Synchronous MALT lymphoma of the colon and stomach and regression after eradication of Strongyloides stercoralis and Helicobacter pylori.

Mucosa-associated lymphoid tissue (MALT) is vital for host immunological surveillance against pathogens. MALT lymphoma, also known as extranodal marginal zone B cell lymphoma, is a non-Hodgkin's lymphoma subtype that predominantly arises in the gastrointestinal tract. Chronic Helicobacter pylori (H. pylori) infection is a common cause of gastric MALT lymphoma, although other infections are reported in association with extragastric MALT lymphomas. To our knowledge, here we report the first case of synchronous MALT lymphomas of the colon and stomach in the presence of Strongyloides stercoralis and H. pylori infections that resolved after eradication of both organisms.

A rare case of thrombotic microangiopathy triggered by acute pancreatitis.

Thrombotic microangiopathy (TMA) occurring after acute pancreatitis is rarely described. Without prompt intervention, TMA can be, and often is, lethal, so prompt recognition is important. Here, we present a case of a 61-year-old woman with a history of alcohol misuse who presented with epigastric pain, nausea and vomiting after binge drinking. Elevated serum lipase and imaging were suggestive of acute-on-chronic pancreatitis. Although the patient's symptoms of acute pancreatitis subsided, her anaemia, thrombocytopenia and acute kidney injury worsened. A peripheral blood smear revealed schistocytes, prompting suspicion for TMA. Therapeutic plasma exchange (TPE) was promptly initiated and she completed 10 TPE sessions that improved her anaemia and serum creatinine and resolved the thrombocytopenia. Since TPE was effective and the ADAMTS13 assay revealed 55% activity in the absence of anti-ADAMTS13 IgG prior to initiation of therapy, a confident diagnosis of TMA caused by acute pancreatitis was made. There was no evidence of relapse 2 years later.

Seizure susceptibility alteration following reversible cholestasis in mice: Modulation by opioids and nitric oxide.

There is an increasing body of evidence that the central nervous system is affected by cholestatic liver disorders. Cholestasis has been shown to result in a decreased seizure propensity which is believed to be mediated by an increased opioidergic tone and nitric oxide (NO) signaling pathway. In this study, we used a reversible chemically-induced cholestasis model in mice to investigate the changes in seizure susceptibility. The cholestasis was induced by intragastric administration of alpha-naphthylisothiocyanate (ANIT) (100 mg/kg) or vehicle (corn oil). The threshold to generalized clonic seizures induced by timed intravenous infusion of pentylenetetrazole (PTZ) was used as an index of seizure propensity. The role of opioid receptors and NO pathway in the changes of seizure threshold, and the responsiveness to the anticonvulsant effect of opioid agonist, morphine, during and after the resolution of cholestasis was studied in this reversible paradigm of cholestatic disease. A significant increase in cholestasis-related biochemical markers as well as in clonic seizure threshold was observed; it was maximal at day 3 after cholestasis induction and slowly decreased to normal thereafter. Seizure threshold rise was inhibited by chronic administration of the opioid antagonist naltrexone or acute administration of N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO production. Co-administration of subeffective doses of L-NAME and naltrexone showed an additive effect. Injection of an anticonvulsant dose of morphine on day 7 after cholestasis induction did not increase seizure threshold, suggestive of a downregulation of receptors even after cholestasis resolution. These data shows that ANIT-induced cholestasis leads to a reversible increased resistance to PTZ-induced seizures through an opioid/NO-mediated pathway, and is probably accompanied by downregulation of opioid receptors.

Opioid system blockade decreases collagenase activity and improves liver injury in a rat model of cholestasis.

BACKGROUND: Following bile duct ligation (BDL) endogenous opioids accumulate in plasma and play a role in the pathophysiology and manifestation of cholestasis. Evidence of centrally mediated induction of liver injury by exogenous opioid agonist administration, prompts the question of whether opioid receptor blockade by naltrexone can affect cholestasis-induced liver injury. METHODS: Cholestasis was induced by BDL and cholestatic and sham-operated rats received either naltrexone or saline for 7 consecutive days. On the 7th day, liver samples were collected for determining matrix metalloproteinase-2 (MMP-2) activity, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) content and blood samples were obtained for measuring plasma nitrite/nitrate and liver enzyme activities. RESULTS: Naltrexone-treated BDL animals had a significant reduction in plasma enzyme activity and nitrite/nitrate level. Liver SAM : SAH ratio and SAM level improved by naltrexone treatment in cholestatic animals compared to saline-treated BDL ones. Naltrexone treatment in BDL rats led to a decrease in the level of liver MMP-2 activity, which had already increased during cholestasis. CONCLUSION: Opioid receptor blockade improved the degree of liver injury in cholestasis, as assessed by plasma enzyme and liver MMP-2 activities. The beneficial effect of naltrexone may be due to its ability to increase liver SAM level and restore the SAM : SAH ratio.

The Microprocessor complex mediates the genesis of microRNAs.

MicroRNAs (miRNAs) are a growing family of small non-protein-coding regulatory genes that regulate the expression of homologous target-gene transcripts. They have been implicated in the control of cell death and proliferation in flies, haematopoietic lineage differentiation in mammals, neuronal patterning in nematodes and leaf and flower development in plants. miRNAs are processed by the RNA-mediated interference machinery. Drosha is an RNase III enzyme that was recently implicated in miRNA processing. Here we show that human Drosha is a component of two multi-protein complexes. The larger complex contains multiple classes of RNA-associated proteins including RNA helicases, proteins that bind double-stranded RNA, novel heterogeneous nuclear ribonucleoproteins and the Ewing's sarcoma family of proteins. The smaller complex is composed of Drosha and the double-stranded-RNA-binding protein, DGCR8, the product of a gene deleted in DiGeorge syndrome. In vivo knock-down and in vitro reconstitution studies revealed that both components of this smaller complex, termed Microprocessor, are necessary and sufficient in mediating the genesis of miRNAs from the primary miRNA transcript.