[Organ transplantation during SARS-CoV-2 epidemic : the 2020-2021 Liege transplant Center experience]. / Face à la COVID-19. La transplantation d'organes en période de pandémie SARS-CoV-2 : l'expérience 2020-2021 du Centre liégeois de Transplantation.

The «Severe Acute Respiratory Syndrome coronavirus 2¼ (SARS-CoV-2) pandemic has disrupted medical care and intra-hospital organization during 2020, both in Belgium and throughout the world. Solid organ transplantation was not spared and in Belgium, the number of organ donors and transplants overall decreased by 20 % for livers and by 33 % for hearts between 2019 and 2020. The aim of this article is to summarize the experience acquired in 2020 and 2021 on the organizational and medical implications of the coronavirus disease 2019 (COVID-19) pandemic with regard to the care of patients transplanted or awaiting for organ transplants, and to draw conclusions both for the aftermath of COVID-19 but also for future pandemics. Vaccination against SARS-CoV-2 is highly recommended and particularly important in organ transplant recipients, even if the response rate is lower than in the non-transplanted population. A third injection is now advised in immunosuppressed patients.

La pandémie de «Severe Acute Respiratory Syndrome coronavirus 2¼ (SARS-CoV-2) a bouleversé les soins médicaux et l'organisation intra-hospitalière durant l'année 2020 en Belgique et dans le monde. La transplantation d'organes ne fut pas épargnée. En Belgique, le nombre de donneurs d'organes et de transplantations a globalement diminué de 20 % pour les foies et de 33 % pour les cœurs entre 2019 et 2020. Le but de cet article est de résumer l'expérience acquise en 2020 et 2021 sur les implications organisationnelles et médicales de la pandémie de «coronavirus disease 2019¼ (COVID-19) quant à la prise en charge des patients transplantés ou en attente de greffe d'organes, et d'en tirer les conclusions à la fois pour les suites de la COVID-19, mais aussi pour les éventuelles futures pandémies. La vaccination anti-SARS-CoV-2 est recommandée et particulièrement importante chez les patients transplantés d'organe, même si le taux de réponse est inférieur à la population non transplantée. Une troisième injection est conseillée chez les patients immunodéprimés.

Potential physiological involvement of nesfatin-1 in regulating swine granulosa cell functions.

Nesfatin-1 has recently been indicated as a pleiotropic molecule that is primarily involved in the metabolic regulation of reproductive functions acting at hypothalamic level. The aim of this study was to explore the local action of nesfatin-1 in swine ovarian follicles. Nucleobindin 2 (NUCB2) was verified using real-time quantitative polymerase chain reaction in swine granulosa cells from different sized follicles and nesfatin-1 was localised by immunohistochemistry in sections of the whole porcine ovary. The effects of different concentrations of nesfatin-1 on cell growth, steroidogenesis and the redox status of granulosa cells were determined invitro. In addition, the effects of nesfatin-1 were evaluated in an angiogenesis bioassay because vessel growth is essential for ovarian follicle function. Immunohistochemistry revealed intense positivity for nesfatin-1 in swine granulosa cells in follicles at all developmental stages. Expression of the gene encoding the precursor protein NUCB2 was higher in granulosa cells from large rather than from medium and small follicles. Further, nesfatin-1 stimulated cell proliferation and progesterone production and interfered with redox status by modifying nitric oxide production and non-enzyme scavenging activity in granulosa cells from large follicles. Moreover, nesfatin-1 exhibited a stimulatory effect on angiogenesis. This study demonstrates, for the first time, that nesfatin-1 is physiologically present in the swine ovarian follicle, where it may impair granulosa cell functions.

Italian acacia honey exhibits lytic effects against the crayfish pathogens Aphanomyces astaci and Fusarium avenaceum.

