Metformin and rapamycin protect cells from vital dye–induced damage in retinal pigment epithelial cells and in vivo

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the effect of autophagy inducers on damage caused by vital dye in adult human RPE (ARPE) cells and in a rat model....     

Acquired paralytic strabismus in Southern Taiwan

BackgroundThird, fourth, and sixth cranial nerve (CN3, CN4, and CN6) palsies are not uncommon in neuro-ophthalmology. The time and quality of recovery depend on the causes of the cranial nerve palsy. The purpose of our study was to evaluate the causes and outcome of acquired paralytic strabismus (PS) in a southern Taiwan population.MethodsThis study involved a retrospective chart review of patients at Kaohsiung Veterans General Hospital from January 2006 through July 2009. A total of 196 patients were enrolled. Outcomes and recovery times were recorded for the patients who exhibited C3, C4, and C6 palsies. The patients were categorized into four etiologic groups: vascular, idiopathic, traumatic, and neoplastic. The onset of PS, its continuing medical management, recovery, and other outcomes were followed up in these patients over a period of up to 10 years.ResultsThe mean age of the 196 patients enrolled was 58.35 ± 17.60 years (range 11–90 years), and the mean follow-up time was 13.6 months. Seventy-seven patients (39.29%) had CN3 palsy, 38 patients (19.39%) had CN4 palsy, and 81 patients (41.33%) had CN6 palsy. The most common causes were vascular diseases (35.20%), followed by trauma (33.67%), and idiopathic causes (21.94%). About 50% of the patients recovered within 6 months. Among the four etiologic groups of patients, the vascular group showed the best recovery: about half of the patients recovered within 3 months. Longer recovery periods were necessary for patients in the neoplastic group than for those in the traumatic, vascular, and idiopathic groups (p = 0.01; p < 0.001; p < 0.001, respectively).ConclusionThe prognosis for patients with PS depended mostly on the cause of their disease. Patients with PS attributable to a vascular cause had a better prognosis than the other patients, and those in the neoplastic group required the longest time to recover.     

Daily melatonin protects the endothelial lineage and functional integrity against the aging process,oxidative stress,and toxic environment and restores blood flow in critical limb ischemia area in mice

We tested the hypothesis that daily melatonin treatment protects endothelial lineage and functional integrity against the aging process, oxidative stress/endothelial denudation (ED), and toxic environment and restored blood flow in murine critical limb ischemia (CLI). In vitro study using HUVECs, in vivo models (ie, CLI through left femoral artery ligation and ED through carotid artery wire injury), and model of lipopolysaccharide‐induced aortic injury in young (3 months old) and aged (8 months old) mice were used to elucidate effects of melatonin treatment on vascular endothelial integrity. In vitro study showed that menadione‐induced oxidative stress (NOX‐1/NOX‐2), inflammation (TNF‐α/NF‐kB), apoptosis (cleaved caspase‐3/PARP), and mitochondrial damage (cytosolic cytochrome c) in HUVECs were suppressed by melatonin but reversed by SIRT3‐siRNA (all P < .001). In vivo, reduced numbers of circulating endothelial progenitor cells (EPCs) (C‐kit/CD31+/Sca‐1/KDR+/CXCR4/CD34+), and angiogenesis (Matrigel assay of bone marrow‐derived EPC and ex vivo aortic ring cultures) in older (compared with younger) mice were significantly reversed through daily melatonin administration (20 mg/kg/d, ip) (all P < .001). Aortic vasorelaxation and nitric oxide release were impaired in older mice and reversed in age‐match mice receiving melatonin (all P < .01). ED‐induced intimal/medial hyperplasia, reduced blood flow to ischemic limb, and angiogenesis (reduced CD31+/vWF+ cells/small vessel number) were improved after daily melatonin treatment (all P < .0001). Lipopolysaccharide‐induced aortic endothelial cell detachment, which was more severe in aged mice, was also alleviated after daily melatonin treatment (P < .0001). Daily melatonin treatment protected both structural and functional integrity of vascular endothelium against aging‐, oxidative stress‐, lipopolysaccharide‐, and ischemia‐induced damage probably through upregulating the SIRT signaling pathway.     

Usefulness of Estimated Pulse Wave Velocity in Prediction of Cardiovascular Mortality in Patients With Acute Myocardial Infarction

BackgroundPulse wave velocity (PWV) is an excellent index of arterial stiffness and can be used to predict long-term cardiovascular (CV) outcome. In recent years, estimated PWV (ePWV), calculated by equations using age and mean blood pressure, was also reported to be a significant predictor of CV outcomes. However, there was no literature discussing about usefulness of ePWV in patients of acute myocardial infarction (AMI) for prediction of long-term CV and overall mortality. Therefore, we conducted this study for further evaluation.MethodsA total of 187 patients with AMI admitted to cardiac care unit were enrolled. ePWV were calculated by the equations for each patient.ResultsThe median follow-up to mortality was 73 months (25th–75th percentile: 8–174 months). There were 35 and 125 patients documented as CV and overall mortality, respectively. Under univariable analysis, ePWV could independently predict long-term CV and overall mortality. However, after multivariable analysis, ePWV could only predict long-term CV mortality in AMI patients.ConclusionsTo the best of our knowledge, our study was the first to evaluate the usefulness of ePWV in AMI patients for prediction of long-term CV and overall mortality. Our study showed ePWV was not only easy to calculate by formula, but also an independent predictor for long-term CV mortality in univariable and multivariable analyses. Therefore, ePWV was a simple and useful tool to measure arterial stiffness and to predict CV mortality outcome in AMI patients without the necessity for equipment to measure PWV.     

