c-Fos expression after neonatal handling in social brain regions: Distinctive profile of RHA-rat schizophrenia model on a social preference test.

Neonatal handling (NH) is an environmental manipulation that induces long-lasting changes in behavioural, neuroendocrine, and neuroanatomical processes in rodents. We have previously reported that NH treatment increases social interaction preference in an animal model of schizophrenia-relevant features, the Roman high-avoidance (RHA) rats. The present study was aimed at evaluating whether the increase of social behaviour/preference due to NH treatment in RHA rats is associated with differences in c-Fos expression levels in some of the brain areas that integrate the "social brain". To this aim, we evaluated the performance of adult male rats from both Roman rat strains (RHA vs. RLA -Roman low-avoidance- rats), either untreated (control) or treated with NH (administered during the first 21 days of life) in a social interaction task. For the analyses of c-Fos activation untreated and NH-treated animals were divided into three different experimental conditions: undisturbed home cage controls (HC); rats exposed to the testing set-up context (CTX); and rats exposed to a social interaction (SI) test. It was found that, compared with their RLA counterparts, NH treatment increased social behaviour in RHA rats, and also specifically enhanced c-Fos expression in RHA rats tested for SI in some brain areas related to social behaviour, i.e. the infralimbic cortex (IL) and the medial posterodorsal amygdala (MePD) regions.

Mechanical properties of animal ligaments: a review and comparative study for the identification of the most suitable human ligament surrogates.

The interest in the properties of animal soft tissues is often related to the desire to find an animal model to replace human counterparts due to the unsteady availability of human tissues for experimental purposes. Once the most appropriate animal model is identified, it is possible to carry out ex-vivo and in-vivo studies for the repair of ligamentous tissues and performance testing of replacement and support healing devices. This work aims to present a systematic review of the mechanical properties of ligaments reported in the scientific literature by considering different anatomical regions in humans and several animal species. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. Moreover, considering the lack of a standard protocol for preconditioning of tissues, this aspect is also addressed. Ninety-six studies were selected for the systematic review and analysed. The mechanical properties of different animal species are reported and summarised in tables. Only results from studies reporting the strain rate parameter were considered for comparison with human ligaments, as they were deemed more reliable. Elastic modulus, ultimate tensile stress, and ultimate strain properties are graphically reported identifying the range of values for each animal species and to facilitate comparison between values reported in the scientific literature in animal and human ligaments. Useful similarities between the mechanical properties of swine, cow, and rat and human ligaments have been found.

Dysregulation of hepatic metabolism with obesity: factors influencing glucose and lipid metabolism.

The liver is a key metabolic organ that undertakes a multitude of physiological processes over the course of a day, including intrahepatic lipid and glucose metabolism which plays a key role in the regulation of systemic lipid and glucose concentrations. It serves as an intermediary organ between exogenous (dietary) and endogenous energy supply to extrahepatic organs. Thus, perturbations in hepatic metabolism can impact widely on metabolic disease risk. For example, the accumulation of intra-hepatocellular TAG (IHTG), for which adiposity is almost invariably a causative factor may result in dysregulation of metabolic pathways. Accumulation of IHTG is likely due to an imbalance between fatty acid delivery, synthesis and removal (via oxidation or export as TAG) from the liver; insulin plays a key role in all of these processes.

Biologic therapies for plaque type psoriasis in patients with previous malignant cancer: long-term safety in a single- center real-life population.

INTRODUCTION: This is an Italian single-center retrospective study evaluating safety and efficacy of biologic agents in psoriatic patients with a previous diagnosis of malignant cancer. AIM: Management of moderate and severe psoriasis patients with a past medical history of malignancies could be difficult because biologic agents are historically associated with a presumptive increased risk of neoplastic reactivation or of a new incoming cancer. The aim of this study is to assess the safety of biologics in patients with a previous cancer diagnosis. MATERIAL AND METHODS: The study analyzed 16 moderate to severe psoriasis patients with a diagnosis of malignant cancer in the previous 10 years treated with biologic agents for up to at least 96 weeks. In five of these patients, cancer was diagnosed in the previous 5 years. RESULTS: We observed a rapid decrease in PASI (psoriasis area severity index) reaching a 90% improvement in 100% of patients. Oncologic follow up did not show any worsening or reactivation of cancer during the entire observation period. No new malignancies were observed in the analyzed sample. CONCLUSIONS: Biologic agents in our experience have demonstrated to be safe and effective in psoriatic patients with a past medical history of malignant cancer.

