The effect of sphingosine‐1‐phosphate on the endothelial glycocalyx during ischemia‐reperfusion injury in the isolated rat heart

Objective: Sphingosine‐1‐phosphate is a natural metabolite that is cardioprotective, but its effects on endothelial glycocalyx damage during ischemia‐reperfusion are unknown. Therefore, we investigated the effect of sphingosine‐1‐phosphate on the endothelial glycocalyx during ischemia‐reperfusion. Methods: Isolated hearts from Wistar rats were perfused on a Langendorff system with Krebs‐Henseleit buffer and pretreated with sphingosine‐1‐phosphate (10 nmol/L) before ischemia‐reperfusion. Infarct size was measured by triphenyl tetrazolium chloride staining (n ≥ 6 per group). Cardiac edema was assessed by calculating total water content (n = 7 per group) and histologically quantifying the interstitial compartment (n ≥ 3 per group). The post‐ischemic coronary release of syndecan‐1 was quantified using ELISA. Syndecan‐1 immunostaining intensity was assessed in perfusion‐fixed hearts (n ≥ 3 per group). Results: Pretreatment with sphingosine‐1‐phosphate decreased infarct size in isolated hearts subjected to ischemia‐reperfusion (P = .01 vs ischemia‐reperfusion). However, sphingosine‐1‐phosphate had no effect on syndecan‐1 levels in the coronary effluent or on the intensity of the syndecan‐1 immunostaining signal in cardiac tissue. Heart total water content was not significantly different between control and ischemic groups but was significantly decreased in hearts treated with sphingosine‐1‐phosphate alone. Conclusion: These results suggest that sphingosine‐1‐phosphate‐induced cardioprotection against ischemia‐reperfusion injury is not mediated by the maintenance of syndecan‐1 in the endothelial glycocalyx

Fulminant Staphylococcus lugdunensis septicaemia following a pelvic varicella-zoster virus infection in an immune-deficient patient: a case report

<p>Abstract</p> <p>Introduction</p> <p>The deadly threat of systemic infections with coagulase negative <it>Staphylococcus lugdunensis </it>despite an appropriate antibiotic therapy has only recently been recognized. The predominant infectious focus observed so far is left-sided native heart valve endocarditis, but bone and soft tissue infections, septicaemia and vascular catheter-related bloodstream infections have also been reported. We present a patient with a fatal <it>Staphylococcus lugdunensis </it>septicaemia following zoster bacterial superinfection of the pelvic region.</p> <p>Case presentation</p> <p>A 71-year old male diagnosed with IgG kappa plasmocytoma presented with a conspicuous weight loss, a hypercalcaemic crisis and acute renal failure. After initiation of haemodialysis treatment his condition improved rapidly. However, he developed a varicella-zoster virus infection of the twelfth thoracic dermatome requiring intravenous acyclovir treatment. Four days later the patient presented with a fulminant septicaemia. Despite an early intravenous antibiotic therapy with ciprofloxacin, piperacillin/combactam and vancomycin the patient died within 48 hours, shortly before the infective isolate was identified as <it>Staphylococcus lugdunensis </it>by polymerase chain reaction.</p> <p>Conclusion</p> <p>Despite <it>S. lugdunensis </it>belonging to the family of coagulase-negative staphylococci with an usually low virulence, infections with <it>S. lugdunensis </it>may be associated with an aggressive course and high mortality. This is the first report on a <it>Staphylococcus lugdunensis </it>septicaemia following a zoster bacterial superinfection of the pelvic region.</p

Vitamin A derivatives in the prevention and treatment of human cancer.

Vitamin A is essential for normal cellular growth and differentiation. A vast amount of laboratory data have clearly demonstrated the potent antiproliferative and differentiation-inducing effects of vitamin A and the synthetic analogues (retinoids). Recent in-vitro work has led to the exciting proposal that protein kinase-C may be centrally involved in many of retinoids' anticancer actions including the effects on ornithine decarboxylase induction, intracellular polyamine levels, and epidermal growth factor receptor number. Several intervention trials have clearly indicated that natural vitamin A at clinically tolerable doses has only limited activity against human neoplastic processes. Therefore, clinical work has focused on the synthetic derivatives with higher therapeutic indexes. In human cancer prevention, retinoids have been most effective for skin diseases, including actinic keratosis, keratoacanthoma, epidermodysplasia verruciformis, dysplastic nevus syndrome, and basal cell carcinoma. Several noncutaneous premaligancies, however, are currently receiving more attention in retinoid trials. Definite retinoid activity has been documented in oral leukoplakia, laryngeal papillomatosis, superficial bladder carcinoma, cervical dysplasia, bronchial metaplasia, and preleukemia. Significant therapeutic advances are also occurring with this class of drugs in some drug-resistant malignancies and several others that have become refractory, including advanced basal cell cancer, mycosis fungoides, melanoma, acute promyelocytic leukemia, and squamous cell carcinoma of the skin and of the head and neck. This report comprehensively presents the clinical data using retinoids as anticancer agents in human premalignant disorders and outlines the ongoing and planned studies with retinoids in combination and adjuvant therapy

Treatment of Psoriasis by Oral PUVA Therapy Combined with Aromatic Retinoid (Ro 10–9359; Tigason®)

The authors discuss results observed in 126 patients affected with severe psoriasis covering more than 40% of the whole body area, some of them representing failures of oral photochemotherapy (PUVA). They were treated according to 5 different schedules, 3 of them combining aromatic retinoid Ro 10–9359 (AR) with PUVA therapy. The most effective results were obtained with a schedule entailing initial treatment for a 2-week period with AR only, followed on the 15th day by the adjunction of classic PUVA therapy with progressive daily decrease of AR dosage (schedule C). It was possible to reduce the frequency and duration of PUVA treatments and the amount of energy used although to a lesser degree than described by other authors. Even more important, far longer remissions were obtained than with PUVA therapy alone, even where the ratio of clearing was identical. This combination therapy made it possible to recover over 70% of the complete or relative failures of PUVA monotherapy. Thus the combination of AR + PUVA therapy (RE-PUVA) as in this schedule appears to be the most important improvement to PUVA since its introduction as a therapy for psoriasis.</jats:p