Analysis and regeneration of hypermedia contents through Java and XML tools

This paper presents a tool for the analysis and regeneration of Web contents, implemented through XML and Java. At the moment, the Web content delivery from server to clients is carried out without taking into account clients' characteristics. Heterogeneous and diverse characteristics, such as user's preferences, different capacities of the client's devices, different types of access, state of the network and current load on the server, directly affect the behavior of Web services. On the other hand, the growing use of multimedia objects in the design of Web contents is made without taking into account this diversity and heterogeneity. It affects, even more, the appropriate content delivery. Thus, the objective of the presented tool is the treatment of Web pages taking into account the mentioned heterogeneity and adapting contents in order to improve the performance on the Web

Cutaneous lesions sensory impairment recovery and nerve regeneration in leprosy patients

It is important to understand the mechanisms that enable peripheral neurons to regenerate after nerve injury in order to identify methods of improving this regeneration. Therefore, we studied nerve regeneration and sensory impairment recovery in the cutaneous lesions of leprosy patients (LPs) before and after treatment with multidrug therapy (MDT). The skin lesion sensory test results were compared to the histopathological and immunohistochemical protein gene product (PGP) 9.5 and the p75 nerve growth factor receptors (NGFr) findings. The cutaneous neural occupation ratio (CNOR) was evaluated for both neural markers. Thermal and pain sensations were the most frequently affected functions at the first visit and the most frequently recovered functions after MDT. The presence of a high cutaneous nerve damage index did not prevent the recovery of any type of sensory function. The CNOR was calculated for each biopsy, according to the presence of PGP and NGFr-immunostained fibres and it was not significantly different before or after the MDT. We observed a variable influence of MDT in the recovery from sensory impairment in the cutaneous lesions of LPs. Nociception and cold thermosensation were the most recovered sensations. The recovery of sensation in the skin lesions appeared to be associated with subsiding inflammation rather than with the regenerative activity of nerve fibres.

How Can Nanotechnology Help to Repair the Body? Advances in Cardiac, Skin, Bone, Cartilage and Nerve Tissue Regeneration

Nanotechnologists have become involved in regenerative medicine via creation of biomaterials and nanostructures with potential clinical implications. Their aim is to develop systems that can mimic, reinforce or even create in vivo tissue repair strategies. In fact, in the last decade, important advances in the field of tissue engineering, cell therapy and cell delivery have already been achieved. In this review, we will delve into the latest research advances and discuss whether cell and/or tissue repair devices are a possibility. Focusing on the application of nanotechnology in tissue engineering research, this review highlights recent advances in the application of nano-engineered scaffolds designed to replace or restore the followed tissues: (i) skin; (ii) cartilage; (iii) bone; (iv) nerve; and (v) cardiac.

Critical role for the lactate transporter, monocarboxylate transporter 1 (mct1), in the regeneration of peripheral nerves

Axons, and particularly regenerating axons, have high metabolic needs in order to maintain critical functions such as axon transport and membrane depolarization. Though some of the required energy likely comes form extracellular glucose and ATP generated in the soma, we and others hypothesize that some of the energy may be supplied by lactate. Unlike glucose that requires glycolytic enzymes to produce pyruvate, lactate can be converted directly to pyruvate by lactate dehydrogenase and transported into mitochondria for oxidative metabolism. In order to be transported into or out of cells, lactate requires specific monocarboxylate transporters (MCTs), the most abundant of which is MCT1. If MCT1 and lactate are critical for nerve function and regeneration, we hypothesize that MCT1 heterozygote null mice, which appear phenotypically normal despite having approximately 40% MCT1 as compared to wildtype littermate mice, would have reduced capacity for repair following nerve injury. To investigate this, adult MCT1 heterozygote null mice or wild-type mice underwent unilateral sciatic nerve crush in the proximal thigh. We found that regeneration of the sciatic nerve, as measured by recovery of compound muscle action potentials (CMAP) in the lateral plantar muscles following proximal sciatic nerve stimulation, was delayed from a median of 21 days in wildtype mice to 38.5 days in MCT1 heterozygote mice. In fact, half of the MCT1 heterozygote null mice had no recovery of CMAP by the endpoint of the study at 42 days, while all of the wild-type mice had recovered. In addition, the maximal amplitude of CMAP recovery in MCT1 heterozygote mull mice was reduced from a mean of 3 mV to 0.5 mV. As would be expected, the denervated gastrocnemius muscle of MCT1 heterozygote null mice remained atrophic at 42 days compared to wild-type mice. Our experiments show that lactate supplied through MCT1 is necessary for nerve regeneration. Experiments are underway to determine whether loss of MCT1 prevents nerve regrowth directly due to reduced energy supply to axons or indirectly by dysfunctional Schwann cells normally dependent on lactate supply through MCT1.

