Sedative effect of central administration of Coriandrum sativum essential oil and its major component linalool in neonatal chicks.

Context Coriandrum sativum L. (Apiaceae) (coriander) is an herb grown throughout the world as a culinary, medicinal or essential crop. In traditional medicine, it is used for the relief of anxiety and insomnia. Systemic hydro-alcoholic and aqueous extract from aerial parts and seeds had anxiolytic and sedative action in rodents, but little is known about its central effect in chicks. Objective To study the effects of intracerebroventricular administration of essential oil from coriander seeds and its major component linalool on locomotor activity and emotionality of neonatal chicks. Materials and methods The chemical composition of coriander essential oil was determined by a gas-chromatographic analysis (> 80% linalool). Behavioural effects of central administration of coriander oil and linalool (both at doses of 0.86, 8.6 and 86 µg/chick) versus saline and a sedative diazepam dose (17.5 µg/chick, standard drug) in an open field test for 10 min were observed. Results Doses of 8.6 and 86 µg from coriander oil and linalool significantly decreased (p < 0.05) squares crossed number, attempted escapes, defecation number and distress calls, and significantly increased (p < 0.05) the sleeping posture on an open field compared with saline and were similar to the diazepam group. Discussion and conclusion The results indicate that intracerebroventricular injection of essential oil from Coriandrum sativum seeds induced a sedative effect at 8.6 and 86 µg doses. This effect may be due to monoterpene linalool, which also induced a similar sedative effect, and, therefore, could be considered as a potential therapeutic agent similar to diazepam.

Induction of anti-anti-idiotype antibodies against sulfated glycosaminoglycans reduces atherosclerosis in apolipoprotein E-deficient mice.

OBJECTIVE: The pathogenesis of atherosclerosis is associated with the early retention of low-density lipoproteins that are trapped in the extracellular matrix of the arterial intima by interaction with glycosaminoglycan side chains of proteoglycans. Mutant mouse/human chimeric antibodies of the murine monoclonal antibody P3, which react with N-glycolyl-containing gangliosides and sulfated glycosaminoglycans, were tested for their potentially antiatherogenic properties through the induction of an idiotypic antibody network that may specifically interfere with the binding of low-density lipoproteins to proteoglycan side chains, low-density lipoprotein modification, and foam cell formation. METHODS AND RESULTS: Apolipoprotein E-deficient mice fed a high-fat, high-cholesterol diet received 5 to 6 doses of chP3R99 or chP3S98 mutant antibodies, showing high and low reactivity, respectively, against their respective antigens. Both chimeric antibodies elicited an immunodominant anti-idiotypic response in the absence of adjuvant. A striking (40%-43%) reduction (P<0.01) in total lesion areas was observed in 18-week-old mice immunized with chP3R99, but not chP3S98, compared with PBS-treated mice. The antiatherosclerotic effect was associated with increased mice sera reactivity against heparin and sulfated glycosaminoglycans, including chondroitin and dermatan sulfate. In addition, purified IgG from chP3R99-immunized mice blocked the retention of apolipoprotein B-containing lipoproteins within the arterial wall of apolipoprotein E(-/-) mice. CONCLUSIONS: The present study supports use of active immunization and the mounting of an idiotypic antibody network response against glycosaminoglycans as a novel approach to target atherosclerosis.

Antiatherosclerotic effect of an antibody that binds to extracellular matrix glycosaminoglycans.

