Matrix metalloproteinases (MMPs) play an important role in degeneration of the matrix associated with bone and cartilage. Regulation of osteoclast activity is essential in the treatment of bone ...disease, including osteoporosis and rheumatoid arthritis. Polyphenols in green tea, particularly epigallocatechin-3-gallate (EGCG), inhibit MMPs expression and activity. However, the effects of the black tea polyphenol, theaflavin-3,3′-digallate (TFDG), on osteoclast and MMP activity are unknown. Therefore, we examined whether TFDG and EGCG affect MMP activity and osteoclast formation and differentiation in vitro. TFDG or EGCG (10 and 100 μM) was added to cultures of rat osteoclast precursors cells and mature osteoclasts. Numbers of multinucleated osteoclasts and actin rings decreased in polyphenol-treated cultures relative to control cultures. MMP-2 and MMP-9 activities were lower in TFDG- and EGCG-treated rat osteoclast precursor cells than in control cultures. MMP-9 mRNA levels declined significantly in TFDG-treated osteoclasts in comparison to control osteoclasts. TFDG and EGCG inhibited the formation and differentiation of osteoclasts via inhibition of MMPs. TFDG may suppress actin ring formation more effectively than EGCG. Thus, TFDG and EGCG may be suitable agents or lead compounds for the treatment of bone resorption diseases.
A shift towards obtaining emergency contraceptives without a prescription have been discussed in Japan. In response to this social background, we aimed at investigating the background of sexual ...intercourse, emergency contraceptive use, and knowledge of sexual and reproductive health education among women of reproductive age in Japan. In this study, we conducted a national wide cross-sectional questionnaire survey using a total of 4 web-based domains (background, sexual history, emergency contraceptives, and sexual and reproduction-related knowledge) composed of 50 questions. We obtained responses from a total of 4,631 participants of varying age groups (18–25, 26–35, and 36–45 years old) and 47 prefectures (84 to 118 from each prefecture). Among participant responses, 69.7% are sexually active, of which 49.0% had experiences of sexual intercourse with an unknown person. The responses from a total of 737 participants who have sexual intercourse, know of emergency contraceptives, and have experienced a situation that necessitated the use of emergency contraceptives, were analyzed. Of these participants, 46.4% (342/737) took emergency contraceptives, while 43.6% (321/737) participants did not take emergency contraceptives. Participants who have the knowledge for obtaining emergency contraceptives through the correct means were 52.6% (2438/4631). This study showed that approximately half of participants may not have correct knowledge of emergency contraceptives. In addition, approximately half of sexually active participants are facing unintended pregnancies due to a lack of sexual and reproductive awareness. Hence, comprehensive sex education is necessary to achieve social and regulatory changes centered on emergency contraceptives.
Children with Kawasaki disease are prescribed acetylsalicylic acid powder as an antipyretic analgesic and antiplatelet agent; however, some of it remains in the mouth, leading to a bitter or sour ...taste. To address this issue, an in-hospital mini-tablet formulation of acetylsalicylic acid was developed. In order to use the mini-tablets safely and effectively, dissolution tests alone are not sufficient. Therefore, an open-label crossover study on six healthy participants was conducted to evaluate comparative pharmacokinetic parameters. The pharmacokinetic parameters of salicylic acid were Cmax: 4.80 ± 0.79 mg/L (powder; P), 5.03 ± 0.97 mg/L (mini-tablet; MT), AUC0–12: 18.0 ± 3.03 mg-h/L (P), 18.9 ± 4.59 mg-h/L (MT), those of acetylsalicylic acid Cmax: 0.50 ± 0.20 mg/L (P), 0.41 ± 0.24 mg/L (MT), AUC0–12: 0.71 ± 0.27 mg-h/L (P), 0.61 ± 0.36 mg-h/L (MT), with no significant differences between the mini-tablet and powder formulations. Although pharmacokinetic results obtained from adults cannot be directly applied to children, the results of this study are important for predicting pharmacokinetics. Furthermore, a formulation that can improve medication adherence in children who have difficulty taking acetylsalicylic acid powder, thus contributing to pediatric drug therapy.
Osteoclasts are important target cells for osteoporosis treatment. Recently, a real-time cell analysis (RTCA) system was developed to observe cell morphology and adhesion; however, the use of RTCA to ...study osteoclastogenesis has not been reported. Here, we investigated whether osteoclast formation could be monitored in real-time using RTCA. The cell index determined via electrical impedance using RTCA, and the number of osteoclasts exhibited a significant positive correlation. RTCA was useful for determining the effect of (−)-epigallocatechin-3-gallate on the inhibition of bone resorption. We established a new method of measuring osteoclast formation in real-time using RTCA.
