Skimming genomes for systematics and DNA barcodes of corals.

Numerous genomic methods developed over the past two decades have enabled the discovery and extraction of orthologous loci to help resolve phylogenetic relationships across various taxa and scales. Genome skimming (or low-coverage genome sequencing) is a promising method to not only extract high-copy loci but also 100s to 1000s of phylogenetically informative nuclear loci (e.g., ultraconserved elements [UCEs] and exons) from contemporary and museum samples. The subphylum Anthozoa, including important ecosystem engineers (e.g., stony corals, black corals, anemones, and octocorals) in the marine environment, is in critical need of phylogenetic resolution and thus might benefit from a genome-skimming approach. We conducted genome skimming on 242 anthozoan corals collected from 1886 to 2022. Using existing target-capture baitsets, we bioinformatically obtained UCEs and exons from the genome-skimming data and incorporated them with data from previously published target-capture studies. The mean number of UCE and exon loci extracted from the genome skimming data was 1837 ± 662 SD for octocorals and 1379 ± 476 SD loci for hexacorals. Phylogenetic relationships were well resolved within each class. A mean of 1422 ± 720 loci was obtained from the historical specimens, with 1253 loci recovered from the oldest specimen collected in 1886. We also obtained partial to whole mitogenomes and nuclear rRNA genes from >95% of samples. Bioinformatically pulling UCEs, exons, mitochondrial genomes, and nuclear rRNA genes from genome skimming data is a viable and low-cost option for phylogenetic studies. This approach can be used to review and support taxonomic revisions and reconstruct evolutionary histories, including historical museum and type specimens.

Radiofrequency ablation of the occipital nerves for treatment of neuralgias and headache.

OBJECTIVE: The purpose of this study was to retrospectively assess the efficacy of radiofrequency ablation (RFA) therapy as a treatment for occipital neuralgias and headaches at health clinics in the United States between January 1, 2015 and June 20, 2022. We hypothesize that RFA is a minimally invasive treatment that provides significant pain relief long-term for occipital neuralgias and associated headaches. METHODS: This retrospective analysis studies data collected from 277 occipital nerve RFA patients who had adequate pre-procedure and post-procedure follow-up for data analysis. Data collected includes the patient's age, biological sex, BMI, headache diagnosis, pre-procedure, and post-procedure pain score using the visual analog scale (VAS), subjective percent improvement in symptom(s), and duration of symptom relief. Statistical analysis used SPSS software, version 26 (IBM), using a paired t-test to assess the significance between pre and post-occipital RFA therapy pain scores. p-values were significant if found to be ≤0.05. RESULTS: The mean pre-procedure pain score before RFA therapy for patients who completed at least 6 months of follow-up was 5.57 (SD = 1.87) and the mean post-procedure pain score after RFA therapy was 2.39 (SD = 2.42). The improvement in pain scores between pre-procedure and post-procedure was statistically significant with a p-value < 0.001. The mean patient-reported percent improvement in pain following RFA therapy was 63.53% (SD = 36.37). The mean duration of pain improvement was 253.9 days after the initiation of therapy (SD = 300.5). When excluding patients who did not have any relief following their RFA procedure, the average pre-procedure pain score was 5.54 (SD = 1.81) and post-procedure pain score was 1.71 (SD = 1.81) with a p-value < 0.001. CONCLUSION: This study demonstrates the minimally invasive, safe, and effective treatment of RFA in patients with refractory occipital neuralgias and headaches. Additional studies are necessary to illuminate ideal patient characteristics for RFA treatment and the potential for procedural complications and long-term side effects associated with occipital nerve RFA therapy.

Disulfiram-Mitigating Unintended Effects.

