High-sensitivity method for the determination of LSD and 2-oxo-3-hydroxy-LSD in oral fluid by liquid chromatography‒tandem mass spectrometry

Forensic Toxicology - We have developed and validated a high-sensitivity method to quantify lysergic acid diethylamide (LSD) and 2-oxo-3-hydroxy-LSD (OH-LSD) in oral fluid samples using...     

Rates of adverse reactions to first and second doses of BCG vaccination: results of a large community trial in Brazilian schoolchildren.

OBJECTIVE: To evaluate the incidence of adverse reactions to first and second bacille Calmette-Guérin (BCG) vaccination in schoolchildren. SETTING AND DESIGN: Enhanced surveillance in a Brazilian trial. Suspected reactions were reported to a nurse who visited cases and completed a standard form. RESULTS: Among 71341 schoolchildren studied, 33 reactions were reported. Of these, 25 fulfilled the criteria, resulting in a rate of one per 2854 vaccinations, with no deaths or BCG-osis. Reactions to second doses were more common than to first BCG vaccinations, but this difference was not statistically significant. CONCLUSIONS: Adverse reactions to a second dose of BCG may be more frequent than reactions to a first dose, but they are still rare events.     

Time-dependent modulation of AMPA receptor phosphorylation and mRNA expression of NMDA receptors and glial glutamate transporters in the rat hippocampus and cerebral cortex in a pilocarpine model of epilepsy

The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. It has been demonstrated in this model that the phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit is increased 1 h after pilocarpine treatment. Moreover, alterations in the levels of glutamate transporters have been associated with chronic epilepsy in humans. Despite these studies, the profile of these changes has not yet been addressed. We analyzed the protein content and phosphorylation profile of the AMPA receptor GluR1 subunit by western blotting. We also used quantitative real-time polymerase chain reaction to analyze the expression of glial glutamate transporters and the N-methyl-d-aspartate receptor NR1 subunit in the hippocampus (Hip) and cerebral cortex (Ctx) at different time points after pilocarpine-induced status epilepticus (Pilo-SE) in male adult Wistar rats. Biochemical analysis was performed in the Hip and Ctx at 1, 3, 12 h (acute period), 5 days (latent period), and 50 days (chronic period) after Pilo-SE. Key findings include an increase in the phosphorylation of GluR1-Ser⁸⁴⁵ in the Ctx and GluR1-Ser⁸³¹ in the Hip at different times during the acute period, and a decrease in the total content of the GluR1 subunit in the Ctx in the latent period. There was a down-regulation of the mRNA expression and protein levels of EAAT1 and EAAT2, and a decrease of the NR1 mRNA expression, in the Ctx during the latent period. Notably, during the chronic period, the EAAT2 mRNA expression and protein levels decreased while the NR1 mRNA levels increased in the Hip. Taken together, our findings suggest a time- and structure-dependent imbalance of glutamatergic transmission in response to Pilo-SE, which might be associated with either epileptogenesis or the seizure threshold in MTLE-HS.     

Acute Depletion and Recovery of Peritoneal B-1 Lymphocytes in BALB/c Mice after a Single Injection of Mercury Chloride

The acute toxicity of mercury (Hg) to B cells was studied in the peritoneal cavity of BALB/c mice, a coelomic space where both B-1 and B-2 subsets of B lymphocytes are present. Up to 24 hr after a single in situ Hg injection, the peritoneal cavity became virtually devoid of lymphocytes, particularly of the B-1 subset. Lymphocyte depletion was more severe for B than T cells. This depletion was associated with partial lymphocyte activation (CD69⁺) at 6 hr of treatment and it was due to apoptosis rather than to necrosis. Partial recovery of both B and T cells was observed in the peritoneal cavity 48 hr after the Hg injection. The phenomenon was followed by a second decrease in peritoneal lymphocytes 72 hr after Hg. Neutrophils that entered the peritoneal cavity because of the Hg injection were resistant to apoptosis. No significant changes in lymphocyte number or subpopulation were found in the spleen and thymus of the mice up to 72 hr after the Hg treatment. We concluded that B lymphocytes were severely affected by the toxic effects of Hg. Our data suggest that Hg-induced unbalance in the repertoire of B cells, of the B-1 subset in particular, may result later in the secretion of the high titres of pathogenic autoantibodies that are found in the Hg-induced lupus disorder of BALB/c mice.     

