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Hyperbaric oxygen therapy (HBOT) has been used as treatment for different clinical conditions, including fibromyalgia (FM). HBOT modulates brain activity, ameliorates chronic pain and modifies the ratio of immune cells. Clinical studies have provided evidence that FM is associated with immune system dysregulation. In the present study we aimed to evaluate the effect of HBOT on immune system and on the quality of life-style of FM patients.Patients with primary FM and controls were treated with HBOT. Physical, emotional and social assessment, quality of sleep, tender points, intensity score, WPI and symptom severity were evaluated before and after HBOT. Furthermore, a characterisation of CD4 T lymphocytes and their cytokine production was performed by flow cytometry. The expression of TNF-α, IFN-γ, IL-17, IL-9 and IL-22 was also assessed by RT-PCR. Finally, the serum levels of serotonin were evaluated by ELISA.Our results confirm the participation of immune system in the pathogenesis of FM and highlight the impact of HBOT treatment, with particular regard to the changes on proinflammatory cytokines production by CD4 T cells subsets.FM patients show a Th1 signature and the activation of this subset is modulated by HBOT.

Ca(2+) sensitivity of smooth muscle (SM) contraction is determined by CPI-17, an inhibitor protein for myosin light chain phosphatase (MLCP). CPI-17 is highly expressed in mature SM cells, but the expression level varies under pathological conditions. Here, we determined the expression of CPI-17 in embryonic SM tissues and arterial neointimal lesions using immunohistochemistry. As seen in adult animals, the predominant expression of CPI-17 was detected at SM tissues on mouse embryonic sections, whereas MLCP was ubiquitously expressed. Compared with SM alpha-actin, CPI-17 expression doubled in arterial SM from embryonic day E10 to E14. Like SM alpha-actin and other SM marker proteins, CPI-17 was expressed in embryonic heart, and the expression was down-regulated at E17. In adult rat, CPI-17 expression level was reduced to 30% in the neointima of injured rat aorta, compared with the SM layers, whereas the expression of MLCP was unchanged in both regions. Unlike other SM proteins, CPI-17 was detected at non-SM organs in the mouse embryo, such as embryonic neurons and epithelium. Thus, CPI-17 expression is reversibly controlled in response to the phenotype transition of SM cells that restricts the signal to differentiated SM cells and particular cell types.

Obiettivo. La fascite necrotizzante (FN) è una rara infezione dei tessuti molli. È caratterizzata da una diffusa necrosi fascia- le principalmente causata da Streptococcus hemolyticus. Può essere fatale se non gestita correttamente, per cui diviene mandatoria una diagnosi precoce ed un trattamento multidi- sciplinare che includa l’ossigenoterapia iperbarica (HBOT), che viene utilizzata sia come trattamento primario o adiuvan- te nel trattamento di infezioni come la gangrena gassosa, la fascite necrotizzante. Materiali e metodi. Descriviamo tre casi clinici di FN. Il primo è un donna di 49 anni con diabete mellito di tipo II, che presentava una FN a livello della mammella sinistra. È stato ammessa in terapia intensiva per una sepsi severa. Sono stati eseguiti un rapido debridement chirurgico, una corretta antibiotico terapia e 10 cicli di HBOT a 2,8 ATA. Il secondo caso è una donna di 69 anni con diabete mellito di tipo I; un ascesso perianale è progredito fino a determinare una gangre- na di Fournier del perineo e dello scroto. Anche in questocaso, sono stati eseguiti un rapido intervento chirurgico e 15 cicli di HBOT, oltre ad una antibioticoterapia ad ampio spet- tro. Il terzo paziente era un uomo di 56 anni che ha avuto FN del collo secondario ad una verosimile lesione chimica da col- luttorio. È stato ricoverato in terapia intensiva per sepsi seve- ra con insufficienza respiratoria da restrizione dello spazio respiratorio. Una idonea antibioticoterapia e 15 cicli di HBOT a 2,8 ATA hanno permesso una restituzio ad integrum senza intervento chirurgico. Risultati. Una antibioticoterapia di combinazione e la terapia adiuvante con ossigeno iperbarico (HBOT) hanno permesso un ottimo debridement chirurgico e dopo la stabilizzazione delle ferite e la formazione di tessuto di granulazione fresco, i difetti dei tessuti molli sono stati trattati utilizzando metodi ricostrutti- vi complessi nei primi due casi. Il terzo caso è stato risolto con la sola antibioticoterapia e ossigenoterapia iperbarica. Discussione e conclusioni. L’HBOT risulta essere un tratta- mento essenziale nelle infezioni dei tessuti molli perchè agisce come battericida/batteriostatico nei confronti di batteri anaerobici aumentando la formazione di radicali liberi dell’ossige- no e ripristina la capacità battericida dei leucociti nelle ferite ipossiche, aumentando la tensione di ossigeno dei tessuti; inoltre, l’HBOT agisce sinergicamente con numerosi antibio- tici potenziandone l’effetto.

