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Biomedical subjects

J Ferin

Publications and source records attributed to J Ferin.

At least 19 recordsLinked to original sources

Pulmonary retention of ultrafine and fine particles in rats.

In aerosol research, particle size has been mainly considered in the context of the role it plays in particle deposition along the respiratory tract. The possibility that the primary particle size may affect the fate of particles after they are deposited was explored in this study. Rats were exposed for 12 wk to aerosolized ultrafine (integral of 21 nm diameter) or fine (integral of 250 nm diameter) titanium dioxide (TiO2) particles. Other rats were exposed to TiO2 particles of various sizes (12, 21, 230, and 250 nm) by intratracheal instillation. After the rat lungs were extensively lavaged, analysis of particle content in the lavaged lungs, lavage fluid, and of lymphatic nodes was performed. Electron and light microscopy was also performed using unlavaged lungs. Both acute instillation and subchronic inhalation studies showed that ultrafine particles (integral of 20 nm) at equivalent masses access the pulmonary interstitium to a larger extent than fine particles (integral of 250 nm). An increasing dose in terms of particle numbers and a decreasing particle size promoted particle access into the interstitium. The translocation of particles into the interstitium appeared to be a function of the number of particles, and the process appeared to be related to the particle size, the delivered dose, and the delivered dose rate. A net effect of the preferential translocation of the smaller particles into the interstitium was a prolongation in their lung retention. After the 12-wk inhalation exposure, pulmonary clearance of ultrafine particles was slower (t1/2 = 501 days) than of larger particles (t1/2 = 174 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols

Role of the alveolar macrophage in lung injury: studies with ultrafine particles.

We conducted a series of experiments with ultrafine particles (approximately 20 nm) and larger particles (less than 200 nm) of "nuisance" dusts to evaluate the involvement of alveolar macrophages (AM) in particle-induced lung injury and particle translocation in rats. After intratracheal instillation of both ultrafine particles and larger particles of TiO2, we found a highly increased interstitial access of the ultrafine particles combined with a large acute inflammatory reaction as determined by lung lavage parameters. An additional experiment revealed that intratracheal instillation of phagocytized ultrafine TiO2 particles (inside AM) prevented both the pulmonary inflammatory reaction and the interstitial access of the ultrafine particles. Another experiment showed that the influx of polymorphonuclear cells (PMN) into the alveolar space unexpectedly decreased with higher doses of ultrafine particles, whereas alveolar epithelial permeability (protein leakage) increased. The divergence between PMN influx into the alveolar space and changes in alveolar epithelial permeability implies that they are separate events. Pulmonary inflammatory parameters determined by lung lavage analysis correlated best with the surface area of the retained particles rather than with their mass, volume, or numbers. Because higher doses resulted in an increased interstitialized fraction of particles, we suggest that inflammatory events induced by particles in the interstitial space can modify the inflammation in the alveolar space detectable by lung lavage. Our results demonstrate the dual role of AM for modifying particle-induced lung injury, i.e., both preventing such injury and contributing to it. We conclude that the increased pulmonary toxicity of ultrafine particles is related to their larger surface area and to their increased interstitial access.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of aerosol exposures to cadmium chloride on the clearance of titanium dioxide from the lungs of rats.

This study deals with the hypothesis that the lymphatic uptake of particles from the lung parenchyma increases when phagocytosis by pulmonary macrophages is inhibited. Cadmium chloride was chosen as the toxicant to inhibit phagocytosis and was administered as an aerosol to rats at concentrations of 1.5 mg Cd/m3 (mass median aerodynamic diameter = 0.4 micron, sigma g = 1.4) and 5.0 mg Cd/m3 (MMAD = 0.4 micron, sigma g = 1.6), each for 30 min. Control animals were exposed to a saline aerosol. Lung clearance and lymphatic uptake were assayed after exposing the cadmium-exposed rats to titanium dioxide (TiO2) dust at concentrations of 12-15 mg/m3 (MMAD = 1.0 micron, sigma g = 2.3) for 6 h. Preexposure to 5 mg Cd/m3 decreased the initial deposition of TiO2 by 40% compared to a saline preexposure. Although the overall clearance of TiO2 from the lungs was not different in the cadmium-exposed animals, the lymph node burden was 2.7 times higher in the CdCl2-exposed animals than in the controls. Exposures to 1.5 mg Cd/m3 had no effect on lung clearance or lymphatic uptake of TiO2. When TiO2 exposure preceded a 5.0 mg Cd/m3 exposure, the results were similar; i.e., more TiO2 was found in the lymph nodes of the animals. This study supports the concept that lymphatic uptake of dust particles increases when phagocytosis by alveolar macrophages is decreased.

