Daijokito Administration in Critically III Patients Increasing the Stool Volume: A Retrospective Observational Study

Introduction:Daijokito, a traditional Japanese herbal medicine (Kampo), has been used to treat abdominal distention of the middle yang stage pattern. The use of Daijokito has not been thoroughly investigated in critical care. To investigate a new Kampo approach to defecation control in critically ill patients, our study aimed to assess the effects of Daijokito on fecal management.Methods: We analyzed 30 consecutive patients treated with Daijokito in the intensive care unit (ICU) between March 2017 and February 2021. The eligibility criteria were patients who were newly prescribed Daijokito in the ICU during the study period. Exclusion criteria were patients who were started on other laxatives within one day of beginning Daijokito. The study's primary outcome was defecation volume three days before and three days after starting Daijokito. We recorded the most dominant stool quality within three days after the start of Daijokito.Results: Twenty-one patients were included in the analysis. The median age was 69.0 years, and the median sequential organ failure assessment score on admission to the ICU was 6.0. Major diseases included trauma, pancreatitis, and burns. Administration of Daijokito resulted in defecation in 17 of twenty-one patients (81.0%). Comparison of defecation volume between 3 days before Daijokito administration and three days, including the day of Daijokito administration, showed that defecation volume increased significantly after Daijokito administration, with a median of 0 to 360 g (p < 0.001). At the three-day follow-up, six of 17 (35.3%) patients defecated on the day of Daijokito administration, and nine (52.9%) defecated on the day after administration. One patient was judged to have excessive defecation, and Daijokito administration was discontinued. Stool quality was normal in one (5.9%) of the 17 patients, soft-formed in two (11.8%), loose-unformed in 11 (64.7%), and liquid in three (17.6%).Discussion:Daijokito administration in critically ill patients caused defecation in 81% of the patients and significantly increased stool volume. The novelty of this study is that it sheds light on the Kampo treatment of defecation control in critically ill patients. In addition to the present report, further studies are warranted to quantify the therapeutic efficacy and safety of Daijokito

A case of tetanus treated with Kampo medicines such as Kakkonto and Shakuyakukanzoto

CaseA 74-year-old man developed tetanus 3 days after working with cow and poultry manure. Kakkonto and shakuyakukanzoto, traditional Japanese herbal medicines that are effective for the relief of pain primarily related to muscle contraction, were given to control the trismus and painful contracture of the neck. Generalized convulsions were controlled without the use of muscle relaxants.OutcomeAfter 30 days, the patient was discharged from the hospital without any sequelae.ConclusionKakkonto and shakuyakukanzoto may be useful for the control of muscle spasms resulting from generalized tetanus

Comparison of quality of human serum albumin preparations in two pharmaceutical products

AimHuman serum albumin (HSA) is known for its multiple functions, such as maintenance of colloid osmotic pressure, transport of endogenous and exogenous substances, and antioxidation. The aim of this study was to measure the redox state and concentrations of β-d-glucan and endotoxin to compare the quality of 5% HSA preparations from two different manufacturers.MethodsThe quality of 5% HSA preparations in two different pharmaceutical products (groups A and B) was compared in terms of the percentage of reduced and oxidized albumin and the contaminant level of β-d-glucan and endotoxin.ResultsThe percentage of human mercaptoalbumin in group A was significantly higher than that in group B (P < 0.01), whereas that of human non-mercaptoalbumin-2 in group A was significantly lower (P < 0.01). The concentration of β-d-glucan in group A was significantly lower than in group B (P < 0.01).ConclusionsThe present findings indicate the need for quality control of HSA preparations in applications involving the use of large volumes

Survey on the current status of self-immolation attempts in Akita Prefecture: A cross-sectional survey

ObjectiveGiven the up to 70% fatality rate of self-immolation, with tragic consequences for survivors, proposals have been made for a global task force to prevent self-immolation. However, little research has recently been conducted on the actual situation of patients who attempt self-immolation in Japan. The current study aimed to investigate the actual situation of patients who attempt self-immolation in Akita Prefecture.ResultWithin Akita Prefecture, 13 individuals had attempted self-immolation in the past 5 years, with a predominance of a history of psychiatric disorders (46%). The following three novel findings were also revealed. First, patients with low a prognostic burn index tended to commit arson, while those with a high prognostic burn index tended to self-immolate. Second, patients attempting suicide tended to have a higher incidence of carbon monoxide poisoning. Third, those whose clothes caught on fire tended have more severe burns, regardless of whether suicide was attempted.ConclusionSelf-immolation tends to be serious, and prevention is imperative. In Akita Prefecture, the percentage of patients with a history of psychiatric disorders may be higher than commonly believed, and a more detailed understanding of the mental state of self-immolation is necessary in the future to develop effective prevention measures

