Unique and outstanding physical and chemical properties of zeolite materials make them extremely useful in a variety of applications including agronomy, ecology, manufacturing, and industrial processes. Recently, a more specific application of one naturally occurring zeolite material, clinoptilolite, has been widely studied in veterinary and human medicine. Due to a number of positive effects on health, including detoxification properties, the usage of clinoptilolite-based products in vivo has increased enormously. However, concerns have been raised in the public about the safety of clinoptilolite materials for in vivo applications. Here, we review the scientific literature on the health effects and safety in medical applications of different clinoptilolite-based materials and propose some comprehensive, scientifically-based hypotheses on possible biological mechanisms underlying the observed effects on the health and body homeostasis. We focus on the safety of the clinoptilolite material and the positive medical effects related to detoxification, immune response, and the general health status.

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Drosophila melanogaster can be used to identify genes with novel functional roles in neuronal plasticity induced by repeated consumption of addictive drugs. Behavioral sensitization is a relatively simple behavioral output of plastic changes that occur in the brain after repeated exposures to drugs of abuse. The development of screening procedures for genes that control behavioral sensitization has stalled due to a lack of high-throughput behavioral tests that can be used in genetically tractable organism, such as Drosophila. We have developed a new behavioral test, FlyBong, which combines delivery of volatilized cocaine (vCOC) to individually housed flies with objective quantification of their locomotor activity. There are two main advantages of FlyBong: it is high-throughput and it allows for comparisons of locomotor activity of individual flies before and after single or multiple exposures. At the population level, exposure to vCOC leads to transient and concentration-dependent increase in locomotor activity, representing sensitivity to an acute dose. A second exposure leads to further increase in locomotion, representing locomotor sensitization. We validate FlyBong by showing that locomotor sensitization at either the population or individual level is absent in the mutants for circadian genes period (per), Clock (Clk,) and cycle (cyc). The locomotor sensitization that is present in timeless (tim) and pigment dispersing factor (pdf) mutant flies is in large part not cocaine specific, but derived from increased sensitivity to warm air. Circadian genes are not only integral part of the neural mechanism that is required for development of locomotor sensitization, but in addition, they modulate the intensity of locomotor sensitization as a function of the time of day. Motor-activating effects of cocaine are sexually dimorphic and require a functional dopaminergic transporter. FlyBong is a new and improved method for inducing and measuring locomotor sensitization to cocaine in individual Drosophila. Because of its high-throughput nature, FlyBong can be used in genetic screens or in selection experiments aimed at the unbiased identification of functional genes involved in acute or chronic effects of volatilized psychoactive substances.

As complexities of addictive behaviors cannot be fully captured in laboratory studies, scientists use simple addiction‐associated phenotypes and measure them in laboratory animals. Locomotor sensitization, characterized by an increased behavioral response to the same dose of the drug, has been extensively used to elucidate the genetic basis and molecular mechanisms of neuronal plasticity. However, to what extent it contributes to the development of addiction is not completely clear. We tested if the development of locomotor sensitization to methamphetamine affects voluntary self‐administration, and vice versa, in order to investigate how two drug‐associated phenotypes influence one another. In our study, we used the genetically tractable model organism, Drosophila melanogaster, and quantified locomotor sensitization and voluntary self‐administration to methamphetamine using behavioral tests that were developed and adapted in our laboratory. We show that flies express robust locomotor sensitization to the second dose of volatilized methamphetamine, which significantly lowers preferential self‐administration of methamphetamine. Naive flies preferentially self‐administer food with methamphetamine over plain food. Exposing flies to volatilized methamphetamine after voluntary self‐administration abolishes locomotor sensitization. We tested period null (per01) mutant flies and showed that they do not develop locomotor sensitization, nor do they show preferential self‐administration of methamphetamine. Our results suggest that there may be partially overlapping neural circuitry that regulates the expression of locomotor sensitization and preferential self‐administration to methamphetamine and that this circuitry requires a functional per gene.

In this work we hypothesize novel anti‐oxidative role for the stable gastric pentadecapeptide BPC 157 and we test this using a model organism, Drosophila melanogaster. BPC 157 was originally an anti‐ulcer peptide used in trials for ulcerative colitis and now is in trials for the treatment of multiple sclerosis where it largely interacts with NO‐system (Curr Pharm Des 2014;20(7):1126–35). BPC 157 is also thought to be a novel mediator of Robert's cytoprotection in rat studies, where its endothelium and mucosal protection is believed to be related to oxidative stress injury (Curr Pharm Des 2014;20(7):1126–35).To explore anti‐oxidative properties of BPC 157 we used the animal model of hydrogen peroxide (H2O2) induced oxidative stress in Drosophila melanogaster. Addition of increasing concentrations of H2O2 to regular Drosophila medium dose‐dependently shortened the lifespan of wild type (wt) Canton S Drosophila males (maximal survival on H2O2 is 8 days, compared to average lifespan of 80 days on regular fly food medium). Longevity of H2O2 fed males increased when they were grown on H2O2 medium supplemented with BPC 157. At 7 days, 54% of H2O2 wt males survived, compared to 84% of 0.6% H2O2 + 3.5 ng/ml BPC 157; at 12 days there was no survival on 0.6% H2O2, and 4% survival on 0.6% H2O2 + 3.5 ng/ml BPC 157.These results shows that; first, BPC 157 is biologically active in this invertebrate model system, and second, that that BPC 157 and H2O2 likely act on similar molecular pathways regulating longevity. Doses effective in promoting increased survival on H2O2 were extrapolated from biologically active doses in mammals. In conclusion, this suggests likely conservation of mechanisms by which BPC 157 antagonizes Reactive Oxidative Species (ROS) in invertebrates and vertebrates. Based on these intriguing observations we will investigate mechanisms by which BPC 157 exerts its anti‐oxidant actions. Because of the significant genetic and mechanistic conservation between Drosophila and vertebrates, discoveries made in this simple model organism will have significant translational potential and relevance for human health.Support or Funding InformationUniversity of Zagreb, Zagreb, Croatia (Grant number BM099)