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Background: Pectus carinatum may be a major issue for adolescent patients, as chest-wall malformations can have a negative impact on body image and induce self-esteem disorders. Bracing has become the first line treatment for adolescent patients whose anterior chest wall is still flexible. The main obstacle is the tolerability of the bracing device along with the patient's compliance to the device. The aim of this study was to examine the quality of life of adolescent patients treated with bracing to correct pectus carinatum in our institution. From November 2021 to July 2023, 28 patients with pectus carinatum were treated with bracing therapy in our chest wall deformities unit. We used a bivalve brace, manufactured with computer-aided design. All patients were asked to answer a multiple-choice questionnaire designed to assess how bracing therapy impacts their daily life, treatment compliance, and overall satisfaction. Patients who wore the brace for at least 3 months, and at least 5 days per week and 10 h per day, are defined as compliant with the bracing protocol. Results: The mean age of the patients was 14 ± 1.36 years. Patients wore the brace for an average of 10.1 ± 6.9 months in the compliance group (n = 18), and 2.2 ± 2.5 months in the non-compliance group (n = 10). Our results show that compliant patients are fairly satisfied of the comfort of the brace, with a limited impact of the device on their daily activities and social life. However, non-compliant patients report the following dissatisfactions regarding the brace: higher pain scores, difficulty in breathing, and issues sleeping with the brace. The compliant patients noted a significant improvement in the appearance of their chest, and were satisfied with the appearance of their chest. The non-compliant patients did not notice any changes. Conclusions: Compliant patients treated with a bi-valve brace for pectus carinatum seem to have a good quality of life with a limited impact on their daily life and social activities. The bi-valve brace also seems to be an effective therapy in compliant patients. [ABSTRACT FROM AUTHOR]

We describe the first microfluidic device for in vitro testing of brachytherapy (BT), with applications in translational cancer research. Our PDMS-made BT-on-chip system allows highly precise manual insertion of clinical BT seeds, reliable dose calculation using standard clinically-used TG-43 formalism and easy culture of naturally hypoxic spheroids in less than 3 days, thereby increasing the translational potential of the device. As the BT-on-chip platform is designed to be versatile, we showcase three different goldstandard post-irradiation bioassays and recapitulate, for the first time on-chip, key clinical observations such as dose rate effect and hypoxia-induced radioresistance. Our results suggest that BT-on-chip can be used to safely and efficiently integrate BT and radiotherapy to translational research and drug development pipelines, without expensive equipment or complex workflows. [ABSTRACT FROM AUTHOR]

Introduction: Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) are clonal myeloid malignancies, characterized by bone marrow failure leading to cytopenias (and possible myeloproliferation for CMML) and a high propensity to evolve to Acute Myeloid Leukemia (AML). Objective and Methods: The aim of our retrospective study was to evaluate the clinical and hematological features; the prevalence of MDS subtypes, R‐IPSS, and the outcome of 106 Armenian MDS/CMML patients diagnosed over the 2008–2020 period in a single Armenian Hematology center and compare them to French MDS patients included in the GFM registry. Results: Median age in the Armenian cohort was 64 years (range 19–84) and 55% were males. The main MDS subtypes were MDS‐MLD (29.2%) and MDS‐SLD (27.3%), the least frequent was del 5q (0.9%). By comparison, a higher prevalence of MDS‐MLD, MDS‐EB2, and MDS‐RS was found in the French cohort. Armenian patients' cohort generally had poor access to standard MDS treatment and 42.3% of the patients were transfusion dependent. Overall survival, however, did not significantly differ between Armenian and French cohorts. Conclusion: Our study stresses issues regarding epidemiology, access to diagnosis, difficulties of risk stratification, and access to treatment. [ABSTRACT FROM AUTHOR]

