Astragaloside IV attenuates orbital inflammation in Graves' orbitopathy through suppression of autophagy.

INTRODUCTION: Graves' orbitopathy (GO) is an autoimmune inflammatory disorder affecting the orbit around the eye. Astragaloside IV (AS-VI) is the main active ingredient of the Chinese herbal medicine Huangqi (Radix Astragali Mongolici). AS-IV exhibits antioxidant and anti-inflammatory properties, and shows therapeutic potential in a number of ischemic and inflammatory diseases; however, its pharmaceutical activities in GO remain undefined. MATERIALS AND METHODS: In this study, we investigated the effects of AS-IV on interleukin (IL)-1ß-induced orbital fibroblast inflammation in vitro and GO orbital inflammation and ocular histopathological changes in vivo, as well as the underlying mechanisms responsible for these effects. RESULTS AND CONCLUSION: The results show that IL-1ß increased mRNA expression of the inflammatory cytokines IL-6, IL-8, TNF-α, and MCP-1 in cultured orbital fibroblasts. This IL-1ß-induced inflammation was accompanied by increased autophagic activity as reflected in increased Beclin-1 and Agt-5 expression, as well as LC3-I to LC3-II conversion. Pretreatment with the autophagy inhibitors 3-MA and bafilomycin A1, or silencing of autophagy-related proteins Beclin-1 and Atg-5, prevented IL-1ß-induced orbital fibroblast inflammation, while pretreatment with the autophagy activator rapamycin had the opposite effects. These data suggested that autophagy was involved in GO orbital inflammation. AS-IV treatment significantly decreased IL-1ß-induced inflammatory cytokine production in orbital fibroblasts in vitro and attenuated GO orbital inflammation, fat accumulation, collagen deposition, and macrophage infiltration in vivo. These in vitro and in vivo protective effects of AS-IV against GO were accompanied by decreased autophagic activities in orbital fibroblasts and GO orbital tissues, respectively. Collectively, our findings suggested that AS-IV protects against GO through suppression of autophagy. Thus, AS-IV may have preventive benefits for GO.

Successful Treatment of Rhino-Orbital-Cerebral Mucormycosis in a Child With Leukemia.

Rhino-orbital-cerebral mucormycosis (ROCM) is a rare fulminant opportunistic fungal infection that despite relevant treatment has high mortality. We present a case of a 3-year-old girl with acute lymphoblastic leukemia and ROCM, who was treated successfully with excessive surgery, systemic antifungal treatment with amphotericin B (AmB), posaconazole, and terbinafine as well as hyperbaric oxygen. Surgery included, beside extracranial and intracranial removal of infected areas, endoscopic sinus and skull base surgery with local AmB installation and in addition placement of an Ommaya reservoir for 114 intrathecal administrations of AmB. In addition, we review the literature of ROCM in pediatric patients with hematological diseases.

Therapeutic Effect of Protocatechuic Aldehyde in an In Vitro Model of Graves' Orbitopathy.

PURPOSE: Protocatechuic aldehyde (3,4-dihydroxybenzaldehyde; PCA) is extracted from Salvia miltiorrhiza, and has been reported to possess antiproliferative, antioxidant, and antiadipogenesis properties in various in vivo and in vitro experiments. This study aimed to outline the antioxidant and suppressive effects of PCA on adipogenesis and hyaluronan production in orbital fibroblasts to help with designing therapeutic approaches for Graves' orbitopathy (GO). METHODS: We assessed the in vitro effects of PCA on orbital fibroblasts, which were cultured from orbital fat tissue obtained from patients undergoing orbital decompression for severe GO. Control tissue was obtained from patients undergoing orbital surgery with no history of GO or Graves' hyperthyroidism. RESULTS: The 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt assay results confirmed the free radical scavenging effect of PCA after treatment. Protocatechuic aldehyde exhibited a suppressive effect on intracellular reactive oxygen species generation and upregulated heme oxygenase-1 expression in Western blot analysis. Protocatechuic aldehyde attenuated TNF-α and IL-1ß-induced hyaluronan production. Oil Red-O staining results revealed a decrease in lipid droplets and suppressed expression of the adipogenesis-related proteins peroxisome proliferator-activated receptor (PPAR)-γ, CCAAT/enhancer binding protein (c/EBP)-α, and c/EBP-ß upon treatment with PCA during adipose differentiation. CONCLUSIONS: In this study, PCA exerted significant antioxidant and antiadipogenic effects and inhibited the production of hyaluronan in GO orbital fibroblasts. Accordingly, PCA potentially could be used as a novel treatment option for GO.