SARS-CoV-2 systemic infection in a kidney transplant recipient: sequence analysis in clinical specimens.

OBJECTIVE: Herein we report clinical and virological data in a patient with COVID-19 infection and a prior history of kidney transplantation who had a good clinical recovery despite systemic infection. PATIENTS AND METHODS: Reverse transcriptase quantitative PCR analysis for the RdRp, N and E target genes detected viral RNA in different types of biological specimens. Whole viral genome sequences were obtained and analyzed from respiratory tract, feces and blood. RESULTS: Viral sequences showed high (~99.9%) homology with the Wuhan seafood market pneumonia virus. Phylogenetic analysis assigned of the SARS-CoV-2 strains to clade G. A rare variant in the orf1ab gene was present in both sequences, while a missense variant was detected only in viral RNA from stool. CONCLUSIONS: The evolution of the COVID-19 systemic infection in the patient presented here was favorable to the hypothesis that immunosuppressive therapy in organ transplant recipients might be involved in viral dissemination. A missense mutation was present in only one specimen from the same patient implying the occurrence of a mutational event in viral RNA, which is suggestive for the presence of an active virus, even though viral isolation is necessary to demonstrate infectivity.

Use of a Dual mobility cup to prevent hip early arthroplasty dislocation in patients at high falls risk.

INTRODUCTION: Hip fracture is a common serious injury that occurs mainly in elderly. Dual-mobility hip arthroplasty or bipolar emiarthroplasty for its treatment remains a controversial decision. Co-morbidities and risk of fall represent additional aspects to be considered. The aim of our study was to determine the rate of mechanical complications for these two types of implants related to fall risk status of patients. PATIENTS AND METHODS: Our study is a retrospective clinical trial of patients operated with a biarticular hemiarthroplasty or a dual-mobility total hip arthroplasty. Primary outcome was dislocation rate and need for any revision procedure. Patients were treated in a single center from January 2013 to March 2017. In all cases Morse Fall Scale (MSF) was calculated at patient admission to evaluate the risk of postoperative fall. Inclusion criteria to the study were: subcapital or femoral neck fracture of non-pathologic nature, patients with neuromuscular disorders or cognitive dysfunction, age > 75 years with MFS ≥ 45. The patients were reviewed postoperatively at 8 weeks, 6 months, 12 months, and then annually. Patients had clinical (Harris hip score) and radiological assessment. RESULTS: The mean duration of the follow-up was 283 months. There were five dislocations in Group A (5,6%) and no dislocations in Group B (0%). All dislocations occurred within the first 6 months after surgery. The mean Harris Hip score was 81,7 in Group A patients and 79, 8 in Group B patients. DISCUSSION: Treatment of hip fractures on non-cooperative patients still represents a dilemma. Falls and runaway motions represent high risk factors of dislocation. Use of dual-mobility cup has been found to be associated with a not statistically proved decrease of dislocation compared to traditional cups. CONCLUSION: Dual-mobility cups might be considered a valuable option to prevent postoperative dislocation but further study is needed before extending the indications for dual-mobility following a fracture of the femoral neck, to assess the potential cost and complications of a longer procedure. So far, despite a lower dislocation risk, the authors actually cannot recommend widely use of a dual-motility cup instead of emiarthroplasty in high falls risk patients.

Suicidal jumper's fracture - sacral fractures and spinopelvic instability: a case series.

