[Research status and existing problems of lumbar pedicle double-trajectory screw technique].

Lumbar pedicle double-trajectory screw technique refers to the placement of traditional pedicle screw combined with cortical bone trajectory screw in the same pedicle, which has been proved to provide higher fixation strength in osteoporotic vertebral body fixation, and is also a less invasive surgical choice for revision of adjacent segment disease. At present, related basic research and clinical application exploration of double-trajectory screw technique have been carried out, but there are still many problems that need to be further investigated and clarified. The clinical application and existing problems of double screw technique were discussed in this paper for clinical reference.

[Application expansion and related problems of lumbar cortical bone trajectory screw technique].

At the beginning of clinical application, CBT technique was mainly used for lumbar degenerative diseases in Elderly Patients, and single or double segments of lower lumbar vertebrae accounted for the majority. With the technical proficiency and equipment improvement, the types of diseases continue to expand, and CBT technique can be used in conjunction with traditional pedicle screw technology, which plays an important role in the revision of adjacent segment disease and fixation in lumbar vertebrae of patients with severe osteoporosis. However, CBT technology has not been widely used, and there are still related problems that need to be clarified and further studied.

[Clinical observation of the low back pain and posterior thigh pain in the early stage after percutaneous endoscopic lumbar discectomy].

Objective: To evaluate the incidence, causes and prognosis of the low back pain and posterior thigh pain in the early stage after percutaneous endoscopic lumbar discectomy (PELD). Methods: A total of 88 patients who underwent PELD from December 2017 to June 2018 in the First Affiliated Hospital of Anhui Medical University were enrolled in this study. PELD was performed by posterior-lateral approach and the interlaminar approach in 44 cases, respectively. During the 3-month of follow-up post PELD, the number of cases who suffered low back pain and posterior thigh pain, complications and postoperative treatments were all followed and evaluated. Results: All the 88 cases underwent PELD successfully. Twelve cases (27.3%) suffered low back pain after PELD by posterior-lateral approach totally, 4 patients (9.1%) were new cases and the low back pain aggravated after PELD in the other 8 cases (18.2%). The posterior thigh pain occurred in 9 cases (20.4%) after PELD in posterior-lateral approach group, of them, 5 patients (11.4%) were new cases and it was aggravated in 4(9.1%) cases after the surgery. As for the low back pain after PELD performed by the interlaminar approach, 7(15.9%) cases suffered low back pain and 1 case (2.3%) occurred after surgery. The posterior thigh pain happened in 5 cases (11.4%) after PELD in the interlaminar approach group, 2 cases (4.6%) were new cases and the pain was aggravated in 3 cases (6.8%) after surgery. According the classification of MacNab, 42 of 88 cases were classified excellent, 25 cases good, 17 cases fair and 4 cases poor after PELD. Totally 18 cases were classified into fair and poor because of the low back pain or the posterior thigh pain during the follow-up. Furthermore, none of 88 cases had infection or nerve root injury after surgery. All cases suffering the low back pain or the posterior thigh pain treated conservatively and no one needed surgery again. Conclusions: The pain in low back or posterior thigh may be one of the complications after PELD, and it can be treated conservatively. Incidence of the low back pain or the posterior thigh pain after PELD with posterior-lateral approach is higher than that in patients with interlaminar approach, and it may affect the efficacy of PELD.

Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial.

