Effects of patient‐tailored atorvastatin therapy on ameliorating the levels of atherogenic lipids and inflammation beyond lowering low‐density lipoprotein cholesterol in patients with type 2 diabetes

Aims/Introduction

Recently, patient‐tailored statin therapy was proven effective for achieving target low‐density lipoprotein (LDL) cholesterol levels. It is unclear, however, whether this therapeutic modality would be effective for atherogenic lipid profiles and inflammation in patients with type 2 diabetes.

Materials and Methods

The present study was an 8‐week, multicenter, single‐step titration trial of patient‐tailored atorvastatin therapy (10, 20 and 40 mg) according to baseline LDL cholesterol levels in 440 patients with type 2 diabetes. We measured the LDL particle size by polyacrylamide gel electrophoresis, and used high‐sensitivity C‐reactive protein (hsCRP) and adiponectin as surrogate markers of inflammation.

Results

In the intention‐to‐treat analysis, 91% of the patients achieved their LDL cholesterol targets (<2.6 mmol/L) at week 8. There were significant reductions at week 8 in total cholesterol, triglycerides, non‐high‐density lipoprotein cholesterol (HDL) cholesterol, and the total cholesterol:HDL cholesterol ratio compared with the baseline values for all of the doses. The mean LDL particle size was significantly increased, and the small, dense LDL cholesterol levels were decreased in a dose‐dependent manner over the study period. In addition, the hsCRP levels were decreased in those high‐risk patients with baseline hsCRP levels over 3 mg/L (P < 0.001), and the adiponectin levels tended to increase with all of the doses (P = 0.004) at 8 weeks.

Conclusions

Patient‐tailored atorvastatin therapy based on LDL cholesterol at baseline was effective in ameliorating atherogenic LDL particle size and inflammation, in addition to achieving the target LDL cholesterol level without an undesirable effect on glycemic control in patients with type 2 diabetes. This trial was registered with ClinicalTrials.gov (no. NCT01239849).     

Colitis causes delay in puberty in female mice out of proportion to changes in leptin and corticosterone

Background  

Inflammatory bowel disease that begins prior to puberty frequently causes a delay in puberty resulting in losses of growth, bone mineralization, and self-esteem. A major cause of this pubertal delay is likely due in part to the effect of decreased levels of leptin on the function of the hypothalamic–pituitary–gonadal axis, though systemic inflammation is also thought to play a role.     

A novel primate model of delayed wound healing in diabetes: dysregulation of connective tissue growth factor

Aims/hypothesis  

Chronic non-healing wounds are a common complication of diabetes. Prolonged inflammation and decreased matrix accumulation may contribute. Connective tissue growth factor (CTGF) is induced during normal wound healing, but its regulation in diabetic wounds is unknown. We developed a primate model for the study of in vivo wound healing in baboons with long diabetes duration.     

Melatonin Expresses Powerful Anti-inflammatory and Antioxidant Activities Resulting in Complete Improvement of Acetic-Acid-Induced Colitis in Rats

Introduction  

Increased free-radical production, decreased antioxidant capacity, and excessive inflammation are well-known features in the pathogenesis of inflammatory bowel disease. Melatonin is a powerful antioxidant and a scavenger of hydroxyl radicals. Melatonin has also been shown to have anti-inflammatory activities in tissues. Our study objective is to investigate the effects of melatonin on tissue inflammatory activities using an ulcerative colitis (UC) model induced by acetic acid (AA) in rats.     

Rifaximin has minor effects on bacterial composition,inflammation, and bacterial translocation in cirrhosis: A randomized trial

Background and Aim

Decompensated cirrhosis is characterized by disturbed hemodynamics, immune dysfunction, and high risk of infections. Translocation of viable bacteria and bacterial products from the gut to the blood is considered a key driver in this process. Intestinal decontamination with rifaximin may reduce bacterial translocation (BT) and decrease inflammation. A randomized, placebo‐controlled trial investigated the effects of rifaximin on inflammation and BT in decompensated cirrhosis.

Methods

Fifty‐four out‐patients with cirrhosis and ascites were randomized, mean age 56 years (± 8.4), and model for end‐stage liver disease score 12 (± 3.9). Patients received rifaximin 550‐mg BD (n = 36) or placebo BD (n = 18). Blood and fecal (n = 15) sampling were conducted at baseline and after 4 weeks. Bacterial DNA in blood was determined by real‐time qPCR 16S rRNA gene quantification. Bacterial composition in feces was analyzed by 16S rRNA gene sequencing.