BACKGROUND: Sacral fractures with spinopelvic dissociation are rare, and hard to diagnose and treat. Fractures with a H- or U-shaped line are severely unstable, due to a dissociation of the spine and of the upper body of the sacrum from the pelvis. They are commonly due to high-energy trauma events, with severe neurological injuries in 80% of cases. CASES PRESENTATION: Five polytraumatized Caucasian patients, three women and two men (mean age: 34 years old) with spinopelvic dissociation were selected. All patients underwent level I-II examinations with radiographs and computed tomography total-body scans; all patients needed damage-control procedures. Sacral fractures were classified according to Denis and Roy-Camille classifications, and neurologic injuries of cauda equina according to Gibbons classification. Patients' outcome was analyzed with the Majeed score. Definitive surgical treatment was appropriate for two patients (lumbar-pelvic fixation or transverse bar). Clinical and radiographic outcomes were analyzed periodically. Four patients survived, all of them suffered severe neurologic deficits. One case of osteomyelitis was treated with the removal of the fixation implants 23 months after the accident. CONCLUSIONS: Diagnosis of spinopelvic dissociation is frequently overlooked due to the severe associated injuries affecting these patients. In cases of a fall from high height, this lesion should be investigated with a lateral sacral radiographic view and computed tomography scan of the pelvis. If untreated, it can lead to severe and progressive neurologic deficit with muskuloskeletal deformities and persistent pain. Early decompression treatment is controversial, but an early lumbopelvic fixation is recommended. A correct diagnosis and early treatment can reduce morbidity and strongly improve the outcome of these patients.

Is 2-Hydroxypropyl-ß-cyclodextrin a Suitable Carrier for Central Administration of Δ9 -Tetrahydrocannabinol? Preclinical Evidence.

Preclinical Research Δ9 -Tetrahydrocannabinol (THC) is a hydrophobic compound that has a potent antinociceptive effect in animals after intrathecal (IT) or intracerebroventricular (ICV) administration. The lack of a suitable solvent precludes its IT administration in humans. 2-Hydroxypropyl-ß-cyclodextrin (HPßCD) increases the water solubility of hydrophobic drugs and is approved for IT administration in humans. To investigate whether HPßCD might be a suitable carrier for ICV administration of THC in rats, two formulations containing THC complexed with HPßCD (30 and 135 µg of THC per animal) and vehicle were administered to Wistar rats. The antinociceptive effect (using the tail flick test), locomotor activity, and body temperature were evaluated. ICV injection of 135 µg of THC/HPßCD complex increased tail flick latency, reduced locomotor activity, and had a dual effect on body temperature. The 30 µg THC/HPßCD formulation only produced a hyperthermic effect. All animals appeared healthy, with no difference between the groups. These results were similar to those obtained in other preclinical studies in which THC was administered centrally using solvents that are unsuitable for IT administration in humans because of their toxicity. Our findings suggest that HPßCD may be a useful carrier for IT administration of THC in humans. Drug Dev Res 78 : 411-419, 2017. © 2017 Wiley Periodicals, Inc.

Strain response of thermal barrier coatings captured under extreme engine environments through synchrotron X-ray diffraction.

The mechanical behaviour of thermal barrier coatings in operation holds the key to understanding durability of jet engine turbine blades. Here we report the results from experiments that monitor strains in the layers of a coating subjected to thermal gradients and mechanical loads representing extreme engine environments. Hollow cylindrical specimens, with electron beam physical vapour deposited coatings, were tested with internal cooling and external heating under various controlled conditions. High-energy synchrotron X-ray measurements captured the in situ strain response through the depth of each layer, revealing the link between these conditions and the evolution of local strains. Results of this study demonstrate that variations in these conditions create corresponding trends in depth-resolved strains with the largest effects displayed at or near the interface with the bond coat. With larger temperature drops across the coating, significant strain gradients are seen, which can contribute to failure modes occurring within the layer adjacent to the interface.

NATIVE LARVAL PARASITOIDS ASSOCIATED WITH TUTA ABSOLUTA (MEYRICK) IN GREENHOUSE TOMATO CROPS OF SOUTHERN SARDINIA.