Tocotrienols have shown bone-protective effect in animals. This study showed that a 12-week tocotrienol supplementation decreased concentrations of bone resorption biomarker and bone remodeling regulators via suppressing oxidative stress in postmenopausal osteopenic women. INTRODUCTION: Tocotrienols (TT) have been shown to benefit bone health in ovariectomized animals, a model of postmenopausal women. The purpose of this study was to evaluate the effect of 12-week TT supplementation on bone markers (serum bone-specific alkaline phosphatase (BALP), urine N-terminal telopeptide (NTX), serum soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), and serum osteoprotegerin (OPG)), urine calcium, and an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine (8-OHdG)) in postmenopausal women with osteopenia. METHODS: Eighty-nine postmenopausal osteopenic women (59.7 ± 6.8 year, BMI 28.7 ± 5.7 kg/m2) were randomly assigned to three groups: (1) placebo (430 mg olive oil/day), (2) low TT (430 mg TT/day, 70% purity), and (3) high TT (860 mg TT/day, 70% purity). TT, an extract from annatto seed with 70% purity, consisted of 90% delta-TT and 10% gamma-TT. Overnight fasting blood and urine samples were collected at baseline, 6, and 12 weeks for biomarker analyses. Eighty-seven subjects completed the 12-week study. RESULTS: Relative to the placebo group, there were marginal decreases in serum BALP level in the TT-supplemented groups over the 12-week study period. Significant decreases in urine NTX levels, serum sRANKL, sRANKL/OPG ratio, and urine 8-OHdG concentrations and a significant increase in BALP/NTX ratio due to TT supplementation were observed. TT supplementation did not affect serum OPG concentrations or urine calcium levels throughout the study period. There were no significant differences in NTX level, BALP/NTX ratio, sRANKL level, and sRANKL/OPG ratio between low TT and high TT groups. CONCLUSIONS: Twelve-week annatto-extracted TT supplementation decreased bone resorption and improved bone turnover rate via suppressing bone remodeling regulators in postmenopausal women with osteopenia. Such osteoprotective TT's effects may be, in part, mediated by an inhibition of oxidative stress. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02058420. TITLE: Tocotrienols and bone health of postmenopausal women.

A study of predictors for hyponatraemia in patients with cervical spinal cord injury.

STUDY DESIGN: A retrospective study. OBJECTIVES: The objectives of the study were to investigate the predictors for hyponatraemia in patients with cervical spinal cord injuries (CSCIs) and to define the relationship between magnetic resonance imaging (MRI) scans and hyponatraemia. SETTING: The study was carried out at The First Affiliated Hospital of Anhui Medical University. METHODS: A total of 292 patients with CSCIs were retrospectively reviewed to determine the predictors of hyponatraemia. Fourteen variables were extracted from the medical records: age, sex, blood pressure (BP), tracheostomy, serum potassium, serum chloride, serum bicarbonate, serum albumin, intravenous fluid intake and urine volume for 24 h, haematocrit, haemoglobin, neurological assessment and four MRI signal patterns. Univariate and multivariate analyses were used to determine the effect of each variable on hyponatraemia. RESULTS: Eighty-two of the 270 patients (30%) developed hyponatraemia. Univariate analyses indicated that the following variables were significant predictors of hyponatraemia: tracheostomy; the initial American Spinal Injury Association (ASIA) Impairment Scale (AIS) A assessment; and haemorrhage changes on T2-weighted MRI scans, and low BP. Multivariate regression analyses revealed two variables were significant predictors of hyponatraemia: haemorrhage changes on T2-weighted MRI scans and low BP. CONCLUSIONS: Haemorrhage changes on MRI scans were closely associated with the onset of hyponatremia and could provide objective data for forecasting hyponatraemia in CSCI patients. Low BP was also a reasonable predictor of hyponatremia.

Clinical features and surgical outcomes of cervical spondylotic myelopathy in patients of different ages: a retrospective study.

STUDY DESIGN: Retrospective chart audit. OBJECTIVES: This study aims to compare the clinical features and surgical outcomes in patients with cervical spondylotic myelopathy (CSM) among different age groups. SETTING: The first Affiliated Hospital of Anhui Medical University, China. METHODS: A total of 460 patients with CSM who were surgically treated over the period of 1995-2009 were investigated. Considering the peak age (40-60 years old) for the onset of symptoms, we divided the patients into three groups by age: young (<40), middle-aged (40-60), and old (>60). The differences in symptoms, symptom durations, involved levels, surgical approaches and outcomes were evaluated. RESULTS: The number of symptoms and involved levels, symptom duration and posterior approach significantly increased with increasing age, whereas preoperative Japanese Orthopedic Association score decreased among the three groups. Spinal cord function improved after surgery in all groups. The highest degree of recovery occurred during the first 6 months after surgery, especially within the first week, and then reached a plateau. After 6 months, however, recovery continuously improved, stabilized and declined in the young, middle-aged, old groups, respectively. The recovery rate was not significantly different at an immediate period (1 week) after operation among the three groups, but was significantly different at later periods (3 or more months postoperatively). Three groups showed no difference in postoperative complication rates. CONCLUSION: The severity of CSM increased with increasing age. Age was inversely correlated with recovery, and recovery decreased as age increased. Six months post operation was the prime time for the recovery of spinal cord function.

