Interstitial Inflammatory Infiltration Research Articles

Dermatomyositis Associated With Urachal Adenocarcinoma

Dermatomyositis affects children and adults, females more often than males, and is traditionally closely associated with internal malignancy. Approximately 30% of patients with dermatomyositis have a malignancy, most commonly of the lung, ovary, breast or stomach.1 Urogenital malignancies associated with dermatomyositis are relatively rare although several cases associated with transitional cell carcinoma of the bladder have been documented.2 To our knowledge we report the first case of dermatomyositis associated with urachal adenocarcinoma. CASE REPORT A 47-year-old female presented with a 4-month history of gross hematuria and edema of the upper body. The patient also reported a 10 kg. weight loss. Physical examination revealed erythema affecting the face, shoulders, chest and back. The face was especially swollen with edema and erythema. Cystoscopy and computerized tomography (CT) demonstrated a solid mass in the dome of the bladder (fig. 1). Biopsy of the skin and deltoid muscle showed epidermal atrophy with a thickened basement membrane, and perivascular and interstitial inflammatory infiltrates. The muscle revealed myofiber degeneration and atrophy, increased interstitial collagen and endomysial inflammatory infiltrates (fig. 2, A). These findings were consistent with dermatomyositis. Laboratory tests demonstrated increased creatine phosphokinase (937 units per l., normal 35 to 165), increased lactic dehydrogenase (1,027 units per l., normal 203 to 450) and increased carcinoembryogenic antigen (46.3 ng./ml., normal less than 5.0). Transurethral resection of the bladder tumor showed moderately differentiated adenocarcinoma invading the bladder wall (fig. 2, B). Consequently, the clinical diagnosis was dermatomyositis associated with urachal adenocarcinoma. For the treatment of dermatomyositis 1 mg./kg. prednisolone per day was administered, and an immediate effect was observed with regard to the skin and muscle symptoms. Total cystectomy was not recommended because of a lung metastasis detected on CT, and the patient instead underwent pelvic irradiation (total 50 Gy.) and 2 courses of systemic chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin. The response to these therapies was minimal. One year after diagnosis, the patient died of multiple metastases to the liver and lung. However, the characteristic symptoms of dermatomyositis were well controlled by prednisolone until the end of her life.

Viral pneumonias in adults: radiologic and pathologic findings.

Numerous viruses, including influenza virus, measles virus, Hantavirus, adenovirus, herpesviruses, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus, can cause lower respiratory tract infection in adults. Viral pneumonia in adults can be classified into two clinical groups: so-called atypical pneumonia in otherwise healthy hosts and viral pneumonia in immunocompromised hosts. Influenza virus types A and B cause most cases of viral pneumonia in immunocompetent adults. Immunocompromised hosts are susceptible to pneumonias caused by cytomegalovirus, herpesviruses, measles virus, and adenovirus. The radiographic findings, which consist mainly of patchy or diffuse ground-glass opacity with or without consolidation and reticular areas of increased opacity, are variable and overlapping. Computed tomographic findings, which are also overlapping, consist of poorly defined centrilobular nodules, ground-glass attenuation with a lobular distribution, segmental consolidation, or diffuse ground-glass attenuation with thickened interlobular septa. The radiologic findings reflect the variable extents of the histopathologic features: diffuse alveolar damage (intraalveolar edema, fibrin, and variable cellular infiltrates with a hyaline membrane), intraalveolar hemorrhage, and interstitial (intrapulmonary or airway) inflammatory cell infiltration. Clinical information such as patient age, immune status, community outbreaks, symptom onset and duration, and presence of a rash remain important aids in diagnosis of viral causes.

