Abnormal bone regeneration induced by FK506 in medaka fin revealed by in vivo imaging.

OBJECTIVES: Bone tissue in bony fish demonstrates a remarkable ability to regenerate, particularly evident following induction of extensive bone defects, such as fin amputation. This regenerative capacity has been reported to be promoted by the immunosuppressant FK506, yet its precise effects on bone cells during fin regeneration remains insufficiently elucidated. This study aims to investigate the effects of FK506 treatment on bone morphology, osteoblasts, and osteoclasts in the bony fin rays of osterix promoter-DsRed/TRAP promoter-EGFP double transgenic (Tg) medaka. METHODS: The caudal fin of double Tg medaka was amputated, followed by a 20-day treatment with FK506 (1.0 µg/ml) to observe its effects on fin regeneration. Additionally, the regenerated caudal fin area underwent evaluation using genetic analysis and cell proliferation assays. RESULTS: FK506 treatment significantly increased osterix-positive osteoblast formation, resulting in both a significantly longer fin length and fewer joints in the bony fin rays formed during fin regeneration. Notably, TRAP-positive osteoclast formation and bone resorption were observed to occur primarily during the latter stages of fin regeneration. Furthermore, while the expression levels of osteoblast-related genes in the regenerated area remained unchanged following FK506 treatment, a heightened cell proliferation was observed at the tip of the fin. CONCLUSIONS: Our findings suggest that treatment with FK506 promotes bone regeneration by increasing the number of osteoblasts in the amputated area of the fin. However, long-term treatment disrupts regular bone metabolism by inducing abnormal osteoclast formation.

Immediate curative effects of exercise therapy in patients with myalgia of the masticatory muscles.

BACKGROUND: Exercise therapy is occasionally considered as an initial treatment for temporomandibular disorders. However, pain can be exacerbated during exercise therapy. OBJECTIVE: To investigate the immediate curative effects of exercise therapy in patients with masticatory muscle myalgia. METHODS: Fifty-nine patients with masticatory muscle myalgia were included. Therapists performed exercise therapy (stretched the painful masseter and/or cervical muscles along the direction of muscle contraction) in 10 rounds of traction, each lasting 10 s. The patient's pain-free maximum mouth opening distance and degree of pain (VAS value) before and immediately after exercise therapy were compared using the Wilcoxon signed-rank test. The Mann-Whitney U test was used for the subgroup comparisons. RESULTS: Mouth opening increased from 41 (IQR 38-43) to 46 (IQR 43-48) mm and pain alleviation from 48 (IQR 31-56) to 21 (IQR 10-56) immediately following exercise therapy (p < .001 for both). None of the patients experienced pain exacerbation or reduction in mouth opening post-exercise. No difference in mouth opening distance changes according to sex, painful side, painful site and therapist were observed (p > .05 for all). Pain reduction was greater in patients with unilateral pain (26, IQR 12-39) than those with bilateral (13, IQR 5-25) (p = .019). There were no differences in the change in the degree of pain according to sex, painful site and therapist (p > .05 for all). CONCLUSION: Exercise therapy immediately enlarged the mouth opening distance and reduced myalgia; therefore, it could be helpful in managing masticatory muscle myalgia.

MIG12 is involved in the LXR activation-mediated induction of the polymerization of mammalian acetyl-CoA carboxylase.

Liver X receptors (LXR) α and ß are a family of nuclear receptors that regulate lipogenesis by controlling the expression of the genes involved in the synthesis of fatty acids. MID1IP1, which encodes MIG12, is a target gene of LXR. MIG12 induces fatty acid synthesis by stimulating the polymerization-mediated activation of acetyl-CoA carboxylase (ACC). Here, we show that LXR's activation stimulates ACC polymerization in HepG2 cells by increasing the expression of MIG12. A knockdown of MID1IP1 abrogated the stimulation completely. The mutations of MIG12's leucine-zipper domain reduced the interaction between MIG12 and ACC, thus decreasing the MIG12's capacity to stimulate ACC polymerization. These results indicate that LXR's activation stimulates lipogenesis not only through the induction of the genes encoding lipogenic enzymes but also through MIG12's stimulation of ACC polymerization.

Intracranial plasmacytoma arising from dura mater secondary to multiple myeloma and presenting with sudden lethal intracerebral hemorrhage: A case report and literature review.

