Methylglyoxal Induces Inflammation,Metabolic Modulation and Oxidative Stress in Myoblast Cells

Uremic sarcopenia is a serious clinical problem associated with physical disability and increased morbidity and mortality. Methylglyoxal (MG) is a highly reactive, dicarbonyl uremic toxin that accumulates in the circulatory system in patients with chronic kidney disease (CKD) and is related to the pathology of uremic sarcopenia. The pathophysiology of uremic sarcopenia is multifactorial; however, the details remain unknown. We investigated the mechanisms of MG-induced muscle atrophy using mouse myoblast C2C12 cells, focusing on intracellular metabolism and mitochondrial injury. We found that one of the causative pathological mechanisms of uremic sarcopenia is metabolic flow change to fatty acid synthesis with MG-induced ATP shortage in myoblasts. Evaluation of cell viability revealed that MG showed toxic effects only in myoblast cells, but not in myotube cells. Expression of mRNA or protein analysis revealed that MG induces muscle atrophy, inflammation, fibrosis, and oxidative stress in myoblast cells. Target metabolomics revealed that MG induces metabolic alterations, such as a reduction in tricarboxylic acid cycle metabolites. In addition, MG induces mitochondrial morphological abnormalities in myoblasts. These changes resulted in the reduction of ATP derived from the mitochondria of myoblast cells. Our results indicate that MG is a pathogenic factor in sarcopenia in CKD.     

Ovariectomy Aggravated Sodium Induced Hypertension Associated With Altered Platelet Intracellular Ca in Dahl Rats

Our purpose was to determine the effect of ovariectomy on intracellular Ca²⁺ mobilization and platelet aggregation in sodium induced hypertension. At the age of 12 weeks ovariectomy or sham operation was performed in female Dahl-Iwai salt sensitive rats on a 0.3% NaCl diet. Four weeks later we assessed the effects of ovariectomy and an 8% NaCl diet on agonist induced intracellular Ca²⁺ mobilization in fura-2 loaded platelets and platelet aggregation. Ovariectomy enhanced the increase of systolic blood pressure and heart to body weight ratio on an 8% NaCl diet. However, thrombin evoked intracellular Ca²⁺ was not correlated with systolic blood pressure (r = −0.338, P = .17), and was lowered by sodium loading and ovariectomy (360 ± 23 to 285 ± 9, 296 ± 10 nmol/L, P < .05). Furthermore, the ionomycin induced intracellular calcium fraction in the absence of external Ca²⁺ that reflected internal Ca²⁺ discharge capacity was reduced in ovariectomized rats compared with sham operated rats on an 8% NaCl diet (648 ± 15 v 768 ± 35 nmol/L, P < .05). The internal Ca²⁺ discharge capacity was inversely correlated with systolic blood pressure (r = −0.506, P = .03). In addition to the decreased internal Ca²⁺ discharge capacity, intracellular Ca²⁺-independent platelet aggregation by phorbol 12-myristate 13-acetate, a protein kinase C activator, was significantly enhanced in hypertensive rats. We concluded that ovariectomy enhanced sodium induced hypertension associated with the decreased internal Ca²⁺ discharge capacity and increased platelet aggregation in Dahl-Iwai salt-sensitive rats.     

Relationship between exercise motivation and social support in a support facility for persons with disabilities in Japan

PurposeExercise motivation (EM) is related to individual capabilities and social support. However, in support facilities for people with disabilities, it is susceptible to a lack of social support. In this study, we classified EM into Autonomous Motivation (AM) and controlled motivation (CM) and then examined the influence of social support.MethodThirty-three residents from a support facility for people with disabilities in Japan participated in this study. We conducted a hierarchical multiple regression analysis in which age, gender and time since admission were entered in Step 1, mobility and self-efficacy as individual capabilities in Step 2, and family support, facility support and peer support as social support in Step 3.ResultA significant increase in variance from Step 2 to Step 3 was found for both AM (ΔR² = 0.504, ΔF = 12.18, p < .001) and CM (ΔR² = 0.269, ΔF = 3.491, p = .031). The results also showed that AM was higher among those with high family and facility support, and CM was higher among those with low family and high peer support.ConclusionsSocial support was a more significant predictor of EM among participants than individual capabilities.

KEY MESSAGES

• Among residents of support facilities for people with disabilities, assessing not only individual capabilities but also social support status can lead to better understandings of exercise motivation (EM).
• To enhance facility residents’ autonomous motivation (AM), it is necessary to intervene after evaluating family and facility support.
• When family support is not readily available among facility residents, efforts should be made to encourage residents to interact with each other to increase peer support.