Reduced Motivation in Perinatal Fluoxetine-Treated Mice: A Hypodopaminergic Phenotype

Early life is a sensitive period, in which enhanced neural plasticity allows the developing brain to adapt to its environment. This plasticity can also be a risk factor in which maladaptive development can lead to long-lasting behavioral deficits. Here, we test how early-life exposure to the selective-serotonin-reuptake-inhibitor (SSRI), fluoxetine, affects motivation, and dopaminergic signaling in adulthood. We show for the first time that mice exposed to fluoxetine in the early postnatal period exhibit a reduction in effort-related motivation. These mice also show blunted responses to amphetamine and reduced dopaminergic activation in a sucrose reward task. Interestingly, we find that the reduction in motivation can be rescued in the adult by administering bupropion, a dopamine-norepinephrine reuptake inhibitor used as an antidepressant and a smoke cessation aid but not by fluoxetine. Taken together, our studies highlight the effects of early postnatal exposure of fluoxetine on motivation and demonstrate the involvement of the dopaminergic system in this process.SIGNIFICANCE STATEMENT The developmental period is characterized by enhanced plasticity. During this period, environmental factors have the potential to lead to enduring behavioral changes. Here, we show that exposure to the SSRI fluoxetine during a restricted period in early life leads to a reduction in adult motivation. We further show that this reduction is associated with decreased dopaminergic responsivity. Finally, we show that motivational deficits induced by early-life fluoxetine exposure can be rescued by adult administration of bupropion but not by fluoxetine.     

Ventricular remodeling in growing rats with experimental diabetes: The impact of swimming training

Diabetic cardiomyopathy is associated with cardiac muscle remodeling, resulting in myocardial dysfunction, whereas exercise training (ET) is a useful nonpharmacological strategy for the therapy of cardiac diseases. This study tested the effects of low-intensity swimming-training on the structural remodeling of the left ventricle (LV) in growing rats with unmanaged experimental diabetes. Thirty-day-old male Wistar rats were divided into four groups (n = 5/group): sedentary-control (SC), exercised-control (EC), sedentary-diabetic (SD), and exercised-diabetic (ED). Swimming-training rats exercised 5 days/week, 90 min/day, with a load of 5% BW during 8 weeks. Sections of LV were stained with Periodic acid-Schiff, Sirius Red, and Gomori's reticulin. Seven days and 8 weeks after streptozotocin (STZ) induction (60 mg kg⁻¹ BW), blood glucose (BG) in the diabetic groups (SD = 581.40 ± 40.48; ED = 558.00 ± 48.89) was greater (p < 0.05) than in their controls (SC = 88.80 ± 21.70; EC = 85.60 ± 11.55). Swimming-training reduced BG by 23 mg/dL in the diabetics (p > 0.05). The LV of diabetic rats had increased interstitial collagen and reticular fibers on the extracellular matrix and presented glycogen accumulation. More importantly, all these adverse tissue changes induced by STZ were attenuated by ET. Together, these findings support the idea of a beneficial role of exercise in the LV remodeling in rats with unmanaged type-1 diabetes mellitus.     

Homogeneity of Trypanosoma cruzi I, II, and III populations and the overlap of wild and domestic transmission cycles by Triatoma brasiliensis in northeastern Brazil

The genetic variability of 24 Trypanosoma cruzi isolates from humans (11) and triatomines (13) in northeastern Brazil was analyzed by random amplified polymorphic DNA (RAPD) and compared with taxonomic groups, host, and geographical origin of the parasite. TcI (12.5 %), TcII (45.8 %), and TcIII (41.6 %) showed a similarity coefficient (SC) of 0.74 using the mean of three primers and 0.80, 0.75, and 0.66 for λgt11-F, M13-40F, and L15996 primers, respectively. The samples were clustered according to their phylogenetic origin in two polymorphic and divergent branches: one associated with TcI and the other with two subbranches corresponding to TcII and TcIII. TcI was only identified in humans and correlated with the Id homogenous group (0.80 SC). TcII from humans and Triatoma brasiliensis showed 0.86 SC and was clustered according monoclonal or polyclonal populations with similar RAPD profiles detected among the vector and/or humans in different municipalities. TcIII was isolated exclusively in sylvatic cycles from T. brasiliensis and Panstrongylus lutzi and showed low variability (0.84 SC) and high homology mainly among isolated populations at the same locality. The homology of T. cruzi among different hosts and locations suggests the distribution of principal clones circulating and reveals an overlapping between the sylvatic and domestic cycles in this area, where T. brasiliensis infected with TcII acts as link in both environments. This species is important to maintain TcII and TcIII in wild cycles and deserves particular attention due an emergent risk of these populations being introduced into the domestic cycle; moreover, its clinical and epidemiological implications remain unknown.     

Accuracy of three-dimensional virtual simulation of the soft tissues of the face in OrtogOnBlender for correction of class II dentofacial deformities: an uncontrolled experimental case-series study

Oral and Maxillofacial Surgery - To assess whether virtual simulations of the projection of the soft tissues of the face after class II bimaxillary orthognathic surgery, generated from 3D...