Inflammatory Tissue Reaction Research Articles

Endovascular Infections Caused by Histoplasma capsulatum: A Case Series and Review of the Literature

Endovascular infection is an uncommon but devastating manifestation of histoplasmosis, which is often diagnosed late in disease. To evaluate the clinical and pathologic characteristics of patients with endovascular infections caused by Histoplasma capsulatum. All cases of patients with documented endovascular histoplasmosis at a single tertiary care center in an endemic region during the period 1993-2010 were reviewed. Patients presented with a subacute febrile illness and a history of endovascular devices. All patients had positive Histoplasma serology. Routine bacterial culture results were negative for all patients. In addition to yeast forms typical of histoplasmosis, pathologic findings also revealed mycelial forms in 4 of 5 patients. Inflammation was scant. Urinary antigen detection was positive in 4 of 5 patients and Histoplasma blood culture results were positive for 3 of 5 patients. Four patients were treated with a combination of surgical and medical therapy, which consisted of amphotericin B followed by itraconazole; these 4 patients had complete resolution of symptoms and no documented relapse. One patient died before planned surgery. Histoplasma capsulatum endovascular infections are clinically characterized by a subacute febrile illness with negative bacterial cultures in patients with prosthetic endografts or valves. Noninvasive diagnostics are often the initial clue to the diagnosis. Combined medical and surgical treatment is associated with survival. On histopathologic examination both mycelial and yeast forms are often observed, with absent to minimal tissue inflammatory reaction.

The onchocerciasis chronicle: from the beginning to the end?

The year 2012 marks the 25th anniversary of the donation of ivermectin to fight onchocerciasis and the projected date for elimination of transmission of the disease in the Americas. This review looks at the history of onchocerciasis, from its discovery through to 2025, by which time it is projected that the disease will have been eliminated as a public health problem, except in a handful of sub-Saharan countries, where it should be well on the way towards elimination.

Regenerative effect of adipose tissue-derived stem cells transplantation using nerve conduit therapy on sciatic nerve injury in rats

This study proposed a biodegradable GGT nerve conduit containing genipin crosslinked gelatin annexed with tricalcium phosphate (TCP) ceramic particles for the regeneration of peripheral nerves. Cytotoxicity tests revealed that GGT-extracts were non-toxic and promoted proliferation and neuronal differentiation in the induction of stem cells (i-ASCs) derived from adipose tissue. Furthermore, the study confirmed the effectiveness of a GGT/i-ASCs nerve conduit as a guidance channel in the repair of a 10-mm gap in the sciatic nerve of rats. At eight weeks post-implantation, walking track analysis showed a significantly higher sciatic function index (SFI) (P < 0.05) in the GGT/i-ASC group than in the autograft group. Furthermore, the mean recovery index of compound muscle action potential (CMAP) differed significantly between GGT/i-ASCs and autograft groups (P < 0.05), both of which were significantly superior to the GGT group (P < 0.05). No severe inflammatory reaction in the peripheral nerve tissue at the site of implantation was observed in either group. Histological observation and immunohistochemistry revealed that the morphology and distribution patterns of nerve fibers in the GGT/i-ASCs nerve conduits were similar to those of the autografts. These promising results achieved through a combination of regenerative cells and GGT nerve conduits suggest the potential value in the future development of clinical applications for the treatment of peripheral nerve injury.

In vivo evaluation of titanium oxide and hydroxyapatite as an artificial cornea skirt

Keratoprosthetic devices are subject to chronic inflammatory, pathological processes and the external environment that affect their stability and biocompatibility with the ocular surface and adjacent ocular tissues. We compared the corrosion resistance property and tissue-implant reaction of titanium oxide (TiO(2)) with hydroxyapatite (HA) in artificial tear fluid and a rabbit skin implantation model. The dissolution properties of the implant surfaces were evaluated with scanning electronic microscope (SEM) and atomic force microscope (AFM). Tissue inflammatory reactions were evaluated by Hematoxylin & Eosin staining, avidin biotin peroxidase complex (ABC) immunoassay and immunofluorescence. SEM and AFM images showed that there was less pitting corrosion on the surface of TiO(2) implants compared with HA. TiO(2) and HA exhibited a similar pattern of foreign body capsule formation and inflammatory cellular responses. The Collagen I/Collagen III ratio of the TiO(2) capsule was higher than that of the HA capsule. TiO(2) implants possess a high corrosion resistance property both in vitro and in vivo and the inflammatory cellular response to TiO(2) is similar to HA. With regards to corrosion resistance and inflammatory tissue responses, TiO(2) appears to be a promising material for keratoprosthetic skirt devices.

