Biomedical subjects

N R Grande

Publications and source records attributed to N R Grande.

At least 19 recordsLinked to original sources

PubMed2005

Differential expression of collagens type I and type IV in lymphangiogenesis during the angiogenic process associated with bleomycin-induced pulmonary fibrosis in rat.

In order to assess the role of collagens I and IV during the angiogenic process associated with bleomycin-induced pulmonary fibrosis in rat, in situ hybridization and immunocytochemical studies were carried out. An increased expression of collagen IV was observed before an enhanced expression of collagen I after intratracheal instillation of bleomycin. Deposits of both collagen types were detected on the 21st day after treatment with bleomycin, surrounding the new blood vessels formed during the fibrotic process. At this time, the presence of new lymphatic vessels was associated uniquely with deposition of collagen I. These observations lead us to conclude that, at least during pulmonary fibrosis, lymphangiogenesis takes place after blood angiogenesis.

Animals↗

PubMed2003

Zonation of ciliated cells on the epithelium of the rat trachea.

We have used scanning electron microscopy (SEM) to screen the entire epithelial surface of the cervical trachea of the adult rat. This scrutiny revealed that the density of ciliated cells along this epithelium follows a repetitive pattern: circular strips of high density of ciliated cells alternate with areas of low density of the same cells. Cilia-poor strips of the tracheal epithelium were seen on areas of cartilage rings; here, ciliated cells made up 32% of the total surface of the tracheal lining. Cilia-rich areas filled the epithelial surface at the tracheal ligaments (i.e., the regions located in-between the rings); here, ciliated cells occupied 65% of the tracheal lumen. In the cilia-poor zones, the density of ciliated cells decreased from its periphery into its center, where cilia were virtually absent. No differences in this pattern of the tracheal epithelium were seen between young adult and older rats. We conclude that the respiratory epithelium expresses density zonation of ciliated cells on the trachea of adult rats. We propose that the high concentration of ciliated cells on the regions of epithelium located at the tracheal ligaments suggests that these zones are electively committed in the clearance of the respiratory airway.

Animals↗

PubMed2003

Bulging mesothelial cells of the visceral pleura of the rat mimic the network of subpleural lymphatics.

The mesothelial surface of the visceral pleura of the Wistar rat was viewed at high resolution by scanning electron microscopy (SEM). The pleural surface showed exquisite linear arrangements made up of bulging mesothelial cells. They were organized in irregular circles that often presented anastomotic junctures. This arrangement of pleural mesothelial cells mimics the organization of subpleural lymphatics of the lung. A low density of microvilli was seen inside the irregular circles, contrasting with the microvilli-rich mesothelial cells seen on or outside these arrangements. These SEM features of the mesothelium may be related with the formation of microdomains for fluid absorption across the visceral pleura into subpleural lymphatics.

Animals↗

PubMed2002

Morphology of trachea in benign human tracheal stenosis: a clinicopathological study of 20 patients undergoing surgery.

Prolonged tracheal intubation of patients often leads to tracheal stenosis (TS), which may require surgical removal of the narrowed portion of the airway. We studied 20 patients with TS who underwent surgical ablation of the stenotic portion of trachea. The morphology of the tracheal segments was characterized and compared with clinical data and with the prognosis for the disease. We found that TS was usually due to an increase in the width of the mucosa as a result of the fibrosis associated with the chronic inflammation. Plasma cells were the predominant leukocyte type seen in the inflammatory infiltrates of the surgically removed portions of narrowed trachea. In the majority of TS samples, the epithelial surface was intact and presented cilia; in contrast, cilia disappeared when the tracheal lumen was completely obliterated. Mucosal cells and glands were also well preserved in TS samples. The need to remove TS segments was often related to previous tracheal surgery, which was also associated with closing of the tracheal lumen and ossification of cartilage rings. We conclude that (a). chronic inflammation and fibrosis are responsible for the narrowing of trachea in TS patients, (b). metaplastic ossification of cartilage rings only occurs after complete obliteration of the tracheal lumen, and (c). loss of cilia and presence of metaplastic bone tissue are indicators of a poor prognosis for TS.