Results

Circulating markers of inflammation, including tumor necrosis factor alpha, interleukins 6, 10, and 18, stromal cell‐derived factor 1‐α, transforming growth factor β‐1, and high sensitivity C‐reactive protein, were unaltered by rifaximin treatment. Rifaximin altered abundance of bacterial taxa in blood marginally, only a decrease in Pseudomonadales was observed. In feces, rifaximin decreased bacterial richness, but effect on particular species was not observed. Subgroup analyses on patients with severely disturbed hemodynamics (n = 34) or activated lipopolysaccharide binding protein (n = 37) revealed no effect of rifaximin.

Conclusion

Four weeks of treatment with rifaximin had no impact on the inflammatory state and only minor effects on BT and intestinal bacterial composition in stable, decompensated cirrhosis (NCT01769040).     

Evaluation of Fecal Myeloperoxidase as a Biomarker of Disease Activity and Severity in Ulcerative Colitis

Background  

Subclinical inflammation in ulcerative colitis (UC) can predispose to relapses and biomarkers can detect mucosal inflammation.     

Ultrasonography‐detected subclinical inflammation in patients with hand osteoarthritis and established rheumatoid arthritis: a comparison between two different pathologies using the same ultrasound examination protocol

Objectives

A recent review of ultrasound (US) studies in osteoarthritis (OA) showed very limited data about hand OA. Previous US studies in patients with OA described a degree of overlap between the US appearance of rheumatoid arthritis (RA) and OA joints. The present study aimed to assess the US features of subclinical inflammation in RA and hand OA, using the same US examination protocol.

Methods

A retrospective, cohort study compared patients with established RA (n = 224) and hand OA (n = 73), with respect to several demographic, clinical, laboratory and US parameters. We used a 22‐hand joint US examination protocol (wrists, metacarpophalangeal and proximal interphalangeal joints bilaterally – Outcome Measures in Rheumatology Clinical Trials [OMERACT] scoring system) for all patients.

Results

Subclinical joint inflammation in the context of equivocal clinical examination was found in 9.6% of OA patients compared with 46.4% of RA patients (p = 0.0001), despite the fact that there was no significant difference between the degree of chronic joint swelling (synovial hypertrophy grades 2 and 3; p = 0.75 and p = 0.11, respectively). The presence of osteophytes was more common in patients with hand OA, as expected (p = 0.0001).

Conclusions

Our study findings reflected differences between the incidence and characteristics of subclinical inflammation in patients with RA and OA, which could be helpful in patients with an equivocal clinical examination or history of both diseases. Almost one in 10 patients with hand OA had active synovitis, while almost one in two patients with RA had uncontrolled inflammation in at least one joint.     

Therapy with the Opioid Antagonist Naltrexone Promotes Mucosal Healing in Active Crohn’s Disease: A Randomized Placebo-Controlled Trial

Background  

Endogenous opioid peptides have been shown to play a role in the development and/or perpetuation of inflammation. We hypothesize that the endogenous opioid system is involved in inflammatory bowel disease, and antagonism of the opioid–opioid receptor will lead to reversal of inflammation.     

Chronic insulin therapy reduces adipose tissue macrophage content in LDL-receptor-deficient mice

Aims/hypothesis  

Insulin has anti-inflammatory effects in short-term experiments. However, the effects of chronic insulin administration on inflammation are unknown. We hypothesised that chronic insulin administration would beneficially alter adipose tissue inflammation and several circulating inflammatory markers.     

STAT3 signaling within hepatocytes is required for anemia of inflammation in vivo

Background

Anemia of inflammation, commonly observed in patients with chronic diseases, is associated with decreased serum iron. Hepcidin, mainly produced by hepatocytes in a STAT3- and/or SMAD-dependent manner, is involved in iron homeostasis. What remains to be established is whether or not the hepatic IL-6/STAT3 signal has a role in anemia of inflammation in vivo.

Methods

Turpentine oil was subcutaneously injected into wild-type mice or hepatocyte-specific STAT3-deficient mice (L-STAT3KO) to induce inflammation.

Results

Turpentine injection increased serum IL-6 levels. It activated liver STAT3 in wild-type mice, but not in L-STAT3KO mice. In chronic inflammation, wild-type mice showed decreased serum iron levels and anemia with up-regulation of hepcidin levels in the liver. In contrast, L-STAT3KO mice showed no increase in hepatic hepcidin levels or anemia.

Conclusions

Liver STAT3 is critically involved in the development of anemia of inflammation via the expression of hepcidin. The liver regulates anemia of inflammation through STAT3 signaling.     

