Gender differences in learning and study strategies impact medical students' preclinical and USMLE step 1 examination performance.

BACKGROUND: Evaluation of students' learning strategies can enhance academic support. Few studies have investigated differences in learning strategies between male and female students as well as their impact on United States Medical Licensing Examination® (USMLE) Step 1 and preclinical performance. METHODS: The Learning and Study Strategies Inventory (LASSI) was administered to the classes of 2019-2024 (female (n = 350) and male (n = 262)). Students' performance on preclinical first-year (M1) courses, preclinical second-year (M2) courses, and USMLE Step 1 was recorded. An independent t-test evaluated differences between females and males on each LASSI scale. A Pearson product moment correlation determined which LASSI scales correlated with preclinical performance and USMLE Step 1 examinations. RESULTS: Of the 10 LASSI scales, Anxiety, Attention, Information Processing, Selecting Main Idea, Test Strategies and Using Academic Resources showed significant differences between genders. Females reported higher levels of Anxiety (p < 0.001), which significantly influenced their performance. While males and females scored similarly in Concentration, Motivation, and Time Management, these scales were significant predictors of performance variation in females. Test Strategies was the largest contributor to performance variation for all students, regardless of gender. CONCLUSION: Gender differences in learning influence performance on STEP1. Consideration of this study's results will allow for targeted interventions for academic success.

Student Performance on Course Objectives in a First-Year Medical School Foundational Science Course Correlate with USMLE Step 1 Scores.

Purpose: Early identification of students at risk for poor United States Medical Licensing Examination® (USMLE) Step 1 examination (Step 1) performance allows medical schools to provide targeted intervention for those students. Therefore, determination of metrics that identify struggling students is necessary for proper intervention. We hypothesize that; 1) student performance on pre-matriculation metrics will correlate with their Molecular and Cellular Foundations of Medicine (FDNS) course performance and 2) student performance in the FDNS course and on specific FDNS course objectives will correlate with their Step 1 performance. Methods: This was a retrospective cohort study analyzing data for students matriculating to the University of South Carolina School of Medicine Greenville in 2018 and 2019. Linear regression analysis was conducted to assess the correlation between pre-matriculation metrics, performance in the FDNS course, performance on FDNS objectives, and USMLE Step 1 performance. Adjusted R-squared (adjusted r2) values were compared with a p-value at <0.05. Results: The FDNS course grade correlated with pre-matriculation metrics of science undergraduate grade point average (uGPA), total uGPA, and the Medical College Admission Test (MCAT), adjusted r2 of 0.139, 0.121, 0.223, respectively. The FDNS course grade showed a stronger correlation to USMLE Step 1 performance (adjusted r2 = 0.257) than pre-matriculation metrics. USMLE Step 1 performance strongly correlated with FDNS course performance when two objectives, pertaining to anabolic and catabolic processes, regulation of cell cycle, and DNA replication and repair, were combined, adjusted r2 of 0.357. Conclusion: The FDNS course grade and performance on specific course objectives could serve as a predictor for USMLE Step 1 performance and provides a more targeted and concise approach to identification of low-performing students and subsequent intervention.

Attendance of Near-Peer Tutoring Sessions Improves Academic Performance of First-Year Medical Students.

Introduction: Many medical schools have implemented near-peer tutoring (NPT) programs based on the substantial benefits of these programs to both tutors and tutees. This study correlated the frequency of attending weekly NPT sessions to students' academic performance, and also compared performance of high and low attending students. Methods: Twenty-one weekly NPT sessions were delivered by fourth-year (M4) students to first-year (M1) students. Attendance was recorded, and accordingly students were divided into three groups, high (15-21 sessions), moderate (7-14 sessions), and low (0-6 sessions) attendance groups. Pearson product-moment correlation coefficient was computed to assess the relationship between students' frequency of attendance and their overall performance on overall basic medical sciences at the end of M1 year and M2 mid-year NBME® CBSE. Students' performance was also analyzed using ANCOVA and Bonferroni post hoc test to compare differences between the three attendance groups. Results: An increase in number of attended NPT weekly sessions corresponds with an increase in students' performance on overall M1 basic sciences weighted average (r(196) = .240, p ≤ 0.001) and the M2 mid-year NBME® CBSE (r(196) = .325, p ≤ 0.001). High attending students performed significantly higher than low attending students on overall M1 weighted average of basic science courses (F(2, 192) = 8.518, p < .001) and M2 mid-year NBME® CBSE (F(2, 192) = 15.494, p < .001). Conclusion: Attending NPT weekly sessions is a valuable experience that is associated with an improvement in M1 medical students' academic performance. However, low performing students tend to miss attending NPT weekly sessions.

