The research presented in this thesis started with the idea to study alcohols as modifiers and dopants in differential ion mobility spectrometry (d-IMS) to produce complicated chemical signatures to ...explore a concept of chemical labels for product security application. D-IMS is a gas phase atmospheric pressure separation and detection technique which distinguishes compounds based on differences in their ions mobility as their travel under a low and high electric field. The hypothesis was that alcohols will form typical d-IMS products such as protonated monomers and proton bound cluster ions. However, the very first experiments revealed unexpected phenomena which included changes in the mobility of ions over a narrow range of concentrations that could not be explained by existing theory. Another observation was the apparent regeneration of reactant ions. It became evident that the observed phenomena had not been described in the open literature and that addressing the research-questions that were being raised would be essential for the determination of alcohols by d-IMS and its use in medical applications for toxicity screening and monitoring of alcohols. The above discovery shifted the research objective towards a fundamental and comprehensive study on the behaviour of alcohols in d-IMS. This thesis describes designed experiments and constructed systems allowing the efficient study of effect of concentration, electric field and temperature on the d-IMS responses of alcohols. The results of those studies demonstate: extensive fragmentation of alcohols, including previously undescribed fragmentation patterns with regeneration of the hydrated proton; new phenomena of adduct ion formation within the d-IMS drift tube, observed in the case of methanol within a narrow range of concentration; and self-modification of the alpha function of alcohols. This knowledge was exploited by developing an non-invasive analytical method for recovery, separation and detection of toxins from human saliva (including alcohols, diols and GHB) using TD-GC-d-IMS (thermal desorption - gas chromatography d-IMS) within a full range of toxicological concentration levels.
Aim: To determine potential effects of modern treatment on growth in diabetic children. Methods: Retrospective analysis of growth in diabetic children stratified by their year of diagnosis between ...1974 and 1995. A total of 451 children and adolescents attending the Diabetes Outpatient and Outreach Clinics of Royal Alexandra Hospital for Children in Sydney and rural NSW, Australia were studied. Standard deviation scores (SDS) for height and body mass index (BMI) were assessed at diagnosis, five years later (n = 451), and 10 years later (n = 111). Results: After five years of diabetes duration height SDS loss correlated with higher HbA1c and fewer injections. BMI SDS gain correlated with HbA1c and age at diagnosis. Although there was no significant difference in their height SDS or age at diagnosis, children diagnosed 1974–90 were significantly shorter than children diagnosed 1991–95 (height SDS 0.07 v 0.37) after five years diabetes duration. Furthermore, over 5 and 10 years, the 1979–90 group had lost significant height SDS (mean change −0.20 at 5 years, −0.29 at 10 years); this did not occur in the 1991–95 group (−0.01 at 5 years, −0.13 at 10 years). The BMI SDS increased significantly after 10 years in the 1974–90 group (mean change 0.37) but not in the 1991–95 group. There was no significant difference in the 174 females’ age of menarche (13.0 v 12.8 years). Conclusions: Children with diabetes treated with modern regimens maintain their increased height from diagnosis better, and after five years diabetes duration, were taller than children diagnosed before 1991.
Insufficient sedation in pediatric magnetic resonance imaging (MRI) results in prolonged examination time. To describe the efficacy and side effects of sedation with Phenobarbital short-time infusion ...followed by continuous gamma-hydroxybutyric acid (GHB) infusion in neonates and children for MRI examinations in a retrospective study.
With Institutional Review Board approval 94 children (Group I: 1-4 weeks; Group II: >1 to 6 months; Group III: >6 months) were sedated with phenobarbital 10 mg/kg (maximum 200 mg) intravenously 30 min prior to examination. Than intravenous sedation was maintained with GHB 10 mg/kg/h after a priming dose of 30 mg/kg in 20 min.
In group 1 all neonates (n=8) were well sedated without side effect. One of 21 infants in group 2 showed restlessness and the MRI failed. Two of 65 patients of group 3 were not sufficiently sedated and one of them vomited.
Non-invasive diagnostic procedures in neonates and children may be managed by phenobarbital and GHB sedation with side effects or failure of 3%.
