Endotoxin Induces Severe Inflammatory Reactions with Necrosis at Sites Primed with Delayed-Type Hypersensitivity Reactions in Guinea Pigs

Guinea pigs immunized with Freund's complete adjuvant received challenge injection of the purified protein derivative of Mycobacterium tuberculosis in the flanks and the corneas to prepare delayed-type hypersensitivity (DTH) reactions. The animals were injected subcutaneously with lipopolysaccharide (LPS) or a synthetic lipid A (LA-15-PP). At the skin site primed with DTH reaction, increased swelling and hemorrhagic reaction followed by a definite necrotic reaction occurred. Severe corneal reactions were also observed in the animals. These findings indicate that bacterial endotoxin modulates DTH reactions and induces severe inflammatory reactions.     

Studies of Defence Mechanisms and Inflammatory Reactions in the Bovine Teat using a New Experimental Method

Bovine intramammary infections are usually caused by microorganisms entering through the teat canal. The teat canal normally acts as a mechanical and physiological barrier preventing bacteria from entering the teat cistern. This barrier can be broken, e.g. if the teat end is damaged, making it possible for bacteria to invade the teat cistern. If an infection is established inflammatory reac-tions will occur in the udder.     

Notch Signaling Regulates Microglial Activation and Inflammatory Reactions in a Rat Model of Temporal Lobe Epilepsy

The inflammatory response mediated by microglia in the central nervous system is closely related to epilepsy. Notch signaling plays an important role in the microglial activation during hypoxia. This study aimed to investigate whether Notch signaling is involved in microglial activation and subsequent inflammation-related neuronal injury during the process of epileptogenesis in a rat model of temporal lobe epilepsy. By using western blotting, real-time quantitative PCR, immunohistochemistry and immunofluorescence labeling, we found that the expression of Notch signaling increased after status epilepticus and that a γ-secretase inhibitor could significantly inhibit the upregulation of Notch signaling, the activation of microglia, and the release of proinflammatory cytokines. Likewise, the neuronal apoptosis and loss in the hippocampus after SE were attenuated by the γ-secretase inhibitor. These results suggest that Notch signaling plays a key role in neuroinflammation and inflammation-related neuronal damage in epilepsy, and γ-secretase inhibitors may become a novel prospective therapeutic agent for epilepsy.     

Association between Thiopurine S-methyltransferase Polymorphisms and Thiopurine-Induced Adverse Drug Reactions in Patients with Inflammatory Bowel Disease: A Meta-Analysis

Purpose

Thiopurine drugs are well established treatments in the management of inflammatory bowel disease (IBD), but their use is limited by significant adverse drug reactions (ADRs). Thiopurine S-methyltransferase (TPMT) is an important enzyme involved in thiopurine metabolism. Several clinical guidelines recommend determining TPMT genotype or phenotype before initiating thiopurine therapy. Although several studies have investigated the association between TPMT polymorphisms and thiopurine-induced ADRs, the results are inconsistent. The purpose of this study is to evaluate whether there is an association between TPMT polymorphisms and thiopurine-induced ADRs using meta-analysis.

Methods

We explored PubMed, Web of Science and Embase for articles on TPMT polymorphisms and thiopurine-induced ADRs. Studies that compared TPMT polymorphisms with-ADRs and without-ADRs in IBD patients were included. Relevant outcome data from all the included articles were extracted and the pooled odds ratio (OR) with corresponding 95% confidence intervals were calculated using Revman 5.3 software.

Results

Fourteen published studies, with a total of 2,206 IBD patients, which investigated associations between TPMT polymorphisms and thiopurine-induced ADRs were included this meta-analysis. Our meta-analysis demonstrated that TPMT polymorphisms were significantly associated with thiopurine-induced overall ADRs and bone marrow toxicity; pooled ORs were 3.36 (95%CI: 1.82–6.19) and 6.67 (95%CI: 3.88–11.47), respectively. TPMT polymorphisms were not associated with the development of other ADRs including hepatotoxicity, pancreatitis, gastric intolerance, flu-like symptoms and skin reactions; the corresponding pooled ORs were 1.27 (95%CI: 0.60–2.71), 0.97 (95%CI: 0.38–2.48), 1.82 (95%CI: 0.93–3.53), 1.28 (95%CI: 0.47–3.46) and 2.32 (95%CI: 0.86–6.25), respectively.

Conclusions

Our meta-analysis demonstrated an association of TPMT polymorphisms with overall thiopurine-induced ADRs and bone marrow toxicity, but not with hepatotoxicity, pancreatitis, flu-like symptoms, gastric intolerance and skin reactions. These findings suggest that pretesting the TPMT genotype could be helpful in clinical practice before initiating thiopurine therapy. However, white blood cell count analysis should be the mainstay for follow-up.     

Inflammatory myofibroblastic tumour of the gallbladder

BACKGROUND: Inflammatory myofibroblastic tumour (IMT) is a benign, nonmetastasizing proliferation of myofibroblasts with a potential for local infiltration, recurrence and persistent local growth. CASE REPORT: We report a case of a 51 year-old female, who had excision of a gallbladder tumour. Histopathology showed it to be IMT of the gallbladder. CONCLUSION: The approach to these tumours should be primarily surgical resection to obtain a definitive diagnosis and relieve symptoms. IMT has a potential for local infiltration, recurrence and persistent local growth.     

Inflammatory malignant fibrous histiocytoma of the retroperitoneum

The authors present a case of inflammatory malignant fibrous histiocytoma located in the left retroperitoneum. The tumor was resected enblock with kidney and suprarenal gland. During the resection the system of retractors called the pillars of Kocman was used which allowed wide exposure of the abdominal cavity. The tumor measured 23 x 17 x 10 cm with the left kidney and suprarenal incorporated. The tumor was centrally pseudocystic made of xanthomatous cells, foamy cells and rare giant cells with storiform formations and infiltrated with neutrophils. Imunohistochemically, the tumor cells were vimentin and CD 68 positive and CD 20, CD3, EMA, S-100, HMB 45, CD 34 and CD 1a negative. Neutrophils were CD 15 positive.