Estrogen synthesis in the brain—Role in synaptic plasticity and memory

Estrogen and androgen are synthesized from cholesterol locally in hippocampal neurons of adult animals. These neurosteroids are synthesized by cytochrome P450s and hydroxysteroid dehydrogenases (HSDs) and 5alpha-reductase. The expression levels of enzymes are as low as 1/200–1/50,000 of those in endocrine organs, however these numbers are high enough for local synthesis. Localization of P450(17alpha), P450arom, 17beta-HSD and 5alpha-reductase is observed in principal glutamatergic neurons in CA1, CA3 and the dendate gyrus. Several nanomolar levels of estrogen and androgen are observed in the hippocampus.Estrogen modulates memory-related synaptic plasticity not only slowly but also rapidly in the hippocampus. Rapid action of 17beta-estradiol via membrane receptors is demonstrated for spinogenesis and long-term depression (LTD). The enhancement of LTD by 1–10 nM estradiol occurs within 1 h. The density of spine is increased in CA1 pyramidal neurons within 2 h after application of estradiol. The density of spine-like structure is, however, decreased by estradiol in CA3 pyramidal neurons. ERalpha, but not ERbeta, induces the same enhancement/suppression effects on both spinogenesis and LTD.     

Cell proliferation in the dentate gyrus of rat hippocampus is inhibited by soft diet feeding

BACKGROUND: Recently it has become well accepted that neurogenesis occurs in the dentate gyrus of the hippocampus, a region important to memory and learning function in rodents and humans. Reports show that neurogenesis in the hippocampus is regulated by certain factors, such as exposure to an enriched environment, physical activity, aging and stress. The relationship between the change in the task of chewing as one oral environmental factor, and the mechanisms of hippocampal neuron generation are unclear. OBJECTIVE: We examined whether cell proliferation varies by chewing tasks with different food textures in the dentate gyrus of the rat hippocampus. METHODS: Wistar rats were divided into two groups, one was fed a solid diet, known as the hard-diet feeding group, and the soft-diet feeding group, which was fed a powder diet containing the same components as the solid one for 3, 7, 16 and 24 weeks. Thymidine analog 5-bromo-2'-deoxyuridine (BrdU) was used as a marker of cell proliferation within the dentate gyrus of the hippocampus and olfactory bulb. RESULTS: The results of this study indicated that the total number of BrdU-positive cells in the hippocampal dentate gyrus significantly decreased with aging and were significantly fewer in the soft-diet feeding group than in hard-diet feeding group in 7-, 16- and 24-week-old rats after the BrdU injection. The change of BrdU-positive cell expression between soft and hard diets in 3- and 24-week-old rats was not observed in the olfactory bulb. CONCLUSION: It has been suggested that cell proliferation in the dentate gyrus of the rat hippocampus is characteristically suppressed by soft diet feeding.     

ADMA regulates angiogenesis: genetic and metabolic evidence

Endothelium-derived nitric oxide (NO) plays an important role in transducing the effects of angiogenic factors. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase (NOS). We used a murine model of hindlimb ischemia to investigate whether genetic or metabolic changes in ADMA levels could impair angiogenic response in vivo. Hindlimb ischemia was surgically induced in C57BL/6J mice, apo E-deficient mice, or transgenic mice overexpressing dimethylarginine dimethylaminohydrolase (DDAH). Some animals were also treated with the NOS antagonist L-nitro-arginine, or the NO precursor L-arginine. Angiogenesis was quantified in the hindlimb skeletal muscle by capillary/myocyte ratio. Plasma or tissue ADMA levels were measured by HPLC. In normal mice, hindlimb ischemia increased tissue ADMA twofold, and reduced DDAH and NOS expression. This was associated with a reduced NOS activity (by over 80%) three days following surgery. On day seven, a threefold increase in DDAH expression and a fall in tissue ADMA levels were associated with a sevenfold increase in NOS activity, whereas NOS expression did not increase above baseline. In DDAH transgenic mice, the elevation of ADMA and decrement in NOS activity was blunted during hindlimb ischemia. Plasma ADMA levels were increased in apo E-mice (1.79 +/- 0.45 versus 1.07 +/- 0.08 pmol/l; p = 0.008). Capillary index was significantly reduced in apo E-mice up to seven weeks after surgery (0.25 +/- 0.05 versus 0.62 +/- 0.08; p < 0.001). The effect of hypercholesterolemia on capillary index was reversed by L-arginine, and (in wild-type mice) mimicked by administration of the NOS antagonist L-nitro-arginine. In conclusion, metabolic or genetic changes in plasma and tissue ADMA levels affect tissue NO production and angiogenic response to ischemia.     