Since its first detection in Sardinia (Italy), Tuta absoluta (Meyrick) has been reported as a major pest of greenhouse tomatoes. In recent years, however, a tendency toward a progressive reduction of tomato borer infestation levels has been observed. The reasons behind this decline are probably diverse, including both the increase in growers' ability to manage the pest and the adaptation of native predators and parasitoids to the new prey/host. In order to assess the species composition of the parasitoid complex associated with T. absoluta larvae in Sardinian greenhouse tomatoes, a two-year (2010/11) survey was conducted in one of the island's major horticultural areas (Pula, Cagliari). An estimate of the levels of parasitism caused by native wasps was also carried out. The occurrence of larval parasitoids of T. absoluta was detected in approximately half of the crops monitored. The average parasitism rate recorded in tomato plants infested by tomato borer larvae was 1.3%. Moreover, while no parasitism was observed in 76.4% of the samples collected, only 3.0% of the samples showed a parasitism rate exceeding 10%. The highest rates were recorded in spring and summer, with a peak in July (4.8%). Of 159 adult parasitoids recovered from infested leaves, 62.9% were found to belong to a Necremnus sp. near artynes (Walker), 34.6% to a Necremnus sp. near tidius (Walker), and 2.5% to Neochrysocharis formosa (Westwood) (Hymenoptera: Eulophidae). These results show that some native parasitoids have adapted to T. absoluta in the study area. Although parasitoid abundance in tomato crops appeared to be low, their contribution for the control of tomato borer infestation could possibly be enhanced through the application of conservation biological control measures.

Synchrotron X-ray measurement techniques for thermal barrier coated cylindrical samples under thermal gradients.

Measurement techniques to obtain accurate in situ synchrotron strain measurements of thermal barrier coating systems (TBCs) applied to hollow cylindrical specimens are presented in this work. The Electron Beam Physical Vapor Deposition coated specimens with internal cooling were designed to achieve realistic temperature gradients over the TBC coated material such as that occurring in the turbine blades of aeroengines. Effects of the circular cross section on the x-ray diffraction (XRD) measurements in the various layers, including the thermally grown oxide, are investigated using high-energy synchrotron x-rays. Multiple approaches for beam penetration including collection, tangential, and normal to the layers, along with variations in collection parameters are compared for their ability to attain high-resolution XRD data from the internal layers. This study displays the ability to monitor in situ, the response of the internal layers within the TBC, while implementing a thermal gradient across the thickness of the coated sample. The thermal setup maintained coating surface temperatures in the range of operating conditions, while monitoring the substrate cooling, for a controlled thermal gradient. Through variation in measurement location and beam parameters, sufficient intensities are obtained from the internal layers which can be used for depth resolved strain measurements. Results are used to establish the various techniques for obtaining XRD measurements through multi-layered coating systems and their outcomes will pave the way towards goals in achieving realistic in situ testing of these coatings.

An epidemiological survey of TYLCD in southern Sardinia (Italy).

Tomato yellow leaf curl Sardinia virus (TYLCSV) and Tomato yellow leaf curl virus (TYLCV) are among the most virulent pathogens of greenhouse tomatoes in Sardinia (Italy). To investigate the relationship between seasonal population trends of the vector Bemisia tabaci and the dynamics of TYLCD spread to susceptible crops, between May and October 2007 we carried out a survey in a tomato growing area located in the south of the island. On three farms specialized in the production of fresh market tomatoes we monitored, outside commercial greenhouses, the following parameters related to TYLCD epidemiology: mean weekly catches of the whiteflies B. tabaci and Trialeurodes voporariorum on yellow sticky traps, ratio between the two whitefly species and proportion of B. tabaci adults carrying TYLCSV/TYLCV in adult samples collected on hosts not susceptible to the disease, proportion of tomato plants infected by TYLCSV/TYLCV after a two-week exposure to open field conditions. Generally speaking, the flight activity of whiteflies increased during spring, reached a peak in May or June and gradually declined in summer. At the beginning of the survey, T. vaporariorum was found to be the prevalent species, but after a shift in composition of whitefly populations during July, B. tabaci became predominant. While the percentage of vector adults carrying the viral agents of the disease was relatively high up to July, with maximum values ranging between 14 and 25%, during the following months it decreased to less than 5%. The incidence of TYLCD in the plants exposed outside the greenhouses showed a similar trend in the sites surveyed, with two peaks roughly coinciding with the beginning and end of summer. Therefore, two distinct phases of TYLCD spread were observed: from spring to midsummer when the disease was transmitted by low 8. tabaci populations with relatively high proportions of virus carriers; from midsummer to autumn, when the disease was spread by larger vector populations with low percentages of individuals carrying the viruses. Further studies are necessary to gain a better understanding of the interactions among B. tabaci biotypes, TYLCSV/TYLCV and their hosts.

