Degree Of Acute Inflammation Research Articles

Exploring breath biomarkers in BLM-induced pulmonary fibrosis mice with associative ionization time-of-flight mass spectrometry

Pulmonary fibrosis (PF) is a common but fatal disease that threatens human health worldwide. Developing effective diagnostic methods is of great importance for the early detection of PF in patients. In this study, bleomycin (BLM) was used in mice to mimic idiopathic pulmonary fibrosis (IPF). The exhaled breath of BLM-induced PF, PF plus DDAH1 overexpression, and healthy control mice were analyzed in real-time using a newly developed associative ionization time-of-flight mass spectrometry method (AI-TOFMS), which is uniquely sensitive, especially to oxygenated volatile organic compounds (VOCs). Multivariate data analyses and discriminant modeling analyses revealed that four exhaled compounds, i.e., acrolein, ethanol, nitric oxide, and ammonia, had a strong correlation with PF symptoms. An Orthogonal Partial Least Square Discriminant Analysis (OPLS-DA) score plot showed an excellent separation between these three groups. The area under the receiver operating characteristic (ROC) curve for these four compounds distinguished PF mice from healthy controls at 0.989. In addition, the degrees of acute inflammation and fibrosis were assessed with Hematoxylin and Eosin (H&E) staining and Masson's Trichrome staining. Finally, combined with pathological characteristics and mRNA expression levels, the formation of the above-mentioned volatile compounds was explored. The obtained experimental results indicated that these four breath compounds, acrolein, ethanol, nitric oxide, and ammonia, were potential exhaled biomarkers for pulmonary fibrosis.

Activation of a Central Immunosuppressive Cascade Prevents Ischemia Reperfusion Injury After Acute Compartment Syndrome in a Murine Model

Purpose: Occurring when interstitial pressure exceeds perfusion pressure, acute compartment syndrome (ACS) results in warm ischemia and cell death due to impaired aerobic metabolism. Following surgical decompression and reperfusion of the extremity, there is a robust innate inflammatory response that results in further tissue injury due to the production of reactive oxygen species and local capillary dysfunction. In addition to prompt diagnosis and reperfusion of the compartment, therapies which limit the secondary ischemia reperfusion injury (IRI) may be helpful to improve outcomes in patients with ACS. Varenicline (Chantix™) activates a novel immunosuppressive cascade and is effective at reducing IRI in following testicular torsion and pyelonephritis. We hypothesized that varenicline administration would reduce IRI following a compartment syndrome model in a mouse. 
 Methods: Using an established model, warm hindlimb ischemia was induced in mature CD-1 mice by placing an orthodontic rubber band around the hindlimb for 90 minutes. In the treatment group, varenicline (1µg/gram) was administered as an intraperitoneal injection 60 minutes after the onset of ischemia. The degree of acute inflammation was quantified using Fluorescent Activated Cell Sorting, 24 hours following reperfusion. The expression of pro-fibrotic genes in the gastrocnemius muscle were evaluated 7 days following reperfusion and histologic evaluation of fibrosis with trichrome staining was performed 14 days following reperfusion of the limb. 
 Results: Treatment with varenicline reduced the acute leukocyte infiltrate 24 hours after reperfusion (3.08% vs 0.86%, P≤0.01, n=16). Treatment with varenicline reduced the expression of the pro-fibrotic genes (measured in relative expression) (Collagen1a1 (1.73 vs. 0.31), Collagen1a3 (1.85 vs. 0.42), Vimentin (2.11 vs 0.38) and Actin (1.82 vs. 0.56) P≤0.05, n=16 7 days following reperfusion. Histologic evidence of collagen deposition was also significantly reduced (3.45% vs. 1.89%, P≤0.005, n=20) 14 days following reperfusion in animals treated with varenicline.
 Conclusions: Varenicline administration reduces acute inflammation and long-term fibrosis of the gastrocnemius muscle following warm hindlimb ischemia in a mouse.
 Significance: Varenicline represents a potentially novel FDA approved adjunct to the current management of acute compartment syndrome and extremity ischemia. Administration of this medication appears to have the potential to mitigate post-injury inflammation and fibrosis which may lead to improved functional outcomes following this condition. Further studies are needed to define the optimal dosing and administration regimens.

