28 In addition, Peng et al. have shown that Fas ligand (FasL) gene expression is mediated by NF-κB and inhibition of NF-κB-attenuated apoptosis, but not TNF-α expression.32 In addition to expression of TNF-α and activation of the NF-κB pathway, increased ROS and OS also promote apoptosis by activation of the Jun N-terminal kinase (JNK)/activation protein

1 serine kinase-signaling cascade.33, 34 Tsukamoto and others have shown that addition of iron activates KCs both in vitro and by erythrophagocytosis, inducing LPO, NF-κB activation, and NF-κB-mediated TNF-α expression and release, which was abrogated by iron chelation treatment.31, 35-39 Last, phagocytosis by KCs results in expression of TNF-α and death receptors FasL and TNF-related apoptosis-inducing ligand, suggesting a feed-forward amplification of apoptosis.40 Taken together, these studies suggest a role of KC iron in apoptosis by the FAS, JNK, and TNFR pathways through production of ROS, cytokines, NF-κB and Selleck BIBW2992 TNF-α, which could then be amplified through phagocytosis of erythrocytes and iron-containing apoptotic hepatocytes. There are a number of cellular conditions that are thought to favor either necrosis or apoptosis, which potentially https://www.selleckchem.com/products/PD-0332991.html could explain our observations that HC iron may promote greater necrosis, compared to the other iron phenotypes. Apoptosis is a deliberate,

adenosine triphosphate (ATP)-dependent process that usually occurs gradually, whereas necrosis is a rapid event involving plasma membrane rupture subsequent to ATP depletion; thus, availability of ATP is recognized as a key determinant for which mode of cell death predominates.10 Iron-mediated mitochondrial LPO contributes to pore formation in mitochondrial membranes or mitochondria permeability transition (MPT) and subsequent release of mitochondrial ROS.41, 42 Both necrosis through ATP depletion or caspase-dependent apoptosis induced by cytochrome c release are consequences of MPT, but the degree of mitochondria involvement may determine the extent of ATP depletion and hence the development of necrosis or apoptosis.29 Casein kinase 1 Depletion of the antioxidant, glutathione (GSH), in both the mitochondrial and cytosolic compartments has been shown to promote

OS-induced necrosis, whereas selective cytosolic GSH depletion sensitizes hepatocytes to TNF-α-induced apoptosis independent of OS.43, 44 Several studies have investigated the origins of cell death by necrosis or apoptosis in cultured hepatocytes or using in vivo animal models subsequent to chemically induced superoxide formation using menadione or diquat.33, 45 Evidence from these studies suggests that when extensive oxidant damage overwhelms the cellular antioxidant capacity, necrosis may result, whereas with moderate OS, apoptotic pathways predominate. There are some limitations of our study worth noting, such as the possible effect of elevated MDA levels after prolonged serum storage,46 potentially explaining higher levels in subjects with hepatic iron.

19 In one series of HCT survivors undergoing liver MRI, incidental focal nodular hyperplasia lesions were present in 12%.50 These lesions have characteristic central scars that differentiate them from hepatocellular carcinoma and fungal lesions. The likely cause is sinusoidal injury caused by myeloablative conditioning regimens. Long-term survivors appear to have an increased incidence of gallstones and gallstone complications, probably related to formation of calcium bilirubinate https://www.selleckchem.com/products/PLX-4032.html microliths following myeloablative conditioning therapy. Chronic cyclosporine

or tacrolimus dosing may also lead to biliary symptoms and acute pancreatitis. Liver problems caused by infection, cholestasis and sinusoidal liver injury in the months following

HCT have become less frequent because of preventive and pre-emptive strategies. When patients develop jaundice after transplant, the Ferroptosis cancer time to search for treatable causes is early in the course of jaundice, as the risk of mortality rises steeply with small increments of serum bilirubin above normal. Chronic hepatitis C, persistent GVHD, cirrhosis and hepatocellular carcinoma are significant liver problems in the longest-lived survivors of HCT. I gratefully acknowledge the work of my distinguished colleague, Dr. Howard Shulman, who provided the photomicrographs. (Refer to the online Supporting material for a more comprehensive reading list.) Additional Supporting Information may be found in the online version of this article. “
“Endoscopic resection (ER) refers to an endoscopic procedure during which tissue acquisition occurs by electrosurgical incision of the mucosa or submucosa. Endoscopic mucosal resection (EMR) refers to techniques in which the intent is to remove primarily mucosal tissue. The two most common EMR techniques Idoxuridine are (1) cap technique (“suck” and cut);