Adult↗

PubMed2001

In utero and postnatal exposure of Wistar rats to low frequency/high intensity noise depletes the tracheal epithelium of ciliated cells.

Chronic exposure of men or rodents to low frequency/high intensity (LFHI) noise causes a number of systemic changes that make up the so-called vibroacoustic disease (VAD), a disorder that includes alterations of the respiratory system, namely, of its epithelial layer. We have investigated here the susceptibility of the tracheal epithelium of Wistar rats to in utero and postnatal exposure to LFHI noise by comparing its ultrastructure with that of the tracheal epithelium of control rats and of animals exposed to LFHI noise only after reaching adulthood (8 weeks of age). Scanning electron microscopy (SEM) of the inner surface of rat trachea was used to determine the relative areas covered by ciliated and non-ciliated cells. In rats that were exposed in utero and postnatally to LFHI noise, we observed that out of 100 microm(2) of tracheal epithelium only 31 +/- 14 microm(2) were covered by cilia, whereas in control rats; ciliated cells occupied an average of 60 +/- 18 microm(2) out of 100 microm(2) of the epithelium; this difference between the two groups was statistically significant (p <0.05). In rats that were exposed to LFHI noise only after reaching adulthood, cilia covered 55 +/- 22 microm(2) out of 100 microm(2) of the luminal surface of the trachea, a value that, although lower than that of controls, was not found to be statistically different. We conclude that (1) the tracheal ciliated cells are damaged by exposure of rats to LFHI noise if the animals are kept under this environmental aggression during in utero and postnatal periods; (2) tracheal ciliated cells from adult rats are more resistant to the deleterious effects of LFHI noise than pleura or lung alveolar cells that were shown before to undergo marked changes upon chronic exposure of rats to LFHI noise. These findings suggest a note of caution regarding pregnant women and young children: they should be prevented from areas where LFHI noise occurs, namely, in aircraft and textile industries where this type of environmental hazard is often present.

Animals↗

PubMed2001

Tracheal transplantation: cytological changes studied by scanning and transmission electron microscopy in the rabbit.

OBJECTIVES: Our goal was to offer a comprehensive cytological study of the changes in the trachea after experimental transplantation of the organ. STUDY DESIGN: Autografting of four tracheal rings was done in rabbits and tracheal samples were observed by electron microscopy from 1 week to 6 months after the surgery was performed. METHODS: Transmission and scanning electron microscopy were used to investigate the fine structure of tracheal samples of rabbits submitted to autotransplantation, and quantitative methods were used to compare several cytological parameters of the different groups of animals. RESULTS: We found that tracheal autografting was associated with acute injury of ciliated cells expressed by loss of more than 90% of cilia density on the tracheal epithelium 1 week after the transplantation was performed. The loss of cilia was balanced by an increase in mucous cells present on the tracheal lumen. Recovery of ciliated cells was observed 1 month after the tracheal autografting was performed. In contrast, only mild cytological modifications were seen in the cartilage tissue of the autografted trachea during the first weeks of transplantation; the structural alterations of the cartilage progressed up to the third month after transplantation, resulting in a moderate tracheal stenosis. CONCLUSIONS: The data indicate that 1) autotransplantation of four tracheal rings is a viable surgical procedure; 2) tracheal grafting causes severe acute changes of the epithelium that are, however, reversible in nature; whereas 3) the initial mild alterations induced by the autografting in the cartilage may evolve into tracheal stenosis.

Animals↗

PubMed1999

Limb immobilization and intimal hyperplasia--an echo-Doppler study in man.

The authors studied the circulatory alterations observed in the upper limbs of patients showing muscular atrophy due to flaccid paralysis of traumatic origin. Ten patients who had suffered avulsion of the nerve roots from C4 to D1 that occurred 9 to 216 months previously, presented a significant degree of muscular atrophy of the affected upper limb, despite physiotherapy. We performed echo-doppler examinations of the patients to measure the lumen of the subclavian, axillary, brachial, radial and ulnar arteries and also of the veins of both upper limbs. The measurements from both upper limbs in each patient were statistically compared. The data revealed a significant reduction of the width of the lumen of the arteries and veins and a reduced arterial blood flow in the affected limb in comparison with the normal one. The greater echogenicity and the abnormal Doppler waves of the affected vessels suggest that they presented an increased thickness and a hardened wall. The authors propose that this finding may be related to an intimal hyperplasia brought about by muscular atrophy or by the observed blood flow reduction.