It has been previously described that γ-hydroxybutyrate (GHB) provides significant protection against transient global cerebral ischemia in the rat (four vessel occlusion model), when given 30 min ...before or 10 min after artery occlusion. Here, we show that in the same rat model, significant protection can also be obtained when treatment is started 2 h after the ischemic episode. In saline-treated animals, 30 min of global ischemia followed by reperfusion caused a massive loss of neurons in the hippocampal CA1 subfield (examined 63 days after the ischemic episode), and an impairment of sensory-motor performance (tested on the 51st and 63rd days after ischemia) and of spatial learning and memory (evaluated starting 46 days after the ischemic episode). Treatment with GHB—300 mg/kg intraperitoneally (i.p.) 2 h after the ischemia–reperfusion episode, followed by 100 mg/kg i.p. twice daily for the following 10 days—afforded a highly significant protection, against both histological damage and sensory-motor and learning-memory impairments. These data further suggest the possible therapeutic effectiveness of GHB in brain ischemia, and indicate that the underlying mechanism of action involves non-immediate steps of the ischemia-induced cascade of events.
It has been observed that agents with agonist activity at 5-HT
2A receptors prevent neurotoxicity induced by the non-competitive NMDA antagonist, dizocilpine (MK-801). Subsequent behavioral studies ...reported complete antagonism by LSD and DOM of the stimulus effects of the related NMDA antagonist, phencyclidine PCP. The present study sought to extend those observations to include other psychoactive drugs. Male F-344 rats were trained in a 2-lever, fixed-ratio 10, food-reinforced task with PCP (3.0 mg/kg; IP; 30 min pretreatment) as a discriminative stimulus. Tests of generalization were then conducted using the training dose of PCP in combination with a range of doses of DOM, LSD,
d-amphetamine, MDMA, psilocybin, buspirone, and GHB. All of the drugs tested in combination with PCP produced a statistically significant diminution of PCP-appropriate responding but for none was antagonism complete. These data, obtained using a stimulus control model of the hallucinogenic effects of PCP, fail to support the hypothesis that LSD and DOM completely antagonize stimulus control by PCP. Instead, the data suggest complex interactions between PCP-induced stimulus control and a variety of psychoactive drugs including GHB, an agent with no known affinity for serotonergic receptors.
Succinic semialdehyde dehydrogenase (SSADH) deficiency and
d-2-hydroxyglutaric aciduria (
d-2-HGA) are rare inborn errors of metabolism primarily revealed by urinary organic acid screening. Three ...patients with proven SSADH deficiency excreted, in addition to GHB considerable amounts of
d-2-HG. We examined whether these patients suffered from two inborn errors of metabolism by measuring
d-2-HG concentrations in the culture medium of cells from these patients. In addition, mutation analysis of the
d
-2-hydroxyglutarate dehydrogenase gene was performed. Normal concentrations of
d-2-HG were measured in the culture media of fibroblasts or lymphoblasts derived from the three patients. In one patient, we found a heterozygous likely pathogenic mutation in the
d
-2-hydroxyglutarate dehydrogenase gene. These combined results argue against the hypothesis that the patients are affected with “primary”
d-2-HGA in combination with their SSADH deficiency. Moderately increased levels of
d-2-HG were also found in urine, plasma, and cerebrospinal fluid samples derived from 12 other patients with SSADH deficiency, revealing that
d-2-HG is a common metabolite in this disease. The increase of
d-2-HG in SSADH deficiency can be explained by the action of hydroxyacid-oxoacid transhydrogenase, a reversible enzyme that oxidases GHB in the presence of 2-ketoglutarate yielding SSA and
d-2-HG.
