The Role of Human U Three Protein 14a as a Predictor for Hepatocellular Carcinoma Recurrence After Microwave Ablation.

BACKGROUND: Human U three protein 14a (hUTP14a) is a nucleolar protein which promotes carcinogenesis by causing degradation of the tumor suppressor protein, p53. AIMS: This study aimed to investigate hUTP14a expression in hepatocellular carcinoma (HCC) and its value as a predictor for HCC recurrence after treatment with microwave ablation (MWA). MATERIALS AND METHODS: The hUTP14a expression was evaluated using immunohistochemistry on ultrasound-guided fine needle aspiration biopsy material from the tumor and the surrounding cirrhotic nontumor tissues. The relation between hUTP14a expression and clinic-pathologic variables was analyzed. RESULTS: Nuclear hUTP14a showed significant high expression in HCC tumor tissue compared with corresponding nontumor tissue (P<0.001). Tumoral hUTP14a expression was significantly higher in patients who experienced recurrence than those who were recurrence-free after MWA (P<0.001). CONCLUSION: We concluded that, hUTP14a has an oncogenic potential, as it is highly expressed in HCC tissues compared with surrounding nontumor cirrhotic tissues. Moreover, nuclear hUTP14a could be used as a promising prognostic biomarker for prediction of HCC recurrence after treatment with MWA.

Aggressive angiomyxoma of the female urethra.

Aggressive angiomyxoma is a rare locally invasive mesenchymal neoplasm of unknown pathogenesis arising predominantly in pelvic and perineal tissues of adult women. Surgical excision is the classical management but is associated with the risk of recurrence, especially with incomplete excision. There is a proposed role for adjuvant hormonal therapy. We report a very rare case of urethral aggressive angiomyxoma, managed by surgical excision, in a 40-year-old woman who presented with severe hematuria with clot retention.

Does faecal calprotectin differentiate between inflammatory bowel disease colitis and non-inflammatory bowel disease colitides?

INTRODUCTION: Chronic colitis is a major problem worldwide with high morbidity. Causes of chronic colitis are heterogeneous. A cut-off level of faecal calprotectin to predict inflammatory bowel disease (IBD) as a cause of chronic colitis is lacking. AIM: To study the level of faecal calprotectin in different causes of colitis and to measure the cut-off level to differentiate between IBD and non-IBD colitides. MATERIAL AND METHODS: This prospective study was conducted from June 2018 to May 2019. The study included all patients aged 2 months up to 18 years who were confirmed to have chronic colitis endoscopically and histopathologically attending the Gastroenterology Clinic at Alexandria University Children's Hospital. Faecal calprotectin level was measured. RESULTS: We included 110 patients. Allergic colitis was the commonest cause followed by IBD followed by infectious colitis (50.9%, 38.1% and 6.3% respectively). Faecal calprotectin above 744 µg/g could predict IBD as a cause of chronic colitis with 86.8% specificity and 66.7% sensitivity. Significant elevation of faecal calprotectin was detected in IBD patients. Faecal calprotectin was significantly correlated with C-reactive protein level and erythrocyte sedimentation rate. CONCLUSIONS: Faecal calprotectin could predict the cause of colitis and could aid the paediatrician for early referral of patients with chronic colitis.

Initial characterization of an autoclaved Toxoplasma vaccine in mice.

Toxoplasmosis is a zoonotic protozoal disease that has a major significance from the perspectives of public health and veterinary medicine. Therefore, an obvious long-term goal of many scientists would be the development of an effective vaccine. In this study, autoclaved vaccine was evaluated for its ability to protect mice against Toxoplasma gondii RH challenge as an acute infection model. Results showed that autoclaved Toxoplasma vaccine (ATV) when combined with BCG as an adjuvant was effective in triggering cell mediated immunity as shown by a significant increase in the percentage of splenic CD8+ T-lymphocytes. Following challenge, death of mice vaccinated with ATV was delayed for nine days. There was a significant decrease in parasite density in different organs, and a marked reduction of pathological changes in the liver suggesting that significant immune responses were mounted following vaccination. Future studies are warranted to test the vaccine against challenge with brain cysts as a chronic infection model and to evaluate it with other recent immunization strategies that can further enhance its immunogenicity.

Miltefosine, a promising novel agent for schistosomiasis mansoni.

This research aims towards developing an alternative antischistosomal drug using miltefosine, which is primarily used in the treatment of leishmaniasis. The treatment and control of schistosomiasis, a notable neglected tropical disease (NTD), rely on a single drug, praziquantel (PZQ). The dependency on PZQ exclusively is quite alarming, given the spread of the disease (over 200 million people infected and close to 800 million people at risk in three continents) and the threat of drug resistance. This study shows that the oral administration of miltefosine in a daily dose of 20mg/kg for five successive days to mice infected with either invasive, juvenile or adult stages of Schistosoma mansoni resulted in significant reduction of worm burden, hepatic granulomata size and amelioration of hepatic pathology. Scanning Electron Microscopy revealed that miltefosine induced severe tegumental damage in adult schistosomes. In conclusion, we believe this is the first study highlighting miltefosine as a promising novel agent for schistosomiasis mansoni.

Experimental trichinosis: parasitological, electrophysiological and biochemical studies.

