Some phytotoxicity was observed at 10 mm. Exogenous application of benzothiadiazole in the range 1–10 mm provided locally a 30–40% reduction in infection frequency. At least 5 mm was needed to reduce rust infection systemically in first upper leaf, and 10 mm in upper ones. Exogenous application of dl-3-amino-n-butyric acid (BABA) provided locally a 45–58% reduction in infection frequency, while systemically a 33–58 and 49–58% reduction of rust symptoms was achieved on leaves at second and third nodes respectively. BABA application was not associated with symptoms of phytotoxicity. “
“A triplex PCR method has been developed for the race-specific detection of Xanthomonas oryzae pv. oryzae (Xoo), the bacterial

blight (BB) pathogen of www.selleckchem.com/products/MS-275.html rice. For this, three primer sets were designed: for specific Torin 1 mw internal regions of two genes (hpaA and XorII very-short-patch-repair endonuclease) and for a genomic locus derived from an amplified fragment length polymorphism (AFLP) fragment specific for the K3 and K5 races.

The sizes of the PCR products when using XOOF/XOOR, XRMF/XRMR and XAF3F/XAF3R primer pairs were 327, 427 bp and 1 kb, respectively, when the assay was applied to detect the pathogen in solution and lesion exudates, and as a template. Amplicons were obtained without the need for any prior processing (e.g. DNA preparation from infected leaf or bacterial cell isolation from the lesion). Furthermore, Celecoxib the pathogen could be quickly detected in the asymptomatic rice leaf 3 days after inoculation and at a distance of 6 cm from the lesion site. This PCR-based simple and rapid assay will be a useful method for the detection and identification of Xoo as well as for disease forecasting in paddy fields. “
“Barley yellow dwarf virus (BYDVs) is an emerging threat for wheat and may

seriously threaten its production, especially as climate change may result in increased infestation by aphids, the insect vectors of the virus. To assess the possibility of using pathogen-derived resistance against the virus, the genetic diversity of BYDVs originating from different wheat-growing areas of Pakistan where its incidence has been higher was investigated. Wheat samples with suspected symptoms of BYDVs were screened for the presence of Barley yellow dwarf and Cereal yellow dwarf viruses (B/CYDVs) subgroup 1 (Barley yellow dwarf virus-PAV, BYDV-MAV, BYDV-SGV) and subgroup II (BYDV-RPV, CYDV-RPV, BYDV-GPV) by PCR using basic multiplex oligonucleotides designed on coat protein (CP) of the virus. Of 37 samples tested, 13 were positive for BYDV subgroup I and only one sample was positive for BYDV subgroup II. Samples positive for subgroup I were further tested by PCR, and results showed that 10 samples were positive for BYDV-PAV and three for BYDV-MAV. DNA sequences of CP region of nine isolates (BYDV-PAV) were determined and compared with available sequences in databases.

Some phytotoxicity was observed at 10 mm. Exogenous application of benzothiadiazole in the range 1–10 mm provided locally a 30–40% reduction in infection frequency. At least 5 mm was needed to reduce rust infection systemically in first upper leaf, and 10 mm in upper ones. Exogenous application of dl-3-amino-n-butyric acid (BABA) provided locally a 45–58% reduction in infection frequency, while systemically a 33–58 and 49–58% reduction of rust symptoms was achieved on leaves at second and third nodes respectively. BABA application was not associated with symptoms of phytotoxicity. “
“A triplex PCR method has been developed for the race-specific detection of Xanthomonas oryzae pv. oryzae (Xoo), the bacterial

blight (BB) pathogen of Ivacaftor manufacturer rice. For this, three primer sets were designed: for specific selleck kinase inhibitor internal regions of two genes (hpaA and XorII very-short-patch-repair endonuclease) and for a genomic locus derived from an amplified fragment length polymorphism (AFLP) fragment specific for the K3 and K5 races.