In this work, the adsorption mechanism of phenol on activated carbon from aqueous solutions was investigated. Batch experiments were performed as a function of adsorbent rate, solution temperature, phenol initial concentration, stirring speed, and pH. The optimal operating condition of phenol adsorption were: mass/volume ratio of 0.6 g.L−1, temperature of 20 °C and stirring speed of 300 rpm. The equilibrium data for the adsorption of phenol were analyzed by Langmuir, Freundlich, and Temkin isotherm models. It was found that the Freundlich and Temkin isotherm models fitted well the phenol adsorption on the activated carbon and that the adsorption process is favorable. The Langmuir equilibrium isotherm provides a maximum adsorption of 156.26 mg.g−1 at 20 °C. The pseudo-first-order, pseudo-second-order, intraparticle diffusion, and Boyd models were used to fit the kinetic data. The adsorption kinetics data were well described by the pseudo-second-order model. The kinetic was controlled by the external diffusion by macropore and mesopore, as well as by the micropore diffusion. The thermodynamic study revealed the exothermic and spontaneous nature of phenol adsorption on activated carbon with increased randomness at the solid-solution interface. On the other hand, a very large model based on the optimization parameters of phenol adsorption using k-nearest neighbor coupled with the gray wolf optimizer algorithm was launched to predict the amount of phenol adsorption. The KNN_GWO model showed an advantage in giving more precise values related to very high statistical coefficients (R = 0.9999, R2 = 0.9998 and R2adj = 0.9998) and very low statistical errors (RMSE = 0, 0070, MSE = 0.2347 and MAE = 0.2763). These advantages show the efficiency and performance of the model used. [ABSTRACT FROM AUTHOR]

The Boutaleb massif is a massif located in the Hodna Mountains constituting a hinge between the high plateaus of Setif and the Saharan atlas. The Boutaleb massif extends from an altitude of 700m in the south at the edge of the forest. The work carried out in the Boutaleb massif clearly demonstrates the presence of phytosociological classes of degradation, one cites the Onido-Rosmarinetea class; the class of Lygeo-Stipetea, the plant groups within each phytocenosis, corresponds to a stage in a regressive series of vegetation and the relationship which then binds these groups, is of a dynamic order. This study made it possible to make a floristic inventory of the whole massif: the flora is very rich, containing more than 338 species and 213 genera, belonging to 54 botanical families. The endemic element is relatively well represented, with 4.30% of the flora of the region (14 species listed). To this is added a significant faunal wealth with 72 bird species, 11 mammalian species and 7 reptile species. The interest presented by these northern plant and animal species at the southern limit of their habitat, hence the need for their protection and the preservation of their ecological habitat, which must be included in a development model which will serve as a to decision makers. [ABSTRACT FROM AUTHOR]

The clinical importance of radiotherapy in the treatment of cancer patients justifies the development and use of research tools at the fundamental, pre-clinical, and ultimately clinical levels, to investigate their toxicities and synergies with systemic agents on relevant biological samples. Although microfluidics has prompted a paradigm shift in drug discovery in the past two decades, it appears to have yet to translate to radiotherapy research. However, the materials, dimensions, design versatility and multiplexing capabilities of microfluidic devices make them well-suited to a variety of studies involving radiation physics, radiobiology and radiotherapy. This review will present the state-of-the-art applications of microfluidics in these fields and specifically highlight the perspectives offered by radiotherapy on-a-chip in the field of translational radiobiology and precision medicine. This body of knowledge can serve both the microfluidics and radiotherapy communities by identifying potential collaboration avenues to improve patient care. [ABSTRACT FROM AUTHOR]

Background: MDS‐RS patients are characterized by chronic anemia and a low risk of Acute Myeloid Leukemia (AML) progression and they generally become Red Blood Cell (RBC) transfusion dependent (TD). Study design and methods: We performed a retrospective "real‐life" observational study of 6 months in 100 MDS‐RS TD patients, recruited in 12 French centers, to describe transfusion characteristics, and evaluate the frequency and causes of hospitalizations, health costs, and morbidity, associated with transfusion dependency, in a French population of RBC transfusion‐dependent MDS‐RS patients. Results: 79% of the patients had high transfusion burden (HTB) and 21% low transfusion burden (LTB). HTB patients had a longer disease duration (6 vs. 3.7 years, p = 0.0078), more frequent iron chelation (82% vs. 50%, p = 0.0052) and higher serum ferritin (p = 0.03). During the 6‐month study period, 22% of the patients required inpatient hospitalization, 36% of them for symptomatic anemia requiring emergency RBC transfusion. The 6‐month median transfusion costs, including the cost of the day care facility, transportation to and from the hospital, iron chelation, and lab tests, was 16,188€/patient. Discussion: MDS‐RS represents the archetypal type of chronically transfused lower‐risk MDS. Most of those patients have a high transfusion burden and thus frequently need visits to the hospital's day care facility, and frequent hospitalizations, with an overall high median treatment cost. Those costs should be compared with costs of new treatments potentially able to avoid RBC transfusion dependence and to reduce the complications of chronic anemia in MDS‐RS patients. [ABSTRACT FROM AUTHOR]