Overexpression of a Minimal Domain of Calpastatin Suppresses IL-6 Production and Th17 Development via Reduced NF-κB and Increased STAT5 Signals

Calpain, a calcium-dependent cysteine protease, is reportedly involved in the pathophysiology of autoimmune diseases such as rheumatoid arthritis (RA). In addition, autoantibodies against calpastatin, a natural and specific inhibitor of calpain, are widely observed in RA. We previously reported that E-64-d, a membrane-permeable cysteine protease inhibitor, is effective in treating experimental arthritis. However, the exact role of the calpastatin-calpain balance in primary inflammatory cells remains unclear. Here we investigated the effect of calpain-specific inhibition by overexpressing a minimal functional domain of calpastatin in primary helper T (Th) cells, primary fibroblasts from RA patients, and fibroblast cell lines. We found that the calpastatin-calpain balance varied during Th1, Th2, and Th17 development, and that overexpression of a minimal domain of calpastatin (by retroviral gene transduction) or the inhibition of calpain by E-64-d suppressed the production of IL-6 and IL-17 by Th cells and the production of IL-6 by fibroblasts. These suppressions were associated with reductions in RORγt expression and STAT3 phosphorylation. Furthermore, inhibiting calpain by silencing its small regulatory subunit (CPNS) suppressed Th17 development. We also confirmed that overexpressing a minimal domain of calpastatin suppressed IL-6 by reducing NF-κB signaling via the stabilization of IκBα, without affecting the upstream signal. Moreover, our findings indicated that calpastatin overexpression suppressed IL-17 production by Th cells by up-regulating the STAT5 signal. Finally, overexpression of a minimal domain of calpastatin suppressed IL-6 production efficiently in primary fibroblasts derived from the RA synovium. These findings suggest that inhibiting calpain by overexpressing a minimal domain of calpastatin could coordinately suppress proinflammatory activities, not only those of Th cells but also of synovial fibroblasts. Thus, this strategy may prove viable as a candidate treatment for inflammatory diseases such as RA

Involvement of SIK3 in Glucose and Lipid Homeostasis in Mice

Salt-inducible kinase 3 (SIK3), an AMP-activated protein kinase-related kinase, is induced in the murine liver after the consumption of a diet rich in fat, sucrose, and cholesterol. To examine whether SIK3 can modulate glucose and lipid metabolism in the liver, we analyzed phenotypes of SIK3-deficent mice. Sik3−/− mice have a malnourished the phenotype (i.e., lipodystrophy, hypolipidemia, hypoglycemia, and hyper-insulin sensitivity) accompanied by cholestasis and cholelithiasis. The hypoglycemic and hyper-insulin-sensitive phenotypes may be due to reduced energy storage, which is represented by the low expression levels of mRNA for components of the fatty acid synthesis pathways in the liver. The biliary disorders in Sik3−/− mice are associated with the dysregulation of gene expression programs that respond to nutritional stresses and are probably regulated by nuclear receptors. Retinoic acid plays a role in cholesterol and bile acid homeostasis, wheras ALDH1a which produces retinoic acid, is expressed at low levels in Sik3−/− mice. Lipid metabolism disorders in Sik3−/− mice are ameliorated by the treatment with 9-cis-retinoic acid. In conclusion, SIK3 is a novel energy regulator that modulates cholesterol and bile acid metabolism by coupling with retinoid metabolism, and may alter the size of energy storage in mice

Kampo Medicines for Frailty in Locomotor Disease

Frailty is a syndrome that includes broad problems of senility and consists of three domains: physical, psychological, and social. Kampo medicine is used for intervention in cases of hypofunction in a mental or physical state. Kampo treatment, using Hojin formulations such as Hachimijiogan and Gosyajinkigan, is useful in patients with “jinkyo,” or kidney hypofunction. Ketsu includes both blood and its metabolic products that circulate throughout the body. Oketsu is a disturbance of ketsu and is considered to be a microcirculation disorder. Anti-oketsu formulations, such as Keishibukuryogan and Jidabokuippo, are useful in the treatment of trauma patients who are experiencing swelling and pain. “Ki” is the universal energy that exists in the world. Hoki formulations, such as Rikkunshito and Hochuekkito, are useful in patients with poor appetites for reinforcing vital energy. Juzentaihoto and Ninjinyoeito are useful in patients with hypofunction of ki and ketsu, which are accompanying symptoms of coldness or cutaneous dryness. Thus, Kampo medicines can be used as a superior approach for the management of frailty