In vivo evidence that the cannabinoid receptor 2-63 RR variant is associated with the acquisition and/or expansion of HIV infection.

OBJECTIVES: The aim of the study was to investigate whether the rs35761398 variants of the cannabinoid receptor 2 (CB2) gene may influence the acquisition of HIV infection and the clinical presentation of HIV/hepatitis C virus (HCV) coinfection. METHODS: We compared 166 HIV/HCV-coinfected patients with 186 HCV-monoinfected patients, all with biopsy-proven chronic hepatitis (using the Ishak scoring system), naïve for anti-HCV treatment and tested for the CB2 rs35761398 polymorphism (using the TaqMan assay). RESULTS: The HIV/HCV-coinfected patients were more frequently male (P < 0.002), were younger (P < 0.001), and had lower median BMI (P < 0.001) and HCV RNA (P < 0.05) and higher median aspartate aminotransferase (AST; P < 0.001), alanine aminotransferase (ALT; P < 0.001) and gamma glutamyl transferase (GGT; P < 0.001) levels than the HCV-monoinfected patients. The CB2 RR variant predominated in HIV/HCV-coinfected patients (45.8% vs. 31.2% in HCV-monoinfected patients; P < 0.001) and the CB2 QR variant in HCV-monoinfected patients (57.5% vs. 38.6% in HIV/HCV-coinfected patients; P < 0.00001), and the CB2 QQ variant was equally distributed. Focusing on patients with the CB2 QQ variant, the 26 HIV/HCV-coinfected patients, compared with the 21 HCV-monoinfected patients, showed less severe liver necroinflammation [lower histological activity index (HAI)] (P < 0.05). Of the patients with the CB2 RR variant, the 76 HIV/HCV-coinfected patients, compared with the 58 HCV-monoinfected patients, were more frequently male (P < 0.05), were younger (P < 0.001), and had a lower median body mass index (BMI; P < 0.001), a higher median AST level (P < 0.001), a higher mean HAI score (P < 0.05) and a higher rate of cases with severe steatosis (P = 0.05). In an analysis of variance (anova) of HCV/HIV-coinfected and HCV-monoinfected patient data, those with the CB2 RR variant (P = 0.003) and of male sex (P = 0.002) were more prevalent in the HCV/HIV-coinfected group. CONCLUSIONS: There is the suggestion of a positive effect of the CB2 RR variant on HIV acquisition and/or spread, which is in accordance with previous in vitro observations.

Chemosensory recognition of the marbled whiptail lizard, Aspidoscelis marmorata (Squamata: Teiidae) to odors of sympatric lizards (Crotophytus collaris, Coleonyx brevis, Eumeces obsoletus and Uta stansburiana) that represent different predation risks.

The ability of the whiptail lizard Aspidoscelis marmorata (Teiidae) to detect and discriminate chemical stimuli associated with the integument of a sympatric saurophagous lizard (Crotaphytus collaris) was tested. Females of A. marmorata were presented with cotton swabs containing chemical cues from C. collaris and three species of nonsaurophagous lizards, as well as water and cologne (pungency control), and total number of tongue-flick (TF) recorded. Other responses were assessed including directed TF rate, time from initial presentation of the stimulus to first TF (latency), time spent fleeing from the stimulus, and number of flight bouts. The number of TFs, directed TF rate, and number of attempts at fleeing exhibited by were significantly greater when females were presented with swabs containing cues from C. collaris as compared to nonsaurophagous lizards and both control treatments. A. marmorata required significantly less time to elicit their first TF when presented with cues from C. collaris as compared to all other treatments. Most previous studies have focused on the responses of lizards to cues associated with snake predators. This study provides the first available data on responses of a teiid to cues associated with a saurophagous lizard.

Use of tactile cues by Notiosorex crawfordi (Insectivora) in response to topographical features in the environment.

The present studies were conducted on the ability of males of the gray shrew, Notiosorex crawfordi to use tactile cues to detect and respond to changes in topographical features of their environment. The animals were videotaped, digitized, and analyzed through video recordings. All subjects showed habituation (decrease in distance traveled) to arena conditions, followed by dishabituation when positions of the blocks were changed. Intact (INT) and sham controls (SHC) shrews traveled significantly greater distances and showed higher exploration velocities as compared to animals with shaved vibrissae (SHV). Results provide empirical evidence that N. crawfordi can effectively use tactile cues to detect and respond to changes in its environment.

