this review was to gather the current knowledge about the role of pro-inflammatory cytokines, namely IL-1β, IL-6, IL-8, IL-17 and TNFα in SARS-CoV-2 CRS, the probable causes and clinical outcomes of this phenomenon in severe cases of COVID-19.

Objective: The prognosis for chronic myeloid leukemia (CML) has been significantly improved in the era of tyrosine kinase inhibitors (TKIs) whose leader is Imatinib mesylate (IM). Obtaining a major molecular response (MMR) is a major objective to achieve. However, the difference in response between the two sexes is often controversial. This work aims to evaluate the molecular response according to sex in Algerian patients with chronic phase CML (CML-CP) treated with IM in first intention. Methods: All Novo CML patients benefited from molecular follow-up by quantification of transcripts by real-time quantitative PCR (RQ-PCR). The cumulative incidence of MMR (CIMMR) was estimated by the Kaplan-Meier method. The comparison was made using the parametric Log-Rank test. A value of P ≤ 0.05 is considered significant. Results: Fifty-five patients were included in this study, with a mean age of 45.7 ± 13.9 including 29 men (53%) and 26 women (47%). For women, the incidence of Mb3a2 transcript was higher than that of Mb2a2 (72% vs. 28%, P=0.12). Men, on the other hand, had an almost equal distribution (52% vs. 48%, P = 0.88). The CIMMR for men was lower than that for women (45% vs. 80%, P=0.018). Conclusion: Women seem to respond more favorably to IM than men.

International audience; Herein we describe the drug design steps developed to increase the radical scavenging and β-amyloid aggregation inhibitory activities of a previously described series of benzylidenephenylpyrrolizinones. Among the newly synthesized derivatives, some benzylphenylpyrrolizinones exhibited interesting results in regard to those activities. Initial druggability parameters were measured, and suggest these compounds as a suitable starting point for potential alternatives in treating Alzheimer's disease

We previously reported that the cinnamylpiperazinyl group in the side chain of the chenodeoxycholic acid showed apoptosis-inducing activity on multiple myeloma cancer cell line KMS-11. In the present study, we synthesized and tested the pro-apoptotic potency of fifteen new piperazinyl bile carboxamide derived from cholic, ursodeoxycholic, chenodeoxycholic, deoxycholic and lithocholic acids on human colon adenocarcinoma cell lines DLD-1, HCT-116, and HT-29. Cell viability was first measured using XTT assay. The most of the synthetic bile carboxamide derivatives decreased significantly cell viability in a dose-dependent manner. HCT-116 and DLD-1 cell lines were more sensitive than HT-29 to tested compounds. 9c, 9d showed the best in vitro results in term of solubility and dose–response effect on the three colon adenocarcinoma cell lines. Additionally, flow cytometric and Western-blotting analysis showed that 9c induced pro-apoptosis in DLD-1 and HCT-116 whereas 9d did not. We conclude that the benzyl group improved anti-proliferative activity and that the α-hydroxyl group was found to be more beneficial at the 7-position in steroid skeleton.

AIMS The purpose of this study was to evaluate the efficacy, risks, safety, and follow-up of radiofrequency (RF) catheter ablation of atrioventricular nodal re-entrant tachycardia (AVRNT) in patients (pts) > or = 75 years old (n=42) (GpI) compared with pts younger than 75 years (n=234) (GpII). METHODS AND RESULTS The study population consisted of 276 consecutive pts (39.5% men/60.5% women), from 15 to 98-year-old (average 56+/-17 years) with AVRNT referred for RF ablation (RFA) from October 1997 to January 2004. Combined anatomical and electrogram approaches were used to guide RFA. The cumulative risk of AVRNT recurrence was analysed by the Kaplan-Meier method and log-rank test. The average follow-up was 34+/-18 months. GpI (80+/-4 years) differed significantly from GpII (51+/-14 years) regarding: heart rate tachycardia (160+/-20 vs. 180+/-30 bpm; P=0.0001), the slow pathway antegrade refractory period (370+/-70 vs. 340+/-60 ms; P=0.01), the fast pathway antegrade refractory period (360+/-60 vs. 330+/-60 ms; P=0.003), retrograde refractory period (360+/-60 vs. 330+/-60 ms; P=0.0007), left ventricular ejection fraction (60+/-12 vs. 65+/-7%; P=0.0009), and ischaemic ECG signs during tachycardia (76.2% vs. 61%; P=0.09). RFA was successfully obtained in 275/276 (99.6%), 42/42 in GpI (100%), and 233/234 (99.6%) in GpII. Five complications occurred (1.8%): major complications in two pts (0.7%) and minor complications in three pts (1.1%). Major complications were deep venous thrombosis with pulmonary embolus (n=1) and pericardial effusion (n=1), minor complications were groin haematoma (n=3). One complication was observed in GpI (groin haematoma) (2.4%) and four in GpII (deep venous thrombosis with pulmonary embolus in one, groin haematoma in two, and pericardial effusion in one) (1.7%). The number of recurrences was not statistically different between the two groups (0 vs. 3.4%; P=0.5) with a respective average follow-up of 28+/-18 and 35+/-18 months, respectively. CONCLUSION Catheter ablation of AVRNT in elderly and very elderly pts appears to be a reasonable approach regarding feasibility and effectiveness without increasing the risk of AV block.

