Tracheobronchial Nodes Research Articles

Development of a model of natural infection with Mycobacterium bovis in white-tailed deer.

The objective of this study was to develop a suitable experimental model of natural Mycobacterium bovis infection in white-tailed deer (Odocoileus virginianus), describe the distribution and character of tuberculous lesions, and to examine possible routes of disease transmission. In October 1997, 10 mature female white-tailed deer were inoculated by intratonsilar instillation of 2 x 10(3) (low dose) or 2 x 10(5) (high dose) colony forming units (CFU) of M. bovis. In January 1998, deer were euthanatized, examined, and tissues were collected 84 to 87 days post inoculation. Possible routes of disease transmission were evaluated by culture of nasal, oral, tonsilar, and rectal swabs at various times during the study. Gross and microscopic lesions consistent with tuberculosis were most commonly seen in medial retropharyngeal lymph nodes and lung in both dosage groups. Other tissues containing tuberculous lesions included tonsil, trachea, liver, and kidney as well as lateral retropharyngeal, mandibular, parotid, tracheobronchial, mediastinal, hepatic, mesenteric, superficial cervical, and iliac lymph nodes. Mycobacterium bovis was isolated from tonsilar swabs from 8 of 9 deer from both dosage groups at least once 14 to 87 days after inoculation. Mycobacterium bovis was isolated from oral swabs 63 and 80 days after inoculation from one of three deer in the low dose group and none of four deer in the high dose group. Similarly, M. bovis was isolated from nasal swabs 80 and 85 days after inoculation in one of three deer from the low dose group and 63 and 80 days after inoculation from two of four deer in the high dose group. Intratonsilar inoculation with M. bovis results in lesions similar to those seen in naturally infected white-tailed deer; therefore, it represents a suitable model of natural infection. These results also indicate that M. bovis persists in tonsilar crypts for prolonged periods and can be shed in saliva and nasal secretions. These infected fluids represent a likely route of disease transmission to other animals or humans.

Intranasal immunization confers protection against murine Pneumocystis carinii lung infection.

To evaluate the feasibility of mucosal immunization against Pneumocystis carinii (Pc) experimental infection, female BALB/c mice were intranasally immunized three times with soluble Pc antigens plus cholera toxin fraction B (Pc-CTB); control groups received either Pc antigen, CTB, or phosphate-buffered saline (PBS) alone. Two weeks after the last immunization, five animals from each group were sacrificed, and cellular and humoral immune responses were evaluated. The remaining five mice were CD4 depleted using a monoclonal antibody against mouse CD4 and inoculated with viable Pc. Significantly higher specific lymphoproliferative responses from tracheobronchial lymph node cells, immunoglobulin M (IgM) and IgG antibody levels in serum, and bronchoalveolar lavage (BAL)-derived IgA antibody concentrations were observed in the Pc-CTB group of mice relative to control groups (P < 0.01). Five weeks after challenge, no Pc organisms were observed in the lung smears of the Pc-CTB group, while the animals receiving antigen, adjuvant, or PBS had progressively higher numbers of Pc microorganisms. By Western blot analysis, a strongly reactive 55- to 60-kDa antigen was recognized by BAL IgA and by serum IgG. In summary, mucosal immunization elicited specific cellular and humoral immune responses and protected against Pc lung infection after immunosuppression.

CT imaging of intrathoracic lymph nodes in dogs with bronchoscopically administered iodinated nanoparticles

The purpose of the study was to determine if airway instillation of iodinated nanoparticles results in contrast material enhancement of tracheobronchial lymph nodes in dogs. Eight dogs underwent intrabronchial instillation of iodinated nanoparticles; six dogs received 900 mg each, and two dogs received 450 mg each. Spiral computed tomography (CT) was then performed 2-34 days later. CT scans obtained 2 days after instillation showed the presence of contrast material within the lung parenchyma but no nodal enhancement. Scans obtained 6-34 days after instillation showed enhancement of the right, left, and middle tracheobronchial lymph nodes (analogous to the mediastinal nodes in humans). Mean nodal attenuation on CT images was 117 HU +/- 43, and the mean nodal volume was 129 mm3 +/- 113. Histologic specimens of the nodes showed macrophage hyperplasia. Iodinated nanoparticles instilled into small airways are transported to the tracheobronchial lymph nodes, where they result in contrast enhancement.