P0208DIFFERENTIAL ADAPTATION OF RENAL FUNCTION IN TWO TYPES OF INTENSE PHYSICAL EXERCISE

Abstract Background and Aims Marathon running induces AKI even in adequately prepared and healthy athletes. Heat stress, maintained during more than 2h, has been proposed as one of the leading causes of AKI in marathons runners. Other possible explanations of AKI in this setting could be associated with a reduction of blood supply to the kidneys during the exercise, inadequate hydration or actual structural damage due to microtraumatisms. However, the effect of vigorous exercise of shorter duration on renal function has not been previously described although most risk factors described could also affect kidney function in this type of physical activity. Method 40 volunteer healthy athletes were enrolled in this study. Subjects participated in two physical tests (10km running, 1.5km swimming) which were separated by at least two weeks from each other. These tests were chosen because of their similar oxygen consumption rate and metabolic load. Vitals, blood and urine samples were collected immediately before and after each test. Informed consent was obtained from all participants. The project was funded by Consejería de Sanidad, Junta de Castilla y León (GRS1732/A/18). Results Athletes ranged from 23 to 53 years old. 35% were female. A comparison of hemodynamic and analytical parameters is summarized in Table 1. Running induced a significantly higher rise of serum creatinine and inflammatory markers compared to swimming. Additionally, running caused an increment of serum phosphorus and uric acid levels. Both types of exercise caused a mild increase of urinary albumin/creatinine ratio. Conclusion Compared to swimming, running was associated with a greater rise of serum creatinine, possibly linked to a higher degree of acute inflammation and blood flow redistribution to the muscles. The rise of serum uric acid levels may be associated with increased metabolism and reduced elimination of this molecule while running.

Silk fibroin scaffold as a potential choice for female pelvic reconstruction: A study on the biocompatibility in abdominal wall, pelvic, and vagina

The aim of this study was to compare the tissue reactions to silk fibroin scaffolds in the abdominal wall, vagina, and pelvic vesico-uterine of rats. Silk fibroin scaffolds were implanted subcutaneously in the abdominal, pelvic vesico-uterine space, and under the vaginal mucosa of 16 rats. The animals were euthanized at 2, 4, 8, and 12 weeks postoperatively. Hematoxylin and eosin staining was performed to evaluate cellular infiltration, the percentage of macrophages and granulocytes inside and around the scaffolds. The amounts of M1/M2 macrophages at the interface of scaffolds and host tissue were evaluated through an immunofluorescence assay. The degree of acute inflammation was similar among the three groups, and lasted no more than 4 weeks. A faster ingrowth of fibroblasts was found in the abdominally implanted silk fibroin scaffolds, while vaginal implanted scaffolds committed a slower tissue ingrowth rate and much more macrophages infiltration than the pelvic and abdominal group. However, a significantly higher amount of M2 cells were seen in the three groups. In general, silk fibroin has nice biocompatibility in the abdominal, vagina, and pelvic tissue, eliciting healthy tissue formation, and might be a potential choice for female pelvic reconstruction. Microsc. Res. Tech. 80:291-297, 2017. © 2016 Wiley Periodicals, Inc.

Foreign Body Reaction to Implantable Biosensors: Effects of Tissue Trauma and Implant Size.

Implantable biosensors for continuous glucose monitoring can greatly improve diabetes management. However, their applications are still associated with some challenges and one of these is the gradual functionality loss postimplantation as a consequence of the foreign body response (FBR). Sensor miniaturization in combination with drug-eluting biocompatible coatings is a promising strategy to enhance in vivo performance. However, limited study has been performed to understand the effect of initial trauma and implant size on foreign body reaction as well as in vivo performance of implantable glucose sensors. Different initial trauma was induced by implanting composite coated dummy sensors into rats using various sized needles and 3 different-sized dummy sensors were implanted to examine the size effect. Histological evaluation was performed to relate the inflammatory cell counts and foreign body capsule thickness with the implantation needle size and sensor size respectively. The effect of biocompatible coating on the performance of implantable glucose sensors was determined using both coated amperometric glucose sensors and microdialysis probes. The results revealed that the degree of acute inflammation was mainly controlled by the extent of the initial trauma: the greater the trauma, the greater the acute inflammatory response. Implant size did not affect the acute inflammatory phase. However, the extent of chronic inflammation and fibrous encapsulation were affected by sensor size: the smaller the size the less the extent of chronic inflammation and fibrous encapsulation. Glucose sensors implanted using 14 gauge needles showed significantly lower initial in vivo response compared to those implanted using 16 gauge needles. This was not observed for sensors with dexamethasone-eluting biocompatible coatings since inflammation was suppressed. The results of the current study indicate that the extent of the inflammatory response post-sensor implantation varies as a function of the initial tissue trauma as well as the sensor size. Accordingly, miniaturization of implantable biosensors together with the utilization of a drug-eluting biocompatible composite coating may be a promising strategy to achieve long-term reliable continuous glucose monitoring.