International audience; Nine new 17-(piperazin-1-yl)pyridin-5-yl)steroids as abiraterone analogues were synthesized. Compounds 5d and 5g showed selective activities against 17α-hydroxylase/C17,20-lyase (CYP17A1) and aromatase (CYP19), respectively. IC50 values of 5d were 5.09 and >50 μm, whereas these values for 5g were >50 μm and 7.40 μm, respectively, for CYP17A1 and CYP19. Molecular modelling highlighted that the inhibitor designed to bind cytochrome P450 haem iron is a necessary condition but not the only rationale to explain inhibitory activity. These abiraterone analogues were then evaluated on hormone-independent prostate cancer cell lines DU-145 and PC-3 and on hormone-dependent breast and prostate cancer cell lines MCF-7 and LNCaP, respectively. Compounds 5e, 5g and 5i have showed potent activities only on hormone-independent prostate cancer cell lines DU-145 and PC-3 with 60–85% inhibition of both cell viability and growth at 10 nm with pro-apoptotic mechanism as illustrated in PC-3 cells by DNA ladder assay and Western blotting of Bax, Casp-3 and its substrate, the poly (ADP–ribose) polymerase. We conclude that hybrid heterocycle steroids could be good lead compounds in the drug design especially against hormone-independent prostate cancer.

International audience; This work describes the synthesis and the biological evaluation of novel benzylidenephenylpyrrolizinones as potential antioxidant, metal chelating or amyloid β (βA) aggregation inhibitors. Some derivatives exhibited interesting results in regard to several of the performed evaluations and appear as valuable Multi-Target Directed Ligands with potential therapeutic interest in Alzheimer's disease. Among them, compound 29 particularly appears as a valuable radical and NO scavenger, a Cu(II) and Fe(II) chelating agent and exhibits moderate βA aggregation inhibition properties. These activities, associated to a good predictive bioavailability and a lack of cytotoxicity, design it as a promising hit for further in vivo investigation

Dehydroepiandrosterone (DHEA) is a multifunctional steroid with a broad range of biological effects in humans and animals. DHEA can be converted to multiple oxygenated metabolites in the brain and peripheral tissues. The mechanisms by which DHEA exerts its effects are not well understood. However, evidence that the effects of DHEA are mediated by its oxygenated metabolites has accumulated. This paper will review the panel of oxygenated DHEA metabolites (7, 16 and 17-hydroxylated derivatives) including a number of 5α-androstane derivatives, such as epiandrosterone (EpiA) metabolites. The most important aspects of the oxidative metabolism of DHEA in the liver, intestine and brain are described. Then, this article reviews the reported biological effects of oxygenated DHEA metabolites from recent findings with a specific focus on cancer, inflammatory and immune processes, osteoporosis, thermogenesis, adipogenesis, the cardiovascular system, the brain and the estrogen and androgen receptors.

This work deals the application of the artificial immune system to discriminate between healthy and people with Parkinson’s disease (PWP). As the symptoms of Parkinson’s disease (PD) occur gradually and mostly targeting the elderly people for whom physical visits to the clinic are inconvenient and costly, telemonitoring of the disease using measurements of dysphonia (vocal features) has a vital role in its early diagnosis. Taking inspiration from natural immune systems, we try to grab useful properties such as automatic recognition, memorization and adaptation. The developed algorithms have as a base the algorithm of training bio inspired CLONCLAS. The results obtained are satisfactory and show a great reliability of the approach.

