OBJECTIVETo study the potential function and mechanism of heme oxygenase-1 (HO-1) in regulating platelet reactivity and arterial thrombosis.

METHODSHO-1-deficient (HO-1(-/-)) mice were generated by gene knock-out technique, and the genotyping of the mice was performed by PCR analysis of tail DNA. Thrombus formation was induced by applying FeCl(3) to the exposed carotid artery, and the occlusion time was monitored for each animal. Western blot and chemical assays were used to detect HO-1 and cGMP levels in platelets. Platelet aggregation induced by ADP was also studied.

RESULTSThe difference between mean occlusion time of wild-type mice [(15.56 +/- 1.25) min, n = 16] and HO-1(-/-) mice [(12.85 +/- 0.55) min, n = 14] was not statistically significant. However, after challenge with hemin, which induces HO-1 expression, mean occlusion time was significantly longer in wild-type mice [(16.25 +/- 1.20) min, n = 15] than in HO-1(-/-) mice [(11.96 +/- 0.98) min, n = 19; P < 0.05]. Hemin administration which induced oxidative stress could markedly elevate HO-1 level and cGMP concentration in platelet, while suppress ADP induced platelet aggregation in wild type mice.

CONCLUSIONUnder conditions that stimulate HO-1 production, platelet-dependent thrombus formation is inhibited by HO-1 through the pathway of cGMP expression. It suggests that enhanced platelet HO-1 expression in response to physiological stress may represent an adaptive response mechanism to down-regulate platelet activation under pro-thrombotic conditions.

Animals ; Blood Platelets ; metabolism ; physiology ; Cyclic GMP ; blood ; Female ; Heme Oxygenase-1 ; blood ; genetics ; physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oxidative Stress ; physiology ; Platelet Aggregation ; Thrombosis ; metabolism ; physiopathology

Despite successful treatment of Parkinson's disease (PD) with a wide variety of symptomatic therapy, the disease continues to progress and drug-resistance symptoms become the predominant factors producing the disability of PD patients. Neuroprotective therapies have been tested, but clinically effective drugs have not been found yet. New insights gained from studies of genetic forms of PD point to the common pathogenic mechanisms that have been suspected in sporadic forms of the disease and may provide new approaches for the future neuroprotective therapies.
Genetics ; Humans ; Parkinson Disease*

BACKGROUND/AIMS: Sleep dysfunction is associated with altered gastrointestinal function and subsequently exacerbations of gastrointestinal problems. We aimed to investigate whether sleep dysfunction would influence anorectal motility as determined by anorectal manometry. The effect of anxiety on anorectal motility was also determined. METHODS: A total of 24 healthy volunteers underwent anorectal manometry. The anorectal parameters included resting and squeeze sphincter pressure, sensory thresholds in response to balloon distension, sphincter length, rectal compliance, and rectoanal inhibitory reflex. Sleep dysfunction was subjectively assessed by using Pittsburgh Sleep Quality Index (PSQI). Anxiety was assessed by the application of the State-Trait Anxiety Inventory questionnaire. RESULTS: There were sixteen subjects without sleep dysfunction (7 women; mean age, 22 years) and eight subjects with sleep dysfunction (2 women; mean age, 22 years). There was no group difference in the volume threshold for rectoanal inhibitory reflux, rectal compliance or sphincter length (P = NS). Anal sphincter pressure did not differ between the groups (P = NS). The rectal sensitivity for different levels of stimulation did not differ between the groups (P = NS). Sleep quality as determined by PSQI correlated with rectal compliance (r = 0.66, P = 0.007). Although there was no differences in any manometric parameters between subjects with and without anxiety, the anxiety score correlated with rectal compliance (r = 0.57, P = 0.003). CONCLUSIONS: Despite a positive association between rectal compliance and the level of subjective sleep or anxiety, sleep dysfunction did not apparently affect most of anorectal function in healthy subjects, nor did anxiety.
Anal Canal ; Anxiety ; Compliance ; Humans ; Manometry ; Reflex ; Sensory Thresholds

No abstract available.
Female ; Mammaplasty* ; Mastodynia* ; Neuroma* ; Superficial Back Muscles*

OBJECTIVESTo investigate the relationship between H. pylori infection, gastric cancer and other gastric diseases through the changes in gastric mucosa and the status of different gastric diseases within 5 years after H. pylori eradication in H. pylori-positive subjects in a high incidence region of gastric cancer.

METHODSOne thousand and six adults were selected from the general population in Yantai, Shandong province, a high incidence region for gastric cancer in China. Gastroscopy and Campylobacter-like organism (CLO) testing were performed on all subjects. Biopsy samples from the gastric antrum and body were obtained for histology and assessment of H. pylori infection. All H. pylori-positive subjects were then randomly divided into two groups: treatment group receiving Omeprazole Amoxicillin Clarythromycin (OAC) triple therapy and placebo as controls. These subjects were endoscopically followed up in the second and fifth year. We compared the endoscopic appearance and histology of the biopsy specimens from the same site obtained at the first and last visits.

RESULTSAll 552 H. pylori-positive subjects were randomly and evenly divided into treatment group or control group. During the five-year follow-up, the numbers of patients who continued to be negative or positive for H. pylori were 161 and 198, respectively. Statistical analysis revealed that: (1) At the initial visit, there were no significant differences in the severity and activity of inflammation, atrophy and intestinal metaplasia between the biopsy specimens from the antrum and body respectively in both groups. (2) The severity and activity of inflammation in both the antrum and body were markedly reduced after H. pylori eradication (P = 0.000). (3) Within five years after H. pylori eradication, intestinal metaplasia in the antrum either regressed or had no progression, while the proportion of intestinal metaplasia in the H. pylori-positive group increased significantly (P = 0.032). (4) After H. pylori eradication, the atrophy in both the antrum and body had no significant regression. The P value was 0.223 and 0.402, respectively.

CONCLUSIONSH. pylori eradication results in remarkable reduction in the severity and activity of chronic gastritis, marked resolution of intestinal metaplasia in the antrum. On the other hand, continuous H. pylori infection leads to progressive aggravation of atrophy and intestinal metaplasia.

Adult ; Aged ; Double-Blind Method ; Follow-Up Studies ; Gastric Mucosa ; pathology ; Gastritis ; etiology ; Helicobacter Infections ; complications ; drug therapy ; pathology ; Helicobacter pylori ; Humans ; Metaplasia ; Middle Aged ; Stomach Neoplasms ; etiology

We present the case of a patient who developed new-onset asymptomatic sinus tachycardia after undergoing treatment for a right ventricular myocardial infarction. Even after excluding heart failure, infection and bleeding, the sinus tachycardia persisted. Computed tomography pulmonary angiography showed multiple bilateral pulmonary emboli. The vital sign abnormality resolved after treatment with an anticoagulant. We postulate that the pulmonary emboli originated from thrombi that were formed in the infarcted and dysfunctional right ventricle. Pulmonary embolism is a very rare complication of right ventricular myocardial infarction, and patients usually present with pleuritic chest pain. Our case highlights that asymptomatic sinus tachycardia could be a presenting feature of pulmonary embolism after the occurrence of a right ventricular myocardial infarction. A high index of suspicion is warranted in order to detect this potentially lethal complication.
Adult ; Echocardiography ; Electrocardiography ; Heart Ventricles ; diagnostic imaging ; Humans ; Male ; Myocardial Infarction ; complications ; diagnosis ; Pulmonary Embolism ; complications ; diagnosis ; Tachycardia, Sinus ; diagnosis ; etiology

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.