Niclosamide Ethanolamine Salt Alleviates Idiopathic Pulmonary Fibrosis by Modulating the PI3K-mTORC1 Pathway.

Idiopathic pulmonary fibrosis (IPF) is an interstitial pneumonia characterized by chronic progressive fibrosis, ultimately leading to respiratory failure and early mortality. Although not fully explored, the major causative factors in IPF pathogenesis are dysregulated fibroblast proliferation and excessive accumulation of extracellular matrix (ECM) deposited by myofibroblasts differentiated from pulmonary fibroblasts. More signalling pathways, including the PI3K-Akt-mTOR and autophagy pathways, are involved in IPF pathogenesis. Niclosamide ethanolamine salt (NEN) is a highly effective multitarget small-molecule inhibitor reported in antitumor studies. Here, we reported that in an IPF animal model treated with NEN for 14 days, attractive relief of pulmonary function and hydroxyproline content were observed. To further explore, the therapeutic effect of NEN in IPF and pathological changes in bleomycin-challenged mouse lung sections were assessed. Additionally, the effects of NEN on abnormal proliferation and ECM production in IPF cell models established with TGF-ß1-stimulated A549 cells or DHLF-IPF cells were studied. In nonclinical studies, NEN ameliorated lung function and histopathological changes in bleomycin-challenged mice, and the lung hydroxyproline content was significantly diminished with NEN treatment. In vitro, NEN inhibited PI3K-mTORC1 signalling and arrested the cell cycle to prevent uncontrolled fibroblast proliferation. Additionally, NEN inhibited TGF-ß1-induced epithelial-mesenchymal transition (EMT) and ECM accumulation via the mTORC1-4EBP1 axis. Furthermore, NEN-activated noncanonical autophagy resensitized fibroblasts to apoptosis. The above findings demonstrated the potential antifibrotic effect of NEN mediated via modulation of the PI3K-mTORC1 and autophagy pathways. These data provide strong evidence for a therapeutic role for NEN in IPF.

Safety Profile of Sclerosing Agents: An Analysis From the World Health Organization Pharmacovigilance Database VigiBase.

BACKGROUND: Several sclerosing agents are used to treat chronic venous diseases. Although they do not seem to differ in terms of efficacy, their safety profiles might differ. OBJECTIVE: To compare the safety profile of sclerosing agents through an analysis of the World Health Organization pharmacovigilance database. METHODS: The authors performed a disproportionality analysis using the proportional reporting ratio (PRR) method to compare pharmacovigilance signals between each sclerosing agent among 6 adverse event syndromes of interest: hypersensitivity reactions, arterial thromboembolic disorders, venous thromboembolic disorders, cardiac arrhythmias, visual/neurological disturbances, and skin ulcerations. The cutoff for signal detection was defined by a logPRR lower boundary 95% confidence interval (CI) ≥0 and number of cases n ≥3. RESULTS: Of 1,227 Individual Case Safety Reports (ICSRs) identified, after removal of ICSRs with unselected indications, the authors selected 472 reports for the analysis. The authors found that polidocanol is associated with more reporting of venous embolic/thrombotic events (logPRR = 1.38 [95% CI 1.27-1.49]), ethanolamine with the higher pharmacovigilance disproportionality signal of cardiac arrhythmias (logPRR = 0.80 [95% CI 0.51-1.09]), and STS with more reporting of allergic reactions (logPRR = 1.79 [95% CI 1.59-1.98]). CONCLUSION: The safety profile of sclerosing agents significantly differs and should guide benefit-risk ratio assessment of such agents.

Bronchoscopic sclerosis of post-resectional bronchial fistulas.

BACKGROUND: Pulmonary resection is, by far, the primary cause of bronchial fistula. This is a severe complication because of its morbidity and mortality and the related consumption of resources. Definitive closure continues to be a challenge with several therapeutic options, but none are optimal. We describe our experience in bronchoscopic application of ethanolamine and lauromacrogol 400 for the treatment of post-resection bronchial fistulas. METHODS: Clinical records of 8 patients treated using this technique were collected prospectively. The diagnosis of a fistula was confirmed by flexible bronchoscopy. Sclerosis was indicated in the context of multimodal treatment. Sclerosant injection was performed under general anesthesia with a Wang 22G needle through a flexible bronchoscope. The procedure was repeated at 2-week intervals until definitive closure of the fistula was confirmed. RESULTS: Fistula closure was achieved in 7 (87.5%) of the 8 patients, with persistence of the fistula in one patient who could not complete the treatment because of recurrence of his neoplastic pathology. No recurrence or complications related to the technique were registered. CONCLUSIONS: Bronchoscopic sclerosis by means of submucosal injection of lauromacrogol 400 or ethanolamine should be part of the multimodal treatment of bronchopleural fistula after lung resection, pending further studies that contribute to the accurate establishment of optimal indications for this procedure.

