The promoter region of the ribosomal RNA (rRNA) genes of Leishmania amazonensis was characterised and the transcription start point, defined by primer extension, was shown to be a T residue, 1048 nucleotides upstream of the beginning of the 18S sequence. A repetitive element of 60 bp was identified in the intergenic spacer. This element did not show sequence similarity with the region around the transcription start point. Conserved sequences were found in the external transcribed spacer of L. amazonensis, Trypanosoma cruzi and Crithidia fasciculata rRNA genes, 150 nucleotides downstream of the transcription start point. These sequences might be involved in processing events of the rRNA precursor molecule. The general organisation of the gene resembles the pattern observed for the ribosomal cistron in eukaryotic cells. Constructs containing the L. amazonensis promoter region upstream of the chloramphenicol acetyltransferase (cat) gene were able to drive the expression of the reporter gene in transient transfection experiments. CAT expression could be detected even when no trans-splicing acceptor sequence was added to the constructs, although its presence enhanced 5-fold the level of CAT activity. Species-specificity of the RNA polymerase I promoter activity was also demonstrated since constructs containing the L. amazonensis promoter region were unable to drive CAT expression when transfected into the related trypanosomatids, T. cruzi, C. fasciculata and Endotrypanum schaudini.

Animals↗

PubMedDate not supplied

Progressive decline in spatial learning and integrity of forebrain cholinergic neurons in rats during aging.

Rats distributed over five different age groups, 3, 12, 18, 24 and 30 months of age, were screened for their spatial learning and memory ability in the Morris water maze, and the degree of place navigational impairments was correlated with morphological changes in the four major forebrain cholinergic cell groups (medial septum, MS; vertical limb of the diagonal band of Broca, VDB; nucleus basalis magnocellularis, NBM; and striatum) using choline acetyltransferase (ChAT) and nerve growth factor receptor (NGFr) histochemistry. Impaired place navigation developed progressively with age, such that 8% of the 12-month-old rats, 45% of the 18-month-old, 53% of the 24-month-old, and over 90% of the 30-month-old rats were behaviorally impaired. Significant reductions in the number of ChAT/NGFr-positive cell bodies, amounting to between 19 and 45%, were observed in all four cell groups, and the remaining cells were reduced in size (6-24% reduction in cross-sectional area in the oldest age groups). Although the morphological changes were less severe and tended to develop later than the behavioral impairments, there was overall a significant correlation between water maze performance and ChAT/NGFr-positive cell counts, and to a lesser degree also cell size in all four cell groups. These changes were also highly correlated with age. The highest correlations were seen in MS, VDB and NBM, which are known to play a role in spatial memory performance in young rats. The results indicate that degenerative and/or atrophic changes in the forebrain cholinergic system and decline in spatial learning ability are parallel processes during aging. Although the magnitude of the morphological changes does not appear to be substantial enough, by itself, to explain the severe spatial learning impairments that develop in the oldest animals, the present data are consistent with the view that impaired function in the forebrain cholinergic system can contribute to age-dependent cognitive decline in rodents.

Aging↗

PubMedDate not supplied

Decline in visual attention and spatial memory in aged rats.

The present study was a longitudinal study of age-related changes in performance of the 5-choice serial reaction time task, a test of visual attention. Following acquisition of the task, animals were tested on two occasions on their ability to perform the 5-choice task. In Test 1 (Young: 7 months; Aged: 13-14 months) no age-related effects on baseline performance were revealed. However, increasing the attentional load of the task revealed an impairment in choice accuracy by animals of the Aged group. In Test 2 (Young: 10-11 months; Aged 23-24 months), animals of the Aged group were significantly impaired on the baseline schedule of the task compared to the Young group. The deficit in accuracy on the task could be improved in the Aged animals by decreasing the attentional load. The results of the present study suggest a deficit in attentional function as a result of the aging process, markedly similar to that observed following lesions of the basalo-cortical cholinergic system.

Aging↗

PubMedDate not supplied

Phosphocholine of pneumococcal teichoic acids: role in bacterial physiology and pneumococcal infection.

Pneumococci have an absolute nutritional requirement for choline. Choline is incorporated as phosphocholine (PCho) into lipoteichoic (LTA) and teichoic acid (TA). The PCho residues are required for transformability, the activity of autolysins, the separation of daughter cells after cell division and for anchoring a family of surface proteins which play important roles in pneumococcal infection. The genes encoding the enzymes for PCho incorporation are described. Two strains that acquired the ability to grow in the absence of choline are discussed.

Animals↗

PubMedDate not supplied

Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor.

