Effect of coordinator-based osteoporosis intervention on quality of life in patients with fragility fractures: a prospective randomized trial.

We examined the effects of the coordinator-based intervention on quality of life (QOL) in the aftermath of a fragility fracture, as well as factors predictive of post-fracture QOL. The coordinator-based interventions mitigated the decrease in QOL. Secondary fracture after primary fracture, however, was a significant predictor of lower QOL. PURPOSE: This study aimed to determine the effects of the coordinator-based intervention on QOL in the aftermath of a fragility fracture, as well as factors predictive of post-fracture QOL, in an Asian population. METHODS: Patients with new fractures in the intervention group received the coordinator-based intervention by a designated nurse certified as a coordinator, within 3 months of injury. QOL was evaluated using the Japanese version of the EuroQol 5 Dimension 5 Level (EQ-5D-5L) scale  before the fracture (through patient recollections) and at 0.5, 1, and 2 years after the primary fracture. RESULTS: Data for 141 patients were analyzed: 70 in the liaison intervention (LI) group and 71 in the non-LI group. Significant intervention effects on QOL were observed at 6 months after the fracture; the QOL score was 0.079 points higher in the LI group than in the non-LI group (p=0.019). Further, the LI group reported significantly less pain/discomfort at 2 years after the fracture, compared to the non-LI group (p=0.037). In addition, secondary fractures were found to significantly prevent improvement and maintenance of QOL during the recovery period (p=0.015). CONCLUSION: Short-term intervention effects were observable 6 months after the primary fracture, with the LI group mitigated the decrease in QOL. Few patients in the LI group reported pain/discomfort 2 years after the fracture, but there is uncertainty regarding its clinical significance. Secondary fracture after initial injury was a significant predictor of lower QOL after a fracture.

Efficiency of coordinator-based osteoporosis intervention in fragility fracture patients: a prospective randomized trial.

We examined the effectiveness of coordinators' interventions to prevent secondary fractures in patients with fragility fractures. These coordinator-based interventions improved bone density assessment implementation and treatment rates, and enhanced treatment persistence rates in the early stages following fractures. INTRODUCTION: This study aimed to determine the efficiency of coordinator-based osteoporosis intervention in fragility fracture patients during a 2-year period. METHODS: A prospective intervention randomized control study was conducted at seven medical facilities from January 2015 to March 2017. Postmenopausal women and men over 50 years old with fragility fractures were randomly divided into the coordinator intervention (LI; 70 patients) and without intervention (non-LI; 71 patients) groups. The osteoporosis treatment rate, osteoporosis treatment persistence rate, fall rate, fracture incidence rate, and bone density measurement rate 3 months, 6 months, 1 year, and 2 years after registration were compared between the two groups. Non-parametric tests were used to analyze data at each inspection period. RESULTS: The osteoporosis treatment initiation rate was significantly higher in the LI group than in the non-LI group (85.7% vs. 71.8%; p = 0.04). The LI group had significantly higher bone density assessment implementation rates than the non-LI group at the time of registration (90.0% vs. 69.0%; p = 0.00) and 6 months after registration (50.0% vs. 29.6%; p = 0.01), but not 1 or 2 years after registration. In addition, no significant differences in fall or fracture incidence rates were found between the two groups. CONCLUSION: The coordinator-based interventions for fragility fractures improved bone density assessment implementation and treatment rates and enhanced treatment persistence rates in the early stages following bone fractures. The findings suggest that liaison intervention may help both fracture and osteoporosis physicians for the evaluation of osteoporosis and initiation and continuation of osteoporosis medication.

Metabolomics analysis of saliva from patients with primary Sjögren's syndrome.