Histological Evaluation on Biocompatibility of Porcine Liver Derived ECM Matrix

As promising transplantable biomedical strategies for liver supports, decellularized porcine matrix have been explored. For safe medical application of xenogenic biomaterials, studies would be required to focus on the biocompatibility and host cellular responses to implanted biologic materials. This study was assessed the biocompatibility of extracellular matrix (ECM)-rich matrix from porcine liver as transplantable biomaterials. Porcine liver tissues were decellularized with 0.1% Sodium dodeocyl sulfate solution. To compare host remodeling responses of liver matrix, native and decellularized liver samples are implanted into subcutaneous of pig for 10weeks. After 1, 2, 4, and 10 weeks of surgery, the implanted samples were harvested and examined by Hematoxylin and Eosin staining. The degree of acute inflammation, chronic inflammation, eosinophilic infiltration, vascularity, and stromal reaction was graded on a scale of 0(+) to 4(++++). Decellularized matrix implants represented only minimal chronic inflammatory responses. No acute inflammatory responses, eosinophilc infiltrations, and vascularities were represented in the decellularized matrix implant groups. Mild to moderate degree of fibroblasts infiltration was seen around and within the both native liver and decellularized matrix implant groups. Complete degradation of all implanted tissues was occurred within10 weeks. Porcine liver biologic scaffolds would be beneficial for diverse studies related to liver regeneration. Although additional in-depth studies would be required to analysis mechanisms of host immune responses to biologic scaffolds, our data provide useful information of vivo remodeling properties of porcine liver biologic matrix. This work was supported by a grant from the Next-Generation BioGreen 21 program (No.P J008030,J008032), Rural Development Administration, Republic of Korea.

Safety of Bevacizumab on Extraocular Muscle in a Rabbit Model

PurposeThe purpose of this study was to investigate the myotoxicity of bevacizumab on extraocular muscles in a rabbit model.MethodsThirty New Zealand white rabbits were used for this study. The animals were evenly divided into two groups. In the first group, 15 rabbits were treated with intramuscular injections of bevacizumab (1.25 mg/0.05 mL) in the right superior rectus muscle and normal saline solution (0.05 mL) in the left superior rectus muscle. In the second group, 15 rabbits were treated with subconjunctival injections of bevacizumab (2.5 mg/0.1 mL) in the right superior subconjunctival area and normal saline solution (0.1 mL) in the left superior subconjunctival area. Five rabbits in each group were sacrificed at one day, two weeks and four weeks after the injections. Extraocular muscle samples were prepared for light microscopic (LM) and electron microscopic (EM) examination. Degrees of acute inflammation were evaluated via CD-11b immunohistochemistry, and global muscle change was investigated using hematoxylin and eosin stains. Intensity of fibrosis was evaluated using Masson trichrome stains, and ultrastructural changes were observed on EM.ResultsWe observed no significant inflammatory cell infiltration, muscle necrosis or fibrotic change in treated and control eyes. EM findings revealed no significant damage to muscle or vascular tissue after bevacizumab injection.ConclusionsWe found no signs of extraocular muscle toxicity after LM and EM intramuscular and subconjunctival bevacizumab injections in a rabbit model.

