Astaxanthin: Past, Present, and Future.

Astaxanthin (AX), a lipid-soluble pigment belonging to the xanthophyll carotenoids family, has recently garnered significant attention due to its unique physical properties, biochemical attributes, and physiological effects. Originally recognized primarily for its role in imparting the characteristic red-pink color to various organisms, AX is currently experiencing a surge in interest and research. The growing body of literature in this field predominantly focuses on AXs distinctive bioactivities and properties. However, the potential of algae-derived AX as a solution to various global environmental and societal challenges that threaten life on our planet has not received extensive attention. Furthermore, the historical context and the role of AX in nature, as well as its significance in diverse cultures and traditional health practices, have not been comprehensively explored in previous works. This review article embarks on a comprehensive journey through the history leading up to the present, offering insights into the discovery of AX, its chemical and physical attributes, distribution in organisms, and biosynthesis. Additionally, it delves into the intricate realm of health benefits, biofunctional characteristics, and the current market status of AX. By encompassing these multifaceted aspects, this review aims to provide readers with a more profound understanding and a robust foundation for future scientific endeavors directed at addressing societal needs for sustainable nutritional and medicinal solutions. An updated summary of AXs health benefits, its present market status, and potential future applications are also included for a well-rounded perspective.

In Vitro Evaluation of Skin-Related Physicochemical Properties and Biological Activities of Astaxanthin Isomers.

Dietary astaxanthin exists predominantly as the all-E-isomer; however, certain amounts of the Z-isomers are universally present in the skin, whose roles remain largely unknown. The aim of this study was to investigate the effects of the astaxanthin E/Z-isomer ratio on skin-related physicochemical properties and biological activities using human dermal fibroblasts and B16 mouse melanoma cells. We revealed that astaxanthin enriched in Z-isomers (total Z-isomer ratio = 86.6%) exhibited greater UV-light-shielding ability and skin antiaging and skin-whitening activities, such as anti-elastase and anti-melanin formation activities, than the all-E-isomer-rich astaxanthin (total Z-isomer ratio = 3.3%). On the other hand, the all-E-isomer was superior to the Z-isomers in singlet oxygen scavenging/quenching activity, and the Z-isomers inhibited type I collagen release into the culture medium in a dose-dependent manner. Our findings help clarify the roles of astaxanthin Z-isomers in the skin and would help in the development of novel skin health-promoting food ingredients.

Depletion of CD206+ M2-like macrophages induces fibro-adipogenic progenitors activation and muscle regeneration.

Muscle regeneration requires the coordination of muscle stem cells, mesenchymal fibro-adipogenic progenitors (FAPs), and macrophages. How macrophages regulate the paracrine secretion of FAPs during the recovery process remains elusive. Herein, we systemically investigated the communication between CD206+ M2-like macrophages and FAPs during the recovery process using a transgenic mouse model. Depletion of CD206+ M2-like macrophages or deletion of CD206+ M2-like macrophages-specific TGF-ß1 gene induces myogenesis and muscle regeneration. We show that depletion of CD206+ M2-like macrophages activates FAPs and activated FAPs secrete follistatin, a promyogenic factor, thereby boosting the recovery process. Conversely, deletion of the FAP-specific follistatin gene results in impaired muscle stem cell function, enhanced fibrosis, and delayed muscle regeneration. Mechanistically, CD206+ M2-like macrophages inhibit the secretion of FAP-derived follistatin via TGF-ß signaling. Here we show that CD206+ M2-like macrophages constitute a microenvironment for FAPs and may regulate the myogenic potential of muscle stem/satellite cells.

Astaxanthin, a Marine Carotenoid, Maintains the Tolerance and Integrity of Adipose Tissue and Contributes to Its Healthy Functions.

Recently, obesity-induced insulin resistance, type 2 diabetes, and cardiovascular disease have become major social problems. We have previously shown that Astaxanthin (AX), which is a natural antioxidant, significantly ameliorates obesity-induced glucose intolerance and insulin resistance. It is well known that AX is a strong lipophilic antioxidant and has been shown to be beneficial for acute inflammation. However, the actual effects of AX on chronic inflammation in adipose tissue (AT) remain unclear. To observe the effects of AX on AT functions in obese mice, we fed six-week-old male C57BL/6J on high-fat-diet (HFD) supplemented with or without 0.02% of AX for 24 weeks. We determined the effect of AX at 10 and 24 weeks of HFD with or without AX on various parameters including insulin sensitivity, glucose tolerance, inflammation, and mitochondrial function in AT. We found that AX significantly reduced oxidative stress and macrophage infiltration into AT, as well as maintaining healthy AT function. Furthermore, AX prevented pathological AT remodeling probably caused by hypoxia in AT. Collectively, AX treatment exerted anti-inflammatory effects via its antioxidant activity in AT, maintained the vascular structure of AT and preserved the stem cells and progenitor's niche, and enhanced anti-inflammatory hypoxia induction factor-2α-dominant hypoxic response. Through these mechanisms of action, it prevented the pathological remodeling of AT and maintained its integrity.

