Histone deacetylase inhibitors: a novel class of therapeutic agents in diabetic nephropathy

Histone deacetylase (HDAC) inhibitors are currently being tested as anticancer agents in clinical trials. Chromatin remodeling, such as through histone acetylation, is a fundamental phenomenon in eukaryotic cell biology, bearing implications to numerous physiological and pathological phenomena. Here, we discuss recent data from our own laboratory and those of others demonstrating antifibrotic and renoprotective effect of HDAC inhibitors in diabetic kidneys, and the possible mechanisms including the role of reactive oxygen species. HDAC inhibitors may prove to be a novel class of multitarget agents in the treatment of diabetic nephropathy.     

Yoga Training Improves Metabolic Parameters in Obese Boys

Yoga has been known to have stimulatory or inhibitory effects on the metabolic parameters and to be uncomplicated therapy for obesity. The purpose of the present study was to test the effect of an 8-week of yoga-asana training on body composition, lipid profile, and insulin resistance (IR) in obese adolescent boys. Twenty volunteers with body mass index (BMI) greater than the 95th percentile were randomly assigned to yoga (age 14.7±0.5 years, n=10) and control groups (age 14.6±1.0 years, n=10). The yoga group performed exercises three times per week at 40~60% of heart-rate reserve (HRR) for 8 weeks. IR was determined with the homeostasis model assessment of insulin resistance (HOMA-IR). After yoga training, body weight, BMI, fat mass (FM), and body fat % (BF %) were significantly decreased, and fat-free mass and basal metabolic rate were significantly increased than baseline values. FM and BF % were significantly improved in the yoga group compared with the control group (p<0.05). Total cholesterol (TC) was significantly decreased in the yoga group (p<0.01). HDL-cholesterol was decreased in both groups (p<0.05). No significant changes were observed between or within groups for triglycerides, LDL-cholesterol, glucose, insulin, and HOMA-IR. Our findings show that an 8-week of yoga training improves body composition and TC levels in obese adolescent boys, suggesting that yoga training may be effective in controlling some metabolic syndrome factors in obese adolescent boys.     

Lycopene supplementation suppresses oxidative stress induced by a high fat diet in gerbils

The effect of lycopene supplementation on the antioxidant system was investigated by analyzing lipid peroxide levels, glutathione contents, and antioxidant enzyme activities in Mongolian gerbils fed a high fat diet. Gerbils were fed on each experimental diet for 6 weeks; normal diet (NC), normal diet with 0.05% lycopene (NL), high fat diet (HF), and a high fat diet with 0.05% lycopene (HFL). Dietary supplementation of lycopene increased hepatic lycopene level in gerbils fed a normal or high fat diet (P < 0.05). Liver and erythrocyte concentrations of lipid peroxide increased in gerbils fed a high fat diet, whereas lycopene supplementation decreased liver and erythrocyte concentrations of lipid peroxide (P < 0.05). Hepatic total glutathione content was higher in the NL group than that in the NC group (P < 0.05). Total antioxidant status in plasma increased following lycopene supplementation compared with that of the non-lycopene supplemented groups (P < 0.05). Hepatic catalase activity increased following dietary lycopene supplementation (P < 0.05). Superoxide dismutase activity in liver remained unchanged with lycopene supplementation, but erythrocyte superoxide dismutase activity increased in NL group compared with NC group (P < 0.05). Glutathione-S-transferase activity increased in the NL group compared to NC group (P < 0.05). Liver and erythrocyte glutathione peroxidase activity increased significantly in the NL group compared to that in the HF group (P < 0.05). Liver glutathione reductase activity was higher in the NL group than that in the NC group (P < 0.05). These results suggest that lycopene supplementation may be efficient for preventing chronic diseases induced by oxidative stress related to high fat diet.     

Technological development and advances in single-photon emission computed tomography/computed tomography

Single-photon emission computed tomography/computed tomography (SPECT/CT) has emerged during the past decade as a means of correlating anatomical information from CT with functional information from SPECT. The integration of SPECT and CT in a single imaging device facilitates anatomical localization of the radiopharmaceutical to differentiate physiological uptake from that associated with disease and patient-specific attenuation correction to improve the visual quality and quantitative accuracy of the SPECT image. The first clinically available SPECT/CT systems performed emission-transmission imaging using a dual-headed SPECT camera and a low-power x-ray CT subsystem. Newer SPECT/CT systems are available with high-power CT subsystems suitable for detailed anatomical diagnosis, including CT coronary angiography and coronary calcification that can be correlated with myocardial perfusion measurements. The high-performance CT capabilities also offer the potential to improve compensation of partial volume errors for more accurate quantitation of radionuclide measurement of myocardial blood flow and other physiological processes and for radiation dosimetry for radionuclide therapy. In addition, new SPECT technologies are being developed that significantly improve the detection efficiency and spatial resolution for radionuclide imaging of small organs including the heart, brain, and breast, and therefore may provide new capabilities for SPECT/CT imaging in these important clinical applications.     