The regulation of GABA release from the inhibitory input to dopamine cells in the substantia nigra pars compacta (SNc) plays a key role in different reward-related behaviors. Gamma-hydroxybutyrate ...(GHB) has therapeutical properties in various psychiatric disorders, especially in alcohol abuse. GHB is also used as a drug of abuse, which induces sedation and euphoria. Using whole-cell patch-clamp recordings, we studied the effects of GHB on GABA release in the SNc by recording spontaneous inhibitory postsynaptic currents (sIPSCs) in brain slices of 21- to 25-day-old rats. We found that GHB depressed the frequency and amplitude of sIPSCs, while the frequency and the amplitude of miniature inhibitory postsynaptic currents (mIPSCs), recorded in the presence of TTX, were not affected. However, in the presence of high extracellular potassium (15 mM), which increases the contribution of voltage-dependent calcium channels, GHB induced a reduction in the frequency of the mIPSCs without any effect on their amplitude. All of these effects were GABA(B)-independent and they were blocked by the GHB receptor antagonist NCS-382. The present results indicate that GHB inhibits spontaneous inhibitory synaptic transmission recorded from dopaminergic neurons in the SNc likely by reducing voltage-dependent calcium influx involved in presynaptic GABA release.
GHB and driving impairment Couper, F J; Logan, B K
Journal of forensic sciences,
07/2001, Letnik:
46, Številka:
4
Journal Article
Recenzirano
Gamma hydroxybutyrate (GHB) was identified in the blood of 13 subjects arrested for impaired driving. GHB concentrations ranged from 26 to 155 mg/L (mean 87 mg/L, median 95 mg/L). In eight cases, GHB ...was the only drug detected, and signs of impairment were consistent with those of a CNS depressant, including erratic driving (weaving, swerving, ignoring road signs), confusion, incoherent speech, unresponsiveness, lack of balance, unsteady coordination, poor performances on field sobriety tests, and varying states of wakefulness. Given the ability of GHB to induce sleep and unconsciousness, it is evident from these cases that recreational use of the drug has the potential to impair a person's driving ability.
Zusammenfassung
Insbesondere wird der Einsatz von γ- Hydroxybuttersäure (GHB, „Liquid Ecstasy“) und seinen Vorstufen γ-Butyrolakton (GBL) und 1,4-Butandiol (BDO), die im menschlichen Körper zu GHB ...umgewandelt werden, als K.O.-Mittel im Rahmen der Sexualdelinquenz beobachtet. Bei einer geringen Einzeldosis GHB (bei Erwachsenen etwa 1 bis 2 g p.o.) wirkt GHB bei nicht gewöhnten Personen leicht berauschend, euphorisierend, anxiolytisch und entspannend. Mit steigender Dosierung (ab etwa 2,5 g) treten folgende Symptome in den Vordergrund: Schläfrigkeit, Schwindel, Übelkeit, Erbrechen, Desorientiertheit, Agitiertheit, körperliche Symptome wie Myoklonie und Bradykardie. Bei oraler Aufnahme von 3 bis 4 g stellt sich bei Erwachsenen innerhalb weniger Minuten Bewusstlosigkeit mit Gefahr der Atemdepression ein, bei 4 bis 5 g ist schließlich mit einem tiefen Koma zu rechnen.
2008 gelangten 22 Fälle mit Verdacht auf K.O.-Mittelbeibringung im Zusammenhang mit einem Sexualdelikt zur toxikologischen Analyse in unser Institut: 11 Fälle mit Blut und Urinprobe, 7 Fälle nur mit Blutprobe, 4 Fälle nur mit Urinprobe. Zeitraum zwischen Vorfall und Blutentnahme im Durchschnitt 6,2 h, zwischen Vorfall und Urinabgabe im Durchschnitt 14,6 h. In keinem Fall gelang der Nachweis einer GHB-Konzentration oberhalb des physiologischen Wertes. In 12 Fällen wurden nachgewiesen: Cannabis (n = 7), Amphetamin (n = 2), Cocain (n = 1), Diazepam (n = 3) sowie Fluoxetin, Citalopram und Dihydrocodein (jeweils n = 1).
Im Hinblick auf die kurze Halbwertszeit von GHB ist eine rasche Blutentnahme und Urinabgabe bei Verdacht auf GHB-Beibringung von erheblicher Bedeutung. Wesentliches Gewicht kommt hier auch der Anamnese zu, insbesondere zur Rausch- und zur Aufwachphase.