Emergency Medical Technician Training in Medical School on Preparation for Required National Board Exams and Clerkship Rotations: Results from a Student Survey.

Purpose: The University of South Carolina School of Medicine Greenville has incorporated Emergency Medical Technician (EMT) training into the first semester curriculum with students becoming state-certified EMTs and completing one ambulance shift per month throughout their pre-clerkship years. Although there have been programs that have reported EMT experiences in the pre-clinical years of medical education, student perceptions of how the EMT experiences help prepare them for board exams and clerkships is limited. Therefore, the aim of this study was to measure student perceptions regarding the impact of an EMT course and training in the pre-clerkship curriculum in medical school on helping prepare them for national board exams (ie USMLE® Step 1, 2 Clinical Knowledge (CK), 2 Clinical Skills (CS)) and clerkship rotations. Methods: Second-, third-, and fourth-year medical students at the University of South Carolina School of Medicine Greenville completed an anonymous voluntary survey with response rates of 66.3%, 55.2%, and 56.9%, respectively. The study was reviewed and exempted by the University of South Carolina Institutional Review Board. Results: Seventeen percent, 14%, and 41% of students agreed/strongly agreed an EMT course helped prepare them for the USMLE Step 1, Step 2 CK, and Step 2 CS exam, respectively. Sixty-four percent of students agreed/strongly agreed that an EMT course and experience helped prepare them for clerkship rotations. Conclusion: The findings in this study support EMT training and experience as an EMT as one method to help prepare students for clerkship rotations.

A Student Survey: Influence of Emergency Medical Technician Training on Student's Application, Matriculation, and Transition into Medical School.

Purpose: Medical education seeks to develop active methods of learning in addition to skills for patient interaction. With this in mind, the University of South Carolina (UofSC) School of Medicine Greenville developed a curriculum with an integrated emergency medical technician (EMT) certification course designed to provide a meaningful clinical experience for students; however, no data exists on whether this type of course influences a student's decision to apply to or attend a medical school and how such a course affects the transition to the medical school environment. The purpose of this study was to determine if an EMT course, as part of the medical school curriculum, influences students' decision to apply and attend a particular medical school and if this course influences students' transition to medical school while providing awareness of patients' lives and circumstances. Methods: A voluntary anonymous survey was distributed in Spring 2019 to first-, second-, third-, and fourth- year medical students at the UofSC School of Medicine Greenville. Response rates were 68.5%, 66.3%, 55.2%, and 56.9%, respectively. Results: Forty-three percent of students agreed/strongly agreed that the EMT course at UofSC School of Medicine Greenville factored into their decision to apply while 52% of students agreed/strongly agreed that it factored into their decision to attend. Students agreed/strongly agreed (82%) that the program helped with medical school transition. Ninety-one percent of students reported that EMT experiences increased awareness of patients' lives and circumstances. Conclusion: Students felt an EMT certification course at the beginning of the first year helped with the transition to medical school and increased awareness of patients' lives and circumstances.

Retinal Physiology and Circulation: Effect of Diabetes.

In this article, we present a discussion of diabetes and its complications, including the macrovascular and microvascular effects, with the latter of consequence to the retina. We will discuss the anatomy and physiology of the retina, including aspects of metabolism and mechanisms of oxygenation, with the latter accomplished via a combination of the retinal and choroidal blood circulations. Both of these vasculatures are altered in diabetes, with the retinal circulation intimately involved in the pathology of diabetic retinopathy. The later stages of diabetic retinopathy involve poorly controlled angiogenesis that is of great concern, but in our discussion, we will focus more on several alterations in the retinal circulation occurring earlier in the progression of disease, including reductions in blood flow and a possible redistribution of perfusion that may leave some areas of the retina ischemic and hypoxic. Finally, we include in this article a more recent area of investigation regarding the diabetic retinal vasculature, that is, the alterations to the endothelial surface layer that normally plays a vital role in maintaining physiological functions. © 2020 American Physiological Society. Compr Physiol 10:933-974, 2020.

