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Abstract Background Restoration of the natural joint line is a cornerstone for kinematically aligned total knee arthroplasty (TKA). The purpose of this study was to investigate the relative orientation of the tibial growth plate (GP) with respect to the tibial plateau (TP) for possible application in predicting natural joint line for knees with highly advanced osteoarthritis patient at the time of kinematically aligned TKA. Methods Images from computed tomography (CT) of 27 normal knees (9 males, 18 females; mean age, 31.6 years) were studied. Geometry of the GP was extracted from CT images, and its moment-of-inertia axes were calculated for the whole GP and the medial and lateral halves. Angular orientations of each GP axis with respect to the TP plane were measured in anatomical coordinates. Results The TP and GP planes were oriented in 2.3 ± 1.8° of varus and 1.1 ± 1.9° of valgus relative to the tibial mechanical axis, respectively. With respect to the TP plane, the whole GP plane was inclined in 3.4 ± 1.5° of valgus. Orientation of the GP plane differed drastically between medial and lateral halves. The medial GP was in 4.9 ± 2.9° of varus and 1.8 ± 2.5° of anterior inclination, and the lateral half was in 10.4 ± 2.4° of valgus and 18.6 ± 4.0° of anterior inclination relative to the TP. Conclusions Angular orientation of the original TP plane can be predicted in reference to the GP plane and may provide reasonable guidance for the target bone resection angle of the tibia in kinematically aligned TKA.

Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB) appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA). Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional foods or beverages to counteract the accumulation of body fat.

BACKGROUND: The photopigment melanopsin has been suggested to act as a dominant photoreceptor in nonvisual photoreception including resetting of the circadian clock (entrainment), direct tuning or masking of vital status (activity, sleep/wake cycles, etc.), and the pupillary light reflex (PLR). Pituitary adenylate cyclase-activating polypeptide (PACAP) is exclusively coexpressed with melanopsin in a small subset of retinal ganglion cells and is predicted to be involved extensively in these responses; however, there were inconsistencies in the previous reports, and its functional role has not been well understood. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that PACAP-deficient mice exhibited severe dysfunctions of entrainment in a time-dependent manner. The abnormalities in the mutant mice were intensity-dependent in phase delay and duration-dependent in phase advance. The knockout mice also displayed blunted masking, which was dependent on lighting conditions, but not completely lost. The dysfunctions of masking in the mutant mice were recovered by infusion of PACAP-38. By contrast, these mutant mice show a normal PLR. We examined the retinal morphology and innervations in the mutant mice, and no apparent changes were observed in melanopsin-immunoreactive cells. These data suggest that the dysfunctions of entrainment and masking were caused by the loss of PACAP, not by the loss of light input itself. Moreover, PACAP-deficient mice express an unusually early onset of activities, from approximately four hours before the dark period, without influencing the phase of the endogenous circadian clock. CONCLUSIONS/SIGNIFICANCE: Although some groups including us reported the abnormalities in photic entrainments in PACAP- and PAC(1)-knockout mice, there were inconsistencies in their results. The time-dependent dysfunctions of photic entrainment in the PACAP-knockout mice described in this paper can integrate the incompatible data in previous reports. The recovery of impaired masking by infusion of PACAP-38 in the mutant mice is the first direct evidence of the relationship between PACAP and masking. These results indicate that PACAP regulates particular nonvisual light responses by conveying parametric light information--that is, intensity and duration. The "early-bird" phenotype in the mutant mice originally reported in this paper supposed that PACAP also has a critical role in daily behavioral patterns, especially during the light-to-dark transition period.

Beneficial effects of sesame lignans, especially antioxidative effects, have been widely reported; however, its potential effects on autonomic nerves have not yet been investigated. Therefore, the current study aimed to investigate the effect of sesame lignans on the autonomic nervous system. The sympathetic nerve activity in rat skeletal muscle was measured using electrophysiological approaches, with blood flow determined using the laser Doppler method. Sesame lignans were administered intragastrically at 2 and 20 mg/kg, and after 60 min, the sympathetic nerve activity was observed to increase by 45.2% and 66.1%, respectively. A significant increase in blood flow (39.6%) was also observed for the 20-mg/kg dose when measured at 55 min after administration. These sympathomimetic effects were completely prevented by subdiaphragmatic vagotomy, and the increase in blood flow was eliminated in the presence of the ß2-adrenergic receptor inhibitor butoxamine. Thus, it is proposed that sesame lignans can increase the blood flow of skeletal muscle, possibly by exciting sympathetic nerve activity through the afferent vagal nerve. [ABSTRACT FROM AUTHOR]