OBJECTIVE: Subendothelial retention of proatherogenic lipoproteins by proteoglycans is critical in atherosclerosis. The aim of this study was to characterize the recognition and antiatherogenic properties of a chimeric monoclonal antibody (mAb) that reacts with sulfated molecules. METHODS AND RESULTS: chP3R99 mAb recognized sulfated glycosaminoglycans, mainly chondroitin sulfate (CS), by ELISA. This mAb blocked ≈70% of low-density lipoprotein (LDL)-CS association and ≈80% of LDL oxidation in vitro, and when intravenously injected to Sprague-Dawley rats (n=6, 1 mg/animal), it inhibited LDL (4 mg/kg intraperitoneally, 1 hour later) retention and oxidation in the artery wall. Moreover, subcutaneous immunization of New Zealand White rabbits (n=19) with chP3R99 mAb (100 µg, 3 doses at weekly intervals) prevented Lipofundin-induced atherosclerosis (2 mL/kg, 8 days) with a 22-fold reduction in the intima-media ratio (P<0.01). Histopathologic and ultrastructural studies showed no intimal alterations or slight thickening, with preserved junctions between endothelial cells and scarce collagen fibers and glycosaminoglycans. In addition, immunization with chP3R99 mAb suppressed macrophage infiltration in aorta and preserved redox status. The atheroprotective effect was associated with the induction of anti-CS antibodies in chP3R99-immunized rabbits, capable of blocking CS-LDL binding and LDL oxidation. CONCLUSION: These results support the use of anti-sulfated glycosaminoglycan antibody-based immunotherapy as a potential tool to prevent atherosclerosis.

Anti-NeuGcGM3 antibodies, actively elicited by idiotypic vaccination in nonsmall cell lung cancer patients, induce tumor cell death by an oncosis-like mechanism.

1E10 is a murine anti-idiotypic mAb specific for an idiotypic mAb that reacts with NeuGc-containing gangliosides, sulfatides, and Ags expressed in some human tumors. In melanoma, breast, and lung cancer patients, this anti-idiotypic Ab was able to induce a specific Ab response against N-glycosylated gangliosides, attractive targets for cancer immunotherapy as these glycolipids are not naturally expressed in humans. A clinical study with nonsmall cell lung cancer patients showed encouraging clinical benefits. Immunological studies performed in 20 of these patients suggested a correlation between the induction of Abs against NeuGcGM3 and longer survival times. The induced anti-NeuGcGM3 Abs recognized and directly killed tumor cells expressing the Ag, by a mechanism independent of complement activation. In the present work, we show that this cytotoxicity differs from apoptosis because it is temperature independent, no chromatin condensation or caspase 3 induction are detected, and the DNA fragmentation induced has a different pattern than the one characteristic for apoptosis. It is a very quick process and involves cytosqeleton reorganization. The Abs induce cellular swelling and the formation of big membrane lesions that allow the leakage of cytoplasm and the loss of the cell membrane integrity. All of these characteristics resemble a process of oncotic necrosis. To our knowledge, this is the first report of the active induction in cancer patients of NeuGcGM3-specific Abs able to induce complement independent oncotic necrosis to tumor cells. These results contribute to reinforcing the therapeutic potential of anti-idiotypic vaccines and the importance of NeuGcGM3 ganglioside as antitumor target.

Partial Thrombosis of Corpus Cavernosum.

Thrombosis of the corpus cavernosum is a rare disease of unknown cause that usually affects young men. We present the case of a 25-year-old man with an unilateral, painful perineal mass and ultrasound scan compatible with this entity. The magnetic resonance and tomography computarised scan images corroborate the diagnosis. Anticoagulants were prescribed which solved the clinical picture.

Characterization of the antibody response against NeuGcGM3 ganglioside elicited in non-small cell lung cancer patients immunized with an anti-idiotype antibody.

1E10 mAb is an anti-Id murine mAb (Ab2 mAb) specific for an Ab1 mAb that reacts with NeuGc-containing gangliosides, sulfatides, and Ags expressed in some human tumors. In preclinical studies, this Ab2 Ab was able to mimic NeuGc-containing gangliosides only in animals lacking expression of these Ags in normal tissues. In this study, we report on the immune responses elicited in 20 non-small cell lung cancer patients treated with 1 mg of aluminum hydroxide-precipitated 1E10 mAb. In the hyperimmune sera from 16 of 20 patients, a strong specific Ab response of both IgM and IgG isotypes against NeuGcGM3 ganglioside was observed. Patient immune sera were able to induce complement-independent cell death of NeuGcGM3-expressing X63 murine myeloma target cells. Significant immunoreactivity to NeuGcGM3 was still detected after the complete abrogation of the reactivity against 1E10 mAb by the adsorption of patient sera with this Ab. We hypothesize that Id(-)Ag(+) Abs could reflect the activation of an autologous idiotypic cascade into the patients. Both Id(+)Ag(+) and Id(-)Ag(+) fractions were separated by affinity chromatography and characterized. Although IgG isotype Abs were found in both fractions, IgM isotype Abs were found only in the Id(-)Ag(+) fraction. Both Id(+)Ag(+) and Id(-)Ag(+) Abs were able to specifically recognize and induce cell death in NeuGcGM3-expressing X63 myeloma target cells. Patients that developed IgG and/or IgM Abs against NeuGcGM3 showed longer median survival times.

