The aim of this study was to prepare nonwoven materials from poly(epsilon-caprolactone) (PCL) and their antibiotic containing forms by electrospinning, so as to prevent postsurgery induced abdominal adhesions in rats. epsilon-Caprolactone was first polymerized by ring-opening polymerization, and then it was processed into matrices composed of nanofibers by electrospinning. A model antibiotic (Biteral) was embedded within a group of PCL membranes. In the rat model, defects on the abdominal walls in the peritoneum were made to induce adhesion. The plain or antibiotic embedded PCL membranes were implanted on the right side of the abdominal wall. No membrane implantation was made on the left side of the abdominal wall that served as control. Macroscopical and histological evaluations showed that using these barriers reduces the extent, type, and tenacity of adhesion. The antibiotic embedded membranes significantly eliminated postsurgery abdominal adhesions, and also improved healing.
Limb-girdle muscular dystrophy (LGMD) is a genetically heterogeneous group of inherited muscular disorders manifesting symmetric, proximal, and slowly progressive muscle weakness. Using Affymetrix 250K SNP Array genotyping and homozygosity mapping, we mapped an autosomal-recessive LGMD phenotype to the telomeric portion of chromosome 8q in a consanguineous Turkish family with three affected individuals. DNA sequence analysis of PLEC identified a homozygous c.1_9del mutation containing an initiation codon in exon 1f, which is an isoform-specific sequence of plectin isoform 1f. The same homozygous mutation was also detected in two additional families during the analysis of 72 independent LGMD2-affected families. Moreover, we showed that the expression of PLEC was reduced in the patient's muscle and that there was almost no expression for plectin 1f mRNA as a result of the mutation. In addition to dystrophic changes in muscle, ultrastructural alterations, such as membrane duplications, an enlarged space between the membrane and sarcomere, and misalignment of Z-disks, were observed by transmission electron microscopy. Unlike the control skeletal muscle, no sarcolemmal staining of plectin was detected in the patient's muscle. We conclude that as a result of plectin 1f deficiency, the linkage between the sarcolemma and sarcomere is broken, which could affect the structural organization of the myofiber. Our data show that one of the isoforms of plectin plays a key role in skeletal muscle function and that disruption of the plectin 1f can cause the LGMD2 phenotype without any dermatologic component as was previously reported with mutations in constant exons of PLEC.
We performed genome-wide homozygosity mapping and mapped a novel myopathic phenotype to chromosomal region 1q25 in a consanguineous family with three affected individuals manifesting proximal and distal weakness and atrophy, rigid spine and contractures of the proximal and distal interphalangeal hand joints. Additionally, cardiomyopathy and respiratory involvement were noted. DNA sequencing of torsinA-interacting protein 1 (TOR1AIP1) gene encoding lamina-associated polypeptide 1B (LAP1B), showed a homozygous c.186delG mutation that causes a frameshift resulting in a premature stop codon (p.E62fsTer25). We observed that expression of LAP1B was absent in the patient skeletal muscle fibres. Ultrastructural examination showed intact sarcomeric organization but alterations of the nuclear envelope including nuclear fragmentation, chromatin bleb formation and naked chromatin. LAP1B is a type-2 integral membrane protein localized in the inner nuclear membrane that binds to both A-and B-type lamins, and is involved in the regulation of torsinA ATPase. Interestingly, luminal domain-like LAP1 (LULL1)-an endoplasmic reticulum-localized partner of torsinA-was overexpressed in the patient's muscle in the absence of LAP1B. Therefore, the findings suggest that LAP1 and LULL1 might have a compensatory effect on each other. This study expands the spectrum of genes associated with nuclear envelopathies and highlights the critical function for LAP1B in striated muscle.
Reconstruction of large bone defects is still a major problem. Tissue-engineering approaches have become a focus in regeneration of bone. In particular, critical-sized defects do not ossify spontaneously. The use of electrospinning is attracting increasing attention in the preparation of tissue-engineering scaffolds. Recently, acellular scaffolds carrying bioactive agents have been used as scaffolds in "in situ" tissue engineering for soft and hard tissue repair. Poly(epsilon-caprolactone) (PCL) with two different molecular weights were synthesized, and the blends of these two were electrospun into nonwoven membranes composed of nanofibers/micropores. To stimulate bone formation, an active drug, "simvastatin" was loaded either after the membranes were formed or during electrospinning. The matrices were then spiral-wound to produce scaffolds with 3D-structures having both macro- and microchannels. Eight-millimeter diameter critical size cranial defects were created in rats. Scaffolds with or without simvastatin were then implanted into these defects. Samples from the implant sites were removed after 1, 3, and 6 months postimplantation. Bone regeneration and tissue response were followed by X-ray microcomputed tomography and histological analysis. These in vivo results exhibited osseous tissue integration within the implant and mineralized bone restoration of the calvarium. Both microCT and histological data clearly demonstrated that the more successful results were observed with the "simvastatin-containing PCL scaffolds," in which simvastatin was incorporated into the PCL scaffolds during electrospinning. For these samples, bone mineralization was quite significant when compared with the other groups.
