Magnesium exposure increases hip fracture risks in patients with chronic kidney disease: a population-based nested case-control study.

This population-based study demonstrates a strong link between Mg-containing antacid exposure and hip fracture risk in nondialysis CKD and dialysis patients. As an Mg-containing antacid, MgO is also commonly used as a stool softener, which can be effortlessly replaced by other laxatives in CKD patients to maintain bone health. PURPOSE: Bone fracture is a severe complication in chronic kidney disease (CKD) patients, leading to disability and reduced survival. In CKD patients, blood magnesium (Mg) concentrations are usually above the normal range due to reduced kidney excretion of Mg. The present study examines the association between Mg-containing antacid exposure and the risk of hip fracture of CKD patients. METHODS: In this nationwide nested case-control study, we enrolled 44,062 CKD patients with hip fracture and 44,062 CKD matched controls, among which the mean age was 77.1 years old, and 87.9% was nondialysis CKD. RESULTS: As compared to non-users, Mg-containing antacid users were significantly more likely to experience hip fracture (adjusted odds ratio (OR) 1.36, 95% CI, 1.32 to 1.41; p < 0.001). Subgroup analysis showed that such risk exists in both nondialysis CKD patients and long-term dialysis patients. In contrast, aluminum or calcium-containing-antacid use did not reveal such association. Next, we examined the influence of Mg-containing antacid dosage on hip fracture risk, the adjusted ORs in the first quartile (Q1), Q2, Q3, and Q4 were 1.20 (95% CI, 1.15 to 1.25; p < 0.001), 1.35 (95% CI, 1.30 to 1.41; p < 0.001), 1.49 (95% CI, 1.43 to 1.56; p < 0.001), and 1.54 (95% CI, 1.47 to 1.61; p < 0.001), respectively, showing that such risk exists regardless of the antacid dosage. A receiver operating characteristic curve analysis demonstrated that the best cutoff value of the exposed Mg dose to discriminate the hip fracture is 532 mEq during the follow-up period. CONCLUSION: This population-based study demonstrates a strong link between Mg-containing antacid exposure and the hip fracture risk in both nondialysis CKD and dialysis patients.

Is removal of the implants needed after fixation of burst fractures of the thoracolumbar and lumbar spine without fusion? a retrospective evaluation of radiological and functional outcomes.

METHODS: In this study of patients who underwent internal fixation without fusion for a burst thoracolumbar or lumbar fracture, we compared the serial changes in the injured disc height (DH), and the fractured vertebral body height (VBH) and kyphotic angle between patients in whom the implants were removed and those in whom they were not. Radiological parameters such as injured DH, fractured VBH and kyphotic angle were measured. Functional outcomes were evaluated using the Greenough low back outcome scale and a VAS scale for pain. RESULTS: Between June 1996 and May 2012, 69 patients were analysed retrospectively; 47 were included in the implant removal group and 22 in the implant retention group. After a mean follow-up of 66 months (48 to 107), eight patients (36.3%) in the implant retention group had screw breakage. There was no screw breakage in the implant removal group. All radiological and functional outcomes were similar between these two groups. Although solid union of the fractured vertebrae was achieved, the kyphotic angle and the anterior third of the injured DH changed significantly with time (p < 0.05). DISCUSSION: The radiological and functional outcomes of both implant removal and retention were similar. Although screw breakage may occur, the implants may not need to be removed. TAKE HOME MESSAGE: Implant removal may not be needed for patients with burst fractures of the thoracolumbar and lumbar spine after fixation without fusion. However, information should be provided beforehand regarding the possibility of screw breakage.

The prognosis for patients with osteosarcoma who have received prior manipulative therapy.

We evaluated the long-term outcome of patients with an osteosarcoma who had undergone prior manipulative therapy, a popular treatment in Asia, and investigated its effects on several prognostic factors. Of the 134 patients in this study, 70 (52%) patients had manipulative therapy and 64 (48%) did not. The age, location, and size of tumour were not significantly different between the groups. The five-year overall survival rate was 58% and 92% in the groups with and without manipulative therapy (p = 0.004). Both the primary and overall rates of lung metastasis were significantly higher in the manipulative group (primary: 32% vs 3%, p = 0.003; overall lung metastasis rate: 51.4% vs 18.8%, p < 0.001). Patients who had manipulative therapy had higher local recurrence rates in comparison to patients who did not (29% vs 6%, p = 0.011). The prognosis for patients with osteosarcoma who had manipulative therapy was significantly poorer than those who had not. Manipulative therapy was an independent factor for survival. This form of therapy may serve as a mechanism to accelerate the spread of tumour cells, and therefore must be avoided in order to improve the outcome for patients with an osteosarcoma.