and (2) band ligation (ligate and snare). Endoscopic mucosal resection has been shown to be effective and safe in patients with high-grade intraepithelial neoplasia (HGIN) and mucosal carcinoma of the esophagus (squamous cell carcinoma and Barrett’s carcinoma). [See tables X, Y and Z] For these lesions, the risk of lymph-node metastasis is very low and the procedure may obviate the need for esophagectomy, which has a higher morbidity and mortality. Endoscopic submucosal dissection (ESD) is an attractive new treatment approach with the ability to provide en bloc resection of larger neoplastic lesions. Both EMR and ESD should be performed by experienced endoscopists. “
“Background and Aim:  The early detection of hepatocellular carcinoma (HCC) and opportunity to select appropriate treatment are important benefits of HCC screening. Our aim in the present study was to investigate the survival rate, prognostic factors and treatment effects in HCC patients of community-based screening.

Using just the high values for a given year, Schell (2000) compiled an isotopic time series for the Bering Sea. The study raised questions on two grounds. First, the shifts Schell (2000) detected may relate more to changes in whale migration or diet than to any shift in δ13C values of Bering Sea phytoplankton. Second, as noted by Cullen et al. (2001), phytoplankton δ13C values should have dropped over the last 60 yr due to the rise in atmospheric CO2, because fossil fuel combustion pumps 13C-depleted Staurosporine solubility dmso carbon into global ecosystems, and because high aqueous [CO2] leads to increased photosynthetic

fractionation. The concern about the “reality” of the drop in North Pacific δ13C values has been addressed through study of additional time series from other species, including pinnipeds and sea birds (Hirons et al. 2001a, Hobson et al. 2004b). The most controlled study in temporal, spatial, and taxonomic PLX3397 in vivo terms is Newsome

et al. (2007b). The authors sampled dentin from the third dental annulus of male northern fur seals from a single rookery on Saint Paul Island in the Pribilofs, with intensive sampling (∼5 samples/yr) from 1948 to 2000, as well as a few scattered samples from the early 20th century. Mean annual δ13C values declined by approximately 1.1‰ from 1948 to 2000 (Fig. 5A), while long-term mean annual δ15N values did not change significantly (Fig. 5B). The relatively small but significant long-term drop in δ13C values can be entirely explained by the anthropogenic changes in surface ocean carbon reservoirs

noted by Cullen et al. (2001) and need not entail a decline in primary productivity as posited by Schell (2000, 2001). Finally, both δ13C and δ15N time series showed low amplitude oscillations with a frequency of 20–25 yr that may be related to shifts in climatic and/or oceanographic conditions resulting from the Pacific Decadal Oscillation. The Pleistocene epoch, beginning approximately 1.8 mya, was marked by many dramatic climatic shifts, the waxing and waning of massive continental Palmatine ice sheets, and large (∼120 m), rapid fluctuations in sea level. The changes must have had profound impacts on marine mammal populations. For example, at the last glacial maximum, just 20,000 yr ago, the Pribilof islands (where most northern fur seals breed today) were not islands at all, but rather were uplands at the edge of a vast low lying plain extending from Siberia to Alaska that was inhabited by a host of large carnivores (lions, sabertooths, gray wolves, brown bears, short-faced bears) (Manley 2002, Guthrie 2004). For the last 10,000 yr (the Holocene), climatic variations have been more subdued, but not absent.

Generally, hypercaloric diet, especially rich in trans/saturated fat and cholesterol,

and fructose-sweetened beverages seem to increase visceral adiposity and stimulate hepatic lipid accumulation and progression selleck inhibitor into non-alcoholic steatohepatitis, whereas reducing caloric intake, increasing soy protein and whey consumption, and supplement of monounsaturated fatty acids, omega-3 fatty acids, and probiotics have preventive and therapeutic effects. In addition, choline, fiber, coffee, green tea, and light alcohol drinking might be protective factors for NAFLD. Based on available data, at least 3–5% of weight loss, achieved by hypocaloric diet alone or in conjunction with exercise and behavioral modification, generally