Medical Student Perceptions of Emergency Medical Technician Training During the First Year of Medical School.

PURPOSE: Medical schools look for ways to provide clinical experiences and skill development in connection with knowledge. One method used is to provide emergency medical technician (EMT) training to medical students; however, limited data are available concerning EMT training in medical education. Therefore, the aim of this study was to review student feedback about the EMT curriculum through multiple iterations of the curriculum. METHODS: Students completed a voluntary school administered survey upon completion of their first year of medical school. Student responses to statements related to the EMT course and program were analyzed for classes matriculating in academic years 2012-2017. A one-way ANOVA with post hoc Tukey Honestly Significant Difference (HSD) was performed across all years for each survey statement. RESULTS: Mean response scores to statements related to the EMT course were higher when the EMT course was a standalone course and lower when integrated with biomedical science coursework. Students "strongly agreed" or "agreed" with most statements related to experiences and clinical skill development provided by the EMT program. Response rates ranged between 46-52 (88-100%) for 2012, 40-46 (74-85%) for 2013, 72-79 (88-96%) for 2014, 73-86 (71-83%) for 2015, 47-65 (46-63%) for 2016, 62-82 (59-78%) for 2017. CONCLUSION: Our data show that first year medical students liked the course design best when the EMT course was a standalone course at the start of the M.D. program while students liked experiences and clinical skill development provided by the EMT program regardless of course design.

Relationship between students' perceptions of the adequacy of M1 and M2 curricula and their performance on USMLE step 1 examination.

BACKGROUND: Performance on United States Medical Licensing Exam® (USMLE®) Step 1 examination (Step 1) is an important milestone for medical students. It is necessary for their graduation, and selection to interview for the National Resident Match Program®. Success on Step 1 examination requires content alignment, and continuous evaluation and improvement of preclinical curriculum. The purpose of this research was to observe the association between students' perceptions of deficits in the curriculum based on core disciplines and organ systems in relation to students' performance in those disciplines and systems on USMLE® Step 1 examination. METHODS: An anonymous survey with closed-ended and open-ended questions was sent to 174 medical students, the class of 2018 (77), and 2019 (97) within 2-3 weeks of taking Step 1 examination. Students' feedback as well as students' performance on Step 1 examination were organized into disciplines and organ systems to allow for more specific curriculum analyses. The closed-ended questions provide three selections (yes, no and not sure) regarding students' agreement to the adequacy of M1 and M2 curricula to prepare students for Step 1 examination. Students' responses on the closed-ended questions were reviewed in conjunction with their Step 1 performance. The open-ended feedback was qualitatively analyzed for emergent themes or similarity with closed-ended questions in identifying any shortcoming of the curriculum. RESULTS: The data show an apparent relationship between students' evaluations and students' performance on Step 1 examinations. A high percentage of students' disagreement of the curriculum adequacy was also reflected in a lower performance on Step 1 examination. Additionally, the themes that emerged from the qualitative analysis have confirmed the areas of curricular deficiency. CONCLUSION: The data collected from this research provides insight into the degree of usefulness of students' evaluations as a way of assessing curriculum deficits in preparing students for their Step 1 examination.

U.S. medical school curricula on working with medical interpreters and/or patients with limited English proficiency.

