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New insights into the vitamin D requirements during pregnancy

Bone Research 2017年第3期5卷 161-176页

作者： Bruce W Hollis carol l wagner Department of Pediatrics Darby Children's Research Institute Medical University of South Carolina

Pregnancy represents a dynamic period with physical and physiological changes in both the mother and her developing fetus. The dramatic 2-3 fold increase in the active hormone 1,25（OH）2D concentrations during the early weeks of pregnancy despite minimal increased calcium demands during that time of gestation and which are sustained throughout pregnancy in both the mother and fetus suggests an immunomodulatory role in preventing fetal rejection by the mother. While there have been numerous observational studies that support the premise of vitamin D＇s role in maintaining maternal and fetal well-being, until recently, there have been few randomized clinical trials with vitamin D supplementation. One has to exhibit caution, however, even with RCTs, whose results can be problematic when analyzed on an intent-to-treat basis and when there is high non-adherence to protocol （as if often the case）, thereby diluting the potential good or harm of a given treatment at higher doses. As such, a biomarker of a drug or in this case ＂vitamin＂ or pre-prohormone is better served. For these reasons, the effect of vitamin D therapies using the biomarker circulating 25（OH）D is a far better indicator of true ＂effect.＂ When pregnancy outcomes are analyzed using the biomarker 25（OH）D instead of treatment dose, there are notable differences in maternal and fetal outcomes across diverse racial/ethnic groups, with improved health in those women who attain a circulating 25（OH）D concentration of at least 100 nmol. l-1 （40 ng. ml-1）. Because ,an important issue is the timing or initiation of vitamin D treatment/supplementation, and given the potential effect of vitamin D on placental gene expression and its effects on inflammation within the placenta, it appears crucial to start vitamin D treatment before placentation （and trophoblast invasion）; however, this question remains unanswered. Additional work is needed to decipher the vitamin D requirements of pregnant women and the optimal timing of s

关键词： New insights into the vitamin D requirements during pregnancy

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Maternal and infant vitamin D status during lactation: Is latitude important?

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Health 2013年第12期5卷 2004-2013页

作者： carol l. wagner Cynthia R. Howard Thomas C. Hulsey Ruth A. lawrence Myla Ebeling Judy Shary Pamela G. Smith Kristen Morella Sarah N. Taylor Bruce W. Hollis Department of Pediatrics Medical University of South Carolina Charleston South Carolina USA Department of Pediatrics University of Rochester Rochester New York USA

Background: The effect of latitude on maternal and infant vitamin D status during lactation is presumed to be strongly associated with higher rates of deficiency in those living at higher latitudes, yet with lifestyle changes, this conclusion may no longer be correct. Objective: To ascertain if higher latitude adversely affects the vitamin D status of lactating women and their fully breastfeeding infants. Study Design/Methods: Fully breastfeeding women and their infants were eligible for participation in this study as part of a larger prospective vitamin D supplementation trial. Women were recruited from two sites of differing latitude: Charleston, SC at 32°N and Rochester, NY at latitude 43°N. Maternal and infant baseline vitamin D status, intact parathyroid hormone (IPTH), serum calcium and phosphorus as a function of site/latitude were measured. The primary outcome was maternal and infant total circulating 25(OH)D at baseline by center/latitude, and the secondary outcome was the percent of women and infants who had achieved a baseline concentration of at least 20 ng/ml, meeting the Institute of Medicine’s definition of sufficiency at 4 to 6 weeks postpartum. Statistical analysis was performed using SAS version 9.3. Results: Higher latitude adversely affected vitamin D status only in lactating Caucasian women. African American and Hispanic women and infants living in Rochester compared to Charleston had improved vitamin D status, an effect that was no longer significant when controlling for socioeconomic factors and season. Overall, there was a significant vitamin D deficiency at baseline in lactating mothers, and a far greater deficiency in their infants. Maternal baseline 25(OH)D concentration remained positively associated with being Caucasian, BMI and summer months. Breastfeeding infant vitamin D status mirrored maternal status and remained positively associated with being Caucasian and summer months. Those infants who had been on a vitamin D supplement at the

关键词： Vitamin D Cholecalciferol lactation latitude

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Impact of asialoglycoprotein receptor deficiency on the development of liver injury

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World Journal of Gastroenterology 2009年第10期15卷 1194-1200页

作者： Serene Ml lee carol A Casey Benita l McVicker Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States liver Study Unit Department of Veterans Affairs Medical Center and Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States