Differences in musculoskeletal health due to gender in a rural multiethnic cohort: a Project FRONTIER study.

BACKGROUND: Very few studies have investigated differences in musculoskeletal health due to gender in a large rural population. The aim of this study is to investigate factors affecting musculoskeletal health in terms of hand grip strength, musculoskeletal discomfort, and gait disturbance in a rural-dwelling, multi-ethnic cohort. METHODS: Data for 1117 participants (40 years and older, 70% female) of an ongoing rural healthcare study, Project FRONTIER, were analyzed. Subjects with a history of neurological disease, stroke and movement disorder were excluded. Dominant hand grip strength was assessed by dynamometry. Gait disturbance including stiff, spastic, narrow-based, wide-based, unstable or shuffling gait was rated. Musculoskeletal discomfort was assessed by self-reported survey. Data were analyzed by linear, logistic regression and negative binomial regressions as appropriate. Demographic and socioeconomic factors were adjusted in the multiple variable analyses. RESULTS: In both genders, advanced age was a risk factor for weaker hand grip strength; arthritis was positively associated with musculoskeletal discomfort, and fair or poor health was significantly associated with increased risk of gait disturbance. Greater waist circumference was associated with greater musculoskeletal discomfort in males only. In females, advanced age is the risk factor for musculoskeletal discomfort as well as gait disturbance. Females with fair or poor health had weaker hand grip strength. Higher C-reactive protein and HbA1c levels were also positively associated with gait disturbance in females, but not in males. CONCLUSION: This cross-sectional study demonstrates how gender affects hand grip strength, musculoskeletal discomfort, and gait in a rural-dwelling multi-ethnic cohort. Our results suggest that musculoskeletal health may need to be assessed differently between males and females.

Phenotypic correction and stable expression of factor VIII in hemophilia A mice by embryonic stem cell therapy.

Hereditary deficiency of factor VIII (FVIII) leads to hemophilia A, a severe X-linked bleeding disorder. Current therapies include fixed-dose FVIII prophylaxis, factor replacement therapy, and most recently, gene therapy. Prophylaxis and FVIII replacement therapies are limited by incomplete efficacy, high cost, restricted availability, and development of neutralizing antibodies in chronically treated individuals. Limited success has been obtained in preclinical trials using gene therapy for the treatment of hemophilia. Therefore, new options for therapy for hemophilia A are needed. We evaluated the potential of embryonic stem cells for correcting hemophilia A in mice. FVIII-deficient mouse blastocysts were collected and injected with mouse embryonic stem cells stably expressing green-fluorescent protein (GFP) and transferred to pseudopregnant recipient mice. Expression of FVIII was measured in the liver and plasma of the 5 chimeric mice that were produced. Three of these mice were GFP-positive at the age of 6 months. The plasma FVIII activity levels were equal to those of wild-type mice. These data demonstrate that embryonic stem cell transplantation at an early embryonic stage has potential as therapy for this progressively debilitating, life-threatening bleeding disorder.

Effect of green tea and Tai Chi on bone health in postmenopausal osteopenic women: a 6-month randomized placebo-controlled trial.