The forest vegetation of Djebel Boutaleb is experiencing degradation in its entirety under the effect of burly anthropogenic pressure and climatic risks. Hence, the vegetation cover requires analyzes to conserve and protect it with a better knowledge of the composition and the vegetation dynamics of this ecosystem. For that, spatio-temporal studies of vegetation evolution have been applied using multitemporal Landsat imagery. An NDVI classification technique was used to generate thematic maps, with 4 major classes. The use of remote sensing data and geographic information system (GIS) has made it possible to detect important changes in vegetation cover over 35 years. The results showed that between 1984 and 2019, the overall estimation of the evolution of the vegetation of Djebel Boutaleb is positive; with a negligible strong gain estimated 0.17% and an insignificant progression estimated at 72.67%. [ABSTRACT FROM AUTHOR]

Copyright of Algerian Journal of Arid Environment (AJAE) is the property of University of Kasdi Merbah Ouargla and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article, titled "Giant thoracic calcinosis," discusses a case of a 21-year-old patient with dermatomyositis, a rare condition that is complicated by subcutaneous calcinosis on the right lateral thoracic wall. The article includes images of the lesion and describes the surgical procedure used to remove it. The authors declare no conflicts of interest, and all relevant data are available within the manuscript. The article is authored by Anaëlle Chermat, Hugues Begueret, Jeremy Tricard, Jacques Jougon, Yaniss Belaroussi, and Matthieu Thumerel from the Service de chirurgie thoracique, cervicale et de transplantation pulmonaire, Hôpital Haut-Lévêque—CHU de Bordeaux in France. [Extracted from the article]

OBJECTIVES The association of unstable heart disease and resectable lung cancer is rare. The impacts of staged management, cardiac surgery with cardiopulmonary bypass (CPB) versus angioplasty, on long-term survival and cancer recurrence remain debated. We report our experience using staged management. METHODS From 1997 to 2016, 107 patients were treated at the Quebec Heart and Lung Institute: 72 underwent cardiac surgery with CPB (group 1), 35 were treated with angioplasty (group 2), followed by oncological pulmonary resection. RESULTS Two postoperative deaths (3%) and 1 ischaemic heart complication (1%) were reported in group 1. One death (3%) was reported in group 2. Two-year overall survival was 82% (59/72) in group 1 and 80% (28/35) in group 2; 5-year overall survival was 62% (33/53) in group 1 and 63% (19/30) in group 2. Two-year disease-free survival in group 1 was 79% (57/72) and 77% (27/35) in group 2; 5-year disease-free survival was 58% (31/53) in group 1 and 60% (18/30) in group 2. The independent risk factors for death after thoracic surgery were transfusions (P  = 0.004) and grade ≥3 complications (P  = 0.034). Independent risk factors for recurrence included the cancer stage (P  < 0.001) and, paradoxically, a shorter delay between cardiac and lung procedures (P  = 0.031). CONCLUSIONS When a staged management remains feasible after cardiac procedure, oncological outcomes of patients with cardiopathy and lung cancer are satisfactory. CPB does not seem to be deleterious. The delay between procedures should intuitively be as small as possible but not at the expense of good recovery after the cardiac procedure. [ABSTRACT FROM AUTHOR]

Our study aims to develop the first list of taxa endemic to the Sétif region. In this research, we mainly relied on floristic work carried out on a North-South transect covering two types of bioclimate and including forest and steppe massifs. Thus, we have counted 148 endemic taxa including 25 subspecies. Belonging to 33 botanical families and dominated by Asteraceae with 15.54%. The endemics of North Africa are the most representative with 62 taxa. The region of Sétif is very impacted; its plant cover is subject to climatic and anthropogenic constraints, which would certainly contribute to more scarcity or even to the gradual disappearance of endemic and rare species very soon. [ABSTRACT FROM AUTHOR]