Development of a Novel Thyroid Function Fluctuated Animal Model for Thyroid-Associated Ophthalmopathy.

BACKGROUND: The establishment of a suitable and stable animal model is critical for research on thyroid-associated ophthalmopathy (TAO). In clinical practice, we found that patients treated with I-131 often exhibit TAO; therefore, we aimed to establish a novel thyroid function fluctuated animal model of TAO by simulating the clinical treatment process. METHODS: We treated SD rats with I-131 to damage the thyroid and then used sodium levothyroxine (L-T4) to supplement the thyroid hormone (TH) levels every seven days, leading to a fluctuating level of thyroid hormones that simulated the status of clinical TAO patients. Rats administered normal saline were considered as a control. The weight, intraocular pressure, and serum T3, T4, TSH and TRAb levels of the rats were measured, and the pathological changes were analyzed by H&E staining and transmission electron microscopy (TEM). RESULTS: The experimental rats (TAO group) exhibited significantly reduced weight and elevated intraocular pressure compared with the control rats. Meanwhile, the serum levels of T3 and T4 were up-regulated in the TAO group, but the TSH level decreased during the 10-week study. Moreover, increased numbers of blood vessels and inflammatory cell infiltrations were observed in the orbital tissues of the TAO rats, while no abnormal changes occurred in the control rats. The orbital myofibrils in the TAO rats appeared fractured and dissolved, with twisted structures. Mitochondrial swelling and vacuoles within the endoplasmic reticulum, swelling nerve fibers, shedding nerve myelin, and macrophages were found in the TAO group. CONCLUSION: Rats treated with I-131 and sodium levothyroxine exhibited characteristics similar to those of TAO patients in the clinic, providing an effective and simple method for the establishment of a stable animal model for research on the pathogenesis and treatment of TAO.

Diagnostic value of high-resolution peripheral quantitative computed tomography (HR-pQCT) in the qualitative assessment of cribra orbitalia: a preliminary study.

Cribra orbitalia are a porotic or sieve-like lesions in the bony orbital roof. This characteristic has frequently been detected in palaeopathological skulls from many parts of the world and has been the object of extensive research. Our objective was to determine if high-resolution peripheral quantitative computed tomography (HR-pQCT) could produce reliable information in the study of cribra orbitalia. Seven skulls displaying cribra orbitalia were investigated by HR-pQCT. The two-dimensional slices were compared with histological sections. The HR-pQCT images and histological sections showed similar results, i.e. two groups of lesions with different characteristics. HR-pQCT can be of great value in palaeopathological research. It is a nondestructive, fast and precise technique that allows an easy evaluation of the bone architecture without destruction of the sample.

The tyrosine kinase inhibitor dasatinib effectively blocks PDGF-induced orbital fibroblast activation.

BACKGROUND: Graves' ophthalmopathy (GO) remains hard to treat. Excessive orbital fibroblast activation by platelet-derived growth factor (PDGF)-BB contributes to GO. The tyrosine kinase inhibitors (TKIs) imatinib mesylate and dasatinib both target PDGF-receptor tyrosine kinase activity, albeit with a different potency. We compared the efficacy of these TKIs on PDGF-BB-induced proliferation, and on cytokine and hyaluronan production by orbital fibroblasts. Also the capacity of dasatinib to suppress GO-associated gene expression in orbital tissue was examined. METHODS: Orbital fibroblasts from four GO patients and five control subjects were used. The efficacy of the two TKIs was tested by: 1) pre-incubating orbital fibroblasts overnight with different TKI concentrations, followed by 24 h stimulation with PDGF-BB, 2) adding TKI and PDGF-BB simultaneously to the orbital fibroblasts in 24 h cultures. Proliferation was assessed by colorimetric assay. Hyaluronan and cytokine production were measured by ELISA. Furthermore, orbital tissue was obtained from a patient with active GO, and the effect of dasatinib on the expression levels of HAS2-, CCL2-, IL6-, and IL8-mRNA expression was examined by real-time quantitative PCR. RESULTS: Pre-incubation of orbital fibroblasts with imatinib mesylate or dasatinib resulted in significant and dose-dependent inhibition of PDGF-BB-induced orbital fibroblast proliferation, and hyaluronan and cytokine production. Dasatinib exhibited these effects at far lower concentrations. The same results were observed in the setting where TKI and PDGF-BB treatments were commenced simultaneously. In orbital tissue from active GO, dasatinib significantly suppressed HAS2-, CCL2-, IL6- and IL8-mRNA levels. CONCLUSION: Dasatinib may be a promising alternative to high-dose steroids in the treatment of GO.

