Effect of vitamin K2 on cortical and cancellous bones in orchidectomized young rats

OBJECTIVES: The purpose of the present study was to compare the effect of vitamin K(2) on cortical and cancellous bones in orchidectomized young rats. METHODS: Forty male Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into four groups with 10 rats in each group: baseline controls (BLC), age-matched controls (AMC), orchidectomy (ORX), and ORX+vitamin K(2) administration (K). Vitamin K(2) (menatetrenone) was administered subcutaneously twice a week at dose of 30 mg/kg each. The experimental period was 8 weeks, and cortical and cancellous bone histomorphometry was performed on the tibial shaft and the proximal tibia, respectively. RESULTS: Cortical area (Ct Ar) and cancellous bone volume (BV/TV) were significantly greater in the AMC group than in the BLC group. Ct Ar was significantly lower in the ORX group than in the AMC group, and cancellous BV/TV was also significantly lower in the ORX group than in the AMC group as a result of significantly increased eroded surface (ES/BS). Although Ct Ar in the ORX+K group did not differ significantly from that in the ORX group, cancellous BV/TV was significantly greater in the ORX+K group than in the ORX group, but still significantly lower than in the AMC group. This protective effect of vitamin K(2) on cancellous bone was attributable to normalizing increased ES/BS. CONCLUSIONS: Vitamin K(2) appears to act more strongly on cancellous bone than on cortical bone in ORX young rats. High dose vitamin K(2) could partially prevent the reduction of cancellous bone gain by normalizing raised bone resorption in ORX young rats.     

Effect of stimulated neutrophils from the synovial fluid of patients with rheumatoid arthritis on lymphocytes—A possible role of increased oxygen radicals generated by the neutrophils

Neutrophils from the synovial fluid (SFN) of 10 patients with active rheumatoid arthritis (RA) were investigated to determine the generation of oxygen intermediates (OI) (O2-, H2O2, OH .), chemiluminescence, and lysosomal enzymes (lysozyme and beta-glucuronidase). Lymphocytes from healthy individuals were cocultured at 37 degrees C for 17 hr with SFN from the patients and the number of OKT4+, OKT8+, and OKT3+ cells and the response to mitogens were determined. A markedly increased OI and slightly elevated lysosomal enzyme levels were observed in SFN from patients. Coculture of lymphocytes with SFN resulted in a decreased number of OKT4+ and OKT8+ cells and a greatly reduced response to Con A and mildly diminished response to PHA, while OKT3+ cells were not affected. The simultaneous addition of superoxide dismutase and catalase restored the impairment of monoclonal antibody reaction and lymphocyte responsiveness almost to control levels. It is suggested that the disturbed immunoreactivity of synovial fluid lymphocytes from RA patients may be due to increased OI generated by stimulated neutrophils.     

Reduced NR2A expression and prolonged decay of NMDA receptor-mediated synaptic current in rat vagal motoneurons following axotomy

To elucidate characteristic changes in the N -methyl- d -aspartate (NMDA) receptor on neurons following axotomy, subunit expressions and functional features of the NMDA receptor were examined in the dorsal motor nucleus of vagus (DMV) of rats receiving vagal axotomy at the neck. Western blotting analysis demonstrated that the expression of NR2A decreased 2–3 days after in vivo axotomy, while expression of NR1 and NR2B, NR2C and NR2D subunits did not change significantly. To examine the functional changes, patch clamp recordings in whole-cell mode were employed on the axotomized DMV neurons identified by retrograde labelling with fluorescent dye. The amplitude ratios of ifenprodil-sensitive components of NMDA response and d , l -2-amino-5-phosphovaleric acid (APV)-sensitive evoked postsynaptic current increased after axotomy. In addition, APV-sensitive postsynaptic currents exhibited a longer decay time in identified axotomized vagal motoneurons than in control neurons. No significant differences in the current density of the NMDA response and the peak amplitude of APV-sensitive synaptic currents were observed between axotomized and intact DMV neurons. In conclusion, a decrease in NR2A expression results in the appearance of functional characteristics of the NMDA receptor predominantly containing the NR2B subunit. This might lead to a long-term increase of the susceptibility of neurons to excitotoxicity.     

Personality of seasonal affective disorder analyzed by Tri-dimensional Personality Questionnaire

BACKGROUND: Although there have been numerous reports in personality of mood disorders, there have been few reports in regard with personality of winter seasonal affective disorder (SAD). Furthermore, no reports have been published concerning summer SAD personality characteristics. Thus, this study was conducted to assess the personality of winter and summer SAD using Tri-dimensional Personality Questionnaire (TPQ) that have been used in a variety of mental disorders. METHODS: A total of 6135 Japanese were evaluated with TPQ, the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Self-rating Depression Scale (SDS). Winter, summer and non-SAD groups were classified by SPAQ. We compared the difference of personality trait among these three groups in consideration of gender, age and SDS score influence. RESULTS: Winter SAD demonstrated higher "Novelty Seeking" and "Harm Avoidance"; summer SAD showed higher "Harm Avoidance" than the non-SAD group. "Harm Avoidance" in both SAD groups was re-analyzed using SDS score as a covariate, and "Novelty Seeking" in winter SAD using age as a covariate. As a result, the significance of high "Novelty Seeking" and high "Harm Avoidance" in winter SAD was excluded. However, "Harm Avoidance" remained the significant difference between summer and non-SAD. LIMITATION: SAD was diagnosed only by SPAQ and not by interview. The state-dependency of "Harm Avoidance" was not confirmed in identical patients over lapse of time. CONCLUSION: Patients with winter SAD have high "Harm Avoidance" dependent on the depressive state that is in accordance with non-seasonal depression. Patients with summer SAD have high "Harm Avoidance" possibly independent from the depressive state.     

