Cytokine profiles of women with vulvodynia: Identification of a panel of pro-inflammatory molecular targets.

OBJECTIVE: The vulvar pain syndrome (VPS) is a multifactorial disease severely influencing the lifestyle of affected women. Among possible etiological factors, local injury, peripheral and/or central sensitization of the nervous system, and a chronic inflammatory status have been positively associated with the development of VPS. The identification of a constitutive altered local inflammatory profile in VPS women may represent an important point in the characterization of patients' phenotype as a useful marker influencing the vulvar micro-environment. The aim of this study was to investigative the possible role of the local cytokines production in women with VPS in comparison to healthy women. STUDY DESIGN: In this study were collected vaginal swabs from 57 healthy women (HC) who never suffered from VPS and from 30 patients diagnosed with vulvodynia (VPS) by at least 3 years and currently symptomatic. All patients included in this study showed the absence of Sexually Transmitted (STD) diseases and Reproductive Tract Infection. Real-time PCR was performed to assess the genomic sequences of ST pathogens. The Luminex Bio-Plex platform was used for the analysis of a panel of 48 immune factors. RESULTS: Eleven molecules, specifically involved in the pro-inflammatory pathway were significantly modulated in VPS patients in comparison to healthy women, suggesting a persistent inflammatory process. CONCLUSIONS: Therefore, these inflammatory factors could be possible biological markers involved in this disease. Nevertheless, other studies are needed to consider this specific immune profile as a valid marker of the vulvodynia.

Highlights in muscle relaxants.

The aim of this article is to provide an overview on neuromuscular blocking agents and a rational selection of the most appropriate agents, along with pharmacological and pharmacoeconomic considerations on neuromuscular blockers and their antagonists. Neuromuscular blocking agents are used during anesthesia to facilitate endotracheal intubation and provide surgically required paralysis. There is continuing development in the field of neuromuscular blocking agents, with new products appearing at regular intervals. All new agents come at increased costs. The proportion of anesthesia-related drug costs on a per-patient basis are small and vary from country to country, but account for no more than 12% of hospital drug budgets. However, given the large number of anesthetics performed over time, the total cost is significant. Moreover, such costs should be put into the perspective of the operating theater and patient admission costs. Appropriate selection of neuromuscular blocking agents can help not only to reduce biological costs secondary to complications, but also to make operating lists proceed smoothly and without incident. The paucity of outcome studies in relation to anesthetic drugs is not surprising given that anesthesia is used to facilitate the provision of therapy rather than being therapeutic in its own right. Accordingly, the assessment of anesthetic drugs has a different priority to therapeutic drugs. As anesthetic drugs are nontherapeutic, it is also difficult to determine the best choice of agent. However, new neuromuscular blocking agents are marketed on the basis of improvements in the frequency of side effects, safety, reliability, duration, reversibility and undesirable hemodynamic effects.

Effects of nitrosopropofol on mitochondrial energy-converting system.

Nitrosopropofol (NOPR) is a relatively stable compound obtained from the reaction between the general anesthetic 2,6 diisopropylphenol (propofol) and nitrosoglutathione (GSNO) and bearing a more acidic phenol group than propofol. It interfered with mitochondrial energetic metabolism in a concentration-dependent manner. Concentrations as high as 100 or 200 microM disrupted both oxidative phosphorylation and electron transport. Low concentrations of NOPR (50 microM) markedly slowed down the electron transport rate which was insensitive both to ADP and uncoupler stimulation and spontaneously gradually stopped. Consequently, both the transmembrane potential production and the ATP synthesis system were affected. In the presence of 10 or 20 microM NOPR, mitochondria respired but showed a worsening of the respiratory control and produced a transmembrane potential useful to respond to a phosphorylation pulse, but were not able to restore it. These results were consistent with ATP synthesis and swelling experiments. NOPR was effective at concentrations lower than those required by the combination of propofol and GSNO, suggesting that mitochondria might be able to catalyze the reaction between GSNO and propofol and that the resulting metabolite was more active on mitochondrial membrane structure than the parent compounds. Although the details of the process are yet unknown, the mechanism presented may be of potential relevance to rationalize the pathophysiological effects of propofol.