Evaporation drift of pesticides active ingredients.

Losses of pesticide active ingredients (a.i.) into the atmosphere can occur through several pathways. A main pathway is evaporation drift. The evaporation process of pesticide a.i., after application, is affected by three main factors: Physicochemical properties of the pesticide a.i., weather conditions and crop structure. The main physicochemical parameters are the Henry coefficient, which is a measure for the volatilization tendency of the pesticide a.i. from a dilute aqueous solution, and the vapour pressure, which is a measure for the volatilization tendency of the pesticide a.i. from the solid phase. Five pesticide a.i., with various Henry coefficients and various vapour pressures, were selected to conduct laboratory experiments: metalaxyl-m, dichlorovos, diazinon, Lindane and trifluralin. Evaporation experiments were conducted in a volatilization chamber. It was found that the evaporation tendencies significantly differed according to the physicochemical properties of the a.i.

Increased sensitivity to seizures in repeated exposures to hyperbaric oxygen: role of NOS activation.

Nitric oxide is involved in the mechanism of hyperbaric oxygen (HBO(2)) brain toxicity as nitric oxide synthase (NOS) inhibitors delay latent time before the onset of seizures. The purpose of this study was to investigate if seizures affect sensitivity to convulsions during subsequent exposure to HBO(2) and to determine if NOS activity and expression is changed after HBO(2) seizures. Rats were exposed to 5 atm (gauge pressure) 100% O(2) until seizures recorded by electroencephalograph (EEG) and reexposed 1, 2, or 6 days later. Latency to seizures was significantly shorter (P<0.05) in animals reexposed 1 or 2 days after the first exposure. Activity of calcium-dependent NOS activity in cortex was significantly higher 1 and 2 days after seizures compared with controls (P<0.05), while calcium-independent NOS activity was not changed during the 6-day post-seizure interval. The expression of neuronal NOS (nNOS) protein determined by Western blot was higher 1 and 2 days after seizures (P<0.05), while the expression of endothelial (eNOS) and inducible (iNOS) remained unchanged. nNOS upregulation 1 and 2 days after seizures and protection against HBO(2) seizures by nNOS-specific inhibitor 7-nitroindazole (7-NI) suggest possible involvement of NO in the mechanism of increased sensitivity to HBO(2) in reexposures.

Electrophysiological changes in hippocampal slices isolated from rats embedded with depleted uranium fragments.

Although nephrotoxicity is considered to be the most serious consequence of uranium exposure, several studies have previously suggested the potential for neurotoxicity. In Operation Desert Storm, U.S. military personnel were wounded by fragments of depleted uranium (DU). This study was initiated to test the potential for DU fragments to cause electrophysiological changes in the central nervous system. Rats were surgically implanted with pellets of DU or tantalum (Ta) as a control metal. After 6, 12 and 18 months rats were euthanized, hippocampi removed and electrophysiological potentials analyzed by extracellular field potential recordings. Six months after implantation, synaptic potentials in DU-exposed tissue were less capable of eliciting spikes (E/S coupling). At 12 months, amplitudes of synaptic potentials were significantly increased in tissue from DU treated rats compared to Ta controls. E/S coupling was reduced. The differences between the electrophysiological measurements in DU-treated and control tissue were no longer evident at the 18 month time point. An analysis of the changes in the synaptic potentials and E/S coupling over the three time points suggests that by 18 months, the effects of aging and DU exposure converge, thereby obscuring the effects of the metal. Since kidney toxicity was not evident in these animals, effects secondary to nephrotoxicity are unlikely. This study raises the possibility that physiological changes occur in the brain with chronic exposure to DU fragments, which could contribute to neurological deficits.

Stage T1-2 prostate cancer with pretreatment prostate-specific antigen level < or = 10 ng/ml: radiation therapy or surgery?