Anthropometric indices of central obesity, waist circumference (WC), conicity index (CI), and a-body shape index (ABSI), are prognostic indicators of cardiovascular (CV) risk. The association of CI ...and ABSI with other CV risk indices, markers of nutritional status and inflammation, and clinical outcomes in chronic kidney disease (CKD) stage 5 (CKD5) patients was investigated.
In a cross-sectional study with longitudinal follow up of 203 clinically stable patients with CKD5 (median age 56 years; 68% males, 17% diabetics, 22% with CV disease, and 39% malnourished), we investigated CI and ABSI and their associations with atherogenic index of plasma (AIP), Framingham CV risk score (FRS), Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC), handgrip strength (HGS), high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). CV events (CVE) and all-cause mortality during up to 10-years follow up were analyzed by multivariate survival analysis of restricted mean survival time (RMST).
Chronic kidney disease patients with middle and highest CI and ABSI tertiles (indicating greater abdominal fat deposition), compared to those with the lowest CI and ABSI tertiles, tended to be older, more often men and diabetic, had significantly higher levels of hsCRP, IL-6, AIP, FRS, CAC and AVC scores. CI and ABSI were positively correlated with CAC, FRS, AIP, hsCRP and IL-6. Both CI and ABSI were negatively correlated with HGS. In age-weighted survival analysis, higher CI and ABSI were associated with higher risk of CVE (Wald test = 4.92,
= 0.027; Wald test = 4.95,
= 0.026, respectively) and all-cause mortality (Wald test = 5.24,
= 0.022; Wald test = 5.19,
= 0.023, respectively). In RMST analysis, low vs. high and middle tertiles of CI and ABSI associated with prolonged CVE-free time and death-free time, and these differences between groups increased over time.
Abdominal fat deposit indices, CI and ABSI, predicted CV outcomes and all-cause mortality, and were significantly associated with the inflammatory status in CKD patients.
Abstract
Background and Aims
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and fourth case of kidney failure worldwide. Treatment options for ADPKD ...include therapy with vasopressin (ADH) receptor 2 antagonist, nephroprotection, and eventually renal replacement therapy. The earliest and most prevalent systemic complication of ADPKD is hypertension. The pathogenesis of hypertension in ADPKD is multifactorial, including endothelial dysfunction and activation of renin-angiotensin-aldosterone system (RAAS). Antihypertensive therapy with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is expected to decrease the left ventricular hypertrophy and proteinuria in ADPKD patients, according to HALT-PKD study. Data about preferences of second choice therapy and safety of other medications is lacking. Diuretics are commonly prescribed drugs in essential hypertension but carry risk of provoking ADH stimulation that may be potentially harmful in ADPKD because ADH stimulates cyst proliferation. We analyzed real-life data on antihypertensive prescriptions to determine and compare trends in treatment of hypertension in ADPKD patients in Poland and Japan.
Method
Patterns of antihypertensive prescriptions of ACEi, ARB, and diuretics were analyzed in patients from Poland (n = 131, median age 40 years; data 2014-2019) and Japan (n = 180, median age 44 years, data 2005-2017) diagnosed with ADPKD. The number of different medications used in combination was counted. For diuretics, even if multiple diuretics were used, they were counted as a single item. Furthermore, combination drug products were decomposed into their individual components, which were counted as either antihypertensive drugs or diuretics, respectively.
Results
The patterns of the number of prescriptions of antihypertensive drugs were similar in the two countries, see Figure 1. In Polish patients, the commonest pattern was no antihypertensive drugs (45.0%), followed by one (28.2%), two (16.8%), three (9.2%), and four (0.8%) prescriptions. In Japanese patients, the corresponding figures were: no antihypertensive drugs (41.1%), followed by one (32.2%), two (20.6%), three (4.4%), and four (1.7%) prescriptions in decreasing order. ACEi and ARBs were used for more than half of the patients, both Polish and Japanese. The utilization of ACEi/ARB in Polish individuals as a first-choice medication was 78.4% (75.0% in men, 81.0% in women) while in Japan 65.5% (66.7% in men, 63.2% in women). When patients were prescribed 3 or more antihypertensive drugs, ACEi/ARB was chosen in 100%, in both countries. Regarding diuretics, 15.3% of Polish patients and 6.7% of Japanese patients used them. Among patients who had one antihypertensive drug, 7.6% of Polish and 2.2% of Japanese patients also used diuretics. 44.2% of Polish and 38.9% of Japanese did not use either antihypertensive drugs or diuretics.
Conclusion
The patterns of number of prescriptions of antihypertensive drugs were similar among ADPKD patients in Poland and Japan while the use of diuretics was more common in Polish than in Japanese patients. In both countries, ACEi/ARB was the most frequent choice, which is in concordance with current recommendations. Unexpectedly, anti-RAAS were as frequently prescribed in women than in men, suggesting that the teratogenicity risk of the drugs did not limit access to the benefits of the treatment in both sexes.
Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs, tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained at the Institute ...for Animal Experimentation, St. Marianna University Graduate School of Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its frequency, we bred the dwarf rats and investigated their characteristics in order to identify the causative factors of their phenotypes and whether they could be used as a human disease model. One male and female that produced dwarf progeny were selected, and reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among the resultant litter, and dwarfism occurred in both genders, suggesting that it was inherited in an autosomal recessive manner. At 12 weeks of age, the body weights of the male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In soft X-ray radiographic and histological examinations, shortening and hypoplasia of the long bones, such as the tibia and femur, were observed, which were suggestive of endochondral ossification abnormalities. An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats. We hypothesized that the principal characteristics of the dwarf rats were systemically induced by insufficient cartilage calcification in their long bones; thus, we named them cartilage calcification insufficient (CCI) rats.
Abstract
BACKGROUND AND AIMS
Atherogenic index of plasma (AIP), a logarithmically transformed ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C), is a biomarker of dyslipidemia ...and cardiovascular disease (CVD) risk. However, its applicability in end-stage kidney disease (ESKD) is not clear. We examined the association of AIP with all-cause and CVD mortality in two cohorts of ESKD patients, one from China and one from Sweden.
METHOD
In 1276 Chinese incident peritoneal dialysis (PD) patients (median age 50 years, 56% males) and 559 Swedish ESKD patients starting on dialysis (n = 392) or undergoing hemodialysis (n = 109) or PD 58 (median age 58 years, 62% males), baseline AIP and other biochemical and metabolic biomarkers were analysed in relation to mortality during follow-up period of up to 5 years. All-cause and CVD mortality risk were analysed with competing-risk regression models with transplantation as competing risk adjusting for age, sex, smoking, diabetes, serum albumin, hemoglobulin and calendar year.
RESULTS
Chinese patients median (IQR) BMI 21 (19–23) kg/m2 TG 1.4 (1.0–1.8) and HDL-C 1.0 (0.9–1.3) mmol/L compared with Swedish patients median (IQR) BMI 24 (22–28) kg/m2 TG 1.6 (1.2–2.2) and HDL-C 1.2 (1.0–1.6) mmol/L were significantly younger (P < 0.01) and had lower BMI (P < 0.01), TG (P < 0.001), HDL-C (P < 0.001), and Framingham risk score (P < 0.01) while sex distribution was similar. ‘Chinese patients’: After median 3.6 years of follow-up, all-cause mortality rate was 16%, and 91 (46%) of the 199 deaths were caused by CVD. The highest tertile of AIP was associated with higher all-cause sub-hazard ratio sHR (95% CI) 1.52 (1.05); Fig. 1A and CVD mortality sHR 1.82 (1.02–3.27); Fig. 1B risk, after adjusting for confounders. ‘Swedish patients’: After median 2.1 years of follow-up, all-cause mortality rate was 36%, and 89 (44%) of the 204 deaths were caused by CVD. The highest tertile of AIP was associated with lower all-cause sHR 0.66 (0.47–0.94); Fig. 2A and CVD mortality sHR 0.59 (0.35–0.97); Fig. 2B risk after adjusting for confounders.
CONCLUSION
The highest tertile of AIP was independently associated with higher mortality risk in Chinese ESKD patients while it was associated with lower mortality risk in Swedish ESKD patients suggesting that AIP is context dependent, which limits is usefulness as a risk-assessment tool for predicting clinical outcomes in ESKD patients.
Matrix metalloproteinases (MMPs) play an important role in degeneration of the matrix associated with bone and cartilage. Regulation of osteoclast activity is essential in the treatment of bone ...disease, including osteoporosis and rheumatoid arthritis. Polyphenols in green tea, particularly epigallocatechin-3-gallate (EGCG), inhibit MMPs expression and activity. However, the effects of the black tea polyphenol, theaflavin-3,3'-digallate (TFDG), on osteoclast and MMP activity are unknown. Therefore, we examined whether TFDG and EGCG affect MMP activity and osteoclast formation and differentiation in vitro. TFDG or EGCG (10 and 100 μM) was added to cultures of rat osteoclast precursors cells and mature osteoclasts. Numbers of multinucleated osteoclasts and actin rings decreased in polyphenol-treated cultures relative to control cultures. MMP-2 and MMP-9 activities were lower in TFDG- and EGCG-treated rat osteoclast precursor cells than in control cultures. MMP-9 mRNA levels declined significantly in TFDG-treated osteoclasts in comparison to control osteoclasts. TFDG and EGCG inhibited the formation and differentiation of osteoclasts via inhibition of MMPs. TFDG may suppress actin ring formation more effectively than EGCG. Thus, TFDG and EGCG may be suitable agents or lead compounds for the treatment of bone resorption diseases.
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