Pyrvinium Pamoate and Structural Analogs Are Early Macrofilaricide Leads.

Onchocerciasis and lymphatic filariasis are neglected tropical diseases caused by infection with filarial worms. Annual or biannual mass drug administration with microfilaricidal drugs that kill the microfilarial stages of the parasites has helped reduce infection rates and thus prevent transmission of both infections. However, success depends on high population coverage that is maintained for the duration of the adult worm's lifespan. Given that these filarial worms can live up to 14 years in their human hosts, a macrofilaricidal drug would vastly accelerate elimination efforts. Here, we have evaluated the repurposed drug pyrvinium pamoate as well as newly synthesized analogs of pyrvinium for their efficacy against filarial worms in vitro and in vivo. We found that pyrvinium pamoate, tetrahydropyrvinium and one of the analogs were highly potent in inhibiting worms in in vitro whole-worm screening assays, and that all three compounds reduced female worm fecundity and inhibited embryogenesis in the Brugia pahangi-gerbil in vivo model of infection.

QuEChERS-based method for the determination of carbamate residues in aromatic herbs by UHPLC-MS/MS.

A new reliable, fast and highly sensitive method based on ultra-high performance liquid chromatography tandem mass spectrometry has been developed and validated for the determination of 28 carbamates in aromatic herbs. A modified QuEChERS-based method was optimized for the extraction of carbamate residues from a wide variety of fresh herbal products. The proposed method allowed recoveries higher than 72%, achieving quantification limits of 2µgkg(-1), therefore below maximum residue limits established for this type of samples. The combination of QuEChERS with UHPLC-MS/MS introduces a high-throughput methodology for the monitoring of these residues in this type of matrices scarcely explored. The analysis of the real samples revealed that several samples sold in the European Union and in the North West region of Cameroon contain pesticides in concentrations below the maximum residue limits.

Effect of environmental contaminants on mammalian testis.

Exposure of humans and wildlife to pollutants released in the environment is a centre of attention nowadays. Many of these chemicals (generally referred to as environmental pollutants) have been shown to interfere with normal hormonal signalling and biological functions, leading to reproductive disorders or infertility, which has been a matter of concern within the recent decades. The present paper reviews adverse effects of these toxicants on mammalian testes, with emphasis on alteration of steroidogenesis, spermatogenesis, and histopathological effects. From the publications reviewed, it appears that environmental toxicants, especially heavy metals and organic chemicals of synthetic and microbiological origins, disrupt hormone production and action in the mammalian testes. Endocrine disruption leads to disorders of testicular function and thereby compromises the normal phenotypic development of male sexual characteristics, initiation and maintenance of spermatogenesis. The toxicants also induce impairment of testicular cells function, testicular histology, and sperm cells function directly. The release of the toxicants in the environment is still ongoing, despite alarming quantities that already exist in the atmosphere. If appropriate measures are not taken, their impact on the male reproductive function and especially on testicular function will be more serious.