3-(4-Hydroxy-3-methoxyphenyl) propionic acid contributes to improved hepatic lipid metabolism via GPR41.

3-(4-hydroxy-3-methoxyphenyl) propionic acid (HMPA) is a metabolite produced by the gut microbiota through the conversion of 4-hydroxy-3-methoxycinnamic acid (HMCA), which is a widely distributed hydroxycinnamic acid-derived metabolite found abundantly in plants. Several beneficial effects of HMPA have been suggested, such as antidiabetic properties, anticancer activities, and cognitive function improvement, in animal models and human studies. However, the intricate molecular mechanisms underlying the bioaccessibility and bioavailability profile following HMPA intake and the substantial modulation of metabolic homeostasis by HMPA require further elucidation. In this study, we effectively identified and characterized HMPA-specific GPR41 receptor, with greater affinity than HMCA. The activation of this receptor plays a crucial role in the anti-obesity effects and improvement of hepatic steatosis by stimulating the lipid catabolism pathway. For the improvement of metabolic disorders, our results provide insights into the development of functional foods, including HMPA, and preventive pharmaceuticals targeting GPR41.

Pharmacokinetic profiles of 3-(4-hydroxy-3-methoxyphenyl) propionic acid and its conjugates in Sprague-Dawley rats.

3-(4-hydroxy-3-methoxyphenyl)propionic acid (HMPA) is one of the end-products from gut microbiota from dietary polyphenols, which might contribute to their health benefits. This study aims to investigate the absorption, metabolism, and tissue accumulation of HMPA in Sprague-Dawley (SD) rats. After HMPA (10 mg/kg body weight) was orally administered, intact and conjugated HMPAs in the bloodstream were detected and reached the maximum concentration in 15 min (HMPA, 2.6 ± 0.4 nmol/mL; sulfated HMPA, 3.6 ± 0.9 nmol/mL; glucuronidated HMPA, 0.55 ± 0.09 nmol/mL). HMPA and its conjugates were also detected in the target organs 6 h postadministration, indicating that HMPA undergoes rapid conversion into conjugates, and they broadly distribute to organs with similar profiles (kidneys > liver > thoracic aorta > heart > soleus muscle > lungs). This study demonstrated that orally administered HMPA (10 mg/kg) in SD rats undergoes rapid metabolism and wide tissue distribution with ≥1.2% absorption ratio.

Orbital T-Cell Lymphoma with Discrete Enlargements of All Extraocular Muscles Bilaterally in Patient with Moon Face Countenance.

Purpose. To report our findings in a case of orbital T-cell lymphoma in which all of the extraocular muscles (EOMs) were bilaterally and discretely enlarged and the patient had a moon face countenance. Case. A 59-year-old woman presented with visual disturbances in her left eye, hyperemia in both eyes, and a moon face countenance. Examinations showed limited upward gaze in the right eye, blepharoptosis, hypertropia, and limited downward and rightward gaze in the left eye. Slit-lamp examination showed only chemosis and hyperemia of both eyes. Magnetic resonance imaging with contrast revealed discrete enlargements of the muscle bellies in all EOMs without abnormalities of the orbital fat in both eyes. Blood examinations excluded thyroid- and IgG4-related ophthalmopathy, and EOM biopsy revealed peripheral T-cell lymphoma. After beginning aggressive chemotherapy, the enlarged EOMs, limited eye motility, and moon face countenance improved. Unfortunately, the patient died of sepsis during the chemotherapy. Conclusions. A lymphoma should be included in the differential diagnosis of eyes with enlarged EOMs. Because lymphomas can lead to death, it is important for clinicians to consider lymphomas in eyes with enlarged EOMs.

Apolipoprotein E2 and E3, but Not E4, Promote Retinal Pathologic Neovascularization.

Purpose: To determine the relationship between the different isoforms of apolipoprotein E (ApoE) and retinal neovascularization. Methods: The concentrations of ApoE and VEGF in vitreous humor samples with either a macular hole (MH), or diabetic macular edema (DME), or proliferative diabetic retinopathy (PDR) with or without intravitreal injection of bevacizumab (IVB) were measured by ELISA. The effects of each isoform of ApoE on human retinal microvascular endothelial cells (HRMECs) in culture or on the retina of oxygen-induced retinopathy (OIR) mice were investigated. Results: The concentrations of ApoE and VEGF were significantly higher in the vitreous humor of patients with PDR and DME than in patients with an MH. There was a significant positive correlation between the concentrations of ApoE and VEGF in vitreous humor of patients. In vitro assays showed that ApoE2 and ApoE3, but not ApoE4, promoted the VEGF-induced cell proliferation and migration. In vivo assays showed that intravitreal injections of ApoE2 and ApoE3 increased the number and area of nodes in the retina of OIR mice. Moreover, ApoE was expressed in the vascular endothelial cell in both normal and OIR retinas, but their expression levels were different at postnatal day (P) 12 and P17. Conclusions: These results demonstrate that ApoE2 and ApoE3, but not ApoE4, have proangiogenic effects, and the increased expression of ApoE in the vitreous humor of patients with PDR and DME indicates that ApoE2 and ApoE3 are involved in the development of retinal neovascularization in eyes.