BACKGROUND: Intracranial and central nervous system's involvement with multiple myeloma (MM) is a clinically rare manifestation. Furthermore, the development of intracranial plasmacytoma without bone involvement is much rarer. Herein, we report the case of massive intracerebral hemorrhage form intracranial plasmacytoma that arose from the dura mater without bone involvement. CASE DESCRIPTION: A 71-year-old woman, who had been diagnosed as MM and treated 2 years prior, developed sudden lethal intracerebral hemorrhage from the intracranial plasmacytoma. Massive hemorrhage was observed after a rapid tumor growth in the middle fossa. Immediate hematoma evacuation and tumor resection allowed the patient to avoid severe neurological deficits and lethal conditions. CONCLUSION: A close follow-up by neuroimaging studies is essential in cases of intracranial plasmacytoma in MM patients and early intervention with surgical resection or radiotherapy should be considered.

Short-term effects of range-of-motion exercise on temporomandibular joints of patients who undergo disc displacement with reduction of temporomandibular joint.

[Purpose] We investigated the short-term effects of an exercise therapy program that combined a range-of-motion exercise for the temporomandibular joint with self-traction therapy for patients with temporomandibular joint disorders who undergo disc displacement with reduction of the painful temporomandibular joint. [Participants and Methods] The program involved 31 patients with moderate or higher functional pain. The range-of-motion exercise for the temporomandibular joint was performed at the first visit by the therapist, and the patients were instructed to perform self-traction therapy in the morning and while bathing for the next 2 weeks, until their next visit. The maximum mouth opening distance and the visual analog scale scores at the first consultation and 2 weeks later were compared to assess the changes in pain on motion and mastication as well as the impact of the program on daily activities. [Results] All symptoms of the patients showed significant improvements after 2 weeks of starting the treatment. [Conclusion] The results of this study suggest that an exercise therapy program combining range-of-motion exercises for the temporomandibular joint and self-traction therapy may be an effective conservative therapy for reducing the pain and obstacles experienced by patients with temporomandibular joint disorders who undergo disc displacement with reduction of the painful temporomandibular joint.

Prediction of the difficulty of proximal vascular control using 3D-CTA for the surgical clipping of internal carotid artery-posterior communicating artery aneurysms.

OBJECTIVE: During surgical clipping of internal carotid artery (ICA)-posterior communicating artery (PCoA) aneurysms, proximal vascular control (PVC) is difficult to achieve in some cases because of variations in the anatomy of this type of aneurysm and its parent arteries. The authors investigated morphometric features that may be predictive for the necessity of anterior clinoidectomy (ACL) or cervical ICA exposure for PVC. METHODS: The authors retrospectively reviewed 65 patients with an ICA-PCoA aneurysm treated with clipping during the previous 3 years. The factors considered for assessing the difficulty of attaining PVC included the following: the maximum diameter of the aneurysm; the distance between the tip of the anterior clinoid process (ACP) and the proximal aneurysmal neck; the presence of calcification at the ophthalmic segment of the ICA; and the angles between the communicating segment of the ICA and the ophthalmic segment of the ICA and a line perpendicular to the cranial base, which reflect the tortuosity of the ICA. These parameters were measured based on preoperative CTA results. RESULTS: In a total of 21 patients (32.3%), PVC was difficult to perform with the usual pterional approach. In 6 patients, temporary artery occlusions (TAOs) were difficult to achieve because of severe atherosclerotic wall changes in the ophthalmic segment of the ICA. For 15 patients, the ACPs overhanging the ophthalmic segment of the ICA obstructed the ability to secure a space for TAO. In the 21 patients with PVC difficulty, ACL alone, cervical ICA exposure alone, and both ACL and cervical ICA exposure were conducted in 6, 8, and 7 patients, respectively. Multivariate analysis with binary logistic regression revealed that the maximum diameter of the aneurysm (p = 0.041), the distance between the proximal neck of the aneurysm and the ACP tip (p = 0.002), and calcification of the ICA ophthalmic segment (p = 0.001) were significant predictive factors for difficulties with PVC. A receiver operating characteristic curve analysis revealed that a distance between the proximal aneurysmal neck and the ACP tip of ≤ 5.4 mm was the best cutoff value for predicting the difficulty of attaining PVC (area under the curve 0.800, sensitivity 80.0%, specificity 80.0%). CONCLUSIONS: A short distance between the proximal aneurysmal neck and the ACP tip and the presence of calcification at the ophthalmic segment of the ICA on preoperative CTA are helpful for predicting the difficulty of achieving PVC.

Sphenoparietal sinus transposition technique: optimization of the surgical corridor with preservation of prominent bridging veins between the brain and the cranial base during aneurysm clipping via the pterional approach.