Accuracy of a portable accelerometer-based navigation system for cup placement and intraoperative leg length measurement in total hip arthroplasty: a cross-sectional study.

BACKGROUND: Complications after total hip arthroplasty (THA) are frequently the consequence of malpositioned components or leg length discrepancy after surgery. Recently, a new version of a portable, accelerometer-based hip navigation system (New HipAlign) was made available with a change in the method of measuring cup abduction and the addition of a leg length measurement function. The purposes of this study were to investigate cup positioning and to examine the accuracy of leg length measurement with New HipAlign. METHODS: Cups were implanted and intraoperative leg length change was measured using New HipAlign in 60 THAs through a posterior approach in the lateral decubitus position. The cup position and radiographic leg length change were determined postoperatively on pelvic radiograph and computed tomography scans. We previously compared cup positioning with a previous version of a portable, accelerometer-based hip navigation system (Previous HipAlign) and conventional surgical techniques. Cup positioning in this study was compared with the results of out previous study using Previous HipAlign. RESULTS: The mean cup abduction of 40.3° ± 4.9° (range, 26° to 53°) and the mean cup anteversion of 15.8° ± 5.6° (range, 6.7° to 29.5°) were found. The deviation of the postoperative measured angles from the target cup position was 3.7° ± 3.3° for cup abduction and 5.9° ± 3.6° for cup anteversion. 56/60 of the cups were inside the Lewinnek safe zone. Compared with our previous study using Previous HipAlign, there were no significant differences with regard to cup abduction, cup anteversion, the deviation from the target cup position for cup abduction, the value of deviation for cup anteversion, and the number of cups inside the Lewinnek safe zone (P = 0.218, 0.334, 0.651, 0.797, 0.592). The mean difference between the intraoperative and radiographic leg length changes was + 0.8 ± 3.4 mm. There was significant correlation between the intraoperative and radiographic leg length changes (r = 0.804, P = 0.000). CONCLUSIONS: Use of New HipAlign allowed for accurate cup placement and reliable leg length measurement during THA. TRIAL REGISTRATION: Clinical trial is defined as 'any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcome' by the World Health Organization (WHO). Because this study is not a clinical trial, trial registration is not needed.

Astaxanthin as a Novel Mitochondrial Regulator: A New Aspect of Carotenoids, beyond Antioxidants.

Astaxanthin is a member of the carotenoid family that is found abundantly in marine organisms, and has been gaining attention in recent years due to its varied biological/physiological activities. It has been reported that astaxanthin functions both as a pigment, and as an antioxidant with superior free radical quenching capacity. We recently reported that astaxanthin modulated mitochondrial functions by a novel mechanism independent of its antioxidant function. In this paper, we review astaxanthin's well-known antioxidant activity, and expand on astaxanthin's lesser-known molecular targets, and its role in mitochondrial energy metabolism.

NAD+ Metabolism Regulates Preadipocyte Differentiation by Enhancing α-Ketoglutarate-Mediated Histone H3K9 Demethylation at the PPARγ Promoter.