PURPOSE: The United States has an increasing population of individuals with limited English proficiency (LEP). Language access is a right for individuals with LEP in the health care system. As such, it is important for medical providers to be appropriately trained to work with individuals with LEP. Therefore, the purpose of this study was to describe curricula offered by United States medical schools to teach medical students to work with medical interpreters and/or patients with LEP. METHODS: An electronic survey was sent in March 2017 to administration at the 147 Liaison Committee on Medical Education® accredited medical schools as of November 7, 2016. The survey consisted of the following question: "As part of your medical school's curriculum, are students provided specific instruction addressing how to work with medical interpreters and/or patients with limited English proficiency (LEP)?" with different follow-up questions for schools that responded "Yes" vs "No". RESULTS: Responses were received from 26% (38/147) of medical schools. Among schools responding to the survey, 76% (29/38) offered a curriculum that provides instruction of how to work with medical interpreters and/or patients with LEP. Of schools that provide instruction, teaching methods included didactic sessions (34% [10/29]) and standardized patient experiences (34% [10/29]). In addition, 76% (22/29) offer training in the first 2 years of medical school and 28% (8/29) offer training in the third and fourth years of the curriculum. Sixty-two percent (18/29) of respondents that offered a formal curriculum have been administering a formal curriculum for ≤10 years. CONCLUSION: The majority of the responding medical schools offer formal instruction of how to work with medical interpreters and/or patients with LEP. Most schools started this type of instruction in the last 10 years with most instruction occurring in the first 2 years of an undergraduate medical curriculum.

A national survey: use of the National Board of Medical Examiners® basic science subject exams and Customized Assessment Services exams in US medical schools.

PURPOSE: The National Board of Medical Examiners® (NBME®) offers basic science subject exams and exams developed using the Customized Assessment Services (CAS) program. The scope and utilization of these exams by US medical schools has not been reported. Therefore, this survey aimed to measure US medical school usage of NBME® basic science subject exams and exams administered using the CAS program. METHODS: In May 2016 a survey was sent to 139 US medical schools with provisional or full accreditation by the Liaison Committee on Medical Education®. Schools were asked if they administered NBME® basic science subject exams or exams developed using the NBME® CAS program. Follow-up questions were asked if the school responded "Yes" to administering the exams. RESULTS: Responses were received from 46-48 schools (33%-35% response rate). Of the schools responding, 7-13 schools (15%-28%) administer an NBME® basic science subject exam and 14 schools (30%) administer an exam developed using the CAS program. Of the schools that administer an NBME® basic science exam, 7-12 (83%-100%) use the exam for summative assessment for a course and 6-11 (77%-100%) use the exam results for curricular revision. Twelve schools (86%) that administer an NBME® exam developed using the CAS program use the exam for summative assessment for a course. Time of administration within the curriculum for NBME® basic science subject exams varied between 1 month prior to >6 months prior to students taking the United States Medical Licensing Examination® Step 1. CONCLUSION: According to our data, most US medical schools responding to the survey do not administer NBME® basic science subject exams or exams developed using the NBME® CAS program. Schools that do administer NBME® basic science subject exams use the exams for summative assessment for a course and curricular revision, while exams administered using the CAS program are used predominately for summative assessment for a course.

Use of the National Board of Medical Examiners® Comprehensive Basic Science Exam: survey results of US medical schools.

PURPOSE: The National Board of Medical Examiners® (NBME) Comprehensive Basic Science Exam (CBSE) is a subject exam offered to US medical schools, where it has been used for external validation of student preparedness for the United States Medical Licensing Examination® (USMLE) Step 1 in new schools and schools undergoing curricular reform. Information regarding the actual use of the NBME CBSE is limited. Therefore, the aim of the survey was to determine the scope and utilization of the NBME CBSE by US medical schools. METHODS: A survey was sent in May 2016 to curriculum leadership of the 139 US medical schools listed on the Liaison Committee on Medical Education (LCME®) website with provisional or full accreditation as of February 29, 2016. Responses were received from 53 schools (38% response rate). A series of different follow-up questions were asked if respondents stated "yes" or "no" to the initial question "Does your institution administer the NBME CBSE prior to the USMLE Step 1?". RESULTS: A total of 37 schools (70%) administered the NBME CBSE. In all, 36 of the 37 schools responded to follow-up questions. Of 36 schools, 13 schools (36%) used the NBME CBSE for curriculum modification. Six schools (17%) used the NBME CBSE for formative assessment for a course, and five schools (14%) used the NBME CBSE for summative assessment for a course. A total of 28 schools (78%) used the NBME CBSE for identifying students performing below expectations and providing targeted intervention strategies. In all, 24 schools (67%) of the 36 responding schools administering the NBME CBSE administered the test once prior to the administration of the USMLE Step 1, whereas 10 (28%) schools administered the NBME CBSE two or more times prior to the administration of the USMLE Step 1. CONCLUSION: Our data suggest that the NBME CBSE is administered by many US medical schools. However, the objective, timing, and number of exams administered vary greatly among schools.

