A 9 years and 8 months old girl was prescribed procaterol hydrochloride oral solution (procaterol) 25 μg (5 ml) twice daily for cough and asthma. The girl mistakenly took 25 ml of procaterol because her grandmother thought it was 25 μg. After 30 minutes, the girl developed restlessness, shortness of breath, trembling hands, and vomiting. Physical examination showed heart rate 148 beats/min, cardiac auscultation showed arrhythmia, electrocardiogram showed frequent ventricular premature beat, and laboratory tests showed blood potassium 2.5 mmol/L. Procaterol poisoning was considered. Oxygen inhalation, electrocardiographic monitoring, metoprolol tartrate tablets 25 mg orally, and symptomatic and supportive treatments such as coenzyme A, adenosine triphosphate, and potassium chloride, were given immediately. Two hours alater, the child′s restlessness disappeared and shortness of breath was improved; the electrocardiogram reexamination showed no ventricular premature beat. Ten hours later, the heart rate returns to normal. The next day, her blood potassium level returned to normal.

A 9 years and 8 months old girl was prescribed procaterol hydrochloride oral solution (procaterol) 25 μg (5 ml) twice daily for cough and asthma. The girl mistakenly took 25 ml of procaterol because her grandmother thought it was 25 μg. After 30 minutes, the girl developed restlessness, shortness of breath, trembling hands, and vomiting. Physical examination showed heart rate 148 beats/min, cardiac auscultation showed arrhythmia, electrocardiogram showed frequent ventricular premature beat, and laboratory tests showed blood potassium 2.5 mmol/L. Procaterol poisoning was considered. Oxygen inhalation, electrocardiographic monitoring, metoprolol tartrate tablets 25 mg orally, and symptomatic and supportive treatments such as coenzyme A, adenosine triphosphate, and potassium chloride, were given immediately. Two hours alater, the child′s restlessness disappeared and shortness of breath was improved; the electrocardiogram reexamination showed no ventricular premature beat. Ten hours later, the heart rate returns to normal. The next day, her blood potassium level returned to normal.

Metastasis is the essential character of biological behaviors in malignancies,which is also the main reason for the death of patients with tumor. So it is very important to research the metastasis for the pre-vention and treatment of carcinomas. Rectal cancer is one of the most common gastrointestinal cancer,and its prognosis is bad. lymphatic metastasis is one important factor in the determination of colon cancer' s progno-sis. More than 50% patients are found lymphatic metastasis when taking operation. The ralationship of lym-phatic metastasis and prognosis is more important than the original tumor's invasiving. So it is meaningful to study the mechanism of tumor metastasis, and to provide a scientific approach to the prediction of tumor me-tastasis, the precise assessment of prognosis and the treatment of tumor metastasis.

BACKGROUND: There is a growing recognition that the adipose tissue is an endocrine organ that secretes signaling molecules such as adiponectin and resistin. The peroxisome proliferator activated receptor γ (PPARγ) is expressed in high levels in the adipose tissue. Thiazolidinediones are selective PPARγ agonists with insulin-sensitizing properties. It has been postulated that thiazolidinediones such as rosiglitazone exert their pharmacodynamic effects in part through modulation of resistin (implicated in insulin resistance) and adiponectin (an insulin-sensitizing molecule) expression subsequent to activation of PPARγ. There are conflicting data, however, on the biological direction in which resistin expression is modulated by PPARγ agonists and whether an increase in adiponectin expression can occur in the face of an upregulation of resistin. METHODS: Using the murine 3T3-L1 adipocytes as a model, we evaluated the changes in resistin and adiponectin gene expression after vehicle, rosiglitazone (10 μmol/L, a PPARγ agonist), GW9662 (5 μmol/L, a selective PPARγ antagonist) or GW662 and rosiglitazone co-treatment.RESULTS: In comparison to vehicle treatment, rosiglitazone increased the average adiponectin and resistin mRNA expression by 1.66- and 1.55-fold, respectively (P＜0.05). Importantly, GW9662 also upregulated adiponectin expression (by 1.57-fold, P＜0.05) but did not influence resistin expression (P＞0.05). Co-treatment with rosiglitazone and GW9662 maintained the adiponectin upregulation (1.87-fold increase from vehicle, P＜0.05) while attenuating resistin upregulation (1.31-fold increase from vehicle, P＜0.05) induced by rosiglitazone alone (1.55-fold increase from vehicle, P＜0.05). CONCLUSION: This study presents new evidence that adiponectin transcript is upregulated with both a PPARγ agonist (rosiglitazone) and antagonist (GW9662), while GW9662 co-treatment does not block rosiglitazone-induced adiponectin upregulation. These data collectively suggest that biological mechanisms independent from PPARγ may underlie thiazolidinedione pharmacodynamics on adiponectin expression. Moreover, increased adiponectin expression by GW9662, in the absence of an upregulation of resistin expression, lends further support on the emerging clinical potential of PPARγ antagonists in treatment of insulin resistance. Decreased resistin expression may not be crucial for the insulin-sensitizing effect of rosiglitazone. These findings may serve as a foundation for future dose-ranging and time-course studies of thiazolidinedione pharmacodynamics on adipocytokine expression in human adipocytes.

BACKGROUND: Metoprolol is a selective β1-Blocker commonly used in essential hypertension. It is metabolized by CYP2D6. CYP2D6*10, which was identified to decrease activity of CYP2D6, is the main variance in Chinese population. β1-adrenergic receptor, with Ser49Gly and Gly389Arg polymorphisms, is the target of metoprolol. It was still unknown that whether the CYP2D6 and β1-adrenergic receptor had a synergic effect on metoprolol antihypertension therapy. AIM: To clarify the genetic polymorphism associated with metoprolol pharmacokinetics and pharmacodynamics in antihypertension therapy. METHODS: 125 mild-to-med essential hypertension patients were enrolled in this study. Patients were mono-therapied with metoprolol for 12 weeks. Blood pressure was monitored every 4 weeks. PCR-RFLP method was use to identify CYP2D6*10 and β1-adrenergic receptor Ser49Gly and Gly389Arg polymorphisms. Plasma metoprolol concentration was measured by HPLC- fluorescence detection. RESULTS: Trough blood level (C0) of metoprolol was associated with CYP2D6*10 variance in a gene-dose-effect manner, whereas the extent of blood pressure decrease was not significant different in CYP2D6*1*1, *1*10 and CYP2D6*10*10 patients. After 12 weeks metoprolol therapy, Gly49 carriers had stronger decrease in systolic and diastolic blood pressure than that of Ser49 homozygotes. Similarly, subjects homozygous for Arg389 had stronger decrease in blood pressure than that of Gly389 carriers. CONCLUSION: CYP2D6*10 variance significantly change the pharmacokinetics of metoprolol, and the genetic polymorphisms of β1-adrenergic receptor were associated with the pharmacodynamics of metopolol in antihypertension therapy.