Immunogenicity of autologous immunoglobulins: principles and practices.

The immunogenicity of immunoglobulin idiotypes in syngeneic systems is a rather rare phenomenon. Very few studies have attempted to determine the mechanisms underlying the anti-idiotypic response that certain autologous idiotypes can elicit. Furthermore, the studies addressing a possible physiological role for such behaviors are even less. In the present article, the results of the characterization of a highly immunogenic idiotype are reviewed and compared with some related works on the subject. We finally propose a possible immunoregulatory role for idiotypic immunogenicity.

Gangliosides, Ab1 and Ab2 antibodies IV. Dominance of VH domain in the induction of anti-idiotypic antibodies by gene gun immunization.

The heavy chain of anti-N-glycolyl-ganglioside P3 mAb plays the main role in its binding properties. At least one hybrid idiotype consisting on the P3 VH and an unrelated VL domain retains antigen recognition. Moreover, the unusual immunogenic properties of P3 idiotype could be modified by single mutations of H-CDR residues. Here, we show that DNA gene gun immunization with the P3 VH combined with an unrelated VL domain or with itself (VH dimer, VHD) is enough for inducing anti-idiotypic antibodies, independently of antigen recognition by the resulting molecule. The scFv fragment of P3 mAb was also able to induce an anti-idiotypic response. For both the P3 and the P3 anti-idiotypic 1E10 mAbs, heavy chains dominate the induction of antibodies against the respective idiotypes.

Gangliosides, Ab1 and Ab2 antibodies II. Light versus heavy chain: An idiotype-anti-idiotype case study.

The antibody heavy chain is generally more important than the light chain for the interaction with the antigen, although many reports demonstrate the influence of the light chain in the antibody binding properties. The heavy chains of anti-N-glycolyl-ganglioside P3 mAb and anti-idiotypic 1E10 mAb display complementary charged residues in their H-CDRs, particularly in H-CDR3. A basic residue in P3 mAb H-CDR1 was shown to be crucial for the interaction with the antigen and 1E10 mAb. The immunogenetic features of three other P3 mAb anti-idiotypic mAbs are now analyzed. One of them bears the same heavy chain as 1E10 mAb and a different light chain, but differs in its binding to P3 mAb mutants where H-CDR basic residues were replaced and in the binding to 1E10-specific phagotopes. Chimeric hybrid antibodies with P3 and 1E10 mAb heavy chains and unrelated light chains were obtained to further determine the importance of heavy chains in P3 and 1E10 mAb binding properties. One of the P3 heavy chain hybrid antibodies retained the specificity of P3 mAb with slight affinity differences. The heavy chains appear to play the main role in these mAb interactions, with the light chains modulating the affinity to their ligands.

Gangliosides, Ab1 and Ab2 antibodies III. The idiotype of anti-ganglioside mAb P3 is immunogenic in a T cell-dependent manner.

P3 mAb is an IgM monoclonal antibody specific for N-glycolyl-containing gangliosides. The immunogenicity of the P3 idiotype has been previously described by immunizing syngeneic BALB/c mice with the purified murine IgM or the mouse-human chimeric IgG antibody. In the present work we study the antibody response against the idiotype of P3 mAb through immunization with DNA. We used small immune proteins (SIP) consisting on the idiotype in the scFv format, covalently linked to gamma1CH3, the self-dimerizing domain of murine IgG1. SIPs were previously shown to be appropriate to induce specific anti-idiotypic responses. By gene gun immunization, a polyspecific response was occasionally generated, particularly with the P3 idiotype. A single shot of DNA was sufficient to induce a strong and long-lasting anti-P3 idiotype response. In addition, by delivery of the same DNA construct with a recombinant adeno-associated virus the unique immunogenicity of the P3 idiotype was demonstrated. The requirement of T cells in the anti-P3 idiotype response was indicated by the lack of P3-specific anti-idiotypic antibodies following immunization of both, allogeneic C57BL/6 and athymic BALB/c mice.