Lemon Verbena Infusion Consumption Attenuates Oxidative Stress in Dextran Sulfate Sodium-Induced Colitis in the Rat

Background  

Inflammatory bowel diseases (IBD) consist of an uncontrolled intestinal inflammation leading to mucosal disruption. This inflammation is accompanied by an excessive production of reactive oxygen species (ROS). Polyphenols are micronutrients with antioxidative and anti-inflammatory properties, and may play an interesting role in the prevention of intestinal inflammation. Lemon verbena (Aloysia triphylla) infusion is a popular herbal infusion rich in polyphenols (flavones and verbascoside).     

Increased systemic inflammation overnight correlates with insulin resistance among children evaluated for obstructive sleep apnea

Purpose  

Obstructive sleep apnea (OSA) in children is associated with obesity, insulin resistance, and elevated baseline inflammation as measured by high-sensitivity C-reactive protein (hsCRP). Our goal was to evaluate whether inflammation increases overnight among children suspected of having OSA and to determine whether worsened inflammation is associated with the degree of OSA severity, obesity, and/or insulin resistance.     

Early cardiac abnormalities and increased C-reactive protein levels in a cohort of children with sleep disordered breathing

Background  

This study aims to evaluate left ventricular (LV) structure and function and inflammation in a paediatric population with sleep disordered breathing (SDB) and in control subjects.     

Exposure to the common food additive carrageenan leads to glucose intolerance, insulin resistance and inhibition of insulin signalling in HepG2 cells and C57BL/6J mice

Aims/hypothesis  

The aim of this study was to determine the impact of the common food additive carrageenan (E407) on glucose tolerance, insulin sensitivity and insulin signalling in a mouse model and human hepatic cells, since carrageenan is known to cause inflammation through interaction with toll-like receptor (TLR)4, which is associated with inflammation in diabetes.     

Changes in Exhaled Nitric Oxide Levels After Bronchial Allergen Challenge

Background  

Fractional exhaled nitric oxide (FeNO) is a marker of inflammation of the airways accompanying changes in the clinical condition of asthma. Allergen exposure has been associated with a delayed elevation of FeNO. The aim of this study was to assess airway inflammation with FeNO measurements during bronchial allergen challenge (BAC), and to determine the diagnostic performance of FeNO changes.     

Spiral ligament fibrocyte-derived MCP-1/CCL2 contributes to inner ear inflammation secondary to nontypeable <Emphasis Type="Italic">H. influenzae</Emphasis>-induced otitis media

Background  

Otitis media (OM), one of the most common pediatric infectious diseases, causes inner ear inflammation resulting in vertigo and sensorineural hearing loss. Previously, we showed that spiral ligament fibrocytes (SLFs) recognize OM pathogens and up-regulate chemokines. Here, we aim to determine a key molecule derived from SLFs, contributing to OM-induced inner ear inflammation.     

Relationships Between Airway Hyperresponsiveness,Inflammation, and Calibre in Asthma

Background  

Previous studies have focused upon the relationship between airway inflammation and hyperresponsiveness with different conclusions. We re-examined the relationship between airway inflammation (FE_NO), hyperresponsiveness to methacholine (AHR), and calibre (FEV₁ % predicted) in mild-to-moderate asthmatics.     

Mucosal inflammation as a potential etiological factor in irritable bowel syndrome: a systematic review

Background  

The causes of irritable bowel syndrome (IBS) remain obscure. Some investigators have proposed chronic low-grade mucosal inflammation as a potential etiological factor. We performed a systematic review to examine this issue in detail.     

HMGB1 cytoplasmic translocation in patients with acute liver failure

Background  

High-mobility group box 1 (HMGB1) is a late mediator of lethal systemic inflammation. Acute liver failure (ALF) has been shown to trigger systemic inflammation in clinical and animal studies. To evaluate the possibility of HMGB1 cytoplasmic translocation in ALF, we determined whether HMGB1 is released in hepatocytes and end organ in patients with liver failure/injury.     

Bifidobacterium infantis strains with and without a combination of Oligofructose and Inulin (OFI) attenuate inflammation in DSS-induced colitis in rats

Background  

Pathogenesis of inflammatory bowel disease is thought to be through different factors and there is a relationship between the gut flora and the risk of its development. Probiotics can manipulate the microflora in chronic inflammation and may be effective in treating inflammation. Bifidobacterium are saccharolytic and their growth in the gut can be promoted by non-absorbable carbohydrates and its increase in the colon appears to be of benefit.