Total sleep deprivation elevates blood pressure through arterial baroreflex resetting: a study with microneurographic technique

STUDY OBJECTIVES: Sleep deprivation has a profound effect on cardiovascular regulation through the autonomic nervous system. This study examined the effect of 24-hour total sleep deprivation on muscle sympathetic nerve activity (MSNA), which is a direct measurement of the postganglionic sympathetic efferent innervating the vascular bed in the skeletal muscle and other circulatory structures. DESIGN: The study was performed on 6 young healthy men. The factors exerting influence on MSNA, such as aging, obesity, body posture, activity, intensity of illumination, and food and beverage consumption were strictly controlled. Burst rate and burst incidence were used as parameters of MSNA. The burst rate, burst incidence, heart rate, and systolic and diastolic blood pressure were measured after total sleep deprivation and control sleep. To perform a linear regression analysis of arterial baroreflex (ABR), the incidence of MSNA bursts corresponding to a given diastolic blood pressure (%MSNA) was examined. MEASUREMENT AND RESULTS: The diastolic blood pressure was significantly higher after total sleep deprivation than after control sleep (66.5 +/- 1.7 vs 57.4 +/- 3.3 mm Hg). The burst rate (9.6 +/- 1.8 vs 13.3 +/- 2.7 bursts/min) and burst incidence (21.6 +/- 4.5 vs 30.3 +/- 8.9 bursts/100 heart beats) of MSNA were significantly lower after total sleep deprivation than after control sleep (P < .05). Analysis of the ABR disclosed a significant linear regressive relation between %MSNA and diastolic blood pressure in every subject after both total sleep deprivation and control sleep. This result implies that the ABR regulates the occurrence of MSNA bursts under different diastolic blood pressure conditions. The threshold (X-axis intercept) of the blood pressure regression line (ie, an indicator of the ABR set point) shifted by 12 +/- 4.3 mm Hg toward a higher blood pressure level after total sleep deprivation (P < .05). The ABR sensitivity, or the slope of the regression line, tended to be less steep after total sleep deprivation than after control sleep, although it was not statistically significant (P = .09). CONCLUSIONS: The diastolic blood pressure increased and both burst rate and burst incidence of MSNA decreased after total sleep deprivation. The results show that resetting of the ABR toward a higher blood pressure level occurred after total sleep deprivation. This ABR resetting probably brings about an increase in arterial blood pressure after total sleep deprivation.     

Peliosis Hepatis in a Child with X-Linked Myotubular Myopathy Treated with Living-Donor Liver Transplant: A Case Report

BackgroundMyotubular myopathy is a rare disease sometimes accompanied by peliosis hepatis, a leading cause of fatal liver hemorrhage.Case ReportWe present a case of a 2-year-old boy with myotubular myopathy who developed liver hemorrhage because of peliosis hepatis and was successfully treated with living-donor liver transplant. The patient initially presented with fever, anemia, and liver dysfunction. A computed tomographic scan revealed hemorrhages in the liver, and the patient underwent hepatic artery embolization twice. After the second embolization, multiple peliosis hepatis cavities appeared in the left lobe of the liver that had increased in size. Therefore, the patient underwent ABO-incompatible living-donor liver transplant using a lateral segment graft from his father. The patient developed severe septic shock with an unknown focus on postoperative day 18, which resolved with antibiotic therapy. On postoperative day 62, he was discharged. Fourteen months after undergoing living-donor liver transplant, the patient showed no recurrence of peliosis hepatis.ConclusionsAlthough the long-term prognosis of peliosis hepatis due to myotubular myopathy after living-donor liver transplant remains unclear, liver transplant may be a curative treatment for patients with myotubular myopathy who have uncontrollable peliosis hepatis.     

Neuroimmune system-mediated renal protection mechanisms

Clinical and Experimental Nephrology - The autonomic nervous system plays an important role in maintaining homeostasis in organisms. Recent studies have shown that it also controls inflammation by...     

Combined treatment with vitamin k2 and bisphosphonate in postmenopausal women with osteoporosis

Vitamin K2, as well as bisphosphonates, such as etidronate, alendronate, and risedronate, is widely used in the treatment with osteoporosis in Japan. Etidronate increases the lumbar bone mineral density (BMD), and prevents new vertebral fractures, in patients with osteoporosis, while alendronate and risedronate increase the lumbar and femoral neck BMDs, and prevent new vertebral and femoral neck fractures. Vitamin K2 enhances gamma-carboxylation of bone glutamic acid residues and the secretion of osteocalcin, sustains the lumbar BMD, and prevents osteoporotic fractures in patients with osteoporosis. Bisphosphonates, such as alendronate and risedronate, rather than vitamin K2, should be initially chosen for the treatment of osteoporosis, because they are more efficacious than vitamin K2. Available evidence suggest that risedronate prevents deterioration of the connectivity of the trabeculae in ovariectomized rats, whereas vitamin K2 increase the trabecular thickness, and that a combination of risedronate and vitamin K2 has a synergistic effect on preventing the deterioration of trabecular bone architecture induced by estrogen deficiency. Some studies have shown that combined treatment with etidronate and vitamin K2 appears to be more effective than etidronate alone in the prevention of new osteoporotic vertebral fractures. Based on these findings, combined treatment with vitamin K2 and bisphosphonates may be more efficacious in the prevention new vertebral fractures than a single treatment with bisphosphonate in postmenopausal women with osteoporosis. Thus, this combined treatment should be recommended for the treatment of postmenopausal osteoporosis. It is proposed that the role of vitamin K2 should be emphasized, when used in combination with bisphosphonates, especially in patients with vitamin K deficiency.