Dina ElTantawy

First insight into the effect of single oral dose therapy with artemisinin-naphthoquine phosphate combination in a mouse model of Schistosoma mansoni infection.

Praziquantel is the current drug of choice against schistosomiasis. The dependency on praziquantel exclusively is problematic, given the spread of the disease and the threat of drug resistance. This study investigates an alternative antischistosomal drug using the compound naphthoquine phosphate tablet, which is a novel single oral dose antimalarial drug, containing a combination of naphthoquine phosphate and artemisinin. In the present study, the therapeutic efficacies of different artemisinin-naphthoquine phosphate combination-dosing protocols were evaluated in experimentally infected mice harbouring juvenile or adult stages of Schistosoma mansoni (Egyptian strain). The study shows that the oral administration of artemisinin-naphthoquine phosphate combination in a single dose of 400 mg/kg on day 7 p.i. resulted in a significant worm burden reduction of 95.07%. When used at a dose of 600 mg/kg on day 21 p.i., all female worms were killed before depositing eggs, resulting in complete absence of eggs in hepatic and intestinal tissues. The same dose given on day 42 p.i. reduced total and female worm burdens by 93.36% and 94.17%, respectively. In addition, artemisinin-naphthoquine phosphate combination induced significant reductions of 80.18% and 76.73% in the hepatic and intestinal tissue egg loads, respectively. Artemisinin-naphthoquine phosphate combination also induced significant alterations in the oogram pattern with elevated levels of dead eggs. Antipathological activities were evident in the amelioration of hepatic granulomata. Our findings hold promise for the development of a novel antischistosomal drug using an artemisinin-naphthoquine phosphate combination. Further in vitro and in vivo studies should be launched to elucidate the possible mechanism/s of action and to study the effect of artemisinin-naphthoquine phosphate combination on other human schistosomes.

In vivo effect of single oral dose of artemether against early juvenile stages of Schistosoma mansoni Egyptian strain.

The current treatment and control of schistosomiasis, rely on a single drug, praziquantel, although, it has minor activity against juvenile stages of the parasite. Studies have shown that artemether (ART) exhibits effects against juveniles of Schistosoma mansoni Liberian and Puerto Rican strains, Schistosoma japonicum and Schistosoma haematobium. Aiming to assess the in vivo activity of single oral dose of ART against early juvenile stages of S. mansoni Egyptian strain, this study was established. Mice were treated with ART (400 mg/kg) at two time points evenly spaced over the period of larval development (7 and 21 days post-infection; pi), and a third treatment point (day 49 pi) was included to elucidate when susceptibility decreases. Administration of ART on day 7 pi reduced the total worm burden by 85.94%. The greatest reductions were seen when treatment was given on day 21 pi, with total and female worm burden reductions of 91.52% and 90.57%, respectively, and cessation of oviposition. Similar dose given on day 49 pi reduced total worm burden by 55.17% and female worm burden by 66.51%. Moreover, it induced significant reduction in the tissue egg load and significant alterations in the oogram pattern with decreased immature eggs and increased dead eggs. Antipathological activities were evident in significant reductions in granulomata count and diameter. In conclusion, ART exhibits major in vivo schistosomicidal effects against the early larval migratory stages of S. mansoni Egyptian strain, mainly the 21-day old schistosomula, hence preventing disease progression and morbidity.

Diagnostic role of glypican 3 and CD34 for differentiating hepatocellular carcinoma from nonmalignant hepatocellular lesions

Well-differentiated hepatocellular carcinoma (HCC) may be difficult to distinguish from a benign lesion. Glypican 3 (GPC-3) is an oncofetal protein, which has been demonstrated to be up-regulated in HCC. The aim of this study is to evaluate the diagnostic role of combined GPC-3 and CD34 immunoassaying in the distinction between HCC and benign hepatic mimickers. This study was performed on 100 cases of formalin-fixed, paraffin-embedded cases of hepatic focal lesions obtained from the files of pathology laboratory of our university from 2009 to 2012. The following groups were studied: group A (n = 60) (hepatocellular malignant lesions) and group B (n = 40) (Hepatocellular nonmalignant lesions). All cases were stained with GPC-3 and CD34. Sensitivity, specificity, and positive and negative predictive values were calculated for both antibodies. Glypican 3 and complete CD34 staining pattern expression in group A was significantly higher than in group B. The results of costaining showed that, in HCCs, almost all the GPC-3-positive cases had a complete CD34 staining pattern, whereas in the 40 hepatocellular nonmalignant lesions, none stained up with the 2 markers. Therefore, although the sensitivity declined (82%), the specificity and positive predictive value (PPV) of costaining reached 100% and were greater than that observed for single staining with GPC-3 (specificity, 92.5%; PPV, 94.3%) or CD34 (specificity, 97.5%; PPV, 98.3%). Our data demonstrate that GPC-3 and CD34 costaining has better diagnostic value for differentiating HCC from nonmalignant hepatocellular lesions than does single staining.