Lyme disease caused by infection with a multitude of vector-borne organisms can sometimes be successfully treated in its very early stages. However, if diagnosis is delayed, this infection can become disseminated and, like another spirochetal infection syphilis, can affect multiple organ systems in the body, causing a wide variety of life-altering symptoms. Conventional antibiotic therapy may not be effective in eradicating the symptoms of the disease we know as Lyme disease. The recent literature has suggested that disulfiram (DSM) may be a potent drug in the armamentarium of physicians who treat chronic Lyme disease. The use of disulfiram in the treatment of Lyme disease started with a researcher who determined that DSM is bactericidal to spirochete. Encouraged by published case reports of apparent recovery from chronic Lyme disease, having prescribed DSM ourselves in the past for alcoholics who had a desire to stop drinking and prescribing it now for patients with chronic Lyme disease, we observed both predictable and potentially avoidable side effects not necessarily related to the ingestion of alcohol. We reviewed the published literature in PubMed and Google Scholar, using the following key words: Lyme Disease; Borrelia burgdorferi treatment; and disulfiram toxicity. This paper outlines the results of that research to help avoid some of the pitfalls inherent in this novel use of an old and established medication in the practice of clinical medicine.

Endovascular treatment of trigeminal neuralgia with cranial autonomic symptoms due to a right-sided petrous ridge dAVF.

Dural arteriovenous fistula represents a rare cause of secondary Trigeminal Neuralgia. To date, there have been 18 reported cases of successful treatment of trigeminal neuralgia with endovascular embolization. Here we describe a unique case of a 51-year-old man with right-sided petrous ridge dural arteriovenous fistula causing ipsilateral V1 pain and cranial autonomic dysfunction. Cerebral angiography confirmed a Cognard type 3 right-sided tentorial dAVF supplied by an enlarged meningo-hypophpyseal vessel from the extradural ICA and by the middle meningeal artery. The fistula drains towards the midline via deep cerebral veins, the internal cerebral vein and the straight sinus with likely variceal compression of the right trigeminal nerve root entry zone. Transarterial Onyx embolization resulted in complete obliteration of the dural arteriovenous fistula with immediate resolution of facial pain and autonomic symptoms. After 24 months, the patient remains symptom-free and has no radiographic or clinical evidence of fistula recurrence. To date, there have been no other cases reported of trigeminal neuralgia with cranial autonomic symptoms or SUNCT syndrome due to a dural arteriovenous fistula. The presence of cranial autonomic symptoms with trigeminal neuralgia or a diagnosis of SUNCT should not deter endovascular treatments of dural arteriovenous fistulas or treatment of other compressive vascular lesions.

Availability of a final abdominopelvic CT report before emergency department disposition: risk-adjusted outcomes in patients with abdominal pain.

OBJECTIVE: To determine whether availability of a final radiologist report versus an experienced senior resident preliminary report prior to disposition affects major care outcomes in emergency department (ED) patient presenting with abdominal pain undergoing abdominopelvic CT. MATERIALS AND METHODS: This single-institution, IRB-approved, HIPAA-compliant retrospective cohort study included 5019 ED patients with abdominal pain undergoing abdominopelvic CT from October 2015 to April 2019. Patients were categorized as being dispositioned after either an experienced senior resident preliminary report (i.e., overnight model) or the final attending radiologist interpretation (i.e., daytime model) of the CT was available. Multivariable regression models were built accounting for demographic data, clinical factors (vital signs, ED triage score, laboratory data), and disposition timing to analyze the impact on four important patient outcomes: inpatient admission (primary outcome), readmission (within 30 days), second operation within 30 days, and death. RESULTS: In the setting of an available experienced senior resident preliminary report, timing of the final radiologist report (before vs. after disposition) was not a significant multivariable predictor of inpatient admission (p = 0.63), readmission within 30 days (p = 0.66), second operation within 30 days (p = 0.09), or death (p = 0.63). Unadjusted event rates for overnight vs daytime reports, respectively, were 37.2% vs. 38.0% (inpatient admission), 15.9% vs. 16.5% (30-day readmission), 0.65% vs. 0.3% (second operation within 30 days), and 0.85% vs. 1.3% (death). CONCLUSION: Given the presence of an experienced senior resident preliminary report, availability of a final radiology report prior to ED disposition did not affect four major clinical care outcomes of patients with abdominal pain undergoing abdominopelvic CT.

Impacting Satisfaction, Learning, and Efficiency Through Structured Interdisciplinary Rounding in a Pediatric Intensive Care Unit: A Quality Improvement Project.