UNLABELLED: Postmenopausal women with osteopenia received green tea polyphenols (GTP) supplement and/or Tai Chi exercise for 6 months. Bone turnover biomarkers, calcium metabolism, and muscle strength were measured. This study showed that GTP supplementation and Tai Chi exercise increased bone formation biomarkers and improved bone turnover rate. Tai Chi exercise increased serum parathyroid hormone. GTP supplementation, Tai Chi exercise, and the combination of the two all improved muscle strength in postmenopausal women with osteopenia. INTRODUCTION: This study evaluated the effect of GTP supplementation and Tai Chi (TC) exercise on serum markers of bone turnover (bone-specific alkaline phosphatase, BAP, and tartrate-resistant acid phosphatase, TRAP), calcium metabolism, and muscle strength in postmenopausal osteopenic women. METHODS: One hundred and seventy-one postmenopausal osteopenic women were randomly assigned to four groups: (1) placebo (500 mg starch/day), (2) GTP (500 mg GTP/day), (3) placebo + TC (placebo plus TC training at 60 min/session, three sessions/week), and (4) GTP + TC (GTP plus TC training). Overnight fasting blood and urine samples were collected at baseline, 1, 3, and 6 months for biomarker analyses. Muscle strength was evaluated at baseline, 3, and 6 months. One hundred and fifty subjects completed the 6-month study. RESULTS: Significant increases in BAP level due to GTP intake (at 1 month) and TC (at 3 months) were observed. Significant increases in the change of BAP/TRAP ratio due to GTP (at 3 months) and TC (at 6 months) were also observed. Significant main effect of TC on the elevation in serum parathyroid hormone level was observed at 1 and 3 months. At 6 months, muscle strength significantly improved due to GTP, TC, and GTP + TC interventions. Neither GTP nor TC affected serum TRAP, serum and urinary calcium, and inorganic phosphate. CONCLUSION: In summary, GTP supplementation and TC exercise increased BAP and improved BAP/TRAP ratio. TC exercise increased serum parathyroid hormone. GTP supplementation, TC exercise, and the combination of the two all improved muscle strength in postmenopausal women with osteopenia.

Green tea polyphenols attenuate deterioration of bone microarchitecture in female rats with systemic chronic inflammation.

UNLABELLED: Green tea polyphenols (GTP) are promising agents for preventing bone loss. GTP supplementation sustained microarchitecture and improved bone quality via a decrease in inflammation. Findings suggest a significant role for GTP in skeletal health of patients with chronic inflammation. INTRODUCTION: This study evaluated whether GTP can restore bone microstructure along with a molecular mechanism in rats with chronic inflammation. A 2 [placebo vs. lipopolysaccharide (LPS)]× 2 [no GTP vs. 0.5% GTP (w/v) in drinking water] factorial design was employed. METHODS: Female rats were assigned to four groups: placebo, LPS, placebo + GTP, and LPS + GTP for 12 weeks. Efficacy was evaluated by examining changes in bone microarchitecture using histomorphometric and microcomputed tomographic analyses and by bone strength using the three-point bending test. A possible mechanism was studied by assessing the difference in tumor necrosis factor-α (TNF-α) expression in tibia using immunohistochemistry. RESULTS: LPS lowered trabecular volume fraction, thickness, and bone formation in proximal tibia while increasing osteoclast number and surface perimeter in proximal tibia and eroded surface in endocortical tibial shafts. GTP increased trabecular volume fraction and number in both femur and tibia and periosteal bone formation rate in tibial shafts while decreasing trabecular separation in proximal tibia and eroded surface in endocortical tibial shafts. There was an interaction between LPS and GTP in trabecular number, separation, bone formation, and osteoclast number in proximal tibia, and trabecular thickness and number in femur. GTP improved the strength of femur, while suppressing TNF-α expression in tibia. CONCLUSION: In conclusion, GTP supplementation mitigated deterioration of bone microarchitecture and improved bone integrity in rats with chronic inflammation by suppressing bone erosion and modulating cancellous and endocortical bone compartments, resulting in a larger net bone volume. Such a protective role of GTP may be due to a suppression of TNF-α.

Microstructure and crystallization kinetics analysis of the (In15Sb85)(100-x)Zn(x) phase change recording thin films.