Osteopontin Biomarker in Inflammatory Bowel Disease, Animal Models and Target for Drug Discovery

Inflammatory bowel disease (IBD) is an immune-mediated disease caused by abnormal mucosal T-cell response to bacteria in the intestinal lumen. In Crohn’s disease (CD), mucosal T cells exhibit the TH1 phenotype, whereas ulcerative colitis (UC) is believed to have a TH2 phenotype [1]. In the absence of a single test, calculating disease activity in IBD remains a complicated task. An accurate and reliable marker for measuring CD or UC activity for routine clinical practice and in clinical trials has to be based on clinical judgment of histologic and endoscopic imaging. Therefore, validated accurate and objective measures of inflammatory activity in IBD using a reliable, non-invasive biomarker is needed [2]. Proteonome biomarkers are used in the diagnostics of IBD, but they are expensive and not all of them are validated [3]. Several recent reports have suggested an important role for osteopontin (OPN) in the pathogenesis of IBD as well as its possible use as a biomarker [4–10]. Masuda et al. demonstrated that expression of OPN is significantly elevated in the mucosa of patients with UC [6]. Elevated OPN expression in UC was demonstrated using immunohistochemistry and ultrastructure analysis [7, 8]. In CD, Gassler et al. reported an elevated OPN expression in plasma cells, but not in epithelial cells [9]. Moreover, Sato et al. observed an elevated plasma OPN and significant correlation with disease activity in CD, but not in UC [10]. Osteopontin, a Th1 cytokine, is up-regulated in relation to the severity of the disease [11]. Moreover, since it is an adhesive glycoprotein containing the peptide sequence glycine ± arginine ± aspartate ± serine it promotes cell attachment [12]. Osteopontin and tumor necrosis factor receptor signaling (TNFRS) F14 are genes associated with fibrosis/cell adhesion molecules [1, 13]. Blockade of these cell adhesion molecule interactions prevents the trafficking of leukocytes across the vascular endothelium and, subsequently, into the parenchymal tissue [14–16]. Alpha-4 integrins bind additional ligands in tissues, including OPN and epitopes of fibronectin. This is the rationale for using the mechanism of monoclonal antibodies in clinical practice. The scope may be to suppress ongoing inflammatory reactions in diseased tissues by inhibition of a4-positive leukocytes with ligands. Inhibiting the existing inflammatory activity at the disease site, along with inhibition of further recruitment of immune cells into inflamed tissue, via interaction with adhesion molecules such as the vascular adhesion molecule will reduce the inflammation and intestinal fibrosis [17–19]. On the basis of these findings, several researchers described animal models that can mimic the OPN-induced colitis in vivo as well as block OPN-induced inflammation [20–23]. In this issue is the article ‘‘Osteopontin ablation attenuates progression of TNBS-induced colitis model.’’ In this study, Oz et al. elegantly demonstrate that by ablating the OPN activity the colitis is suppressed [24]. The developmental stages of colonic inflammation in a modified trinitrobenzene sulfonic acid (TNBS) model that mimics Crohn’s disease have been defined as acute, subacute, and chronic. The researchers used OPN deficient mice, with a targeted disruption of the opn gene in a C57BL/6. TNBStreated wildtype mice developed severe colitis but OPNdeficient mice were significantly protected. M. G. Neuman (&) In Vitro Drug Safety and Biotechnology, Department of Pharmacology and Toxicology, Faculty of Medicine, Institute of Drug Research, University of Toronto, MaRS Discovery District, 101 College Street, Suite 300, Lab 351, South Tower, Toronto, ON M5G 1L7, Canada e-mail: m_neuman@rogers.com

Cilostazol suppression of arterial intimal hyperplasia is associated with decreased expression of sialyl Lewis X homing receptors on mononuclear cells and E-selectin in endothelial cells

