Mobile phone short message service for adherence support and care of patients with tuberculosis infection: Evidence and opportunity.

To attain the Global End Tuberculosis (TB) goals, the treatment of persons with TB requires advancements in coordinated approaches that are low-cost and highly accessible. Treating TB successfully requires prolonged medication regimens with good adherence, which in turn requires patients to be adequately supported. Furthermore, TB care-providers often wish to monitor treatment-taking by patients in order to track the success of their programs and ensure adequate completion of therapies by individuals.

In silico validation of the Autoinflammatory Disease Damage Index.

Introduction: Autoinflammatory diseases can cause irreversible tissue damage due to systemic inflammation. Recently, the Autoinflammatory Disease Damage Index (ADDI) was developed. The ADDI is the first instrument to quantify damage in familial Mediterranean fever, cryopyrin-associated periodic syndromes, mevalonate kinase deficiency and tumour necrosis factor receptor-associated periodic syndrome.

Antiaversive effects of 5HT2C receptor agonists and fluoxetine in a model of panic-like anxiety in rats.

Dose-dependent increases in threshold for operant fear/escape responses of rats submitted to aversive stimulation of the dorsolateral periaqueductal gray (dPAG) were recorded following intraperitoneal injection of three chemically unrelated but selective 5HT2C receptor agonists (Ro 60-0175, Org 12962 and Ro 60-0332) and fluoxetine. The decreased sensitivity of rats to the acute panic-like aversion elicited by stimulation of this limbic periventricular region was detected at dosages devoid of impairing effects on the latencies needed for operant brain stimulation interruption. In this paradigm which has been validated as a simulation of acute anxiety with relevance to panic disorder, the selective activation of 5HT2C receptors by Ro 60-0175, Org 12962 or Ro 60-0332 induces effects analogous to those observed following benzodiazepine receptor activation by antipanic agents such as clonazepam or alprazolam or following non-selective and indirect 5HT receptor activation by fluoxetine.

5-HT2C receptor agonists: pharmacological characteristics and therapeutic potential.

In vitro, (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C4H4O4 and (S)-2-(4,4,7-trimethyl-1,4-dihydro-indeno[1, 2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 exhibited high-affinity binding to the serotonin2C (5HT2C) receptors and stimulated turnover of inositol 1,4,5-triphosphate. Affinity to several of the other 5-HT receptor subtypes and to numerous nonserotonergic receptors was much lower. In rats, both compounds elicited behavioral signs of 5-HT2C receptor agonism but not 5-HT2A receptor agonism.

Differences in modulation of noradrenergic and serotonergic transmission by the alpha-2 adrenoceptor antagonists, mirtazapine, mianserin and idazoxan.

The effects of three compounds with alpha-2 adrenoceptor antagonistic properties, mirtazapine (Org 3770; Remeron), mianserin and idazoxan, were measured on hippocampal noradrenergic and serotonergic transmission in freely moving rats by using microdialysis. Dihydroxyphenylacetic acid (DOPAC) was measured as a correlate of noradrenergic presynaptic activity. Infusing 1 microM tetrodotoxin decreased extracellular serotonin (5-HT) and DOPAC by 65 and 40%, respectively.

Genomic organisation and functional expression of the gene encoding the human serotonin 5-HT2C receptor.

The 5-HT2C receptor gene is unique among the members of the 5-HT receptor family by virtue of its genomic organisation. The human 5-HT2C receptor gene, unlike many other genes for guanine nucleotide binding (G)-proteins, contains three introns which interrupt the coding sequence into four exons. The first two introns are at equivalent positions as compared to the intervening sequences previously found in the 5-HT2(A) receptor gene, suggesting a close evolutionary relationship between both genes.

Reversal by NGF of cytostatic drug-induced reduction of neurite outgrowth in rat dorsal root ganglia in vitro.

Cytostatic drugs, like cisplatin, vincristine and taxol, when given to cancer patients may cause peripheral neuropathies. We were interested in the potential neuroprotective effects of neurotrophic factors against such neuropathies. To this aim we studied the effects of these cytostatic agents on sensory fibers located in the dorsal root ganglia (DRG) in vitro and studied whether nerve growth factor (NGF) could reverse the cytostatic induced morphological changes on intact DRG (1 DRG/well, n = 10 per dose).

The effect of the potential antipsychotic ORG 5222 on local cerebral glucose utilization in freely moving rats.

The effects of administration of different doses of the potential antipsychotic Org 5222 (0.01 and 0.1 mg/kg i.

Depletion of brain serotonin differently affects behaviors induced by 5HT1A, 5HT1C, and 5HT2 receptor activation in rats.

