At least 50 % of female migraineurs experience migraine associated with the perimenstrual period, even though they may also suffer from attacks at other times of the cycle (menstrually related ...migraine, MRM). MRM attacks tend to be longer and more intense than those arising in other phases of the menstrual cycle, and are often aggravated by more pronounced vegetative phenomena. In this open preliminary trial, we tested the efficacy of associating frovatriptan and dexketoprofen for the treatment of an acute attack of MRM, diagnosed according to the criteria of the International Headache Society, in 24 patients between 19 and 45 years of age (mean 31.33 ± 7.33). Twenty-one of them completed the study. Pain relief was achieved by 76 % of patients at 2 h and by 86 % at 4 h. A pain-free state was achieved by 48 % at 2 h and by 62 % at 4 h from taking the product. A pain-free state at 24 h was present in 76 % of MRM sufferers, 33 % of whom showed a sustained pain-free state at 24 h. A rescue medication was needed by eight patients. While decidedly encouraging, the data of this study obviously need confirmation with double blind studies involving a greater number of patients.
Acupuncture has a long tradition of use for the treatment of many pain conditions, including headache. Its effectiveness has been studied mainly for primary headaches, particularly for migraine and ...tension-type headache (TTH). Traditional Chinese Medicine (TCM) has two diagnostic frameworks for headaches:
meridian diagnoses
, based on the location of the pain and on the meridians (or channels) that pass through it;
syndrome diagnoses
, dependent on external or internal factors and on the characteristics of the pain. The four meridians involved in headache are
Shaoyang
(TE-GB channels, on the temporal sides of the head);
Taiyang
(SI-BL channels, occiput);
Yangming
(LI-ST channels, forehead) and
Jueyin
(PC-LR channels, vertex). The syndromes may be due to excess or deficit. Very generally, the excess syndromes correspond in the majority of cases to migraine and the deficit syndromes to TTH. Acupuncture is a complex intervention, which is also characterized by a close interaction between patient and therapist. The complicated system of TCM classification of headaches has frequently generated great diversity among the various therapeutic approaches used in the different studies on acupuncture in headache treatment. Despite these differences, the recent Cochrane systematic reviews on acupuncture in migraine and in TTH suggest that acupuncture is an effective and valuable option for patients suffering from migraine or frequent TTH. Moreover, acupuncture seems to be a cost-effective treatment.
Most epidemiological studies demonstrate that women suffering from migraine note a significant improvement in their headaches during pregnancy. Both headache specialists and gynecologists commonly ...hold that migraine does not involve any risks to either the mother, or the fetus. Despite this, recent studies into the medical complications of pregnancy in migrainous women have cast doubts on this assumption. Indeed, most of these studies have revealed a significant association between migraine and hypertension in pregnancy (i.e. preeclampsia and gestational hypertension). Migraine has also been recently postulated as one of the major risk factors for stroke during pregnancy and the puerperium. Therefore, there is an urgent need for prospective studies on large numbers of pregnant women to determine the real existence and extent of the risks posed by migraine during pregnancy. In the meantime, while awaiting verification of this hypothesis, a pregnant woman with migraine must be subject to a particularly attentive screening by both the obstetrician and the headache specialist.
Migraine is a disabling neurological disorder, aggravated by accompanying symptomatology, such as nausea. One of the most interesting approaches to nausea adopted by traditional Chinese medicine is ...the stimulation of the acupoint PC6
Neiguan.
Actually there are no studies in medical literature as to the efficacy of treating PC6 acupoint for gastrointestinal symptoms in migraine attacks. Our study aimed at verifying if pressure applied to the acupoint PC6 was effective on nausea during migraine. Forty female patients suffering from migraine without aura were enrolled, if nausea was always present as accompanying symptomatology of their migraine. The patients were treated randomly for a total of six migraine attacks: three with the application of a device, the Sea-Band
®
wristband, which applies continual pressure to the PC6 acupoint (phase SB), and three without it (phase C). The intensities of nausea at the onset, at 30, 60, 120 and 240 min were evaluated on a scale from 0 to 10. The values were always significantly lower in phase SB than in phase C. Also the number of patients who reported at least a 50 % reduction in the nausea score was significantly higher in phase SB than in phase C at 30, 60 and 120 min. Moreover, the consistency of the treatment (response in at least two out of three treated attacks) was reached in 28 % patients at 60 min; in 40 % at 120 min and 59 % at 240 min. Our results encourage the application of PC6 acupressure for the treatment of migraine-associated nausea.