Isolation and characterization of stem cells from the human parathyroid gland.

OBJECTIVES: Somatic stem cells can be obtained from a variety of adult human tissues. However, it was not clear whether human parathyroid glands, which secrete parathyroid hormones and are essential in maintaining homeostasis levels of calcium ions in the circulation, contained stem cells. We aimed to investigate the possibility of isolating such parathyroid-derived stem cells (PDSC). MATERIALS AND METHODS: Surgically removed parathyroid glands were obtained with informed consent. Cell cytogenetics was used to observe chromosomal abnormalities. Surface phenotypes were characterized by flow cytometry. Telomerase repeat amplification protocol (TRAP) assay was performed to observe the telomerase activity. RT-PCR and real-time PCR was was used to detect gene expressions. Real-time calcium uptake imaging was performed for extent of calcium uptake and transmission electron microscopy and immunofluorecent staining for smooth muscle actin. RESULTS: After enzymatic digestion and primary culture, plastic-adherent, fibroblast-like cells appeared in culture and a morphologically homogeneous population was derived from subsequent limiting dilution and clonal expansion. Karyotyping was normal and doubling time of clonal cell growth was estimated to be 70.7 +/- 14.5 h (mean +/- standard deviation). The surface phenotype of the cells was positive for CD73, CD166, CD29, CD49a, CD49b, CD49d, CD44, CD105, and MHC class I, and negative for CD34, CD133, CD117, CD114, CD31, CD62P, EGF-R, ICAM-3, CD26, CXCR4, CD106, CD90 and MHC class II, similar to mesenchymal stem cells (MSC). Detectable levels of telomerase activity along with pluripotency Sall4 gene expression were observed from the isolated PDSCs. Expression of calcium-sensing receptor gene along with alpha-smooth muscle actin was induced and cellular uptake of extracellular calcium ions was observed. Furthermore, PDSCs possessed osteogenic, chondrogenic and adipogenic differentiation potentials. CONCLUSIONS: Our results reveal that PDSCs were similar phenotypically to MSCs and further studies are needed to formulate induction conditions to differentiate PDSCs into parathyroid hormone-secreting chief cells.

Isolation and characterization of multipotent stem cells from human cruciate ligaments.

OBJECTIVES: Mesenchymal stem cells have great potential for tissue regeneration, and these cells can be harvested from a variety of tissues; however, up to now it has not been clear whether stem cells could be isolated from cruciate ligaments of the knee joint. The aim of our study was to isolate and characterize stem cells from both anterior and posterior cruciate ligaments (ACL and PCL) of humans. MATERIALS AND METHODS: Cruciate ligaments were obtained from patients receiving total knee arthroplasty for advanced osteoarthritis and plastic-adherent cells were serially passaged. In vitro chondrogenic, osteogenic and adipogenic abilities of the cells were evaluated by reverse transcriptase-polymerase chain reaction and histological study. Karyotyping and surface immunophenotyping of the cells were performed. RESULTS: It was found that a population of ligament-derived cells could be expanded and subcultured extensively. These cells were able to differentiate into osteoblasts, chondrocytes and adipocytes under appropriate inductions. Their phenotypic characteristics were similar to those of bone marrow mesenchymal stem cells. Karyotyping was normal after serial passage. CONCLUSIONS: In summary, our study demonstrates that human multipotent stem cells can be isolated and expanded from human ACL and PCL, which are easily obtained from patients following total knee or cruciate ligament reconstructive surgery. Self-renewal and mesodermal differentiation potential of these cells make them a viable alternative source for use in regenerative medicine.

Thymosin beta-4 upregulates anti-oxidative enzymes and protects human cornea epithelial cells against oxidative damage.