Adult↗

PubMed1999

The human pericardium in vibroacoustic disease.

INTRODUCTION: One of the main features of vibroacoustic disease (VAD) is the proliferation of the extra-cellular matrix which induces cardiovascular morphological and dynamic changes, and has been evaluated through echo-Doppler. While all subjects exposed to large pressure amplitude (> or =90 dB SPL) and low frequency (< or =500 Hz) (LPALF) for at least 15 yr have thickening of some cardiac structure, most frequently the pericardium, no significant diastolic changes accompany these observations. Echocardiography has become the diagnostic method of choice for the VAD. However, there have been no studies relating the echo-images of pericardial thickening to gross anatomy. METHODS: We present the histology and ultrastructure of the pericardia of four patients who underwent cardiac surgery. RESULTS: The most important findings concern the real thickening of the pericardium (values: 1.11, 1.35, 2.19, and 2.33 mm vs. norm: < or = 0.5 mm), the dynamic arrangements of mesothelial cells in the serosa layer, and the plasticity of the cells found among the multifascicular waveform collagen fibers. We found that the fibrosa of VAD patients has three layers: sandwiched between two thickened layers of normal fibrosa there is a loose tissue layer with vascular, nervous, and adipose structures. CONCLUSION: These features may partially explain why no important diastolic changes are observed in VAD patients in spite of the pericardium thickening.

Adult↗

PubMed1999

Morphological changes in rat lung parenchyma exposed to low frequency noise.

BACKGROUND: Airway flow limitation is has been identified in nonsmoker aeronautical technicians who are exposed to long term (> or =10 yr) large pressure amplitude and low frequency (LPALF) noise (> or =90 dB, < or =500 Hz). Considering this work environment, some kind of pulmonary impairment would be expected, given the probable, but not de facto, existence of fuel exhausts and vapors. In the course of morphofunctional studies of rat pleura exposed to LPALF noise environments, intense subpleural fibrosis was identified. Thus, we decided to study the deep lung parenchyma of these noise-exposed rodents. METHODS: One group of five Wistar rats was exposed to LPALF noise for a cumulative 4000 h, and another of five rats were exposed for a cumulative of 5000 h. The control group consisted of 10, age-matched, Wistar rats that were kept in the same conditions, but in silence. Fragments of lung parenchyma were extracted after sacrifice, and processed for light microscopy, and for scanning and transmission electron microscopy. RESULTS: Focal interstitial fibrosis of the deep lung parenchyma were identified as well as changes in the small bronchial cilia. The amount of brush cells was increased in the locations where microvilli were abnormal. An obvious increase of alveolar type II pneumocyte cells was observed with numerous, large and confluent lamellar bodies. DISCUSSION: In contrast with the normal lung morphology observed in the control group, changes in the extra-cellular matrix and epithelial cells were identified in the exposed rats. No fuel exhaust, vapors or dust were present in the environment of the noise-exposed rats. These results, linked with the respiratory disorders identified in noise-exposed humans, strongly suggest that LPALF noise is an agent of pulmonary fibrosis.

Animals↗

PubMed1999

Morphofunctional study of rat pleural mesothelial cells exposed to low frequency noise.