Transferrinuria in type 2 diabetic patients with early nephropathy and tubulointerstitial injury

Background: Transferrinuria is thought to be a marker for early stages of diabetic nephropathy. Transferrin has also been proposed as a mediator of tubular toxicity because the reabsorption of transferrin results in the release of reactive iron in proximal tubular cells, promoting the formation of hydroxyl radicals. We evaluated the role of urinary transferrin excretion in diabetic patients with early nephropathy by comparing tubulointerstitial injury in renal biopsy specimens. Patients and methods: 45 type 2 diabetic patients with normoalbuminuria (urinary albumin excretion <30 mg/24 h) or microalbuminuria (30–300 mg/24 h) were studied. All patients with microalbuminuria underwent renal biopsy, and the severity of the tubulo-interstitial lesions was determined by a semiquantitative estimate of interstitial fibrosis, tubular atrophy, and interstitial inflammatory infiltrates. Subjects were classified into group A (normoalbuminuria, n=25), group B (microalbuminuria without tubulointerstitial changes, n=11) or group C (microalbuminuria with tubulointerstitial changes, n=9). Results: Urinary transferrin excretion (UTf), as well as UTf/creatinine clearance (Ccr), and transferrin clearance (CTf/Ccr), was significantly higher in groups B and C than in group A, and it was significantly higher in group C than in group B. There were no significant differences in urinary albumin excretion or mesangial expansion rate (MR% estimated by quantitative morphometric studies) between groups B and C. Although urinary β2-microglobulin excretion was significantly higher in group C than in groups A and B, urinary N-acetyl-β- d-glucosaminidase activity was significantly higher in groups B and C than in group A. Conclusions: Increased transferrinuria in the microalbuminuric stage may lead to the development of tubulointerstitial injuries in type 2 diabetic patients.

Zonal distribution of glomerular collapse in renal allografts: Possible role of vascular changes

Collapsing glomerulopathy (CG), an aggressive variant of focal segmental glomerular sclerosis, is a renal disease with severe proteinuria and rapidly progressive renal failure. The pathogenesis of CG is unknown. It strongly resembles human immunodeficiency virus (HIV)-associated nephropathy, but the patients are HIV negative. The characteristic glomerular lesion is capillary loop collapse with prominent podocytes filling Bowman's space. Interestingly, these glomerular changes are usually associated with severe tubulointerstitial injury, including tubular epithelial degenerative changes, microcystic dilation of several tubules, and interstitial inflammatory cell infiltrate. Recently, it became evident that the morphologic pattern of CG may appear not only in native kidneys, but also de novo in renal allografts, and that the pattern of CG in renal transplants is not always associated with severe proteinuria. Studies describing CG in renal allografts are all based on biopsies. We report 3 allograft nephrectomy specimens that showed a zonal distribution of the characteristic collapsing glomerular changes with associated tubulointerstitial injury. All 3 kidneys had obliterative vascular changes. One nephrectomy specimen had chronic obliterative transplant arteriopathy, 1 had acute vascular rejection, and 1 had thrombotic microangiopathy. None of the patients had severe proteinuria. Our cases suggest that the morphologic pattern of CG in renal allografts may not represent the same disease process as CG in native kidneys and provide further evidence that collapsing glomerular changes do not define the disease entity of CG, but rather represent a pattern of renal injury. Among other factors, hemodynamic disturbance may play a role in the development of the pattern of CG in renal allografts. HUM PATHOL 33:437-441. Copyright 2002, Elsevier Science (USA). All rights reserved.

Renal calcium phosphate and oxalate deposition in prolonged vitamin B6 deficiency: studies on a rat model of urolithiasis.

To determine the effect on kidney oxalate-salt deposition of a prolonged diet which induced vitamin B6 deficiency in adult rats, as there are reports of the pathogenic involvement of vitamin B6 deficiency in the formation of renal calcium oxalate calculi. The study comprised 24 6-month-old male albino Wistar rats; 12 were fed with a purified vitamin B6-deficient diet and the others provided with the same diet but supplemented with 6 mg/kg of vitamin B6. After 12 weeks, all rats were killed, and their kidneys fixed in formalin and routinely processed to paraffin for morphological examination; some fragments were fixed in glutaraldehyde and prepared for ultrastructural examination. From each rat consecutive sections of both kidneys were cut and stained with haematoxylin and eosin, periodic-acid Schiff, Sirius red and the Von Kossa method for calcium. Sections were examined in polarized light and by electron microscopy. The histopathological and ultrastructural features of the kidney of vitamin B6-deficient rats were those of tubular-interstitial nephritis, characterized by tubular atrophy, interstitial fibrosis and chronic inflammatory infiltration. Oxalate and phosphate crystals were present in the papillary and parenchymal connective tissue. Ultrastructural features confirmed severe tubular epithelial lesions and the presence of an interstitial and intraepithelial inflammatory infiltrate; there was mild interstitial fibrosis. None of these features were apparent in the kidney of control rats. Histopathological and ultrastructural data indicate that a prolonged vitamin B6-deficient diet may contribute to the formation and deposition of calcium phosphate and oxalate crystals, which lead to severe damage of the renal parenchyma. This phenomenon may occur not only in growing rats, which have more active protein metabolism and consequently higher vitamin B6 requirements, but also in adult rats.