HEALTH EFFECTS OF SULFUR-RELATED ENVIRONMENTAL AIR POLLUTION. III. Nonspecific Respiratory Defense Capacities

Recently concern has been raised about health effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on respiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to 1.0 mum neutral sulfite aerosol with a particle associated sulfur (IV) concentration of 0.32 mg m-3 and for 6 h/ day to 1.1 mum acidic sulfate aerosol providing an hydrogen ion concentration of 15.2 mumol m-3 for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each dog. A second group of eight dogs (control) was kept for the entire study under clean air conditions. Nonspecific defense mechanisms in the airways and in the peripheral lung were studied during chronic exposure of the combination of neutral sulfur(IV) and acidic sulfur(VI) aerosols. No functional changes of tracheal mucus velocity were found, in agreement with unchanged morphometry of the airways. However, the exposure resulted in changes of several alveolar macrophage (AM) mediated particle clearance mechanisms: (1) Based on in vivo clearance analysis and cultured AM studies using moderately soluble cobalt oxide particles, intracellular particle dissolution was significantly reduced since phagolysosomal proton concentration was decreased. We deduce exposure-related malfunction of proton pumps bound to the phagolysosomal membrane as a result of an increase of cytosolic proton concentration. (2) Based on in vivo clearance analysis using insoluble polystyrene particles, AM-mediated particle transport from the lung periphery toward ciliated terminal bronchioli and further to the larynx was significantly reduced. Activation of epithelial type II cells at the entrance of alveoli was inferred from observed type II cell proliferation at those alveolar ridges and enhanced secretion of alkaline phosphatase in the fluid of bronchoalveolar lavages. As a result, hypersecretion of chemotactic mediators by activated type II cells at these loci led to the observed decrease of particle transport toward ciliated bronchioli. (3) Based on in vivo clearance analysis using insoluble polystyrene particles, particle transport from the alveolar epithelium into interstitial tissues was increased and (4) particle transport to the tracheobronchial lymph nodes was significantly enhanced. Particle transport into interstitial tissues is the most prominant clearance pathway from the canine alveolar epithelium. We conclude that the deteriorated particle transport toward ciliated terminal bronchioli resulted in an enhanced particle transport across the epithelial membrane into interstitial tissues and the lymphatic drainage. The observed alterations in alveolar macrophage-mediated clearance mechanisms during chronic exposure of these air pollutants indicate an increased risk of health.

気管・食道のリンパ系の局所解剖

In function-preserving operations of the esophagus and lung, it is crucial to have a precise knowledge of the mediastinal and deep cervical lymphatics and their relationships to surrounding structures. The lymphatics of the mediastinum and neck, which are associated with the esophagus and run along the trachea, were dissected in detail in several anatomical specimens. The actual photographs taken during the dissection are included for a more complete understanding of the intricate topographical relationships. Although there are numerous transverse connections, the mediastinal lymphatics can be roughly divided into two major ascending pathways: the right and the left. Each pathway can then be subdivided into a superficial pathway along the major blood vessels and a deep pathway along the trachea and esophagus. Various deep right ascending pathways are shown to illustrate the problem of the differing levels at which lymph vesseles leave the paratracheal nodes to reach the right venous angle. Further, the brachiocephalic node group is discussed as the critical intermediary nodes between the superficial and deep pathways. Numerous deep left pathways are also dissected from the left tracheobronchial nodes. Some lymphatics ascend along the left recurrent nerve to finally reach the left venous angle, while some pathways traverse to the right side. Still other pathways directly connect to the thoracic duct.