The recent development of salivary proteomics has led to the identification of potential biomarkers for diagnosing patients with primary Sjögren's syndrome (pSS). Here we sought to identify differentially produced salivary metabolites from pSS patients and healthy controls (HCs) that might be used to characterize this disease. We obtained salivary samples from 12 female pSS patients (mean age 44.2 ± 13.01) and 21 age-matched female HCs. The metabolite profiles of saliva were analysed by gas chromatography-mass spectrometry. The total metabolite levels in each of the samples were calculated and compared across the study participants. A total of 88 metabolites were detected across the study samples, 41 of which were observed at reduced levels in the samples from pSS patients. Principal component analysis (PCA) revealed a loss in salivary metabolite diversity in the pSS patient samples compared to the HC samples. The reduced presence of glycine, tyrosine, uric acid and fucose, which may reflect salivary gland destruction due to chronic sialoadenitis, contributed to the loss of diversity. Comparative PCA of the pSS patients revealed the presence of two subpopulations based on their metabolite profiles, and these two subpopulations showed a significant difference in the prevalence of major salivary glanditis (P = 0.014). In this study, we found that the salivary metabolite profile of pSS patients was less diverse than that of HCs and that the metabolite profiles in pSS patients were affected by the presence of major salivary glanditis.

Heat-killed bacillus Calmette-Guérin and Mycobacterium kansasii antigen 85B combined vaccination ameliorates dermatitis in a mouse model of atopic dermatitis by inducing regulatory T cells.

BACKGROUND: Atopic dermatitis (AD) is a recurrent inflammatory skin disease characterized by dominant T-helper (Th) 2 cytokine response. Bacillus Calmette-Guérin (BCG) has been used for preventing tuberculosis, and is regarded as a strong Th1 cytokine inducer. Antigen (Ag) 85B is a secretory protein present in Mycobacterium species that induces Th1 cytokine production. OBJECTIVES: We investigated the effects of combined vaccination of heat-killed BCG (hkBCG) and Mycobacterium kansasii Ag85B in an AD mouse model. METHODS: For the AD model, keratin 14 promoter-derived caspase-1 overexpressing mice (KCASP1Tg) were used. The mice received a combination therapy of hkBCG at age 3 weeks and Ag85B twice weekly for 11 weeks from the 4th week; Ag85B monotherapy from the 4th week; hkBCG monotherapy at the 3rd week; or control saline. Areas of skin lesions, cytokine mRNA expression and serum interleukin (IL)-18 and immunoglobulin (Ig) E levels were analysed. Inducible Foxp3+ regulatory T cells (iTreg), IL-10-producing T cells (Tr1), and interferon (IFN)-γ/IL-4/IL-17-producing T cells were evaluated in the spleen. RESULTS: Saline-treated mice and hkBCG monotherapy mice spontaneously developed severe dermatitis. However, combined therapy with hkBCG and Ag85B significantly suppressed the development of skin lesions and mast cell infiltrations. Elevations of the serum IgE and IL-18 levels were significantly suppressed with combined therapy. Mice treated with hkBCG and Ag85B had a normal number of iTreg in the spleen, and decreased number of both IL-4- and IL-17-producing CD4+ T cells. The effect of Ag85B monotherapy was limited. CONCLUSIONS: Combined vaccination with hkBCG and Ag85B decreases AD skin lesions by inducing regulatory T cells, suggesting that this vaccination is a potent and novel therapeutic strategy for AD.

Improvement of precision in refinements of structure factors using convergent-beam electron diffraction patterns taken at Bragg-excited conditions.

A local structure analysis method based on convergent-beam electron diffraction (CBED) has been used for refining isotropic atomic displacement parameters and five low-order structure factors with sin θ/λ ≤ 0.28 Å-1 of potassium tantalate (KTaO3). Comparison between structure factors determined from CBED patterns taken at the zone-axis (ZA) and Bragg-excited conditions is made in order to discuss their precision and sensitivities. Bragg-excited CBED patterns showed higher precision in the refinement of structure factors than ZA patterns. Consistency between higher precision and sensitivity of the Bragg-excited CBED patterns has been found only for structure factors of the outer zeroth-order Laue-zone reflections with larger reciprocal-lattice vectors. Correlation coefficients among the refined structure factors in the refinement of Bragg-excited patterns are smaller than those of the ZA ones. Such smaller correlation coefficients lead to higher precision in the refinement of structure factors.

