RhoGDIβ-induced hypertrophic growth in H9c2 cells is negatively regulated by ZAK

We found that overexpression of RhoGDIβ, a Rho GDP dissociation inhibitor, induced hypertrophic growth and suppressed cell cycle progression in a cultured cardiomyoblast cell line. Knockdown of RhoGDIβ expression by RNA interference blocked hypertrophic growth. We further demonstrated that RhoGDIβ physically interacts with ZAK and is phosphorylated by ZAK in vitro, and this phosphorylation negatively regulates RhoGDIβ functions. Moreover, the ZAK-RhoGDIβ interaction may maintain ZAK in an inactive hypophosphorylated form. These two proteins could negatively regulate one another such that ZAK suppresses RhoGDIβ functions through phosphorylation and RhoGDIβ counteracts the effects of ZAK by physical interaction. Knockdown of ZAK expression in ZAK- and RhoGDIβ-expressing cells by ZAK-specific RNA interference restored the full functions of RhoGDIβ

ZAK negatively regulates RhoGDIβ-induced Rac1-mediated hypertrophic growth and cell migration

RhoGDIβ, a Rho GDP dissociation inhibitor, induced hypertrophic growth and cell migration in a cultured cardiomyoblast cell line, H9c2. We demonstrated that RhoGDIβ plays a previously undefined role in regulating Rac1 expression through transcription to induce hypertrophic growth and cell migration and that these functions are blocked by the expression of a dominant-negative form of Rac1. We also demonstrated that knockdown of RhoGDIβ expression by RNA interference blocked RhoGDIβ-induced Rac1 expression and cell migration. We demonstrated that the co-expression of ZAK and RhoGDIβ in cells resulted in an inhibition in the activity of ZAK to induce ANF expression. Knockdown of ZAK expression in ZAK-RhoGDIβ-expressing cells by ZAK-specific RNA interference restored the activities of RhoGDIβ

Effect of Antrodia

Antrodia camphorata is a rare Taiwanese medicinal mushroom. Antrodia camphorata extract has been reported to exhibit antioxidant, anti-inflammation, antimetastasis, and anticancer activities and plays a role in liver fibrosis, vasorelaxation, and immunomodulation. Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Platelet activation plays a crucial role in intravascular thrombosis, which is involved in a wide variety of cardiovascular diseases. However, the effect of Antrodia camphorata on platelet activation remains unclear. We examined the effects of Antrodia camphorata on platelet activation. In the present study, Antrodia camphorata treatment (56–224 μg/mL) inhibited platelet aggregation induced by collagen, but not U46619, an analogue of thromboxane A2, thrombin, and arachidonic acid. Antrodia camphorata inhibited collagen-induced calcium (Ca2+) mobilization and phosphorylation of protein kinase C (PKC) and Akt. In addition, Antrodia camphorata significantly reduced the aggregation and phosphorylation of PKC in phorbol-12, 13-dibutyrate (PDBu) activated platelets. In conclusion, Antrodia camphorata may inhibit platelet activation by inhibiting of Ca2+ and PKC cascade and the Akt pathway. Our study suggests that Antrodia camphorata may be a potential therapeutic agent for preventing or treating thromboembolic disorders

Mortality risk factors in patients with Acinetobacter baumannii ventilator-associated pneumonia

Background/PurposeVentilator-associated pneumonia (VAP) caused by Acinetobacter baumannii has contributed to high mortality rate, prolonged stays in the intensive care unit, and the rapid development of antimicrobial resistance to commonly used antimicrobials. This study sought to determine predictors of mortality and carbapenem resistance for patients with A baumannii VAP.MethodsWe retrospectively reviewed 541 adult patients with A baumannii pneumonia, who were admitted to a medical center between 2005 and 2007; of which 180 (33.3%) had been treated with mechanical ventilation. Of the 180 patients, 98 (54.4%) who survived were categorized as the survivor group, and 82 (45.6%) who died as the mortality group. Eighty-seven (48.3%) with imipenem-sensitive A baumannii VAP were categorized as the IS-AB group, and the remaining 93 (51.7%) with imipenem-resistant VAP as the IR-AB group.ResultsCompared with the survivor group, the mortality group had significantly higher Charlson comorbidity index scores, and more neoplastic disease, other sites of infection, bloodstream infections, altered mental status, confusion, urea >7 mmol/L, respiratory rate >30/min, low blood pressure (systolic <90 mmHg or diastolic <60 mmHg), age >65 years (CURB-65) ≥ 3, creatinine > 1.6 mg/dL, C-reactive protein ≥ 100 mg/L, and imipenem resistance. The survivor group had more cases of tracheostomy and diabetes mellitus than the mortality group had. Compared with the IS-AB group, the IR-AB group had higher Charlson comorbidity index scores, longer stays before VAP onset, an increase in other sites of infection, white blood cell count <4/μL or >1.1 × 104/μL, and higher hospital mortality rates.ConclusionInadequate initial empiric antimicrobial therapy and higher disease severity scores, including CURB ≥ 3 and C-reactive protein ≥ 120 mg/L, were independent risk factors associated with higher mortality rates for A baumannii pneumonia. Length of stay before VAP and white blood cell count <4/μL or >1.1 × 104/μL were independent risk factors for carbapenem resistance

Perforated Sigmoid Colon Cancer within an Irreducible Inguinal Hernia: a Case Report

A perforated sigmoid colon cancer within an inguinal hernia is extremely rare. This unexpected finding is usually discovered during surgery and causes an unavoidable septic evolution. Here, we describe the case of an 84-year-old man who presented with fever, abdominal distension, and a painful, enlarged, left scrotum. A CT showed a left, incarcerated, inguinal hernia containing a perforated sigmoid adenocarcinoma (which was confirmed by histopathology). The possibility of an irreducible inguinal hernia in association with perforated sigmoid colon cancer should be considered in the array of diagnoses. A pre-operative CT scan would be helpful in facilitating an accurate diagnosis

The design of a prospective, randomized, open-labeled study to compare the efficacy of lercanidipine with amlodipine on renal function in hypertensive patients aged at least 55 years (LEADER study)

AbstractBackgroundAlthough all classes of antihypertensive treatment can successfully reduce morbidity and mortality of cardiac pathology, prevention of target organ damages is of great importance beyond blood pressure lowering. Unlike most dihydropyridines, lercanidipine dilates both afferent and the efferent arterioles of nephrons, so it may provide renoprotective effects, which other CCBs may not have. The main purpose of this study is to compare the renoprotective effect of lercanidipine and amlodipine among hypertensive people aged 55years and older with newly diagnosed hypertension or those who were treatment-naïve for one month.MethodsThe study is a prospective, open-labelled, randomized, controlled trial to enrol 232 hypertensive patients aged ≥55 years. Subjects will be randomized into lercanidipine arm (10–20mg/day) and amlodipine arm (5–10mg/day) by 1:1 ratio. The dosage can be up-titrated to 20mg/day (lercanidipine group) and 10mg/day (amlodipine group), respectively, at week 4 or any following visit thereafter. Efficacy and safety data will be collected at week 4, 12 and 24 by evaluating the blood pressure lowering, estimated glomerular filtration rate, creatinine clearance, and urine albumin-creatinine ratio.ConclusionsThe reno-protective effects of new generation of CCBs such as lercanidipine administered to patients with hypertension are not investigated well. After all, this study will bring benefit to older patients who need drugs with both excellent anti-hypertensive and reno-protective efficacy. And the results will be provided for future treatment guideline of elder population in Taiwan