PURPOSE: To detect differences in biochemical failure rates by treatment modality (radiation therapy or radical prostatectomy) in patients with early-stage prostate cancer presenting with pretreatment prostatic-specific antigen (PSA) levels < or = 10.0 ng/ml. METHODS AND MATERIALS: A total of 1467 consecutive patients with prostate carcinoma were treated with either radiotherapy (RT) or radical prostatectomy (RP) between January 1987 and June 1996. Patients with the following were excluded from the present study: initial PSA (iPSA) level > 10 ng/ml (n = 444), clinical Stage T3 disease (n = 73), adjuvant or neoadjuvant treatment (n = 173), no available iPSA level (n = 31), no available biopsy Gleason score (GS) (n = 33), incomplete pathologic information (n = 16), and no available follow-up PSA levels (n = 90). The analysis was performed on 607 cases: 354 treated with RP and 253 with RT (median dose 68.4 Gy). The outcome of interest was biochemical relapse-free survival (bRFS), with biochemical relapse being defined as either a detectable PSA level after RP or elevation in PSA levels of > or = 1.0 ng/ml above the nadir after RT. Proportional hazards were used to analyze the effect of treatment modality and confounding variables (i.e., age, stage, biopsy GS, iPSA levels) on treatment outcome. RESULTS: Seventy-nine percent of patients (n = 478) had clinical Stage T1 or T2A disease at presentation (RP vs. RT: 84% vs. 71%, p < 0.001). Twenty-one percent of patients (n = 127) had iPSA levels < or = 4 ng/ml (RP vs. RT: 24% vs. 17%, p = 0.027). Seventy-six percent of patients (n = 460) had biopsy GS < or = 6 (RP vs. RT: 79% vs. 71%, p = 0.014). The median follow-up time was 24 months (range 3-110). For the 607 patients, the 5-year bRFS rate was 76%. The 5-year RFS rates for RP versus RT were 76% versus 75%, respectively (p = 0.09). After adjustment for all confounding variables, iPSA levels (p < 0.001) and biopsy GS (p = 0.001) were the only independent predictors of relapse, whereas age, clinical stage, and treatment modality were not (p = 0.20; p = 0.09; and p = 0.10, respectively). CONCLUSION: In patients with clinical Stage T1-2 prostate cancer and pretreatment PSA < or = 10 ng/ml, there is no difference in biochemical failure rates between those treated with radiation and those treated with surgery.

Regional differences in glial cell modulation of synaptic transmission.

Metabolic integrity of glial cells in field CA1 of the guinea pig hippocampus is critical to maintenance of synaptic transmission (Keyser and Pellmar [1994] Glia 10:237-243). To determine if this tight glial-neuronal coupling is equally important in other brain regions, we compared the effect of fluoroacetate (FAC), a glial specific metabolic blocker, on synaptic transmission in field CA1 to synaptic transmission in area dentata (DG). FAC was significantly more effective in decreasing synaptic potentials in CA1 than in DG. A similar regional disparity in the FAC-induced decrease in ATP levels was evident. Isocitrate, a glial specific metabolic substrate, prevented the FAC-induced synaptic depression in both CA1 and DG. The results suggest that glia of CA1 and dentate respond differently to metabolic challenge. Modulation of this glial-neuronal coupling could provide a regionally specific mechanism for synaptic plasticity. Additionally, site-specific glial-neuronal interactions can impact on a variety of physiological and pathophysiological conditions.

Synaptic transmission in the hippocampus: critical role for glial cells.

The importance of glial cells in controlling the neuronal microenvironment has been increasingly recognized. We now demonstrate that glial cells play an integral role in hippocampal synaptic transmission by using the glial-specific metabolic blocker fluoroacetate (FAC) to selectively inhibit glial cell function. FAC inhibits evoked intracellular postsynaptic potentials (PSPs; IC50 = 39 microM) as well as population PSPs (IC50 = 65 microM) in field CA1 of the guinea pig hippocampal slice. Spontaneous synaptic transmission is concurrently decreased. These effects are time and dose dependent. ATP concentrations in glial but not neuronal elements are also significantly reduced with FAC treatment. Simultaneous application of the metabolic substrate isocitrate with FAC prevents both the reduction in glial ATP concentrations and the decrease in evoked PSPs. Given that isocitrate is selectively taken up by glia, these data further support a glial specific metabolic action of FAC. Additionally, FAC has no postsynaptic effects as peak responses to iontophoretically applied glutamate are unchanged. However, the decay of both iontophoretic and evoked PSPs are prolonged following FAC treatment suggesting inhibition of glutamate uptake may contribute to the FAC-induced depression of synaptic potentials. These results show, for the first time, that glial cells are critical for maintenance of synaptic transmission and suggest a role for glial cells in the modulation of synaptic efficacy.

