HIPECT4: multicentre, randomized clinical trial to evaluate safety and efficacy of Hyperthermic intra-peritoneal chemotherapy (HIPEC) with Mitomycin C used during surgery for treatment of locally advanced colorectal carcinoma.

BACKGROUND: Local relapse and peritoneal carcinomatosis (PC) for pT4 colon cancer is estimated in 15,6% and 36,7% for 12 months and 36 months from surgical resection respectively, achieving a 5 years overall survival of 6%. There are promising results using prophylactic HIPEC in this group of patients, and it is estimated that up to 26% of all T4 colon cancer could benefit from this treatment with a minimal morbidity. Adjuvant HIPEC is effective to avoid the possibility of peritoneal seeding after surgical resection. Taking into account these results and the cumulative experience in HIPEC use, we will lead a randomized controlled trial to determine the effectiveness and safety of adjuvant treatment with HIPEC vs. standard treatment in patients with colon cancer at high risk of peritoneal recurrence (pT4). METHODS/DESIGN: The aim of this study is to determine the effectiveness and safety of adjuvant HIPEC in preventing the development of PC in patients with colon cancer with a high risk of peritoneal recurrence (cT4). This study will be carried out in 15 Spanish HIPEC centres. Eligible for inclusion are patients who underwent curative resection for cT4NxM0 stage colon cancer. After resection of the primary tumour, 200 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously after the primary resection. Mitomycin C will be used as chemotherapeutic agent, for 60 min at 42-43 °C. Primary endpoint is loco-regional control (LC) in months and the rate of loco-regional control (%LC) at 12 months and 36 months after resection. DISCUSSION: We assumed that adjuvant HIPEC will reduce the expected absolute risk of peritoneal recurrence from 36% to 18% at 36 months for T4 colon-rectal carcinoma. TRIAL REGISTRATION: NCT02614534 ( clinicaltrial.gov ) Nov-2015.

The fusogenic peptide HA2 impairs selectivity of CXCR4-targeted protein nanoparticles.

We demonstrate here that the genetic incorporation of the fusogenic peptide HA2 into a CXCR4-targeted protein nanoparticle dramatically reduces the specificity of the interaction between nanoparticles and cell receptors, a factor to be considered when designing tumor-homing drug vehicles displaying endosomal-escape agents. The loss of specificity is concomitant with enhanced cell penetrability.

Characteristics and treatment of pyoderma gangrenosum in inflammatory bowel disease.

BACKGROUND: Pyoderma gangrenosum is a serious cutaneous complication seen in approximately 1 % of patients with inflammatory bowel disease (IBD). Oral corticosteroids are the mainstay treatment, although the evidence supporting their use is weak. AIMS: The purpose of this study was to investigate the characteristics of pyoderma gangrenosum associated with Crohn's disease or ulcerative colitis and which treatments are prescribed in Spanish clinical practice. METHODS: In this retrospective, observational study, the medical records from all patients with IBD and a diagnosis of pyoderma gangrenosum attended by the gastroenterology departments of 12 Spanish hospitals were reviewed. Data on patient demographics and characteristics, underlying IBD and treatment, and pyoderma gangrenosum characteristics, treatment, and outcome were collected and analyzed. RESULTS: The data from 67 patients were analyzed (41 [61.2 %] women, 41 [61.2 %] with Crohn's disease, 25 [37.3 %] with ulcerative colitis, and 1 [1.5 %] with indeterminate disease). The underlying disease was in remission in approximately one-third of patients at the time of presentation of pyoderma gangrenosum. Healing was achieved in all patients (in 3 without any systemic therapy). Oral corticosteroids were taken by 51 patients (76.1 %), almost always as first-line treatment, although definitive healing was attained in 19 (28.4 %). Biologic agents such as infliximab and adalimumab were taken by 31 patients (46.3 %) at some point (first-line in 6 patients [9.0 %]), with definitive healing in 29 patients (93.5 %). CONCLUSIONS: Oral corticosteroid therapy remains the most common treatment for pyoderma gangrenosum associated with inflammatory bowel disease. Biologic therapies such as infliximab and adalimumab should also be considered.