Regional arterial stiffness associated with ischemic heart disease in type 2 diabetes mellitus

Arterial stiffness is increased in type 2 diabetes mellitus, and diabetes preferentially affects arterial stiffness of the central (elastic, capacitive) over peripheral (muscular, conduit) arteries. We hypothesized that arterial stiffness of the central artery may be more closely associated with ischemic heart disease (IHD) than stiffness of peripheral arteries in type 2 diabetes mellitus. The subjects were 595 type 2 diabetes patients including 70 with IHD. Arterial stiffness was measured as pulse wave velocity (PWV) in the heart-carotid, heart-femoral, heart-brachial, and femoral-ankle regions. The PWV values of the four segments correlated with each other in patients without IHD. However, the correlations were less impressive in those with IHD, suggesting unequal stiffening of regional arteries in IHD. As compared with patients without IHD, the IHD group showed significantly higher PWV values of the four arterial segments, particularly of the heart-femoral region. The presence of IHD was significantly associated with higher heart-femoral PWV, and this association remained significant and independent of other factors in a multiple logistic regression analysis. Pulse pressure was more strongly correlated with PWV of the heart-femoral than other arterial regions. Thus, diabetic patients with IHD have increased stiffness of arteries, particularly of the aorta, supporting the concept that central arterial stiffness plays an important role in the development of IHD.     

Prevalence of and risk factors for low bone mineral density in Japanese female patients with systemic lupus erythematosus

To examine the prevalence of and risk factors for low bone mineral density (BMD) (osteoporosis or osteopenia) in Japanese female patients with systemic lupus erythematosus (SLE). We performed BMD measurements by dual X-ray absorptiometry at the lumbar spine and the hip and collected basic and lifestyle-related, clinical and treatment characteristics among 58 SLE patients. Odds ratios (ORs) and their 95% confidence intervals (CIs) were assessed for associations between low BMD and selected factors among SLE patients. The mean BMD?±?SD was 0.90?±?0.17?g/cm² at the lumbar spine and 0.76?±?0.17?g/cm² at the hip. The prevalence of osteopenia (2.5 SD?<?T score?<?1 SD) was 50.0% and that of osteoporosis (T score?<?2.5 SD) was 13.8% in our SLE patients. After adjustment for age and disease duration, we found the number of deliveries (OR?=?5.58, 95% CI?=?1.31?C26.06; P?=?0.02) to be a risk factor for overall low BMD (T score?<?1 SD) and a maximal dosage of >50?mg/day of oral corticosteroids (OR?=?0.25, 95% CI?=?0.07?C0.91; P?=?0.035) as a preventive factor for low BMD at the lumbar spine. Reduced BMD, especially in spinal trabecular bone, was pronounced in Japanese female patients with SLE, particular in those with a history of delivery. A history of high-dose oral corticosteroids was associated with the preservation of BMD at the lumbar spine, however, further study is needed considering the limited sample size.     