Seasonal trends of whitefly populations in a Mediterranean tomato growing area.

The whiteflies Bemisia tabaci and Trialeurodes vaporariorum and their associated viruses constitute a major threat to tomato crops in the Mediterranean region. Continuous host availability and mild climate are thought to be among the factors contributing to the outbreaks of whitefly-related problems in this area. We carried out a year-long survey to investigate the relative contribution of different plants, agricultural and not, and indoor/outdoor crops as hosts of the two whiteflies and the tomato yellow leaf curl disease (TYLCD) in a multi-crop system typical of tomato growing areas in southern Sardinia (S. Margherita di Pula, Cagliari, Italy). For this purpose, during 2005 we monitored whitefly population trends in different plots of a horticulture farm, evaluated seasonal changes in the infestation density of the two pests on the most represented host species and assessed the incidence of TYLCD on tomato crops and susceptible weeds. Whitefly catches on yellow sticky traps were found to be higher inside et along the external perimeter of greenhouses compared to open field crops or uncultivated areas, thus suggesting significant adult movement between indoor and outdoor patches. In most plots flight activity increased between late spring and late summer, peaking in July. The number of immatures of the two whitefly species showed similar dynamics, but while T. vaporariorum reached the highest densities in greenhouse tomato crops in June, peak levels of 8. tabaci were recorded between July and August in outdoor horticultural crops and weeds. The occurrence of TYLCD was detected all year round on weed hosts, but the highest number of infected plants was observed in June on long cycle tomato crops. The present survey has demonstrated the contribution of non-agricultural plants the maintenance of tomato yellow leaf curl disease in the study site. However, tomato crops established in summer as major reservoirs of TYLCD-associated viruses and presumably played a key role in the spread of the disease to autumn tomato crops. The implementation of a crop-free period between successive susceptible crops, or at least the avoiding of whitefly movement through greenhouse openings and the complete destruction of plants after final harvest, would probably reduce the severity of TYLCD epidemics in this area.

Biological agents for whitefly control in Sardinian greenhouse tomatoes.

To evaluate the effectiveness of alternative options for biocontrol of whiteflies in greenhouse tomatoes, an experiment was carried out during the cropping season 2005-2006 in one of Sardinia's major horticultural districts (S. Margherita di Pula, Cagliari, Italy). Twelve long-cycle and 17 short-cycle tomato crops (8 autumn and 9 spring crops) were surveyed. All of them were treated for insect pest control at the beginning of the growing season, but in 19 out of 29 cases whitefly natural enemies were also released (BCA greenhouses), at least four weeks after the last treatment. The following release programmes were tested: on autumn crops, 1 Macrolophus caliginosus and 12 Eretmocerus mundus/m2; on long-cycle crops, 1 M. caliginosus (released in autumn or spring) and 24 Encarsia formosa/m2 or 48 E. formosa/m2; on spring crops, 1 M. caliginosus and 24 E. formosa/m2 or 48 E. formosa/m2. The cost of each option was fixed at approximately 0.25 Euros/m2. The remaining greenhouses were maintained as controls (no BCA greenhouses). While whitefly and mirid populations were monitored monthly, whitefly species composition and mortality of immature stages were estimated at least twice during the growing season. On short-cycle autumn crops, the release of M. caliginosus and E. mundus produced negligible results in terms of Bemisia tabaci control. On long-cycle and spring crops, even though in June mortality rates in BCA greenhouses were found to be 2- to 3-fold higher than in no-BCA greenhouses, Trialeurodes vaporariorum population growth was not significantly affected by natural enemies. Among the beneficials tested, E. formosa proved to be the most effective; E. mundus and M. caliginosus did not establish well, probably owing to the persistence of insecticide residues, scarce prey availability and intense plant de-leafing. The presence of indigenous natural enemies of whiteflies was observed in most sites, but in general they contributed little to biological control. The present experiment showed that in Sardinian tomato greenhouses the use of beneficial insects may result in inadequate biocontrol of whiteflies. In particular, the application of cultural practices which may disrupt the establishment and development of predator and parasitoid populations should be critically reexamined.