Experimental study on surgical timing for obstructive biliary injury repair

Objective To observe the pathological changes of tissues of the injured bile duct, and to provide theoretical basis for bile duct repair. Methods Dog models of obstructive biliary injury were established.Sixty dogs were equally divided into five groups according to the duration of biliary obstruction: biliary obstruction for 5 days (BDL5 group), 10 days (BDL10 group), 15 days (BDL15 group), 20 days (BDL20 group) and 30 days (BDL30 group). The morphological and pathological changes of bile duct and local tissues were observed, and biliary-enteric Roux-en-Y anastomosis was applied to repair the injured bile duct and postoperative complications were observed. All data were analyzed by LSD test, independent sample t test, one-way analysis of variance and chi-square test. Results Proximal bile duct rapidly expanded as the pressure increased in the early stage, and the bile duct expanded to ( 15.6 ± 1.8)mm in the BDL10 group. The expansion rate decreased in the later stage,and the bile duct expanded to (18.9 ± 1.9)mm in the B DL15 group. Acute inflammation was observed in injured local tissues. The acute inflammation was severe in the BDL5 group with white blood cell count of 54 ± 6, and the acute inflammation was relatively mild in the BDL15 group with white blood cell count of 42 ± 7. There was a significant difference between the BDL5 group and BDL15 group in the degree of acute inflammation (t =4. 688,P ＜ 0. 05). The content of the collagen was increased in the injured bile duct as time passed by. Bile duct repair was successfully performed on 57 dogs. Ten dogs ( three in the BDL5 group, four in the BDL10 group, one in the BDL15 group, one in the BDL20 group and one in the BDL30 group) died of bile leakage after the operation. The incidences of bile leakage was 30% (7/23) within 10 days and 9% (3/34) beyond 10 days, with a significant difference between the two groups (x2 =4.429, P＜0.05). Conclusion Ten days after obstructive biliary injury,an obvious reduction of bile duct expansion and edema of the bile duct is observed, the difficulty of the operation is reduced and the incidence of bile leakage is low, so 10 days after the incidence of obstructive biliary injury is the proper timing for the surgical repair. Key words: Bile duct injury; Obstructive jaundice; Bile duct repair; Timing

α-Lipoic acid has anti-inflammatory and anti-oxidative properties: an experimental study in rats with carrageenan-induced acute and cotton pellet-induced chronic inflammations

α-Lipoic acid (ALA) has been termed the 'ideal' antioxidant, a readily absorbed and bioavailable compound capable of scavenging a number of free radicals, and it has been used for treating diseases in which oxidative stress plays a major role. The present study was designed to gain a better understanding for the positive effects of ALA on the models of acute and chronic inflammation in rats, and also determine its anti-oxidative potency. In an acute model, three doses of ALA (50, 100 and 200mg/kg) and one dose of indomethacin (25mg/kg) or diclofenac (25mg/kg) were administered to rats by oral administration. The paw volumes of the animals were calculated plethysmometrically, and 0·1ml of 1% carrageenan (CAR) was injected into the hind paw of each animal 1h after oral drug administration. The change in paw volume was detected as five replicates every 60min by plethysmometry. In particular, we investigated the activities of catalase, superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), inducible NO synthase (iNOS) and myeloperoxidase (MPx), and the amounts of lipid peroxidation (LPO) or total GSH in the paw tissues of CAR-injected rats. We showed that ALA exhibited anti-inflammatory effects on both acute and chronic inflammations, and a strongly anti-oxidative potency on linoleic acid oxidation. Moreover, the administration of CAR induced oedema in the paws. ALA significantly inhibited the ability of CAR to induce: (1) the degree of acute inflammation, (2) the rise in MPx activity, (3) the increases of GST and iNOS activities and the amount of LPO and (4) the decreases of GPx, GR and SOD activities and the amount of GSH. In conclusion, these results suggest that the anti-inflammatory properties of ALA, which has a strong anti-oxidative potency, could be related to its positive effects on the antioxidant system in a variety of tissues in rats.

