Circulating Levels of Calcitonin Gene-Related Peptide in Patients with Medullary Thyroid Carcinoma

Peer Reviewe

Beneficial Effect of Brewers' Yeast Extract on Daily Activity in a Murine Model of Chronic Fatigue Syndrome

The aim of this study was to assess the effect of Brewers' yeast extract (BYE) on daily activity in a mouse model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. BYE was orally administered to mice in a dose of 2 g per kg per day for 2 weeks before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving BYE as compared with that in untreated mice. Weekly variation of body weight (BW) and survival in both groups was monitored during the observation period. Spleen weight (SW), SW/BW ratio, percent splenic follicular area and expression levels of interferon-γ (IFN-γ) and interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity during 2 weeks after the second BA injection was significantly higher in the treated group than in the control. There was no difference in BW between both groups through the experimental course. Two mice in the control died 2 and 7 days after the second injection, whereas no mice in the treated group died. Significantly decreased SW and SW/BW ratio were observed in the treated mice together with elevation of splenic follicular area. There were suppressed IFN-γ and IL-10 mRNA levels in spleens from the treated mice. Our results suggest that BYE might have a protective effect on the marked reduction in activity following repeated BA injection via normalization of host immune responses

SLPI is a critical mediator that controls PTH-induced bone formation

Osteoclastic bone resorption and osteoblastic bone formation/replenishment are closely coupled in bone metabolism. Anabolic parathyroid hormone (PTH), which is commonly used for treating osteoporosis, shifts the balance from osteoclastic to osteoblastic, although it is unclear how these cells are coordinately regulated by PTH. Here, we identify a serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI), as a critical mediator that is involved in the PTH-mediated shift to the osteoblastic phase. Slpi is highly upregulated in osteoblasts by PTH, while genetic ablation of Slpi severely impairs PTH-induced bone formation. Slpi induction in osteoblasts enhances its differentiation, and increases osteoblast–osteoclast contact, thereby suppressing osteoclastic function. Intravital bone imaging reveals that the PTH-mediated association between osteoblasts and osteoclasts is disrupted in the absence of SLPI. Collectively, these results demonstrate that SLPI regulates the communication between osteoblasts and osteoclasts to promote PTH-induced bone anabolism.Morimoto A., Kikuta J., Nishikawa K., et al. SLPI is a critical mediator that controls PTH-induced bone formation. Nature Communications 12, 2136 (2021); https://doi.org/10.1038/s41467-021-22402-x

Mao-to Prolongs the Survival of and Reduces TNF-α Expression in Mice with Viral Myocarditis

Goal of this study was to evaluate effects of Mao-to on development of myocarditis induced by encephalomyocarditis (EMC) virus in mice. Mice were randomly divided into five groups. Group N included uninfected controls (n = 18), while group A, B and C underwent intraperitoneal injection of EMC virus. Group A was administered oral saline from day 0 to day 4. Group B was administered oral Mao-to (500 mg−1 kg−1 day−1) from day 0 to day 4. Group C was administered Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10. Treated mice were followed for survival rates during 2 weeks after infection. Body weight (BW) and organ weights including heart (HW), lungs, thymus and spleen were examined on days 4, 6 and 14. Survival rate of group C (36.4%) was significantly improved compared with group A, B or D (0% of each, P < 0.05). HW and HW/BW ratio in group C was significantly (P < 0.05) lower than those in group A, B or D. Viral titers of hearts were significantly different among groups A, B and C. Cardiac expression in tumor necrosis factor-α (TNF-α) was significantly reduced in group C in comparison with group A, B or D on day 6 by immunohistochemical study. Administration of Mao-to starting on day 2 improves mortality resulting from viral myocarditis in mice with reduced expression of cardiac TNF-α. These findings suggest that timing of Mao-to is crucial for preventing cardiac damage in mice with viral myocarditis

Direct cell–cell contact between mature osteoblasts and osteoclasts dynamically controls their functions in vivo

Bone homeostasis is regulated by communication between bone-forming mature osteoblasts (mOBs) and bone-resorptive mature osteoclasts (mOCs). However, the spatial–temporal relationship and mode of interaction in vivo remain elusive. Here we show, by using an intravital imaging technique, that mOB and mOC functions are regulated via direct cell–cell contact between these cell types. The mOBs and mOCs mainly occupy discrete territories in the steady state, although direct cell–cell contact is detected in spatiotemporally limited areas. In addition, a pH-sensing fluorescence probe reveals that mOCs secrete protons for bone resorption when they are not in contact with mOBs, whereas mOCs contacting mOBs are non-resorptive, suggesting that mOBs can inhibit bone resorption by direct contact. Intermittent administration of parathyroid hormone causes bone anabolic effects, which lead to a mixed distribution of mOBs and mOCs, and increase cell–cell contact. This study reveals spatiotemporal intercellular interactions between mOBs and mOCs affecting bone homeostasis in vivo

