Significant Differences In Blood Concentrations Research Articles

Features of Benzodiazepine Poisoning in the Elderly and Senile Patients

AIM OF THE STUDY To study benzodiazepine poisoning in geriatric patients compared to patients of working age.MATERIAL AND METHODS We examined 82 patients with benzodiazepine poisoning, hospitalized in the Department of Acute Poisoning and Somatopsychiatric Disorders of the N.V. Sklifosovsky Research Institute for Emergency Medicine in 2020–2021, which were divided into age categories: young (18–44 years old), middle (45–59 years old) and older (over 60 years old) age. The presence of benzodiazepines in urine was confirmed by immunochromatographic analysis and gas chromatography–mass spectrometry (GC-MS). The concentration of phenazepam in the blood and urine was determined in 45 patients by GC-MS. Statistical processing of the material was performed using the IBM program SPSS Statistics 27.0. The median (Me), 25th and 75th percentiles were determined. The comparison of quantitative data was performed using non-parametric criteria, the level of significance was taken as p<0.05.RESULTS It was found that acute phenazepam poisoning prevailed in all age groups (90% of patients). Among young and middle-aged patients, moderate and deep stunning (GCS score 12–14) prevailed, and in older people moderate and severe poisoning prevailed (GCS score 3–12), with no statistically significant differences in blood concentrations of phenazepam between the groups. In patients of the older age group with benzodiazepine poisoning, compared to people of working age, the development of respiratory failure was statistically significantly more frequent — 13.8-fold, pneumonia — 12.6-fold, vein thrombosis of the lower extremities — 7.8-fold, trophic skin changes — 29-fold. The duration of treatment in older patients with benzodiazepine poisoning was 3.5-fold higher than in young and middle-aged patients, mortality in the older age group was 41%.CONCLUSION The course of acute poisoning with benzodiazepines, including phenazepam, in the elderly and senile age differs in comparison with persons of working age with a high incidence of complications and adverse outcomes.

Kratom-Associated Fatalities in Northern Nevada—What Mitragynine Level Is Fatal?

Mitragyna speciosa, commonly known as the kratom tree, has been utilized in Southeast Asia for centuries for its opioid-like effects. Kratom has been available in the United States for the past decade and has grown increasingly popular despite a lack of clinical research to determine its safety. With its widespread use, there have been an increasing number of fatalities. This study aims to establish a potential lethal range for mitragynine, the active compound in kratom, by investigating the toxicology reports of 35 deaths in Northern Nevada between 2015 and 2020. Mitragynine concentrations ranged from 8.7 to 1800 ng/mL (n = 27) in cases with drug toxicity as the cause of death; in 1 case, the sole intoxicant was mitragynine with a blood concentration of 950 ng/mL. In cases with nonmitragynine causes of death, the concentration was 110 to 980 ng/mL (n = 8). There was no statistically significant difference in blood concentrations between cases where mitragynine was not listed as a cause of death (mean, 315 ± 297.2 ng/mL) and cases in which mitragynine contributed to death (mean, 269.4 ± 382.5 ng/mL; P < 0.201). A literature review is also presented.

Clinical and hematological evaluation in dogs with myoclonus derived from canine distemper supplemented with vitamin D3

