Effects of antiarrhythmic drugs on the extraneuronal accumulation of isoprenaline in perfused rat hearts

Summary The effects of class I, II, III and IV antiarrhythmic drugs (as classified by Vaughan Williams 1974), tetrodotoxin and ₂-adrenoceptor antagonists on the extraneuronal accumulation of isoprenaline were examined in isolated rat hearts perfused with ³H-isoprenaline (1 mol/l) and tropolone (100 mol/l) for 30 min at a constant flow rate (6.5 ml/min) at 40°C. Quinidine (class I), verapamil (IV), diltiazem (IV), dilazep (IV), nifedipine (IV), tetrodotoxin and butoxamine, at a concentration of 10 mol/l, significantly decreased the extraneuronal accumulation of isoprenaline.The present study demonstrated that quinidine (class I) and all of the calcium channel blockers (class IV) had potent inhibitory effects on the extraneuronal accumulation of isoprenaline. The concentrations of these drugs needed for this decrease were nearly comparable to those needed to suppress isoprenaline-tropolone-induced ventricular fibrillation (Sone et al. 1985a). The antiarrhythmic effects of quinidine and calcium channel blockers in this experimental model may be partly due to a decrease in the extraneuronal accumulation of isoprenaline.This study was supported in part by a Grant-in-Aid for Scientific Research (59570980) from the Ministry of Education, Science and Culture, Japan     

The emerging role of clinical informatics fellows in service learning during the COVID-19 pandemic

ObjectiveThe study sought to describe the contributions of clinical informatics (CI) fellows to their institutions’ coronavirus disease 2019 (COVID-19) response.Materials and MethodsWe designed a survey to capture key domains of health informatics and perceptions regarding fellows’ application of their CI skills. We also conducted detailed interviews with select fellows and described their specific projects in a brief case series.ResultsForty-one of the 99 CI fellows responded to our survey. Seventy-five percent agreed that they were “able to apply clinical informatics training and interest to the COVID-19 response.” The most common project types were telemedicine (63%), reporting and analytics (49%), and electronic health record builds and governance (32%). Telehealth projects included training providers on existing telehealth tools, building entirely new virtual clinics for video triage of COVID-19 patients, and pioneering workflows and implementation of brand-new emergency department and inpatient video visit types. Analytics projects included reports and dashboards for institutional leadership, as well as developing digital contact tracing tools. For electronic health record builds, fellows directly contributed to note templates with embedded screening and testing guidance, adding COVID-19 tests to order sets, and validating clinical triage workflows.DiscussionFellows were engaged in projects that span the breadth of the CI specialty and were able to make system-wide contributions in line with their educational milestones.ConclusionsCI fellows contributed meaningfully and rapidly to their institutions’ response to the COVID-19 pandemic.     

In vitro evaluation of plant-derived agents to preserve dentin collagen

Objective

Biomodification of dentin by a natural crosslinker has been recommended to improve a mechanical property of demineralized dentin. This study investigated the effect of various plant-derived agents (hesperidin, proanthocyanidin, epigallocatechin gallate and genipin) on the stability of dentin collagen matrix to resist collagenase degradation.

Methods

The dentin specimens were treated with glutaraldehyde (0.5% and 5.0%) and each plant-derived test solution (0.5%). They were subjected to ultimate tensile strength (UTS) and swelling ratio measurements. Demineralized human dentin powder was incubated with 0.02%, 0.1% and 0.5% of each test agent and followed by bacterial collagenase digestion. The extent of collagen degradation was investigated using hydroxyproline assay.

Results

The UTS and swelling ratio measurements revealed that the mechanical property of dentin was improved by the use of these natural agents. The greatest reduction in collagen degradation was shown following the use of hesperidin, proanthocyanidin, and epigallocatechin gallate at 0.5%.

Significance

The use of hesperidin, proanthocyanidin, and epigallocatechin gallate could improve the mechanical properties of collagen and resist enzymatic degradation, leading to functional repair of pathological dentin lesion.     

The effect of Assertive Community Treatment in Japan

Ito J, Oshima I, Nishio M, Sono T, Suzuki Y, Horiuchi K, Niekawa N, Ogawa M, Setoya Y, Hisanaga F, Kouda M, Tsukada K. The effect of Assertive Community Treatment in Japan. Objective: The aim of this study was to evaluate the effects of the Assertive Community Treatment (ACT) program in a Japanese mental health service setting. Method: This study was a randomized controlled trial. ACT was the intervention condition (n = 59), and the usual hospital‐based rehabilitation program was the control condition (n = 59). Outcome indicators include in‐patient days, psychiatric symptoms, social functioning, quality of life, and client satisfaction. The follow‐up period was 12 months after the intervention. Results: We found a significant reduction of in‐patient days for the ACT group demonstrated by t‐test (t = 2.33, P = 0.02). However, the results of ancova did not show significant differences for in‐patient days between the two groups (F = 1.85, P = 0.18). The depression score for Brief Psychiatric Rating Scale for the ACT group was significantly lower than the control group at the 12‐month follow‐up assessment (F = 5.57, P = 0.03). According to the t‐test, the ACT group had a higher client satisfaction than the control group (t = 2.08, P = 0.05). Conclusion: We concluded that ACT had a positive influence, as evidenced by a reduction of in‐patient days, lower depressive symptoms, and higher client satisfaction.     

