Aim of this study was to develop and validate a Sinhala version o

Aim of this study was to develop and validate a Sinhala version of the CLDQ (sCLDQ) and to test its correlation with the degree of liver dysfunction in a cohort of Sri Lankan patients with cirrhosis. Methods: A standard translation method was used to develop the sCLDQ. Pilot testing was done with relevant cultural and language adaptations. The final version was self-administered to stable CLD patients, together with the WHO Quality of Life-BREF (WHOQOL-BREF) validated Sinhala version, for comparison. INK 128 mw sCLDQ was re-administered 4 weeks

later to test internal consistency and reliability. The validation was assessed by Cronabach’s alpha, intraclass correlation coefficient (ICC) and Pearson’s correlation coefficient. ANOVA and Pearson’s correlation were used to test correlation with the degree of liver dysfunction. Results: Validation was done with 214 subjects, mean age 55.6 (SD 10.4) years; male 77.6%. Overall Cronabach’s alpha was

0.926. Itra-class correlations varied from 0.431 to 0.912 and all were significant (p 0.000). Retesting was done on a sub-sample of 18 subjects. Test-retest correlation was 0.695 (p 0.008). WHO-BREF was applied on a sub-sample of 48 subjects. There was a significant correlation (Pearson’s r = 0.391; p = 0.004) between sCLDQ and WHOQOL BREF. sCLDQ was significantly Bortezomib in vivo associated with MELD (r = −0.13; p = 0.038), MELD Sodium (r = −0.223; p = 0.002), Bilirubin (r = −0.124; p = 0.036), Serum Sodium (r = 0.172; p = 0.009), Serum Albumin (r = 0.201; p = 0.003) and Child grade (f = 3.687; p = 0.027). Conclusion: sCLDQ is a reliable and valid

tool to assess click here QoL of Sri Lankan cirrhotics and correlates well with known indices of disease severity. Key Word(s): 1. Cirrhosis; 2. CLDQ; 3. Sinhala; 4. Quality of Life; Presenting Author: YINPENG JIN Additional Authors: GUANGFENG CHEN, QINGCHUN FU, XIAOQING LIU, CHENGWEI CHEN, HENG ZHOU Corresponding Author: QINGCHUN FU, XIAOQING LIU, CHENGWEI CHEN Affiliations: Shanghai Liver Diseases Research Center, the Nanjing Military Command; Tongji University Objective: Acute liver failure is a highly lethal disease with rare effective therapeutic methods. Allogeneic liver transplantation is a viable treatment for acute liver failure. However, there is a serious shortage of liver donors. Stem cell transplantation is a more promising alternative approach for acute liver failure. Here we show that the human adipose-derived stem cells (hADSCs) have promising therapeutic potential for rats with acute liver failure. Methods: HADSCs were isolated from fat tissue, purified by adherence screening method and cultured in serum-free medium.

pylori-infected

patients at risk of gastric carcinogenesi

pylori-infected

patients at risk of gastric carcinogenesis before the occurrence of pre-cancer changes. Since spasmolytic polypeptide expressing metaplasia (SPEM) has been considered as a pre-cancerous lesion present before the formation of intestinal metaplasia, the present study aim to validate whether CGI correlates with SPEM development in the first-degree gastric cancer relatives. Methods: We enrolled 63 first-degree gastric cancer relatives and 82 sex- and age-matched duodenal ulcer patients as controls. Each subject received endoscopy to gather topographic gastric specimens. H. pylori infection and its related histological features were tested LDK378 cost and translated into the operative link on

gastritis Selleck SCH727965 assessment (OLGA), operative link on gastric intestinal metaplasia assessment (OLGIM) stages, and the presence of CGI. We assessed Spasmolytic polypeptide-expressing metaplasia (SPEM) by immunohistochemistry staining of trefoil factor 2. Results: The 1st-degree relatives of the gastric cancer patients had a higher rate of the presence of CGI, but not OLGA or OLGIM stage II-IV

