Caramiphen edisylate as adjunct to standard therapy attenuates soman-induced seizures and cognitive deficits in rats.

The progression of epileptiform activity following soman (GD) exposure is characterized by a period of excessive cholinergic activity followed by excessive glutamatergic activity resulting in status epilepticus, which may lead to neuropathological damage and behavioral deficits. Caramiphen edisylate is an anticholinergic drug with antiglutamatergic properties, which conceptually may be a beneficial therapeutic approach to the treatment of nerve agent exposure. In the present study, rats were exposed to 1.2 LD50 GD or saline, treated with atropine sulfate (2mg/kg, im) and HI-6 (93.6mg/kg, im) 1min after GD exposure, and monitored for seizure activity. Rats were treated with diazepam (10mg/kg, sc) and caramiphen (0, 20 or 100mg/kg, im) 30min after seizure onset. Following GD exposure, performance was evaluated using a battery of behavioral tests to assess motor coordination and function, sensorimotor gating, and cognitive function. Caramiphen as adjunct to diazepam treatment attenuated GD-induced seizure activity, neuropathological damage, and cognitive deficits compared to diazepam alone, but did not attenuate the GD-induced sensorimotor gating impairment. These findings show that physiological, behavioral, and neuropathological effects of GD exposure can be attenuated by treatment with caramiphen as an adjunct to therapy, even if administration is delayed to 30min after seizure onset.

The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: synergism with the benzodiazepine diazepam.

Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of γ-aminobutyric acid A (GABA(A)) receptors. However, seizure activity itself causes the endocytosis of GABA(A) receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-d-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20mg/kg, im) and DZP (10mg/kg, sc), administered both separately and in combination, at 10, 20 or 30min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD(50); 132µg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20-30min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity.

Convergent evolution of levee building behavior among distantly related ant species in a floodplain ant assemblage.

Flooding impacts ground nesting ant colonies by destroying the infrastructure housing and organizing societal function. Here, we report the convergent evolution in distantly related ant species of a behavioral trait that minimizes costs of flooding: the construction of earthen levees around nest entrances. In a South American floodplain ecosystem, we observed five ant species constructing prominent earthen berms encircling nest entrances shortly after large rainfall events. In four of these species, experimental flooding of nests demonstrated that earthen berms sufficed to prevent floodwaters from entering the below ground portions of the nest. Additional manipulations revealed that levee breaching caused, pronounced, and extended reductions in food collection for two distantly related species. Foraging was preempted by the allocation of workers to repair the internal structure of the nest. These findings represent convergent evolution of a functionally important nest construction behavior in response to comparable selective forces.

A bioassessment approach for mid-continent great rivers: the Upper Mississippi, Missouri, and Ohio (USA).

The objectives of the Environmental Monitoring and Assessment Program for Great River Ecosystems (EMAP-GRE) are to (1) develop and demonstrate, in collaboration with states, an assessment program yielding spatially unbiased estimates of the condition of mid-continent great rivers; (2) evaluate environmental indicators for assessing great rivers; and (3) assess the current condition of selected great river resources. The purpose of this paper is to describe EMAP-GRE using examples based on data collected in 2004-2006 with emphasis on an approach to determining reference conditions. EMAP-GRE includes the Upper Mississippi River, the Missouri River, and the Ohio River. Indicators include biotic assemblages (fish, macroinvertebrates, plankton, algae), water chemistry, and aquatic and riparian physical habitat. Reference strata (river reaches for which a single reference expectation is appropriate) were determined by ordination of the fish assemblage and examination of spatial variation in environmental variables. Least disturbed condition of fish assemblages for reference strata was determined by empirical modeling in which we related fish assemblage metrics to a multimetric stressor gradient. We inferred least disturbed condition from the y-intercept, the predicted condition when stress was least. Thresholds for dividing the resource into management-relevant condition classes for biotic indicators were derived using predicted least disturbed condition to set the upper bound on the least disturbed condition class. Also discussed are the outputs of EMAP-GRE, including the assessment document, multimetric indices of condition, and unbiased data supporting state and tribal Clean Water Act reporting, adaptive management, and river restoration.

Maternal separation alters drug intake patterns in adulthood in rats.