Aerosols

Effect on ovulation of surgically induced endometriosis in rabbits.

To study the effect of endometriosis on follicular rupture, endometrial tissue was autografted to New Zealand White rabbits. Endometrium was surgically implanted into the peritoneal cavity or into the rectus muscle. Human chorionic gonadotropin was administered to induce ovulation. During three subsequent laparotomies, the number of corpora lutea and stigmata were counted. The viability of the implants was demonstrated histologically. Ovaries were removed during the last laparotomy and ovarian serial sections were examined. In rabbits with peritoneal induced endometriosis, the percentage of stigmata/corpora lutea was significantly decreased. Macroscopic study was confirmed by histological examination. Indeed, a high incidence of entrapped oocytes was found in rabbits with peritoneal endometriosis. Extraperitoneal endometriosis had no effect on ovulation. Our data demonstrated that endometriosis induced a failure of follicular rupture. After endometriumectomy, no failure to ovulate was observed, suggesting that the effect of endometriosis on the ovulation disappeared with excision of endometrial implants.

Animals

Loss of adrenergic innervation in induced rabbit hydrosalpinx.

Ligation of the proximal and distal ends of the rabbit oviducts was used to induce hydrosalpinges. The adrenergic innervation of the induced hydrosalpinx was studied. Depletion of adrenergic innervation in rabbit hydrosalpinges was found. Our findings suggest that not only mucosal changes, but also loss of adrenergic nerves must be taken into account as factors in the pathology of hydrosalpinx.

Animals

Cyclic changes in ciliation, cell height, and mitotic activity in human tubal epithelium during reproductive life.

The percentage of ciliated cells, the height, and the mitotic index of human oviductal epithelium were studied during the menstrual cycle and under progestogens. A total of 141 fallopian tubes were examined. During the menstrual cycle, a process of ciliation and deciliation was observed. Maximal ciliation was attained around the time of ovulation, particularly in the fimbria where significant differences were noted. Deciliation was observed under progestogen therapy, but this progestogen effect was easily reversible. The decrease of epithelial height observed after ovulation was also found after progestogen therapy. Cyclic mitotic activity was noted during the menstrual cycle. Estrogens influence the mitotic activity of tubal epithelium, whereas endogenous progesterone and progestogens inhibit this estrogenic effect.

Cell Cycle

Biological effects and toxicity assessment of titanium dioxides: anatase and rutile.

Anatase and rutile are titanium dioxides (TiO2) with different crystal lattices. The particles of TiO2 are considered a "nuisance" dust. It has been reported that rutile can be considered "inert". However, anatase, because of its hemolytic activity in vitro and slow lung clearance, should warrant further research regarding its toxicity. We exposed rats to an aerosol of either anatase or rutile and determined the TiO2 retention in the lung up to 132 days post exposure. Particle clearance from the lung, calculated from the retention data, was similar in both the anatase and the rutile groups with T1/2 of 51 or 53 days, respectively. In addition a pulmonary cell response test was performed on other rats. After intratracheal instillation of anatase and rutile in doses of 0.5 or 5.0 mg/rat, lung lavage was performed and the harvested cells counted. The counts of all cells, alveolar macrophages (AM), peroxidase positive AM, and polymorphonuclear leukocytes were compared. The pulmonary cell response test also yielded similar results for both types of TiO2. Thus there was no indication that the crystal lattices of TiO2 altered the biological effects of TiO2 particles. The evidence suggests that both anatase and rutile are "nuisance" dusts.