BACKGROUND: Daily rounds in many pediatric intensive care units (PICUs) vary in quality, duration, and participation. We hypothesized that implementing structured interdisciplinary bedside rounds (SIBR®) would improve our rounding process. METHODS: This was a quality improvement initiative in a 25-bed multidisciplinary PICU in a tertiary children's hospital. Baseline data included rounding duration; participation of nurses, respiratory care practitioners (RCP), parents; and physician order read-back practices. Interventions were implementing pre-rounding huddles, changing the start of the rounding week, and instituting a SIBR model. All staff, consecutive patients and parents participated over 18 months. We used Mann-Whitney, z-test, and t-tests for statistical analysis with a significance level of 0.05. We tracked data with a statistical process control chart. RESULTS: Rounds participation increased for nurses (88% to 100%), RCPs (13% to 61%), and families (24% to 49%) (all p <0.001). Physician order read-back increased (41% to 79%) (p<0.001). The median length of stay (LOS) decreased from 2.1 to 1.9 days (p=0.004) with no changes in mortality or readmissions. The proportion of top responses from family surveys increased from 0.69 to 0.76 (p<0.001). PICU rounding duration (minutes/patient) decreased from 17.1 to 11.3. Most resident physicians felt SIBR positively impacted their education (70%), was more effective than rounds without structure (97%), and that family presence positively impacted learning (70%). CONCLUSIONS: Implementing a SIBR process in our PICU resulted in greater family and staff satisfaction, improved workflow and decreased rounding time by 34% without compromising education. LOS decreased significantly with no increases in mortality or readmissions.

Gradual hypertension induction in middle-aged Cyp1a1-Ren2 transgenic rats produces significant impairments in spatial learning.

Hypertension is a major health concern in the developed world, and its prevalence increases with advancing age. The impact of hypertension on the function of the renal and cardiovascular systems is well studied; however, its influence on the brain regions important for cognition has garnered less attention. We utilized the Cyp1a1-Ren2 xenobiotic-inducible transgenic rat model to mimic both the age of onset and rate of induction of hypertension observed in humans. Male, 15-month-old transgenic rats were fed 0.15% indole-3-carbinol (I3C) chow to slowly induce renin-dependent hypertension over a 6-week period. Systolic blood pressure significantly increased, eventually reaching 200 mmHg by the end of the study period. In contrast, transgenic rats fed a control diet without I3C did not show significant changes in blood pressure (145 mmHg at the end of study). Hypertension was associated with cardiac, aortic, and renal hypertrophy as well as increased collagen deposition in the left ventricle and kidney of the I3C-treated rats. Additionally, rats with hypertension showed reduced savings from prior spatial memory training when tested on the hippocampus-dependent Morris swim task. Motor and sensory functions were found to be unaffected by induction of hypertension. Taken together, these data indicate a profound effect of hypertension not only on the cardiovascular-renal axis but also on brain systems critically important for learning and memory. Future use of this model and approach may empower a more accurate investigation of the influence of aging on the systems responsible for cardiovascular, renal, and neurological health.

Improving operating room efficiency in academic children's hospital using Lean Six Sigma methodology.

BACKGROUND/PURPOSE: Lean Six Sigma (LSS) is a process improvement methodology that utilizes a collaborative team effort to improve performance by systematically identifying root causes of problems. Our objective was to determine whether application of LSS could improve efficiency when applied simultaneously to all services of an academic children's hospital. METHODS: In our tertiary academic medical center, a multidisciplinary committee was formed, and the entire perioperative process was mapped, using fishbone diagrams, Pareto analysis, and other process improvement tools. Results for Children's Hospital scheduled main operating room (OR) cases were analyzed, where the surgical attending followed themselves. RESULTS: Six hundred twelve cases were included in the seven Children's Hospital operating rooms (OR) over a 6-month period. Turnover Time (interval between patient OR departure and arrival of the subsequent patient) decreased from a median 41min in the baseline period to 32min in the intervention period (p<0.0001). Turnaround Time (interval between surgical dressing application and subsequent surgical incision) decreased from a median 81.5min in the baseline period to 71min in the intervention period (p<0.0001). CONCLUSION: These results demonstrate that a coordinated multidisciplinary process improvement redesign can significantly improve efficiency in an academic Children's Hospital without preselecting specific services, removing surgical residents, or incorporating new personnel or technology. STUDY TYPE: Prospective comparative study, Level II.

