Retroperitoneal and compartmental bleeding (retropharingeal, exte

Retroperitoneal and compartmental bleeding (retropharingeal, extensive musle haematomata with compression of nervous and vascular structure) are challenging and often misdiagnosed. Haemarthroses are less frequent than in congenital haemophilia: in the Italian series, 7.3% of 96 patients at presentation and 16.1% of 31 patients at relapse [3]. Intracranial bleeding is rare (2% in the Italian survey), but catastophic. Severe bleeding can ensue surgical interventions because of an overlooked prolonged

activated partial thromboplastin time (APTT). In the Italian survey, the preoperative APTT, when carried out, was always prolonged [3]. Anaemia is frequent; its severity is related to the severity of bleeding. PXD101 supplier The diagnosis of acquired haemophilia is easily

suspected when the APTT is prolonged in the proper clinical setting. A prolonged APTT with normal prothrombin time should always arouse suspicion. The APTT is reported as the ratio of patient/normal plasma. The subsequent step is to carry out the mixing test. The APTT is carried out in a mixure (1:1) of normal and patient’s plasma, after incubation for 2 h at 37°C (the interaction inhibitor-FVIII:C is temperature- and time-dependent) with no correction. Further testing of FVIII:C and the inhibitor titre is available only in specialized laboratories. A prolonged APTT is also found in the lupus anticoagulant (LA), the anti phospholipid 上海皓元医药股份有限公司 (APA)

syndromes and during unfractionated heparin PD-0332991 chemical structure therapy. The LA and APA syndromes are acquired thrombophilic factors and heparin treatment is easily ruled out. The objectives of the management are control of bleeding and suppression of inhibitor. The sudden onset of clinically significant bleeding with a prolonged APTT, suggesting acquired haemophilia, requires urgent consultation and transfer of the patient to the reference centre. Control of the acute bleeding is the priority because of the high early mortality. The inhibitor titre and the FVIII:C levels are not correlated with the clinical picture; therefore, being at variance with patients with congenital haemophilia, they are not valuable in guiding therapy [1]. The most significant criteria are clinical: the site and the intensity of bleeding. First-line haemostatic treatment includes recombinant activated FVII recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrate (APCC). The published studies are retrospective and include a limited number of patients with different primary clinical conditions. No prospective randomized trial comparing their efficacy has been carried out to date as such a study is not practicable. Neither one is effective in every patient. The dosage of these agents is derived largely from the experience of the treatment of congenital haemophilia with inhibitor. No information on duration of treatment is available.

As noted before, “conventional” medicine is a moving target, as i

As noted before, “conventional” medicine is a moving target, as it should be. Finally, there are those patients who literally have tried everything and come to you in desperation.

If “everything” does, in fact, include adequate trials of the usual approaches, broaching the possibility of nontraditional medicine can provide a service to these desperate patients that will have the “blessing” of a recognized medical authority and give them “permission” to move outside conventional medicine. For many patients, this is important. DAPT The above approach to CAM might be considered the “passive” approach, one in which these interventions are viewed as second or third line, behind more conventional medicine approaches. However,

there is a more “proactive” relationship that is the basis of integrative medicine. In this view, the decision to move toward nonconventional modalities is significantly different. Some Western-trained physicians have become interested in select CAMs and have sought out additional education and training in those systems. Among the most common are classical Chinese medicine techniques, including acupuncture, pulses, herbs and moxabustion, and Ayurveda with diagnosis based on each patient’s balance of doshas. Having a referral base that includes some of these practitioners is Lumacaftor in vivo very helpful. Integrating these approaches into one’s own practice can be even more helpful but requires considerable commitment in time and refocusing of the practice. A less intensive, but often equally satisfying approach is to become familiar with select modalities, such as certain vitamins and supplements or other treatment modalities for which your level of comfort is adequate and integrating those activities into your initial treatment plan. There are a variety of supplements, including

butterbur, riboflavin, magnesium, and coenzyme Q10 about medchemexpress which there is considerable familiarity and evidence within the medical literature. These vitamins and supplements are still largely regarded as CAM but are slowly moving into the realm of conventional medicine. While most of us discuss acute, preventive, and behavioral strategies with every patient, some physicians have begun to include a “fourth estate” in these discussions, having to do with other approaches to managing headaches. This may take the form of “down the road” options or occupy an ongoing place in the treatment plan. But by establishing CAM as part of the treatment plan, you open the door, often improving communication and broadening treatment options. Some patients have bought into the same view that many physicians have, namely, if it doesn’t require a prescription and have a black box warning, it isn’t a real medicine. These patients, as the physicians who feel the same way, will miss real opportunities to improve their situation.