Small and long non-coding RNAs in cardiac homeostasis and regeneration

Cardiovascular diseases and in particular heart failure are major causes of morbidity and mortality in the Western world. Recently, the notion of promoting cardiac regeneration as a means to replace lost cardiomyocytes in the damaged heart has engendered considerable research interest. These studies envisage the utilization of both endogenous and exogenous cellular populations, which undergo highly specialized cell fate transitions to promote cardiomyocyte replenishment. Such transitions are under the control of regenerative gene regulatory networks, which are enacted by the integrated execution of specific transcriptional programs. In this context, it is emerging that the non-coding portion of the genome is dynamically transcribed generating thousands of regulatory small and long non-coding RNAs, which are central orchestrators of these networks. In this review, we discuss more particularly the biological roles of two classes of regulatory non-coding RNAs, i.e. microRNAs and long non-coding RNAs, with a particular emphasis on their known and putative roles in cardiac homeostasis and regeneration. Indeed, manipulating non-coding RNA-mediated regulatory networks could provide keys to unlock the dormant potential of the mammalian heart to regenerate. This should ultimately improve the effectiveness of current regenerative strategies and discover new avenues for repair. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.

Effect of controlled co-delivery of synergistic neurotrophic factors on early nerve regeneration in rats.

Present interventions to repair severed peripheral nerves provide slow and poor early axonal regeneration, which may cause unsatisfactory functional reinnervation. To improve early axonal regeneration in a 10 mm rat sciatic nerve gap model, we developed collagen nerve conduits loaded with the synergistically acting glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). For controlling the concomitant GDNF and NGF release, the collagen tubes were cross-linked by a dehydro-thermal treatment (110 degrees C; 20 mbar; 5 days) prior to impregnating the tubes with GDNF and NGF and by coating drug-loaded tubes with layers of poly(lactide-co-glycolide). The conduits made of cross-linked collagen released low initial amounts of GDNF and NGF (2% of both during first 3 days) and enhanced significantly the early (2 weeks) nerve regeneration in terms of axonal outgrowth and Schwann cell migration in a 10 mm rat sciatic nerve gap model, as compared to the conduits made of non-cross-linked collagen releasing higher initial amounts of GDNF and NGF (12-16% within 3 days), or those releasing GDNF alone. The enhancement of early axonal regeneration using controlled co-delivery of multiple synergistic neurotrophic factors is an important requisite for eventually establishing functional connections with the target organ.

Natural Regeneration of Oak in Iowa, December 1998

The oak and oak/hickory forests make up about 46% of Iowa's forestland. Approximately a third of these woodlands have adequate oak regeneration for the woodlands of the future. This report explains what is happening with Iowa's forestland.

Wound repair and regeneration.

The repair of wounds is one of the most complex biological processes that occur during human life. After an injury, multiple biological pathways immediately become activated and are synchronized to respond. In human adults, the wound repair process commonly leads to a non-functioning mass of fibrotic tissue known as a scar. By contrast, early in gestation, injured fetal tissues can be completely recreated, without fibrosis, in a process resembling regeneration. Some organisms, however, retain the ability to regenerate tissue throughout adult life. Knowledge gained from studying such organisms might help to unlock latent regenerative pathways in humans, which would change medical practice as much as the introduction of antibiotics did in the twentieth century.

Thyroid hormone in biodegradable nerve guides stimulates sciatic nerve regeneration: a potential therapeutic approach for human peripheral nerve injuries.