Early progressive interstitial fibrosis in human renal allografts.

Early fibrosis has been described in renal allografts and implicated in the progression of chronic allograft nephropathy (CAN). The precise factors implicated in the initiation and progression of early allograft fibrosis remain uncertain. We studied retrospectively 23 cadaveric renal allograft recipients over a 3-year period, who had paired renal biopsies (Bx) (at implantation and as clinically indicated) within 3 months of transplantation (Tx). Eight of them have progressed over an average period of 3.16 +/- 0.83 years to CAN. Histological evaluation of interstitial fibrosis (IF) relied on point count analysis of Masson's trichrome (MT) staining as well as immunostainable collagens III (iCol III) and IV (iCol IV). The severity of the IF scores was correlated with the clinical, biochemical and histological parameters. The nature and severity of the interstitial inflammatory infiltrate were also evaluated by immunofluorescence. In addition, patients were subdivided into those whose fibrosis progressed (> 50% increase in IF/iCol IlI; Group 1) and non-progressors (< 50% increase in fibrosis score; Group 2) in an attempt to determine discriminatory features. In the whole group, there was a significant increase in the IF score, as estimated by MT staining and iCol III, from implantation to follow-up Bx (p = 0.0027 and p = 0.0088, respectively). The changes in iCol IV were not significant. Further, the increase in interstitial inflammatory infiltrate of total T lymphocytes, and not of macrophages, from implantation (modal category = 2) to follow-up (modal category = 0) was significant (p = 0.0121). The predictive value of such increase was significant (R2 = 0.617, p = 0.03). The donor's age (R2 = 0.892, p = < 0.0001), death from cerebrovascular accident (CVA) (R2 = 0.822, p = 0.047), as well as recipient's body weight (R2 = 0.892, p = 0.001), male gender (R2 = 0.687, p = 0.041) and elevated mean arterial pressure (MAP) (R2 = 0.892, p = < 0.0001) were all significant risk factors for early IF. Delayed graft function (DGF) proved to be a significant predictor of early IF (R2 = 0.822, p = 0.003) and became more significant in the presence of superimposed acute rejection (AR) (p = 0.0001). Proteinuria > 1 g/day (R2 = 0.882, p = 0.004) and hypertriglyceridemia > 2.25 mmol/l (R2 = 0.808, p = < 0.0001) were also associated with early IF. Of the implantation histological parameters, iCol III proved to be a highly significant predictor of early IF (R2 = 0.892, p = < 0.0001). Interestingly, the predictive value of iCol III for graft survival in terms of CAN was significant (Cox p = 0.088). Group 1 progressor patients (n = 10) were all males (p = 0.038) and received their kidneys from donors who died from CVAs in 90% of cases (p = 0.011). They had, compared to non-progressors, a lower cyclosporin A level (p = 0.047), a higher incidence of AR episodes (80% versus 54%), a higher serum creatinine at 10 days post-Tx (p = 0.005), a higher proteinuria (2.07 +/- 3.89 g/l vs 0.96 +/- 0.97 g/l, p = 0.041) and a higher serum triglyceride (2.48 +/- 1.37 mmol/l vs 1.69 +/- 0.81 mmol/l, p = 0.039) level. 8% of Group 1 patients had DGF compared to 30% in Group 2 (p = 0.023). Of note, the modal category of cytotoxic: helper T lymphocytes ratio was greater than 1 in Group 1 (2:1) patients and not in Group 2 (1:1). Implantation histology, and in particular iCol III, is a predictor of early IF in a subgroup of patients with DGF and AR. Additional risk factors include hypertension, proteinuria and hypertriglyceridemia especially in patients receiving kidneys from older donors who died of CVAs.

