An unusual case of haemobilia

Arterio-biliary fistula is an uncommon cause of haemobilia. We describe a case of right hepatic artery pseudo-aneurysm causing arterio-biliary fistula and presenting as severe melaena and cholangitis. Gastroduodenoscopy failed to establish the exact source of bleeding and hepatic artery angiography and selective embolization of the pseudo-aneurysm successfully controlled the bleeding. Pseudo-aneurysm of the hepatic artery is mostly iatrogenic due to biliary intervention, as demonstrated in this case. Difficulty in diagnosis and management is discussed together with a review of the literature.     

Anti-eosinophil peroxidase antibodies detected in patients with primary biliary cirrhosis.

OBJECTIVE:: The possible involvement of eosinophils in primary biliary cirrhosis (PBC) has been suggested for many years. Activated eosinophils release basic granule proteins and are thought to be involved in the tissue damage of PBC. Eosinophil peroxidase (EPO) is one of the eosinophilic granule proteins and is toxic to epithelial cells. In this study, we examined whether autoantibodies to EPO are present in sera of patients with PBC and we evaluated the relationship between the presence of anti-EPO antibodies and the clinical features of PBC. METHODS:: Sera obtained from 61 patients with PBC, 31 patients with autoimmune hepatitis (AIH), 87 patients with chronic viral hepatitis (CVH), 27 patients with bronchial asthma, and 20 healthy controls were examined. Enzyme-linked immunosorbent assay (ELISA) and Western blot methods were used for detection of anti-EPO antibodies. RESULTS:: The mean OD value of anti-EPO antibodies, as determined by ELISA, was significantly (p<0.01) higher in patients with PBC (0.197+/-0.121) than in patients with AIH (0.124+/-0.077), CVH (0.090+/-0.038) or bronchial asthma (0.073+/-0.025) and in healthy controls (0.072+/-0.029). The results of ELISA showed that 32 (52.5%) of the 61 patients with PBC, 9 (29.0%) of the 31 patients with AIH, 7 (8.0%) of the 87 patients with CVH, and 1 (3.7%) of the 27 patients with bronchial asthma were positive for anti-EPO antibodies. In addition, PBC patients who were positive for anti-EPO antibodies had a significantly smaller number of peripheral eosinophils than did patients who were negative for anti-EPO antibodies (99.2+/-54.4cells/mul versus 176.9+/-117.5cells/mul, p<0.01). However, there was no correlation between the titers of anti-EPO antibodies and those of AMA or AMA-M2, ANA or serum levels of IgM. CONCLUSIONS:: This is the first report of the detection of anti-EPO antibodies in patients with PBC. Further study is needed to clarify the role of anti-EPO antibodies in the pathogenesis of PBC.     

MALDI mass sequencing and biochemical characterization of Setaria cervi protein tyrosine phosphatase

A 30-kDa acid phosphatase with protein tyrosine phosphatase activity was identified in Setaria cervi (ScPTP). The enzyme was purified to homogeneity using three-step column chromatography. Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis of purified ScPTP yielded a total of eight peptides matching most closely to phosphoprotein phosphatase of Ricinus communis (RcPP). A hydrophilicity plot of RcPP revealed the presence of these peptides in the hydrophilic region, suggesting their antigenic nature. The substrate specificity of ScPTP with ortho-phospho-l-tyrosine and inhibition with sodium orthovanadate and ammonium molybdate affirmed it as a protein tyrosine phosphatase. ScPTP was also found to be tartrate resistant. The Km and Vmax were 6.60 mM and 83.3 μM/ml/min, respectively, with pNPP and 8.0 mM and 111 μM/ml/min, respectively, with ortho-phospho-l-tyrosine as the substrate. The Ki value with sodium orthovanadate was calculated to be 16.10 mM. Active site modification with DEPC, EDAC and pHMB suggested the presence of histidine, cysteine and aspartate at its active site. Thus, on the basis of MALDI-TOF and biochemical studies, it was confirmed that purified acid phosphatase is a PTP.     

