A 75 kDa glycoprotein isolated from Cudrania tricuspidata Bureau induces colonic epithelial proliferation and ameliorates mouse colitis induced by dextran sulfate sodium.

Cudrania tricuspidata Bureau (CTB), a species of the Moraceae plant, has been used as a bruise recovery treatment. This study aimed to determine whether the 75 kDa phytoglycoprotein extracted from CTB has a regulatory effect on the proliferation of human colon epithelial cells and the pathological process of inflammatory bowel disease (IBD). We found that CTB glycoprotein significantly induces the proliferation of human colon epithelial HT-29 cells by activating protein kinase C. CTB glycoprotein stimulated the phosphorylation of c-Jun N-terminal kinase and transcription factor nuclear factor-κB, which are responsible for the expression of cell-cycle-related proteins (CDK2, CDK4, cyclin D1 and cyclin E) during its promotion of cell proliferation. Experimental colitis was induced in mice by adding dextran sulfate sodium to their drinking water at a concentration of 4% (W/V) for seven days. We found that CTB glycoprotein ameliorates the pathological process of IBD and lowers the disease activity index score, which was composed of body weight change, diarrhea, and hematochezia in ICR mice treated with dextran sulfate sodium. Hence, we suggest that CTB glycoprotein has the ability to prevent IBD by promoting cell proliferation signaling events via the activation of PKC, JNK and NF-κB in colon epithelial cells.

Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study.

PURPOSE: Doubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up-titration of the nifedipine gastrointestinal therapeutic system (GITS) with up-titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies. METHODS: This prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic. FINDINGS: Of the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up-titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition, escalating the dose of either nifedipine GITS or valsartan revealed a similar occurrence of adverse effects with low-dose monotherapy or the low-dose combination. IMPLICATIONS: Compared with up-titration of the angiotensin receptor blocker valsartan, up-titration of the calcium channel blocker nifedipine GITS provided no additional increased safety concerns and revealed better mean reductions in BP without affecting short-term BP variability. ClinicalTrials.gov identifier: NCT01071122.

Randomized trial comparing the effects of a low-dose combination of nifedipine GITS and valsartan versus high-dose monotherapy on central hemodynamics in patients with inadequately controlled hypertension: FOCUS study.

OBJECTIVES: Measurement of central blood pressure provides prognostic information beyond conventional peripheral blood pressure (BP). However, few studies have directly compared the effects of antihypertensives on central hemodynamics. This study investigated the effects of a low-dose combination of nifedipine Gastrointestinal Therapeutic System (GITS) and valsartan versus high-dose monotherapy with either agent in reducing central BP in essential hypertension inadequately controlled by low-dose monotherapy. MATERIALS AND METHODS: In this prospective, open-label, randomized, active-controlled, multicenter 8-week study, patients not meeting the target BP after 4 weeks of treatment with low-dose monotherapy were randomized to receive nifedipine GITS 30 mg plus valsartan 80 mg (N30+V80), nifedipine GITS 60 mg (N60), or valsartan 160 mg (V160) for a further 4 weeks. Central hemodynamics were measured by applanation tonometry. RESULTS: A total of 391 patients were enrolled. Reduction in central systolic BP from baseline to week 8, the primary efficacy variable, was significantly greater in the N30+V80 group (-27.2±14.7 mmHg) and the N60 group (-27.1±16.5 mmHg) compared with V160 group (-14.4±16.6 mmHg). Decrease in the augmentation index in the N60 group was significantly greater compared with V160 alone, without differences between combination therapy and either high-dose monotherapy. Decreases in brachial systolic BP were significantly greater in the N30+V80 and N60 groups than in the V160 group. By multiple regression analysis, most differences in drug effects on central hemodynamics disappeared after controlling for changes in peripheral BP. A low rate of adverse events occurred in all treatment groups. CONCLUSION: A low-dose combination of nifedipine GITS plus valsartan or high-dose nifedipine was more effective in improving central hemodynamics than high-dose valsartan in patients with hypertension, mostly because of the improvement in peripheral (brachial) hemodynamics.

Anxiety and depression propensities in patients with acute toxic liver injury.

AIM: To investigate anxiety and depression propensities in patients with toxic liver injury. METHODS: The subjects were divided into three groups: a healthy control group (Group 1, n = 125), an acute non-toxic liver injury group (Group 2, n = 124), and a group with acute toxic liver injury group caused by non-commercial herbal preparations (Group 3, n = 126). These three groups were compared and evaluated through questionnaire surveys and using the Hospital Anxiety-Depression Scale (HADS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and the hypochondriasis scale. RESULTS: The HADS anxiety subscale was 4.9 ± 2.7, 5.0 ± 3.0 and 5.6 ± 3.4, in Groups 1, 2, and 3, respectively. The HADS depression subscale in Group 3 showed the most significant score (5.2 ± 3.2, 6.4 ± 3.4 and 7.2 ± 3.4 in Groups 1, 2, and 3, respectively) (P < 0.01 vs Group 1, P < 0.05 vs Group 2). The BAI and BDI in Group 3 showed the most significant score (7.0 ± 6.3 and 6.9 ± 6.9, 9.5 ± 8.6 and 8.8 ± 7.3, 10.7 ± 7.2 and 11.6 ± 8.5 in Groups 1, 2, and 3, respectively) (BAI: P < 0.01 vs Group 1, P < 0.05 vs Group 2) (BDI: P < 0.01 vs Group 1 and 2). Group 3 showed a significantly higher hypochondriasis score (8.2 ± 6.0, 11.6 ± 7.5 and 13.1 ± 6.5 in Groups 1, 2, and 3, respectively) (P < 0.01 vs Group 1, P < 0.05 vs Group 2). CONCLUSION: Psychological factors that present vulnerability to the temptation to use alternative medicines, such as herbs and plant preparations, are important for understanding toxic liver injury.