The (In15Sb85)(100-x)Zn(x) films (x = 0 - 17.4) were deposited on nature oxidized Si wafer and glass substrate at room temperature by magnetron co-sputtering of Sb target and InZn composite target. The thermal property of the films was examined by a homemade reflectivity thermal analyzer. Microstructures of the films were analyzed by transmission electron microscope (TEM). We examined the effects of Zn addition on the thermal property, crystallization kinetics, and crystallization mechanism of the In15Sb85 recording film. As x = 0 - 17.4, thermal analysis shows that the (In15Sb85)(100-x)Zn(x) films have two phase transition temperature ranges which are 189 degrees C-215 degrees C and 300 degrees C-350 degrees C. It is found that the activation energy is increased with Zn content. This indicates that the thermal stability of amorphous state is improved by doping Zn. The optical contrasts of the films are all larger than 15%, as x = 0 - 6.2, indicating that the films have the potential in blue laser optical recording media application.

Effect of Ag underlayer on microstructures and perpendicular magnetic properties of CoPt nanocomposite thin films.

CoPt/Ag films were prepared by magnetron sputtering on glass substrates and subsequent annealing. The dependence of degree of ordering and magnetic properties on Ag film thickness and annealing conditions were investigated. It was found that the Ag underlayer played a dominant role in inducing the (001) texture of the CoPt film after annealing. CoPt films with a thickness about 20 nm and Ag underlayers with a thickness about 70 nm are easy to obtain a large degree of ordering and a perpendicular magnetic anisotropy after annealing at 700 degrees C for 30 min. CoPt/Ag films with out-of-plane coercivity (Hc (perpendicular)) in the range of 13.5-14.0 kOe and a out-of-plane squareness (S(perpendicular)) of 0.97 were obtained after annealing at 700 degrees C for 30 min. Ag underlayer is beneficial to enhance the Hc(perpendicular)and S(perpendicular) of CoPt film significantly. The degree of ordering and perpendicular magnetic properties of the CoPt films which deposited on Ag underlayer are larger than those of the single layer CoPt films.

Crystallization mechanisms of phase change (GeSbSn)(100-x)Co(x) optical recording films.

In this study, the (GeSbSn)(100-x0Co(x) films (x = 0-13.3) were deposited on natural oxidized silicon wafer and glass substrate by dc magnetron co-sputtering of GeSbSn and Co targets. The ZnS-SiO2 films were used as protective layers. The thicknesses of the (GeSbSn)(100-x)Co(x) films and protective layer were 100 nm and 30 nm, respectively. We investigated the effects of Co addition on the thermal property, crystallization kinetics, and crystallization mechanism of the GeSbSn recording film. The crystallization temperatures of (GeSbSn)(100-x)Co(x) films were decreased with Co content. It was found that the activation energy of the (GeSbSn)(100-x)Co(x) films will decrease from 1.53 eV to 0.55 eV as Co content increased from 0 at.% to 13.3 at.%.

Synergistic effects of green tea polyphenols and alphacalcidol on chronic inflammation-induced bone loss in female rats.

UNLABELLED: Studies suggest that green tea polyphenols (GTP) or alphacalcidol is promising agent for preventing bone loss. Findings that GTP supplementation plus alphacalcidol administration increased bone mass via a decrease of oxidative stress and inflammation suggest a significant role of GTP plus alphacalcidol in bone health of patients with chronic inflammation. INTRODUCTION: Studies have suggested that green tea polyphenols (GTP) or alphacalcidol are promising dietary supplements for preventing bone loss in women. However, the mechanism(s) related to the possible osteo-protective role of GTP plus D(3) in chronic inflammation-induced bone loss is not well understood. METHODS: This study evaluated bioavailability, efficacy, and related mechanisms of GTP in combination with alphacalcidol in conserving bone loss in rats with chronic inflammation. A 12-week study of 2 (no GTP vs. 0.5% GTP in drinking water) × 2 (no alphacalcidol vs. 0.05 µg/kg alphacalcidol, 5×/week) factorial design in lipopolysaccharide-administered female rats was performed. In addition, a group receiving placebo administration was used to compare with a group receiving lipopolysaccharide administration only to evaluate the effect of lipopolysaccharide. RESULTS: Lipopolysaccharide administration resulted in lower values for bone mass, but higher values for serum tartrate-resistant acid phosphatase (TRAP), urinary 8-hydroxy-2'-deoxyguanosine, and mRNA expression of tumor necrosis factor-α and cyclooxygenase-2 in spleen. GTP supplementation increased urinary epigallocatechin and epicatechin concentrations. Both GTP supplementation and alphacalcidol administration resulted in a significant increase in bone mass, but a significant decrease in serum TRAP levels, urinary 8-hydroxydeoxyguanosine levels, and mRNA expression of tumor necrosis factor-α and cyclooxygenase-2 in spleen. A synergistic effect of GTP and alphacalcidol was observed in these parameters. Neither GTP nor alphacalcidol affected femoral bone area or serum osteocalcin. CONCLUSION: We conclude that a bone-protective role of GTP plus alphacalcidol during chronic inflammation bone loss may be due to a reduction of oxidative stress damage and inflammation.