Heat therapies such as hyperthermia and thermoablation are very promising approaches in the treatment of cancer. Compared with available hyperthermia modalities, magnetic fluid hyperthermia ͑MFH͒ yields better results in uniform heating of the deeply situated tumors. In this approach, fluid consisting of superparamagnetic particles ͑magnetic fluid͒ is delivered to the tumor. An alternating ͑ac͒ magnetic field is then used to heat the particles and the corresponding tumor, thereby ablating it. However, one of the most serious shortcomings of this technique is the unwanted heating of the healthy tissues. This results from the magnetic fluid diffusion from the tumor to the surrounding tissues or from incorrect localization of the fluids in the target tumor area. In this study, the authors demonstrated that by depositing appropriate static ͑dc͒ magnetic field gradients on the alternating ͑ac͒ magnetic fields, focused heating of the magnetic particles can be achieved. A focused hyperthermia system was implemented by using two types of coils: dc and ac coils. The ac coil generated the alternating magnetic field responsible for the heating of the magnetic particles; the dc coil was used to superimpose a static magnetic field gradient on the alternating magnetic field. In this way, focused heating of the particles was obtained in the regions where the static field was dominated by the alternating magnetic field. In vitro experiments showed that as the magnitude of the dc solenoid currents was increased from 0 to 1.8 A, the specific absorption rate ͑SAR͒ of the superparamagnetic particles 2 cm apart from the ac solenoid center decreased by a factor of 4.5, while the SAR of the particles at the center was unchanged. This demonstrates that the hyperthermia system is capable of precisely focusing the heat at the center. Additionally, with this approach, shifting of the heat focus can be achieved by applying different amounts of currents to individual dc solenoids. In vivo experiments were performed with adult rats, where magnetic fluids were injected percutaneously into the tails ͑with homogeneous fluid distribution inside the tails͒. Histological examination showed that, as we increased the dc solenoid current from 0.5 to 1.8 A, the total burned volume decreased from 1.6 to 0.2 cm 3 verifying the focusing capability of the system. The authors believe that the studies conducted in this work show that MFH can be a much more effective method with better heat localization and focusing abilities.
The results of the study indicate that short-pulse laser setup (laser I) looks more promising regarding the attachment, spreading, and orientation of PDL cells.
The purpose of this study was to investigate whether a grafting technique using either periosteum or bone marrow as an adjunct, would reconstitute more favorable tendon anchorage morphology with improved tensile strength in a bone tunnel model. We hypothesized that autogenous bone marrow aspirate can enhance the tendon-bone attachment as well as a freshly harvested periosteum, because both tissues contain pluripotent cells. Thirty-six skeletally mature New Zealand white rabbits were utilized. For the tendon graft healing in a bone tunnel model, the extensor digitorum longus tendon was detached from its femoral insertion and transplanted through a bone tunnel into the proximal tibia. Three groups were compared. For the group P (periosteum), a periosteum-wrapped tendon was fixed into the tunnel through the proximal tibial metaphysis. For the group BM (bone marrow), instead of periosteum augmentation, fresh bone marrow was injected into the tendon graft that would sit inside the tunnel. For the group C (control), the limb underwent a similar operation with neither the periosteum enveloping nor bone marrow injecting the tendon. At 6 and 12 weeks after surgery, two rabbits were used for light and electron microscopic examinations, and ten rabbits were used for biomechanical tests in each group. The interface tissue between bone and tendon was thicker and less organized in group C compared to groups P and BM at 6 weeks. Ultra-structurally, the interface tissue was loosely organized in group C, compared to others. Bone ingrowth into tendon was more obvious in groups P and BM, compared to group C. The proliferation of cartilage islands was observed within bone tunnels of both groups P and BM; but a well-defined fibrocartilage zone was noted only in group BM at the interface at week 12. Biomechanical findings: (1) at 6 weeks, the average failure load of group P was significantly higher than the others (P < 0.01). At same time point, in terms of stiffness, while group P was significantly higher than the other groups (P < 0.01), group BM was also significantly higher than that of group C (P < 0.05); (2) at 12 weeks, in terms of failure loads, there was a statistical significant difference only between groups BM and C (P < 0.05). At the same time point, stiffness values were not statistically different among the three groups. Based on the histological and biomechanical findings, the present study demonstrated that periosteum had a positive effect when compared to bone marrow and control groups on the tendon-to-bone healing at an early time point (6 weeks), and bone marrow was also effective at 12 weeks time point compared to the control group in an extra-articular bone tunnel in rabbits. The presence of pluripotent cells in both the bone marrow and the periosteum may be the possible mechanism for enhanced healing. Periosteum had a positive effect at an early time point (6 weeks). Bone marrow was more effective at 12 weeks. Therefore, it is possible that a combination of wrapping periosteum and injecting bone marrow to the te...
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