Animals

Fimbrial ciliated cells percentage and epithelial height during and after salpingitis.

Microbiopsies of 191 fimbriae were obtained from 146 patients undergoing laparotomy for acute salpingitis, or tubal surgery after salpingitis. The biopsies were classified in four groups according to the diagnosis at laparotomy: salpingitis, distal occlusion, peritubal adhesions or tuberculosis. The biopsies belonging to the group of distal occlusion were further classified in four sub-groups according to the extent of the lesions observed during the hysterosalpingography and laparoscopy. Since the crucial role of the ciliated epithelium in the ovum transport has been established, the percentage of ciliated cells and the epithelial height were determined in the groups and compared to those observed in fimbriae obtained from fertile women during an ovulatory cycle. Significant differences were noted in all groups when compared to fertile women. Acute salpingitis provoked a rapid and severe deciliation which recovered 3 months after triantibiotherapy. In the groups of distal occlusion, there was a significant correlation between the rate of deciliation and the extent of lesions. This suggests that deciliation of tubal epithelium is a sequela of salpingitis and that the extent of disease allows a prognosis of the percentage of ciliated cells.

Biopsy

Tubal polyps, epithelial inclusions, and endometriosis after tubal sterilization.

Histologic findings in 133 previously ligated fallopian tubes of women who underwent subsequent hysterectomy and bilateral salpingectomy were compared with those of 50 normal fallopian tubes and related to four surgical procedures for sterilization. Dilatation of proximal tubal lumen, flattening of the folds, polyps, and increase of mitotic activity of the epithelium was subsequent to tubal occlusion in any case, regardless of the type of sterilization. After sterilization by ring, ligation, and coagulation, the incidence of epithelial inclusions was significantly different from that observed after sterilization by clips. Focal endometriosis was only found after tubal ligation and coagulation. It is suggested that epithelial inclusions were the result of surviving fragments of tubal epithelium translocated in the tubal wall during the procedure, and that endometriosis was caused by implantation of expelled menstrual products through the open lumen into the healed ligation area.

Endometriosis

The effect of aerosol charge on the deposition and clearance of TiO2 particles in rats.

A titanium dioxide aerosol when generated by a Wright dust feed will have a higher electrostatic charge by a factor of 5.5 than one which has been discharged by a bipolar ion field produced by a 7.5 mCi 85Kr source. The deposition of particles in the lung of rats was lower by approximately 21% when an aerosol discharger was used. Particle clearance from the lung alveoli was not affected by the use of the discharger.

Aerosols

Changes in ciliation and cell height in human tubal epithelium in the fertile and post-fertile years.

A total of 162 fallopian tubes was obtained from a sample of subjects comprising fertile women with regular ovulatory cycles, post-menopausal women taking no hormonal drugs and post-menopausal women receiving oestrogen therapy in various forms. During the menstrual cycle the highest percentage of ciliated cells was found, in all of the three tubal portions studied, around ovulation time. The epithelial height decreased significantly subsequent to ovulation. After more than 1 yr had elapsed following the menopause, the percentage of ciliated cells and epithelial height decreased significantly. Very low values were observed in women 10 yr after the menopause. In women receiving oestrogen therapy for more than 10 yr following the onset of menopause - conjugated equine oestrogens (CEE), 1.25 mg/day - the percentage of ciliated cells was significantly higher than that in subjects not receiving hormonal therapy. Similar data were obtained in the case of women taking oestriol (2 mg/day). The data presented demonstrate that oestrogen therapy influences the ciliation and height of oviductal epithelium.

Cell Count

Effect of intrabronchially instilled amosite on lavagable lung and pleural cells.