Effect of hand dermatitis on the total body burden of chromium after ferrous sulfate application in cement among cement workers

Background:  Ferrous sulfate (FeSO₄) added to cement has been used to reduce the prevalence of dermatitis in workers. However, the effect of dermatitis on the total uptake of chromium in cement with or without FeSO₄ has not been previously explored.
Objective:  The objective of this study was to compare the urinary chromium levels before and after FeSO₄ addition among cement workers with or without hand dermatitis.
Methods:  Thirty-five male workers were recruited in this study for two consecutive years: 2003 without using FeSO₄ and 2004 after adding FeSO₄. Urinary chromium was used as a biomarker to estimate the total body burden of chromium.
Results:  Urinary chromium concentration showed significant decreases after FeSO₄ was used, and a larger decrease of urinary chromium was observed in workers with hand dermatitis than for those without hand dermatitis. Moreover, a significant decrease of urinary chromium was observed in workers with hand dermatitis in both 2003 and 2004.
Conclusion:  FeSO₄ decreases the total body burden of chromium, especially in workers with severe and continuous hand dermatitis.     

Perihepatic nodes detected by point-of-care ultrasound in acute hepatitis and acute-on-chronic liver disease

AIM: To study the manifestations of perihepatic lymph nodes during the episode of acute hepatitis flare by point-of-care ultrasonography.METHODS: One hundred and seventy-six patients with an episode of acute hepatitis flare(ALT value 5 × upper normal limit) were enrolled retrospectively. Diagnosis of etiology of the acute hepatitis flare was based on chart records and serological and virological assays. The patients were categorized into two groups(viral origin and non-viral origin) and further defined into ten subgroups according to the etiologies. An ultrasonograpy was performed within 2 h to 72 h(median, 8 h). The maximum size of each noticeable lymph node was measured. Correlation between clinical parameters and nodal manifestations was analyzed RESULTS: Enlarged lymph nodes(width ≥ 5mm)were noticeable in 110(62.5%) patients, mostly in acute on chronic hepatitis B(54.5%). The viral group had a higher prevalence rate(89/110 = 80.9%) and larger nodal size(median, 7 mm) than those of the non-viral group(21/66 = 31.8%; median, 0 mm)(P 0.001 for both). Meanwhile, there were significant differences in the nodal size between acute and chronic viral groups(P 0.01), and between acute hepatitis A and non-hepatitis A viral groups(P 0.001). In logistical regression analysis, the nodal width still showed strong significance in multivariate analysis(P 0.0001) to stratify the two groups. The area under the curve of ROC was 0.805, with a sensitivity of 80.9%, a specificity of 68.2%, positive predictive value of 80.92%, negative predictive value of 68.18%, and an accuracy of 76.14%. CONCLUSION: Point-of-care ultrasonography to detect perihepatic nodal change is valuable for clarifying the etiologies in an episode of acute hepatitis flare.     

A Biological Model of Acupuncture and Its Derived Mathematical Modeling and Simulations

(Aims) Acupuncture was employed since 2 millenaries, but the underlying mechanisms are not globally handled. The present study is aimed at proposing an explanation by pointing out involved processes and a convincing modeling to demonstrate its efficiency when carried out by trained practitioners.(Method) In the absence of global knowledge of any mechanism explaining the acupuncture process, a biological model is first developed, based on stimulation in a given domain around the needle tip of a proper mastocyte population by a mechanical stress, electrical, electromagnetic, or heat field. Whatever the type of mechanical or physical stimuli, mastocytes degranulate. Released messengers either facilitate the transfer of main mediators, or target their cognate receptors of local nerve terminals or after being conveyed by blood their receptors on cerebral cells. Signaling to the brain is fast by nervous impulses and delayed by circulating messengers that nevertheless distribute preferentially in the brain region of interest due to hyperemia. The process is self-sustained due to mastocyte chemotaxis from the nearby dense microcirculatory circuit and surrounding mastocyte pools, which are inadequate for acupuncture, but serve as a signal relay. A simple mathematical model is solved analytically. Numerical simulations are also carried out using the finite element method with mesh adaptivity.(Results) The analytical solution of the simple mathematical model demonstrates the conditions filled by a mastocyte population to operate efficiently. A theorem gives the blow-up condition. This analytical solution serves for validation of numerical experiments. Numerical simulations show that when the needle is positioned in the periphery of the acupoint or outside it, the response is too weak. This explains why along training is necessary as the needle implantation requires a precision with a magnitude of the order of 1 mm.(Conclusion) The acupoint must contain a highly concentrated population of mastocytes (e.g., very-high–amplitude, small-width Gaussian distribution) to get an initial proper response. Permanent signaling is provided by chemotaxis and continuous recruitment of mastocytes. Therefore, the density and distribution of mastocytes are crucial factors for efficient acupuncture as well as availability of circulating and neighboring pools of mastocytes.