Severe Inflammatory Changes Research Articles

Effects of chronic intrathecal infusion of a partial differential opioid agonist in dogs.

To define the effects of chronic spinal exposure to a highly selective partial differential opioid agonist c[DPen(2),DPen(5)]enkephalin (DPDPE), adult beagles were prepared with chronic lumbar intrathecal catheters. Groups of dogs received intrathecal infusions (100 micro l/h) of saline (vehicle), DPDPE 3 mg/ml or 6 mg/ml for 28 days. Over the 28-day period, saline or 3 mg/ml showed minimal changes in neurological function, whereas in the 6 mg/ml animals, prominent hind limb dysfunction evolved over the 28-day interval. Histopathology in control animals displayed a modest pericatheter reaction considered normal for this model. Dogs receiving DPDPE (three of four at 6 mg/ml and one of four at 3 mg/ml) but not saline (zero of four) developed large inflammatory masses (granulomas) in the intrathecal space located proximal to the catheter tip. In these masses, severe chronic inflammatory changes in combination with necrosis and fibrosis was detected. Occasional focal destruction of neuropil was detected also in the adjacent spinal cord parenchyma. These masses contained extensive accumulation of mouse antihuman macrophages (MAC)-positive inflammatory cells expressing tumor necrosis factor-alpha (TNF-alpha), revealing infiltration of macrophages, granulocytes, and monocytes. In separate animals, prepared with dual intrathecal catheters, lumbar CSF was sampled at specified time points following intrathecal bolus (3 mg/ml) and 24 h DPDPE infusion (3 mg/ml and 6 mg/ml). Steady-state cerebrospinal fluid (CSF) DPDPE levels were 18.6 +/- 1.0 and 22.6 +/- 4.0 micro g/ml for 3 mg/ml and 6 mg/ml infusions respectively. These results indicate that this partial differential opioid agonist DPDPE produces a concentration and time-dependent formation of an intrathecal inflammatory mass.

Serum and mucosal nitric oxide levels and efficacy of sodium nitroprussid in experimentally induced acute sinusitis.

Experimental acute sinusitis was induced in 21 New Zealand hybrid rabbits by occluding the ostium and inoculating them with Streptococcus pneumonia. While a group of rabbits with sinusitis was left untreated, two other groups were administered parenteral sodium nitroprussid (SNP) and oral levofloxacin for ten days. While staphylococci species, non-hemolytic streptococcus and contaminated flora were isolated from the sinuses of controls, Streptococcus pneumonia was re-isolated in two of six untreated rabbits, in one of six SNP administered rabbits and none of the levofloxacin treated rabbits. Serum and maxillary sinus mucosal nitric oxide (NO) levels were correlated. While the mean maxillary sinus NO level of controls was significantly higher than that of untreated rabbits, the mean maxillary sinus and serum NO levels were significantly higher in SNP administered rabbits than in the others. Although goblet cell hyperplasia and squamous cell metaplasia were detected in some slides, edema and neutrophil infiltration were the prominent findings. The most severe inflammatory changes were found in the untreated sinusitis group on the third and fifth days. The earliest improvement was observed in the levofloxacin treated rabbits. It was concluded that NO level is decreased during acute sinusitis and that SNP administration hastens the bacteriological and histological recovery.

Osteoclasts are essential for TNF-alpha-mediated joint destruction.

The detailed cellular and molecular mechanisms leading to joint destruction in rheumatoid arthritis, a disease driven by proinflammatory cytokines, are still unknown. To address the question of whether osteoclasts play a pivotal role in this process, transgenic mice that express human TNF (hTNFtg) and that develop a severe and destructive arthritis were crossed with osteopetrotic, c-fos-deficient mice (c-fos(-/-)) completely lacking osteoclasts. The resulting mutant mice (c-fos(-/-)hTNFtg) developed a TNF-dependent arthritis in the absence of osteoclasts. All clinical features of arthritis, such as paw swelling and reduction of grip strength, progressed equally in both groups. Histological evaluation of joint sections revealed no difference in the extent of synovial inflammation, its cellular composition (except for the lack of osteoclasts), and the expression of matrix metalloprotein-ase-3 (MMP-3) and MMP-13. In addition, cartilage damage, proteoglycan loss, and MMP-3, -9, and -13 expression in chondrocytes were similar in hTNFtg and c-fos(-/-)hTNFtg mice. However, despite the presence of severe inflammatory changes, c-fos(-/-)hTNFtg mice were fully protected against bone destruction. These data reveal that TNF-dependent bone erosion is mediated by osteoclasts and that the absence of osteoclasts alters TNF-mediated arthritis from a destructive to a nondestructive arthritis. Therefore, in addition to the use of anti-inflammatory therapies, osteoclast inhibition could be beneficial for the treatment of rheumatoid arthritis.

