Effect of escitalopram on Aβ levels and plaque load in an Alzheimer mouse model

BackgroundSeveral neurotransmitter receptors activate signaling pathways that alter processing of the amyloid precursor protein (APP) into β-amyloid (Aβ). Serotonin signaling through a subset of serotonin receptors suppresses Aβ generation. We proposed that escitalopram, the most specific selective serotonin reuptake inhibitor (SSRI) that inhibits the serotonin transporter SERT, would suppress Aβ levels in mice.ObjectivesWe hypothesized that acute treatment with escitalopram would reduce Aβ generation, which would be reflected chronically with a significant reduction in Aβ plaque load.MethodsWe performed in vivo microdialysis and in vivo 2-photon imaging to assess changes in brain interstitial fluid (ISF) Aβ and Aβ plaque size over time, respectively, in the APP/presenilin 1 mouse model of Alzheimer disease treated with vehicle or escitalopram. We also chronically treated mice with escitalopram to determine the effect on plaques histologically.ResultsEscitalopram acutely reduced ISF Aβ by 25% by increasing α-secretase cleavage of APP. Chronic administration of escitalopram significantly reduced plaque load by 28% and 34% at 2.5 and 5 mg/d, respectively. Escitalopram at 5 mg/kg did not remove existing plaques, but completely arrested individual plaque growth over time.ConclusionsEscitalopram significantly reduced Aβ in mice, similar to previous findings in humans treated with acute dosing of an SSRI.

Prevalence of Candida yeasts in oral samples from children with AIDS and children exposed and not exposed to HIV served by SUS in the state of Bahia, Brazil

OBJECTIVE: This study aimed to determine the prevalence of Candida albicans and non-albicans yeast species isolated from oral samples of children with AIDS and of children exposed and not exposed to HIVduring pregnancy and served by the public health system in a county located in the interior of the state of Bahia, Brazil. METHODS: Saliva samples from 50 children aged between 2 and 12 years treated by SUS (group I = control group, group II = group exposed to HIV without seroconversion, and group III = AIDS carriers) were collected, seeded in Sabouraud dextrose agar with chloramphenicol, and fungal cultures were grown at 35 ± 2° C for 24 hours. Three isolated colonies were randomly selected from each individual plaque for identification using the API20 AUX Biomerieux® method. RESULTS: The most frequent fungal species in samples from children not exposed to HIV, exposed to HIV, and AIDS carriers was Candida albicans (48.80%, 25.64%, and 58.13%, respectively). Species of Candida non-albicans were also isolated from all groups studied. CONCLUSIONS: Despite the higher prevalence of Candida albicans in these groups, non-albicans species represented a significant percentage of Candida isolates.

Dental Plaque Flora of the Dog with Reference to Fastidious and Anaerobic Bacteria Associated with Bites

Animal bite wounds are amongst the most common types of traumatic injuries in humans. The organisms isolated from these wounds generally reflect the oral flora of the biting animal and may be fastidious in nature and difficult to identify. This study was undertaken to determine the prevalence of Eikenella corrodens, Actinobacillus actinomycetemcomitans, Porphyromonas and Prevotella spp. in supragingival dental plaque collected from the right maxillary canine and carnassial teeth and the right mandibular canine tooth of dogs. In part one of the study, 30 dogs were used. E. corrodens was found in 62% of these dogs and 44% of individual plaque samples. A. actinomycetemcomitans was not detected in any of the dogs sampled. In pan two, 34 dogs were used to determine the prevalence of the black pigmented anaerobic bacilli (Porphyromonas and Prevotella spp.). Porphyromonas gingivalis was present in 68% of these dogs and 47% of individual plaque samples. Prevotella intermedia was present in 44% of the dogs and 23% of individual plaque samples. The recently described Porphyromonas canoris, Porphyromonas salivosa, Porphyromonas cangingivalis, Porphyromonas cansulci, Porphyromonas crevioricanis and Prevotella denticola species were isolated from only 9%, 6%, 3%, 3%, 3% and 3% of dogs respectively. Porphyromonas gingivicanis was not isolated from any of the animals sampled. In conclusion, black-pigmented anaerobic bacilli were isolated from 91% of the animals sampled and therefore constitute a significant risk with respect to bite wound infections. It is also suggested that the prevalence of E. corrodens in wound infections has been underestimated in previous reports because of use of inappropriate techniques for detecting this organism.