Right Upper Lobe Sleeve Resection

The first plastic-reconstructive procedures of the airway were performed after traumatic injury and tuberculous bronchostenosis.' The success of these early procedures led to the first bronchial sleeve resection for adenoma2 and c a r c i n ~ m a , ~ ? ~ during 1951 through 1952. Sleeve lobectomy was considered an alternative to pneumonectomy in patients with bronchogenic carcinoma because it preserved lung tissue and improved the quality of postoperative survival. Recent long-term studies of patients with lung carcinoma suggest that the results of sleeve lobectomy are comparable to the expected survival after standard lobectomy or pneumonectomy. Weisel et a15 reported no difference in the actuarial survival of 70 patients undergoing sleeve lobectomy compared with 70 patients undergoing pneumonectomy for stage I or I1 disease. Firmin et a16 showed that sleeve resection of squamous cell carcinoma of the upper lobe, in the absence of nodal metastases, produced a 5-year survival of 71%. In a series of 52 patients with T2NO or T3NO squamous cell carcinoma, sleeve lobectomy produced 5and 10-year survival rates of 59% and 47%.7 In a series of 101 sleeve lobectomies for stage I through stage I11 disease, RushPresbyterian-St. Luke's Medical Center reported overall 5-year survival rates of 30% to 33%.839 The right upper lobectomy is the most common sleeve resection. Surveys in Japan have shown that upper-lobe sleeve resections represent 87% of all sleeve lobectomies performed.I0 Because of the relative length of the bronchus intermedius and the favorable arterial anatomy, right upper-sleeve lobectomies are performed more than twice as frequently as left upper-sleeve lobectomies. lo A review of several published patient series support these findings with 76% of the sleeve lobectomies being performed for cancers of the right upper l 0 b e . ~ 1 ~ J ~ J ~

Induction of protective immunity in rabbits by coadministration of inactivated Pasteurella multocida toxin and potassium thiocyanate extract.

Pasteurella multocida is a bacterial pathogen that causes rhinitis (snuffles), pneumonia, otitis media, septicemia, metritis, and death in domestic rabbits. Currently, there are no effective vaccines to prevent infection by this organism. Subcutaneous (s.c.) immunization with either exotoxin or thiocyanate extracts of P. multocida induces partial protection in rabbits. Since disease begins at mucosal sites, induction of local immunity may be important in preventing systemic disease. Little is known concerning the efficacy of intranasal (i.n. ) administration of these antigens in inducing protective mucosal immunity to P. multocida in rabbits. The purpose of this study was twofold: (i) to investigate the effectiveness of vaccination with purified P. multocida toxin (PMT) and a potassium thiocyanate extract of P. multocida (CN) in combination and (ii) to evaluate the efficacy of administration of these antigens i.n. versus s.c. Forty-eight rabbits were randomly divided into eight different treatment groups. Rabbits received either one or both antigens by either s.c. or i.n. administration. Following vaccination, each group received an i.n. challenge of P. multocida. Rabbits vaccinated with both antigens i.n. or s.c. had a 100% survival rate, few or no bacteria in the liver and lungs, high serum immunoglobulin G (IgG) and IgM antibody titers, and significant numbers of IgG antibody-secreting cells (ASC) in the spleen and tracheobronchial lymph node. Rabbits vaccinated i.n. had significant nasal and bronchoalveolar lavage IgA antibody levels. Rabbits vaccinated with only one antigen, either PMT or CN, had lower antibody titers, moderate to severe liver and lung infections, and fewer ASC compared to rabbits receiving both antigens. Rabbits in the control groups had moderate to severe liver and lung infections. This study indicates that i.n. immunization with both PMT and CN induces an effective response against homologous P. multocida challenge.

Recognition of Pneumocystis carinii antigens by local antibody-secreting cells following resolution of P. carinii pneumonia in mice.