Renal scarring caused by vesicoureteric reflux and urinary infection: a study in pigs.

The diminishing risk of acute renal scarring with urine infections (reflux nephropathy) after infancy is unexplained, but might reflect kidney maturation. The mechanisms of reflux nephropathy scarring are best explained by a piglet model in which vesicoureteric reflux allows infected urine to enter those segments of renal parenchyme that are drained by compound papillae. We carried out a similar study in adult pigs to determine whether protective maturation occurs. Adult pigs were exposed to urine infection after surgery to produce unilateral vesicoureteric reflux. The intravesical portion of one ureter was deroofed in six female adult Gottingen mini-pigs and the bladder and the ureteric mucosae stitched around the perimeter of the new orifice. One week later Escherichia coli was injected into the urinary bladder to produce cystitis. Three weeks later the animals were killed humanely and the urinary tracts were examined. The animals sustained persistent urine infections; the untreated ureters and kidneys remained normal. However, on the operated side, the ureters were thickened and dilated, vesicoureteric reflux was shown in four cases, and the kidneys had one or more flattened area overlying a renal segment, which showed severe inflammatory changes and early scar formation. The risk of reflux nephropathy scarring is not eliminated by maturation of the kidney in pigs. It is unlikely that the much-reduced risk of initiating scarring that is seen in older children with urine infections is due to a protective maturation of the human kidney. A possible explanation is that most children born with risk factors for developing scarring will have already sustained scars when very young.

Male gender: risk factor for severe symptomatic cholelithiasis.

The aim of this study was to determine the effect of male gender on the clinical presentation of symptomatic cholelithiasis. Laparoscopic cholecystectomy (LC) has been accepted as standard procedure for the management of symptomatic cholelithiasis even when the gallbladder is acutely inflamed. With the accumulated experience in the management of acute cholecystitis, some factors including male gender were recognized to influence the clinical presentation of symptomatic cholelithiasis and increase the conversion rate during LC. This retrospective study tried to clarify the correlation between male gender and the clinical presentation of symptomatic cholelithiasis. The medical records of all patients presenting with symptomatic cholelithiasis from January 1994 to August 1999 were evaluated. These cases were divided into four groups as follows: (1) elective LC group: patients with a history of biliary colic or acute attack of cholecystitis but whose LC was performed electively without any inflammatory change in the gallbladder during operation; (2) acute LC group: patients presenting with acute cholecystitis, and LC was performed successfully without conversion; (3) acute conversion group: patients who underwent LC during the course of acute cholecystitis but the procedure were disturbed by severe inflammatory change so they were converted to open surgery; (4) acute open group: patients whose acute cholecystitis was managed by direct open surgery due to the preoperative prediction that LC would not succeed. The correlation of gender, age, and operating time were assessed among these four groups. We found that: (1) the male/female ratio increased (in the patient group sequence of simple LC, acute LC, acute open, and acute conversion group); (2) in the acute LC group male patients had significantly (p = 0.04, t-test) longer operating time than females; (3) although there was no significant difference between the mean age of male (55.7 +/- 13.4) and female (56.3 +/- 15.7) patients in the acute cholecystitis groups (i.e., all patients in the acute LC, acute conversion, and acute open groups), the distribution curve by age in male patients showed a significantly shift to a younger age compared with female patients (p = 0.009, Fisher's exact test).

