156 research outputs found
Cardiovascular and hepatic toxicity of cocaine: potential beneficial effects of modulators of oxidative stress
Oxidative stress (OS) is thought to play an important role in the pharmacological and toxic effects of various drugs of abuse. Herein we review the literature on the mechanisms responsible for the cardiovascular and hepatic toxicity of cocaine with special focus on OS-related mechanisms. We also review the preclinical and clinical literature concerning the putative therapeutic effects of OS modulators (such as N-acetylcysteine, superoxide dismutase mimetics, nitroxides and nitrones, NADPH oxidase inhibitors, xanthine oxidase inhibitors, and mitochondriotropic antioxidants) for the treatment of cocaine toxicity. We conclude that available OS modulators do not appear to have clinical efficacy
Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: clinical and immunological data of a phase I/II clinical trial
Vaccination with priming and expansion of tumour
reacting T cells is an important therapeutic option to be used
in combination with novel checkpoint inhibitors to increase
the specificity of the T cell infiltrate and the efficacy of the
treatment. In this phase I/II study, 14 high-risk disease-free
ovarian (OC) and breast cancer (BC) patients after completion
of standard therapies were vaccinated with MUC1, ErbB2
and carcinoembryonic antigen (CEA) HLA-A2+-restricted
peptides and Montanide. Patients were subjected to 6 doses
of vaccine every two weeks and a recall dose after 3 months.
ECOG grade 2 toxicity was observed at the injection site. Eight
out of 14 patients showed specific CD8+ T cells to at least one
antigen. None of 4 patients vaccinated for compassionate use
showed a CD8 activation. An OC patient who suffered from
a lymph nodal recurrence, showed specific anti-ErbB2 CD8+
T cells in the bulky aortic lymph nodes suggesting homingof the activated T cells. Results confirm that peptide vaccination
strategy is feasible, safe and well tolerated. In particular
OC patients appear to show a higher response rate compared
to BC patients. Vaccination generates a long-lasting immune
response, which is strongly enhanced by recall administrations.
The clinical outcome of patients enrolled in the trial
appears favourable, having registered no deceased patients
with a minimum follow-up of 8 years. These promising data,
in line with the results of similar studies, the high compliance
of patients observed and the favourable toxicity profile, support
future trials of peptide vaccination in clinically disease-free
patients who have completed standard treatments
Minimally Invasive Surgery in Gynecology
The first laparoscopic procedure was performed by 1901 by Georg Kelling in dogs while the first laparoscopic procedure in humans was performed by Hans Chrisitan Jacobaeus in 1910. Minimally invasive surgery offers multiple advantages over conventional laparotomy and is associated with reduced estimated blood loss, a lower incidence of complications and a shorter hospital stay and recovery. Over a century later, the vast majority of surgical procedures in gynecology are performed via minimal invasive technique. These include laparoscopy, minilaparoscopy, robotic surgery, laparoendoscopic single site surgery (LESS) and natural orifices transluminal endoscopic surgery. In this chapter we review these surgical techniques, analyze the main differences among these techniques and comment on their advantages and disadvantages
Cardiovascular and Hepatic Toxicity of Cocaine: Potential Beneficial Effects of Modulators of Oxidative Stress
Oxidative stress (OS) is thought to play an important role in the pharmacological and toxic effects of various drugs of abuse. Herein we review the literature on the mechanisms responsible for the cardiovascular and hepatic toxicity of cocaine with special focus on OS-related mechanisms. We also review the preclinical and clinical literature concerning the putative therapeutic effects of OS modulators (such as N-acetylcysteine, superoxide dismutase mimetics, nitroxides and nitrones, NADPH oxidase inhibitors, xanthine oxidase inhibitors, and mitochondriotropic antioxidants) for the treatment of cocaine toxicity. We conclude that available OS modulators do not appear to have clinical efficacy
Discovery of chemotherapy-associated ovarian cancer antigens by interrogating memory T cells
According to the immunogenic cell death hypothesis, clinical chemotherapy treatments may result in CD8(+) and CD4(+) T-cell responses against tumor cells. To discover chemotherapy-associated antigens (CAAs), T cells derived from ovarian cancer (OC) patients (who had been treated with appropriate chemotherapy protocols) were interrogated with proteins isolated from primary OC cells. We screened for immunogenicity using two-dimensional electrophoresis gel-eluted OC proteins. Only the selected immunogenic antigens were molecularly characterized by mass-spectrometry-based analysis. Memory T cells that recognized antigens associated with apoptotic (but not live) OC cells were correlated with prolonged survival in response to chemotherapy, supporting the model of chemotherapy-induced apoptosis as an adjuvant of anti-tumor immunity. The strength of both memory CD4(+) and CD8(+) T cells producing either IFN- or IL-17 in response to apoptotic OC antigens was also significantly greater in Responders to chemotherapy than in nonresponders. Immunogenicity of some of these antigens was confirmed using recombinant proteins in an independent set of patients. The T-cell interrogation system represents a strategy of reverse tumor immunology that proposes to identify CAAs, which may then be validated as possible prognostic tumor biomarkers or cancer vaccines
HER2-based recombinant immunogen to target DCs through FcÎłRs for cancer immunotherapy
Dendritic cell (DC)-based immunotherapy is an attractive approach to induce long lasting antitumor effector cells aiming to control cancer progression. DC targeting is a critical step in the design of DC vaccines in order to optimize delivery and processing of the antigen, and several receptors have been characterized for this purpose. In this study, we employed the FcγRs to target DCs both in vitro and in vivo. We designed a recombinant molecule (HER2-Fc) composed of the immunogenic sequence of the human tumor-associated antigen HER2 (aa 364–391) and the Fc domain of a human IgG1. In a mouse model, HER2-Fc cDNA vaccination activated significant T cell-mediated immune responses towards HER2 peptide epitopes as detected by IFN-γ ELIspot and induced longer tumor latency as compared to Ctrl-Fc-vaccinated control mice. Human in vitro studies indicated that the recombinant HER2-Fc immunogen efficiently targeted human DCs through the FcγRs resulting in protein cross-processing and in the activation of autologous HER2-specific CD8+ T cells from breast cancer patients
Ultrasonic vocalization in rats self-administering heroin and cocaine in different settings: evidence of substance-specific interactions between drug and setting
Rationale
Clinical and preclinical evidence indicates that the setting of drug use affects drug reward in a substance-specific manner. Heroin and cocaine co-abusers, for example, indicated distinct settings for the two drugs: heroin being used preferentially at home and cocaine preferentially outside the home. Similar results were obtained in rats that were given the opportunity to self-administer intravenously both heroin and cocaine.
Objectives
The goal of the present study was to investigate the possibility that the positive affective state induced by cocaine is enhanced when the drug is taken at home relative to a non-home environment, and vice versa for heroin.
Methods
To test this hypothesis, we trained male rats to self-administer both heroin and cocaine on alternate days and simultaneously recorded the emission of ultrasonic vocalizations (USVs), as it has been reported that rats emit 50-kHz USVs when exposed to rewarding stimuli, suggesting that these USVs reflect positive affective states.
Results
We found that Non-Resident rats emitted more 50-kHz USVs when they self-administered cocaine than when self-administered heroin whereas Resident rats emitted more 50-kHz USVs when self-administering heroin than when self-administering cocaine. Differences in USVs in Non-Resident rats were more pronounced during the first self-administration (SA) session, when the SA chambers were completely novel to them. In contrast, the differences in USVs in Resident rats were more pronounced during the last SA sessions.
Conclusion
These findings indicate that the setting of drug taking exerts a substance-specific influence on the ability of drugs to induce positive affective states
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