1,24-Dihydroxyvitamin D3 (tacalcitol) prevents skin T-cell infiltration.

BACKGROUND: 1,24-Dihydroxyvitamin D3 (tacalcitol), a vitamin D(3) compound, has been used to treat T cell-mediated inflammatory skin diseases such as psoriasis, prurigo and vitiligo. The best-known mechanism of action of this compound is inhibition of the abnormal proliferation of keratinocytes and subsequent maturation; however, its effects on skin T-cell recruitment have not yet been evaluated. Cutaneous lymphocyte-associated antigen (CLA), a surface glycoprotein expressed on T cells, plays a critical role in skin T-cell infiltration. We recently reported that 1,25-dihydroxyvitamin D3 inhibits skin infiltration of CD4+ T cells by suppressing CLA expression on T cells. OBJECTIVES: In this study, we investigated the effect of tacalcitol on CLA epitope decoration and on the levels of gut or lymph node homing receptor expression in human T cells. METHODS: We cultured human T cells with tacalcitol and analysed the effect on CLA expression and skin-homing ability, and evaluated glycosyltransferase mRNAs. We also performed an in vivo study using an antigen-dependent delayed-type hypersensitivity (DTH) mouse model and investigated the effect of tacalcitol on skin-infiltrating CD4+ T cells. RESULTS: Tacalcitol downregulated the expression of CLA and, in parallel, the E- and P-selectin ligand function; however, it exerted no effect on other homing receptors. Subcutaneously and intraperitoneally administered tacalcitol downregulated skin infiltration of effector CD4+ T cells in an in vivo DTH mouse model. CONCLUSIONS: These findings suggest that tacalcitol reduces skin inflammation by partially downregulating CLA expression levels.

Visualization of ferroaxial domains in an order-disorder type ferroaxial crystal.

Ferroaxial materials that exhibit spontaneous ordering of a rotational structural distortion with an axial vector symmetry have gained growing interest, motivated by recent extensive studies on ferroic materials. As in conventional ferroics (e.g., ferroelectrics and ferromagnetics), domain states will be present in the ferroaxial materials. However, the observation of ferroaxial domains is non-trivial due to the nature of the order parameter, which is invariant under both time-reversal and space-inversion operations. Here we propose that NiTiO3 is an order-disorder type ferroaxial material, and spatially resolve its ferroaxial domains by using linear electrogyration effect: optical rotation in proportion to an applied electric field. To detect small signals of electrogyration (order of 10-5 deg V-1), we adopt a recently developed difference image-sensing technique. Furthermore, the ferroaxial domains are confirmed on nano-scale spatial resolution with a combined use of scanning transmission electron microscopy and convergent-beam electron diffraction. Our success of the domain visualization will promote the study of ferroaxial materials as a new ferroic state of matter.

Calcium and sodium contributions to regenerative responses in the embryonic excitable cell membrane.

Ionic dependence of regenerative responses of the embryonic cell mnembrane has been studied successively at each stage of development from the unfertilized egg to the differentiated striated muscle in the tadpole larva of the tunicate. The unfertilized egg cell itself showed a type of regenerative response dependent on both sodium and calcium ions, while the spike potentials exclusively dependent on calcium ions were elicited in the differentiated muscle cell.

Identification of somatostatin receptor subtypes and an implication for the efficacy of somatostatin analogue SMS 201-995 in treatment of human endocrine tumors.