includes functional

training, adaptations, and

includes functional

training, adaptations, and Luminespib adequate analgesia as suggested in Table 1–5. (Level 2) [ [15, 45] ] COX-2 inhibitors have a greater role in this situation. (Level 2) [ [46, 47] ] Other NSAIDs should be avoided. (Level 2) [ [48] ] When pain is disabling, orthopedic surgery may be indicated. (Level 5) [ [49] ] Patients with persisting pain should be referred to a specialized pain management team. Surgery may be required for hemophilia-related complications or unrelated diseases. The following issues are of prime importance when performing surgery on persons with hemophilia: Surgery for patients with hemophilia will require additional planning and interaction with the healthcare team than what is required for other patients. A hemophilia patient

requiring surgery is best managed at or in consultation with a comprehensive hemophilia treatment center. (Level 3) [ [50, 51] ] The anesthesiologist should have experience treating patients with bleeding disorders. Adequate laboratory support is required for reliable monitoring of clotting factor level and inhibitor testing. Preoperative assessment should include inhibitor screening and inhibitor assay, particularly if the recovery of the replaced factor is significantly less than expected. (Level 4) [ [52, Ferrostatin-1 order 53] ] Surgery should be scheduled early in the week and early in the day for optimal laboratory and blood bank support, if needed. Adequate quantities of clotting factor concentrates should be available for the surgery itself and to maintain adequate coverage postoperatively for the length of time required MCE for healing and/or rehabilitation. If clotting factor concentrates are not available, adequate blood bank support for plasma components is needed. The dosage and duration of clotting factor concentrate coverage depend on the type of surgery performed (Tables 7-1, 7-2). Effectiveness of

hemostasis for surgical procedures may be judged as per criteria defined by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (Table 1–6). Patients with mild hemophilia A, as well as patients receiving intensive factor replacement for the first time, are at particular risk of inhibitor development and should be re-screened 4–12 weeks postoperatively. (Level 4) [ [54] ] Careful monitoring for inihibitors is also advisable in patients with non-severe hemophilia A receiving continuous infusion after surgery [55]. Infusion of factor concentrates/hemostatic agents is necessary before invasive diagnostic procedures such as lumbar puncture, arterial blood gas determination, or any endoscopy with biopsy. Intra-operative and postoperative blood loss similar (within 10%) to the non-hemophilic patient.

(HEPATOLOGY 2011;) “
“The aim of this study was to elucidate

(HEPATOLOGY 2011;) “
“The aim of this study was to elucidate the risk of subsequent biliary malignancy in patients undergoing cyst excision for congenital choledochal cysts. A retrospective analysis of 94 patients who had undergone cyst excision for congenital choledochal cysts was conducted. The median age at the time

of cyst excision and median follow-up time after cyst excision were 7 years and 181 months, respectively. Biliary tract cancer developed in four patients at 13, 15, 23, and 32 years after cyst excision. The cumulative incidences of biliary tract cancer at 15, 20, and 25 years after cyst excision were 1.6%, 3.9%, and 11.3%, respectively. The sites of biliary tract cancer were the intrahepatic (n = 2), hilar (n = 1), and intrapancreatic (n = 1) Ulixertinib bile ducts. Of the four patients with biliary tract cancer after cyst excision, three patients underwent surgical resection and one patient received chemo-radiotherapy. The overall cumulative survival rates after treatment in the four patients with biliary tract cancer were 50% at 2 years and 25% at 3 years, with a median survival time of 15 months. The risk of subsequent biliary malignancy in patients undergoing cyst excision for congenital choledochal cysts seems to be relatively high in the