Responses of the whipscorpion, Mastigoproctus liochirus (Arachnida, Uropygi) to environmental humidity.

Experiments were conducted to determine the responses of third-instar nymphs of the whipscorpion Mastigoproctus liochirus to various moisture (relative humidity) levels under constant temperature conditions, using a linear humidity gradient apparatus. No previous data exist on the water relations of this uropygid. Under saturated conditions (100% RH) animals showed no preference for any section of the chamber. When a humidity gradient was established (20 to 100% RH), whipscorpions exhibited a marked preference for an area of the chamber characterized by 70 to 80% RH.

[Inherited disorders of bilirubin metabolism]. / Disordini ereditari del metabolismo della bilirubina.

Jaundice in an infant or older child may reflect accumulation of either unconjugated or conjugated bilirubin and could be related to inherited bilirubin disorders. Three grades of inherited unconjugated hyperbilirubinemia are recognised in humans. This spectrum of disorders is distinguished primarily on the basis of the plasma bilirubin level, the response to phenobarbital administration, and the presence or absence of bilirubin glucoronides in bile. The enzyme responsible for the conjugation of bilirubin is the bilirubin uridine-diphosphate-glucuronosyltransferase (UGT). Mutations in the gene encoding bilirubin-UGT (UGT1A1), lead to complete or partial inactivation of the enzyme causing the rare autosomal recessively inherited conditions, Crigler-Najjar syndrome type 1 (CN-1) and type 2 (CN-2). Gilbert syndrome (GS) is due to an insertional mutation at homozygous state of the TATAA element (seven TA repeats) of UGT1A1 producing a reduced level of expression of the gene. The association of GS with haemolytic anemias, e.g., Hereditary Spherocytosis (HS) or Congenital Dyserythropoietic Anemia type 2 (CDA 2), increase the hyperbilirubinemia level and the risk of cholelithiasis. Forms of chronic conjugated hyperbilirubinemia are Dubin-Johnson syndrome, Rotor syndrome, Alagille syndrome or arteriohepatic dysplasia, Wilson disease or hepatolenticular degeneration. Liver or liver cell transplantation is the therapy in some cases.

Effects of azadirachtin on mortality, fertilization, and swimming speed in larvae of the cane toad, Bufo marinus (Anura: Bufonidae).

Experiments were conducted to assess the effects of azadirachtin (AZ) on survival capacity, fertilization success, and swimming speed in larval stages of the cane toad, Bufo marinus . LC50 values (96-hr) for various larval stages exposed to 0.50 mg/l AZ were as follows: 5.35 (stage 12), 5.77 (stage 16), 787 (stage 20), 13.43 (stage 24), and 21.54 (stage 30). Tadpoles did not exhibit any apparent disorientation or production of mucous in response to AZ concentrations ranging from 0.3 to 0.5 mg/l. Mortality was significantly higher at 0.50 mg/l AZ than at lower concentrations. At 0.50 mg/l, mortality rate decreased significantly from 36% for stage 12 tadpoles, to 24% for stage 20 tadpoles. Mortality for early stages (stage 12) dropped significantly, from 36% at 0.50 mg/l, to 21% at 0.40 mg/l AZ There were no significant differences in percent mortality for any developmental stage at an AZ concentration of 0.3 mg/l, or for controls (no AZ). Exposure of gametes to 0.30 mg/l AZ did not reduce fertilization success as compared to controls (89.8 vs. 83.7%). At 0.40 mg/l, percent fertilization decreased significantly (68.8%). This effect was even more pronounced at 0.50 mg/l. No significant difference was found in swimming speeds between controls and subjects exposed to 0.30 mg/l AZ. However, at a concentration of 0.40 mg/l, tadpoles required a significantly longer period of time to swim a distance of 140 cm as compared to controls. The potential impact of AZ on amphibian populations is discussed.

Effect of lead exposure on spatial learning and running speed in the short-tailed opossum, Monodelphis domestica (Didelphidae).