Prognostic and Pathogenetic Value of Combining Clinical and Biochemical Indices in Patients With Acute Lung Injury

No single clinical or biologic marker reliably predicts clinical outcomes in acute lung injury (ALI)/ARDS. We hypothesized that a combination of biologic and clinical markers would be superior to either biomarkers or clinical factors alone in predicting ALI/ARDS mortality and would provide insight into the pathogenesis of clinical ALI/ARDS. Eight biologic markers that reflect endothelial and epithelial injury, inflammation, and coagulation (von Willebrand factor antigen, surfactant protein D [SP-D]), tumor necrosis factor receptor-1, interleukin [IL]-6, IL-8, intercellular adhesion molecule-1, protein C, plasminogen activator inhibitor-1) were measured in baseline plasma from 549 patients in the ARDSNet trial of low vs high positive end-expiratory pressure. Mortality was modeled with multivariable logistic regression. Predictors were selected using backward elimination. Comparisons between candidate models were based on the receiver operating characteristics (ROC) and tests of integrated discrimination improvement. Clinical predictors (Acute Physiology And Chronic Health Evaluation III [APACHE III], organ failures, age, underlying cause, alveolar-arterial oxygen gradient, plateau pressure) predicted mortality with an area under the ROC curve (AUC) of 0.82; a combination of eight biomarkers and the clinical predictors had an AUC of 0.85. The best performing biomarkers were the neutrophil chemotactic factor, IL-8, and SP-D, a product of alveolar type 2 cells, supporting the concept that acute inflammation and alveolar epithelial injury are important pathogenetic pathways in human ALI/ARDS. A combination of biomarkers and clinical predictors is superior to clinical predictors or biomarkers alone for predicting mortality in ALI/ARDS and may be useful for stratifying patients in clinical trials. From a pathogenesis perspective, the degree of acute inflammation and alveolar epithelial injury are highly associated with the outcome of human ALI/ARDS.

Effect of Roux-en-Y surgery and medical intervention on Barrett's-type changes: anin vivomodel

In animal models, mixed acid and bile reflux into lower esophagus induces histological changes comparable to Barrett's metaplasia (BM) and neoplasia. The aim of this study was to compare the effects of Roux-en-Y (REY) surgery and medical therapy on BM in animals before the development of neoplasia. Vagus preserving esophagojejunostomy operation was performed on Sprague-Dawley rats to achieve gastroduodenal reflux (GDR) into the esophagus in 30 animals. After 3 months, changes were reversed in 10 animals (Group REY) by REY operation, 10 animals (Group proton pump inhibitor [PPI]) were given PPI during the postoperative period, and 10 animals (Group GDR) did not have further intervention. At 4 months, histological examination of the lower esophagus was performed by an experienced pathologist. Physiological parameters were also analyzed in all animals preoperatively and at 4 months postoperatively. The length of columnar mucosa, degree of acute inflammation, degree of metaplasia, and composite BM score were significantly reduced by REY surgery compared with medical therapy and with control (columnar mucosa in cm [mean +/- standard error of the mean] Group REY 0.44 +/- 0.06, Group PPI 0.92 +/- 0.08, P < 0.001/Group GDR 1.17 +/- 0.31, P < 0.03). There was no neoplasia seen in any specimen. At 4 months, postoperatively controls Group REY surgery showed significantly more normalization of physiological parameters to preoperative levels than Group PPI (P < 0.05). REY surgery is potentially more beneficial than medical therapy in reversing the histological and biochemical changes of Barrett's esophagus due to GDR.

