Is There a FADS2-Modulated Link between Long-Chain Polyunsaturated Fatty Acids in Plasma Phospholipids and Polyphenol Intake in Adult Subjects Who Are Overweight?

Dietary polyphenols promote cardiometabolic health and are linked with long-chain polyunsaturated fatty acids in plasma phospholipids (LC-PUFA). The FADS2 polymorphisms are associated with LC-PUFA metabolism and overweight/obesity. This 4-week study examined the link between polyphenol intake, FADS2 variants (rs174593, rs174616, rs174576) and obesity in 62 overweight adults (BMI ≥ 25), allocated to consume 100 mL daily of either: Aronia juice, a rich source of polyphenols, with 1177.11 mg polyphenols (expressed as gallic acid equivalents)/100 mL (AJ, n = 22), Aronia juice with 294.28 mg polyphenols/100 mL (MJ, n = 20), or nutritionally matched polyphenol-lacking placebo as a control (PLB, n = 20). We analyzed LC-PUFA (% of total pool) by gas chromatography and FADS2 variants by real-time PCR. Four-week changes in LC-PUFA, BMI, and body weight were included in statistical models, controlling for gender and PUFA intake. Only upon AJ and MJ, the presence of FADS2 variant alleles affected changes in linoleic, arachidonic, and eicosapentaenoic acid (EPA). Upon MJ treatment, changes in EPA were inversely linked with changes in BMI (β= −0.73, p = 0.029) and weight gain (β= −2.17, p = 0.024). Only in subjects drinking AJ, the link between changes in EPA and anthropometric indices was modified by the rs174576 variant allele. Our results indicate the interaction between FADS2, fatty acid metabolism, and polyphenol intake in overweight subjects.     

Opposite effects of ethanol and nitrendipine on nicotine-induced emesis and convulsions.

The effects of ICV injections were investigated in unanesthetized cats of ethanol alone and in combination with the dihydropyridine calcium antagonist, nitrendipine, on emesis and the convulsions produced by nicotine, which was similarly injected by the ICV route. In the first series of experiments, short lasting convulsions and emesis were the most prominent symptoms after the ICV injection of nicotine in a dose of 1.0 mg. In the second series of experiments the pretreatment of cats with ethanol given ICV in doses of 0.03, 0.2, and 0.3 ml reduced the emesis and prevented the convulsions induced by 1.0 mg dose of ICV nicotine. In the third series of experiments, the ICV injection of nitrendipine in doses of 0.024, 0.16, and 0.24 mg incorporated in the solution of ethanol, given in volumes of 0.03, 0.2, and 0.3 mt, respectively, blocked emesis but not the convulsions induced by the 1.0 mg dose of nicotine given ICV. The results suggest, therefore, that at least two different mechanisms underlie these phenomena. First, the synergistic effects at the neuronal nicotinic ionophores in the brain would act to underlie the antagonistic action of ethanol and nitrendipine on the emetic response. Second, conformational changes brought about by ethanol at voltage-dependent calcium channels in the brain may antagonize the inhibitory effect of the dihydropyridine calcium antagonist, producing the reversal of convulsions.     

The pharmacology of aggressive behavioural phenomena elicited by muscarine injected into the cerebral ventricles of conscious cats

Atropine and scopolamine, injected intraventricularly, abolished typical emotional behaviour with aggression and autonomic and motor phenomena, as well as with clonic-tonic convulsions of intraventricularly injected muscarine. On the other hand, adrenergic and dopaminergic blocking agents, antihistamines, 5-hydroxytryptamine antagonists, antiepileptic drugs, and 5-hydroxytryptamine, administered intraventricularly, failed to antagonize the gross behavioural effects of intraventricular muscarine. However, ganglionic and sometimes neuromuscular blocking agents, as well as catecholamines and histamine injected intraventricularly, antagonized the emotional behaviour with aggression and depressed the autonomic and motor phenomena of small doses of intraventricular muscarine. In addition, emotional behaviour with aggression and autonomic and motor phenomena evoked by high doses of intraventricular muscarine were resistant to these antagonists administered intraventricularly. From these experiments it is concluded that the sites activated by muscarine in the CNS producing aggressive behaviour have the following characteristics: in high doses muscarine acted on muscarinic cholinoceptive sites, while in small doses it activated the cholinoceptive sites having muscarinic and nicotinic characteristics. Finally, the ability of single intraventricular injections of muscarine to trigger and to maintain the long-lasting gross behavioural effects cannot be ascribed to a rapid detonator transmission, but rather to an action that differs from a conventional transmitter function.     

On the origin of schizophrenia: Testing evolutionary theories in the post‐genomic era

Considering the relatively high heritability of schizophrenia and the fact that it significantly reduces the reproductive fitness of affected individuals, it is not clear how the disorder is still maintained in human populations at a disproportionally high prevalence. Many theories propose that the disorder is a result of a trade‐off between costs and benefits of the evolution of exclusively human adaptations. There have also been suggestions that schizophrenia risk alleles are accompanied with increase in fitness of affected persons or their relatives in both past and current social contexts. The discoveries of novel schizophrenia‐related genes and the advancements in comparative genomics (especially comparisons of the human genome and the genomes of related species, such as chimpanzees and extinct hominids) have finally made certain evolutionary theories testable. In this paper, we review the current understanding of the genetics of schizophrenia, the basic principles of evolution that complement our understanding of the subject, and the latest genetic studies that examine long‐standing evolutionary theories of schizophrenia using novel methodologies and data. We find that the origin of schizophrenia is complex and likely governed by different evolutionary mechanisms that are not mutually exclusive. Furthermore, the most recent evidence implies that schizophrenia cannot be comprehended as a trait that has elevated fitness in human evolutionary lineage, but has been a mildly deleterious by‐product of specific patterns of the evolution of the human brain. In other words, novel findings do not support previous hypotheses stating that schizophrenia risk genes have an evolutionary advantage.     

Successful use of sirolimus for refractory atrial ectopic tachycardia in a child with cardiac rhabdomyoma

Cardiac rhabdomyomas are common in tuberous sclerosis. We report a child who developed rhabdomyoma related arrhythmia refractory to antiarrhythmic drug therapy. Reversion of the atrial ectopic tachycardia was achieved with mammalian target of rapamycin pathway (mTOR) inhibitor sirolimus. As per our knowledge, this is the first time that sirolimus has been successfully used in this setting.     

Could Spindle Cell Lung Carcinoma be Considered and Treated as Sarcoma, According to its Clinical Course, Morphology, Immunophenotype and Genetic Finding?

The actual nature of spindle cell carcinoma has been debated extensively because of its rarity. It carries a poor prognosis, even when early-stage disease is diagnosed and resected. In view of the rarity and the significance of the histological diagnosis, we report a patient with rapidly progressing spindle cell lung carcinoma with soft tissue metastasis. Diagnosis was confirmed by immunohistochemistry finding. Analysis of the TP53 gene mutations by polymerase chain reaction and DNA sequencing revealed insertion of single thymine resulting in frameshift mutation in the exon 8. Prognosis of spindle cell lung carcinoma might be determined by the sarcoma component of the tumor and, based on that, we wonder if this type of lung carcinoma could be followed-up and treated by strategies for soft tissue sarcomas, because of its rapid, sarcomatous type of growth, beside the properly lung carcinoma oncological treatment.