reduces hepatic steatosis, and up to 10% weight loss may be needed to improve hepatic necroinflammation. A sustained Torin 1 cell line adherence to diet rather than the actual diet type is a major predictor of successful weight loss. Moreover, a healthy diet has benefits beyond weight reduction on NAFLD patients whether obese or of normal weight. Therefore, nutrition serves as a major route of prevention and treatment of NAFLD, and patients with NAFLD should have an individualized diet recommendation. Non-alcoholic fatty liver disease (NAFLD) is an acquired metabolic stress-related liver disease sharing histological similarities to alcoholic liver disease in the absence of substantial alcohol consumption.[1, 2] The spectrum of NAFLD is from of simple steatosis to non-alcoholic steatohepatitis (NASH), and eventually cirrhosis and hepatocellular carcinoma.[1, 2] NAFLD is strongly associated with obesity, dyslipidemia, hypertension, type 2 diabetes mellitus (T2DM), and metabolic syndrome.[1-3] With the rising incidence of obesity and metabolic syndrome in adults and children worldwide, NAFLD is developing into a new and major health problem.[1-3] Currently, NAFLD/NASH is the most common cause of liver disease worldwide and the third most common indication for liver

transplantation in North America.[1] The management of patients with NAFLD consists of treating steatohepatitis and the associated metabolic comorbidities.[1, 2] However, patient with simple steatosis is only needed to treat the associated conditions to prevent hepatic and metabolic complications.[1, 2] Based on available data, most patients with NAFLD have excessive body weight or recently, weight gain; obesity is a common and well-documented risk factor for metabolic syndrome and NAFLD.[1-3] Although promising pharmacological agents and bariatric surgery are emerging, gradually and maintaining weight loss by lifestyle intervention is safe and the most effective treatment for NAFLD and metabolic disorders.[1, 2, 4-9] On one hand, diet alone or in conjunction with increased physical activity and behavior modification is the important measure for successful weight loss.

Hence, there is only limited experience

with transplanting persons with CHD and liver disease. In addition, the severity of cardiac dysfunction among the above-described cases is not known. Overall survival of patients receiving heart transplants in the United States for CHLT is 83% (3 months), 74% (1 year), and 64% (5 years), respectively. However, this excellent survival may be driven by the unique characteristics of the population. Most patients undergoing CHLT have amyloidosis, and these patients are often young to middle-aged with normal liver synthetic function and minimal Ibrutinib in vivo coagulopathy.41 The risk of the procedure is often determined by the cardiac disease, rather than the liver disease. At our center, we have performed CHLT for 3 patients with complex CHD and cardiac cirrhosis (MELD range, 10-15) with 100% survival (range, 8 months-4 years). In patients with

failed Fontans who have had multiple transfusions, there is the risk of sensitization to donor antibodies, which makes receipt of a suitable organ challenging. The multiple sternotomies and cardiac procedures greatly increase the technical complexity of the cardiac transplant. Transplanting the liver before the heart may serve to absorb donor-specific antibodies, which can cause cardiac rejection, but places the liver at increased risk of ischemia in the absence of adequate cardiac function. In the 3 patients with CHD and cardiac cirrhosis undergoing CHLT, all of the patients were sensitized selleck screening library to donor antibodies; though there were episodes of acute cellular rejection, there were no episodes of antibody-mediated rejection. Patients listed for CHLT often get transplanted based on their cardiac status,

rather than the MELD score. Wait-list mortality for the average candidates listed for the CHLT dual waiting list (cardiac status 2 and MELD scores of 20-29) approximates the waiting-list mortality of those with status 1 or a MELD score higher than 30.40 After CHLT, lower immunosuppression levels are tolerated with a lower risk of graft rejection related to induction of partial tolerance.41, 42 In 93% of patients undergoing CHLT at the Mayo Clinic, both surgeries were completed in a single stage without perioperative mortality.41 As compared Selleckchem Alectinib to a control group undergoing heart transplant alone, rejection rates were lower and pulmonary embolism was higher in the CHLT group, but survival was similar between the two groups. Significant strides have been made in reducing mortality in patients with CHD. However, the long-term sequelae of palliative procedures in early childhood are not yet fully realized, and an increase in morbidity attributed to liver disease, especially with the associated and potentially increased risk of HCC, is expected over the lifespan of this vulnerable population.