Gangliosides, Ab1 and Ab2 antibodies I. Towards a molecular dissection of an idiotype-anti-idiotype system.

This report is focused on the molecular basis for the interaction of a monoclonal antibody (mAb) and its anti-idiotypic mAb. P3 mAb (Ab1) recognizes N-glycolyl-gangliosides, and 1E10 mAb is one of its anti-idiotypic mAbs (Ab2). Chimeric versions of both antibodies retained their specificity. Charged residues in their H-CDRs, particularly H-CDR3, were considered to play a major role in their binding and immunogenic properties. P3 mAb has the unusual property of generating a strong antibody response in syngeneic mice, even when it is administered in saline. We selected phagotopes from a 12mer peptide library displayed on filamentous phage to characterize amino acid motifs recognized by these antibodies. The peptides were enriched in charged amino acids similar to those present in P3 and 1E10 mAb H-CDR3. We also report the construction of four mutants of the P3 antibody, where arginine residues in the heavy chain CDRs were substituted by serine residues, and the characterization of their interaction with 1E10 mAb and GM3(NeuGc) ganglioside, as well as their immunogenic properties in Balb/c mice. H-CDR1 R31 residue appears to have a central role in P3 mAb reactivity and antigenicity. H-CDR3 R100a residue seems to be more involved in the immunogenicity of the P3 idiotype.

Intimal hyperplasia induced by vascular intervention causes lipoprotein retention and accelerated atherosclerosis.

Accelerated atherosclerosis diminishes the long term patency of vascular interventions, such as percutaneous coronary intervention and implantation of saphenous vein grafts. However, the cause of this accelerated atherosclerosis is unclear. In this study, we tested the hypothesis that intimal hyperplasia formed following vascular intervention promotes retention of atherogenic lipoproteins. Intimal hyperplasia was surgically induced in the mouse common carotid artery. The surgery was combined with different mouse models of hypercholesterolemia to obtain different cholesterol levels and to control the onsets of hypercholesterolemia. Three weeks after surgery, samples were immunostained for apoB lipoproteins, smooth muscle cells and leukocytes. Already at mild hypercholesterolemia (193 mg/dL), pronounced apoB lipoprotein retention was found in the extracellular matrix in both intimal hyperplasia and the injured underlying media. In contrast, minimal retention was detected in the uninjured proximal region of the same vessel, or in vessels from mice with normal cholesterol levels (81 mg/dL). Induction of aggravated hypercholesterolemia 3 weeks after surgery, when a mature intimal hyperplasia had been formed, caused a very rapid development of atherosclerotic lesions. Mechanistically, we show that lipoprotein retention was almost exclusively dependent on electrostatic interactions to proteoglycan glycosaminoglycans, and the lipoprotein retention to intimal hyperplasia could be inhibited in vivo using glycosaminoglycan-binding antibodies. Thus, formation of intimal hyperplasia following vascular intervention makes the vessel wall highly susceptible for lipoprotein retention and accelerated atherosclerosis. The increased lipoprotein retention in intimal hyperplasia can be targeted by blocking the interaction between apoB lipoproteins and glycosaminoglycans in the extracellular matrix.

Dose-Dependent Induction of an Idiotypic Cascade by Anti-Glycosaminoglycan Monoclonal Antibody in apoE-/- Mice: Association with Atheroprotection.

