[Vitamins and Immune System Health].

Keeping the immune system healthy forms an effective way to fight infections. Past experience has shown that, in addition to effective interventions including vaccination, drug therapy, and non-pharmaceutical intervention (NPI), dietary nutrition and mental health are also key factors in maintaining immune system health and combating emerging and sudden outbreaks of infections. As the main dietary nutrients, vitamins are active regulators of the immune response and exert a critical impact on the immunity of the human body. Vitamin deficiency causes increased levels of inflammation and decreased immunity, which usually starts in the oral tissues. Appropriate vitamin supplementation can help the body optimize immune function, enhance oral immunity, and reduce the negative impact of pathogen infection on the human body, which makes it a feasible, effective, and universally applicable anti-infection solution. This review focuses on the immunomodulatory effects of vitamin A, B, C, D, and E and proposes that an omics-based new systemic approach will lead to a breakthrough of the limitations in traditional single-factor single-pathway research and provide the direction for the basic and applied research of vitamin immune regulation and anti-infection in all aspects.

Effect of lutein and zeaxanthin on macular pigment and visual function in patients with early age-related macular degeneration.

PURPOSE: To determine whether supplementation with lutein and zeaxanthin improves macular pigment and visual function in patients with early age-related macular degeneration (AMD). DESIGN: Randomized, double-masked, placebo-controlled trial. PARTICIPANTS: Participants with probable AMD who were 50 to 79 years of age were screened for study eligibility from the local communities. One hundred eight subjects with early AMD were recruited. INTERVENTION: Early AMD patients were assigned randomly to receive 10 mg/day lutein (n = 27), 20 mg/day lutein (n = 27), 10 mg/day lutein plus 10 mg/day zeaxanthin (n = 27); or placebo (n = 27) for 48 weeks. Macular pigment optical density (MPOD) and visual function variables were assessed at baseline, 24 weeks, and 48 weeks. MAIN OUTCOME MEASURES: The primary outcome was MPOD. Secondary outcomes were visual function variables including best-corrected visual acuity (BCVA), contrast sensitivity (CS), photorecovery time, and Amsler grid testing results. RESULTS: Macular pigment optical density increased significantly by a mean ± standard error of 0.076 ± 0.022 density unit in the 20-mg lutein group and 0.058 ± 0.027 density unit in the lutein and zeaxanthin group during 48 weeks. There was a significant dose-response effect for lutein supplementation, and the changes in MPOD from baseline to 48 weeks were correlated negatively with baseline MPOD in all active treatment groups (r = -0.56; P<0.001). At 48 weeks, a trend toward improvement was seen in BCVA, and there was a significant between-group difference in CS at 3 and 6 cycles/degree between the 20-mg lutein group and the placebo group. The increase in MPOD related positively to the reduction in the logarithm of the minimum angle of resolution BCVA (r = -0.31; P<0.01) and the increases in CS at 4 spatial frequencies (r ranging from 0.26 to 0.38; all P<0.05). CONCLUSIONS: Among patients with early AMD, supplementation with lutein and zeaxanthin improved macular pigment, which played a causative role in boosting visual function and might prevent the progression of AMD. Future studies are required to evaluate the effect of these carotenoids on the incidence of late AMD.

[Clinical manifestations of retinal artery macroaneurysms].

OBJECTIVE: To summarize the clinical characteristics of retinal arterial macroaneurysm and to improve the diagnosis accuracy in order to differentiate it from other fundus diseases. METHODS: It was a retrospective case series. RESULTS: of fluorescein angiography or indocyanine angiography, associated with ultrasound, OCT and several other examinations were analyzed in 22 patients (22 eyes) with retinal arterial macroaneurysm. RESULTS: There were 6 men and 16 women in the 22 patients. The age of all the patients was from 54 to 82 years, and the mean age was 70 years. In the 22 patients, the patient with a single macroaneurysm was 19, and with two macroaneurysms was 3. All 22 patients were affected unilaterally. Macroaneurysms were found only in the temporal artery branches (16 eyes in superior branch and 6 eyes in inferior branch). All macroaneurysms were located in the branches graded 1 to 3. All patients showed pre-retinal hemorrhage and/or vitreous hemorrhage. Sixteen patients suffered from hypertension and five patients had diabetes mellitus. The patient with best corrected visual acuity < 0.05 was 10, 0.05 to 0.2 was 6, 0.3 to 0.6 was 5 and > or = 0.7 was 1. All patients showed retinal arteriosclerosis. After the treatment, 11 patients were pursued,and the patient with best corrected visual acuity < 0.05 was 1, 0.05 to 0.2 was 4 and > or = 0.7 was 1. CONCLUSIONS: Clinical features of retinal arterial macroaneurysm include focal dilation of retinal artery with hemorrhages and exudates, associated with retinal arteriosclerosis. These clinical characteristics can be used to differentiate retinal arterial macroaneurysm from other fundus diseases.