This study purpose was to evaluate the in vitro inhibitory properties of Italian acacia honey extracts against pathogenic aquatic oomycete/fungal isolates that cause different diseases in crayfish, resulting in an elevated mortality rate. The antimycotic activity of acacia honey aqueous extracts was evaluated against the strain UEF88662 of Aphanomyces astaci (oomycete) and the strain SMM2 of Fusarium avenaceum (fungus). The extracts preparation was carried out with water by a cheap, not complex and organic solvent-free procedure, with low environmental impact and the higher possibility of large-scale reproducibility. The anti-oomycete and antifungal activities were quantitatively evaluated by growth, survival and sporulation microbiological assays. The extracts displayed a dose-dependent inhibitory efficacy on oomycete and fungal growth and survival, as well as on the production of oomycete and fungal spores. Supported by future in vivo studies, our results encourage the use of natural extracts like honey as innovative tools to counteract mycotic infections. SIGNIFICANCE AND IMPACT OF THE STUDY: The continuous spread of aquatic fungal disease as the 'crayfish plague' and the 'burn spot disease' has severe ecological and commercial repercussions. Critical factor to prevent further spread is the availability of effective antifungals possibility derived from local natural resources to use in innovative strategies of control and eradication of these diseases. This study provides relevant information about the in vitro anti-oomycete and antifungal activity of Italian acacia honey aqueous extracts against two highly infectious and dangerous pathogenic species, Aphanomyces astaci and Fusarium avenaceum, that are responsible for important crayfish diseases.

Quality indicators in headache care: an implementation study in six Italian specialist-care centres.

BACKGROUND: Headache disorders are highly prevalent, and have a substantial and negative impact on health worldwide. They are largely treatable, but differences in structure, objectives, organization and delivery affect the quality of headache care. In order to recognize and remedy deficiencies in care, the Global Campaign against Headache, in collaboration with the European Headache Federation, recently developed a set of quality indicators for headache services. These require further assessment to demonstrate fitness for purpose. This is their first implementation to evaluate quality in headache care as a multicentre national study. METHODS: Between September and December 2016, we applied the quality indicators in six Italian specialist headache centres (Bologna, Firenze, Modena, Padova, Roma Campus Bio-Medico and Roma Sapienza). We used five previously developed assessment instruments, translated into Italian according to Lifting The Burden's translation protocol for hybrid documents. We took data from 360 consecutive patients (60 per centre) by questionnaire and from their medical records, and by different questionnaires from their health-care providers (HCPs), including physicians, nurses, psychologists and nursing assistants. RESULTS: The findings, comparable between centres, confirmed the feasibility and practicability of using the quality indicators in Italian specialist headache centres. The questionnaires were easily understood by HCPs and patients, and were not unduly time-consuming. Diagnoses were almost all (> 97%) according to ICHD criteria, and routinely (100%) reviewed during follow-up. Diagnostic diaries were regularly used by 96% of physicians. Referral pathways from primary to specialist care existed in five of the six clinics, as did urgent referral pathways. Instruments to assess disability and quality of life were not used regularly, a deficiency that needs to be addressed. CONCLUSION: This Italy-wide survey confirmed in six specialist centres that the headache service quality indicators are fit for purpose. By establishing majority practice, identifying commonalities and detecting deficits as a guide to quality improvement, the quality indicators may be used to set benchmarks for quality assessment. The next step is extend use and evaluation of the indicators into non-specialist care.

[A CASE OF FLECAINIDE INTOXICATION]. / Intoxication par flécaïnide. Observation d'un cas et revue de la litérature.

Flecainide acetate is an antiarrhythmic agent commonly used in clinical practice, in particular, for the treatment of supraventricular tachycardias. We report a rare case of voluntary poisoning by flecainide. The patient was successfully resuscitated.A review of the literature related to this type of intoxication is presented.

n-3 LC-PUFA deposition efficiency and appetite-regulating hormones are modulated by the dietary lipid source during rainbow trout grow-out and finishing periods.