Minimally invasive treatment of colorectal liver metastases.

Minimally invasive approaches are increasingly used in the treatment of colorectal liver metastases (CRLMs) and for increasingly complex cases. Herein, we review the spectrum of modalities used in the minimally invasive treatment of CRLM, focusing on one of the newest approaches, robotic liver resection, and on local regional therapies, both operative and percutaneous. Oncologic outcomes after minimally invasive therapies are also evaluated. Although there are no randomized trials comparing minimally invasive liver resection to open resection, an increasing quantity of nonrandomized data suggest favorable outcomes with a minimally invasive approach. The future of minimally invasive treatment of CRLM will likely include specifying training and credentialing criteria as well as an enlarging role for the combined surgical treatment of CRLM and extrahepatic colorectal metastases.

Dual Effect of low-level laser therapy (LLLT) on the acute lung inflammation induced by intestinal ischemia and reperfusion: Action on anti- and pro-inflammatory cytokines.

BACKGROUND AND OBJECTIVE: It is unknown if pro- and anti-inflammatory mediators in acute lung inflammation induced by intestinal ischemia and reperfusion (i-I/R) can be modulated by low-level laser therapy (LLLT). STUDY DESIGN/MATERIAL AND METHODS: A controlled ex vivo study was developed in which rats were irradiated (660 nm, 30 mW, 0.08 cm² of spot size) on the skin over the right upper bronchus 1 hour post-mesenteric artery occlusion and euthanized 4 hours later. For pretreatment with anti-tumor necrosis factor (TNF) or IL-10 antibodies, the rats received either one of the agents 15 minutes before the beginning of reperfusion. METHODS: Lung edema was measured by the Evans blue extravasation and pulmonary neutrophils influx was determined by myeloperoxidase (MPO) activity. Both TNF and IL-10 expression and protein in lung were evaluated by RT-PCR and ELISA, respectively. RESULTS: LLLT reduced the edema (80.1 ± 41.8 µg g⁻¹ dry weight), neutrophils influx (0.83 ± 0.02 × 106 cells ml⁻¹), MPO activity (2.91 ± 0.60), and TNF (153.0 ± 21.0 pg mg⁻¹ tissue) in lung when compared with respective control groups. Surprisingly, the LLLT increased the IL-10 (0.65 ± 0.13) in lung from animals subjected to i-I/R. Moreover, LLLT (0.32 ± 0.07 pg ml⁻¹) reduced the TNF-α level in RPAECs when compared with i-I/R group. The presence of anti-TNF or IL-10 antibodies did not alter the LLLT effect on IL-10 (465.1 ± 21.0 pg mg⁻¹ tissue) or TNF (223.5 ± 21.0 pg mg⁻¹ tissue) in lung from animals submitted to i-I/R. CONCLUSION: The results indicate that the LLLT attenuates the i-I/R-induced acute lung inflammation which favor the IL-10 production and reduce TNF generation.

Environmental quality of mussel farms in the Vigo estuary: pollution by PAHs, origin and effects on reproduction.

This work analyzes the influence of environmental and physiological parameters on PAHs accumulation in cultured mussels. Lipid content and reproductive stage are directly related with PAHs accumulation pattern. We observed a rapid accumulation and depuration of PAHs, mainly during periods of nutrients accumulation, spawns and gonadic restorations. Correlations between PAHs accumulation and physiological status indicate when mussels are more susceptible to adverse effects of these pollutants. A positive correlation between mutagenic congener's accumulation and occurrence of gonadic neoplastic disorders is shown for the first time in mussels. Molecular indices were used to identify the origin of hydrocarbons accumulated by Mytilus, showing a chronic pyrolytic pollution and pollutant episodes by petrogenic sources and biomass combustion in the studied area. Multivariate analysis suggests the possibility of including physiological parameters of sentinel organisms in environmental biomonitoring programs, mainly in aquaculture areas, taking into account their two aspects: farms productivity and human food safety.

Low-level laser therapy (LLLT) acts as cAMP-elevating agent in acute respiratory distress syndrome.

