Stress Response and Virulence Potential Modulating Effect of Peppermint Essential Oil in Campylobacter jejuni.

Campylobacter jejuni is one of the most common food-borne bacteria that causes gastrointestinal symptoms. In the present study we have investigated the molecular basis of the anti-Campylobacter effect of peppermint essential oil (PEO), one of the oldest EO used to treat gastrointestinal diseases. Transcriptomic, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and proteomic, two-dimensional polyacryl amid gel electrophoresis (2D-PAGE) methods have revealed that, in the presence of a sublethal concentration of PEO, the expression of several virulence-associated genes was decreased (cheY 0.84x; flhB 0.79x; flgE 0.205x; cadF 0.08x; wlaB 0.89x; porA 0.25x; cbf2 4.3x) while impaired motility was revealed with a functional analysis. Scanning electron micrographs of the exposed cells showed that, unlike in the presence of other stresses, the originally curved C. jejuni cells straightened upon PEO exposure. Gaining insight into the molecular background of this stress response, we have revealed that in the presence of PEO C. jejuni dominantly exerts a general stress response that elevates the expression of general stress genes like dnaK, groEL, groES (10.41x, 3.63x, and 4.77x). The most important genes dps, sodB, and katA involved in oxidative stress responses showed however moderate transcriptional elevations (1,58x, 1,55x, and 1,85x).

Characterization of antinociceptive potency of endomorphin-2 derivatives with unnatural amino acids in rats.

This study reports on the in vivo effects of four endomorphin-2 (EM-2) derivatives (EMD1-4) containing unnatural amino acids, i.e. 2-aminocyclohexanecarboxylic acid (Achc2), para-fluorophenylalanine (pFPhe4), ß-methylphenylalanine (ßMePhe4) and/or 2',6'-dimethyltyrosine (Dmt1). After induction of osteoarthritis by monosodium iodoacetate into the ankle joint of male Wistar rats, a chronic intrathecal catheter was inserted for spinal drug delivery. The mechanical threshold was assessed by a dynamic aesthesiometer. Intrathecal injection of the original EM-2 and the ligands (0.3-10 µg) caused dose-dependent antiallodynic effects. The comparison of the different substances revealed that EMD3 and EMD4 showed more prolonged antinociception than EM-2, and the effects of the highest dose of EMD4 were comparable to morphine, while EMD3 caused paralysis at this dose. The potency of the different ligands did not differ from EM-2. The results show that the derivatives of EM-2 have similar in vivo potency to the original ligand, but their effects were more prolonged suggesting that these structural modifications may play a role in the development of novel endomorphin analogues with increased therapeutic potential.

Interocular amplitude differences of multifocal electroretinograms obtained under monocular and binocular stimulation conditions.

PURPOSE: To compare the interocular amplitude differences of the multifocal electroretinograms (mfERGs) evoked by either monocular or binocular stimulation in healthy subjects with good vision. METHODS: Thirty-five subjects were included in the study. A Roland Consult RETIscan system was used. DTL electrodes were employed. First, the right and left eyes were stimulated separately, then, binocular stimulation was applied. The amplitudes of the scalar products were averaged over five concentric retinal regions (rings). RESULTS: The interocular amplitude differences were 21.55% (SD: ±12.72) under monocular conditions and 18.69% (SD: ±11.64) under binocular conditions. No significant differences were found between the amplitudes and variability values obtained under either monocular or binocular stimulation. CONCLUSIONS: Our results provided no evidence for the advantage of either binocular or monocular stimulating conditions in obtaining mfERGs. A considerable side difference was found between the mfERGs of the two eyes in almost all individual cases.

Etiprednol dicloacetate, a new soft glucocorticoid drug candidate. Development of chemistry.

During development of chemistry of the soft drug candidate etiprednol dicloacetate (BNP-166) 1) optimization studies on the three-step chemical synthesis resulted in a process that could be scaled-up to the kg level, 2) the impurity profile was determined, 3) synthetic routes were developed for the preparation of the radiolabeled target compound, and 4) a series of hydroxylated metabolites was prepared.

Characterization of degradation products of mometasone furoate.

Mometasone furoate (MF) is a synthetic glucocorticoid with anti-inflammatory activity, which is used for the treatment of topical skin disorders, allergic rhinitis and treatment of mild to moderate persistent asthma. The focus of this study is to examine the stability of MF in simulated lung fluid (SLF) and to clearly identify the structure of the degradation products of MF by MS and NMR analysis. Mometasone furoate degradation leads to the formation of two products, D1 and D2 with significant pH dependence. The half-lives for the conversion of MF to D1 and subsequent conversion of D1 to D2 at 37 degrees C in SLF were 1.3 and 4.8 h respectively. LC-MS and NMR analysis confirmed that D1 is 9,11-epoxide mometasone furoate while D2 represents a new chemical structure that shows cyclization within the C17-C21 region. The biological activity of these degradation products was assessed in rat lung glucocorticoid receptor binding studies. D1 showed 4 fold greater receptor affinity to glucocorticoid receptors compared to dexamethasone. However, the receptor affinity for D2 was a log order lower than that for dexamethasone. The instability of MF in SLF resulted in two degradation products, one of the degradation products showing glucocorticoid receptor activity, the other representing a new cyclized structure whose pharmacological properties have not been described. The biological significance of these degradation products is unknown.