Increased angiotensinogen expression, urinary angiotensinogen excretion, and tissue injury in nonclipped kidneys of two-kidney, one-clip hypertensive rats.

In angiotensin II (ANG II)-dependent hypertension, there is an angiotensin type 1 receptor-dependent amplification mechanism enhancing intrarenal angiotensinogen (AGT) formation and secretion in the tubular fluid. To evaluate the role of increased arterial pressure, AGT mRNA, protein expression, and urinary AGT (uAGT) excretion and tissue injury were assessed in both kidneys of two-kidney, one-clip Sprague-Dawley hypertensive rats subjected to left renal arterial clipping (0.25-mm gap). By 18-21 days, systolic arterial pressure increased to 180 ± 3 mmHg, and uAGT increased. Water intake, body weights, 24-h urine volumes, and sodium excretion were similar. In separate measurements of renal function in anesthetized rats, renal plasma flow and glomerular filtration rate were similar in clipped and nonclipped kidneys and not different from those in sham rats, indicating that the perfusion pressure to the clipped kidneys remained within the autoregulatory range. The nonclipped kidneys exhibited increased urine flow and sodium excretion. The uAGT excretion was significantly greater in nonclipped kidneys compared with clipped and sham kidneys. AGT mRNA was 2.15-fold greater in the nonclipped kidneys compared with sham (1.0 ± 0.1) or clipped (0.98 ± 0.15) kidneys. AGT protein levels were also greater in the nonclipped kidneys. The nonclipped kidneys exhibited greater glomerular expansion and immune cell infiltration, medullary fibrosis, and cellular proliferation than the clipped kidneys. Because both kidneys have elevated ANG II levels, the greater tissue injury in the nonclipped kidneys indicates that an increased arterial pressure synergizes with increased intrarenal ANG II to stimulate AGT production and exert greater renal injury.

Repeatability of selective laser trabeculoplasty.

PURPOSE: To determine the intraocular pressure (IOP)-lowering efficacy of repeat 360° selective laser trabeculoplasty (SLT) in patients with open-angle glaucoma having undergone prior successful 360° SLT. METHODS: A retrospective chart review of 38 eyes of 38 patients with open-angle glaucoma (primary, pseudoexfoliation or pigmentary glaucoma) uncontrolled on medical therapy who had undergone two successive 360° SLT treatments, in whom first SLT was deemed clinically successful through a minimum of 6 months follow-up and who were followed for a minimum of 30 days after second SLT. Mean IOP at each postoperative time point (1, 3, 6, 12, 18 and 24 months) was compared with baseline using paired t tests. IOP changes after initial and repeat SLT were evaluated separately. RESULTS: Mean (SD) baseline IOP before initial SLT was 21.6 (4.8) mm Hg. Mean IOP following initial SLT was significantly below baseline through 24 months of follow-up, with mean IOP at months 1-24 ranging from 15.9 to 18.6 mm Hg. Mean baseline IOP before repeat SLT was 19.1 (3.9) mm Hg, with a significant reduction in IOP from baseline through 24 months follow-up with mean IOP ranging from 14.7 to 17.0 mm Hg. Kaplan-Meier survival analysis showed longer median survival time for repeat SLT compared with initial SLT. No safety issues were observed with repeat SLT. CONCLUSIONS: Repeat SLT can restore IOP control in eyes with open-angle glaucoma that have previously undergone successful initial SLT. Repeat SLT achieves comparable absolute level of IOP control achieved by initial SLT.

Use of Advanced Practice Providers as Part of the Urologic Healthcare Team.