than click here the duodenal ulcer controls (P = 0.001). In addition, the 1st-degree GCA relatives had higher proportions of the presence of SPEM (OR 3.65, 95% CI 1.61–8.28, p = 0.003) and advanced SPEM (OR 12.51, 95% CI 1.58–99.13, p = 0.003) than non-CGI DU controls (N = 56). Among the 1st-degree relatives, the presence of CGI increased the presence of SPEM (P = 0.003, OR = 5.5[95%CI 1.8–17.0]) and correlated with higher H. pylori densities at corpus (p = 0.008) and high corpus (p < 0.001). Conclusion: The presence of CGI, as an early marker to identify the H. pylori-infected patients at higher risk of gastric cancer, was highly correlated to SPEM formation in the first-degree gastric cancer relatives. Presenting Author: YI-CHUN YEH Additional Authors: HSIAO-BAI YANG, YAO-JONG YANG, SHEW-MEEI SHEU, HSIU-CHI CHENG, WEI-LUN CHANG, YU-CHING TSAI, WEN-LUN WANG, WEI-YING CHEN, WEI-HSIN HSIAO, BOR-SHYANG SHEU Corresponding Author: YI-CHUN YEH, BOR-SHYANG SHEU Affiliations: National Cheng Kung University Medical Center Objective: H.

However, small numbers of events limit the strength of inferences

However, small numbers of events limit the strength of inferences. “
“(Headache 2010;50:1328-1334) Background.— Religious fasting is associated with headache. This has been documented as “Yom Kippur Headache” and “First-of-Ramadan Headache.” Rofecoxib (Vioxx®), a cyclooxygenase-2 (Cox-2) inhibitor with a PR-171 nmr 17-hour half-life, has been shown to be effective in preventing fasting headache when taken just prior to the 25-hour Yom Kippur fast. Unfortunately for fasters rofecoxib is no longer available. We hypothesized that etoricoxib, another Cox-2 inhibitor with a longer half-life, would also be effective in preventing fasting headache. Methods.—

We performed a double-blind randomized prospective trial of etoricoxib 120 mg vs placebo, taken just prior to the onset of fasting, Yom Kippur 2008. Healthy

adults aged 18-65 years were enrolled from the community. Subjects completed a demographic data form and questions regarding headache history and a post-fast survey on headache during the fast. We compared incidence, time of onset and intensity of headache, general ease of fasting, and side effects in control and treatment groups. Results.— We enrolled 211 patients and 195 completed the post-fast questionnaire (92%). Of those subjects receiving etoricoxib find protocol (n = 99), 36 or 36.4% vs 65 or 67.7% of the placebo group (n = 96) selleck screening library developed any headache during the fast (P < .0001). Median

severity of headache in the treatment group was significantly lower for the treatment group (3.0 vs 5.0 on a visual analog scale of 10; P = .024). Also, participants in the treatment group reported an easier fast than the placebo group, as compared with previous fasting experience (4.0 vs 3.5 on a scale of 1-5; P < .0001). Conclusion.— Etoricoxib 120 mg taken prior to a 25-hour ritual fast decreases incidence of and attenuates fasting headache. NCT number is NCTT00752921. "
“(Headache 2011;51:995-998) “
“Objectives.— The goal of this study was to measure the effect of biofeedback therapy on pediatric headache and to identify factors associated with response to biofeedback therapy. Background.— In the United States, 17% of children have frequent or severe headaches. Biofeedback therapy (BFT) appears to be an effective treatment for headaches in adults and is often recommended for children with headaches, but there are few data in the pediatric population. It is also not clear which patients are most likely to benefit from biofeedback therapy. Methods.— We examined the records of patients, aged 8 to 18 years old, who were referred to a pediatric BFT clinic for management of headache between 2004 and 2008.

Given the role of POLG in mtDNA replication we looked for evidenc

Given the role of POLG in mtDNA replication we looked for evidence of a qualitative or quantitative defect of mtDNA in whole-blood cellular mtDNA because liver tissue was not available from the affected individuals. No mtDNA deletions were detected LDK378 datasheet by long-range PCR and the mtDNA content was no different to age-matched controls (83.9 copies/cell, standard deviation [SD] 58.8; versus 85.8, SD 28.3; Supporting Information Fig. 1A). Following treatment for 10 days with therapeutically relevant doses of VPA (2 and 10 mM) no

significant decrease in mtDNA content was observed (Fig. 3A), nor detectable mtDNA deletions (Supporting Information Fig. 1b) despite the observed cell death. Treatment of control and patient myoblasts with the highest tolerated doses of VPA (50 and 100 mM) still showed no depletion of mtDNA but compromised cell proliferation, with extensive cellular ballooning, vacuolization, and detachment within 3 days of treatment (Supporting