5F). Nearly identical results were obtained using SAM as a methyl donor instead of betaine (Fig. S6A-D). To further test the hypothesis that

the combined HCV-ethanol effect results from FOXO3 demethylation, we generated a FOXO3 R248K_R250K double mutant missing the arginines methylated in FOXO1.[17] This mutant demonstrated less total protein methylation than the WT-FOXO3 (Fig. 6A) and its half-life was significantly reduced (Fig. 6B). The methylation-defective mutant was similar to the WT protein in that it was still transcriptionally active (Fig. 6C), it was primarily NVP-BEZ235 supplier cytosolic in uninfected cells (Fig. 6D,E), and it translocated to the nucleus in response to HCV infection. The FOXO3 R248K_R250K double mutant differed from the WT protein in two respects. Its nuclear translocation was not inhibited by the combination of HCV and ethanol (Fig. 6D,E), and formation of the HCV-specific pI 5.85 peak was not inhibited by ethanol (Fig. 6F, compare to Fig. 2A or S7B). Finally, we used small interfering RNA (siRNA) to knock down expression of PRMT1, the methyltransferase responsible

for the majority of arginine methylation.[17] This knock down reduced nuclear levels and decreased transcriptional activity of WT but not mutant FOXO3 (Figs. 6G, S7C). We compared the pattern of FOXO3 species present in human liver nuclear extracts from normal donor livers, HCV cirrhosis, and nonalcoholic Selleckchem Autophagy Compound Library steatohepatitis (NASH) cirrhosis. We observed the presence of a peak in the region of pI 6.0 for majority of the samples and a peak in the region of pI 5.85 in all HCV-positive and some HCV-negative samples (Fig. 7A). We quantitated the presence of an HCV-like effect as the 5.85 peak area divided by the sum of the areas of the 5.85 + 6.0 peaks. As shown in Fig. 7B, the 5.85 peak accounted for ∼60%-90%

of total in HCV versus only ∼10% in NASH or normal liver (P < 0.01). To determine if this peak was related to JNK activation we simultaneously analyzed the samples for the phosphorylated JNK species (pI 5.3 and 5.6) Fludarabine supplier in our samples by cIEF (Fig. 7C). Figure 7D shows that regardless of disease condition, there was a strong correlation between detection of pJNK species and the proportion of the pI 5.85 form of FOXO3. FOXO transcription factors regulate hepatic growth and metabolism and respond to stress conditions.[20-22] FOXO1 is activated by HCV infection, contributing to insulin resistance,[23, 24] and FOXO3 activity was noted to be increased in HCV infection where it modulated innate immune signaling.[25] The molecular mechanisms of FOXO3 regulation by HCV and how alcohol modifies HCV’s FOXO3 effects in the liver has not been determined. In the present study we have shown that HCV and ethanol induce specific and interactive patterns of FOXO3 posttranslational modifications that alter the function of this transcription factor.

These results indicate that bile acids may coordinately regulate biliary bile acids and cholesterol secretion. Induction of hepatic, but not intestinal cholesterol and bile acid transporters may result in increased biliary cholesterol and bile acid secretion with subsequent fecal elimination in Cyp7a1-tg mice. To test if increased hepatic Abcg5/g8 expression in Cyp7a1-tg mice could be due to bile acid activation of FXR, we treated mouse hepatocytes with bile acids or a specific FXR agonist GW4064 and analyzed Abcg5/g8 mRNA expression levels. As shown in Fig. 4B, CDCA, CA

and learn more GW4064 treatment all significantly induced Abcg5/g8 mRNA expression levels in mouse hepatocytes. CDCA induction of Abcg5/g8 was stronger than CA, which is consistent with CDCA being a more efficacious FXR ligand. Furthermore, treating primary human hepatocytes with CDCA, CA, and GW4064 also induced ABCG5/G8 mRNA (Fig. 4C) and protein expression (Fig. 4D), suggesting that FXR induction of ABCG5/G8 is conserved in human hepatocytes. To our surprise, an LXR agonist TO901317 or cholesterol did not induce ABCG5/G8 mRNA in human hepatocytes (Fig. 4C), in contrast to a previous report that LXR induce mouse Abcg5 and Abcg8 mRNA expression.10 These data suggest that LXR may differentially

regulate ABCG5 and ABCG8 expression Lapatinib mouse in mouse and human hepatocytes. To further elucidate the molecular mechanism of FXR regulation of Abcg5/g8 gene expression, we performed Abcg5 promoter/luciferase (luc) reporter assays in HepG2 cells. We found that the Abcg5 reporter activities of the reporter plasmids −2041-luc, −1420-luc, −1160-luc, and −918-luc were strongly induced by GW4064 treatment. Reporter activities of shorter constructs −679-luc and −431-luc were not affected. These assays defined a functional FXR response element (FXRE) located