The sizes of the PCR products when using XOOF/XOOR, XRMF/XRMR and XAF3F/XAF3R primer pairs were 327, 427 bp and 1 kb, respectively, when the assay was applied to detect the pathogen in solution and lesion exudates, and as a template. Amplicons were obtained without the need for any prior processing (e.g. DNA preparation from infected leaf or bacterial cell isolation from the lesion). Furthermore, RVX-208 the pathogen could be quickly detected in the asymptomatic rice leaf 3 days after inoculation and at a distance of 6 cm from the lesion site. This PCR-based simple and rapid assay will be a useful method for the detection and identification of Xoo as well as for disease forecasting in paddy fields. “
“Barley yellow dwarf virus (BYDVs) is an emerging threat for wheat and may

seriously threaten its production, especially as climate change may result in increased infestation by aphids, the insect vectors of the virus. To assess the possibility of using pathogen-derived resistance against the virus, the genetic diversity of BYDVs originating from different wheat-growing areas of Pakistan where its incidence has been higher was investigated. Wheat samples with suspected symptoms of BYDVs were screened for the presence of Barley yellow dwarf and Cereal yellow dwarf viruses (B/CYDVs) subgroup 1 (Barley yellow dwarf virus-PAV, BYDV-MAV, BYDV-SGV) and subgroup II (BYDV-RPV, CYDV-RPV, BYDV-GPV) by PCR using basic multiplex oligonucleotides designed on coat protein (CP) of the virus. Of 37 samples tested, 13 were positive for BYDV subgroup I and only one sample was positive for BYDV subgroup II. Samples positive for subgroup I were further tested by PCR, and results showed that 10 samples were positive for BYDV-PAV and three for BYDV-MAV. DNA sequences of CP region of nine isolates (BYDV-PAV) were determined and compared with available sequences in databases.

27–29 The transcriptional regulation of HO-1 gene by oxidants is suggestive

of HO-1′s potential role as a form of cellular defence against oxidative stress. Also, under falling concentrations of intracellular anti-oxidants such as glutathione, the potential of oxidants to induce the HO-1 gene is amplified.27–29 This upregulation of HO-1 is thought to be a protective response to stress, for example caused by ischemia, to counter the deleterious effects of heme (and more particularly, release of Fe2+), which is known to promote lipid peroxidation and free radical formation. Of note, the main source of extracellular heme is hemoglobin, and red blood cells (RBCs) are highly susceptible to oxidative stress.30 During IR injury, RBCs become deformed and aggregate, thereby increasing blood viscosity Vorinostat cell line and flow resistance. When RBC lysis occurs, newly released free heme further

exacerbates free radical generation. Biliverdin is the bile pigment produced as a result of heme degradation by HO; it is then reduced to bilirubin. The bilirubin formed is normally processed for elimination by hepatic conjugation and biliary excretion. However, by scavenging various oxygen free radicals, both biliverdin and bilirubin can act as endogenous anti-oxidants that protect cells from oxidative injury (Fig. 1).28,29 In addition, biliverdin can modulate leukocyte infiltration by altering adhesion molecule expression on sinusoidal endothelial cells (SECs), and it can inhibit complement in vitro. CO, released directly from heme may act as a regulatory molecule in varying cellular contexts. Like nitric oxide (NO), CO can activate soluble guanylate Stem Cell Compound high throughput screening cyclase (sGC) leading to smooth muscle relaxation and endothelial vasodilation (Fig. 1).31 Levetiracetam CO also allows microcirculatory blood flow to be maintained by inhibiting the vasoconstriction

that otherwise occurs during reperfusion. The activation of the cyclic GMP pathway also provides CO with the ability to inhibit platelet aggregation, thereby ameliorating the complications of microvascular thrombosis associated with IR injury.31,32 Other CO related cytoprotective mechanisms against hepatic IR include suppression of inducible NO synthase (iNOS), downregulation of stress activated protein kinases (SAPKs), dampening of pro-inflammatory cytokine production and inhibition of apoptosis in SECs.32,33 Interestingly, HO-1 over-expression exerts hepatoprotective effects in a number of liver IR injury transplant models. HO-1 induction by pharmacological means (e.g. hemin, cobalt protoporphyrin) preserves organ function and improves liver graft survival.32–34 Orthotopic liver transplants in animals over-expressing HO-1 (primarily by macrophages) exhibit less inflammatory infiltrate into portal areas and reduced iNOS expression. Further, anti-apoptotic Bcl-2 is induced while caspase-3 expression is significantly diminished.