OBJECTIVE: The sylvian bridging veins between the brain and the dura on the inner surface of the sphenoid wing can restrict brain retraction for widening of the lateral retrocarotid space during clipping surgery for internal carotid artery (ICA)-posterior communicating artery (PCoA) and basilar apex (BX) aneurysms. In such cases, the authors perform extradural anterior clinoidectomy with peeling of the temporal dura propria from the periosteal dura and inner cavernous membrane around the superior orbital fissure, with the incision of the dura mater stretching from the base of the temporal side to just before the distal dural ring of the ICA (termed by the authors as the sphenoparietal sinus transposition [SPST] technique). This technique displaces the bridging segment of the sylvian vein posteriorly and enables widening of the surgical space without venous injury. In this study, the authors observed the operative nuances and investigated the usefulness of this technique. METHODS: The authors retrospectively reviewed the medical charts of 66 consecutive patients with ICA-PCoA and BX aneurysms between January 2016 and July 2018. This technique was performed in 8 patients (5 patients with PCoA aneurysms and 3 with BX aneurysms) in whom the bridging segments of the sylvian veins between the brain and the skull base restricted brain retraction for widening of the surgical space. The surface areas of the lateral retrocarotid space and the aneurysm were measured at the most visible working angle before and after the SPST technique was performed. RESULTS: With the use of the SPST technique, an adequate surgical space for aneurysm clipping was obtained with preservation of the bridging veins in all patients. The mean surface areas of the lateral retrocarotid space (p = 0.002) and aneurysm (p = 0.001) were significantly increased from 18.3 ± 18.8 and 2.8 ± 2.5 cm2 before to 64.2 ± 21.1 and 20.9 ± 20.6 cm2, respectively, after the SPST technique was performed. CONCLUSIONS: The SPST technique enables displacement of the bridging segments of the sylvian veins without venous injury and enables widening of the surgical space around the lateral retrocarotid area.

Management strategy for bilateral complex vertebral artery aneurysms.

Bilateral complex vertebral artery aneurysms (BCoVAAns) have no established strategy of management. We retrospectively reviewed five consecutive patients with unruptured BCoVAAns between January 2006 and December 2012. Considering surgical risks of lower cranial nerve (LCN) injuries and eventual growth of an opposite side lesion after unilateral vertebral artery (VA) occlusion, we proposed a strategy of combined open and interventional treatment using revascularization. We applied the following several specific techniques: (1) proximal clipping and occipital artery-posterior inferior cerebellar artery (OA-PICA) and/or superficial temporary artery (STA)-superior cerebellar artery (SCA) bypasses; (2) Distal blood pressure, motor evoked potentials (MEPs), and somatosensory evoked potentials (SEPs) monitoring after parent artery temporary occlusion for safe permanent occlusion of the proximal portions of VA and PICA; (3) V3 to V4 bypass using radial artery (RA) graft with proximal clipping or trapping, two of them combined with OA-PICA bypass; (4) VA fenestration as an opportunity to preserve the flow of the parent artery. Two patients were treated bilaterally and 3 unilaterally, with modified Rankin scale assessed at 39 months postoperatively in average 0 in 2, 1 in 2, and 2 in 1, respectively, and the untreated opposite side lesions without regrowth or bleeding. Two patients with patent V3-RA-V4 bypass complained of dysphagia due to LCN palsies. One of them however suffered a cerebellar infarction due to occlusion of the OA-PICA bypass. When BCoVAAns require surgical treatment, revascularization or preservation of the VA should be considered at the first operation. By doing so, the opposite aneurysm can be effectively occluded by coil embolization, even with VA sacrifice if required.

Usefulness of V3-radial artery graft-V4 bypass in bilateral fusiform aneurysms of vertebral artery: case report.

A 55-year-old woman with bilateral vertebral artery (VA) aneurysms was transferred to our hospital. She suffered from a minor stroke. Magnetic resonance imaging (MRI) for the stroke incidentally revealed bilateral VA aneurysms. Due to its size, more observation was recommended, and the patient was found eager to be treated. Both side surgeries were found inappropriate because of severe lower cranial nerve disturbances. The right aneurysm involved the posterior inferior cerebellar artery (PICA) and the V4 segment was deviated to the right side. Therefore, the smaller right aneurysm was treated first with an occipital artery (OA)-PICA bypass and a V3-radial artery graft (RAG)-V4 bypass followed by proximal clipping of the PICA and the right VA. The right VA was successfully remade by RAG and the right aneurysm was not revealed on postoperative examination. By doing so, the opposite aneurysm was able to be eliminated by the parent artery occlusion even by using an interventional radiology (IVR). The V3-RAG-V4 bypass is a useful method for treating bilateral VA aneurysms. This is a new bypass which has not been reported so far to the best of our knowledge.