Obesity has become a serious problem in public health worldwide, causing numerous metabolic diseases. Once the differentiation to mature adipocytes is disrupted, adipocyte hypertrophy and ectopic lipid accumulation leads to the inflammation in adipose tissue and systemic metabolic disorders. Intracellular metabolic state is known to change during cell differentiation and it affects the cell fate or the differentiation through epigenetic mechanism. Although the mechanism of preadipocyte differentiation has been well established, it is unknown how metabolic state changes and how it affects the differentiation in predipocyte differentiation. Nicotinamide adenine dinucleotide (NAD+) plays crucial roles in energy metabolism as a coenzyme in multiple redox reactions in major catabolic pathways and as a substrate of sirtuins or poly(ADP-ribose)polymerases. NAD+ is mainly synthesized from salvage pathway mediated by two enzymes, Nampt and Nmnat. The manipulation to NAD+ metabolism causes metabolic change in each tissue and changes in systemic metabolism. However, the role of NAD+ and Nampt in adipocyte differentiation remains unknown. In this study, we employed liquid chromatography-mass spectrometry (LC-MS)- and gas chromatography-mass spectrometry (GC-MS)-based targeted metabolomics to elucidate the metabolic reprogramming events that occur during 3T3-L1 preadipocyte differentiation. We found that the tricarboxylic acid (TCA) cycle was enhanced, which correlated with upregulated NAD+ synthesis. Additionally, increased alpha-ketoglutarate (αKG) contributed to histone H3K9 demethylation in the promoter region of PPARγ, leading to its transcriptional activation. Thus, we concluded that NAD+-centered metabolic reprogramming is necessary for the differentiation of 3T3-L1 preadipocytes.

A simple angle-measuring instrument for measuring cemented stem anteversion during total hip arthroplasty.

BACKGROUND: During total hip arthroplasty (THA), the accurate placement of the femoral components is an important determinant of the success of the procedure. This study assessed the accuracy of cemented stem placement using a new angle-measuring instrument. The primary objective was to investigate the accuracy of the intraoperative measurements of cemented stem anteversion obtained using the angle-measuring instrument. Our secondary objective was to evaluate the accuracy of stem positioning performed using the angle-measuring instrument. METHODS: We compared the intraoperative stem anteversion measurements obtained using the angle-measuring instrument with postoperative stem anteversion measurements obtained using computed tomography in 149 hips (measurement accuracy). We also compared the target angle and postoperative stem anteversion in 105 hips (implantation accuracy). RESULTS: The mean amount of intraoperative stem anteversion was 37.9° ± 10.1°, and the mean amount of postoperative stem anteversion was 37.0° ± 10.4°. The mean measurement accuracy was 0.9° ± 6.1°, and the absolute measurement accuracy was 4.9° ± 3.7°. The correlation coefficient for the relationship between the intraoperative and postoperative stem anteversion measurements was 0.824 (p = 0.000). The mean amount of target angle was 37.4° ± 7.6°, and the mean amount of postoperative stem anteversion was 35.9° ± 9.1°. The mean implantation accuracy was 1.4° ± 5.6°, and the mean absolute implantation accuracy was 4.3° ± 3.6°. The correlation coefficient for the relationship between the target angle and postoperative stem anteversion was 0.795 (p = 0.000). CONCLUSIONS: The angle-measuring instrument measured intraoperative stem anteversion accurately, and cemented stem was implanted accurately during THA with the angle-measuring instrument.

Astaxanthin stimulates mitochondrial biogenesis in insulin resistant muscle via activation of AMPK pathway.

BACKGROUND: Skeletal muscle is mainly responsible for insulin-stimulated glucose disposal. Dysfunction in skeletal muscle metabolism especially during obesity contributes to the insulin resistance. Astaxanthin (AX), a natural antioxidant, has been shown to ameliorate hepatic insulin resistance in obese mice. However, its effects in skeletal muscle are poorly understood. The current study aimed to investigate the molecular target of AX in ameliorating skeletal muscle insulin resistance. METHODS: We fed 6-week-old male C57BL/6J mice with normal chow (NC) or NC supplemented with AX (NC+AX) and high-fat-diet (HFD) or HFD supplemented with AX for 24 weeks. We determined the effect of AX on various parameters including insulin sensitivity, glucose uptake, inflammation, kinase signaling, gene expression, and mitochondrial function in muscle. We also determined energy metabolism in intact C2C12 cells treated with AX using the Seahorse XFe96 Extracellular Flux Analyzer and assessed the effect of AX on mitochondrial oxidative phosphorylation and mitochondrial biogenesis. RESULTS: AX-treated HFD mice showed improved metabolic status with significant reduction in blood glucose, serum total triglycerides, and cholesterol (p< 0.05). AX-treated HFD mice also showed improved glucose metabolism by enhancing glucose incorporation into peripheral target tissues, such as the skeletal muscle, rather than by suppressing gluconeogenesis in the liver as shown by hyperinsulinemic-euglycemic clamp study. AX activated AMPK in the skeletal muscle of the HFD mice and upregulated the expressions of transcriptional factors and coactivator, thereby inducing mitochondrial remodeling, including increased mitochondrial oxidative phosphorylation component and free fatty acid metabolism. We also assessed the effects of AX on mitochondrial biogenesis in the siRNA-mediated AMPK-depleted C2C12 cells and showed that the effect of AX was lost in the genetically AMPK-depleted C2C12 cells. Collectively, AX treatment (i) significantly ameliorated insulin resistance and glucose intolerance through regulation of AMPK activation in the muscle, (ii) stimulated mitochondrial biogenesis in the muscle, (iii) enhanced exercise tolerance and exercise-induced fatty acid metabolism, and (iv) exerted antiinflammatory effects via its antioxidant activity in adipose tissue. CONCLUSIONS: We concluded that AX treatment stimulated mitochondrial biogenesis and significantly ameliorated insulin resistance through activation of AMPK pathway in the skeletal muscle.