Anatomical position of hyaluronic Acid gel following injection to the infraorbital hollows.

PURPOSE: To examine with histology the anatomical location of hyaluronic acid gel injected to the infraorbital hollows of cadaver specimens. METHODS: The authors dissected 5 fresh hemifacial cadaver specimens following preperiosteal injection of hyaluronic acid gel to the infraorbital hollows. Following tissue fixation, full-thickness soft tissue sections were obtained along the medial, central, and lateral lower eyelid/midface of each specimen. Histologic examination of the anatomical location of hyaluronic acid gel was performed using hematoxylin and eosin and Hale colloidal iron stains. RESULTS: Histologic examination of the central and lateral lower eyelid/midface sections revealed a significant portion of hyaluronic acid gel in either a postorbicularis or a subcutaneous plane in 8 of 10 sections. Only 2 sections displayed hyaluronic acid gel solely within a preperiosteal plane. The medial sections revealed hyaluronic acid gel resting in either a preperiosteal or an intraorbicularis plane. Soft tissue structures such as deep fat compartment septa and the orbicularis oculi muscle appeared to play a significant role in influencing the resting position of hyaluronic acid gel. CONCLUSIONS: In most specimens, the location of a significant portion of hyaluronic acid gel following injection to the infraorbital hollows differed from the intended injection plane. Soft tissue structures including fat compartment septa and the orbicularis oculi muscle appear to influence the resting position of hyaluronic acid gel. Careful attention should be used to avoid overfilling the thin soft tissue layers of the medial infraorbital hollows or tear trough.

Multidisciplinary therapy consisting of minimally invasive resection, irradiation, and intra-arterial infusion of 5-fluorouracil for maxillary sinus carcinomas.

BACKGROUND: Current goals for the treatment of maxillary sinus carcinoma include the preservation of vision, eating, communication, and appearance, as well as the achievement of a cure. METHODS: Japanese patients (n = 121) with maxillary sinus carcinoma were analyzed retrospectively. All patients underwent multidisciplinary therapy including minimally invasive resection, 20 Gy irradiation, and intra-arterial infusion of 5-fluorouracil. RESULTS: The 5- and 10-year overall survival rates were 73% and 68%, respectively. In 97 patients with squamous cell carcinoma (SCC), the 5- and 10-year overall survival rates were 76% and 70%, respectively. All 29 patients with orbital invasion retained the orbital contents, and 21 of these patients demonstrated adequate visual acuity. There were 16 complications, including trismus (5 patients), double vision (5 patients), fistula formation (3 patients), and cataract (3 patients). CONCLUSION: A multidisciplinary therapy, consisting of minimally invasive resection, irradiation, and regional chemotherapy, can yield good patient prognosis and quality of life after treatment.

[The atypical course of subperiosteal abscess of the orbital wall].

The authors describe a clinical case of malformation of intranasal structures of the lateral wall and the middle turbinated bone of the nose (bullous middle turbinated bone, lateral position of the middle turbinated bone, hypertrophy of ethmoidal bulla and uncinate process) in combination with expressed deformation of the nasal septum. These malformations were responsible for the development of acute hemisinusitis complicated by subperiosteal abscess of the superomedial orbital wall. Conjunctival chemosis was impossible to remove by traditional medicamental therapy and surgical intervention. Hirudotherapy produced the well-apparent anti-odematous, anti-inflammatory, anti-coagulative, and thrombolytic effects that resulted in reduced conjunctival oedema and marked positive dynamics of the state of the eyeball. Subcutaneous administration of anticoagulants was used to prevent thrombosis of orbital veins and cerebral venous sinuses.

SUNA syndrome with seasonal pattern.