Predictors of short-term outcomes related to central subfield foveal thickness after intravitreal bevacizumab for macular edema due to central retinal vein occlusion.

AIM: To investigate the predictive factors for short-term effects of intravitreal bevacizumab injections on central subfield foveal thickness (CSFT) in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). METHODS: This was a retrospective study in 60 eyes treated with intravitreal bevacizumab injections for ME due to CRVO. Follow-up was three months. The Early Treatment Diabetic Retinopathy Study (ETDRS) score and CSFT measured by spectral-domain optical coherence tomography (SD-OCT) were used to observe the changes in best-corrected visual acuity (BCVA). Baseline BCVA, CSFT, age, CRVO duration and the presence of cystoid macular edema (CME) or subretinal fluid (SRF) were analyzed as potential predictive factors of the effects of intravitreal bevacizumab injections. RESULTS: BCVA improved from 0.9 logMAR at baseline to 0.6 logMAR at 3mo, which was associated with a significant reduction in CSFT from 721 µm to 392 µm 3mo after injection. About 50% of CME cases and more than 90% of SRF cases responded to treatment with a complete resolution at 3mo. Age (P=0.036) and low baseline CSFT (P=0.037) were associated with a good 3-month prognosis. Patients >60 years old achieved better CME resolution (P=0.031) and lower CSFT at 3mo (305 µm vs 474 µm, P=0.003). CONCLUSION: Intravitreal bevacizumab significantly improved visual acuity and CSFT in patients with CRVO after 3mo. Older age and lower baseline CSFT were good predictors of short-term CSFT outcomes. The retinal thickness response to bevacizumab might depend on the resolution of CME rather than SRF.

[Measurement of macular edema in retinal vein occlusion using optical coherence tomography and its visual prognosis].

OBJECTIVE: To examine the type of macular edema in patients with retinal vein occlusion by using optical coherence tomography (OCT). To compare the sensitivity and specificity between OCT and fundus fluorescein angiography (FFA). To investigate the visual prognosis and risk factors in patients with cystoid macular edema (CME). METHODS: Ninety-one eyes of 90 patients with various types of retinal vein occlusion were examined by OCT and FFA. There were 54 cases male and 36 cases female. The age of these patients ranged from 20 to 74 years old and averaged (57.8 +/- 13.8) years old. Right eye was affected in 45 cases, and left eye in 46 cases (both eye in 1 case). Central retinal vein, hemicentral retinal vein and branch retinal vein were affected in 54, 9 and 28 eyes, respectively. The average follow-up period was 6.10 months. The sensitivity and specificity of OCT and FFA were measured. The visual prognosis and risk factors were analyzed. Macular central retinal thickness of 54 opposite normal eye was measured for comparison. RESULTS: (1) The classification of macular edema by OCT was cystoid macular edema in 71 eyes (78.0%); subretinal fluid in 14 eyes and laminar macular hole in 1 eye. The minimal and maximal height of intraretinal cystoid space was 94 microm and 1317 microm, respectively and averaged (668.18 +/- 245.58) microm. The minimal and maximal height of macular central retinal thickness of 54 opposite normal eye was 110 microm and 236 microm, respectively and averaged (154.09 +/- 21.85) microm. The maximal height of subretinal fluid space was 1377 microm or even beyond the detective limit of OCT. (2) The sensitivity of OCT for detection of CME was 98.6% and the specificity was 100%. The sensitivity of FFA was 86.1% and the specificity was 100.0%. (3) The visual prognosis of 61 eyes with CME follow-up over 3 months: The difference between the initial and final VA in branch retinal vein occlusion was statistically significant (P < 0.01), while no difference between initial and final VA in central and hemicentral retinal vein occlusion (P > 0.05). The factors affected visual prognosis of CME included the duration, the presence of hemorrhage in cystoid space and the severity of occlusion, etc. In CME under 3 months, the visual prognosis after therapy is better than that of before the therapy (P < 0.01); while in eyes with duration more than 3 months, no difference of vision could be detected before and after the therapy (P > 0.05). CONCLUSIONS: OCT is a safe, high-resolution, non-invasive, reliable and reproducible new examine method for detecting CME. The visual prognosis of CME is poor. It is possible that the visual prognosis can be improved by early detecting CME using OCT.