Oxygen delivery, consumption, and conversion to reactive oxygen species in experimental models of diabetic retinopathy.

Retinal tissue receives its supply of oxygen from two sources - the retinal and choroidal circulations. Decreases in retinal blood flow occur in the early stages of diabetes, with the eventual development of hypoxia thought to contribute to pathological neovascularization. Oxygen consumption in the retina has been found to decrease in diabetes, possibly due to either a reduction in neuronal metabolism or to cell death. Diabetes also enhances the rate of conversion of oxygen to superoxide in the retina, with experimental evidence suggesting that mitochondrial superoxide not only drives the overall production of reactive oxygen species, but also initiates several pathways leading to retinopathy, including the increased activity of the polyol and hexosamine pathways, increased production of advanced glycation end products and expression of their receptors, and activation of protein kinase C.

Retinal blood flow abnormalities following six months of hyperglycemia in the Ins2(Akita) mouse.

The aim of this study was to characterize the microvascular flow abnormalities and oxygenation changes that are present following six months of hyperglycemia in the diabetic Ins2(Akita) mouse. Previous studies have shown decreased retinal blood flow in the first several weeks of hyperglycemia in rodents, similar to the decreases seen in the early stages of human diabetes. However, whether this alteration in the mouse retina continues beyond the initial weeks of diabetes has yet to be determined, as are the potential consequences of the decreased flow on retinal oxygenation. In this study, male Ins2(Akita) and age-matched C57BL/6 (non-diabetic) mice were maintained for a period of six months, at which time intravital microscopy was used to measure retinal blood vessel diameters, blood cell velocity, vascular wall shear rates, blood flow rates, and transient capillary occlusions. In addition, the presence of hypoxia was assessed using the oxygen-sensitive probe pimonidazole. The diabetic retinal microvasculature displayed decreases in red blood cell velocity (30%, p<0.001), shear rate (25%, p<0.01), and flow rate (40%, p<0.001). Moreover, transient capillary stoppages in flow were observed in the diabetic mice, but rarely in the non-diabetic mice. However, no alterations were observed in retinal hypoxia as determined by a pimonidazole assay, suggesting the possibility that the decreases seen in retinal blood flow may be dictated by a decrease in retinal oxygen utilization.

Influence of glutathione on the electroretinogram in diabetic and non-diabetic rats.

AIMS: The purpose of this study was to investigate the influence of glutathione on the electroretinogram (ERG) in diabetic and non-diabetic rats. MATERIALS AND METHODS: Streptozotocin (STZ: 60 mg/kg) was injected into male RCC Wistar rats to induce hyperglycemia, with buffer instead of STZ injected into age-matched non-diabetic controls. After 8 weeks, ERG measurements were obtained at seven different scotopic flash intensities on the two groups of anesthetized, dark-adapted rats (controls, STZ). Following ERG measurements, eyes were enucleated for measurements of retinal/vitreous GSH and glutathione disulfide (GSSG). RESULTS: Diabetic rats produced delayed b-wave ERG signals (increased implicit times), but had normal a-wave and b-wave amplitudes, a-wave implicit times, and oscillatory potentials. No differences were observed in retinal GSH or GSSG between controls and diabetics; however, correlations between GSH and all ERG parameters (with the exception of b-wave implicit times) were noted, and were not significantly altered by the presence of hyperglycemia. CONCLUSIONS: GSH is likely to play an important role in retinal function as assessed by the ERG, with this role not substantially altered in rats diabetic for 8 weeks.

Increase in retinal hypoxia-inducible factor-2α, but not hypoxia, early in the progression of diabetes in the rat.