Idasanutlin research buy long-term. The risk of biliary malignancy in the remnant bile duct increases more than 15 years after cyst excision. Despite an aggressive treatment approach for this condition, subsequent biliary malignancy following cyst excision for congenital choledochal cysts shows an unfavorable outcome. “
“We aimed to determine whether pretreatment serum interferon-γ-inducible protein (IP)-10 concentration can predict response to telaprevir (TVR)-based triple therapy in patients with genotype 1 chronic hepatitis C (CHC), and to examine the effects of IP-10 concentration on liver histology. Baseline IP-10 concentrations were measured in 97 patients with genotype 1 CHC treated with TVR-based

triple therapy, and the associations between baseline IP-10 and treatment outcome were assessed MCE公司 by univariate and multivariate analyses. Associations between baseline serum IP-10 concentration and laboratory data and liver histological findings were also investigated. Median IP-10 concentration in these patients was 461.83 pg/mL (range, 151.35–4297.62). Multivariate analysis showed that IL28B genotype (P = 0.025) and IP-10 level (P = 0.004) were factors significantly predictive of rapid virological response (RVR), whereas in pretreatment factors only, IL28B genotype (P = 0.001) and liver fibrosis (P = 0.035) were independent predictors of sustained virological response. Using a cut-off IP-10 concentration of 460 pg/mL, patients with IL28B risk allele and low IP-10 had a significantly higher RVR rate than those with high IP-10 (P = 0.005). IP-10 concentration was significantly correlated with liver fibrosis (P = 0.001) and inflammation activity (P = 0.

001) and virologic resistance (P < 0001) In addition, the decli

001) and virologic resistance (P < 0.001). In addition, the decline of serum hepatitis B surface antigen levels, hepatocellular carcinoma development, mortality, disease progression, and the change of renal function were similar. Cox regression analysis showed that pretreatment low albumin level and high model for end-stage liver disease scores were risk factors for disease progression. These results indicated that although LdT and ETV are similar in clinical

outcomes for patients with HBV-related compensated cirrhosis, LdT still had lower HBV undetectablility and higher resistant rate after 2 years treatment, which was a challenge for being as first-line therapy in these patients buy Palbociclib who need lifelong therapy. “
“More effective and better-tolerated therapies are needed for chronic hepatitis C virus (HCV) infection. Among the direct-acting anti-HCV agents in development is the nonstructural 5B protein (NS5B polymerase) non-nucleoside inhibitor filibuvir. We investigated the antiviral activity, pharmacokinetics, safety, and tolerability of multiple doses of filibuvir in treatment-naive and treatment-experienced patients who were chronically infected with HCV genotype 1 in two phase 1b clinical studies (study 1 was a randomized, placebo-controlled

dose escalation study and study 2 was a nonrandomized, open-label study). The filibuvir doses evaluated ranged from 200-1400 mg daily, and the duration of dosing ranged from 3-10 MCE selleck chemicals llc days. Genotypic changes in the NS5B nucleotide sequence following short-term filibuvir therapy were also assessed. Filibuvir potently inhibited viral replication in a dose-dependent manner. Mean maximum HCV RNA change from baseline ranged from −0.97 log10 IU/mL with filibuvir given

at 100 mg twice daily to −2.30 log10 IU/mL with filibuvir given at 700 mg twice daily in treatment-naive patients. In treatment-experienced patients, an HCV RNA reduction of 2.20 log10 IU/mL was achieved with filibuvir given at 450 mg twice daily. Filibuvir was well tolerated in both studies. Adverse events were mild or moderate in severity. No discontinuations, serious adverse events, or deaths were reported. NS5B sequencing identified residue 423 as the predominant site of mutation after filibuvir dosing. Conclusion: Filibuvir administration resulted in significant reductions in HCV RNA concentrations at doses that were well tolerated in patients infected with HCV genotype 1. Filibuvir is currently being evaluated in combination with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients. (Hepatology 2011;) Hepatitis C virus (HCV) infection affects approximately 180 million people worldwide1 and is a leading cause of chronic liver disease.2 The current standard of care for chronic HCV infection is a combination of pegylated interferon alfa (pegIFN) and ribavirin (RBV).