Discordant secretion of relaxin by individual porcine large luteal cells: quantitative analysis by a reverse haemolytic plaque assay

ABSTRACT Individual large luteal cells (LLC) derived from pregnant swine differ conspicuously in their ability to secrete the peptide hormone relaxin under basal and stimulated conditions – the phenomenon of functional heterogeneity. The purpose of this study was to quantitate knowledge of this phenomenon through use of a reverse haemolytic plaque assay, a technique that utilizes antibody-directed, complement-mediated erythrocyte lysis to detect hormone secretion by single LLCs in culture. Measurement of individual plaque areas (an index of the amount of relaxin secreted) demonstrated an approximate 100-fold range in the amount of relaxin secreted by a single cell under basal conditions. This range was doubled by exposure to the phorbol ester, 4β-phorbol 12β-myristate 13α-acetate (PMA; 50 nmol/l). Under basal conditions, 50 and 80% of the total amount of relaxin was secreted by approximately 10 and 30% of all LLCs respectively. The size of these fractions was not influenced by the time of incubation (1–8 h), or by the presence of either of two non-specific stimulatory relaxin secretagogues, PMA (50 nmol/l) or arachidonic acid (1 μmol/l). The unimodal frequency distribution of plaque areas (under basal or stimulated conditions) suggests that relaxin-secreting LLCs comprise a discrete functional population of secretory cells, at least under these experimental conditions. We conclude that a remarkably small fraction of LLCs secretes the majority of relaxin, and that the size of this fraction was not influenced by time or secretagogues. Journal of Endocrinology (1992) 134, 77–83

Ciliary granule plaques: membrane-intercalated particle aggregates associated with Ca2+-binding sites in paramecium

In Paramecium nine rectangular aggregates of membrane-intercalated particles surround the freeze-cleaved membrane of the ciliary base. These “ciliary granule plaques” occur independently of the “ciliary necklace” which is observed in a more basal position on some cilia. In each individual plaque the approximately 10 nm large granules are arranged in a square grid pattern: the granules of one plaque invariably form 3 vertical rows (number of horizontally arranged particles per row: Nh = 3) and 3–6 horizontal rows (mean value fos intrahepatic tributaries then can be approached under direct vision in a relatively bloodless field for safe, accurate liquation and/or reconstruction.

HAPTEN-SPECIFIC TOLERANCE

The induction of tolerance in guinea pigs with a 2,4-dinitrophenyl (DNP) derivative of a copolymer of copolymer of D-glutamic acid and D-lysine (D-GL) leads to a preferential depression of the capacity to produce high affinity anti-DNP antibody in response to immunization with DNP-guinea pig albumin. Thus, immunization 2 wk after tolerance induction with 3 mg of DNP-D-GL results in an immune response in which individual plaque-forming cells (PFC) secreting high affinity anti-DNP antibody are absent and in which the affinity of circulating anti-DNP antibody is reduced. A similar, but less marked, suppression is seen when 0.3 mg of DNP-D-GL is used for tolerance induction. If immunization is delayed until 2 months after tolerance induction, then suppression is restricted to the highest avidity PFC group. Our data is consistent with a state of tolerance in the pool of precursors of anti-DNP antibody-secreting cells induced as a result of their interaction with DNP-D-GL in the absence of specific "helper" cells, which appear to be lacking for DNP-D-GL. In such a situation, the affinity of receptors on precursor cells for tolerogen and the concentration of tolerogen appear to be crucial determinants of whether an individual cell will become tolerant.

RECEPTORS ON IMMUNOCOMPETENT CELLS

During the course of the immune response to dinitrophenylated guinea pig albumin (DNP-GPA), a striking and parallel increase in avidity for ϵ-DNP-L-lysine occurs in the receptors on antigen-binding lymphocytes, antibody secreted by individual plaque-forming cells, and serum antibody molecules. A detailed analysis of the avidity distribution of antibody produced by plaque-forming cells indicates that this "immunologic maturation" is primarily due to a preservation of the high avidity subpopulation and a striking loss in the low avidity population rather than to sequential appearance of these cells. Moreover, the demonstration of the increased avidity of receptors of antigen-binding lymphocytes, which appear to be precursors of antibody-synthesizing cells, strongly suggests that the antigen-driven selectional process operates primarily on this cell type.