Cystic Fibrosis in Rhinologic Practice

Cystic fibrosis (CF) is the most common genetic lethal disorder that affects white populations. Chronic rhinosinusitis (CRS) with extensive nasal polyposis is one of the manifestations of CF. The aim of this study was to determine the prevalence and extent of CRS in CF patients. The study indicated that the signs and symptoms of CRS were present in all patients with CF and they were more advanced than in the control group. The most severe inflammatory changes in the paranasal sinuses were detected in patients with the dF508 gene mutation type who sufferedfrom CRS for >3 years. Massive nasal polyposis, dilated base of the nose, mucociliary clearance impairment, and significant radiological changes (frontal and maxillary sinus hypoplasia, bony destruction, and medial bulging of the lateral nasal wall) were identified to be the characteristic signs of the CRS in CF patients.

Eosinophilia in the Ethmoid Mucosa and Its Relationship to the Severity of Inflammation in Chronic Rhinosinusitis

The aim of this study was to analyze histopathologically mucosal inflammation in patients with chronic rhinosinusitis. In addition, we assessed tissue eosinophilia in relation to the severity of inflammation and to the computer tomographic (CT) findings. Forty-eight pathological sinus mucosa specimens obtained during functional endoscopic sinus surgery were stained by hematoxvlin and eosin. Total inflammatory cells and eosinophils were quantified. The preoperative CT scans were scored by the staging system of Lund-MacKay. The grade of the eosinophilic infiltration in the diseased sinus mucosa correlated significantly with the severity of the mucosal inflammation. Allergy or asthma had no effect on the proportion of the eosinophilic infiltrate. The CT scan scores assessed by the Lund-MacKay system correlated significantly with the severity of the inflammatory cellular infiltrate. The correlation between the CT scan scores and the eosinophilic infiltrate of the mucosa was close to significant. Eosinophilic mucosal inflammation represents the most severe inflammatory changes of the mucosa. Twenty to forty percent of the patients with chronic rhinosinusitis had no eosinophilic inflammation of the mucosa. The CT-staging system of Lund-Mackay correlated with the extent of mucosal inflammation.

The method of bladder drainage in spinal cord injury patients may influence the histological changes in the mucosa of neuropathic bladder – a hypothesis

BackgroundIn spinal cord injury (SCI) patients, no correlation was found between the number of bladder infections per year, the period since injury, the neurologic level of the spinal cord lesion and the histopathology of the urinary bladder mucosa. The use of chronic indwelling urethral and/or suprapubic catheters in SCI patients is often associated with inflammatory and proliferative pathological conditions in neuropathic bladder.Presentation of the hypothesisWe propose a hypothesis that the type of bladder drainage in SCI patients influences the histological changes in the mucosa of neuropathic bladder. This hypothesis implies that SCI patients with long-term indwelling urinary catheters develop certain histological changes in bladder mucosa, which are seen less frequently in SCI patients, who do not use long-term indwelling catheters. The latter group includes patients, who perform regular intermittent catheterisation and those, who wear a penile sheath and empty their bladders satisfactorily by reflex voiding.We hypothesise that the following histological lesions are seen more frequently in the neuropathic bladder of SCI patients with long-term indwelling catheters.(1) Papillary or polypoid cystitis; (2) widespread cystitis glandularis; (3) moderate to severe, acute and chronic inflammatory changes in bladder mucosa; (4) follicular cystitis; (5) squamous metaplasia; and (6) urothelial dysplasiaAs per this hypothesis, it is postulated that the above pathological conditions are seen less often in SCI patients, who achieve complete, low-pressure emptying of the neuropathic bladder by regular intermittent catheterisation, and SCI patients with penile sheath drainage, who empty their bladders satisfactorily by reflex voiding.Testing the hypothesisA large prospective study of bladder biopsies in SCI patients practising different methods of bladder drainage is required to validate this hypothesis that the histological changes in bladder mucosa are related to the method of bladder drainage in SCI patients.Implications of the hypothesisWe propose a hypothesis that the method of bladder drainage in SCI patients influences histological changes in the bladder mucosa. If this hypothesis is validated, methods of bladder drainage such as intermittent catheterisation, which do not require the use of chronic indwelling catheters, should be recommended, in order to minimise adverse histological changes in the mucosa of neuropathic bladder of spinal cord injury patients.