Elderly onset vitreous opacities as the initial manifestation in hereditary transthyretin (ATTR Val30Met) carries.

Familial amyloid polyneuropathy (FAP) is a systemic disorder transmitted as an autosomal dominant trait and is characterized by deposits of protein fibrils in various organs leading to physiologic dysfunction. In cases with FAP in Japanese endemic foci, their signs and symptoms often develop before the age of 40 years. We report on two elderly patients (an 80-year-old woman and an 83-year-old man) with progressive vitreous opacities (VOs) as the initial manifestation of hereditary transthyretin (ATTR Val30Met) carries, who had no evidence of systemic involvement or family history of amyloidosis and lived in non-endemic areas. Therapeutic vitrectomy with extensive vitreous removal combined with cataract surgery was performed. Clinicians should consider the possibility of hereditary transthyretin carries in cases presenting with VOs of undetermined etiology to avoid misdiagnosis.

Seven cases of localized invasive sino-orbital aspergillosis.

PURPOSE: To describe the clinical manifestations and prognoses in 7 patients with invasive sino-orbital aspergillosis (ISOA). METHODS: This was a retrospective study of consecutive patients who were diagnosed as having ISOA at the Gifu University Hospital and Gifu Municipal Hospital between January 1993 and December 2015. Data were collected on demographics, initial manifestations, examination findings, treatments, clinical course, and outcomes. RESULTS: The median age of the 7 patients with ISOA was 68 years; 5 of them had diabetes. The initial symptoms were reduced blurred vision (57%), unilateral headaches (43%), unilateral abnormal sensations or numbness of the periorbital area (43%), and external ophthalmoplegia (43%). The medical department that the patients first visited was the ophthalmology department in 57% of the cases. The initial CT showed bone destruction in 71% and calcification in 14% of the patients. Six of the 7 cases were misdiagnosed. The definitive diagnosis of ISOA was made by histopathologic examinations of the biopsy specimens, with an average of 2.6 biopsies. All patients received aggressive antifungal treatments after the diagnosis. However, the final visual outcome was no light perception in 86% and death related to the ISOA in 43% of the patients. Patients who were older at the onset had lower survival rates. CONCLUSIONS: The prognosis for patients with ISOA is poor in terms of both vision and life. Ophthalmologists are often the first examiner. ISOA should be considered in the differential diagnosis for patients with a gradually progressive orbital mass, unilateral headaches, numbness of the periorbital area, and a decrease in visual acuity of unknown origin.

Late-onset bleb-related endophthalmitis caused by Streptococcus pseudopneumoniae.

We report our findings in a 63-year-old male who developed late-onset bleb-related endophthalmitis. The patient had undergone glaucoma surgery 46 years earlier, and had a thin-walled cystic bleb prior to the endophthalmitis in his right eye. He underwent immediate vitrectomy with intravitreal injections of ceftazidime and vancomycin. After surgery, he was given topical 0.5 % moxifloxacin and 1 % vancomycin, intravenous doripenem, and oral minocycline. Culture of the vitreous specimen identified Streptococcus pseudopneumoniae by 16S rRNA sequence analysis, by optochin susceptibility test, and by bile solubility test. Our findings indicate that S. pseudopneumoniae can be isolated from a late-onset bleb-related endophthalmitis and that molecular analysis and phenotypic testing can be accurate methods to identify S. pseudopneumoniae.

Intraocular penetration of itraconazole in patient with fungal endophthalmitis.

The purpose of this study was to determine the penetration of itraconazole, a type of azole antifungal agent, into the aqueous humor and vitreous after repeated oral administrations. Fungal endophthalmitis developed bilaterally in a 21-year-old man who had a history of intravenous hyperalimentation following abdominal surgery. Itraconazole capsules (200 mg/day) were taken orally for 12 consecutive days. Vitrectomy was performed on the left eye 30 h after the last oral itraconazole. Samples of blood, aqueous, and vitreous were collected during the vitrectomy. The concentration of itraconazole was determined by high performance liquid chromatography. The concentration of itraconazole was 0.492 µg/mL in the plasma, 0.020 µg/mL in the vitreous, and none in the aqueous of the left eye. Although no fungal organisms were isolated from the plasma and vitreous samples from both eyes, fungal DNA was detected in the vitreous from the left eye. Our findings indicate that oral itraconazole has limited penetration in eyes with fungal endophthalmitis.

