From Physiology to Pharmacy: Developments in the Pathogenesis and Treatment of Recurrent Urinary Tract Infections

Urinary tract infections (UTIs) are common, and over half of women report having had at least one in their lifetime. Nearly a third of these women experience recurrent UTI episodes, but the mechanisms of these recurrences are not fully elucidated. Frequent use of antimicrobials for treatment and prevention of UTIs and other infections has contributed to the evolution of multidrug-resistant microorganisms globally. This is a looming worldwide crisis that has created an urgent need for novel strategies for the treatment and prevention of UTIs. Furthering our understanding of the mechanisms of recurrent UTIs, from both host and bacterial perspectives, will be paramount in developing targeted management strategies. In this review, we discuss recent findings regarding recurrent UTIs in women, including progress in our understanding of the mechanisms of recurrence as well as emerging treatments.     

Applicability of available methods for incidence estimation among blood donors

Incidence rates of major transfusion transmissible viral infections have been estimated through widely used seroconversion approaches and recently developed methods.A quality database for blood donors and donations with the capacity to track donation history of each donor is the basis for incidence estimation and many other epidemiological studies.Depending on available data,different ways have been used to determine incidence rates based on conversion from uninfected to infected status among repeat donors.Reports of incidence estimates need to clearly describe specific ways that are used to derive such estimates so that readers can take into account any methodological differences that may exist when they compare incidence estimates from different studies.The recently developed methods,including the sensitive/less sensitive testing strategy for HIV,the NAT yield method and the HBsAg yield method as well as the prevalence-based approaches,are alternative options for estimating incidence,especially in donor populations where seroconversion approaches are not feasible.Their applicability needs to be examined before their use and results derived from these methods need to be reviewed with their assumptions and potential limitations in mind.     

The four As associated with pathological Parkinson disease gamblers: anxiety, anger, age, and agonists

Several studies have related pathological gambling in PD to dopamine agonist therapy. A mail-in survey was sent to PD patients seen at the University of Florida Movement Disorders Center to determine gambling frequency and behavior, and any lifestyle or environmental factors associated with compulsive gambling in PD. 462 surveys were sent and 127 completed surveys were returned, of which ten were from patients who met criteria for compulsive gambling. All ten were taking dopamine agonists coincident with the compulsive gambling. Compulsive gamblers were younger, and psychological distress measures revealed that compulsive gamblers exhibited higher levels of anxiety, anger, and confusion. Thus in this cohort, we have uncovered the several characteristics of the most likely PD compulsive gambler, namely: (young) age, “angry”, “anxious”, and using a (dopamine) agonist.     

Triiodothyronine Increases Contractility Independent of beta-Adrenergic Receptors or Stimulation of Cyclic-3',5'-Adenosine Monophosphate

Background: Triiodothyronine regulates cardiac contractility; however, the mechanisms by which it produces its acute contractile effects remains unknown. We compared the acute effects of thyroid hormones (triiodothyronine [T3] and thyroxine [T4]) and of isoproterenol on the contractility of isolated rat hearts. In addition, we sought to determine whether the acute inotropic effects of thyroid hormones were mediated by beta-adrenergic receptors or by increased production of cyclic-3',5'-adenosine monophosphate (cAMP).

Methods: A Langendorff heart preparation harvested from euthyroid male Sprague-Dawley rats was used. Drugs were administered through an aortic perfusion catheter. A pressure-transduced left-ventricular balloon catheter measured pressure and heart rate changes. Changes in the maximum positive rate of change in pressure (dP/dT) and maximum negative dP/dT were determined. Responses to varying doses of T3, T sub 4, and isoproterenol were assessed in the presence and absence of beta-adrenergic receptor blockade with propranolol, cAMP production, measured by radioimmunoassay, was determined in myocardial cell suspensions after incubation with T3 or isoproterenol.

Results: T3 0.74 nmol rapidly and significantly increased maximum dP/dT by 335 plus/minus 38 mmHg/s within 30 s after bolus injection; however, contractility was unchanged after as much as 12.9 nmol T4. The maximal increase in dP/dT after 0.8 nmol isoproterenol was comparable to that produced by T3. However, the cardiotonic actions of isoproterenol were significantly slower to develop (peaking at 60 vs. 15 s) and lasted longer than those of T3. Pretreatment with propranolol 1 micro mol diminished the contractile effects of isoproterenol but had no effect on those of T3. Concentrations of isoproterenol that increase contractility also significantly increased cAMP production in isolated rat myocardial cells. However, T3 failed to increase cAMP production.     

C‐terminal agrin fragment is inversely related to neuromuscular fatigue in older men

Introduction: The aim of this study was to examine the relationship between serum C‐terminal agrin fragment (CAF) concentrations and neuromuscular fatigue in older adults. Methods: Twenty‐two healthy older men and women volunteered for this study. Resting fasted blood samples were collected and prepared for measurement of serum CAF concentration by a commercially available ELISA kit. The onset of neuromuscular fatigue was measured by monitoring electromyographic fatigue curves from the vastus lateralis muscle using the physical working capacity at fatigue threshold (PWC_FT) test. Results: A significant inverse correlation for men was observed between CAF and PWC_FT (r = ?0.602; P = 0.05), but not for women (r = 0.208; P = 0.54). After controlling for age and body mass index, significant correlations (r = ?0.69; P = 0.042) remained for men, but not for women (r = 0.12; P = 0.76). Conclusions: These data suggest that serum CAF concentrations were significantly related to the onset of neuromuscular fatigue independent of age and BMI in men only. Muscle Nerve 51 : 132–133, 2015