Information Fig. 2). The presence of mtDNA deletions was not investigated in these cells due to the short culture period, making the appearance of deletions highly unlikely. By contrast, EtBr-treated cells grown in parallel showed the expected decrease in mtDNA content after 10 days but no defect of cellular proliferation and no evidence of cell death (Fig. 3B). There was no evidence of apoptosis in any of the cell lines after 10 days Sorafenib of treatment. Multiple mtDNA deletions were not detected in any of the cell pellets, there were no differences in COX activity observed, and β-oxidation metabolites remained within normal limits (Supporting Information Table 2). We therefore extended our studies to postmitotic myotubes, which more closely model mtDNA depletion in vivo.12 MtDNA levels were significantly lower in AHS and Q1236H myotubes than in controls (Fig. 3C). To determine whether mtDNA depletion itself predisposes to further mtDNA loss after VPA exposure, we depleted the myotubes with

didanosine selleck screening library and stavudine, which induce less severe myotube mtDNA depletion than EtBr.12 MtDNA depletion levels in Q1236H myotubes were less than in controls, and similar to the AHS cell lines, but there was no further decrease in mtDNA content with the addition of 10 mM VPA (Fig. 3C). VPA is a branched medium chain fatty acid known to inhibit mitochondrial β-oxidation,16 possibly through the microsomal production of toxic metabolites including 4-ene-VPA,17 or cytosolic and mitochondrial CoA sequestration effects.18 However, we saw no evidence of a β-oxidation defect, making this mechanism unlikely in this context. We also saw no evidence of a secondary mtDNA defect, despite the VPA dose-related growth inhibition and cell death. By contrast, treating identical cell lines with EtBr, didanosine, or stavudine caused profound but recoverable mtDNA depletion without cell death.

29, P = 0033) (data not shown)

29, P = 0.033) (data not shown). Galunisertib order Up-regulation of HLA-DR expression by cirrhotic plasma, which could also be induced by exposure to LPS or CpG, was abrogated by the antagonism of either TLR4 or TLR9 (Fig. 6D). Abrogation of HLA-DR up-regulation was detected with three different approaches to TLR4 blockade: LPS-RS, which inhibits LPS binding to LPS-binding protein (LBP), neutralization of sCD14, and direct blockade of TLR4 (Fig. 6E). Last, similar to LPS and CpG, cirrhotic plasma protected

B cells from apoptosis in 72-hour culture, an effect that was abrogated by TLR4 and/or TLR9 blockade (Fig. 6F). Thus, soluble factors associated with bacterial translocation, such as LPS and CpG motifs, that are elevated in cirrhotic plasma are capable of activating B cells in vitro. Though the long-term effects of such activation cannot be modeled ex vivo, these data suggest a possible mechanism underlying the phenotypic and functional perturbations of peripheral blood B cells in cirrhosis. In our study, we have uniquely found that among patients with chronic HCV, only those that have progressed to cirrhosis display a loss of CD27+ memory

B cells with associated functional abnormalities. The noncirrhotic and cirrhotic HCV-infected patients we studied were similar in age, gender, ethnicity, viral genotype, and duration of infection, making viral or demographic factors very unlikely to explain the observed differences. Furthermore, this phenotype was also identified in patients with non-HCV-related cirrhosis, strongly implicating hepatic fibrosis and/or portal hypertension in the development Talazoparib datasheet of this phenotype. The loss of CD27+ memory B cells appears to be a phenomenon common to several immunocompromised states, such as advanced solid tumors,23 human immunodeficiency virus (HIV) infection,28 and common variable immunodeficiency (CVID).29 Though HIV and cirrhosis are both associated with bacterial translocation, a common underlying pathophysiology with CVID and advanced malignancy is not immediately obvious, but perhaps may be this website related to splenic

dysfunction. The loss of CD27+ memory B cells in cirrhosis was associated with several functional consequences, including impaired activation, impaired TNF-β and IgG production, and impaired allostimulatory capacity. This impaired activation and reduced capacity to recruit T-cell help may explain the observed vaccine hyporesponsiveness in cirrhotic patients.14, 15 Paradoxically, overall Ig levels are elevated in cirrhotics because of increased levels of pathogen-specific Igs, such as antibodies against Saccharomyces cerevisiae and against Galα1-3Galβ1-3GlcNAc, a glycan epitope found in bacterial cell walls.16, 17 Quite strikingly, we have shown that cirrhosis is associated with profound reductions of CD27+IgM+ B cells, a subset of memory B cells thought to be generated in response to T-independent antigens.