Altered relationship between body fat and plasma adiponectin in end-stage renal disease

Patients with end-stage renal disease (ESRD) show an inverse association between body mass index and risk of death from cardiovascular disease. Paradoxical epidemiology may suggest some beneficial effects of body fat in ESRD. Because an antiatherogenic adipocytokine adiponectin is increased in uremic plasma, we tested a hypothesis that, in ESRD, plasma adipocytokine profile may be less atherogenic or that the relationship between body fat and adipocytokines may be altered. The subjects were 103 patients with ESRD undergoing hemodialysis and 166 healthy subjects comparable in age and sex. We measured body fat mass by dual-energy x-ray absorptiometry and plasma levels of adiponectin and leptin by enzyme-linked immunosorbent assay. The ESRD group showed a significant increase in plasma adiponectin, leptin, and adiponectin/leptin ratio than the healthy subjects. Although sex and fat mass were significant factors correlating with plasma adiponectin level in the healthy group, none of these were significantly associated with plasma adiponectin in the patients with ESRD. In contrast, leptin showed significant relationships with sex and fat mass regardless of the presence of ESRD. Plasma adiponectin correlated negatively with plasma triglycerides and positively with high-density lipoprotein cholesterol in both healthy and ESRD groups, suggesting that uremic adiponectin retains its actions in favor of its antiatherogenicity. Thus, plasma adipocytokine profile was altered in ESRD, and the effects of body fat and sex on adiponectin were less significant in the patients with ESRD.     

RP105-lacking B cells from lupus patients are responsible for the production of immunoglobulins and autoantibodies

OBJECTIVE: We previously reported that B cells lacking the RP105 molecule, which proved to be highly activated B cells, are increased in the peripheral blood of patients with systemic lupus erythematosus (SLE). In the present study, we attempted to determine whether RP105-negative B cells obtained from SLE patients would be capable of producing autoantibodies as well as immunoglobulins. METHODS: RP105-positive and RP105-negative B cells, sorted by cell sorter, were cultured for 5 days without stimulation, or were stimulated with Staphylococcus aureus Cowan 1 strain (SAC) or recombinant interleukin-6 (IL-6). For the assay of autoantibodies, RP105-positive and RP105-negative B cells were cultured separately for 10 days with anti-CD3 antibody-stimulated T cells. The production of immunoglobulins and autoantibodies was determined by enzyme-linked immunosorbent assay. RESULTS: We demonstrated that RP105-negative B cells, but not RP105-positive B cells, obtained from SLE patients could spontaneously produce IgG and IgM in vitro until day 5. SAC and IL-6 enhanced production of IgG and IgM by RP105-negative B cells but failed to induce such production by RP105-positive B cells. The latter cells, however, when cocultured with activated T cells in the presence of IL-10, produced IgG, although the amount was very small compared with that produced by RP105-negative B cells. Most important, under these conditions, anti-double-stranded DNA antibodies were produced only by the RP105-negative B cells obtained from SLE patients. CONCLUSION: These data indicate that RP105-negative B cells, constituting a subset of B cells in SLE patients, are highly activated and may be responsible for the production of autoantibodies as well as polyclonal immunoglobulins.     

Quality of life in Japanese female patients with systemic lupus erythematosus: Evaluation using the Short Form 36 Health Survey

Objective. Aspects of health-related quality of life (HRQoL) are important for assessing perceived health status and treatment burden. We evaluated HRQoL using Short Form 36 Health Survey (SF-36) and factors associated with HRQoL.

Methods. We collected basic and lifestyle-related, clinical, and treatment characteristics among 119 female Japanese patients with systemic lupus erythematosus (SLE). Odds ratios (ORs) and their 95% confidence intervals were assessed for associations between HRQoL and selected factors.

Results. Irregularity of sleep was significantly associated with risk of lower role physical (RP) (OR = 8.27), vitality (VT) (OR = 8.45), and role emotional (OR = 10.7) domains. Compared with clerical work, non-clerical work was significantly associated with risk of lower RP (OR = 7.39), and unemployment was significantly associated with risk of lower VT (OR = 41.0). Daily soybean intake was associated with improved General Health or GH (OR = 0.17). Compared with Systemic Lupus Collaborative Clinics Damage Index (SDI) = 0, SDI > 2 was associated with risk of lower PF (OR = 7.88), RP (OR = 4.29), and bodily pain (OR = 3.06) domains.

