Lactobacillus johnsonii LJO02 (DSM 33828) Cell-Free Supernatant and Vitamin D Improve Wound Healing and Reduce Interleukin-6 Production in Staphylococcus aureus-Infected Human Keratinocytes

Methicillin-resistant biofilm-forming Staphylococcus spp. are found in about 25% of the overall cases of chronic wounds, which can undergo malignant degeneration and be associated with skin cancer. Although antimicrobial agents are clinically used to counteract pathogens and promote wound healing, they are increasingly ineffective against multi-drug resistant bacteria. Moreover, they can induce dysbiosis, which favors opportunistic pathogen infections and alters immune responses. Consequently, research on pathogen containment strategies is crucial. We aimed to evaluate the potential beneficial effect of Lactobacillus johnsonii LJO02 cell-free supernatant (CFS) and vitamin D, as single treatments or in combination, on cell viability, wound healing, and the pro-inflammatory interleukin-6 (IL-6) production of a Staphylococcus aureus-infected human immortalized keratinocyte cell line (HaCaT) in vitro model. The analysis showed that LJO02 CFS 20% v/v ratio and 100 nM vitamin D promoted infected cell viability and wound healing and significantly reduced IL-6 production. However, their effect was not synergic, since no significant difference between the single and combined treatments was observed. LJO02 CFS topic application and vitamin D supplementation could provide a valuable strategy for attenuating S. aureus-induced pathogenesis, promoting wound healing and opening new therapeutic strategies supporting the conventional approaches

Enfermedad renal crónica : una epidemia

Fil: Alabart, E.. Universidad Nacional de TucumánFil: González, Roxana. Universidad Nacional de TucumánFil: Alós, B.. Universidad Nacional de TucumánFil: Romero, A.. Universidad Nacional de TucumánFil: Barada, C.. Universidad Nacional de TucumánFil: Zanetta, D.. Universidad Nacional de TucumánFil: Colli, G.. Universidad Nacional de Tucumá

Patients with ischaemic, mixed and nephrotoxic acute tubular necrosis in the intensive care unit – a homogeneous population?

INTRODUCTION: Acute tubular necrosis (ATN) is usually studied as a single entity, without distinguishing between ischaemic, nephrotoxic and mixed aetiologies. In the present study we evaluated the characteristics and outcomes of patients with ATN by aetiological group. METHOD: We conducted a retrospective comparison of clinical features, mortality rates and risk factors for mortality for the three types of ATN in patients admitted to the general intensive care unit of a university hospital between 1997 and 2000. RESULTS: Of 593 patients with acute renal failure, 524 (88%) were classified as having ATN. Their mean age was 58 years, 68% were male and 52% were surgical patients. The overall mortality rate was 62%. A total of 265 patients (51%) had ischaemic ATN, 201 (38%) had mixed ATN, and 58 (11%) had nephrotoxic ATN. There were no differences among groups in terms of age, sex, APACHE II score and reason for ICU admission. Multiple organ failure was more frequent among patients with ischaemic (46%) and mixed ATN (55%) than in those with nephrotoxic ATN (7%; P < 0.0001). The complications of acute renal failure (such as, gastrointestinal bleeding, acidosis, oliguria and hypervolaemia) were more prevalent in ischaemic and mixed ATN patients. Mortality was higher for ischaemic (66%; P = 0.001) and mixed ATN (63%; P = 0.0001) than for nephrotoxic ATN (38%). When ischaemic ATN patients, mixed ATN patients and all patients combined were analyzed by multivariate logistic regression, the independent factors for mortality identified were different except for oliguria, which was the only variable universally associated with death (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.64–5.49 [P = 0.0003] for ischaemic ATN; OR 1.96, 95% CI 1.04–3.68 [P = 0.036] for mixed ATN; and OR 2.53, 95% CI 1.60–3.76 [P < 0.001] for all patients combined]). CONCLUSION: The frequency of isolated nephrotoxic ATN was low, with ischaemic and mixed ATN accounting for almost 90% of cases. The three forms of ATN exhibited different clinical characteristics. Mortality was strikingly higher in ischaemic and mixed ATN than in nephrotoxic ATN. Although the type of ATN was not an independent predictor of death, the independent factors related to mortality were different for ischaemic, mixed and all patients combined. These data indicate that the three types of ATN represent different patient populations, which should be taken into consideration in future studies

Minimally invasive transplantation of iPSC-derived ALDHhiSSCloVLA4+ neural stem cells effectively improves the phenotype of an amyotrophic lateral sclerosis model