The presence of somatostatin receptors has been demonstrated in various endocrine tumors as well as in normal tissues. We recently have cloned five human somatostatin receptor subtypes (SSTR1-SSTR5). These mRNAs are expressed in a tissue-specific manner. In this study, we have determined the somatostatin receptor subtypes expressed in various endocrine tumors using a reverse transcriptase polymerase chain reaction method. In two cases of glucagonoma and its metastatic lymph nodes in one case, all the SSTR subtype mRNAs except SSTR5 mRNA were expressed. In four cases of insulinoma, SSTR1 and SSTR4 mRNAs were detected, but SSTR2 mRNA was not detected in one case and SSTR3 mRNA was not detected in two cases, indicating a heterogeneous expression of SSTR subtypes in insulinomas. Interestingly, SSTR3 mRNA, which is highly expressed in rat pancreatic islets, is not expressed in normal human pancreatic islets, while SSTR1, SSTR2, and SSTR4 mRNAs are expressed. In three cases of pheochromocytoma, SSTR1 and SSTR2 mRNAs were detected, showing an expression pattern identical to that of normal adrenal gland. In a carcinoid, SSTR1 and SSTR4 mRNAs were detected. We have also found that human SSTR2 shows a high affinity for SMS 201-995, which has been used clinically for the treatment of endocrine tumors. Since SMS 201-995 was effective in the treatment of a patient with glucagonoma in which SSTR2 mRNA was present, but had no effect in a patient with carcinoid in which SSTR2 mRNA was not detected, this study suggests that the efficacy of SMS 201-995 may depend, at least in part, on the expression of SSTR2 in tumors.

[Genetic evidence of extensive introgression of short-tailed ground squirrel genes in a hybridization zone of Spermophilus major and S. erythrogenys, inferred from sequencing of the mtDNA cytochrome b gene].

We have completely sequenced the mtDNA cytochrome b gene of ground squirrels from the zone of overlapping ranges of Spermophilus major and S. erythrogenys in the Tobol-Ishim interfluve, which is a putative hybridization zone of these species. The results of the sequencing showed extensive introgression of mtDNA genes of the short-tailed ground squirrel S. e. brevicauda, whose haplotype had fully replaced the S. major haplotype. All of the ground squirrels from the Tobol-Ishim interfluve had a variant of the S. e. brevicauda mtDNA haplotype that was specific for this zone. On average, 119 substitutions (10.44%) were found between S. major from Ul'yanovsk oblast and S. e. brevicauda from the northern Kazakhstan, the mean genetic distance (D) between them being 0.115, which conforms to the corresponding parameters for the S. e. brevicauda-S. pygmaeus pair (122 substitutions, D = 118). Insignificant differences (seven substitutions, D = 0.043) were found between the S. major and S. pygmaeus haplotypes, which suggest that these species have similar mitochondrial haplotypes. Five to ten nucleotide substitutions (0.44--0.88%) were detected between the animals from the Tobol--Ishim interfluve and S. e. brevicauda. The mtDNA haplotype divergence D within the genus Spermophilus (ten species) for all codon positions ranged from 0.035 to 0.158. Phylogenetic reconstructions (MP, ML, and NJ trees) showed two well-differentiated clusters with high bootstrap support. However, there was different branching topology within the cluster and their species composition varied. The maximum likelihood tree, ML, differentiating the species into two subgenera, Citellus and Colobotis, most reliably reflected taxonomic relationships of the species from the genus Spermophilus, inferred from morphological and genetic biochemical data. The morphologically pure S. major (subgenus Colobotis) animals, used in the analysis, proved to carry the haplotype of another species, S. pygmaeus (subgenus Citellus). This poses a question on the existence of the specific haplotype of S. major, the reason of its replacement by haplotype of other species, and possible consequences of this phenomenon for survival of the species.

Rat alpha1-acid glycoprotein. Purification and immunological estimation of its serum concentration.