Advanced practice providers (APPs) are advanced practice nurses (APN)/nurse practitioners (NP) or physician assistants. Over half of urologists currently employ APPs to extend and enhance their practice. Because APPs can fulfill a variety of roles from surgical assisting to running their own subspecialty clinic, they have emerged as a vital solution to alleviating the looming workforce shortage in urology practice. About 40 % of practicing urologists have not yet incorporated APPs into their practices. Some may still be unfamiliar with the concept of utilizing advanced practice providers, some have concerns about liability or scope of practice, and some are just getting started. Recently, the American Urological Association (AUA) published a consensus statement on advanced practice providers that provides urologists a comprehensive review regarding the education, training, Medicare reimbursement policies, applicable state laws, liability concerns, and examples of utilization of advanced practice providers within a urology practice. The consensus statement represented one of the most comprehensive compendiums of information specific to advanced practice providers in a urologic practice. This review will touch on the AUA Consensus Statement on Advanced Practice Providers, background information that informed that statement, as well as recent responses to the publication.

Renoprotective effects of direct renin inhibition in glomerulonephritis.

The development of glomerulonephritis causes glomerular injury and renal dysfunction and is thought to increase renin release, thus activating the renin-angiotensin system (RAS). The aims of this study were to demonstrate activation of the intrarenal RAS and determine the effects of direct renin inhibition (DRI) on the progression of glomerulonephritis. Rats were treated with anti-Thy1.1 antibody with or without DRI, aliskiren (30 mg/kg/d). In the glomerulonephritic rats, protein, microalbumin excretion levels, urinary angiotensinogen excretion, glomerular expansion score and intrarenal transforming growth factor-ß and plasminogen activator inhibitor-1 mRNA levels were augmented compared with control rats; however, hypertension was not observed in the glomerulonephritic rats, and aliskiren treatment did not modify their blood pressure. The increases in urinary protein (94.7 ± 13.0 mg/d) and microalbumin (7.52 ± 2.6 mg/d) excretion were reduced by aliskiren (43.6 ± 4.5 mg/d of protein and 2.57 ± 0.7 mg/d of microalbumin). Furthermore, the progression of glomerular expansion and elevation of intrarenal transforming growth factor-ß and plasminogen activator inhibitor-1 levels were prevented by aliskiren. Importantly, aliskiren suppressed the augmentation of urinary angiotensinogen levels, the increased angiotensinogen expression in the kidneys and the increases in Ang II levels in renal medulla induced by the anti-Thy1.1 antibody. These results suggest that DRI with aliskiren prevents intrarenal RAS activation leading to mitigation of the development of glomerulonephritis. In addition, the renoprotective effects of DRI on glomerulonephritis occur in a blood pressure-independent manner. Accordingly, treatment with aliskiren may be an effective approach to treat glomerulonephritis and other intrarenal RAS-associated kidney diseases.

Renal nitric oxide synthase and antioxidant preservation in Cyp1a1-Ren-2 transgenic rats with inducible malignant hypertension.

BACKGROUND: Dietary administration of 0.30% indole-3-carbinol (I3C) to Cyp1a1-Ren2 transgenic rats (TGRs) generates angiotensin II (ANG II)-dependent malignant hypertension (HTN) and increased renal vascular resistance. However, TGRs with HTN maintain a normal or slightly reduced glomerular filtration rate. We tested the hypothesis that maintenance of renal function in hypertensive Cyp1a1-Ren2 TGRs is due to preservation of the intrarenal nitric oxide (NO) and antioxidant systems. METHODS: Kidney cortex, kidney medulla, aortic endothelial (e) and neuronal (n) nitric oxide synthase (NOS), superoxide dismutases (SODs), and p22phox (nicotinamide adenine dinucleotide phosphate-oxidase subunit) protein abundances were measured along with kidney cortex total antioxidant capacity (TAC) and NOx. TGRs were fed a normal diet that contained 0.3% I3C or 0.3% I3C + candesartan (AT1 receptor antagonist; 25mg/L in drinking water) (n = 5-6 per group) for 10 days. RESULTS: Blood pressure increased and body weight decreased in I3C-induced TGRs, while candesartan blunted these responses. Abundances of NOS, SOD, and p22phox as well as TAC were maintained in the kidney cortex of I3C-induced TGRs with and without candesartan, while kidney cortex NOx production increased in both groups. Kidney medulla eNOS and extracellular (EC) SOD decreased and nNOS were unchanged in both groups of I3C-induced TGRs. In addition, a compensatory increase occurred in kidney medulla Mn SOD in I3C-induced TGRs + candesartan. Aortic eNOS and nNOS∝ fell and p22phox and Mn SOD increased in hypertensive I3C-induced TGRs; all changes were reversed with candesartan. CONCLUSIONS: The preservation of renal cortical NO and antioxidant capacity is associated with preserved renal function in Cyp1a1-Ren2 TGRs with ANG II-dependent malignant HTN.