BACKGROUND: Vibroacoustic disease (VAD) is a noise-induced pathology occurring in workers occupationally exposed to large pressure amplitude (> or =90 dB SPL) and low frequency (< or = 500 Hz) (LPALF) noise, over long periods of time (> or = 10 yr). Patient complaints frequently involve the respiratory tract. There have been three cases of pleural effusion of unknown etiology and with unusually long recovery times. To better understand what may be occurring we studied the effects of LPALF noise on the morphological and functional characteristics of pleural mesothelial cells of Wistar rats. METHODS: The animals were exposed to LPALF noise for periods ranging from 24-600 h. An intrapleural instillation of calcium tungstate was performed, and after sacrifice the pleural visceral and parietal leaflets were studied by scanning electron microscopy. RESULTS: Acute exposure to LPALF noise caused a temporary decrease in the number of mesothelial microvilli, and prolonged exposure resulted in a definite decrease in their number as well as an impairment of their capacity to absorb particles within in the pleural space. CONCLUSION: These results explain the pleural pathology found in human patients with VAD and confirm the deleterious effect of LPALF noise on the respiratory system.

Absorption↗

PubMed1999

The effect of chronic exposure to low frequency noise on rat tracheal epithelia.

INTRODUCTION: Vibroacoustic Disease (VAD) is a multi-systemic entity caused by occupational or chronic exposure to large pressure amplitude and low frequency (LPALF) noise (> or = 90 dB SPL, < or = 500 Hz). The clinical picture involves extra-auditory pathology, such as neurological disturbances, respiratory disorders and cardiovascular problems. Among the first complaints of VAD patients are coughing, bronchitis, and inflammation or infection of the oral cavity and the upper respiratory pathways. The goal of ths study was to investigate the effects of occupationally simulated LPALF noise exposure on rat tracheal epithelium to determine if they could explain the symptoms found in VAD patients. METHODS: We exposed 20 Wistar rats to occupationally simulated (8 h x d(-1), 5d x wk(-1)) LPALF noise for an accumulated total of 1236 h. The control group consisted of 10 age-matched rats, kept in equal conditions but in silence. Histological and ultrastructural studies were performed on the tracheal epithelia of both populations. RESULTS: The most dramatic changes were identified in the ciliated cells of the exposed rats. There were frequent images of shaggy or necrotic cilia as well as regularly to partially sheared cilia. Also, there were frequent images of different stages of cilia recovery. CONCLUSION: Occupationally simulated exposure to LPALF noise can cause important changes in ciliated cells rat tracheal epithelia. This may partially explain the clinical findings observed in VAD patients.

Animals↗

PubMed1999

Acceleration of lupus erythematosus-like processes by low frequency noise in the hybrid NZB/W mouse model.

INTRODUCTION: We investigated the effect of low frequency noise on the natural history of autoimmune diseases using hybrid New Zealand Black (NZB) and White (NZW) male mice that are prone to spontaneously develop systemic lupus erythematosus after 6 mo of age. METHODS: We exposed 3-mo-old mice to periods of low frequency noise (> or = 90 dB SPL, < or = 500 Hz) for a total of 216 h; the animals were studied up to 12 mo of age and data were compared with results obtained with age-matched controls. RESULTS: We found that noise exposure caused an earlier expression of proteinuria, a change that was associated with acceleration of kidney lesions and increased mortality. At 8 mo of age, after 3 mo of chronic exposure to noise, the exposed mice presented significantly higher numbers of splenic IgM+ lymphocytes and CD8+ T cells than the age-matched controls. CONCLUSION: Exposure of lupus-prone mice to low frequency noise accelerates the expression of the autoimmune disease and it affects the immune system by raising the number of splenic IgM+ B lymphocytes and CD8+ T cells.

Animals↗

PubMed1999

Effects of low frequency noise upon the reaction of pleural milky spots to mycobacterial infection.