Portable Accelerometer-Based Navigation System for Cup Placement of Total Hip Arthroplasty: A Prospective, Randomized, Controlled Study.

BACKGROUND: Malposition of the acetabular component during total hip arthroplasty (THA) is associated with increased risk of dislocation, reduced range of motion, and accelerated wear. The purpose of this study is to compare cup positioning with a portable, accelerometer-based hip navigation system and conventional surgical technique. METHODS: In a prospective, randomized, clinical study, cups were implanted with a portable, accelerometer-based hip navigation system (navigation group; n = 55) or conventional technique (conventional group; n = 55). THA was conducted in the lateral position and through posterior approach. The cup position was determined postoperatively on pelvic radiograph and computed tomography scans. RESULTS: An average cup abduction of 39.2° ± 4.6° (range, 27° to 50°) and an average cup anteversion of 14.6° ± 6.1° (range, 1° to 27.5°) were found in the navigation group, and an average cup abduction of 42.9° ± 8.0° (range, 23° to 73°) and an average cup anteversion of 11.6° ± 7.7° (range, -12.1° to 25°) in the conventional group. A smaller variation in the navigation group was indicated for cup abduction (P = .001). The deviations from the target cup position were significantly lower in the navigation group (P = .001, .016). While only 37 of 55 cups in the conventional group were inside the Lewinnek safe zone, 51 of 55 cups in the navigation group were placed inside this safe zone (P = .006). The navigation procedure took a mean of 10 minutes longer than the conventional technique. CONCLUSION: Use of the portable, accelerometer-based hip navigation system can improve cup positioning in THA.

Hip stability after total hip arthroplasty predicted by intraoperative stability test and range of motion: a cross-sectional study.

BACKGROUND: Dislocation continues to be a common complication following total hip arthroplasty (THA). A larger intraoperative range of motion (ROM) is believed to minimize dislocation risk, and intraoperative stability tests have been used to assess the ROM. However, it is not clear whether or not intraoperative stability tests can predict hip stability after THA. It is also unclear which angles are required in intraoperative stability tests. We investigated the usefulness of intraoperative stability tests, and other risk factors to predict hip stability after THA. METHODS: Patients operated by single surgeon at one hospital from June 2009 to December 2013 were evaluated. This study included 185 hips with 32 mm metal femoral head. The range of internal rotation with 90° hip flexion (IR angle) was measured as an intraoperative stability test. The variables studied as risk factors included age, height, weight, gender, cerebral dysfunction, preoperative diagnosis, history of previous hip surgery, and IR angle. RESULTS: Mean IR angle was statistically different between patients with dislocation and patients without dislocation (59.5° vs 69.6°: p = 0.006). Cerebral dysfunction and a history of previous hip surgery were statistically related with prevalence of dislocation (p = 0.021, and p = 0.011). The receiver-operating characteristic curve analysis suggested that the cutoff points for IR angle were 51° and 67°. Dislocation rate in larger IR angle group was significantly lower than the rate in smaller IR angle group when patients were divided by 51° (p = 0.002). Logistic regression analyses showed that significant risk factors were cerebral dysfunction (OR: 5.3 (95%CI 1.1-25.9); p = 0.037), history of previous hip surgery (OR: 8.6 (95%CI 1.2-63.0); p = 0.035), and IR angle (OR: 10.4 (95%CI 1.9-57.1); p = 0.007). CONCLUSIONS: The results showed that intraoperative stability test, especially the IR angle, was a useful method to predict hip stability after THA, and a larger intraoperative ROM reduced the likelihood of dislocation. 51° and 67° were indicated as cutoff points for IR angle. Cerebral dysfunction and a history of previous hip surgery are also risk factors for the incidence of dislocation after THA. TRIAL REGISTRATION: This is a retrospective study, not a clinical trial defined by the World Health Organization (WHO).

