Therapeutics and delivery vehicles for local treatment of osteomyelitis

Osteomyelitis, or the infection of the bone, presents a major complication in orthopedics and may lead to prolonged hospital visits, implant failure, and in more extreme cases, amputation of affected limbs. Typical treatment for this disease involves surgical debridement followed by long-term, systemic antibiotic administration, which contributes to the development of antibiotic-resistant bacteria and has limited ability to eradicate challenging biofilm-forming pathogens including Staphylococcus aureus—the most common cause of osteomyelitis. Local delivery of high doses of antibiotics via traditional bone cement can reduce systemic side effects of an antibiotic. Nonetheless, growing concerns over burst release (then subtherapeutic dose) of antibiotics, along with microbial colonization of the nondegradable cement biomaterial, further exacerbate antibiotic resistance and highlight the need to engineer alternative antimicrobial therapeutics and local delivery vehicles with increased efficacy against, in particular, biofilm-forming, antibiotic-resistant bacteria. Furthermore, limited guidance exists regarding both standardized formulation protocols and validated assays to predict efficacy of a therapeutic against multiple strains of bacteria. Ideally, antimicrobial strategies would be highly specific while exhibiting a broad spectrum of bactericidal activity. With a focus on S. aureus infection, this review addresses the efficacy of novel therapeutics and local delivery vehicles, as alternatives to the traditional antibiotic regimens. The aim of this review is to discuss these components with regards to long bone osteomyelitis and to encourage positive directions for future research efforts.     

The biomechanics of vibration and low back pain

This work is a review of the mechanical factors related to low back pain production in a vibration environment. The sitting posture is an extreme orientation for the lumbar intervertebral disc that 1) increases its internal pressure, 2) increases its anteroposterior shear flexibility, while: 3) decreasing its resistance to buckling instability and 4) stressing the posterior region of the disc. Vibration is an additional mechanical stressor. Several studies suggest that the following preventive measures be taken to reduce the risk of low back pain due to driving: 1) minimize the vibration reaching the driver, 2) avoid lifting or bending immediately following driving, and 3) walk around for a few minutes following driving. © 1993 Wiley-Liss, Inc.     

Energy cost and mechanical efficiency of riding a four-wheeled, human-powered, recumbent vehicle

Oxygen consumption at steady state (V˙O ₂, l · min⁻¹) and mechanical power (W˙, W) were measured in five subjects riding a human-powered vehicle (HPV, the Karbyk, a four-wheeled recumbent cycle) on a flat concrete road at constant sub-maximal speeds. The external mechanical work spent per unit of distance (W, J · m⁻¹), as calculated from the ratio of W˙ to the speed (v, m · s⁻¹), was found to increase with the square of v: W˙=8.12+(0.262 ·v ²) (r=0.986, n=31), where the first term represents the mechanical energy wasted, over a unit of distance, against frictional forces (rolling resistance, R_r), and the second term (k · v ²) is the work performed, per unit distance, to overcome the air drag. The rolling coefficient (C_r, obtained dividing R_r by m · g, where m is the overall mass and g is the acceleration of gravity) amounted to [mean (SD)] 0.0084 (0.0008), that is about 60% higher than that of a racing bicycle. The drag coefficient was calculated from the measured values of k, air density (ρ) and frontal area (A) [C_x=k · (0.5 · A · ρ)⁻¹], and amounted to 1.067 (0.029), that is about 20% higher than that of a racing bicycle. The energy cost of riding the HPV (C_k, J · m⁻¹) was measured from the ratio of metabolic power above rest (net V˙O ₂, expressed in J · s⁻¹) to the speed (v, m · s⁻¹); the value of this parameter increased with the square of v, as described by: C_k=61.45 + (0.675 · v ²) (r=0.711, n=23). The net mechanical efficiency (η) was calculated from the ratio of W to C_k: over the investigated speed range this turned out to be 0.22 (0.021). Best performance times (BPTs) of a “typical”élite athlete riding the Karbyk were calculated over the distances of 1, 5 and 10 km: these were about 8% longer than the BPTs calculated, on the same subjects, when riding a conventional racing bicycle. Accepted: 7 August 2000     

Placental tissue stem cells and their role in neonatal diseases

Neonatal diseases such as hypoxic ischemic encephalopathy, diseases of prematurity and congenital disorders carry increased morbidity and mortality. Despite technological advancements, their incidence remains largely unabated. Stem cell (SC) interventions are novel therapies in the neonatal world. In pre-clinical models of neonatal diseases, SC applications have shown encouraging results. SC sources vary, with the bone marrow being the most utilized. However, the ability to harvest bone marrow SCs from neonates is limited. Placental-tissue derived SCs (PTSCs), provide an alternative and highly attractive source. Human placentas, the cornerstone of fetal survival, are abundant with such cells. Comparing to adult pools, PTSCs exhibit increased potency, decreased immunogenicity and stronger anti-inflammatory effects. Several types of PTSCs have been identified, with mesenchymal stem cells being the most utilized population. This review will focus on PTSCs and their pre-clinical and clinical applications in neonatology.     