13 The high rate of emergence of the protease resistant variant, R155K, in genotype 1a–infected, but not in genotype 1b–infected, patients IDH inhibitor drugs has also been described previously with this class of agent and is reflective of single-nucleotide change required for the development of resistance in genotype 1a patients, but two-nucleotide changes in the majority of genotype 1b patients. 27 It is of note that single-nucleotide change is required for both mutations at NS3 R155 and D168 in genotype

1a patients; however, a mutation at only R155, and not D168, was identified in genotype 1a patients by population sequencing. The R155 nucleotide sequence may be more susceptible to change than D168, or the R155K may be more fit than mutations at D168 in this genotype. Mutations at D168 were commonly selected in genotype

1b–infected patients, consistent with genotype 1b replicon data. The Y448H mutation observed with BTK inhibitor molecular weight tegobuvir has been observed frequently in monotherapy studies and is consistent with in vitro mutational data, indicating the tegobuvir interaction likely involves the β-hairpin in the thumb subdomain of the NS5B polymerase. 20 In the present study, 7 of 8 genotype 1a patients developed dual-class resistance: R155K against the NS3 protease inhibitor and Y448H for the NS5B polymerase inhibitor. However, with the addition of RBV, the incidence of resistance was significantly reduced, with none of genotype 1a patients (n = 3) exhibiting drug-resistant variants. Though RBV has been shown to have modest antiviral activity, 28 its ability to significantly reduce the development of resistance highlights a distinct mechanism of action. This may indicate

a broader mutational effect of RBV on viral fitness, which renders a proportion of virus noninfectious, regardless of oral antiviral-resistance mutations. Although similar trials have been reported on, 29 the present study is the first report of an IFN-free NS5B polymerase/NS3 protease combination both with and without RBV, thus allowing for a prospective evaluation Montelukast Sodium of the contribution of RBV to the antiviral effect of the regimen. The emergence of various classes of DAAs for treating chronic HCV infection has enabled an evaluation of multiple combination approaches either with or without Peg-IFN and RBV. 19, 30, 31 Specifically, the strategy of quadruple therapy with a non-nucleoside analog, a protease inhibitor, and Peg-IFN and RBV has been supported by results from a recently reported study, in which the non-nucleoside NS5B polymerase inhibitor, VX-222, telaprevir, and peg-IFN/RBV resulted in RVR in 51 of 59 (86%) of treatment-naïve patients, 19 which is higher than those reported with telaprevir and Peg-IFN/RBV. 6, 9 In this study, 100% of patients receiving quadruple therapy achieved RVR at week 4, and a high proportion of patients (71%) had HCV RNA below 25 IU/mL at week 2.

4 ± 7.7). At week 1 there was significant PI3K inhibitor decrease (p < 0.05) in LSM (61 ± 14 vs 54 ± 11 kPa), MELD score (22 ± 5 vs 19 ± 5), DF score (60 ± 19 vs 54 ± 22) but not in CTP score (9 ± 1 vs 9 ± 2, p = 0.5) in patients who were discharged. However there was no such difference in non survivors with regards to LSM, DF score, MELD and CTP score though there was significant fall in ALT and AST levels. At week 1 rate of change of ΔLSM (0.737, p = 0.008), ΔMELD (0.755, p = 0.004) and ΔDF score (0.67, p = 0.05) could predict mortality while ΔCTP score (0.559, p = 0.5) could not. A decrease of 17.5% ΔLSM could predict discharge with a sensitivity of 76% and specificity

of 80%, Δ MELD of 8.7% had sensitivity of 81% and specificity of 73% while ΔDF of 7% had sensitivity of 73% and specificity of 67% only. Patients who had both (17.5%

ΔLSM and 8.7% Δ MELD decrease) had specificity of 100% for discharge from hospital. Conclusion: The present study indicates that the role of LSM in patients with alcoholic hepatitis, at admission, first week, and first week change in LSM for predicting in-hospital mortality. Key Word(s): 1. Liver stiffness; 2. Alcoholic hepatitis; Presenting Author: CHANG ZHENG LI Additional Authors: QING SHAN LI, REN XIU JIANG Corresponding Author: CHANG ZHENG LI Affiliations: Chinese Second Artillery General Hospital Objective: Enhanced nutrition Selleckchem Cisplatin has been approved as an additional method of improving survival and quality of life for liver cirrhosis patients in recent years. The importance of enhanced nutrition may be more significant in patients with esophageal varices, who cares more on food and usually needs endoscopic therapy.

