1,720,989 research outputs found
Hepatitis B: prevention, protection, and occupational risk.
Full text linkSince 1992, the inclusion of hepatitis B (HBV) vaccination has been recommended by the World Health Organization for all immunisation programmes implemented by nations. In Europe, the introduction of HBV vaccination has markedly reduced the incidence of acute HBV, and before the introduction of HBV vaccine, health care workers (HCW) were at considerable risk of infection. The present review discusses the main problems regarding three fundamental issues in hospital settings: 1) prevention of HBV in HCW, 2) protection induced by vaccination (problems regarding non-responders), and 3) risk for HCW exposed to blood-borne pathogens (occupational risk). The screening of HBV markers plays a decisive role in evaluating the degree of immune coverage in subjects exposed to biological risk and permits an increase immune coverage through of vaccine implementation
Modulation of the Mitochondrial Cyclosporin A-Sensitive Permeability Transition Pore by Matrix pH. Evidence That the Pore Open-Closed Probability Is Regulated by Reversible Histidine Protonation
No full textEnergized mitochondria in sucrose medium take up a Ca2+ pulse but do not show opening of the permeability transition pore (MTP) upon membrane depolarization by uncoupler. This is due to locking of the pore in the closed conformation by matrix acidification and fast Ca2+ efflux following membrane depolarization (Petronilli, V., Cola, C., & Bernardi P. (1993) J. Biol. Chem. 268, 1011-1016). Here we show that addition of diethyl pyrocarbonate (DPC) prior to membrane depolarization restores the ability of uncoupler to induce MTP opening. Since DPC does not modify the rate and extent of matrix acidification and the rate and extent of Ca2+ release following addition of uncoupler, its effects on pore opening appear to be due to modification of histidyl residues regulating the pore open-closed probability. This hypothesis was confirmed in studies with deenergized mitochondria incubated in potassium thiocyanate medium. While at acidic pH values pore opening is otherwise prevented, DPC allows Ca..
The search of the target of promotion: Phenylbenzoate esterase activities in hen peripehral nerve.
No full textCertain esterase inhibitors, such as carbamates, phosphinates and sulfonyl halides, do not cause neuropathy as some organophosphates, but they may exacerbate chemical or traumatic insults to axons. This phenomenon is called promotion of axonopathies. Given the biochemical and toxicological characteristics of these compounds, the hypothesis was made that the target of promotion is a phenyl valerate (PV) esterase similar to neuropathy target esterase (NTE), the target of organophosphate induced delayed polyneuropathy. However, attempts to identify a PV esterase in hen peripheral nerve have been, so far, unsuccessful. We tested several esters, other than PV, as substrates of esterases from crude homogenate of the hen peripheral nerve. The ideal substrate should be poorly hydrolysed by NTE but extensively by enzyme(s) that are insensitive to non-promoters, such as mipafox, and sensitive to promoters, such as phenyl methane sulfonyl fluoride (PMSF). When phenyl benzoate (PB) was used as substrate, about 65% of total activity was resistant to the non-promoter mipafox (up to 0.5 mM, 20 min, pH 8.0), that inhibits NTE and other esterases. More than 90% of this resistant activity was sensitive to the classical promoter PMSF (1 mM, 20 min, pH 8.0) with an IC(50) of about 0.08 mM (20 min, pH 8.0). On the contrary, the non-promoter p-toluene sulfonyl fluoride caused only about 10% inhibition at 0.5 mM. Several esterase inhibitors including, paraoxon, phenyl benzyl carbamate, di-n-butyl dichlorovinyl phosphate and di-isopropyl fluorophosphate, were tested both in vitro and in vivo for inhibition of this PB activity. Mipafox-resistant PMSF-sensitive PB esterase activity(ies) was inhibited by promoters but not by non promoters and neuropathic compounds
'Snake eyes' MRI sign: possible role of cobalt toxicity?
No full text‘Snake eyes’ sign is the magnetic resonance imaging (MRI) occurrence of bilateral hyperintensities of the anterior horns of spinal cord on axial T2-weighted MR images. This neuroradiological sign has been commonly attributed to lower motor neuron (LMN) syndromes, such as Hirayama disease, but also in cervical spondylotic myelopathy and spinal cord infarction. We report on a patient with upper limb LMN syndrome and MRI snake eyes sign secondary to cobalt neurotoxicity
Regulation of the Permeability Transition Pore, a Voltage-dependent Mitochondrial Channel Inhibited by Cyclosporin A
No full textMitochondria from a variety of sources possess a regulated inner membrane channel, the permeability transition pore (MTP), which is responsible for the 'permeability transition', a sudden permeability increase to solutes with molecular masses < or = 1500 Da, most easily observed after Ca2+ accumulation. The MTP is a voltage-dependent channel blocked by cyclosporin A with Ki in the nanomolar range. The MTP open probability is regulated by both the membrane potential and matrix pH. The probability of pore opening increases as the membrane is depolarized, while it decreases as matrix pH is decreased below 7.3 through reversible protonation of histidine residues. Many physiological and pathological effectors, including Ca2+ and ADP, modulate MTP operation directly through changes of the gating potential rather than indirectly through changes of the membrane potential (Petronilli, V., Cola, C., Massari, S., Colonna, R. and Bernardi, P. (1993) J. Biol. Chem. 268, 21939-21945). Here we present recent work from our laboratory indicating that (i) the voltage sensor comprises at least two vicinal thiols whose oxidation-reduction state affects the MTP gating potential; as the couple becomes more oxidized the gating potential increases; conversely, as it becomes more reduced the gating potential decreases; (ii) that MTP opening is fully reversible, as mitochondria maintain volume homeostasis through several cycles of pore opening/closure; and (iii) that the mechanism of MTP inhibition by cyclosporin A presumably involves a mitochondrial cyclophilin but does not utilize a calcineurin-dependent pathway
Are rats the appropriate experimental model to understand age-related renal drug metabolism and toxicity?