Efficacy of Resuscitative Transfusion With Hemoglobin Vesicles in the Treatment of Massive Hemorrhage in Rabbits With Thrombocytopenic Coagulopathy and Its Effect on Hemostasis by Platelet Transfusion.

INTRODUCTION: We have developed hemoglobin vesicles (HbVs) as a substitute for red blood cells (RBCs). We investigated the efficacy of HbV transfusion in the treatment of massive hemorrhage in rabbits in the setting of thrombocytopenic coagulopathy, focusing on the efficacy of hemostasis by subsequent platelet transfusion. METHODS: Thrombocytopenic coagulopathy was induced in rabbits by repeated blood withdrawal and isovolemic retransfusion of autologous RBC (platelet counts <45,000/µL). A penetrating liver injury was then made. For 30 min, bleeding volume was measured every 10 min, after which subjects were transfused with an equivalent volume of stored RBC, HbV, or platelet poor plasma (PPP) to compensate for blood loss, simulating initial prehospital resuscitation. Thereafter, we transfused platelet rich plasma (PRP) to stop bleeding, which simulated inhospital resuscitation. RESULTS: During the initial resuscitation, the HbV group was similar to the RBC group (but not the PPP group) in their hemodynamics and tissue circulation/oxygenation as assessed by plasma lactate levels. All rabbits showed similar bleeding volumes (20-30 mL) in this period. HbV-transfused rabbits sustained hemoglobin levels, but showed lower hematocrit levels compared with RBC-transfused rabbits. Subsequent PRP transfusion effectively stopped bleeding in all RBC-transfused rabbits (6/6) and most HbV-transfused rabbits (7/8) but not PPP-transfused rabbits (2/8). In addition, 83% of RBC-transfused rabbits and 75% of HbV-transfused rabbits survived for 24 h, although no PPP-transfused rabbits survived. HbV transfusion did not scavenge nitric oxide in rabbits. CONCLUSIONS: HbV transfusion effectively rescued rabbits from severe hemorrhage with coagulopathy, without disturbing hemostasis after the platelet transfusion. HbV transfusion may be practical and useful in prehospital resuscitation.

Erythropoietin, a putative neurotransmitter during hypoxia, is produced in RVLM neurons and activates them in neonatal Wistar rats.

Recent studies indicate that erythropoietin (EPO) is present in many areas of the brain and is active in the restoration of impaired neurons. In this study, we examined the presence of EPO and its role in bulbospinal neurons in the rostral ventrolateral medulla (RVLM). Hypoxia is often accompanied by a high blood pressure (BP). We hypothesized that EPO is produced in response to hypoxia in RVLM neurons and then activates them. To investigate whether RVLM neurons are sensitive to EPO, we examined the changes in the membrane potentials (MPs) of bulbospinal RVLM neurons using the whole cell patch-clamp technique during superfusion with EPO. A brainstem-spinal cord preparation was used for the experiments. EPO depolarized the RVLM neurons, and soluble erythropoietin receptor (SEPOR), an antagonist of EPO, hyperpolarized them. Furthermore, hypoxia-depolarized RVLM neurons were significantly hyperpolarized by SEPOR. In histological examinations, the EPO-depolarized RVLM neurons showed the presence of EPO receptor (EPOR). The RVLM neurons that possessed EPORs showed the presence of EPO and hypoxia-inducible factor (HIF)-2α. We also examined the levels of HIF-2α and EPO messenger RNA (mRNA) in the ventral sites of the medullas (containing RVLM areas) in response to hypoxia. The levels of HIF-2α and EPO mRNA in the hypoxia group were significantly greater than those in the control group. These results suggest that EPO is produced in response to hypoxia in RVLM neurons and causes a high BP via the stimulation of those neurons. EPO may be one of the neurotransmitters produced by RVLM neurons during hypoxia.

Reflex arc of the teeth clenching-induced pressor response in rats.

