Effects of the acupoints PC 6 Neiguan and LR 3 Taichong on cerebral blood flow in normal subjects and in migraine patients.

Acupuncture has been proven to be effective in the treatment of various cardiovascular disorders; it acts both on the peripheral flow and on the cerebral flow. Our study aimed to evaluate the effects of the insertion of PC 6 Neiguan and LR 3 Taichong acupoints on the cerebral blood flow (CBF) in the middle cerebral artery (MCA). These effects were measured in a group of patients suffering from migraine without aura (Group M) and in a healthy control group (Group C). In the study, we included 16 patients suffering from migraine without aura, classified according to the criteria of the International Headache Society, and 14 healthy subjects as a control group. The subjects took part in the study on two different days, and on each day, the effect of a single acupoint was evaluated. Transcranial Doppler was used to measure the blood flow velocity (BFV) in the MCA. Our study showed that the stimulation of PC 6 Neiguan in both groups results in a significant and longlasting reduction in the average BFV in the MCA. After pricking LR 3 Taichong, instead, the average BFV undergoes a very sudden and marked increase; subsequently, it decreases and tends to stabilize at a slightly higher level compared with the baseline, recorded before needle insertion. Our data seem to suggest that these two acupoints have very different effects on CBF. The insertion of PC 6 Neiguan probably triggers a vasodilation in MCA, while the pricking of LR 3 Taichong determines a rapid and marked vasoconstriction.

Combinatorial immune checkpoint blockade increases myocardial expression of NLRP-3 and secretion of H-FABP, NT-Pro-BNP, interleukin-1ß and interleukin-6: biochemical implications in cardio-immuno-oncology.

Background: Immune checkpoint blockade in monotherapy or combinatorial regimens with chemotherapy or radiotherapy have become an integral part of oncology in recent years. Monoclonal antibodies against CTLA-4 or PD-1 or PDL-1 are the most studied ICIs in randomized clinical trials, however, more recently, an anti-LAG3 (Lymphocyte activation gene-3) antibody, Relatlimab, has been approved by FDA in combination with Nivolumab for metastatic melanoma therapy. Moreover, Atezolizumab is actually under study in association with Ipilimumab for therapy of metastatic lung cancer. Myocarditis, vasculitis and endothelitis are rarely observed in these patients on monotherapy, however new combination therapies could expose patients to more adverse cardiovascular events. Methods: Human cardiomyocytes co-cultured with human peripheral blood lymphocytes (hPBMCs) were exposed to monotherapy and combinatorial ICIs (PD-L1 and CTLA-4 or PD-1 and LAG-3 blocking agents, at 100 nM) for 48 h. After treatments, cardiac cell lysis and secretion of biomarkers of cardiotoxicity (H-FABP, troponin-T, BNP, NT-Pro-BNP), NLRP3-inflammasome and Interleukin 1 and 6 were determined through colorimetric and enzymatic assays. Mitochondrial functions were studied in cardiomyocyte cell lysates through quantification of intracellular Ca++, ATP content and NADH:ubiquinone oxidoreductase core subunit S1 (Ndufs1) levels. Histone deacetylases type 4 (HDAC-4) protein levels were also determined in cardiomyocyte cell lysates to study potential epigenetic changes induced by immunotherapy regimens. Results: Both combinations of immune checkpoint inhibitors exert more potent cardiotoxic side effects compared to monotherapies against human cardiac cells co-cultured with human lymphocytes. LDH release from cardiac cells was 43% higher in PD-L1/CTLA-4 blocking agents, and 35.7% higher in PD-1/LAG-3 blocking agents compared to monotherapies. HDAC4 and intracellular Ca++ levels were increased, instead ATP content and Ndufs1 were reduced in myocardial cell lysates (p < 0.001 vs. untreated cells). Troponin-T, BNP, NT-Pro-BNP and H-FABP, were also strongly increased in combination therapy compared to monotherapy regimen. NLRP3 expression, IL-6 and IL-1ß levels were also increased by PDL-1/CTLA-4 and PD-1/LAG-3 combined blocking agents compared to untreated cells and monotherapies. Conclusions: Data of the present study, although in vitro, indicate that combinatorial immune checkpoint blockade, induce a pro- inflammatory phenotype, thus indicating that these therapies should be closely monitored by the multidisciplinary team consisting of oncologists, cardiologists and immunologists.

