K-ras mutations, rectal crypt cells proliferation, and meat consumption in patients with left-sided colorectal carcinoma.

It has been suggested that N-nitroso compounds derived from meat may increase the risk of K-ras mutations in the human colon. We sought evidence of associations between red meat consumption, frequency and type of K-ras mutations in resected tumours, and the rate of crypt cell proliferation (CCP) in the normal mucosa of patients with left-sided colorectal carcinoma. Meat consumption was assessed by food frequency questionnaire, and CCP was determined in rectal biopsies obtained prior to surgery. K-ras mutations in the resected tumours were determined using a PCR-based oligonucleotide hybridization assay. Fifteen K-ras mutations were detected in tumours from 43 patients; 13/15 in codon 12, 3/15 in codon 13, and 1/15 in both codons 12 and 13. All mutations were G-->A or G-->T transitions. There was no statistically significant difference between intakes of red meat in patients with a K-ras mutation (92.4 +/- 9.7 g/day) and those without (82.3 +/- 7.7 g/day). Rectal CCP was significantly higher in patients than in healthy controls, but there was no correlation with meat consumption or K-ras mutation. These data do not support the hypothesis that meat consumption is a risk factor for acquisition of K-ras mutations during colorectal carcinogenesis.     

18F-sodium fluoride PET/CT provides prognostic clarity compared to calcium and Framingham risk scoring when addressing whole-heart arterial calcification

European Journal of Nuclear Medicine and Molecular Imaging - To investigate the benefit of utilizing 18F-sodium fluoride (NaF) PET/CT over calcium and Framingham scoring for potential preventative...     

Combined 1-Deoxynojirimycin and Ibuprofen Treatment Decreases Microglial Activation,Phagocytosis and Dopaminergic Degeneration in MPTP-Treated Mice

Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson’s disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH⁺) and microglia markers (Iba-1⁺; CD68⁺) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68⁺/ Iba-1⁺ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.

     

Metabolic actions of FGF21: molecular mechanisms and therapeutic implications

Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF family that functions as an endocrine factor. In obese animals, elevation of plasma FGF21 levels by either pharmacological or genetic approaches reduces body weight, decreases hyperglycemia and hyperlipidemia, alleviates fatty liver and increases insulin sensitivity. FGF21 exerts its pleiotropic metabolic effects through its actions on multiple targets, including adipose tissue, liver, brain and pancreas. The expression of FGF21 is under the control of both peroxisome proliferator-activated receptor gamma (PPARγ) and peroxisome proliferator-activated receptor alpha (PPARα). A growing body of evidence suggests that the metabolic benefits of these two nuclear receptors are mediated in part by induction of FGF21. In humans, plasma levels of FGF21 are elevated in obese subjects and patients with type 2 diabetes, but are reduced in patients with autoimmune diabetes. This review summarizes recent advances in understanding the physiological roles of FGF21 and the molecular pathways underlying its actions, and also discusses the future prospective of developing FGF21 or its agonists as therapeutic agents for obesity-related medical complications.     

First-case postpartum psychoses in Eastern Turkey: a clinical case and follow-up study.

OBJECTIVE: The aim of this study was to investigate the clinicodemographic features and long-term course of postpartum psychosis (PPP). METHOD: A total of 64 in-patients with psychotic postpartum disorder, who were admitted for the first time to a psychiatry clinic, were reexamined retrospectively and then compared with 64 control patients. Follow-up investigation was carried out either by interviewing the patients personally or with the help of general practitioners (GPs). All patients were rediagnosed according to DSM-IV. RESULTS: The majority of PPP patients were young, married, primiparae, had a low educational level and were living in rural areas. The mean onset time of PPP after delivery was 3.62 weeks. More than 75% of the patients with PPP had further psychotic episodes during the follow-up period of 11 years; 42% of the puerperal cases were diagnosed as schizophrenia at the follow-up investigation, and 59.3% of the patients had confuso-oneiroid syndrome. CONCLUSION: These findings, unlike those of the Western studies, demonstrate that PPP is not uniform in different populations.