Search NEL Online

Clinical Trial 2013; 34(6): 553-558 PubMed PMID: 24378443 Citation  Keywords:  Adult, Female, Fenoterol:administration & dosage, Fetus:blood supply, Heart Rate:drug effects, Heart Rate, Fetal:drug effects, Humans, Infusions, Intravenous, Obstetric Labor, Premature:diagnostic imaging, Placenta:blood supply, Pregnancy, Tocolytic Agent.   

OBJECTIVES: The aims were to investigate whether any changes in placental and fetal circulation were observed during fenoterol tocolysis within the first 48 hours of therapy.

MATERIAL AND METHODS: Doppler evaluation of placental and fetal circulation was performed prior to fenoterol administration and then after 24 and 48 hours. Maternal heart rate and pulsatility index (PI) in uterine arteries were assessed. FHR, RI and PI of umbilical artery and middle cerebral artery were measured. E/A ratio for A-V valves, the myocardial performance index (MPI) and shortening fraction (SF) were calculated for both ventricles independently. The blood flow pattern in DV was assessed using PI, S/a ratio and peak velocity index for the vein. To determine changes over time in all study variable analysis of variance (ANOVA) for repeated measurements followed by Tukey-Kramer's multiple comparison test was used. The effects of additional clinical covariates were checked.

RESULTS: Uterine and fetal arterial blood flow patterns were not altered significantly during 48 hours of tocolysis. No significant changes were observed in fetal cardiac function parameters as well. The evaluation of Doppler parameters in the DV revealed a significant increase in PVIV after 48 hours. Additionally after 48 hours of successful tocolysis S/a ratio values were significantly lower.

CONCLUSIONS: Short term intravenous administration of fenoterol seems not to alter uterine and fetal arterial blood flow pattern. Direct fetal cardiac function remained unaffected. However significant changes of selected Doppler parameters in DV may suggest further studies should be performed to assess more precisely fetal venous blood flow....

Read abstract  Full text PDF

Clinical Trial 2013; 34(6): 549-552 PubMed PMID: 24378442 Citation  Keywords:  Adult, Female, Fenoterol:administration & dosage, Fetus:blood supply, Heart Rate:drug effects, Heart Rate, Fetal:drug effects, Humans, Infusions, Intravenous, Obstetric Labor, Premature:diagnostic imaging, Pregnancy, Tocolytic Agents:administration & dosa.   

OBJECTIVE: to investigate whether any changes in the preload index (PLI) occur within the first 48 hours of fenoterol intravenous tocolysis.

MATERIAL AND METHODS: Doppler evaluation of placental and fetal circulation was performed in 36 pregnant women prior to fenoterol administration and after 24/48 hours. Measurements were obtained from a longitudinal section of the inferior vena cava (IVC) and preload index was calculated. To determine changes over time, an all study variable analysis of variance (ANOVA) for repeated measurements, followed by Tukey-Kramer's multiple comparison test was used. The effects of additional clinical covariates were checked.

RESULTS: The maternal heart rate values were significantly increased after 24 hours and 48 hours in comparison to pre-treatment values. No significant changes in fetal heart rate were observed during treatment. The fetal IVC PLI values were significantly reduced after 24 hours and 48 hours of treatment. The increase in PLI values when comparing 24 and 48 hours results were not statistically significant. These observations were consistent with ANOVA post-hoc analysis.

CONCLUSIONS: 48 hours intravenous administration of fenoterol appears not to alter inferior vena cava blood flow by itself. The reduction in PLI values may reflect lower fetal preload conditions during the course of successful tocolytic treatment. Therefore, Doppler IVC PLI measurement should be considered as a possible additional assessment method of effectiveness of treatment. However, other Doppler venous blood flow parameters should be assessed to confirm the results and clarify whether maternal corticosteroids administration may be interfering with the results....

Read abstract  Full text PDF

Comparative Study 2013; 34(Suppl 2): 74-78 PubMed PMID: 24362096 Citation  Keywords:  Absorption, Animals, Biological Availability, Chlorides:administration & dosage, Cholinesterase Reactivators:administration & dosage, Female, Injections, Intramuscular, Injections, Intravenous, Oximes:administration & dosage, Pyridinium Compounds:administ.   

OBJECTIVES: Oxime HI-6 is an acetylcholinesterase reactivator therapeutically efficient against nerve agents. Because of their physico-chemical properties, oximes are typically applied intramuscularly (i.m.). This route of administration has also some disadvantages, and alternative strategies ought to be examined. We evaluated the pharmacokinetic profiles of two HI-6 salts after their intravenous (i.v.) administration, and compare the results with the known pharmacokinetics after i.m. administration.

METHODS: Pigs were administered with HI-6 salts (i.v), either HI-6 dichloride (10.71 mg/kg) or molar equivalent HI-6 dimethansulphonate (13.59 mg/kg). Doses of the HI-6 salts corresponded with a standard HI-6 dichloride dose in one autoinjector (500 mg) and were recalculated for one kilogram of body weight.