[Clinical manifestations, treatment and outcome of ocular infections caused by Paecilomyces species].

PURPOSE: To report the predisposing factors, patient background, treatment and outcomes of ocular infections caused by Paecilomyces spp. in Japan. METHODS: We reviewed the medical records and the published literature in Japan on ocular infections caused by microbiologically-proven Paecilomyces spp. Nineteen eyes of 18 patients; 4 eyes of 4 of our patients and 15 eyes of 14 published Japanese patients were studied. RESULTS: Ten men and 8 women (9 OD, 8 OS, 1 OU) were diagnosed with ocular infections caused by Paecilomyces spp. The mean age was 69 years (range 33 to 90 years). The initial diagnosis of ocular infection caused by Paecilomyces spp. was keratitis in 14 eyes and endophthalmitis in 5 eyes. The final diagnosis was keratitis in 2 eyes, keratitis with involvement of the anterior segment of the eye, i.e., hypopyon or corneal rupture, in 12 eyes, and endophthalmitis in 5 eyes. The predisposing factors had a history of ocular surgery, corneal trauma and soft contact lens use. Other factors were diabetes and old age. The infections developed more often in the fall and winter. The identified Paecilomyces spp. had a high sensitivity to micafungin and voriconazole, but low sensitivity to amphotericin B, flucytosine and fluconazole. The prognosis of Paecilomyces spp. ocular infections was very poor, viz., final vision was counting fingers or worse in 60%, ocular perforation in 42%, and eye enucleation in 11%. The percentage of eyes with a final visual acuity worse than counting fingers was 0% in those with keratitis, 50% in those with involvement of the anterior segment, and 100% in those with endophtalmitis (p = 0.0446). Among the antifungal agents, the percentage of cases with final vision of counting fingers or worse was 90% with fluconazole, 80% with itraconazole, 100% with miconazole, and 71% with voriconazole. CONCLUSION: The results show that if the Paecilomyces spp. infection spreads intraocularly, it is difficult to mitigate the clinical damage even with antifungal agents with high sensitivity.

Gemella species-associated late-onset endophthalmitis after trabeculectomy with adjunctive mitomycin C.

PURPOSE: To report 2 cases of delayed-onset, bleb-related endophthalmitis induced by Gemella species. METHODS: Interventional case report. RESULTS: Two patients developed bleb-related ocular infection attributable to Gemella haemolysans and Gemella morbillorum after trabeculectomy with adjunctive mitomycin C. Both patients had thin-walled cystic filtering blebs before ocular infection. One patient underwent urgent vitrectomy with intravitreal injection of ceftazidime and vancomycin. The other received an intraocular injection of vancomycin and ceftazidime. After surgical intervention, 2 cases were administered topical levofloxacin and sulfobenzylpenicillin, and intravenous cefpirome. The DNA from the microorganism was sequenced and identified as G. haemolysans and G. morbillorum. CONCLUSIONS: Gemella species should be added to the long list of organisms that may rarely cause bleb-associated endophthalmitis.

Neuroprotective effect of nipradilol [3,4-dihydro-8-(2-hydroxy-3-isopropylamino)-propoxy-3-nitroxy-2H-1-benzopyran] in a rat model of optic nerve degeneration.

PURPOSE: Currently, nipradilol, an alpha-1 beta-blocker with a nitric oxide donative action, is used as an ocular hypotensive agent for glaucoma patients in Japan. The aim of the present study was to investigate the neuroprotective effect of nipradilol on optic nerve injury in rats. MATERIALS AND METHODS: Using a calibrated cross-action forceps, a crush lesion was inflicted unilaterally on the optic nerve 2 mm behind the globe of adult Wistar albino rats and followed by topical instillation of either 0.25% nipradilol or the vehicle in both eyes twice daily until killing. A sham operation was conducted on the contralateral eye. Intraocular pressure measurement was performed 3 days before and 4, 7, 14, 21, and 28 days after acute injury of the optic nerve. One week before killing, Fluoro-Gold was injected into the bilateral superior colliculi to identify surviving retinal ganglion cells (RGCs). RESULTS: Twenty-eight days after injury, retinal damage was assessed morphologically. There was no significant difference in the intraocular pressure of both eyes between the nipradilol and control groups. Within 1 month, the mean RGC density in the vehicle-treated group had decreased to 71.58+/-0.102% of that of the contralateral eye, whereas the optic nerve crush with topical application of nipradilol showed a considerably smaller decrease to 89.60+/-0.027% (P<0.001). No significant morphologic difference between sham-operated animals and animals from the experimental groups was observed in the retinal layers owing to the crush force. CONCLUSIONS: Our findings might indicate that nipradilol can alleviate RGC death induced by optic nerve crush injury in the rat.