During the period of January 2009 to March 2011,

During the period of January 2009 to March 2011, HIF inhibitor we enrolled hepatitis B e antigen–positive mothers with HBV DNA >6 log10 copies/mL in China. At gestation week 28, the mothers received LdT or LAM until postpartum week 4 or no treatment (NTx). The study endpoints were the safety of LdT/LAM use and MTCT rates. Of the 700 mothers enrolled, 648 (LdT/LAM/NTx = 252/51/345) completed the 52-week study with 661 infants (LdT/LAM/NTx = 257/52/352). On treatment,

viral rebound occurred in 1.6% of mothers, all resulting from medication noncompliance. There was no genotypic mutation detected. At delivery, significantly lower HBV DNA levels were noted in mothers who received LdT or LAM versus NTx. Alanine aminotransferase flares were observed in 17.1% of treated mothers versus 6.3% of untreated mothers (P < 0.001). At birth, hepatitis B surface antigen (HBsAg) was detected in 20% and 24% of newborns in the treated and NTx groups, respectively. At week 52, an intention-to-treat analysis indicated 2.2%

(95% confidence [CI]: 0.6-3.8) of HBsAg+ infants from the treated group versus 7.6% (95% CI: 4.9-10.3) in the NTx group (P = 0.001) and no difference of HBsAg+ rate between infants in the LdT and LAM groups (1.9% vs. 3.7%; P = 0.758). On-treatment analysis indicated 0% of HBsAg+ infants in the treated group versus 2.84% in the

NTx group (P = 0.002). There were no differences for gestational age or infants’ see more LBH589 clinical trial height, weight, Apgar scores, or birth defect rates between infants from the treated and untreated groups. Conclusions: LdT and LAM use in late pregnancy for highly viremic mothers was equally effective in reducing MTCT. The treatment was well tolerated with no safety concerns identified. (Hepatology 2014;60:468–476) “
“Background and Aims:  It is difficult to approach certain gastric regions due to the limited bending ability of transnasal esophagogastroduodenoscopy (TN-EGD). We analyzed the TN-EGD biopsied specimens according to where they were obtained inside the stomach. Methods:  Two hundred and eighty-nine gastric biopsy specimens were obtained during diagnostic TN-EGD. The gastric biopsied specimens were quantified according to their diameter and depth in micrometers, and depth in layers (superficial mucosa, deep mucosa, muscularis mucosa and submucosa). The quality was measured by the degrees of anatomical orientation (good, intermediate and poor), presence of crush artifact (none to minimal, mild and moderate) and overall diagnostic adequacy (adequate, suboptimal and inadequate). Results:  Poor orientation, presence of crush and overall diagnostic inadequacy were present in 33 (11.4%), 26 (9.0%) and 37 (12.8%) of the 289 specimens, respectively.

So investigation of proteine kinase inhibitor pyrrol derivative 5

So investigation of proteine kinase inhibitor pyrrol derivative 5-amyno-4-(1,3-benzothyazol-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3Н-pyrrol-3-one (D1) effects on intestine mucosa proliferation in normal and experienced colon cancer rats compared with a common therapeutic 5-fluorouracil (5-FU) ones was aimed. Methods: 1,2-Dimethylhydrazine (DMH)-induced rat colon cancer model was used. Mitotic index (MI) in jejunum, colon and rectum mucosa epithelial cells and crypt fission index (CFI) in colon and rectum mucosa, tumor number (Ntumor), tumor mean and total area (Stumor, Stotal) per animal were counted;

correlation analysis was conducted. Results: Colon MI decrease by 27%, 37% and 46% was observed in groups II, VI, VIII respectively. Jejunum MI decrease by 31% in VII, colon MI decrease by 41% BMN 673 and 42% in III and VII respectively compared with I was observed. Ntumor decrease by 41%, 50%, 46% in V, VII and IX

respectively, and Stotal decrease by 41% and 46%, 43%, 54% in III, V, VII and IX respectively, were revealed. Correlation coefficients between Ntumor and Stotal and colon mucosa МI and CFI were computed. Direct relation to Ntumor of МI and CFI, direct relation to Stotal of MI and inverse relation to Stotal of CFI were demonstrated, indicating the relative independence of crypt fission of cell proliferation and their different roles in tumor initiation and growth processes. Conclusion: Lower inhibition of gut mucosa cells proliferation caused this website by D1 in comparison