Cannabinoid CB1 receptors in the paraventricular nucleus and central control of penile erection: immunocytochemistry, autoradiography and behavioral studies.

[N-(piperidin-1-yl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxyamide] (SR 141716A), a selective cannabinoid CB1 receptor antagonist, injected into the paraventricular nucleus of the hypothalamus (PVN) of male rats, induces penile erection. This effect is mediated by the release of glutamic acid, which in turn activates central oxytocinergic neurons mediating penile erection. Double immunofluorescence studies with selective antibodies against CB1 receptors, glutamic acid transporters (vesicular glutamate transporters 1 and 2 (VGlut1 and VGlut2), glutamic acid decarboxylase-67 (GAD67) and oxytocin itself, have shown that CB1 receptors in the PVN are located mainly in GABAergic terminals and fibers surrounding oxytocinergic cell bodies. As GABAergic synapses in the PVN impinge directly on oxytocinergic neurons or on excitatory glutamatergic synapses, which also impinge on oxytocinergic neurons, these results suggest that the blockade of CB1 receptors decreases GABA release in the PVN, increasing in turn glutamatergic neurotransmission to activate oxytocinergic neurons mediating penile erection. Autoradiography studies with [(3)H](-)-CP 55,940 show that chronic treatment with SR 141716A for 15 days twice daily (1 mg/kg i.p.) significantly increases the density of CB1 receptors in the PVN. This increase occurs concomitantly with an almost twofold increase in the pro-erectile effect of SR 141716A injected into the PVN as compared with control rats. The present findings confirm that PVN CB1 receptors, localized mainly in GABAergic synapses that control in an inhibitory fashion excitatory synapses, exert an inhibitory control on penile erection, demonstrating for the first time that chronic blockade of CB1 receptors by SR 141716A increases the density of these receptors in the PVN. This increase is related to an enhanced pro-erectile effect of SR 141716A, which is still present 3 days after the end of the chronic treatment.

[Urinary and blood markers of internal mercury dose in workers from a chlorakali plant and in subjects not occupationally exposed: relation to dental amalgam and fish consumption]. / Indicatori urinari ed ematici di dose interna di mercurio in lavoratori di un impianto clorosoda e in soggetti non professionalmente esposti: relazione con gli amalgami dentali ed il consumo di pesce di mare.