Infection imaging using [18F]FDG-labelled white blood cell positron emission tomography–computed tomography

Localizing the sites of infection in the body is possible in nuclear medicine using a variety of radiopharmaceuticals that target different components of the infective and inflammatory cascade. Gamma(γ)-emitting agents such as [67Ga]gallium citrate were among the first tracers used, followed by development of positron-emitting tracers like 2-deoxy-2-[18F]fluoro-D-glucose (¹⁸F-FDG). Though these tracers are quite sensitive, they have limited specificity for infection due to their concentration in sites of non-infective inflammation. White blood cells (WBC) labelled with γ or positron emitters have higher accuracy for differentiating the infective processes from the non-infective conditions that may show positivity with tracers such as ¹⁸F-FDG. We present a pictorial review of potential clinical applications of PET/CT using ¹⁸F-FDG labelled WBC.     

Discovery of Novel SPAK Inhibitors That Block WNK Kinase Signaling to Cation Chloride Transporters

Upon activation by with-no-lysine kinases, STE20/SPS1-related proline–alanine-rich protein kinase (SPAK) phosphorylates and activates SLC12A transporters such as the Na⁺-Cl⁻ cotransporter (NCC) and Na⁺-K⁺-2Cl⁻ cotransporter type 1 (NKCC1) and type 2 (NKCC2); these transporters have important roles in regulating BP through NaCl reabsorption and vasoconstriction. SPAK knockout mice are viable and display hypotension with decreased activity (phosphorylation) of NCC and NKCC1 in the kidneys and aorta, respectively. Therefore, agents that inhibit SPAK activity could be a new class of antihypertensive drugs with dual actions (i.e., NaCl diuresis and vasodilation). In this study, we developed a new ELISA-based screening system to find novel SPAK inhibitors and screened >20,000 small-molecule compounds. Furthermore, we used a drug repositioning strategy to identify existing drugs that inhibit SPAK activity. As a result, we discovered one small-molecule compound (Stock 1S-14279) and an antiparasitic agent (Closantel) that inhibited SPAK-regulated phosphorylation and activation of NCC and NKCC1 in vitro and in mice. Notably, these compounds had structural similarity and inhibited SPAK in an ATP-insensitive manner. We propose that the two compounds found in this study may have great potential as novel antihypertensive drugs.     

Association of methylenetetrahydrofolate reductase (<Emphasis Type="Italic">MTHFR</Emphasis>) gene C677T polymorphism with autism: evidence of genetic susceptibility

Autism (MIM 209850) is a heterogeneous neurodevelopmental disease that manifests within the first 3 years of life. Numerous articles reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme of this pathway and MTHFR C677T polymorphism reported as risk factor for autism in several case control studies. However, controversial reports were also published. Hence the present meta-analysis was designed to investigate the relationship of the MTHFR C677T polymorphism with the risk of autism. Electronic databases were searched for case control studies with following search terms - ‘MTHFR’, ‘C677T’, in combination with ‘Autism’. Pooled OR with its corresponding 95 % CI was calculated and used as association measure to investigate the association between MTHFR C677T polymorphism and risk of autism. Total of thirteen studies were found suitable for the inclusion in the present meta-analysis, which comprises 1978 cases and 7257 controls. Meta-analysis using all four genetic models showed significant association between C677T polymorphism and autism (OR_Tvs.C = 1.48; 95 % CI: 1.18–1.86; P = 0.0007; OR_{TT + CT vs. CC} = 1.70, 95 % CI = 0.96–2.9, p = 0.05; OR_{TT vs. CC} = 1.84, 95 % CI = 1.12–3.02, p = 0.02; OR_{CT vs.CC} = 1.60, 95 % CI = 1.2–2.1, p = 0.003; OR_{TT vs.CT+CC} = 1.5, 95 % CI = 1.02–2.2, p = 0.03). In total 13 studies, 9 studies were from Caucasian population and 4 studies were from Asian population. The association between C677T polymorphism and autism was significant in Caucasian (OR_Tvs.C = 1.43; 95 % CI = 1.1–1.87; p = 0.009) and Asian population (OR_Tvs.C = 1.68; 95 % CI = 1.02–2.77; p = 0.04) using allele contrast model. In conclusion, present meta-analysis strongly suggested a significant association of the MTHFR C677T polymorphism with autism.