Purification of a chymotrypsin-like enzyme present on adult Schistosoma mansoni worms from infected mice and its characterization as a host carboxylesterase

A serine protease-like enzyme found in detergent extracts of Schistosoma mansoni adult worms perfused from infected mice has been purified from mouse blood and further characterized. The enzyme is approximately 85 kDa and hydrolyses N-acetyl-DL-phenylalanine β-naphthyl–ester, a chromogenic substrate for chymotrypsin-like enzymes. The enzyme from S. mansoni worms appears to be antigenically and enzymatically similar to a molecule that is present in normal mouse blood and so is seemingly host-derived. The enzyme was partially purified by depleting normal mouse serum of albumin using sodium chloride and cold ethanol, followed by repeated rounds of purification by one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis. The purified material was subjected to tandem mass spectrometry and its derived peptides found to belong to mouse carboxylesterase 1C. Its ability to hydrolyse α- or β-naphthyl acetates, which are general esterase substrates, has been confirmed. A similar carboxylesterase was purified and characterized from rat blood. Additional evidence to support identification of the enzyme as a carboxylesterase has been provided. Possible roles of the enzyme in the mouse host–parasite relationship could be to ease the passage of worms through the host's blood vessels and/or in immune evasion

Circulating tumor cells: approaches to isolation and characterization

Circulating tumor cells (CTCs) shed from primary and metastatic cancers are admixed with blood components and are thus rare, making their isolation and characterization a major technological challenge. CTCs hold the key to understanding the biology of metastasis and provide a biomarker to noninvasively measure the evolution of tumor genotypes during treatment and disease progression. Improvements in technologies to yield purer CTC populations amenable to better cellular and molecular characterization will enable a broad range of clinical applications, including early detection of disease and the discovery of biomarkers to predict treatment responses and disease progression

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Hepatic haemangioma, a Diagnostic Dilemma in a Developing Sub-Saharan Country: A Report of Two Cases

Hepatic haemangioma is an uncommon benign tumour that often presents a diagnostic challenge as it could be mistaken for other focal hepatic lesion. Two cases managed in our facility are presented: Case 1-A 57 years old male with right hypochondrial pain and ultrasonographic finding of large focal hyperechoeic (10 x 9cm) mass. Computerised tomographic scan (CT scan) and Magnetic resonance imaging (MRI) were inconclusive but liver biopsy confirmed a cavernous haemangioma. Case 2-A 41 years old male who presented with similar right hypochondrial pain; ultrasound revealed a homogenous focal lesion (4.2 x 4.5cm). Dynamic CT and MRI indicated hepatic haemangioma. Both patients had normal biochemical parameters including tumour markers. The absence of symptoms in a patient withliver mass and normal laboratory findings should raise an index of suspicion of haemangioma. Dynamic imaging is vital where possible and if inconclusive, liver biopsy with histology.Key words: Hepatic, haemangioma, imaging

Case Report: Recurrent Pancreatitis-Challenges in Management

Background Recurrent Acute Pancreatitis (RAP), is an uncommon clinical condition, usually seen in the setting where the underlying risk factors remain unresolved. Diseases of the pancreas peak in the 3rd and 4th decades and are commonly caused by gall-stones (Cholelithiasis) which are detectable by abdominal ultrasonography and computerised tomography. Microlithiasis, a leading cause of RAP, often presents with diagnostic challenges in resource limited settings. Case Report We present a case of a 19 year old female with recurrent bouts of epigastric pain within a two year period. Laboratory investigation revealed fluctuating levels (high and normal) of serum amylase and lipase while repeated abdominal Ultrasonography were normal. Computerised tomography was initially normal but later scans revealed features of pancreatitis. Microlithiasis was identified following Endoscopic Ultrasonography which had to be done outside the shores of the country as this facility is not available in our practice. She had laparoscopic cholecystectomy and after an episode of abdominal pain has remained pain free. Conclusion This case has highlighted the constraints faced by practising physicians as well as the morbidity suffered by patients with this uncommon condition due to non-availability of appropriate diagnostic tools in our setting necessitating our patient seeking assistance abroad. It underscores the need to ensure their availability as well as that of adequate skilled personnel by stakeholders in the health sector. Key Words: Acute Pancreatitis, Microlithiasis, Endoscopic Ultrasoun

Safety, Efficacy and Tolerability of Meprasilm in the Treatment of Dyspepsia among Nigerians.