Largely attributable to concerns surrounding sustainability, the utilisation of omega-3 long-chain polyunsaturated fatty acid-rich (n-3 LC-PUFA) fish oils in aquafeeds for farmed fish species is an increasingly concerning issue. Therefore, strategies to maximise the deposition efficiency of these key health beneficial fatty acids are being investigated. The present study examined the effects of four vegetable-based dietary lipid sources (linseed, olive, palm and sunflower oil) on the deposition efficiency of n-3 LC-PUFA and the circulating blood plasma concentrations of the appetite-regulating hormones, leptin and ghrelin, during the grow-out and finishing phases in rainbow trout culture. Minimal detrimental effects were noted in fish performance; however, major modifications were apparent in tissue fatty acid compositions, which generally reflected that of the diet. These modifications diminished somewhat following the fish oil finishing phase, but longer-lasting effects remained evident. The fatty acid composition of the alternative oils was demonstrated to have a modulatory effect on the deposition efficiency of n-3 LC-PUFA and on the key endocrine hormones involved in appetite regulation, growth and feed intake during both the grow-out and finishing phases. In particular, n-6 PUFA (sunflower oil diet) appeared to 'spare' the catabolism of n-3 LC-PUFA and, as such, resulted in the highest retention of these fatty acids, ultimately highlighting new nutritional approaches to maximise the maintenance of the qualitative benefits of fish oils when they are used in feeds for aquaculture species.

Cost of a population-based programme of chest x-ray screening for lung cancer.

BACKGROUND: After the implementation of a population-based programme of chest x-ray (CXR) screening on smokers in Varese, Italy, lung cancer (LC) mortality was significantly reduced. Analysis of the incremental costs due to this type of screening programme is needed to evaluate its economic impact on the healthcare system. METHODS: In July 1997 a population-based cohort, consisting of all high-risk smokers (n=5,815) identified among 60,000 adult residents from the Varese province, was invited to a LC screening programme (an annual CXR for five years) in a general practice setting, and was observed through 2006. Invitees received National Health Service (NHS) usual care, with the addition of CXRs in screening participants. At the end of observation, among the 245 LCs diagnosed in the entire screening-invited cohort the observed LC deaths were 38 fewer than expected. To estimate the incremental direct cost due to screening in the invited cohort for the period July 1997-2006, we compared the direct cost of screening administration, CXR screens and LC management in the invited cohort and in the uninvited and unscreened controls in NHS usual care setting. RESULTS: Over the 9.5 years, the total incremental direct healthcare costs (including screening organization/administration, CXR screens, additional procedures prompted by false-positive tests, overdiagnosed LCs) were estimated to range from euro 607,440 to euro 618,370 (in euros as of 2012), equating to between euro 15,985- euro 16,273 per patient out of the 38 LC deaths averted. CONCLUSIONS: In a general practice setting, the incremental cost for a CXR screening programme targeted at all high-risk smokers in a population of 60,000 adults was estimated to be about euro 65,000 per annum, approx. euro 16,000 for each LC death averted.

Surgeon eye lens dose monitoring in interventional neuroradiology, cardiovascular and radiology procedures.

PURPOSE: This study investigated the radiation dose to surgeon eye lens for single procedure and normalised to exposure parameters for eight selected neuroradiology, cardiovascular and radiology interventional procedures. METHODS: The procedures investigated were diagnostic study, Arteriovenous Malformations treatment (AVM) and aneurysm embolization for neuroradiology procedures, Coronary Angiography and Percutaneous Transluminal Coronary Angioplasty (CA-PTCA), Pacemaker and Implantable Cardioverter-Defibrillator implantation (PM-ICD), Endovascular Aortic Repair (EVAR) and Fenestrated Endovascular Aortic Repair (FEVAR) for cardiovascular and electrophysiology procedures. CT-guided lung biopsy was also monitored. All procedures were performed with table-mounted and ceiling-suspended shields (0.5 mm lead equivalent thickness), except for FEVAR and PM-ICD where only a table mounted shield was present, and CT-guided lung biopsy where no shield was used. Dose assessment was performed using a dosemeter positioned close to the most exposed eye of the surgeon, outside the protective eyewear. RESULTS: The surgeon most exposed eye lens median Hp(3) equivalent dose for a single procedure, without protective eyewear contribution, was 18 µSv for neuroradiology diagnostic study, 62 µSv for AVM, 38 µSv for aneurysm embolization, 33 µSv for CA-PTCA, 39 µSv for PM-ICD, 49 µSv for EVAR, 2500 µSv for FEVAR, 153 µSv for CT-guided lung biopsy. CONCLUSIONS: In interventional procedures, the 20 mSv/year dose limit for surgeon eye lens exposure might be exceeded if shields or protective eyewear are not used. Surgeon eye lens doses, normalised to single procedures and to exposure parameters, are a valuable tool for determining appropriate radiation protection measures and dedicated eye lens dosemeter assignment.

