Effects of hPTH (1-34) and Gosha-jinki-gan on the trabecular bone microarchitecture in ovariectomized rat tibia

Although human parathyroid hormone (1-34) [hPTH (1-34)] was reported to improve osteoporotic bone loss, little is known about the anti-osteoporotic effect of the traditional Chinese medicine, Gosha-jinki-gan (GJG). The purpose of this present study was to clarify and compare the effects of hPTH (1-34) and GJG on trabecular bone microarchitecture in ovariectomized (OVX) rat tibia by using microcomputed tomography (micro-CT). Thirty 12-week-old Sprague-Dawley female rats were underwent ovariectomy (OVX) or sham operation. Four weeks later, the ovariectomized rats were further divided into OVX, OVX + PTH, and OVX + GJG groups. hPTH (1-34) was administered subcutaneously at a dose of 20 microg/kg, 3 times/week, and OVX + GJG group received 0.05% aqueous solution of GJG as the only drinking fluid for 8 weeks respectively. The three-dimensional (3D) trabecular microarchitecture of the bone in the proximal tibial metaphysis was evaluated by micro-CT. In the OVX + PTH group, trabecular bone volume (BV/ TV), number (Tb.N) and thickness (Tb.Th) were significantly increased, structure model index (SMI) and trabecular bone pattern factor (TBPf) decreased when compared with the OVX group. In comparison to the OVX group, BV/TV and Tb.N were significantly greater, while SMI and TBPf had no marked changes in the OVX + GJG group. These results suggest that the administration of hPTH (1-34) restore the trabecular bone volume and improve the microstuctural property as well, while GJG reduce the bone loss without affecting its microstructural property in ovariectomized rats.     

In situ localization of gelatinolytic activity during development and resorption of Meckel's cartilage in mice

Degradation of Meckel's cartilage in the middle portion is accompanied by hypertrophy and death of chondrocytes, calcification of the cartilaginous matrix, and chondroclastic resorption. We hypothesize that the gelatinolytic activity of matrix metalloproteinases (MMPs) largely contributes to the degradation of extracellular matrix (ECM) in the process. The activity in Meckel's cartilage of mouse mandibular arches at embryonic days 14-16 (E14-E16) was examined by a combination of in situ zymography (ISZ), using quenched fluorescent dye-labeled gelatin as a substrate, with CTT (a selective inhibitor of MMP-2 and -9) or with EDTA (a general MMP inhibitor). On E14 and E15, ISZ showed fluorescence in the perichondrium, in the intercellular septa between chondrocytes, and in the nucleus of chondrocytes. CTT attenuated fluorescence, and EDTA eliminated it. On E16, calcified cartilaginous matrix showed intense fluorescence, and dot-like fluorescence was observed in as-yet uncalcified intercellular septa, even after CTT treatment. EDTA inhibited fluorescence, but unexpectedly intense fluorescence was found in the cytoplasm of hypertrophic chondrocytes facing the resorption front. MMP-2, -9, and -13 immunoreactivity was detected in the perichondrium and chondrocytes of Meckel's cartilage. These findings suggest that MMPs and other proteinases capable of degrading gelatin play an integral role in the development, calcification, and resorption of Meckel's cartilage through ECM reconstitution.     

COVID‐19: A global transplant perspective on successfully navigating a pandemic

The COVID‐19 pandemic has rapidly evolved and changed our way of life in an unprecedented manner. The emergence of COVID‐19 has impacted transplantation worldwide. The impact has not been just restricted to issues pertaining to donors or recipients, but also health‐care resource utilization as the intensity of cases in certain jurisdictions exceeds available capacity. Here we provide a personal viewpoint representing different jurisdictions from around the world in order to outline the impact of the current COVID‐19 pandemic on organ transplantation. Based on our collective experience, we discuss mitigation strategies such as donor screening, resource planning, and a staged approach to transplant volume considerations as local resource issues demand. We also discuss issues related to transplant‐related research during the pandemic, the role of transplant infectious diseases, and the influence of transplant societies for education and disseminating current information.     

Histological analysis of appendices removed during interval appendectomy after conservative management of pediatric patients with acute appendicitis with an inflammatory mass or abscess

Background/purpose

To clarify the role of interval appendectomy (IA) in pediatric patients with acute appendicitis with an appendiceal inflammatory mass or abscess, we histologically analyzed the appendices removed during IA.

Patients and methods

We treated 355 consecutive pediatric patients with acute appendicitis and reviewed the admission charts of patients who started conservative management (CM). The histology of the appendix removed during IA was also examined. The relationships among the clinical features, appendicolith formation at the time of IA and histological findings were analyzed by stepwise regression analyses.

Results

(1) CM was started in 48 patients (13.5 %). Recurrence or a remaining abscess was observed in nine patients (18.8 %). (2) Histopathological changes, particularly foreign body reaction with fibrosis and infiltration of inflammatory cells, were observed in about half of the specimens. (3) In a stepwise regression analysis, the presence of an appendicolith at IA was correlated with an appendicolith at diagnosis, foreign body reaction in the appendix and a decrease in the inflammatory reaction at diagnosis.