Hypoxia and the associated hypoxia-inducible factors (HIFs) may be influential in the progression of diabetic retinopathy. However, little is known of the extent of hypoxia and the levels of HIFs early in the progression of the disease. In the current study, we injected the oxygen-dependent probe pimonidazole (Hypoxyprobe™-1) into diabetic rats, and also performed immunohistochemistry to determine the retinal levels of HIF-1α and HIF-2α. The rats were made diabetic using a single injection of streptozotocin (STZ; 60 mg/kg), with vehicle-injected rats used as non-diabetic controls. The measurements of hypoxia and HIF levels were obtained three weeks following STZ injection, at which time we have previously found significant decreases in retinal blood flow in the same model. In the current experiments, no increases in either HIF-1α or hypoxia were observed in the diabetic rats (compared with controls), and there was even a tendency for hypoxia levels to be decreased (tissue more highly oxygenated). However, we did observe an increase in HIF-2α in the retinas of the diabetic rats. Therefore, we conclude that early diabetes-induced increases in HIF-2α occur independently of hypoxia.

Thromboxane-prostanoid receptor expression and antagonism in dextran-sodium sulfate-induced colitis.

OBJECTIVE: In the current study of murine colitis, the potential roles of thromboxane and the thromboxane-prostanoid (TP) receptor were investigated, in as much as thromboxane signaling has been implicated in human inflammatory bowel disease. METHODS: Colitis was induced in C57BL/6 mice via ingestion of dextran sodium sulfate (DSS), with or without co-administration of the thromboxane synthase inhibitor ozagrel (25 mg/kg/day) or the TP receptor antagonist vapiprost (2.5 mg/kg/day). RESULTS: Immunohistochemistry of colonic tissue demonstrated a DSS-induced increase in TP receptor expression, but not of thromboxane synthase. Moreover, tissue levels of the metabolite thromboxane B(2) were unchanged by DSS. Vapiprost, but not ozagrel, partially attenuated histologic signs of inflammation induced by DSS, with vapiprost allowing a smaller increase in colon weight per unit length than ozagrel. Vapiprost also tended to attenuate DSS-induced alterations in intestinal transit. CONCLUSIONS: In summary, TP receptor antagonism was more effective than thromboxane synthase inhibition in alleviating DSS-induced colitis in mice.

Hypoxia and the expression of HIF-1alpha and HIF-2alpha in the retina of streptozotocin-injected mice and rats.

Decreases in retinal blood flow in diabetics could render the retina hypoxic. In mouse and rat models of diabetes, a decrease in retinal blood flow occurs early, within 3-4 weeks of the induction of hyperglycemia, although information is scarce on whether this early decrease in flow induces hypoxia. The purpose of the current study was to determine whether hypoxia-inducible factor (HIF) levels increase following 4 and/or 12 weeks of hyperglycemia in streptozotocin (STZ)-injected mouse (C57BL/6) and rat (Wistar) retinas. Additionally, retinal tissue hypoxia was measured with pimonidazole following 12 weeks of hyperglycemia. These aims were accomplished via immunostaining of cross-sections from enucleated eyes. In mice, staining for HIF-1alpha and HIF-2alpha showed a contrasting pattern, with HIF-1alpha higher in the inner retina than outer, but HIF-2alpha higher in the outer retina than inner. However, in rats, staining for both HIF-1alpha and HIF-2alpha was more intense in the inner retina. The HIF-1alpha staining intensities and patterns were similar between diabetic animals and their non-diabetic counterparts following 4 and 12 weeks of hyperglycemia. The same was true for HIF-2alpha except for a trend toward an increase following 12 weeks of hyperglycemia in mice. Pimonidazole staining showed significant decreases throughout all layers of the central retina and most layers of the peripheral retina of rats (but not mice), following 12 weeks of hyperglycemia. In summary, despite early decreases in flow in rats and mice, retinal HIF-1alpha and HIF-2alpha were not found to be increased, and the extent of hypoxia may even decrease after 12 weeks of hyperglycemia in rats.

Expression of thromboxane synthase and the thromboxane-prostanoid receptor in the mouse and rat retina.