No full textFor many years, toxicological investigations have shown that the sensitivity of kidney to xenobiotics evolves depending on the stage of life. The increasing requirement for information on the potential nephrotoxic effect of drugs during human embryonic development, childhood, adulthood and senescence has potentiated toxicological studies in vivo. Rodents, specifically rats, are the primary animal models used in toxicology testing. Despite the popularity of this approach, there are a number of doubts about the appropriateness of rats for the examination of changes in toxicological responses during different stages of life. This perspective tackles the issue of evaluating whether rats fail to adequately mimic the human kidney response to xenobiotic agents through a critical analysis of the literature. We conclude that rats constitute a good model for toxicological investigations during embryonic development, youth and adulthood. However, senescent rats frequently undergo spontaneous kidney degeneration caused by chronic progressive nephropathy, making them a poor model for the study of kidney responses to xenobiotics
Course of Metal Ions after a Revision of Malfunctioning Metal-on-Metal Total Hip Prostheses
Full text linkThe present research evaluated the course of cobalt and chromium in the blood and urine after the revision of metal-on-metal with a ceramic-on-polyethylene total hip arthroplasty. Seven patients were enrolled for hip prosthesis revision owing to ascertained damage of the implant. Metals in the blood and urine were evaluated before and after the hip revision. The double measurement before the total hip revision revealed high levels of metal ions (on average, 88.1 μg/L of cobalt in the blood, 399.0 μg/g of creatinine cobalt in the urine, 46.8 μg/L of chromium in the blood, and 129.6 μg/g of creatinine chromium in the urine at the first measurements), with an increasing trend between the first and second dosage. Within a week after the hip revision, the levels of metal ions significantly decreased by approximately half. Four to six months after the operation, the cobalt levels were found near to the reference values, whereas the chromium levels reached 25% of the values measured before the revision. The revision of malfunctioning metal-on-metal implants produced a dramatic decrease of metal ions in biological fluids, although it did not completely rescue the chromium level
The Permeability Transition Pore. Pathophysiology of a Cyclosporin A-sensitive Mitochondrial Channel
No full textRilascio di metalli da protesi d’anca metallo-su-metallo
Full text linkLe protesi d’anca metallo-su-metallo possono essere causa di un aumento della concentrazione ematica de metalli che costituiscono la protesi, in particolare cromo (Cr) e cobalto (Co). In genere un incremento dei metalli nei liquidi biologici è osservabile circa tre mesi dopo la sostituzione dell’anca con la nuova protesi, senza ulteriori aumenti ad un anno. Il livello di metalli sembra quindi declinare lentamente nei successivi cinque anni. Qualora la protesi sia ben funzionante, la quota circolante di Cr e Co è generalmente modesta, mentre l’usura sembra essere il responsabile di un più rilevante incremento, dovuto ad un effetto combinato della corrosione dell’impianto e delle particelle rilasciate. A livello tissutale, il Co si trova in genere allo stato metallico mentre il Cr si trova sotto forma di fosfato [Cr(III)PO4] nel suo stato di ossidazione 3+. Una causa importante di usura e quindi di rilascio di metalli è la mobilizzazione della protesi. Ulteriori significativi fattori di rischio sembrano essere il sesso femminile e il diametro della testa, maggiore è il diametro, maggiore è il rischio di usura. Fattore non favorente sembra invece essere l’attività fisica. Il rischio principale è la metallosi, ovvero l’eccessiva usura della protesi con infiltrazione di detriti metallici accompagnata da flogosi cronica nei tessuti periprotesici, evento che può essere causa di intossicazione da metalli anche grave. Il presente studio ha preso in esame le concentrazioni ematiche e urinarie di Cr e Co in 30 pazienti portatori di protesi metallo-su-metallo senza segni di usura (19 maschi e 11 femmine, età media 61 anni, mediamente 3 anni dopo l’intervento) e di 6 pazienti (4 maschi e 2 femmine, età media 54 anni, mediamente 5 anni dopo l’intervento) con protesi recanti chiari segni di usura e metallosi. Nessuno dei 36 pazienti presentava una anamnesi significativa per esposizione lavorativa a metalli pesanti. La determinazione nei liquidi biologici ha dimostrato nei portatori di protesi non usurate una concentrazione dei metalli (media geometrica) solo modicamente aumentata (CoS 0,5 μg/l, CoU 5,7 μg/l, CrS 0,8 μg/l, CrU 3,4 μg/l) rispetto ai valori di riferimento, mentre l’usura è stata causa di un rilevante aumento della concentrazione sia del Co (CoS 94,6 μg/l, CoU 334,5 μg/l) che del Cr (CrS 57,7 μg/l, CrU 89,4 μg/l). Come dimostrano i risultati, le protesi ben funzionanti non sembrano essere causa di particolari rischi per i pazienti, in accordo con la letteratura, mentre all’usura si associano elevati livelli dei metalli nei liquidi biologici. In caso di metallosi, sono stati descritti casi di polineuropatia legata alla tossicità dei metalli. Al momento, i 6 pazienti con usura della protesi non presentano segni e sintomi collegabili ad una intossicazione da metalli, ma l’elevata concentrazione potrebbe essere causa di insorgenza di danni soprattutto renali, neurologici, tiroidei e cardiaci. Le protesi metallo-su-metallo usurate associate a metallosi dovrebbero essere sostituite per prevenire potenziali danni ai pazienti, anche se sono necessari ulteriori studi prospettici per valutare l’effettiva correlazione tra elevate concentrazioni di metalli e conseguenti effetti tossici
- …