A seven-step synthesis of (2E,4E)-5-[4-hydroxy-3-methoxyphenyl]penta-2,4-dienoic acid from ferulic acid was developed. The use of a natural by-product found in rice bran as a raw material provided the ferulic acid vinylogous in an overall high yield. This compound will be useful for the preparation of a wide variety of avenalumic carboxamide derivatives.

Six new synthetic bile acid derivatives were synthesized and tested in vitro against various human cancer cells (glioblastoma multiforme (GBM), multiple myeloma (KMS-11), and colonic carcinoma (HCT-116) cell lines. The best activity was obtained with compound IIIb on multiple myeloma cells (LD50: 8.5 ± 0.5 μM). This activity was associated with Mcl-1 and PARP-1 cleavage, inhibition of NFκB signaling, and DNA fragmentation, demonstrating an apoptotic cell death signaling pathway.

Imidazobenzodiazepine derivatives were obtained by cyclization of the condensation products 7‐amino‐2,5,6‐trimethylbenzimidazole with acetylacetone and ethyl acetoacetate. By careful examination of spectroscopic data and the open‐chain intermediate isolation, we have identified the formed compound structure.

Unimodal biometric have improved the possibility to establish systems capable of identifying and managing the flow of individuals according to the available intrinsic characteristics that we have. However, a reliable recognition system requires multiple resources. This is the main objective of the multimodal systems that consists of using different resources. Although multimodality improves the accuracy of the systems, it occupies a large memory space and consumes more execution time considering the collected information from different resources. Therefore we have considered the feature selection, that is, the selection of the best attributes that enhances the accuracy and reduce the memory space as a solution. As a result, acceptable recognition performances with less forge and steal can be guaranteed. In this paper we propose an identification system using multimodal fusion of finger-knuckle-print, fingerprint and finger's venous network by adopting several techniques in different levels for multimodal fusion. A feature level fusion and decision level is proposed for the fusion of these three biological traits. An optimization method for this multimodal fusion system by enhancing the feature level fusion is introduced. The optimization consists of the space reduction by using different methods., This work was supported by the Erasmus Mundus program EU-MARE NOSTRUM (EUMN) grant agreement number: 2011-4050/001-001-EMA2., info:eu-repo/semantics/publishedVersion

Efficient syntheses of new DHEA analogues, and their apoptotic and necrotic effects on Leydig cells and TM4 Sertoli cells are described. The key step in the synthetic strategy of 7-amino-DHEA derivatives involves a bromination on C-7 position to give an epimeric mixture of bromides which were substituted by azides and reduced to give 7alpha- and 7beta-amino-3beta-hydroxyandrost-5-en-17-ones. No cytotoxic effect induced by apoptosis mechanism was observed on Leydig and TM4 Sertoli cells by treatment with these amino-DHEA analogues. A necrotic effect was induced only in TM4 Sertoli cells. The best activity was obtained with 7alpha,beta-amino-androst-5-en-3beta-ol and 7beta-amino-3beta-hydroxy-androst-5-en-17-one.

