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A B S T R A C T

Several lines of evidence suggest that exposures to Endocrine Disrupting Chemicals (EDCs) such as pesticides increase the risks of neuropsychiatric disorders. Despite extended residual persistence of dichlorodiphenyltrichloroethane (DDT) in the environment, the mechanisms of perinatal actions of DDT that could account for adult-onset of depression are largely unknown. This study demonstrated the isomer-specific induction of depressive-like behavior and impairment of Htr1a/serotonin signaling in one-month-old mice that were prenatally exposed to DDT. The effects were reversed by the antidepressant citalopram as evidenced in the forced swimming (FST) and tail suspension (TST) tests in the male and female mice. Prenatally administered DDT accumulated in mouse brain as determined with gas chromatography and tandem mass spectrometry, led to global DNA hypomethylation, and altered the levels of methylated DNA in specific genes. The induction of depressive-like behavior and impairment of Htr1a/serotonin signaling were accompanied by p,p’-DDT-specific decrease in the levels of estrogen receptors i.e. ESR1 and/or GPER1 depending on sex. In contrast, o,p’-DDT did not induce depressive-like effects and exhibited quite distinct pattern of biochemical alterations that was related to aryl hydrocarbon receptor (AHR), its nuclear translocator ARNT, and ESR2. Exposure to o,p’-DDT increased AHR expression in male and female brains, and reduced expression levels of ARNT and ESR2 in the female brains. The evolution of p,p’-DDT-induced depressive-like behavior was preceded by attenuation of Htr1a and Gper1/GPER1 expression as observed in the 7-day-old mouse pups. Because p,p’-DDT caused sex- and age-independent attenuation of GPER1, we suggest that impairment of GPER1 signaling plays a key role in the propagation of DDT-induced depressive-like symptoms.

ANGPTL8 as a new determinant of type 2 diabetes remission after bariatric surgery

Posted by M Ejarque, M Borlaug, N Vilarrasa, et al. on 2017-03-22 19:24:23

ABSTRACT                                                                                                                                                                                                                             This work aimed to explore the link between ANGPTL8 and weight loss after metabolic surgery. In the cross-sectional study (n=100), circulating ANGPTL8 concentrations were significantly lower in morbidly obese than in lean subjects, and strikingly lower in morbidly obese patients with type 2 diabetes mellitus (T2DM). Conversely, ANGPTL8 expression in subcutaneous adipose tissue (SAT) was higher in morbidly obese patients, particularly in those with T2DM, whereas its expression in visceral adipose tissue (VAT) was unchanged. The main predictors for circulating levels of ANGPTL8 were BMI and T2DM, whereas ANGPTL8 expression in SAT was determined by the presence of T2DM. The prospective cohort studies before and one year after bariatric surgery in morbidly obese patients with (n=45) and without (n=30) T2DM, revealed a significant increase of circulating ANGPTL8 levels one year after bariatric surgery. Intriguingly, this increment, which was predicted by basal ANGPTL8 concentrations, appeared as a determinant of T2DM remission. In conclusion, circulating ANGPTL8 levels have an inverse relationship with SAT expression. Low basal levels of ANGPTL8 rebound after bariatric surgery. The increment in ANGPTL8 concentrations at one month of follow-up after weight loss emerged as a significant predictor of the T2DM remission at one year of follow-up.