OBJECTIVES: The aim of this paper was both to evaluate the internal dose of Hg in occupationally exposed workers (35 Chloralkali workers) compared to that of non occupationally exposed controls (40 workers of the same plant of Portotorres and 22 residents on the island of Carloforte, usual consumers of local fish, mostly tuna fish with relatively high Hg levels) and to assess the relevance of environmental and individual exposure factors linked to lifestyle, sea fish consumption and amalgam fillings. METHODS: All subjects filled out a questionnaire concerning the working history and lifestyle. The amalgam fillings area was measured by medical inspection using a standardised schedule attached to the questionnaire. Mercury in urine (HgU) was measured in all cases, while in a subgroup of our study total blood mercury (HgB) and its organic and inorganic component were also assessed. Furthermore, for 8 of the Carloforte group mercury in hair was also available. RESULTS: Values of urinary mercury excretion of the Chloralkali workers were significantly higher (median value of 15.4, range 4.8-35.0 micrograms/g creatinine, 94.3% of the cases having values > 5 micrograms/g creatinine) than those observed both among the reference group (median value of 1.9, range 0.4-5.6 micrograms/g creatinine, 12.5% of the cases having values a little greater than 5 micrograms/g creatinine) and among the residents in Carloforte (median value of 6.5, range 1.8-21.5 micrograms/g creatinine, 59.1% of the cases having values > 5 mcg/g creatinine). The HgU values observed in this group were in turn significantly higher than those of the non occupationally exposed workers living near Sassari (p = 0.03). Only in this last group were the HgU concentrations statistically significantly related to the extension of the amalgam fillings area (Pearson r = 0.53, p < 0.01). In the Carloforte group HgU was significantly related to the number of fish meal consumed per week (Pearson r = 0.48, p < 0.02). HgB (median value of 5.9, range 3.4-21.6 micrograms/l) as well as its inorganic component (median value of 2.4, range 1.8-4.6 micrograms/l) were significantly higher in the Chloralkali group compared to the other two groups. In all cases of the Carloforte group the ratio between the organic component and the total HgB was higher than 85%, while this ratio was significantly lower in the other two groups. The relationship between HgU and HgB was statistically significant, considering both total blood mercury and the inorganic and the organic components separately. A statistically significant relationship between the sea fish consumption per week and both total HgB (Pearson r = 0.82) and the organic component in this matrix (Pearson r = 0.84, p < 0.001) was observed among 16 non-occupationally exposed subjects. However, the significant relationship between organic blood mercury and sea fish consumption was almost entirely supported by the data observed in the Carloforte group. Total hair mercury levels analysed in 8 subjects of the Carloforte group were high (median value of 9.6, range 1.4-34.5 micrograms/g) and significantly related to sea fish consumption, and to both the individual Hg urinary excretion (Pearson r = 0.83) and to the organic component of blood mercury (Pearson r = 0.87). CONCLUSIONS: According to several experimental human and animal trials and to some recent studies on methylmercury toxicokinetic models, our results suggest that the organic compounds absorbed by usual sea fish consumption may be partially demethylated, increasing the inorganic Hg concentration in the kidney and consequently its urinary excretion, as was observed in the Carloforte group.

[Neuroendocrine and neurobehavioral effects associated with exposure to low doses of mercury from habitual consumption of marine fish]. / Effetti neuroendocrini e neurocomportamentali associati con esposizione a basse dosi di mercurio derivanti da consumo abituale di pesce di mare.

OBJECTIVES: To evaluate neuroendocrine and neurobehavioral effects possibly associated with increased dietary intake of organic mercury (Hg), a group of 22 subjects living on the island of Carloforte (south-west Sardinia) was examined, who were regular consumers of tuna fish with relatively high Hg content. This group, never exposed occupationally to either Hg or to other neurotoxic substances, was compared with 22 age-matched controls employed at a chemical plant in Portotorres (northern Sardinia). METHODS: Hg in urine (HgU) and serum prolactin (PRL) were measured in all cases, whereas measurements of total (HgB) and organic blood mercury were available only for 10 subjects from Carloforte and 6 controls. Data about working history and lifestyle (education, smoking habit, alcohol and sea fish consumption) were collected by an interviewer using a standardised questionnaire. Neurotoxic symptoms were evaluated by a self-administered questionnaire, whereas a test battery, including some computerised tests of the Swedish Performance Evaluation System (SPES) to assess vigilance and psychomotor performance, some tests on motor coordination (Luria-Nebraska and Branches Alternate Movement Task) and one memory test for numbers (Digit Span) was administered to assess neurobehavioral changes associated with exposure to dietary intake of organic mercury. In all cases, characteristics of hand tremor were evaluated by the CATSYS System 7.0. RESULTS: HgU values were significantly higher in the Carloforte group (median 6.5, range 1.8-21.5 micrograms/g creatinine) compared with controls (median 1.5, range 0.5-5.3 micrograms/g creatinine). Serum PRL was significantly higher among subjects from Carloforte and correlated with both urine and blood Hg levels. The scores of each item of the questionnaire investigating neurological symptoms were not statistically different in the two groups. In some tests of the SPES battery (Color Word Vigilance, Digit Symbol and Finger Tapping) the performance of the Carloforte group was significantly worse than that of controls, whereas in the other neurobehavioral tests poorer performances by the Carloforte group were not statistically significant. None of the tremor parameters was significantly different comparing the two groups. Multivariate analysis--controlling for education level and other covariates--carried out for the Symbol-Digit Reaction Time and for the Branches Alternate Movement Task (BAMT) showed that organic Hg concentration in blood was the most significant factor negatively affecting individual performance in these tests. Serum PRL was correlated with some neurobehavioral tests (Digit Symbol, Finger Tapping and BAMT). CONCLUSIONS: Some of the neurobehavioral tests were sensitive enough to discriminate groups with different Hg body burden, even in the low-dose range. However, the pattern of results suggests adverse neurobehavioral effects, especially on psycho-motor coordination, with a significant dose-effect relationship, mostly associated with long-term exposure to low levels of organic mercury due to the usual consumption of large fish with relatively high levels of Hg in the flash.