Feasibility study of immediate pharyngeal cooling initiation in cardiac arrest patients after arrival at the emergency room

AIM: Cooling the pharynx and upper oesophagus would be more advantageous for rapid induction of therapeutic hypothermia since the carotid arteries run in their vicinity. The aim of this study was to determine the effects of pharyngeal cooling on brain temperature and the safety and feasibility for patients under resuscitation. METHODS: Witnessed non-traumatic cardiac arrest patients (n=108) were randomized to receive standard care with (n=53) or without pharyngeal cooling (n=55). In the emergency room, pharyngeal cooling was initiated before or shortly after return of spontaneous circulation by perfusing physiological saline (5 °C) into a pharyngeal cuff for 120 min. RESULTS: There was a significant decrease in tympanic temperature at 40 min after arrival (P=0.02) with a maximum difference between the groups at 120 min (32.9 ± 1.2°C, pharyngeal cooling group vs. 34.1 ± 1.3°C, control group; P<0.001). The return of spontaneous circulation (70% vs. 65%, P=0.63) and rearrest (38% vs. 47%, P=0.45) rates were not significantly different based on the initiation of pharyngeal cooling. No post-treatment mechanical or cold-related injury was observed on the pharyngeal epithelium by macroscopic observation. The thrombocytopaenia incidence was lower in the pharyngeal cooling group (P=0.001) during the 3-day period after arrival. The cumulative survival rate at 1 month was not significantly different between the two groups. CONCLUSIONS: Initiation of pharyngeal cooling before or immediately after the return of spontaneous circulation is safe and feasible. Pharyngeal cooling can rapidly decrease tympanic temperature without adverse effects on circulation or the pharyngeal epithelium

Dietary Lactoferrin Alleviates Age-Related Lacrimal Gland Dysfunction in Mice

BACKGROUND: Decrease in lacrimal gland secretory function is related to age-induced dry eye disease. Lactoferrin, the main glycoprotein component of tears, has multiple functions, including anti-inflammatory effects and the promotion of cell growth. We investigated how oral administration of lactoferrin affects age-related lacrimal dysfunction. METHODS AND FINDINGS: Twelve-month-old male C57BL/6Cr Slc mice were randomly divided into a control fed group and an oral lactoferrin treatment group. Tear function was measured at a 6-month time-point. After euthanasia, the lacrimal glands were subjected to histological examination with 8-hydroxy-2'-deoxyguanosine (8-OHdG) antibodies, and serum concentrations of 8-OHdG and hexanoyl-lysine adduct (HEL) were evaluated. Additionally, monocyte chemotactic protein-1(MCP-1) and tumor necrosis factor-α (TNF-α) gene expression levels were determined by real-time PCR. The volume of tear secretion was significantly larger in the treated group than in the control. Lactoferrin administration reduced inflammatory cell infiltration and the MCP-1 and TNF-α expression levels. Serum concentrations of 8-OHdG and HEL in the lactoferrin group were lower than those in the control group and were associated with attenuated 8-OHdG immunostaining of the lacrimal glands. CONCLUSION: Oral lactoferrin administration preserves lacrimal gland function in aged mice by attenuating oxidative damage and suppressing subsequent gland inflammation

Association of severe hypertension with pneumonia in elderly patients with acute ischemic stroke

Pneumonia is one of the most frequent complications in elderly patients with acute ischemic stroke. Although severe hypertension is often observed in the early phase of acute stroke, there are few studies of acute hypertension as a factor influencing the incidence of stroke-associated pneumonia (SAP) in elderly subjects with acute ischemic stroke. To assess the association of acute phase blood-pressure elevation with the incidence of SAP, we compared 10 elderly patients with acute ischemic stroke complicated with severe hypertension (⩾200/120 mm Hg) with 43 patients with moderate hypertension (160–199/100–119 mm Hg), as well as with 65 control normotensive or mildly hypertensive (<160/100 mm Hg) controls on admission. Data were collected on known risk factors, type of ischemic stroke and underlying chronic conditions. The significance of differences in risk factors was analyzed using univariate and multivariate comparisons of 38 SAP cases and others, 8 SAP death cases and others, and 28 patients with poor outcome associated with in-hospital death or artificial feeding at discharge and others. After adjustment for potential confounding factors, the relative risk estimates for SAP, SAP death and poor outcome were 2.83 (95% confidence interval 1.14–7.05), 5.20 (1.01–26.8) and 6.84 (1.32–35.4), respectively, for severe hypertension relative to normotensive or mildly hypertensive controls. We conclude that severe hypertension on admission is an independent predictive factor for SAP in elderly patients with acute ischemic stroke