Isolation and characterisation of colistin-resistant Enterobacterales from chickens in Southeast Nigeria.

OBJECTIVES: Resistance to colistin (CST) mediated by mobile genetic elements has had a broad impact worldwide. There is an intensified call for epidemiological surveillance of mcr in different reservoirs to preserve CST for future generations. In Nigeria, the poultry industry is a key livestock sector. This study was undertaken to screen putative colistin-resistant Enterobacterales (CST-r-E) from poultry birds in Southeast Nigeria and to determine the genetic relatedness of mcr-harbouring isolates. METHODS: Faecal and cloacal swab samples (n = 785) were collected from chickens in 17 farms located in three contiguous states in Southeast Nigeria between March-November 2018. Following selective culture, CST-r-E were isolated. Confirmation of CST resistance, antimicrobial susceptibility testing, molecular detection of genes mcr-1 to mcr-10, multilocus sequence typing (MLST) and randomly amplified polymorphic DNA (RAPD) analysis were performed on the isolates. A questionnaire was distributed to investigate the knowledge about CST and its use of chicken farm caretakers. RESULTS: Of the 785 samples evaluated, 45 (5.7%) were positive for 48 CST-r-E, among which 23 harboured the mcr-1 gene (22 Escherichia coli and 1 Klebsiella pneumoniae). In two E.coli isolates, a new allelic variant (mcr-1.22) was detected. RAPD analysis allowed the identification of 11 different fingerprints. MLST also revealed 11 STs, with 3 of them being novel. CONCLUSION: mcr has significantly spread in poultry birds of Southeast Nigeria, which poses a worrisome risk to veterinary and human health. Strategies to prevent indiscriminate use of CST in farms should be quickly adopted before CST resistance becomes a huge global health issue.

Prospective multicentre study on azole resistance in Aspergillus isolates from surveillance cultures in haematological patients in Italy.

OBJECTIVES: This study was conducted to assess the prevalence of azole resistance in Aspergillus isolates from patients with haematological malignancies or who were undergoing haematopoietic stem cell transplantation and to identify the molecular mechanism of resistance. METHODS: In this 28-month prospective study involving 18 Italian centres, Aspergillus isolates from surveillance cultures were collected and screened for azole resistance, and mutations in the cyp51A gene were identified. Resistant isolates were genotyped by microsatellite analysis, and the allelic profiles were compared with those of resistant environmental and clinical isolates from the same geographical area that had been previously genotyped. RESULTS: There were 292 Aspergillus isolates collected from 228 patients. The isolates belonged mainly to the section Fumigati (45.9%), Nigri (20.9%), Flavi (16.8%) and Terrei (4.8%). Three isolates showed itraconazole resistance: Aspergillus fumigatus sensu stricto, Aspergillus lentulus (section Fumigati) and Aspergillus awamori (section Nigri). The itraconazole resistance rates were 1% and 1.48% considering all Aspergillus spp. isolates and the Aspergillus section Fumigati, respectively. The prevalence of azole resistance among all the patients was 1.3%. Among patients harbouring A. fumigatus sensu stricto isolates, the resistance rate was 0.79%. The A. fumigatus isolate, with the TR34/L98H mutation, was genotypically distant from the environmental and clinical strains previously genotyped. CONCLUSIONS: In this study, the Aspergillus azole resistance rate was 1% (3/292). In addition to A. fumigatus sensu stricto, A. lentulus and A. awamori azole-resistant isolates were identified. Therefore, it is important have a correct identification at the species level to address a rapid therapy better, quickly understand the shift towards cryptic species and have an updated knowledge of the local epidemiology.

