Epithelial Degenerative Changes Research Articles

STRUCTURAL CHANGES OF THE COLON WALL IN CASE OF DEVELOPMENT OF ENTERAL INSUFFICIENCY CAUSED BY EXPERIMENTAL PERITONITIS

Objective: to study structural changes of the colon wall and development of enteral dysfunction in an experimental course of acute peritonitis. Materials and Methods. Experimental studies were conducted on 21 mature albino nonlinear rats. Under thiopental anaesthesia peritonitis was caused by puncture of the ascending colon and the introduction of freshly prepared 15% solution in the dose of 0.5 ml per 100 g of the body weight of a rat. On the 1st, 3rd and 7th day of experimental peritonitis animals were decapitated under calypsol anesthesia. The pieces of the small intestine were taken for histological examination determining changes histologically. Results. Structural changes were found to occur on the first, third, and 7 day of experimental peritonitis in the lining of the colon and continued to grow over time, manifested by its consolidation at the expense of pronounced lymph and histiocytic infiltration and combined focal leukocyte infiltration, corresponding to morphological structure of colitis. Lumen of crypts is reduced at the expense of an increased activity of secretory epithelial cells and degenerative changes. Uneven blood supply of the vessels combined with perivascular edema is found in the subepithelial layer. Conclusion. Increased secretory activity and development of degenerative changes in the superficial epithelium occur in the colon mucosa during experimental peritonitis. Epithelial degenerative changes with pronounced histiocytic and lymph infiltration of the stroma and its edema increase from 3 to 7 days.

Influence of indigenous microbiota on experimental toxoplasmosis in conventional and germ-free mice.

Toxoplasmosis represents one of the most common zoonoses worldwide. Its agent, Toxoplasma gondii, causes a severe innate pro-inflammatory response. The indigenous intestinal microbiota promotes host animal homoeostasis and may protect the host against pathogens. Germ-free (GF) animals provide an important tool for the study of interactions between host and microbiota. In this study, we assessed the role of indigenous microorganisms in disease development utilizing a murine toxoplasmosis model, which includes conventional (CV) and GF NIH Swiss mice. CV and GF mice orally inoculated with T.gondii had similar survival curves. However, disease developed differently in the two animal groups. In CV mice, intestinal permeability increased and levels of intestinal pro-inflammatory cytokines were altered. In GF animals, there were discrete epithelial degenerative changes and mucosal oedema, but the liver and lungs displayed significant lesions. We conclude that, despite similar survival curves, CV animals succumb to an exaggerated inflammatory response, whereas GF mice fail to produce an adequate systemic response.

Intranasal delivery of nanomicelle curcumin promotes corneal epithelial wound healing in streptozotocin-induced diabetic mice.

Corneal nerves are mainly derived from the ophthalmic branch of the trigeminal ganglion (TG). Corneal neuropathy contributes to epithelial degenerative changes in diabetic keratopathy. Efficient drug delivery to TG may be beneficial for the treatment of diabetic keratopathy. This article described intranasal delivery of nanomicelle curcumin to correct pathophysiological conditions in TG to promote corneal epithelial/nerve wound healing in streptozotocin-induced diabetic mice. A diabetic mice model with corneal epithelium abrasion was established. Ocular topical and/or intranasal nanomicelle curcumin treatments were performed, and treatment efficacy and mechanisms of action were explored. Results showed that intranasal nanomicelle curcumin treatment promoted corneal epithelial wound healing and recovery of corneal sensation. Enhanced accumulation of reactive oxygen species, reduced free radical scavengers, increased mRNA expressions of inflammatory cytokines, and decreased mRNA expressions of neurotrophic factors in the cornea and TG neuron were observed in diabetic mice with corneal epithelium abrasions. Intranasal nanomicelle curcumin treatment effectively recovered these pathophysiological conditions, especially that of the TG neuron, and a strengthened recovery was observed with ocular topical combined with intranasal treatment. These findings indicated that intranasal curcumin treatment effectively helped promote diabetic corneal epithelial/nerve wound healing. This novel treatment might be a promising strengthened therapy for diabetic keratopathy.

Epithelial and stromal alterations in prostate after cypermethrin administration in adult albino rats (histological and biochemical study).