Clinical And Pathological Investigation Of Psychrobacter Immobilis Infection In Rainbow Trour (Oncorhynchus Mykiss, Walbaum)

The pathogenicity of Psychrobacter immobilis, isolated from naturally infected rainbow trout Oncorhynchus mykiss, was investigated. In experimentally-infected trout, no mortality was recorded during 35 days but the following external and internal symptoms were observed. Externally, skin was darkened, gills were pale and swimming was abnormal. Internally, there were dilatations of the vascular structures on cross-sections of the liver; vascular congestion, inflammatory mononuclear cell infiltration and degeneration in the gills; interstitial inflammatory mononuclear cell infiltration and free bleeding in patches of the posterior kidney; vascular con- gestion and free bleeding in the spleen; degeneration, atrophy, polymorphonuclear leukocyte infiltration and liquefaction necrosis in muscle fibers; edema, inflammatory mononuclear cell infil- tration and basophilic degeneration among muscle fibers of the heart; and congestion in vascu- lar structures on cross-sections of the brain tissue. It is suggested that P. immobilis is an oppor- tunist pathogen that causes secondary infections.

Is midazolam effective as an antioxidant in preventing reperfusion injury in rat kidney?

This experimental study was designed to investigate whether midazolam has antioxidant effects in reperfused rat kidneys following ischemia. Twenty Wistar Albino rats were included in the study. Rats were anesthetized with the mixture of ketamine 90 mg/kg and xylazine 10 mg/kg administered intraperitoneally. Following anesthesia, the rats were divided into two groups. The first group was considered as the control group, whereas the second group received additional midazolam 3.5 mg/kg intraperitoneally. The left kidney was approached via a transabdominal incision and the left renal artery was dissected. Left renal ischemia was created by clamping the left renal artery for 45 minutes. Following the ischemia period, the kidney was reperfused for one hour. Both kidneys were then removed. Half of the left kidneys were immediately immersed in liquid nitrogen for transportation and then frozen at -70 C until measurements of tissue malondialdehyde (MDA) and glutathione (GSH) levels. The remaining halves of the left kidneys and right kidneys were fixed in 10% formalin. The changes which developed during the ischemia-reperfusion period in the left kidney were investigated by histopathological examination and compared with those of the normal contralateral kidney. When compared with the control group, tissue MDA and GSH levels were similar in the midazolam group (p > 0.05). Tubular damage with tubulitis and focal interstitial inflammatory infiltration were observed in histopathological examinations of reperfused left kidneys of the control group. There was PMNL infiltration only in perirenal fat tissue of the midazolam group. Right kidneys were histopathologically normal in both groups. We concluded that within this dosage midazolam does not have any antioxidant effect in reperfused rat kidneys following ischemia.

Pentosan polysulfate prevents glomerular hypertension and structural injury despite persisting hypertension in 5/6 nephrectomy rats.

Five/six nephrectomy induces systemic and glomerular hypertension, glomerulosclerosis, proteinuria, and tubulointerstitial fibrosis. Polysulfate pentosan (PPS) decreases mesangial proliferation and extracellular matrix accumulation. The aim of this study was to determine whether PPS prevents glomerular hemodynamic changes and renal damage. Micropuncture studies were performed in three groups of eight male Wistar rats. Two groups included rats with 5/6 nephrectomy-one of which was treated with PPS in drinking water (100 mg/kg body wt) and the second of which received normal drinking water-and the third group consisted of normal rats that served as controls. Five/six nephrectomy produced systemic hypertension, a 50% reduction in GFR, and a 67% increase in single-nephron GFR due to elevated glomerular pressure and single-nephron plasma flow as well as proteinuria. Hypertension persisted in PPS-treated animals. Despite a similar reduction in GFR, PPS prevented the rise in single-nephron GFR, glomerular capillary hydrostatic pressure, and proteinuria. By morphometry, glomerular volume was increased by 46% and mesangial area by 94%. Fractional glomerular capillary area decreased by 24%. PPS prevented these changes. Tubular dilatation, epithelial cell atrophy, and increased interstitial area were largely prevented by PPS, as was the interstitial inflammatory infiltrate. These results suggest that the renal protection conferred by PPS was mediated both by prevention of glomerular hypertension as well as suppression of the inflammatory response. It was postulated that this was partly due to the preservation of a greater fraction of functional nephrons.