Increased expression of vascular endothelial growth factor and its receptor in enlarging brain arteriovenous malformations--a case report.

CASE: A 24-year-old man with Spetzler-Martin (S-M) Grade III arteriovenous malformation (AVM). He was conservatively treated, but AVM significantly increased in size over 5 years, judged as Grade IV. Subsequently, he developed intracerebral hemorrhage. AVM was totally removed. Immunohistochemistry showed that the endothelial cells in the dura and nidus were positive for VEGF and VEGF-R.

Cilostazol may suppress restenosis and new contralateral carotid artery stenosis after carotid endarterectomy.

Carotid artery restenosis is a serious complication following carotid endarterectomy (CEA), so preventative management of the risk factors is important. The present study investigated the potential of cilostazol, a mediator of vascular stabilization as well as inhibitor of platelet aggregation, to suppress restenosis on the ipsilateral carotid artery and new plaque development on the contralateral carotid artery. Eighty-two patients treated by CEA were divided into two groups according to the postoperative antiplatelet aggregation drugs into the cilostazol and other groups. Patients were periodically examined for recurrence of the plaque on the ipsilateral side, development of plaque on the contralateral side, and the bilateral intermedia thicknesses measured by ultrasonographic examination for up to 6 years. Restenosis and development of the contralateral plaque were not detected in any patients in the cilostazol group, whereas such changes were found in seven patients in the other group. Cilostazol might be effective to inhibit the growth mechanism of plaque.

Relationship of serum brain-derived neurotrophic factor level with other markers of disease severity in patients with atopic dermatitis.

Elevated serum levels of neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been reported in allergic and autoimmune diseases. The aim of this study was to assess serum levels of BDNF in patients with atopic dermatitis (AD) and to investigate the relationship of the BDNF level with other markers of disease severity. Serum BDNF concentration was significantly higher in patients with AD (n=62) compared to control subjects (n=20) (P<0.01). Stepwise multiple regression analysis showed a significant influence of the peripheral blood eosinophil counts (F=6.90) and the percentage of CD4(+)IL-4(+) (Th2) cells (F=6.61). Moreover, after remission of AD patients with conventionally treated AD patients (n=14), serum levels of BDNF, eosinophil counts and percentage of Th2 cells were decreased significantly. These results suggest that serum BDNF may be a useful marker of disease activity in AD and that both eosinophils and Th2 cells are major cellular sources of serum BDNF.

Intracerebral infusion of glial cell line-derived neurotrophic factor promotes striatal neurogenesis after stroke in adult rats.

BACKGROUND AND PURPOSE: Stroke triggers increased progenitor proliferation in the subventricular zone (SVZ) and the generation of medium spiny neurons in the damaged striatum of rodents. We explored whether intrastriatal infusion of glial cell line-derived neurotrophic factor (GDNF) promotes neurogenesis after stroke. METHODS: Adult rats were subjected to 2-hour middle cerebral artery occlusion (MCAO). GDNF was infused into the ischemic striatum either during the first week after MCAO, with the animals being killed directly thereafter, or during the third and fourth weeks, with the rats being killed 1 week later. New cells were labeled with 5'-bromo-2'deoxyuridine (BrdU) on day 7 or during the second week, respectively. Neurogenesis was assessed immunocytochemically with antibodies against BrdU and neuronal, glial, or progenitor markers. GDNF receptor expression was analyzed in SVZ tissue and neurospheres by reverse transcription-polymerase chain reaction and immunocytochemistry. RESULTS: GDNF infusion increased cell proliferation in the ipsilateral SVZ and the recruitment of new neuroblasts into the striatum after MCAO and improved survival of new mature neurons. The GDNF receptor GFRalpha1 was upregulated in the SVZ 1 week after MCAO and was coexpressed with markers of dividing progenitor cells. CONCLUSIONS: Intrastriatal infusion of GDNF in the postischemic period promotes several steps of striatal neurogenesis after stroke, partly through direct action on SVZ progenitors. Because delivery of GDNF has biological effects in the human brain, our data suggest that administration of this factor may promote neuroregenerative responses in stroke patients.