Changes following supplementation with lutein and zeaxanthin in retinal function in eyes with early age-related macular degeneration: a randomised, double-blind, placebo-controlled trial.

AIMS: To investigate functional and macular pigment (MP) changes in patients with early age-related macular degeneration (AMD) after multiple supplementation with lutein and zeaxanthin. METHODS: 112 patients with early AMD were randomly (1:1:1:1) assigned to receive 10 mg lutein, 20 mg lutein, lutein (10 mg)+zeaxanthin (10 mg), or placebo daily for 2 years. MP optical density (MPOD) was recorded at baseline, 48 weeks and 2 years. Retinal sensitivities were measured by multifocal electroretinogram for peak-to-trough amplitude (N1P1) at baseline and at 48 weeks, and in terms of microperimeter-determined mean retinal sensitivity (MRS) at 48 weeks and 2 years. RESULTS: Supplementation with lutein and zeaxanthin augmented MPOD significantly in active treatment groups (all p<0.05). N1P1 response densities showed significant increases in ring 1 and ring 2 after 48 weeks of supplementation, while no significant changes were seen in rings 3-6. Significant increases in MRS were detected after supplementation with either 10 or 20 mg lutein, whereas no such increases were seen in the placebo arm. CONCLUSIONS: Supplementation with lutein and/or zeaxanthin increases MPOD, and supplemental lutein enhances retinal sensitivity, in patients with early AMD. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT10528605.

Increase in cholesterol and cholesterol oxidation products, and role of cholesterol oxidation products in kainate-induced neuronal injury.

Little is known about changes in sterols, in particular cholesterol, and cholesterol oxidation products (COPs) in oxidative injury in neural tissues. We have therefore examined changes in cholesterol and COPs using a model of excitotoxic injury. Intracerebroventricular injections of kainate in rats resulted in an increase in immunoreactivity to cholesterol in the affected CA fields of the hippocampus. The increase was confirmed by increased filipin staining of cholesterol in adjacent sections from the same animals, and in hippocampal slice or neuronal cultures after kainate treatment. In neuronal cultures, addition of lovastatin, an inhibitor of cholesterol synthesis, attenuated the increased filipin staining after kainate treatment, indicating that the increase in cholesterol could involve increased cholesterol synthesis. Furthermore, gas chromatographic mass spectrometric (GC/MS) analysis of cholesterol and COPs in kainate-injected rat brain showed a marked increase in cholesterol and COPs including 7-ketocholesterol, 3 days after kainate treatment. The addition of some COPs, including 7-ketocholesterol and cholesterol epoxides to hippocampal slices resulted in neuronal injury as reflected by decreased staining of a neuronal marker in the affected CA fields. The ability of these COPs to produce neuronal injury was attenuated by glutathione, suggesting that oxidative mechanisms are involved in neuronal injury induced by these products. These results, together with GC/MS results that showed significant increase in 7-ketocholesterol at 3 days post-kainate injury suggest that 7-ketocholesterol may be a factor in aggravating oxidative damage to neurons, after the initial stages of kainate-induced neuronal injury.

Improvement of retinal function in early age-related macular degeneration after lutein and zeaxanthin supplementation: a randomized, double-masked, placebo-controlled trial.

