Novel Acid-Activated Fluorophores Reveal a Dynamic Wave of Protons in the Intestine of Caenorhabditis elegans

Unlike the digestive systems of vertebrate animals, the lumen of the alimentary canal of C. elegans is unsegmented and weakly acidic (pH ~ 4.4), with ultradian fluctuations to pH > 6 every 45 to 50 seconds. To probe the dynamics of this acidity, we synthesized novel acid-activated fluorophores termed Kansas Reds. These dicationic derivatives of rhodamine B become concentrated in the lumen of the intestine of living C. elegans and exhibit tunable pKa values (2.3–5.4), controlled by the extent of fluorination of an alkylamine substituent, that allow imaging of a range of acidic fluids in vivo. Fluorescence video microscopy of animals freely feeding on these fluorophores revealed that acidity in the C. elegans intestine is discontinuous; the posterior intestine contains a large acidic segment flanked by a smaller region of higher pH at the posterior-most end. Remarkably, during the defecation motor program, this hot spot of acidity rapidly moves from the posterior intestine to the anterior-most intestine where it becomes localized for up to 7 seconds every 45 to 50 seconds. Studies of pH-insensitive and base-activated fluorophores as well as mutant and transgenic animals revealed that this dynamic wave of acidity requires the proton exchanger PBO-4, does not involve substantial movement of fluid, and likely involves the sequential activation of proton transporters on the apical surface of intestinal cells. Lacking a specific organ that sequesters low pH, C. elegans compartmentalizes acidity by producing of a dynamic hot spot of protons that rhythmically migrates from the posterior to anterior intestine

Infecções em cateteres venosos centrais de longa permanência: revisão da literatura Infection of long-term central venous catheters: review of the literature

Cateteres venosos de longa permanência são amplamente utilizados em pacientes com necessidade de acesso venoso por período prolongado. A infecção relacionada a esses cateteres permanece um desafio na prática clínica. Revisamos a literatura acerca da epidemiologia e tratamento das infecções relacionadas a cateteres. Staphylococcus aureus é a bactéria mais comumente isolada. Os cateteres semi-implantáveis apresentam taxas de infecção maiores que os totalmente implantáveis. O tratamento pode ser feito com locks, antibioticoterapia sistêmica e até mesmo com retirada do cateter, dependendo do tipo de infecção, do microrganismo isolado e das condições clínicas do paciente. O salvamento do cateter deve ser tentado sempre que possível.<br>Long-term venous catheters are widely used in patients with needs of venous access for prolonged periods. The infection related to these catheters remains a challenge in clinical practice. We reviewed the literature about infection epidemiology and treatment related to catheters. Staphylococcus aureus is the most common isolated bacteria. Tunneled catheters present higher infection rates than implanted ports. Treatment may consist in the use of locks, systemic antibiotics, and even catheter removal, depending on the kind of infection, the isolated microorganism, and the patient's clinical conditions. Catheter salvation should be tried whenever possible

Fungal biofilms in human disease

Fungal biofilms are an important clinical problem. A number of factors including the increasing use of indwelling medical devices wider prescription of broad spectrum antibiotics and an aging and more immuno-compromised patient population has combined to create an opportunity for yeasts and moulds to cause infection. It is also becoming increasingly clear that for a number of serious infections the development of a fungal biofilm is important in the pathophysiology of the infection.&lt;p&gt;&lt;/p&gt; This chapter will discuss the importance of fungal biofilms in different anatomical areas, will try to provide insights into how fungal biofilm infection should be diagnosed and treated and provide an explanation as to why biofilms may be difficult to treat effectively with routine antifungal regimens.&lt;p&gt;&lt;/p&gt; Finally it will discuss how our current level of knowledge of the development and biology of fungal biofilms may, in future, lead to a wider choice of therapeutic interventions.&lt;p&gt;&lt;/p&gt