Unraveling effects of anti-aging drugs on C. elegans using liposomes

Liposome-mediated delivery is a possible means to overcome several shortcomings with C. elegans as a model for identifying and testing drugs that retard aging. These include confounding interactions between drugs and the nematodes' bacterial food source and failure of drugs to be taken up into nematode tissues. To explore this, we have tested liposome-mediated delivery of a range of fluorescent dyes and drugs in C. elegans. Liposome encapsulation led to enhanced effects on lifespan, requiring smaller quantities of compounds, and enhanced uptake of several dyes into the gut lumen. However, one dye (Texas red) did not cross into nematode tissues, showing that liposomes cannot ensure the uptake of all compounds. Of six compounds previously reported to extend lifespan (vitamin C, N-acetylcysteine, glutathione (GSH), trimethadione, thioflavin T (ThT), and rapamycin), this effect was reproduced for the latter four in a condition-dependent manner. For GSH and ThT, antibiotics abrogated life extension, implying a bacterially mediated effect. With GSH, this was attributable to reduced early death from pharyngeal infection and associated with alterations of mitochondrial morphology in a manner suggesting a possible innate immune training effect. By contrast, ThT itself exhibited antibiotic effects. For rapamycin, significant increases in lifespan were only seen when bacterial proliferation was prevented. These results document the utility and limitations of liposome-mediated drug delivery for C. elegans. They also illustrate how nematode-bacteria interactions can determine the effects of compounds on C. elegans lifespan in a variety of ways

Etiologies and outcome of osteonecrosis of the femoral head: Etiology and outcome study in a Taiwan population

Background: Osteonecrosis of the femoral head (ONFH) is an important indication for total hip arthroplasty in Taiwan. We demonstrated the etiologies of ONFH and outcomes based on stratification of patients according to different etiologies. Methods: We reviewed medical records and images from January 2000 to May 2010 in our database with the diagnosis of “osteonecrosis of the femoral head.” We categorized all patients into different etiologies, including corticosteroid, alcohol, and idiopathic. All patients received subsequent follow up for ipsilateral precollapse ONFH and contralateral disease-free femoral head status after initial diagnosis. Results: Of the 1153 patients who had undergone 1674 hip surgeries including core decompression and total hip replacement, alcohol use was the most prevalent etiology in our population (45.2%). Patients with corticosteroid- and alcohol-associated ONFH were younger and more likely to have bilateral disease. Patients with alcohol- or steroid-associated ONFH were found to have a higher rate of contralateral disease and faster progression of precollapse ONFH than patients who had or had not undergone core decompression. Conclusion: Alcohol use had the greatest impact on ONFH in our population. Nonidiopathic ONFH patients had the worst outcome. Understanding the nature of progression of ONFH and incidence of contralateral disease may provide great prognostic value to detect and perform early intervention

Effectiveness of plate augmentation for femoral shaft nonunion after nailing

Background: Treatment options for nonunion of the femoral shaft fracture after intramedullary nail fixation are controversial. The methods of exchanging an existing nail with a larger-sized nail, dynamization, removal of the nail followed by plating, and bone grafting have all been reported. From those options, exchange nailing seems to be the most popular choice. In our study, we used plate augmentation and bone grafting with retention of the nail. The purpose of our study was to evaluate the effectiveness of this method in treating femoral shaft nonunion after open reduction and internal fixation with intramedullary nail fixation. Methods: Between January 2003 and December 2009, 22 patients who had nonunion after open reduction and internal fixation with intramedullary nail for femoral shaft fracture were included in our study. There were 13 men and nine women participants, with a mean age of 34.3 years (range, 17–77 years). The mean period of nonunion after surgery was 20.0 months (range, 7–63 months). The patients were classified into three groups, atrophic, oligotrophic, and hypertrophic. We retained the nail and performed plate augmentation for all patients, with simultaneous autologous bone grafting as indicated. We followed up on all patients with plain film examination, and to assess functional recovery status to determine osseous union condition. Results: All 22 of the patients achieved postoperative bony union uneventfully at a mean time of 22.1 weeks (range, 12–40 weeks). The mean operative time was 105 minutes (range, 60–150 minutes), and the mean blood loss was 340 ml (range, 150–700 ml). All of the patients could walk bearing full weight without pain within 3 months. There were no significant complications such as broken hardware, implant back-out, axial or rotational malalignment, or deep infections. Conclusion: Plate augmentation with retention of the nail with autologous bone grafting may be an effective and reliable alternative in treating nonunion of the femoral shaft fracture after open reduction and internal fixation with intramedullary nail