An inflammatory reaction in vascular tissue is a potential factor linking restenosis after angioplasty. Although cilostazol, a selective phosphodiesterase type 3 inhibitor that is a unique antiplatelet drug and vasodilator, has been reported to be anti-inflammatory, its effect on the inflammatory action of mononuclear cells homing to endothelial cells is not clearly understood. In this study, whether cilostazol inhibits neointimal formation and improves inflammatory actions by inhibiting sialyl Lewis X (SLX) expression on mononuclear cells and E-selectin expression on endothelial cells was evaluated. The effect of cilostazol (1, 3, 10, 30 μM) on expression of E-selectin in human umbilical vein endothelial cells and SLX in rat mononuclear cells stimulated with lipopolysaccharide by immunofluorescence and real-time polymerase chain reaction (n = 3) was studied. Additionally, a double-balloon injury model was used on rat carotid arteries to evaluate vascular intimal hyperplasia. 0.1% cilostazol was administered 3 days before the first balloon injury, and the second balloon injury was performed 7 days after the first injury. Cilostazol administration was continued until rats were sacrificed 14 days after the second angioplasty. The expression of SLX on mononuclear cells and E-selectin on endothelial cells by immunofluorescence (n = 10) and real-time polymerase chain reaction (n = 5) were studied. Cilostazol effectively inhibited the expression of SLX on mononuclear cells and E-selectin on endothelial cells. Cilostazol inhibited the migration of mononuclear cells in neointimal regions and neointimal hyperplasia after balloon injury. The numbers of macrophages and T-lymphocytes and the hyperplasia area in neointimal regions decreased from 71.06 ± 20.04, 1121 ± 244.4 cells per section, 206,400 ± 96,150 mm(2) to 29.65 ± 16.73, 374.2 ± 124.5 cells per section, and 101,900 ± 16,150 mm(2) due to the administration of cilostazol. These results demonstrate that the protective effect of cilostazol against neointimal hyperplasia may be mediated by its anti-inflammatory actions of mononuclear cells homing to endothelial cells by decreasing SLX and E-selectin expression. It is reported that cilostazol inhibits neointimal hyperplasia by decreasing the expression of some cell-adhesion molecules. We evaluated the effects of cilostazol for the expression of sialyl Lewis X (SLX) on mononuclear cells and E-selectin on endothelial cells, which interaction is the first step of inflammation action. Cilostazol was thought to show the anti-inflammatory actions by decreasing SLX and E-selectin expression in addition to decreasing the expression of some cell-adhesion molecules.

Diagnostic and Therapeutic Challenges of a Large Pleural Inflammatory Myofibroblastic Tumor

We report a 48-year-old woman with a pleural pseudoneoplasm requiring different diagnostic and therapeutic strategies. After initial presentation with increasing dyspnoea, temperature, dry cough, and interscapular pain diagnostic processing showed a large mediastinal mass with marked pleural effusion and high metabolic activity in the 18F-FDG-PET/CT. Extensive CT-guided biopsy of the tumor reaching from the visceral pleura into the right upper lobe revealed no malignancy, but a marked inflammatory tissue reaction containing foam cells. Initial empiric antibiotic therapy was temporarily successful. However, in the further course the mass relapsed and was resistant to antibiotics and a corticosteroid trial. With the working hypothesis of an inflammatory myofibroblastic tumor the patient underwent surgical tumor resection, finally confirming the suspected diagnosis. Due to residual disease intravenous immunoglobulins were administered leading to sustained response. This case with a pleural localisation of a large inflammatory pseudotumor with responsiveness to immunomodulation after incomplete resection extends the reported spectrum of thoracopulmonary manifestations of this rare entity.

