Down-regulation of rat β-adrenoceptors by clenbuterol or desipramine does not require chronic treatment: [H]CGP-12177 binding reveals rapid (24 hour) modulation

Desipramine (DMI, 15 mg/kg, s.c.) decreased [³H]CGP-12177-labelled cortical β-adrenoceptor density (B_max) by 30% upon chronic (14 day) treatment. However, even a single dose (in mg/kg) of DMI (15) or the β-adrenoceptor agonist, clenbuterol (20), induced a rapid (24 hour) and significant reduction of β-adrenoceptor B_max (−15%; p<0.01). Acute treatment with amitryptiline (10), clorgyline (1), fluoxetine (10), nomifensine (10) or maprotiline (20) had no significant effect on [³H]CGP-12177-labelled β-adrenoceptors, suggesting that rapid down-regulation may not be a general property of antidepressant drugs. None of the antidepressants altered the B_max of [³H]ketanserin-labelled 5-HT_2A receptors on acute treatment. These results show that β-adrenoceptor down-regulation by clenbuterol and DMI is not dependent on chronic treatment and may, therefore, be a poor correlate of the gradual onset of therapeutic efficacy seen clinically with antidepressant drugs.     

Glial cell line-derived neurotrophic factor (GDNF) gene expression in the human brain: A post mortem in situ hybridization study with special reference to Parkinson's disease

Summary Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for dopaminergic neurons. Since dopaminergic neurons degenerate in Parkinson's disease, this factor is a potential therapeutical tool that may save dopaminergic neurons during the pathological process. Moreover, a reduced GDNF expression may be involved in the pathophysiology of the disease. In this study, we tested whether altered GDNF production may participate in the mechanism of cell death in this disease. GDNF gene expression was analyzed by in situ hybridization using riboprobes corresponding to a sequence of the exon 2 human GDNF gene. Experiments were performed on tissue sections of the mesencephalon and the striatum from 8 patients with Parkinson's disease and 6 control subjects matched for age at death and for post mortem delay. No labelling was observed in either group of patients. This absence of detectable expression could not be attributed to methodological problems as a positive staining was observed using the same probes for sections of astroglioma biopsies from human adults and for sections of a newborn infant brain obtained at post-mortem. These data suggest that GDNF is probably expressed at a very low level in the adult human brain and its involvement in the pathophysiology of Parkinson's disease remains to be demonstrated. GDNF may represent a powerful new therapeutic agent for Parkinson's disease, however.     

Expression of the beta-nerve growth factor gene in male sex organs of the mouse, rat, and guinea pig.

Steady-state nerve growth factor (NGF) mRNA levels were estimated in male sex organs of the mouse, rat, and guinea pig by RNA blot hybridization analysis. The abundance of NGF mRNAs was in the order vas deferens greater than epididymis greater than or equal to seminal vesicles much greater than testis. NGF mRNA levels in these organs were compared with those estimated for other rat peripheral tissues and were found to correlate with the density of their sympathetic innervation, with the exception of guinea pig prostate. Castration had no significant effect on NGF mRNA levels in the guinea pig prostate, suggesting that NGF synthesis in this tissue is not under direct androgen control. NGF-like and proNGF-like immunoreactivities were localized by immunohistochemical techniques in the secretory cells of the glandular epithelium of the guinea pig prostate and in germ cells in the seminiferous tubules of the mouse testis.     

Thalamo-peduncular germinoma]

A 24 year-old patient presented with chronic intracranial hypertension, palsy of both abducens nerves and upward gaze, and right hypoesthesia. CT scan and MRI showed a left thalamic tumor infiltrating the left cerebral peduncle. A stereotactic biopsy revealed a germ cell tumor. Following radiotherapy the patient recovered except for ophthalmoplegia. The tumor totally disappeared on CT scan and MRI.     

Different clinical types of degenerative aphasia

The authors report 3 cases of slowly progressive aphasia with different language disturbances: anomia, pure word deafness and Broca's aphasia. All patients were independent in daily life activities. Insight, judgement and overall behaviour were intact. There was no major disturbance of other cognitive functions, but psychometric tests showed mild deficits suggesting widespread involvement. CT scans and magnetic resonance imaging showed focal dilatation of the left sylvian fissure. A positron emission tomographic study showed left perisylvian hypometabolism. A review of the literature yielded an increasing number of cases of this degenerative syndrome affecting dominant hemisphere language areas. Our cases confirm the clinical heterogeneity of degenerative aphasia. Postmortem neuropathological examinations are rare and many causes are found: Pick's disease, Alzheimer's disease or aspecific gliosis.     