A rapid method is described for the preparation of serum alpha1-acid glycoprotein from rats with inflammation induced with turpentine oil injection. The protein obtained by two purification steps, batchwise adsorption with DEAE-cellulose followed by chromatography on CM-cellulose, was proved to be native alpha1-acid glycoprotein in a high degree of purity by electrophoretical, immunological, ultracentrifugal and carbohydrate analysis. The monospecific and potent antiserum to this protein was prepared by immunizing rabbits with the desialyzed material emulsified with Freund's incomplete adjuvant. Using purified alpha1-acid glycoprotein and its specific antiserum, the concentration of alpha1-acid glycoprotein in rat serum was determined by single radial immunodiffusion. Abnormally high levels of its concentration (5-6 times higher than the control) were observed in inflammatory and tumor bearing rats.

Disordered expression of the sucrase-isomaltase complex in the small intestine in Otsuka Long-Evans tokushima fatty rats, a model of non-insulin-dependent diabetes mellitus with insulin resistance.

To clarify the relationship between diabetes mellitus and carbohydrate digestion, the activities of sucrase and isomaltase, which form a complex enzyme (SI complex) on the brush border membranes, were compared in the progression of diabetes mellitus in Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of human non-insulin-dependent diabetes mellitus with insulin resistance, and Long-Evans Tokushima Otsuka (LETO) rats as non-diabetic controls. Until 40 weeks of age, OLETF rats were obese and had a high plasma glucose level, compared to age-matched LETO rats, but the sucrase and isomaltase activities showed no significant differences between the two strains. Oral glucose tolerance test revealed that during 40-48 weeks of age, NIDDM became very severe with advancing insulin resistance in OLETF rats. In OLETF rats, in contrast to LETO rats, at 48 weeks of age, abnormal increases in the sucrase and isomaltase activities occurred, along with a remarkable decrease in body weight and a further great increase in the plasma glucose level in the non-fasting state. Hyperinsulinemia occurred in 20-week-old OLETF rats; however, at 40 and 48 weeks of age, the plasma insulin level in the non-fasting state in OLETF rats was not significantly different from that in LETO rats. The level of mRNA encoding the SI complex increased abnormally in 48-week-old OLETF rats. These results suggest that the advance of insulin resistance leads to an increase in the expression of the SI complex on the transcriptional level.

Starvation-induced changes of somatostatin, glucagon, and insulin secretion from the isolated perfused rat pancreas.

The effect of 16- and 48-h fasting on pancreatic somatostatin, insulin, and glucagon secretion was studied, using the isolated perfused rat pancreas. In the presence of 4.4 mM glucose, basal somatostatin and insulin concentrations in the perfusate were significantly lower in 48-h fasted rats than in fed animals, whereas basal glucagon secretion was significantly elevated in fasted rats. The infusion of 19 mM arginine significantly augmented secretion of somatostatin and glucagon and attenuated insulin secretion in 48-h fasted rats. It is concluded that fasting causes a decrease in basal pancreatic somatostatin secretion in vitro, although the response to arginine is rather exaggerated. Insulin and glucagon secretion also changed during the fasting. These results suggest that not only insulin and glucagon, but also somatostatin contribute to nutrient homeostasis.

Somatostatin-like immunoreactivity in human peripheral plasma measured by radioimmunoassay following affinity chromatography.

Somatostatin-like immunoreactivity (SLI) concentrations were determined in human peripheral plasma using affinity chromatography followed by radioimmunoassay. In normal subjects, fasting SLI ranged from 2.9 to 22.0 pg/ml with a mean +/- SE value of 10.2 +/- 2.1 pg/ml. In totally pancreatectomized or gastrectomized patients, fasting SLI levels were not different from the values in normal subjects. In patients with medullary thyroid carcinoma, fasting SLI ranged from 11.8 to 71.0 pg/ml with a mean of 29.3 +/- 12.3 pg/ml, which was significantly higher than normal values (P less than 0.01). Following meal ingestion, plasma SLI increased significantly in normal subjects from a basal level of 9.1 +/- 2.1 pg/ml to a peak value of 15.4 +/- 2.9 pg/ml (P less than 0.02). These results indicate that radioimmunoassay combined with affinity chromatography provides an accurate method of measuring SLI in human plasma.