In aged rodents, impairments in learning and memory have been associated with an age-dependent decline in forebrain of cholinergic function, and recent evidence indicates that the cholinergic neurons in the nucleus basalis magnocellularis, the septal-diagonal band area and the striatum undergo age-dependent atrophy. Thus, as in Alzheimer-type dementia in man, degenerative changes in the forebrain cholinergic system may contribute to age-related cognitive impairments in rodents. The cause of these degenerative changes is not known. Recent studies have shown that the central cholinergic neurons in the septal-diagonal band area, nucleus basalis and striatum are sensitive to the neurotrophic protein nerve growth factor (NGF). In particular, intraventricular injections or infusions of NGF in young adult rats have been shown to prevent retrograde neuronal cell death and promote behavioural recovery after damage to the septo-hippocampal connections. It is so far not known, however, whether the atrophic cholinergic neurons in aged animals are responsive to NGF treatment. We report here that continuous intracerebral infusion of NGF over a period of four weeks can partly reverse the cholinergic cell body atrophy and improve retention of a spatial memory task in behaviourally impaired aged rats.

Acetylcholinesterase↗

PubMedDate not supplied

[The influence of psychosocial factors on mental well-being and physical complaints before and after undergoing an in-patient abortion].

In this study, 57 women were examined in terms of the influence of different psychosocial factors on their subsequent mental well-being and physical complaints one day before, one day after, and 3 months after undergoing an in-patient abortion. Furthermore a control group of 40 in-patients (women with pregnancy related problems) were included in the study. The results show that prior to the abortion, most women reported a multitude of psychological and physical problems. However, it was also shown that for the majority of the women interviewed, mental well-being and physical complaints improved significantly one day and 3 months after the abortion. While feelings such as relief predominated immediately postoperatively, after 3 months, participants reported feeling cheerful and interested in activities. Further, it was demonstrated that women whose general mood was more pronouncedly anxious-depressive one day prior to operation later (after 3 months) reported many complaints and worse well-being. It appears that these women were not able to experience the abortion as a problem solutions. Finally, the great importance of the quality of their relationship and cohesion was demonstrated in the decision to abort, while pregnancy counselling was found to have no effect.

Abortion, Induced↗

PubMedDate not supplied

Antipsychotic efficacy of the antidepressant trimipramine: a randomized, double-blind comparison with the phenothiazine perazine.

BACKGROUND: The tricyclic antidepressant trimipramine exhibits several features (e. g., dopaminergic effect, molecular structure similar to a neuroleptic, receptor-binding profile similar to clozapine) that suggest its potential as an antipsychotic medication. The aim of the study was to investigate the antipsychotic potential of trimipramine in a controlled clinical trial comparing its antipsychotic efficacy with that of a neuroleptic. METHOD: In a German multi-center, randomized, double-blind trial, the antipsychotic efficacy of trimipramine was compared with that of the phenothiazine neuroleptic perazine, using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impressions (CGI). Antidepressant efficacy of both agents was measured by use of the Bech-Rafaelsen Melancholia Scale (BRMES). Ninety-five patients with acute schizophrenia (DSM-III-R) and a BPRS total score > 40 at baseline were treated with either 300-400 mg trimipramine or 450-600 mg perazine for 5 weeks. RESULTS: Therapeutic equivalence of both treatments (in the dosages used) could not be demonstrated (change in BPRS total score, per-protocol [PP] analysis, one-sided equivalence testing). However, intention-to-treat (ITT) as well as PP analysis showed a statistically significant decrease in the BPRS total scores in both treatment groups (PP: trimipramine, 56.5 +/- 9.8 to 44.1 +/- 17.9; perazine, 56.4 +/- 10.8 to 37.9 +/- 12.9). Significant decreases in all BPRS and PANSS subscores as well as CGI results and response rate support the antipsychotic efficacy of trimipramine. The BRMES total scores significantly decreased in both treatment groups without showing a significant difference between the two agents. Trimipramine was better tolerated than perazine and did not elicit extrapyramidal symptoms. CONCLUSION: Trimipramine failed to exhibit therapeutic equivalence to perazine in the dosages used. However, there was evidence of a substantial antipsychotic effect of trimipramine. It may be a useful medication if depressive symptoms in psychotic patients require antidepressant treatment or if other antipsychotics cannot be administered.

Antidepressive Agents↗

PubMedDate not supplied

Upper airway epithelial cells support eosinophil survival in vitro through production of GM-CSF and prostaglandin E2: regulation by glucocorticoids and TNF-alpha.

