Developmental changes in the expression of creatine synthesizing enzymes and creatine transporter in a precocial rodent, the spiny mouse

Background : Creatine synthesis takes place predominately in the kidney and liver via a two-step process involving AGAT (L-arginine:glycine amidinotransferase) and GAMT (guanidinoacetate methyltransferase). Creatine is taken into cells via the creatine transporter (CrT), where it plays an essential role in energy homeostasis, particularly for tissues with high and fluctuating energy demands. Very little is known of the fetal requirement for creatine and how this may change with advancing pregnancy and into the early neonatal period. Using the spiny mouse as a model of human perinatal development, the purpose of the present study was to comprehensively examine the development of the creatine synthesis and transport systems.

Results : The estimated amount of total creatine in the placenta and brain significantly increased in the second half of pregnancy, coinciding with a significant increase in expression of CrT mRNA. In the fetal brain, mRNA expression of AGAT increased steadily across the second half of pregnancy, although GAMT mRNA expression was relatively low until 34 days gestation (term is 38–39 days). In the fetal kidney and liver, AGAT and GAMT mRNA and protein expression were also relatively low until 34–37 days gestation. Between mid-gestation and term, neither AGAT or GAMT mRNA or protein could be detected in the placenta.

Conclusion : Our results suggest that in the spiny mouse, a species where, like the human, considerable organogenesis occurs before birth, there appears to be a limited capacity for endogenous creatine synthesis until approximately 0.9 of pregnancy. This implies that a maternal source of creatine, transferred across the placenta, may be essential until the creatine synthesis and transport system matures in preparation for birth. If these results also apply to the human, premature birth may increase the risk of creatine deficiency.

Management of cardiovascular diseases with micro systems and nanotechnology

Cardiovascular diseases are the leading cause of death and morbidity in industrialized nations and are becoming an urgent health problem for all nations due to the unstoppable trend of an ageing and obese population. Due to the rapid development of micro total analysis systems (μTAS) and nanotechnology in recent years, they will play an important role in the diagnosis, management, and therapy of cardiovascular diseases. It is envisaged that the micro and nanotechnologies developed for treating other diseases shall be explored for cardiovascular applications to reduce the research effort required for commercializing the devices and drugs to meet the increasing demand of the cardiovascular patients.

A new rodent model to assess blood stage immunity to the plasmodium falciparum antigen merozoite surface protein 119 reveals a protective role for invasion inhibitory antibodies

Antibodies capable of inhibiting the invasion of Plasmodium merozoites into erythrocytes are present in individuals that are clinically immune to the malaria parasite. Those targeting the 19-kD COOH-terminal domain of the major merozoite surface protein (MSP)-119 are a major component of this inhibitory activity. However, it has been difficult to assess the overall relevance of such antibodies to antiparasite immunity. Here we use an allelic replacement approach to generate a rodent malaria parasite (Plasmodium berghei) that expresses a human malaria (Plasmodium falciparum) form of MSP-119. We show that mice made semi-immune to this parasite line generate high levels of merozoite inhibitory antibodies that are specific for P. falciparum MSP-119. Importantly, protection from homologous blood stage challenge in these mice correlated with levels of P. falciparum MSP-119–specific inhibitory antibodies, but not with titres of total MSP-119–specific immunoglobulins. We conclude that merozoite inhibitory antibodies generated in response to infection can play a significant role in suppressing parasitemia in vivo. This study provides a strong impetus for the development of blood stage vaccines designed to generate invasion inhibitory antibodies and offers a new animal model to trial P. falciparum MSP-119 vaccines.

Promises of nanotechnology for drug delivery to brain in neurodegenerative diseases

Brain is a delicate organ, isolated from general circulation and characterized by the presence of relatively impermeable endothelial cells with tight junctions, enzymatic activity and the presence of active efflux transporter mechanisms. These formidable obstacles often block drug delivery to the brain across the blood-brain barrier (BBB). Although several promising molecules have the potential in the in vitro settings but lack of in vivo response is probably because the molecule cannot reach the brain in a sufficient concentration. Drug delivery across the BBB is a major limitation in the treatment of central nervous system (CNS) disorders and CNS infections. This review deals with the role of nanobiotechnology in CNS drug delivery, in which three categories of carbon nanotubes, nanowires and nanoparticles (NPs) are explained. The small size of the NPs makes them an ideal choice to penetrate the BBB. Several mechanisms are involved in this process and various strategies are used. There are some concerns about the safety of NP entry in the brain that need to be resolved before human use. Although there is no approved nanotechnology-based CNS drug available the future for such neuro-nanobiotechnology based delivery system developments is promising.

Applications of aptamers in nanodelivery systems in cancer, eye and inflammatory diseases

Aptamers are an interesting class of molecules that have potential in many facets of human health. They are characterized by high affinity and specificity to their targets, are small in size, have similar properties to antibodies, but are made synthetically. All of these properties, among others, give aptamers the potential to diagnose, image and treat like no other molecules. By combining the unique properties of aptamers with the ever expanding field of nanotechnology and all it has to offer, we are entering a very promising new area of targeted nanodelivery treatments. These treatments have found success in the complex disease processes of cancer, eye and inflammatory diseases.

MicroRNA in human cancer and chronic inflammatory diseases

MicroRNAs (miRNAs) are the non-coding RNAs that act as post-translational regulators to their complimentary messenger RNAs (mRNA). Due to their specific gene silencing property, miRNAs have been implicated in a number of cellular and developmental processes. Also, it has been proposed that a particular set of miRNA spectrum is expressed only in a particular type of tissue. Many interesting findings related to the differential expression of miRNAs in various human diseases including several types of cancers, neurodegenerative diseases and metabolic diseases have been reported. Deregulation of miRNA expression in different types of human diseases and the roles various miRNAs play as tumour suppressors as well as oncogenes, suggest their contribution to cancer and/or in other disease development. These findings have possible implications in the development of diagnostics and/or therapeutics in human malignancies. In this review, we discuss various miRNAs that are differentially expressed in human chronic inflammatory diseases, neurodegenerative diseases, cancer and the further prospective development of miRNA based diagnostics and therapeutics.

Nonpharmacologic interventions need outcomes for evaluating complex interventions in rheumatic diseases

Introduction. Nonpharmacologic interventions are themselves complex and are often combined with drugs and other interventions in the treatment of rheumatic diseases. Therefore, overall strategies for treatment are complex interventions. These should be evaluated regarding their processes and outcomes.
Methods. The CARE network, an international organization of health professionals (physicians and nonphysicians) and patients conducted a survey in 2008 to identify core outcomes in the ICF perspective, completed with a second survey (2009–2010) with patients in routine practice. These surveys have provided new information about domains to investigate as a basis for evaluating complex interventions.
Results. Outcome Measures in Rheumatology Clinical Trials (OMERACT) participants in this Special Interest Group agreed that current outcomes used in pharmacological research are not sufficient if the nonpharmacologic independent or combined contributions are to be assessed; other domains need to be addressed. This is an area of interest for further development.
Conclusion. Recommendations are proposed to develop research in the area of outcome for evaluation of complex interventions in rheumatic diseases.