Conclusion. Reduced HRQoL was observed in our SLE patients. Interventions addressing sleep and work disturbances, as well as daily soybean consumption, could alter the HRQoL of SLE patients.     

Antialbuminuric advantage of cilnidipine compared with L-type calcium channel blockers in type 2 diabetic patients with normoalbuminuria and microalbuminuria

We evaluated the antialbuminuric advantage of cilnidipine, an N/L-type calcium channel blocker (CCB), compared with L-type CCBs in diabetic patients with normoalbuminuria and microalbuminuria. The study was a multicenter, non-randomized crossover trial. Participants were 90 type 2 diabetic patients exhibiting either normo- or microalbuminuria, and undergoing CCB treatment for ≥6 months prior to study entry. The CCB at the time of entry was continued for the first 6 months (Period 1). Treatment was subsequently switched from cilnidipine to an L-type CCB, or vice versa, for the second 6-month observation period (Period 2). During Period 1, the L-type CCB group showed a significant increase of urinary albumin excretion (UAE) over time, while the cilnidipine group showed no significant elevation. During Period 2, switching of the treatment from the L-type CCB to cilnidipine resulted in significant reduction of the UAE, whereas switching from cilnidipine to the L-type CCB resulted in no significant change in the UAE. This study demonstrated that the antialbuminuric effect of Cilnidipine, but not the L-type CCBs, was sustained even in patients treated for a long time. In addition, the antialbuminuric effect can be anticipated after switching from an L-type CCB to cilnidipine, but not vice versa.     

Effect of implant-supported or retained dentures on masticatory performance: a systematic review

STATEMENT OF PROBLEM: While subjective patient-based measures have been increasingly recognized as critical outcomes for prosthodontic treatment, there continues to be a need to validate for patients what changes in masticatory function can be expected with the provision of new implant-supported or retained dentures. PURPOSE: The purpose of this review was to evaluate the critical factors impacting change in masticatory performance following the provision of new implant-supported or retained dentures. MATERIAL AND METHODS: Information retrieval followed a systematic approach using PubMed and the Cochrane Library. English articles published from 1966 to June 2007, in which the masticatory performance of subjects with implant-supported or retained dentures was assessed by objective methods and compared to performance with conventional dentures, were included. Ratings of the evidence provided in each article followed United States Agency for Healthcare Research and Quality recommendations. RESULTS: From 281 articles identified, 18 peer-reviewed articles met prespecified criteria for inclusion. Specific outcomes of significance identified by these articles rated as level II are: (1) fixed implant-supported partial dentures do not provide significant improvement in masticatory performance compared to conventional removable partial dentures for Kennedy Class I and II partially edentulous mandibles; (2) the combination of a mandibular implant-supported or retained overdenture (IOD) and maxillary conventional complete denture (CD) provides significant improvement in masticatory performance compared to CDs in both the mandible and maxilla for a limited population having persistent functional problems with an existing mandibular CD due to severely resorbed mandible; and (3) the type of implant and attachment system for mandibular IODs has a limited impact. Specific outcomes of significance identified by articles rated as having a moderate level of evidence (level III) are: (1) mandibular fixed implant-supported complete dentures provide significant improvement in masticatory performance compared to mandibular CDs in subjects dissatisfied with their CDs; and (2) implant-supported mandibular resection dentures have an advantage over conventional dentures in masticatory performance on the defect side of the mouth. CONCLUSIONS: Objective benefits in masticatory performance of implant-supported or retained dentures compared to conventional dentures are limited to a mandibular IOD in edentulous patients with a resorbed mandible and/or difficulty adapting to CDs.