RESULTS: The main pharmacokinetic parameters are comparable after i.v. and i.m. HI-6 administration. The compared pharmacokinetic parameters were half-life, terminal rate constant, mean residence time of the molecule in the body, clearance, and the apparent volume in the terminal phase. The bioavailability after i.m. administration was comparable with that of i.v.; these results suggest that the oxime is well released from the muscle depot. Significant differences were found in parameters Cmax and Tmax which are important in cases of emergency when rapidity and bioavailability are paramount for the success of treatment.

CONCLUSIONS: I.v. administration should solve the problem of rapid clearance. Infusion or bolus administration may be considered as a logical subsequent step in oxime treatment strategy. The main advantage is in maintenance of an effective therapeutic plasma concentration, a more easily achievable effective therapeutic concentration, and fewer local adverse reactions....

Read abstract  Full text PDF

Journal Article 2013; 34(4): 287-293 PubMed PMID: 23803871 Citation  Keywords:  Adult, Antidepressive Agents:therapeutic use, Cross-Over Studies, Depressive Disorder, Major:drug therapy, Double-Blind Method, Female, Hallucinogens:therapeutic use, Humans, Infusions, Intravenous, Ketamine:therapeutic use, Male, Middle Aged, Receptors, .   

OBJECTIVES: Ketamine and other NMDA (N-methyl-D-aspartate) antagonists produce fast-acting antidepressant-like effects, although the underlying mechanism is unclear. Furthermore, high affinity NMDA antagonists such as ketamine are associated with psychotomimetic effects. To date the link between the antidepressant and psychotomimetic effects of ketamine has not been explored. We examined the relationship between the antidepressant and psychotomimetic effects of a single ketamine infusion in subjects diagnosed with major depressive disorder.

METHODS: In a double-blind, cross-over, placebo-controlled, two weeks clinical trial we studied the effects of ketamine (0.54 mg/kg within 30 min) in a group of 27 hospitalized depressive patients.

RESULTS: Higher intensity of psychotomimetic symptoms, measured using BPRS, during ketamine administration correlated with alleviation in mood ratings during the following week with maximum on day seven. Ketamine was superior to placebo in all visits (day 1, 4, and 7) assessed by MADRS with effect size (Cohen´s d) of 0.62, 0.57, and 0.44 respectively. There was no significant correlation between ketamine and nor-ketamine plasma levels and MADRS score change at any study time point.

CONCLUSION: The substantial relationship between ketamine's antidepressant and psychotomimetic effects was found. This relationship could be mediated by the initial steps of ketamine's action, trough NMDA receptors, shared by both ketamine's clinical effects....

Read abstract  Full text PDF

Journal Article 2012; 33(2): 191-195 PubMed PMID: 22592200 Citation  Keywords:  Animals, Ghrelin:administration & dosage, Half-Life, Injections, Intravenous, Iodine Radioisotopes, Male, Rats, Rats, Wistar, Tissue Distribution,.   

OBJECTIVES: Ghrelin presents a multiplicity of biological functions, what is consistent with widespread expression of this peptide and its receptors. Ghrelin may act locally, but it may also influence distant cells. The aim of the study was to assess plasma activity of exogenous ghrelin and its distribution in rats.

DESIGN: Plasma radioactivity of (125)I-ghrelin (cpm) was analyzed in blood specimens collected after (125)I-ghrelin administration. Tissue uptake of (125)I-ghrelin (cpm/mg) was evaluated in 27 tissues obtained during an autopsy performed 1, 2 and four hours after (125)I-ghrelin administration. The radioactivity of the tissue specimen (cpm) was divided by the weight of the specimen (mg).

RESULTS: Plasma (125)I-ghrelin radioactivity decreased rapidly after peptide administration. The half-life time of (125)I-ghrelin was 15-18 minutes. The analysis of (125)I-ghrelin distribution revealed three profiles of its tissue uptake. The first profile was characterized by decreasing radioactivity (e.g. brain, kidney, liver). Increasing tissue radioactivity followed by a gradual decrease (second profile) was observed for example in stomach, intestine and thyroid. The third profile was described as a relatively stable radioactivity (e.g. lung, myocardium). Despite of Lugol's solution administration, thyroid uptake of (125)I-ghrelin was notably higher than in other tissues (second and third profile).

CONCLUSIONS: Exogenous ghrelin uptake in tissues that produce this peptide suggests, that ghrelin influences the biology and function of these cells also in endocrine way. Similarly, the accumulation of peptide observed in the third profile (e.g. thyroid) may reflect a potential role of ghrelin in these organs....