The asialoglycoprotein （ASGP） receptor is a wellcharacterized hepatic receptor that is recycled via the common cellular process of receptor-mediated endocytosis （RME）. The RME process plays an integral part in the proper trafficking and routing of receptors and ligands in the healthy cell. Thus, the missorting or altered transport of proteins during RME is thought to play a role in several diseases associated with hepatocyte and liver dysfunction. Previously, we examined in detail alterations that occur in hepatocellular RME and associated receptor functions as a result of one particular liver injury, alcoholic liver disease （AlD）. The studies revealed profound ethanol- mediated impairments to the ASGP receptor and the RME process, indicating the importance of this receptor and the maintenance of proper endocytic events in normal tissue. To further clarify these observations, studies were performed utilizing knockout mice （lacking a functional ASGP receptor） to which were administered several liver toxicants. In addition to alcohol, we examined the effects following administration of anti- Fas （CD95） antibody, carbon tetrachloride （CCh） and lipopolysaccharide （lPS）/galactosamine. The results of these studies demonstrated that the knockout mice sustained enhanced liver injury in response to all of the treatments, as shown by increased indices of liver damage, such as enhancement of serum enzyme levels, histopathological scores, as well as hepatocellular death. Overall, the work completed to date suggests a possible link between hepatic receptors and liver injury. In particular, adequate function and content of the ASGP receptor may provide protection against various toxinmediated liver diseases.

关键词： Asialoglycoprotein receptor Asialoglycoproteinreceptor deficient mice Receptor-mediatedendocytosis Alcohol Carbon tetrachloride Anti-Fas lipopolysaccharide/galactosamine Toxicant-induced liverinjury

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Effect of ethanol on pro-apoptotic mechanisms in polarizedhepatic cells

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World Journal of Gastroenterology 2007年第37期13卷 4960-4966页

作者： Benita l McVicker Dean J Tuma carol A Casey liver Study Unit Department of Veterans Affairs Medical Center and Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States

Chronic ethanol consumption is associated with serious and potentially fatal alcohol-related liver injuries such as hepatomegaly, alcoholic hepatitis and cirrhosis. Moreover, it has been documented that the clinical progression of alcohol-induced liver damage may be associated with an increase in hepatocellular death that involves apoptotic mechanisms. Although much information has been learned about the clinical manifestations associated with alcohol-related diseases, the search continues for a better understanding of the molecular and/or cellular mechanisms by which ethanol exerts its deleterious effects such as the induction of pro-apoptotic mechanisms and related cell damaging events. As part of the effort to enhance our understanding of those particular cellular pathways and mechanisms associated with ethanol toxicity, researchers over the years have utilized a variety of model systems. Recently, work has come forth demonstrating the utility of a hybrid cell line (WIF-B) as a cell culture model system for the study of alcohol-associated alterations in hepatocellular mechanisms. Success with such emerging model systems could aid in the development of potential therapeutic treatments for the prevention of alcohol- induced apoptotic cell death that may ultimately serve as a significant target in delaying the onset and/or progression of clinical symptoms of alcohol-mediated liver disease. This review article summarizes the current understanding of ethanol-mediated modifications in cell survival and thus the promotion of pro-apoptotic events with emphasis on analyses made in various experimental model systems, particularly the more recently characterized WIF-B cell system.

关键词： Hepatoma hybrid cells Ethanol Apoptosis Fas receptor Caspase

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Optical coherence tomography for ocular surface and corneal diseases: a review

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Eye and Vision 2018年第1期5卷 126-136页

作者： Nandini Venkateswaran Anat Galor Jianhua Wang carol l.Karp Bascom Palmer Eye Institute University of Miami Miller School of MedicineMcKnight Building Room 202A1638 NW 10th Avenue900 NW 17th StreetMiamiFL 33136USA Department of Ophthalmology Miami Veterans Administration Medical Center1201 NW 16th StreetMiamiFL 33125USA

The advent of optical coherence tomography(OCT)imaging has changed the way ophthalmologists image the ocular surface and anterior segment of the *** ability to obtain dynamic,high and ultra-high resolution,cross-sectional images of the ocular surface and anterior segment in a noninvasive and rapid manner allows for ease of *** this review,we focus on the use of anterior segment OCT,which provides an“optical biopsy”or in vivo imaging of various ocular surface and corneal pathologies,allowing the clinician to diagnose diseases otherwise not visualized by traditional *** utility of anterior segment OCT for various anterior segment pathologies is reviewed.

