Topical thermal therapy with hot packs suppresses physical inactivity-induced mechanical hyperalgesia and up-regulation of NGF

We focused on the analgesic effect of hot packs for mechanical hyperalgesia in physically inactive rats. Male Wistar rats were randomly divided into four groups: control, physical inactivity (PI), PI + sham treatment (PI + sham), and PI + hot pack treatment (PI + hot pack) groups. Physical inactivity rats wore casts on both hind limbs in full plantar flexed position for 4 weeks. Hot pack treatment was performed for 20 min a day, 5 days a week. Although mechanical hyperalgesia and the up-regulation of NGF in the plantar skin and gastrocnemius muscle were observed in the PI and the PI + sham groups, these changes were significantly suppressed in the PI + hot pack group. The present results clearly demonstrated that hot pack treatment was effective in reducing physical inactivity-induced mechanical hyperalgesia and up-regulation of NGF in plantar skin and gastrocnemius muscle.     

Multimers and adiponectin gene 276G>T polymorphism in the Japanese population residing in rural areas.

BACKGROUND: Although it has been shown that high-molecular weight adiponectin is an active form, few studies have attempted to clarify the relationship between high molecular weight adiponectin and markers linked with cardiovascular diseases in the general population. METHODS: We screened 236 Japanese study participants recruited from the general population, residing in one large and four small islands. In addition to serum lipids and lipoproteins, serum total adiponectin and each multimer were measured. The genotype single-nucleotide polymorphism 276G>T was detected in real-time PCR with LightCycler hybridization probes, using fluorescent-labeled nucleotides. RESULTS: Multiple linear regression analysis showed that high-molecular weight adiponectin, as well as total adiponectin, were significantly correlated with body weight, body mass index, high-density lipoprotein cholesterol and triglycerides. Total adiponectin and high-molecular weight adiponectin concentrations were not significantly different between GG and TX (GT and TT) genotypes of 276G>T polymorphism in the adiponectin gene. Interestingly, no differences were observed for participants from the large island between GG and TX genotypes with regard to both total adiponectin and high-molecular weight adiponectin, whereas significant differences were observed for those from the small islands. CONCLUSIONS: Our results show that total adiponectin and high-molecular weight adiponectin are associated with similar factors in the general population. Furthermore, different effects of 276G>T for participants from small and large islands suggest that regional background due to geographic barriers may control the effects of 276G>T on adiponectin concentrations.     

An autopsy case of pulmonary and central nervous system metastatic osteosarcoma treated with thirty-six courses of chemotherapy over four years]

A 32-year-old man presented with cough, dyspnea and orthopnea ten years after amputation of the right humerus because of osteosarcoma. Chest radiographs and chest computed tomographs showed left pleural effusion, pericardial effusion and a giant intrathoracic mass, which was histologically diagnosed as a recurrence of the osteosarcoma. After 4 courses of chemotherapy combined with CDDP, the mass in the left upper lobe of the lung decreased in size, and it was then resected. Three months later, new metastatic lesions were detected in the thoracic area. Therefore, 29 additional courses of chemotherapy were administered (36 courses in total over 4 years; including regimens combined with CDDP, carboplatin, high-dose methotrexate, ifosfamide, dacarbazine, vindesine, etoposide, vincristine, taxotere and gemcitabine). In spite of the several courses of chemotherapy, brain and spinal cord metastases appeared, and the patient eventually died of cerebral hemorrhage. During the four years after the first recurrence he had good quality of life as a result of the chemotherapy.     

Identification and detection method for genetically modified papaya resistant to papaya ringspot virus YK strain

Unauthorized genetically modified (GM) papaya (Carica papaya LINNAEUS) was detected in a commercially processed product, which included papaya as a major ingredient, in Japan. We identified the transgenic vector construct generated based on resistance to infection with the papaya ringspot virus (PRSV) YK strain. A specific detection method to qualitatively monitor papaya products for contamination with the GM papaya was developed using the real-time polymerase chain reaction.     

Hip fracture incidence in Japan: estimates of new patients in 2007 and 20-year trends

Summary

We estimated the number of hip fracture patients in 2007 in Japan and investigated the trends in incidence during a 20-year period from 1987 to 2007. Despite the increasing number of new patients, the incidence of hip fracture in some age groups showed the possibility of decline.

