Model-based analysis for kinetic complexation study of Pizda and Cu(II).

In the present work, the multivariate kinetic complexation of a new synthesized ligand, 1-(2''-hydroxyl cyclohexyl)-3'-[aminopropyl]-4-[3'-aminopropyl]piperazine (Pizda) and Cu(2+) in 50% ethanol-water solution is investigated using the UV-vis stopped-flow technique and state-of-the-art multi-wavelength numerical analysis. Model-based least squares fitting analysis or hard modeling is a specific part of chemometrics which is based on mathematical relationships for describing the measurements. Some recent developments include the incorporation of the effects of non-ideal experimental conditions into the fitting algorithm so it can substantially simplify experimental procedures. In this study no buffers are required because pH changes are taken into computations. Some 21 multi-wavelength kinetic measurements, taken at various initial concentrations of [H(+)] were analyzed globally, i.e. simultaneously applying an all inclusive reaction mechanism and a common set of species spectra. Using numerical analysis, the pH of the experimental solutions was allowed to vary as a consequence of the proceeding reactions. This enabled the complete kinetic analysis of the formation and dissociation of Cu(Pizda)(n+). Here protonation equilibria have been directly incorporated into the rate law, so thus variable pH values have been allowed during each measurement. Using the independently estimated stability constants (from spectrophotometric and potentiometric measurements) for the Cu(Pizda)(n+) complexes, a total of six rate constants and one protonation constant could be elucidated. The results of the analysis include the concentration distribution and spectra of all chemical species involved in the reaction. A low standard deviation and residual profiles obtained validate the results.

Recording of ECG signals on a portable MiniDisc recorder for time and frequency domain heart rate variability analysis.

Analysis of heart rate variability (HRV) is a non-invasive technique useful for investigating autonomic function in both humans and animals. It has been used for research into both behaviour and physiology. Commercial systems for human HRV analysis are expensive and may not have sufficient flexibility for appropriate analysis in animals. Some heart rate monitors have the facility to provide inter-beat interval (IBI), but verification following collection is not possible as only IBIs are recorded, and not the raw electrocardiogram (ECG) signal. Computer-based data acquisition and analysis systems such as Po-Ne-Mah and Biopac offer greater flexibility and control but have limited portability. Many laboratories and veterinary surgeons have access to ECG machines but do not have equipment to record ECG signals for further analysis. The aim of the present study was to determine whether suitable HRV data could be obtained from ECG signals recorded onto a MiniDisc (MD) and subsequently digitised and analysed using a commercial data acquisition and analysis package. ECG signals were obtained from six Thoroughbred horses by telemetry. A split BNC connecter was used to allow simultaneous digitisation of analogue output from the ECG receiver unit by a computerised data acquisition system (Po-Ne-Mah) and MiniDisc player (MZ-N710, Sony). Following recording, data were played back from the MiniDisc into the same input channel of the data acquisition system as previously used to record the direct ECG. All data were digitised at a sampling rate of 500 Hz. IBI data were analysed in both time and frequency domains and comparisons between direct recorded and MiniDisc data were made using Bland-Altman analysis. Despite some changes in ECG morphology due to loss of low frequency content (primarily below 5 Hz) following MiniDisc recording, there was minimal difference in IBI or time or frequency domain analysis between the two recording methods. The MiniDisc offers a cost-effective approach to intermediate recording of ECG signals for subsequent HRV analysis and also provides greater flexibility than use of human Holter systems.

Night terrors in adults: phenomenology and relationship to psychopathology.

BACKGROUND: Night terrors have been classically described in children. Night terrors occurring in adults have been linked to psychopathology. Recent descriptions of sleep panic attacks have raised questions about their relationship to night terrors. METHOD: Evaluations from a medically affiliated sleep disorders program were reviewed to identify adult patients presenting with events consistent with night terrors. Eleven patients were identified, 10 of whom had polysomnographic evaluation, and their records were reviewed for information relevant to night terrors and psychiatric symptoms. Six of these patients were available for further assessment which included inquiry regarding sleep events, a Structured Clinical Interview (SCID) for psychiatric disorders, and the Millon Clinical Multiaxial Inventory II (MCMI-II) for personality-related measurements. RESULTS: In the original sample, night terror episodes featured confused behaviors, motor activity, and absent or fragmented recall. Polysomnography documented arousals from slow wave sleep in 9 of 10 patients. All of the original patients reported psychiatric symptoms. All 6 patients who received the subsequent structured evaluation met lifetime criteria for Axis I conditions (most commonly affective and substance use disorders) and had elevated scores on the personality scales of the MCMI-II. Night terrors were not limited to psychiatric episodes. CONCLUSION: Night terrors occur in adults that are similar to episodes described in children. While distinct from sleep panic attacks, night terrors appear to occur in adults with histories of psychopathology.

Sleep disturbances in men with asymptomatic human immunodeficiency (HIV) infection.