In dogs, the synthesis of vitamin D in the skin is considered inefficient, making dietary supplementation the main source of this vitamin for these animals. In humans, there are established values for 25-hydroxyvitamin D (25(OH)D) deficiency, insufficiency and sufficiency levels, however in dogs, the serum concentrations of these values are not well established. The purposes of this study were to evaluate the 25(OH)D serum levels in dogs carrying myoclonus as sequelae of distemper, to evaluate the response to vitamin D levels on oral supplementation, to evaluate PTH, calcium, phosphorus, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood count and leukogram levels, in addition to conduct clinical observations of myoclonus. Venous blood samples were collected from nine dogs carrying myoclonus derived from distemper, however with no other clinical or laboratorial change, of varied breeds and same age group (1 - 8 years old). Screening laboratory tests were performed to attest to the health of the animals in a 30-day period and the collections were divided into three periods: days 0, 15 and 30. After the initiation of treatment, the animals underwent physical and laboratorial evaluations every 15 days, for 90 days, completing a total of 120 days. The dose used for oral supplementation of vitamin D3 was 1000IU/kg administered every day, once a day, during the entire experimental period. For clinical evaluation, parameters of anatomical distribution, speed and rhythm, and distribution of myoclonic changes over time were observed. The laboratory results were subjected to analysis of variance and, when significant (P&lt;0.05), submitted to regression analysis. Descriptive statistics were used to analyze clinical results. There was a significant difference in blood concentrations of 25(OH)D, PTH, calcium and phosphorus, however there was no significant effect of vitamin D on the other parameters evaluated. It was possible to conclude that the dose of vitamin D3 used was sufficient to increase 25(OH)D serum levels in the blood, to levels of sufficiency, having influence on PTH, phosphorus and calcium levels, not changing the other hematological and clinical parameters evaluated. However, the dose and duration of the treatment used did not change the myoclonus derived from distemper in dogs.

The influences of SCN3A gene polymorphism on the efficacy of valproic acid sodium in the treatment of epilepsies

Objective To investigate the influences of SCN3A gene polymorphism(c.905A>G/p.N302S and c. 1441C>T/p.L481L) on the efficacy of valproic acid sodium in the treatment of Zhuangzu epilepsies. Methods Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)technique and the way of direct sequence, the SCN3A gene c. 905A>G/p.N302S and c. 1441C>T/p.L481L genotypes in peripheral blood were detected in 244 epileptic patients (85 cases in effective group and 139 cases of ineffective group) in the standardized treatment of valproic acid sodium.The blood concentration of valproic acid sodium was detected by LC-MS.Evaluating the correlation between the genotype and alleles of two groups of patients and the efficacy of valproic acid sodium and analyzing the difference of valproic acid sodium's blood concentration between different genotypes.The linkage disequilibrium of c. 905A>G/p.N302S and c. 1441C>T/p.L481L were analyzed by software SHEsis. Results The allele and genotype distribution in c. 905A>G/p.N302S loci between effective group(A, G allele: 50.6%, 49.4%, AA, AG, GG genotype: 27.1%, 47.1%, 25.8%) and ineffective group(A, G allele: 37.4%, 62.6%, AA, AG, GG genotype: 16.6%, 41.7%, 41.7%) had statistically significant difference(χ2=7.501, P=0.006; χ2=7.907, P=0.019). There was no significant difference in allele and genotype distribution of c. 1441C>T/p.L481L loci between effective group(C, T allele: 47.1%, 52.9%, CC, CT, TT genotype: 23.5%, 47.1%, 29.4%) and ineffective group(C, T allele: 38.8%, 61.2%, CC, CT, TT genotype: 18.7%, 40.3%, 41.0%)(χ2=2.920, P=0.088; χ2=3.099, P=0.212). Compared with the AA + AG genotype, the GG genotype at c. 905A>G/p.N302S locus significantly reduced the efficacy of valproic acid sodium (OR=2.051, 95%CI=1.136-3.703). Compared with genotypes AA+ AG, there were no significant differences in blood concentration of genotype GG of c. 905A>G/p.N302S (t=3.256, P=0.137). Compared with genotypes CC+ CT, there were no significant differences in blood concentration of genotype TT of c. 1441C>T/p.L481L(t=4.628, P=0.082). c.905A>G/p.N302S and c. 1441C>T/p.L481L were without linkage disequilibrium. Conclusion These results suggest that the single nucleotide polymorphisms of c. 905A>G/p.N302S in SCN3A genes may play a role in the resistivity of valproic acid sodium in Zhuangzu epilepsies. Key words: Polymorphism of SCN3A genes; Zhuangzu epilepsie; Valproic acid sodium; Efficacy

Influence of overwinter distribution on exposure to persistent organic pollutants (POPs) in seabirds, ancient murrelets (Synthliboramphus antiquus), breeding on the Pacific coast of Canada

