Evaluation using latent class models of the diagnostic performances of three ELISA tests commercialized for the serological diagnosis of Coxiella burnetii infection in domestic ruminants.

ELISA methods are the diagnostic tools recommended for the serological diagnosis of Coxiella burnetii infection in ruminants but their respective diagnostic performances are difficult to assess because of the absence of a gold standard. This study focused on three commercial ELISA tests with the following objectives (1) assess their sensitivity and specificity in sheep, goats and cattle, (2) assess the between- and within-herd seroprevalence distribution in these species, accounting for diagnostic errors, and (3) estimate optimal sample sizes considering sensitivity and specificity at herd level. We comparatively tested 1413 cattle, 1474 goat and 1432 sheep serum samples collected in France. We analyzed the cross-classified test results with a hierarchical zero-inflated beta-binomial latent class model considering each herd as a population and conditional dependence as a fixed effect. Potential biases and coverage probabilities of the model were assessed by simulation. Conditional dependence for truly seropositive animals was high in all species for two of the three ELISA methods. Specificity estimates were high, ranging from 94.8% [92.1; 97.8] to 99.2% [98.5; 99.7], whereas sensitivity estimates were generally low, ranging from 39.3 [30.7; 47.0] to 90.5% [83.3; 93.8]. Between- and within-herd seroprevalence estimates varied greatly among geographic areas and herds. Overall, goats showed higher within-herd seroprevalence levels than sheep and cattle. The optimal sample size maximizing both herd sensitivity and herd specificity varied from 3 to at least 20 animals depending on the test and ruminant species. This study provides better interpretation of three widely used commercial ELISA tests and will make it possible to optimize their implementation in future studies. The methodology developed may likewise be applied to other human or animal diseases.

Determinants of influenza vaccination uptake in pregnancy: a large single-Centre cohort study.

BACKGROUND: Although vaccination of pregnant women against influenza is recommended, the vaccination rate remains low. We conducted a study to identify determinants of influenza vaccination uptake in pregnancy in order to identify strategies to improve seasonal influenza vaccination rates. METHODS: Prospective observational hospital-based study in the French hospital performing the highest number of deliveries, located in the city of Lille, among all women who had given birth during the 2014-2015 influenza season. Data were collected through a self-completed questionnaire and from medical files. The vaccination uptake was self-reported. Determinants of vaccination uptake were identified using logistic regression analysis. RESULTS: Of the 2045 women included in the study, 35.5% reported that they had been vaccinated against influenza during their pregnancy. The principal factors significantly associated with greater vaccination uptake were previous influenza vaccination (50.9% vs 20.2%, OR 4.1, 95% CI 3.1-5.5), nulliparity (41.0% vs 31.3%, OR 2.5, 95% CI 1.7-3.7), history of preterm delivery < 34 weeks (43.4% vs 30.3%, OR 2.3, 95% CI 1.1-4.9), the mother's perception that the frequency of vaccine complications for babies is very low (54.6% vs 20.6%, OR 1.1, 95% CI 0.5-2.2), the mother's good knowledge of influenza and its vaccine (61.7% vs 24.4%, OR 3.1, 95% CI 2.2-4.4), hospital-based prenatal care in their first trimester of pregnancy (55.0% vs 30.2%, OR 2.1, 95% CI 1.2-3.7), vaccination recommendations during pregnancy by a healthcare worker (47.0% vs 2.7%, OR 18.8, 95% CI 10.0-35.8), receipt of a vaccine reimbursement form (52.4% vs 18.6%, OR 2.0, 95% CI 1.5-2.7), and information from at least one healthcare worker about the vaccine (43.8% vs 19.1%, OR 1.8, 95% CI 1.3-2.6). CONCLUSIONS: Our findings suggest that in order to increase flu vaccination compliance among pregnant women, future public health programmes must ensure cost-free access to vaccination, and incorporate education about the risks of influenza and the efficacy/safety of vaccination and clear recommendations from healthcare professionals into routine antenatal care.

Prenatal molecular diagnosis in RASA1-related disease.