汽车内空气污染状况分析

目的 对新车内空气中苯、甲苯和甲醛浓度进行分析，了解其车内空气的污染程度。方法 采用甲醛分析仪，气相色谱仪进行测定。结果 65辆新车中甲醛、苯、甲苯的总合格率分别为85％、65％、58％。第2、3、4个月甲醛浓度合格率分别为81％、59％、91％；苯浓度合格率分别为66％、45％、82％；甲苯浓度合格率分别为38％、64％、73％。结论 甲醛超标程度较小，苯和甲苯超标比较严重。     

不同基质对全缘千里光碱凝胶剂体外释放和透皮特性的影响

目的:通过体外释放和透皮实验,优选全缘千里光碱凝胶剂基质,为制备全缘千里光碱透皮给药抗肿瘤的新制剂提供参考.方法:利用溶出仪建立体外释放实验,体外透皮采用改良的Franz扩散池法,并通过RP-HPLC法测定释放液和接收液中全缘千里光碱的含量.结果:全缘千里光碱三种基质的凝胶体外释放符合Higuchi方程,释放速率CMC-Na凝胶＞HPMC凝胶＞Carbopol凝胶.体外透皮符合零级动力学过程,稳态透皮速率HPMC凝胶＞CMC-Na凝胶＞Carbopol凝胶.结论:凝胶剂作为全缘千里光碱透皮吸收新剂型是可行的,首选HPMC作为凝胶基质,不宜选择Carbopol作基质.     

Risk Factors for Injury in Rural Iowa

SUMMARY

Preliminary analyses of data from one third of the Keokuk County Rural Health Study cohort suggest that risk factors for injury among rural populations are not uniformly distributed and that the pattern varies with the risk factor. For some, such as expo-sure to all-terrain vehicles, the occupation of farmer determines the degree of exposure to the risk factor. Similarly, farmers seem less likely than other rural people to wear their seat belts. Although farm-ers are not more likely than rural nonfarmers to have firearms in their homes, they are more likely to have used them in the last year. How-ever, for other injury risk factors such as alcohol consumption, there do not appear to be differences among farmers, rural nonfarmers, and townspeople. These early results suggest that the Keokuk County Rural Health Study will yield important information for tar-geting specific rural injury prevention interventions.     

Locally-Delivered T-Cell-Derived Cellular Vehicles Efficiently Track and Deliver Adenovirus Delta24-RGD to Infiltrating Glioma

Oncolytic adenoviral vectors are a promising alternative for the treatment of glioblastoma. Recent publications have demonstrated the advantages of shielding viral particles within cellular vehicles (CVs), which can be targeted towards the tumor microenvironment. Here, we studied T-cells, often having a natural capacity to target tumors, for their feasibility as a CV to deliver the oncolytic adenovirus, Delta24-RGD, to glioblastoma. The Jurkat T-cell line was assessed in co-culture with the glioblastoma stem cell (GSC) line, MGG8, for the optimal transfer conditions of Delta24-RGD in vitro. The effect of intraparenchymal and tail vein injections on intratumoral virus distribution and overall survival was addressed in an orthotopic glioma stem cell (GSC)-based xenograft model. Jurkat T-cells were demonstrated to facilitate the amplification and transfer of Delta24-RGD onto GSCs. Delta24-RGD dosing and incubation time were found to influence the migratory ability of T-cells towards GSCs. Injection of Delta24-RGD-loaded T-cells into the brains of GSC-bearing mice led to migration towards the tumor and dispersion of the virus within the tumor core and infiltrative zones. This occurred after injection into the ipsilateral hemisphere, as well as into the non-tumor-bearing hemisphere. We found that T-cell-mediated delivery of Delta24-RGD led to the inhibition of tumor growth compared to non-treated controls, resulting in prolonged survival (p = 0.007). Systemic administration of virus-loaded T-cells resulted in intratumoral viral delivery, albeit at low levels. Based on these findings, we conclude that T-cell-based CVs are a feasible approach to local Delta24-RGD delivery in glioblastoma, although efficient systemic targeting requires further improvement.     

High Martensitic Steel after Welding with Micro-Jet Cooling in Microstructural and Mechanical Investigations

Modern means of transport will play a significant role in the smart city. In the automotive industry, high-strength steels such as Docol are employed more often. This kind of material is relatively not very well weldable. The main reason is related to the Heat Affect Zone, the region in which cracks occur. Another disadvantage is connected with differences in values of ultimate strength of parent and weld material. The differences can be diminished using the correct welding process, which employs nickel and molybdenum electrode wires at much lower sulfur content. The weld metal deposit contains mainly martensite and bainite with coarse ferrite, while the parent material contains mainly martensite and rather fine ferrite. New technology, micro-jet cooling after the joining process enables to obtain the microstructure of weld metal deposit at acceptable parameters. Welding with micro-jet cooling could be treated as a very promising welding Docol steels process with high industrial application. Results of non-destructive inspections on macro samples corresponded with further destructive test results (tensile strength, hardness, fatigue, metallographic structure analyses). This article aims to verify fatigue behavior of Docol 1200 M steel after welding supported by the cooling using the micro-jet technique. For the first time, micro-jet cooling was used to weld this kind of steel to check the mechanical properties of the joint, especially to determine the fatigue limit. This study is formulated as follows: investigating fatigue resistance of the Docol 1200 M weld manufactured at the cooling process with micro-jets. The joints were produced in the MAG (Metal Active Gas) technology modified by micro-jet cooling. The results collected in the fatigue test were processed in the form of the Wöhler’s S–N diagram following the fatigue limit of the weld examined. All data have indicated the possibility of obtaining a new method of welded joints with high fatigue limit minimum of 480 MPa. It could be important to achieve a tensile strength of 700 MPa while maintaining the best relative elongation at the level of the base material.