Arachidonic acid (AA)-derived lipid mediators are called eicosanoids. Eicosanoids have emerged as key regulators of a wide variety of physiological responses and pathological processes, and control important cellular processes. AA can be converted into biologically active compounds by metabolism by cyclooxygenases (COX). Beneficial effect of COX-2 inhibitor celecoxib add-on therapy has been reported in early stage of schizophrenia. Moreover, add-on treatment of celecoxib attenuated refractory depression and bipolar depression. Further, the COX/prostaglandin E pathway play an important role in synaptic plasticity and may be included in pathophysiology in autism spectrum disorders (ASD). In this regard, plasma transferrin, which is an iron mediator related to eicosanoid signaling, may be related to social impairment of ASD. COX-2 is typically induced by inflammatory stimuli in the majority of tissues, and the only isoform responsible for propagating the inflammatory response. Thus, COX-2 inhibitors considered as the best target for Alzheimer’s disease.

We investigated, in 36 healthy volunteers, the effects of prednisone and ketotifen on recovery of lymphocyte j2-adrenoceptor density (determined by (-)-'"iodocyanopindolol binding) and responsiveness (assessed by lymphocyte cyclic AMP IcAMPI responses to 10 AtM (-)-isoprenaline) after desensitization by the p2-agonist terbutaline. Terbutaline (3 X 5 mg/d) decreased lymphocyte #2-adrenoceptor density by -40-50%; concomitantly, lymphocyte cAMP responses to 10 ,gM (-)-isoprenaline were significantly reduced. After withdrawal of terbutaline 2-adrenoceptor, density and responsiveness gradually increased, reaching predrug levels after 4 d.Prednisone (1 X 100 mg orally) accelerated ,f2-adrenoceptor recovery; only 8-10 h after administration of the steroid ,62-adrenoceptor density and cAMP responses to (-)-isoprenaline had reached values not significantly different from pretreatment levels. Similar effects were obtained with ketotifen (2 mg; thereafter 2 X 1 mg/d for 4 d): 24 h after application of the drug (32-adrenoceptor density and cAMP responses to (-)-isoprenaline had reached pretreatment levels. Furthermore, ketotifen simultaneously applied with terbutaline completely prevented terbutaline-induced decrease in lymphocyte i2-adrenoceptor density and responsiveness. Prednisone (1 X 100 mg orally) or ketotifen (2 mg; thereafter 2 X 1 mg/d for 2 d) had no significant influence on lymphocyte #2-adrenoceptor density in healthy volunteers not pretreated with terbutaline, but shifted the ratio high-to-low affinity state of the lymphocyte j#2-adrenoceptor toward high affinity state.We conclude that glucocorticoids as well as ketotifen can accelerate recovery of density and responsiveness of lymphocyte B2-adrenoceptors desensitized by long-term treatment with 2-agonists. Such an effect may have clinical implications for preventing tachyphylaxis of asthmatic patients against therapy with 02-agonists.

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Background: Positive associations have been observed between cardiovascular disease (CVD) and type 2 diabetes mellitus (DM), but their causal relationship has not been clarified. Nevertheless, guidelines from relevant medical societies recommend using cholesterol lowering medication (statin) for both types of patients. Medicines with several different action mechanisms have been developed, and the effectiveness of different lifestyle modifications has been studied extensively for the prevention of DM, which was successful in improving clinical marker status in relatively short-term treatments, but none have been shown to be effective in improving long-term outcomes (mortality from CVD and all causes). Summary: Statin-induced suppression of prenyl intermediates in the cholesterol biosynthetic pathway has been linked to stimulated atherosclerosis and heart failure. On the other hand, certain types of vegetable oil and hydrogenated oil shortened the survival of stroke-prone spontaneously hypertensive rats by decreasing platelet number, increasing hemorrhagic tendency and damaging kidney functions, which could not be accounted for by their fatty acid and phytosterol compositions. These vegetable oils and medicines such as statin and warfarin share, in part, a common mechanism to inhibit vitamin K₂-dependent processes, which was interpreted to lead to increased onset of CVD, DM, chronic kidney disease, bone fracture and even mental disorder. Impaired vitamin K₂-dependent processes by some types of vegetable oils and medicines, but not plasma high low density lipoprotein cholesterol, were proposed as the cause of CVD, DM and other lifestyle-related diseases. High n-6/n-3 fatty acid ratio of ingested foods, but not animal fats, was emphasized to be another risk factor for many of the diseases described above. Key Messages: To date, no randomized controlled trials (RCTs) have been performed to prove the above interpretation. However, the opposite types of RCT trials have been performed by increasing the intake of high-linoleic vegetable oils and reducing that of animal fats, which resulted in increased CVD and all-cause mortality. The amounts of these vegetable oils to exhibit adverse effects in animal studies are not huge (<6 energy %), which should not be overlooked nor disregarded.

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