Novel roles of peroxiredoxins in inflammation, cancer and innate immunity

Peroxiredoxins possess thioredoxin or glutathione peroxidase and chaperone-like activities and thereby protect cells from oxidative insults. Recent studies, however, reveal additional functions of peroxiredoxins in gene expression and inflammation-related biological reactions such as tissue repair, parasite infection and tumor progression. Notably, peroxiredoxin 1, the major mammalian peroxiredoxin family protein, directly interacts with transcription factors such as c-Myc and NF-κB in the nucleus. Additionally, peroxiredoxin 1 is secreted from some cells following stimulation with TGF-β and other cytokines and is thus present in plasma and body fluids. Peroxiredoxin 1 is now recognized as one of the pro-inflammatory factors interacting with toll-like receptor 4, which triggers NF-κB activation and other signaling pathways to evoke inflammatory reactions. Some cancer cells release peroxiredoxin 1 to stimulate toll-like receptor 4-mediated signaling for their progression. Interestingly, peroxiredoxins expressed in protozoa and helminth may modulate host immune responses partly through toll-like receptor 4 for their survival and progression in host. Extracellular peroxiredoxin 1 and peroxiredoxin 2 are known to enhance natural killer cell activity and suppress virus-replication in cells. Peroxiredoxin 1-deficient mice show reduced antioxidant activities but also exhibit restrained tissue inflammatory reactions under some patho-physiological conditions. Novel functions of peroxiredoxins in inflammation, cancer and innate immunity are the focus of this review.

Periapical tissue reactions to calcium hydroxide and MTA after external root resorption as a sequela of delayed tooth replantation

Clinical experience has shown that most avulsed teeth are replanted after a long extra-alveolar time and dry or inadequate wet storage, causing necrosis of periodontal ligament cells. This condition invariably leads to development of external root resorption, leaving the filling material in contact with the periapical connective tissues. In this study, the periapical tissue reactions to calcium hydroxide (CH) and mineral trioxide aggregate (MTA) were evaluated after occurrence of external root resorption as an expected sequela of delayed tooth replantation. Twenty male Wistar rats (Rattus norvegicus, albinus) had their right upper incisor extracted and maintained in dry storage for 60 min. Then, the dental papilla, enamel organ, pulp tissue, and periodontal ligament were removed, and the teeth were immersed in a 2% acidulated phosphate sodium fluoride solution, pH 5.5, for 10 min. The teeth were randomly assigned into two groups (n = 10), in which the canals were filled with either a CH and saline paste (CH group) or MTA (MTA group). The sockets were irrigated with saline, and the teeth were replanted. After 80 days, it was possible to observe large areas of replacement root resorption and some areas of inflammatory root resorption in both groups. More severe inflammatory tissue reaction was observed in contact with calcium hydroxide compared with the mineral trioxide aggregate. New bone formation was more intense at the bottom of the socket in the MTA group. In conclusion, as far as periapical tissue compatibility is concerned, intracanal MTA can be considered as a viable option for root canal filling in delayed tooth replantation, in which external root resorption is an expected sequela.

Prenatal repair of myelomeningocele with aligned nanofibrous scaffolds—a pilot study in sheep

Background/Purpose Spinal cord damage in myelomeningocele (MMC) results from abnormal cord development and subsequent local trauma. Prenatal surgery prevents additional neural injury. However, existing damage is not reversed. Biodegradable nanofibrous scaffolds (NSs) promote regeneration of neural tissues. They mimic the microtopography of the extracellular matrix and guide tissue formation and organization. The purpose of this pilot study was to evaluate the practicality and safety of using biodegradable NS as a regenerative device in prenatal MMC repair. Methods Two fetal lambs underwent a surgically induced MMC defect followed by open fetal repair using aligned biodegradable NS. Lambs were killed at day 138. Spinal cords were examined for inflammation or fibrosis and stained for spinal cord architecture, myelin, and neuron cell bodies. Results Prenatal repair with NS demonstrated technical feasibility. There was no evidence of a surrounding inflammatory response or foreign-body reaction to the scaffold. Conclusion Biodegradable NS can be used surgically for the prenatal repair of MMC in a large animal model and does not appear to elicit an inflammatory or fibrotic reaction in fetal tissue. Further studies will determine their potential for neural cell infiltration, delivery of growth factors, drugs or stem cells, and functional recovery greater than standard repair.