Although "teeth clenching" induces pressor response, the reflex tracts of the response are unknown. In this study, dantrolene administration inhibited teeth clenching generated by electrical stimulation of the masseter muscles and completely abolished the pressor response. In addition, trigeminal ganglion block or hexamethonium administration completely abolished the pressor response. Local anesthesia of molar regions significantly reduced the pressor response to 27 ± 10%. Gadolinium (mechanoreceptor blocker of group III muscle afferents) entrapment in masticatory muscles also significantly reduced the pressor response to 62 ± 7%. Although atropine methyl nitrate administration did not change the pressor response, a significant dose-dependent augmentation of heart rate was observed. These results indicate that both periodontal membrane and mechanoreceptors in masticatory muscles are the receptors for the pressor response, and that the afferent and efferent pathways of the pressor response pass through the trigeminal afferent nerves and sympathetic nerves, respectively.

CD206+ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors.

Adipose tissue resident macrophages have important roles in the maintenance of tissue homeostasis and regulate insulin sensitivity for example by secreting pro-inflammatory or anti-inflammatory cytokines. Here, we show that M2-like macrophages in adipose tissue regulate systemic glucose homeostasis by inhibiting adipocyte progenitor proliferation via the CD206/TGFß signaling pathway. We show that adipose tissue CD206+ cells are primarily M2-like macrophages, and ablation of CD206+ M2-like macrophages improves systemic insulin sensitivity, which was associated with an increased number of smaller adipocytes. Mice genetically engineered to have reduced numbers of CD206+ M2-like macrophages show a down-regulation of TGFß signaling in adipose tissue, together with up-regulated proliferation and differentiation of adipocyte progenitors. Our findings indicate that CD206+ M2-like macrophages in adipose tissues create a microenvironment that inhibits growth and differentiation of adipocyte progenitors and, thereby, control adiposity and systemic insulin sensitivity.Adipose tissue contains macrophages that can influence both local and systemic metabolism via the secretion of cytokines. Here, Nawaz et al. report that M2-like macrophages, present in adipose tissue, create a microenvironment that inhibits proliferation of adipocyte progenitors due to the secretion of TGF-ß1.

Estrogen Status Gates Effects of Kappa-Opioid Receptor on Temporomandibular Joint-Responsive Neurons at the Spinomedullary Junction in Female Rats.

AIMS: To determine whether estrogen status alters κ-opioid inhibition of nociceptive processing by affecting temporomandibular joint (TMJ) input to neurons in the trigeminal subnucleus caudalis [Vc]/C1-2 region at the spinomedullary junction in female rats. METHODS: TMJ-responsive neurons were recorded in laminae I-II of the Vc/C1-2 region at the spinomedullary junction of ovariectomized female rats treated for 2 days with low-dose estradiol (LE group; 2 mg/day) or high-dose estradiol (HE group; 20 mg/day). Under isoflurane anesthesia, TMJ neurons were activated by adenosine triphosphate (ATP; 1 mM, 20 µl), which was injected into the joint space before and after cumulative doses of a κ-opioid receptor (KOR) agonist (U50488) given systemically (0.03, 0.3, and 3 mg/kg, intravenously) or by local application to the dorsal surface of the Vc/C1-2 region (1 and 10 nmol/30 µl). Analysis of variance and Newman-Keuls test were performed to compare the data. RESULTS: Systemic U50488 caused a dose-related inhibition of ATP-evoked neuronal activity in HE rats and reduced the size of the neuronal cutaneous receptive field (RF), while effects in LE rats were not significant. Systemic U50488 reduced the spontaneous activity of TMJ-responsive neurons to similar levels in LE and HE groups. Locally applied U50488 inhibited ATP-evoked neuronal activity in HE rats, but not in LE rats. Systemic and local administration of the KOR antagonist nor-binaltorphinine (nor-BNI) partially reversed the decrease in Rmag induced by U50488, but had no effect on neurons from LE rats. CONCLUSION: These results indicate that KOR-dependent effects on TMJ-responsive neurons in the superficial laminae of the Vc/C1-2 region in female rats are differentially modified by high and low estrogen status. The site of action for estrogen-induced modulation of TMJ neuronal activity by KOR likely includes second-order neurons in the Vc/C1-2 region.

Dynamic femoral head translations in dysplastic hips.