An audit of 24-hour creatinine clearance measurements at Tygerberg Hospital and comparison with prediction equations.

BACKGROUND: Internationally, clinical guidelines recommend the use of creatinine-based equations to estimate glomerular filtration rate (GFR) for assessment and follow-up of kidney disease. The routine use of 24-hour creatinine clearances (CrCl) is no longer advocated. OBJECTIVES: To examine the indications for requesting CrCl at Tygerberg Hospital, identify problems associated with the procedure, and evaluate the utility of the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations with different levels of renal dysfunction in the ethnic groups of the Western Cape. METHODS: A clinical audit of CrCl was performed. The estimated GFR as predicted by the modified CG and MDRD formulae was compared with CrCl in 252 patients, representing three local ethnic groups. MDRD formulae with and without the correction factor for black ethnic group (MDRD-B) were evaluated. RESULTS: Problems with urine collection or data supplied were identified in one-third of CrCl requests, leading to unreliable results. The CG correlated best with CrCl in the group as a whole. The average absolute and percentage differences from CrCl in the different ethnic groups were as follows: coloured (mixed ethnicity) (N = 186) - CG 13.4 ml/min/1.73 m(2) (18%), MDRD 16.8 ml/min/1.73 m(2) (23%) and MDRD-B 27.9 ml/ min/1.73 m(2) (38%); black (N = 21) - CG 14.8 ml/min/1.73 m(2) (19%), MDRD 12.9 ml/min/1.73 m(2) (17%) and MDRD-B 25.1 ml/min/1.73 m(2) (33%); white (N = 45) CG 13.5 ml/min/1.73 m2 (19%), MDRD 15.3 ml/min/1.73 m(2) (21%) and MDRD-B 24.8 ml/min/1.73 m(2) (35%). Throughout the renal function levels (chronic kidney disease stages 1 - 5) CG correlated better with CrCl than MDRD. CONCLUSIONS: Possible reasons for poor correlations include a high prevalence of obesity, underweight and normal GFR in the study population. There is a need for further research, using a gold standard, into the accuracy of these prediction equations in our unique patient populations before firm recommendations can be made regarding their use. Until then CrCl will continue to be widely used. Greater efforts at patient and health care worker education are required to ensure proper collections.     

Long-term hypertransaminasemia disclosing a muscular disease

Prolonged increase in serum transaminase activity is usually seen in chronic liver disease. Evaluation in one patient with such a prolonged increase having no evidence of liver disease including histological examination, revealed a limb girdle muscular dystrophy. This case suggests that a muscular disease should be suspected in all children with persistent increase in serum transaminase activity when the liver is apparently normal.     

Evaluation of the end-expiratory lung volume as an indirect index of bronchial constriction in asthma

The purpose of this study was to evaluate the merits of the end expiratory lung volume as an indirect ventilatory index of bronchial obstruction and to show an application of continuous monitoring of lung volume in asthmatic patients. The accuracy of the external measurements (IS) of functional residual capacity (FRC) was controlled by comparing them with the helium measurements (DS) obtained during nine methacholine tests (IS = 0.06 + 1.065 DS in litres: R2 = 0.99). Seven asthmatics (18-48 yr) were monitored by measuring rib cage and abdominal perimeter variations. This was done in basal condition, after methacholine-induced bronchoconstriction and after bronchodilation by either salbutamol or oxytropium bromide inhalation. All the subjects were investigated on two separate days and were their own control. Bronchoconstriction produced a significant increase (p less than 0.01) of tidal volume (VT: + 67%), external minute ventilation (VE: + 58%), mean inspiratory flow (VT/TI: + 78%) and FRC (+ 26.5%) while frequency (f) and fractional inspiratory time (TI/TT) fluctuated non significantly. In the group of seven tested subjects, there was a significant correlation (p less than 0.01) between forced expiratory volume in one second (FEV1) and VE, FEV1 and VT/TI, FEV1 and FRC. However, the individual regression line showed a significant relationship only between FEV1 and FRC (R2 = 0.80 +/- 0.04). We therefore conclude that the variation of the end expiratory level can be chosen as an indirect index of bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)