Neurologic complications of drugs. Tardive dyskinesias, neuroleptic malignant syndrome, and cocaine-related syndromes.

Drugs, either self-administered or prescribed by physicians, can result in substantial neurologic disability in psychiatric patients. It is clear that the use of neuroleptic agents to treat psychiatric illness may result in a variety of tardive movement disorders. Most commonly, these take the form of orobuccal dyskinesias, but choreic movements of the trunk and extremities, dystonic postures, myoclonus, tics, parkinsonism, and akathisic syndromes also may occur. The choreic tardive syndromes are thought to occur more commonly in the elderly female population, but tardive variants may affect a different population. The neuroleptic malignant syndrome carries a significant mortality and remains a diagnostic and therapeutic challenge. Early detection and vigorous treatment reduces the morbidity and mortality from this condition. Stroke, seizures, and various movement disorders may complicate the illicit use of cocaine and complicate the rehabilitation of those patients dependent on its use. The unsatisfactory treatment of tardive syndromes, neuroleptic malignant syndrome, and cocaine-induced neurologic disease underscores our incomplete understanding of the neurochemistry of dopamine, the function of newly discovered dopamine receptors, and the role they play in maintaining normal emotional and motoric function. For now, awareness of the varied neurologic syndromes related to neurotransmitter-modulating agents should provide the impetus for careful use of these agents and for the continued development of improved drugs for the treatment of psychiatric disease.

Neuroleptic malignant syndrome in Parkinson's disease after withdrawal or alteration of dopaminergic therapy.

Neuroleptic malignant syndrome is characterized by altered consciousness, fever, extrapyramidal signs, autonomic instability, elevated creatine kinase level, and leukocytosis. Although originally described in patients receiving neuroleptic drugs, this syndrome may also occur in patients with Parkinson's disease during withdrawal or reduction of levodopa therapy or other dopaminergic drug therapy. We have encountered three cases of neuroleptic malignant syndrome related to withdrawal of levodopa therapy. These cases illustrate the variety of circumstances in which alteration of therapy with dopaminergic drugs can cause this syndrome and the relative unfamiliarity of the neuroleptic malignant syndrome-levodopa relationship among physicians who do not treat large numbers of patients with Parkinson's disease. An understanding of the role of brain dopamine in the pathogenesis of neuroleptic malignant syndrome and an appreciation of the great variety of drugs whose manipulation can result in this potentially fatal syndrome will aid its proper and timely recognition, especially when the offending pharmacologic manipulation does not involve neuroleptic drugs.

Arachidonic acid modulates hippocampal calcium current via protein kinase C and oxygen radicals.

Arachidonic acid (AA) is a second messenger liberated via receptor activation of phospholipase A2 or diacylglycerol-lipase. We used whole-cell voltage clamp of acutely isolated hippocampal CA1 pyramidal cells to investigate the hypothesis that AA modulates Ca2+ channel current (ICa) via activation of protein kinase C (PKC) and generation of free radicals. AA depressed ICa in a dose- and time-dependent manner similar to that previously reported for the action of phorbol esters on ICa. A similar depression was seen with a xanthine-based free radical generating system. The specific PKC inhibitor PKCI (19-36), the protein kinase inhibitor H-7, and the superoxide free radical scavenger SOD each blocked ICa depression by 70%-80%. Complete block of the AA response occurred when SOD was used simultaneously with a PKC inhibitor. These data suggest that PKC and free radicals play a role in AA-induced suppression of ICa.

Neurologic complications of late prosthetic valve endocarditis.

