Age-related motor and catecholomine alterations in mice on levodopa supplemented diet

Old mice reared on regular diet show reduced motor activity, decreased basal adenylate cyclase, and increased MAO activities compared to adults. Brain DDC and COMT activities, DA, NE levels and DA-stimulated adenylate cyclase remained unchanged. By contrast, mice fed levodopa for life did not develop decreased motor activity with aging, lived about 50% longer, had slightly elevated whole brain DA and NE levels and failed to develop the expected rise in MAO activity with aging. Levodopa did not alter the number of dopaminergic and muscarinic cholinergic receptors or the adenylate cyclase activity in the striatum during aging. On levodopa, hepatic and renal DA, dopa, and HVA increased but the latter two returned to basal levels by mid life. In liver, DDC was unchanged but MAO tended to be higher in levodopa-fed mice. Thus, motor impairment is an age-related phenomenon in mice associated with selective alterations in brain dopaminergic systems, which may be prevented by dietary levodopa. Extracerebral tissues, through possibly adaptive metabolic mechanisms, play a significant role in regulating brain catecholamines during chronic administration of large doses of levodopa.     

Origin of hydrogen in methane produced by Methanobacterium thermoautotrophicum.

The production of deuterated methane by Methanobacterium thermoautotrophicum in H2O-D2O mixtures was examined by high-resolution mass spectrometry. The hydrogen in the methane arose solely from water and not from hydrogen gas. Hydrogen gas served only as an electron source in methanogenesis. A whole-cell product isotope discrimination of 1.5 favoring hydrogen over deuterium was observed in methane production in 81 atom% deuterated water. The distribution of deuterated methane species is described by a simple model of the overall reaction.     

Fluorometric assay for 1-deoxyfructose

A sensitive fluorometric assay has been developed for the measurement of 1-deoxyfructose in biological fluids. Samples containing 1-deoxyfructose are incubated with an equal volume of 0.01 m 3,5-diaminobenzoic acid in 5.0 m phosphoric acid in a boiling-water bath for 15 min. The fluorescent product has an emission maximum at 502 nm and an excitation maximum at 396 nm. Fluorescence is proportional to 1-deoxyfructose concentrations over a range from 0.002 to 1.0 mm. The method can be used to detect as little as 0.03 μmol of 1-deoxyfructose in deproteinized blood and in urine and no interference is observed with glucose, fructose, pyruvate, or ketone bodies. The method will also detect 1-deoxytagatose, 2-deoxyaldohexoses, and -pentoses, 2,5-anhydromannose, and a number of 2-, 3-, 4-, and 5-mono- or bis(hydroxymethyl)furans. The fluorescence properties of the products formed from all of the above compounds are similar suggesting structural similarities of the adducts formed and possible mechanistic similarities of the reactions involved.     

Studies on the mechanism of suppression of delayed hypersensitivity by the antischistosomal compund niridazole.

Niridazole given in a single oral dose of 100 mg/kg to guinea pigs sensitized to ortho-chlorobenzoyl chloride-bovine gamma-globulin (OCB-BGG) regularly abolished delayed cutaneous reactivity. Little effect was observed, however, when cells from these animals were tested in vitro with either direct or indirect assays for migration inhibitory factor (MIF). On the other hand, sera taken from nonsensitized guinea pigs after they had received 100 mg/kg of niridazole markedly diminished antigen-induced inhibition of migration of sensitized peritoneal exudate cells in vitro. The immunosuppressive effects of such sera could not be produced by niridazole itself, thereby suggesting an effect of niridazole metabolites. This suppressive activity was readily removed from the serum by dialysis. The active serum blocked the production of MIF by sensitized lymph node cells but did not affect the action of preformed MIF on macrophages. The effect of this serum was reversible; lymph node cells incubated for 24 hr with active serum, then washed and reincubated with antigen in normal serum, produced normal amounts of MIF. These studies suggest that metabolites of niridazole, but not the parent compound itslef, suppress delayed hypersensitivity in guinea pigs and prevent MIF production by lymphocytes without affecting the macrophage response to MIF.     

Influence of induced delayed parturition on fetal survival in pigs

Pregnancy was prolonged as long as 23 days in gilts receiving daily oral 6-methyl-17 acetoxy-progesterone (MAP) at a level of 0.27–0.41 mg/kg body weight. These levels of progestin did not effect fetal welfare if administered throughout gestation and did not interfere with normal parturition and live litter size if treatment was terminated at the calculated term date which corresponded with the day of milk let-down. The initiation of milk let-down was not effected by treatment. Severe fetal death occurred in all gilts delivering young naturally during prolonged pregnancy and in gilts whose litters were delivered surgically 12 days or more after milk let-down. Mean live litter size was normal in gilts whose young were delivered surgically within 11 days of milk let-down. Fetal death at 12 days or more of prolonged pregnancy was attributed to placental insufficiency. The reproductive parameters studied were unaffected by the addition of 0.001 to 0.013 mg/kg body weight of diethylstilbestrol (DES) to the progestin treatment or the use of this agent alone.     

Colony aging affects the reproductive performance of Swiss Webster females used as recipients for embryo transfer

The objective was to evaluate the influence of colony aging in a Swiss Webster (SW) outbred stock used as recipients for embryo transfer. In the first study, a retrospective analysis was performed throughout several generations during a 38-month period in 2,398 embryos transferred to 108 SW recipients. A decrease in the percentage of live pups from transferred embryos was found at the end of the period. Impairment occurred due to the incidence of maternal cannibalism that increased from 0% to 67-100% (P<0.05), while pregnancy rate (pregnant/transferred recipients) and number of pups per delivered female were not affected throughout the period (P=NS). A following study was carried out to compare the reproductive performance of SW stock vs. B6D2F1 hybrid females in a 5-year interval. The study was conducted on a total of 893 embryos transferred to 40 females (20 SW and 20 B6D2F1) in Year #1, and 514 embryos transferred to 30 females (15 SW and 15 B6D2F1) in Year #5. No cases of maternal cannibalism were found on Year #1 in any of the strains (0/10 and 0/10). However, an incidence of 44,4% (4/9) was seen on Year #5 for SW, while for B6D2F1 the incidence was 0% (0/12) (P<0.05). Further examination of the uterus showed endometrial cysts and abnormal implantation sites in SW on Year #5 but not in B6D2F1 females. In conclusion, this study reports an impairment of the reproductive performance of an early aged SW outbred stock colony mainly due to the occurrence of maternal cannibalism. This finding has important implications for embryo transfer programs conducted in mouse facilities.     

Elabela/toddler: New peptide with a promising future in cancer diagnostic and therapy

Elabela/toddler is the second endogenous ligand recently identified after Apelin, that binds to the G protein-coupled receptor APJ. Elabela is a 54-amino acid peptide initially identified in fish and human genomes and classified as noncoding. This precursor can be cleaved to shorter sequences (32, 21, and 11 amino acids), which bind and activate APJ, and can be blocked by APJ antagonists. Contrary to Apelin and APJ, widely distributed in organs and tissues, Elabela expression is more restricted, and different studies have revealed the potential role of Elabela in cancers. This review summarizes the current studies focusing on the role of Elabela in different cancers.