Histological and biochemical alterations induced in prostate by cypermethrin insecticide exposure were investigated in adult albino rats. 60 mg/kg/day of cypermethrin were given orally to experimental group for 15 days then prostatic specimens were processed for light and electron microscopic examinations and for assessment of oxidative stress markers; prostatic glutathione (GSH), glutathione peroxidase enzyme (GPx) and malondialdehyde (MDA). Masson's trichrome and anti-α-actin antibodies immunohistochemical staining were done. Blood samples were collected for measurement of total and prostatic acid phosphatase enzymes. Morphometric and statistical analyses were conducted. Cypermethrin treated group showed decrease in acinar epithelial height with detection of heterochromatic nuclei, cytoplasmic vacuolations and few apical microvilli. The stroma surrounding the acini was widened with significant increase in collagen fibers and significant decrease in smooth muscle cell α-actin immunoexpression. This was accompanied by a significant decrease of prostatic GSH level, activity of GPx enzyme with a significant increase in MDA level. Significant decrease in total and prostatic enzyme activities was also detected. In conclusion, cypermethrin induced epithelial degenerative changes in prostate which were accompanied by stromal alterations that seemed to be due to oxidative stress. More attention is required to the role of stromal microenvironment and oxidative stress markers in prostatic diseases.

Pathology of Human Metapneumovirus Infection: Insights into the Pathogenesis of a Newly Identified Respiratory Virus

Human metapneumovirus (hMPV) is a recently discovered human virus that causes significant respiratory infections. Pathologic features of hMPV infection have not been described. A total of 1257 pediatric respiratory samples submitted for routine clinical virologic testing were additionally tested for hMPV by reverse transcriptase polymerase chain reaction (PCR). Pathology specimens, available in 6 of 53 hMPV-positive patients, were examined by light and electron microscopy and included 6 bronchoalveolar lavage (BAL) and 3 lung biopsy specimens from 6 patients (3 girls and 3 boys) ranging in age from 1 to 16 years. BAL from three patients performed within 4 days of the positive hMPV assay showed epithelial degenerative changes and eosinophilic cytoplasmic inclusions within epithelial cells, multinucleate giant cells, and histiocytes. Inclusions were not seen in three patients with BAL performed = 1 month from the time of their positive assay. Lung biopsy, performed in three patients, all = 1 month from the time of their positive assay, showed chronic airway inflammation and intraalveolar foamy and hemosiderin-laden macrophages; all three patients had an underlying pulmonary/systemic disorder. Our findings delineate the clinicopathologic features in hMPV-infected patients undergoing anatomic sampling, which may provide diagnostic guidance to a practicing pathologist. Further, they contribute toward understanding the pathogenesis of hMPV infection.

Oral, nasal, and cutaneous eosinophilic granulomas in the black rhinoceros (Diceros bicornis): a lesion distinct from superficial necrolytic dermatitis.

Oral, nasal, and cutaneous lesions resembling eosinophilic granulomas (EGs) were observed in eight captive black rhinoceroses (Diceros bicornis). Oral lesions were observed in all affected animals and occurred most often behind the prehensile lip. The typical clinical history of affected animals included oral bleeding or epistaxis from multilobulated, fungating, proliferative masses with areas of ulceration. Histologically, lesions were characterized by prominent infiltrates of eosinophils and rare foci of collagen degeneration on a background of marked submucosal or dermal neovascularization. Mucosal or epidermal hyperplasia was also present sometimes in association with distinctive epithelial degenerative changes consistent with superficial necrolytic dermatopathy of black rhinoceroses. Lesions of EG and superficial necrolytic dermatopathy were interpreted as being concurrently manifested in these cases. EG lesions spontaneously resolved over periods of 30 days-7 mo and were recurrent in three animals. Lesions were responsive to treatment with corticosteroids or to local cryotherapy with liquid nitrogen. Two animals treated with systemic corticosteroids died of disseminated fungal infections, emphasizing that corticosteroids should be used cautiously in black rhinoceroses.

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.

Comparison of intraocular light scatter in carriers of choroideremia and X-linked retinitis pigmentosa