Atherosclerosis, the underlying pathology of most cardiovascular diseases, is triggered by the retention of apolipoprotein B (apoB)-containing lipoproteins in the arterial wall through electrostatic interactions with glycosaminoglycan (GAG) side chains of proteoglycans. Previously, we reported the antiatherogenic properties of the chimeric monoclonal antibody (mAb) chP3R99-LALA, which binds sulfated GAGs, inhibits low-density lipoprotein (LDL)-chondroitin sulfate (CS) association, and abrogates LDL oxidation and foam cell formation. In preventive and therapeutic settings, apoE-deficient (apoE-/-) mice immunized with 50 µg of this mAb showed reduced atherosclerotic lesions related with the induction of autologous anti-GAG antibodies. Knowing that age and sex are major non-modifiable risk factors in the development of atherosclerosis, the present study aimed to assess the influence of these variables on the capacity of chP3R99-LALA mAb to generate an anti-CS antibody response. Also, we aimed at defining the impact of the dose of chP3R99-LALA on the anti-CS antibody induction and the atheroprotective effect of this mAb in apoE-/- mice. Neither age nor sex had an impact in the IgG anti-CS antibody response induced by s.c. immunization with this mAb. Moreover, chP3R99-LALA mAb reduced atherosclerotic lesions to a similar extent in both young male and female apoE-/- mice fed a hypercholesterolemic diet and, in middle-aged female apoE-/- mice, with spontaneous lesions. On the other hand, increasing the dose of chP3R99-LALA (200 vs. 50 µg) elicited an anti-idiotype antibody cascade characterized by higher levels of anti-idiotype (Ab2), anti-anti-idiotype (Ab3), and anti-CS antibody responses. Moreover, this dose increment resulted in a striking reduction of aortic atherosclerotic lesions in immunized mice.

Generation of anti-Neu-glycolyl-ganglioside antibodies by immunization with an anti-idiotype monoclonal antibody: A self versus non-self-matter.

We have previously generated a murine anti-idiotype (Ab2) monoclonal antibody (mAb) to a murine Ab1 mAb, named P3, which selectively binds Neu-glycolyl (NeuGc)-sialic acid on several monosialo- and disialogangliosides, and also reacts with sulfatides and antigens expressed in human melanoma and breast tumors. This Ab2 mAb, designated as 1E10, induced anti-anti-idiotype antibodies (Ab3) in mice and cancer patients. These Ab3 generated by 1E10 mAb were characterized by bearing P3 mAb idiotopes (Ab3, Id +). But when the specificity of these Ab3 antibodies was tested, no specific humoral response against NeuGc-containing gangliosides was detected in sera from immunized mice. However, hyperimmune sera from melanoma and breast cancer patients vaccinated with this Ab2 mAb were able to react specifically with these gangliosides. The different expression of NeuGc-containing gangliosides in the normal tissues of mice and humans could explain these results. In order to demonstrate these findings in other animal species with a different NeuGc-sialic acid expression, we performed similar studies in monkeys and chickens. In monkeys, as in most mammals, NeuGc-containing gangliosides are self-antigens. In contrast, chickens, like humans, lack the expression of these antigens in normal tissues. Here we report that the antibody response against NeuGc-containing gangliosides induced by immunization with 1E10 mAb was completely different in both species. No specific antibody response against these gangliosides was detected in hyperimmune monkey sera. In contrast, a strong and specific Ab3 response against GM3(NeuGc) and GM2(NeuGc) gangliosides (Ab3, Ag+) was generated in chickens due to the administration of 1E10 mAb.

A monoclonal antibody against NeuGc-containing gangliosides contains a regulatory idiotope involved in the interaction with B and T cells.

P3 (IgM-kappa) is a monoclonal antibody (mAb) reacting with N-glycolyl neuraminic acid (NeuGc)-containing gangliosides and sulfated glycolipids. To explore the nature of the idiotope defined by 1E10, we used a phage-displayed random peptide library. After three rounds of selection, seven different phagotopes were isolated. Noteworthy, all the sequences were found to bear the basic amino acid-rich motifs KPPR (3) or RRPR/K (4). This recursive selection of basic sequences by 1E10 mAb confirmed previous suggestions of the involvement of charged residues in the interaction between gamma-type Ab2 and P3 mAb. The binding of 1E10 to phage peptides representing each group was completely inhibited by P3 mAb. In addition, other Ab2 to P3 were able to recognize these peptides. Thus, phage peptides seem to be mimotopes of the idiotope recognized by anti-idiotypic antibodies in P3. Phage motifs were represented in the lineal sequence of P3's heavy chain H-CDR3 and a 14-mer peptide representing this region was able to specifically inhibit 1E10 binding to P3. Previous studies showed that P3's idiotype was autoimmunogenic and shared by antibodies with different specificities. Now, we demonstrated that P3 mAb is able to activate a network cascade involving autologous anti-idiotypic and anti-anti-idiotypic T cells. Thus, P3's idiotype fulfill the three criteria previously established to define a "regulatory idiotype". Particularly, data presented here revealed the immunodominance of the H-CDR3 of this mAb as a T cell epitope. Thus, H-CDR3 is simultaneously involved in the interaction of P3 mAb with anti-idiotypic B and T cells, behaving as a potential regulatory idiotope.