RASA1-related disease is a rare autosomal dominant disease characterized by capillary malformations, arteriovenous malformations (AVMs), and/or arteriovenous fistulas (AFVs). Penetrance is nearly complete and vascular malformations may cause serious complications such as organ injury due to oxygenation disorder, brain abscess, hemorrhage, and stroke. Early diagnosis is useful in order to discuss optimal management, including AVMs/AVFs embolization or surgical procedures, and try to prevent some of the complications. In this context, molecular testing of RASA1 gene mutation in relatives may help to better manage the family. All arteriovenous malformations are however not accessible to such procedures. In addition, these therapeutic procedures may result in potential side effects and complications. A couple was referred to our genetics unit and asked us for prenatal genetic testing about a RASA1 mutation. Here, we discuss about arguments that led our team to accept prenatal testing. To the best of our knowledge, no molecular prenatal diagnosis was reported until now in RASA1-related diseases. This first report of prenatal diagnosis in RASA1-related diseases may also offer perspectives for a more general discussion in the field of inherited arteriovenous malformations.

Advanced backcross QTL analysis and comparative mapping with RIL QTL studies and GWAS provide an overview of QTL and marker haplotype diversity for resistance to Aphanomyces root rot in pea (Pisum sativum).

Aphanomyces euteiches is the most damaging soilborne pea pathogen in France. Breeding of pea resistant varieties combining a diversity of quantitative trait loci (QTL) is a promising strategy considering previous research achievements in dissecting polygenic resistance to A. euteiches. The objective of this study was to provide an overview of the diversity of QTL and marker haplotypes for resistance to A. euteiches, by integrating a novel QTL mapping study in advanced backcross (AB) populations with previous QTL analyses and genome-wide association study (GWAS) using common markers. QTL analysis was performed in two AB populations derived from the cross between the susceptible spring pea variety "Eden" and the two new sources of partial resistance "E11" and "LISA". The two AB populations were genotyped using 993 and 478 single nucleotide polymorphism (SNP) markers, respectively, and phenotyped for resistance to A. euteiches in controlled conditions and in infested fields at two locations. GWAS and QTL mapping previously reported in the pea-Aphanomyces collection and from four recombinant inbred line (RIL) populations, respectively, were updated using a total of 1,850 additional markers, including the markers used in the Eden x E11 and Eden x LISA populations analysis. A total of 29 resistance-associated SNPs and 171 resistance QTL were identified by GWAS and RIL or AB QTL analyses, respectively, which highlighted 10 consistent genetic regions confirming the previously reported QTL. No new consistent resistance QTL was detected from both Eden x E11 and Eden x LISA AB populations. However, a high diversity of resistance haplotypes was identified at 11 linkage disequilibrium (LD) blocks underlying consistent genetic regions, especially in 14 new sources of resistance from the pea-Aphanomyces collection. An accumulation of favorable haplotypes at these 11 blocks was confirmed in the most resistant pea lines of the collection. This study provides new SNP markers and rare haplotypes associated with the diversity of Aphanomyces root rot resistance QTL investigated, which will be useful for QTL pyramiding strategies to increase resistance levels in future pea varieties.

On the interaction of acetone with electrophilic metallocavitands having extended cavities.

We report the synthesis and characterization of tantalum-boronate trimetallic clusters of general formula {[Cp*Ta](3)(µ(2)-RB(O)(2))(3)(µ(2)-OH)(µ(2)-O)(2)(µ(3)-OH)} (R= 4-(C(6)H(5))(C(6)H(4)) (Ta(3)-4Ph), 4-(C(6)H(5)O)(C(6)H(4)) (Ta(3)-4OPh), 4-(C(7)H(7)O)(C(6)H(4)) (Ta(3)-4OBn), 4-(C(8)H(5))(C(6)H(4)) (Ta(3)-4PhEt), and 4-(C(12)H(7))(C(6)H(4)) (Ta(3)-4Napht)). All complexes have been characterized by NMR spectroscopy and X-ray diffraction. The trimetallic species feature a large Lewis acid type cavity allowing for substrate binding in both the solid and the liquid state using a unique electrostatic interaction and a hydrogen bond. ΔH° and ΔS° values for association of acetone with the complexes vary between -2.0 and -4.1 kcal·mol(-1) and -3 and 2 cal·mol(-1)·K(-1), respectively, showing weaker binding than smaller cavitands of the same type. The barrier for acetone exchange at equilibrium is similar for all complexes, and ΔH(‡) values vary between 8.2 and 11.4 kcal·mol(-1).

Effect of in utero wi-fi exposure on the pre- and postnatal development of rats.