Center of cutaneous leishmaniasis, the Setif steppes is currently experiencing a significant upsurge in this endemic and parasitic disease. To treat themselves the majority of the rural population has resorted mainly to toxic plants known for their magical and healing properties. The present study focused on the plant species potentially used in the treatment of these diseases. The floristic inventory identified six vascular species, including Peganum harmala L., Carlina gummifera (L.) Less., Deverra scoparia Coss. and two cryptogam species of scaly lichens (Lecanora esculenta Evernsmann and Rhizoplaca melanophtalma (DC.) Leuckert). These taxes constitute the most natural and effective antileishmanian remedy in the rural community. For the therapeutic route, our follow-up surveys are based on participatory observation, the knowledge held by the healers, the attitude of the users, the practices and the treatment time. These have enabled us to refine our knowledge and perception of the application of traditional herbal treatment, which is of great importance at the regional level where the nomadic and sedentary populations still have knowledge of leishmanicide species. It turns out that more in-depth scientific research will have to develop this empirical knowledge for a better management and preservation of this floristic heritage by fighting against this epidemiology which prevails in Algeria. [ABSTRACT FROM AUTHOR]

Rare endemic and threatened with extinction, Pistacia atlantica Desf. is one of the heritage species of Algeria, it occupies a very important place from an ecological and socio-economic point of view. The Atlas pistachio tree is distinguished by very high resistance and known for its high plasticity and its adaptation to arid and semi - arid climates. In the region of Sétif Pistacia atlantica Desf. exists only in the semi-arid Setifian steppe, in djebel Boutaleb, djebel Youssef and djebel Zdimm. Faced with its vulnerability, this species confined to a very restricted area, requires protection and sustainability of its development to ensure its sustainability within the Sétif region. [ABSTRACT FROM AUTHOR]

Copyright of Revue des BioRessources is the property of University of Kasdi Merbah Ouargla and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We report an unusual case of giant intracardiac medullary thyroid cancer metastasis. A 76‐year‐old woman with a 9‐year history of medullary thyroid cancer presented an unexpected 7.5 cm mass in the right ventricle. Complete resection and tricuspid valve replacement led to 40 months survival. [ABSTRACT FROM AUTHOR]

This work aims to consider the combination of different technologies regarding energy production and management with four possible configurations. We present an energy management algorithm to detect the best design and the best configuration from the combination of different sources. This combination allows us to produce the necessary electrical energy for supplying habitation without interruption. A comparative study is conducted among the different combinations on the basis of the cost of energy, diesel consumption, diesel price, capital cost, replacement cost, operation, and maintenance cost and greenhouse gas emission. Sensitivity analysis is also performed. [ABSTRACT FROM AUTHOR]

The article looks at a study regarding the addition of suberoylanilide hydroxamic acid to azacitidine for patients with higher risk myelodysplastic syndromes and azacitidine failure. It mentions DNA methylation and histone deacetylation (HDAC) are synergistic in terms of gene silencing and the combination of inhibitors. It also mentions toxicity and efficacy of new drugs in combination with hypomethylating agents (HMAs).

Erythropoiesis-stimulating agents (ESAs) remain the first-line treatment of anemia in lower risk myelodysplastic syndromes (MDS) without 5q deletion. A preliminary report suggested that adding all-trans retinoic acid (ATRA) to ESAs may improve their erythroid response, particularly in patients with high endogenous erythropoietin (EPO) level, and may improve other cytopenias. We conducted a prospective multicenter study of EPO-β and ATRA in anemic MDS patients with marrow blasts <10% and either previous ESA failure or relapse, endogenous EPO >500 U/l or other cytopenia(s) (absolute neutrophilic count <1.0 G/l or platelets <50 G/l). A total of 59 patients were evaluable after 12 weeks of treatment. The erythroid response rates according to IWG 2000 and 2006 criteria, respectively, were as follows: overall: 49 and 36%; patients with previous ESA failure (n=28): 43 and 32%; patients with endogenous EPO >500 U/l (n=18): 11 and 19%; patients transfused >2 red blood cells units/month (n=28) 43 and 39%. Only one neutrophil, but no platelet response, and no major side effect were observed. EPO-β–ATRA combination appears a possible therapeutic option in anemia of MDS having failed an ESA alone, but not in patients with high endogenous EPO level, and does not improve neutropenia and thrombocytopenia.Leukemia (2009) 23, 673–678; doi:10.1038/leu.2008.362; published online 8 January 2009 [ABSTRACT FROM AUTHOR]