Restricted growth and insulin-like growth factor-1 deficiency in mice lacking presenilin-1 in the neural crest cell lineage

Presenilin-1 (PS1) is a transmembrane protein that is in many cases responsible for the development of early-onset familial Alzheimer's disease. PS1 is essential for neurogenesis, somitogenesis, angiogenesis, and cardiac morphogenesis. We report here that PS1 is also required for maturation and/or maintenance of the pituitary gland. We generated PS1-conditional knockout (PS1-cKO) mice by crossing floxed PS1 and Wnt1-cre mice, in which PS1 was lacking in the neural crest-derived cell lineage. Although the PS1-cKO mice exhibited no obvious phenotypic abnormalities for several days after birth, reduced body weight in the mutant was evident by the age of 3–5 weeks. Pituitary weight and serum insulin-like growth factor (IGF)-1 level were also reduced in the mutant. Histologic analysis revealed severe atrophy of the cytosol in the anterior and intermediate pituitary lobes of the mutant. Immunohistochemistry did not reveal clear differences in the expression levels of thyroid-stimulating hormone, adrenocorticotropic hormone, or prolactin in the mutant pituitary. In contrast, growth hormone expression levels were reduced in the anterior lobe of the mutant. PS1 was defective in the posterior lobe, but not the anterior or intermediate lobes, in the mutant pituitary. These findings suggest that PS1 indirectly mediates the development and/or maintenance of the anterior and intermediate lobes in the pituitary gland via actions in other regions, such as the posterior lobe.     

Gadolinium-enhanced magnetic resonance imaging for detection and quantification of fibrosis in human myocardium in vitro

Background The availability of a non-invasive test to detect and quantify interstitial and replacement fibrosis would be a useful advance for evaluation of cardiac therapies that could prevent fibrosis progression. There is an established role for magnetic resonance imaging (MRI) in the assessment of replacement fibrosis (when fibrosis replaces myocytes), but the potential for assessment of interstitial fibrosis (when amount of fibrosis increases between myocytes) has not been evaluated. Methods A novel in vitro MRI technique was developed for comparison of gadodiamide contrast distribution volume as a measure of both kinds of myocardial fibrosis, with histologically determined myocardial collagen volume fraction, the current gold standard for quantification of myocardial fibrosis. Eight samples of human myocardium were obtained postmortem and a fast spin-echo sequence (3 Tesla) with non-slice selective inversion pulse performed before and after immersion in a gadodiamide saline solution for determination of the gadodiamide partition coefficient. T1 values were calculated from the inversion recovery signal curves. The same samples were fixed in formalin, and collagen volume fraction was determined by the picrosirius red method using a semi-automated, polarized, digital microscopy system. Results Both gadodiamide distribution volumes as well as CVF values were significantly different in normal myocardium versus interstitial fibrosis (P = 0.001), and normal versus replacement fibrosis (P = 0.015). Moreover, there was a significant positive correlation between the two methods, across all three histological categories of myocardial fibrosis (r = 0.73; P = 0.017). Conclusion These findings indicate an expanded potential for gadodiamide enhanced MRI as a novel, non-invasive alternative to histological evaluation, for the quantification of both interstitial and replacement myocardial fibrosis.     

Family needs and related factors in caring for a family member with mental illness: adopting assertive community treatment in Japan where family caregivers play a large role in community care

Aim: In Japan the family plays a large role in community care for persons with mental illness; therefore the aim of the present study was to describe the needs of family caregivers related to assertive community treatment (ACT) and to analyze the relationship of these needs to underlying factors. Methods: Participants were recruited from the membership of three family associations of persons with mental illness. Of the 224 family members, 152 (67.9%) completed a self‐report questionnaire consisting of the following measures: demographic variables, family life difficulty scale, global burden, general life satisfaction, subjective health status, family rejection scale, quantity of supportive behaviors, and needs for ACT. Results: More than 70% of participants reported that service components of ACT would be beneficial, especially in the future. Functions that helped maintain the ordinary routine of family life were significantly correlated with current needs for ACT. Conclusions: When a person has chronic mental illness the family has many needs related to ACT. When functions that maintained the ordinary routine of family life were disturbed, the need for ACT support increased. Elderly parents or siblings were also concerned about the future, when caring for the member with mental illness would become more difficult.     

Regulation of mitochondrial biogenesis by lipoprotein lipase in muscle of insulin-resistant offspring of parents with type 2 diabetes

Recent studies reveal a strong relationship between reduced mitochondrial content and insulin resistance in human skeletal muscle, although the underlying factors responsible for this association remain unknown. To address this question, we analyzed muscle biopsy samples from young, lean, insulin resistant (IR) offspring of parents with type 2 diabetes and control subjects by microarray analyses and found significant differences in expression of ~512 probe pairs. We then screened these genes for their potential involvement in the regulation of mitochondrial biogenesis using RNA interference and found that mRNA and protein expression of lipoprotein lipase (LPL) in skeletal muscle was significantly decreased in the IR offspring and was associated with decreased mitochondrial density. Furthermore, we show that LPL knockdown in muscle cells decreased mitochondrial content by effectively decreasing fatty acid delivery and subsequent activation of peroxisome proliferator-activated receptor (PPAR)-δ. Taken together, these data suggest that decreased mitochondrial content in muscle of IR offspring may be due in part to reductions in LPL expression in skeletal muscle resulting in decreased PPAR-δ activation.