Assessing the fate of both legacy and newer persistent organic pollutants (POPs) is an ongoing challenge. Top predators, including seabirds, are effective monitors of POPs because they forage over a range of marine habitats, integrating signals over space and time. However, migration patterns can make unravelling contaminant sources, and potentially assessments of the effectiveness of regulations, challenging if chemicals are acquired at distant sites. In 2014, we fitted geolocators on ancient murrelets (Synthliboramphus antiqueus) at four colonies on the Pacific Coast of Canada to obtain movement data throughout an annual cycle. All birds underwent a post-breeding moult in the Bering Sea. Around one-third then returned to overwinter on the British Columbia (BC) coast while the rest migrated to overwinter in waters along the north Asian coast. Such a stark difference in migration destination provided an opportunity to examine the influence of wintering location on contaminant signals. In summer 2015, we collected blood samples from returned geo-tagged birds and analyzed them for a suite of contaminants, including polybrominated diphenyl ethers (PBDEs), non-PBDE halogenated flame retardants, perfluoroalkyl substances (PFASs), organochlorines, and mercury. Feathers were also collected and analyzed for stable isotopes (δ13C, δ15N, and δ34S). We found no significant differences in blood concentrations of any contaminant between murrelets from the two different overwinter areas, a result that indicates relatively rapid clearance of POPs accumulated during winter. Spatial variation in diet (i.e., δ13C) was associated with both BDE-47 and -99 concentrations. However, individual variation in trophic level had little influence on concentrations of any other examined contaminants. Thus, blood from these murrelets is a good indicator of recent, local contaminants, as most signals appear independent of overwintering location.

Association of CYP1A2 and CYP2D6 gene polymorphism with therapeutic efficacy of duloxetine on depression in southern region of Fujian

Objective To explore the influence of CYP1A2 and CYP2D6 gene polymorphism on blood concentration, therapeutic efficacy and adverse effects of anti-depression drug duloxetine on depression patients in southern region of Fujian. Methods 82 patients with depression were selected from southern region of FuJian, China, and all participates received duloxetine for two weeks. Blood concentrations of duloxetine were detected by HPLC-MS, and CYP1A2 and CYP2D6 genotypes were determined by sequencing with the amplified PCR products from peripheral blood DNA.The therapeutic efficacy and adverse effects of duloxetine were evaluated by Hamilton depression scale (HAMD) and treatment emergent symptom scale (TESS) respectively. Results Subjects were divided into GG, GA and AA three groups based on CYP1A2*1C genotyping. There was no significant difference in blood concentrations of duloxetine, dose-corrected blood concentrations, the reduction rate of HAMD and the reduction rate of TESS among the three groups. Results were the same with CYP1A2*1F, which were divided into CC, CA and AA three groups. Subjects was divided into CC, CT, TT three groups based on CYP2D6*10 locus genotyping.Blood concentrations of duloxetine were (13.89±3.22)ng·ml-1, (16.08±4.24)ng·ml-1, (17.25±4.62)ng·ml-1 respectively and there was significant difference(F=3.21, P 0.05). Dose-corrected blood concentrations were (304.84±103.76), (368.13±143.49), (444.50±195.58) respectively and there was significant difference(F=4.19, P<0.05), and CC group was significantly lower than TT group(P<0.05). The reduction rate of HAMD were 0.42±0.11, 0.46±0.11, 0.52±0.09 respectively and there was significant difference(F=6.29, P<0.05), and CC and CT group was significantly lower than TT group(P<0.05). The reduction rate of TESS were 1.14±0.66, 1.48±0.69, 1.69±0.69 respectively and there was significant difference(F=3.38, P<0.05). CC group was significantly lower than TT group(P<0.05). Conclusion Among the 3 loci studied, only CYP2D6*10 locus within CYP2D6 gene can affect blood concentration, efficacy and adverse effects of duloxetine, which indicate that CYP2D6 gene polymorphism may contribute to therapeutic efficacy of duloxetine on depression in southern region of Fujian. Key words: Duloxetine; CYP1A2; CYP2D6; Gene polymorphism; Blood concentration

Effects of exercise with or without light exposure on sleep quality and hormone reponses.