[Effect of customized zirconia abutment on peri-implant tissue: a one-year prospective study].

Objective: To observe the changes of peri-implant tissue around the individualized abutment that was grinded from zirconia provisional crown in one year. Methods: In this research, a prosthodontic-driven virtual implant planning and immediate provisionalization were conducted in computer assisted design software. And computer-aided design/computer-aided manufacturing (CAD/CAM) techniques were used to fabricate the zirconia provisional crown and surgical guide template before surgery. The implant was accurately placed with the surgical guide, and the zirconia provisional crown was immediately delivered after surgery. Three months later, the implant osseointegration was completed, and zirconia provisional crown was prepared intraorally to generate customized zirconia abutment for final prosthesis. The study included 30 patients with single anterior tooth loss, including 18 males and 12 females, aged from 26 to 50 years old, and the mean age was (36.2±6.1) years old. The patients were from the Center of Oral Implantology, The First Affiliated Hospital of Zhejiang University Medical College from January 2017 to February 2018. After cementation of the final prosthesis, the cases were followed up at 6 and 12 months time intervals. Implant survival rate, probing depth, bleeding on probing, marginal bone level loss and papilla index score (PIS) were recorded in every appointment. Results: The survival rate of 30 implants was 100%, and the probing depths were less than 5 mm. The bone resorption at 6 and 12 months follow-up after the final delivery was 0 (0, 0) mm and 0 (-0.2, 0) mm, respectively, and the difference was not statistically significant (P>0.05). The PIS was 3.0 (2.0, 4.0), 3.0 (2.8, 4.0) and 3.0 (3.0, 4.0) on the final delivery, 6 and 12 months after final delivery, respectively. Conclusions: Marginal bone level and bone loss were stable with this new implant clinical protocol at the one-year follow-up.

DNMT3A-mediated down-regulation of microRNA-105 promotes gastric cancer cell proliferation.

OBJECTIVE: It has been well-established that microRNAs (miRNAs), a class of short non-coding RNA molecules, play an important role in the development of gastric cancer. In the present study, we focused on miR-105, a novel miRNA not previously linked to gastric cancer. PATIENTS AND METHODS: 36 paired surgically resected gastric cancer tissues and matched adjacent normal tissues were used to detect the expression of miR-105. AGS cells were used to overexpress or silence of miR-105 and to determine its effect on several tumorigenic properties. A cell proliferation enzyme-linked immunosorbent assay was used to analyze the incorporation of BrdU during DNA synthesis of AGS cells. Total cDNA from AGS cells was used to amplify the 3'-UTR of YY1 by PCR and luciferase activity was determined using the Dual-Luciferase Reporter Assay System RESULTS: We found that expression of miR-105 was reduced in gastric cancer tissues, compared with adjacent normal tissues, due to hypermethylation at its promoter region. Overexpression of miR-105 suppressed, whereas its inhibition promoted cell viability and proliferation. We further identified Yin Yang 1 (YY1) as a direct target of miR-105, by which miR-105 exerted its anti-proliferative role. Moreover, we found that DNMT3A was responsible for the down-regulation of miR-105 in gastric cancer cells. CONCLUSIONS: Our data demonstrate that miR-105 inhibits gastric cancer cell proliferation and progression, which might provide a therapeutical target for cancer therapy.

