LaShon Sturgis

TNF‐α Knockout Mice Have Increased Corpora Cavernosa Relaxation

INTRODUCTION Erectile dysfunction is considered an early clinical manifestation of vascular disease and an independent risk factor for cardiovascular events associated with endothelial dysfunction and increased levels of pro-inflammatory cytokines. Tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, suppresses endothelial nitric oxide synthase (eNOS) expression. AIM Considering that nitric oxide (NO) is of critical importance in penile erection, we hypothesized that blockade of TNF-alpha actions would increase cavernosal smooth muscle relaxation. METHODS In vitro organ bath studies were used to measure cavernosal reactivity in wild type and TNF-alpha knockout (TNF-alpha KO) mice and NOS expression was evaluated by western blot. In addition, spontaneous erections (in vivo) were evaluated by videomonitoring the animals (30 minutes). Collagen and elastin expression were evaluated by Masson trichrome and Verhoff-van Gieson stain reaction, respectively. MAIN OUTCOME MEASURES Corpora cavernosa from TNF-alpha KO mice exhibited increased NO-dependent relaxation, which was associated with increased eNOS and neuronal NOS (nNOS) cavernosal expression. RESULTS Cavernosal strips from TNF-alpha KO mice displayed increased endothelium-dependent (97.4 +/- 5.3 vs. CONTROL 76.3 +/- 6.3, %) and nonadrenergic-noncholinergic (93.3 +/- 3.0 vs. CONTROL 67.5 +/- 16.0; 16 Hz) relaxation compared to control animals. These responses were associated with increased protein expression of eNOS and nNOS (P < 0.05). Sympathetic-mediated (0.69 +/- 0.16 vs. CONTROL 1.22 +/- 0.22; 16 Hz) as well as phenylephrine-induced contractile responses (1.6 +/- 0.1 vs. CONTROL 2.5 +/- 0.1, mN) were attenuated in cavernosal strips from TNF-alpha KO mice. Additionally, corpora cavernosa from TNF-alpha KO mice displayed increased collagen and elastin expression. In vivo experiments demonstrated that TNF-alpha KO mice display increased number of spontaneous erections. CONCLUSION Corpora cavernosa from TNF-alpha KO mice display alterations that favor penile tumescence, indicating that TNF-alpha plays a detrimental role in erectile function. A key role for TNF-alpha in mediating endothelial dysfunction in ED is markedly relevant since we now have access to anti-TNF-alpha therapies.

THE ROLE OF ALDOSTERONE IN MEDIATING THE DEPENDENCE OF ANGIOTENSIN HYPERTENSION ON IL-6

Knockout (KO) of IL-6 has been shown to attenuate ANG II hypertension, and mineralocorticoid receptors (MR) have been reported to contribute to the increase in IL-6 during acute ANG II infusion. This study determined whether that MR action is sustained with chronic ANG II infusion and whether it plays a role in mediating ANG II hypertension. ANG II infusion (90 ng/min) increased plasma IL-6 from 1.6 +/- 0.6 to 22.7 +/- 2.2 and 19.9 +/- 3.2 pg/ml on days 7 and 14, respectively, and chronic MR blockade with spironolactone attenuated that only at day 7 (7.2 +/- 2.2 pg/ml). ANG II increased MAP (19 h/day with telemetry) approximately 40 mmHg, but in ANG II+spironolactone mice (25 or 50 mg*kg(-1)*day(-1)), mean arterial pressure (MAP) was not significantly different despite a tendency for lower pressure the first 6 days. To isolate further the mineralocorticoid link to IL-6 and blood pressure, DOCA-salt hypertension was induced in IL-6 KO and wild-type (WT) mice. Plasma IL-6 increased from 4.1 +/- 1.7 to 34.5 +/- 7.0 pg/ml by day 7 of DOCA treatment in the WT mice but was back to control levels by day 14. An IL-6 bioassay using the murine B9, B-cell hybridoma cell line demonstrated that plasma IL-6 measurements reflected actual IL-6 bioactivity. The hypertension was not different and virtually superimposable in WT vs. IL-6 KO mice, averaging 145 +/- 2 and 144 +/- 3 mmHg, respectively. Both experiments confirm chronic stimulation of IL-6 by mineralocorticoids but show that it is transient. In addition, IL-6 was not required for mineralocorticoid hypertension. This suggests that aldosterone contributes to the increase in plasma IL-6 in the early stage of ANG II hypertension but that the blood pressure actions of IL-6 in that model are linked most likely to ANG II rather than aldosterone.