T-cell differentiation leads to cells that can be distinguished b

T-cell differentiation leads to cells that can be distinguished by functional assays and their production of characteristic cytokines. This cellular differentiation is commonly viewed as a kind of lineage commitment associated with the expression of master regulators within this process, i.e. the transcription factors T-bet, Gata-3, RorγT, Bcl6, and FoxP3 that drive differentiation of Th1, Th2, Th17, follicular T helper (Tfh), and regulatory Treg cells, respectively. However, Inhibitor Library supplier there is growing evidence for plasticity

in this process, and in the context of Th cell function in chronic infections such as H. pylori, one should keep in mind that subtype populations may not be as committed as generally believed [38]. The generation and maintenance of a T-cell response depends on DC, and it has been a longstanding challenge to decipher whether DCs are present in noninflamed gastric mucosa. Studies in mice had shown that H. pylori-specific responses might be induced more

distally in the gastrointestinal system, in Peyer’s patches, by passing H. pylori, implying that this was a functional consequence of the gastric mucosa lacking DC [39,40]. Several groups have now re-addressed this issue. Bimczok et al. [41] showed that cells with typical DC markers such as MHC selleck chemicals llc II, CD11c, DC-SIGN, and CD206 can be isolated from biopsies taken from both normal and H. pylori-infected patients. The frequency of these cells increased around fivefold in biopsies from infected patients in which DCs also exhibited an activated phenotype and molecules which act as co-stimulatory ligands to T cells, such as CD86, were upregulated. In vitro, these gastric DCs phagocytose and process H. pylori. DCs secreted IL-6, -8, and

-10 as well as triggering expansion of Th1 cells. Presence of DCs in normal human gastric mucosa and their increase in H. pylori colonized mucosa were confirmed by Necchi et al. [42]. It is interesting in this context that Khamri et al. also detected monocyte-derived DCs in inflamed mucosa, and using DCs derived by IL-4 and GM-CSF from blood monocytes, they found that these cells express IL-23 and IL-12, but the former was produced earlier [43]. IL-23 is a positive regulator of Th17 cells, and Kamzi et al. could visualize IL-23 上海皓元 expressing DCs as well as Th17 cell in inflamed gastric mucosa. They also showed that in vitro stimulated CD4+ T cells produce more IL-17 in response to H. pylori exposed DCs, a process mediated by IL-23 and IL-1. Kao et al. reported essentially similar findings when analyzing mice [44]. They showed that bone marrow-derived DCs (which are more accessible) preferentially induced Treg and Th17 cells. Differentiation of these CD4+ subsets requires TGF-β, but Th17 cells also need IL-6 and are further promoted by IL-23 and IL-1. The bias toward Treg cells in the murine system was probably because H.

The Use of probiotics prior to liver transplant should be conside

The Use of probiotics prior to liver transplant should be considered as a part of the transplant protocol. Disclosures: The following people have nothing to disclose: Tarek Sawas, Shadi Al Halabi, Mubarak W. Sayyar, Won Kyoo Cho Several factors have been reported

to influence the survival outcome following liver transplantation. The principal six identified variables that influence outcomes are the transplant center’s experience and outcome statistics, recipient age, donor age, gender, MELD score, and liver disease etiology. The aim of this study was to compare the most recent outcome data from United States liver transplant centers which have performed at least 50 Liver Transplants (LT) per year. Methods/Results: Data were collected from the Scientific Sorafenib supplier Registry buy Seliciclib of Transplant Recipients ( and the data was compared between the liver transplant centers in the US. The parameters assessed included but were not limited to: 3-year graft survival, 3-year patient survival, wait list mortality, composite 3-year mortality. Despite adjusting for all of the main variables, it was apparent that major differences in the three-year patient survival at liver transplant centers in the

US varied widely and ranged from 60-94% with a national average of approximately 79%. Wait list mortality also varied (10 folds) from a value 0.04% at the better performing LT centers to 0.40% in the poorer performing centers. Furthermore, the composite 3-year mortality rate range varied from 17.6- 67.0%. This 上海皓元医药股份有限公司 large variation in 3-year patient survival outcome between US LT centers performing more than 50 LT per year could not be explained after adjusting for the identified predictive variables and was not related to the level of competitiveness between centers or the centers’ access to organs. Importantly, performing < 50 liver transplantation per year was not found to correlate negatively with the 3-year patient survival data. Based upon these data obtained from the SRTR, it can be concluded that: 1) post- transplant survival varies widely between US liver transplant centers; 2) a favorable outcome is not predicted by: a) the

number of liver transplants performed, b) the various patient and donor characteristics examined, c) the MELD score, or d) the availability of organs for the individual transplant center. 3) The practice of substituting less toxic immunosuppressive agents at some centers was positively associated with a better overall 3-year survival outcome. These data suggest that the hospital and transplant team skills are the most important factors that contribute to the marked variation in adjusted post- LT survival between centers. Factors that may reduce this variation between centers in the future potentially consist of: 1) Standardization of the protocols used for the management of pre- and post-LT care. 2) Consideration for the use of less toxic and lower doses of immunosuppression.

