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  • myc pathway Glucose permeability studies demonstrated a high

    2024-02-09

    Glucose permeability studies demonstrated a high glucose flux through the SF films used in the present work. Recent diffusion studies, including small molecular drugs and oxygen permeation through SF membranes [32], further support the quality of SF and its possible application as a material for bioincubators suitable for cell-based drug delivery.
    Conclusion
    Acknowledgments
    Introduction The parasitic protozoan, Toxoplasma gondii, is the etiologic agent for toxoplasmosis, a parasitic disease wide spread among various warm-blooded animals including man [1]. Approximately 25% of the people worldwide, including 10% of the population in the US [2], are seropositive to T. gondii. This high prevalence of toxoplasmosis is attributed to its efficient spread through the food chain. Consequently, T. gondii is an important cause of foodborne infection in humans [3]. Infection with T. gondii is asymptomatic (90% of cases) in the general population and typically results in a mild flu-like syndrome that resolves without the need for intervention [4]. By contrast, the disease represents a major health problem for immunocompromised individuals, such as AIDS patients [5], [6], organ transplant recipient patients [7], cancer chemotherapy patients [8] and the unborn children of infected mothers [1], [9], [10]. In such cases, toxoplasmic encephalitis is recognized as the most common cause of intracerebral mass lesions in AIDS patients and possibly the most commonly recognized opportunistic infection of the central nervous system [5], [9]. Congenital toxoplasmosis is as high as 1/1000 live births [9]. Effects range in severity from asymptomatic to stillbirth, with the most common ailments being retinochoroiditis, cerebral calcifications, psychomotor disorder or mental retardation, and severe myc pathway damage [9]. Additionally, T. gondii has recently been recognized as an important cause of ocular disease in healthy adults [11], [12]. Recent reports indicate that chronic T. gondii infection may be a predisposing factor for the development of schizophrenia [13], [14], [15], an effect that may be driven by inflammation in the CNS [16]. Despite these tragic implications, the current therapy has not changed in the past few decades. The efficacy of the current therapy for toxoplasmosis (a combination of pyrimethamine and sulfadiazine) is limited, primarily by serious host toxicity and ineffectiveness against tissue cysts. Furthermore, as many as 50% of patients do not respond to therapy. In addition, prolonged exposure to this regimen induces serious host toxicity such as bone marrow suppression and severe skin rashes forcing the discontinuation of the therapy [5], [9], [17], [18]. Other therapies, e.g. clindamycin, spiramycin or atovaquone, have been met with limited success, particularly in the long-term management of these patients. Hence, there is a critical need to develop new and effective drugs with low host toxicity for the acute and chronic management of toxoplasmosis. Rational drug design is usually based on biochemical and physiological differences between the pathogen and the host. One potential target for chemotherapeutic intervention against T. gondii is purine metabolism. These parasites replicate rapidly and require large amounts of purines for the synthesis of their nucleic acids and other vital components. In contrast to their host, T. gondii are purine auxotrophs and must rely on the salvage of their purine requirements from the host [19], [20]. Another striking difference between toxoplasma and their host is the nature of adenosine salvage. Adenosine is preferentially incorporated into the parasite nucleotide pool by at least a 10-fold higher rate than any other purine nucleobase or nucleoside tested [21], [22]. Furthermore, adenosine is directly phosphorylated to AMP, from which all other purine nucleotides can be synthesized to fulfill the parasite purine requirements. This reaction is catalyzed by the enzyme adenosine kinase (EC 2.7.1.20) which is almost 10 times more active than any other purine salvage enzyme in this parasite [22]. This contrasts sharply with most mammalian cells where adenosine is predominantly deaminated by adenosine deaminase (EC 3.5.4.4) to inosine, which is then cleaved by purine nucleoside phosphorylase (EC 2.4.2.1) to hypoxanthine as previously reviewed [6], [7]. Neither of these two enzymes have any appreciable activity in T. gondii[8].