Dysbaric accidents are usually referred to compressed air-supplied diving. Nonetheless, diving accidents are known to have occurred among breath-hold divers also and some cases are reported in medical literature. A male professional breath hold diver (57 year old) presented neurological disorders as dizziness, sensory numbness, blurred vision and left phronto-parietal pain after many dives to a 30-35 meters seawater depth. He went home after the regression of the symptoms and runned 8 Km the following morning. Pain, sensory numbness and dizziness occurred after running. He went by himself to the hospital where he had a grand mal seizure and lost consciousness. A magnetic resonance imaging of the brain disclosed one cortical T1- weighted hypointensity in temporal region corresponding to infarction with partial hemorrhage. All clinical and radiological manifestations were likely to be referred to the very rare Taravana diving syndrome induced by repetitive prolonged deep breath-hold dives. The reappearance of signs after 17-hour free time make it thought as an atypical case.

Cellular activity of the myosin light chain phosphatase (MLCP) determines agonist-induced force development of smooth muscle (SM). CPI-17 is an endogenous inhibitor protein for MLCP, responsible for mediating G-protein signaling into SM contraction. Fluctuations in CPI-17 expression occur in response to pathological stresses, altering excitation-contraction coupling in SM. Here, we determined the signaling pathways regulating CPI-17 expression in rat aorta tissues and the cell culture using a pharmacological approach. CPI-17 transcription was suppressed in response to the proliferative stimulus with platelet-derived growth factor (PDGF) through the ERK1/2 pathway, whereas it was elevated in response to inflammatory, stress-induced and excitatory stimuli with tranforming growth factor-β, IL-1β, TNFα, sorbitol, and serotonin. CPI-17 transcription was repressed by inhibition of JNK, p38, PKC, and Rho-kinase (ROCK). The mouse and human CPI-17 gene promoters were governed by the proximal GC-boxes at the 5′-flanking region, where Sp1/Sp3 transcription factors bound. Sp1 binding to the region was more prominent in intact aorta tissues, compared with the SM cell culture, where the CPI-17 gene is repressed. The 173-bp proximal promoter activity was negatively and positively regulated through PDGF-induced ERK1/2 and sorbitol-induced p38/JNK pathways, respectively. By contrast, PKC and ROCK inhibitors failed to repress the 173-bp promoter activity, suggesting distal enhancer elements. CPI-17 transcription was insensitive to knockdown of myocardin/Kruppel-like factor 4 small interfering RNA or histone deacetylase inhibition. The reciprocal regulation of Sp1/Sp3-driven CPI-17 expression through multiple kinases may be responsible for the adaptation of MLCP signal and SM tone to environmental changes.

We previously reported that substantial amounts of IL-10, an immunomodulatory cytokine, are produced by cell suspensions of fresh human metastatic melanoma tissues. Production diminished with continuous culturing of cells, which suggests a pivotal interactive role between melanoma cells and the tumor microenvironment. In this study, we found that the culture media obtained from LPS-stimulated peripheral blood mononuclear cells induced IL-10 production by metastatic melanoma cells. Of the multiple cytokines present in the conditioned culture media, IL-6 was identified as the inducer of IL-10 production. A neutralizing antibody against IL-6 completely blocked the conditioned medium-induced IL-10 production. Metastatic melanoma cells that constitutively produce low amount of IL-10 increased IL-10 production in response to recombinant human IL-6 in a dose-dependent fashion. The response to exogenously added IL-6 was less significant in melanoma cells that produced high amounts of IL-6, probably due to pre-existing autocrine stimulation of IL-10 by endogenous IL-6. On the other hand, metastatic melanoma cells that do not constitutively produce IL-10 protein did not respond to exogenous IL-6. In IL-6-responsive melanoma cells, IL-6 increased STAT3 phosphorylation and inhibition of STAT3 signaling using siRNA or inhibitors for JAKs diminished IL-6-induced IL-10 production. In addition, inhibition of MEK and PI3K, but not mTOR, interfered with IL-10 production. Taken together, the data suggest that blocking of these signals leading to IL-10 production is a potential strategy to enhance an anti-melanoma immune response in metastatic melanoma.