虫垂S状結腸瘻の1例

A 64-year-old man presenting with lower abdominial pain and fever was referred to our hospital. A barium enema examination showed an irregular shaped wall and extravasation of barium of the sigmoid colon. Computed tomography showed a high density area coincident with the extravasated barium near the sigmoid colon and ileoceacal region, but no tumorous lesion was noted. The abdominal pain and fever improved after one and a half months of conservative therapy. Open laparotomy was subsequently performed, because a malignant disease could not be ruled out. Severe inflammatory changes were found in the appendix, of which the distal end adhered to the sigmoid colon. En bloc resection of the appendix and sigmoid colon was performed, and a fine fistula was found between them. Histopathological examination confirmed severe inflammatory changes in the appendix and that appendiceal-sigmoid fistula had been caused by appendicitis. In cases of appendiceal-sigmoid fistula, careful observation or low-invasive treatment such as laparoscopic surgery should be also considered in the future.

Osteoclasts are essential for TNF-mediated joint destruction

Recent studies suggest that osteoclasts may contribute to bone erosions in the joints of animal models of arthritis and human rheumatoid arthritis. We therefore adressed the question, can bone destruction occur in an osteoclast free model of arthritis? To answer this question, c-Fos knockout mice (c-fos-/-) were crossed with mice overexpressing human soluble TNF (huTNFtg). C-fos-/- mice lack osteoclasts and are therefore osteopetrotic since c-fos is essential for the signaling of osteoclast differentiation. HuTNFtg mice develop a severe and destructive arthritis through the signaling of huTNF via the p55 TNF receptor. The resulting four groups of mice (wildtype, huTNFtg, c-fos-/- and c-fos-/-/huTNFtg) were followed over 10 weeks and assessed for joint inflammation and joint destruction. Clinical features of arthritis, such as paw swelling and reduction in grip strength progressed equally in both huTNFtg and c-fos-/-/huTNFtg mice. Clinical features of arthritis were absent in c-fos-/- and wildtype mice. Quantitative histological evaluation of joint sections revealed no difference between huTNFtg and c-fos-/-/huTNFtg mice in the size of inflammatory synovial lesions. As previously described, huTNFtg mice showed severe bone erosions in all joint compartments. Bone resorption was characterized by the abundant presence of osteoclasts, as confirmed by cells positive staining for TRAP and the calcitonin receptor. Furthermore, the number of osteoclasts and the size of bone erosions were significant. In contrast, c-fos-/-/huTNFtg mice did not show any form of bone destruction despite the presence of severe inflammatory changes. C-fos-/-/huTNFtg mice were confirmed to lack osteoclasts by negative TRAP staining and the presence of osteopetrosis. Controls (c-fos-/- mice and wildtype mice) did not show histological signs of inflammation or bone erosion. In conclusion, these data clearly show that TNF-mediated bone erosion is triggered by osteoclasts, and the absence of osteoclasts turns TNF-mediated arthritis from destructive to non-destructive arthritis.

Cystic Meckel's diverticulum: A rare cause of cystic pelvic mass presenting with urinary symptoms

An atypical form of Meckel's diverticulum is presented. A 5-year-old girl was admitted with recurrent urinary tract infections. Ultrasonography showed a cystic mass, which pressed and displaced the urinary bladder on its posterosuperior aspect. Laparotomy results showed a cystic mass originating from the antimesenteric border of the ileum, which was attached tightly to the urinary bladder. It was diagnosed as a cystic Meckel's diverticulum, which had undergone abscess formation with preservation of the ileal mucosa in some areas and had severe inflammatory changes on its wall. The case is unique both in the mode of presentation and type of complication. J Pediatr Surg 36:1855-1858. Copyright © 2001 by W.B. Saunders Company.

Development of rat prostatitis model by oral administration of isoflavone and its characteristics.