The aim of this work was to investigate if the low-level laser therapy (LLLT) on acute lung inflammation (ALI) induced by lipopolysaccharide (LPS) is linked to tumor necrosis factor (TNF) in alveolar macrophages (AM) from bronchoalveolar lavage fluid (BALF) of mice. LLLT has been reported to actuate positively for relieving the late and early symptoms of airway and lung inflammation. It is not known if the increased TNF mRNA expression and dysfunction of cAMP generation observed in ALI can be influenced by LLLT. For in vivo studies, Balb/c mice (n = 5 for group) received LPS inhalation or TNF intra nasal instillation and 3 h after LPS or TNF-α, leukocytes in BALF were analyzed. LLLT administered perpendicularly to a point in the middle of the dissected bronchi with a wavelength of 660 nm and a dose of 4.5 J/cm(2). The mice were irradiated 15 min after ALI induction. In vitro AM from mice were cultured for analyses of TNF mRNA expression and protein and adenosine3':5'-cyclic monophosphate (cAMP) levels. One hour after LPS, the TNF and cAMP levels in AM were measured by ELISA. RT-PCR was used to measure TNF mRNA in AM. The LLLT was inefficient in potentiating the rolipram effect in presence of a TNF synthesis inhibitor. LLLT attenuated the neutrophil influx and TNF in BALF. In AM, the laser increased the cAMP and reduced the TNF-α mRNA. LLLT increases indirectly the cAMP in AM by a TNF-dependent mechanism.

Efeito do gel da babosa (Aloe barbadensis Mill. ) associado ao ultrassom em processo inflamatório agudo / Effect of aloe (Aloe barbadensis Mill. ) gel combined with ultrasound in the acute inflammatory process

O presente trabalho teve por objetivo analisar a ação antiinflamatória do gel da Babosa a 2 por cento (Aloe barbadensis Mill.) associado ao Ultrassom pulsátil no modelo de edema de pata. Foram utilizados 25 ratos Wistar, (200-250 g), divididos em 5 grupos de 5 animais cada. Grupo1 (controle): ratos tratados com solução salina a 0,9 por cento; Grupo 2: ratos tratados topicamente com gel de A. barbadensis Mill. a 2 por cento; Grupo 3: animais tratados com Ultrassom; Grupo 4: ratos tratados com gel de A. barbadensis Mill. a 2 por cento associado ao Ultrassom; Grupo 5 (controle positivo): ratos tratados com Indometacina na dose de 5 mg Kg-1. Os animais dos grupos 1 e 5 receberam os respectivos tratamentos por via intra-peritoneal 30 minutos antes da injeção intra-plantar de carragenina e os grupos 2, 3 e 4 foram tratados por aplicação tópica de gel de A. barbadensis Mill. a 2 por cento, Ultrassom pulsátil e gel de A. barbadensis Mill. associado ao Ultrassom respectivamente 15 minutos após a indução do edema. Os animais do grupo 04 demonstraram redução significativa do edema quando comparados ao grupo controle, ao mesmo tempo, que se mostrou comparável à indometacina. Observou-se que o gel de aloe associado à fonoforose é capaz reduzir a formação do edema de pata em ratos.

This work aimed to evaluate the anti-inflammatory action of 2 percent aloe (Aloe barbadensis Mill.) gel combined with pulsed ultrasound in the paw edema model. Twenty-five Wistar rats (200-250 g) were divided into 5 groups of 5 animals each. Group1 (control): rats treated with 0.9 percent saline; Group 2: rats topically treated with 2 percent aloe gel; Group 3: rats treated with ultrasound; Group 4: rats treated with 2 percent aloe gel combined with ultrasound; Group 5 (positive control): rats treated with indomethacin at 5 mg Kg-1. Animals of groups 1 and 5 were intraperitoneally treated 30 min before intraplantar carrageenan injection and groups 2, 3 and 4 were treated by topical application of 2 percent aloe gel, pulsed ultrasound and aloe gel combined with ultrasound, respectively, 15 min after edema induction. Animals of group 4 had a significant reduction in edema relative to controls and showed to be comparable to indomethacin. Aloe gel combined with phonophoresis is capable of reducing paw edema formation in rats.