The aim of the present study was to investigate the effect of enhanced nutrition on patients of liver cirrhosis and esophageal varices receiving endoscopic therapy. Methods: Altogether 50 cases of liver cirrhosis and esophageal varices receiving endoscopic therapy were divided into 25 cases see more of enhanced nutrition group and 25 cases of control group. Cases in control group received routine medical and endoscopic therapy per week. Cases in enhanced nutrition group received additional liver nutritional elements 15 g, bid. Difference in transformation of esophageal varices was compared between the 2 groups. Results: Rate of ulcer at injection point was lower in enhanced nutrition group comparing to control group (16/25 vs. 23/25, p = 0.037). Minimal bleeding under endoscopy was found in only 1 cases in enhanced nutrition group, which was lower than 7 cases in control group (p = 0.049). Averagely 3.8 sessions of endoscopic treatment were needed for eradication of varices in enhanced nutrition group, which was lower than 4.1 sessions in control group (p = 0.044). Conclusion: Enhanced nutrition therapy promotes recovery of injury and accelerates occlusion of varices after endoscopic therapy for patients of liver cirrhosis and esophageal varices. Key Word(s): 1. enhanced nutrition; 2. liver cirrhosis; 3.

Chaetocin decreased intracellular ATP levels under both normoxic and hypoxic conditions (Supporting Information Fig. 4B). In addition, it attenuated the productions of pyruvate and lactate during hypoxia (Supporting Information Fig. 4C,D). These results suggest that chaetocin blocks glycolytic ATP production due to HIF-1α suppression. We also confirmed that chaetocins obtained from three different sources have similar effects on HIF-1 activity and HIF-1α expression (Supporting Information Fig. 5A,B). We next studied the mechanism

Sorafenib by which chaetocin down-regulates HIF-1α. We first examined whether Suv39H1, oxidative stress, or thioredoxin reductase-1 is involved in HIF-1α suppression.12-14 However, HIF-1α expression and the chaetocin

effect occurred regardless of these factors (Fig. 4A-C). A novel mechanism might underlie HIF-1α suppression by chaetocin and, thus, we investigated the mechanism Sirolimus stepwise. Initially, we examined if chaetocin destabilizes HIF-1α protein. As a consequence, the oxygen-dependent degradation of HIF-1α was not altered by chaetocin (Fig. 4D). Even after HIF-1α had been oxygen-independently stabilized by MG132 (proteasome inhibitor) or desferrioxamine (prolyl-hydroxylase domain protein [PHD] inhibitor), chaetocin suppressed HIF-1α (Fig. 4E, Supporting Information Fig. 6A). Given that pVHL and p53 facilitate HIF-1α degradation,15 we checked the effect of chaetocin in VHL-null RCC4 and in p53-null HCT116, but these efforts were in vain (Supporting Information Fig. 6B). We next checked the synthesis of HIF-1α protein in the presence of MG132 and found that it was attenuated

by chaetocin (Fig. 4F). Because the PI3K-AKT-mTOR (mammalian target of rapamycin) pathway determines the translation Tolmetin of HIF-1α,16 we examined the effect of chaetocin on the pathway, but AKT and mTOR were not inactivated by chaetocin (Supporting Information Fig. 6C). These results hinted that chaetocin suppresses HIF-1α at the pretranslational level. In human hepatoma cells, HIF-1α mRNA was down-regulated by chaetocin at the concentrations which suppressed HIF-1α (Fig. 5A) as early as 4 hours after treatment (Fig. 5B). However, HIF-1α mRNA was not destabilized by chaetocin (Fig. 5C). Next, we investigated chromatin state at the promoter region of the HIF1A gene using chromatin-immunoprecipitation. The proximal promoter was predominantly associated with euchromatic histone H3 (methyl-K4 and acetyl-K9), but not with heterochromatic histone H3 (methyl-K9). Also, the promoter was targeted by transcription factors STAT3 and nuclear factor kappaB (NF-κB) and by RNA polymerase II (Fig. 5D).17, 18 This indicates that HIF-1α is actively transcribed. However, chaetocin did not affect the chromatin state, suggesting that chaetocin does not control the transcription of HIF-1α.

6% of those identified as having CM by ICHD-2R-MO criteria also met S-L TM ± MO and S-L TM-MO criteria for TM. Specificity was more variable. Of those identified as not having CM by ICHD-3-MO = ICHD-2R, 97.4% did not meet criteria for TM by SL TM-MO, and 34.5% did not meet S-L TM ± MO criteria. These differences in specificity arise from differences in the way the S-L case definitions treat medication overuse. Level of agreement with ICHD-3-MO = ICHD-2R was highest for S-L TM-MO (Cohen’s kappa 0.95) because both sets of criteria exclude medication

overuse. When ICHD-3-MO = ICHD-2R was considered the gold standard, PPV was variable and ranged between 33.2% and 92.7%. The probability was learn more high (92.7%) that those with SL TM-MO would be diagnosed as having CM when using