Production of GM-CSF by epithelial cells has been implicated in eosinophil survival within the airways, although GM-CSF promotes neutrophil and monocyte survival as well. Using primary cultures of human airway epithelial cells, we undertook a comprehensive examination of factors that enhance eosinophil survival or apoptosis. Unstimulated epithelial cells were compared to epithelial cells stimulated with TNF-alpha in the presence or absence of dexamethasone. A striking increase in survival was observed when peripheral blood eosinophils were cultured with supernatants derived from unstimulated and TNF-alpha-stimulated epithelial cells. Cultured epithelial cells were examined for transcripts of cytokines shown to enhance eosinophil survival (GM-CSF, IL-3, IL-5, IL-13, and IFN-gamma), and transcripts for cytokines promoting apoptosis (IL-10 and TGF-beta). GM-CSF transcripts, but not the other cytokines, were present in unstimulated epithelial cells, and levels were increased with TNF-alpha stimulation. TNF-alpha stimulation increased the levels of GM-CSF and PGE2 in epithelial cell supernatants and dexamethasone suppressed the TNF-alpha induced increases. The survival effects of the TNF-alpha-stimulated supernatants were effectively blocked by neutralizing antibodies to GM-CSF or by dexamethasone treatment of epithelial cells. Selectivity of GM-CSF for eosinophil versus neutrophil survival was demonstrated and suggests that epithelial cell regulation of GM-CSF and PGE2 contribute to eosinophil survival in vitro and may contribute to eosinophil accumulation in allergic disease.

Apoptosis↗

PubMedDate not supplied

[Diarrhea caused by Campylobacter in patients with hematologic diseases].

Diarrhoea caused by Campylobacter infection in two adult patients was observed: one with erythroleukemia, and another with non-Hodgkin lymphoma. An infection developed in both cases during the period of agranulocytosis and decreased specific immunologic response to cytostatics. In case of the second patient, it has also been due to the underlying disease. The course of the disease has been different in both patient. It was dramatic with high fever and multiple fetid stools in one patient, and mild, successfully treated within a few days, in the second.

Adult↗

PubMedDate not supplied

[Effect of livex on hypochromic anemia].

Livex is a lyophilised preparation of the bovine blood which contains 70% of proteins and 0.3% of iron. Livex was given to 25 patients with iron deficiency anemia (group I), and 25 patients with lymphoreticular malignancies accompanied by iron deficiency with or without anemia. The dose was 5 g t.i.d. for 3 months. The majority of patients of group I were women. Excessive menstrual bleeding and chronic gastritis were most common causes of iron deficiency in this group. Livex statistically significantly increased hemoglobin, hematocrit, corrected reticulocyte count, mean erythrocyte hemoglobin, serum iron, percent transferrin saturation, and leukocyte count. Therapy produced significant increase in serum iron, total iron binding capacity, and percent transferrin saturation in patients with lymphoreticular malignancies.

Adult↗

PubMedDate not supplied

Anticonvulsant effects of propranolol and their pharmacological modulation.

The anticonvulsant activity of propranolol was investigated in mice and rats using the electroshock seizure test (MES) and in special cases the electrically evoked hippocampal afterdischarges as a model. The results show that racemic propranolol as well as the two enantiomers were effective against MES. (+)-propranolol, the isomer with negligible beta-adrenoceptor blocking capacity revealed the stronger effect, its efficacy was comparable with the potency of phenobarbital, an overadditive synergism could be demonstrated. Subchronic administration of the two enantiomers led to a significantly reduced ED50 value of (-)-propranolol 24 h after the last application, the (-)-isomer became more effective. The (+)-propranolol did not reveal significant differences. In unrestrained rats with chronically implanted electrodes propranolol increased the stimulation threshold and reduced the duration of electrically evoked hippocampal afterdischarges. Investigations with drugs affecting monoaminergic systems in the CNS demonstrated that the noradrenergic system might play a predominant role in modulating the anticonvulsant effectiveness of propranolol. Pharmacological suppression (6-hydroxydopamine, reserpine, phenoxybenzamine) or stimulation (maprotiline, yohimbine, clenbuterol) reduced or enhanced the activity of propranolol against MES. On the other hand, manipulation of the serotonergic or dopaminergic system seemed to be less effective. In general, the findings confirm the results of previous studies that the membrane stabilizing property and not the blocking action on beta adrenergic (or serotonergic) receptors accounts for the anticonvulsant activity of propranolol.

Animals↗

PubMedDate not supplied

[Indications for the use of loop vesicoplasty and the different methods].

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Female↗

PubMedDate not supplied

Effect of different preservation solutions and substrates on metabolic viability of kidney tubules.

Glucose production, pyruvate uptake and lactate production were taken as metabolic viability tests for isolated rat kidney tubules preserved in hypothermia. The results depend on the type of preservation solution used. Species specific serum is the only solution sustaining cellular metabolism at a normal level. Using Collins solution all viability parameters showed the lowest results. Addition of certain substrates to the Krebs-Henseledt solution improves metabolic viability.

Animals↗