Opposing parasympathetic and sympathetic signals determine the autonomic output of the brain to the body and the change in balance over the sleep-wake cycle. The suprachiasmatic nucleus (SCN) organizes the activity/inactivity cycle and the behaviors that go along with it, but it is unclear how the hypothalamus, in particular the SCN, with its high daytime electrical activity, influences this differentiated autonomic balance. In a first series of experiments, we visualized hypothalamic pre-sympathetic neurons by injecting the retrograde tracer Fluoro-Gold into the thoracic sympathetic nuclei of the spinal cord. Pre-parasympathetic neurons were revealed by injection of the retrograde trans-synaptic tracer pseudorabies virus (PRV) into the liver and by sympathetic liver denervation, forcing the virus to infect via the vagus nerve only. This approach revealed separate pre-sympathetic and pre-parasympathetic neurons in the brainstem and hypothalamus. Next, selective retrograde tracing with two unique reporter PRV strains, one injected into the adrenal and the other into the sympathetic denervated liver, demonstrated that there are two separate populations of pre-sympathetic and pre-parasympathetic neurons within the paraventricular nucleus of the hypothalamus. Interestingly, this segregation persists into the SCN, where, as a result, the day-night balance in autonomic function of the organs is affected by specialized pre-sympathetic or pre-parasympathetic SCN neurons. These separate preautonomic SCN neurons provide the anatomical basis for the circadian-driven regulation of the parasympathetic and sympathetic autonomic output. J. Comp. Neurol. 464:36–48, 2003. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that activation of platelets by collagen results in a dramatic increase in tyrosine phosphorylation of several cellular proteins, including pp125FAK, through the interaction of collagen with integrin α2β1 (GP Ia-IIa). In this study, we report that p75syk is a potential candidate for the protein-tyrosine phosphorylation event following collagen stimulation in porcine platelets. Washed platelets were stimulated with collagen and the activation of p75syk was assessed in an immunoprecipitation kinase assay. The activity of p75syk increased within 1 min, reached a maximum at 5 min after stimulation by collagen, and the phosphorylation at tyrosine residues of p75syk in platelets also occurred in the same time course as the activation of p75syk. Prior treatment of platelets with cytochalasin D to inhibit actin polymerization, or with aspirin and apyrase to inhibit the secondary reaction, or EGTA and the acetoxymethyl ester of 5,5'-dimethyl-bis-(o-aminophenoxy)-ethane-N,N,N'N'-tetraacetic acid to chelate both extracellular and intracellular Ca2+, did not affect the activation of p75syk induced by collagen. Furthermore, herbimycin A, a potent protein-tyrosine-kinase inhibitor, was capable of reducing collagen-evoked p75syk activation, Ca2+ mobilization and platelet aggregation. These results suggest that upon stimulation by collagen p75syk is physically activated by a process that is independent of the effects of Ca2+, ADP, and actin polymerization, and may participate in the regulation of Ca2+ mobilization mediated by collagen in platelets. [ABSTRACT FROM AUTHOR]

Chlorella pyrenoidosa and other Chlorella species may be a natural source of immune boosting nutrients. We investigated whether Chlorella pyrenoidosa affects splenic sympathetic nerve activity (splenic-SNA), which is involved in the immune response, and inhibits cancer cell proliferation. We conducted two experiments. Experiment 1 focused on the interaction of Chlorella pyrenoidosa and splenic-SNA. Experiment 2 examined the effects of Chlorella pyrenoidosa on the growth of tumors in nude mice that had been injected with human colon cancer cells (HCT116). We confirmed Chlorella pyrenoidosa suppressed splenic-SNA. In addition, the proliferation of HCT116 cells is suppressed by treated with Chlorella pyrenoidosa. This study is the first to suggest that an effective substance in the treatment of cancer of Chlorella pyrenoidosa may be attributable to suppression of splenic-SNA. [ABSTRACT FROM AUTHOR]

Previously, we found that intraduodenal administration of heat-killed Lactobacillus brevis SBC8803 (SBC8803) elevates both the efferent gastric vagal nerve activity (efferent GVNA) and the afferent intestinal vagal nerve activity (afferent IVNA) in rats. In this study, the effects of vagotomy and serotonin (5-HT) receptor antagonists on the above changes due to SBC8803 were examined in rats to clarify the mechanism. It was found that the elevation of efferent GVNA induced by SBC8803 was eliminated by subdiaphragmatic vagotomy, and inhibited by intracerebroventricular but not intravenous administration of ketanserin (5-HT2 antagonist), Moreover, both the efferent GVNA and the afferent IVNA elevations were suppressed by intracerebroventricular administration of granisetron (5-HT3 antagonist). Combining this with our previous findings that granisetron can produce the same effects intravenously, these findings suggest the following: 1) the efferent GVNA enhancement requires afferent vagal nerves, central but not peripheral 5-HT2 receptors, and both central and peripheral 5-HT3 receptors, and 2) the afferent IVNA enhancement requires central and peripheral 5-HT3 receptors. Moreover, these results implicate the afferent IVNA in the mechanism of the SBC8803-induced increase in efferent GVNA. [ABSTRACT FROM AUTHOR]

Chlorella pyrenoidosa (C. pyrenoidosa) has higher content of chlorophyll than any known other plants, and also has vitamins, minerals, dietary fiber and other substances. To identify the effect of C. pyrenoidosa on skin condition, we measured cutaneous arterial sympathetic nerve activity (CASNA), cutaneous blood flow and transepidermal water loss (TEWL) in rats in three separate trials. We further attempted to determine if C. pyrenoidosa was targeting the histamine H3 receptors by pretreating a separate group with thioperamide, a histamine H3 antagonist, and then observing the CASNA and cutaneous blood flow response to C. pyrenoidosa in a fourth trial. Intraduodenal administration of C. pyrenoidosa caused marked inhibition of CASNA as well as significant elevation of cutaneous blood flow in rats. TEWL, furthermore, significantly decreased on the dorsal skin of conscious hairless rats when their only source of fluids was C. pyrenoidosa suspended in water. However, when animals were pretreated with thioperamide, C. pyrenoidosa eliminated the response of CASNA and cutaneous blood flow. These findings suggest that C. pyrenoidosa reduces CASNA, increases cutaneous blood flow, and enhances the water-retaining ability of the skin, and that histamine H3 receptors may be involved in the CASNA and cutaneous blood flow response. [ABSTRACT FROM AUTHOR]