Importance of imparied insulin-gene expression in occurrence of diabetes in obese rats.

To investigate the role of the beta-cell in the occurrence of diabetes in obesity, longitudinal changes of insulin-gene expression and pancreatic insulin content were compared among genetically obese diabetic (Wistar fatty) rats, genetically obese nondiabetic (Zucker fatty) rats, and ventromedial hypothalamus (VMH)-lesioned obese rats. Plasma glucose levels were significantly elevated with age in Wistar fatty rats, whereas they were virtually unchanged in VMH-lesioned and Zucker fatty rats. Obesity and hyperinsulinemia were evident in VMH-lesioned rats 1 wk after the operation and in Zucker and Wistar fatty rats at 5 wk of age. In VMH-lesioned rats, the pancreatic preproinsulin I mRNA (pplmRNA) level and pancreatic insulin content markedly increased approximately two- to threefold (P less than 0.001) with the development of hyperinsulinemia, whereas sham-operated rats showed no significant change. In Zucker and Wistar lean rats, the pplmRNA level and pancreatic insulin content increased with age, corresponding to increases in body weight. In Zucker fatty rats, the pplmRNA level and pancreatic insulin content at 5 and 14 wk of age were significantly higher than those of lean littermates. The pplmRNA level in Zucker fatty rats at 14 wk of age reached 290% of that of their lean littermates (P less than 0.001). On the other hand, the pplmRNA level and pancreatic insulin content in Wistar fatty rats at 5 and 14 wk of age did not increase more than those of their lean littermates at the corresponding ages and were therefore significantly lower than in Zucker fatty rats, which had a higher grade of hyperinsulinemia at 14 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of two missense mutations in the GIP receptor gene: a functional study and association analysis with NIDDM: no evidence of association with Japanese NIDDM subjects.

Gastric inhibitory polypeptide (GIP) potently stimulates insulin secretion from pancreatic islets in the presence of glucose as an incretin. Because the insulinotropic effect of GIP is reduced in NIDDM, it should be clarified whether defects in the GIP receptor gene contribute to the impaired insulin secretion in NIDDM. Using genomic DNA samples from Japanese NIDDM and non-NIDDM subjects, we have investigated the entire coding region of the GIP receptor gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP). We have identified two missense mutations, Gly198-->Cys (Gly198Cys) in exon 7 and Glu354-->Gln (Glu354Gln) in exon 12. Investigation of the function of GIP receptor with either of these mutations reveals a half-maximal stimulation value of GIP-induced cAMP response in Chinese hamster ovary cells expressing the GIP receptor with Gly198Cys of 6.3 +/- 1.2 x 10(-10) mol/l (n = 3), which was considerably higher than that of the normal GIP receptor, 9.4 +/- 3.8 x 10(-12) mol/l GIP (n = 3), whereas that of the GIP receptor with Glu354Gln was not significantly different from that of the normal GIP receptor. To assess the possible role of the GIP receptor gene in genetic susceptibility to NIDDM, we have examined the allelic frequencies of Gly198Cys and Glu354Gln in NIDDM and control subjects. Association studies show no relationship between NIDDM and either of the two mutations.

Activating transcription factor-2 is a positive regulator in CaM kinase IV-induced human insulin gene expression.

