Biomedical subjects

A Florence

Publications and source records attributed to A Florence.

6 recordsLinked to original sources

PubMed1992

Chemical and structural characterisation of iron cores of haemosiderins isolated from different sources.

The elemental content of the iron cores of haemosiderins isolated from animal and human tissues has been determined to ascertain whether changes in composition are correlated with structural differences previously identified in these mineralisation products. Significant differences were observed in the elemental composition of haemosiderins isolated from patients subjected to desferrioxamine-chelation therapy compared to patients who had been venesected. The P/Fe molar ratio was considerably higher in haemosiderin isolated from treated primary haemochromatosis (0.83), compared to untreated primary haemochromatosis (0.10) and treated secondary haemochromatosis (0.25), and this could account for the amorphous nature of these iron cores. The levels of M/Fe (M = Ca, Cu, Zn) were reduced in the haemosiderins derived from treated secondary haemochromatosis patients, possibly due to the chelation of these ions by desferrioxamine therapy. In an experimentally iron-loaded rat, receiving either desferrioxamine or 1,2-diethyl-3-hydroxypyrid-4-one, selective decreases in these three elements were also observed after two weeks of desferrioxamine therapy. Such changes may be important determinants in the modification of biomineralisation of the iron cores.

Animals↗

PubMed1992

Studies of in vivo iron mobilization by chelators in the ferrocene-loaded rat.

The oral efficacy of the oral iron chelators 1,2-dimethyl-3-hydroxypyrid-4-one (CP20), 1,2-diethyl-3-hydroxypyrid-4-one (CP94) and desferrioxamine B (DFO) has been compared with intraperitoneal DFO in an experimental model of iron overload with similar biochemical and biophysical characteristics to those observed for human genetic haemochromatosis. The hepatic iron stores in the ferrocene-loaded rat were relatively stable and did not decrease at the end of the loading period. In contrast, the iron dextran rat model showed a rapid depletion of its iron stores 2 weeks after cessation of intraperitoneal injection. When CP20 and CP94 were administered to the ferrocene-loaded rat model in combination with an iron-free diet there were significant decreases in (i) total homogenate iron and (ii) hepatic ferritin iron when compared to the iron-loaded rat receiving the iron-free diet alone. Desferrioxamine, when administered by gavage, only showed chelation of ferritin iron, while intraperitoneal injection of desferrioxamine showed significant depletion of iron both in the total homogenate and ferritin. Subcellular fractionation of the hepatic organelle clearly showed that where there was depletion of homogenate iron there was a net decrease in the lysosomal fraction, while changes in ferritin iron were reflected by decreases in the cytosolic iron content. Although no assessment of net iron excretion was made, we suggest that the use of this animal model should ascertain the site of chelation by iron chelators.

Animals↗

PubMed1991

Vestibular neurotomy by retrosigmoid approach: technique, indications, and results.

During the past 15 years, 96 retrosigmoid vestibular neurotomies have been used in the surgical management of incapacitating Meniere's disease for the control of vertigo and preservation of hearing. This posterior approach of the pontocerebellar angle gives the best view on the acousticofacial nerve bundle, through a 2 x 2 cm suboccipital craniotomy immediately behind the mastoid and sigmoid sinus. Then the vestibular nerve is easily identified, separated from the cochlear nerve and sectioned, the facial nerve not being at risk, as it lies much deeper. Actually, the majority of authors agree that vestibular neurotomy is the most effective surgical treatment in relieving disabling vertigo (96% of cases) with serviceable hearing, but few surgeons know that the retrosigmoid approach is simpler and more reliable than the middle fossa or retrolabyrinthine approaches, with a low incidence of complications. The purpose of this paper is to emphasize the routine use of the retrosigmoid approach.

Aged↗

PubMed1990

[Otospongiosis: different surgical technics, identical results. Why?].

