Autoradiographic mapping of μ opioid receptor changes in rat brain after long-term haloperidol treatment: relationship to the development of vacuous chewing movements

Brain opioid systems modulating basal ganglia function may be involved in the development of neuroleptic-induced orofacial dyskinesias. This study examined changes in μ opioid receptors labeled with [³H]D-Ala², N-MePhe⁴, Gly-ol⁵-enkephalin ([³H]DAMGO) in 79 different brain regions of rats showing vacuous chewing movements after 21 weeks of treatment with haloperidol decanoate (HAL). Dopamine D₂ receptors labeled with [³H]raclopride were also examined in the adjacent sections of the same brains. For brain analyses HAL-treated rats were divided into a group showing high incidence of vacuous chewing movements (VCMs) and a group showing low incidence of VCMs. As expected, long-term HAL resulted in a pronounced elevation of D₂ receptors in caudate-putamen, n. accumbens, globus pallidus and olfactory bulbs (range: 27–70% increases) compared to controls. These changes were equal in magnitude in both HAL-treated groups, irrespective of the frequency of VCMs. In HAL-treated rats [³H]DAMGO was significantly decreased in several parts of the basal ganglia, including n. accumbens (−21%, P < 0.01), patchy area of the anterior caudate-putamen (−12%, P < 0.05), ventral pallidum (−27%, P < 0.01) and globus pallidus (−21%, P < 0.02). Statistically significant decreases were also seen in the subthalamic nucleus (−12%, P < 0.05) and ventrolateral thalamus (−21%, P < 0.05), both of which are targets of basal ganglia output. However, as in the case of [³H]raclopride binding, [³H]DAMGO changes were generally seen both in the High VCM and the Low VCM groups. These results confirm that long-term haloperidol leads to a decrease in μ-opioid binding in basal ganglia and related structures, similar to what is seen after 6-OHDA denervation. The observed μ-receptor binding changes may be a contribution factor, but do not appear sufficient to account for the differential development of neuroleptic-induced vacuous chewing movements. Received: 2 February 1996 / Final version: 10 June 1996     

Innate profiles of cytokines implicated on oral tolerance correlate with low- or high-suppression of humoral response

Oral tolerance (OT) is being studied with great interest because of its therapeutic potential in allergy and autoimmunity. In the present study, two mouse strains with extreme phenotypes of OT susceptibility (TS) or resistance (TR) to ovalbumin (OVA) were used to demonstrate whether the tr and ts genes, cumulated during 18 generations of bi‐directional genetic selection, influence expression of immunobiological traits in naive or antigen‐gavaged TR/TS mice. The difference in anti‐OVA titres was 2048‐fold between OVA‐gavaged TS and TR mice. Tolerance susceptibility to OVA gavage in individuals from a (TS × TR)F₂ population was 24% high‐susceptibility, 62% low‐susceptibility and 14% non‐tolerant. Different antigens, unrelated to OVA, were tested by gavage and TS mice were generally susceptible while TR mice were resistant. The stability of TS and TR phenotypes was not affected by the use of strict protocols of intraperitoneal immunization or feeding over 30 consecutive days. The levels of interleukin‐2 (IL‐2), IL‐4, interferon‐γ and IL‐10 cytokines evaluated in concanavalin A‐stimulated spleen cells from naive mice and in OVA‐stimulated spleen cells from OVA‐gavaged mice were higher in TS mice. Interleukin‐10 was up‐regulated in OVA‐gavaged TS mice and down‐regulated in TR mice. In naive mice, the percentage of CD4⁺ CD25⁺ and CD4⁺ Foxp3⁺ spleen cells and IL‐10 expression by CD4⁺ cells was significantly higher in TS mice. These results indicate that regulation of IL‐10 expression could be an important factor contributing to the mechanisms controlling OT susceptibility, and that the OT responses of TR and TS individuals strongly correlate with their innate potential to secrete this cytokine.     

Ambulatory blood pressure monitoring

Ambulatory blood pressure monitoring (ABPM) in adults is proving to be useful. The aim of this study was to determine if ABPM is accurate in the lower blood pressure range encountered in children and, equally important, whether it is acceptable to children. Thirty one children, between the ages of 6 and 18 years, were assessed using an ambulatory blood pressure monitor that uses an auscultatory method. Blood pressure was measured in the contralateral arm with a mercury sphygmomanometer and an oscillometric device at the beginning and end of the study for comparison. Over a blood pressure range of 90-130 mm Hg systolic and 40-80 mm Hg diastolic, a close agreement was found with the sphygmomanometer; the limits of agreement (+/- 2 SD) were 11.6 mm Hg for systolic blood pressure and 13.6 mm Hg for diastolic blood pressure. The bias was less than 1.0 mm Hg. The ambulatory device was worn by all patients for at least 16 hours with an average of 52 recordings per patient. The majority found the device comfortable to wear and were not woken from sleep.     