[Purpose]The objectives of the present study were to determine the effect of sun exposure and aerobic exercise on quality of sleep and investigate sleep-related hormonal responses in college-aged males.[Methods]In this study, the cross-over design was utilized. The subjects (N = 10) without any physical problems or sleep disorders participated in the experimental performed 4 protocols in only sun exposure (for 30 minutes, EG1) protocol, only aerobic exercise (walking and jogging for 30 minutes, EG2) protocol, aerobic exercise with sun exposure (EG3) protocol, and control (no exercise and no sun exposure, EG4) protocol. Each protocol was 5 times per week with one-week break (wash-out period) between protocols to prevent the effects of the previous protocol. Total test period was should be 7 weeks (one week of protocol and one week of break). Before and after each aerobic exercise session, the subjects completed stretching to warm up for 5 to 10 minutes. Surveys consisting of (bedtime, wake-up time, sleep onset latency, and (Pittsburgh Sleep Quality Index (PSQI) were obtained before the test and after each protocol. After each protocol, the following sleep-related hormonal responses were measured: blood concentrations of melatonin, cortisol, epinephrine, and norepinephrine. One-way ANOVA was used to determine differences between protocols. Statistical significance was set at p < 0.05.[Results]Bedtime of EG4 was significantly later than that of the EG1 or EG3. Wake-up time in the EG4 was significantly later than that of the EG1 or the EG3. Sleep onset latency in the EG4 was longer than that of the EG3. The quality of sleep in the EG4 was lower than that of the EG3. Sleep cycle in the EG4 was significantly shorter than that of the EG1. Blood melatonin concentrations of the EG3 was significantly higher than that of the EG4. There were no significant differences in blood concentrations of cortisol, epinephrine, or norepinephrine among protocols, with the order from the lowest to the highest values of EG1 < EG2 < EG3 < EG4.[Conclusion]The present data found that EG1 and EG3 showed positive sleep-related hormonal responses, sleep habits, and quality of sleep, indicating that sun exposure or exercise with sun exposure may improve the physical status and quality of life.

Effect of expression of P-glycoprotein in tumor tissue on analgesic efficacy of fentanyl and lornoxicam in patients with cancer pain

Objective To evaluate the effect of the expression of P-glycoprotein (P-gp) in the tumor tissue on the analgesic efficacy of fentanyl and lornoxicam in patients with cancer pain. Methods One hundred advanced cancer patients with pain aged 49-64 yr weighing $$-65 kg were included in this study. The expression of Pgp was positive in the tumor tissue in 50 patients (groups F1 and L1, n = 25 each) and negative in 50 patients (groups F2 and L2, n = 25 each). The patients in 4 groups received 48 h of pstient-controlled intravenous analgesia (PCIA). A loading dose of fentanyl 0.05 mg was administered before PCIA was started in groups F1 and F2 .The PCIA solution contained fentanyl 1 mg and droperidol 5 mg in 100 ml of normal saline in groups Ft and F2, or lomoxicam 64 mg and droperidol 5 mg in 100 ml of normal saline in groups L1 and L2. The PCA pump was set to deliver a background infusion of 2 ml/h and a bolus dose of 0.5 ml at 15 min lockout interval. Pain was assessed with VAS scores (0 = no pain, 10 = worst pain), and VAS score was maintained at ≤3 during PCIA. Flurbiprofen 50 mg was injected intravenously when VAS score≥4 and the consumption of flurbiprofen was recorded. The consumption of fentanyl and lornoxicam during PCIA was recorded. Blood samples from the internal jugular vein were taken at the beginning of PCIA (T0), and at 4, 12, 24, 48 h of PCIA (T1-4) for determination of blood fentanyl and lornoxicam concentrations. Results Flurbiprofen was not used in groups F2, L1 and L2. The consumption of flurbiprofen was ( 184 ± 41 ) mg in group F1 . There was no significant difference in the consumption of fentanyl during PCIA between groups F1 and F2 ( P ＞ 0.05). Blood fentanyl concentrations were not detected at all the time points in groups F1 and F2 . The VAS score during PCIA ≤ 3 in groups L1 and L2, and there was no significant difference in blood concentrations of lornoxicam at each time point and the consumption of lornoxicam during PCIA between groups L1 and L2 ( P ＞ 0.05). Conclusion Positive P-gp expression in the tunor tissue can decrease the analgesic efficacy of fentanyl, but exerts no effect on the analgesic efficacy of lornoxicam in patients with cancer pain. Key words: Glycoproteins; Fentanyl; Cyclooxygenase inhibitors; Neoplasms; Analgesia