BACKGROUND: The increase in exposure to the Wireless Fidelity (Wi-Fi) wireless communication signal has raised public health concerns especially for young people. Animal studies looking at the effects of early life and prenatal exposure to this source of electromagnetic fields, in the radiofrequency (RF) range, on development and behavior have been considered as high priority research needs by the World Health Organization. METHODS: For the first time, our study assessed the effects of in utero exposure to a 2450 MHz Wi-Fi signal (2 hr/day, 6 days/week for 18 days) on pregnant rats and their pups. Three levels in terms of whole-body specific absorption rate were used: 0.08, 0.4, and 4 W/kg. The prenatal study on fetuses delivered by caesarean (P20) concerned five females/group. The dams and their offspring were observed for 28 days after delivery (15 females/group). RESULTS: For all test conditions, no abnormalities were noted in the pregnant rats and no significant signs of toxicity were observed in the pre- and postnatal development of the pups, even at the highest level of 4 W/kg. CONCLUSIONS: In the present study, no teratogenic effect of repeated exposures to the Wi-Fi wireless communication signal was demonstrated even at the highest level of 4 W/kg. The results from this screening study aimed at investigating Wi-Fi effects, strengthen the previous conclusions that teratology and development studies have not detected any noxious effects of exposures to mobile telephony-related RF fields at exposure levels below standard limits.

Effect of a postpartum prescription for pertussis vaccine: a before-and-after study.

BACKGROUND: Among the strategies to encourage pregnant women to be vaccinated against pertussis in the postpartum period, that of giving them a prescription has been evaluated only sparsely. OBJECTIVE: To measure the effect of giving women who are not immunized against pertussis a prescription for the vaccine at discharge from the maternity unit. MATERIAL AND METHODS: Single-center before-and-after study (2011: before; 2015: after). All women received both oral and written information about vaccination against pertussis. During the after period, they were also specifically asked their immunization status during pregnancy. Those currently unimmunized received a written prescription for it at discharge. RESULTS: Among the women unimmunized at delivery, the percentage who were vaccinated postpartum climbed from 17 to 42% between 2011 and 2015 (p < 0.001), while the percentage of their unimmunized partners who were vaccinated remained stable (27 and 29%, p = 0.74). During this time, the percentage of women immunized against pertussis at the beginning of pregnancy rose from 32 to 52% (p < 0.001). Finally, the percentage of all women protected against this disease postpartum climbed from 44 to 72% between these two periods (p < 0.001). CONCLUSIONS: In the postpartum period, giving a prescription for pertussis vaccine to women unimmunized is accompanied by a significant elevation in their vaccination rate. Nevertheless, this rate remains low and better strategies have to be implemented.

Type of breech presentation and prognosis for delivery.

BACKGROUND: Although its role in the prognosis for delivery remains controversial, the type of breech is sometimes taken into account in the decision about mode of delivery. Objective of our study was to compare maternal and neonatal morbidity for trial of vaginal delivery according to the type of breech (complete or frank). MATERIAL AND METHOD: Single-center retrospective study of women with trials of vaginal delivery of a singleton fetus in breech presentation at of after 37 weeks of gestation. Neonatal status was assessed by the composite variable of the Term Breech Trial, first considered alone, and then with the addition of a 5-min Apgar score < 7 or a neonatal arterial pH<7.0. RESULTS: Of the 495 trials of vaginal delivery during the study period, approximately one third of them were complete breech (35.8 %) and two thirds frank (64.2 %). The frequency of cesareans during labor was similar regardless of the type of breech (16.4 for complete vs 12.6 % for frank, p=0.24), nor did neonatal morbidity differ (1.7 for complete vs 4.1 % for frank, p=0.15). On the other hand, cord prolapse occurred almost exclusively in complete breech presentations (4.5 vs 0.3 %, p<0.01), and prognosis was good in all cases. Complete breech presentations were also associated with more frequent use of forceps to the after-coming head (16.2 vs 9.7 %, p<0.05). Finally, there were non significant difference between the two types of breech concerning severe acidosis but it seemed to have it more in frank breech (2.3 vs 1.2 %, p=0.34). CONCLUSION: Among women eligible for vaginal delivery, the type of breech presentation (complete or frank) has little influence on delivery maternal and neonatal morbidity. The type of breech need not be taken into account in deciding the route of delivery.

