Association between chronic pain with presarcopenia and central sensitization in Japanese community-dwelling older adults: A cross-sectional study

Older people with chronic pain are at higher risk of developing sarcopenia. Central sensitization (CS) has been implicated in chronic pain among community-dwelling older adults. However, a relationship between CS and chronic pain with sarcopenia has not been established. This cross-sectional study aimed to clarify the relationship between chronic pain with sarcopenia or presarcopenia and CS among community-dwelling older adults. We assessed chronic pain and sarcopenia in 104 older adults participating in community health checks. We defined sarcopenia using the Asian Working Group for Sarcopenia (AWGS) consensus recommendations based on the following outcomes: low muscle mass, low muscle strength, and slow gait speed. Pain-related assessments included pain intensity, the Pain Catastrophizing Scale, the CS Inventory-9, the pressure pain threshold, the Tampa Scale of Kinesiophobia-11, and the EuroQol 5-dimension 5-level (EQ5D-5L). Chronic pain was defined by related symptoms within the month prior to the health check that had continued for ≥ 3 months and corresponded to a numerical rating scale score of ≥ 1 at the site of maximum pain. The prevalence of chronic pain was 43.3%. In addition, the prevalence of chronic pain with sarcopenia or presarcopenia was 29.8%. A logistic regression analysis revealed that the pressure pain threshold (odds ratio: 0.82, 95% CI: 0.95–1.02) and the EQ5D-5L (odds ratio: 0.58, 95% CI: 0.36–0.76) were significantly associated with the presence of chronic pain with sarcopenia or presarcopenia. Chronic pain with sarcopenia or presarcopenia was affected by central sensitization. Therefore, CS should be evaluated in the elderly.     

Oncological problems in pancreatic cancer surgery

Despite the development of more sophisticated diagnostic techniques, pancreatic carcinoma has not yet been detected in the early stage. Surgical resection provides the only chance for cure or long-term survival. The resection rate has increased due to recent advances in surgical techniques and the application of extensive surgery. However, the postoperative prognosis has been poor due to commonly occurring liver metastasis, local recurrence and peritoneal dissemination. Recent molecular-biological studies have clarified occult metastasis, micrometastasis and systemic disease in pancreatic cancer. Several oncological problems in pancreatic cancer surgery are discussed in the present review.     

Nonlinear mixed effect modeling of the pharmacodynamics of natriuretic peptides in rats

Natriuretic peptides have not only natriuretic/diuretic but also hypotensive activities, and the decreased renal perfusion caused by the excessive hypotension is known to attenuate the diuretic actions. The present study was designed to examine the relationship between the dosing (intravenous constant infusion) rates and the diuretic actions of -rat atrial natriuretic peptide (-rANP) and rat brain natriuretic peptide (rBNP) in rats, and population (nonlinear mixed effect model) analysis was applied to these complicated diuretic actions. The intrinsic diuretic activities of -rANP and rBNP could be analyzed, and the effects of blood pressure, heart rate, and also inhibition of degradation enzyme on the diuresis of natriuretic peptides were estimated simultaneously. The population analysis was useful for analyzing such pharmacodynamic data for which the individual analysis could not be applied easily.     

Ontogenic studies on the rat brain capillaries in relation to the human brain tumor vessels

Summary One of the major morphological disparities of brain capillaries between newborn or young and adult rats might be reflected in the aspect of development of the basement membrane. The basement membrane in young animals is clearly evident to be poorly developed up to 15 days of age, and then better developed to possess some similarity to that in adult animals. In addition, it also should be emphasized that slightly distended extracellular space is evident in the nervous tissue of newborn animals.Although in malignant astrocytoma some small blood vessels do not possess any perivascular space around them, others evidently have narrow or relatively wide perivascular spaces where some fibrils of mesodermal origin and fibrocytes can be clearly seen. Also, in some astrocytomas, wide extracellular space is distributed extensively all over the tumor tissue.However, in this context the immaturity of endothelial and glial cells in both young animals and brain tumors should be duly considered.The permeability of the brain capillaries in both young animals and brain tumors has been very well known to be higher than that of the adult brain tissue. However, the higher permeability has another significance, from the morphological point of view, in young animals than it has in brain tumors.

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Zusammenfassung Einer der hervorstechendsten morphologischen Unterschiede zwischen den Hirncapillaren neugeborener und junger oder erwachsener Ratten kommt in der Entwicklung der Basalmembran zum Ausdruck. Bei jungen Tieren bis zu einem Alter von 15 Tagen ist die Basalmembran wenig ausgebildet, mit fortschreitendem Alter der Tiere tritt die Ähnlichkeit mit der Basalmembran von erwachsenen Tieren ausgeprägter in Erscheinung. Außerdem ist zu betonen, daß im Nervengewebe neugeborener Tiere etwas erweiterte extracelluläre Räume zu beobachten sind.Im maligen Astrocytom gibt es kleine Blutgefäße, die keine perivasculären Räume besitzen, andere dagegen haben deutliche engere oder verhältnismäßig weite perivasculäre Räume, in denen mesodermale Fibrillen und Fibrocyten zu finden sind. In manchen Astrocytomen sind im gesamten Tumorgewebe weite extracelluläre Räume vorhanden.Allerdings müßte hier die Unreife der Endothelzellen und der Gliazellen bei jungen Tieren wie auch bei Hirntumoren in Rechnung gestellt werden.Es ist bekannt, daß sowohl bei jungen Tieren wie auch bei Hirntumoren die Permeabilität der Hirncapillaren höher ist als bei erwachsenen Tieren. Vom morphologischen Standpunkt jedoch bestehen in den Voraussetzungen der erhöhten Permeabilität bei jungen Tieren einerseits und bei Hirntumoren andererseits deutliche Unterschiede.

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With 11 Figures in the Text

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This study was made possible by a grant from the Rockfeller Foundation GAMNS 59117.     

Intracellular signaling in the induction of apoptosis in a human breast cancer cell line by water extract of Mekabu

Background We previously reported that water extract of Mekabu, a kind of seaweed, induced apoptosis in a human breast cancer cell line. In the present study we investigated intracellular signaling in apoptosis, with a focus on caspases.Methods Mekabu extract, obtained with ultrapure water, was used to induce apoptosis in a human breast cancer cell line, MDA-MB231, and DNA fractionation was investigated by flow cytometry and electrophoresis. In addition, using the caspase detection kit Caspa Tag, activation of caspases 3, 6, 8, and 9 was observed under a fluorescence microscope. Furthermore, using antibodies to caspases 3, 8, 9, and Bid, we conducted a protein analysis by Western blotting to determine the activation of these substances.Results Obvious ladder formation demonstrating DNA fractionation was seen, confirming that Mekabu extract induced apoptosis. In the fluorescence microscope observations, activation of caspases 3, 6, and 8, but not caspase 9, was seen. Activated caspases 3 and 8 were detected in the Western blotting analysis, but no proteins of activated caspase 9 or Bid were detected.Conclusion Mekabu extract activates caspases 3, 6, and 8 and contributes to intracellular signaling to induce apoptosis in a human breast cancer cell line. This signaling is not via the mitochondria.