Corrosion-Electrochemical behavior of a commercial API5CT grade L80 type 13Cr tubing enriched with microalloying elements is studied in 6, 7.5, 9, 12 and 15% HCl solutions by electrochemical methods. The objective is to contribute to the comprehension of corrosion phenomena caused by HCl of similar concentrations, generally used in acidizing job. The corrosion morphology is examined by scanning electron microscopy (SEM) coupled with EDAX. The soluble corrosion products are analyzed by atomic absorption spectroscopy and colorimetric methods. General, as well as localized, corrosion is present. The severest general corrosion with a maximum rate of 26 mm/year is obtained at 15% HCl. The localized corrosion which morphologically differs as function of HCl concentrations is revealed by SEM investigation. In all the above HCl solutions, the commercial 13% Cr martensitic stainless steel tubing shows no passive state. Above 6% HCl, the microalloying elements promote forming a discontinuous film of the corrosion products. The corrosion rate slightly decreases in 15% HCl compared to the published data on a conventional 13% Cr martensitic stainless steel tubing. This is due to both the chemical composition (silicon, manganese and vanadium) and microstructural properties. Copper seems to additionally accelerate the corrosion of the alloy. [ABSTRACT FROM AUTHOR]

Simple Summary: Hypoxia is found in half of the solid cancers and is a major contributor to treatment resistance and promotion of metastasis, leading to shortened patient survival. No user-friendly in vitro preclinical tool exists to study natural chronic hypoxia. The aim of this study was to design a microfluidic device allowing easy culture, maintenance, treatment, and analysis of naturally hypoxic sarcoma spheroids. We confirmed that our jumbo spheroids (>750 µm) contained hypoxic cores, as they expressed the hypoxic marker protein Carbonic Anhydrase IX (CAIX). Quantification of DNA strand breaks from radiotherapy and a hypoxia pro-drug demonstrated hypoxia-dependent treatment responses. Our novel microfluidic device is versatile and convenient for both fundamental and preclinical research, to better understand and treat hypoxic tumors. Hypoxia is a key characteristic of the tumor microenvironment, too rarely considered during drug development due to the lack of a user-friendly method to culture naturally hypoxic 3D tumor models. In this study, we used soft lithography to engineer a microfluidic platform allowing the culture of up to 240 naturally hypoxic tumor spheroids within an 80 mm by 82.5 mm chip. These jumbo spheroids on a chip are the largest to date (>750 µm), and express gold-standard hypoxic protein CAIX at their core only, a feature absent from smaller spheroids of the same cell lines. Using histopathology, we investigated response to combined radiotherapy (RT) and hypoxic prodrug Tirapazamine (TPZ) on our jumbo spheroids produced using two sarcoma cell lines (STS117 and SK-LMS-1). Our results demonstrate that TPZ preferentially targets the hypoxic core (STS117: p = 0.0009; SK-LMS-1: p = 0.0038), but the spheroids' hypoxic core harbored as much DNA damage 24 h after irradiation as normoxic spheroid cells. These results validate our microfluidic device and jumbo spheroids as potent fundamental and pre-clinical tools for the study of hypoxia and its effects on treatment response. [ABSTRACT FROM AUTHOR]

Handling-induced convulsions in the quaking mouse can be blocked by: phenobarbital, pentobarbital or phenytoin; postsynaptic alpha-adrenoceptor agonists (noradrenaline, phenylephrine, CRL 40028); presynaptic alpha-adrenoceptor blockers (yohimbine, mianserine); catecholamine liberating agent (amphetamine); noradrenaline reuptake inhibitors (cocaine, imipramine, desipramine). Moreover, the protective effect of yohimbine was antagonized by clonidine, prazosin or alpha-methylparatyrosine, and the protective effect of CRL 40028 was antagonized by prazosin but not by alpha-methyltyrosine. Drugs acting by other mechanisms (pilocarpine, atropine, trihexyphenidyl, (−)-5-HTP, methysergide, pimozide, clonidine, alpha-methyl DOPA, prazosin, isoprenaline, salbutamol) did not protect against convulsions. A slight protection was obtained with high doses of apomorphine and also with (±)-propranolol. This effect is probably not related, to blockade of betaadrenoceptors because the same effect was obtained with (+)propranolol. In young quaking mice, where susceptibility to convulsions is low, both postsynaptic alpha-adrenoceptor blockers and presynaptic alpha-adrenoceptor antagonist lowered the convulsive threshold. Thus, this seems to constitute an interesting model for the in vivo study of substances which affect the central alpha-adrenoceptors either pre- or postsynaptically. [ABSTRACT FROM AUTHOR]