Ablation of Tacr2 in mice leads to gastric emptying disturbance.

BACKGROUND: Tacr2 is one of the G protein-coupled receptors(GPCRs) that mediate the biological actions of tachykinins. It is abundantly expressed in the gastrointestinal (GI) system and is thought to play an important role in GI motility, secretion, and visceral sensitivity. Previously, the physiological and pathophysiological functions of Tacr2 were mainly studied using Tacr2 selective agonists or antagonists. Here, we seek to investigate the effect of Tacr2 disruption in mice to provide further insights. METHODS: The Tacr2 knockout mice were generated by homologous recombination and the phenotypic changes of the Tacr2-null mice were analyzed and compared with their wild type (wt) littermates. KEY RESULTS: Increased food retention was detected in Tacr2-/- mice. The stomach of Tacr2-/- mice had thinner muscularis externa and less neurons in the myenteric plexus. The stomach and small intestine exhibited longer duration of electrical field stimulation (EFS)-induced inhibition in the gastric fundus and decreased frequency of migrating motor complex (MMC), respectively. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were significantly up-regulated due to Tarc2 deficiency, contributing to enhanced nitric oxide (NO) signaling in the stomach of Tacr2-/- mice. Intraperitoneal application of 7-nitroindazole (7-NI) to Tacr2-/- mice effectively relieved the gastric emptying disturbance. Moreover, Creb and NF-κB signalings were involved in the regulation of these physiological changes initiated by Tacr2 deficiency. CONCLUSIONS & INFERENCES: Tacr2 negatively regulated the expression of nNOS and VIP both in vivo and in vitro. Its ablation in mice elevated the expression of nNOS and VIP, enhanced NO signaling and changed the Creb and NF-κB signalings, finally leading to the gastric emptying disturbance of Tacr2-/- mice.

Dietary (n-3) and (n-6) polyunsaturates and acetylsalicylic acid alter ex vivo PGE2 biosynthesis, tissue IGF-I levels, and bone morphometry in chicks.

This study examined the effects of dietary (n-6) and (n-3) polyunsaturated fatty acids (PUFA) and acetylsalicylic acid (ASA) on bone ash content, morphometry, fatty acid composition, ex vivo PGE2 biosynthesis, tissue IGF-I concentration, and serum alkaline phosphatase (ALPase) activity in chicks. Newly hatched chicks were fed a semipurified diet containing soybean oil (S) or menhaden oil / safflower oil (M) at 90 g/kg. At 4 days of age, chicks were divided into four equal treatment groups receiving 0 mg [symbol: see text] or 500 mg [symbol: see text] of ASA/kg of diet: S[symbol: see text]ASA, M[symbol: see text]ASA, S[symbol: see text]ASA, and M[symbol: see text]ASA. Lipid and ASA treatments did not affect bone length, bone ash, or bone mineral content in chicks. Chicks fed M had increased fractional labeled trabecular surface and tissue level bone formation rates, independent of ASA treatment, compared with those given S. A significant fat x ASA interaction effect was found for trabecular bone volume, thickness, separation, and number. Chicks fed S had higher 20:4(n-6) but lower 20:5(n-3) concentrations in liver and bone compared with those given M. Ex vivo PGE2 biosynthesis was higher in liver homogenates and bone organ cultures of chicks fed S compared with the values for those given M at 17 days. ASA treatment decreased ex vivo PGE2 production in liver homogenates and bone organ cultures of chicks, independent of the dietary lipids. Chicks fed ASA had a lower concentration of IGF-I in tibiotarsal bone compared with those not given ASA at 19 days. Serum ALPase activity was higher in chicks given M compared with those fed S, but the values were reversed with ASA feeding. This study demonstrated that both dietary fat and ASA modulated bone PGE2 biosynthesis, and that (n-3) PUFA and fat x ASA interactions altered bone morphometry.