Safety Assessment of Ethanolamine and Ethanolamine Salts as Used in Cosmetics.

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of ethanolamine and 12 salts of ethanolamine as used in cosmetics. Ethanolamine functions as a pH adjuster. The majority of the salts are reported to function as surfactants, and the others are reported to function as pH adjusters, hair fixatives, or preservatives. The Panel reviewed available animal and clinical data, as well as information from previous relevant CIR reports. Because data were not available for each individual ingredient and because the salts dissociate freely in water, the Panel extrapolated from those previous reports to support safety. The Panel concluded that these ingredients are safe in the present practices of use and concentrations (rinse-off products only) when formulated to be nonirritating, and these ingredients should not be used in cosmetic products in which N-nitroso compounds may be formed.

Role of combination inhaled corticosteroids and long acting beta agonists in the treatment of adult asthma.

An inhaled corticosteroid (ICS) and a long acting beta agonist (LABA) are combined in an inhaler for treatment of persistent asthma. There is evidence that maintenance therapy with a combination ICS/LABA inhaler improves clinical outcomes and reduces airflow obstruction in patients with persistent asthma, who are not well controlled even when using ICS maintenance therapy. There is evidence that a combination ICS/LABA inhaler may also play a role in initial maintenance therapy for patients with mild persistent asthma, who have never used ICS therapy. There is no evidence regarding the use of combination therapy in intermittent asthma. Oral candidal infections, hoarseness and pharyngolaryngeal pain are the most frequently reported adverse events. Combination inhaler therapy can improve compliance with guidelines that recommend a LABA only be used with concurrent ICS administration.

Practical use of labile protein as an index of hair.

Because of small fluctuations, it is difficult to evaluate hair damage caused by bleaching using previously utilized hair damage indexes. Application of commercial bleaching products elevates partially extractable labile hair protein amounts in the range of 0.4-1.2 mg/g of hair. Within this range, the level of labile protein fluctuates greatly, depending on the extent of bleaching. In the current study, it was found that the effects of alkaline constituents and various peptides contained in bleaching lotions on hair damage could be evaluated by measuring labile protein amounts without employing harsher bleaching conditions.

Daño arterial y uso de fleboesclerosantes / Arterial damage and use of fleboesclerosing agents

Aunque el tratamiento con agentes fleboesclerosantes constituye una alternativa para las várices, éste no está exento de complicaciones, las que pueden ser de tipo general y local. De estas últimas, la inyección intraarterial accidental es la más temida y devastadora, ya que puede llevar a la pérdida de la extremidad. Presentamos un caso clínico de esta complicación que fue tratado en forma algo tardía con un resultado aceptable, a través de una infusión sistémica con estreptoquinasa. Se concluye que si bien este tratamiento es una buena alternativa para tratar las várices, éste debe ser restringido a casos muy seleccionados, evitando los sitios de riesgo de punción arterial y hecho por profesionales entrenados en la materia

Oils and cancer.

Epidemiologic evidence on the relationship between mineral oil exposure and cancer is reviewed. The review is restricted to occupations involving substantial dermal and inhalational exposure and for which an epidemiologic literature exists: metal machining, print press operating, and cotton and jute spinning. Mineral oils are complex mixtures of aliphatic hydrocarbons, naphthenics, and aromatics, the relative distribution of which depends on the source of the oil and the method of refinement. End-use products contain a variety of additives, and contamination by other agents generally occurs during use. Suspect agents include polycyclic aromatic hydrocarbons (PAH) (particularly benz[a]pyrene), nitrosamines, chlorinated paraffins, long-chain aliphatics, sulfur, N-phenyl-2-naphthylamine, and formaldehyde. The heterogeneity of this exposure makes epidemiologic study difficult and meta-analysis inappropriate. Nonetheless, several associations emerge from the literature with varying degrees of support. There is clear evidence that early formulations of mineral oils used in cotton and jute spinning and in metal machining were carcinogenic to the skin. Associations of mineral oil exposure with laryngeal and rectal cancer have received some support in the literature, particularly with respect to straight oils. Evidence is suggestive that grinding operations (which can entail either mineral oil-based or ethanolamine-based fluids) are associated with excess risk of cancer of the esophagus, stomach, and pancreas. A number of bladder cancer case-control studies have noted an association with work as a machinist. There is limited evidence of an association with cancer of the colon, prostate, and sinonasal region. Several studies of printers have yielded positive findings for lung cancer, whereas studies in metal machinists have been generally negative. The PAH and nitrosamine content of current formulations is lower than in the past and the implications of these changes in composition to the carcinogenicity of the formulations are not yet known.