Silicotuberculosis in the elderly: report of two cases

Silicotuberculosis is observed rarely in the current clinical practice. We present two patients (a 72-year-old man and a 84-year-old woman) who developed silicosis after having worked for several decades in the ceramics industry. In both, pulmonary tuberculosis complicated the clinical picture several years after retirement. The first subject presented a multicavitary lesion in the apex of the right lung, which subsequently evolved with fibrosis. The other developed bilateral tubercular bronchopneumonia and right tubercular pleurisy, that improved after prolonged antimycobacterial polychemotherapy. The two cases confirm that patients with silicosis are at an increased risk of developing tuberculosis, and show that, nowadays, silicotuberculosis may represent a geriatric problem. In the elderly, recognition of tuberculosis associated with silicosis is often difficult. Occupational history, radiology (conventional chest radiography and computed tomography) and microbiology (identification of Mycobacterium tuberculosis in sputum and pleural exudate) are helpful for the correct diagnosis, which, in turn, is important for prognosis and treatment, as well as in relation to medico-legal issues and occupational-related compensation claims

Inhibition of muscarinic receptor- and G-protein-dependent phosphoinositide metabolism in cerebrocortical membranes from neonatal rats by ethanol

Phosphoinositide (PtdIns) metabolism activated by cholinergic muscarinic receptors appears to play a role in brain development and has been recently suggested as a possible biochemical target for the developmental neurotoxicity of ethanol (EtOH). Recent experimental evidence indicates that, in rat brain, muscarinic receptor stimulation is coupled to PtdIns hydrolysis through regulatory GTP-binding proteins (G-proteins). We investigated the effect of various alcohol concentrations (10-500 mM) on guanine nucleotide-, fluoride-, and muscarinic-dependent PtdIns hydrolysis in [3H]inositol-labelled cerebral cortical membranes from neonatal (7-day-old) and adult rats. At both ages, EtOH exerted slight inhibitory effects on GTP(S) (100 microM)- and NaF (5 mM)-induced [3H]inositol phosphates accumulation. The presence of GTP(S) was necessary to unmask the stimulatory effect of the muscarinic agonist carbachol. Under these experimental conditions EtOH markedly inhibited carbachol (100 microM)-induced PtdIns hydrolysis. This effect was concentration-dependent and was more pronounced in the cortex from immature animals, where a statistically significant inhibition was observed at EtOH concentrations as low as 50 mM, comparable to the hematic concentrations reached following in vivo administration of doses of ETOH able to induce developmental neurotoxicity. These results confirm that EtOH exerts an age-specific inhibition of muscarinic-dependent PtdIns metabolism and suggest that this action might be exerted through an interaction with receptor-G-protein coupling

Interaction of sigma-compounds with receptor-stimulated phosphoinositide metabolism in the rat brain

Sigma-receptors are nonopioid, nondopaminergic receptors that bind with high affinity several antipsychotic drugs and appear to be involved in regulation of posture and movement. The second messenger system coupled to these receptors is still unknown. Recently, an inhibitory effect of various sigma-compounds on carbachol-stimulated phosphoinositide metabolism has been reported. We have investigated the effect of six sigma-compounds on carbachol- and norepinephrine-stimulated 3H-inositol phosphate accumulation in rat cerebral cortex slices. All compounds tested had a dose-dependent inhibitory effect on both systems, although their order of potency differed between neurotransmitters. Pentazocine and 1,3-di-o-tolylguanidine were the most potent inhibitors of carbachol-stimulated phosphoinositide turnover (IC50 = 31.5 and 45.7 microM, respectively), while haloperidol showed the greatest potency on the norepinephrine-coupled system (IC50 = 3.5 microM). In the presence of IC50 concentrations of these inhibitors, the dose-response curves for the agonists were shifted to the right and the EC50 values were significantly increased. Sigma-compounds also inhibited the binding of [3H]quinuclidinyl benzilate to muscarinic receptors and of [3H]prazosin to alpha 1-adrenoceptors in cortical membranes. In the presence of IC50 concentration (11 microM) of 1,3-di-o-tolylguanidine, no differences were found in the maximal number of muscarinic binding sites, whereas the dissociation constant increased approximately fivefold, indicating a decrease of the radioligand's affinity for the receptor. These results indicate that sigma-compounds, at micromolar concentrations, inhibit muscarinic and alpha 1-adrenergic receptor-coupled phosphoinositide metabolism, probably through an interaction with the neurotransmitter recognition sites

Interaction of σ‐Compounds with Receptor‐Stimulated Phosphoinositide Metabolism in the Rat Brain