SUNA is a trigeminal autonomic cephalalgia (TAC) characterized by short unilateral attacks centered on the ophthalmic trigeminal distribution, and accompanied by at least one of a number of cranial autonomic symptoms that can include lacrimation, redness of the ipsilateral eye, nasal congestion, rhinorrhea, and eyelid edema. It exists in episodic and chronic form. We have described an atypical case of episodic SUNA with an exclusive seasonal pattern as previously reported in other trigeminal autonomic cephalalgia, commonly known as TACs.

Quantitative analysis of exposure of staged orbitozygomatic and retrosigmoid craniotomies for lesions of the clivus with supratentorial extension.

OBJECTIVE: A two-stage approach using orbitozygomatic (OZ) and retrosigmoid (RS) craniotomies is one option for the management of petroclival lesions with supratentorial extension. The goal of this study was to investigate the supratentorial and infratentorial exposures of the clivus obtained through this staged approach. METHODS: Formalin-fixed, silicon-injected specimens underwent stereotactic imaging. Six paired OZ and RS craniotomies were performed. Neuronavigation was used to determine the areas and limits of exposure and to plot these areas on three-dimensional reconstructions of the skull base. RESULTS: The mean area of exposure of the parasellar region and clivus through the OZ craniotomy was 640 +/- 75 mm. Visualization of the parasellar region, cavernous sinus, and upper cranial nerves was achieved. The ventral brainstem corresponding to the cranial quarter of the clivus was visualized. The mean area of exposure of the clivus and petrous bone through the RS was 1930 +/- 250 mm. In the cranial quarter of the clivus, there was a small region of overlap in exposure between the two craniotomies. The limits of exposure are described. CONCLUSION: OZ and RS craniotomies provide complementary exposure with limited redundancy. Significant visualization of the parasellar region, clivus, and surrounding bony landmarks is obtained. The primary limitation is exposure of the contralateral half of Zones II and III of the clivus. This strategy represents a reasonable option for accessing paracentral petroclival lesions with a supratentorial extension.

Fluoroscopic intralesional injection with pingyangmycin lipiodol emulsion for the treatment of orbital venous malformations.

OBJECTIVE: The objective of our study was to evaluate the efficacy and safety of percutaneous intralesional injection under fluoroscopy with pingyangmycin Lipiodol emulsion (PLE) for the treatment of orbital venous malformations. MATERIALS AND METHOD: . This study is a retrospective analysis of 19 consecutive patients with distensible orbital venous malformations. Of the 19 patients, two had diffuse lesions. These patients presented with proptosis (n = 19), pain and orbital swelling (n = 11), reduction in visual acuity (n = 4), diplopia (n = 2), disk swelling (n = 5), and motility disturbance (n = 3). RESULTS: All 19 patients underwent technically successful percutaneous intralesional PLE injection under fluoroscopy. Complete resolution of proptosis, swelling, and pain was achieved in 17 patients 3-9 months after the procedure. In the other two patients with diffuse lesions, light proptosis was still present after the first procedure. A second procedure was performed in these two patients, and the symptom disappeared 3 months later. All four patients with reduced visual acuity recovered their vision, and diplopia in two patients disappeared. Examinations of the fundus revealed normal findings in the five patients with preprocedural disk swelling. None of the patients presented with a motility disturbance after the procedure. Local swelling in the eyelid and epiphora were present for 1 month in one patient and disappeared after treatment. No other complications, including acute orbital compartment syndrome, were observed during follow-up periods. The mean follow-up was 23 months. CONCLUSION: PLE sclerotherapy under fluoroscopic guidance is safe and effective for the treatment of orbital venous malformations and can be used as one of the treatment alternatives.

To modulate or not to modulate: differing results in uniquely shaped Williams syndrome brains.

Voxel based morphometry (VBM) studies of Williams syndrome (WS) have demonstrated remarkably consistent findings of reduced posterior parietal gray matter compared to typical controls. Other WS VBM findings have been inconsistent, however. In particular, different findings have been reported for hypothalamus and orbitofrontal gray matter regions. We examined a sample of 8 WS and 9 control adults and show that the hypothalamus and orbitofrontal cortex results depend on whether the images undergo Jacobian modulation. Deformation based morphometry (DBM) analysis demonstrated that major brain shape differences between the groups accounted for the Jacobian modulated gray matter findings. These results indicate that cautious interpretations of modulated gray matter findings are warranted when there are gross shape and size differences between experimental groups. This study demonstrates the importance of methodological choices towards understanding a disorder like WS, but also highlights the consistency of parietal lobe, orbitofrontal, and midbrain findings for this disorder across methodologies, participants, and research groups.