the ICHD-3-MO = ICHD-2R criteria and relatively low (33.2%) that those meeting criteria for S-L TM ± MO would be diagnosed as CM when using the ICHD-3-MO = ICHD-2R. NPV was far less variable. The probability was high (99.6-99.9%) that those not meeting criteria for S-L TM-MO or S-L TM ± MO would not be diagnosed as having CM when buy Idasanutlin using the ICHD-3-MO = ICHD-2R criteria. When S-L TM was considered the gold standard, 33.2% of those identified as having TM by S-L TM ± MO also met criteria for CM by ICHD-3-MO = ICHD-2R and 94.5% by ICHD-3 ± MO. Specificity ranged from 99.6% to 100.0%. Of those not identified as having TM by S-L TM criteria, the majority did not meet criteria for ICHD-3-MO = ICHD-2R

or ICHD-3β ± MO. Level of agreement with S-L TM was highest for ICHD-3β ± MO (Cohen’s kappa 0.90) and lowest for ICHD-3-MO = ICHD-2R (Cohen’s kappa 0.20). When S-L TM was considered the gold standard, PPV ranged from 99.6% to 100.0%. Therefore, probability was extremely high that those with ICHD-3-MO = ICHD-2R, ICHD-3 ± MO, and S-L TM-MO would Tolmetin be diagnosed as having TM when using the S-L TM criteria. NPV ranged between 34.5% and 86.4%. The ICHD-3-MO = ICHD-2R criteria for CM continue to undergo field testing. Considered in aggregate, results of field tests available to date suggest that the ICHD-3-MO = ICHD-2R criteria for CM are an improvement upon the ICHD-2 criteria with respect to applicability in both clinical practice and clinical trials. Further, the ICHD-2R criteria, now the ICHD-3 criteria, which includes both those with and without medication overuse, agree with the S-L criteria for TM. The ICHD-3β criteria for CM (Table 2) constitute an advance over older diagnostic approaches because they allow acute medication overuse as defined by MOH criteria and they allow both migraine with and without aura,[18, 44] but areas for improvement remain. The ICHD-3β criteria are difficult to operationalize in clinical practice.

Furthermore, increased risk of breast cancer with PBC was found in only three studies,11, 12, 26 all of which were conducted before 1990. These results further quantitatively confirmed the conclusion by Piscaglia and Sagrini,8 who suggested that the incidence of breast cancer was not increased in PBC patients and a higher reported incidence may be attributed to immunosuppressive agents, which were used

commonly before 1990. Moreover, the present meta-analysis also did not show any significant association between PBC and several other site-specific malignancies including colon cancer, rectum cancer, colorectal cancer, lung this website cancer, kidney cancer, esophagus cancer, uterus cancer, cervical cancer, prostate cancer, bladder cancer, thyroid cancer, skin melanoma, skin nonmelanoma

malignancy, Hodgkin disease, and non-Hodgkin lymphoma. However, the conclusion should be addressed with caution, since subgroup meta-analysis could not be performed for these malignancies due to too small number of available studies. The present study has some limitations that should be addressed. First, the study included a wide variety of articles that looked at risks of KU-57788 supplier malignancy in PBC. Therefore, we had to acknowledge that the specific differences between those articles which could account for different results might be a potential source of bias. Second, we could not include some studies that failed to report data with which relative risk of some cancers could be calculated. These unidentified studies may reduce the power of our analysis, but were unlikely to bias its results. Third, the impact of confounding inherent in the included studies can not be completely Dapagliflozin excluded, which might bias the results either toward overestimation or underestimation of risk estimates. Although subgroup analyses

with some known confounders such as age, sex, region, case ascertainment, and type of effect size were performed for overall cancer, HCC and breast cancer risks, other confounders cannot be excluded as a potential explanation for the observed findings. Furthermore, for other cancer risks, subgroup analyses could not be performed due to the small number of studies. Fourth, as described in the previous study, it is impossible to completely exclude potential publication bias because small studies with null results tend not to be published,36 even though no significant publication bias was found by funnel plot analysis and formal statistical tests. Finally, data regarding PBC and risks of the majority of malignancies were extremely sparse, limiting our ability to draw firm conclusions. In conclusion, the present systematic review and meta-analysis demonstrated that PBC is significantly associated with increased risk of overall malignancy, especially with HCC.