To examine the repertoire of Pneumocystis carinii antigens recognized by antibody-secreting B cells from tracheobronchial lymph nodes isolated immediately following recovery from P. carinii pneumonia, monoclonal antibodies (MAbs) were produced from these cells. In contrast to previous studies of systemic immunity, P. carinii gpA was not the immunodominant antigen recognized by these B cells. Forty-nine (91%) of 54 P. carinii-specific hybridoma culture supernatants reacted with P. carinii antigens other than gpA. Many of the resulting MAbs recognized a previously uncharacterized antigen expressed on the surface of both cysts and trophozoites. Western blotting using one of the cloned MAbs revealed reactivity with a broad range of antigenic material, with the most intense reactivity in the 50- to 65-kDa region of the blot. The antigens identified by these MAbs merit further investigation regarding protective immunity to P. carinii because they were recognized by B cells in the context of recovery from P. carinii pneumonia.

A comparison of239+240Pu post-mortem measurements with estimates based on current ICRP models

Measurements of239+240Pu in human tissues, from nuclear weapons testing, provide an invaluable source of data for verifying the uptake and distribution of radionuclides in the body. Measured concentrations of239+240Pu in lung, tracheobronchial lymph nodes, liver and skeleton have been compared with concentrations calculated using estimated plutonium intakes, the ICRP Publication 66 Respiratory Tract Model and the ICRP Publication 67 biokinetic model for plutonium. Measurement data tend to fall between the concentrations estimated on the basis of Type M and Type S absorption parameters. This indicates that the models represent the movement of plutonium through the body reasonably well.

Inhalation of High Concentrations of Low Toxicity Dusts in Rats Results in Impaired Pulmonary Clearance Mechanisms and Persistent Inflammation

This study was carried out to assess the time course of pulmonary clearance impairment and persistence of inflammation following high-dose inhalation exposures to titanium dioxide (TiO2) or carbonyl iron (CI) particles. Male rats were exposed to air, TiO2or CI particles 6 hr/day, 5 days/week, for 4 weeks at concentrations of 5, 50, and 250 mg/m3and evaluated at selected intervals through 6 months postexposure. Indices of pulmonary inflammation as well as alveolar macrophage clearance functions (i.e., morphology,in vivoandin vitrophagocytosis, and chemotaxis), cell proliferation, and histopathology endpoints were measured at several postexposure time periods through 6 months. In addition, amounts of TiO2or CI in lungs and tracheobronchial lymph nodes were measured to allow an evaluation of particle clearance and translocation patterns. Four-week exposures to TiO2or CI particles at concentrations of 250 mg/m3resulted in lung burdens of 12 mg titanium and 17 mg iron, respectively, with particle retention half-times ranging from 68 days for 5 mg/m3TiO2to approximately 330 days for 250 mg/m3. The impact of this TiO2dust load and similar lung burdens of CI particles produced a sustained pulmonary inflammatory response measured through a period of 3–6 months postexposure concomitant with increases in BrdU cell labeling of terminal airway and pulmonary parenchymal cells. The impairment of particle clearance mechanisms was accounted for by deficits inin vitrophagocytic and chemotactic potential of alveolar macrophages recovered from the lungs of high-dose, TiO2- or CI-exposed rats. Free granular pigment (TiO2or CI) was present on the hypertrophic mucosal surfaces of bronchioles and bronchi, and particle-laden macrophages, found individually, were numerous throughout alveoli and within lymphoid tissues immediately after exposure. Aggregates of particle-laden macrophages were present within alveoli and alveolar ducts from 1 week postexposure through the entire 6-month recovery period. Macrophage accumulations increased in size and number from 1 week through 1 month postexposure and then appeared to remain constant through the remaining 5-month postexposure period. Minimal cellular hypertrophy and hyperplasia were evident at alveolar duct bifurcations adjacent to macrophage aggregates, and this effect was most prominent at 3 to 6 months postexposure. The results of this study clearly demonstrate that exposure to high dust concentrations of two different innocuous particle types produced sustained pulmonary inflammation, enhanced proliferation of pulmonary cells, impairment of particle clearance, deficits in macrophage function, and the appearance of macrophage aggregates at sites of particle deposition. In addition, the mass deposition rate determination appears to be a less sensitive indicator of “overload” when compared to biomarkers of pulmonary toxicity, such as macrophage function and cellular inflammation and proliferation indices.