Rural ED transfers due to lack of radiology services

PURPOSE Our objectives were to determine the frequency of patient transfers to a tertiary care emergency department (Tertiary ED) due to a lack of radiology services in rural hospital EDs (Rural EDs), and examine the community and patient attributes that are associated with these transfers. METHODS This was a retrospective chart review of patients transferred to a Tertiary ED from Rural EDs. Transfers excluded from the study included pediatric patients (age <18 years old) and patients transferred for trauma surgeon evaluation. Only those patients who were transferred for radiology services were included in the final analysis. RESULTS Over a 12-month period, 1445 patients were transferred to the Tertiary ED with 73.8% (n = 1066) of this population being transferred from a Rural ED. Excluding 381 trauma and pediatric patients, 64.3% (n = 685) of patients were transferred from a Rural ED and were included in the study. Of these 685 transfers, 24.5% (n = 168) were determined to be due primarily to a lack of a radiology service. DISCUSSION Lack of radiology services in Rural EDs leads to numerous patient transfers to the Tertiary ED each year. A disproportionate number of these transfer patients are African American. These transfers place additional financial and social burdens on patients and their families. This study discusses these findings and alternative diagnostic options (ie, telemedicine and ultrasound video transfer) to address the lack of radiology services available in Rural EDs. The use of these alternate diagnostic options will likely reduce the number of patient transfers to Tertiary EDs.

LACK OF BLOOD PRESSURE SALT-SENSITIVITY SUPPORTS A PREGLOMERULAR SITE OF ACTION OF NITRIC OXIDE IN TYPE I DIABETIC RATS

1 The relationship between sodium intake and blood pressure is affected differently by changes in angiotensin (Ang) II and preglomerular resistance, and this study measured that relationship to evaluate the link between nitric oxide and blood pressure early in diabetes. 2 Rats were chronically instrumented, placed on high‐sodium (HS = 12 mEq/d) or low‐sodium (LS = 0.07 mEq/d) intake diets and assigned to either vehicle‐ (V) or Nw‐nitro‐l‐arginine methyl ester‐ (l‐NAME; L) treated groups. Mean arterial pressure (MAP) was measured 18 h/day for a 6‐day control and 14‐day streptozotocin diabetic period in each animal. 3 The MAP of the control period averaged 95 ± 1 and 94 ± 1 mmHg in the LSV and HSV rats and 116 ± 2 and 124 ± 1 mmHg in the LSL and HSL rats, respectively (LSL vs HSL was significant at P < 0.05). Diabetes increased MAP only in the LSL and HSL rats to 141 ± 2 mmHg and 152 ± 2, respectively, similar to our previous reports, and those respective 25 and 28 mmHg increases were a parallel shift in the pressure natriuresis relationship. However, the apparent difference between the LSL and HSL groups when compared was a parallel of the control MAP difference. Plasma renin activity (PRA) in the control period averaged 1.5 ± 0.5 and 8.1 ± 1.8 ng AI/mL per h in the HSV and LSV rats, and 0.8 ± 0.2 and 2.8 ± 0.5 ng AI/mL per h in the HSL and LSL rats, respectively, and increased similarly by 4.6‐fold in the HSL and 4.8‐fold in the LSL rats during diabetes. Glomerular filtration rate (GFR) increased in the vehicle but not the l‐NAME‐treated groups, consistent with our previous reports. 4 Thus, the hypertension caused by the onset of diabetes in l‐NAME‐treated rats was not salt‐sensitive. The normal modulation of PRA by salt intake and the failure of GFR to increase are consistent with our hypothesis that nitric oxide may protect against hypertension early in diabetes by preventing preglomerular vasoconstriction by AngII.

The utility of routine reticulocyte count in uncomplicated vaso-occlusive events due to sickle cell disease

Labs are routinely ordered for patients admitted to the emergency room for uncomplicated vaso-occlusive events (VOE), however, there are no “standard” screening practices. Review articles and expert opinions regarding routine testing vary widely in their recommendations [1-3]. In addition, recent literature has called into question the need for routine screening laboratory analysis in clinically uncomplicated VOE [1,4,5]. The objective of this study was to evaluate the utility of one measure, reticulocyte count, in cases of uncomplicated VOE in Sickle Cell Disease.