Studies were conducted to assess the spatial learning ability in adult males of the short-tailed opossum, Monodelphis domestica using a T-maze, complex maze and elevated radial 8-arm maze. This is the first study of maze learning in opossums. In the T-maze, the performance of these animals improved over an 8-day training period. Eighty percent of the subjects initially trained to turn to the right for food reinforcement reached criterion (80% correct responses) by day 3 and all reached criterion by day 4. Reversal training (subjects then trained to turn to the left) was more difficult and required 8 days for all subjects to reach criterion. In the complex maze, 89% of the animals achieved the criterion level of performance (3 consecutive trials with 5 or fewer errors) on the eighth day of training and all reached criterion by day 10. The relative importance of intramaze vs. extramaze cues in directing choice behavior was investigated in the radial arm maze. A discrimination procedure was used which selectively rewarded subjects for following only one set of cues. Animals in the intramaze group obtained a food pellet from a cup at the end of each arm. In the extramaze group, the food cups were placed on a small platform just beyond the end of each arm. All subjects were initially trained to visit each arm with the maze in a fixed position (controls) and did so within 15 test sessions. Following these initial trials, the maze was rotated to a different position after each choice. For subjects in the intramaze group, the food moved in conjunction with the rotation of the arms thereby increasing the relevance of intramaze cues. In the extramaze group, extramaze cues became more important because the food remained on the platforms in the same position in the room. Animals in the extramaze group performed significantly better than chance whereas the intramaze subjects did not. This indicates that intramaze cues are not as important as extramaze cues for accurate choice behavior in this marsupial. In addition, animals injected with tetraethyllead showed a significant impairment in running speed and T-maze learning ability as compared to saline-injected controls.

Early-life nutritional environment and spatial navigation in the water shrew, Sorex palustris (Insectivora).

Studies were conducted to study the effects of early-life nutritional environment on spatial navigation ability in the water shrew (Sorex palustris), as well as to provide information on life history traits and husbandry. The mean longevity of males and females in captivity was 652.3 +/- 33.8 SD and 616.2 +/- 22.5 days, respectively. Litter sizes ranged from 5 to 8 and neonatal mass ranged from 0.71 to 0.83 g. Spatial navigation was examined by use of the Morris water apparatus, where animals were required to locate the position of an escape platform in a circular tank of water. The platform was visible (proximal cue version of the task) in some tests. In other tests it was hidden beneath the surface (distal cue version) by making the water opaque using a non-toxic white dye. The tank was divided into 4 quadrants and the position of the plafform in any quadrant could be fixed for any subject or varied between subjects. Early-life under-nutrition was achieved by maintaining some shrews on a restricted diet (received half the amount of food as did controls). Under-nutrition was found to have an adverse effect on spatial navigation. Regardless of nutritional status, shrews were able to locate a hidden plafform that was placed at the center of a given quadrant more rapidly (escape latency) when it was visible (44 to 69 sec) than when it was hidden (83 to 164 sec). Results also showed that these shrews utilize both proximal and distal cues in this spatial task. Control subjects spent more time at a location where the platform had been in a previous test (69% of the trial period) than their undernourished counterparts (45 to 51%). This is the first experimental analysis of spatial navigation and the effects of early-life under-nutrition on this task, for S. palustris.

The effects of early experience on subsequent feeding responses in the Tegu, Tupinambis teguixin (Squamata : Teiidae).

The purpose of this study was to assess the effects of early feeding experiences on subsequent responses to prey in the tegu, Tupinambis teguixin. Five-day old lizards were exposed to the odors of various prey and control substances on cotton-tipped applicators with the tongue-flick attack score (TFAS) chosen as the dependent variable. Each lizard was exposed to four stimuli: two controls (deionised water and cologne), and extracts from a mouse Mus musculus, and a lizard Ameiva ameiva, in a repeated measures, randomized block design, receiving one stimulus training session / day over a 40-day period. Tongue-flicks directed toward the applicator were counted over a 1 min period as well as the amount of time that elapsed from the first tongue flick to any bite that may have occurred. Live neonatal mice (but not A. ameiva), offered on a weekly basis, were used as a food source for tegus over a 10-month period. After 10 months, tegus were exposed to applicators containing control odors as well as those containing extracts from mice and lizards (A. ameiva). Mouse extracts elicited significantly higher TFAS as compared to those elicited by A. ameiva or control odors, suggesting that prey odors encountered in the environment shortly after hatching can influence prey preferences by these lizards later in life. These results also indicate that tegu lizards can learn to use specific odor cues associated with naturally occurring prey as releasers for subsequent hunting behaviors.