BACKGROUND: Developmental dysplasia of the hip is an important disease leading to osteoarthritis. Recently, researchers have focused on hip instability as a potentially important dynamic factor for osteoarthritis, but the detailed kinematics of dysplastic hips during weight-bearing gait have not been reported. The purpose of this research is to contrast femoral translation in contralateral healthy hips and dysplastic hips during weight-bearing stepping. METHODS: Twelve dysplastic hips and eight healthy hips were investigated. Hip joint kinematics were analyzed using 3D-2D model-image registration with dynamic fluoroscopic images of each hip during a stepping-in-place activity. Femoral translation relative to the acetabular center was quantified as instability. FINDINGS: Total femoral head translations were significantly different between dysplastic and contralateral healthy hips. Mean translation was 1.0mm in dysplastic hips and 0.4mm in contralateral healthy hips during swing-phase, and consisted of inferior translation during early swing phase with a complementary superior translation just before foot strike. Total femoral translation was significantly correlated to several radiographic indices of hip dysplasia. INTERPRETATION: Superior translations of the femur during the end of swing phase may result in altered articular contact mechanics, abnormal stresses on the labrum and lost lubricant sealing. All of these factors may contribute to joint degeneration and osteoarthritis in dysplastic hips.

Optical coherence tomography angiography in eyes with good visual acuity recovery after treatment for optic neuritis.

OBJECTIVE: To evaluate the retinal perfusion using optical coherence tomography (OCT) angiography in eyes with good visual acuity recovery after treatment for optic neuritis (ON). METHODS: Seven eyes of seven patients with good visual acuity recovery after treatment for monocular ON and seven eyes of each fellow eye used as controls were studied. Retinal perfusion around the disc and at the macula was evaluated using OCT angiography. The retinal nerve fiber layer thickness was measured around the disc. The ganglion cell layer complex thickness or the ganglion cell layer plus the inner plexiform layer thickness were measured at the macula. RESULTS: The retinal perfusions in all eyes with ON decreased around the disc and at the macula compared with those of the fellow eyes, as shown by OCT angiography (disc, P = 0.003; macula, P = 0.001). The retinal thicknesses in all eyes with ON also decreased around the disc and at the macula compared with those of the fellow eyes (disc, P < 0.001; macula, P = 0.003). CONCLUSIONS: Optic neuritis may cause not only retinal structural damage but also decreased retinal perfusion, even after the visual acuity recovered well after treatment.

Direct effects of glucose, insulin, GLP-1, and GIP on bulbospinal neurons in the rostral ventrolateral medulla in neonatal wistar rats.

Although patients with diabetes mellitus (DM) often exhibit hypertension, the mechanisms responsible for this correlation are not well known. We hypothesized that the bulbospinal neurons in the rostral ventrolateral medulla (RVLM) are affected by the levels of glucose, insulin, or incretins (glucagon like peptide-1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP]) in patients with DM. To investigate whether RVLM neurons are activated by glucose, insulin, GLP-1, or GIP, we examined changes in the membrane potentials of bulbospinal RVLM neurons using whole-cell patch-clamp technique during superfusion with various levels of glucose or these hormones in neonatal Wistar rats. A brainstem-spinal cord preparation was used for the experiments. A low level of glucose stimulated bulbospinal RVLM neurons. During insulin superfusion, almost all the RVLM neurons were depolarized, while during GLP-1 or GIP superfusion, almost all the RVLM neurons were hyperpolarized. Next, histological examinations were performed to examine transporters for glucose and receptors for insulin, GLP-1, and GIP on RVLM neurons. Low-level glucose-depolarized RVLM neurons exhibited the presence of glucose transporter 3 (GLUT3). Meanwhile, insulin-depolarized, GLP-1-hyperpolarized, and GIP-hyperpolarized RVLM neurons showed each of the respective specific receptor. These results indicate that a low level of glucose stimulates bulbospinal RVLM neurons via specific transporters on these neurons, inducing hypertension. Furthermore, an increase in insulin or a reduction in incretins may also activate the sympathetic nervous system and induce hypertension by activating RVLM neurons via their own receptors.

Optical Coherence Tomography Angiography in a Patient with Optic Atrophy After Non-arteritic Anterior Ischaemic Optic Neuropathy.

A 75-year-old female noticed a lower visual field (VF) defect in the right eye. A diagnosis of non-arteritic anterior ischaemic optic neuropathy (NAION) was made. The lower VF defect in the right eye did not change after onset. Optical coherence tomography (OCT) angiograms on the disc and the macula showed decreased retinal perfusion in the upper retina of the right eye. Retinal nerve fibre layer loss and ganglion cell complex loss in the upper retina were also seen in the right eye. OCT angiography could non-invasively detect the decrease of the retinal perfusion due to NAION.