[Extra-auditory effects of noise]. / Effetti extrauditivi del rumore.

In the last thirty years, several studies have demonstrated a correlation between exposure to noise and the development of alterations and/or pathologies in organs and apparatus, apart from the auditory one. Exposure to noise can induce biochemical, physiological, or psychosocial modifications that can remain either inside the range of biological normality or alter and compromise the psychophysical well-being of the individual depending on the extent of the functional alterations of organic systems and psychosocial functions; both the reversibility and duration of the alterations and the adaptation could be related to the recovery capabilitiy of the human organism and to the environmental condition. Among the factors that can influence the effects of noise we can find: intrinsic characteristics of the physical insult (pressure, sound intensity, emission frequency), extrinsic characteristics (duration of the exposure, way of emission, presence of impulsive components, masking effects), spectral characteristics (infrasounds, ultrasounds, time of recovery) genetic factors (susceptibility) and acquired factors of the human organism (acoustic isolation of the living houses and the social necessity for the industrial activities that generate noise). Other factors that influence the damage are the surprise effect, the semantic content and the identification of the noise source. It can be hypothesized that the extra-auditory effects of noise show themselves through a series of nervous circuits that use the autonomic nervous system and interfere on neuro-immune-endocrine parameters. The organs which are more studied are: cardiovascular, gastro-enteric and endocrine systems, nervous system and psychological effects, respiratory system, fetus and effects on reproductive system, immune system and genetic material.

[Type A intramural hematoma of aorta: An undervalued clinical entity]. / Hématome intramural aortique de type A : une entité clinique sous-évaluée.

Intramural hematoma of the ascending aorta occurs after rupture of the vasa vasorum. Previously considered as a first step of acute aortic dissection, it was later defined as a separate entity that may or may not lead to arterial dissection. The debate about the most appropriate treatment for a 69-year-old patient with intramural hematoma of the ascending aorta, led to this extensive review of the literature demonstrating that intramural hematoma type A is a life-threatening condition requiring urgent surgical support.

Neurotrophin-4 in the brain of adult Nothobranchius furzeri.

Neurotrophin-4 (NT-4) is a member of the well-known family of neurotrophins that regulate the development of neuronal networks by participating in neuronal survival and differentiation, the growth of neuronal processes, synaptic development and plasticity, as well as myelination. NT-4 interacts with two distinct receptors: TrkB, high affinity receptor and p75 low-affinity neurotrophin receptor (p75(NTR)). In the present survey, we identified the gene encoding NT-4 in the teleost Nothobranchius furzeri, a model species for aging research. The identified gene shows a similarity of about 72% with medaka, the closest related species. The neuroanatomical localization of NT-4 mRNA is obtained by using an LNA probe. NT-4 mRNA expression is observed in neurons and glial cells of the forebrain and hindbrain, with very low signal found in the midbrain. This survey confirms that NT-4 is expressed in the brain of N. furzeri during adulthood, suggesting that it could also be implicated in the maintenance and regulation of neuronal functions.

Personnel real time dosimetry in interventional radiology.

Interventional radiology and hemodynamic procedures have rapidly grown in number in the past decade, increasing the importance of personnel dosimetry not only for patients but also for medical staff. The optimization of the absorbed dose during operations is one of the goals that fostered the development of real-time dosimetric systems. Indeed, introducing proper procedure optimization, like correlating dose rate measurements with medical staff position inside the operating room, the absorbed dose could be reduced. Real-time dose measurements would greatly facilitate this task through real-time monitoring and automatic data recording. Besides real-time dose monitoring could allow automatic data recording. In this work, we will describe the calibration and validation of a wireless real-time prototype dosimeter based on a new sensor device (CMOS imager). The validation measurement campaign in clinical conditions has demonstrated the prototype capability of measuring dose-rates with a frequency in the range of few Hz, and an uncertainty smaller than 10%.

