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Biomedical subjects

A Grimaldi

Publications and source records attributed to A Grimaldi.

At least 55 records · Page 3Linked to original sources

PET in psychopharmacology.

Emission tomography techniques and, in particular, positron emission tomography (PET) enable the in vivo study of several physiological and neurochemical variables in human subjects using methods originally developed for quantitative autoradiography. In particular, PET allows one to evaluate in human subjects: (a) the effect of specific neurochemical challenges on regional brain function at rest or under activation; (b) the activity of neurotransmitters and the regional expression of specific molecular targets during pathology including their modulation by drug treatment; (c) the kinetics of drug disposition and activity directly in the target organ. This is of primary interest in the field of biological psychiatry and in psychoactive drugs development, where it is particularly difficult to reproduce human diseases using animal models in view of the peculiarity of this field and the large heterogeneity of each psychiatric illness also inside the same clinical definition. The aim of this paper is to review the principal strategies and the main results of the use of PET in psychopharmacology.

Animals↗

Hirudo medicinalis: a new model for testing activators and inhibitors of angiogenesis.

An increasing body of evidence indicates that in the leech Hirudo medicinalis the angiogenic process is finely regulated and coordinated by the botryoidal tissue. In this paper we provide evidence on the involvement of botryoidal tissue cells in angiogenesis induced in H. medicinalis by a variety of stimuli including surgical wounds or the administration of modulators of neovascularization. Interestingly, we show that either human activators of vascular cell growth, or anti-angiogenic peptides like angiostatin and endostatin, or the drug mitomycin, can induce a prompt biological response in H. medicinalis. We show as well that angiogenesis in this invertebrate shares a surprising degree of similarity with neovascularization in vertebrates, both at the biochemical and cellular levels, because it involves similar growth factors/growth factor receptors, and relies on analogous cell-cell or cell-matrix interactions. For these reasons we suggest that H. medicinalis can be used as a reproducible model for testing activators or inhibitors of angiogenesis, and for investigating the biochemical, ultrastructural and cellular processes involved in new vessel formation.

Angiogenesis Inhibitors↗

Ultrastructure and functional versatility of hirudinean botryoidal tissue.

In leeches, the botryoidal tissue is composed of two different cell types--granular botryoidal cells and flattened endothelial-like cells--localized in the loose connective tissue between the gut and the body wall sac. We have observed that the botryoidal tissue undergoes functional and structural modifications in response to the different needs arising during the life-cycle of the animal. In healthy, untreated leeches, botryoidal cells are organized in cords or clusters, sometimes surrounding few, small lacunae. Conversely, in wounded animals we have observed the transition of the botryoidal tissue from cluster/cord-like structures to a hollow/tubular architecture, typical of pre-vascular structures. We have documented in botryoidal cell cytoplasm the presence of large calcium storage. Moreover, the cytoplasm of botryoidal cells was filled with granules of different form and size, containing iron or melanin, as tested by classic histochemical methods. The presence of elements like iron and calcium was confirmed by the well-established EDS analysis. In response to a surgical wound, botryoidal tissue cells changed their shape and formed new capillary vessels. Concurrently, botryoidal cells secreted iron from cytoplasmic granules into the new cavity: this secretory activity appeared to be related to intracellular calcium fluctuations. At the end of the angiogenic process, botryoidal cells lost their contact with the basal lamina and moved freely in the circulating fluid towards the lesioned area. Interestingly, circulating botryoidal cells were found to carry melanin in the wounded area. This function is probably involved in defense processes. Thus, we have shown that stimulated botryoidal tissue displays a variety of striking structural, secretory and defensive activities.

Animals↗

[Posterior echocardiography windows: usefulness in clinical practice].