Gallbladder Disease among Obese Patients in Taiwan

Obesity is a risk factor for gallbladder disease. The authors analyze the prevalence and clinicopathology of gallbladder disease among obese patients in Taiwan. Prevalence and various clinical factors associated with cholelithiasis were studied in 199 patients who were undergoing bariatric surgery for obesity. Clinical data (gender, age, BMI and associated diseases), laboratory evaluation and immunoglobulin G antibodies against Helicobacter pylori were obtained from the patient records. The histopathologic findings of the gallbladder were also examined retrospectively. The degree of acute inflammation, chronic inflammation, cholesterolosis, cholesterol polyp and gastric metaplasia was determined and scored. Of the patients, 91% (n=181) were females and 9% (n=18) were males, age 34.26 +/- 8.41 years, with mean BMI 35.28 +/- 6.11 kg/m2. The prevalence of cholelithiasis was 10.1%. Increased diastolic blood pressure and HBsAg carrier were the only significant factors associated with cholelithiasis. All obese patients in our study presented with variable degrees of chronic mononuclear cell infiltration in the gallbladder mucosa. Cholesterolosis was present in 100 patients (50.3%), followed by gastric metaplasia (27.1%), cholesterol polyp (16.1%) and acute inflammation (9.5%). Multivariate analysis showed an association between cholelithiasis and acute and chronic inflammation. The predictors of cholesterolosis were BMI, waist circumference and high-sensitivity C-reactive protein. The seroprevalence of H. pylori was 42.2%. Older age, abnormal liver function tests, calcium and HBsAg carrier were significantly different between H. pylori-seropositive and H. pylori-seronegative obese patients. However, we could rarely find H. pylori within the gallbladder mucosa. Cholelithiasis in Asian obese patients is significantly associated with increased diastolic blood pressure and hepatitis B surface antigen carriers. Because chronic liver disease seems to be a risk factor for cholelithiasis in both non-obese and obese populations, prophylactic cholecystectomy can be considered in obese patients with HBsAg positivity. We did not find evidence that H. pylori has a role in the pathogenesis of gallbladder disease and gallstone by histologic and serologic examinations. Furthermore, mucosal abnormalities of acute and chronic inflammatory cell infiltration are common in obese patients, which related to cholelithiasis.

Histological evaluation of Permacol™ as a subcutaneous implant over a 20-week period in the rat model

This study assessed the suitability of Permacol (a porcine derived, isocyanate cross linked collagen based biomaterial) as an alternative to autologous tissue in soft tissue reconstruction. The Sprague-Dawley rat was used as a model for subcutaneous implantation over a 20 week period and comparison made with two other porcine biomaterials (small intestinal submucosa and glycerol treated-ethylene oxide sterilised porcine dermis). Implants were scored histometrically on the degree of acute inflammation, chronic inflammation, fibrosis and stromal response. The vascularity and percentage composition of collagen within Permacol were assessed by stereology and seescan image analysis, respectively. In general terms, Permacol was well tolerated as a subcutaneous implant, with only a minor chronic inflammatory response remaining after a 20 week period of implantation. There was evidence of collagen degradation during this period and vascular ingrowth into Permacol was limited. Permacol has the potential for a broad range of applications in plastic surgery, but may benefit from modification to promote a more rapid degree of vascularisation.

Histopathological Study on Non-Aneurysmal Coronary Arteries in Kawasaki Disease

To evaluate coronary arterial changes found in most Kawasaki disease (KD) patients who recover without aneurysms, histopathologial observation was performed using autopsy KD patients. Materials and Methods: Fifteen KD autopsy patients without coronary artery aneurysms by macroscopical observation, ranged from 6 days to 14 years after the onset of illness, were used in this study. Coronary arteries were fixed in 10% formalin and embedded in paraffin. Hematoxylin and eosin, Elastica van Gieson and azan-Mallory stain were performed for routine histological examination. Results:Acute phase: In coronary arteries of the patients who died on 6th day after the onset, a few inflammatory cells were observed in the intima and adventitia. In coronary arteries of 9th to 13th illness day, histological findings varied from no inflammation unto marked panarteritis showing severe inflammatory cells infiltration and disruption of internal elastic lamina. After 17th day, inflammation became much milder than former lesions, and the lesions showed subsiding tendency. The causes of death of these patients were myocarditis, valvulitis or interstitial pneumonia. Remote phase: All patients died of causes other than sequelae of KD. In five of six patients, scarring of arteritis such as concentric intimal thickening and extension of internal elastic lamina was observed in coronary arteries. However, remarkable change was not seen in one patient. Summary: The degree of acute inflammation in coronary arteries varied in each patient. Especially, we must point out the existence of the patients having no inflammation at coronary arteries even in acute phase. In addition, there was a case without apparent arterial change also in remote phase. In this patient, it is suggested that no or very slight inflammation in coronary arteries had occurred at acute phase.

Prevalence of different periapical lesions associated with human teeth and their correlation with the presence and extension of apical external root resorption.