Eleven benzodiazepines were evaluated in the staircase test in mice. The behavioural parameters measured were the number of steps climbed and the number of rears during a 3-min test. Climbing and to a lesser extent rears were enhanced at low doses, whereas both parameters, particularly rearing, were reduced at higher doses. The differential effects of the drugs on the two parameters were used to determine indices of anxiolytic efficacy for each drug where increases in climbing were taken to indicate the onset of anxiolytic activity and decreases in rearing the onset of sedative activity. The compounds could be ranked according to these indices in a manner which appears to reflect their therapeutic profile in man. [ABSTRACT FROM AUTHOR]

A novel test procedure for antidepressants was designed in which a mouse is suspended by the tail from a lever, the movements of the animal being recorded. The total duration of the test (6 min) can be divided into periods of agitation and immobility. Several psychotropic drugs were studied: amphetamine, amttriptyline, atropine, desipramine, mianserin, nomifensine and viloxazine. Antidepressant drugs decrease the duration of immobility, as do psychostimulants and atropine. If coupled with measurement of locomotor activity in different conditions, the test can separate the locomotor stimulant doses from antidepressant doses. Diazepam increases the duration of immobility. The main advantages of this procedure are (1) the use of a simple, objective test situation, (2) the concordance of the results with the validated 'behavioral despair' test from Porsolt and, (3) the sensitivity to a wide range of drug doses. [ABSTRACT FROM AUTHOR]

Male Wistar rats were trained to press a lever with food reinforcement according to a continuously reinforced schedule (CRF). Afterwards, rats were subjected to three experimental sessions (30 min each) during which responding was rewarded according to a progressive ratio schedule (following an initial 2-min CRF period, the number of presses necessary for the pellet delivery was doubled every second minute). Responding during the first half of each session, i.e., pressing for food, was maintained at a significant level, whereas it was almost suppressed during the second part of the session. As compared to controls (200±20 presses/30 min) animals given amfonelic acid (0.5, 1 mg/kg IP), methylphenidate (4, 8 mg/kg IP), caffeine (16 mg/kg IP), cocaine (4 mg/kg IP), oxolinic acid (32 mg/kg IP), nomifensine (4 mg/kg IP), DR 250 (2, 4 mg/kg IP) and d-amphetamine (0.25, 0.5, 1 mg/kg IP) showed an increased rate of responding ranging from 400 to 950 presses/30 min. In contrast, apomorphine, MK 486+ l-dopa, trihexyphenidyl, imipramine, salbutamol and diazepam did not increase responding. These results suggested that this test is highly sensitive for psychomotor stimulants and perhaps for their ability to enhance the reinforcing value of the reward or stimuli associated with the reward. Such activity seemed related to a catecholaminergic substrate since the increase of responding induced by amphetamine was blocked by pimozide, d,l-propranolol and prazosin. [ABSTRACT FROM AUTHOR]

The antagonism of hypothermia induced by two doses of apomorphine (1 or 16 mg/kg) is proposed as an improved screening test for both neuroleptics and antidepressants. Low dose apomorphine-induced hypothermia (1 mg/kg) differentiates sulpiride-like neuroleptics (which better antagonize this effect of apomorphine than other effects such as stereotyped behavior) from haloperidol-like drugs. The latter equally antagonize the two effects of apomorphine. The effects of sulpiride are also distinct from those of chlorpromazine-like drugs which strongly antagonize stereotyped behavior, but not hypothermia induced by apomorphine. Hypothermia induced by a high dose of apomorphine (16 mg/kg) is not antagonized by neuroleptics, but is strongly antagonized by antidepressants (imipramine-like drugs, amineptine, amoxapine, nomifensine, viloxazine) and potential antidepressants (beta-adrenergic stimulants). The use of these two tests rapidly screens both antidepressants and neuroleptics and classifies neuroleptics according to their profile of action on the dopaminergic system. [ABSTRACT FROM AUTHOR]