Purpose

The aims of this study were to estimate the number of hip fracture patients in 2007, to investigate the trends in incidence during a 20-year period from 1987 to 2007, and to show the regional differences in Japan.

Methods

Data were collected through a nationwide survey based on hospitals by the mailing method. Hip fracture incidences by sex and age and standardized incidence ratios by region were calculated.

Results

The estimated numbers of new hip fracture patients in 2007 were 148,100 in total (95% CI, 144,000–152,200), 31,300 (30,500–32,100) for men, and 116,800 (113,900–119,700) for women. The incidence rate in men aged 60–69 years and that in women aged 60–79 years were the lowest in the 15-year period from 1992 to 2007. The incidence was higher in western areas of Japan than in eastern areas in both men and women.

Conclusions

Despite the increasing number of new patients, the incidence of hip fracture in some age groups for both men and women showed the possibility of decline. The exact reasons for this are unknown, but drug therapy for osteoporosis and fall prevention programs might have influenced the results. Some nutrient intakes might explain the regional differences not only in Japan but also in some other countries.     

Relapsed and refractory multiple myeloma: A systematic review and network meta-analysis of the efficacy of novel therapies

The prognosis of multiple myeloma (MM) has dramatically improved with the development of new drugs, and it has become important to determine the appropriate combinations of these novel agents. This study was a systematic review and network meta-analysis (NMA) of randomized trials in patients with relapsed and/or refractory (RR) MM. The PubMed, Cochrane, and Embase databases were searched for randomized trials from 1 January 2002 to 28 February 2022 of patients treated for MM. The primary end-point was progression-free survival (PFS), evaluated as a hazard ratio (HR) with a 95% confidence interval (95% CI) compared to dexamethasone (DEX). The p-score was used to rank treatments. Of a total of 1136 abstracts screened, 37 studies were selected, including 34 treatment options for RRMM. Daratumumab, lenalidomide and DEX was found to be the best treatment for RRMM, with the best HR compared to DEX (HR, 0.13; 95% CI, 0.08–0.20; p-score 0.9796). There was no evidence of significant heterogeneity (I², 41.3%; p = 0.146). The current NMA confirmed the excellent efficacy of three-drug regimens including anti-CD38 antibodies to treat RRMM and provides background data to evaluate the efficacy of chimeric antigen receptor T-cell treatments and bispecific T-cell engager therapies.     

Characteristics and course of bone mineral densities among fast bone losers in a rural Japanese community: the Miyama Study

The aim of this study was to clarify and compare the temporal course of bone mineral density (BMD) between fast bone losers and normal residents in Miyama Village, a rural Japanese community. BMD was measured over a 10-year period in a cohort study in Miyama Village, Wakayama Prefecture, Japan, to provide information on rate of bone loss in the mature and elderly population. Subjects (n=400) were selected by sex and age stratum from the full list of residents born in 1910–1949, with 50 men and 50 women in each age decade. Baseline BMD of the lumbar spine and proximal femur was measured using dual energy X-ray absorptiometry in 1990, 1993, 1997 and 2000. In the cohort, 171 men and 189 women completed the follow-up survey performed in 1993. After calculating the rate of bone loss between 1990 and 1993, the greatest tertile from the distribution of bone loss was categorized as fast bone losers, with the remainder considered as normal subjects. Changes in BMD were compared between normal subjects and fast bone losers over the 10-year period. Mean rate of change for BMD at both lumbar spine and femoral neck in fast bone losers recovered to levels similar to those in normal subjects over 7 years of observation. By contrast, BMD at the lumbar spine and femoral neck decreased steeply over the 10-year period in both groups, and mean BMD for fast bone losers was significantly lower than that of normal subjects (P<0.05). These differences were apparent only at the lumbar spine in both men and women, even after adjusting for age. These results indicate that fast bone loss is a transient phenomenon rather than a fixed status, although individuals who have been categorized as fast bone losers at some stage continue to display low BMD in the lumbar spine.     