QUARTZ DUST RETENTION IN RAT LUNGS UNDER CHRONIC EXPOSURE SIMULATED BY A MULTICOMPARTMENTAL MODEL: FURTHER EVIDENCE OF THE KEY ROLE OF THE CYTOTOXICITY OF QUARTZ PARTICLES

Several years ago, Bellmann et al. (1991) obtained data on pulmonary lung burdens and tracheobronchial lymph node burdens of quartz dust in long-term inhalation studies with Fischer 344 rats exposed for 30 h/wk to 1 g/m3 of DQ12 quartz particles. The pooled retention data of male and female rats are used here for a simulation study by means of a previously developed multicompartmental mechanistic model that has been successfully applied to long-term retention studies with different samples of quartzite and titanium dioxide. The relative alveolar deposition rate of the DQ12 aerosol as assessed by the model approximation proved to be identical with the relative deposition rate in our previous quartzite study. All the transfer rate coefficients that presumably are affected by inherent particle cytotoxicity, which is higher for DQ12 quartz than for quartzite dust, were changed accordingly, and the model gave a satisfactory simulation of the time patterns of DQ12 quartz mass burden in the pulmonary region and in the lung-associated lymph nodes. Together with the modeling results with far less cytotoxic titanium dioxide particles, our successful simulation seems to corroborate the hypothesis underlying our model, that is, the key role of cytotoxicity in the retention kinetics of insoluble dusts and their disposition in lungs and lung-associated lymph nodes.

Chronic granulomatous pneumonia and lymphocytic responses induced by inhaled beryllium metal in A/J and C3H/HeJ mice.

Inhalation of beryllium (Be) has been associated with 2 syndromes: an acute chemical pneumonitis and a granulomatous lung disease known as chronic beryllium disease (CBD). Key to the pathogenesis of CBD is a delayed-type hypersensitivity reaction, in which Be most likely functions as a hapten and acts as a Class II-restricted antigen, stimulating local proliferation and accumulation in the lung of Be-specific CD4+ T cells. The purpose of this study was to establish a mouse model of CBD using the inhalation route of exposure. A/J (H-2a haplotype) and C3H/HeJ (H-2a) mice were exposed once for 90 min in nose-only exposure tubes to aerosols of Be metal. Six mo later, lung histopathologic responses were assessed. Further analyses defined the phenotypic profile of lymphocytes in pulmonary lesions and evaluated proliferation of lymphocytes in situ and in response to Be in vitro. Responses were similar in both strains of mice. The lungs of all Be-exposed mice had interstitial compact aggregates of lymphocytes, and granulomatous pneumonia characterized by vacuolated macrophages and giant cells in alveoli, neutrophils in alveoli and alveolar septa, multifocal interstitial granulomas, and interstitial infiltrates of lymphocytes, plasma cells, monocytes, and macrophages. Most Be-exposed mice had minimal to mild interstitial fibrosis. The majority of lymphocytes in interstitial infiltrates and in microgranulomas were CD4+ T cells. Interstitial compact aggregates of lymphocytes contained B cells centrally and CD4+ cells peripherally. Lymphocyte labeling indices, used to assess proliferation in situ, were significantly greater within microgranulomas compared to compact lymphocytic aggregates. Lymphocyte stimulation indices in response to BeSO4 in vitro were not positive in blood, spleen, or tracheobronchial lymph node samples. Be-specific immune responses and nonspecific inflammatory responses to toxic and foreign-body properties of Be may have contributed to the histopathology in both strains of mice. The interstitial mononuclear cell infiltrates, presence of microgranulomas, multinucleated foreign-body and Langhans' giant cells, interstitial fibrosis, and CD4+ T-cell predominance with local proliferation are features similar to CBD in humans. The chronic lung disease induced in these mice by inhaled Be can be used to investigate the importance of variables such as dose, exposure pattern, and physicochemical form of Be in producing this disease.