Read abstract  Full text PDF

Comparative Study 2011; 32(1): 82-89 PubMed PMID: 21407156 Citation  Keywords:  Animals, Corticosterone:blood, Eating:physiology, Fasting:physiology, Injections, Intravenous, Injections, Intraventricular, Leptin:blood, Male, Nerve Tissue Proteins:genetics, Pituitary Gland:drug effects, Pituitary Hormones, Anterior:blood, Rats, Rats, .   

OBJECTIVE: CART is involved in the control of food intake and hormonal secretion. We aimed to evaluate the effects of CART on hormonal profile in starved rats.

METHODS: Study group included 100 male rats. Under conditions of food limitation CART (55-102) was given centrally (icv) or peripherally (iv). Non-starved animals underwent identical procedure. Vehicle (aCSF or saline)-injected rats served and as a controls. 60 minutes after CART or vehicle administration blood was collected to assess pituitary hormones (LH, FSH, PRL, GH, ACTH, TSH), corticosterone and leptin concentrations.

RESULTS: Itracerebroventricular CART injection resulted in a significant increase in PRL, GH and corticosterone concentrations in non-starved rats compared with vehicle injected animals. However, in a group of starved animals only leptin levels were decreased in comparison with fasted controls. Peripheral CART administration caused a significant increase in PRL, GH and TSH levels in non-starved rats but no changes in investigated hormone levels were observed in starved animals when compared to saline injected controls.

CONCLUSIONS: Our results indicate that CART is able to modulate hormonal profile in a non-starved rats. However, the modulatory effect depends on the CART administration method. Interestingly, CART administration, both icv and iv, does not have an impact on pituitary hormones and corticosterone levels in a course of food limitation....

Read abstract  Full text PDF

Journal Article 2010; 31(Suppl 2): 57-61 PubMed PMID: 21187822 Citation  Keywords:  Adipose Tissue:cytology, Animals, Blood-Brain Barrier, Brain:cytology, Female, Fluorescein:administration & dosage, Fluorescent Dyes:administration & dosage, Gastrointestinal Tract:cytology, Injections, Intravenous, Kidney:cytology, Lung:cytology, Microsc.   

OBJECTIVE: Confocal laser scanning endomicroscopy (CLSE) is a diagnostic technology that produces virtual histology of the mucosal layer using fluorescence technique. Fluorescein (FSC) is the most commonly used fluorescence agent. Fluorescence light coming from a horizontal special focal plane is detected during confocal laser endomicroscopy of the gastrointestinal tract. FSC causes intensive yellowish discoloration of tissues, including skin and mucous membranes. This pre-clinical study was aimed to evaluate the tissue distribution and pharmacokinetics of FSC after its intravenous administration.

METHODS: The study was performed in an adult experimental pig. A reversed-phase high-performance liquid chromatographic method with fluorescence detection was used for the determination of fluorescein in blood plasma and tissue samples.

RESULTS AND CONCLUSION: The pharmacokinetic study of fluorescein determined the optimum time interval for diagnostic scanning (5-10 min.) The biodistribution study of fluorescein (aimed on the potential organ accumulation) proved the high concentration in the renal system followed by levels in bile > lung > adipose tissue > all other organs (including gastrointestinal wall) and these were relatively similar to each other. Fluorescein has a significantly low distribution in the brain (contrast with the level in adipose tissue indicates the low ability to penetrate the blood-brain barrier)....

Read abstract  Full text PDF

Journal Article 2009; 30(5): 663-670 PubMed PMID: 20035259 Citation  Keywords:  Animals, Behavior, Animal:drug effects, Central Nervous System Stimulants:administration & dosage, Estradiol:pharmacology, Female, Humans, Infusions, Intravenous, Male, Methamphetamine:administration & dosage, Ovariectomy, Rats, Rats, Wistar, Reinforcemen.   

OBJECTIVE: The female animals were already recorded to respond differently to methamphetamine (MET) abuse than males. This gender dissimilarity may be caused by the influence of estral cycles and different susceptibility to behavioural sensitization.

METHODS: Influences of gender and pre-exposure to MET were studied in the rat model of MET intravenous self-administration (IVSA). The fixed ratio (FR) paradigm was employed in male rats (M) and estrogenized (F-ESTR) and non-estrogenized ovariectomized female rats (F-OVX) either pre-exposed or not-exposed to MET pretreatment.

RESULTS: In rats that were not pre-exposed to MET, F-ESTR self-administered more MET infusions than each of the other groups, but F-OVX self-administered less than each of the other groups; the same trend was apparent in the MET pretreated groups. MET pre-exposure decreased subsequent MET IVSA in all groups except F-OVX.

CONCLUSION: Thus, pre-exposure to MET and the loss of inherent estrogen in females notably decreased the intake of MET by rats, suggesting that abuse liability was reduced. Estrogen's effects on MET self-administration here correspond with accumulating evidence of stronger behavioural responses of females to drugs of abuse....

Read abstract  Full text PDF