Pleural fluid/serum immunoglobulin ratio is a diagnostic marker for congenital chylothorax in utero

OBJECTIVE: To distinguish congenital chylothorax from other causes of hydrothorax in utero. METHODS: Serum and pleural fluid samples from 8 fetuses with congenital chylothorax and 5 control fetuses with other causes of hydrothorax were tested for total protein, albumin, IgG, IgA, and IgM. RESULTS: Fetuses with congenital chylothorax had higher levels of IgG in pleural fluid, but not the other four proteins, than control fetuses (P<0.05). There were no significant differences in serum proteins among fetuses. When we examined pleural fluid to serum ratios, the IgG ratio in fetuses with congenital chylothorax was significantly higher than that of control fetuses (P<0.05). The IgG ratio in chylothorax was greater than 0.6 regardless of lymphocyte count. CONCLUSION: Pleural fluid/serum IgG ratio may be a diagnostic marker for congenital chylothorax in utero.     

A new noninvasive measurement system for wave intensity: evaluation of carotid arterial wave intensity and reproducibility

Wave intensity (WI) is a new hemodynamic index that provides information about the dynamic behavior of the heart and the vascular system and their interaction. Carotid arterial wave intensity in normal subjects has two positive peaks. The first peak, W₁, occurs during early systole, the magnitude of which increases with increases in cardiac contractility. The second peak, W₂, which occurs towards the end of ejection, is related to the ability of the left ventricle to actively stop aortic blood flow. Between the two positive peaks, a negative area, NA, is often observed, which signifies reflections from the cerebral circulation. The time interval between the R-wave of ECG and the first peak (R − W₁) corresponds to the pre-ejection period, and that between the first and second peaks (W₁ − W₂) corresponds to ejection time. We developed a new ultrasonic on-line system for obtaining WI and arterial stiffness (β). The purpose of this study was (1) to report normal values of various indices derived from WI and β measured with this system, and (2) to evaluate the intraobserver and interobserver reproducibility of the measurements. The measurement system is composed of a computer, a WI unit, and an ultrasonic machine. The WI unit gives the instantaneous change in diameter of the artery and the instantaneous mean blood velocity through the sampling gate. Using these parameters and blood pressure measured with a cuff-type manometer, the computer gives WI and β. We applied this method to the carotid artery in 135 normal subjects. The mean values of W₁, W₂, NA, R − W₁, and W₁ − W₂ were 8 940 ± 3 790 mmHg m/s³, 1 840 ± 880 mmHg m/s³, 27 ± 13 mmHg m/s², 104 ± 14 ms, and 270 ± 19 ms, respectively. These values did not show a significant correlation with age. The mean value of β was 10.4 ± 4.8 and the values significantly correlated with age (men: r = 0.66, P < 0.0001; women: r = 0.81, P < 0.0001). The reproducibility was evaluated by intraobserver intrasession (IA), intraobserver intersession (IE), and interobserver intrasession variability (IO). The reproducibility of R − W₁ and W₁ − W₂ was high: the mean coefficient of variation (mCV) of IA was less than 3%; 95% confidence limits from the mean values (CL) were less than 8% for IE and less than 4% for IO. The reproducibility of W₁ and β was good: mCV for IA was less than 10%; CL for IE and IO were less than 17%. W₂ and NA showed a higher variability than other indices: mCV for IA was less than 13%, and CL for IE and IO were less than 36%. However, two sessions by the same observer and two sessions by different observers were not biased. Wave intensity measurements with this system are clinically acceptable. Received: March 25, 2002 / Accepted: June 17, 2002 Acknowledgments K.N. and M.S. were supported by Grants-in-Aid for Scientific Research (B)-11695092 and (C)-11670713 from the Ministry of Education, Science, Sports and Culture of Japan. Correspondence to K. Niki     

Ozone production by amino acids contributes to killing of bacteria

Reactive oxygen species produced by phagocytosing neutrophils are essential for innate host defense against invading microbes. Previous observations revealed that antibody-catalyzed ozone formation by human neutrophils contributed to the killing of bacteria. In this study, we discovered that 4 amino acids themselves were able to catalyze the production of an oxidant with the chemical signature of ozone from singlet oxygen in the water-oxidation pathway, at comparable level to antibodies. The resultant oxidant with the chemical signature of ozone exhibited significant bactericidal activity in our distinct cell-free system and in human neutrophils. The results also suggest that an oxidant with the chemical signature of ozone produced by neutrophils might potentiate a host defense system, when the host is challenged by high doses of infectious agents. Our findings provide biological insights into the killing of bacteria by neutrophils.