Tubular‐interstitial interactions in proteinuric renal diseases

SUMMARY: Progressive chronic renal disease of all types is characterized by a relatively uniform set of tubular (atrophy, hypertrophy, hyperplasia) and interstitial (inflammatory cell infiltration, fibrosis) pathological changes, the severity of which correlates well with the degree of proteinuria and the decline in glomerular filtration. Complex and redundant pathophysiological events underlie the relationship between proteinuria, tubular injury and interstitial damage, forming potential targets for therapy. The outcome of these events is also determined by additional factors not limited to proteinuric diseases, including tissue hypoxia, complement activation and mediators produced in response to glomerular damage. In response to proteinuria and these additional factors, tubular cells are activated to produce a large number of chemoattractants, proinflammatory and profibrotic cytokines and matrix proteins, which cause, at least in part, interstitial inflammation and fibrosis. In turn, soluble products of interstitial inflammatory cells (predominantly T lymphocytes and macrophages), dendritic cells and fibroblasts are at least partially responsible for altering the phenotype of tubular cells. Abnormal tubular‐interstitial interactions may also depend on direct cell contact rather than soluble mediators, as evidenced by up‐regulation of integrins and cell adhesion molecules. Myofibroblasts, a key cell in the production of interstitial fibrosis, may arise in response to the above mediators by trans‐differentiation of fibroblasts, perivascular cells and tubular cells. In addition, tubular cells have been shown to be capable of the induced expression of the signalling molecules necessary for them to behave as antigen‐presenting cells and thereby potentially initiate interstitial inflammation through the classic interactions of cognate immunity. It is probable that several, but not all, of this bewildering number of pathophysiological events are of prime importance to the development of tubulointerstitial damage in proteinuria. The immediate challenge for investigators is to define the relative importance of these events and, thus, the most appropriate targets for new treatments.

Drug-induced acute interstitial nephritis

Drug-induced acute interstitial nephritis

Renal interstitial tenascin immunostaining and immune cell infiltration in IgA nephropathy

SUMMARY: Interstitial expression of tenascin and interstitial leucocyte infiltration were examined by an indirect immunoperoxidase method using monoclonal antibodies against tenascin, CD45 (all leucocytes), CD45RO (T cells) and CD68 (monocytes/macrophages) on renal biopsy specimens from 25 patients with mesangial proliferative IgA‐positive glomerulonephritis (IgAN). Ten biopsy kidney specimens, which were removed because of renal trauma, were used as the control group. In patients with IgAN, the mean interstitial expression of tenascin was significantly higher than in the control group. Strong tenascin staining was detected in areas with interstitial damage. In patients with IgAN there were positive correlations between the interstitial expression of tenascin and the relative interstitial cortical volume, as well as serum creatinine. In the IgAN patents, a significant increase in the total number of interstitial CD45‐immunopositive cells, CD45RO‐positive and CD68‐positive cells was seen compared with the control group. In patients with IgAN, immunostaining of tenascin did not correlate with the number of T‐cells, monocytes/macrophages or all leucocytes in the renal interstitium. These results suggest that in patients with IgAN the interstitial accumulation of tenascin did not depend on the type or the density of interstitial inflammatory infiltrates.