Artistic assault: an unusual penetrating head injury reported as a trivial facial trauma.

The authors report a case of penetrating head injury that presented with a deceptively mild complaint. To our knowledge, it is the first report of a paint brush penetrating the brain. The patient reported being punched in the left eye and presented with a minor headache, swelling around the left orbit, a small cut on the cheek and slightly reduced left eye abduction. After radiological evaluation, a penetrating head injury was diagnosed. Under general anesthesia, through a lateral eyelid incision a 10.5 cm long paint brush, which had penetrated from the left orbit to the right thalamus, was removed. No post-operative infection was seen at six months follow-up. This brief report serves to highlight that penetrating brain injury can occur without neurological deficit and that a minimally invasive surgical approach was successful in avoiding any complications.

Perioral soft-tissue rejuvenation techniques to enhance esthetic restorative dentistry.

Every practitioner has the obligation to offer his or her patients the latest advances in their profession. Dentistry has made a shift over the past 50 years from caries restoration and prosthetic replacement to preventative and esthetic rejuvenation. Related dental specialties have also blossomed with new procedures and an expanded scope of practice. This shift has also included more comprehensive care and treatment of the oral and maxillofacial region. Modern esthetic dentists realize the facial soft tissues serve as a frame for their restorative artwork. Contemporary oral and maxillofacial surgery includes cosmetic facial surgery. Procedures for such surgery are taught in oral and maxillofacial surgery residency programs, are part of the oral and maxillofacial surgery board exams, and are covered by oral and maxillofacial surgery malpractice companies. Esthetic dentists should understand facial aging, as well as the basic procedures available for facial rejuvenation by the oral and maxillofacial surgeon. Contemporary esthetic dentistry goes beyond the oral cavity, and the smile is truly enhanced by simultaneous facial rejuvenation. This article discusses the process of perioral facial aging and various cosmetic facial surgery options.

Effect of posterior temporal-parietal hematoma on orbital frontal chemistry in relation to a cognitive and anxiety state: a combined 1H-MRS and neuropsychological study of an unusual case as compared with 16 healthy subjects.

The authors report the unusual case of a 58-year-old woman (MJP) suffering from left temporal throbbing headache, associated with confusion. Magnetic resonance imaging showed a 5 x 3 x 2 cm hematoma at the left posterior temporal--parietal junction (PTPJ). Repeated MRI of MJP's brain performed during a 4-month follow-up period showed decrease in hematoma size (2.3 x 1.5 x 1) with evidence for development of encephalomalacia and resorption of blood products involving the area of hemorrhage. MJP had mild transcortical sensory aphasia characterized by difficulty with reading and processing, with semantic paraphasic errors while speaking and some difficulty with repetition. MJP had remained normotensive and seizure free, on Vasotec therapy and Dilantin prophylaxis. An in vivo proton magnetic resonance spectroscopy (1H-MRS) performed during an 8-month follow-up period showed reduced concentration for N-acetyl aspartate (NAA) by 19.3% (F=4.09, P<0.04), and myo-inositol by 32.0% (F=5.16, P<0.02) in the left orbital frontal cortex (OFC) as compared with 16 healthy subjects (age- and sex-matched). Cognitive tests (the Wechsler abbreviated scale of intelligence (WASI) and the Stroop color--word interference) showed a significant impairment suggesting involvement of higher-order cognitive functioning (memory, learning, and general intelligence) and attentional system. The Spielberger state-trait anxiety inventory (STAI) showed increased anxiety at the moment of the current examination and decreased tendency to be anxious over a long period of time. The Beck Anxiety and Depression Inventory revealed minimal anxiety and mild to moderate levels of depression. It is hypothesized that the PTPJ hematoma triggered long-distance pathways linking PTPJ area and frontal lobe, including OFC, which resulted in abnormal chemical changes in the left OFC and in cognitive tests impairment, and in long-term anxiety state changes.