Massive Sodium Nitrite Overdose: A Case for Prehospital Methylene Blue.

Sodium nitrite overdose leads to profound methemoglobinemia and may quickly progress to death. It is an increasingly common method of suicide and is often fatal. Methylene blue is an effective but time-sensitive antidote that has the potential to save lives when administered early. In this case report, we describe a fatal sodium nitrite overdose and the subsequent creation of a prehospital protocol for our large urban Emergency Medical Services system.

The human, F-actin-based cytoskeleton as a mutagen sensor.

BACKGROUND: Forty years ago the actin cytoskeleton was determined to be disrupted in fibroblasts from persons with DNA repair-defective, hereditary colon cancer, with no clear connection between the cytoskeleton and DNA repair defects at that time. Recently, the large number of sequenced genomes has indicated that mammalian mutagenesis has a large stochastic component. As a result, large coding regions are large mutagen targets. Cytoskeletal protein-related coding regions (CPCRs), including extra-cellular matrix proteins, are among the largest coding regions in the genome and are indeed very commonly mutated in cancer. METHODS: To determine whether mutagen sensitivity of the actin cytoskeleton could be assessed experimentally, we treated tissue culture cells with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and quantified overall cytoskeleton integrity with rhodamine-phalloidin stains for F-actin. RESULTS: The above approach indicated cytoskeletal degradation with increasing mutagen exposure, consistent with increased mutagenesis of CPCRs in TCGA, smoker samples, where overall mutation rates correlate with CPCR mutation rates (R2 = 0.8694; p < 0.00001). In addition, mutagen exposure correlated with a decreasing cell perimeter to area ratio, raising questions about potential decreasing, intracellular diffusion and concentrations of chemotherapy drugs, with increasing mutagenesis and decreasing cytoskeleton integrity. CONCLUSION: Determination of cytoskeletal integrity may provide the opportunity to assess mutation burdens in nonclonal cell populations, such as in intact tissues, where DNA sequencing for heterogeneous mutation burdens can be challenging.

Chronic potentiation of cardiac L-type Ca(2+) channels by pirfenidone.

AIMS: On the basis of its ability to inhibit fibrosis, pirfenidone has drawn the attention as an intriguing candidate for treating cardiac disease. However, its precise electrophysiological effects have yet to be elucidated. Here, we have investigated its potential to modulate ion channels. METHODS AND RESULTS: Adult rat cardiac myocytes were investigated using whole-cell patch-clamp, western-blot and qRT-PCR techniques. Pirfenidone increased the density of L-type Ca(2+) current (I(CaL,) 50-100%), without significantly altering Na(+), K(+), or T-type Ca(2+) currents. The effect was dose-dependent, with an EC(50) of 2.8 µM. Its onset was slow, with a lag period larger than 1 h and time to maximum of 24-48 h. Concomitant changes were observed in the voltage-dependent activation of I(CaL) (-5 mV shift in both V(1/2) and k). In contrast, the following properties of I(CaL) remained normal: steady-state inactivation, Ca(V)1.2 levels (mRNA and protein), and intramembrane charge movement. Indeed, the conductance-to-charge ratio, or G(max)/Q(max), was increased by 80%. The effect on I(CaL) was mimicked by an inhibitor of nitric oxide (NO) synthase (NOS), and attenuated by both cyclic adenosine monophosphate (cAMP) and cAMP-dependent protein kinase (PKA) inhibitors. Conversely, cytokines, reactive oxygen species, and Ca(2+) were all ruled out as possible intermediaries. Additional experiments suggest that pirfenidone increases action potential duration by ∼50%. CONCLUSION: Pirfenidone augments I(CaL), not through higher expression of L-type channels, but through promoting their Ca(2+)-conducting activity. A possible inhibition of NOS expression is likely involved, with subsequent reduced NO production and stimulated cAMP/PKA signalling. These findings may be relevant to the cardioprotective effect of pirfenidone.

Role of TGF-beta on cardiac structural and electrical remodeling.

The type beta transforming growth factors (TGF-betas) are involved in a number of human diseases, including heart failure and myocardial arrhythmias. In fact, during the last 20 years numerous studies have demonstrated that TGF-beta affects the architecture of the heart under both normal and pathological conditions. Moreover, TGF-beta signaling is currently under investigation, with the aim of discovering potential therapeutic roles in human disease. In contrast, only few studies have investigated whether TGF-beta affects electrophysiological properties of the heart. This fact is surprising since electrical remodeling represents an important substrate for cardiac disease. This review discusses the potential role of TGF-beta on cardiac excitation-contraction (EC) coupling, action potentials, and ion channels. We also discuss the effects of TGF-beta on cardiac development and disease from structural and electrophysiological points of view.

[Treatment of chronic skin lesions]. / Tratamiento de las lesiones cutáneas crónicas.

Leg Ulcers as well as Pressure Sore Ulcers are a pathology, although considered different due to their ethiology, that have a common denominator of the possibility to be healed using a moist wound healing environment. Taking advantage of this interesting therapeutic alternative, a multicentric, open, prospective study was carried out in order to evaluate the behaviour and efficiency of the new alveolar tridimensional structure hydropolymetric dressing, in the treatment of both leg ulcers and pressure sore ulcers, all with moderate to high exudate. The results obtained confirm the efficiency of the dressing in the pathology studied, along with the high acceptance of the hydropolimetric dressing chosen by the professionals and the excellent adaptation to the patients needs.

[Pure calcium-sodium alginate dressing. Multicenter evaluation of chronic cutaneous lesions]. / Apósito de alginato cálcico-sódico puro. Evaluación multicéntrica en lesiones cutáneas crónicas.

By means of a descriptive, non-comparative study of a series of clinical cases, the authors analyze the behavior of a dressing of pure calcic-sodium alginate with a stabilizing network in the treatment of pressure sores and profusely bleeding and/or infected vascular uclers. Based on the results of their studies, the authors confirm the effectiveness of this dressing under these conditions: no adverse reactions; the shrinking of the lesion in area or degree of severity; if there is tissue debridement accompanied by sloughing and necrotic tissue, the elimination of infection; ease of application and the reduction of the lesions; use as part of a non-daily cure treatment plan.