Whether chronic typical atrial flutter differs from paroxysmal atrial flutter regarding electrophysiological properties of reentry pathways and cardiac function remains unknown. If so, can remodeling due to long duration of persistently rapid atrial or ventricular rates explain these changes? The aim of the study was to compare RA local conduction velocities and heart function parameters between three groups: (1) chronic atrial flutter, (2) paroxysmal atrial flutter, and (3) controls. The study evaluated 52 patients undergoing radiofrequency ablation for typical atrial flutter. There were 35 patients with chronic atrial flutter (62.7 +/- 14 years) and 17 patients with paroxysmal atrial flutter (62.7 +/- 10 years). Underlying structural heart disease was present in 20 (57%) of 35 chronic atrial flutter patients and in 7 (41%) of 17 paroxysmal atrial flutter patients (P = 0.1). Chronic atrial flutter duration was 10.9 +/- 17 months and paroxysmal atrial flutter duration was 8.5 +/- 10 (P = 0.06). RA conduction velocity measurements were carried out before ablation during sinus rhythm under pacing (600-ms cycle length) with a 12-pole steerable catheter positioned in the high lateral RA (poles 11-12 [H6]), mid-lateral RA (poles 9-10 [H5]), and along the inferior vena caval tricuspid isthmus (poles 7-8 [H4]; 5-6 [H3]; 3-4 [H2]) with its distal electrode pair at the coronary sinus origin (pole 1-2 [H1]). Counter-clockwise RA conduction velocities were assessed from H6 to H1 and clockwise RA conduction velocities from H1 to H6. After successful ablation, RA and LA areas, LV volumes, LVEF, inferior vena caval tricuspid annulus, and coronary sinus tricuspid annulus (septal isthmus) lengths were measured by two-dimensional echocardiography. The control group included 12 patients without structural heart disease, referred for electrophysiological evaluation of AVN reentry. Counter-clockwise RA conduction velocities at the inferior vena caval tricuspid isthmus were lower in chronic atrial flutter than in paroxysmal atrial flutter (H4, 1.19 +/- 0.4 vs 1.89 +/- 1 m/s, P = 0.0051; H3, 1.14 +/- 0.4 vs 1.6 +/- 0.7 m/s, P = 0.0015; H2, 1.16 +/- 0.4 vs 1.53 +/- 0.5 m/s, P < 0.0056 and H1, 1.2 +/- 0.4 vs 1.5 +/- 0.4 m/s, P = 0.03, respectively). Counter-clockwise RA conduction velocities were identical at the high and mid-lateral RA. Counter-clockwise caval isthmus RA conduction velocities from H3 to H1 were significantly different between chronic atrial flutter and controls (H3, 1.14 +/- 0.4 vs 1.7 +/- 0.3 m/s, P = 0.0014; H2, 1.16 +/- 0.4 vs 1.83 +/- 0.4 m/s, P < 0.0001 and H1, 1.2 +/- 0.4 vs 1.94 +/- 0.4 m/s, P < 0.0001, respectively). A difference was found regarding clockwise isthmus RA conduction velocities between the two groups of atrial flutter and controls but not between chronic atrial flutter and paroxysmal atrial flutter. Respectively, chronic atrial flutter had greater RA and LA areas (24.5 +/- 5 vs 13 +/- 2 cm2; P < 0.0001 and 23 +/- 5 vs 16 +/- 3 cm2, P < 0.0001), LV end-systolic and end-diastolic volumes (50 +/- 25 vs 32 +/- 13 cm3, P = 0.0084 and 112 +/- 40 vs 85 +/- 25 cm3, P = 0.01), septal isthmus length (21 +/- 3 vs 13 +/- 2 mm, P < 0.0001), and inferior vena caval tricuspid isthmus length (39 +/- 6 vs 23 +/- 5 mm; P < 0.0001). Chronic common atrial flutter is characterized by more prolonged counter-clockwise conduction times and larger anatomic conduction pathways than the paroxysmal form, the causal relationship between electrophysiological and anatomic characteristics remains to be demonstrated.

Since the introduction of the first antibiotic (penicillin, 1942) into medical practice, to date, there has been an ongoing “race” between scientists creating new drugs and pathogenic bacteria. Antibiotic-bacteria are becoming progressively common, and to make matters worse, more and more bacteria are becoming resistant to all known antibiotics. The traditional method for this problem is to introduce new antibiotics that kill the resistant mutants. This specific “arms race” resulted into thousands of potentially active chemicals are synthesized in laboratories around the world every day.1,3,4-Oxadiazole; 1,3,4-thiadiazole; 1,2,4-triazole and some of their derivatives are involved in modifications at the following axes: First, attaching a thio-group into heterocyclic rings. Second, introducing different substitutions at position 5 which often are the residuals of the synthetic starting materials such as simple aliphatic, substituted aliphatic chains, aromatic carbocyclic and heterocyclic residues. Keywords: Mercapto-1,3,4-oxadiazole, 1,3,4-Thiadiazole, 1,2,4-Triazole, Antibacterial agents