Trichinosis is a parasitic infection affecting the gut and the muscles causing mild gastrointestinal symptoms followed by periorbital oedema, muscle pains, fever and eosinophilia. The infection evokes functional disturbances in physiological effector systems. Furthermore, several biochemical changes are associated with the infection. Therefore, this work was carried out to study the electrophysiological changes in intestine, striated and cardiac muscles by electromyography (EMG) and to assess the biochemical changes through measurement of serum cholinesterase and intestinal myeloperoxidase activity (MPO) in both light and heavy infected experimental animals by Trichinella spiralis (T. spiralis). Electrophysiological results showed increased contractility of the smooth muscle layers of the intestine only early in the infection, whereas both striated and cardiac muscles showed increase in the contractility with the progress of infection in both light and heavy infection. Significant myocardial dysfunction in the form of bradycardia, in addition to major histopathological changes in the heart occurred from the beginning of the infection and increased till the end of the study. Biochemical study showed gradual increase in serum cholinesterase, while, the intestinal MPO showed increase only in the early stage of the infection. It was noticed that all changes were more pronounced in the heavily infected group than the lightly infected one.

Comparative clinical prospective therapeutic study between cyclophosphamide, cyclosporine and azathioprine in the treatment of lupus nephritis.

Systemic Lupus Erythrematosus (SLE) is an inflammatory autoimmune disorder that may affect multiple organ systems. The clinical course is marked by spontaneous remission and relapses. Severity may vary from mild episodic disorder to a rapidly fulminant life threatening illness. Clinical manifestations of Lupus Nephritis (LN) are varied according to the renal pathologic lesions. Treatment of LN remains controversial. As a chronic disease with periods of remission and relapses, it is unclear whether relapses should be treated as the initial presentation of the disease. This prospective study was designed to compare between three different modalities of therapy for treating LN patients. The study includes all systemic lupus patients seen in Alexandria University Hospital since January 2004 for 6 months. Forty-three patients with SLE were presented to us by SLE, only 31 had LN and 22 were included in the study. The patients were classified randomly into 3 arms. All patients received steroid therapy plus from the beginning either Cyclophosphamide (CYP) [Group I, n=7], or Cyclosporine (CsA) [Group II, n=7], or Azathioprine (AZA) [Group III, n=8], Full history and examination were done. Laboratory investigations included routine and immunological studies of ANA, Anti-DNA, C3 and C4. Renal biopsy was done in all patients. After 6 months of follow up; Serum creatinine was stationary in CYP group from 2.2 +/- 1.1 to 2.1 +/- 1.7; while significantly decreased in CsA from 2.8+1.7 to 1.0 +/- 0.5 mg/dl. Moreover; while proteinuria decreased in CYP from 2.7 +/- 0.7 to 1.8 +/- 2.2; there was more pronounced decreased from 6.9 +/- 10.0 to 2.4 +/- 1.2 g/24 hr in CsA group despite very huge increase in glomerular filtration rate (GFR). 2 out 7 cases of CsA group; while 2 of 6 of CYP group did not show improvement. Moreover; 3 of 6 of CYP group and 1 of 6 of AZA group needed to be shifted to CsA group because of side effects and/or no response to CYP and showed good response. These patients were either class V or IV. However; only one case in this study with signs of acute CsA toxicity was reversed by monitoring the dose. In conclusion, CsA in this study proved to be superior over CYP in LN at least in the short term follow up; provided to be given with appropriate doses even if it is used in class IV, which was thought to be very responsive to CYP.

Tissue transglutaminase and the progression of human renal scarring.

Experimental renal scarring indicates that tissue transglutaminase (tTg) may be associated with the accumulation of extracellular matrix (ECM), both indirectly via TGF-beta1 activation and directly by the formation of epsilon(gamma-glutamyl) lysine dipeptide bonds within the ECM. The latter potentially accelerates deposition and confers the ECM with resistance to proteolytic digestion. Studied were 136 human renal biopsy samples from a range of chronic renal diseases (CRD) to determine changes in tTg and epsilon(gamma-glutamyl) lysine crosslinking. Immunofluorescence for insoluble tTg showed a 14-fold increase in the kidneys of CRD patients (5.3 +/- 0.5 versus 76 +/- 54 mV/cm(2)), which was shown to be active by a similar 11-fold increase in the epsilon(gamma-glutamyl) lysine crosslink (1.8 +/- 0.2 versus 19.3 +/- 14.2 mV/cm(2)). Correlations were obtained with renal function for tTg and crosslink. In situ hybridization for tTg mRNA showed that tubular epithelial cells were the major source of tTg; however, both mesangial and interstitial cells also contributed to elevated levels in CRD. This mRNA pattern was consistent with immunohistochemistry for soluble tTg. Changes in renal tTg and its product, the epsilon(gamma-glutamyl) lysine crosslink, occur in progressive renal scarring in humans independently of the original etiology and in a similar manner to experimental models. tTg may therefore play a role in the pathogenesis of renal scarring and fibrosis in patients with CRD and can therefore be considered a potential therapeutic target.

Vaccination trial against experimental trichrinellosis using autoclaved Trichinella spiralis larvae vaccine (ATSLV).

The autoclaved Trichinella spiralis larvae vaccine (ATSLV) was tested and showed a surprising and somewhat unpredictable effect on the immune system of mice experimentally infected with T. spiralis. The vaccine was given with Bacille Calmette Guerin (BCG) as an adjuvant at different durations and by different routes of administration. The best result was achieved by given the vaccine twice intradermally with two weeks interval, as evidenced by a significant reduction in adult and larval count, as well as reproductive capacity index. Histopathologically, there was significant reduction in number of the encysted larvae which showed degeneration and hyalinization of the cyst wall accompanied by early pericystic fibrosis.