Low-level laser therapy associated to N-acetylcysteine lowers macrophage inflammatory protein-2 (MIP-2) mRNA expression and generation of intracellular reactive oxygen species in alveolar macrophages.

OBJECTIVE: The aim of this work was to investigate the low-level laser therapy (LLLT) effect on alveolar macrophages (AM) activated by oxidative stress and lipopolysaccharide (LPS). BACKGROUND DATA: LLLT has been reported to actuate positively relieving the late and early symptoms of airway and lung inflammation. It is not known if the increased MIP-2 mRNA expression and intracellular reactive oxygen species (ROS) generation observed in acute lung inflammation (ALI) can be influenced by LLLT. MATERIALS AND METHODS: Rat AM cell line (AMJ2-C11) was cultured with LPS or H(2)O(2) and laser irradiated. MIP-2 mRNA and ROS production in the AM were evaluated by Real Time-PCR and the 2',7'-dichlorofluorescin diacetate (DCFH-DA) respectively. The NF-κB protein in the AM was measured by the enzyme linked immunoassay method. To investigate the antioxidant effect of laser, the AM were prebathed with N-acetylcysteine (NAC) and then irradiated with laser. LLLT was also studied in the presence of an inhibitor of NF-κB (BMS 205820). In addition, the effect of LLLT on NF-κB protein was investigated. RESULTS: LLLT attenuated the MIP-2 mRNA expression and intracellular ROS generation after LPS or H(2)O(2). When the AM were pretreated with NAC, the laser effect was potentiated. BMS 205820 suppresses the effect of LLLT on MIP-2 mRNA expression and ROS generation, stimulated by LPS or H(2)O(2). On NF-κB transcription factor, both the LLLT and NAC reduced this protein in the AM exposed to LPS or H(2)O(2). The synergistic effect between LLLT and NAC on the reduction the NF-κB was also evidenced. CONCLUSION: Results indicate that there is a synergistic action of LLLT with NAC on MIP-2 mRNA expression from LPS- or H(2)O(2)-stimulated AM, and that both ROS intracellular generation and NF-kB signaling seem to be involved.

Low intensity laser therapy (LILT) in vivo acts on the neutrophils recruitment and chemokines/cytokines levels in a model of acute pulmonary inflammation induced by aerosol of lipopolysaccharide from Escherichia coli in rat.

It has been suggested that low intensity laser therapy (LILT) acts on pulmonary inflammation. Thus, we investigate in this work if LILT (650nm, 2.5mW, 31.2mW/cm(2), 1.3J/cm(2), laser spot size of 0.08cm(2) and irradiation time of 42s) can attenuate edema, neutrophil recruitment and inflammatory mediators in acute lung inflammation. Thirty-five male Wistar rats (n=7 per group) were distributed in the following experimental groups: control, laser, LPS, LPS+laser and dexamethasone+LPS. Airway inflammation was measured 4h post-LPS challenge. Pulmonary microvascular leakage was used for measuring pulmonary edema. Bronchoalveolar lavage fluid (BALF) cellularity and myeloperoxidase (MPO) were used for measuring neutrophil recruitment and activation. RT-PCR was performed in lung tissue to assess mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin (IL-10), cytokine-induced neutrophil chemoattractant-1 (CINC-1), macrophage inflammatory protein-2 (MIP-2) and intercellular adhesion molecule-1 (ICAM-1). Protein levels in both BALF and lung were determined by ELISA. LILT inhibited pulmonary edema and endothelial cytoskeleton damage, as well as neutrophil influx and activation. Similarly, the LILT reduced the TNF-α and IL-1ß, in lung and BALF. LILT prevented lung ICAM-1 up-regulation. The rise of CINC-1 and MIP-2 protein levels in both lung and BALF, and the lung mRNA expressions for IL-10, were unaffected. Data suggest that the LILT effect is due to the inhibition of ICAM-1 via the inhibition of TNF-α and IL-1ß.