Conclusion

More than half the patients had strong histopathological changes in the appendix, suggesting a high possibility of recurrence. The presence of appendicolith formation at IA, which is a risk factor for recurrence, was influenced by the presence of an appendicolith at diagnosis, foreign body reaction in the appendix and the inflammatory status of patients at diagnosis. These clinical findings are indications for IA.     

Non-high-density lipoprotein cholesterol and the development of coronary heart disease and stroke subtypes in a general Japanese population: The Hisayama Study

Background and purpose

It has not been fully determined whether non-high-density lipoprotein cholesterol (non-HDLC) levels are involved in vascular events, especially stroke, in general Asian populations. We evaluated the association between non-HDLC levels and the risk of type-specific cardiovascular disease in a prospective cohort study in Japan.

Methods

A total of 2452 community-dwelling Japanese subjects aged ≥40 years were followed prospectively for 24 years.

Results

The age- and sex-adjusted incidence of coronary heart diseases (CHD) significantly increased with elevating non-HDLC levels (P for trend < 0.001), but no such association was observed for ischemic and hemorrhagic strokes. With regard to ischemic stroke subtypes, the age- and sex-adjusted incidence of lacunar infarction significantly increased with elevating non-HDLC levels (P for trend < 0.01), and such tendency was seen for atherothrombotic infarction (P for trend = 0.098), while a significant inverse association was observed for cardioembolic infarction (P for trend = 0.007). After adjustment for confounders, namely, age, sex, diabetes, body mass index, systolic blood pressure, electrocardiogram abnormalities, current drinking, current smoking, and regular exercise, the associations remained significant for CHD [adjusted hazard ratio (HR) for a 1 standard deviation of non-HDLC concentrations = 1.17, 95% confidence interval (CI) = 1.02 to 1.35], atherothrombotic infarction (adjusted HR = 1.39, 95% CI = 1.09 to 1.79), and cardioembolic infarction (adjusted HR = 0.64, 95% CI = 0.47 to 0.85).

Conclusions

Our findings suggest that elevated non-HDLC levels are a significant risk factor for the development of atherothrombotic infarction as well as CHD but reduce the risk of cardioembolic infarction in the general Japanese population.     

Pneumonectomy for node-positive non-small cell lung cancer: can it be a treatment option for N2 disease?

Objective

The feasibility of multimodality therapy in patients with node-positive non-small cell lung cancer (NSCLC) requiring pneumonectomy and the role of pneumonectomy in N2 disease remain controversial. This study evaluated outcomes in patients with node-positive NSCLC undergoing pneumonectomy in a community hospital.

Methods

Perioperative and long-term outcomes of 37 patients with node-positive (pN1–2) NSCLC undergoing pneumonectomy from September 1994 to April 2010 as a clinical practice were retrospectively analyzed.

Results

Twenty patients received induction therapy, and 17 received preoperative chemoradiation (30–40 Gy). Fifteen patients and 22 patients underwent right and left pneumonectomy, respectively. A postoperative complication occurred in 8 patients. In-hospital mortality occurred in 1 patient. Induction therapy did not increase the operative risk including operative time, blood loss and postoperative complications. Nineteen patients were given a diagnosis of pN2. Although 7 bulky N2 patients and 10 multi-station N2 patients were included, 5-year overall survival was 34.3 % in pN1 and 28.0 % in pN2 (p = 0.998), respectively. Twenty-three patients received additional postoperative therapy. Five patients died within 3 months postoperatively due to distant metastases. Induction therapy and laterality did not influence survival. Extended resection, such as vagus nerve or chest wall resection, predicted an unfavorable outcome in multivariate analysis (Hazard ratio 2.81, p = 0.032).

Conclusions

The safety and acceptable long-term outcome of pneumonectomy as a general clinical practice were shown for both pN1 and pN2 patients with various preoperative or postoperative therapies. Extended resection due to the extrapleural or extranodal involvement of tumor was an unfavorable prognostic factor.     

Comparative analysis of LTR and structural genes in an equine infectious anemia virus strain isolated from a feral horse in Japan

Although equine infectious anemia virus (EIAV) poses a major threat to the equine industry worldwide, the molecular epidemiology of this virus is poorly understood. Recently, an EIAV strain (EIAV_{Miyazaki2011-A}) representing a new monophyletic group was discovered in feral horses in southern Japan. In the present study, the EIAV_{Miyazaki2011-A} proviral genome is compared with evolutionarily divergent EIAV isolates to investigate conservation of functional elements or motifs within the long terminal repeats (LTRs) and structural genes. This analysis represents a significant step forward in increasing understanding of the molecular conservation and variation between geographically distinct strains of this equine lentivirus.