Experimental evaluation of the usefulness of feathers as a non-destructive biomonitor for polychlorinated biphenyls (PCBs) using silastic implants as a novel method of exposure

Risk assessment of pollutants requires both monitoring studies in the field and experimental exposure studies. In this study, we evaluated silastic implants as an alternative method of exposure for use in toxicological studies and at the same time evaluated the usefulness of feathers as a non-destructive biomonitor for PCBs. European starlings ( Sturnus vulgaris) were exposed to different doses (including a control group) of environmentally relevant concentrations of PCB 153 during a 15-week period using silastic implants with both ends/only one end sealed. After implantation, there was a rapid and significant increase in PCB 153 blood concentration in the exposed groups. The significant differences in blood concentrations among the treatment groups show that silastic implants are useful as a method of exposure. Moreover, the ratio between the tissue concentrations of two treatment groups reflected the difference in implantation doses between these groups. There was also a clear difference in tissue concentrations among the treatment groups, although we could not test this statistically due to the small sample sizes. The slow release kinetics for a prolonged period and the relatively stable blood concentrations during the 15-week period render silastic tubes very interesting to study the effects of chronic exposure to pollutants. Our results also revealed that sealing both ends of the implant instead of only one did not significantly affect the exposure. There were strong, significant positive correlations between the blood and the tissues, which confirm the use of blood to monitor PCBs. To evaluate the usefulness of feathers as a non-destructive biomonitor for PCBs, we plucked the original and newly grown wing and tail feathers. We observed strong, significant positive correlations between the concentrations in the newly grown feathers and concentrations in the muscle, liver, brain and blood. PCB 153 concentrations in the newly grown feathers differed among the treatment groups. To our knowledge, our results provide the first experimental evidence that feathers are useful as a non-destructive biomonitoring tool for PCBs.

The Effects of Sex, Menstrual Cycle, and Oral Contraceptives on the Number and Activity of Natural Killer Cells

Objectives. The aim of this study was to study the impact of sex, the menstrual cycle, and the use of oral contraceptives (OC) on the number and activity of natural killer (NK) cells.Methods. Both the number and the activity of NK cells were assessed per milliliter of blood, and NK activity (NKA) per NK cell and per lymphocyte was calculated. NKA was measured in each subject using a whole blood assay, which preserves the plasma and all blood cells, and using a washed blood assay, in which plasma is replaced with an artificial medium. The subjects were young (20–29 years old) women with a regular menstrual cycle (n = 39; 26 tested on both the follicular and the luteal phases), age-matched women who use OC (n = 26), and age-matched men (n = 20).Results. Men showed markedly and significantly higher NKA than women with regular menstrual cycles or women using OC, who had the lowest levels of NKA. No significant differences in blood concentration of NK cell were found. Differences in NKA were of similar magnitude in the whole and washed blood assays per milliliter of blood, per NK cell, or per lymphocyte. The menstrual cycle had no significant effect on activity levels of NK cells, but during the periovulatory phase, the number of NK cells per milliliter of blood increased significantly.Conclusions. The observed differences are independent of the presence of serum factors during the in vitro assessment of NKA, but may be related to chronic exposure to sex steroids and to fluctuation in the NK cell expression of β-adrenoceptors.

Effect of first-pass metabolism on enantioselective pharmacokinetics after oral administration of (+)-, (-)- and racemic homochlorcyclizine to rats.