sNCAM as a specific marker of peripheral demyelination

Posted by A Niezgoda, S Michalak, J Losy, et al. on 2017-03-22 18:58:54

Abstract                                                                                                                                                                                                                             Adhesion molecules are involved in nerve growth, synaptic plasticity and myelin formation and maintenance process. Neural cell adhesion molecule (CD56 or NCAM) seems to play a crucial role in all the above-mentioned events. Having found polysialylated NCAM increased re-expression on demyelinated axons within multiple sclerosis plaques we assessed soluble NCAM (sNCAM) in sera of patients with various types of peripheral nerve affections – demyelinating, axonal “inflammatory”, axonal metabolic polyneuropathies and healthy controls. These data were compared with the clinical state using Overall Neuropathy Limitations Scale (ONLS) and nerve conduction studies. We found significantly increased sNCAM concentration in demyelinating polyneuropathies in comparison to axonal group and healthy controls as well as significantly increased sNCAM level in axonal group in comparison to healthy subjects. We also found high positive correlation between sNCAM and ONLS and strong negative correlation between sNCAM level and the lowest conduction velocity (Vmin) found in a patient. We conclude that sNCAM might be thought as specific marker of peripheral nerve demyelination and as a sensitive marker of peripheral nerve injuries.

Protective effect of cardamonin against acetic acid-induced ulcerative colitis in rats

Posted by AA Ali, ENAA Haleem, SA Khaleel, et al. on 2017-03-28 00:06:19

A B S T R A C T                                                                                                                                                                                                 Background: Ulcerative colitis (UC) is an inflammatory bowel disease with significant morbidity. Cardamonin is a natural chalcone derivative with considerable anti-inflammatory activity. Herein, the potential protective effect of cardamonin against UC was tested in a rat model.

Methods: Rats were given 10 or 30 mg/kg/day of cardamonin orally for 14 days before induction of UC. On the 14th day of treatment, UC was induced by intrarectal instillation of 2 ml 3% acetic acid. Twenty four h after acetic acid instillation, rats were sacrificed and colons were analyzed by macroscopic and histopathological examination. Colon lipid peroxidation was examined by biochemical evaluation of malondialdehyde (MDA). Myeloperoxidase (MPO), iNOS, NF-kB, TNFa levels were measured by ELISA. Moreover, caspase-3 and COX-2 were assessed by immunohistochemical analysis.

Results: Cardamonin at 10 and 30 mg/kg decreased the disease activity index and macroscopic damage index scores, and significantly reduced histopathological deterioration. Additionally, cardamonin reduced levels of MPO, iNOS, NF-kB, TNFa and MDA (p < 0.05). Immunohistochemistry revealed downregulation of COX-2 and caspase-3 in groups treated with cardamonin.

Conclusion: Cardamonin has a protective effect against acetic acid-induced colitis. This effect may be due to reducing inflammation, oxidative stress and apoptosis.

A B S T R A C T

Aim: Epidemiological studies suggest a possible link between osteoporosis and cardiovascular diseases. Mevalonate pathway was pointed to as a part of this link. This study was done to investigate the effects of Alendronate (Al) and Simvastatin (Sim), both act on the mevalonate pathway, on osteoporosis, dyslipidemia and atherosclerotic changes in ovariectomized (OVX) rats fed high fat diet (HFD). Main methods: 60 female albino rats were equally divided into 5 groups: control sham, OVX-HFD untreated, OVX HFD treated with Al (3 mg/kg/d) or/and Sim (6 mg/kg/d). Treatments were taken for 4 weeks by oral gavage and were started 8 weeks after ovariectomy. Results: OVX-HFD untreated group exhibited a significant negative alteration in lipid profile and on different bone markers e.g. alkaline phosphatase, hydroxyproline and osteocalcin. A significant increase in body weights and on serum levels of TNFa, iNOS and leptin were also found compared to control sham group. Vascular reactivity studies revealed a significant decrease in effective concentration 50 of phenylephrine and in acetylcholine% of relaxation and a significant increase in maximum contractile response of phenylephrine. The atherosclerotic and osteoporotic changes were further confirmed histopathologically. Treatment of OVX-HFD with Al or/and Sim significantly improved these deleterious effects compared to OVX-HFD untreated group. Comparing the combination therapy versus the monotherapy exhibited a significant improvement in different tested parameters which came in favor of the combination therapy. Conclusion: Al and Sim have anti-osteoporotic, anti-dyslipidemic and anti-atherosclerotic beneficial effects. Their combination has more promising effects in treatment of osteoporosis, dyslipidemia and atherosclerosis.

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