A clinical trial was carried out to establish the tolerability, safety and efficacy of Meprasil brand of omeprazole among Nigerians with acid peptic disease using 20mg daily or 20mg bid of Meprasil. Forty patients were enrolled for the study and were asked to rate their abdominal pains pre-commencement of therapy using a scale of mild, moderate or severe. Serum alanine transaminase (ALT), urinalysis, electrolytes, creatinine and urea were carried out before and after treatment. Patients were then evaluated on days 0, 1, 3, 7, 14, and 28, thereafter monthly for 4 months for relief of symptoms and adverse drugs effect. Only 32 patients completed the study, 17 (Group I) and 15 (Group II).fe, efficacious and well tolerated in amelioration of pain of acid peptic disorder among Nigerian patients

Detection of p53 codon 249 mutation in Nigerian patients with hepatocellular carcinoma using a novel evaluation of cell-free DNA

Objectives: This case-control study was done to determine the association and prevalence of p53 codon 249 mutation using cell-free DNA in the plasma of patients with hepatocellular carcinoma (HCC) in South-Western Nigeria. Method: Eighty-five adults with HCC and seventy-seven age and gender matched controls without evidence of liver disease or malignancy involving any part of the body, were recruited. Plasma DNA was analyzed for p53 codon 249 by restriction fragment length polymorphism. Patient evaluation was done by means questionnaire interview, clinical examination, laboratory and radiological tests. The prevalence of the p53 codon 249 mutation was expressed as a percentage amplifiable DNA samples analyzed from HCC patients while that of controls was expressed in the same way. Fisher’s exact test or the student t-test where appropriate were used to assess statistical significance of prevalence between both groups as well as comparison of some characteristics in the HCC cases between those who had codon 249 mutation and those who did not. Associations between the various parameters assessed were determined by odds ratio and significant difference was specified at p < 0.05. Results: p53 codon 249 mutation was present in 6 (7.6%) of the 79 samples from the HCC patients with amplifiable plasma DNA while none (i.e. 0%) of the 73 samples with amplifiable plasma DNA from the controls had this mutation. This prevalence is significantly higher among HCC patients than controls (0.029). The mutation was also found to be significantly associated with HCC (odds ratio = 2.00; 95% C I: 1.70 – 2.35). Conclusion: The prevalence of the p53 codon 249 mutation from plasma DNA of hepatocellular carcinoma patients is significantly higher than among controls in South-Western Nigeria and the presence of this mutation is significantly associated with HCC in this region

Western blot immunoreactivity of acid-eluted antibodies and control rabbit antisera monospecific for <i>S</i>. <i>mansoni</i> egg antigens; IPSE/alpha-1 and kappa-5 against <i>S</i>. <i>manson</i>i egg antigens.

<p>M = molecular size markers. Primary antibodies: 1 = anti-SmSEA; 2 = anti-SmSEA antibodies eluted from the 43 kDa latex molecule; 3 = rabbit antiserum specific for <i>S</i>. <i>mansoni</i> egg antigen IPSE/alpha-1; 4 = rabbit antiserum specific for <i>S</i>. <i>mansoni</i> egg antigen kappa-5.</p

PAGE and electroblots of allergen extracts probed with rabbit anti-SmSEA antiserum.

<p><b>(a</b>) Coomassie blue-stained SDS-PAGE gel of allergen extracts and <i>S</i>. <i>mansoni</i> SEA (SmSEA). <b>(b)</b> Western immunoblot of allergen extracts and SmSEA electro-transferred to nitrocellulose film from a replicate of the gel in (a) and probed with a rabbit anti-SmSEA antiserum. <b>(c)</b> Western immunoblot replicate of (b) except for treatment of the nitrocellulose film with 10 mM sodium meta-periodate after electro-transfer of allergen/SmSEA molecules and before incubation in primary rabbit anti-SmSEA antiserum. M = molecular size markers; Lanes and (amount of BSA-equivalent protein added to each lane):1 = latex (0.20 mg); 2 = SmSEA (0.010 mg); 3 = banana (0.16 mg); 4 = tomato (0.27 mg); 5 = peanut (0.10 mg); 6 = melon (0.24 mg); 7 = avocado (0.22 mg); 8 = Kiwi fruit (0.19 mg); 9 = chestnut (0.22 mg).</p