Posterior cardiac structures cannot always be imaged by means of standard transthoracic echocardiography. Left pleural effusion leading to pulmonary atelectasis and/or to displacement of air-filled pulmonary tissue displacement, allows ultrasound transmission from a patient's back to his heart through a liquid interface. In this study we present the clinical usefulness of echocardiographic posterior windows for the diagnosis of constrictive pericarditis and aortic dissection in 2 patients in whom the standard transthoracic approach did not permit diagnostic imaging. We conclude that, in the case of left pleural effusion, the use of posterior windows should be encouraged.

Aged↗

How type 1 diabetic patients with good or poor glycemic control cope with diabetes-related stress.

OBJECTIVE: To determine the link between glycemic control and the strategies adopted by patients in coping with diabetes-related stress. MATERIAL AND METHODS: In a cross-sectional study of 122 type 1 diabetic patients, glycemic control was evaluated on the basis of the last mean annual HbA(1c) level, and a comparison was made of two groups of patients, i.e., those with "good control" (HbA(1c)<7.5%) and "poor control" (HbA(1c) > 8.5%). Sociodemographic were collected for all patients by the referring physician. The nature of the diabetes-related stress and the coping strategies adopted by patients were determined by analyzing validated self-assessment questionnaires. RESULTS: Comparison showed that there was no significant difference between the two groups in terms of the patients' age, level of education, age at onset, duration of the diabetes, or the nature of diabetes-related stress factors. In contrast, the difference between the groups was significant in that patients in the "well controlled" group carried out more home blood glucose tests (p<0.02), had fewer complications (p<0.003), and made greater use of so-called "task oriented" strategies (p=0.023), regardless of the existence of any complications. CONCLUSIONS: Even though the nature of the diabetes-related stress appears to be the same for the two groups, type 1 diabetic patients with good glycemic control manage their condition differently (more frequent home blood glucose tests) and use coping strategies that place greater emphasis on problem solving.

Adaptation, Psychological↗

Predictors of response to glimepiride in patients with type 2 diabetes mellitus.

OBJECTIVE: The purpose of DIAMETRE (DIabète et Amarel en Monothérapie. Etude de Titration pour la définition des Répondeurs) was to identify factors predictive of response to glimepiride monotherapy in type 2 diabetic patients in the setting of a prospective multicentre open study. MATERIAL AND METHODS: Patients aged 35-70 years with poorly controlled diabetes [fasting plasma glucose (FPG) > or =1,40 g/l and < 3 g/l at baseline] were treated with glimepiride for 6 months, with dosage titrated from 1-6 mg daily, depending on the monthly FPG measurement. Responders were defined as patients with a) FPG < 7.78 mmol/l (1.40 g/l) and HbA(1c) < 7.5% at endpoint, or b) decrease in FPG > or = 20% and/or HbA1c > or = 10%. Stepwise logistic regression analysis was used to identify factors predictive of response. RESULTS: Of 849 patients evaluable for efficacy, 483 (56.9%) were responders. The response was independently influenced by prior treatment with OADs [OR: 0.399 (0.290-0.549), p=0.0001] and diabetes duration [OR: 0.912 (0.877-0.948), p=0.0001]. Ninety patients (9.2%) experienced 124 episodes of symptomatic hypoglycaemia. Multivariate analysis revealed that a high level of HbA(1c) decreased the risk of symptomatic hypoglycaemia [OR: 0.734 (0.628; 0.858), p=0.0001] whereas a family history of type 2 diabetes doubled this risk [OR: 1.956 (1.246; 3.072), p=0.003]. CONCLUSION: This large-scale study, conducted under conditions approximating to current medical practice, confirms that glimepiride has a favourable risk-benefit ratio in type 2 diabetes mellitus. Diabetes duration and previous treatment with OADs reduced the likelihood of being a responder to treatment.

Adult↗

Effect on compliance, acceptability of blood glucose self-monitoring and HbA(1c) of a self-monitoring system developed according to patient's wishes. The ACCORD study.