The stimulant effects of oxolinic acid were investigated in rats and mice. This drug, given orally, consistantly induced, in doses ranging from 16 to 256 mg·kg, locomotor stimulation and stereotyped behavior. These effects were antagonized by pimozide (1 mg·kg), α-methyltyrosine (64 mg·kg) or reserpine (4 mg·kg, 24 h before testing) pretreatment, suggesting a facilitatory role of oxolinic acid on catecholaminergic processes. Diazepam (4-16 mg·kg) reduced the stimulant effects induced by oxolinic acid but not those induced by amphetamine; oxolinic acid (8 mg·kg) markedly reduced the antipunishment effect elicited in rats by diazepam (2 mg·kg). Since benzodiazepines have been reported to enhance GABA functioning, these data suggest that oxolinic acid may impair GABA transmission. However, neither muscimol (0.5-1 mg·kg) or γ-acetylenic-GABA (16-64 mg·kg) selectively reduced the stimulant effects elicited by oxolinic acid. Therefore, the possible facilitation exerted by this drug on catecholaminergic systems may not derive from the release of an inhibitory GABAergic control. [ABSTRACT FROM AUTHOR]

Common effects of four beta-adrenergic blocking drugs have been investigated in mice using classical and new psychopharmacological tests. Propranolol, alprenolol, practolol and penbutolol reduced the increase in locomotor activity produced by reserpine after MAO inhibition; they produce hypothermia when associated with amphetamine and they increase oxotremorine-induced hypothermia. Regarding these three tests the studied substances ranged themselves in the same order of potency: penbutolol > propranolol > alprenolol > practolol. Propranolol and penbutolol decreased the toxicity provoked in crowded mice by amphetamine or by the association pargyline-reserpine; alprenolol and practolol did not. Propranolol, penbutolol and alprenolol antagonized the amphetamine-induced increase in motor activity; practolol did not. When used at doses for which d-l propranolol was active, the dextrogyre isomer of propranolol was without effect whatever the test studied. It is suggested that for the selection of a beta-blocking drug, regarding central effects in man, the tests described would deserve consideration. [ABSTRACT FROM AUTHOR]

Behavioral and pharmacological tests were performed on rats (males Wistar A.F.) maintained either during 6 weeks at 20 or 5 in a cage (40×40×17 cm) or during 6 weeks at 20 and during 8 days at 5 in cage. When compared to 5/cage-reared rats, overcrowded rats (20/cage) exhibit a lessened locomotor activity in the open field, staircase test, and Y maze; rearings, intrasession habituation, and spontaneous alternation were not altered. It seems difficult to relate this lessened locomotor activity to an enhanced emotionality level. Although overcrowded rats showed heavier adrenals, their susceptibility to restraint-induced gastric ulcers, their 'neophobic' responses to new food, and their sensitivity to the stimulating effect of oxazepam in the Y maze were not modified. Sensitivity to amphetamine-induced stereotyped behavior and to pentobarbital-induced hypnosis was found to be increased in overcrowded rats. Apomorphine-induced stereotypy and barbital sleeping time were not modified. All these data (except the fact that barbital onset of hypnosis was delayed in overcrowded rats) may suggest an altered hepatic metabolism in rats reared at 20 in a cage. In overcrowded rats an enhanced amphetamine-induced stereotyped behavior was associated with a lessened locomotor activity. Moreover, after 8 days at 5 in a cage, this increased sensitivity to amphetamine (and to pentobarbital) completely disappeared, whereas locomotor activity was not fully restored. This suggests that amphetamine sensitivity is not related to the predrug activity level of the animals. [ABSTRACT FROM AUTHOR]

The following behavioral modifications were observed after a single i.p. administration of T.R.H. (thyreo-tropin-releasing hormone) in mice or rats at doses higher than 4mg · kg: I. an increased reactivity to stimuli, II. periods of excitation alternating with periods of aggressivity, III. unusual movements ('tail-rattling' and 'wet-dog'), IV. the reserpine- or oxotremorine-induced hypothermia was antagonized in mice by T.R.H. in doses of 1 mg · kg and higher, but only a few other symptoms were influenced. The prochlorperazine-induced catalepsy in rats was antagonized by T.R.H.; under the experimental conditions, sudden hyperkinetic episodes were observed. The toxicity of pargyline- l-Dopa association was slightly increased, amphetamine- or apomorphine-induced stereotyped behavior was unchanged. This spectrum of activity is different from other known psychotropic drugs. [ABSTRACT FROM AUTHOR]

