Effects of Silybum marianum L. Seed Extracts on Multi Drug Resistant (MDR) Bacteria.

Wound infections became a great challenge, especially after the emergence of bacterial resistance to commonly used antibiotics. Medicinal plants can be the source of alternative antibacterial agents effective against multi drug resistant (MDR) bacteria. This research aimed to evaluate the effectiveness of different Silybum marianum seed extracts in fighting MDR bacteria that infect wounds. First, thirty purified bacterial cultures obtained from superficial, infected wounds were subjected to antibiotic sensitivity tests. The selected MDR isolates were then used to test the antimicrobial effects of different S. marianum seed extracts. The most potent extract was evaluated for its impact on the ultrastructure of the cells of sensitive bacterial isolates using transmission electron microscopy (TEM). The bioactive ingredients of this extract were analyzed by means of gas chromatography-mass spectroscopy (GC-MS). Then, in-silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were predicted for the main components. The results indicated that four out of 30 bacterial isolates were considered MDR bacteria. Primary morphological features of colonies, secondary (automatic) identification using the Biomerieux Vitek 2 System, and 16S rRNA sequencing of the four isolates confirmed that they represent Staphylococcus aureus, Stenotrophomonas maltophilia, Klebsiella pneumoniae, and Escherichia coli. Among different extracts of S. marianum seeds, ethanol extract showed the strongest inhibitory effect on both Gram-positive and Gram-negative bacteria, with minimum inhibitory concentration (MIC) values between 9.375 and 1.172 mg/mL. However, at concentrations four times higher, this extract was unable to kill bacterial cells, indicating that it had a bacteriostatic effect on the tested MDR strains. TEM revealed denaturation and distorted cell ultrastructure in S. aureus and S. maltophilia after exposure to ethanol extract. In addition, GC-MS analysis of the ethanol extract identified nine compounds known to have important biological activities, and ADMET analysis showed good drug-likeness for two of these compounds. Consequently, S. marianum seeds could be a good source of alternative bacteriostatic agents effective against MDR bacterial strains that cause wound infections.

Neural grafting reverses prenatal drug-induced alterations in hippocampal PKC and related behavioral deficits.

Administration of heroin or phenobarbital to pregnant mice evokes neurochemical and behavioral deficits consequent to disruption of septohippocampal cholinergic innervation. The present study evaluates the relationship between the drug-induced biochemical changes and the behavioral deficits, applying two different approaches: neural grafting and within-individual correlations of biochemistry and behavior. Mice were exposed transplacentally to phenobarbital or heroin on gestational days 9-18 and tested in adulthood. Drug-exposed mice displayed impaired radial arm maze performance, increases in presynaptic choline transporter sites (monitored with [(3)H]hemicholinium-3 binding), upregulation of membrane-associated protein kinase C (PKC) activity, and desensitization of the PKC response to a cholinergic agonist, carbachol. Grafting of cholinergic cells to the impaired hippocampus reversed the behavioral deficits nearly completely and restored basal PKC activity and the PKC response to carbachol to normal; the drug effects on hemicholinium-3 binding were also slightly obtunded by neural grafting, but nevertheless remained significantly elevated. There were significant correlations between the performance in the eight-arm maze and both basal PKC activity and PKC desensitization, and to a lesser extent, between behavioral performance and hemicholinium-3 binding. Taken together, these findings indicate an inextricable link between the biochemical effects of prenatal drug exposure on the PKC signaling cascade and adverse behavioral outcomes. The ability of neural grafting to reverse both the drug-induced changes in PKC and behaviors linked to septohippocampal cholinergic function suggest a mechanistic link between this signaling pathway and neurobehavioral teratology caused by heroin or phenobarbital.

Fusariotoxicoses of farm animals and mycotoxic leucoencephalomalacia of the equine associated with the finding of trichothecenes in feedstuffs.

Mycotoxicoses involving horses, rabbits and cattle have been studied. Fusarium tricinctum and T-2 toxin were isolated from all incriminated feedstuffs. Other isolated trichothecenes from the feed included HT-2, verrucarins and roridin. The toxins were separated, identified and quantitated using thin-layer chromatography, gas-liquid chromatography and mass spectrometry. T-2 toxin was detected in amounts varying from 0.5-204 ppm. The contaminated feedstuffs in connection with the affected horses and rabbits, included cereal grains (corn, cornstalks, bran and barley), whereas fescue hay was associated with the mucocutaneous findings in the bovine episode. The effects of the toxin(s) seemed to be host specific and varied according to the different animal species. Horses and rabbits developed primarily central nervous disorders with conspicuous pathological findings in the brain. Hepatitis and nephritis were also seen in naturally intoxicated horses and experimentally fed rats. Affected cattle developed mucocutaneous eruptions around the mouth and nostrils. In addition, dermonecrotic findings were observed involving the extremities, ear and tail. Fusariotoxicoses are toxic conditions of farm animals and man caused by the ingestion of cereal grains and forages contaminated by different fungal species of the genus Fusarium. A variety of clinical and pathological findings have been reported (5,6,10,13,15,17,31). This study concerns neuropathic findings in horses and rabbits and mucocutaneous lesions in cattle in association with T-2 toxin contamination.