This study uses the Dahl SS/jr rat as a preclinical model of spontaneous superimposed preeclampsia to demonstrate uncoupling of cerebral vascular permeability and blood-brain barrier disruption from cerebral blood flow autoregulatory dysfunction and myogenic tone. Additionally, the data presented in this study lay the foundational framework on which future experiments assessing specific transcellular transport components such as individual transporter protein expression and components of the vesicular transport system (caveolae) can be built to help reveal a potential direct mechanistic insight into the causes of cerebrovascular complications during preeclamptic pregnancies.

Autoimmune diseases such as psoriasis, rheumatoid arthritis, and systemic lupus erythematosus (SLE) have high rates of hypertension and cardiovascular disease. Systemic lupus erythematosus is a prototypic autoimmune disorder that primarily affects women of childbearing age and is associated with a loss of self-tolerance, autoreactive B and T lymphocytes, and the production of autoantibodies, especially to nuclear components. In this study, we hypothesized that the pristane-inducible model of SLE would develop hypertension and vascular dysfunction as the disease progressed. To test this hypothesis, female C57BL/6 mice were administered PBS or pristane. Seven months after pristane administration, mice developed various autoantibodies, including anti-dsDNA IgG, anti-ssDNA IgG, and anti-nRNP IgG, as well as hypergammaglobulinemia. Several other immunological changes, including increased circulating neutrophils and increased CD4- CD8- (double negative) thymocytes were also detected. Mean arterial pressure (MAP) was elevated in pristane-treated mice when compared to PBS-treated mice. In addition, second-order mesenteric arteries from pristine-treated mice had impaired relaxation to the endothelium-dependent vasodilator acetylcholine compared to PBS-treated mice. These data suggest that the immune system dysfunction present in the pristane model of lupus contributes to the development of hypertension and vascular dysfunction.

Purpose:Treatment of infectious keratitis is chosen by identification of infection source with associated antibiotic susceptibilities. Because culturing corneas may take days to weeks to result, the mainstay of treatment is empirical therapy with broad-spectrum antimicrobials that are started before culture results return. We aim to record the microbiological profiles with associated antibiotic susceptibility patterns isolated from corneal cultures in patients with infectious keratitis, as well as visual outcomes over a 5-year period.Methods:A retrospective analysis of medical records of patients who presented to UMMC from 1/1/2014 to 12/31/2018 with keratitis or corneal ulcer were included in this study based off diagnosis codes.Results:Of 563 corneal infections analyzed, 202 (35.9%) had positive cultures. The most frequently isolated organism was Coagulative negative Staphylococcus/ Staphylococcus epidermidis , followed by Pseudomonas aeruginosa , and Staphylococcus aureus . Pseudomonas aeruginosa was isolated in 37.2% contact lens wearers. We found that 93.3% of gram-positive cultured bacteria were susceptible to vancomycin with no resistance, and 81.8% of gram-negative bacteria were highly susceptible to tobramycin with no resistance. Regardless of treatment, 19.8% of patients needed some type of additional procedure, with the most common procedures being corneal transplant & evisceration. Conclusion:CNS, Pseudomonas aeruginosa, and Staphylococcus aureus were the most common microbes causing infectious keratitis. Pseudomonas aeruginosa remains the most commonly identified organism in contact lens wears. The empirical treatment of vancomycin and tobramycin used at our institution remains an excellent treatment for these microbes.

