Effects of metronidazole and probiotics oligosaccharide on bacterial translocation in protein malnutrition

The present study aims to evaluate the effects of metronidazole, probiotics oligosaccharide on indigenous microflora and bacterial translocation (BT) in protein malnourished rats. Thirty male Wistarrats were divided into three groups: protein malnourished rats PM (group1, n = 10) were fed with maize only, protein malnourished rats (group 2, n = 10) were received metronidazole and protein malnourished rats (group 3, n = 10) were received both metronidazole and probiotics-oligosaccharide for fifteen days. Metronidazole (1000 mg/kg/day) was given via an orogastric feeding tube to the second and third groups. Lyophilized probiotics-oligosaccharide (0.5 mg/g body weight/day) was given in two doses via the same route to the third group. All animals were sacrificed after fifteen days of protein malnutrition and cultures of the mesenteric lymph nodes (MLNs), liver, spleen and cecal contents were done. Theincidence of bacterial translocation (BT) was 30% (3/10) in protein malnourished group 1,60% (06/10) in group 2 where protein malnutrition was associated with metronidazole and 25% (2.5/10) in group 3whose animals were subjected to protein malnutrition associated with metronidazole and probiotics oligosaccharide. A significant increase in the BT incidence was found in group 2 (P < 0.05), while a significant decrease was found in group 3 when compared to group 1. The total bacterial count of cecal flora was significantly low in group 3 than in group 1 (P < 0.01). These results suggest that the incidence of BT in protein malnutrition is increased by using an antibiotic while probioticsoligosaccharide decreases this incidence in protein malnutrition induced by antibiotic. Thus, weconclude that probiotics-oligosaccharide can effectively protect the intestinal mucosa and prevent BT in protein malnourished infants

Interventricular Differences in β‐Adrenergic Responses in the Canine Heart: Role of Phosphodiesterases

Background RV and LV have different embryologic, structural, metabolic, and electrophysiologic characteristics, but whether interventricular differences exist in β‐adrenergic (β‐AR) responsiveness is unknown. In this study, we examine whether β‐AR response and signaling differ in right (RV) versus left (LV) ventricles. Methods and Results Sarcomere shortening, Ca2+ transients, ICa,L and IKs currents were recorded in isolated dog LV and RV midmyocytes. Intracellular [cAMP] and PKA activity were measured by live cell imaging using FRET‐based sensors. Isoproterenol increased sarcomere shortening ≈10‐fold and Ca2+‐transient amplitude ≈2‐fold in LV midmyocytes (LVMs) versus ≈25‐fold and ≈3‐fold in RVMs. FRET imaging using targeted Epac2camps sensors revealed no change in subsarcolemmal [cAMP], but a 2‐fold higher β‐AR stimulation of cytoplasmic [cAMP] in RVMs versus LVMs. Accordingly, β‐AR regulation of ICa,L and IKs were similar between LVMs and RVMs, whereas cytoplasmic PKA activity was increased in RVMs. Both PDE3 and PDE4 contributed to the β‐AR regulation of cytoplasmic [cAMP], and the difference between LVMs and RVMs was abolished by PDE3 inhibition and attenuated by PDE4 inhibition. Finally LV and RV intracavitary pressures were recorded in anesthetized beagle dogs. A bolus injection of isoproterenol increased RV dP/dtmax≈5‐fold versus 3‐fold in LV. Conclusion Canine RV and LV differ in their β‐AR response due to intrinsic differences in myocyte β‐AR downstream signaling. Enhanced β‐AR responsiveness of the RV results from higher cAMP elevation in the cytoplasm, due to a decreased degradation by PDE3 and PDE4 in the RV compared to the LV

Cyclic Nucleotide Phosphodiesterases and Compartmentation in Normal and Diseased Heart

International audienceCyclic nucleotide phosphodiesterases (PDEs) degrade the second messengers cAMP and cGMP, thereby regulating multiple aspects of cardiac function. This highly diverse class of enzymes encoded by 21 genes encompasses 11 families which are not only responsible for the termination of cyclic nucleotide signalling, but are also involved in the generation of dynamic microdomains of cAMP and cGMP controlling specific cell functions in response to various neurohormonal stimuli. In myocardium, the PDE3 and PDE4 families are predominant to degrade cAMP and thereby regulate cardiac excitation-contraction coupling. PDE3 inhibitors are positive inotropes and vasodilators in human, but their use is limited to acute heart failure and intermittent claudication. PDE5 is particularly important to degrade cGMP in vascular smooth muscle, and PDE5 inhibitors are used to treat erectile dysfunction and pulmonary hypertension. However, these drugs do not seem efficient in heart failure with preserved ejection fraction. There is experimental evidence that these PDEs as well as other PDE families including PDE1, PDE2 and PDE9 may play important roles in cardiac diseases such as hypertrophy and heart failure. After a brief presentation of the cyclic nucleotide pathways in cardiac cells and the major characteristics of the PDE superfamily, this chapter will present their role in cyclic nucleotide compartmentation and the current use of PDE inhibitors in cardiac diseases together with the recent research progresses that could lead to a better exploitation of the therapeutic potential of these enzymes in the future