关键词： Anterior segment optical coherence tomography Ocular surface imaging Ocular surface lesions

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Utility of high-resolution anterior segment optical coherence tomography in the diagnosis and management of sub-clinical ocular surface squamous neoplasia

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Eye and Vision 2019年第1期6卷 229-235页

作者： Ann Q.Tran Nandini Venkateswaran Anat Galor carol l.Karp Department of Ophthalmology Bascom Palmer Eye InstituteUniversity of Miami Miller School of Medicine900 NW 17th StMiamiFL 33136USA

Background:To evaluate the frequency and characteristics of sub-clinical ocular surface squamous neoplasia(OSSN)detected by high-resolution anterior segment tomography(HR-OCT)in patients with clinically unapparent disease following topical ***:A retrospective chart review of patients with OSSN identified through a pharmacy database at the Bascom Palmer Eye Institute from January 2013 to December 2018 was *** undergoing primary therapy with topical 5-fluorouracil 1%(5-FU)(4 times a day for 7 days with a 21-day break)or interferon-alpha-2b(IFN)(4 times a day)were *** were separated into two *** 1 included individuals whose clinical resolution of OSSN aligned with complete resolution on *** 2(sub-clinical OSSN group)included individuals with clinical OSSN resolution but with features of persistent disease on *** excluded included those treated at an outside institution and those who used topical therapy as a surgical ***:A total of 95 patients(95 eyes)were ***-clinical OSSN was detected at a frequency of 17%in our study patients(n=16 patients,9 treated with 5-FU and 7 treated with IFN).In the 16 individuals,the mean time to clinical resolution was 3.6±1.0 cycles for 5-FU and 4.0±0.0 months for *** additional 2.1±0.8 cycles for 5-FU and 1.2±0.4 months for IFN were needed to achieve HR-OCT resolution of *** in Group 1 was noted in 10 patients(12%)while no recurrences occurred in Group 2,the cohort with subclinical disease that received the extended medical *** mean follow-up was 24.0±17.9 ***:We found that at least 17%of individuals with apparent clinical resolution of OSSN have sub-clinical disease detected on *** information can be used to optimize treatment and extend therapy past the point of clinical resolution.

关键词： Ocular surface squamous neoplasia,High-resolution optical coherence tomography,Sub-clinical ocular surface squamous neoplasia,Ocular surface imaging ocular surface lesions

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Update on Diagnosis and Management of Conjunctival Papilloma

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Eye and Vision 2019年第1期6卷 131-147页

作者： Despoina Theotoka Melina I.Morkin Anat Galor carol l.Karp Department of Ophthalmology Bascom Palmer Eye InstituteUniversity of Miami Miller School of Medicine900 NW 17th StreetMiamiFL 33136USA Miami Veterans Administration Medical Center 1201 NW 16th StreetMiami 33125FLUSA

Conjunctival papilloma is an acquired benign squamous cell tumor that can present at any age,but most frequently in the third and fourth decades of *** have been associated with human papilloma virus(HPV)infection,usually types 6 and *** histopathological diagnosis remains the gold standard,the advent of newer non-invasive imaging modalities such as optical coherence tomography(OCT)is transforming the way we diagnose and treat ocular surface tumors,including conjunctival *** of these lesions can prove a challenge to the treating physician since not all lesions respond to medical and/or surgical therapy and in fact may worsen after surgical *** this review,the epidemiology,pathophysiology,clinical characteristics,and diagnosis of conjunctival papilloma including the use of OCT are ***,efficacy,and side effects of currently available management options are also reviewed to guide the selection of the best treatment approach.

关键词： Conjunctival papilloma Squamous cell papilloma Optical coherence tomography Treatment Interferon Mitomycin Surgery Cryotherapy Human papilloma virus

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Epidemiology of ocular surface squamous neoplasia in veterans: a retrospective casecontrol study

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Eye and Vision 2019年第1期6卷 99-104页

作者： logan M.Smith Shiv lamba carol l.Karp Anat Galor Miami Veterans Administration Medical Center 1201 NW 16th StMiamiFL 33125USA Bascom Palmer Eye Institute Department of OphthalmologyUniversity of Miami900 NW 17th StreetMiamiFL 33136USA Flint Hill School OaktonVirginiaUSA

Background:A number of risk factors have been evaluated in ocular surface squamous neoplasia,but few studies have assessed risk factors specific to the armed forces veteran ***:We conducted a retrospective case-control study on 55 patients and 55 age-matched controls with biopsy-proven ocular surface squamous neoplasia from the Miami Veterans Administration Hospital Eye Clinic to investigate potential risk factors encountered by veterans,including service-specific ***-specific risk factors included ionizing radiation exposure,Agent Orange exposure,deployment to Southwest Asia,and exposure to the series of biochemical warfare tests known as Project Shipboard Hazard and *** was analyzed with SPSS(SPSS Inc.,Chicago,Il)using t-tests,chi-squared,and logistic regression analysis,with a p-value oflly ***:The strongest risk factor for ocular surface squamous neoplasia was lifetime sun exposure both directly assessed via historical quantification of exposure by dermatology practitioners(Odds Ratio(OR)5.4,95%Confidence Interval(CI)2.27–12.847,pl cell carcinoma(OR 3.157,95%CI 1.286–7.748,p=0.010)and pingueculae(OR 5.267,95%CI 2.104–13.186,ployment were not associated with an increased risk of ocular surface squamous *** to ionizing radiation and involvement in Project Shipboard Hazard and Defense were not documented among any cases or ***:The results of our study are consistent with prior established risk factors,namely highlighting the important role of sun exposure in ocular surface squamous neoplasia among veterans.