Severe inflammatory reaction induced by peritoneal trauma is the key driving mechanism of postoperative adhesion formation

BackgroundMany factors have been put forward as a driving mechanism of surgery-triggered adhesion formation (AF). In this study, we underline the key role of specific surgical trauma related with open surgery (OS) and laparoscopic (LS) conditions in postoperative AF and we aimed to study peritoneal tissue inflammatory reaction (TIR), remodelling specific complications of open surgery (OS) versus LS and subsequently evaluating AF induced by these conditions.MethodsA prospective randomized study was done in 80 anaesthetised female Wistar rats divided equally into 2 groups. Specific traumatic OS conditions were induced by midline incision line (MIL) extension and tissue drying and specific LS conditions were remodelled by intraperitoneal CO2 insufflation at the 10 cm of water. TIR was evaluated at the 24th, 72nd, 120th and 168th hour by scoring scale. Statistical analysis was performed by the non-parametric t test and two-way ANOVA using Bonferroni post-tests.ResultsMore pronounced residual TIR was registered after OS than after LS. There were no significant TIR interactions though highly significant differences were observed between the OS and LS groups (p < 0.0001) with regard to surgical and time factors. The TIR change differences between the OS and LS groups were pronounced with postoperative time p < 0.05 at the 24th and 72nd; p < 0.01 - 120th and p < 0.001 - 168th hrs. Adhesion free wounds were observed in 20.0 and 31.0% of cases after creation of OS and LS conditions respectively; with no significant differences between these values (p > 0.05). However larger adhesion size (41.67 ± 33.63) was observed after OS in comparison with LS (20.31 ± 16.38). The upper-lower 95% confidential limits ranged from 60.29 to 23.04 and from 29.04 to 11.59 respectively after OS and LS groups with significant differences (p = 0.03). Analogous changes were observed in adhesion severity values. Subsequently, severe TIR parameters were followed by larger sizes of severe postoperative adhesions in the OS group than those observed in the LS group.ConclusionsMIL extension and tissue drying seem to be the key factors in the pathogenesis of adhesion formation, triggering severe inflammatory reactions of the peritoneal tissue surrounding the MIL resulting in local and systemic consequences. CO2 insufflation however, led to moderate inflammation and less adhesion formation.

Usefulness of Histopathological Examination in Nontraumatic Perforation of Small Intestine

IntroductionNontraumatic perforation of small intestine (NTPSI) is a fairly common cause of peritonitis in developing world requiring early surgical intervention. Various etiological factors have been proposed for the cause of small bowel perforation. This retrospective study was conceded with an aim to determine the prevalence patterns of the different etiologies of NTPSI. Materials and MethodsA total of 164 patients were included in the study who had segments of small intestine removed for perforation during emergency procedures. Preoperative definitive diagnoses were not known in these cases. On gross examination, most of the small intestine perforations, n = 110 (67%), were found in the terminal ileum. On microscopy, the most frequent category was that of ulcers of nonspecific etiology, n = 61 (37.2%), which showed general features like inflammatory granulation tissue, serositis, and foreign body giant cell reaction. ResultsIn cases where a definite opinion could be established, infection was the commonest cause, n = 71 (43.3%), wherein tuberculosis (49, 29.9%) and typhoid (22, 13.4%) constituted the greatest number of cases. There were two cases of lymphoma and one case of metastatic adenocarcinoma involving the small intestine. Thus, histopathological examination of operated specimen is a useful guide for the surgeon to decide further management of the patient especially in the case of infections.

Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, acinar cell damage, and systemic inflammation in acute pancreatitis

In acute pancreatitis, endoplasmic reticulum (ER) stress prompts an accumulation of malfolded proteins inside the ER, initiating the unfolded protein response (UPR). Because the ER chaperone tauroursodeoxycholic acid (TUDCA) is known to inhibit the UPR in vitro, this study examined the in vivo effects of TUDCA in an acute experimental pancreatitis model. Acute pancreatitis was induced in Wistar rats using caerulein, with or without prior TUDCA treatment. UPR components were analyzed, including chaperone binding protein (BiP), phosphorylated protein kinase-like ER kinase (pPERK), X-box binding protein (XBP)-1, phosphorylated c-Jun NH(2)-terminal kinase (pJNK), CCAAT/enhancer binding protein homologues protein, and caspase 12 and 3 activation. In addition, pancreatitis biomarkers were measured, such as serum amylase, trypsin activation, edema formation, histology, and the inflammatory reaction in pancreatic and lung tissue. TUDCA treatment reduced intracellular trypsin activation, edema formation, and cell damage, while leaving amylase levels unaltered. The activation of myeloperoxidase was clearly reduced in pancreas and lung. Furthermore, TUDCA prevented caerulein-induced BiP upregulation, reduced XBP-1 splicing, and caspase 12 and 3 activation. It accelerated the downregulation of pJNK. In controls without pancreatitis, TUDCA showed cytoprotective effects including pPERK signaling and activation of downstream targets. We concluded that ER stress responses activated in acute pancreatitis are grossly attenuated by TUDCA. The chaperone reduced the UPR and inhibited ER stress-associated proapoptotic pathways. TUDCA has a cytoprotective potential in the exocrine pancreas. These data hint at new perspectives for an employment of chemical chaperones, such as TUDCA, in prevention of acute pancreatitis.