between nucleotides −680 and −918 on the Abcg5 promoter (Fig. 5A). Analysis of nucleotide sequences in this region identified an inverted repeat with one-base spacing (IR1) located between Sitaxentan nucleotides −682 to −669 on the Abcg5 promoter (or +309 and +322 of abcg8 in intron 1), which is a typical FXRE (Fig. 5A). EMSA showed that FXR/RXRα heterodimer bound to this putative FXRE, and that binding was abolished by excess of unlabeled probes containing the known FXRE from small heterodimer partner (SHP), or fatty acid synthase (FAS) genes, or by antibody supershift assay using an antibody against FXR (Fig. 5B). We then performed ChIP assays using mouse liver and intestine nuclei. ChIP assays showed that FXR occupied the Abcg5/g8 promoter in the mouse liver (Fig. 5C), but not in mouse intestine (Fig. 5D). A positive control showed that FXR occupied the Shp gene promoter in both mouse liver and mouse intestine (Fig. 5C,D).

The APASL Guideline published in 2010 were authored by a 25-member multi-disciplinary group comprising hepatologists, medical oncologists, surgeons and radiologists in the Asia-Pacific who first met at a monothematic conference on HCC in Bali in 2008.27 The APASL Guideline reflect the practices, not only of

major academic surgical centers in the Asia-Pacific, but its recommendations for surgical resection also mirrored that of some centers outside of the region that have dedicated HPB services (discussed below). These recommendations are a significant departure from those of the AASLD Guideline. The authors of the APASL guideline justified the more aggressive surgical approach on the basis of improved updated clinical outcomes from the published literature. Like the AASLD Guideline, www.selleckchem.com/products/ink128.html the APASL Guideline considers the presence of distant metastases and main portal vein and inferior vena cava involvement Gemcitabine as definite contraindications

for liver resection in HCC.27 The number of tumors and the involvement of branch vasculature, however, were not considered contraindications. Bi-lobar HCC was also not considered a contraindication, and combined resection with radio-frequency ablation was specifically recommended in such cases.40,41 However, radio-frequency ablation was considered to be an acceptable alternative to resection for tumors less than 3 cm, even in CTP A patients, and this recommendation Galeterone was largely based on a huge evidence base (but not from RCTs) generated in Japan. The philosophical premise was that if resection is technically feasible and safe, the long-term survival of resection is superior to current non-surgical therapies in such patients. In support of these recommendations, APASL noted that the reported long-term survival after resection for HCC with multi-focal nodules and/or vascular invasion is superior to that of the current mainstream alternative therapy, namely trans-arterial chemo-embolization

(TACE).35,36 Ng reported a 5-year OS of 39% after resection of large or multi-focal HCC.36 Ishizawa et al. reported a 58% 5-year OS for multifocal tumors and did not consider portal hypertension a contraindication to resection.42 Ikai et al. reported 5-year OS of 46% after resection in patients with vascular invasion.43 These results all compare well with TACE, where 2-year OS is between 24–63%, and there are no robust data on 5-year OS with TACE39,44 (Table 1). On the basis of these data, the patient would be best treated by resection if this is technically safe and feasible. A recent retrospective report from Asia similarly supports resection over TACE for stage BCLC B patients.45 Many academic surgical units in the West pursue a more aggressive surgical approach to HCC than might be suggested by the AASLD or BCLC Guidelines. These western views are well articulated by several recent reviews in the surgical literature. Truty et al.

In the latter experiment, filters were attached to the upper surface of the ice so that the algae were exposed in situ to treatments of ambient levels of PAR and UV radiation, ambient radiation minus UVB, and ambient radiation minus all UV. After 16 d, significant increases in chl a and cell numbers were recorded for all treatments, but there were no significant differences www.selleckchem.com/products/Gefitinib.html among the different treatments. Bottom-ice algae exposed in vitro were considerably less tolerant to UVB than those in situ, but this tolerance improved when algae were retained within a solid block of ice. In addition, algae extracted from brine channels in the upper meter of sea ice and exposed

to PAR and UVB in the laboratory were much more tolerant of high UVB doses than were any bottom-ice isolates. This finding indicates that brine algae may be better adapted to high PAR and UVB than are bottom-ice algae. The data indicate that the impact of increased levels of UVB resulting from springtime ozone depletion on Antarctic