Furthermore, increased risk of breast cancer with PBC was found in only three studies,11, 12, 26 all of which were conducted before 1990. These results further quantitatively confirmed the conclusion by Piscaglia and Sagrini,8 who suggested that the incidence of breast cancer was not increased in PBC patients and a higher reported incidence may be attributed to immunosuppressive agents, which were used

commonly before 1990. Moreover, the present meta-analysis also did not show any significant association between PBC and several other site-specific malignancies including colon cancer, rectum cancer, colorectal cancer, lung www.selleckchem.com/products/MLN-2238.html cancer, kidney cancer, esophagus cancer, uterus cancer, cervical cancer, prostate cancer, bladder cancer, thyroid cancer, skin melanoma, skin nonmelanoma

malignancy, Hodgkin disease, and non-Hodgkin lymphoma. However, the conclusion should be addressed with caution, since subgroup meta-analysis could not be performed for these malignancies due to too small number of available studies. The present study has some limitations that should be addressed. First, the study included a wide variety of articles that looked at risks of Selleckchem AZD9668 malignancy in PBC. Therefore, we had to acknowledge that the specific differences between those articles which could account for different results might be a potential source of bias. Second, we could not include some studies that failed to report data with which relative risk of some cancers could be calculated. These unidentified studies may reduce the power of our analysis, but were unlikely to bias its results. Third, the impact of confounding inherent in the included studies can not be completely Y-27632 supplier excluded, which might bias the results either toward overestimation or underestimation of risk estimates. Although subgroup analyses

with some known confounders such as age, sex, region, case ascertainment, and type of effect size were performed for overall cancer, HCC and breast cancer risks, other confounders cannot be excluded as a potential explanation for the observed findings. Furthermore, for other cancer risks, subgroup analyses could not be performed due to the small number of studies. Fourth, as described in the previous study, it is impossible to completely exclude potential publication bias because small studies with null results tend not to be published,36 even though no significant publication bias was found by funnel plot analysis and formal statistical tests. Finally, data regarding PBC and risks of the majority of malignancies were extremely sparse, limiting our ability to draw firm conclusions. In conclusion, the present systematic review and meta-analysis demonstrated that PBC is significantly associated with increased risk of overall malignancy, especially with HCC.

IBS and FD were the

most frequent combinations in overlapping FGID. Most cases of FD are possibly parts of functional bowel disorders. “
“Department of Endocrinology, People’s Hospital of Gansu Province Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Jinan, China Elevated thyroid-stimulating hormone (TSH) and hypercholesterolemia commonly coexist, as typically seen in hypothyroidism, but there is no known mechanism directly linking the two. Here, we demonstrated that in liver cells, TSH promoted the expression of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR), a rate-limiting enzyme in cholesterol synthesis, by acting on the TSH receptor in hepatocyte membranes and stimulating the cyclic adenosine monophosphate / protein kinase A / cyclic adenosine monophosphate–responsive element binding protein (cAMP/PKA/CREB) signaling system. In thyroidectomized

rats, the production of endogenous thyroid CP673451 hormone was eliminated and endogenous TSH was suppressed through pituitary suppression with constant administration of exogenous thyroid hormone, and hepatic HMGCR expression was increased by administration of exogenous TSH. These results suggested that TSH could up-regulate hepatic HMGCR expression, which indicated a potential mechanism see more for hypercholesterolemia involving direct action of TSH on the liver. (HEPATOLOGY 2010) Hypothyroidism is well known to be associated with elevated serum TC, which can result in hypercholesterolemia.1, 2 The underlying mechanism is widely thought to be TH deficiency. However, elevation of serum TC has also been observed in patients Thiamine-diphosphate kinase with subclinical hypothyroidism (SCH), in which TSH is elevated but TH stays within its normal range.1, 3, 4 Thus, the development of hypercholesterolemia in SCH cannot be explained only by the role of TH. This raises the question of whether elevated TSH also plays a role in the development of hypercholesterolemia in hypothyroidism. Several clinical studies in recent years addressed this issue

and showed a correlation in hypothyroidism between high serum cholesterol and high TSH levels, the latter being usually used as an indication of the severity of the hypothyroidism.5-7 In these studies, however, it was impossible to delineate a direct role of TSH as abnormal TH level (usually deficiency) was usually a coexisting factor. Thus, a molecular mechanism by which TSH might affect cholesterol level has never been established. The TSHR is expressed in thyroid cells and plays a central role in up-regulating its function, including the synthesis of TH. Increasing data showed that the TSHR was also expressed in many nonthyroid tissues, and it might actually play a physiological role in these tissues.8, 9 We recently demonstrated that TSHR was expressed in hepatocytes and that stimulation of cultured liver cells with TSH increased the production of cAMP.