Protective effect of polyenylphosphatidyl choline on liver in rat with sepsis

To investigate the protective effect of polyenylphosphatidyl choline (PPC) on liver in rat with sepsis. A total of 50 healthy male SD rats were randomly divided into four groups according to random number table: normal control group (NS group, n=10), sepsis model group (LPS group, n=15), PPC control group (PPC group, n=10) and PPC protection group (P+L group, n=15). A single dose of lipopolysaccharide (LPS) 6 mg/kg was injected to the peritoneal cavity to reproduce the sepsis model, while in NS group and PPC group, same volume of normal saline was used. PPC 10 ml/kg (232.5 mg/kg) was injected 24 hours and 6 hours before LPS via the tail vein in PPC group and P+L group, while in NS group and LPS group 5% glucose solution in the same volume was given. Behavioral changes and mortality rate of rats were recorded, and all survived rats were sacrificed 24 hours after LPS injection. Venous blood was taken for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) determination. Ratios of liver weight/body weight (L/Wb) and wet weight/dry weight of liver (W/D) were calculated. Histopathology changes in liver tissue were observed with hematoxylin eosin (HE) stain, and intercellular adhesion molecule-1 (ICAM-1) expression with instant two-step immunohistochemistry. Twenty-four hours after LPS injection (LPS group), the rats became lethargic, with less activity and drinking, while rats in P+L group, showed much better mental status, water intake and activity than LPS group. The mortality rate of P+L group was significantly lower than that of LPS group [6.7% (1/15) vs. 46.7% (7/15),P<0.05]. Compared with LPS group, rats in P+L group had lower levels of plasma ALT and AST, L/Wb, W/D , and liver ICAM-1 positive expression ratio [ALT (U/L): 157.71 ± 32.63 vs. 225.63 ± 43.47; AST (U/L): 53.21 ± 13.85 vs. 85.25 ± 18.91; L/Wb: (4.09 ± 0.28)% vs. (4.50 ± 0.25)%; W/D : 3.52 ± 0.27 vs. 3.84 ± 0.18; ICAM-1 positive expression ratio: 35.7% (5/14) vs. 87.5 (7/8),P<0.05 or P <0.01]. All parameters were normal in NS group and PPC group, and no statistical significance was observed between them (all P >0.05). LPS-injection led to severe inflammatory reaction in hepatic tissue , including obvious edema of hepatic parenchymal cells, exudation and aggregation of inflammatory cells, while in P+L group, these morphological changes were milder than that in LPS group but more obvious than that of NS group. Pre-treatment of rats with PPC alleviates progressive inflammatory disturbances of hepatic tissue caused by endotoxin injection, and it attenuates liver edema and ICAM-1 expression, protects liver function and decreases mortality rate in rats with sepsis.