We reviewed the records of 20 patients with late prosthetic valve endocarditis who were hospitalized at the University of Iowa between 1985 and 1988. There were 14 men and six women, aged 20-80 (mean 57.9) years. The infected valves were mechanical in 11 patients (six aortic and five mitral) and bioprosthetic in the other nine. Echocardiography in 12 patients demonstrated vegetations in one. Among the 20 patients, neurologic complications occurred in eight (40%), six of whom had mechanical valves (five mitral and one aortic). Infection with Staphylococcus aureus occurred in four of the eight patients (50%) with neurologic complications. Of the eight patients with neurologic complications, ischemic stroke was diagnosed in four, transient ischemic attacks in one, and intracranial hemorrhage in three. Prothrombin times at the time of the intracranial hemorrhage were 2.2, 1.5, and 1.3 times control in these three patients. Cerebral angiography done in four of the eight patients with neurologic complications failed to show mycotic aneurysms. Nine of the 20 patients (seven men and two women, mean age 66.8 years) died less than or equal to 90 days after the diagnosis of late prosthetic valve endocarditis. Half of the eight patients with neurologic complications died (three men and one woman, mean age 62.3 years), and all three patients with intracranial hemorrhage died. Our data suggest that the neurologic complications of late prosthetic valve endocarditis are more common with mechanical valves, particularly in the mitral position, and are associated with a high mortality.

Sterilization of contrast media (Isovist) containing liposomes by ethylene oxide.

Liposomes containing Isovist were prepared by controlled detergent dialysis as well as by reverse phase evaporation. After preparation these liposomes were lyophilized and then submitted to sterilization by ethylene oxide. Prior to lyophilization, trehalose was added as a protective agent to preserve the size of the liposomes. After each step in the preparation size distribution was determined by photon correlation spectroscopy. The computer program CONTIN was adapted for the data analysis and proved to be applicable for polydisperse solutions of liposomes. Neither freeze-drying nor sterilization had negative effects on the morphological quality of the samples when using 4 g of trehalose per 1 g of lipid. In addition, the quality of the liposomes was controlled by scanning electron microscopy. At the end of seven days, no growth of microorganisms occurred in any of the samples.

Status epilepticus facilitated by pilocarpine in amygdala-kindled rats.

A novel model of status epilepticus based on the kindling model of epilepsy is described. The model involves the administration of a small dose of pilocarpine (20 mg/kg) to rats that have been previously kindled. Stimulation of these pretreated rats produces seizures which continue uninterrupted for approximately 4 h before spontaneous termination. The electroencephalographic discharge pattern showed characteristic changes in polarity and amplitude throughout the duration of status epilepticus. Behaviorally, the animals showed motor seizures which varied between stages I through IV, with evidence of extensive bilateral hemispheric involvement through much of the seizure episode. Animals that had been partially kindled to stage II seizures did not develop status epilepticus after stimulation when pretreated with pilocarpine, indicating that prior kindling is integral to the development of status epilepticus in this model. Administration of scopolamine was ineffective in terminating the condition when it had begun, suggesting that cholinergic stimulation is necessary for the initiation, but not the maintenance, of status epilepticus. This model holds promise for the study of status epilepticus because the condition develops in a seizure-prone (kindled) rat, and the seizures are self-sustaining, without the presence of exogenous chemicals or neurotoxins.

Comparison of the nutritional status of pregnant adolescents with adult pregnant women. I. Biochemical findings.

Biochemical findings on blood samples from 102 pregnant women in four age groups, 12-17, 18-19, 20-24, and 25-32, are reported. Samples represent 8 antepartum periods of 4 weeks each and 3 postpartum periods over 6 weeks. Blood analyses were carried out for hemoglobin, plasma iron, plasma total protein, glucose, plasma alkaline phosphatase, plasma ascorbic acid, plasma vitamin A and carotene, erythrocyte transketolase as a measure of thiamine status, plasma cholesterol, plasma lipid phosphorus, plasma total fatty acids, and triglyceride fatty acids. For the most part, means of these nutrients were in acceptable ranges for all age groups. Although adolescents had better levels than anticipated, the two younger groups on several occasions had means significantly lower than those of the two older groups, indicating that they needed greater nutritional support during pregnancy than older women.