Opioid peptides and testicular activity in the lizard Podarcis s. sicula Raf.

In mammals endorphinergic systems have been shown to modulate reproductive processes and beta-endorphin (beta-EP) has been found to influence sexual functions, acting at the hypothalamus-pituitary-gonadal axis level. Using immunocytochemical and in vitro studies, evidence for a diffuse pro-opiomelanocortin-related opioid system in the lizard Podarcis s. sicula was produced. In the testis, beta-EP immunoreactivity showed seasonal variation, being most pronounced in the interstitial cells of sexually quiescent lizards (December). Reverse-phase high-performance liquid chromatography, coupled with radioimmunoassay and immunocytochemistry, showed that beta-EP and acetyl beta-EP increased during December, while their concentrations were low during April, when the highest testicular activity occurred. Using in vivo studies, it was found that naltrexone treatment, blocking pituitary opioid receptor, increased androgen levels in the plasma and in the testis. It was also found with in vitro studies that the endogenous opioid system inhibits gonadotrophin release and therefore androgen production by the testis. The data reported here provide evidence for the physiological role played by opioid peptides at the pituitary level to regulate the seasonal reproductive activity of the lizard Podarcis s. sicula.

Estradiol receptor in the lizard liver (Podarcis s. sicula). Seasonal changes and estradiol and growth hormone dependence.

This study shows that in the liver of the oviparous lizard, Podarcis s. sicula, the estrogen receptor (ER) level increases during the reproductive period (spring) when vitellogenesis occurs. This phenomenon interested both unfilled and filled ER present in the cytosolic and nuclear fractions. The increase in unfilled cytosolic and filled nuclear receptor was positively correlated to the plasma level of vitellogenin. The level of liver ER approximated that of mammalian liver ER and, therefore, it is higher than that reported for the liver of several nonmammalian species. At electrofocusing, liver ER distributes in two pH ranges (pH 6.5-7.5 and 8.0-8.8, respectively). The first form predominated in nuclei of reproductive females or of spayed estrogenized females and could represent the activated form of receptor. Ovariectomy was followed by a decrease in liver ER which can be induced in spayed females by estradiol administration. Pituitary growth hormone (GH) seemed to exert a synergic effect on estradiol liver estrogen receptor regulation. In lizards treated both with estradiol and GH, in fact, there was a significant increase in nuclear filled ER rather than an increase in the level of total nuclear ER.

Relationship between molecular connectivity and carcinogenic activity: a confirmation with a new software program based on graph theory.

For a database of 826 chemicals tested for carcinogenicity, we fragmented the structural formula of the chemicals into all possible contiguous-atom fragments with size between two and eight (nonhydrogen) atoms. The fragmentation was obtained using a new software program based on graph theory. We used 80% of the chemicals as a training set and 20% as a test set. The two sets were obtained by random sorting. From the training sets, an average (8 computer runs with independently sorted chemicals) of 315 different fragments were significantly (p < 0.125) associated with carcinogenicity or lack thereof. Even using this relatively low level of statistical significance, 23% of the molecules of the test sets lacked significant fragments. For 77% of the molecules of the test sets, we used the presence of significant fragments to predict carcinogenicity. The average level of accuracy of the predictions in the test sets was 67.5%. Chemicals containing only positive fragments were predicted with an accuracy of 78.7%. The level of accuracy was around 60% for chemicals characterized by contradictory fragments or only negative fragments. In a parallel manner, we performed eight paired runs in which carcinogenicity was attributed randomly to the molecules of the training sets. The fragments generated by these pseudo-training sets were devoid of any predictivity in the corresponding test sets. Using an independent software program, we confirmed (for the complex biological endpoint of carcinogenicity) the validity of a structure-activity relationship approach of the type proposed by Klopman and Rosenkranz with their CASE program.

Effects of Gonadotrophin-Releasing Hormone Variants on Reproductive Organs and Plasma Testosterone in the Male Lizard, Podarcis s. sicula.

