Sodium butyrate is a sodium salt of a volatile short-chain fatty acid (butyric acid) used to prevent Salmonella Enteritidis infection in birds. Three groups of fifty 1-d-old broilers each were fed the following diets: T0 = standard broiler diet (control); T1 = standard broiler diet supplemented with 0.92 g/kg of an additive with free sodium butyrate (Gustor XXI B92); and T2 = standard broiler diet supplemented with 0.92 g/kg of an additive with sodium butyrate partially protected with vegetable fats (Gustor XXI BP70). Twenty percent of the birds were orally infected with Salmonella Enteritidis at d 5 posthatching and fecal Salmonella shedding was assessed at d 6, 9, 13, 20, 27, 34, and 41 of the trial. At d 42, all birds were slaughtered and 20 of them dissected: crop, cecum, liver, and spleen were sampled for bacteriological analyses. Both butyrate-based additives showed a significant reduction (P < 0.05) of Salmonella Enteritidis infection in birds from d 27 onward. However, the partially protected butyrate additive was more effective at the late phase of infection. Partially protected butyrate treatment successfully decreased infection not only in the crop and cecum but also in the liver. There were no differences in the spleen. These results suggest that sodium butyrate partially protected with vegetable fats offers a unique balance of free and protected active substances effective all along the gastrointestinal tract because it is slowly released during digestion.

Methionine adenosyltransferase (MAT) catalyzes the synthesis of s-adenosylmethionine (AdoMet), a metabolite that plays an important role in a variety of cellular functions, such as methylation, sulfuration, and polyamine synthesis. In this study, genomic DNA from the protozoan parasite Leishmania infantum was cloned and characterized. L. infantum MAT, unlike mammalian MAT, is codified by two identical genes in a tandem arrangement and is only weakly regulated by AdoMet. L. infantum MAT mRNA is expressed as a single transcript, with the enzyme forming a homodimer with tripolyphosphatase in addition to MAT activity. Expression of L. infantum MAT in Escherichia coli proves that the MAT and tripolyphosphatase activities are functional in vivo. MAT shows sigmoidal behavior and is weakly inhibited by AdoMet, whereas tripolyphosphatase activity has sigmoidal behavior and is strongly activated by AdoMet. Plasmids containing the regions flanking MAT2 were fused immediately upstream and downstream of the luciferase-coding region and transfected into L. infantum. Subsequent examination of luciferase activity showed that homologous expression in L. infantum promastigotes was dramatically dependent on the presence of polypyrimidine tracts and a spliced leader junction site upstream of the luciferase gene, whereas downstream sequences appeared to have no bearing on expression.

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Neglected Tropical Diseases (NTD) represent a serious threat to humans, especially for those living in poor or developing countries. Almost one-sixth of the world population is at risk of suffering from these diseases and many thousands die because of NTDs, to which we should add the sanitary, labor and social issues that hinder the economic development of these countries. Protozoan-borne diseases are responsible for more than one million deaths every year. Visceral leishmaniasis, Chagas disease or sleeping sickness are among the most lethal NTDs. Despite not being considered an NTD by the World Health Organization (WHO), malaria must be added to this sinister group. Malaria, caused by the apicomplexan parasite Plasmodium falciparum, is responsible for thousands of deaths each year. The treatment of this disease has been losing effectiveness year after year. Many of the medicines currently in use are obsolete due to their gradual loss of efficacy, their intrinsic toxicity and the emergence of drug resistance or a lack of adherence to treatment. Therefore, there is an urgent and global need for new drugs. Despite this, the scant interest shown by most of the stakeholders involved in the pharmaceutical industry makes our present therapeutic arsenal scarce, and until recently, the search for new drugs has not been seriously addressed. The sources of new drugs for these and other pathologies include natural products, synthetic molecules or repurposing drugs. The most frequent sources of natural products are microorganisms, e.g., bacteria, fungi, yeasts, algae and plants, which are able to synthesize many drugs that are currently in use (e.g. antimicrobials, antitumor, immunosuppressants, etc.). The marine environment is another well-established source of bioactive natural products, with recent applications against parasites, bacteria and other pathogens which affect humans and animals. Drug discovery techniques have rapidly advanced since the beginning of the millennium. The combination of novel techniques that include the genetic modification of pathogens, bioimaging and robotics has given rise to the standardization of High-Performance Screening platforms in the discovery of drugs. These advancements have accelerated the discovery of new chemical entities with antiparasitic effects. This review presents critical updates regarding the use of High-Throughput Screening (HTS) in the discovery of drugs for NTDs transmitted by protozoa, including malaria, and its application in the discovery of new drugs of marine origin.

Leishmaniasis is a group of zoonotic diseases caused by a trypanosomatid parasite mostly in impoverished populations of low-income countries. In their different forms, leishmaniasis is prevalent in more than 98 countries all over the world and approximately 360-million people are at risk. Since no vaccine is currently available to prevent any form of the disease, the control strategy of leishmaniasis mainly relies on early case detection followed by adequate pharmacological treatment that may improve the prognosis and can reduce transmission. A handful of compounds and formulations are available for the treatment of leishmaniasis in humans, but only few of them are currently in use since most of these agents are associated with toxicity problems such as nephrotoxicity and cardiotoxicity in addition to resistance problems. In recent decades, very few novel drugs, new formulations of standard drugs or combinations of them have been approved against leishmaniasis. This review highlights the current drugs and combinations that are used medical practice and recent advances in new treatments against leishmaniasis that were pointed out in the recent 2nd Conference, Global Challenges in Neglected Tropical Diseases, held in San Juan, Puerto Rico in June 2018, emphasizing the plethora of new families of molecules that are bridging the gap between preclinical and first-in-man trials in next future.