Low-level laser therapy decreases local effects induced by myotoxins isolated from bothrops jararacussu snake venom

The prominent myotoxic effects induced by Bothrops jararacussu crude venom are due, in part, to its polycationic myotoxins, BthTX-I and BthTX-II. Both myotoxins have a phospholipase A2 structure: BthTX-II is an active enzyme Asp-49 PLA2, while BthTX-I is a Lys-49 PLA2 devoid of enzymatic activity. In this study, the effect of low-level laser therapy (LLLT), 685 nm laser at a dose of 4.2 J/cm2 on edema formation, leukocyte influx and myonecrosis caused by BthTX-I and BthTX-II, isolated from Bothrops jararacussu snake venom, was analyzed. BthTX-I and BthTX-II caused a significant edema formation, a prominent leukocyte infiltrate composed predominantly by neutrophils and myonecrosis in envenomed gastrocnemius muscle. LLLT significantly reduced the edema formation, neutrophil accumulation and myonecrosis induced by both myotoxins 24 hours after the injection. LLLT reduced the myonecrosis caused by BthTX-I and BthTX-II, respectively, by 60 and 43 percent; the edema formation, by 41 and 60.7 percent; and the leukocyte influx, by 57.5 and 51.6 percent. In conclusion, LLLT significantly reduced the effect of these snake toxins on the inflammatory response and myonecrosis. These results suggest that LLLT should be considered a potential therapeutic approach for treatment of local effects of Bothrops species venom.

Effect of progesterone and ionomycin on domestic cat sperm motility patterns and acrosome reaction.

This study was aimed at assessing the changes in sperm motion patterns and the percentage of acrosome reaction (AR) in domestic cat semen after treatment with either ionomycin or progesterone (P(4)). Ten ejaculates were collected from five tomcats using an artificial vagina, and were diluted, centrifuged and resuspended in a capacitation medium. Samples were evaluated and divided into seven equal aliquots and, after 2 h at 25 degrees C, were incubated for 30 min at 38 degrees C in 5% CO(2) and then analyzed. Computer-assisted sperm analysis and a combination of three fluorescent probes were used to assess sperm plasma, acrosomal membrane integrity and mitochondrial transmembrane potential. Thirty minutes after the start of incubation, P(4) was added (10 microg/ml) to the P1 group. Groups P2 and P3 were supplemented with P(4) (10 and 20 microg/ml, respectively) only after 2 h of incubation, and groups I1 and I2 were supplemented with ionomycin (4 and 8 mum, respectively) 2 h after incubation. Group E was supplemented with ethanol (0.6%) at 2 h after incubation and group C received no supplementation. Ionomycin and P(4) treatments led to a hyperactivation-like sperm motion and an increase (p < 0.05) in the percentage of AR. Although a higher (p < 0.05) percentage of AR was obtained in group I2 when compared with all P(4) groups, a decrease (p < 0.05) in total and progressive motility was observed in I2 group. As I1 group was similar to I2 to induce AR without diminishing sperm motility, we can conclude that ionomycin at 4 microm seems to be more suitable to trigger AR in domestic cat sperm.

Lung inflammation and endothelial cell damage are decreased after treatment with phototherapy (PhT) in a model of acute lung injury induced by Escherichia coli lipopolysaccharide in the rat.

Lipopolysaccharide (LPS) mimics the symptoms of acute lung injury (ALI), which is characterized by the accumulation in the lungs of neutrophils producing inflammatory mediators. Because of the lack of information about phototherapy (PhT) effects on ALI, we investigated whether PhT (685nm InGaAlP) attenuates LPS-induced ALI. PhT reduced lung edema, the accumulation of TNF-alpha in the lung, and myeloperoxidase (MPO) activity. However, PhT was not efficient in reducing of TNF-alpha concentration in both serum and neutrophils of blood after LPS. In another series of experiments, in vitro assays of the effects of PhT effect on mouse pulmonary arterial endothelium cells (MPAECs) after TNF-alpha showed that the laser restores the MPAECs damage induced at 6 or 24h after TNF-alpha. These results suggest the PhT effect on ALI is partly due to inhibition of TNF-alpha release from neutrophils and lung cells.