Experimental models of the diabetic retina have suggested a pathological role for thromboxane. To date however, little information is available as to the cellular locations of retinal thromboxane synthase (TxS), or its receptor, even in non-diabetic controls. In this study, C57BL/6 mice and Wistar rats were injected with streptozotocin to induce diabetes, or with buffer for non-diabetic controls. Four weeks following the injection, eyes were enucleated and labeled for TxS and the thromboxane-prostanoid (TP) receptor. Immunofluorescent intensity was quantified in the ganglion cell plus inner plexiform layers, inner nuclear layer, outer plexiform layer, outer nuclear layer, and photoreceptor inner segment. Even in control mice and rats, all layers of the retina showed immunoreactivity for TxS and the TP receptor: however, the pattern of expression demonstrated an inverse relationship, with the highest TxS staining in the inner retina, and the highest TP receptor staining in the outer retina (more specifically, in the photoreceptor inner segment). Four weeks of hyperglycemia did not increase the retinal levels of TxS or TP receptor; however, TP receptor intensities in the outer retina of diabetic rats were highly variable (mostly high but some low), with no values from the photoreceptor inner segment in the same range as obtained from controls.

Attenuation of diabetes-induced retinal vasoconstriction by a thromboxane receptor antagonist.

Retinal blood flow has been reported to decrease early in human diabetes as well as in diabetic animal models. The purpose of the present study is to investigate the role of thromboxane receptor binding in the decrease of flow. C57BL/6 mice were injected with streptozotocin (STZ) at 11-12 weeks of age and remained hyperglycemic for 4 weeks. The mice were treated with a selective thromboxane receptor antagonist, GR32191B (vapiprost), in drinking water for the final three weeks at a dose of 1mg/kg/day. In separate experiments, vapiprost was administered only once, as an acute injection 25min prior to the experimental measurements. The measurements included retinal arteriolar and venular diameters and red blood cell (RBC) velocities, from which retinal blood flow was calculated. STZ induced decreases in vascular diameters and RBC velocities, resulting in an approximate 30% decrease in overall retinal blood flow. However, these decreases were not seen in mice given the three-week administration of vapiprost. Acute administration to diabetic mice of 1mg/kg vapiprost, but not 0.1mg/kg, induced arteriolar vasodilation, with the dilation more substantial in smaller feed arterioles. In summary, STZ-induced decreases in retinal blood flow can be attenuated by the thromboxane receptor antagonist vapiprost.

Ozagrel attenuates early streptozotocin-induced constriction of arterioles in the mouse retina.

Retinal blood flow in human diabetics has been reported to follow a biphasic time course in which an initial period of reduced flow and ischemia is often followed by a hyperemic and angiogenic phase in which flow can exceed normal levels. The purpose of the present study is to investigate the mechanisms of the initial decrease in flow, since early interventions could provide the most effective treatment strategies. C57BL/6 mice were injected with streptozotocin (STZ) at 12 weeks of age and remained hyperglycemic until data were gathered 4 or 8 weeks later. Experimental measurements included retinal arteriolar red blood cell velocity and arteriolar diameters, with the diameters measured prior to and following an intravenous injection of the thromboxane synthase inhibitor ozagrel (100 mg/kg). Arterioles leading out of the optic disk constricted significantly at 4 weeks post-STZ (p<0.001) compared to age-matched controls, but not at 8 weeks post-STZ. Calculations of retinal blood flow indicated a 45% decrease at 4 weeks post-STZ, but only a 26% decrease by 8 weeks. Not all arterioles constricted equally in response to STZ; the most substantial constrictions were present in arterioles that were more closely arranged with countercurrent venules leading back into the optic disk. Injection of ozagrel provided significant dilation of constricted retinal arterioles. In addition, the pattern of dilation was consistent with the sites of the most severe constriction, i.e., ozagrel-induced dilation in the STZ mice occurred to the greatest extent in the arterioles more closely paired with the venules draining the microvascular bed. In summary, STZ induces a biphasic alteration in retinal blood flow in mice, in which thromboxane contributes to the initial reduction in blood flow at 4 weeks. Moreover, the thromboxane-induced arteriolar constriction is dependent on the proximity of the retinal arterioles to countercurrent venules.