The apicomplexan protozoan Toxoplasma gondii has a striking predilection for infecting the centra... more The apicomplexan protozoan Toxoplasma gondii has a striking predilection for infecting the central nervous system and has been suggested as a risk factor for schizophrenia. Here, we address some of the mechanisms by which T. gondii achieves this by manipulating signaling pathways of the host brain cells. Recent years have brought notable progress in the understanding of how the opportunistic parasite T. gondii establishes a successful infection in mammalian brain by secreting effector molecules that manipulate multiple cell functions. Many pathways involved in this inter-kingdom signaling, such as dopaminergic, GABAergic and kynurenine pathways, also have key roles in the development of schizophrenia. More understanding of T. gondii-brain cell interaction holds the key to unlocking the mystery of T. gondii-mediated schizophrenia pathogenesis. T. gondii usurps a variety of host signaling pathways to ensure physiological adaptation, evasion of host immune defense systems, and efficient replication. A detailed knowledge of T. gondii signaling molecules involved in this cross-kingdom communication with host brain cells will probably provide novel means of pharmacologically manipulating host cellular pathways to promote efficient elimination of the parasite and may permit the development of new schizophrenia-modifying therapeutics.
Journal of the Egyptian Society of Parasitology, Aug 1, 2009
The sero-markers of Toxoplasma gondii and oxidative stress (OS) were determined in a group of 260... more The sero-markers of Toxoplasma gondii and oxidative stress (OS) were determined in a group of 260 blood donors attending blood banks in Greater Cairo. Twenty-four blood donors with the highest anti-T. gondii IgG titre were tested for IgG avidity. Of whom 4 (16.6%) had low IgG avidity antibodies, documenting recent infection, 6 (25%) had borderline avidity and 14 (58.3%) showed high avidity, ruling out recent infection. The plasma level of malondialdehyde (MDA) was significantly higher and activity of glutathione peroxidase (GSH-Px) and level of tocopherol (alpha, gamma, & lambda) fractions (P < 0.001) were lower in T. gondii-seropositive than in seronegative blood donors. This significant alteration in redox status between seropositive and seronegative donors suggested a degradation of their antioxidant enzymes caused by OS induced by increased free radicals attributable to toxoplasmosis infection. T. gondii infection also had a prominent influence on the association between OS biomarkers and immune-suppression status in seropositive donors.
Journal of the Egyptian Society of Parasitology, May 1, 2007
Water samples were collected different water sources and different districts of Dakahlia G., from... more Water samples were collected different water sources and different districts of Dakahlia G., from September 2005 to August 2006, were investigated for pathogenic protozoa. Water specimens were examined by concentration technique followed by modified Ziehl-Neelsen (MZN) and Truant auramine-rhodamine (AR) stains for Giardia sp. cysts, Cryptosporidium sp. oocysts, and other protozoa species. In the 1st survey, 94/480 (19.6%) water samples had protozoa. Prevalence rates were in summer 38/120 (31.6%), autumn 27/ 120 (22.5%), spring 20/ 120 (16.6%) and lastly winter 9/120 (7.5%). Protozoa were less common in treated potable water tanks 15/120 (12.5%), followed by River Nile (Demiatta branch) 22/120 (18.3%) and sub-branch Bahr-El-Saghear 24/120 (20%). The highest prevalence was in water of the main local draining 33/120 (27.5%). In the 2nd survey, 840 potable water samples from seven districts were examined. Prevalence in descending order was C. parvum (3.1%), G. intestinalis (2.1%), E. histolytica (1%), Blastocystis homi-nis (1%), Iodamoeba sp, (0.5%), Isospora belli (0.47%), E. coli (0.36%), Cyclospora cayetanensis (0.24%), and Chilomastix mesnilli (0.12%). Data suggested that C. parvum and G. intestinalis were the commonest disease-agent. The implementation of preventive measures to protect water system from protozoa contamination was given.
Journal of the Egyptian Society of Parasitology, Aug 1, 2009
No doubt, Toxoplasma gondii and toxoplasmosis superimposed many zoonotic diseases from geographic... more No doubt, Toxoplasma gondii and toxoplasmosis superimposed many zoonotic diseases from geographical and zoological distribution world wide.
Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still n... more Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while th...