A novel fully human antitumour immunoRNase targeting ErbB2-positive tumours.

BACKGROUND: ErbB2 is an attractive target for immunotherapy, as it is a tyrosine kinase receptor overexpressed on tumour cells of different origin, with a key role in the development of malignancy. Trastuzumab, the only humanised anti-ErbB2 antibody currently used in breast cancer with success, can engender cardiotoxicity and a high fraction of patients is resistant to Trastuzumab treatment. METHODS: A novel human immunoRNase, called anti-ErbB2 human compact antibody-RNase (Erb-hcAb-RNase), made up of the compact anti-ErbB2 antibody Erbicin-human-compact Antibody (Erb-hcAb) and human pancreatic RNase (HP-RNase), has been designed, expressed in mammalian cell cultures and purified. The immunoRNase was then characterised as an enzymatic protein, and tested for its biological actions in vitro and in vivo on ErbB2-positive tumour cells. RESULTS: Erb-hcAb-RNase retains the enzymatic activity of HP-RNase and specifically binds to ErbB2-positive cells with an affinity comparable with that of the parental Erb-hcAb. Moreover, this novel immunoRNase is endowed with an effective and selective antiproliferative action for ErbB2-positive tumour cells both in vitro and in vivo. Its antitumour activity is more potent than that of the parental Erb-hcAb as the novel immunoconjugate has acquired RNase-based cytotoxicity in addition to the inhibitory growth effects, antibody-dependent and complement-dependent cytotoxicity of Erb-hcAb. CONCLUSION: Erb-hcAb-RNase could be a promising candidate for the immunotherapy of ErbB2-positive tumours.

Two novel human anti-ErbB2 immunoagents are active on trastuzumab-resistant tumours.

BACKGROUND: Overexpression of ErbB2 receptor in breast cancer is associated with disease progression and poor prognosis. Trastuzumab, the only humanised anti-ErbB2 antibody currently used in breast cancer, has proven to be effective; however, a relevant problem for clinical practice is that a high fraction of breast cancer patients shows primary or acquired resistance to trastuzumab treatment. METHODS: We tested on trastuzumab-resistant cells two novel human anti-tumour immunoconjugates engineered in our laboratory by fusion of a human anti-ErbB2 scFv, termed Erbicin, with either a human RNase or the Fc region of a human IgG1. Both Erbicin-derived immunoagents (EDIAs) are selectively cytotoxic for ErbB2-positive cancer cells in vitro and vivo, target an ErbB2 epitope different from that recognised by trastuzumab and do not show cardiotoxic effects. RESULTS: We report that EDIAs are active also on trastuzumab-resistant tumour cells both in vitro and in vivo, most likely because of the different epitope recognised, as EDIAs, unlike trastuzumab, were found to be able to inhibit the signalling pathway downstream of ErbB2. CONCLUSION: These results suggest that EDIAs are immunoagents that could not only fulfil the therapeutic need of patients ineligible to trastuzumab treatment due to cardiac dysfunction but also prove to be useful for breast cancer patients unresponsive to trastuzumab treatment.

Development of a structured sensory honey analysis: application to artisanal Madrid honeys.

