Permeability characteristics of monovalent cations in atrial myocytes of the rat heart

We investigated the permeability of Cs+ and Na+ through various ion channels in rat atrial myocytes using the whole-cell voltage-clamp technique. With isotonic CsCl (140 mM) on both sides of the membrane and nominally [Ca2+]o-free conditions, depolarising clamp pulses induced an increase of outward currents which showed a biphasic time course. Repolarisation to the holding potential induced inward tail currents. With isotonic NaCl, depolarisation also induced outward currents which showed a monotonic decay, but inward tail currents were not observed. Both in NaCl and CsCl, currents were hardly affected by TEA (10 mM), 4-AP (5 mM) and DIDS (100 microM). Nicardipine (1 M) almost completely blocked time-dependent outward currents in isotonic NaCl solution, leaving only time-independent currents which showed linear I-V relationship. In isotonic CsCl conditions, nicardipine blocked outward current considerably, but there still remained time-dependent outward currents and inward tail currents. Addition of E-4031 (2-20 M) which is known as a specific blocker of the rapidly activating delayed rectifier K+ current (IKr) completely blocked these time-dependent outward and inward currents, leaving only a time-independent current. Time-independent currents recorded in the presence of nicardipine and E-4031 were inhibited by GdCl3, which is known to block non-selective cation (NSC) currents. From these results, it was suggested that NSC current in atrial myocytes can be investigated in isotonic Cs+ or Na+ solution in the presence of Ca2+ channel and IKr blockers.     

3D CT analysis of femoral and tibial tunnel positions after modified transtibial single bundle ACL reconstruction with varus and internal rotation of the tibia

IntroductionWe analyzed the location of femoral and tibial tunnels by three-dimensional (3D) CT reconstruction images after modified transtibial single bundle (SB) anterior cruciate ligament (ACL) reconstruction, creating a femoral tunnel with varus and internal rotation of the tibia.Material and methodsData from 50 patients (50 knees) analyzed by 3D CT after modified transtibial SB ACL reconstructions were evaluated. 3D CT images were analyzed according to the quadrant method by Bernard at the femur and the technique of Forsythe at the tibia.ResultsThe mean distance of the femoral tunnel center locations parallel to the Blumensaat's line was 29.6% ± 1.9% along line t measured from the posterior condylar surface. The mean distances perpendicular to the Blumensaat's line were 37.9% ± 2.5% along line h measured from the Blumensaat's line. At the tibia, the mean anterior-to-posterior distance for the tunnel center location was 37.8% ± 1.2% and the mean medial-to-lateral distance was 50.4% ± 0.9%.DiscussionThe femoral and tibial tunnels after modified transtibial SB ACL reconstruction creating a femoral tunnel with varus and internal rotation of the tibia (figure-of-4 position) were located between the anatomical anteromedial and posterolateral footprints.     

Urban-Rural Differences Explain the Association between Serum 25-Hydroxyvitamin D Level and Insulin Resistance in Korea

An increasing number of studies report associations between low serum 25-hydroxyvitamin D [25(OH)D] level and insulin resistance; however, whether low vitamin D levels directly contribute to increased insulin resistance is unclear. We investigated the impact of residential area on the association between 25(OH)D and insulin resistance in elderly Koreans. Using data from the Korean Urban Rural Elderly study, we conducted cross-sectional analyses in 1628 participants (505 men and 1123 women). Serum 25(OH)D was analyzed as both continuous and categorized variables. Homeostasis model assessment for insulin resistance (HOMA-IR) was calculated using fasting blood glucose and insulin levels. In men, 25(OH)D level was inversely associated with HOMA-IR (standardized β = −0.133, p < 0.001) after adjustment for age, body mass index, waist circumference, smoking, alcohol intake, exercise, and study year. However, we noted significant urban-rural differences in 25(OH)D level (43.4 versus 65.6 nmol/L; p < 0.001) and HOMA-IR (1.2 versus 0.8 mmol·pmol/L²; p < 0.001). When we additionally adjusted for residential area, the association between 25(OH)D and HOMA-IR was attenuated (standardized β = −0.063, p = 0.115). In women, the association between 25(OH)D and HOMA-IR was not significant before or after adjustment for residential area. Environmental or lifestyle differences in urban and rural areas may largely explain the inverse association between serum 25(OH)D and insulin resistance.     

Uptake and Cytotoxicity of Docetaxel-Loaded Hyaluronic Acid-Grafted Oily Core Nanocapsules in MDA-MB 231 Cancer Cells

Purpose

It is hypothesized that docetaxel (Doc)-loaded hyaluronic acid (HA)-polyethylene glycol/poly(ε-caprolactone)-grafted oily core nanocapsules (NCs) can enhance the drug cytotoxicity and uptake in CD44 expressing breast cancer (BC) cells (MDA-MB 231).

Methods

NCs were prepared, optimized and characterized by dynamic light scattering, transmission electron microscopy (TEM), and powder X-ray diffraction (PXRD). In vitro cytotoxicity tests [MTS, level of reactive oxygen species (ROS) and level of reduced glutathione (GSH)] were performed in BC cells. The contribution of CD44 to the NCs cellular uptake was elucidated using an anti CD44 antibody blockage and a CD44 negative NIH3T3 cell line.