OBJECTIVES: To test a blood glucose monitor developed upon diabetic's recommendations (Glucotrend Premium). Self-monitoring of blood glucose (SMBG) generates hope when introduced, however several studies questioned its efficacy and many diabetics judge it too constraining. MATERIAL AND METHODS: Thirty diabetes centres in France, for 6 months in 179 insulin-treated diabetics, using SMBG but non optimally and with HbA(1c) (>=130% of the upper limit). Randomisation to 3 groups: either their previous system (Group A), or to the Glucotrend Premium monitor with a memory to assess compliance (Group B), or to another monitor, new for the patient, and with a memory too, the One Touch Profile (Group C). At entry, and then at 3 and 6 months, patients had an acceptability and compliance questionnaire, HbA(1c), count of weekly hypoglycaemia, record of insulin doses and an assessment of the key compliance factors. RESULTS: HbA(1c) improved significantly in the 3 groups, more markedly in groups B (Glucotrend) and C (One Touch), e.g. - 0.6 +/- 1.1% (group A), - 0.9 +/- 1.2% (group B) and - 1.0 +/- 0.9% (group C) at M6. Acceptability was judged better for groups B and C, an additional benefit for Glucotrend: better accuracy vs laboratory blood glucose (C/L) determinations and a lower utilisation cost. Intermediate (lente) and regular insulin doses only significantly decreased (26% and 10% respectively) in group B (Glucotrend) despite a decrease in HbA(1c). Compliance (defined as 75-150% of recommended self-monitoring) improved within the 3 groups (from 34% to 65%), this improvement was maintained after month 3 (M6: 76%) only in group B (Glucotrend), vs a worsening in groups A and C (M6: 62 and 57% respectively). A better accuracy of C/L was observed with Glucotrend at M0, M3 and M6. CONCLUSION: SMBG has limits due to various causes, and to specific difficulties of this invasive and repetitive technique. The development of a system based on advices formulated by patients themselves, Glucotrend Premium, has resulted in a marked improvement on acceptability, compliance and glucose control.

Adult↗

Recent techniques for tracing pathways in the central nervous system of developing and adult mammals.

Over the last 20 years, the choice of neural tracers has increased manyfold, and includes newly introduced anterograde tracers that allow quantitation of single-axon morphologies, and retrograde tracers that can be combined with intracellular fills for the study of dendritic arbors of neurons which have a specific projection pattern. The combination of several different tracers now permits the comparison of multiple connections in the same animal, both quantitatively and qualitatively. Moreover, the finding of new virus strains, which infect neural cells without killing them, provides a tool for studying multisynaptic connections that participate in a circuit. In this paper, the labeling characteristics, mechanism of transport and advantages/disadvantages of use are discussed for the following recently introduced neural tracers: carbocyanine dyes, fluorescent latex microspheres, fluorescent dextrans, biocytin, dextran amines, Phaseolus vulgaris leucoagglutinin, cholera toxin and viruses. We also suggest the choice of specific tracers, depending on the experimental animal, age and type of connection to be studied, and discuss quantitative methodologies.

Animals↗

Different types of response to foreign antigens by leech leukocytes.

We used morphological and immunocytochemical approaches to characterize and to show the behavior of cells involved in leech inflammatory responses. Leeches were injected with bacterial lipopolysaccharide, fluoresceinated yeasts, sulfate spheres and ciliates (Protozoa). Shortly after injection, migrating cells appeared in the area of injection. The response of the cells occurred in relation to the injected micro or macro antigens. Each injection first provoked a migration of cells towards the non-self material. Afterwards, different responses (degranulation, phagocytosis, encapsulation, melanization) occurred. The migrating cells involved in these series of processes have a similar behavior and are characterized by CD markers of macrophages, NK cells and granulocytes, which are typical of many invertebrates and vertebrates.

Animals↗

Structural and biochemical analysis of the parasite Gordius villoti (Nematomorpha, Gordiacea) cuticle.