Objective To compare the extent of intraocular straylight in carriers of choroideremia (CHM) and X-linked recessive retinitis pigmentosa (XLRP) to clarify further the relationship between photoreceptor cell degeneration and intraocular light scatter in retinal diseases. Design Prospective case-control study. Participants Six obligate carriers of CHM, 12 obligate carriers of XLRP, and 30 age-similar control subjects with normal vision. The controls had no posterior subcapsular (PSC) lens opacities, and the carriers had minimal or no PSC lens opacities, as assessed by slit-lamp biomicroscopy. Main outcome measures Straylight levels were measured using a van den Berg Straylightmeter. Visual acuity and Goldmann visual field area using a II/4e target were assessed for both eyes of each carrier. Electroretinogram (ERG) data were available on four of six carriers of CHM and all carriers of XLRP. The extent of retinal pigment epithelial degenerative changes was evaluated by fundus examination. Results All six carriers of CHM had typical fundus abnormalities with normal visual fields. Five of the six carriers of CHM had age-normal levels of intraocular light scatter, and one showed minimally elevated intraocular light scatter. The 12 carriers of XLRP had a spectrum of fundus abnormalities and varying severity of functional impairment as derived from visual field areas and ERG amplitudes. Seven of the 12 carriers of XLRP showed an elevated level of intraocular light scatter in at least one eye. The degree of straylight elevation above the normal mean age value was correlated significantly with both visual field area and amplitude of the maximal-intensity, dark-adapted ERG b-wave. Conclusions The carriers of XLRP who had evidence of photoreceptor cell dysfunction (as determined by visual field loss and reduced ERG amplitudes) had increased levels of intraocular straylight, whereas the carriers of CHM, who showed fundus abnormalities alone, in the absence of demonstrable photoreceptor cell dysfunction, had normal or minimally elevated levels. This finding supports the hypothesis that the increased levels of intraocular light scatter observed in some patients with hereditary retinal degenerations result from subclinical changes in the PSC region of the lens as a consequence of photoreceptor cell degeneration.

Eccrine gland infiltration by mycosis fungoides.

After identifying prominent eccrine infiltration by atypical lymphocytes in a biopsy of tumor stage mycosis fungoides (MF), we sought to determine the pattern of eccrine epithelial infiltration in MF. The frequency, intensity, and distribution of infiltration of eccrine gland structures, including acrosyringium, duct and coil epithelium, was studied by examining 71 biopsy specimens from 42 patients with MF in which eccrine structures were present. These were obtained from a retrospective review of pathologic specimens from Duke University Medical Center from 1992 and 1993. At least focal eccrine infiltration was noted in 23 of the 71 biopsy specimens (32%). Immunohistochemical confirmation of T-lymphocyte phenotype was performed in the 23 cases with positive reaction to antibodies CD3 and CD45RO and negative reaction with CD20. Folliculosebaceous units were present in 22 of the 71 biopsy specimens and were at least focally involved by MF in 11 (50%) in this series. A control group of biopsy specimens of reactive dermatoses were characterized by more superficial location of lymphocytes, with more spongiosis and epithelial degenerative changes. These findings further illustrate the epitheliotropic behavior of MF.

Pathologic changes of gastric mucosa colonized by Helicobacter pylori

One hundred eighty-nine consecutive gastric biopsies showing colonization by Helicobacter pylori (HP) were studied. Epigastric pain and bleeding were the clinical presentations in 167 cases (88.4%). Major endoscopic findings were gastritis (n = 72, 38.1%) and ulceration (n = 101, 53.4%). Duodenal ulcer was associated with 32 (44.4%) and 29 (28.7%) cases of gastritis and gastric ulcer, respectively. Histologically, the HP-colonized gastric epithelium showed characteristic degenerative changes that were topographically related to the bacteria but unrelated to the inflammatory infiltrate. Disintegration and loss of apical mucus with formation of epithelial pits was seen in nearly all cases. Other changes included microerosion, conventional erosion, and frank ulceration. Only the disintegration of apical mucus, epithelial pit, and microerosion were specific for HP colonization. These conditions were absent in areas not colonized by HP and in 79 consecutive HP-negative gastric biopsies seen during the same study period. The epithelial degenerative changes in HP-colonized gastric mucosa are easy to recognize in routine hematoxylin-eosin-stained sections and they could serve as histologic guides to the localization of the bacteria. It is proposed that HP-colonized gastric mucosa is a distinct pathologic entity with a pathologic spectrum ranging from active chronic gastritis to erosion and frank ulcer. Damage to the mucin-containing portion of the gastric epithelial cells appears to be the basic cytopathologic effect of HP on the gastric mucosa. As effective specific treatment for HP infection is available, identification of HP colonization in gastric biopsies should be attempted in all cases of gastritis and gastric ulcer.

Follicular mucinosis: A detailed morphologic and immunopathologic study

Two patients with the benign type of follicular mucinosis (FM) are presented. Their clinical features and course were characteristic for this subgroup of FM. Light and electron microscopy, direct immunofluorescence, and immunoperoxidase cell marker studies were undertaken to characterize the nature of the disease process. Light microscopy confirmed the follicular outer root sheath and sebaceous gland epithelial degenerative changes. The infiltrating inflammatory cells were morphologically benign. Electron microscopy detailed the cellular associations in the areas of degenerative change. Disattached keratinocytes were closely apposed to significant numbers of macrophages and Langerhans cells. Direct immunofluorescence studies demonstrated primarily complement (C3) and fibrinogen/fibrin in areas of reticular degeneration. Immunoperoxidase studies revealed large numbers of T cells and macrophages and a striking increase in the number of Langerhans cells in the affected follicular epithelium. The findings suggest that cell-mediated immune mechanisms may play a role in the pathogenesis of this disorder.