Cell growth and cholesterol metabolism in human glucose-6-phosphate dehydrogenase deficient lymphomononuclear cells.

Atherosclerosis is an inflammatory-fibroproliferative response of the arterial wall involving a complex set of interconnected events where cell proliferation (lymphomonocytes, and endothelial and smooth-muscle cells) and substantial perturbations of intracellular cholesterol metabolism are considered to be among the main features. Glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the hexose-monophosphate shunt pathway, is an essential enzyme involved in both cell growth and cholesterol metabolism, raising the question as to whether G6PD deficiency may have metabolic and growth implications in a deficient population. In the present study, we investigated cell growth and cholesterol metabolism in peripheral blood lymphomononuclear cells (PBMC) from G6PD-normal (n = 5) and -deficient (n = 5) subjects stimulated with lectins (phytohaemoagglutinin and Concanavalin A). G6PD activity, DNA ([3H]-thymidine incorporation) cholesterol synthesis and esterification ([14C]-acetate and [14C]-oleate incorporation), and G6PD, HMGCoA reductase and low density lipoprotein (LDL) receptor mRNA levels (RT-PCR) all increased following lectin stimulation in both normal and G6PD-deficient cells. However, these parameters were significantly lower in G6PD-deficient cells (P < 0.05). It is of interest that G6PD-deficient PBMC, which showed lower expression of G6PD and higher expression of the LDL receptor gene than normal PBMC under basal conditions, exhibited an opposite pattern after stimulation: G6PD and HMGCoA reductase being expressed at significantly higher levels in deficient than in normal cells (P < 0.05). We conclude that the reduced capability of G6PD-deficient cells to respond to mitogenic stimuli and to synthesize cholesterol esters may represent favourable conditions for reducing the risk of cardiovascular diseases.

Opposite pattern of MDR1 and caveolin-1 gene expression in human atherosclerotic lesions and proliferating human smooth muscle cells.

Cholesterol esterification and smooth muscle cell (SMC) proliferation are the crucial events in the development of atherosclerotic lesions. The objective of this study was to analyse cholesterol esterification and the expression of MDR1 (multidrug resistance), ACAT (acyl-CoA:cholesterol acyltransferase) and caveolin-1 genes in atherosclerotic and healthy vascular walls, in SMCs obtained from atherosclerotic lesions and saphenous veins. Results demonstrated higher levels of cholesterol esters, ACAT and MDR1 mRNAs and lower levels of caveolin-1 mRNA in atherosclerotic segments compared to adjacent serial sections of the same artery and the corresponding non-atherosclerotic arteries from cadaveric donors. SMCs isolated from atherosclerotic plaques manifested an increased capacity to esterify cholesterol and to grow at a faster rate than SMCs isolated from saphenous veins. In addition, when SMCs from atherosclerotic plaques were cultured in the presence of progesterone, a potent inhibitor of cholesterol esterification, significant growth suppression was observed. An increase in ACAT and MDR1 expression and a concomitant decrease in caveolin-1 expression were also observed in SMCs isolated from atherosclerotic arteries as early as 12 h after serum stimulation. An opposite pattern was found when SMCs were treated with progesterone. These findings support the idea that cholesterol esterification plays a role both in early atherogenesis and in clinical progression of advanced lesions and raise the possibility that the cholesterol ester pathway might directly modulate the proliferation of SMCs.