Association of Periodontal Disease and Histologic Lesions in Multiple Organs from 45 Dogs

Forty-five mixed breed dogs were evaluated for the presence and extent of periodontal disease. Histopathology was performed on samples of lung, myocardium, liver, kidney, tonsil, spleen, submandibular lymph node and tracheobronchial lymph node. Mitral valves were evaluated grossly. Statistical analysis was used to determine if there was a relationship between the extent of periodontal disease and histopathologic changes in the tissues examined. In the forty-five dogs studied, an association was found between periodontal disease and histopathologic changes in kidney, myocardium (papillary muscle), and liver.

Growth and metastasis of two canine mast cell tumors in SCID mice.

Intermediately differentiated mast cell tumors in two dogs were subcutaneously xenotransplanted into severe combined immunodeficiency (SCID) mice. Both tumors primarily grew and were serially transplantable in SCID mice. The histological features of the xenografts were similar to those of original tumors in dogs. Both of these subcutaneous tumors were judged as connective tissue mast cells by toluidine blue stain. One of the two xenografts metastasized to the tracheobronchial lymph nodes, omentum, mesentery, subpleural region and retroperitoneum of the SCID mouse. These canine mast cell tumor xenografts in SCID mice may be valuable tools for investigating the growth and metastatic behaviors of the tumor.

Hematogenous metastases of pancreatic ductal carcinoma.

To investigate the heterogeneity of hematogenous metastases of pancreatic ductal carcinoma, we investigated carcinomatous spread in 130 autopsy cases. Hepatic metastases occurred most frequently, in 81 cases (62%), which may be explained by the fact that all veins draining the pancreas flow into the portal system. We closely examined the 49 cases without hepatic metastases. Sixteen patients had pulmonary metastases without hepatic metastases, whereas seven had peculiar hematogenous metastases without hepatic or pulmonary metastases. Fifteen of these 23 patients had pancreatic body carcinomas. The unusual patterns of spread might be due to (a) hepatofugal portosystemic shunting induced by splenic vein obstruction, (b) retrograde lymphatic infiltration from metastatic tracheobronchial lymph nodes, or (c) aggressive characteristics of the tumors indicated by peculiar histologic features such as pleomorphic or mucoepidermoid carcinoma, etc. Sixteen patients showed only lymph node metastases and 10 had no distant metastases. Seventeen of these 26 cases had pancreatic head carcinoma. Histologically, two patients had mucinous cystadenocarcinomas, and six had adenocarcinomas producing rich mucin. The average age of the group with no distant metastases was higher.

Rhodococcus equi-associated necrotizing lymphadenitis in a llama

A case of Rhodococcus equi-associated necrotizing lymphadenitis in a 2-year-old male llama is described. Caseous necrosis, resembling macroscopically that seen in ovine caseous lymphadenitis, was observed diffusely in the tracheobronchial and mediastinal lymph nodes, and in an extensive lesion in the lungs. Necrosis was present to a lesser extent in the spleen and hepatic and gastric lymph nodes. Numerous bacteria-laden macrophages were present around the necrotic areas. The findings suggest that, as in cattle and pigs, the primary targets of R. equi infection in the llama are the lymphoid organs.

Thoracoscopic mediastinal lymph node dissection: an experimental study in pigs

Thoracoscopic lobectomy is feasible and can be performed correctly in terms of anatomy. Its application in bronchial carcinoma is often criticized, partly because of incomplete mediastinal lymph node dissection (MLD). We therefore developed the technique and studied the completeness of MLD in an animal experiment. Ten pigs were anesthetized and intubated with a double-lumen tube and the left lung was excluded from ventilation. Four trocars were inserted. Using a modified endo-Babcock clamp for traction we resected all ipsilateral tracheobronchial, pretracheal and paratracheal and paraesophageal lymph nodes (LNs) as well as nodes in the aortopulmonary window. An average of 19 +/- 5 mediastinal LNs were removed. Macroscopic control through a thoracotomy did not show any residual LNs at the site of operation. Complete resection of all ipsilateral LNs in the paratracheal and paraesophageal region as well as the aortopulmonary window can be performed thoracoscopically in pigs. This may offer further perspectives in the thoracoscopic treatment of bronchial carcinoma.