The aim of this study was to determine the prevalence of various periapical pathologies and their association with the presence and extent of apical external inflammatory root resorption in human teeth. One hundred and four root apices from extracted teeth with periapical lesions were examined. Semi-serial sections of soft tissue lesions were stained with HE. The lesions were classified as noncystic or cystic, each with different degrees of acute inflammation: 0, 1, 2 and 3, increasing in severity. The root apices were analysed by SEM. External root resorption was classified according to site, as periforaminal or foraminal, and the extension of the resorbed area graded in increasing area as 0, 1, 2 or 3. Cysts accounted for 24.5% of the samples, 84% of which were associated with marked inflammation. The most prevalent diagnosis was noncystic periapical abscess with varying degrees of severity (63.7%). Periapical granuloma was not a frequent finding. SEM analysis showed that 42.2% of the root apices had periforaminal resorption extending over 50% of their circumference. When the foraminal resorption was evaluated, 28.7% had resorption affecting >50% of the periphery. Only 8.9% of the samples showed no periforaminal or foraminal resorption. In the sample of extracted teeth investigated, 24.5% of the periapical lesions were cysts. Most periapical lesions (84.3%) displayed acute inflammation, whether cystic or not. Periforaminal resorption was present in 87.3% of the cases, and foraminal resorption in 83.2%. Periforaminal and foraminal resorptions were independent entities. There was no association between external root resorption and the nature of the periapical lesions.

Biophysical profile in predicting acute ascending infection in preterm rupture of membranes before 32 weeks

Objective: To assess the performance of the biophysical profile (BPP) and its components within 24 hours of delivery in predicting histopathologic evidence of severe acute placental inflammation in women with premature rupture of membranes (PROM) before 32 weeks’ gestation. Methods: We examined placentas from a series of consecutive, nonanomalous, live-born, singleton infants delivered before 32 weeks’ gestation after PROM. In 166 cases, biophysical profiles (BPP) were done within 24 hours of birth. Histologic evidence of acute inflammation was assessed in the maternal (amnion) and fetal (chorionic and umbilical cord vessels) compartments, and scored on a severity scale of 0–4 by a single pathologist masked to clinical data. The presence and severity of acute inflammation was related to BPP results and its individual components. Results: The overall prevalence of severe acute inflammation, ie, a score of 3 or 4, was 59% (98 of 166). In 30 (18%) cases it was present in the amnion, in 49 (30%) cases in chorionic or umbilical cord vessels, and in 19 (11%) cases in maternal and fetal compartments. There was no association between abnormal BPP score and presence or absence of severe acute placental inflammation (48% versus 46%, P = .7). Our study had a 90% power to detect a 0.26 difference between them. When rates of abnormal BPP scores were compared in cases with different degrees of acute inflammation in the maternal, fetal, or both compartments, no association was found. When the individual components of the BPP were analyzed in relation to site and severity of acute inflammation, no association was detected. Conclusion: We did not find evidence of a dose-response relationship between acute placental inflammation and BPP score or its individual components in cases of PROM with infants delivered before 32 weeks. Mediators other than infection might affect BPP in preterm PROM.

Correlation of histological inflammation in needle biopsy specimens with serum prostate- specific antigen levels in men with negative biopsy for prostate cancer

Objectives. To reveal the possible contribution of histological inflammation within the prostate to the abnormal elevation of serum prostate-specific antigen (PSA) levels in patients with needle biopsy negative for prostate cancer. Methods. We reviewed negative needle biopsy specimens obtained in 93 patients. The degree of acute and chronic inflammation as evaluated histologically was compared with serum PSA levels in conjunction with age and prostate volume. Results. Both age ( P <0.01) and prostate volume ( P <0.0001) correlated significantly with serum PSA levels and were significantly greater in patients with abnormal serum PSA levels (greater than 4.0 ng/mL) than in those with normal serum PSA levels (4.0 ng/mL or less) ( P <0.01). The presence of histological inflammation within the prostate also correlated significantly with serum PSA levels. Multiple regression analysis demonstrated prostate volume to be the only independent determinant of serum PSA levels ( P <0.01). In patients with a prostate volume larger than 25 mL, only prostate volume correlated significantly with serum PSA levels ( P <0.05). On the other hand, the degree of acute inflammation as represented by polymorphonuclear leukocyte infiltration was the only parameter correlating significantly with serum PSA levels ( P <0.05) in patients with a prostate volume smaller than 25 mL. Conclusions. Histologically defined acute inflammation within the prostate is a significant contributor to elevated serum PSA levels, especially in patients with small prostates. In the assessment of needle biopsy results negative for prostate cancer, it might be helpful to evaluate the degree of histological inflammation, especially in terms of the necessity of subsequent repeated biopsies.

