Increased serum triglyceride clearance and elevated high-density lipoprotein 2 and 3 cholesterol during treatment of primary hypertriglyceridemia with bezafibrate

Background

Hypertriglyceridemia accompanied by low levels of high-density lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease. High-density lipoprotein 2 (HDL₂) and 3 (HDL₃) are believed to suppress the progress of atherosclerosis through reverse cholesterol transport. As a result, peripheral tissues can be protected against excessive accumulation of cholesterol. Although bezafibrate is known to accelerate the increase of HDL-C, results are not standardized regarding increases of HDL₃ and HDL₂ subfractions.

Objective

This study assessed the effects of bezafibrate on serum triglyceride (TG) fractional clearance rate (K₂) and HDL₂ and HDL₃ cholesterol (HDL₂-C and HDL₃-C, respectively) levels in patients with primary hypertriglyceridemia (serum TG ≥150 mg/dL).

Methods

Outpatients with primary hypertriglyceridemia were enrolled in this 8-week study conducted at the Third Department of Internal Medicine, Nagoya City University Hospital (Nagoya, Japan). Oral bezafibrate was administered at a dose of 400 mg/d (200-mg tablet BID, morning and evening) for 8 weeks. After 8 weeks, serum levels of total cholesterol (TC), TG, HDL-C, HDL₂-C, and HDL₃-C were measured. A fat emulsion tolerance test to assess K₂ and measurements of plasma lipoprotein lipase (LPL) mass, LPL activity, and hepatic triglyceride lipase (HTGL) activity in postheparin plasma were performed before bezafibrate administration and after the course of treatment.

Results

Sixteen patients (10 men, 6 women; mean [SD] age, 54 [12] years [range, 30-69 years]; mean [SD] body mass index, 23 [2] kg/m²) entered the study. The following findings were observed in male and female patients after 8 weeks of treatment. A statistically significant reduction was observed in mean serum TG level (P<0.01). Significant increases were seen in HDL-C, HDL₂-C, and HDL₃-C (all P<0.01), K₂ (P<0.01), and in plasma LPL mass (P<0.01) and LPL activity (P<0.05). TC level and HTGL activity did not change significantly. No adverse effects related to the use of bezafibrate were documented.

Conclusions

In this study, bezafibrate treatment resulted in significant decreases in serum TG level and significant increases in HDL₂-C and HDL₃-C levels and plasma LPL mass and activity. We hypothesize that bezafibrate may increase HDL₃-C by promoting TG-rich lipoprotein catabolism and may increase HDL₂-C by promoting the conversion of HDL₃ to HDL₂.     

Microscopic polyangiitis presenting with liver dysfunction preceding rapidly progressive necrotizing glomerulonephritis

The authors describe a 52-year-old woman diagnosed with microscopic polyangiitis. She presented with abnormal liver function tests accompanied by fever, headache, and fatigue. Two months later, rapidly progressive necrotizing glomerulonephritis developed together with seropositivity for perinuclear antineutrophil cytoplasmic antibody. Although liver dysfunction from microscopic polyangiitis is very rare, especially at presentation, this diagnostic possibility should be kept in mind to permit prompt consideration of steroid therapy.     

Quadrant Analysis of Quantitative Computed Tomography Scans of the Femoral Neck Reveals Superior Region-Specific Weakness in Young and Middle-Aged Men With Type 1 Diabetes Mellitus

We have previously shown that the intertrochanter of young and middle-aged patients with type 1 diabetes mellitus (T1DM) showed higher buckling ratio (an index of cortical instability) and lower volumetric bone mineral density (vBMD). However, we have not yet reported the detailed findings regarding the mechanical and density properties of the femoral neck. Therefore, we present a subanalysis of our previous study with the aim of further evaluating the middle third of the femoral neck via quadrant quantitative computed tomography in young and middle-aged patients with T1DM. Bone parameters in 4 anatomical quadrants (superoanterior [SA], inferoanterior [IA], inferoposterior [IP], and superoposterior [SP]) were cross-sectionally evaluated in 17 male T1DM patients and 18 sex-matched healthy controls aged between 18 and 49?yr using quadrant quantitative computed tomography analysis. Patients with T1DM had a thinner cortical thickness in the SP quadrant and a significantly lower cortical vBMD in the SA quadrant than the controls. The serum insulin-like growth factor-1 values in patients with T1DM were positively correlated with the average cortical thickness in the SA quadrant and the average trabecular vBMD in the SP quadrant of the femoral neck. The cortical thickness in controls was negatively correlated with age in the SP and IP quadrants. The cortical thickness in patients with T1DM showed no correlation with age in all quadrants. The fragility of the femoral neck was remarkable in the superior region of patients with T1DM. Insulin-like growth factor-1 may play an important role in superior cortical thinning and in lowering cortical vBMD. Furthermore, in young and middle-aged men with T1DM, the structure of the femoral neck exhibits similar changes as those observed with aging.     