INTRODUCTION: Milky Spots (m.s.), also known as Kampmeier's foci, are confined to the parietal leaflet and act as a barrier to mediastinum infections, having very important phagocytic functions. Previous studies have made clear that large pressure amplitude and low frequency (LPALF) noise (> or = 90 dB, < or = 500 Hz) induces morphofunctional changes on the pleural mesothelium. The purpose of this study was to investigate the dynamics of m.s., namely the response to infectious agents reaching the pleural space under noise stress. METHODS: Wistar rats (n = 20) were used; 5 as control and sham operated, 5 exposed to infection but not to noise, 5 exposed to 1696 cumulative hours of LPALF noise, and 5 exposed to 2184 cumulative hours. Following noise exposures, all rats except the 5 controls were injected with 0.2 ml of saline solution containing 2 x 10(8) viable mycobacterium avium bacilli (ATCC-25291 strain, sereotype 2). The rats were sacrificed 21 d after infection and sections of the retrocardiac pleural leaflets were observed with a light microscope using the Ziehl-Neelsen staining method. RESULTS: There was an increase in the number and diameter of the m.s. due to hypercellularity, mainly caused by the increase of mononuclear cells, and there was formation of large granulomas containing many mycobacteria. Rats submitted to noise also presented alterations of the standard morphological changes, namely partial necrosis of the m.s. CONCLUSION: The data suggest that exposure to LPALF noise can interfere with the normal immune response to bacterial infection in rats. This can be an important contribution to the understanding of the disorders in the pleural space of vibroacoustic disease patients.

Animals↗

PubMed1999

Increase in CD8+ and CD4+ T lymphocytes in patients with vibroacoustic disease.

INTRODUCTION: Some workers employed by the aviation industry are exposed to large pressure amplitude and low frequency (LPALF) noise (> or =90 dB SPL, < or = 500 Hz) and have developed vibroacoustic disease (VAD), a whole-body noise-induced pathology. Since VAD patients have an increased prevalence of respiratory and skin infections, we investigated whether these individuals had any quantitative changes in the number of peripheral blood cell populations. Also, we investigated whether different types of noise environments are related to cell quantification. METHODS: Quantification of peripheral blood cell populations was performed in venous blood samples of 34 VAD-diagnosed patients, and 41 controls. Leukocytes, monocytes, granulocytes, and surface phenotypes of CD8+ and CD4+ T lymphocytes were considered. RESULTS: We found that VAD patients showed a statistically significant elevation in the number of circulating CD8+ and CD4+ T lymphocytes when compared with the control population, but not when compared among different noise-environments. Monocyte and granulocyte populations did not register significant differences. CONCLUSION: VAD patients present enhancement in the number of circulating cytotoxic T lymphocytes (CD8+ and CD4+ T cells) thus indicating that this environmental disease is associated with quantitative changes in immune cells.

Adult↗

PubMed1995

Identification of vascular sphincters at the junction between alveolar capillaries and pulmonary venules of the mouse lung.

BACKGROUND: A peculiar feature of lung circulation in the lung is the pronounced variations in blood volume observed in alveolar capillaries that occur because of the changes in the conformation of the alveolar wall that are associated with the respiratory movements. This phenomenon has led to the postulate that mechanisms of postcapillary control of blood flow are to be present in the lung vessels. In the present study we searched for microanatomical evidence of vascular sphincters in the deep lung tissue of mice, namely in alveolar capillaries and pulmonary veins. METHODS: We have used scanning electron microscopy (SEM) to examine two types of samples of normal lung tissue of CD-1 mice: 1) vascular corrosion casts made by vascular perfusion with Mercox resin, and 2) routinely made gold/platinum-coated replicas of sectioned lung tissue. RESULTS: Careful scrutiny of the vessels of the deep lung tissue led to the identification of sphincters in alveolar capillaries. These sphincters were located at the junction between capillary and pulmonary veins. They corresponded to areas of the vascular wall showing circular swellings where a radial organization was observed, since they were made up of alternating grooves and bulges. Transmission electron microscopy showed that smooth muscle cells participated in the formation of the sphincters. CONCLUSIONS: Our data reveal a new location for vascular sphincters in pulmonary vessels and, because these novel sphincters are located at the capillary-vein junction, they offer a structural setting for the existence of postcapillary control of blood flow in the pulmonary circulation of mice.

Animals↗

PubMed1995

Variations in the anatomical organization of the human aortic arch. A study in a Portuguese population.