Anti-inflammatory effects of low-level laser therapy (LLLT) with two different red wavelengths (660 nm and 684 nm) in carrageenan-induced rat paw edema.

It has been suggested that low-level laser therapy (LLLT) can modulate inflammatory processes. The aim of this experiment was to investigate what effects red laser irradiation with two different wavelengths (660 nm and 684 nm) on carrageenan-induced rat paw edema and histology. Thirty two male Wistar rats were randomly divided into four groups. One group received a sterile saline injection, while inflammation was induced by a sub-plantar injection of carrageenan (1 mg/paw) in the three other groups. After 1 h, LLLT was administered to the paw in two of the carrageenan-injected groups. Continuous wave 660 nm and 684 nm red lasers respectively with mean optical outputs of 30 mW and doses of 7.5 J/cm(2) were used. The 660 nm and 684 nm laser groups developed significantly (p<0.01) less edema (0.58 ml [SE+/-0.17] ml and 0.76 ml [SE+/-0.10] respectively) than the control group (1.67 ml [SE+/-0.19]) at 4h after injections. Similarly, both laser groups showed a significantly lower number of inflammatory cells in the muscular and conjunctive sub-plantar tissues than the control group. We conclude that both 660 nm and 684 nm red wavelengths of LLLT are effective in reducing edema formation and inflammatory cell migration when a dose of 7.5 J/cm(2) is used.

Clinical impact of conventional endosonography and endoscopic ultrasound-guided fine-needle aspiration in the assessment of patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma who have been referred for endoscopic ablation therapy.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection and photodynamic therapy are exciting, minimally invasive curative techniques that represent an alternative to surgery in patients with Barrett's esophagus and high-grade dysplasia or intramucosal adenocarcinoma. However, there is lack of uniformity regarding which staging method should be used prior to therapy, and some investigators even question whether staging is required prior to ablation. We report our experience with a protocol of conventional endoscopic ultrasound staging prior to endoscopic therapy. PATIENTS AND METHODS: A total of 25 consecutive patients with a diagnosis of high-grade dysplasia or intramucosal adenocarcinoma in Barrett's esophagus who had been referred to the University of Chicago for staging in preparation for endoscopic therapy between March 2002 and November 2004 were included in the study. All 25 patients underwent repeat diagnostic endoscopy and conventional endosonography with a radial echo endoscope. Any suspicious lymph nodes that were detected were sampled using endoscopic ultrasound-guided fine-needle aspiration. RESULTS: Baseline pathology in the 25 patients (mean age 70, range 49-85) revealed high-grade dysplasia in 12 patients and intramucosal carcinoma in 13 patients. Five patients were found to have submucosal invasion on conventional endosonography. Seven patients had suspicious adenopathy, six regional (N1) and one metastatic to the celiac axis (M1a). Fine-needle aspiration confirmed malignancy in five of these seven patients. Based on these results, five patients (20%) were deemed to be unsuitable candidates for endoscopic therapy. CONCLUSIONS: By detecting unsuspected malignant lymphadenopathy, conventional endosonography and endoscopic ultrasound with fine-needle aspiration dramatically changed the course of management in 20% of patients referred for endoscopic therapy of Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma. Based on our results, we believe that conventional endosonography and endoscopic ultrasound with fine-needle aspiration when nodal disease is present should be performed routinely in all patients referred for endoscopic therapy in this setting.

Analgesic effect of He-Ne (632.8 nm) low-level laser therapy on acute inflammatory pain.

