CD40 activation mediates p53-dependent cell cycle regulation in human multiple myeloma cell lines

It has been reported that the activation of multiple myeloma (MM) cells by CD40 induces proliferation, growth arrest, and apoptosis. To determine whether the biologic sequelae of CD40 activation in MM cells depends on p53 function, we identified temperature-sensitive p53 mutations in the RPMI 8226 (tsp53E285K) and the HS Sultan (tsp53Y163H) MM cell lines. These cells were then used as a model system of inducible wtp53-like function because wild-type-like p53 is induced at permissive (30 degrees C) but not at restrictive (37 degrees C) temperatures. Using p21-luciferase reporter assays, we confirmed that CD40 induces p53 transactivation in RPMI 8226 and HS Sultan cells cultured under permissive, but not restrictive, conditions. Furthermore, CD40 activation of these MM cells under permissive, but not restrictive, temperatures increased the expression of p53 and p21 mRNA and protein. Importantly, CD40 activation induced the proliferation of RPMI 8226 and HS Sultan cells at restrictive temperatures and growth arrest and increased subG1 phase cells at permissive temperatures. These data confirmed that CD40 activation might have distinct biologic sequelae in MM cells, depending on their p53 status.     

Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD

The accumulation of uremic toxins is involved in the progression of CKD. Various uremic toxins are derived from gut microbiota, and an imbalance of gut microbiota or dysbiosis is related to renal failure. However, the pathophysiologic mechanisms underlying the relationship between the gut microbiota and renal failure are still obscure. Using an adenine-induced renal failure mouse model, we evaluated the effects of the ClC-2 chloride channel activator lubiprostone (commonly used for the treatment of constipation) on CKD. Oral administration of lubiprostone (500 µg/kg per day) changed the fecal and intestinal properties in mice with renal failure. Additionally, lubiprostone treatment reduced the elevated BUN and protected against tubulointerstitial damage, renal fibrosis, and inflammation. Gut microbiome analysis of 16S rRNA genes in the renal failure mice showed that lubiprostone treatment altered their microbial composition, especially the recovery of the levels of the Lactobacillaceae family and Prevotella genus, which were significantly reduced in the renal failure mice. Furthermore, capillary electrophoresis–mass spectrometry-based metabolome analysis showed that lubiprostone treatment decreased the plasma level of uremic toxins, such as indoxyl sulfate and hippurate, which are derived from gut microbiota, and a more recently discovered uremic toxin, trans-aconitate. These results suggest that lubiprostone ameliorates the progression of CKD and the accumulation of uremic toxins by improving the gut microbiota and intestinal environment.     

The 11-item Medication Adherence Reasons Scale: reliability and factorial validity among patients with hypertension in Malaysian primary healthcare settings

INTRODUCTION

The aim of this study was to assess the reliability and validity of a modified Malaysian version of the Medication Adherence Reasons Scale (MAR-Scale).

METHODS

In this cross-sectional study, the 15-item MAR-Scale was administered to 665 patients with hypertension who attended one of the four government primary healthcare clinics in the Hulu Langat and Klang districts of Selangor, Malaysia, between early December 2012 and end-March 2013. The construct validity was examined in two phases. Phase I consisted of translation of the MAR-Scale from English to Malay, a content validity check by an expert panel, a face validity check via a small preliminary test among patients with hypertension, and exploratory factor analysis (EFA). Phase II involved internal consistency reliability calculations and confirmatory factor analysis (CFA).

RESULTS

EFA verified five existing factors that were previously identified (i.e. issues with medication management, multiple medications, belief in medication, medication availability, and the patient’s forgetfulness and convenience), while CFA extracted four factors (medication availability issues were not extracted). The final modified MAR-Scale model, which had 11 items and a four-factor structure, provided good evidence of convergent and discriminant validities. Cronbach’s alpha coefficient was > 0.7, indicating good internal consistency of the items in the construct. The results suggest that the modified MAR-Scale has good internal consistencies and construct validity.

CONCLUSION

The validated modified MAR-Scale (Malaysian version) was found to be suitable for use among patients with hypertension receiving treatment in primary healthcare settings. However, the comprehensive measurement of other factors that can also lead to non-adherence requires further exploration.     

A randomized outcome evaluation of group exercise programs in long-term care institutions