We have studied the anatomical features of human aortic arches in a sample of the Portuguese population using postmortem measurements of the arches and their branches in 33 cadavers. We found that there is a significant minority of individuals (18% of the total) who did not present the usual 3-branched aortic arch; interestingly, all 2-branched arches were seen in women and all 4-branched arches were observed in men. The arterial branches could spring either from the ascending segment of the arch (61% of total) or from its horizontal segment (39% of total). Our measurements showed that the springing of the branches was associated with the narrowing of the aortic arch, so that the difference in the diameter of the aortic arch between the origin of the first and last branches could reach up to 11 millimeters. We found that the relative caliber of the arterial branches of the aortic arch depended on the position of its origin at the arch: in aortic arches with branches that were originated at the horizontal segment of the arch the first arterial branch was always the widest of the three, whereas in aortic arches with branches coming out at the ascending segment of the arch the widest arterial branch was the third one. Our data support the view that there is a wide spectrum of variations in the anatomical arrangement of the aortic arch in humans, and offer information on the prevalence of aortic arch variations in a Portuguese population.

Adult↗

PubMed1994

Neoformation of blood vessels in association with rat lung fibrosis induced by bleomycin.

We have used intratracheal instillation of bleomycin in rats to study the microanatomical changes of blood vessels associated with lung fibrosis. Bleomycin is a toxic cytostatic drug employed in classical models of lung fibrosis. Wistar rats were submitted to intratracheal injection of 1.5 units of bleomycin and sacrificed 2.5 months later, a timing when marked fibrosis of the lung is observed. We casted the vascular tree of the rat lungs by perfusion with a methacrylate resin. These casts were studied by scanning electron microscopy. Lung tissue was also studied by light microscopy and thin section electron microscopy. The major vascular modifications observed in the bleomycin-treated rats were: (1) neoformation of an elaborate network of vessels located in the peribronchial domains of the lung, and (2) distortion of the architecture of alveolar capillaries. By light microscopy, it was clear that the newly formed vascular network was located in regions of fibrosis (which in the resin casts were digested away). These neoformed vessels appeared to originate from bronchial arteries. Thin section electron microscopy revealed that endothelial cells of the neoformed vessels were plump, presented large nuclei, and showed numerous pinocytotic vesicles that were also observed in subendothelial pericytes. The alveoli of the bleomycin-treated rats were heterogeneous in size and shape in contrast with the homogeneity of alveoli of control animals. The alveolar capillaries of fibrotic lungs appeared to occupy a larger volume of the alveolar wall than alveolar capillaries of control rats. Our findings indicate that lung fibrosis encompasses marked changes of the vascular system, namely, the neoformation of vessels and the rearrangement of alveolar capillaries. These structural changes suggest that fibrotic transformation of the lung is associated with the local generation of angiogenic stimuli.

Animals↗

PubMed1994

Anatomical basis for the separation of four cardiac zones in the walls of human heart ventricles.

The coronary vessels of 70 human hearts were visualized postmortem by injection of the coronary arteries with a X-ray opaque substance (for angiographic studies) or with a low viscosity resin (to obtain vascular casts). Analysis of the data suggests a new anatomical systematization of the vascularization of the myocardial tissue of human heart ventricles: it can be divided into four zones each having a different origin of the arterial vessels. These four components of the heart ventricles are the antero-septal (AS), postero-septal (PS), left-lateral (LL), and right-lateral (RL) zones. They correspond to the territories of the anterior interventricular branch of the left coronary artery (AS zone), of the posterior interventricular branch of the right coronary artery (PS zone), of the left circumflex artery (LL zone), and of the right coronary artery (RL zone) up to the origin of the posterior interventricular artery. This systematization of the arterial heart ventricles in zones offers a balanced division of the myocardial tissue, since each of the four zones occupied about one fourth of the total volume of the ventricles. In our samples, the most common distribution of segments in the wall of heart ventricles was the following: 16 segments in the AS zone, 11 segments in the PS zone, 5 segments in the LL zone, and 4 segments in the RL zone. The separation of four zones in the walls of heart ventricles, each of them made up of different segments, may be helpful in the understanding of the pathophysiology of myocardial ischemia, and also in the choice of surgical strategies to treat aneurisms of the heart ventricle wall.

Adolescent↗