Psychometric properties of the Quick Inventory of Depressive Symptomatology (QIDS-SR) in UK primary care.

It is widely believed that severity of depressive disorder should guide treatment selection and many guidelines emphasise this factor. The Quick Inventory of Depressive Symptomatology (QID-SR16) is a self-complete measure of depression severity which includes all DSM-IV criterion symptoms for major depressive disorder. The object of this study was to assess the psychometric properties of the QIDS-SR16 in a primary care sample. Adult primary care patients completed the QIDS-SR16 and were assessed by a psychiatrist (blind to QIDS-SR16) with the 17-item Hamilton Rating Scale for Depression (GRID-HAMD). Internal consistency, homogeneity and convergent and discriminant validity of the QIDS-SR16 were assessed. Severity cut-off scores for QIDS-SR16 were assessed for convergence with HRSD-17 cut-offs. Published methods for converting scores to HRSD-17 were also assessed. Two hundred and eighty-six patients participated: mean age = 49.5 (s.d. = 13.8), 68% female, mean HRSD-17 = 12.6 (s.d. = 7.6). The QIDS-SR16 exhibited acceptable internal consistency (Cronbach's alpha = 0.86), a robust factor structure indicating one underlying dimension and correlated highly with the HRSD-17 (r = 0.79) but differed significantly in how it categorised the severity of depression relative to the HRSD-17 (Wilcoxon Signed Rank Test p < 0.001). Using published methods to convert QIDS-SR16 scores to HRSD-17 scores did not result in alignment of severity categorisation. In conclusion, psychometric properties of the QIDS-SR16 were found to be strong in terms of internal consistency, factor structure and convergent and discriminant validity. Using conventional scoring and conversion methods the scale was found not to concur with the HRSD-17 in categorising the severity of depressive symptoms.

Increased neuronal activity in the OVLT of Cyp1a1-Ren2 transgenic rats with inducible Ang II-dependent malignant hypertension.

The contribution of angiotensin II (Ang II) to the pathophysiology of hypertension is established based on facts that high levels of circulating Ang II increase vasoconstriction of peripheral arteries causing a rise in blood pressure (BP). In addition, circulating Ang II has various effects on the central nervous system, including the osmosensitive neurons in the organum vasculosum of the lamina terminalis (OVLT). Osmosensitive neurons in the OVLT transduce hypertonicity via the activation of the nonselective cation channel known as transient receptor potential vanilloid 1 (TRPV1), causing membrane depolarization, followed by increased action potential discharge. This effect is absent in mice lacking expression of the TRPV1 gene. Most observations related to the importance of the OVLT in cardiovascular control are mainly based on models of lesion of the entire preoptic periventricular tissue. However, it remains unclear whether neuronal activity and TRPV1 protein expression levels alter in the OVLT of Cyp1a1-Ren2 transgenic rats with inducible Ang II-dependent malignant hypertension. C-fos was used as a marker of neuronal activity. Immunostaining was used to demonstrate distribution of c-fos positive neurons in the OVLT of Cyp1a1Ren2 transgenic rats. Western blot analysis showed increased c-fos and TRPV1 total protein expression levels in the OVLT of hypertensive rats. The present findings demonstrate increased c-fos and TRPV1 expression levels in the OVLT of Cyp1a1-Ren2 transgenic rats with Ang II-dependent malignant hypertension.

Chronic direct renin inhibition with aliskiren prevents the development of hypertension in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent hypertension.