OBJECTIVE: The aim of this study was to evaluate the analgesic effect of the low level laser therapy (LLLT) with a He-Ne laser on acute inflammatory pain, verifying the contribution of the peripheral opioid receptors and the action of LLLT on the hyperalgesia produced by the release of hyperalgesic mediators of inflammation. BACKGROUND DATA: All analgesic drugs have undesired effects. Because of that, other therapies are being investigated for treatment of the inflammatory pain. Among those, LLLT seems to be very promising. MATERIAL AND METHODS: Male Wistar rats were used. Three complementary experiments were done. (1) The inflammatory reaction was induced by the injection of carrageenin into one of the hind paws. Pain threshold and volume increase of the edema were measured by a pressure gauge and plethysmography, respectively. (2) The involvement of peripheral opioid receptors on the analgesic effect of the laser was evaluated by simultaneous injection of carrageenin and naloxone into one hind paw. (3) Hyperalgesia was induced by injecting PGE2 for the study of the effect of the laser on the sensitization increase of nociceptors. A He-Ne laser (632.8 nm) of 2.5 J/cm2 was used for irradiation. RESULTS: We found that He-Ne stimulation increased the pain threshold by a factor between 68% and 95% depending on the injected drug. We also observed a 54% reduction on the volume increase of the edema when it was irradiated. CONCLUSION: He-Ne LLLT inhibits the sensitization increase of nociceptors on the inflammatory process. The analgesic effect seems to involve hyperalgesic mediators instead of peripheral opioid receptors.

A mathematical approach to molecular organization and proteolytic disintegration of bacterial inclusion bodies.

The in vivo proteolytic digestion of bacterial inclusion bodies (IBs) and the kinetic analysis of the resulting protein fragments is an interesting approach to investigate the molecular organization of these unconventional protein aggregates. In this work, we describe a set of mathematical instruments useful for such analysis and interpretation of observed data. These methods combine numerical estimation of digestion rate and approximation of its high-order derivatives, modelling of fragmentation events from a mixture of Poisson processes associated with differentiated protein species, differential equations techniques in order to estimate the mixture parameters, an iterative predictor-corrector algorithm for describing the flow diagram along the cascade process, as well as least squares procedures with minimum variance estimates. The models are formulated and compared with data, and successively refined to better match experimental observations. By applying such procedures as well as newer improved algorithms of formerly developed equations, it has been possible to model, for two kinds of bacterially produced aggregation prone recombinant proteins, their cascade digestion process that has revealed intriguing features of the IB-forming polypeptides.

[Transdermal iontophoresis with dexamethasone and verapamil for Peyronie's disease]. / Iontoforesis transdérmica con dexametasona y verapamilo para la enfermedad de la Peyronie.

OBJECTIVES: To evaluate the effects of transdermal iontophoresis with verapamil and dexamethasone in patients with Peyronie's disease of less than one year of evolution. MATERIAL AND METHODS: We have treated ten patients twice a week during six consecutive weeks using iontophoresis with a Miniphysionizer dispositive. This device generates a 2mA electric current during 20 min which triggers the transdermal penetration of medication. In every session dexamethasone 8 mg and verapamil 5mg were administered inside a small self-adhesive receptacle on the penile skin overlying the fibrosis plaque. To evaluate the efficacy, penile curvature was measured by Kelami's test, while the plaque size was assessed by penile ultrasound. Other parameters like pain, erectile function and ability for vaginal intercourse were recorded using questionnaires. Safety parameters were also assessed during treatment. RESULTS: No improvement or progression in penile curvature was evidenced in any of the patients. The hardness of the plaque was reduced in 5 patients, becoming impalpable in 2 of them. Decrease in plaque volume was observed by penile ultrasound in 6. Pain improved in 8 patients, disappearing in 6 of them. One patient recovered his erectile function at the end of the treatment; whereas 3 referred that their ability for intercourse enhanced while 2 reported that treatment improved their sexual life in general. We didn't record any significantly side effects, except for a transitory and slight dermal redness on the site of electrode placement. CONCLUSIONS: Transdermal iontophoresis is an effective treatment for pain control in early stages of Peyronie's disease. Efficacy in reducing penile curvature seems to be limited. Controlled clinical trials are needed, and perhaps reviewing indications in order to obtain more relevant clinical effects.

Effect of GaInAIP (685 nm) radiation on lipopolyssacharide induced rat trachea hyperreactivity

O objetivo do presente estudo foi investigar o efeito do laser de baixa potência (LLLT) na hiper-reatividade da traquéia de ratos Wistar macho(RTHR) depois da administração de lipopolissacarídeo (LPS)