Immunomodulatory effects of stem cells

Adult‐derived mesenchymal stem cells have received considerable attention over the past two decades for their potential use in tissue engineering, principally because of their potential to differentiate into multiple stromal‐cell lineages. Recently, the immunomodulatory properties of mesenchymal stem cells have attracted interest as a unique property of these cells that may be harnessed for novel therapeutic approaches in immune‐mediated diseases. Mesenchymal stem cells have been shown to inhibit the proliferation of activated T‐cells both in vitro and in vivo but to stimulate T‐regulatory cell proliferation. Mesenchymal stem cells are also known to be weakly immunogenic and to exert immunosuppressive effects on B‐cells, natural killer cells, dendritic cells and neutrophils through various mechanisms. Furthermore, intravenous administration of allogeneic mesenchymal stem cells has shown a marked suppression of host immune reactions in preclinical animal models of large‐organ transplant rejection and in various autoimmune‐ and inflammatory‐based diseases. Some clinical trials utilizing human mesenchymal stem cells have also produced promising outcomes in patients with graft‐vs.‐host disease and autoimmune diseases. Mesenchymal stem cells identified from various dental tissues, including periodontal ligament stem cells, also possess multipotent and immunomodulatory properties. Hence, dental mesenchymal stem cells may represent an alternate cell source, not only for tissue regeneration but also as therapies for autoimmune‐ and inflammatory‐mediated diseases. These findings have elicited interest in dental tissue mesenchymal stem cells as alternative cell sources for modulating alloreactivity during tissue regeneration following transplantation into human leukocyte antigen‐mismatched donors. To examine this potential in periodontal regeneration, future work will need to assess the capacity of allogeneic periodontal ligament stem cells to regenerate periodontal ligament in animal models of periodontal disease. The present review describes the immunosuppressive effects of mesenchymal stem cells on various types of immune cells, the potential mechanisms through which they exert their mode of action and the preclinical animal studies and human clinical trials that have utilized mesenchymal stem cells, including those populations originating from dental structures.     

The adenosine A2A receptor is associated with methamphetamine dependence/psychosis in the Japanese population

Background

Suicide and major depressive disorders (MDD) are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene rs7305115 SNP may predispose to suicide attempts in MDD.

Methods

We genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according to genotypic variation were investigated by logistic regression analysis.

Results

There were no significant differences between MDD patients with suicide and controls in genotypic (AG and GG) frequencies for rs7305115 SNP, but the distribution of AA genotype differed significantly (14.4% vs. 29.3%, p < 0.001). The G-allele frequency was significantly higher in cases than control group (58.1% vs.45.6%, p < 0.001), but the A-allele carrier indicated a decreased trend in MDD with suicide behaviors than control group (41.9% vs.54.4%, p < 0.001). The multivariate logistic regression analysis indicated that TPH2 rs7305115 AA (OR 0.33, 95% CI 0.22-0.99), family history of suicide (OR 2.98, 95% CI 1.17-5.04), negative life events half year ago (OR 6.64, 95% CI 2.48-11.04) and hopelessness (OR 7.68, 95% CI 5.79-13.74) were significantly associated with the suicide behaviors in MDD patients.

Conclusions

The study suggested that hopelessness, negative life events and family history of suicide were risk factors of attempted suicide in MDD while the TPH2 rs7305115A remained a significant protective predictor of suicide attempts.     

Cysteamine-induced duodenal ulcer and the hepatoduodenal branch of the vagus nerve

We investigated the role of the autonomic nervous system in gastric acid secretion, somatostatin concentration and PAS-positive mucus production in Brunner’s glands in cysteamine-induced duodenal ulcer. Vagotomized rats were used. No ulcers occurred in the groups with vagotomies of the hepatoduodenal, truncal or gastric branches after cysteamine administration. However, in the hepatoduodenal branch vagotomized group, there was an increases in gastric acid secretion after cysteamine administration. A similar increase was observed in the control group, but the decreases in somatostatin concentration and PAS-positive mucus seen in the control group were not found in the hepatoduodenal vagotomized group. These results suggest that the hepatoduodenal branch of the vagus nerve might play an important role in the ulcerogenic process of cysteamine-induced duodenal ulcer.     