Inflammation of the prostate can be induced experimentally in rats by the subcutaneous administration of estrogen. However, it is usually achieved at the price of some alteration in the sex steroid hormone balance and morphological changes in the prostate. In this study, a soy-extracted isoflavone mixture with weak estrogenic activity was administered orally in an attempt to induce prostatitis in a more physiologic way and to characterize the inflammation induced. A total of 36 male Sprague-Dawley rats, 8 weeks old, were divided into 2 groups. The control group was fed with only an AIN-76A diet containing no detectable phytoestrogen and the experimental group was fed with AIN-76A and a soy- extracted isoflavone mixture (genistein 60.0% and daidzein 19.6%), 300 mg/kg body weight for 9 weeks. The sequential body weight and prostate weight at necropsy were measured. A histologic examination and histomorphometry assessed the changes in the prostate. The serum concentrations of testosterone and dihydrotestosterone were measured to estimate the effects on the androgen level. Intraprostatic concentrations of genistein and daidzein were measured by gas chromatography/ mass spectroscopy (GC/MS). While no sign of prostate inflammation was apparent in the control group, severe inflammatory changes in the stroma, increased epithelial detachment and inflammatory exudates within the glandular lumen of the dorsolateral prostate were observed in more than 80%(15/18) of the experimental group. However, there was no significant difference in the ventral prostate between the two groups. The daidzein and genistein concentrations in both the lateral and ventral prostates were significantly higher in the experimental group than in the control group where no isoflavone was detectable. In addition, the concentrations were much higher in the dorsolateral than in the ventral prostate. Although the body weight gain was not consistent in the experimental group, there were no significant differences in the prostate weight and serum androgen level between groups. In summary, when a soy-extracted genistein and daidzein-rich isoflavone mixture was administered orally into rats, prostatic inflammation with characteristic lobe specificity developed. The present method of inducing prostatitis seems to be a more physiologic than an estrogen-induced experimental model, and sequential pharmacokinetic studies might help in establishing this model as a more valuable tool in assisting future research in this field.

Histological and macroscopic changes in the pelvic pouch: long-term follow up after restorative proctocolectomy for ulcerative colitis (UC).

Our aim was to evaluate macroscopic and histological (inflammatory) changes in ileal pouch mucosa after restorative proctocolectomy with J-pouch-ileoanal anastomosis for UC during long-term follow up. Thirty-six (56%) out of 64 consecutive patients operated at our Institute during 1985-90 underwent endoscopy of the reservoir in the years 1994 and 1998. Functional outcome and macroscopic changes were recorded and histological samples taken from the three levels of the pelvic pouch. Acute and chronic inflammation were graded in accordance with a well-established histopathologic scoring system. The functional outcome was unchanged in 26 (72%), became worse in eight (22%) and better in two (6%) cases during follow up. The number of macroscopic changes increased during follow up and there was a tendency for them to become more common in the distal pouch. Microscopic acute and chronic inflammation decreased during follow up. There were more severe inflammatory changes in the distal pouch. Both acute and chronic inflammatory scores were higher through the reservoir in the cases of chronic pouchitis. Chronic pouchitis occurred more often in males. Macroscopic and inflammatory changes in the pelvic pouch seem to have separate progress during long-term follow up. In chronic pouchitis both acute and chronic inflammation are pronounced and spread over the entire pelvic pouch mucosa.

The chronic proliferative dermatitis mouse mutation ( cpdm): mapping of the mutant gene locus

Summary The chronic proliferative dermatitis (cpdm) mouse mutation was mapped to mouse Chromosome 15 using an intraspecific cross between C57BL/KaLawRij cpdm/cpdm and BALB/cJ mice. A second autosomal recessive mutation that resulted in a phenotype similar to that of cpdm arose spontaneously in a colony of OcB-3/Dem recombinant congenic mice. This new mutation was found to be allelic with cpdm. Therefore, the gene symbol for the allelic mutation is cpdmDem. The phenotype of these mutant mice consists of eosinophil-driven severe and progressive inflammatory changes in multiple organs including the skin and lungs.