Abstract The effects of various gonadotrophin-releasing hormone (GnRH) forms (mammalian GnRH (mGnRH), chicken I GnRH (cGnRH-I), chicken II GnRH (cGnRH-II) and salmon GnRH (sGnRH)) on the genital apparatus and plasma testosterone level in the male lizard, Podarcis s. sicula, have been investigated. In short duration experiments (20 min to 76 h) GnRH forms did not affect testicular and epididymal morphology. A single dose (0.05 mug) of mGnRH, cGnRH-II and sGnRH, however, induced a rise in plasma testosterone after 20 to 40 min. Variable results were obtained in the animals given GnRH variants every 12 h for 3 days since mGnRH and cGnRH-I caused a decrease of circulating hormone; cGnRH-II and sGnRH a slight increase. Daily peptide administration, for 15 to 30 days, caused severe inhibition of both testicular and epididymal activity and a significant drop of circulating testosterone. In Podarcis s. sicula, species specificity of pituitary sensitivity to GnRH variants appeared to be low. On the other hand, this gland seemed to show some desensitization after chronic peptide administration.

Estrogen receptors and aromatase activity in the hypothalamus of the female frog, Rana esculenta. Fluctuations throughout the reproductive cycle.

It is well known that certain actions of androgen are mediated through in situ aromatization to estrogen in neural target tissues. This study was undertaken to investigate androgen utilization in the hypothalamus of the female frog, Rana esculenta, through a quantification of estrogen receptors and aromatase activity during the reproductive cycle. 3H-estradiol-binding molecules were present in both the cytosol and the nuclear extract of the hypothalamus. These molecules bound specifically 3H-estradiol with high affinity (Kd 10(-10) M) and low capacity (cytosol: 1.2+/-0.4 fmol/mg protein; nuclear extract: 7.9+/-0.6 fmol/mg protein). Aromatase activity was detected in the microsomal fraction of the hypothalamus using a sensitive in vitro radiometric assay. Both aromatase activity and nuclear estrogen receptor binding fluctuated in synchrony throughout the reproductive cycle. Western blot analysis of aromatase protein revealed one immunoreactive band with a molecular weight of approximately 56 kDa. In contrast to aromatase enzyme activity, the relative levels of aromatase protein changed little during the reproductive cycle suggesting that post-translational mechanisms may be involved in regulating estrogen synthesis in the frog brain. A possible role for estrogens in the modulation of the reproductive behavior in this species is suggested.

A computerized connectivity approach for analyzing the structural basis of mutagenicity in Salmonella and its relationship with rodent carcinogenicity.

We have applied a new software program, based on graph theory and developed by our group, to predict mutagenicity in Salmonella. The software analyzes, as information in input, the structural formula and the biological activities of a relatively large database of chemicals to generate any possible molecular fragment with size ranging from two to ten nonhydrogen atoms, and detects (as predictors of biological activity) those fragments statistically associated with the biological property investigated. Our previous work used the program to predict carcinogenicity in small rodents. In the current work we applied a modified version of the program, which bases its predictions solely on the most important fragment present in a given molecule, considering as practically negligible the effects of additional less important fragments. For Salmonella mutagenicity we used a database of 551 compounds, and the program achieved a level of predictivity (73.9%) comparable to that obtained by other authors using the Computer Automated Structure Evaluation (CASE) program. We evaluated the relative contributions of biophores and biophobes to overall predictivity: biophores tended to be more important than biophobes, and chemicals containing both biophores and biophobes were more difficult to predict. Many of the molecular fragments identified by the program as being strongly associated with mutagenic activity were similar to the structural alerts identified by the human experts Ashby and Tennant. Our results tend to confirm that structural alerts useful to predict Salmonella mutagenicity are generally not very strong predictors of rodent carcinogenicity. Although the predictivity level achieved for oncogenic activity improved when the program was directly trained with carcinogenicity data, carcinogenicity as a biological endpoint was still more difficult to predict than Salmonella mutagenicity.