BACKGROUND: The ability to scavenge reactive oxygen species (ROS) is crucial for cornea epithelial cells to resist oxidative damage. The authors previously demonstrated that exogenous thymosin beta-4 (T beta(4)) was able to protect human cornea epithelial (HCE-T) cells against H(2)O(2)-induced oxidative damage, and its cellular internalisation was essential. The aim of this study is to further elucidate its protective mechanism. METHODS: HCE-T cells with or without T beta(4) pretreatment were exposed to H(2)O(2), and the differences in caspase activity, intracellular ROS levels, cell viability, and the expression of anti-oxidative enzymes, were measured and compared. RESULTS: Besides reducing caspase-9 activation and intracellular ROS levels induced by H(2)O(2), treatment of T beta(4) could also increase cell viability and stimulate the expression of manganese superoxide dismutase (SOD) and copper/zinc SOD. Moreover, both transcription and translation levels of catalase were also upregulated by T beta(4) in the presence of exogenous H(2)O(2). Furthermore, it was demonstrated that the addition of catalase inhibitor abrogated the protective effect of T beta(4) against H(2)O(2)-induced oxidative damage. CONCLUSION: To the best of the authors' knowledge, this is the first report to show that T beta(4 )was capable of upregulating anti-oxidative enzymes in human corneal epithelial cells, and these findings further support its role in cornea protection.

Use of mesenchymal stem cells to facilitate bone regeneration in normal and chemotherapy-treated rats.

Reconstructing segmental bone defects after resection of malignant bone tumors is a long-standing clinical problem. Treatment of bone tumors such as osteosarcoma involves chemotherapy. These chemotherapeutic agents are potent inhibitors of cell division and these drugs may affect regeneration of bone from osteoprogenitor cells. It may be possible to reconstruct segmental bone defects by a tissue-engineering approach. The aim of this study was to investigate the use of mesenchymal stem cells (MSCs) in a fibrin glue carrier to enhance bone regeneration after chemotherapy. Bone marrow was harvested from young adult male rats of the Wistar strain; stem cells were isolated and expanded. Bone regeneration in normal and chemotherapy-treated rats was investigated in 1.5-mm rat femoral defects created by osteotomizing the femur and stabilizing the femoral fragments by external fixation. The osteotomy gap was left either unfilled, filled with fibrin glue alone, or filled with glue containing stem cells. Bone formation within the gap was determined by radiography, dual-energy X-ray absorptiometry, and histology. It was shown that MSCs encapsulated within fibrin glue could remain viable for up to 96 h in tissue culture. Chemotherapy significantly reduced bone formation in unfilled defects and defects filled only with fibrin glue. When MSCs were used in conjunction with fibrin glue, even in non-chemotherapy-treated rats bone formation in the gap was significantly increased. Using stem cells, the effects of chemotherapy on bone formation could be alleviated by bone formation in the gap similar to that seen in non-chemotherapy-treated animals with MSCs. These studies demonstrated that a tissue-engineering approach in patients undergoing chemotherapy may be beneficial for treating segmental bone defects after tumor resection.

In vitro and in vivo characteristics of a heme oxygenase inhibitor: ZnBG.

The authors evaluated the in vitro and in vivo efficacy and photosensitizing effects of zinc deuteroporphyrin 2,4-bis glycol (ZnBG) as an inhibitor of adult Wistar rat tissue heme oxygenase (HO) activity and bilirubin production. Concentrations of 0.02-0.05 microM ZnBG inhibited the HO activity in postmitochondrial supernatants of liver, spleen, brain, and kidney by at least 50%. Administration of 4 mumole ZnBG/kg body weight to adult rats significantly reduced the total body carbon monoxide (CO) excretion, an index of bilirubin formation, from 1 to 6 hours posttreatment. At 6 hours posttreatment, the HO activity in postmitochondrial supernatants of the liver and spleen, but not of the brain, was significantly lowered. ZnBG also behaved as an in vitro photooxidizer by degrading, in the presence of cool white light, the reduced form of nicotinamide adenine dinucleotide phosphate and histidine to CO and other nonidentified products. ZnBG also enhanced the natural photodegradation of bilirubin. Furthermore, administration of ZnBG to 1-day-old neonatal rats caused mortality within 12 hours in light-exposed animals, with a lethal dose 50 of 23 microM/kg body weight.