In this work a methodology to evaluate the sensory properties of honeys has been developed. The sensory analysis was carried out by means of a quantitative descriptive analysis (QDA) method, based on several reference scales, for the coverage of the designed range for each descriptor. The peculiarity of this sensory analysis is that the reference scales have been constituted by common foodstuffs agreed upon by consensus of the panel. The main sensory attributes evaluated in the analyses were: adhesiveness, viscosity, bitterness, aroma, sweetness, acidity, color and granularity. Both the intensity and persistence of honey aromas have also been estimated, together with the classification of the identified aromatic attributes into different groups. The method was applied to 55 artisanal honeys from Madrid (Spain) with the following results: (i) the developed sensory profile sheet allowed a satisfactory description of Madrid honeys; (ii) correlations between sensory attributes of three broad groups of Madrid honeys were obtained and (iii) aroma persistence, sweetness, bitterness, color and granularity appeared as the main sensorial characteristics of honey with discrimination power between floral and honeydew honeys.

Virome of crab-eating (Cerdocyon thous) and pampas foxes (Lycalopex gymnocercus) from southern Brazil and Uruguay.

Crab-eating (Cerdocyon thous) and Pampas foxes (Lycalopex gymnocercus) are wild canids distributed in South America. Domestic dogs (Canis lupus familiaris) and wild canids may share viral pathogens, including rabies virus (RABV), canine distemper virus (CDV), and canine parvovirus 2 (CPV-2). To characterize the virome of these wild canid species, the present work evaluated the spleen and mesenteric lymph node virome of 17 crab-eating and five Pampas foxes using high-throughput sequencing (HTS). Organ samples were pooled and sequenced using an Illumina MiSeq platform. Additional PCR analyses were performed to identify the frequencies and host origin for each virus detected by HTS. Sequences more closely related to the Paramyxoviridae, Parvoviridae and Anelloviridae families were detected, as well as circular Rep-encoding single-stranded (CRESS) DNA viruses. CDV was found only in crab-eating foxes, whereas CPV-2 was found in both canid species; both viruses were closely related to sequences reported in domestic dogs from southern Brazil. Moreover, the present work reported the detection of canine bocavirus (CBoV) strains that were genetically divergent from CBoV-1 and 2 lineages. Finally, we also characterized CRESS DNA viruses and anelloviruses with marked diversity. The results of this study contribute to the body of knowledge regarding wild canid viruses that can potentially be shared with domestic canids or other species.

Cardiotoxicity and pro-inflammatory effects of the immune checkpoint inhibitor Pembrolizumab associated to Trastuzumab.

BACKGROUND: The immunotherapy has revolutionized the world of oncology in the last decades with considerable advantages in terms of overall survival in cancer patients. The association of Pembrolizumab and Trastuzumab was recently proposed in clinical trials for the treatment of Trastuzumab-resistant advanced HER2-positive breast cancer. Although immunotherapies are frequently associated with a wide spectrum of immune-related adverse events, the cardiac toxicity has not been properly studied. PURPOSE: We studied, for the first time, the putative cardiotoxic and pro-inflammatory effects of Pembrolizumab associated to Trastuzumab. METHODS: Cell viability, intracellular calcium quantification and pro-inflammatory studies (analyses of the production of Interleukin 1ß, 6 and 8, the expression of NF-kB and Leukotriene B4) were performed in human fetal cardiomyocytes. Preclinical studies were also performed in C57BL6 mice by analyzing fibrosis and inflammation in heart tissues. RESULTS: The combination of Pembrolizumab and Trastuzumab leads to an increase of the intracellular calcium overload (of 3 times compared to untreated cells) and to a reduction of the cardiomyocytes viability (of 65 and 20-25%, compared to untreated and Pembrolizumab or Trastuzumab treated cells, respectively) indicating cardiotoxic effects. Notably, combination therapy increases the inflammation of cardiomyocytes by enhancing the expression of NF-kB and Interleukins. Moreover, in preclinical models, the association of Pembrolizumab and Trastuzumab increases the Interleukins expression of 40-50% compared to the single treatments; the expression of NF-kB and Leukotriene B4 was also increased. CONCLUSION: Pembrolizumab associated to Trastuzumab leads to strong cardiac pro-inflammatory effects mediated by overexpression of NF-kB and Leukotriene B4 related pathways.