The role of atrial distension and/or adrenergic mechanisms in the regulation of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP, norepinephrine (NE), epinephrine (E) and left atrial diameter at rest, during and after graded bicycle exercise has been studies in 8 healthy male subjects after single doses of placebo, tertatolol 5 mg (a non-selective β-adrenoceptor blocker), prazosin 1 mg (an α-adrenoceptor antagonist) and their combination. Systolic and diastolic left atrial diameters were measured before, during and just after exercise by bidimensional echocardiography. Exercise caused an increase in plasma ANP, which was greater after tertatolol alone, and tertatolol plus prazosin, than after placebo or prazosin alone; the mean area under the plasma ANP concentration curve was increased by 35% after tertatolol alone, by 45% after tertatolol and prazosin compared to placebo, and by 82% and 94%, respectively when compared to prazosin alone. The rise in plasma ANP was more marked during the post-exercise period: 80% after tertatolol alone, 67% after tertatolol and prazosin compared to placebo, and 133% and 115%, respectively, compared to prazosin alone. The rise in plasma ANP was accompanied by an increase in both the systolic and diastolic atrial diameter, which was also significantly greater after tertatolol alone and the combination than placebo, or after prazosin alone. β-Adrenoceptor blockade alone did not affect the plasma catecholamine concentrations, but the exercise-induced increase in plasma norepinephrine was significantly potentiated by prazosin and by prazosin plus tertatolol, and that of plasma epinephrine by the drug combination. We conclude that potentiation of the exercise-induced increase in plasma ANP by β-blockers may be due to atrial stretching consequent on the decreased myocardial contractility and relaxation, and not to alpha-1 adrenoceptor stimulation. Any increase in plasma catecholamines did not play an important role in ANP secretion. [ABSTRACT FROM AUTHOR]

The influence of three beta-adrenergic blocking agents was studied on the stereotyped behavior induced in rats by a range of doses of d-amphetamine or apomorphine. The stereotyped behavior was assessed either clinically (quotation from 0 to 3 at various times for each rat) or using the confinement motor activity test. From 8 mg/kg (i.p.) onwards, propranolol and prinodolol clearly potentiated the amphetamine-induced stereotyped behavior without any modification of the apomorphine-induced stereotyped behavior. Practolol, known for its poor passage through the blood-brain barrier had only a slight effect. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) defines a group of heterogeneous hematologic malignancies that often progresses to acute myeloid leukemia (AML). The leading treatment for high-risk MDS patients is azacitidine (Aza, Vidaza®), but a significant proportion of patients are refractory and all patients eventually relapse after an undefined time period. Therefore, new therapies for MDS are urgently needed. We present here evidence that acadesine (Aca, Acadra®), a nucleoside analog exerts potent anti-leukemic effects in both Aza-sensitive (OCI-M2S) and resistant (OCI-M2R) MDS/AML cell lines in vitro. Aca also exerts potent anti-leukemic effect on bone marrow cells from MDS/AML patients ex-vivo. The effect of Aca on MDS/AML cell line proliferation does not rely on apoptosis induction. It is also noteworthy that Aca is efficient to kill MDS cells in a co-culture model with human medullary stromal cell lines, that mimics better the interaction occurring in the bone marrow. These initial findings led us to initiate a phase I/II clinical trial using Acadra® in 12 Aza refractory MDS/AML patients. Despite a very good response in one out 4 patients, we stopped this trial because the highest Aca dose (210 mg/kg) caused serious renal side effects in several patients. In conclusion, the side effects of high Aca doses preclude its use in patients with strong comorbidities. [ABSTRACT FROM AUTHOR]

A double-blind, crossover study was carried out in general practice on the hypnotic activity of 0.25 mg brotizolam in patients aged between 18 and 70 years complaining of insomnia (11 men, 28 women). Patients reported that they slept better, that they awoke less frequently and that they slept longer with brotizolam than with placebo. Overall the patients preferred brotizolam to placebo, and subjective assessments of well-being after brotizolam did not differ from those after placebo. Brotizolam was well tolerated and there were no incidents of note. [ABSTRACT FROM AUTHOR]

In mice, pilocarpine - or oxotremorine - induced decrease in locomotor activity and increase of the reaction time to pain were antagonized by atropine and not by methylatropinium. Identical doses of atropine and methylatropinium suppressed the antagonism of the cholinergics towards reserpine-induced palpebral ptosis. Cholinergics-induced hypothermia was not clearly antagonized by atropine or methylatropinium. [ABSTRACT FROM AUTHOR]