Dural substitute with polyglycolic acid mesh and fibrin glue for dural repair: technical note and preliminary results

Background An ideal dural substitute that enables watertight closure, has sufficient strength, and can be absorbed without remnant materials that induce inflammation, adhesion, and infection is not available. The purpose of this study was to evaluate the efficacy of a bioabsorbable polyglycolic acid (PGA) mesh and fibrin glue as a substitute for dural repair. Methods Altogether, 10 patients with noted dural tears during extradural spinal surgery and 20 patients who underwent durotomy for intradural spinal surgery were included in this study. In a series of 20 consecutive cases, dural closure was performed by suture and fibrin glue. In the subsequent 10 consecutive patients, dural closure was performed by suture and fibrin glue with the use of absorbable PGA mesh. The medical records and magnetic resonance imaging (MRI) of the surgical site were retrospectively reviewed to evaluate the presence of a cerebrospinal fluid (CSF) fistula or leakage after the surgery. Results A CSF fistula occurred in five patients who underwent dural repair with fibrin glue alone, and postoperative MRI showed CSF leakage in two patients with incidental dural tears after laminectomy for ossification of ligamentum flavum. No CSF fistula was present in patients who underwent dural repair using PGA mesh and fibrin glue, and no adverse effects or complications were encountered postoperatively. Follow-up MRI revealed no evidence of CSF leakage around the reconstructed dura mater. Conclusions The use of PGA mesh and fibrin glue for the repair of dura mater is a useful method of preventing CSF leakage in spinal surgery.     

Quantitative measurements of hip abduction strength in lumbar surgery patients

BackgroundWe sought to evaluate the hip abduction strength in patients before and after lumbar surgery.Materials and methodsEighty-four patients (51 males and 33 females) undergoing surgery for lumbar disc herniation or lumbar canal stenosis were selected. Mean age was 64.7 ± 13.8 years. Seven patients (8.3%) had surgery at multiple levels, including L2-L3 (group A), 27 (32.1%) patients had surgery at multiple levels including L3-L4 (group B), 32 (38.1%) patients had surgery at the L4-L5 level only (group C), and 18 (21.4%) patients had surgery at the L5-S1 level only (group D). Hip abduction strength was measured in the 84 patients preoperatively and in 49 patients postoperatively.ResultsIn all patients, preoperative mean hip abduction strength on the symptomatic side and the asymptomatic side was 71.4 ± 34.5 N and 90.7 ± 36.5 N, respectively (p = 0.0008). In groups A and B, there were no significant differences between the mean hip abduction strength on the symptomatic and contralateral side. In group C, those on the symptomatic and contralateral side were 68.0 ± 33.5 N and 89.3 ± 34.8 N, respectively (p = 0.0181). In group D, those on the symptomatic and contralateral side were 74.3 ± 42.4 N and 101.7 ± 44.7 N, respectively (p = 0.0314). In the 49 patients of all groups that could be measured postoperatively, there were no significant differences between the mean hip abduction strength on both sides.ConclusionsIt was confirmed that the gluteus medius, which was main hip abductor, was mainly innervated by L5 and its mean strength significantly improved postoperatively. The possibility of improvement of hip abduction strength, especially with unchanged tibialis anterior strength, could be very useful for operative decisions.     

Nitric oxide inhalation as a chemical assist for circulation in patients after cardiovascular surgery

The objective of this study was to investigate whether nitric oxide (NO) inhalation might be an alternative strategy as a chemical assist for the circulation in patients showing a deterioration in oxygen delivery. Twelve adult patients whose oxygen delivery indices (DO2I) were less than 400 ml/min/m2 after cardiovascular surgery were included in this study. NO was administered via a premixing system or a side stream system at doses between 1 and 10 (5.1+/-2.4) ppm. Data obtained before and during a 120 min NO inhalation were compared using the paired Student's t-test. The increase in PaO2/FiO2 resulting from NO inhalation was significant (from 162 to 251 mm Hg). DO2I increased significantly from 326 to 417 ml/min/m2 concomitantly with significant increases in both arterial oxygen content (CaO2) and cardiac index (CI) (from 14.1 to 15.4 vol% and from 2.31 to 2.71 L/min/m2 , respectively). The increase in SvO2 during NO inhalation was significant (from 55.2 to 62.6%). Among the other hemodynamic parameters, both total pulmonary resistance and systolic pulmonary arterial pressure (SPAP) showed significant decreases during NO inhalation, but right atrial pressure did not change significantly. There was a close relationship between the baseline SPAP level (bSPAP) and the decrease in SPAP during NO inhalation (dSPAP) (r = -0.88). However, negative correlations were observed between bSPAP and percentage increase in CI (%CI) (r = -0.61) and between bSPAP and percentage increase in DO2I (%DO2I) (r = -0.48). Moreover, positive relationships were observed between dSPAP and %CI (r = 0.62) and between dSPAP and %DO2I (r = 0.45). Hemoglobin (Hb) increased significantly from 11.0 to 11.4 g/dl. There were no significant changes in Fio2, pH, PacO2, or base excess (BE) during NO inhalation. The level of methemoglobin measured during the study period remained within the normal range (0.86+/-0.23%). In conclusion, NO inhalation could be an efficient and alternative assist for the circulation in patients whose oxygen delivery deteriorates after cardiovascular surgery.     