to 5FU and their similar antitumor effects were concluded. Key Word(s): 1. colon cancer; 2. mucosa proliferation; 3. pyrrol derivative; 4. 5-fluorouracil; Presenting Author: JING JIANG Additional Authors: XUEYUAN CAO, FEI KONG, ZHIFANG JIA, DONGHUI CAO, MEI-SHAN JIN Corresponding Author: JING JIANG Affiliations: First Hospital of Jilin University Objective: Both CD44 and CD24 are known to contribute to cellular signaling and cell adhesion, and considered as are cancer stem cell markers. The aim of this study is to explore the alteration of CD44 and CD24 expression in gastric cancer selleckchem and to assess its prognostic values. Methods: Two hundred and ninety consecutive cases of gastric cancer were enrolled in the study. CD24 and CD44 expression was carried out in 290 gastric cancer specimens, of which 77 had paired adjacent normal gastric mucus samples by performing a tissue microarray immunohistochemistry method. Correlations were analyzed between expression levels of CD24 and CD44 protein and tumor parameters or clinical outcomes. Serum anti-Helicobacter pylori (H.pylori) IgG were detected by enzyme-linked immunosorbent assay method.

The idea of a surgical “solution” to migraine is inherently attra

The idea of a surgical “solution” to migraine is inherently attractive to patients. Interest in surgical approaches to migraine has been motivated by serendipitous improvement in headaches noted in patients who have undergone various plastic surgery

“forehead rejuvenation” procedures. These procedures are based on the premise that contraction of facial or other muscles impinges on peripheral branches of the trigeminal nerve. The procedures involved are often referred to collectively as “migraine deactivation surgery,” although a variety of surgical sites and procedures are involved. These include resection of the corrugator supercilii muscle with the placement of fat grafts in the Venetoclax site, “temporal release” procedures involving dissection of the glabellar area, transection of the zygomatical temporal branch of the trigeminal nerve, and resection of the semispinalis capitus muscle with placement of fat grafts in the area with the aim of reducing pressure on the occipital nerve.

Finally, some surgeons also perform nasal septoplasty or otherwise attempt to address possible intranasal trigger points.[17] Because the decision about which surgical procedure to perform is often made on an individual basis, it is difficult to objectively study the outcomes of surgery. When initial surgery is unsuccessful, patients may undergo additional procedures to deactivate other trigger points. Patients are often selected for surgery on the basis of improvement Ceritinib in headaches with the injection of OnabotulinumtoxinA and/or occipital nerve blockade, on the theory that response to such temporary procedures is proof of nerve impingement.[18] see more However, there is limited evidence to support the view that such surgery is effective or safe. Several randomized studies have been performed, but these have serious methodological weaknesses. Additionally, most studies in the literature have been performed by the same group of surgical proponents and published

in a single subspecialty journal.[18, 21] Despite the lack of good quality evidence about the balance of benefits and harms from surgical treatments of migraine, the procedures are becoming more common. A recent survey of members of the American Society of Plastic Surgeons found that 18% of respondents had performed migraine surgery. Sixty percent of those who had not performed the surgery said they “would be interested if an appropriate patient was referred to them by a neurologist.”[19] The American Headache Society has issued a statement urging “patients, healthcare professionals and migraine treatment specialists themselves, to exercise caution in recommending or seeking such therapy.” This statement went on to say “In our view, surgery for migraine is a last-resort option and is probably not appropriate for most sufferers. To date, there are no convincing or definitive data that show its long-term value.