Coxiella burnetii shedding routes and antibody response after outbreaks of Q fever-induced abortion in dairy goat herds.

Q fever is a zoonosis caused by Coxiella burnetii, a bacterium largely carried by ruminants and shed into milk, vaginal mucus, and feces. The main potential hazard to humans and animals is due to shedding of bacteria that can then persist in the environment and be aerosolized. The purpose of this study was to evaluate shedding after an outbreak of Q fever abortion in goat herds and to assess the relationship with the occurrence of abortions and antibody responses. Aborting and nonaborting goats were monitored by PCR for C. burnetii shedding 15 and 30 days after the abortion episodes. PCR analysis of all samples showed that 70% (n = 50) of the aborting and 53% (n = 70) of the nonaborting goats were positive. C. burnetii was shed into vaginal mucus, feces, and milk of 44%, 21%, and 38%, respectively, of goats that aborted and 27%, 20%, and 31%, respectively, of goats that delivered normally. Statistical comparison of these shedding results did not reveal any difference between these two groups. PCR results obtained for the vaginal and fecal routes were concordant in 81% of cases, whereas those for milk correlated with only 49% of cases with either vaginal or fecal shedding status. Serological analysis, using enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and complement fixation tests, showed that at least 24% of the seronegative goats shed bacteria. Positive vaginal and fecal shedding, unlike positive milk shedding, was observed more often in animals that were weakly positive or negative by ELISA or IFA. Two opposite shedding trends were thus apparent for the milk and vaginal-fecal routes. Moreover, this study showed that a nonnegligible proportion of seronegative animals that delivered normally could excrete C. burnetii.

Evaluation of the recombinant Heat shock protein B (HspB) of Coxiella burnetii as a potential antigen for immunodiagnostic of Q fever in goats.

Coxiella burnetii is an intracellular bacterium that causes a worldwide zoonosis, the Q fever. Currently, to diagnose the infection in ruminants, whole cell antigens-based ELISAs are used. In this study a heat shock protein, the HspB, was evaluated for its ability to be recognized by the goat immune system and its capacity to sign a stage of infection. The htpB gene of C. burnetii was cloned and sequenced. A high identity (>90%) was observed among the htpB genes of four ruminant strains tested. A recombinant protein was expressed in a prokaryotic expression system. The rHspB protein was used to determine the IgG reactivity by ELISA. Sera from experimentally and naturally infected goats were tested. The rHspB is recognized early during the infection course, at 18 days post-infection. Moreover, 80-90% of the animals tested were positive at 39-60dpi. In addition, animals presenting a reactivation of the infection displayed a higher reactivity, statistically significant (p<0.05), than that of the animals in latent infection. These findings suggest that the rHspB could be a good candidate for the development of an ELISA test making possible the detection of recent C. burnetii infection in goats as well as reactivation in those with latent infection.

Phytoplankton growth control and risk of cyanobacterial blooms in the lower Senegal River delta region.

Eutrophication, and the resulting proliferation of phytoplankton can affect water quality. Although environmental and ecological processes that lead to phytoplankton proliferations in temperate areas have received considerable attention, scientific background regarding this topic in tropical areas, especially West Africa, are scarce. In this study, bioassays in batch cultures were carried out in order to identify factors that may be stimulating or limiting the biomass of phytoplankton at various sites in the lower Senegal River delta region. Complete factorial designs were used to test several factors both alone and combined (nitrogen, phosphorus, sulfate, EDTA and trace elements, stirring). The effects of these factors on the growth of the whole phytoplankton communities were followed by the daily measurement of in vivo fluorescence. At all but two of the sites, enrichment with certain nutrients significantly stimulated phytoplankton biomass growth, with nitrogen and/or phosphorus appearing to be the primary limiting factor(s). Nitrogen was the primary limiting factor in coastal ocean waters and in the Senegal River estuary. In the freshwater ecosystems studied, nitrogen and phosphorus acted as alternating or concomitant limiting factors. We assessed the changes in the phytoplankton composition induced by nutrient enrichments in Lake Guiers, a drinking water reservoir for the population of Dakar. Our findings lead us to define the conditions of a possible proliferation of the potentially toxic cyanobacterium Cylindrospermopsis raciborskii mainly in response to phosphorus inputs.

Seroprevalence of horses to Coxiella burnetii in an Q fever endemic area.