Proliferation and apoptosis in gastric antral epithelial cells of patients infected with Helicobacter pylori

We measured cell proliferation and apoptosis in the antral epithelial cells of Helicobacter pylori-infected and H. pylori-uninfected persons, and examined these processes in relation to diagnosis and the histologic parameters of inflammation to investigate their role in cellular turnover in diseases of the upper gastrointestinal tract. The subjects were: 25 patients with antral gastric cancers, 20 with antral gastric ulcers, 18 with duodenal ulcers, and 28 with chronic gastritis, and 4 subjects with normal gastric mucosa. Seventy-two subjects were infected with H. pylori, and 23 subjects, including the 4 with normal gastric mucosa, were uninfected. H. pylori infection was associated with increased apoptosis and cell proliferation in the gastric mucosa, which correlated with the degree of acute inflammation and the density of H. pylori, and these latter two factors correlated with each other. Intestinal metaplasia and glandular atrophy were significantly higher in gastric cancers and gastric ulcers than in duodenal ulcers. Cell proliferation was significantly lower in gastric cancers than in gastric ulcers, but the apoptotic count did not show a significant difference between these diseases. This decreased proliferation in the adjacent mucosa in gastric cancers compared with findings in the other diseases is thought to be closely related to the relatively decreased acute inflammation, which may, partly, contribute to glandular atrophy in the adjacent mucosa of gastric cancer.

Protection of mitomycin C induced skin extravasation with the nitroxide, 3-carbamoyl-PROXYL (3-CP)

Extravasation tissue injury from chemotherapeutic drugs is a serious clinical problem. A swine model has been useful for studying skin extravasation and evaluating potential antidotes. Mitomycin C (MMC) skin extravasation was studied. Nitroxides, a class of compounds which are protective against a variety of oxidative stresses in vitro, including MMC, were tested as antidotes. Miniature swine were anesthetized and given intradermal (ID) injections of MMC. MMC alone caused skin necrosis and ulceration. Several nitroxides were screened as protectors of MMC induced skin necrosis. 3-carbamoyl-PROXYL (3-CP) was the lone nitroxide which protected if given 5 min after extravasation. Administration of 3-CP 10 min after MMC injection was not protective. In vitro studies with monolayered V79 cells showed that 3-CP had a direct protective effect against MMC cytotoxicity in a concentration-dependent fashion. Therefore, in the swine model doses of 3-CP ranging from 25-100 mM were tested and found to protect against MMC skin necrosis 90 days after injection. Histologic sections of the 3-CP- and MMC-treated pig skin showed a marked reduction in the degree of acute inflammation and the absence of deep dermal scarring when compared to MMC alone.

Acute inflammation is the harbinger of glomerulosclerosis in anti-glomerular basement membrane nephritis.

The degree of glomerular inflammation and injury during immune-mediated glomerulonephritis is felt to be critical to the eventual development of glomerulosclerosis, although the relative contributions of acute and chronic inflammation are uncertain. By grading the initial dose of antibody in accelerated anti-glomerular basement membrane nephritis, we observed that only animals with the most substantial acute inflammation (in terms of neutrophil influx and acute proteinuria) developed sustained proteinuria followed by an increase in serum creatinine and evidence of severe glomerulosclerosis. Chronic inflammation (i.e., glomerular macrophage influx and evidence of glomerular cell proliferation), in contrast, was evident without the development of glomerulosclerosis. Decreasing the degree of acute inflammation during severe nephritis by complement depletion diminished both the initial and sustained proteinuria and the influx of neutrophils, prevented the terminal increase in serum creatinine, and attenuated the evolution of glomerulosclerosis. Complement depletion, however, did not affect peak proteinuria, macrophage influx, or glomerular cell proliferation. Regression analysis of the entire data set demonstrated that acute (day 1) proteinuria was predictive of the eventual histopathological index, more so than chronic (day 7) proteinuria. To recapitulate, glomerulosclerosis following antiglomerular basement membrane nephritis appears to be substantially dependent on the degree of acute inflammatory injury.