Although combined oral contraceptives (COCs) are a safe and highly effective method of birth control, they may also give rise to problems of clinical tolerability in migraine patients. Indeed, ...headache is among the most common side effects reported with the use of COCs, frequently leading to their being discontinued. The latest International Classification of Headache Disorders identified at least two entities evidently related to the use of COCs, i.e., exogenous hormone-induced headache and estrogen-withdrawal headache. As to the former, the newest formulations of COCs are generally well tolerated by migraine without aura patients, but can worsen headache in migraine with aura patients. Headache associated with COCs, generally, tends to improve as their use continues. However, although it is not yet clear if there is an association between headache and the composition of COCs (both in the type and amount of hormones), it has been observed that the incidence of headache during COC use seems greater if migraine is associated with menstrual trigger. The estrogen-withdrawal headache is a headache that generally appears within the first 5 days after cessation of estrogen use and resolves within 3 days, even if in some cases it may appear on the sixth or seventh day after pill suspension and lasts more than 3 days.
Oral contraceptive-induced menstrual migraine (OCMM) is a poorly defined migraine subtype mainly triggered by the cyclic pill suspension. In this pilot, open-label trial we describe its clinical ...features and evaluate the efficacy of frovatriptan in the treatment of its acute attack. During the first 3 months of the study 20 women (mean age 32.2±7.0, range 22–46) with a 6-month history of pure OCMM recorded, in monthly diary cards, clinical information about their migraine. During the 4th menstrual cycle they treated an OCMM attack with frovatriptan 2.5 mg. The majority of attacks were moderate/severe and lasted 25–72 h or more, in the presence of usual treatment. Generally an OCMM attack appeared within the first 5 days after the pill suspension, but in 15% of cases it started later. After frovatriptan administration, headache intensity progressively decreased (2.4 at onset, 1.6 after 2 h, 1.1 after 4 h and 0.8 after 24 h;
p
=0.0001). In 55% of patients pain relief was reported after 2 h. Ten percent of subjects were pain-free subjects after 2 h, 35% after 4 h and 60% after 24 h (
p
=0.003 for trend); 36% relapsed within 24 h. Rescue medication was needed by 35% of patients; 50% of frovatriptan-treated required a second dose. Concomitant nausea and/or vomiting, photophobia and phonophobia decreased significantly after drug intake. OCMM is a severe form of migraine; actually its clinical features are not always exactly identified by the ICHD-II classification. However, treatment with frovatriptan 2.5 mg might be effective in its management.
We have previously shown that in pancreatic ductal adenocarcinoma (PDA) cells, the glycolytic enzyme alpha-enolase (ENO1) also acts as a plasminogen receptor and promotes invasion and metastasis ...formation. Moreover, ENO1 silencing in PDA cells induces oxidative stress, senescence and profoundly modifies PDA cell metabolism. Although anti-ENO1 antibody inhibits PDA cell migration and invasion, little is known about the role of ENO1 in regulating cell-cell and cell-matrix contacts. We therefore investigated the effect of ENO1 silencing on the modulation of cell morphology, adhesion to matrix substrates, cell invasiveness, and metastatic ability.
The membrane and cytoskeleton modifications that occurred in ENO1-silenced (shENO1) PDA cells were investigated by a combination of confocal microscopy and atomic force microscopy (AFM). The effect of ENO1 silencing was then evaluated by phenotypic and functional experiments to identify the role of ENO1 in adhesion, migration, and invasion, as well as in senescence and apoptosis. The experimental results were then validated in a mouse model.
