First Evidence of Cardiac Stem Cells From the Left Ventricular Apical Tip in Patients With Left Ventricular Assist Device Implantation.

BACKGROUND: Recent studies have challenged the dogma that the adult heart is a postmitotic organ and raise the possibility of the existence of resident cardiac stem cells (CSCs). Our study aimed to explore if these CSCs are present in the "ventricular tip" obtained during left ventricular assist device (LVAD) implantation from patients with end-stage heart failure (HF) and the relationship with LV dysfunctional area extent. METHODS: Four consecutive patients with ischemic cardiomyopathy and end-stage HF submitted to LVAD implantation were studied. The explanted "ventricular tip" was used as a sample of apical myocardial tissue for the pathological examination. Patients underwent clinical and echocardiographic examination, both standard transthoracic echocardiography (TTE) and speckle tracking echocardiography (STE), before LVAD implantation. RESULTS: All patients presented severe apical dysfunction, with apical akinesis/diskinesis and very low levels of apical longitudinal strain (-3.5 ± 2.9%). Despite this, the presence of CSCs was demonstrated in pathological myocardial samples of "ventricular tip" in all 4 of the patients. It was found to be a mean of 6 c-kit cells in 10 fields magnification 40×. CONCLUSIONS: Cardiac stem cells can be identified in the LV apical segment of patients who have undergone LVAD implantation despite LV apical fibrosis.

In vivo characterisation of a novel water-soluble Cyclosporine A prodrug for the treatment of dry eye disease.

Cyclosporine A (CsA) has been demonstrated to be effective for the treatment of a variety of ophthalmological conditions, including ocular surface disorders such as the dry eye disease (DED). Since CsA is characterised by its low water solubility, the development of a topical ophthalmic formulation represents an interesting pharmaceutical question. In the present study, two different strategies to address this challenge were studied and compared: (i) a water-soluble CsA prodrug formulated within an aqueous solution and (ii) a CsA oil-in-water emulsion (Restasis, Allergan Inc., Irvine, CA). First, the prodrug formulation was shown to have an excellent ocular tolerance as well as no influence on the basal tear production; maintaining the ocular surface properties remained unchanged. Then, in order to allow in vivo investigations, a specific analytical method based on ultra high pressure liquid chromatography coupled with triple quadrupole mass spectrometer (UHPLC-MS/MS) was developed and optimised to quantify CsA in ocular tissues and fluids. The CsA ocular kinetics in lachrymal fluid for both formulations were found to be similar between 15 min and 48 h. The CsA ocular distribution study evidenced the ability of the prodrug formulation to penetrate into the eye, achieving therapeutically active CsA levels in tissues of both the anterior and posterior segments. In addition, the detailed analysis of the in vivo data using a bicompartmental model pointed out a higher bioavailability and lower elimination rate for CsA when it is generated from the prodrug than after direct application as an emulsion. The interesting in vivo properties displayed by the prodrug solution make it a safe and suitable option for the treatment of DED.

Colloidal systems for the delivery of cyclosporin A to the anterior segment of the eye.

Due to the eye's specific anatomical and physiological conformation, the treatment of eye diseases is a real challenge for pharmaceutical therapy. The presence of efficient protective barriers (i.e., the conjunctival and corneal membranes) and protective mechanisms (i.e., blinking and nasolachrymal drainage) makes this organ particularly impervious to local drug therapy. To overcome these issues, numerous strategies have been envisioned using pharmaceutical technology. Many formulations currently on the market or still under development are emulsions or colloidal systems intended to enhance precorneal residence time and corneal penetration, causing a consequent increase in drug bioavailability after instillation. After a review of some recent developments in the field of cyclosporin A formulations for the eye, a novel micellar formulation of cyclosporine A based on a diblock methoxy-poly(ethylene glycol)-hexysubstituted poly(lactides) (MPEG-hexPLA) is described.

Wound levobupivacaine continuous infusion for postoperative analgesia in living kidney donors: case-control study.

INTRODUCTION: The objective of this study was to evaluate the efficacy of an analgesic regimen based on levobupivacaine continuous infusion into the surgical wound of living kidney donors (LKDs). PATIENTS AND METHODS: Fifty adult LKDs (mean age, 53.1 +/- 5.3 years; age range, 52-68 years) were retrospectively assigned to a no wound infusion (NWI) group (n = 25) or a wound infusion (WI) group (n = 25). At the end of surgery, patients in the WI group received 10 mg intramuscular morphine; a peridural catheter was placed 10 cm between the intercostal muscles fibers close to the lower rib extremity, and a solution of levobupivacaine, 150 mg/100 mL, was started at 5 ml/h(-1). Patients in the NWI group received intramuscular morphine, 10 mg, every 8 hours; intravenous tramadole, 100 mg, was planned as a rescue drug for incidental pain. Pain was measured using a visual analog scale (VAS) ranging from 1 (no pain) to 10 (maximum pain) in both the basal condition (VASb) and during coughing (VASc) at 1 hour after leaving the operating room and 6, 12, and 24 hours thereafter. RESULTS: At 1, 6, 12, and 24 hours, VASb values in the NWI vs the WI group were 5.2 vs 3.1, 6.8 vs 4.1, 5.8 vs 4.9 (all p < .01), and 5.4 vs 5.1, respectively, and VASc values were 8.2 vs 6.3, 8.8 vs 5.9, 7.1 vs 5.3, and 6.8 vs 5.1 (all p < .01). Mean VAS score was significantly higher between 1 and 6 hours in the NWI group for all VASb measurements vs VASc values. Tramadole consumption was higher in the NWI group than in the WI group. CONCLUSIONS: Continuous wound infusion with 5 mL/h(-1) levobupivacaine, 1.5 mg/mL(-1), resulted in a safe and effective analgesic protocol in LKDs both in the immediate postoperative period and in the first day after surgery, a result that was more effective than a morphine-tramadole regimen. No adverse effects were recorded, which confirmed the safety of the technique. It is probable that better results could be achieved with dedicated administration devices.