The value of parasternal mediastinoscopy in staging bronchial carcinoma.

Computed tomography (CT) is the non-invasive staging procedure of choice for assessment of metastasis to mediastinal lymph nodes in patients with bronchial carcinoma. Cervical mediastinoscopy can provide histologic evidence of mediastinal spread to the peritracheal, tracheobronchial and subcarinal lymph nodes. Sub-aortic and para-aortic nodes cannot be sampled via this route. The present study was performed to assess the staging value of the parasternal mediastinoscopy as a separate entity. Cervical and parasternal mediastinoscopy was performed in 37 patients with a proven diagnosis of non-small cell carcinoma of the left upper lobe. In 16 patients lymph node or tumor tissue could be biopsied via the parasternal route, in 21 patients no parasternal biopsy was taken. Of the 16 cases with biopsies, only one was positive (6%). Histologic examination of lymph node biopsy tissue was false negative in one other patient (6%). Of the 21 patients without biopsies taken during parasternal mediastinoscopy, three (14%) had proven lymphogenic spread to the subaortic and para-aortic nodes, detected at thoracotomy. The parasternal procedure changed treatment in only one patient (3%). Diagnostic sensitivity was 20%. It is concluded that parasternal mediastinoscopy should not be used as a routine staging procedure in patients with left upper lobe lung cancer.

Enhanced translocation of particles from lungs by jaggery.

Because industrial workers in dusty or smoky environments seemed to experience no discomfort if they consumed the sugar cane product jaggery, experimental studies were undertaken to observe the effects of jaggery on dust-exposed rats. Rats with and without a single intratracheal instillation of coal dust (50 mg/rat) were orally gavaged with jaggery (0.5 g/rat, 5 days/week for 90 days). The enhanced translocation of coal particles from lungs to tracheobronchial lymph nodes was observed in jaggery-treated rats. Moreover, the jaggery reduced the coal-induced histological lesions and hydroxyproline contents of lungs. The lesions induced in omental tissue and regional lymph nodes by a single intraperitoneal injection of 50 mg each of coal and silica dust were modified by jaggery (0.5 g/rat, 5 days/week for 30 days). These findings along with the preventive action of jaggery on smoke-induced lung lesions suggest the potential of jaggery as protective agent for workers in dusty and smoky environments.

Prediction of the comparative intensity of pneumoconiotic changes caused by chronic inhalation exposure to dusts of different cytotoxicity by means of a mathematical model.

A multicompartmental mathematical model has been used to simulate variations in the cytotoxicity of dusts in the kinetics of the retention, in the pulmonary region and tracheobronchial lymph nodes, of practically insoluble quartzite and titanium dioxide dust particles deposited on the free surfaces of the acini from alveolar air. Experiments with these dusts were conducted on rats exposed to virtually the same dust concentrations in the air for an experimental period of 20 weeks and a period of 10 weeks after exposure. Satisfactory approximation to the experimental data on the retention of these dusts is obtained by using the model parameters that depend either on damage to lung macrophages by phagocytosed particles or on the response of the host organism to this damage by enhanced recruitment of neutrophilic leucocytes; all the other variables of the model being unchanged. The values of the "action integral" computed from this model and multiplied by the index of comparative cytotoxicity of particles in vitro satisfactorily approximate to quantitative differences in the intensity of pneumoconioses caused by the dusts under study by the end of the experimental period. On the whole, the results of the mathematical model agree with the hypothesis that the cytotoxicity of particles plays a key part in both the process of retention of dust in the lung parenchyma and lung associated lymph nodes, and the pathological process caused by the retained dust. Thus given the factors and conditions on which the deposition of practically insoluble dusts in the pulmonary region depends, it is necessary to take into account the multiplicative nature of these two effects of cytotoxicity when predicting the comparative risk of pneumoconiosis.