We observed a significant increase in the roughness of the cell membrane due to ENO1 silencing, a feature associated with an impaired ability to migrate and invade, along with a significant downregulation of proteins involved in cell-cell and cell-matrix adhesion, including alpha v/beta 3 integrin in shENO1 PDA cells. These changes impaired the ability of shENO1 cells to adhere to Collagen I and IV and Fibronectin and caused an increase in RGD-independent adhesion to vitronectin (VN) via urokinase plasminogen activator receptor (uPAR). Binding of uPAR to VN triggers integrin-mediated signals, which result in ERK1-2 and RAC activation, accumulation of ROS, and senescence. In shENO1 cancer cells, the use of an anti-uPAR antibody caused significant reduction of ROS production and senescence. Overall, a decrease of in vitro and in vivo cell migration and invasion of shENO1 PDA cells was observed.
These data demonstrate that ENO1 promotes PDA survival, migration, and metastasis through cooperation with integrins and uPAR.
α-enolase (ENOA) is a metabolic enzyme involved in the synthesis of pyruvate. It also acts as a plasminogen receptor and thus mediates activation of plasmin and extracellular matrix degradation. In ...tumor cells, ΕΝΟΑ is upregulated and supports anaerobic proliferation (Warburg effect), it is expressed at the cell surface, where it promotes cancer invasion, and is subjected to a specific array of post-translational modifications, namely acetylation, methylation and phosphorylation. Both ENOA overexpression and its post-translational modifications could be of diagnostic and prognostic value in cancer. This review will discuss recent information on the biochemical, proteomics and immunological characterization of ENOA, particularly its ability to trigger a specific humoral and cellular immune response. In our opinion, this information can pave the way for effective new therapeutic and diagnostic strategies to counteract the growth of the most aggressive human disease.
In the last 5 years, novel knowledge on tumor metabolism has been revealed with the identification of critical factors that fuel tumors. Alpha-enolase (ENO1) is commonly over-expressed in tumors and ...is a clinically relevant candidate molecular target for immunotherapy. Here, we silenced ENO1 in human cancer cell lines and evaluated its impact through proteomic, biochemical and functional approaches. ENO1 silencing increased reactive oxygen species that were mainly generated through the sorbitol and NADPH oxidase pathways, as well as autophagy and catabolic pathway adaptations, which together affect cancer cell growth and induce senescence. These findings represent the first comprehensive metabolic analysis following ENO1 silencing. Inhibition of ENO1, either alone, or in combination with other pathways which were perturbed by ENO1 silencing, opens novel avenues for future therapeutic approaches.
Pancreatic ductal adenocarcinoma (PDAC) is becoming the second leading cause of cancer-related death in the Western world. The mortality is very high, which emphasizes the need to identify biomarkers ...for early detection. As glutamine metabolism alteration is a feature of PDAC, its
evaluation may provide a useful tool for biomarker identification. Our aim was to identify a handy method to evaluate blood glutamine consumption in mouse models of PDAC. We quantified the
glutamine uptake by Mass Spectrometry (MS) in tumor cell supernatants and showed that it was higher in PDAC compared to non-PDAC tumor and pancreatic control human cells. The increased glutamine uptake was paralleled by higher activity of most glutamine pathway-related enzymes supporting nucleotide and ATP production. Free glutamine blood levels were evaluated in orthotopic and spontaneous mouse models of PDAC and other pancreatic-related disorders by High-Performance Liquid Chromatography (HPLC) and/or MS. Notably we observed a reduction of blood glutamine as much as the tumor progressed from pancreatic intraepithelial lesions to invasive PDAC, but was not related to chronic pancreatitis-associated inflammation or diabetes. In parallel the increased levels of branched-chain amino acids (BCAA) were observed. By contrast blood glutamine levels were stable in non-tumor bearing mice. These findings demonstrated that glutamine uptake is measurable both
and
. The higher
avidity of PDAC cells corresponded to a lower blood glutamine level as soon as the tumor mass grew. The reduction in circulating glutamine represents a novel tool exploitable to implement other diagnostic or prognostic PDAC biomarkers.
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