Joint replacement in human immunodeficiency virus-infected patients

Background: Human immunodeficiency virus (HIV)-infected patients are at risk for bacterial and opportunistic infections with worsening immunosuppression. Methods: From June 2000 to January 2009, six patients who were diagnosed with HIV infection underwent 10 joint replacement procedures, including six total hip arthroplasties, two total knee arthroplasties, and one shoulder hemiarthroplasty. An ordinary dose of postsurgical-empirical antibiotics was prescribed, with an average follow-up period of 38.6 months. All prostheses of total knee arthroplasty and shoulder hemiarthroplasty were fixed with vancomycin-impregnated bone cement. Results: The rate of postoperative infection for HIV infected patients is supposed to be higher than for HIV negative patients. However, in our institution, there have been no HIV- positive patients who have suffered postoperative infection. Conclusion: HIV-positive patients can have excellent outcomes after undergoing various arthroplastic surgeries. This revelation, coupled with the advances in antiviral therapy that have helped to lengthen HIV patient lifespans, strongly suggests that these patients should receive arthroplastic surgery

Primary Hyperparathyroidism With Brown Tumor Mimicking Metastatic Bone Malignancy

Bone and joint pain are commonly encountered conditions in daily practice. In the elderly, when osteolytic lesions are identified in imaging studies, metastatic bone tumor is the first impression that comes to the clinician's mind. Although the worst-case scenario should be ruled in, other differential diagnoses such as metabolic bone disease should be considered as well. We report a case of brown tumor caused by parathyroid adenoma. The patient had initial presentation of diffuse bone pain and multiple osteolytic lesions on imaging studies similar to metastatic bone tumor. With a systematic approach and awareness of metabolic bone disease, an accurate diagnosis was finally reached. Appropriate treatments, including preventive internal fixation of the impending femoral fracture and surgical excision of the parathyroid adenoma were performed accordingly. The key treatment for the condition was surgical excision of the parathyroid adenoma. After normalization of serum intact-parathyroid hormone level, the bony lesions resolved and required no further orthopedic surgery. The patient is now symptom-free. In addition to suspecting malignancy, the clinician should be highly alert to other possible causes of bony lesions. Brown tumor should be kept in mind during daily practice

C. elegans ageing is accelerated by a self-destructive reproductive programme

Abstract In post-reproductive C. elegans, destructive somatic biomass repurposing supports production of yolk which, it was recently shown, is vented and can serve as a foodstuff for larval progeny. This is reminiscent of the suicidal reproductive effort (reproductive death) typical of semelparous organisms such as Pacific salmon. To explore the possibility that C. elegans exhibits reproductive death, we have compared sibling species pairs of the genera Caenorhabditis and Pristionchus with hermaphrodites and females. We report that yolk venting and constitutive, early pathology involving major anatomical changes occur only in hermaphrodites, which are also shorter lived. Moreover, only in hermaphrodites does germline removal suppress senescent pathology and markedly increase lifespan. This is consistent with the hypothesis that C. elegans exhibit reproductive death that is suppressed by germline ablation. If correct, this would imply a major difference in the ageing process between C. elegans and most higher organisms, and potentially explain the exceptional plasticity in C. elegans ageing