The Pathophysiological Link between Right Atrial Remodeling and Functional Tricuspid Regurgitation in Patients with Atrial Fibrillation: A Three-Dimensional Echocardiography Study

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Chlorpromazine and pimozide alter reinforcement efficacy and motor performance

This study evaluated the effects of chlorpromazine and pimozide on reinforced responding. In each session, rats were exposed to a series of five variable-interval reinforcement schedules. The response requirement was a lever press, the reward was a small portion of water, and the reinforcement rate varied from about 20 to 660 reinforcers per hour. Response rate was a negatively accelerated function of reinforcement rate, and the relationship between the two variables was described by the equation for a rectangular hyperbola (the matching law). One parameter of the hyperbola is equivalent to the asymptotic response rate and the other parameter is equivalent to the rate of reinforcement that maintains a one-half asymptotic response rate. Chlorpromazine (0.75–3.0 mg/kg) and pimozide (0.1–0.4 mg/kg) dose-dependently decreased response rates. At low doses, the response rate decreases were, for the most part, restricted to the low reinforcement rate schedules. In contrast, the highest dose tested decreased response rates at both low and high reinforcement rates. The patterns of response rate decreases resulted in dose-dependent changes in the parameters of the matching law equation. The shifts in the matching law parameters were discussed in terms of the motoric and motivational interpretations of neuroleptic-induced response rate changes. Offprint requests to: G.M. Heyman     

Thermal Properties and Flammability Characteristics of a Series of DGEBA-Based Thermosets Loaded with a Novel Bisphenol Containing DOPO and Phenylphosphonate Units

Despite a recent sustained preoccupation for developing biobased epoxies with enhanced applicability, such products have not been widely accepted for industry because of their inferior characteristics compared to classic petroleum-based epoxy thermosets. Therefore, significant effort is being made to improve the flame retardance of the most commonly used epoxies, such as diglycidyl ether-based bisphenol A (DGEBA), bisphenol F (DGEBF), novalac epoxy, and others, while continuously avoiding the use of hazardous halogen-containing flame retardants. Herein, a phosphorus-containing bisphenol, bis(4-(((4-hydroxyphenyl)amino)(6-oxido-6H-dibenzo[c,e][1,2]oxaphosphinin-6-yl)methyl)phenyl) phenylphosphonate (BPH), was synthesized by reacting bis(4-formylphenyl)phenylphosphonate with 4-hydroxybenzaldehyde followed by the addition of 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) to the resulting azomethine groups. Environmentally friendly epoxy-based polymer thermosets were prepared by using epoxy resin as polymer matrix and a mixture of BPH and 4,4′-diaminodiphenylsulfone (DDS) as hardeners. A hyperbranched phthalocyanine polymer (HPc) and BaTiO₃ nanoparticles were incorporated into epoxy resin to improve the characteristics of the final products. The structure and morphology of epoxy thermosets were evaluated by infrared spectroscopy and scanning electron microscopy (SEM), while the flammability characteristics were evaluated by microscale combustion calorimetry. Thermal properties were determined by thermogravimetric analysis and differential scanning calorimetry. The surface morphology of the char residues obtained by pyrolysis was studied by SEM analysis.     

Effect of orange juice and tryptamine on the behavior and c-fos expression of Wistar rats

Metabolic Brain Disease - Recent reports have shown that commercial orange juice is rich in biogenic amines. Consumption of foods containing large amounts of biogenic amines increase hypertensive...     

Modulation of Adriamycin cytotoxicity and transport in drug-sensitive and multidrug-resistant Chinese hamster ovary cells by hyperthermia and cyclosporin A

