The epidemiology and management of severe hypertension

Hypertension guidelines stress that patients with severe hypertension (systolic blood pressure (BP)⩾180 or diastolic BP⩾110 mm Hg) require multiple drugs to achieve control and should have close follow-up to prevent adverse outcomes. However, little is known about the epidemiology or actual management of these patients. We retrospectively studied 59 207 veterans with hypertension. Patients were categorized based on their highest average BP over an 18-month period (1 July 1999 to 31 December 2000) as controlled (<140/90 mm Hg), mild (140–159/90–99 mm Hg), moderate (160–179/100–109 mm Hg) and severe hypertension. We examined severe hypertension prevalence, pattern, duration, associated patient characteristics, time to subsequent visit, percentage of visits with a medication increase, and final BP control and antihypertensive medication adequacy. Twenty-three per cent had ⩾1 visit with severe hypertension, 42% of whom had at least two such visits; median day with severe hypertension was 80 (range 1–548). These subjects were significantly older, more likely black, and with more comorbidities than other hypertension subjects. Medication increases occurred at 20% of visits with mild hypertension compared to 40% with severe hypertension; P<0.05). At study end, 76% of patients with severe hypertension remained uncontrolled; severe hypertension subjects with uncontrolled BP were less likely to be on adequate therapy than those with controlled BP (43.7 vs 45.4%). Among hypertensive veterans, severe hypertension episodes are common. Many subjects had relatively prolonged elevations, with older, sicker subjects at highest risk. Although, follow-up times are shorter and antihypertensive medication use greater in severe hypertension subjects, they are still not being managed aggressively enough. Interventions to improve providers' management of these high-risk patients are needed

Investigation of Natural Products as Novel Antimicrobial Agents Against the Pseudomonas aeruginosa Type III Secretion System

As antibiotic resistance among bacterial pathogens continues to escalate, posing an immense threat to global health, the discovery and development of alternative antimicrobial therapies has become critical. The type III secretion system (T3SS) is a virulence factor used by dozens of Gram-negative bacterial pathogens to cause disease. The T3SS acts as a needle-like apparatus to modulate host defenses through the injection of effector proteins into target host cells. This extracellular appendage is an attractive target for new antimicrobial therapies due to its high conservation among pathogenic bacteria such as Salmonella, Chlamydia, and Pseudomonas, its widespread absence in commensal flora, and its critical role in causing disease. In a campaign to discover molecules that inhibit the T3SS, we have screened four unique and diverse natural product-derived libraries for their inhibitory bioactivity against a strain of P. aeruginosa harboring a T3SS promoter-controlled luciferase. One marine bacterial extract was shown to inhibit T3SS-driven bioluminescence and, importantly, did not act as a general luciferase inhibitor, affect bacterial viability, or perturb mammalian cell viability. The purified bioactive compound, identified as sebastenoic acid, inhibited T3SS effector protein secretion in a dose-dependent manner. Interestingly, sebastenoic acid was previously found to affect motility and biofilm formation in Vibrio cholera, both of which are linked to cyclic-di-GMP. In Pseudomonas, synthesis of the T3SS global regulator, ExsA, is inhibited by cyclic di-GMP through cAMP-Vfr signaling, suggesting that sebastenoic may play a role in modulating cyclic-di-GMP levels. In addition to sebastenoic acid, we also identified marine fungal-derived penicillic acid as a T3SS inhibitor. Penicillic acid inhibited T3SS effector secretion in a dose dependent manner without affecting bacterial viability, however, its known toxicity to mammalian cells complicates its further development as a potential therapeutic. Notably, penicillic acid was previously shown to be bioactive against both biofilm alginate biosynthesis and quorum sensing, two processes which are typically anti-regulated with the T3SS. Lastly, we identified an additional six bioactive extracts from Burkholderia-derived natural products and five bioactive extracts from marine-derived natural products for future small molecule inhibitor discovery

PRACTICAL AND QUANTITATIVE ASPECTS IN THE ANALYSIS OF FITC AND DTAF AMINO-ACID DERIVATIVES BY CAPILLARY ELECTROPHORESIS AND LIF DETECTION.

Practical aspects related to the preparation of the fluorescein isothiocyanate (FITC) and dichlorotriazinylaminofluorescein (DTAF) derivatives of amino acids for purposes of quantitative analysis are examined and factors affecting quantification are discussed. It is shown that the labelling reaction for both reagents can be speeded up by operating at 40 degrees C. The difficulties with derivatizing amino acids at detectable concentrations are highlighted. In spite of the high sensitivity of CE-LIF, detection sensitivity in real applications is limited by factors external to the analytical process, such as the label chemistry.Practical aspects related to the preparation of the fluorescein isothiocyanate (FITC) and dichlorotriazinylaminofluorescein (DTAF) derivatives of amino acids for purposes of quantitative analysis are examined and factors affecting quantification are discussed. It is shown that the labelling reaction for both reagents can be speeded up by operating at 40 degrees C. The difficulties with derivatizing amino acids at detectable concentrations are highlighted. In spite of the high sensitivity of CE-LIF, detection sensitivity in real applications is limited by factors external to the analytical process, such as the label chemistry.A