Insulin plays a crucial role in the regulation of glucose-homeostasis, and its synthesis is regulated by several stimuli. The transcription of the human insulin gene, enhanced by an elevated intracellular concentration of calcium ions, was completely blocked by Ca2+/calmodulin-dependent protein kinase inhibitor. The activity of the transcription factor activating transcription factor-2 (ATF-2), which binds to the cAMP responsive elements of the human insulin gene, was enhanced by Ca2+/calmodulin-dependent protein kinase IV (CaMKIV). Mutagenesis studies showed that Thr69, Thr71, and Thr73 of ATF-2 are all required for activation by CaMKIV. CaMKIV-induced ATF-2 transcriptional activity was not altered by activation of cJun NH2-terminal protein kinase (JNK) or p38 mitogen-activated protein (MAP) kinase. Furthermore, when transfected into rat primary cultured islets, ATF-2 enhanced glucose-induced insulin promoter activity, whereas cAMP response element-binding protein (CREB) repressed it. These results suggest a mechanism in which ATF-2 regulates insulin gene expression in pancreatic beta-cells, with the transcriptional activity of ATF-2 being increased by an elevated concentration of calcium ions.

Electron paramagnetic resonance investigation on modulatory effect of 17beta-estradiol on membrane fluidity of erythrocytes in postmenopausal women.

Many studies have shown that estrogen may exert cardioprotective effects and reduce the risk of hypertension and coronary events. On the other hand, it has been proposed that cell membrane abnormalities play a role in the pathophysiology of hypertension, although it is not clear whether estrogen would influence membrane function in essential hypertension. The present study was performed to investigate the effects of 17beta-estradiol (E(2)) on membrane fluidity of erythrocytes in normotensive and hypertensive postmenopausal women. We determined the membrane fluidity of erythrocytes by means of an electron paramagnetic resonance and spin-labeling method. In an in vitro study, E(2) significantly decreased the order parameter for 5-nitroxide stearate and the peak height ratio for 16-nitroxide stearate obtained from electron paramagnetic resonance spectra of erythrocyte membranes in normotensive postmenopausal women. The finding indicates that E(2) might increase the membrane fluidity of erythrocytes. The effect of E(2) was significantly potentiated by the NO donor, S-nitroso-N-acetylpenicillamine, and a cGMP analogue, 8-bromo-cGMP. In contrast, the change in the membrane fluidity evoked by E(2) was attenuated in the presence of the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester, and asymmetric dimethyl-L-arginine. In hypertensive postmenopausal women, the membrane fluidity of erythrocytes was significantly lower than that in normotensive postmenopausal women. The effect of E(2) on membrane fluidity was significantly more pronounced in the erythrocytes of hypertensive postmenopausal women than in the erythrocytes of normotensive postmenopausal women. The results of the present study showed that E(2) significantly increased the membrane fluidity and improved the microviscosity of erythrocyte membranes, partially mediated by an NO- and cGMP-dependent pathway. Furthermore, the greater action of E(2) in hypertension might be consistent with the hypothesis that E(2) could have a beneficial effect in regulating rheological behavior of erythrocytes and could have a crucial role in the improvement of the microcirculation in hypertension.

Erythrocyte sodium-lithium countertransport activity as a marker of predisposition to hypertension and diabetic nephropathy in NIDDM.

OBJECTIVE: To evaluate the potentiality of erythrocyte sodium-lithium countertransport activity (SLC) as a marker of predisposition to hypertension and diabetic nephropathy in non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: We examined 96 patients with NIDDM and 26 healthy control subjects. SLC and other data were compared among subgroups of the patients classified on the basis of hypertension, family history of hypertension, and stages of nephropathy. Data were also analyzed by stepwise multiple regression analyses. RESULTS: SLC was significantly higher in patients with hypertension than in those with normotension and significantly higher in patients with a positive family history of hypertension than in the negative group. Further analysis revealed that a family history of hypertension has independent influence on SLC, but hypertension itself does not. SLC was significantly higher in patients with macroalbuminuria than with microalbuminuria and higher in patients with microalbuminuria than with normalbuminuria. In stepwise multiple regression analyses, a family history of hypertension was the most important determinant of SLC, and SLC was the most important determinant of nephropathy. CONCLUSIONS: These data suggest that SLC strongly reflects a predisposition to hypertension and that it can be a useful marker of diabetic nephropathy in NIDDM.