Molecular characterization and sequence analysis of polyomavirus BKV-strain in a renal-allograft recipient

The significance of polyomavirus (PV) infection was investigated in a 53-year-old patient who underwent renal transplantation and was treated with triple immunosuppressive therapy (tacrolimus, prednisone, and azathioprine). A renal biopsy taken because of the suspicion of acute rejection showed focal inflammatory interstitial infiltration, tubulitis, and tubular cell nuclear changes consistent with the hypothesis of viral infection. Both the tubular and decoy cells identified by means of urinalysis positively stained for anti-SV40 antibody. Polymerase chain reaction performed on the DNA extracted from renal tissue and isolated from urine showed the presence of an antigenic variant (AS) of the BKV archetype after sequence analysis of the transcription control region (TCR). On the basis of the diagnosis of BKV infection, immunosuppressive therapy was reduced. The patient's renal function improved and was still stable 8 months later when urinalysis showed only a few decoy cells, which were found to be infected by JC but not BK virus. These data suggest that only the BKV, probably favoured by immunosuppressive therapy (tacrolimus), causes renal damage. It is worth underlining that even small and sporadic viral genome mutations may lead to pathologic effects. HUM PATHOL 32:656-659. Copyright © 2001 by W.B. Saunders Company

Inhibition of inducible nitric oxide synthase (iNOS) prevents lung neutrophil deposition and damage in burned rats.

This study was designed to investigate the role of NO and effect of iNOS inhibitor on the lung neutrophil deposition and damage after burn. In Experiment 1, specific pathogen-free (SPF) Sprague-Dawley rats underwent 35% total body surface area (TBSA) burn. On the 4th, 8th, 16th, and 24th h after burn, blood was collected for peroxynitrite-mediated dihydrorhodamine 123 (DHR 123) oxidation assay, and lung tissues were harvested for myeloperoxidase (MPO) test and histologic study. Pulmonary microvascular dysfunction was quantitated by measuring the extravasation of Evans blue dye (EBD). In Experiment 2, S-methylisothiourea (SMT) was given (7.5 mg/kg, intraperitoneal immediately post-burn) to suppress iNOS activity. On the 8th h after burn, the effect of SMT on blood DHR 123 oxidation, lung MPO, lung damage, and lung iNOS expression were evaluated. Lung MPO activity increased up to a maximum of 2-fold 8 h after burn. Blood DHR 123 oxidation increased up to a maximum of 2-fold 8 h after burn. Lung permeability increased up to a maximum of 2.5-fold 4 h after burn. SMT significantly decreased lung MPO activity, blood DHR 123 oxidation, and lung permeability by 31%, 41%, and 54%, respectively. SMT markedly decreased the thermal injury-induced perivascular and interstitial inflammatory cell infiltration and iNOS staining in bronchiolar epithelium, endothelial cells, and perivascular and interstitial inflammatory cells. In conclusion, thermal injury induces blood DHR 123 oxidation, lung neutrophil deposition, lung iNOS expression, and lung damage. Peroxynitrite might play an important role in thermal injury-induced lung neutrophil deposition and damage. Specific inhibition of lung iNOS expression and blood DHR 123 oxidation with SMT on thermal injury not only attenuated the lung neutrophil deposition, but also reduced lung damage.

Pathological, Immunohistochemical and Bacteriological Findings in Kidneys of Cattle with Contagious Bovine Pleuropneumonia (CBPP)

Between 1990 and 1993, 61 outbreaks of contagious bovine pleuropneumonia (CBPP) were reported in Lombardy, Northern Italy. In this study, gross pathological examination was carried out on 3129 slaughtered cattle, 716 of which (22·9%) showed typical CBPP pulmonary lesions. Single or multiple renal infarcts at different stages of development were observed in 88 (12·2%) of these 716 cattle. The kidneys of 77 cattle whose lungs showed typical CBPP lesions and were bacteriologically and immunohistochemically positive for the small colony type of Mycoplasma mycoides subspeciesmycoides (M. m. mycoides SC) were selected and submitted to histological, immunohistochemical and bacteriological examination. Histologically, in chronic CBPP cases, infarcts were characterized by fibrosis, calcification of cortical tubules and tubular atrophy, accompanied by the presence of interstitial inflammatory infiltrates composed of lymphocytes, plasma cells and histiocytes. M. m. mycoides SC antigen was detected immunohistochemically in 65 (84·4%) of the 77 kidneys examined. The antigen was detected in the lumen of blood vessels and in glomerular cells. Immunolabelled interstitial cells and tubular epithelial cells were seen in chronic cases only. M. m. mycoides SC was isolated from the kidneys of 12 animals (15·6%) and more frequently in cases with renal infarcts. This study confirms previous observations that demonstrated a renal involvement in cases of CBPP. Moreover, the immunohistochemical results indicated that M. m. mycoides SC antigen was frequently detectable in different renal structures and cells in spontaneous cases of CBPP.