Total hip replacement with a cementless acetabular component and a cemented femoral component in patients younger than fifty years of age

BACKGROUND: We have been using hybrid total hip arthroplasty (a cementless acetabular component and a cemented stem) in young patients. The purpose of this study was to determine the prevalence of aseptic loosening, polyethylene wear, and osteolysis after the use of this technique. METHODS: We studied a prospective consecutive series of sixty-four primary hybrid total hip replacements in fifty-five patients younger than fifty years old. There were forty-three men and twelve women; the average age at the time of the index operation was 43.4 years. The average duration of follow-up was 9.4 years. We used a cementless acetabular component without screw-holes and a cemented femoral component with a 22-mm head in all hips. Clinical follow-up with use of Harris hip ratings and radiographic follow-up were performed at six weeks; at three, six, and twelve months; and yearly thereafter. The sequential annual linear and volumetric wear rates were measured, and bone-remodeling and osteolysis were assessed. RESULTS: The mean preoperative Harris hip score was 44 points, which increased to 95 points at the time of final follow-up. No hip had aseptic loosening. One hip (2%) was revised because of late infection. The average linear wear (and standard deviation) was 0.96 +/- 0.066 mm, with an average annual rate of 0.096 +/- 0.013 mm. The average volumetric wear was 364.7 +/- 25.2 mm (3), with an average annual rate of 43.4 +/- 3.5 mm (3). Six hips (9%) had an osteolytic lesion of <1 cm in diameter in the calcar femorale (zone 7). CONCLUSIONS: Our results show that a hybrid arthroplasty with a cementless acetabular component and a smooth cemented femoral component (Ra, 0.6 mm) is effective for primary total hip replacement in young patients. Although there was no aseptic loosening and a low prevalence of osteolysis at the latest follow-up evaluation, the high rates of linear and volumetric wear of the polyethylene liner in these young patients remain a concern.     

Renal damage caused by warm ischaemia during laparoscopic and robot-assisted partial nephrectomy: an assessment using Tc 99m-DTPA glomerular filtration rate

Background

Few studies assessing the functional change of each kidney following warm ischaemia after partial nephrectomy are available.

Objectives

Our aim was to identify the effects of the warm ischaemic time (WIT) on renal function after partial nephrectomy under the pneumoperitoneum.

Design, setting, and participants

Forty-four consecutive patients who underwent laparoscopic partial nephrectomy (LPN) or robot-assisted partial nephrectomy (RAPN) from June 2008 to May 2009 for a single cT1 renal tumour were included in this prospective protocol.

Measurements

Technetium Tc 99m-diethylenetriaminepentaacetic acid (Tc 99m-DTPA) renal scintigraphy was used to determine the glomerular filtration rate (GFR) of both kidneys and each kidney individually. Tc 99m-DTPA GFR was performed preoperatively and 3 mo postoperatively. In addition, we analysed Tc 99m-DTPA scintigraphy GFR regionally in the healthy areas of the affected kidney.

Results and limitations

Patients with WIT >28 min had a significantly greater decrease in the GFR of the affected kidney (p = 0.031). The GFR of the affected kidney showed a significant decrease perioperatively (46.4 ± 14.3 to 37.9 ± 11.9 ml/min per 1.73 m²; p = 0.003). The functional change of the nonaffected kidney showed an increasing trend (47.5 ± 13.8 to 51.4 ± 14.3 ml/min per 1.73 m²), although it was not statistically significant (p = 0.103). Regional Tc 99m-DTPA GFR of both affected kidney and nonaffected kidney showed no significant differences perioperatively (6.3 ± 1.8 to 6.1 ± 1.9 ml/min per 1.73 m²; p = 0.641; 6.6 ± 1.9 to 7.1 ± 2.0 ml/min per 1.73 m²; p = 0.200). On multivariate analysis, preoperative GFR, resected volume of marginal healthy tissue, and WIT were independent predictors for functional reduction of the affected kidney (p < 0.05). The study was limited by small numbers and short follow-up periods.

Conclusions

Stationary overall renal function after LPN or RAPN is masked possibly by functional compensation of the contralateral healthy kidney. The damage of the affected kidney estimated by scintigraphy occurs when WIT exceeds 28 min during partial nephrectomy under the pneumoperitoneum.     

Case report of endotracheal intubation using AirWay Scope (Pentax-AWS) in a Forestier's disease patient

A Forestier's disease patient was scheduled for endoscopic mucosal resection under general anesthesia, because of his hypoxic episode during gastric endoscopy. Endotracheal intubation was planned while awake, because he was suspected as a case of difficult airway. By using AWS, we could easily confirm his larynx and aditus of trachea in spite of his narrow pharynx caused by Forestier's disease. The procedure was successful with no complications. AWS seems to be a useful device for endotracheal intubation in Forestier's disease.     

Total hip replacement with a short metaphyseal-fitting anatomical cementless femoral component in patients aged 70 years or older

We reviewed the results of 84 total hip replacements performed with a short metaphyseal-fitting anatomical cementless femoral component in 84 unselected consecutive patients with a mean age of 78.9 years (70 to 88). The mean follow-up was 4.6 years (4 to 5). The mean pre-operative Harris hip score was 26 points (0 to 56), which improved to 89 (61 to 100) at the final follow-up. No patient had thigh pain. The mean pre-operative Western Ontario and McMaster Universities osteoarthritis index score was 61 points (48 to 75), which improved to 21 (6 to 46). The mean University of California, Los Angeles activity score was 5.5 points (3 to 7) at the final follow-up. Osseointegration was seen in all femoral and acetabular components. All hips had grade 1 stress shielding of the proximal femur. No acetabular or femoral osteolysis was identified. These results demonstrate that a short metaphyseal-fitting femoral component achieves optimal fixation without diaphyseal anchorage in elderly patients.