Vascular endothelial growth factor-C and -D are involved in lymphangiogenesis in mouse unilateral ureteral obstruction.

Lymphatic remodeling in inflammation has been found in tracheal mycoplasma infection, human kidney transplant, skin inflammation, peritonitis, and corneal inflammation. Here we investigated lymphangiogenesis in fibrotic area in unilateral ureteral obstruction, a model of progressive renal fibrosis, and evaluated the roles of vascular endothelial growth factor (VEGF)-C and -D in the obstructed kidney. Compared to sham-operated mice, the number of LYVE-1-positive lymphatic vessels, the proliferation of LYVE-1-positive lymphatic endothelial cells, along with VEGF-C and -D mRNA expression were all significantly increased following ureteral obstruction. Depletion of macrophages with clodronate decreased lymphangiogenesis in the obstructed kidney. VEGF-C expression was higher in M2- than in M1-polarized macrophages from bone marrow-derived macrophages, and also increased in Raw 264.7 or renal proximal tubule cells by stimulation with TGF-ß1 or TNF-α. VEGF-D reversed the inhibitory effect of TGF-ß1 on VEGF-C-induced migration, capillary-like tube formation, and proliferation of human lymphatic endothelial cells. Additionally, the blockade of VEGF-C and VEGF-D signaling decreased obstruction-induced lymphangiogenesis. Thus, VEGF-C and VEGF-D are associated with lymphangiogenesis in the fibrotic kidney in a mouse model of ureteral obstruction.

Drug Information Association Pharmacovigilance and Risk Management Strategies 2017: Overview of the Generic Drug Program and Surveillance.

The US Food and Drug Administration's (FDA's) generic drug program has dramatically increased the availability of affordable, high quality generic drugs. The foundation of generic drug approvals is a two-tiered regulatory framework of pharmaceutical equivalence and bioequivalence. Intrinsic to both of these is consideration of the clinical relevance of formulation and bioequivalence data to support an inference of therapeutic equivalence, based on clear evidence that there are no significant differences between the generic drug and the brand name drug. These analyses allow FDA to determine that the generic drug will perform in the patient in the same way, with the same safety and efficacy profiles, as the brand name drug. Allowable differences and the precise definition of what is meant by equivalence are critical to maintaining the quality, efficacy, and safety of generic drugs. The FDA Office of Generic Drugs' (OGD's) Clinical Safety Surveillance Staff (CSSS) has developed investigative processes that complement the broader FDA safety efforts that focus on the potential impact of allowable differences and equivalence determinations for generic drugs. Two recent examples of the CSSS's processes include a clonidine transdermal system and lansoprazole oral disintegrating tablet. Ongoing efforts of the CSSS result in improvements to the FDA's review processes and the quality of generic drugs in the US market.

Pseudonocardia carboxydivorans sp. nov., a carbon monoxide-oxidizing actinomycete, and an emended description of the genus Pseudonocardia.

A bacterial strain, Y8(T), capable of oxidizing carbon monoxide, was isolated from a soil sample collected from a roadside in Seoul, Korea. On the basis of 16S rRNA gene sequence similarity analyses, strain Y8(T) was shown to belong to the genus Pseudonocardia and was related most closely to the type strain of Pseudonocardia alni (99.6 % similarity). The cells were aerobic and stained Gram-positive, with white aerial mycelium and brown substrate mycelium. The predominant fatty acids were 16 : 0 iso and 16 : 1 iso. The cell-wall peptidoglycan of strain Y8(T) contained meso-diaminopimelic acid. The DNA G+C content was 77 mol%. Strain Y8(T) contained MK-9 as the major menaquinone, which is different from the major menaquinone reported previously in the genus Pseudonocardia, MK-8(H(4)). DNA-DNA relatedness between strain Y8(T) and the type strains of P. alni and Pseudonocardia antarctica was respectively 10 and 63 %. Based on phylogenetic, morphological and chemotaxonomic evidence, it is proposed that strain Y8(T) (=KCCM 42678(T) =JCM 14827(T)) be classified as the type strain of a novel species, Pseudonocardia carboxydivorans sp. nov. An emended description of the genus Pseudonocardia is also presented.