Coxiella burnetii can infect many animal species, but its circulation dynamics in and through horses is still unclear. This study evaluated horse exposure in an area known to be endemic for ruminants and humans. We assessed antibody prevalence in horse serum by ELISA, and screened by qPCR horse blood, ticks found on horses and dust from stables. Horse seroprevalence was 4% (n = 335, 37 stables) in 2015 and 12% (n = 294, 39 stables) in 2016. Of 199 horses sampled both years, 13 seroconverted, eight remained seropositive, and one seroreverted. Seropositive horses were located close to reported human cases, yet none displayed Q fever-compatible syndromes. Coxiella DNA was detected in almost 40% of collected ticks (n = 59/148 in 2015; n = 103/305 in 2016), occasionally in dust (n = 3/46 in 2015; n = 1/14 in 2016) but never in horse blood. Further studies should be implemented to evaluate if horses may be relevant indicators of zoonotic risk in urban and suburban endemic areas.

Comparative diagnostic potential of three serological tests for abortive Q fever in goat herds.

Performances of an ELISA, an immunofluorescence assay (IFA) and a complement fixation test (CFT) were assessed for detecting antibodies against Coxiella burnetii after Q fever abortions in naturally infected goats. The goal of the study was to provide information useful for veterinary serodiagnosis in regard to categories of goats either experiencing Q fever abortion or not, blood sampling times and recommended cut-offs. The study was conducted on eight goat herds with evidence of C. burnetii abortions. In each herd, at least 5 goats that had aborted and 10 goats prior to parturition or at term were monitored 15, 30 and 60 days (D15, D30, D60) after the onset of Q fever abortion. The overall CFT results distribution did not differ between the two groups of goats and showed poor agreement with the ELISA results. In contrast, the ELISA and IFA results revealed comparable significant differences, but overall the ELISA test was slightly more sensitive than the IFA test. Seroprevalence, according to ELISA and IFA respectively, was higher in the aborting (88% and 82%) than in the non-aborting group (60% and 50%). High levels of serum antibodies were detected in goats post-abortion with an average of 114 %OD using ELISA and a log10(titer) of 2.4 using IFA. Strongly positive ELISA (%OD>80) and positive IFA results (log10(titers)>1.9) were significantly associated with abortion. Sampling on D15 gave the best association with ORs of 10 for ELISA and 6 for IFA. The practical interest of these results is discussed.

Rapid Bacterial Identification, Resistance, Virulence and Type Profiling using Selected Reaction Monitoring Mass Spectrometry.

Mass spectrometry (MS) in Selected Reaction Monitoring (SRM) mode is proposed for in-depth characterisation of microorganisms in a multiplexed analysis. Within 60-80 minutes, the SRM method performs microbial identification (I), antibiotic-resistance detection (R), virulence assessment (V) and it provides epidemiological typing information (T). This SRM application is illustrated by the analysis of the human pathogen Staphylococcus aureus, demonstrating its promise for rapid characterisation of bacteria from positive blood cultures of sepsis patients.

Community-acquired methicillin-resistant Staphylococcus aureus infections in France: emergence of a single clone that produces Panton-Valentine leukocidin.

To characterize the clinical and bacteriologic characteristics of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, we reviewed 14 cases that were diagnosed in previously healthy patients during an 18-month period in France. Eleven patients had skin or soft-tissue infections. Two patients died of CA-MRSA necrotizing pneumonia. A case of pleurisy occurred in a child who acquired CA-MRSA from his mother, who had a breast abscess. The Panton-Valentine leukocidin genes and the lukE-lukD leukocidin genes were detected in all 14 isolates. The clonal origin of all of the isolates was demonstrated on the basis of their pulsotypes and antibiotic resistance profiles. All isolates had an agr3 allele. The combination of the Panton-Valentine leukocidin determinant (which encodes a virulence factor for primary skin infection and pneumonia) with the mecA gene (which confers antibiotic resistance and epidemicity) appears to have created a superadapted S. aureus strain that is spreading in the community.

Maternal Bartter's syndrome in pregnancy treated by amiloride.

BACKGROUND: Bartter's syndrome is a rare condition during pregnancy. The prenatal management is difficult to maintain normal potassium serum levels. CASE: We describe a 26-year-old woman with Bartter's syndrome. During pregnancy, she required increasing potassium and magnesium supplementations. Amiloride, a sparing potassium diuretic, was continued. She delivered an unaffected girl at term. CONCLUSION: When Bartter's syndrome is associated with pregnancy, the management must be careful. Amiloride can be used to support potassium supplementation.