Cytokine production in the tumor microenvironment is a key regulatory mechanism for tumor progression. We reported that IL-10 is produced in more than 85% of freshly isolated metastasic melanoma cell suspensions. That IL-10 production decreases when melanoma cells are maintained in vitro suggested that an interaction between melanoma cells and the tumor microenvironment is important for IL-10 production by melanoma cells. We have demonstrated that IL-10 production by both fresh and established metastatic melanoma cells is increased in response to recombinant human IL-6 (rhIL-6) (Invitrogen). The stimulative effect of rhIL-6 is completely blocked by anti-IL-6 antibody (BD bioscience) and anti-IL-6 receptor antibody (BD bioscience). We concluded that a pro-inflammatory cytokine, IL-6 has a key role on the induction of IL-10 production by melanoma cells. In this study, we investigated the signal pathways that transduce IL-6 receptor activation into IL-10 production in a metastatic human melanoma cell line (JB) using pharmacological inhibitors or siRNAs for various kinases. Inhibitors were added to quiescent JB cells, 1 hour prior to a submaximum dose of IL-6 (2 ng/ml). After 24 hour stimulation, aliquots of culture media were assayed for IL-10 by ELISA. It was found that a JAK inhibitor, JAK inh1, suppressed 90% of IL-6-induced IL-10 production by JB cells compare to control. In parallel, cells were fixed with TCA, and the total proteins were subjected to phospho-immunoblotting assay. IL6 stimulation induced a 96-fold increase in STAT3 phosphorylation within 30 min, and the phosphorylation was sustained for 24 hours leading IL-10 production. JAK inhibitor-1 eliminated IL-10 production and STAT3 phosphorylation, suggesting a dominant role of JAK/STAT3 in IL-6-induced signals. ERK1/2 phosphorylation was spontaneously high in quiescent JB cells, and elevated 37% in response to IL-6 stimulation. Inhibition of ERK phosphorylation with inhibitors for c-Raf (GW5074) and MEK (U0126) eliminated IL-6-induced IL-10 production. A PI3K inhibitor (LY294002) suppressed IL-10 production without the inhibition of STAT3 or ERK phosphorylation. Rapamycin, an mTOR inhibitor, showed only a marginal effect on IL-10 production, indicating a minimum contribution of mTOR to the PI3K-mediated IL-10 production in melanoma. Thus, the spontaneous ERK phosphorylation and PI3K activity are necessary for STAT3-mediated IL-10 production in melanoma. IL-10 is purported to surpress anti-tumor cellular immune responses. Therefore, inhibitors that block IL-6-induced IL-10 production are expected to potentiate an anti-tumor immune response at tumor sites. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1913.

Key Clinical Message Taravana syndrome is a rare dysbaric disease characterized by neurologic signs and symptoms. Differently from others decompression illness, it has unspecified pathophysiology and unclear predisposing factors. Our cases suggest that thrombophilic state due to hyperhomocysteinemia could increase the risk to develop Taravana syndrome.

Dysbaric accidents are usually referred to compressed air-supplied diving. Nonetheless, some cases of decompression illness are known to have occurred among breath-hold (BH) divers also, and they are reported in the medical literature. A male BH diver (57 years old), underwater fishing champion, presented neurological disorders as dizziness, sensory numbness, blurred vision, and left frontoparietal pain after many dives to a 30–35 meters sea water depth with short surface intervals. Symptoms spontaneously regressed and the patient came back home. The following morning, pain and neurological impairment occurred again and the diver went by himself to the hospital where he had a generalized tonic-clonic seizure and lost consciousness. A magnetic resonance imaging of the brain disclofsed a cortical T1-weighted hypointense area in the temporal region corresponding to infarction with partial hemorrhage. An early hyperbaric oxygen therapy led to prompt resolution of neurological findings. All clinical and imaging characteristics were referable to the Taravana diving syndrome, induced by repetitive prolonged deep BH dives. The reappearance of neurological signs after an uncommon 21-hour symptom-free interval may suggest an atypical case of Taravana syndrome.

hyme is characteristic of the Mediterranean and is of interest for its multifunctional nature. It is widely used in seasoning and flavouring, in herbal products and cosmetics. The versatility of this species means it is also useful in the protection of areas prone to erosion or an ornamental plant when designing low-maintenance gardens. Thyme germplasm constitutes a large part of the wild flora in Sicily and is a potentially useful source of genetic variability. On the basis of this, in the two-year period from 2004-2005, research was carried out on wild thyme accessions. These were used to evaluate both its productivity and individual biotypes with the functional characteristics most sough-after by the various sectors which use this species.