During the clinical latency phase of human immunodeficiency virus (HIV) disease the central nervous system may be infected and begin to manifest subtle dysfunction. Our early investigations demonstrated persistent alterations in the sleep architecture of HIV-infected asymptomatic men. The major aims of this study were to delineate alterations of sleep architecture in asymptomatic HIV-infected men, to identify and describe sleep behavior complaints and to seek a correlation between objective sleep parameters and subjective complaints of sleep behavior. The study sample consisted of 24 men, 14 HIV-infected and 10 HIV-negative, age-matched controls. The protocol included a comprehensive history and physical, two polysomnograms, urine toxicity, detailed written sleep questionnaire, the Pittsburgh Sleep Quality Index, the Spielberger State-Trait Anxiety Test and the Beck Depression Inventory. Our results indicated that sleep architecture differed from controls in that wakefulness, slow-wave sleep [SWS-stage 3 and 4 nonrapid eye movement (NREM) sleep] and stage rapid eye movement (REM) sleep were more evenly dispersed throughout the night. In particular, SWS was prevalent during the second half of recorded sleep. The observed changes in the NREM/REM cycle could not be explained on the basis of underlying psychopathology. Just as the course of individuals with HIV infection varies, it is expected that sleep abnormalities will vary. Considering the known relationships between NREM stage 3 and 4 and immune system function, it is possible that the observed alterations in the NREM/REM cycle are related to coincident changes in immunologic function. Quantitative measures of NREM sleep, especially SWS and REM sleep, are perhaps of greater significance than relative measures of sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Sleep disturbances in HIV-infected homosexual men.

To provide a better understanding of the etiology of subjective sleep complaints in HIV-infected individuals, a study to evaluate sleep/wake disturbances in 10 healthy HIV-infected male volunteers was performed. All subjects were HIV-infected but had no history of AIDS-related infections, and considered clinically asymptomatic. Interviews and sleep questionnaires revealed sleep complaints in nine subjects. Five healthy HIV-seronegative male subjects, with no history of sleep complaints, were also evaluated. Sleep architecture analyses detected that, in comparison to published normative data and to negative controls, there was a significant increase in the total percentage of slow wave sleep (SWS) and an increase in the percentage of SWS in the later sleep cycles. When compared with normative data, an increase in stage 1 shifts, rapid eye movement (REM) periods, and arousals were also observed in the HIV-infected group. Significant decreases in sleep latency, total percentage stage 2 sleep, and average REM durations were also observed in the HIV-infected group compared with normative data. These sleep architecture abnormalities could not be attributed to known sole primary sleep disorders, first night effect, medications, anxiety or depression. This study indicates that sleep disturbances occur early in the course of HIV infection and suggests that the observed alterations of sleep physiology may be a consequence of central nervous system involvement and/or immune defense mobilization in the early phases of HIV infection.

Proteinase inhibitors protect Leishmania amazonensis amastigotes from destruction by amino acid esters.

Lysosomotropic amino acid esters and amides kill Leishmania amazonensis amastigotes by a mechanism which probably involves enzymatic hydrolysis of the compounds and rapid accumulation of less permeant amino acid within the parasites. We show here that, in agreement with this model, the proteinase inhibitors antipain and chymostatin prevented the killing of intracellular and isolated parasites by L-leucine methyl ester (Leu-OMe). Survival of Leishmania within macrophages was assessed microscopically, and that of isolated amastigotes was measured by tetrazolium (MTT) reduction. Near maximal protection of intracellular parasites was obtained after 24 h incubation of macrophage cultures with 50 micrograms ml-1 antipain or chymostatin. Incubation for greater than 1 h with chymostatin or greater than 4 h with antipain alone resulted in loss of viability of the parasites. Protective activity was only slightly diminished by 20 h chase of isolated parasites in inhibitor-free medium. Two synthetic chymostatin analogues, Z-Val-Phe-Sc and Z-Ile-Phe-Sc, protected isolated amastigotes at 4 or 10 micrograms ml-1. With the exception of Trp-NH2, the toxicity of which was only minimally inhibited, antipain and chymostatin also prevented parasite destruction by other amino acid derivatives. Finally, in concentration-dependent fashion, the inhibitors reduced the accumulation of [3H]leucine in isolated amastigotes incubated with [3H]Leu-OMe. Since uptake of labelled ester was unaffected, we postulate that protection involves inhibition of the parasite enzymes which hydrolyse the amino acid derivatives.

Methsuximide for complex partial seizures: efficacy, toxicity, clinical pharmacology, and drug interactions.

Methsuximide (MSM; Celontin) was administered for 8 weeks to 26 patients with complex partial seizures (CPS) refractory to phenytoin and carbamazepine and phenobarbital or primidone. A 50% or greater reduction in CPS frequency was obtained in eight patients. MSM therapy was continued chronically in these eight patients, and five continued to have a 50% or greater reduction in CPS frequency after 3 to 34 months of follow-up. Drowsiness, gastrointestinal disturbance, hiccups, irritability, and headache were the common side effects of MSM. No serious toxicity occurred. N-desmethylmethsuximide was the principal substance detected in plasma and had the following pharmacokinetic values: accumulation half-life, 49.7 hours; time to steady state, 10.4 days; elimination half-life, 72.2 hours; therapeutic range of plasma concentration, 10 to 30 mg per liter. Plasma concentrations of phenytoin and phenobarbital derived from primidone rose significantly (p less than 0.05) after addition of MSM.