5-hydroxytryptamine (5HT)-depleted rats were subjected to behavioral experiments in which the response to activation of 5HT1A, 5HT1c, and 5HT2 receptor subtypes was measured. Depletion of 5HT was produced by unilateral intracerebroventricular injection of 5,7-dihydroxytryptamine (100 micrograms/rat) or by systemic injection of p-chlorophenylalanine (150 mg/kg injected intraperitoneally 72, 48, and 24 h before the test). The dose-response curve of the 5HT1A-mediated, 8-hydroxy-2-(di-n-propylamino)tetralin (0.

Antagonism of 8-OH-DPAT-induced behaviour in rats.

Selective activation of the 5-HT1A receptor induces lower lip retraction (LLR) in rats. 8-Hydroxy-dipropylamino tetralin (8-OH-DPAT)-induced LLR could not be antagonised by the 5-HT antagonists methysergide, metergoline or mesulergine. In fact, some 5-HT antagonists induced LLR.

Neurochemical studies with the potential antipsychotic compound trans-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1H- dibenz[2,3:6,7]oxepino[4,5-c]pyrrolidine maleate.

trans-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz [2,3:6,7]oxepino[4,5-c]pyrrolidine maleate (Org 5222) has dopamine D2 antagonistic and negligible anticholinergic properties of the classical neuroleptic haloperidol. In addition it combines the strong antiserotonergic and antihistaminergic properties of chlorpromazine and clozapine with the potent dopamine D-1 antagonistic properties of Sch 23390 (R-(+)-delta-chloro-2,3,4,5-tetrahydro-3-methyl-5- phenyl-1H-3-benazepin-7-ol(Z)-2-buteneoate). This in conjunction to its behavioural properties, warrants clinical testing in psychotic patients.

Behavioural pharmacology of trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro- 1H-dibenz[2,3:6,7]oxepino-[4,5-c]pyrrolidine maleate, a compound interacting with dopaminergic and serotonergic receptors.

trans-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1H- dibenz[2,3:6,7]oxepinol[4,5-c]pyrrolidine maleate (Org 5222) is a new compound with effects on animal behaviour indicating strong antipsychotic potential based on antagonism of dopaminergic and serotonergic effects. The compound inhibits apomorphine-induced climbing behaviour, mouse locomotor activity, rat activity in an open field, shuttle box behaviour in rats, pergolide induced circling in 6-hydroxydopamine(6-OHDA) lesioned rats, serotonin agonist-induced forepaw treading, head shakes and penile erections. The compound is less effective in inducing catalepsy, and antagonising SKF-38393 (tetrahydro- 1-phenyl-1H-3-benzazepine-7,8-diol HCl)-induced circling in 6-OHDA-lesioned rats and it does not induce perioral movements in rats.

The effect of antidepressants on aversive periaqueductal gray stimulation in rats.

The selective serotonin (5-HT) uptake inhibitors fluvoxamine and sertraline had anti-aversive effects when administered acutely. Imipramine and clomipramine, which combine noradrenaline (NA) and 5-HT uptake blocking properties, did not have significant effects, whereas the mixed dopamine (DA)/NA uptake blocker nomifensine decreased the thresholds for escape from aversive periaqueductal gray stimulation. These results suggest that indirect 5-HT receptor activation suppresses periaqueductal gray aversion.

5-HT1C receptors in the serotonergic control of periaqueductal gray induced aversion in rats.

The functional role of brain 5-HT and 5-HT receptor subtypes in periaqueductal gray (PAG) induced aversion has been investigated in rats. Antiaversive effects were found with the serotonin agonists TFMPP, mCPP and DOI but not with RU 24969 which was found to facilitate PAG aversion. The first three serotonin agonists share potent 5-HT1C activity while RU 24969 differs with a high 5-HT1A activity.

A large scale, high resolution, automated system for rat sleep staging. I. Methodology and technical aspects.

An automatic rat sleep classification system is described which records and analyses bioelectrical signals from 32 rats over extended periods of time. At present this system is used routinely for the screening of drug effects on sleep. The analysis is based on 3 signals, the parieto-occipital EEG, nuchal EMG and a movement indicator signal.

Local cerebral glucose uptake in anatomically defined structures of freely moving rats.

Two limitations of the classical [14C]2-deoxyglucose (DG) method are the severe stress to which the restrained animals are exposed, and the difficulties with the anatomical analysis of the autoradiograms. The present study describes modifications which circumvent these limitations. Firstly, rats are provided with two chronic indwelling cannulas to allow blood sampling under unrestrained conditions.

Opposite control mediated by central 5-HT1A and non-5-HT1A (5-HT1B or 5-HT1C) receptors on periaqueductal gray aversion.