Abstract: σ‐Receptors are nonopioid, nondopaminergic receptors that bind with high affinity several antipsychotic drugs and appear to be involved in regulation of posture and movement. The second messenger system coupled to these receptors is still unknown. Recently, an inhibitory effect of various σ‐compounds on carbachol‐stimulated phosphoinositide metabolism has been reported. We have investigated the effect of six σ‐compounds on carbachol‐ and norepinephrine‐stimulated 3H‐inositol phosphate accumulation in rat cerebral cortex slices. All compounds tested had a dose‐dependent inhibitory effect on both systems, although their order of potency differed between neurotransmitters. Pentazocine and 1,3‐di‐o‐tolylguanidine were the most potent inhibitors of carbachol‐stimulated phosphoinositide turnover (IC50= 31.5 and 45.7 μM, respectively), while haloperidol showed the greatest potency on the norepinephrine‐coupled system (IC50= 3.5 μM). In the presence of IC50 concentrations of these inhibitors, the dose‐response curves for the agonists were shifted to the right and the EC50 values were significantly increased. σ‐Compounds also inhibited the binding of [3H]quinuclidinyl benzilate to muscarinic receptors and of [3H]prazosin to α1‐adrenoceptors in cortical membranes. In the presence of IC50 concentration (11 μM) of 1,3‐di‐o‐tolylguanidine, no differences were found in the maximal number of muscarinic binding sites, whereas the dissociation constant increased approximately fivefold, indicating a decrease of the radioligand's affinity for the receptor. These results indicate that σ‐compounds, at micromolar concentrations, inhibit muscarinic and α1‐adrenergic receptor‐coupled phosphoinositide metabolism, probably through an interaction with the neurotransmitter recognition sites. Copyright © 1990, Wiley Blackwell. All rights reserve

Interaction of aluminum ions with phosphoinositide metabolism in rat cerebral cortical membranes

Aluminum (Al) is believed to exert a primary role in the neurotoxicity associated with dialysis encephalopathy and has been suggested to be involved in a number of other neurological disorders, including Alzheimer's disease. Al, complexed with fluoride to form fluoroaluminate (AlF4-), can activate the GTP-binding (G) proteins of the adenylate cyclase and retinal cyclic GMP phosphodiesterase systems. Since an involvement of G-proteins with cerebral phosphoinositide (PtdIns) metabolism has also been suggested, in this study we investigated the interaction of the stable GTP analogue GTP(S), Al salts and NaF with this system. In rat cerebral cortical membranes, GTP(S) dose-dependently stimulated [3H]inositol phosphates ([3H]InsPs) accumulation. This effect was potentiated by carbachol and was partially prevented by the GTP-binding antagonist GDP(S), indicating that CNS muscarinic receptor activation is coupled to PtdIns hydrolysis via putative G-protein(s). GTP(S) stimulation was also inhibited by phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, which is known to exert a negative feedback control on agonist-stimulated PtdIns metabolism. Both Al salts and NaF mimicked the action of GTP(S) in stimulating PtdIns turnover. Their actions were highly synergistic, suggesting that AlF4- could be the active stimulatory species. However, the stimulatory effects of AlCl3 and/or NaF were not potentiated by carbachol and were not inhibited by GDP(S) and PMA, suggesting that separate sites of action might exist for GTP(S) and AlF4-. In the nervous tissue, activation of PtdIns hydrolysis by Al (probably as AlF4-) may be mediated by activating a regulatory G-protein at a location distinct from the GTP-binding site or by a direct stimulation of phospholipase C

Heterogeneity of cholinergic muscarinic receptors coupled to phosphoinositide metabolism in immature rat brain

The effects of muscarinic agonists and antagonists on phosphoinositide (PtdIns) metabolism were examined in the cerebral cortex and brainstem of 7-day-old rats, in order to evaluate the role of muscarinic receptor subtypes in this process. Additionally, comparative experiments were performed in cortices from adult animals. Accumulation of [3H]inositol phosphates ([3H]InsPs) in [3H]inositol pre-labeled brain slices was taken as an index of PtdIns hydrolysis. In neonatal cortex, maximal stimulation induced by the full agonists acetylcholine, carbachol and methacholine was 8-10 fold over basal [3H]InsPs accumulation. The effect of the partial agonists bethanechol, pilocarpine and oxotremorine varied from 3 to 4 fold over basal. Smaller responses to cholinergic stimulation were found in the brainstem and in the adult cortex. In neonatal cortex, muscarinic antagonists inhibited the stimulatory responses with the following order of potency: 4-DAMP > pirenzepine > AF-DX 116 approximately p-F-HHSiD. Pirenzepine inhibition of full agonist-induced [3H]InsPs accumulation showed biphasic curves, with two thirds of the response being inhibited with high affinity. When partial agonists were used, the resulting pirenzepine curves were better described by interaction at one high affinity site. No differences were found between immature and adult rats in the effect of pirenzepine on [3H]InsPs accumulation induced by carbachol, methacholine, or bethanechol. Inhibition by pirenzepine of PtdIns hydrolysis induced by carbachol or methacholine showed biphasic curves also in the brainstem. In this area, only one third of the response was inhibited with high affinity, and p-F-HHSiD was more potent as an antagonist.(ABSTRACT TRUNCATED AT 250 WORDS