     

Possible antipsychotic effects of minocycline in patients with schizophrenia

We present two cases of patients with schizophrenia treated with minocycline. Minocycline (a second-generation tetracycline) is an established and safe broad-spectrum antibiotic that crosses the blood-brain barrier, with additional efficacy for diseases such as acne and rheumatoid arthritis. Animal studies have suggested that minocycline may prevent progression of some neurological disorders. Moreover, it has been reported that minocycline might have antidepressant effects. We report two cases of acute schizophrenia with predominant catatonic symptoms that responded to minocycline.     

Factors predicting persistent thrombocytopenia after living donor liver transplantation in pediatric patients

Thrombocytopenia is common after LT for pediatric end-stage liver diseases. Seventy-six pediatric patients (≤15 yr old) who underwent LDLT were evaluated for the incidence and predictive factors of post-transplant thrombocytopenia (PLT <100, 000/mm(3) ). The prevalence of thrombocytopenia at two wk and at 12 months post-transplant was 22/76 (28.9%) and 11/62 (17.7%), respectively. Thrombocytopenia at two wk after LDLT was significantly associated with age at transplant, preoperative PLT, GRWR, acute rejection, and CMV infection in univariate analysis. Moreover, preoperative PLT, GRWR, and acute rejection had a strong correlation in multivariate analysis. Thrombocytopenia at 12 months after LDLT was associated only with preoperative PLT. We also demonstrated that vascular complications caused thrombocytopenia and that successful treatment recovered the PLT. These results showed that, in addition to considering the preoperative PLT, post-operative monitoring of platelets is very helpful for the early detection of adverse events related to the graft liver in pediatric liver transplant patients.     

Repeated social defeat stress induces chronic hyperthermia in rats

Psychological stressors are known to increase core body temperature (T_c) in laboratory animals. Such single stress-induced hyperthermic responses are typically monophasic, as T_c returns to baseline within several hours. However, studies on the effects of repeated psychological stress on T_c are limited. Therefore, we measured T_c changes in male Wistar rats after they were subjected to 4 social defeat periods (each period consisting of 7 daily 1 h stress exposures during the light cycle followed by a stress-free day). We also assessed affective-like behavioral changes by elevated plus maze and forced swim tests.In the stressed rats, the first social defeat experience induced a robust increase in T_c (+ 1.3 °C). However, the T_c of these rats was not different from control animals during the subsequent dark period. In comparison, after 4 periods of social defeat, stressed rats showed a small but significantly higher (+ 0.2-0.3 °C) T_c versus control rats during both light and dark periods. Stressed rats did not show increased anxiety-like behavior versus control rats as assessed by the elevated plus maze test. However, in the forced swim test, the immobility time of stressed rats was significantly longer versus control rats, suggesting an increase in depression-like behavior. Furthermore, hyperthermia and depression-like behavior were still observed 8 days after cessation of the final social defeat session. These results suggest that repeated social defeat stress induces a chronic hyperthermia in rats that is associated with behavior resembling depression but not anxiety.     

Coronavirus infection of rat dorsal root ganglia: ultrastructural characterization of viral replication, transfer, and the early response of satellite cells

Swine hemagglutinating encephalomyelitis virus (HEV) has been shown to have a capability to gain access to the cell bodies of sensory neurons after peripheral inoculation, resulting in ganglionic infection. It is not clearly understood how this virus is replicated within and released from the sensory neurons, and it remains to know how satellite cells response to the HEV invasion. By ultrastructurally examining HEV-infected rat dorsal root ganglia, we found that HEV in the cell bodies of infected neurons budded from endoplasmic reticulum-Golgi intermediate compartments, and were assembled either individually within small vesicles or in groups within large vesicles. The progeny virions were released from the sensory neurons mainly by smooth-surfaced vesicle-mediated secretory pathway, which occurred predominantly at the perikaryal projections and infoldings of sensory neurons. Released HEV particles were subsequently taken up by the adjacent satellite cells. Almost all virus particles in the cytoplasm of satellite cells were contained in groups within vesicles and lysosome-like structures, suggesting that these glial cells may restrict the local diffusion of HEV. These observations give some insights into the pathogenesis of coronavirus infection and are thought to help understand the interactions between sensory neurons and their satellite cells.