Contribution of Hepatitis C Virus to the Progression of Alcoholic Liver Disease

We determined hepatitis C virus (HCV) antibody, HCV RNA, and genotype in patients with alcoholic liver disease and studied the involvement of HCV in alcoholic liver disease. Additionally, we used the histological activity index (HAI) to study the influence of HCV on the severity of inflammation. The subjects were 143 patients with alcoholic liver disease: 7 with fatty liver (FL), 18 with hepatic fibrosis (HF), 24 with alcoholic hepatitis (ALH), 39 with chronic hepatitis (CH), 42 with liver cirrhosis (LC), and 13 with hepatocellular carcinoma (HCC). The HCV RNA positivity rate in each type of disease was 0/7 (0%), 1/18 (6%), 2/24 (8%), 27/39 (69%), 24/42 (57%), and 7/13 (54%), respectively. It was high in the advanced hepatic lesions. Clinically, the serum hepatic function tests after abstinence from drinking improved significantly in the HCV RNA negative patients compared with the positive patients. The proportion of genotype II in each type of disease was 0/0, 0/1 (0%), 1/2 (50%), 18/27 (67%), 18/24 (75%), and 7/7 (100%), respectively. It became high with the advance of pathophysiology. The HCV RNA amount stood at 7.5 +/- 0.4 [log (copies/ml)] in CH, 7.9 +/- 0.4 in LC, and 8.4 +/- 0.8 in HCC, with a statistically significant difference between CH and HCC. However, we found no changes in the HCV RNA amount due to abstinence from drinking. The HAI score was high in the HCV RNA positive patients, but several cases in the HCV RNA negative group showed severe inflammatory changes. Therefore, judging the presence or absence of HCV RNA with the HAI score alone was considered difficult. These results suggest that HCV, particularly genotype II, plays an important role in the advance of disease to LC and HCC in heavy drinkers.

Pathology of upper respiratory tract disease of gopher tortoises in Florida.

Between August 1993 and September 1995, 24 gopher tortoises (Gopherus polyphemus) were received for pathological evaluations from various locations in Florida (USA). All tortoises were examined for clinical signs of upper respiratory tract disease (URTD) including nasal and ocular discharge, palpebral edema, and conjunctivitis. Of the 24 tortoises, 10 had current or previously observed clinical signs of URTD and 14 did not. A blood sample was drawn for detection of anti-mycoplasma antibodies by ELISA, and nasal lavage samples were collected for culture and detection of Mycoplasma agassizii gene sequences by polymerase chain reaction (PCR). Of the 14 clinically healthy tortoises, eight were sero-, culture- and PCR-negative, and six were seropositive for antibodies against M. agassizii. Of those six, five were culture- and/or PCR-positive for M. agassizii, and one was culture- and PCR-negative. Of the 10 ill tortoises, nine were seropositive by the ELISA and one was in the suspect range. Nine of the ill tortoises, including the suspect tortoise, were culture- and/or PCR-positive for M. agassizii, and one was culture- and PCR-negative. For histologic evaluation and discussion, the eight sero-, culture-, and PCR-negative tortoises were designated URTD-negative, and the other 16 were classified as URTD-positive. Histologic evaluation of the upper respiratory tract (URT) indicated the presence of mild to severe inflammatory, hyperplastic, or dysplastic changes in 14 URTD-positive tortoises. Seven of eight URTD-negative tortoises had normal appearing nasal cavities; one had mild inflammatory changes. Transmission electron microscopy revealed an organism consistent with Mycoplasma spp. on the nasal mucosal surface of tortoises with clinical signs and lesions of URTD. Additionally, gram-negative bacteria were isolated more frequently from the nasal cavities of URTD-positive tortoises than URTD-negative tortoises. Because clinical signs of URTD were never observed in six of the URTD-positive tortoises, we also conclude that subclinical URTD can occur in gopher tortoises.

Treatment of venous leg ulcers with clobetasol propionate ointment

BACKGROUND: The use of topical steroids should be minimized in the treatment of venous leg ulcers. However, as a consequence of venous insufficiency poorly understood inflammatory processes may occur. These may impair ulcer healing, so in cases of severe inflammatory changes steroids may be required to permit healing. METHODS: A 71-year-old female had chronic venous ulceration of the right lower leg. Histology showed eczema and ulceration and the patient complained of a 'pain' rather than 'itching'. Treatment commenced with betamethasone to eczematous skin but improvement was slow. After developing acute erythema and exudation of most of the skin of the right lower leg, daily treatment with clobetasol propionate ointment was commenced to the inflamed skin and ulcer beds. RESULTS: The exudation ceased, the 'pain' reduced and the ulcers began to heal. CONCLUSION: This isolated case suggests that a minority of patients with venous leg ulcers may benefit from topical steroid treatment to the ulcer beds. This hypothesis merits to be tested in a doubleblind, vehicle-controlled study. (J Dermatol Treat (2000) 11:53–55)

Middle ear pathologic changes associated with chronic anaerobic sinusitis in rabbits.