Purpose: Chemosensitizers such as cyclosporin A can increase intracellular accumulation of chemotherapeutic agents such as Adriamycin in certain multidrug-resistant (MDR) cell lines with overexpression of P-glycoprotein. It is likely that, when combined with cyclosporin A, hyperthermia could increase membrane permeability to Adriamycin and enhance its cytotoxic effects. The ability of both hyperthermia and cyclosporin A to modulate the cytotoxicity, transport and subcellular distribution pattern of Adriamycin was studied in a pleiotropic MDR Chinese hamster ovary cell line (CH^RC5) and in the drug-sensitive parent line (AuxB1). Methods: Adriamycin cytotoxicity was evaluated by clonogenic cell survival, drug transport using [¹⁴C]-labeled Adriamycin and intracellular drug distribution by fluorescence microscopy. Results: Adriamycin cytotoxicity was increased in both drug-sensitive and MDR cells by cyclosporin A (5 μM) alone, and by hyperthermia alone (41–43 °C) only in sensitive cells. However, when cyclosporin A and 42 °C hyperthermia were used in combination, a large increase in drug cytotoxicity occurred in both cell lines. This effect increased with time and was temperature-dependent. The increase in Adriamycin cytotoxicity caused by cyclosporin A and hyperthermia was accompanied by alterations in membrane permeability to the drug. Cyclosporin A increased [¹⁴C]Adriamycin uptake, while drug efflux decreased, for both AuxB1 and CH^RC5 cells and nuclei. For AuxB1 cells only, drug distribution studies showed that cyclosporin A promoted an increase in both nuclear and cytoplasmic drug accumulation. Hyperthermia, combined with cyclosporin A, increased [¹⁴C]Adriamycin uptake. This effect was seen as an increase in intensity of nuclear and cytosolic drug fluorescence in both cell lines. Cyclosporin A alone diminished drug efflux and caused Adriamycin to remain firmly bound in the nucleus of AuxB1 cells, while it remained primarily in the cytoplasm of CH^RC5 cells. Conclusions: Hyperthermia alone had little effect on Adriamycin cytotoxicity and transport in MDR cells, in contrast to drug-sensitive cells. This suggests that P-glycoprotein is fully functional in these MDR cells. Our findings suggest that cyclosporin A and hyperthermia could be beneficial by increasing intracellular drug accumulation, thus improving the effectiveness of Adriamycin against both drug-sensitive and MDR cells within a localized target region. Received: 17 February 1999 / Accepted: 26 August 1999     

Cortical serotonin and norepinephrine denervation in parkinsonism: preferential loss of the beaded serotonin innervation

Parkinson's Disease (PD) is marked by prominent motor symptoms that reflect striatal dopamine insufficiency. However, non-motor symptoms, including depression, are common in PD. It has been suggested that these changes reflect pathological involvement of non-dopaminergic systems. We examined regional changes in serotonin (5-HT) and norepinephrine (NE) systems in mice treated with two different 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment paradigms, at survival times of 3 or 16 weeks after the last MPTP injection. MPTP caused a decrease in striatal dopamine concentration, the magnitude of which depended on the treatment regimen and survival interval after MPTP treatment. There was significant involvement of other subcortical areas receiving a dopamine innervation, but no consistent changes in 5-HT or NE levels in subcortical sites. In contrast, we observed an enduring decrease in 5-HT and NE concentrations in both the somatosensory cortex and medial prefrontal cortex (PFC). Immunohistochemical studies also revealed a decrease in the density of PFC NE and 5-HT axons. The decrease in the cortical serotonergic innervation preferentially involved the thick beaded but not smooth fine 5-HT axons. Similar changes in the 5-HT innervation of post-mortem samples of the PFC from idiopathic PD cases were seen. Our findings point to a major loss of the 5-HT and NE innervations of the cortex in MPTP-induced parkinsonism, and suggest that loss of the beaded cortical 5-HT innervation is associated with a predisposition to the development of depression in PD.     

Subthalamic 5-HT(1A) and 5-HT(1B) receptor modulation of RU 24969-induced behavioral profile in rats

The effects of systemic administration of the serotonin (5-HT)(1A/1B) agonist 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)1H-indole (RU 24969) on locomotor and investigatory behavior in rats have been well characterized using the behavioral pattern monitor (BPM). To elucidate the neural circuitry underlying this behavioral profile, intracerebral dose--response studies were conducted at two sites with high densities of 5-HT(1B) receptors, the subthalamic nucleus (STN) and substantia nigra. Infusion of RU 24969 into the STN produced systemic RU 24969-like changes in locomotor activity and patterns but an uncharacteristic increase in investigatory holepokes. Intra-STN administration of the selective 5-HT(1A) receptor agonist 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) produced RU 24969-like changes in locomotor patterns only, while the 5-HT(1B) receptor agonist 3(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one dihydrochloride (CP-93,129) increased locomotor activity, produced no change in locomotor patterns and nonsignificantly increased holepokes. Intranigral infusion of RU 24969 produced systemic and intra-STN RU 24969-like increases in locomotor activity. Intranigral RU 24969, however, failed to produce any changes in locomotor patterns or investigatory holepokes. Intranigral infusions of CP-93,129 or 8-OH-DPAT had no effects on locomotor activity, locomotor patterns or investigatory holepokes. These results provide evidence for multiple-site mediation of the locomotor-activating effects of RU 24969 and for a dissociation of the neural substrates underlying locomotor and investigatory components of the RU 24969-induced behavioral profile.