The enantioselective relationship between the pharmacokinetics and hepatic metabolism of homochlorcyclizine hydrochloride (HCZ) was investigated using rats. There were no significant differences in blood concentrations between the three forms after intravenous administration (5 mg/kg) of (+)-, (-)- and racemic HCZ. On the other hand, there were significant differences in the pharmacokinetics between (-)- and (+)-HCZ and between (-)- and racemic HCZ after oral administration (50 mg/kg) of these three forms. The Cmax and AUC0-infinity of (-)-HCZ were lower than those of (+)-isomer and racemate, and its CLo was clearly higher than the others. The (+)-isomer and racemate showed no significant differences in their pharmacokinetic parameters. At a lower dose (10 mg/kg), however, no enantiomeric differences were found in the pharmacokinetic parameters of (+)- and (-)-HCZ. Also examined was the cytochrome p-450-dependent-oxidative metabolism of (+)-, (-)- and racemic HCZ in vitro using rat liver 9000 x g supernatant fraction. The in vitro metabolism of (-)-HCZ was extremely fast, compared with those of the (+)-isomer and the racemate. The Vmax in vitro showed a good correlation with the CLo in vivo after oral administration (50 mg/kg) of all three forms of HCZ. In vitro study of enantiomeric inhibition of the metabolism showed that (+)-HCZ was a competitive inhibitor of (-)-HCZ metabolism, with a Ki of 6.96 microM. (-)-HCZ was also a competitive inhibitor of (+)-HCZ metabolism, with a Ki of 20.4 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

STUDY OF THE POSSIBLE INTERACTION BETWEEN FENTANYL AND PROPOFOL USING A COMPUTER-CONTROLLED INFUSION OF PROPOFOL

A computer-controlled infusion of propofol designed to achieve a target blood concentration of propofol 3 microgram ml-1 was used to investigate the possibility of an interaction between propofol and fentanyl in 32 patients undergoing body surface surgery. In 16 patients who were not receiving a neuromuscular blocker during maintenance anaesthesia with 67% nitrous oxide, there were no significant differences in blood concentrations of propofol between eight patients who received fentanyl 5 micrograms kg-1 before induction of anaesthesia, and eight patients who did not. In a further 16 patients who received vecuronium during maintenance anaesthesia with 67% nitrous oxide, there were no significant differences in blood propofol concentrations between eight patients who received fentanyl 5 micrograms kg-1 before induction of anaesthesia, and eight patients who did not. Fentanyl administered i.v. immediately before a computer-controlled infusion of propofol resulted in more satisfactory anaesthetic conditions than when fentanyl was not used, but did not significantly prolong the recovery time.

Antihypertensive mechanism of oral angiotensin I converting enzyme inhibitor (captopril) in renin-independent essential hypertension

In order to investigate the possible role of bradykinin in the hypotensive mechanism of angiotensin I converting enzyme inhibitor (Captopril) in renin-independent essential hypertension (EHT), we studied the effects of the single administration of 100 mg captopril on plasma bradykinin levels by sensitive radioimmunoassay in 21 EHT, who showed agonistic responses to 1Sar, 8Ile-angiotensin II (A IIA). Fourteen of the patients were low renin and 7 were normal renin EHT. There was no correlation between the baseline plasma renin activity (PRA) and the fall in mean blood pressure (MBP) following captopril administration. When the patients were analyzed according to MBP response, the responders (R) showed a significantly greater bradykinin increment (delta BK, +64%) (p less than 0.05), whereas the nonresponders (NR) did not show such an increase. There was a positive correlation between delta BK and the MBP reduction after captopril in the R group (r = 0.623, p less than 0.05). Plasma aldosterone (PA) decreased profoundly in the R group (-36% from baseline, p less than 0.05). Pretreatment ACE activity was significantly higher in the R group than in the NR group (p less than 0.05). Pressor response to A IIA showed a significantly (p less than 0.05) greater response after captopril administration in the R group. There were no significant differences in blood concentration of captopril between the R and NR groups. The present results suggest that bradykinin may be involved in the hypotensive action of captopril in the EHT subgroup, where the renin-angiotensin system appears to play an inert role for the elevation of blood pressure.