A safety study of a B‐class CpG ODN in Sprague–Dawley rats

Oligodeoxynucleotides containing CpG motifs (CpG ODNs) are potent immune activators and are being tested as anti-tumor, antimicrobial agents and as adjuvants in vaccines. Little has been reported, however, about the systematic and comprehensive safety evaluation on repeated CpG ODN administration. To investigate the safety profile of a newly developed CpG ODN, CpG 684, we conducted a 28-day repeated dose toxicity study in rats, at dose levels of 5, 20 and 150 µg CpG 684 per rat. No abnormalities in clinical observations, growth, urinalysis and bone marrow cell counts were found in CpG 684 treated rats. CpG 684 was proved biologically active, capable of up-regulating the expressions of CD40 and CD86 molecules. The monocyte numbers were increased at the dose levels of 20 and 150 µg per rat. The spleen weights were increased in female rats at the dose level of 150 µg per rat. Microscopically, 5, 20 and 150 µg per rat CpG 684 caused local inflammatory cell infiltration and hyperplasia of fibrous tissue at injection sites; the treatment of 5 and 150 µg per rat CpG 684 induced enhanced inflammatory reaction in inguinal lymphoid tissue, and the dose of 150 µg per rat induced cell hyperplasia in white pulp of spleen and white pulp expansion. CpG 684 at 150 µg per rat led to decreases in peripheral lymphocyte, serum globulin, glucose, alkaline phosphatase and K+ levels in female rats, and induced the decrease in serum albumin and total protein in rats of both sexes. The data from this study will provide an important reference for developing CpG 684 as an adjuvant for vaccines of human use.

Effect of age, impaction types and operative time on inflammatory tissue reactions following lower third molar surgery

BackgroundPostoperative mobidity following third molar surgery is affected by a number of factors. The study of these factors is essential for effective planning and limitation of morbidity. The aim of this study was to determine the effect of age, type of impaction and operative time on immediate postoperative tissue reactions following mandibular third molar surgery.MethodsConsecutive patients with impacted mandibular third molar teeth were studied. All the third molars were classified according to Winter's classification. Surgical extraction was performed on all the patients by a single surgeon under local anaesthesia. The operation time was determined by the time lapse between incision and completion of suturing. Postoperative pain, swelling and trismus were evaluated.ResultsThere were 120 patients with an age range of 19-42 years. Patients in the age range of 35-42 years recorded a lower pain score (p = 0.5) on day 1. The mouth opening was much better in the lower age group on day 2 and 5 (p = 0.007 and p = 0.01 respectively). Pain, swelling and trismus increased with increasing operative time. Distoangular impaction was significantly associated with higher VAS score on day 1 and 2 (p = 0.01, 0.0, 04). Distoangular and horizontal impaction are associated with a higher degree of swelling and reduced mouth opening on postoperative review days. Vertical impaction was associated with the least degree of facial swelling and best mouth opening.ConclusionsIncreasing operating time and advancing age are associated with more postoperative morbidity, likewise distoangular and horizontal impaction types.

Peri-Tumoral Inflammatory Cell Infiltration in OSCC: A Reliable Marker of Local Recurrence and Prognosis? An Investigation Using Artificial Neural Networks

The presence of inflammatory reaction in peri-tumoural connective tissue is generally considered as a defense mechanism against cancer, but inflammation tissue in malignant transformation and early steps of oncogenesis has been recently proven to play a supporting and aggravating role in some carcinomas. Aims of this retrospective study were to evaluate in OSCCs the independent association of peri-tumoral inflammatory infiltrate (PTI) with local recurrence (LR) or survival outcome, and to verify whether PTI can be considered a marker of prognosis. Data from 211 cases of OSCC, only surgically treated between 1990 and 2000, were collected and retrospectively analyzed for PTI and the event LR (5 yrs follow-up at least) by means of univariate-multivariate and neural networks analyses. Patients (mean age 65.3 ± 12.4 yrs, M/F = 2.98) showed presence of PTI in 68.2% (144/211): (+) in 27.0%, (++) in 25.6%, (+++) 15.6%; PTI was found reduced in 24.7% of cases and absent in 7.1%. In overall PTI+ve group (n=144), 66 were TNM Stage I, 33 Stage II, 45 Stage III, none Stage IV. LR (mean 6 ± 4 months) was present in 87/211 (41.2%) patients, of which 43/144 (29.8%) in OSCCs with PTI [23 (+), 13 (++) and 7 (+++)] vs. 44/67 (65.7%) in OSCC with PTI -/+ or PTI-ve ones. By univariate analysis, PTI+ve cases showed a significant lower risk to have LR (p <0.0001; OR= 0.2297; CI= 0.1277:0.4134) vs PTI -/+ or -ve ones, especially among cases with higher PTI value (+++) (OR= 0.1718; CI= 0.0749:0.3939). Multivariate analyses (Logit model and neural networks) confirmed the same datum: presence of PTI was an independent predictive variable accounting for a better tumoural outcome without LR (Logit and neural networks values: OR' 0.226; CI= 0.113:0.454; ROC Area = 0.66, respectively). In terms of prognostic significance, elevated PTI was found to have an independent association with the poorest overall survival rate (P = 0.056). Our findings strongly suggest the importance to investigate routinely PTI in OSCCs, as useful marker of tumoral behavior and prognosis, and warrant further studies.