The cuticle of the nematomorpha Gordius villoti is a proteinaceous extracellular structure that covers the body during the endoparasitic life in the hemocoelic cavity of insect hosts, and of the free-living adult animals. The ultrastructure of the cuticle has a complex spatial organization with several parallel layers of large diameter fibers, interposed thinner fibrous elements and honeycomb-shaped matrix surrounding the fibers. When adult isolated cuticles were partially solubilized by several compounds, the structure revealed a strong insolubility and the main fibers were always observable. HPLC and spectrophotometric assays carried out to investigate the presence of tyrosine cross-linking, indicated such a mechanism as a key-element in the hardening process of the cuticle. Such data strongly suggest that the Gordius cuticle contains dityrosine compounds, whose formation is probably mediated by endogenous peroxidase activity.

Animals↗

Integumental amino acid uptake in a carnivorous predator mollusc (Sepia officinalis, Cephalopoda).

The epithelial cells of the integument of body, arms and tentacles of Sepia officinalis present on their apical membrane a well-organised brush border and show the morphological and histochemical characteristics of a typical absorptive epithelium. The ability of the integument to absorb amino acids was investigated both in the arms incubated in vitro and in a purified preparation of brush border membrane vesicles (BBMV). Autoradiographic pictures of the integument after incubation of the arms in sea-water with or without sodium, showed that proline intake was Na+-dependent, whereas leucine intake appeared to be a largely cation-independent process. Time course experiments of labelled leucine, proline and lysine uptakes in BBMV evidenced that these amino acids are accumulated within the vesicles in the presence of an inwardly directed sodium gradient. The sodium-driven accumulation proves that cationic and neutral amino acids are taken up by the apical membrane of the epithelium of Sepia integument through a secondary active mechanism. For leucine, a 90% inhibition of the uptake was recorded in the presence of a large excess of the substrate. In agreement with the autoradiography results, an analysis of the cation specificity transport in BBMV showed that leucine uptake had a low cation specificity, whereas lysine and proline uptakes were Na+-dependent. An excess of lysine and proline, which share with alanine two different transport systems in the gill epithelium of marine bivalves, reduced eucine uptake. The possible role of the absorptive ability of the integument in a carnivorous mollusc is discussed.

Alanine↗

Lipopolysaccharide-dependent induction of leech leukocytes that cross-react with vertebrate cellular differentiation markers.

We have designed experiments to characterise leech leukocytes that mediate inflammatory responses. Shortly after inflicting injury to the body wall in the presence of lipopolysaccharides, many cells resembling macrophages, NK cells and granulocytes of vertebrates and many invertebrates migrated to the lesioned area. Nuclei of migrating cells incorporated bromodeoxyuridine. Using human monoclonal antibodies, macrophage-like cells were positive for CD25, CD14, CD61, CD68, CD11b and CD11c. NK-like cells were positive for CD25, CD56, CD57 and CD16, and granulocytes were positive for CD11b and CD11c. In blots of leech extracts, the CD25 monoclonal antibody recognised a band of about 55 kD; the CD56 monoclonal antibody, two bands of about 140 and 210 kD; the CD57 monoclonal antibody, two bands of about 106 and 70 kD; the CD14 monoclonal antibody, a band of about 50 kD; the CD16 monoclonal antibody, a band of about 60 kD. CD61 and CD68 both recognised a band of about 110 kD; CD11b recognised a band of 200 kD, and CD11c, a band of 180 kD.

Animals↗

Disseminated Mycobacterium terrae infection in a patient with advanced human immunodeficiency virus disease.

Mycobacterium terrae has been rarely implicated in human disease and never in patients infected with human immunodeficiency virus (HIV). We describe an HIV-infected patient with disseminated infection by M. terrae with pulmonary and cutaneous clinical manifestations. M. terrae was isolated from both sputum and urine, and identified by both conventional tests and high-performance liquid chromatography. Clinical and microbiological characteristics of this case are compared with those reported in the literature.

AIDS-Related Opportunistic Infections↗