Maternal separation/handling (MS/H) is an animal model of early life stress that causes profound neurochemical and behavioral alterations in pups that persist into adulthood. Many recent studies have used the MS/H model to study changes in drug effects in adulthood that are linked to behavioral treatments and stressors in the perinatal period. The drug effects focused on in this review are the reinforcing properties of the abused drugs, cocaine and alcohol. A striking finding is that variations in maternal separation and handling cause changes in ethanol and cocaine self-administration. Further, these changes indicate that various manipulations in the perinatal period can have long lasting effects of interest to biochemical pharmacologists. This article will review recent studies on ethanol and cocaine self-administration using the MS/H model and the neurochemical alterations that may play a role in the effects of MS/H on ethanol and cocaine self-administration. Studying the MS/H model can provide important clues into the vulnerability to drug abuse and perhaps identify a crucial window of opportunity for therapeutic intervention.

CP-154,526, a CRF type-1 receptor antagonist, attenuates the cue-and methamphetamine-induced reinstatement of extinguished methamphetamine-seeking behavior in rats.

RATIONALE: Previous studies from our laboratory and others have indicated a role for the hypothalamo-pituitary-adrenal (HPA) axis in the extinction/reinstatement animal model of cocaine relapse OBJECTIVE: This present study was designed to investigate the potential role for the HPA axis in the cue- and methamphetamine-induced reinstatement of extinguished methamphetamine-seeking behavior by determining the effects of ketoconazole and the corticotropin-releasing hormone (CRF) type 1 receptor antagonist, CP-154,526, on these behaviors. MATERIALS AND METHODS: Male Wistar rats were trained to self-administer methamphetamine (0.03 mg/kg/infusion). The delivery of methamphetamine was paired with the presentation of a tone and the illumination of a house light. Once stable responding was reached, the rats were placed into extinction. The effects of pretreatment with ketoconazole (25, 50, or 100 mg/kg, i.p.) or CP-154,526 (20 or 40 mg/kg, i.p.; 3 micro g, i.c.v) on cue-induced reinstatement were then evaluated. RESULTS: Cue-induced reinstatement was not significantly attenuated by pretreatment with peripherally administered CP-154,526 or by pretreatment with ketoconazole. However, centrally administered CP-154,526 (3 micro g, i.c.v.) significantly attenuated cue-induced reinstatement. In a separate group of rats, CP-154,526 (20 mg/kg, i.p.) attenuated methamphetamine-induced reinstatement (0.12 mg/kg priming infusion); whereas a higher dose (40 mg/kg) was necessary to attenuate reinstatement induced by a priming infusion of 0.24 mg/kg/infusion. Ketoconazole (50 mg/kg) did not affect reinstatement induced by a 0.12 mg/kg priming infusion and, therefore, was not tested at the higher methamphetamine priming dose. CONCLUSIONS: These data suggest an important role for CRF in the cue- and methamphetamine-induced reinstatement of extinguished methamphetamine-seeking behavior.

Telegenetic medicine: improved access to services in an underserved area.

We used telemedicine to improve genetics services to patients in the rural northwestern region of Florida. Patients were first seen via videoconference by a genetic counsellor, who obtained family and medical history. A local paediatrician then performed the physical examination, and a plan for evaluation was established. The videoconferencing equipment was connected at a bandwidth of 384 kbit/s, using three ISDN lines. During the first three telemedicine clinics, seven patients were evaluated and then returned to the centre for a face-to-face consultation with the clinical geneticist. No new diagnoses were made face-to-face that had not been identified by telemedicine. No diagnoses made by telemedicine were judged to be wrong when the child was evaluated face-to-face. During a two-year study of patient satisfaction with 12 telegenetics clinics, the 50 families evaluated via videoconferencing were asked to complete surveys; 40 surveys were returned (a response rate of 80%). All individuals either strongly agreed or agreed that the evaluation of their child was appropriate, sufficient and sufficiently protective of their child's privacy. The waiting time for a new patient consultation with the clinical genetics team was 16.9 months (SD 1.9) at the start and 3.0 months (SD 1.0) at the end of the trial period. The difference was significant (t-test, P < 0.0001). Telegenetics allows more rapid assurance that a genetic syndrome has not been identified, or a quicker initial evaluation and diagnosis for children who do have an identifiable genetic syndrome.

Maternal separation alters serotonergic transporter densities and serotonergic 1A receptors in rat brain.