Rats were instilled intrabronchially with 1 mg UICC amosite suspended in 0.2 mL of filtered saline; control animals received the saline instillation only. Five animals from each group were killed on various days after instillation, up to day 128/129. Total retrieved cell counts and differential cell analysis were performed from lung and pleural lavages. In particular, the appearance of peroxidase-positive macrophages (PPM) as indicators of newly arrived macrophages was investigated. Polymorphonuclear cells (PMN) and PPMs in lung lavages increased in number 24 hr after amosite instillation and remained at increased levels until day 62. Alveolar macrophage numbers were significantly decreased after amosite instillation. There was only a very transient increase of PPMs and PMNs in the saline group. The number of PPMs in pleural lavage fluid was already increased 24 hr after amosite instillation. The pleural PPM increase was sustained throughout the study. No pleural reaction was seen in the saline instilled group. The inflammatory reactions indicated by the composition of the lavaged cells of the lung represent the in vivo toxicity of intrabronchially instilled amosite. The stimulus for recruitment of PMNs and PPMs is different, since no PMN response was detected in the pleural space. It is suggested that the response of the pleural PPMs is caused by the early arrival of fibers at the pleural sites, which results in the recruitment of PPMs to this space by an unknown mechanism.

Animals

Particle binding, phagocytosis, and plastic substrate adherence characteristics of alveolar macrophages from rats acutely treated with chlorphentermine.

The effects of acute treatment with the phospholipidosis-inducing agent chlorphentermine (CP) on alveolar macrophage (AM) function heretofore have not been investigated. We evaluated the effects of acute CP treatment on the functional status of AM by comparing Fc receptor (FcR) and "nonspecific substance receptor"-mediated particle binding and phagocytic activities, as well as the plastic substrate adherence characteristics of AM lavaged from control (CONT-AM) and CP-treated (CP-AM) rats. Acute CP treatment caused an impairment in AM phagocytosis and binding of sheep red blood cells opsonized with immunoglobulin G (IgG). Although CONT-AM and CP-AM avidities for tanned human red blood cells were indistinguishable, phagocytosis of these particles by CP-AM was diminished in a manner similar to that found for FcR-mediated phagocytosis. Analyses of the distributions of test particles in phagocytizing CONT-AM and CP-AM indicated that the phagocytic activity of a subset of CP-AM was compromised by drug treatment. Populations of CP-AM were also found to be less adherent in a plastic substrate adherence assay verified with a poorly adherent AM population. Unlike studies involving chronic CP-treatment, our studies indicate acute CP administration results in an impairment in AM phagocytic activity and a reduction in FcR-mediated particle binding.

Animals

Relaxin in non-pregnant women during ovarian stimulation.

Around pharmacologically induced ovulation, inconstant immunoreactive plasma relaxin concentrations were observed. Increasing levels appear during HCG or LH-RH induced lutinization. These values remain high as long as the corpus luteum is sustained. These observations may suggest that relaxin has a role during early luteinization and during the non-gestational lifespan of the corpus luteum in women.

Clomiphene

Macroscopic and microscopic studies of fallopian tube after laparoscopic sterilization.

Histological study was carried out on human fallopian tubes one hour and one month after various methods of laparoscopic sterilization. Ciliated cells were counted and histological lesions were observed. Deciliation is proved at a distance from the site of sterilization. Taking into account these two data, it has been possible to display the substance loss provoked by each of the usual sterilization methods (unipolar electro-coagulation, bipolar electrocoagulation, silicone ring and Hulka-Clements clip) which have to be taken into consideration in case of surgical re-anastomosis.

Fallopian Tubes

The effect of long-term oestrogen treatment on the development of osteoarthrosis at the small hand joints.

The effect of long-term oestrogen treatment of at least 5 yr on the development of osteoarthrosis was studied in 48 postmenopausal women. Osteoarthrosis at the hand joints was graded according to Kellgren's criteria, using hand X-rays. Data obtained in a normal population of 155 women served as controls as well as data obtained in 24 postmenopausal women who didnot receive oestrogen replacement therapy. No significant difference in osteoarthrosis between the treated and non-treated groups was found. The development of osteoarthrosis at the hand joints seems to be independent of the hormonal status in postmenopausal women.

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