Prevention of ventilatory disturbance while in the face-down position after macular hole surgery

The aim of the present study was to assess the effects of the face-down position on ventilatory function after macular hole surgery. The transcutaneous carbon dioxide tensions (tcPCO2) were measured in five patients who had undergone intraocular tamponade and in 17 normal subjects. The tcPCO2 measurements were done in patients following vitrectomy in the sitting position and in the prone position with their faces down over the semi-closed spaces of the conventional mats. In normal subjects, minute ventilatory volumes (V.E) were measured simultaneously with tcPCO2 in the sitting position and prone position. The newly introduced face-down mats (new mats) for the prone position were also tested in the normal subjects. In normal subjects, VE in the prone position with the conventional mats was significantly lower than that found in the sitting position (5.06 +/- 1.55 vs 6.06 +/- 1.64 L/min; P < 0.002). The tcPCO2 in the prone position was significantly higher than that in the sitting position (41.7 +/- 2.1 vs 38.0 +/- 1.9 mmHg; P < 0.0001). In post-vitrectomy patients, tcPCO2 in the prone position with the conventional mats was significantly higher than that in the sitting position (41.4 +/- 1.7 vs 38.6 +/- 2.2 mmHg; P < 0.02). The tcPCO2 in the prone position in normal subjects was significantly lower using new mats than that when using conventional mats. The use of conventional mats during a prone position, increased the tcPCO2 values when compared to the tcPCO2 values obtained during the sitting position in patients following vitrectomy. This could be due to either a decrease of the VE caused by limited thoracic movement or rebreathing of the exhaled gas over the semi-closed space, or both. The new mats might be useful in alleviating the increase of tcPCO2 by eliminating the rebreathing of the exhaled gas.     

Identification of the hepatic efflux transporters of organic anions using double-transfected Madin-Darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/multidrug resistance-associated protein 2, OATP1B1/multidrug resistance 1, and OATP1B1/breast cancer resistance protein

Until recently, it was generally believed that the transport of various organic anions across the bile canalicular membrane was mainly mediated by multidrug resistance-associated protein 2 (MRP2/ABCC2). However, a number of new reports have shown that some organic anions are also substrates of multidrug resistance 1 (MDR1/ABCB1) and/or breast cancer resistance protein (BCRP/ABCG2), implying MDR1 and BCRP could also be involved in the biliary excretion of organic anions in humans. In the present study, we constructed new double-transfected Madin-Darby canine kidney II (MDCKII) cells expressing organic anion-transporting polypeptide 1B1 (OATP1B1)/MDR1 and OATP1B1/BCRP, and we investigated the transcellular transport of four kinds of organic anions, estradiol-17beta-d-glucuronide (EG), estrone-3-sulfate (ES), pravastatin (PRA), and cerivastatin (CER), to identify which efflux transporters mediate the biliary excretion of compounds using double-transfected cells. We observed the vectorial transport of EG and ES in all the double transfectants. MRP2 showed the highest efflux clearance of EG among these efflux transporters, whereas BCRP-mediated clearance of ES was the highest in these double transfectants. In addition, two kinds of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, CER and PRA, were also substrates of all these efflux transporters. The rank order of the efflux clearance of PRA mediated by each transporter was the same as that of EG, whereas the contribution of MDR1 to the efflux of CER was relatively greater than for PRA. This experimental system is very useful for identifying which transporters are involved in the biliary excretion of organic anions that cannot easily penetrate the plasma membrane.     

Endoscopic diagnosis and treatment of a case of respiratory papillomatosis

Respiratory papilloma is a rare lesion that arises in the larynx, trachea and bronchus. We describe a patient with laryngeal papilloma that spread to the trachea and which was effectively treated by Nd-YAG laser. Two years after the initial treatments of the laryngeal and tracheal papillomas, a recurrent lesion (solitary papilloma) was observed on the membranous portion of the trachea. We examined the recurrent lesion by bronchoscopy including bronchoscopic ultrasound (US), helical computed tomography (CT) and tracheal biopsies. Respiratory papillomatosis sometimes shows either malignant transformation or invasion to tracheal wall without displaying cytohistological atypia. Therefore, we concluded that bronchoscopic US and helical CT were useful for deciding on therapeutic strategy in cases of recurrence of tracheal papilloma.     

Single tuberculous stricture in the jejunum: Report of 2 cases

Intestinal tuberculosis is now considered rare. It usually involves the ileocecal region and often produces multiple ulcers in the small intestine. This is a report of 2 patients who presented with a single tuberculous stricture in the jejunum, an exceedingly rare manifestation of this disease. The stricture in each case consisted of a short girdle ulcer with irregular margins, detected by double-contrast studies of the small intestine.