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by the degeneration of motor neurons. Currently, there is no effective therapy for ALS. Stem cell transplantation is a potential therapeutic strategy for ALS, and the reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) represents a novel cell source. In this study, we isolated a specific neural stem cell (NSC) population from human iPSCs based on high aldehyde dehydrogenase activity, low side scatter and integrin VLA4 positivity. We assessed the therapeutic effects of these NSCs on the phenotype of ALS mice after intrathecal or intravenous injections. Transplanted NSCs migrated and engrafted into the central nervous system via both routes of injection. Compared with control ALS, treated ALS mice exhibited improved neuromuscular function and motor unit pathology and significantly increased life span, in particular with the systemic administration of NSCs (15%). These positive effects are linked to multiple mechanisms, including production of neurotrophic factors and reduction of micro- and macrogliosis. NSCs induced a decrease in astrocyte number through the activation of the vanilloid receptor TRPV1. We conclude that minimally invasive injections of iPSC-derived NSCs can exert a therapeutic effect in ALS. This study contributes to advancements in iPSC-mediated approaches for treating ALS and other neurodegenerative diseases

Vandetanib for the Treatment of Advanced Medullary Thyroid Cancer Outside a Clinical Trial: Results from a French Cohort

BACKGROUND: A randomized phase III trial demonstrated that vandetanib treatment is effective in patients with metastatic medullary thyroid cancer (MTC), leading to regulatory approval, but its use may be associated with toxicities that require specific monitoring and management. The objective of the present study performed in France was to describe the toxicity profile and efficacy of vandetanib treatment when given outside any trial. METHODS: Sixty-eight patients were treated with vandetanib in the frame of a temporary use authorization (ATU) in France from August 2010 to February 2012, when the drug was available on request for patients with locally advanced or metastatic MTC. Patients were registered by the French health authorities, and characteristics, treatment parameters, toxicity profile, and efficacy were retrospectively reviewed. Eight patients were excluded from the analysis because vandetanib treatment was not administered (n=3), had been given in a trial before ATU (n=3), or was given for a non-MTC cancer (n=2). RESULTS: Data from the 60 MTC patients were analyzed. Mean age was 58 years (range 11-83 years), 39 patients were male, and six had hereditary MTC. Fifty-six (93%) had metastatic disease in the mediastinum (82%), bones (65%), liver (53%), or lung (53%), and four had only locally advanced disease. At the time of study evaluation, with a median follow-up of 20 months and a median duration of treatment of 9.7 months (range 0.3-36 months), 15 patients were continuing vandetanib treatment (range 18-36 months). Median progression-free survival was 16.1 months. Twenty-five patients discontinued treatment for disease progression (range 0.3-29 months). Best tumor response was a complete response in one patient, a partial response in 12 (20%), stable disease in 33 (55%), and progression in seven patients (12%). All patients had at least one adverse event (AE) during treatment. The main AEs were skin toxicity, diarrhea, and asthenia. Sixteen patients (27%) discontinued treatment for toxicity, and one patient died from vandetanib-induced cardiac toxicity. CONCLUSIONS: Vandetanib is an effective option for patients with advanced MTC. AEs should be monitored carefully and should be minimized by educating both patients and care providers and by applying symptomatic treatment and dose reduction

Small primary adenocarcinoma in adenomyosis with nodal metastasis: a case report

<p>Abstract</p> <p>Background</p> <p>Malignant transformation of adenomyosis is a very rare event. Only about 30 cases of this occurrence have been documented till now.</p> <p>Case presentation</p> <p>The patient was a 57-year-old woman with a slightly enlarged uterus, who underwent total hysterectomy and unilateral adnexectomy. On gross inspection, the uterine wall displayed a single nodule measuring 5 cm and several small gelatinous lesions. Microscopic examination revealed a common leiomyoma and multiple adenomyotic foci. A few of these glands were transformed into a moderately differentiated adenocarcinoma. The endometrium was completely examined and tumor free. The carcinoma was, therefore, considered to be an endometrioid adenocarcinoma arising from adenomyosis. Four months later, an ultrasound scan revealed enlarged pelvic lymph nodes: a cytological diagnosis of metastatic adenocarcinoma was made.</p> <p>Immunohistochemical studies showed an enhanced positivity of the tumor site together with the neighbouring adenomyotic foci for estrogen receptors, aromatase, p53 and COX-2 expression when compared to the distant adenomyotic glands and the endometrium. We therefore postulate that the neoplastic transformation of adenomyosis implies an early carcinogenic event involving p53 and COX-2; further tumor growth is sustained by an autocrine-paracrine loop, based on a modulation of hormone receptors as well as aromatase and COX-2 local expression.</p> <p>Conclusion</p> <p>Adenocarcinoma in adenomyosis may be affected by local hormonal influence and, despite its small size, may metastasize.</p