关键词： Ocular surface squamous neoplasia Risk factors Veteran population

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lacrimal gland tumors in Turkey：types,frequency,and outcomes

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International Journal of Ophthalmology(English edition) 2018年第8期11卷 1296-1302页

作者： Yagmur Seda Yesiltas Ahmet Kaan Gundiiz Esra Erden carol l. Shields Department of Ophthalmology Ankara University Faculty of Medicine Ankara 06620 Turkey Department of Pathology Ankara University Faculty of Medicine Ankara 06230 Turkey Ocular Oncology Service Wills Eye Hospital Thomas Jefferson University Philadelphia PA 19107 USA

AIM： To evaluate the clinical, radiological, and treatment features of lacrimal gland ***： Retrospective review of 99 eyes of 92 patients with lacrimal gland tumors diagnosed and managed in a single institution between January 1999 and March 2017. Clinical and radiological features, histopathology, treatment methods, and prognosis were ***： The mean patient age was 40.3（range： 7-80）*** diagnosis was made histopathologically in 91（91.9%） tumors and on a clinical and radiological basis in 8（8.1%） tumors. Final diagnoses included idiopathic orbital inflammation（pseudotumor） in 46（46.5%） lesions, pleomorphic adenoma in 14（14.1%）, adenoid cystic carcinoma in 12（12.1%）, granulomatous inflammation in 10（10.1%）, lymphoma in 5（5.0%）, benign reactive lymphoid hyperplasia in 3（3.0%）, dacryops in 3（3.0%）, carcinoma ex pleomorphic adenoma in 2（2.0%）, adenocarcinoma in 1（1.0%）, dermoid cyst in 1（1.0%）, cavernous hemangioma in 1（1.0%）, and leukemic infiltration in 1（1.0%）. Nonepithelial tumors comprised 64.6%（n=64） of all lacrimal gland tumors, epithelial tumors 32.3%（n=32）, dermoid cyst 1%（n=1）, cavernous hemangioma 1%（n=1）, and leukemic infiltration 1%（n=1）. There were in total 78（78.8%） benign and 21（21.2%） malignant tumors. CONClUSION： Overall, 65% of lacrimal gland tumors were of non-epithelial origin and 32% of epithelial origin. By histopathology and clinical evaluation, 79% of lacrimal gland tumors were benign. The most common lacrimal gland tumors include idiopathic orbital inflammation（46.5%）, epithelial（32.3%）, and lymphoproliferative（8.1%） lesions.

关键词： orbit lacrimal gland tumor inflammation epithelial tumor non-epithelial tumor

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Classification, diagnosis, and management of conjunctival lymphoma

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Eye and Vision 2019年第1期6卷 175-190页

作者： Rebecca E.Tanenbaum Anat Galor Sander R.Dubovy carol l.Karp Department of Ophthalmology Bascom Palmer Eye InstituteUniversity of Miami Miller School of Medicine900 NW 17th St.MiamiMiamiFL 33136USA

lymphoma is a malignant lymphoproliferative tumor that can involve the *** 5–15%of all extranodal lymphomas are found in the ocular adnexal region,with approximately 25%of those involving the ***-eight percent of conjunctival lymphomas arise from *** most common subtype of conjunctival lymphoma is extranodal marginal zone lymphoma(80%),followed by follicular lymphoma(8%),diffuse large B-cell lymphoma(3%)and mantle cell lymphoma(3%).Natural killer and T cells(NK/T)are rare causes of *** most conjunctival lymphomas are localized to the ocular adnexa at the time of presentation,systemic examination and management are of key importance in the long-term care of the *** review outlines the classification,etiology,presentation,diagnosis,and management of conjunctival *** novel use of high resolution optical coherence tomography,both as a diagnostic tool and as a means for ongoing evaluation during treatment,is *** options discussed include external beam radiation,chemotherapy,immunotherapy,antibiotic therapy,and combination *** investigation of the etiology and pathogenesis of conjunctival lymphoma is expected to reveal opportunities for innovative and individualized therapeutic *** between multiple disciplines is key in the advancement of the field.

关键词： Conjunctiva Conjunctival tumor Extranodal marginal zone lymphoma lymphoma Optical coherence tomography Salmon patch

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