BACKGROUND: Physical activity programs in nursing homes typically consist of seated, range of motion (ROM) exercises, regardless of resident abilities. The Functional Fitness for Long-Term Care (FFLTC) Program was designed not only to maintain ROM, but also to improve strength, balance, flexibility, mobility, and function. In addition, it was tailored to meet the needs of both high and low mobility residents. METHODS: The feasibility and efficacy of the FFLTC Program were evaluated with 68 residents (mean age 80) from five institutions. Persons were classified as low or high mobility and randomized into either the FFLTC program or a seated ROM program. Classes were conducted in groups of 4 to 10 residents by trained facility staff for 45 minutes, three times per week. Assessments at baseline and 4 months consisted of mobility, balance, gait, flexibility, functional capacity, and several upper and lower extremity strength measures. RESULTS: Attendance averaged 86% for the FFLTC and 79% for the ROM classes. Four months of exercise led to significant improvements in mobility (16%), balance (9%), flexibility (36%), knee (55%), and hip (12%) strength for the FFLTC group. Shoulder strength was the only improvement found for the ROM group. The ROM group significantly deteriorated in some areas, particularly hip strength, mobility, and functional ability. CONCLUSIONS: Institutionalized seniors, even those who are physically frail, incontinent and/or have mild dementia, can respond positively to a challenging exercise program. The FFLTC program demonstrated clear benefits over typical, seated ROM exercises. Moreover, with minimal training, the program can be safely delivered at low cost by institutional staff and volunteers.     

Effects of counter torque and transposition (transfer) of installed implants timing on their integration in dog tibia

PURPOSE

The purpose of this research was to evaluate the amount of reosseointegration after counter torquing (reverse torque) and transposing the installed implants at different times.

MATERIALS AND METHODS

This study was done on ten tibiae of five cross-bred dogs. At the first day one implant was installed in each tibia. After one week half of the implants were randomly counter torqued (1WCT) and the other half were explanted and reimplanted in a new juxtaposition site (transposed)(1WT). At the same time three new implants were installed in each dog, one of them was considered as one week control (1WC) and remaining two as 8 week groups (8WCT&8WT). After eight weeks the 1WCT and 1WT implants were loosened by counter torque and the quantity of needed force for liberation was measured with the digital device (BGI). At the same time one implant was installed in each dog as eight week control (8WC) and the same protocol was repeated for 8 week groups after another 8 weeks.

RESULTS

All implants were osseointegrated. Mean quantities of osseointegration in case groups indicated better amounts rather than control groups.

CONCLUSION

Counter torque or transposition of the installed implants one week or eight weeks after the implantation did lead to osseointegration.     

IL-1 Receptor Antagonist Blocks the Lipopolysaccharide-Induced Inhibition of Gastric Motility in Freely Moving Conscious Rats

Background and Aims

Endotoxin/lipopolysaccharide (LPS) alters gastrointestinal functions. However, little is known as to whether LPS could change gastric antral contractility in freely moving conscious animals. We tried to clarify this problem and the associated mechanisms.

Methods

In this study, we recorded intraluminal gastric pressure waves in freely moving conscious rats by manometric catheter located in the antrum. Area under the manometric trace was evaluated as motor index (MI).

Results

Intraperitoneal injection of LPS at doses of 0.2?mg/kg or more significantly inhibited MI. The inhibition started immediately after the administration of LPS and lasted over 1?h. Intraperitoneal injection of IL-1β potently decreased MI while neither IL-6 nor TNF-α inhibited gastric motility, suggesting IL-1β specifically reduced gastric motility. Next, we examined the hypothesis that endogenous IL-1 mediates the LPS-induced inhibition of gastric motility. To address the speculation, an IL-1 receptor antagonist (IL-1Ra) was used to block IL-1 signaling. Pretreatment with IL-1Ra at a dose of 20?mg/kg significantly blocked the inhibition of gastric contractility by LPS at a dose of 0.2?mg/kg.

Conclusions

These results suggest for the first time that LPS or IL-1β is capable of inhibiting gastric motility in conscious rats and that endogenously released IL-1 may mediate the LPS-evoked inhibition of gastric antral motility. This evidence also led us to speculate that IL-1Ra may be a therapeutic tool for patients with disturbed gastrointestinal functions under septic conditions.     

Prooxidant-Antioxidant Balance and Antioxidized LDL Antibody Level Values and Cardiac Function in Patients with Coronary Artery Disease

Objectives: We studied the association between the prooxidant-antioxidant balance (PAB), anti-malondialdehyde-modified low-density lipoprotein (oxidized LDL, ox-LDL) IgG antibody and indices of cardiac function (systolic and diastolic function) in patients with coronary artery disease (CAD). Methods: Fifty-five patients with established CAD were selected, and serum levels of anti-ox-LDL IgG and PAB values were measured and compared with 40 matched healthy controls. Systolic and diastolic functions were determined for all patients. Results: PAB values were significantly higher in patients than in controls (p < 0.001), whilst serum anti-ox-LDL concentrations were not statistically different between the 2 groups (p = 0.821). However, after adjustment for high-density lipoprotein cholesterol, the patients had higher anti-ox-LDL levels (p = 0.04). Total PAB values were inversely associated with ejection fraction (r = -0.326, p = 0.031), but this was not the case for anti-ox-LDL in either group (p > 0.05). Conclusion: Serum concentrations of a marker of oxidative stress (PAB values) are inversely associated with cardiac function. PAB is a relatively simple index that could be incorporated into risk assessment in CAD patients. Anti-ox-LDL IgG antibody concentration does not appear to reflect total oxidative stress as assessed by PAB.