Epidemiological and Pathological Characterization of Feline Injection Site Sarcomas in Southern Brazil.

Feline injection site sarcoma (FISS) is a mesenchymal neoplasm with highly malignant characteristics. These tumours originate in anatomical sites where there has been previous parenteral administration of medicinal substances or implantation of medical devices. The aim of this study was to investigate the epidemiological and pathological features associated with FISS in the southern region of Brazil. The database of the Department of Veterinary Pathology of the Federal University of Rio Grande do Sul was searched for excisional and incisional biopsy samples compatible with FISS submitted between 2007 and 2017. Biopsy reports were reviewed and epidemiological information, including breed, age and sex of affected cats, as well as gross findings including anatomical location and size of the tumour and the presence of tissue invasion, were extracted. Eighty-nine samples were selected based on the established criteria. Most animals were of undefined breed and were female cats with a median age of 10 years. Grossly, 84.8% of the tumours were >2 cm in diameter. Regarding anatomical location, 34.9% of the tumours were located in the subcutaneous tissue of the thoracic wall, 29.2% in the flank, 21.3% in the interscapular region and 14.6% in the limbs. Histologically, the tumours originated in the subcutaneous tissue and were diagnosed as malignant mesenchymal neoplasms. Most were compatible with fibrosarcomas, but variants with features of pleomorphic sarcoma or chondrosarcoma were recognized. All tumours exhibited areas of necrosis and peripheral inflammatory infiltrate, composed predominantly of lymphocytes, plasma cells and macrophages. The results of this study suggest the need for dissemination of information on FISS epidemiology and guidelines for management of this tumour to veterinarians in the region.

Histiocytic Ulcerative Colitis in an American Staffordshire Terrier.

A 9-year-old female American Staffordshire terrier was presented to a veterinary hospital with diarrhoea, severe prostration, hypothermia, dehydration and anaemia. The dog died 6 days after the first consultation. At necropsy examination the serosa of the large intestine showed a granular appearance and the mucosa was thickened, ulcerated and red, with prominent folding. Histological examination revealed marked inflammatory infiltration of macrophages into the mucosa and submucosa of the large intestine. These cells stained positively by the periodic acid-Schiff reaction. Immunohistochemistry showed marked presence of intracytoplasmic Escherichia coli in the macrophages. Bacteriological examination of intestinal sections yielded E. coli growth and the isolate displayed atypical characteristics when compared with strains associated with previously published cases of histiocytic ulcerative colitis (HUC). The molecular characterization showed that the isolate harboured none of the genes associated with enterotoxigenic E. coli strains and harboured only a limited number of genes associated with extra-intestinal pathotypes. Adherent and invasive E. coli are unlikely to have been involved in the pathogenesis of HUC in the present case. HUC is a rare disease with a predisposition for boxer dogs; however, sporadic occurrence in other breeds may occur. This is the first reported case of HUC in an American Staffordshire terrier.

Two novel Drosophila TAF(II)s have homology with human TAF(II)30 and are differentially regulated during development.

TFIID is a multiprotein complex composed of the TATA binding protein (TBP) and TBP-associated factors (TAF(II)s). The binding of TFIID to the promoter is the first step of RNA polymerase II preinitiation complex assembly on protein-coding genes. Yeast (y) and human (h) TFIID complexes contain 10 to 13 TAF(II)s. Biochemical studies suggested that the Drosophila (d) TFIID complexes contain only eight TAF(II)s, leaving a number of yeast and human TAF(II)s (e.g., hTAF(II)55, hTAF(II)30, and hTAF(II)18) without known Drosophila homologues. We demonstrate that Drosophila has not one but two hTAF(II)30 homologues, dTAF(II)16 and dTAF(II)24, which are encoded by two adjacent genes. These two genes are localized in a head-to-head orientation, and their 5' extremities overlap. We show that these novel dTAF(II)s are expressed and that they are both associated with TBP and other bona fide dTAF(II)s in dTFIID complexes. dTAF(II)24, but not dTAF(II)16, was also found to be associated with the histone acetyltransferase (HAT) dGCN5. Thus, dTAF(II)16 and dTAF(II)24 are functional homologues of hTAF(II)30, and this is the first demonstration that a TAF(II)-GCN5-HAT complex exists in Drosophila. The two dTAF(II)s are differentially expressed during embryogenesis and can be detected in both nuclei and cytoplasm of the cells. These results together indicate that dTAF(II)16 and dTAF(II)24 may have similar but not identical functions.