Protective and Ameliorative Effects of Benidipine Hydrochloride Against Renal Damage in the Stroke-prone Spontaneously Hypertensive Rat(SHR-SP).

The potential of benidipine hydrochloride (BH), a 1,4-dihydropyridine calcium antagonist and a possible vasodilator, to protect against renal damage in the stroke-prone spontaneously hypertensive rat (SHR-SP) was examined using fifty-five males (10 weeks old). The animals were allotted into experiments 1 and 2, in each case subdivided into three groups (control and BH at doses of 3 and 10 mg/kg). Administration of BH was initiated before identification of clinical stroke in Experiment 1 and after its onset in Experiment 2. Measurement of body weight (BW) and systolic blood pressure (SBP) indicated that treatment of BH was associated with increased BW gain and reduced blood pressure in both experiments. Histopathological assessment revealed significant and dose-dependent decrease in the degree of fibrinoid necrosis in renal blood vessels, sclerosis, hyalinization, edematous thickening and Bowman's space dilatation in glomeruli, as well as protein casts, dilated or regenerative tubules, and interstitial inflammatory infiltration with fibrosis in tubulointerstitium in the BH treated groups as compared with the control group. These results indicated that BH exerts vasodilative effects on the kidney with improvement of regional blood flow, then preventing and ameliorating renal damage.

Focal organizing pneumonia: CT and pathologic findings.

The purpose of this study was to describe the CT findings of focal organizing pneumonia and to compare the findings with pathology. CT findings of histologically proven focal organizing pneumonias in 26 consecutive patients were analyzed. In 17 patients who had undergone surgical resections, the findings were correlated with pathology. Focal organizing pneumonias appeared as a nodule (n= 13) or a mass (n=13), ranging from 9 mm to 66 mm in diameter. Ground-glass opacity was seen in 6/13 (46%) nodules and 6.5/13 (50%) masses (k=.48) with an extent ranging from 5% to 75% (mean, 16%). In 4/26 (15%) patients, the extent was more than 50% of the lesion. They showed smooth (n=4), lobulated (n=8), spiculated (n=1), or lobulated and spiculated margin (n=13). On correlative analysis, nodule or mass on CT consisted histologically of intraalveolar exudate or microabscess, chronic inflammatory cell infiltration, fibrotic nodules, and polypoid granulation tissue in the alveolar or bronchiolar spaces. Ground-glass opacity consisted of interstitial fibrosis and chronic inflammatory cell infiltration and intraalveolar polypoid granulation tissue. Focal organizing pneumonia may simulate a lung cancer with variable appearances on CT and the findings reflect underlying histopathology of the disease.

CD4(+) T cells participate in the nephropathy of canine visceral leishmaniasis.