To study the histopathologic changes in association with the inflammatory/immune response present in the middle ears of a rabbit model of unilateral chronic anaerobic sinusitis. New Zealand white rabbits, two at each experimental time point. Normal rabbits and sham-operated animals served as controls. Left maxillary sinusitis was induced by inoculating Bacteroides fragilis surgically after closure of the ostium. Cultures, lavages, and mucosa were harvested from bilateral middle ear and sinus cavities at 1, 2, 3, and 4 weeks following inoculation. Parameters analyzed include tissue for histopathologic study, immunoglobulin G antibody (IgG Ab) against B fragilis, and lactate dehydrogenase (LDH) levels in lavage samples, interferon gamma (IFN gamma) messenger RNA (mRNA) expression in mucosal tissue, and bacterial culture. Despite closure of the ostium of the left sinus, mild to moderate dissemination of B fragilis into the right sinus and left and right ears were observed in some but not all rabbits (2/8, 5/7, and 2/8, respectively). Histopathologic changes in the right sinus and middle ears were much less severe in contrast to the severe inflammatory changes in the left sinus. An immune response against B fragilis appeared to occur in the sinuses and ears bilaterally independent of bacterial dissemination, as evidenced by a rise of IgG Ab in lavage fluid and detection of IFNg mRNA. Neither control nor sham-operated animals had detectable levels of IFNg mRNA or IgG Ab. In B fragilis-inoculated rabbits, the magnitude of IgG Ab responses was equivalent in the right and left ear, independent of B fragilis dissemination; IgG Ab levels in the middle ear positively correlated to each other (P < .01) and to the levels in the sinuses (P < .01 and P < .01). LDH levels were closely associated with bacterial growth and degree of tissue inflammation. This reproducible model of chronic sinusitis provides an opportunity to study the middle ear infection and inflammatory/immune responses occurring with sinusitis. Our results indicate bilateral middle ear mucosal immune responses to an elicited sinus infection, independent of B fragilis dissemination.

Bombesin ameliorates colonic damage in experimental colitis.

In the present study we investigated the possible therapeutic effects of bombesin on an experimentally induced colitis model in rats. Inflammation of the colon was induced by a single intracolonic administration of 30 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS) at 8 cm from the anus. Immediately after the induction of colitis, some rats were given bombesin (10 microg/kg; subcutaneously) three times a day for 14 days, while another group received vehicle treatment. On day 14, the rats were decapitated and plasma carbonyl content and tissue myeloperoxidase level, as an index of granulocyte infiltration into intestinal tissue, were determined in order to obtain an objective evaluation of colonic injury. In the colitis group, increased macroscopic damage score, elevated MPO level and high plasma carbonyl content, together with the microscopic appearance revealed severe inflammatory changes resembling IBD. Bombesin treatment attenuated the TNBS-induced colonic damage and stimulated histopathologically apparent mucosal proliferation, suggesting that bombesin may play a role in protecting gut integrity.

Localization of metallothionein-I and -II in hypertrophic astrocytes in brain lesions of dogs.

To study the neurophysiological functions of metallothioneins (MTs), localization of MT-I and -II was examined immunohistochemically in a variety of brain lesions in dogs, including infarct, laminar cortical necrosis, hemorrhage, invasive growth of tumour, inflammatory lesions in granulomatous meningoencephalitis and distemper encephalitis. MT-I and -II were demonstrated in both nucleus and cytoplasm of hypertrophic astrocytes in most brain lesions examined regardless of the type, size, localization and duration of the lesions. In addition, MT expression was stronger in a population of hypertrophic astrocytes localizing inside of the surviving brain tissue rather than those localizing at the boundary between the surviving brain tissue and necrotic area, where severe inflammatory changes were developing. These results suggest that MT-I and -II may play roles not only in protection of neurons from metals and free radicals ubiquitous in the inflammatory lesions but also in repair of injured neural tissues.