The RFG oligomerization domain mediates kinase activation and re-localization of the RET/PTC3 oncoprotein to the plasma membrane.

The RET/PTC3 oncogene arises from the fusion between the N-terminal encoding domain of the RFG gene and the tyrosine kinase encoding domain of RET receptor. RET/PTC3 is very frequent in papillary thyroid carcinomas, especially in children exposed to the Chernobyl accident. We have studied the functional consequences of the RFG-RET fusion. Here we show that the N-terminal coiled-coil domain of RGF mediates oligomerization and activation of the kinase and of the transforming capability of RET/PTC3. In addition, the RFG coiled-coil domain mediates a physical association between RET/PTC3 and RGF proteins, rendering RFG a bona fide substrate of RET/PTC3 kinase. Finally, we show that the coiled-coil domain of RGF is essential for the distribution of the RET/PTC3 protein at the membrane/particulate cell compartment level, where also most of the RFG protein is localized. We propose that fusion to the RFG coiled-coil domain provides RET kinase with a scaffold that mediates oligomerization and re-localization of the RET/PTC3 protein, a process that may be crucial for the signalling of this specific RET/PTC variant.

Homo-oligomerization domains in the lethal(2)giant larvae tumor suppressor protein, p127 of Drosophila.

The p127 tumor suppressor protein encoded by the lethal(2)giant larvae, l(2)gl, gene of Drosophila melanogaster forms high molecular mass complexes consisting predominantly of p127 molecules. To determine whether p127 can self-assemble in the absence of other binding factors, we analyzed the size of in vitro synthesized p127 by gel filtration and found that p127 is always recovered in a high molecular mass form, demonstrating that p127 can oligomerize on its own. Previous studies have revealed that p127 may contain three homo-oligomerization domains. To more accurately delineate these domains, we have generated a series of 32 chimaeric proteins made of defined portions of p127 fused to protein A, which behaves as a monomeric protein, and determined the level of oligomerization of the fused proteins. This study allowed us to map three discrete homo-oligomerization domains, each of approximately 50 amino acid residues in length. These domains, designated as HD-I, HD-II and HD-III, are located between amino acid residues 160 and 204, 247 and 298, and 706 and 749, respectively. Further analysis showed that the HD-I and HD-II domains can bind to themselves and to each other. We also mapped a domain in p127 between amino acid residues 377 and 438, which strongly reduces the degree of multimerization of chimaeric proteins containing HD-I and/or HD-II. Electron microscopy examination of negatively stained chimaeric proteins showed that protein A fused with either the domain HD-II or the domain HD-III forms discrete structures consistent with the formation of quaternary complexes, whereas protein A fused to a non-self binding domain of p127 appeared monomeric. Our results indicate that p127 alone is able to build quaternary structures forming a network with which other proteins associate. As revealed by the tumorous phenotype resulting from the inactivation of the l(2)gl gene, the organization of the p127 network and its association with other proteins play critical roles in the control of cell proliferation.

Essentiality of Boron for Symbiotic Dinitrogen Fixation in Pea (Pisum sativum) Rhizobium Nodules.