PURPOSE: To examine the effects of lutein and zeaxanthin supplementation on retinal function using multifocal electroretinograms (mfERG) in patients with early age-related macular degeneration (AMD). DESIGN: Randomized, double-masked, placebo-controlled trial. METHODS: One hundred eight subjects with early AMD were randomly assigned to receive 10 mg/d lutein (n = 27), 20 mg/d lutein (n = 27), 10 mg/d lutein plus 10 mg/d zeaxanthin (n = 27), or placebo (n = 27) for 48 weeks. Thirty-six age-matched controls without AMD were also enrolled to compare baseline data with early AMD patients. MfERG responses and macular pigment optical densities (MPODs) were recorded and analyzed at baseline and at 24 and 48 weeks. RESULTS: There were significant reductions in N1P1 response densities in ring 1 to ring 3 in early AMD patients compared with the controls (P < .05), whereas neither N1P1 response densities in ring 4 to ring 6 nor P1 peak latencies significantly changed. After 48-week supplementation, the N1P1 response densities showed significant increases in ring 1 for the 20 mg lutein group and for the lutein and zeaxanthin group, and in ring 2 for the 20 mg lutein group. The increases in MPOD related positively to the increases in N1P1 response density in ring 1 and ring 2 for nearly all active treatment groups. N1P1 response densities in ring 3 to ring 6 or P1 peak latencies in all rings did not change significantly in any group. CONCLUSION: Early functional abnormalities of the central retina in the early AMD patients could be improved by lutein and zeaxanthin supplementation. These improvements may be potentially attributed to the elevations in MPOD.

Serum inflammatory factors in patients with idiopathic choroidal neovascularization.

OBJECTIVE: To investigate serum inflammatory factors in patients with idiopathic choroidal vascularization (CNV), including vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNFα), Interleukin1-beta (IL1-ß), IgG, IgA, IgM, IgE, 50% hemolytic unit of complement (CH50), complement C3, complement C4 and C reactive protein (CRP). METHODS: 21 patients and 20 normal individuals were recruited. They received comprehensive ophthalmic examinations. Serous concentrations of VEGF, TNFα, IL1-ß were assayed by ELISA, and the concentrations of other serum factor were assayed by immunonephelometry. RESULTS: The mean serum VEGF level in the CNV group was significantly greater than that in the control group (p=0.025). The median level of IgE in the CNV group was significantly lower than that in the control group (p=0.006). Statistical analysis revealed no significant difference in the levels of TNFα, IL1-ß, IgG, IgA, IgM, CH50, C3, C4 or CRP between the two groups. CONCLUSION: The possible roles of these factors and mechanisms of idiopathic CNV formation were analyzed. Serum VEGF and IgE levels may play an important role in the formation of idiopathic CNV.

Induction of astrocytic cytoplasmic phospholipase A2 and neuronal death after intracerebroventricular carrageenan injection, and neuroprotective effects of quinacrine.

Glial reaction is often associated with nervous tissue injury, but thus far, few studies have examined whether it can be a cause of neuronal injury. We now study the effect of intracerebroventricular injection of a carrageenan on cytoplasmic phospholipase A(2) (cPLA(2)) expression and neuronal injury in the hippocampus. The enzyme cPLA(2) hydrolyzes neural membrane glycerophospholipids and generates precursors for proinflammatory mediators. An induction of cPLA(2) in astrocytes and death of neurons in the hippocampus were observed following glial reaction induced by intracerebroventricular injections of carrageenan. cPLA(2) levels and neuronal death were modulated by daily intraperitoneal injections of quinacrine, an inhibitor of phospholipase A(2) that can cross the blood brain barrier. These observations support a role for astrocytic cPLA(2) in mediating neuronal death.

Quinacrine abolishes increases in cytoplasmic phospholipase A2 mRNA levels in the rat hippocampus after kainate-induced neuronal injury.

The present investigation was carried out to study the possible effects of quinacrine in modulating cytoplasmic phospholipase A(2) (cPLA(2)) mRNA levels in rat hippocampus after kainate treatment. Injections of kainate into the right lateral ventricle resulted in significant increases in cPLA(2) mRNA levels in the hippocampus, at 3 days and 7 days after injection. The elevation in cPLA(2) mRNA levels is consistent with previous observations of increased cPLA(2) immunoreactivity in degenerating neurons and astrocytes at these times. Rats that received once daily intraperitoneal injections of quinacrine (5 mg/kg) after the intracerebroventricular kainate injections showed almost complete attenuation of increased cPLA(2) expression, at both 3 and 7 days after kainate injection. These results show that in addition to its well-known effect of inhibition of PLA(2) activity, quinacrine could also inhibit cPLA(2) expression, and further supports a role for PLA(2) in kainate-induced neuronal injury.