Patients with systemic autoimmune diseases such as systemic lupus erythematosus (SLE) have an increased risk of developing premature atherosclerotic cardiovascular disease (CVD), which is a major contributor to morbidity and mortality in this patient population. Specifically, patients with SLE have evidence of vascular disease including endothelial dysfunction, arterial stiffness, and coronary perfusion abnormalities, all of which predispose them to the development of atherosclerotic lesions. Our laboratory has shown that an established female mouse model of SLE (NZBWF1) develops impaired endothelial dependent relaxation compared to age matched healthy controls (female NZW mice). In the present study, we hypothesized that SLE mice fed an atherogenic diet will have accelerated vascular injury indicative of premature atherosclerotic disease. In order to test this hypothesis, female control (NZW, n=20) and SLE (NZBWF1, n=20) mice were fed normal chow or a high fat diet supplemented with 0.5% cholate (HFD+cholate) for 14 weeks. Body weight and body composition were monitored by Echo MRI biweekly over the course of the study. At the conclusion of the study both carotid arteries and aortas were isolated from control and SLE mice. Carotid rings were suspended in organ chamber baths where endothelium‐dependent and endothelium‐independent relaxation were the concentration responses (10−8 to10−4 M) to acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in vessels pre‐contracted with the thromboxane mimetic U46619 (0.4 μg/mL). HFD+cholate did not alter maximal ACh (10−4 M) mediated relaxation (70.1±3.4% vs. 75.2±2.1% p=0.33) in control mice. However, SLE mice fed HFD+cholate had an impaired relaxation response to ACh (10−4 M) as compared to SLE mice fed normal chow (65.6±2.3% vs. 43.6±7.2%, p=0.02). SNP‐mediated relaxation was not different between the mice fed different diets in either control or SLE animals, indicating that the impaired ACh response in SLE mice is endothelial dependent. In order to examine the impact of HFD+cholate on atherosclerotic lesion formation, isolated aortas were subjected to en face staining using Sudan IV. Preliminary data suggest that control mice fed HFD+cholate did not develop atherosclerotic plaques, but SLE fed HFD+cholate showed evidence of plaques in the aortic arch. Taken together, these data suggest that the immune system dysfunction present in SLE may accelerate the progression of diet‐induced atherosclerosis.Support or Funding InformationE.B.T. was supported by an individual NIH National Research Service Award (F32HL137393). This work was supported by Veteran's Administration Merit award (BX002604‐01A2) to M.J.R. and NIH NHLBI awards PO1HL051971, P20GM104357 to UMMC‐Department of Physiology and Biophysics.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Preeclampsia is clinically defined as elevated blood pressure after 20 weeks gestation along with other major organ involvement, such as brain, renal, or liver. It impacts 3–8 % of pregnancies, and there is currently no cure other than delivery of the placenta. The mechanisms leading to preeclampsia are not fully understood; however, recent work by our laboratory showed that the pregnant Dahl S rat closely mimics women with preexisting hypertension that develop preeclampsia. Therefore, pregnant Dahl S rats can be utilized to better understand the pathophysiological mechanisms and consequences of superimposed preeclampsia. Impaired cerebral vascular function has been implicated as a potential mechanism contributing to the increased risk of neurological complications associated with preeclampsia. In this study, we tested the hypothesis that pregnancy induces vascular permeability in cerebral arteries in Dahl S rats. Female Dahl S rats were mated at 16–18 weeks of age, while age‐matched virgin littermates were used as controls (n=5 per group). Middle cerebral arteries were isolated on gestational day 19–21, cannulated with glass pipettes, and pressurized to assess arterial permeability by measuring the change in intravascular pressure over time. Starling's Law states that fluid flux across a vessel wall is the result of hydraulic pressures and oncotic pressures due to differences in osmolality. In our model, the oncotic pressure gradient across the vessel wall was 0 mmHg, leaving only hydraulic pressures to determine fluid flux; therefore, the rate in pressure drop measured inside an isolated vessel is an indirect assessment of vascular permeability. Isolated vessels were equilibrated at 37°C for 30 minutes in physiological salt solution and pressurized to 75 mmHg. The diameter of isolated arteries after equilibration was 162±11 μm and 157±11 μm in virgin and pregnant rats, respectively (p=0.51). Intraluminal pressure was recorded every 5 minutes for one hour. As shown in the figure, the drop in intravascular pressure is greater in vessels isolated from pregnant rats compared to the pressure drop in vessels from virgin rats (*p< 0.01 vs virgin, n=5). Over the 60 minute experimental period, there was a significant difference in the drop in pressure permeability between the virgin and pregnant Dahl S rats (24.4±5.0 mmHg vs. 50.2±3.7 mmHg, respectively, P<0.01, n=5). These data indicate that pregnancy increases cerebral arterial permeability in Dahl S rats.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.