This study deals with the design of a new macrofilaricidal drug derived from melphalan and having a lymphotropism to avoid the hepatic first pass effect and enhance bioavailability after oral administration. Melphalan was linked to a ligand leading to a prodrug called 1,3-dp-melphalan which has structural analogy to triglycerides. The Molinema dessetae/Proechimys oris model was used for antiparasitic evaluation. Melphalan was macrofilaricidal in vitro against Molinema dessetae at 1mM, inactive in vivo after an oral single dose at 164 mumol/kg while the prodrug 1,3-dp-melphalan was active against adult worms after a single dose at 82 mumol/kg. After an oral administration of the prodrug to rats, the maximum concentration and the cumulated quantities of melphalan in lymph were about 45-fold higher than those observed with the free drug under the same conditions. Moreover, the plasma concentration of melphalan was 2-fold higher than those observed after the administration of the free drug. These results are in favor of lymphotropic targeting as a novel approach to develop new orally active macrofilaricides.

The novelty of this work derives from the use of nitrogenous heterocycles as building block in the synthesis of conjugate bile acid derivatives. New piperazinyl bile acid derivatives were synthesized and tested in vitro against various human cancer cells (GBM, KMS-11, HCT-116). The best pro-apoptotic activity was obtained with N-[4N-cinnamylpiperazin-1-yl)-3alpha,7beta-dihydroxy-5beta-cholan-24-amide (7b) and N-[4N-cinnamyllpiperazin-1-yl)- 3alpha,7alpha-dihydroxy-5beta-cholan-24-amide (7c) on these human cancer cell lines (IC(50): 8.5-31.4microM). This activity was associated with nuclear and DNA fragmentation, demonstrating that 7b induces cell death by an apoptotic process as 7c. This study shows the possibility of hydrid heterocycle-steroids as new anticancer agents with improved bioactivity and easy to synthesize.

Δ 7 -5-Desaturase catalyses one of the last steps in ergosterol biosynthesis in fungi. Moreover Δ 5 -unsaturation is necessary for the sparking function. Synthesis of three pairs of C-6 epimeric cholestanol derivatives are described as potential growth inhibitors. Preliminary results suggest that 6β-aminocholestanol is a potent antifungal agent.

International audience; Neurosteroids have been reported to modulate memory processes in rodents. Three analogues of dehydroepiandrosterone (DHEA), two of them previously described (7beta-aminoDHEA and 7beta-amino-17-ethylenedioxy-DHEA), and a new one (3beta-hydroxy-5alpha-androstane-6,17-dione) were synthesized, and their effects were evaluated on memory. This study examined their effects on long term and short term memory in male (6 weeks old) NMRI mice in comparison with the reference drug. Long term memory was assessed using the passive avoidance task and short term memory (spatial working memory) using the spontaneous alternation task in a Y maze. Moreover, the effects of DHEA and its analogues on spontaneous locomotion were measured. In all tests, DHEA and analogues were injected at three equimolar doses (0.300-1.350-6.075 microM/kg). DHEA and its three analogues administered immediately post-training at the highest doses (6.075 microM/kg, s.c.) improved retention in passive avoidance test. Without effect per se in the spatial working memory task, the four compounds failed to reverse scopolamine (1mg/kg, i.p.)-induced deficit in spontaneous alternation. These data suggested an action of DHEA and analogues in consolidation of long term memory particularly when emotional components are implied. Moreover, data indicated that pharmacological modulation of DHEA as performed in this study provides derivatives giving the same mnemonic profile than reference molecule.

Darier disease is an uncommon genodermatosis characterized by verrucous papules in a seborrheic distribution. The linear form of this disease is rare and could result from genetic mosaicism in this autosomal dominant disorder. We report a case of linear Darier disease that involved the right lower limb with a zosteriform distribution.

Two sterol families have been synthesized: the first one is nitrogenous sterols containing amino, N-hydroxyimino or cyano group and the second one is oxysterols such as ketosterol and hydroxysterols. These compounds were then evaluated in vitro against Leishmania donovani promastigotes and Trypanosoma brucei brucei trypomastigotes. The most active compounds against L. donovani promastigotes were 7beta-aminomethylcholesterol and 7alpha,beta-aminocholesterol (IC50 in a range from 1 to 3 microM, pentamidine: 2.8 microM). These compounds were active on intramacrophage amastigotes with IC50 of 1.3 microM. Such an activity justifies further in vivo antileishmanial evaluation. Against T. b. brucei, (24R,S)-24-hydroxy-24-methylcholesterol (MEC, 12.5 microM) was the most active compound from these series.