INTRODUCTION: This study was performed to determine whether chronic direct renin inhibition can prevent the development of slowly progressive angiotensin (ANG) II-dependent hypertension and the associated derangements in renal function in Cyplal-Ren2 transgenic rats with inducible expression of the Ren2 gene. METHODS: Male Cyplal-Ren2 rats (n = 6) were fed a normal diet containing 0.15% indole-3-carbinol (I3C) for 16 days to induce slowly progressive ANG II-dependent hypertension. Conscious systolic blood pressure was measured daily using tail-cuff plethysmography. The rats were then anesthetized with pentobarbital sodium and surgically prepared for the measurement of mean arterial pressure (MAP) and renal hemodynamics and excretory function. RESULTS: In rats induced with I3C, systolic blood pressure increased by day 3 (130 ± 7-160 ± 5 mm Hg, P < 0.01) and continued to increase to 191 ± 6 mm Hg (P < 0.001) by day 16. In a separate group of rats (n = 6), chronic administration of the direct renin inhibitor, aliskiren (30 mg/kg/d, sc), prevented the development of hypertension (113 ± 5 versus 114 ± 5 mm Hg, not significant). Rats treated with aliskiren exhibited significantly lower mean arterial pressure (138 ± 4 versus 201 ± 6 mm Hg, P < 0.001), renal vascular resistance (23 ± 4 versus 38 ± 3 mm Hg/mL/min · g, P < 0.01), urine flow (17.6 ± 1.4 versus 25.1 ± 2.9 µL/min, P < 0.05) and urinary sodium excretion (1.11 ± 0.32 versus 2.35 ± 0.28 µEq/min, P < 0.05) and higher renal plasma flow (4.22 ± 0.23 versus 2.56 ± 0.21 mL/min · g, P < 0.01) and glomerular filtration rate (1.19 ± 0.07 versus 0.78 ± 0.08 mL/min · g, P< 0.01), compared with induced rats not treated chronically with aliskiren. CONCLUSIONS: The present findings demonstrate that chronic direct renin inhibition with aliskiren prevents the development of ANG II-dependent hypertension and the associated derangements in renal hemodynamics and excretory function in Cyplal-Ren2 transgenic rats.

Imatinib ameliorates renal morphological changes in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension.

The present study was performed to assess the effects of the platelet-derived growth factor (PDGF) receptor kinase inhibitor imatinib mesylate on the renal morphological changes occurring during the development of malignant hypertension in transgenic rats with inducible expression of the Ren2 gene [TGR(Cyp1a1Ren2)]. Arterial blood pressure was measured by radiotelemetry in male Cyp1a1-Ren2 rats during control conditions and during dietary administration of indole-3-carbinol (I3C; 0.3%) for 14 days to induce malignant hypertension. Rats induced with I3C (n = 5) had higher mean arterial pressures (178 ± 4 vs. 109 ± 2 mmHg, P < 0.001) and increased urinary albumin excretion (Ualb; 13 ± 5 vs. 0.6 ± 0.2 mg/day) compared with noninduced rats (n = 5). Chronic administration of imatinib (60 mg·kg(-1)·day(-1) in drinking water, n = 5) did not alter the magnitude of the hypertension (176 ± 8 mmHg) but prevented the increase in Ualb (1.6 ± 0.3 mg/day). Quantitative analysis of proliferating cell nuclear antigen using immunohistochemistry demonstrated increased proliferating cell number in cortical tubules (38 ± 5 vs. 18 ± 1 cells/mm(2)) and cortical interstitium (40 ± 7 vs. 13 ± 6 cells/mm(2)) of hypertensive rat kidneys. Renal cortical fibrosis evaluated by picrosirius red staining showed increased collagen deposition in kidneys of the hypertensive rats (1.6 ± 0.1 vs. 0.4 ± 0.1% of cortical area). Imatinib attenuated the increase in proliferating cell number in cortical tubules and interstitium (22 ± 5 vs. 38 ± 5 and 22 ± 6 vs. 40 ± 7 cells/mm(2), respectively) and reduced the degree of collagen deposition (0.8 ± 0.2 vs. 1.6 ± 0.1%) in the kidneys of hypertensive rats. These findings demonstrate that the renal pathological changes that occur during the development of malignant hypertension in Cyp1a1-Ren2 rats involve activation of PDGF receptor kinase.