ERYTHROKINETICS IN ALUMINIUM-TREATED ANIMALS

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Analysis of the morbidity with temporary incapacity for work among workers at the ship building and ship repairing company

Aim: To analyse the yearly morbidity with temporary in capacity among workers at the ship building and ship-repairing company as compared to norm groups after Batkis-Lekarev, previously defined values according to groups of disease - standard and registered illnesses of the population aged 18 and above in general hospitals in Varna district for the period 2004-2006. The comparative analysis for the period 2004-2006 shows that the negative tendencies in the morbidity with temporary in capacity for work have decreased during the past year. The structure of morbidity shows that the basic reasons for temporary in capacity for work of the working team as a whole are mainly diseases of the respiratory, musculo-skeletal system and diseases of the peripheral nervous system, which can be explained with the specific type of work. Special attention should be paid to the fact that the frequency of absences from work be cause of malignant growths grows double each following year. The progression of the sickness related to the peripheral nervous system, neuroses and eye diseases is similar. The presence of some of these diseases could be related directly with the working conditions.Scripta Scientifica Medica 2009; 41(2): 191-194

Sexually Dimorphic Effects of Histamine Degradation by Enteric Glial Histamine <i>N</i>-Methyltransferase (HNMT) on Visceral Hypersensitivity

Histamine is a neuromodulator that affects gut motility and visceral sensitivity through intrinsic and extrinsic neural pathways, yet the mechanisms regulating histamine availability in these pathways remain poorly understood. Here, we show that enteric glia contribute to histamine clearance in the enteric nervous system (ENS) through their expression of the enzyme histamine N-methyltransferase (HNMT). Glial HNMT expression was initially assessed using immunolabeling and gene expression, and functionally tested using CRISPR-Cas9 to create a Cre-dependent conditional Hnmt ablation model targeting glia. Immunolabeling, calcium imaging, and visceromotor reflex recordings were used to assess the effects on ENS structure and visceral hypersensitivity. Immunolabeling and gene expression data show that enteric neurons and glia express HNMT. Deleting Hnmt in Sox10+ enteric glia increased glial histamine levels and altered visceromotor responses to colorectal distension in male mice, with no effect in females. Interestingly, deleting glial Hnmt protected males from histamine-driven visceral hypersensitivity. These data uncover a significant role for glial HNMT in histamine degradation in the gut, which impacts histamine-driven visceral hypersensitivity in a sex-dependent manner. Changes in the capacity of glia to clear histamines could play a role in the susceptibility to developing visceral pain in disorders of the gut–brain interaction

New K50R mutant mouse models reveal impaired hypusination of eif5a2 with alterations in cell metabolite landscape

The eukaryotic translation initiation factor 5A1 (eIF5A1) and 5A2 (eIF5A2) are important proteins in a variety of physiological and pathophysiological processes and their function has been linked to neurodevelopmental disorders, cancer, and virology. Here, we report two new genome-edited mouse models, generated using a CRISPR-Cas9 approach, in which the amino acid residue lysine 50 is replaced with arginine 50 (K50R) in eIF5A1 or in the closely related eIF5A2 protein. This mutation prevents the spermidine-dependent post-translational formation of hypusine, a unique lysine derivative that is necessary for activation of eIF5A1 and eIF5A2. Mouse brain lysates from homozygous eif5a2-K50R mutant mice (eif5a2K50R/K50R) confirmed the absence of hypusine formation of eIF5A2, and metabolomic analysis of primary mouse dermal fibroblasts revealed significant alterations in the metabolite landscape compared to controls including increased levels of tryptophan, kyrunenine, pyridoxine, NAD, riboflavin, FAD, pantothenate, and CoA. Further supported by new publicly available bioinformatics data, these new mouse models represent excellent in vivo models to study hypusine-dependent biological processes, hypusination-related disorders caused by eIF5A1 and eIF5A2 gene aberrations or mRNA expression dysregulation, as well as several major human cancer types and potential therapies