The effect of boron deficiency on symbiotic nitrogen fixation in pea (Pisum sativum) was examined. The absence of boron in the culture medium resulted in a decrease of the number of nodules and an alteration of nodule development leading to an inhibition of nitrogenase activity. Examination of boron-deficient nodules showed dramatic changes in cell walls and in both peribacteroid and infection thread membranes, suggesting a role for boron in the stability of these structures. These results indicate that boron is a requirement for normal nodule development and functionality.

Requirement of Drosophila I(2)gl function for survival of the germline cells and organization of the follicle cells in a columnar epithelium during oogenesis.

The lethal(2)giant larvae gene, or 1(2)gl, encodes a widely expressed cytoskeletal protein which acts in numerous biological processes during embryogenesis and oogenesis, including cell proliferation, and morphogenetic movements. Having identified the nucleotide change occurring in the l(2)gl(ts3) sequence, we produced by site-directed mutagenesis the identical change leading to the substitution of a serine by a phenylalanine at position 311 of p127l(2)gl and introduced the modified l(2)glF311 gene into l(2)gl flies. The transgene can fully rescue the development of l(2)gl flies raised at 22 degrees C but causes drastic effects on their development at 29 degrees C confirming the temperature sensitivity of the phenylalanine substitution at position 311. Fertility of females, albeit not of males, was strongly affected. Temperature-shift experiments and microscopic examination of ovaries showed that the mutation blocked egg chamber development at the onset of vitellogenesis (stages 8-9) with growth arrest of the oocyte, incomplete follicle cell migration over the oocyte associated with abnormal organization of the follicular epithelium, and apoptosis of the germline cells, as measured by TUNEL assays. By comparison to wildtype, we found that p127F311 is already reduced in amount at 22 degrees C and delocalized from the cytoskeletal matrix, albeit without affecting the apical localization of myosin II, a major partner of p127. At 29 degrees C, the level of p127F311 is even more reduced and the distribution of myosin-II becomes markedly altered at the apices of the follicle cells. These data indicate that during oogenesis p127 plays a critical function at the onset of vitellogenesis and regulates growth of the oocyte, follicle cell migration over the oocyte and their organization in a palisadic epithelium, as well as viability of the germline cells.

Selective and asymmetric action of trypsin on the dimeric forms of seminal RNase.

Dimeric seminal RNase (BS-RNase) is an equilibrium mixture of conformationally different quaternary structures, one characterized by the interchange between subunits of their N-terminal ends (the MXM form); the other with no interchange (the M=M form). Controlled tryptic digestion of each isolated quaternary form generates, as limit digest products, folded and enzymatically active molecules, very resistant to further tryptic degradation. Electrospray mass spectrometric analyses and N-terminal sequence determinations indicate that trypsin can discriminate between the conformationally different quaternary structures of seminal RNase, and exerts a differential and asymmetric action on the two dimeric forms, depending on the original quaternary conformation of each form. The two digestion products from the MXM and the M=M dimeric forms have different structures, which are reminiscent of the original quaternary conformation of the dimers: one with interchange, the other with no interchange, of the N-terminal ends. The surprising resistance of these tryptic products to further tryptic action is explained by the persistence in each digestion product of the original intersubunit interface.

Crystal structure of the dimeric unswapped form of bovine seminal ribonuclease.

Bovine seminal ribonuclease is a unique case of protein dimorphism, since it exists in two dimeric forms, with different biological and kinetic behavior, which interconvert into one another through three-dimensional swapping. Here we report the crystal structure, at 2.2 A resolution, of the unswapped form of bovine seminal ribonuclease. Besides completing the structural definition of bovine seminal ribonuclease conformational dimorphism, this study provides the structural basis to explain the dependence of the enzyme cooperative effects on its swapping state.

The antitumor action of seminal ribonuclease and its quaternary conformations.

It has been previously shown that the antitumor action of bovine seminal ribonuclease (BS-RNase) is dependent on its dimeric structure. However, two distinct quaternary structures, each in equilibrium with the other, have been described for the enzyme: one in which the two subunits exchange their N-terminal ends, the other with no exchange. Antitumor activity assays, carried out on homogeneous quaternary forms of the enzyme, as well as on dimeric mutants of bovine pancreatic RNase A, reveal that another structural determinant of the antitumor activity of BS-RNase is the exchange of N-terminal ends between subunits.