Background— Cavotricuspid isthmus (CTI) characteristics are rarely documented when comparing catheters in radiofrequency ablation (RFA) of atrial flutter (AFL). Our objectives were (1) to evaluate the impact of CTI morphology and length on ablation procedures and (2) to compare the efficacy of an 8-mm-tip catheter with an irrigated cooled-tip RFA in the subgroup presumed to be more difficult to treat (with a long CTI, >35 mm). Methods and Results— Over a period of 17 months, 185 patients accepted the protocol and underwent an isthmogram in preparation for RFA. Groups were classified according to CTI length and CTI morphology. RFA was performed with an 8-mm-tip catheter for patients with a short CTI, ≤35 mm (n=123), whereas randomization between an 8-mm-tip and a cooled-tip catheter applied to patients with a longer CTI, >35 mm (n=62). For long CTI, 32 patients were assigned to an 8-mm catheter and 30 patients to the cooled-tip RFA ablation group. In this subset, RF application (18.2±17 versus 19±13 minutes) and x-ray exposure (20.8±18 versus 18±13 minutes) did not differ between the 8-mm-tip and the cooled-tip procedures. Number of applications (9.9±11 versus 18.6±15 minutes; P P =0.0001) differed significantly between patients with short and long CTIs. Patients with short and straight CTIs required 3 times fewer RFA applications and shorter x-ray exposure compared with other CTI morphologies (pouch-like recesses and concave characteristics). Conclusions— The number of RF applications required for a complete isthmus block in long CTIs is not influenced by the choice between an 8-mm or cooled-tip catheter. Procedure parameters, however, are significantly influenced by CTI length and morphology. Pouch-like recesses and concave characteristics account for much longer ablation times at all CTI lengths.

Potentially lymphotropic 7 alpha- and 7 beta-aminocholestanol were stereoselectively synthesized. In vitro bioassay studies have shown that these fungicidal lipidic derivatives possess strong antifungal activity against Candida spp resistant strains to amphotericin B, 5-fluorocytosine and azoles.

Δ 7 -5-Desaturase catalyses one of the last steps in ergosterol biosynthesis in fungi. Moreover Δ 5 -unsaturation is necessary for the sparking function. Synthesis of three pairs of C-6 epimeric cholestanol derivatives are described as potential growth inhibitors. Preliminary results suggest that 6β-aminocholestanol is a potent antifungal agent.

Radiofrequency catheter ablation (RFA) of the inferior vena cava–tricuspid isthmus is the treatment of choice for atrial flutter (AFL) given its high efficacy. One controlled study of AFL with medication has been done to date.1 Despite the introduction and high success rate of periablation, questions remained: is transisthmus ablation a definite cure for patients with AFL or can their follow up be characterised by the occurrence of other atrial arrhythmia? Many studies, some recent, have tried to answer these questions2,3 but one question remains: will first line transisthmus ablation alter the long term risk of atrial fibrillation (AF)? The aim of this study was to evaluate the long term risk of subsequent AF after RFA in two groups of patients < 80 years old with lone AFL: group 1, receiving first line RFA treatment; and group 2, receiving RFA after failure of at least one drug treatment after restoration of sinus rhythm. By convention, lone AFL excluded prior evidence of AF. Over 44 months, 318 patients were referred for RFA treatment for AFL (February 1998 to October 2001). Only 176 …

Conclusions: Application of a retrospective algorithmic diagnostic approach applied during ER assessment of pts with sync/presync increased diagnostic yield (15% to 77%), with vasovagal syncope accounting for more than half of the diagnosis. Simple clinical markers obtained from history and physical examination may reduce unnecessary testing, costs and hospital admissions in pts presenting with syncope to the ER.

A new sterol, 7-aminocholesterol, which inhibits growth of Saccharomyces cerevisiae, also displayed antibiotic activity against Gram-positive bacteria. The 50% growth inhibitory concentration against strains of Listeria innocua, L. monocytogenes, Staphylococcus aureus, Enterococcus hirae and Bacillus cereus was 3 microM.