RATIONALE: The basic mechanisms underlying the association between early life maternal separation and adulthood psychiatric disorders are largely unknown. One possible candidate is the central serotonergic system, which is also abnormal in psychiatric illnesses. Neuroadaptational changes in serotonergic transporter and serotonergic 1A receptors may underlie links between early life stress and adulthood psychiatric disorders. OBJECTIVE: The aim of this study was to investigate the consequences of a rat model of maternal separation on serotonergic transporter and serotonergic 1A receptor densities and function in adult rat forebrain. METHODS: Rat pups were separated from dams from postnatal day 2 to postnatal day 14, each day, for zero time, 15 min and 180 min to determine the time-course of effects. A non-handled group was added to control for the effects of handling by an experimenter compared with the animal facility-reared group. Quantitative [(125)I]3beta-(4-iodophenyl)tropan-2beta-carboxylic acid methyl ester and [(125)I]-mPPI autoradiography was used to determine serotonergic transporter and serotonergic 1A densities, respectively. Adult rats were challenged with saline or serotonergic 1A agonist (+) 8-hydroxy-2-(di-n-propylamino)tetralin, 0.4 mg/kg, s.c.) and plasma adrenocorticotropic hormone and corticosterone were determined. RESULTS: serotonergic transporter and serotonergic 1A densities were significantly lower in the non-handled group in the paraventricular, arcuate, dorsomedial and ventromedial nuclei of the hypothalamus. The non-handled group also displayed lower serotonergic transporter and serotonergic 1A densities in the basolateral anterior, basolateral ventral and basomedial amygdaloid nuclei. Serotonergic transporter densities were also decreased in the CA3 area of the hippocampus in the non-handled group. In contrast, the maternal separation 15 min group displayed the highest serotonergic transporter and serotonergic 1A densities in the basomedial nucleus of amygdala, basolateral anterior nucleus of amygdala, basolateral ventral nucleus of amygdala and basomedial nucleus of amygdala amygdaloid nuclei. CONCLUSIONS: Early life maternal separation and the extent of handling can alter adult brain serotonergic transporter and serotonergic 1A levels and function in the forebrain. Alterations in these serotonergic systems by early rearing conditions might increase vulnerability for behavioral disorders in adulthood.

Neither non-contingent electric footshock nor administered corticosterone facilitate the acquisition of methamphetamine self-administration.

Previous research has indicated a role for the hypothalamo-pituitary-adrenal (HPA) axis in the acquisition of intravenous cocaine self-administration since both exposure to stressors and exogenous injections of corticosterone facilitate this behavior. The present experiment was designed to determine whether electric footshock or pretreatment with corticosterone would produce similar effects on the acquisition of methamphetamine self-administration in male Wistar rats. Following initial food training, the rats were allowed to self-administer methamphetamine in ascending doses (0.0075-0.12 mg/kg/infusion) that were doubled weekly. Neither non-contingent electric footshock nor treatment with corticosterone (2.0 mg/kg, i.p.) affected the lowest dose at which the rats first acquired methamphetamine self-administration (0.015 mg/kg/infusion). The treatment groups all had similar inverted "U"-shaped acquisition curves typical of psychostimulants. Although these experiments do not indicate a major role for the HPA axis in the acquisition of methamphetamine self-administration, more studies need to be conducted to further evaluate the effects of the HPA axis on the acquisition of methamphetamine self-administration before a potential role can be ruled out.

Neuropsychological assessment of a group of UK patients with Cohen syndrome.

Cohen syndrome is a rare autosomal recessive syndrome with a distinctive clinical phenotype that includes mental retardation and a characteristic sociable disposition. Variability in the level of learning disability and the behavioural phenotype is seen in the published literature. In a cohort of Finnish Cohen syndrome patients, severe mental retardation and non-maladaptive behaviour were described. Outside of Finland, autistic-spectrum behaviour has been reported in a few isolated Cohen syndrome patients but in a recent UK study was found to be highly prevalent. We report the results of neuropsychological studies in a group of 16 genetically heterogeneous patients, all with the characteristic clinical features of Cohen syndrome. Of the 9 patients who underwent formal neuropsychological testing, all but one was functioning in the severely mentally impaired range. Of the remaining patients, 3 were below the age of formal testing and 4 had such profound learning and behavioural problems that they were deemed unable to participate in testing. Mild maladaptive behaviour was observed in 13 patients and 3 were documented as having significant maladaptive behaviour. In contrast to the Finnish group of Cohen syndrome patients, this UK study identifies significant neuropsychological impairment combined with maladaptive behaviour as a characteristic of Cohen syndrome. Although autistic-type behaviour was observed, an increased prevalence of autism in Cohen syndrome was not confirmed.

A piezoelectric, flexural-disk, neutrally buoyant, underwater accelerometer.