Results

The optimum formulation of Doc-loaded HA oily core NCs had respective mean diameter, polydispersity, and drug encapsulation efficiency of 224.18 nm, 0.32, and 60.38%. The NCs appeared spherical with low drug crystallinity, while the drug release data fitted to first order equation. Compared to that of ungrafted NCs, the cytotoxicity of Doc-loaded HA-grafted NCs was significantly enhanced (p<0.05). A decrease of the intracellular level of ROS was reversely correlated with that of GSH. Interestingly, the cellular internalization of HA-grafted NCs mediated CD44 was dramatically enhanced (3 to 4-fold) with respect to the absence of specific biomarker or targeting ligand.

Conclusions

The use of HA-grafted NCs enhanced the selective drug payload, cytotoxicity and uptake in MDA-MB 231 cells. Therefore, it could be a promising template for safe and effective delivery of Doc and similar chemotherapeutic agents in cancer cells.     

Platycodon grandiflorum extract represses up-regulated adipocyte fatty acid binding protein triggered by a high fat feeding in obese rats

AIM： To investigate the effect of Platycodon grandiflorum extract （PGE） on lipid metabolism and FABP mRNA expression in subcutaneous adipose tissue of high fat diet-induced obese rats.
METHODS： PGE was treated to investigate the inhibitory effect on the pre-adipocyte 3T3-L1 differentiation and pancreatic lipase activity. Male Sprague-Dawley rats with an average weight of 439.03± 7.61 g were divided into four groups： the control groups that fed an experimental diet alone （C and H group） and PGE treatment groups that administered PGE along with a control diet or HFD at a concentration of 150 mg/kg body weight （C ＋ PGE and H ＋ PGE group, respectively） for 7 wk. Plasma total cholesterol （TC） and triglycerol （TG） concentrations were measured from the tail vein of rats. Adipocyte cell area was measured from subcutaneous adipose tissue and the fatty acid binding protein （FABP） mRNA expression was analyzed by northern blot analysis.
RESULTS： PGE treatment inhibited 3T3-L1 pre-adipocyte differentiation and fat accumulation, and also decreased pancreatic lipase activity. In this experiment, PGE significantly reduced plasma TC and TG concentrations as well as body weight and subcutaneous adipose tissue weight. PGE also significantly decreased the size of subcutaneous adipocytes. Furthermore, it significantly repressed the up-regulation of FABP mRNA expression induced by a high-fat feeding in subcutaneous adipose tissue.
CONCLUSION： PGE has a plasma lipid lowering-effect and anti-obesity effect in obese rats fed a high fat diet.From these results, we can suggest the possibility that PGE can be used as a food ingredient or drug component to therapeutically control obesity.     

Postoperative management after total hip and knee arthroplasty

Despite major advances in the field of total joint arthroplasty, a standardized postoperative management protocol currently does not exist following total hip arthroplasty (THA) and total knee arthroplasty (TKA). A survey was mailed to the active members of the American Association of Hip and Knee Surgeons to investigate issues such as postoperative rehabilitation and activity restriction. The information derived from this survey provides the total joint surgeon with a compilation and consensus of responses that can serve as the foundation for a standardized postoperative protocol for THA and TKA surgery.     

The Nuss procedure for pectus excavatum: evolution of techniques and early results on 322 patients

BACKGROUND: The Nuss procedure is a minimally invasive technique using a retrosternal bar to repair pectus excavatum. Although its technical simplicity and cosmetic advantages are remarkable, early applications have been limited to children with symmetrical pectus excavatum. We report a large single-institution experience including technical modifications to correct asymmetric configurations and extend the procedure to adult patients. METHODS: We retrospectively reviewed 322 consecutive patients who underwent repair of pectus excavatum by the Nuss technique and its modifications between August 1999 and June 2002. Of the patients 251 (78%) were children and 71 (22%) were adults. Precise morphologic characterization of the pectus allowed appropriate shaping of the bar to achieve a symmetric repair. RESULTS: Of the 322, 185 (57%) had symmetric and 137 (43%) had asymmetric pectus excavatum. Within the asymmetric group 71 were eccentric, 47 were unbalanced, and 19 were combined. Modifications to the shape of the bar including asymmetric and seagull bars were developed to deal with these types of asymmetry. A double bar or compound bar technique was used in most of the adults. Multipoint wire fixations to ribs were utilized to prevent bar rotation. Postoperative complications included pneumothorax (n = 24, 7.5%) and bar displacement (n = 11, 3.4%). The bar was removed in 42 patients 2 years after the initial procedure. CONCLUSIONS: Precise morphologic classification has led to modifications of the Nuss technique that facilitate correction of virtually all varieties of pectus excavatum including patients with asymmetric varieties and adults.     

Discoid lateral meniscus: evaluation and treatment

Although the etiology of the discoid lateral meniscus (DLM) has been the subject of debate, the entity is now believed to result from abnormal development secondary to a deficiency in normal attachments. In children younger than 10 years, snapping knee syndrome is pathognomonic for an unstable DLM. In adolescents, clinical presentation varies and often includes symptoms typically found with meniscal tears. The asymptomatic DLM does not require surgery. Treatment for the symptomatic stable DLM is directed toward arthroscopic saucerization with preservation of enough meniscus to maintain some biomechanical function. Recent reports of meniscal repair for the unstable Wrisberg meniscus have been encouraging. Optimal treatment for DLM requires a high index of suspicion in the appropriate clinical setting and up-to-date knowledge of available therapeutic modalities.