[122] The bulk of the expenses attributable to migraine derive fr

[122] The bulk of the expenses attributable to migraine derive from its high population prevalence and indirect costs due to occupational disability[123] rather than direct health care costs, which are lower for migraine than for the other neurological conditions. During the past few years, there has been a concerted effort to raise awareness of the enormous public health impact of migraine. In recognition of its high prevalence and burden,

as well as the limited devotion of research resources to migraine, the World Health Organization recently launched a global campaign to reduce the burden of headache (Lifting The Burden 2).[45] This review documents the initial success in terms of the rapid growth of information on the magnitude of migraine in areas of the world that had been previously underrepresented. Despite the high magnitude of disability associated AZD9668 mw with migraine, Ibrutinib chemical structure only approximately one half of those individuals who suffer from debilitating migraine seek professional help.[28, 113, 124] The gap in treatment is remarkably similar across the world despite variation in health systems across the world. Of those who do seek treatment, many do not continue in treatment. Only a minority of those with migraine in the general

population ever seek treatment with clinicians with expertise in headache. As expected, those who seek professional treatment are characterized by greater severity, longer duration, more disability, and more comorbidity.[5, 28] In light of the overwhelming evidence regarding the tremendous burden of migraine, leaders in the headache field have called for increased awareness of the availability of preventive efforts. Operational criteria for prevention have been developed based on headache frequency and attack-related disability, yet few of those with migraine have received preventive interventions.[113] For example, only 25% of those with migraine in the AMPP in the U.S. actually seek professional treatment and receive appropriate medications.[113] selleck products There has been substantial progress in the descriptive epidemiology of migraine

during the past decade. The introduction of the ICHD-II and increasing awareness of the high magnitude, burden, and impact of migraine have stimulated numerous studies of population-based data on the prevalence, correlates, and impact of migraine. In particular, there has been growing international research on migraine in children, and a greater focus on longitudinal studies of the stability, risk factors, and course of migraine. Although the bulk of population research has been conducted in Europe and the U.S., there is growing work on the epidemiology of migraine in Asia, the Middle East, and South America. Across the 19 studies of adults that employed the ICDH-II criteria, the aggregate weighted estimates of the 12-month prevalence of definite migraine are 11.

However, sirtuin 3 is an NAD+-dependent enzyme, and either the ab

However, sirtuin 3 is an NAD+-dependent enzyme, and either the abundance or the availability of NAD+ may have been changed by the absence of Hint2 in mitochondria. Alternatively, Hint2 may have influenced the acetyl-transferase processes in mitochondria. A change in the acetylation status of selected proteins could explain several other Hint2−/− phenotypic changes. Hepatic steatosis may

be related to an impaired, hyperacetylated Hadhsc protein, since there is an association between Hadhsc deficiency and liver steatosis.23 Moreover, mitochondrial hyperacetylation of multiple proteins due to sirtuin 3 deficiency accelerates the development of metabolic syndrome.24 The impaired thermoregulation Hint2−/− mice could also be explained by an effect on acetylation, Fulvestrant ic50 since BAT expresses both sirtuin

325 and Hint2 (Fig. 5) and BAT proteins are regulated by acetylation during fasting.26 The reduced respiration in Hint2−/− and silenced HINT2-HepG2 mitochondria could be a primary defect due to the reduced linked complex II-III electron transport and coenzyme Q levels, which in turn could explain the increased reactive oxygen species production.27 Certain components of the electron transport chain are regulated by acetylation,28 which may have been altered in Hint2−/− mitochondria. The cause of the reduced coenzyme Q was not clarified, but a down-regulation of biosynthetic genes at the transcriptional level could be excluded. The appearance of large deformed Hint2−/− mitochondria was check details an age-dependent feature and different from the structural mTOR inhibitor alterations with cristolysis

described in respiratory chain disorders, where fusion and fission were perturbed.29 Because Hint2 was detected solely in the exocrine pancreatic fraction, the two-fold increase in interprandial insulin levels in Hint2−/− mice remains unexplained but was not indicative of insulin resistance (Supporting Fig. 3B). A steatosis-mediated reduction of hepatic insulin clearance was unlikely because insulin was higher in Hint2−/− even after Hint2+/+ livers showed signs of steatosis. The apparent discrepancy between the increase in interprandial insulin and the decrease in glucose-stimulated insulin secretion, which could account for the lower glucose tolerance in Hint2−/− mice, was also not resolved in our experiments, but it is clear that deletion of Hint2 has affected basal and glucose-stimulated insulin secretion in different ways. The up-regulation of leptin mRNA expression in Hint2−/− WAT was possibly secondary to the higher basal insulin and glucocorticoid concentrations.30, 31 The failure of Hint2−/− mice to mount an appropriate counter-regulatory response to hypoglycemia is also not explained, but an impaired hepatic GDH enzyme combined with a lower expression of Pck1 after insulin (Fig. 4B and Supporting Fig. 3A) may have contributed to the poor ITT recovery phase.