Racotumomab-alum vaccine for the treatment of non-small-cell lung cancer.

Racotumomab-alum vaccine is an anti-idiotypic vaccine able to mimic the tumor-associated antigen NeuGcGM3. Different Phase I clinical trials and compassionate use studies demonstrated its low toxicity and capacity to induce a strong anti-NeuGcGM3 response, able to bind and directly kill tumor cells expressing the antigen. A Phase II/III randomized double-blind clinical trial in advanced non-small cell lung cancer patients showed a significant improvement in overall survival and progression-free survival for racotumomab-alum versus placebo. Patients who developed anti-NeuGcGM3 antibodies capable of binding and killing NeuGcGM3 expressing tumor cells showed significantly longer median survival times. The impact of using racotumomab-alum as switch maintenance followed by second-line therapy is currently being explored in a new randomized, multinational Phase III study.

Microencapsulación de peróxido de hidrógeno para la elaboración de un caramelo de goma blanqueador dental y evaluación in vitro mediante un método colorimétrico / Microencapsulation of hydrogen peroxide for the development of a dental whitening gummy candy and in vitro evaluation using a colorimetric method

INTRODUCCIÓN: La apariencia y el color de los dientes es una preocupación común para los pacientes por lo que hay una creciente necesidad de contar con tratamientos que mejoren la estética dental. Por esa razón, en los últimos 20 años la ciencia dental ha buscado nuevas técnicas y materiales capaces de reducir la discoloración dental. MÉTODO: Se prepararon pastillas de goma fantasía, caramelos de goma o gominolas que contenían dos concentraciones diferentes (7% y 14% m/v) de peróxido de hidrógeno microencapsulado por gelificación iónica. Durante 30 días se realizó un tratamiento diario de blanqueamiento dental in vitro para evaluar la acción blanqueadora de las dos formulaciones. La medición del color de la superficie de los dientes tratados se llevó a cabo utilizando una técnica colorimétrica. RESULTADOS: Se encontraron diferencias significativas entre los tratamientos de blanqueamiento con las dos formulaciones elaboradas en comparación con un grupo de control, siendo el esquema de dos procedimientos diarios con la formulación al 7% de peróxido de hidrógeno más efectivo que el de un único procedimiento diario con la formulación al 14%. CONCLUSIONES: Las dos formulaciones desarrolladas en este estudio tuvieron un mayor efecto de blanqueamiento in vitro en comparación con un grupo de control, y además se encontró que se logran mejores resultados al disminuir la concentración de peróxido si el número de aplicaciones aumenta para dosis diarias iguales

INTRODUCTION: The appearance and color of the teeth are common concerns for patients and are associated with an increased need for treatments that can improve dental aesthetics. For this reason, in the past 20 years, dental science has been searching for new techniques and materials able to reduce dental discoloration. METHOD: Gummy candies containing two different concentrations (7% and 14% w/v) of hydrogen peroxide microencapsulated by ionic gelation were prepared. In vitro tooth whitening treatment was carried out for 30 days to test the bleaching action of these formulations. The surface color of the treated teeth was measured using a colorimetric technique. RESULTS: Significant differences were found on comparing the whitening treatments for the two formulations with a control group, with two daily treatments using the formulation with 7% hydrogen peroxide being more effective for whitening than a daily single treatment using the formulation with 14 %. CONCLUSIONS: The two formulations developed had an in vitro higher bleaching effect in comparison with the control group, and in addition, better results were achieved if the daily dose was provided by more applications at a lower concentration of hydrogen peroxide

A randomized, multicenter, placebo-controlled clinical trial of racotumomab-alum vaccine as switch maintenance therapy in advanced non-small cell lung cancer patients.