bottom-ice communities is likely to be minimal. These algae are likely PCI-32765 in vivo protected by strong UVB attenuation by the overlying ice and snow, by other inorganic and organic substances in the ice matrix, and by algal cells closer to the surface. “
“Diatoms are frequently exposed to high light (HL) levels, which can result in photoinhibition and damage to PSII. Many microalgae can photoreduce oxygen using the Mehler reaction driven by PSI, which could protect PSII. The ability of Nitzschia epithemioides Grunow and Thalassiosira pseudonana Hasle et Heimdal grown at 50 and 300 μmol photons · m−2 · s−1 to photoreduce oxygen was examined by mass spectrometric measurements of 18O2. Both species exhibited significant rates of oxygen photoreduction at saturating light levels, 3-mercaptopyruvate sulfurtransferase with cells grown in HL exhibiting higher rates. HL-grown T. pseudonana

had maximum rates of oxygen photoreduction five times greater than N. epithemoides, with 49% of electrons transported through PSII being used to reduce oxygen. Exposure to excess light (1,000 μmol photons · m−2 · s−1) produced similar decreases in the operating quantum efficiency of PSII (Fq′/Fm′) of low light (LL)- and HL-grown N. epithemoides, whereas HL-grown T. pseudonana exhibited much smaller decreases in Fq′/Fm′ than LL-grown cells. HL-grown T. pseudonana and N. epithemioides exhibited greater superoxide and hydrogen peroxide production, higher activities (in T. pseudonana) of superoxide dismutase (SOD) and ascorbate peroxidase (APX), and increased expression of three SOD- and one APX-encoding genes after 60 min of excess light compared to LL-grown cells. These responses provide a mechanism that contributes to the photoprotection of PSII against photodamage. “
“Siphonous plants represent an alternate scheme to the way most macroscopic plants are constructed.

Ejercicios para el cuello vigoroso, tintes

para el cabello, y los permanentes son contraindicados por 24 horas después del procedimiento. La OnabotA es una intervención preventiva efectiva en muchos pacientes con migraña, pero no todos responden. Por esta razón, es importante mantener un diario de días con cefalea, la intensidad y duración, tanto EPZ-6438 datasheet antes como después de recibir la toxina. Los pacientes pueden tomar hasta 4 semanas después de la inyección en notar los beneficios, aunque muchos ven la mejora antes. Después de 2 series de inyecciones, si no hay ninguna mejora, OnabotA probablemente debería ser descontinuada. Para los que responden, las inyecciones se continúan cada 3 meses. Para probar si las inyecciones se pueden descontinuar, las inyecciones no se hacen tan frecuentemente y

si los dolores de cabeza no aumentan, el tratamiento puede ser detenido. Después de parar de usar OnabotA, se debe mantener un diario de cefaleas para asegurar que no hay un aumento en la frecuencia de la migraña, la intensidad o duración sin su uso. La migraña crónica es un problema importante para al menos un 2% de la población. Esto tiene un impacto negativo en la calidad see more de vida de las personas, así como la de sus familias. La toxina botulínica tipo A es la primera intervención aprobada que se ha encontrado que provee una mejora significativa en esta enfermedad. A pesar de no resultar en una cura,

representa un avance en el tratamiento eficaz. Para encontrar más recursos, visite la Fundación Americana de la Migraña (http://kaywa.me/ir2eb) “
“Tepper and Stillman provide aminophylline an excellent overview of treatment options in refractory cluster headache patients.[1] While they mention noninvasive vagus nerve stimulation (VNS), they fail to discuss a possibly more effective option, from which the idea for noninvasive VNS was derived. This option is VNS using an implanted electrode that provided very good relief in both patients with refractory cluster headaches in whom it was tried.[2] VNS is approved by the Food and Drug Administration for refractory epilepsy and depression, and considering that anticonvulsants and antidepressants are effective in the treatment of headaches, it is likely that VNS will work for headache patients as well. “
“(Headache 2010;50:1198-1200) One can question the clinical relevance of early headache responses after oral and intranasal triptans. Thus, for pain-free the early responses were significant but in absolute values they were only a few percentages: the therapeutic gains (TGs) were 1.8% (95% CI = 0.3-3%) for oral almotriptan 12.5 after 30 minutes and 1.0% (95% CI = 0-2%) after intranasal zolmitriptan 5 mg after 15 minutes. These results are compared with subcutaneous sumatriptan 6 mg which has TGs of 11% (95% CI = 7-15%) to 14% (95% CI = 11-17%) for pain-free after 30 minutes.