Both platinectomy and platinotomy are currently used to treat otosclerosis surgically. Though the techniques are different from one another, especially by the new area ratio between tympanic membrane and stapes foot-plate, the results are similar. It should be clear that the simple "piston model" of the tympanic ossicular system cannot explain this results. If, for the seesaw mechanical view, a vibratory molecular system conducting acoustic energy is substituted, a pertinent explanation can be given for this result. Thus, understanding of the pattern motion of the tympanic ossicular system has to change drastically.

Ear, Middle↗

PubMed1990

[Retraction pockets, pathological entity?].

Retraction pockets are not a pathological entity per se but take after various ear diseases, with which they share the same morphological eardrum alterations. The authors believe that any holistic evaluation of retraction pockets, as though these were forming a single group of like pathogenic origin, i.e., tubal dysfunction, would be artificial and raise therapeutic problems. The statistical analysis of the causes for retraction pocket formation provides little information. Otologists are still looking into chronic otitis media and cholesteatoma as a possible, long-suspected, unproved etiology. Electron microscopy and, more particularly, istological-enzymological analyses of mounts prepared by the authors have shown, in some cases, the anomalous presence, in the pocket, of Langerhans' cells, which the authors consider as strongly indicative of cholesteatoma. While confirming the clinical diagnosis, anatomopathological examination allows to differentiate poor-prognosis retraction pockets from benign ones. The pathogenesis of these pockets is still poorly understood. It is the authors' contention that tympanic invagination is more likely traceable to some biopathological/biochemical phenomenon than to occupational mechanical disorders involving the tube. The clinical characteristics of retraction pockets are the basis for their classification into three groups, according to their evolutional tendency. Thus, developing cholesteatomas bear a poor prognosis; sequelae of benign otitis are associated with small risk; lastly, there is a small group of pockets the evolution of which is hard to specify. The authors believe that such differentiation between retraction pockets is mandatory to have a clear picture of therapeutic indications, and to assess the various outcomes.

Cholesteatoma↗

PubMed1989

Desferrithiocin and desferrioxamine B. Cellular pharmacology and storage iron mobilization.

3H-Desferrithiocin (DFT) has been synthesized from desmethyl desferrithiocin. The uptake and release of this 3H siderophore and of its iron complex have been studied in cultured rat hepatocytes and systematically compared to 14C desferrioxamine B (DFO). At 37 degrees, the uptake of both chelators is strictly proportional to the extracellular concentration and no toxicity is observed up to, at least, 1 mM. Uptake of 3H DFT is rapid and reaches a plateau after ca. 1 hr. The accumulation of 3H DFT attains a maximum three times that of 14C DFO and the plateau is reached much more rapidly. Upon reincubation in a drug-free medium of cells that had accumulated 3H DFT, most of the 3H label is rapidly released in the culture medium. These kinetic parameters suggest that the accumulation of these two chelators results from their diffusion across cellular membranes, as a function of the gradient of concentration between the cellular compartment and the extracellular medium. Differential centrifugation of homogenates from hepatocytes incubated with 3H DFT shows that the bulk of cell associated 3H-label (82%) is found in the cytosol, whereas a small proportion (14.5%) is present in the particulate fraction. Isopycnic centrifugation on sucrose gradients suggests that 3H-label associated with the particulate fraction is localized within mitochondria. In contrast, 14C DFO distributes in almost equal proportions between cytosol and the particulate fraction (MLP). At least part of the 14C-label in MLP is associated with lysosomes. Rat hepatocytes cultivated for long term in synthetic culture medium have been used to study iron mobilization by chelators from 59Fe loaded cells. DFT mobilizes iron more rapidly than DFO. This effect is also observed in vitro with ferritin, where, in addition, DFT is much more efficient than DFO to mobilize iron at acidic pH. These results strongly suggest that different iron mobilization from cultured hepatocytes results from differences in the cellular pharmacology of these two chelators and, in particular, in their rate of uptake, cellular accumulation levels and subcellular localizations. DFT could mobilize iron from cytosol and, possibly, to a small extent from mitochondria, whereas DFO would do so from cytosol and lysosomes.

Animals↗