Lactobezoar and cows' milk protein intolerance

A baby girl of an atopic family who developed eczema, asthma, and cows' milk protein intolerance was found to have a gastric lactobezoar at age 9 1/2 months. She responded well to the removal of the bezoar and to the appropriate dietary treatment.     

冠状动脉搭桥术早期并发症及死亡率(附196例报告)

1985年1月～1987年12月作者于荷兰格罗宁根医学科学院心胸外科主做了196例冠状动脉搭桥术。术后早期死亡2例(1.0％)、内出血3例(1.5％)、胸骨裂开2例(1.0％)、心律紊乱40例(20.4％)、围手术期心肌梗塞5例(2.6％),本文就术后早期并发症进行了讨论。     

Apports des explorations vasculaires ultrasonores à l''étude des néphropathies chez l''enfant

The proximity of child's kidneys from the cutaneous surface allows a particularly sensitive exploration by doppler sonography, which in addition has the major advantage of being a non-invasive, non-irradiating and painless technique. However there are two limitations to this technique: the lack of cooperation of some children and the still limited availability of high quality equipment in intensive care units. Indeed most of the applications described in this paper (ie. pyelonephritis, renovascular hypertension, tumors, acute renal insufficiency and renal vein thrombosis) require, besides an experienced operator, expensive power doppler equipment including high frequency and high resolution probes.     

Annexin A1 subcellular expression in laryngeal squamous cell carcinoma

Aims: Annexin A1 (ANXA1) is a soluble cytoplasmic protein, moving to membranes when calcium levels are elevated. ANXA1 has also been shown to move to the nucleus or outside the cells, depending on tyrosine‐kinase signalling, thus interfering in cytoskeletal organization and cell differentiation, mostly in inflammatory and neoplastic processes. The aim was to investigate subcellular patterns of immunohistochemical expression of ANXA1 in neoplastic and non‐neoplastic samples from patients with laryngeal squamous cell carcinomas (LSCC), to elucidate the role of ANXA1 in laryngeal carcinogenesis. Methods and results: Serial analysis of gene expression experiments detected reduced expression of ANXA1 gene in LSCC compared with the corresponding non‐neoplastic margins. Quantitative polymerase chain reaction confirmed ANXA1 low expression in 15 LSCC and eight matched normal samples. Thus, we investigated subcellular patterns of immunohistochemical expression of ANXA1 in 241 paraffin‐embedded samples from 95 patients with LSCC. The results showed ANXA1 down‐regulation in dysplastic, tumourous and metastatic lesions and provided evidence for the progressive migration of ANXA1 from the nucleus towards the membrane during laryngeal tumorigenesis. Conclusions: ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra‐epithelial neoplasms; it was not found related to prognostic parameters, such as nodal metastases.     

Toll-like receptor 4 (TLR4)-dependent proinflammatory and immunomodulatory properties of the glycoinositolphospholipid (GIPL) from Trypanosoma cruzi

We have demonstrated recently that the glycoinositolphospholipid (GIPL) molecule from the protozoan Trypanosoma cruzi is a TLR4 agonist with proinflammatory effects. Here, we show that GIPL-induced neutrophil recruitment into the peritoneal cavity is mediated by at least two pathways: one, where IL-1beta acts downstream of TNF-alpha, and a second, which is IL-1beta- and TNFRI-independent. Moreover, NKT cells participate in this proinflammatory cascade, as in GIPL-treated CD1d(-/-) mice, TNF-alpha and MIP-2 levels are reduced significantly. As a consequence of this inflammatory response, spleen and lymph nodes of GIPL-treated mice have an increase in the percentage of T and B cells expressing the CD69 activation marker. Cell-transfer experiments demonstrate that T and B cell activation by GIPL is an indirect effect, which relies on the expression of TLR4 by other cell types. Moreover, although signaling through TNFRI contributes to the activation of B and gammadelta+ T cells, it is not required for increasing CD69 expression on alphabeta+ T lymphocytes. It is interesting that T cells are also functionally affected by GIPL treatment, as spleen cells from GIPL-injected mice show enhanced production of IL-4 following in vitro stimulation by anti-CD3. Together, these results contribute to the understanding of the inflammatory properties of the GIPL molecule, pointing to its potential role as a parasite-derived modulator of the immune response during T. cruzi infection.