Journal of the Egyptian Society of Parasitology, May 1, 2008
Besnoitia tissue cysts associated with the skin lesions recovered from the naturally-infected min... more Besnoitia tissue cysts associated with the skin lesions recovered from the naturally-infected miniature donkeys (Equus asinus) during clinical examination were studied by the light and electron microscopy, as well as histochemically to elucidate the specific morphologic features of the cyst causing this disease. The cyst was differentiated phenotypically from those of other Besnoitia spp. The interpretation of results showed that morphometric attributes of the tissue cysts and the associated pathological changes in these donkeys were due to B. bennetti infection. The findings were confirmed by the phylogenetic analysis based on DNA sequences of the first internal transcribed spacer of nuclear rDNA. The cluster analysis showed that B. bennetti was distinct from all other Besnoitia spp. and positioned B. bennetti with parasites described from Besnoitia besnoiti of cattle and B. tarandi of reindeer. The genetic attributes complemented the morphological criteria and verified the accurate delimitation of the Besnoitia cysts isolated from these donkeys.
A total of 206 Virginia opossums ( Didelphis virginiana) collected from the mid-Michigan region, ... more A total of 206 Virginia opossums ( Didelphis virginiana) collected from the mid-Michigan region, United States, during a period extending from 1996 to 2002 were sampled for the presence of Sarcocystis spp sporocysts. All isolates were phenotypically identified as Sarcocystis spp and genotyped to the species level by PCR-based techniques. The overall prevalence of Sarcocystis spp in opossums was 18% (37/206). The prevalence of Sarcocystis spp differed significantly with age ( P<0.001) and adult opossums were more commonly infected (14.6%; 30/206) than juveniles (3.4%; 7/206). No significant difference in the prevalence of Sarcocystis spp infection was observed between male and female ( P<0.15). The highest prevalence was recorded during summer (9.2%; 19/206). PCR-RFLP analyses demonstrated the majority of Sarcocystis isolates to be S. neurona, with some animals co-infected with sporocysts of S. falcatula. Out of the 37 Sarcocystis-infected opossums, 23 (62%) had sporocysts of S. neurona only, four (11%) had sporocysts of S. falcatula only, and eight (22%) had a mixture of S. neurona and S. falcatula sporocysts. These findings indicate that mixed Sarcocystis infections in opossums are common. The propensity for Sarcocystis spp to co-exist in the opossum gut enhances dissemination and environmental contamination with these coccidia. Additionally, this increases the chance for sexual recombination between Sarcocystis spp, given the proclivity of these species to reproduce sexually at high numbers in the intestinal cells of their definitive host.
The apicomplexan protozoan Toxoplasma gondii has a striking predilection for infecting the centra... more The apicomplexan protozoan Toxoplasma gondii has a striking predilection for infecting the central nervous system and has been suggested as a risk factor for schizophrenia. Here, we address some of the mechanisms by which T. gondii achieves this by manipulating signaling pathways of the host brain cells. Recent years have brought notable progress in the understanding of how the opportunistic parasite T. gondii establishes a successful infection in mammalian brain by secreting effector molecules that manipulate multiple cell functions. Many pathways involved in this inter-kingdom signaling, such as dopaminergic, GABAergic and kynurenine pathways, also have key roles in the development of schizophrenia. More understanding of T. gondii-brain cell interaction holds the key to unlocking the mystery of T. gondii-mediated schizophrenia pathogenesis. T. gondii usurps a variety of host signaling pathways to ensure physiological adaptation, evasion of host immune defense systems, and efficient replication. A detailed knowledge of T. gondii signaling molecules involved in this cross-kingdom communication with host brain cells will probably provide novel means of pharmacologically manipulating host cellular pathways to promote efficient elimination of the parasite and may permit the development of new schizophrenia-modifying therapeutics.
Journal of the Egyptian Society of Parasitology, Aug 1, 2009
The sero-markers of Toxoplasma gondii and oxidative stress (OS) were determined in a group of 260... more The sero-markers of Toxoplasma gondii and oxidative stress (OS) were determined in a group of 260 blood donors attending blood banks in Greater Cairo. Twenty-four blood donors with the highest anti-T. gondii IgG titre were tested for IgG avidity. Of whom 4 (16.6%) had low IgG avidity antibodies, documenting recent infection, 6 (25%) had borderline avidity and 14 (58.3%) showed high avidity, ruling out recent infection. The plasma level of malondialdehyde (MDA) was significantly higher and activity of glutathione peroxidase (GSH-Px) and level of tocopherol (alpha, gamma, & lambda) fractions (P < 0.001) were lower in T. gondii-seropositive than in seronegative blood donors. This significant alteration in redox status between seropositive and seronegative donors suggested a degradation of their antioxidant enzymes caused by OS induced by increased free radicals attributable to toxoplasmosis infection. T. gondii infection also had a prominent influence on the association between OS biomarkers and immune-suppression status in seropositive donors.