Effects of Zopiclone on Slow Wave Sleep and Spontaneous K-complexes for Normal Healthy Young Adults

Abstract: Benzodiazepine (BZD) hypnotics have been known to decrease, to some degree, human slow wave sleep (SWS) although they elevate the arousal threshold during sleep. Zopiclone (ZPC), a cyclopyrrolone hypnotic, has attracted the interest of sleep researchers because an increase in human SWS has been reported. Since the increase has not been fully confirmed by all of the studies, the authors investigated the effects of ZPC 10 mg on SWS and the K-complexes for 7 healthy young adults because there is evidence indicating that delta waves consisting of SWS and the spontaneous K-complexes are identical. SWS and st. 4 sleep did not decrease on any of the ZPC nights but st. 3 sleep showed a tendency to reduce on the 1st ZPC night. The frequency of the K-complexes decreased significantly on the 2nd ZPC night and tended to reduce on the 1st ZPC night. Moreover, a significant positive correlation was noted between the decrease rates of SWS and the K-complexes on both the ZPC nights. The authors, therefore, could not obtain any findings suggesting an increase in SWS with ZPC.     

Stigma associated with schizophrenia: Cultural comparison of social distance in Japan and China

Aims:  The aim of the present study was to investigate social attitudes toward schizophrenia in Japan and China in view of social distance and knowledge of psychiatry, as well as sociocultural aspects.
Methods:  Two self-rating scales were used to compare social distance and knowledge regarding schizophrenia in 352 Japanese subjects and 347 Chinese subjects. The Social Distance Scale–Japanese version was used to measure social distance from schizophrenia subjects in Japan. This scale consists of eight questions graded using a 4-point Likert scale (0–3 points), with higher scores representing increased social distance. A translation of the SDSJ into Chinese was used to assess social distance in China. The Knowledge of Illness and Drugs Inventory was used to determine participant knowledge of mental illness and its treatment (medication) through 20 questions (responses are graded as correct or incorrect, with higher scores indicating greater knowledge). A Chinese version of this questionnaire was also created.
Results:  Total scores of both scales were significantly higher in Japanese subjects than in Chinese subjects.
Conclusions:  Social distance associated with schizophrenia is large in both Beijing and Fukuoka, but the features of social distance differ between countries. It is important to determine the features of stigma associated with schizophrenia and develop anti-stigma programs based on trans-cultural considerations.     

A randomized placebo-controlled polysomnographic study of eszopiclone in Japanese patients with primary insomnia

ObjectivesTo evaluate the efficacy and dose–response effect of eszopiclone on sleep latency and sleep maintenance in Japanese patients with primary insomnia.MethodsIn this randomized, double-blind, five-way crossover study, 72 patients received placebo, eszopiclone 1 mg, 2 mg, and 3 mg, and zolpidem 10 mg in random order for two consecutive nights with a washout period between treatments. Objective sleep measures from polysomnography (PSG) and subjective patient reports were collected.ResultsAll active treatments produced significant improvement in objective and subjective sleep latency compared with placebo (P < 0.05 for all comparisons); linear dose–response relationships were observed for eszopiclone. PSG-determined wake time after sleep onset (WASO), sleep efficiency, and number of awakenings (NA), and patient-reported measures of WASO, NA, sleep quality, sleep depth, and daytime functioning significantly improved following treatment with eszopiclone 2 mg and 3 mg and zolpidem 10 mg versus placebo (P < 0.05). Eszopiclone at all doses increased total sleep time and stage 2 sleep time (P < 0.001 for both comparisons), but did not alter REM or slow-wave sleep. Eszopiclone was generally well tolerated; the most frequently reported adverse event was mild dysgeusia.ConclusionsIn Japanese patients with primary insomnia, eszopiclone 2 mg and 3 mg significantly improved PSG-determined and patient-reported sleep latency and sleep maintenance relative to placebo.