PURPOSE: Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. This clinical trial was conducted to provide a preliminary estimate of efficacy and safety of racotumomab as switch maintenance for patients with advanced non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Patients with stage IIIb/IV NSCLC who have at least stable disease after first-line chemotherapy were randomized 1:1 to racotumomab-alum (5 immunizations every 2 weeks and re-immunizations every 4 weeks) or placebo. Treatment was administered beyond progressive disease, until severe performance status worsening or toxicity. At progression, only five patients per group received further anticancer therapy. The primary endpoint was overall survival (OS). RESULTS: One-hundred and seventy-six patients were randomized to racotumomab-alum (n = 87) and placebo (n = 89). Median OS was 8.23 and 6.80 months, respectively [HR, 0.63; 95% confidence interval (CI), 0.46-0.87; P = 0.004]. Median progression-free survival (PFS) in vaccinated patients was 5.33 versus 3.90 months for placebo (HR, 0.73; 95% CI 0.53-0.99; P = 0.039). The most common adverse events in the racotumomab-alum arm were burning and pain at the injection site, bone pain, and asthenia. A high antibody response of IgM and IgG isotype against the NeuGcGM3 ganglioside was obtained. Hyperimmune sera were able to specifically recognize and kill the NeuGcGM3-expressing L1210 cell line. Patients who developed anti-NeuGcGM3 antibodies capable to bind and kill ≥30% L1210 cells showed longer median survival times. CONCLUSIONS: Switch maintenance with racotumomab-alum is an effective and a well-tolerated treatment option for patients with advanced NSCLC.

Miniguía homeopática para instruir sobre el tratamiento de la hipertensión arterial / Homeopathic mini-guide to instruct on the treatment of high blood pressure

Fundamento: la homeopatía es una ciencia que atiende al paciente con un enfoque holístico; ha demostrado su validez en el tratamiento exitoso de determinadas dolencias. Objetivo: elaborar una miniguía como recurso de apoyo al médico homeópata para el tratamiento de la hipertensión arterial. Métodos: se realizó una investigación observacional transversal en la Universidad de Ciencias Médicas de Villa Clara, durante el año 2016. Se emplearon métodos teóricos: histórico-lógico, analítico-sintético, inductivo-deductivo y sistémico-estructural; y empíricos: la encuesta en forma de cuestionario a los médicos diplomados en homeopatía para comprobar su nivel de conocimientos sobre el tema. Resultados: los autores consideran que la literatura sobre homeopatía resulta aún insuficiente, se evidenciaron carencias de conocimientos entre los profesionales encuestados y desactualización bibliográfica en los contenidos, por lo que se elaboró una miniguía homeopática que fue valorada por criterios de especialistas. Conclusiones: contiene la descripción de múltiples medicamentos homeopáticos para combatir la hipertensión arterial y fue valorada como útil, pertinente, factible, actualizada en sus contenidos y de valor científico-pedagógico por los especialistas consultados.

Background: homeopathy is a science that cares for the patient with a holistic approach; it has proven its validity in the successful treatment of certain ailments. Objective: to elaborate a mini-guide as a support resource for the homeopathic doctor for the treatment of high blood pressure. Methods: a cross-sectional observational research was carried out at Villa Clara University of Medical Sciences, during 2016. Theoretical methods were used: historical-logical, analytical-synthetic, inductive-deductive and systemic-structural; and empirical ones: the survey in the form of a questionnaire to doctors qualified in homeopathy to check their level of knowledge on the subject. Results: the authors consider that the literature on homeopathy is still insufficient, there was a lack of knowledge among the professionals surveyed and bibliographic outdating in content, so a homeopathic mini-guide was developed that was assessed by specialists. Conclusions: it contains the description of multiple homeopathic medicines to face high blood pressure and was assessed as useful, pertinent, feasible, updated in its contents and of scientific-pedagogical value by the specialists consulted.