Cardiovascular disease in recent onset diabetes mellitus

Diabetes is associated with a marked increased risk of atherosclerotic vascular disorders, including coronary, cerebrovascular, and peripheral artery disease. Cardiovascular disease (CVD) could account for disabilities and high mortality rates in patients with diabetes. Conventional risk factors, including hyperlipidemia, hypertension, smoking, obesity, lack of exercise, and a positive family history, contribute similarly to macrovascular complications in type 2 diabetic patients and non-diabetic subjects. The levels of these factors in diabetic patients are certainly increased, but not enough to explain the exaggerated risk for macrovascular complications in the diabetic population. Furthermore, recently, macrovascular complications of diabetes have been shown to start before the onset of diabetes. Indeed, several clinical studies have confirmed the increased risk of CVD in patients with impaired glucose tolerance (IGT). Since insulin resistance-related postprandial metabolic derangements are thought to play a central role in the development and progression of CVD in patients with IGT, amelioration of postprandial metabolic disturbance is a therapeutic target for the prevention of CVD in these high-risk patients. Therefore, in this paper, we review the molecular mechanisms for the increased risk of CVD in recent onset diabetes mellitus, especially focusing on postprandial dysmetabolism. We also discuss here the potential therapeutic strategies that specially target the mechanisms responsible for vascular alterations in diabetes.

In situ-forming chitosan/nano-hydroxyapatite/collagen gel for the delivery of bone marrow mesenchymal stem cells

A biomimetic and thermosensitive gel scaffold was prepared from chitosan (CS), nano-hydroxyapatite (HA) and collagen (Col). The changes of storage modulus, loss modulus, pH and conductivity of the CS/HA/Col system as a function of temperature confirmed the liquid-to-gel phase transition process occurred under physiological conditions. The formed gel acted as a biocompatible substrate for the proliferation of rat bone marrow stem cells (rBMSCs) in vitro. rBMSCs suspension was co-injected with CS/HA/Col solution into Wistar rats. The injected rBMSCs survived in the CS/HA/Col gel for 28 days in vivo. The CS/HA/Col/rBMSCs gels induced less inflammatory reaction in the host tissue than the CS/HA/Col gels. Our results suggest that the CS/HA/Col system can be used to load rBMSCs in vitro homogeneously. The CS/HA/Col system can be injected into body in a minimally invasive manner and provides a biocompatible environment for rBMSCs survival in vivo.

Outcome of continence procedures after failed endoscopic treatment with dextranomer-based implants (DEFLUX®)

PurposeTo evaluate outcome of further continence procedures after failure of endoscopic injections of dextranomer-based bulking agent. Materials and methodsFrom 1997, 89 children (3–18 years) and one young adult were treated for incontinence with 145 endoscopic injections of dextranomer. On evaluation, each patient was classified as: dry, significantly improved, or treatment failure. Eighty-five patients had at least 12 months of follow up. Out of 34 (40%) treatment failures, 24 patients had a subsequent bladder neck procedure: artificial urinary sphincter (7), bladder neck plasty (9), bladder neck closure (1), fascial sling (3). Six patients had further endoscopic treatment (including 2 after bladder neck plasty). ResultsAt surgery, Deflux® paste was easily identified with minimal surrounding tissue inflammatory reaction. Artificial urinary sphincter: all 7 dry; bladder neck plasty: 7 dry, 1 improved and 1 still incontinent; 1 bladder neck closure patient dry; fascial sling: 1 significantly improved and 2 dry. Repeated endoscopic treatment: 1 dry, 1 improved and 4 failed. Eleven of the 21 (52%) patients who are either dry or improved have voiding abilities. ConclusionEndoscopic injections with dextranomer do not adversely affect the outcome of further surgical procedures. Repeated injections after a previous endoscopic treatment failure have a low success rate.