Degenerative changes and detection of plasminogen in fetal membranes that rupture prematurely.

Amniochorion obtained at caesarean section and vaginal delivery, at 34-36 weeks gestation and at term, have been studied by electron microscopy and immunofluorescence for evidence of amniotic epithelial degenerative changes and the presence of plasminogen. When delivery was by caesarean section between 34-36 weeks, electron microscopy revealed no degenerative changes in four cases, but in two cases they were widespread. All but one membrane obtained at term showed only minimal amniotic epithelial cell degenerative changes, but extensive change was seen when delivery was premature after premature membrane rupture. Plasminogen was seen in amniotic epithelium proportional to the degree of cell degeneration; it was absent from healthy membranes. These findings demonstrate that degenerative changes are extensively present in membranes that rupture prematurely, particularly before the onset of premature labour, and suggest a role for plasminogen in membrane rupture.

Effects of PBB on Cattle. II. Gross Pathology and Histopathology

Toxicosis was induced in pregnant Holstein heifers by feeding FireMaster BP-6 (polybrominated biphenyls) in daily oral doses of 25 g/head/day for 33--60 days. The individual heifers were dosed until each became moribund (days 33, 36, 39, 40, 41, or 66), at which time they were necropsied. Gross findings included dehydration, subcutaneous emphysema and hemorrhage, atrophy of the thymus, fetal death with concomitant necrosis of cotyledons, thickened wall of the gallbladder, inspissated bile, edema of abomasal folds, mucoid enteritis, linear hemorrhage and edema of the rectal mucosa, and secondary pneumonia. The livers were enlarged approximately 40%. Kidneys were approximately double the normal size and were pale tan to grey in color. The perirenal lymph nodes were enlarged and edematous. Microscopic changes were the most marked in the kidneys, gallbladder and eyelid. Extreme dilatation of collecting ducts and convoluted tubules with epithelial degenerative changes of cloudy swelling, hydropic degeneration and separation from the basement membrane were principal changes in the kidney. Hyperkeratosis with accumulations of keratin in hair follicles of the epidermis and squamous metaplasia with keratin cysts in the tarsal glands were characteristic findings in sections of eyelids. Moderate to marked hyperplasia and cystic dilatation of the mucous glands in the lamina propria were common changes in the gallbladder. Foci of fatty degeneration and glycogen depletion were observed in liver sections. Necropsy of heifers immediately after 60 days exposure to 0.25 and 250 mg/head/day of PBB showed no gross or histopathological signs indicating toxicosis. Following parturition, at approximately 220 days after the PBB doses, heifers from the 0.25 and 250 mg/head/day groups and their calves were necropsied and displayed no signs of toxicosis.

Effects of PBB on cattle. II. Gross pathology and histopathology.

Toxicosis was induced in pregnant Holstein heifers by feeding FireMaster BP-6 (polybrominated biphenyls) in daily oral doses of 25 g/head/day for 33--60 days. The individual heifers were dosed until each became moribund (days 33, 36, 39, 40, 41, or 66), at which time they were necropsied. Gross findings included dehydration, subcutaneous emphysema and hemorrhage, atrophy of the thymus, fetal death with concomitant necrosis of cotyledons, thickened wall of the gallbladder, inspissated bile, edema of abomasal folds, mucoid enteritis, linear hemorrhage and edema of the rectal mucosa, and secondary pneumonia. The livers were enlarged approximately 40%. Kidneys were approximately double the normal size and were pale tan to grey in color. The perirenal lymph nodes were enlarged and edematous. Microscopic changes were the most marked in the kidneys, gallbladder and eyelid. Extreme dilatation of collecting ducts and convoluted tubules with epithelial degenerative changes of cloudy swelling, hydropic degeneration and separation from the basement membrane were principal changes in the kidney. Hyperkeratosis with accumulations of keratin in hair follicles of the epidermis and squamous metaplasia with keratin cysts in the tarsal glands were characteristic findings in sections of eyelids. Moderate to marked hyperplasia and cystic dilatation of the mucous glands in the lamina propria were common changes in the gallbladder. Foci of fatty degeneration and glycogen depletion were observed in liver sections. Necropsy of heifers immediately after 60 days exposure to 0.25 and 250 mg/head/day of PBB showed no gross or histopathological signs indicating toxicosis. Following parturition, at approximately 220 days after the PBB doses, heifers from the 0.25 and 250 mg/head/day groups and their calves were necropsied and displayed no signs of toxicosis.