A piezoelectric, flexural-disk accelerometer for underwater use is composed of two PZT-5A lead zirconate-titanate disks that are bonded to an aluminum substrate. The substrate is edge-supported inside an aluminum housing. The housing is enclosed in syntactic foam so that the sensor is neutrally buoyant. The overall height is 1.0 in. (26 mm), the overall diameter is 1.9 in. (49 mm), and the total mass is 0.054 kg. With 25 ft (7.6 m) of (230 pF/m) cable attached, the sensitivity is -42 dB re 1 V-s(2)/m (-22 dB re 1 V/g), the capacitance is 5.0 nF, and the resonance frequency is 11 kHz. When used in conjuction with a Micro Networks MN3210 preamplifier, the spectral noise-equivalent acceleration floor is approximately -171 dB re 1 m/s(2)- radicalHz (-151 dB re 1 g/ radicalHz) at 5 kHz.

Inositol phosphates modulate binding of thyroid hormone to human red cell membranes in vitro.

D-Myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and D-myo-inositol 4,5-bisphosphate (10(-6) mol/L) displaced specifically bound L-[125I] T4 from human erythrocyte membranes in vitro by up to 80%. D-Myo-inositol 1,3,4,5-tetrakisphosphate, D-myo-inositol 1-monophosphate, and D-myo-inositol 1,4-bisphosphate were ineffective in decreasing thyroid hormone binding to membranes. The effect of Ins(1,4,5)P3 on high affinity binding reflected a change in Kd (5.8 x 10(-11) vs. 1.5 x 10(-11) mol/L) and binding capacity (15 vs. 2 fmol/mg membrane protein) in the absence and presence of Ins(1,4,5)P3, respectively. Ins(1,4,5)P3 also displaced T3 from red cell membranes. Thus, selected inositol phosphates regulate the abundance of sites available for binding of thyroid hormone by human red cell membranes. This stereospecific action of inositol phosphates is among several plasma membrane effects recently described for these members of the signal-transducing phosphoinositide pathway.

Comments, with reply, on ;Characterization of piezoceramics' by M. Brissaud.

The commenters note that when M. Brissaud, in the above-titled paper (see ibid., vol.38, no.6, p.603-617, 1991), attempted to solve several piezoceramic bar, plate, and disk problems by superposition of bulk longitudinal waves, he neglected the shear wave contributions. Therefore, the commenters suggest that his solutions do not satisfy the appropriate stress-free boundary conditions. Brissaud, responding to the comments, discusses the validity of the models used.

The ecology of tropical rain forest canopies.

With the advent of increasingly sophisticated techniques for access, tropical forest canopy research has burgeoned in the last few years. Although an enormous amount of basic descriptive work remains to be done, canopy research is now entering a more advanced and ecological phase.

Bleomycin and tetracycline in malignant pleural effusions: a review.

Pleural effusions remain a distressing and symptomatic problem in cancer patients. Once a malignant pleural effusion is diagnosed, appropriate therapy may provide symptomatic relief and improved quality of life. In this paper, we review previous data on chest tube drainage and pleurodesis in patients with malignant pleural effusions. A comparison is made of the various sclerosing agents. Specifically, recent data from a study comparing bleomycin and tetracycline as sclerosing agents are discussed. These data show a clear advantage with bleomycin at both 30-day and 90-day end points--30-day recurrence, 36% versus 67%; 90-day recurrence, 30% versus 53%.

Extended perinatal outreach.

The perinatal outreach plan of the Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, and the Naples Community Hospital is described. From June 1988 through May 1989, 79 high-risk pregnant patients were evaluated at a monthly clinic at the hospital. The main indications for referral were intrauterine growth retardation (10), twin gestation (9), gestational diabetes (9) and possible fetal anomaly (8). With one exception, all babies were delivered at Naples. The high-risk patients had a 21% incidence of newborns less than 2500 gr, cesarean section rate of 30%, average maternal hospital charge of $2,403/patient, and an average neonatal hospital charge of $1,777/patient. There was a definite change in transport trends from Naples with three more maternal transports and seven fewer neonatal transports over the preceding year. Comprehensive perinatal outreach programs can be implemented at a reasonable cost and provide support and services that strengthen the entire local perinatal health delivery system.

Chemical communication in the dacetine antDaceton armigerum (Hymenoptera: Formicidae).

Contrary to previous assumptions,Daceton armigerum, the largest ant in the myrmicine tribe Dacetini, employs trail communication. We identified two anatomical sources of trail pheromones: Trails drawn with poison gland contents can last for more than seven days. Trails drawn with the newly discovered sternal glands (in the VIth and VIIth abdominal sternites) are effective but relatively short-lived. In addition, our bioassays revealed that the contents of the mandibular glands elicit alarm behavior, and secretions from the pygidial gland release attraction. When tested with artificial poison gland trails from seven other myrmicine species,Daceton did not exhibit trail following behavior. We confirmed, however, previous findings thatAtta respond toDaceton poison gland trails andSolenopsis followDaceton Dufour's gland trails.