Interactions of selenium compounds with other antioxidants in DNA damage and apoptosis in human normal keratinocytes.

Selenite (SeL) or selenomethionine (SeM) are the most common selenium (Se) compounds taken as dietary antioxidants to reduce oxidative stress. Because the public may frequently supplement Se compounds at high doses, the possible pro-oxidant effect of Se becomes a concern. SeL and SeM have entirely different pharmacokinetic effects based on dose-related cytotoxicity. Our laboratory has shown previously that high doses of SeL resulted in cytotoxicity and induction of 8-hydroxydeoxyguanosine (8-OHdG) in DNA of primary human keratinocytes (NHK), compared with those treated with the same doses of SEM: Besides Se compounds, other dietary antioxidants, such as vitamin (Vit) C or Vit E, are often supplemented and taken together with Se compounds. However, the cellular effects of these interactions of Se with antioxidants are still unknown. In addition, copper is commonly present in drinking water, food, soil, or the environment to increase the possibility of subchronic toxicity. Copper has been shown to inhibit SeL-induced cytotoxicity and apoptosis in human colonic carcinoma cells. The present study was designed to investigate the interactive effects of SeL or SeM plus Vit C, trolox (a water-soluble Vit E), or copper sulfate (CuSO(4)) on cell viability and induction of 8-OHdG adduct formation in DNA of NHK. NHK cells were treated with no Se, SeL (126.6 microM Se), or SeM (316.6 microM Se) plus two doses each of Vit C (2.27 and 4.45 microM), trolox (40 and 80 microM), or CuSO(4) (7.85 and 15.7 microM) for 24 h. Coincubation of Vit C or CuSO(4) with SeL appeared to protect NHK against SeL-induced cytotoxicity. However, synergistic effects were observed between SeL and trolox resulting in enhanced cytotoxicity. On the other hand, SeM + Vit C, SeM + trolox, and SeM + CuSO(4) did not affect cell viability. In the absence of Se supplementation, Vit C, trolox, or CuSO(4) alone did not induce 8-OHdG adduct formation, regardless of dose. When NHK cells were coincubated with SeL (126.6 microM Se) and Vit C or CuSO(4), they protected NHK from SeL-induced DNA damage with a reduction in 8-OHdG generation. In contrast, treatment of SeL + trolox elevated generation of 8-OHDG: Furthermore, treatments of SeM plus trolox or CuSO(4) elevated 8-OHdG adduct formation. In terms of apoptosis measured as internucleosomal DNA fragmentation, copper protected NHK against SeL-induced apoptosis in cultured NHK. These data suggest that the use of CuSO(4) may play a protective role in SeL-induced cytotoxicity, DNA oxidative damage, and apoptosis and that there may be potentially deleterious interactions among common high-dose antioxidant supplements taken by the public.

6-Hydroxydopamine induces thymocyte apoptosis in mice.

6-Hydroxydopamine (6-OHDA) induces degeneration of noradrenergic nerves and has been shown to alter the immune responses. In this study, intraperitoneal administration of 6-OHDA induces mouse thymus atrophy. The lowest levels of thymus weight and cell number were reached at days 3 and 5 in mice receiving 6-OHDA treatment; they gradually recovered thereafter. On flow cytometry analysis, the most substantial reductions were recorded for CD4+CD8+ thymocytes, although the numbers of other subpopulations, i.e. CD4+CD8-, CD4-CD8+ and CD4-CD8- cells were also reduced. DNA fragmentation, a characteristic of apoptosis, was detected in the thymocytes following 6-OHDA injection. Pretreatment with desipramine greatly blocked the reduction in thymus size and thymocyte number, the changes in thymocyte subpopulations, the percentage of subdiploid (apoptotic) cells and the appearance of DNA fragmented bands. Furthermore, 6-OHDA-induced thymocyte apoptosis could also be detected in vitro, and was blocked by desipramine treatment. These results indicate that 6-OHDA induces mouse thymocytes to undergo apoptosis both in vivo and in vitro, and this effect is inhibited by catecholamine uptake blocker.