These studies were conducted to assess the effects of lead toxicity on exploratory behavior and running. Effects of lead on exploratory behavior and running speed in the shrew, Blarina brevicauda (Insectivora).

These studies were conducted to assess the effects of lead toxicity on exploratory behavior and running speed in the short-tailed shrew, Blarina brevicauda. Shrews from the experimental group received 25 mg/kg/day of lead acetate in their drinking water for a period of 90 days. Control subjects received sodium acetate. Exploratory behavior was determined using a computerized activity chamber where movements of test subjects broke infrared beams projected onto the floor of the apparatus. Time spent (sec) in exploration was recorded over eight 6-min intervals. Running speed (km/hr) was measured in a microprocessor-controlled rectangular racetrack fitted with photocell timers. With respect to time spent in exploration, there were significant differences between lead-exposed (20.5-23.9 sec per 6-min testing session) and control subjects (6.8-8.1 sec) after the sixth testing interval in the activity chamber. With respect to maximal running speed, control subjects ran significantly faster (mean: 14.8 km/hr) than their lead-exposed counterparts (5.83 km/hr). Lead-exposed animals exhibited hyperactivity and increased random locomotor movements. They would frequently bump into the walls and their movements were more random. Controls typically ran along the racetrack in a straight line. These results represent the first data for the effects of lead exposure on exploratory behavior and running speed for shrews.

Environmental chemical cues associated with prey and subsequent prey preference in the wolf spider Hogna carolinensis Hentz (Araneae, Lycosidae).

The purpose of this study was to determine if environmental chemical cues associated with prey can affect subsequent prey choice in wolf spiderlings (Hogna carolinensis). After emergence from the egg sac, three groups of 10 spiderlings were each fed for one-week on one of three naturally-occurring prey species: group 1 fed on nymphs of the field cricket Gryllus pennsylvanicus; group 2 (house cricket, Acheta domesticus); group 3 (mole cricket, Gryllotalpa hexadactyla). They were then tested for subsequent prey preference in choice tests conducted in a plastic arena. Each spiderlings was presented simultaneously with one individual of each prey species in a randomized design. Spiderlings exhibited a significant first preference for the original diet. Thus, experience with certain foods (environmental chemical cues) encountered by newly hatched spiderlings can affect subsequent prey preference in this species.

Utilization of neuroleptic drugs in Italian mental health services: a survey in Piedmont.

OBJECTIVE: This survey describes neuroleptic prescribing practices in Italian mental health services 15 years after implementation of a mental health reform law that shifted the focus of care from mental hospitals to community services. METHODS: The authors conducted a cross-sectional survey of neuroleptic prescribing practices in several psychiatric services throughout the Piedmont region in northern Italy. The relationship between dosing patterns and patients' characteristics was assessed using multiple regression analysis. RESULTS: Sixty-six community mental health services and 14 psychiatric wards in general hospitals participated in the survey in 1991. Among the 3,823 psychiatric patients seen in these settings for whom survey data were available, 67 percent of outpatients and 84 percent of inpatients were prescribed neuroleptic drugs. Twenty-eight percent of outpatients and 45 percent of inpatients received more than one neuroleptic. The average daily dose of neuroleptics was low to moderate; 89 percent of outpatients and 67 percent of inpatients received 500 mg of chlorpromazine equivalents or less. The neuroleptic dose was significantly associated with patients' age, education, diagnosis, length of treatment, and receipt of polypharmacy. CONCLUSIONS: This survey confirms the low to moderate neuroleptic dosing in Italian mental health services, both in outpatient and inpatient settings. However, it also documents the widespread use of polypharmacy, a pattern that has remained largely unchanged over the past 15 years.

Prescription pattern of antidepressants in out-patient psychiatric practice.

The prescription pattern of antidepressants was reviewed in a large sample of psychiatric out-patients in the Region of Piedmont. Antidepressants were administered to 780 patients; most were diagnosed with mood disorders (62% of prescriptions) and anxiety disorders (34%), the rest with other diagnoses. The mean prescribed dose of antidepressants was at the lower end of, or below, the recommended range for out-patients, with the exception of amineptine and mianserin. The administered dose of tricyclic antidepressants was significantly associated with sex and diagnosis: female patients received a daily dose that was significantly lower than that for males, and patients with a diagnosis of mood disorders received significantly more medication than those with other diagnoses.