Frequency of central nervous system tumors in delta region, Egypt

UNLABELLED INTRODUCTION AND AIM OF WORK: Central nervous system (CNS) tumors represent a major public health problem, and their epidemiological data in Egypt have been rather incomplete except for some regional reports. There are no available frequency-based data on CNS tumors in our locality. The objective of this study was to estimate the frequency of CNS tumors in east delta region, Egypt. MATERIALS AND METHODS The data were collected during the 8-year period from January 1999 to December 2007 from Pathology Department, Mansoura University, and other referred pathology labs. Examination of HandE stained sections from retrieved paraffin blocks were done in all cases for histopathologic categorization of C.N.S. tumors. Immunohistochemical studies were applied to confirm final histopathologic diagnosis in problematic cases. RESULTS Intracranial tumors represented 86.7% of cases in comparison to only 13.3% for spinal tumors. Gliomas were the CNS tumors of the highest frequency (35.2%), followed by meningioma (25.6%), pituitary adenoma (11.6%) and nerve sheath tumors (6.6%). 10.25% of tumors were of children <15 years. CONCLUSION This study provides the largest series of the relative frequency of CNS tumors in Delta region in Egypt till now and may help to give insight into the epidemiology of CNS tumors in our locality.

Regenerative effects of umbilical cord matrix cells (UCMCs) in a rodent model of rotenone neurotoxicity.

Rotenone is one of the pesticides thought to have neurotoxic effect that could potentially play a role in the development of Parkinsons disease (PD). The neurotoxic effects of rotenone have been used to induce PD model in animals that can help in testing suggested therapies. Cell replacement therapies are suggested as new promising approach for treating PD. This study was done to evaluate the regenerative effect of intrathecal administered umbilical cord matrix cells in a rotenone model of PD in mice. Thirty, male BALB/c mice were used and divided into 3 equal groups. The control group (G.1) received only carboxymethyl cellulose orally once daily at a volume of 10ml/kg. The second group was given a daily rotenone oral dose of 30mg/kg for 28days. The third group received rotenone (30mg/(kgday) orally for 28days) and in the 15th day 1×10(5) of UCMCs were given intrathecally and then they completed the rotenone course. At the 23rd day all the animals were evaluated regarding locomotor incoordination through behavioral tests for monitoring PD development. At the end of the 28days all animals were sacrificed by overdose of phenobarbital and their brain were subjected to immunohistochemical analysis for dopaminergic neurons staining for anti TH antibodies. Intrathecal UCMCs revealed regenerative effects in SNpc as evidenced by immunohistochemical staining; this was in parallel with better performance in behavioral tests. In conclusion, the results of this study revealed the regenerative capacities of UCMCs against rotenone neurotoxicity in mice.

The role of pramipexole in a severe Parkinson’s disease model in mice

Background: Pramipexole is one of a new generation of dopamine agonists. Recently there have been questions regarding its neuroprotective effects. These effects have been tested against various insults, which have yielded conflicting results. Methods: In this study, we introduced a combination of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/paraquat to induce a severe Parkinson’s disease model. The mice, after receiving the combination of toxins, were evaluated using mortality rates and immunohistochemistry for degenerating tyrosine hydroxylase-positive neurons. Results and conclusions: Pramipexole was tested for its capacity to offer protection against neurotoxic the effects of MPTP/paraquat in this model; however, the results showed no improvement with pramipexole therapy.

Possible role of nitric oxide in hepatic injury secondary to renal ischemia-reperfusion (I/R) injury.

Hepatic injury secondary to renal I/R injury has been documented in several studies. This study aimed to investigate the role of NO in hepatic injury secondary to renal I/R in rat model. Sprague-Dawley rats (n = 48) were divided into 4 equal groups; sham-operated, I/R injury group (45 min of bilateral renal ischemia), L-arginine group (I/R with 300 mg/kg L-arginine, 20 min before ischemia), L-NAME group (I/R with 50 mg/kg L-NAME, 20 min before ischemia). L-NAME (NO synthase inhibitor) caused significant elevation in serum creatinine, BUN, liver enzymes, liver histopathological damage score (p ≤ 0.05) and MDA production (p ≤ 0.001); on the other hand significantly decreased NO and GSH levels (p ≤ 0.05). L-arginine significantly decreased serum creatinine, BUN and GSH (p ≤ 0.05) and caused significant elevation in liver enzymes and NO (p ≤ 0.05), and also in MDA levels (p ≤ 0.001) in liver tissues. We conclude that endogenous NO might have protective effect against hepatic injury induced by renal I/R injury and inhibition of this endogenous NO by L-NAME or exogenous administration of NO (by L-arginine) might be harmful.