Development of a series of novel o-phenylenediamine-based indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors

A novel series of o-phenylenediamine-based inhibitors of indoleamine 2,3-dioxygenase (IDO) has been identified. IDO is a heme-containing enzyme, overexpressed in the tumor microenvironment of many cancers, which can contribute to the suppression of the host immune system. Synthetic modifications to a previously described diarylether series resulted in an additional degree of molecular diversity which was exploited to afford compounds that demonstrated significant potency in the HeLa human cervical cancer IDO1 assay..     

TETANUS—The Use of Human Hyperimmune Globulin in Treatment

Twenty patients with tetanus were treated with human hyperimmune globulin. The mortality rate in the series was 30 per cent. No complications due to the use of this antitoxin were observed.     

The inter-ovarian distribution of dominant follicles is influenced by the location of the corpus luteum of pregnancy.

The objective was to characterise the distribution of dominant ovarian follicles in the early post-partum period in relation to the side of the preceding pregnancy and its relationship with the left and right ovaries. Primiparous cows were enrolled over a 2-year period (n = 33 in Year 1 and n = 28 in Year 2). Ovarian follicles were observed daily by trans-rectal ultrasonography commencing within 9 days of calving. Dominant follicles (DF) were described as occurring on the ovary ipsilateral to the CL of preceding pregnancy (ipsilateral ovary of pregnancy, IOP) or contralateral to the CL of the preceding pregnancy (contralateral ovary of pregnancy, COP), and as occurring on the left or right ovary. Results in Year 1 were analysed for the effect of breed (Friesian n = 15; Jersey n = 18). There was a bias towards the COP for the first DF post-partum in both breeds (DF1; 70%; p<0.05). A breed interaction was observed with the second DF post-partum with a bias towards the COP in the Friesian (93%; p<0.05); but not the Jersey animals (50%). In Year 2, all cows were Friesians, and there was again a biased distribution of the DF1 towards the COP (89%; p<0.05) and for the combined distribution of the first three DF post-partum (76%; p<0.05) as well as the first ovulatory follicle (71%; p<0.05). A comparison of the pooled data for the location of the DF1 from both years showed that only one DF1 was observed on a left ovary in the 29 cases where the preceding pregnancy was also on the left side. This study demonstrated a bias in the distribution of DL in the early post-partum period towards the ovary on the side opposite that of the preceding pregnancy as well as towards the right side.     

Sensitization of anorexia and locomotion induced by chronic administration of ephedrine in rats.

Repeated daily administration of the sympathomimetic agent ephedrine (EPH) leads to an augmentation (sensitization) of locomotor activity in rats. The present experiments examined the impact of repeated administration of the (-)- and (+)-EPH enantiomers on feeding in rats to assess whether the anorexic activity of EPH exhibits tolerance or sensitization during chronic exposure and whether the time course of these effects follows that observed in studies of locomotion. Adult male rats were injected once daily for 12 days with either vehicle or 5, 10 or 20 mg/kg (-)-EPH or with 10 or 20 mg/kg (+)-EPH. Horizontal locomotion and diet consumption were assessed for 60 min in an activity chamber. Suppression of feeding and the induction of locomotion were augmented over the first four days of administration of either 10 mg/kg or 20 mg/kg of the (-)-EPH enantiomer. In contrast, repeated administration of 20 mg/kg (+)-EPH resulted in augmentation of appetite suppression but not locomotion. These results confirm and extend the phenomenon of locomotor and feeding sensitization for ephedrine, but suggest that these effects may differ for the two enantiomers of ephedrine.     

Phylogenetic utility of the nuclear gene arginine decarboxylase: an example from Brassicaceae

Arginine decarboxylase (ADC) is an important enzyme in the production of putrescine and polyamines in plants. It is encoded by a single or low-copy nuclear gene that lacks introns in sequences studied to date. The rate of Adc amino acid sequence evolution is similar to that of ndhF for the angiosperm family studied. Highly conserved regions provide several target sites for PCR priming and sequencing and aid in nucleotide and amino acid sequence alignment across a range of taxonomic levels, while a variable region provides an increased number of potentially informative characters relative to ndhF for the taxa surveyed. The utility of the Adc gene in plant molecular systematic studies is demonstrated by analysis of its partial nucleotide sequences obtained from 13 representatives of Brassicaceae and 3 outgroup taxa, 2 from the mustard oil clade (order Capparales) and 1 from the related order Malvales. Two copies of the Adc gene, Adc1 and Adc2, are found in all members of the Brassicaceae studied to data except the basal genus Aethionema. The resulting Adc gene tree provides robust phylogenetic data regarding relationships within the complex mustard family, as well as independent support for proposed tribal realignments based on other molecular data sets such as those from chloroplast DNA.