Daidzein and genistein but not their glucosides are absorbed from the rat stomach

AbstractAbsorption of isoflavone aglycones and glucosides was compared in rats. Daidzein, genistein, daidzin and genistin were orally administered at a dose of 7.9 μmol/kg in 25 mM Na2CO3 and next their metabolite concentration in blood plasma was monitored for 30 min. After isoflavone glucosides administration, their metabolites appeared in plasma with a few minutes delay as compared to aglycones, which suggested that aglycones, but not glucosides, were absorbed already in the rat stomach. This observation was confirmed when absorption site was restricted solely to the stomach and absorption was shown to be independent of the vehicle pH used for administration

Expression and Function of Transmembrane-4 Superfamily (Tetraspanin) Proteins in Osteoclasts: Reciprocal Roles of Tspan-5 and NET-6 during Osteoclastogenesis

Background: Osteoclasts are bone-resorbing multinuclear polykaryons essential for bone remodeling, formed through cell fusion of mononuclear macrophage/monocyte lineage precursor cells upon stimulation by the RANK/RANKL system. Recent studies have revealed that a family of tetraspanin proteins, such as CD9, is critically involved in the cell fusion/polykaryon formation of these cell types. Until now, however, there is limited knowledge about the types of tetraspanins expressed in osteoclasts and their precursors. Methods: The expression of different tetraspanin proteins in a monocyte/macrophage-lineage osteoclast precursor cell line, RAW264.7, was cyclopedically investigated using RT-PCR with specific primers and quantitative real-time RT-PCR. The function of two kinds of tetraspanins, Tspan-5 and NET-6, whose expression pattern was altered by RANKL stimulation, was examined by transfecting gene-specific short-interfering RNAs into these cell types. Results: Of the 17 tetraspanins in mammalian hematopoietic cells, RAW264.7 cells express mRNA for 12 different kinds of tetraspanins, namely, CD9, CD37, CD53, CD63, CD81, CD82, CD151, NAG-2, NET-6, SAS, Tspan-3, and Tspan-5. Interestingly, during their maturation into osteoclasts upon RANKL stimulation, the transcript for Tspan-5 is up-regulated, whereas that for NET-6 is down-regulated. Targeted inhibition of Tspan-5 by using gene-specific RNA interference suppressed RANKL-induced cell fusion during osteoclastogenesis, whereas inhibition of NET-6 augmented the osteoclastogenesis itself. These results suggest that Tspan-5 and NET-6 have a reciprocal function during osteoclastogenesis, i.e., positive and negative regulation by Tspan-5 and NET-6, respectively. RANKL regulates osteoclastogenesis by altering the balances of these tetraspanin proteins. Conclusions: These data indicate that a diversity of tetraspanins is expressed in osteoclast precursors, and that cell fusion during osteoclastogenesis is regulated by cooperation of distinct tetraspanin family proteins such as Tspan-5 and NET-6. This study indicates that functional alterations of tetraspanin family proteins may have therapeutic potential in diseases where osteoclasts play a major role, such as rheumatoid arthritis and osteoporosis

PATHOLOGICAL CONSIDERATIONS OF REOPERATIVE VASCULAR PATIENTS

Since vascular disease is always progressive and a perfect vascular prosthesis has yet to be developed, postoperative complications are almost inevitable. In this paper, case histories of those who had to have a second operation or, in other words, re-operated patients, have been examined to ascertain the current problems in vascular surgery.Of 176 vascular reconstructive operations performed between January 1, 1980, and December 31, 1986, 29 re-operations were performed on 19 patients (mean age: 64 years; 15: male). The incidence of late graft failures was 8.4% and, of these, anastomotic aneurysms seemed to be the most serious complication (3.1% incidence rate).Late graft failures included intimal hyperplasia, occurring within two years in five cases, and four cases of progressing atherosclerosis, which appeared three years after the initial operation.In all cases of anastomotic aneurysm, arterial wall failure, possibly combined with the changing of implanted grafts, was considered to be related to the false aneurysmal formation. Knitted Dacron demonstrated susceptibility to atherosclerotic progression, whereas the major fault of polytetrafluoroethylene (PTFE) grafts was the insufficiency of the anastomotic diameter.In conclusion, it was revealed that many factors can provoke late graft failure. Improvement of long-term patency seems to be achieved by a more increased understanding of the pathological meaning of these factors, along with the proper application of medical techniques suited to the causes of vascular obstruction

COMPARISON OF ARTERIOSCLEROSIS OBLITERANS OF LOWER LIMBS BETWEEN CHINA AND JAPAN

Clinical data on 50 patients with arteriosclerosis obliterans (ASO) in China (Group A) and Japan (Group B) respectively were studied for better understanding of these changing trends.The results showed that the incidence of ASO peaked in Group A in the 50 to 69 age range (88%) and in Group B in the 55 to 74 age range (78%). Group A had a lower ratio of smokers and cases of diabetes mellitus than Group B but a higher ratio of hypertension and a higher total cholesterol level. Angiography showed that the prevalence of atherosclerotic lesions in the lower extremities as a whole was similar for both groups. They were different in location, extent and severity of the arteries involved between the two groups. We believe that this study has shown various differences between the two groups but that the causes are probably multifactorial

National trends in the outcomes of subarachnoid haemorrhage and the prognostic influence of stroke centre capability in Japan: retrospective cohort study

Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era