Comparison of three enzyme-linked immunosorbent assays for serologic diagnosis of contagious agalactia in sheep.

Serologic diagnosis of ovine contagious agalactia (Mycoplasma agalactiae) with the enzyme-linked immunosorbent assay (ELISA) developed by Agence Française de Sécurité Sanitaire des Aliments (AFSSA) may produce a few false-positive (FP) and false-negative (FN) results. When the prevalence of disease is low, these erroneous results may generate problems for eradication schemes. To prevent this, 2 commercial ELISAs were compared with the AFSSA ELISA. Flocks of known status were selected and classified into 4 categories: true positive (TP), FP, true negative (TN), and FN; 20 sheep per flock were submitted for blood sampling. A flock was considered positive when at least 1 out of 20 sera was positive or 2 sera were doubtful. In the flock, the diagnostic sensitivity of the 3 kits was very good (100%), and the diagnostic specificity showed an improvement from 46% (AFSSA test) to 88% and 92% (commercial tests). Considering individual animals, very few positive ewes were detected within TN or FP flocks; the proportion of positive ewes varied greatly from one kit to another (48% to 82%) within TP flocks. The kinetics of antibody response in sheep experimentally infected with various field strains of M. agalactiae were quite similar with all 3 ELISAs. The agreement between the 3 tests, assessed using the kappa value, varied from moderate to good (respective values of 0.56, 0.61, and 0.86). The 2 commercial ELISAs showed better performances, probably because of a superior analytical sensitivity, and are a good alternative for the serodiagnosis of contagious agalactia in sheep.

Rat fertility and embryo fetal development: influence of exposure to the Wi-Fi signal.

In recent decades, concern has been growing about decreasing fecundity and fertility in the human population. Exposure to non-ionizing electromagnetic fields (EMF), especially radiofrequency (RF) fields used in wireless communications has been suggested as a potential risk factor. For the first time, we evaluated the effects of exposure to the 2450MHz Wi-Fi signal (1h/day, 6days/week) on the reproductive system of male and female Wistar rats, pre-exposed to Wi-Fi during sexual maturation. Exposure lasted 3 weeks (males) or 2 weeks (females), then animals were mated and couples exposed for 3 more weeks. On the day before delivery, the fetuses were observed for lethality, abnormalities, and clinical signs. In our experiment, no deleterious effects of Wi-Fi exposure on rat male and female reproductive organs and fertility were observed for 1h per days. No macroscopic abnormalities in fetuses were noted, even at the critical level of 4W/kg.

Solid-phase chemical synthesis and in vitro biological evaluation of novel 2ß-piperazino-(20R)-5α-pregnane-3α,20-diol N-derivatives as anti-leukemic agents.

The steroid nucleus is an interesting scaffold for the development of new therapeutic agents. Within the goal of identifying anticancer agents, new pregnane derivatives were prepared by using a sequence of liquid and solid-phase reactions. After we dehydrated epi-allopregnanolone in one step with diethylaminosulfur trifluoride and generated a 2,3α-epoxide, the regio- and stereo-selective aminolysis of this epoxide enabled us to obtain a 2ß-piperazino-pregnane, whose secondary amine was protected as N-Fmoc-derivative. Using the difference in reactivity between OHs 3 and 20, we linked the pregnane nucleus-selectively on the polystyrene diethylbutylsilane resin via the OH in position 20. We next achieved in parallel the coupling of an amino acid (1st level of diversity) and the coupling of a carboxylic acid (2nd level of diversity) to generate two libraries of pregnane derivatives. The compounds inhibited the HL-60 leukemia cell growth and the most potent were three compounds (PD, LPC-37 and LPC-48) with a l-proline as first level of diversity and a cyclohexyl-carbonyl, a naphthalene-2-carbonyl or a 3-acetylbenzoyl as second level of diversity. LPC-48 efficiently inhibited HL-60 cell proliferation with IC(50) value of 1.9 µM and exhibited a low toxicity on normal peripheral blood lymphocytes (IC(50)=31 µM). These results encouraged us to further evaluate the biological activity of these new aminosteroids by investigating their preliminary mechanism of action.