The enrollment goals were a total of 1500 patients, including 112

The enrollment goals were a total of 1500 patients, including 1125 adults and 375 children. Patients were enrolled from October 2004 until February 2008 and were followed until September

2009. PLX4032 clinical trial Comprehensive data, including demographics, medical history, symptoms, medication use, diet and exercise habits, and routine laboratory studies were collected on all patients at entry and at annual visits for up to 4 years after enrollment. Interim liver biopsies were obtained during patient study involvement only when indicated for patient care. Study questionnaires administered at enrollment and at selected follow-up visits included AUDIT; Block Food Questionnaire; Skinner Lifetime Drinking History, Physical Activity Questionnaire, Modifiable Activity Questionnaire; and the MOS 36-Item Short-Form Health Survey.

Specimens including whole blood as a source of DNA, and serum and plasma, were collected at selected time points during follow-up for contemporaneous analysis or storage in a central repository. Data collected and included in this analysis were also from patients entering Dabrafenib concentration the NASH CRN adult treatment trial, PIVENS.8, 9 This study was designed to evaluate whether 96 weeks of treatment with either pioglitazone or vitamin E improved histological features of NASH, and the entry criteria were more stringent than for enrollment in the Database observational study. Eligible patients were 18 years or older and had histological evidence of NASH without cirrhosis obtained no more than 6 months before randomization. The PIVENS trial was 上海皓元医药股份有限公司 limited to patients without diabetes or a history of therapy to treat diabetes. Patients were excluded

if they consumed >20 g alcohol/day for females or >30 g/day for males on average, either currently or for a period of more than 3 consecutive months in the 5 years prior to screening. Additional exclusion criteria included any other form of chronic liver disease, the use of any medications thought to cause or affect NAFLD, the use of nonstable doses of lipid-lowering medications, and alanine aminotransferase levels > 300 U/L or a serum creatinine levels ≥ 2.0 mg/dL. Women of childbearing age who were pregnant, unwilling to use effective birth control, or nursing were excluded. At baseline, all PIVENS patients underwent extensive data collection similar to that for the Database observational study, as well as a new liver biopsy if one had not been obtained in the previous 6 months. Routine laboratory studies were performed on fresh samples in Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories at each clinical site according to standard clinical protocols.

79), PT activity (r = 037) and DBil/TBil ratio (r = 050), whi

79), PT activity (r = 0.37) and D.Bil/T.Bil ratio (r = 0.50), while serum VEGF levels were significantly correlated with platelet counts (r = 0.68) and PT activity (r = 0.38). Conclusions:  We consider that serum levels of PDGF-BB and VEGF are

worth investigating as biomarkers for predicting outcomes Paclitaxel order of FHF patients. “
“Initial hepatitis C virus (HCV) RNA reduction was investigated as a potential index for sustained virological response (SVR) in the treatment of interferon (IFN)-β followed by peginterferon plus ribavirin (PEG IFN/RBV). The treatment course was retrospectively analyzed in 64 genotype 1b patients with a HCV RNA level of 5.0 logIU/mL or higher. IFN-β was administrated twice a day for 2 weeks followed by 24 or 48 weeks of PEG IFN/RBV. The serum HCV RNA level was measured by real-time polymerase chain reaction before administration and at 1, 2 and 4 weeks of therapy. By the duration of PEG IFN administration, the SVR rates were 11% (2/18, <19 weeks), 64% (23/36, 20–24 weeks) and 40% (4/10, 25–72 weeks) (P = 0.0011, χ2-test). The SVR rate