Renal involvement in visceral leishmaniasis (VL) is very frequent. The renal lesions of humans and dogs are similar but their pathogenesis has not been clearly elucidated. There is growing evidence that the cellular immune response is involved in the pathogenesis of immunologically mediated glomerulonephritis. Since T cells could participate in the pathogenesis of nephropathy, in the present study we investigated the possible involvement of CD4(+) and CD8(+) T cells in the nephropathy of canine VL. Six dogs naturally infected with Leishmania (Leishmania) chagasi from the endemic area in the Northeast of Brazil, the town of Teresina in the State of Piauí, were studied. An expressive inflammatory infiltrate of CD4(+) T cells both in glomeruli and in interstitium was present in 4 animals and absent in 2. CD8(+) T cells were detected only in one animal. CD4(+) T cells alone were observed in 3 animals; when CD8+ T cells were present CD4(+) T cells were also present. CD4(+) T cells were observed in cases of focal segmental glomerulosclerosis, diffuse membranoproliferative glomerulonephritis, diffuse mesangial proliferative glomerulonephritis and crescentic glomerulonephritis. CD8(+) T cells were present only in a case of crescentic glomerulonephritis. Leishmania antigen was detected in glomeruli and in interstitial inflammatory infiltrate in 4 animals and immunoglobulins were observed in 4 dogs. In this study we observed that T cells, in addition to immunoglobulins, are present in the renal lesion of canine VL. Further studies are in progress addressing the immunopathogenic mechanisms involving the participation of immunoglobulins and T cells in canine VL nephropathy.

Cardiac troponin T alterations in myocardium and serum of rats after stressful, prolonged intense exercise.

The goal of this study was to determine whether the stress of forced exercise would result in injury to the myocardium. Male rats with 8% of body weight attached to the tail were forced to swim 3.5 h (3.5S), forced to swim 5 h (5S), or pretrained for 8 days and then forced to swim 5 h (T5S). Rats were killed immediately after they swam (0 h PS) and at 3 h (3 h PS), 24 h (24 h PS), and 48 h after they swam (48 h PS). Tissue homogenates of the left ventricle were analyzed by Western blot analysis for cardiac troponin T (cTnT). Serum cTnT was quantified by immunoassay. Results indicated that, in the 3.5S, 5S, and T5S groups, serum cTnT was significantly (P < 0.01) increased at 0 and 3 h PS. The 5S group demonstrated a greater increase in serum cTnT than the 3.5S group (P < 0.01) and the T5S group (P < 0.01) at 0 h PS. Western blot analysis indicated significant decreases (P < 0. 01) in myocardial cTnT in the 5S group only at 0 h PS (P < 0.01) and 3 h PS (P < 0.05). Histological evidence of localized myocyte damage demonstrated by interstitial inflammatory infiltrates consisting of neutrophils, lymphocytes, and histiocytes, as well as vesicular nuclei-enlarged chromatin patterns, was observed in left ventricle specimens from the 5S group at 24 and 48 h PS. Our findings demonstrate that stressful, forced exercise induces alterations in myocardial cTnT and that training before exercise attenuates the exercise-induced heart damage.

Development of monocrotaline-induced pulmonary hypertension is attenuated by a serotonin receptor antagonist.

The significance of serotonin in the pathogenesis of monocrotaline-induced pulmonary hypertension (MCT-PH) in rats, plasma serotonin concentrations, and the effect of a serotonin receptor antagonist administration in association with the number of proliferative cells were investigated. The thickness of the media of the small pulmonary arteries and the weight ratio of the RV to that of LV + S (RV/[LV + S] weight ratio) were used as indices of the severity of PH. Plasma serotonin concentrations were measured by high-performance liquid chromatography. Histopathologic analysis of the lung tissue was performed by hematoxylin-eosin and elastin van Gieson staining. Immunohistopathologic staining for proliferating cell nuclear antigen (PCNA) was performed to identify proliferative cells. The severity of PH as determined by the medial thickness of the small pulmonary arteries and RV/(LV + S) weight ratio in rats with MCT-PH was significantly reduced after treatment with MCI-9042 (p < 0.01 and p < 0.05, respectively). The serotonin concentration was significantly greater in MCT-PH rats than in normal control rats (p < 0.05). The scores for histopathologic changes, such as thickening of the alveolar walls and interstitial inflammatory cell infiltration in MCT-PH rats, were significantly reduced after treatment with MCI-9042 (p < 0.05 and p < 0.01, respectively). The number of PCNA-positive cells was significantly greater in MCT-PH rats than in normal control rats (p < 0.0001) and was reduced after treatment with MCI-9042 (p < 0.0001). Treatment with MCI-9042 significantly inhibited the development of MCT-PH along with a decrease in the number of PCNA-positive cells, suggesting a pivotal role of serotonin in the development of PH induced by MCT.