8-OH-DPAT, a selective 5-HT1A agonist, and mCPP, which has preferential affinity for 5-HT1B and 5-HT1C receptors, were studied for their effects on aversive brain stimulation in rats. Opposite effects were found with these two agonists: D, L-8-hydroxy-N,N-dipropyl-2-aminotetralin HBr (8-OH-DPAT; 0.1-1.

Animal models for anxiety and response to serotonergic drugs.

In examining anxiety and the response of animal models to serotonergic drugs, four aspects should be taken into account: (1) the serotonin receptor is subdivided into at least six receptor subtypes; (2) benzodiazepines have acute anxiety-relieving effects, whereas antidepressants, serotonin-uptake inhibitors, buspirone, and serotonin antagonists have antianxiety effects only after prolonged administration; (3) diagnostic criteria differentiate several distinguishable anxiety disorders that have different responsiveness to serotonin-related drugs, and (4) various types of animal models exist, each responding differently to serotonin-related drugs. Perhaps particular animal models are relevant only for the study of one particular type of anxiety disorder. This differentiated view will be used when discussing the role of 5-hydroxytryptamine (5-HT) receptor subtypes in anxiety disorders and anxiety models.

Ovariectomy and subchronic estradiol-17 beta administration decrease dopamine D1 and D2 receptors in rat striatum.

Ovariectomy and subchronic estradiol-17 beta cause a down-regulation of dopamine D1 and, to a lesser extent, D2 receptors in rat striatum. An intracellular mechanism mediates the DA receptor down-regulation, as various estrogens do not interact with membrane-bound DA receptors in vitro. A common denominator, e.

Effects of serotonin receptor antagonists on PAG stimulation induced aversion: different contributions of 5HT1, 5HT2 and 5HT3 receptors.

The effects of serotonin receptor antagonists with differential selectivity for the various classes of 5HT receptors (5HT1, 5HT2 and 5HT3) were tested for their effects on the response to aversive brain stimulation. Electrical stimulation was administered to the dorsal part of the periaqueductal gray matter (PAG), one of the main cerebral structures subserving negative reinforcement. Stimulation frequency thresholds for escape responses were recorded before and following administration of the compounds.

Effect of metergoline, fenfluramine, and 8-OHDPAT on catalepsy induced by haloperidol or morphine.

The influences of the indirect serotonin agonist fenfluramine (5; 10 mg/kg s.c.), the serotonin antagonist metergoline (5; 10 mg/kg s.

The pharmacological profile of Org 6906, a potential non-sedative antidepressant that combines monoamine uptake inhibition with alpha 2-adrenolytic activity.

(dl)-(5 alpha,8 alpha,9 alpha)-5,8,9,10-Tetrahydro-5,9- methanobenzocycloocten-8-amine hydrochloride (Org 6906) is a potential new antidepressant agent, with a neurochemical profile quite different from that of the classical tricyclic antidepressant drugs. The compound was found active in behavioural tests which are considered to be predictive for antidepressant activity, such as the muricidal test in the rat and the acquired immobility model. Neurochemical studies showed that Org 6906 was an inhibitor of the reuptake of monoamines both in vitro and ex-vivo without having appreciable anticholinergic, antihistaminergic or alpha 1-adrenolytic activity.

Pharmacological evaluation of in vivo tests for alpha 2-adrenoceptor blockade in the central nervous system and the effects of the enantiomers of mianserin and its aza-analog ORG 3770.

A series of compounds with actions on the central nervous system was tested for antagonism of clonidine-induced sleep in chicks and clonidine-induced mydriasis in rats for the purpose of evaluating these methods as tests for demonstrating an in vivo alpha 2-adrenoceptor blocking effect of a novel compound. Clonidine-induced mydriasis was found to be the most selective method. The order of potency for compounds fully antagonizing clonidine-induced mydriasis was MSD 26 greater than physostigmine = idazoxan greater than aptazapine greater than piperoxan greater than yohimbine greater than mianserin greater than tolazoline.

Facilitation of amphetamine-induced rotation by muscarinic antagonists is correlated with M2 receptor affinity.

This study examined the relationship between the affinity of cholinergic drugs for muscarinic receptor subtypes and their potency in potentiating or inhibiting amphetamine-induced rotation. The ascending nigrostriatal dopaminergic pathway was unilaterally lesioned in male Wistar rats using 6-hydroxydopamine. In these rats, ipsiversive rotation induced by amphetamine sulphate (1 mg/kg, s.

Effects of ACTH and related peptides on medial septal self-stimulation.

The effects of ACTH1-24, ACTH4-10, the ACTH4-9 analog Org 2766 and [D-Phe7] ACTH4-10 on medial septal self-stimulation were determined in the rat following intracerebroventricular (ICV) injections. Self-stimulation rates were increased by 0.01-10 micrograms ACTH1-24 or 0.