[Low-dose spiral CT of the lung in the follow-up of non-malignant lung disease]. / Niedrigdosis-Spiral-CT des Thorax in der Verlaufskontrolle nichtmaligner Lungenerkrankungen.

PURPOSE: To assess image quality of chest CT with an 80 to 90 percent dose reduction in follow-up studies of patients with lung disease, dose and image quality of a low-dose protocol was investigated. MATERIALS AND METHODS: A follow-up low-dose CT (ND-CT, 120 kV, 10 mAs/slice, 3 mm slice thickness) was performed on 35 patients with non-malignant lung disease and compared with the initial standard dose CT (= SD-CT, 100 mAs/slice, 3 or 5 mm slice thickness). The dose was measured by thermo-luminescence in an Alderson phantom. Image quality was assessed by four independent radiologists in six perihilar, central and peripheral lung regions using a 4-point-scale ("very good", "good", "moderate", and "poor"). RESULTS: Effective dose was 0.5 mSv for ND-CT and 4.0 - 5.0 mSv for SD-CT. The ratings "very good"/"good" were given in the perihilar regions in ND-CT 97.5 % versus SD-CT 99.3 % (n. s.), in the central regions in ND-CT 96.4 % versus SD-CT 94.6 % (n. s.), and in the peripheral regions in ND-CT 70.0 % versus SD-CT 88.2 % (p < 0.01). CONCLUSION: Follow-up CT of pulmonary structures in patients with chronic lung disease can be performed with substantial dose reduction. A decrease of image quality may result in peripheral lung regions.

Access to databases in complementary medicine.

Access to medical databases is a keystone for obtaining up-to-date and complete information for physicians. In the last few years, the rapid growth of the World Wide Web has given rise to an information revolution, enabling health care providers to gain access (often free) to an expanding volume of information that was previously inaccessible. Search engines and online databases assist the search for health information. In this article we examine the biomedical databases of primary interest in the field of alternative and complementary medicine, dividing them into Web accessible and nonaccessible databases and emphasizing the freely available ones. A further classification is major biomedical bibliographic databases specific to complementary medicine, and dedicated therapy or modality-specific databases.

[Dexketoprofen trometamol in the treatment of acute migraine attack]. / Il dexketoprofene trometamolo nel trattamento dell'attacco acuto di emicrania.

BACKGROUND: Migraine is a common, very disabling pain condition: the occurrence of an acute attack often requires bedrest and prevents from participating in normal activities. Nonsteroidal anti-inflammatory drugs are widely used in the symptomatic treatment of migraine. Aim of this study was to evaluate the efficacy and safety of a potent new formulation, dexketoprofen trometamol (DT), in the treatment of migraine pain. METHODS: The study enrollment was 42 women (mean age 37.2 +/- 12.2, range 21-65) suffering from migraine, with (n = 6) and without (n = 36) aura, diagnosed according to the International Headache Society criteria. Patients were asked to treat a single attack with a 25 mg dose of DT. The primary efficacy criterion was the change in migraine pain, recorded on a Visual Analogue Scale (VAS) immediately before and at 30, 60, 120, 240 minutes after assumption. The presence of accompanying symptoms and the onset of side effects were also considered. RESULTS: Pain intensity significantly decreased after drug intake, showing a tendency toward a reduction along the time. The drop in mean VAS values resulted already significant at 30 minutes after DT assumption. Also the reported incidence of accompanying symptoms (nausea, vomiting, photophobia and phonophobia) significantly decreased after treatment. No serious adverse event was reported during the study. All the adverse events recorded were of mild severity and did not require any specific medical treatment. CONCLUSIONS: DT proved to be an effective and safe oral therapy for the treatment of migraine attack.