Milk-based culture of Penicillium camemberti and its component oleamide affect cognitive function in healthy elderly Japanese individuals: a multi-arm randomized, double-blind, placebo-controlled study

Dairy products and fermented foods have a reported association with maintained cognitive function. Camembert cheese, a dairy product fermented by the white mold Penicillium camemberti, has also been shown to enhance cognitive function in vivo. Oleamide, derived from the fermentation of the white mold, is a candidate for an active component, and expected to improve both cognitive function and sleep conditions. Thus, this study investigated whether the milk-based culture of white mold (MCW), and oleamide, could improve cognitive function and sleep state clinically. A multi-arm randomized, double-blind, placebo-controlled trial was conducted in Tokyo, Japan. 60 healthy Japanese individuals aged 50–75 who were aware of their cognitive decline were randomly and equally divided into three groups of 20 participants using computer-generated random numbers. Participants took either MCW (equivalent to 60 μg/day of oleamide), 60 μg/day of oleamide, or placebo capsules for 12 weeks. Serum BDNF, cognitive function by Cognitrax as primary and MCI Screen as secondary outcome, and sleep status using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) were assessed before and after intervention. The participants, outcome assessors and analysts, and research assistants were blinded to the group assignment. Of the 60 participants, 58 completed the study and were analyzed. No adverse events related to test foods were observed. The placebo group showed a negative rate of change in serum BDNF (−10.5% ± 19.7%), whereas the MCW and oleamide groups showed positive changes (2.0% ± 27.1% and 1.3% ± 13.5%, respectively). Cognitrax scores increased after 12 weeks in all groups. Conversely, the MPI score of the MCI Screen demonstrated a significant improvement in the MCW and oleamide groups compared to the placebo group (p = 0.013 and p < 0.001, respectively). The subscales, immediate free recall and delayed free recall, also significantly increased in them compared to the placebo group. Although PSQI-J revealed no significant differences among groups, the MCW and oleamide groups showed significant improvement after intervention in overall score, subjective sleep quality, and sleep latency. Our results suggest that MCW and its component, oleamide, are safe and contribute to maintaining cognitive functions, particularly short-term and working memory, and improving sleep state.Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000054792, identifier UMIN-CTR UMIN000048084

Drug efficacy against aortic dissection

Objective: Aortic dissection is a life-threatening disease. At present, the only therapeutic strategies available are surgery and antihypertensive drugs. Moreover, the molecular mechanisms underlying the onset of aortic dissection are still unclear. We established a novel aortic dissection model in mice using pharmacologically induced endothelial dysfunction. We then used the Japanese Adverse Drug Event Report database to investigate the role of pitavastatin in preventing the onset of aortic dissection. Methods and results: To induce endothelial dysfunction, Nω-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, was administered to C57BL/6 mice. Three weeks later, angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, were administered with osmotic mini-pumps. False lumen formation was used as the pathological determinant of aortic dissection. The incidences of aortic dissection and death from aneurysmal rupture were significantly higher in the Nω-nitro-L-arginine methyl ester, Ang II, and BAPN (LAB) group than they were in the Ang II and BAPN (AB) group. Pitavastatin was administered orally to LAB mice. It significantly lowered the incidences of dissection and rupture. It also decreased inflammation and medial degradation, both of which were exacerbated in the LAB group. The Japanese Adverse Drug Event Report database analysis indicated that there were 113 cases of aortic dissection out of 95 090 patients (0.12%) not receiving statins but only six cases out of 16 668 patients receiving statins (0.04%) (odds ratio: 0.30; P=0.0043). Conclusion: Our results suggest that endothelial dysfunction is associated with the onset of aortic dissection and pitavastatin can help prevent this condition

Gastric crystal-storing histiocytosis without any underlying disorders: Report of a case

Crystal-storing histiocytosis (CSH) is a rare phenomenon in which crystalline material accumulates in the cytoplasm of histiocytes. Localized gastric CSH is an extremely rare condition. We report a case of localized gastric CSH in a 72-year-old female who presented with diffuse granular mucosa in the gastric fundus and body endoscopically. Biopsy specimens from the stomach showed accumulation of crystal-storing histiocytes, and the crystalline material was immunohistochemically positive for kappa light chains and polyclonal heavy chains. There were no crystal-storing histiocytes in other organs. For the past 5 years, the gastric CSH lesion has remained without any change, and no neoplastic or lymphoproliferative disease has developed. Once the diagnosis of CSH is established, it is necessary to check for an underlying lymphoplasmacytic disorder. However, some cases of localized gastric CSH are not associated with lymphoplasmacytic neoplasia, and these tend to have a good prognosis. Keywords: Crystal-storing histiocytosis, Stomach, Immunohistochemistry, Ultrastructur

Effects on Metabolism in Astrocytes Caused by cGAMP, Which Imitates the Initial Stage of Brain Metastasis

The second messenger 2′3′-cyclic-GMP-AMP (cGAMP) is thought to be transmitted from brain carcinomas to astrocytes via gap junctions, which functions to promote metastasis in the brain parenchyma. In the current study, we established a method to introduce cGAMP into astrocytes, which simulates the state of astrocytes that have been invaded by cGAMP around tumors. Astrocytes incorporating cGAMP were analyzed by metabolomics, which demonstrated that cGAMP increased glutamate production and astrocyte secretion. The same trend was observed for γ-aminobutyric acid (GABA). Conversely, glutamine production and secretion were decreased by cGAMP treatment. Due to the fundamental role of astrocytes in regulation of the glutamine–glutamate cycle, such metabolic changes may represent a potential mechanism and therapeutic target for alteration of the central nervous system (CNS) environment and the malignant transformation of brain carcinomas