Journal of the Egyptian Society of Parasitology, May 1, 2007
Water samples were collected different water sources and different districts of Dakahlia G., from... more Water samples were collected different water sources and different districts of Dakahlia G., from September 2005 to August 2006, were investigated for pathogenic protozoa. Water specimens were examined by concentration technique followed by modified Ziehl-Neelsen (MZN) and Truant auramine-rhodamine (AR) stains for Giardia sp. cysts, Cryptosporidium sp. oocysts, and other protozoa species. In the 1st survey, 94/480 (19.6%) water samples had protozoa. Prevalence rates were in summer 38/120 (31.6%), autumn 27/ 120 (22.5%), spring 20/ 120 (16.6%) and lastly winter 9/120 (7.5%). Protozoa were less common in treated potable water tanks 15/120 (12.5%), followed by River Nile (Demiatta branch) 22/120 (18.3%) and sub-branch Bahr-El-Saghear 24/120 (20%). The highest prevalence was in water of the main local draining 33/120 (27.5%). In the 2nd survey, 840 potable water samples from seven districts were examined. Prevalence in descending order was C. parvum (3.1%), G. intestinalis (2.1%), E. histolytica (1%), Blastocystis homi-nis (1%), Iodamoeba sp, (0.5%), Isospora belli (0.47%), E. coli (0.36%), Cyclospora cayetanensis (0.24%), and Chilomastix mesnilli (0.12%). Data suggested that C. parvum and G. intestinalis were the commonest disease-agent. The implementation of preventive measures to protect water system from protozoa contamination was given.
Journal of the Egyptian Society of Parasitology, Aug 1, 2009
No doubt, Toxoplasma gondii and toxoplasmosis superimposed many zoonotic diseases from geographic... more No doubt, Toxoplasma gondii and toxoplasmosis superimposed many zoonotic diseases from geographical and zoological distribution world wide.
Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still n... more Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while th...
Journal of the Egyptian Society of Parasitology, May 1, 2008
Besnoitia tissue cysts associated with the skin lesions recovered from the naturally-infected min... more Besnoitia tissue cysts associated with the skin lesions recovered from the naturally-infected miniature donkeys (Equus asinus) during clinical examination were studied by the light and electron microscopy, as well as histochemically to elucidate the specific morphologic features of the cyst causing this disease. The cyst was differentiated phenotypically from those of other Besnoitia spp. The interpretation of results showed that morphometric attributes of the tissue cysts and the associated pathological changes in these donkeys were due to B. bennetti infection. The findings were confirmed by the phylogenetic analysis based on DNA sequences of the first internal transcribed spacer of nuclear rDNA. The cluster analysis showed that B. bennetti was distinct from all other Besnoitia spp. and positioned B. bennetti with parasites described from Besnoitia besnoiti of cattle and B. tarandi of reindeer. The genetic attributes complemented the morphological criteria and verified the accurate delimitation of the Besnoitia cysts isolated from these donkeys.
A total of 206 Virginia opossums ( Didelphis virginiana) collected from the mid-Michigan region, ... more A total of 206 Virginia opossums ( Didelphis virginiana) collected from the mid-Michigan region, United States, during a period extending from 1996 to 2002 were sampled for the presence of Sarcocystis spp sporocysts. All isolates were phenotypically identified as Sarcocystis spp and genotyped to the species level by PCR-based techniques. The overall prevalence of Sarcocystis spp in opossums was 18% (37/206). The prevalence of Sarcocystis spp differed significantly with age ( P<0.001) and adult opossums were more commonly infected (14.6%; 30/206) than juveniles (3.4%; 7/206). No significant difference in the prevalence of Sarcocystis spp infection was observed between male and female ( P<0.15). The highest prevalence was recorded during summer (9.2%; 19/206). PCR-RFLP analyses demonstrated the majority of Sarcocystis isolates to be S. neurona, with some animals co-infected with sporocysts of S. falcatula. Out of the 37 Sarcocystis-infected opossums, 23 (62%) had sporocysts of S. neurona only, four (11%) had sporocysts of S. falcatula only, and eight (22%) had a mixture of S. neurona and S. falcatula sporocysts. These findings indicate that mixed Sarcocystis infections in opossums are common. The propensity for Sarcocystis spp to co-exist in the opossum gut enhances dissemination and environmental contamination with these coccidia. Additionally, this increases the chance for sexual recombination between Sarcocystis spp, given the proclivity of these species to reproduce sexually at high numbers in the intestinal cells of their definitive host.
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Papers by Hany ELsheikha