was high in patients in whom the HCV RNA level had decreased Bioactive Compound Library by 2.5 logIU/mL or greater at 1 week of IFN-β (29/55 [53%] vs 0/9 [0%], P = 0.0029, χ2-test). Among these patients, the SVR rate was even higher in those with continuous reduction in the first 2 weeks after the switch to PEG IFN/RBV (27/45 [60%] vs 2/10 [20%], P = 0.0048). Age below 65 years, no previous IFN course and good initial HCV RNA reduction were significantly associated with SVR on multivariate analysis, and the SVR rate was 95% (18/19) among these patients. The 2.5 logIU/mL reduction in HCV RNA at 1 week of IFN-β and

the continuous reduction just after the switch to PEG IFN/RBV are important SVR-predictive indices. “
“Acute liver failure (ALF) is an uncommon clinical condition associated with massive liver injury and the development of hepatic encephalopathy in patients with previously normal liver function and architecture. This condition requires early recognition and discussion with or transfer to a unit that can assess for and provide liver transplantation. Supportive and specific therapy may also be appropriate. The most common cause for ALF in the western world is paracetamol medchemexpress (acetaminophen) poisoning, either as a deliberate suicide attempt or after inadvertent ingestion of excessive amounts. A case of paracetamol-induced ALF is discussed in case 1. Non-paracetamol causes of ALF include non-A–E or seronegative hepatitis, acute viral hepatitis, idiosyncratic drug reactions, and pregnancy-associated causes such as acute fatty liver of pregnancy and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets). Less common causes such as Wilson’s disease are worthy of specific mention; Wilson’s disease produces a characteristic clinical picture (discussed in case 2) that may facilitate early recognition and specific therapy with penicillamine.

The regulation of urease activity is central to acid acclimation

The regulation of urease activity is central to acid acclimation. Inactive urease Small molecule library chemical structure apoenzyme, UreA/B, requires nickel for activation. Accessory proteins UreE, F, G, and H are required for nickel insertion into apoenzyme. The ExbB/ExbD/TonB complex transfers energy from the inner to outer membrane, providing the driving force for nickel uptake. Therefore, the aim of this

study was to determine the contribution of ExbD to pH homeostasis. A nonpolar exbD knockout was constructed and survival, growth, urease activity, and membrane potential were determined in comparison with wildtype. Survival of the ΔexbD strain was significantly reduced at pH 3.0. Urease activity as a function of pH and UreI activation was similar to the wildtype strain, showing normal function of the proton-gated urea channel, UreI. The increase in total urease activity over time in acid seen

in the wildtype strain was abolished in the ΔexbD strain, but recovered in the presence of supraphysiologic nickel concentrations, demonstrating that the effect of the ΔexbD mutant is due to loss of a necessary constant supply of nickel. In acid, ΔexbD also decreased its ability to maintain membrane potential and periplasmic buffering in the presence of urea. ExbD is essential for maintenance of periplasmic buffering and membrane potential by transferring energy required for nickel uptake, making it a potential nonantibiotic target for H. pylori MCE eradication. “
“Although check details Helicobacter pylori have been known to induce vascular endothelial

growth factor (VEGF) production in gastric epithelial cells, the precise mechanism for cellular signaling is incompletely understood. In this study, we investigated the role of bacterial virulence factor and host cellular signaling in VEGF production of H. pylori-infected gastric epithelial cells. We evaluated production of VEGF, activation of nuclear factor nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) and hypoxia-inducible factor-1α (HIF-1α) stabilization in gastric epithelial cells infected with H. pylori WT or isogenic mutants deficient in type IV secretion system (T4SS). H. pylori induced VEGF production in gastric epithelial cells via both T4SS-dependent and T4SS-independent pathways, although T4SS-independent pathway seems to be the dominant signaling. The inhibitor assay implicated that activation of NF-κB and MAPKs is dispensable for H. pylori-induced VEGF production in gastric epithelial cells. H. pylori led to HIF-1α stabilization in gastric epithelial cells independently of T4SS, NF-κB, and MAPKs, which was essential for VEGF production in these cells. N-acetyl-cysteine (NAC), a reactive oxygen species (ROS) inhibitor, treatment impaired H. pylori-induced HIF-1α stabilization and VEGF production in gastric epithelial cells. We defined the important role of ROS-HIF-1α axis in VEGF production of H.