It has been already demonstrated that thyroid hormone (T3) is one of the most important stimulating factors in peripheral nerve regeneration. We have recently shown that local administration of T3 in silicon tubes at the level of the transected rat sciatic nerve enhanced axonal regeneration and improved functional recovery. Silicon, however, cannot be used in humans because it causes a chronic inflammatory reaction. Therefore, in order to provide future clinical applications of thyroid hormone in human peripheral nerve lesions, we carried out comparative studies on the regeneration of transected rat sciatic nerve bridged either by biodegradable P(DLLA-(-CL) or by silicon nerve guides, both guides filled with either T3 or phosphate buffer. Our macroscopic observation revealed that 85% of the biodegradable guides allowed the expected regeneration of the transected sciatic nerve. The morphological, morphometric and electrophysiological analysis showed that T3 in biodegradable guides induces a significant increase in the number of myelinated regenerated axons (6862 +/- 1831 in control vs. 11799 +/- 1163 in T3-treated). Also, T3 skewed the diameter of myelinated axons toward larger values than in controls. Moreover, T3 increases the compound muscle action potential amplitude of the flexor and extensor muscles of the treated rats. This T3 stimulation in biodegradable guides was equally well to that obtained by using silicone guides. In conclusion, the administration of T3 in biodegradable guides significantly improves sciatic nerve regeneration, confirming the feasibility of our technique to provide a serious step towards future clinical application of T3 in human peripheral nerve injuries.

Lack of Smad3 signaling leads to impaired skeletal muscle regeneration.

Smad3 is a key intracellular signaling mediator for both transforming growth factor-β and myostatin, two major regulators of skeletal muscle growth. Previous published work has revealed pronounced muscle atrophy together with impaired satellite cell functionality in Smad3-null muscles. In the present study, we have further validated a role for Smad3 signaling in skeletal muscle regeneration. Here, we show that Smad3-null mice had incomplete recovery of muscle weight and myofiber size after muscle injury. Histological/immunohistochemical analysis suggested impaired inflammatory response and reduced number of activated myoblasts during the early stages of muscle regeneration in the tibialis anterior muscle of Smad3-null mice. Nascent myofibers formed after muscle injury were also reduced in number. Moreover, Smad3-null regenerated muscle had decreased oxidative enzyme activity and impaired mitochondrial biogenesis, evident by the downregulation of the gene encoding mitochondrial transcription factor A, a master regulator of mitochondrial biogenesis. Consistent with known Smad3 function, reduced fibrotic tissue formation was also seen in regenerated Smad3-null muscle. In conclusion, Smad3 deficiency leads to impaired muscle regeneration, which underscores an essential role of Smad3 in postnatal myogenesis. Given the negative role of myostatin during muscle regeneration, the increased expression of myostatin observed in Smad3-null muscle may contribute to the regeneration defects.

Diversity of Calliphoridae and Sarcophagidae (Diptera, Oestroidea) in continuous forest and gaps at different stages of regeneration in the Urucu oilfield in western Brazilian Amazonia

Diversity of Calliphoridae and Sarcophagidae (Diptera, Oestroidea) in continuous forest and gaps at different stages of regeneration in the Urucu oilfield in western Brazilian Amazonia. The diversity of Calliphoridae and Sarcophagidae in continuous forest and gaps at different stages of regeneration was studied in the Urucu river basin, in Coari, state of Amazonas, Brazil. The flies were collected at 16 sampling points, 12 in gaps at different stages of regeneration (early _ C1, mid- C2 and late successional _ C3) and four in continuous forest _ MT. The diversity of blowflies was similar in the two less regenerated habitats (C1 and C2), and lower than that in the late successional (C3) and continuous forests (MT). By contrast, the diversity of flesh flies was much higher in all three types of gaps (C1, C2 and C3) in comparison with continuous forest (MT). Ordination (NMDS) and similarity (ANOSIM) analyses revealed that the blowflies communities were grouped by habitat type, which affected species composition more than diversity. Analysis of the flesh flies revealed two main groupings, gaps (C1, C2 and C3) and continuous forest (MT), with no evidence of any influence of successional stage on the diversity of the community.

Nesting and use of pollen resources by Tetrapedia diversipes Klug (Apidae) in Atlantic Forest areas (Rio de Janeiro, Brazil) in different stages of regeneration

Nesting and use of pollen resources by Tetrapedia diversipes Klug (Apidae) in Atlantic Forest areas (Rio de Janeiro, Brazil) in different stages of regeneration. The nesting in trap-nests and use of pollen sources in larval food by Tetrapedia diversipes Klug, 1810 (Apidae) was compared between regenerating areas of Atlantic Forest. The study was conducted between April 2008 and October 2009 at União Biological Reserve, Rio de Janeiro, Brazil. T. diversipes nested in 66 trap-nests and showed a peak of nesting during the months of highest rainfall. The most frequent pollen type in brood cells during the wet season was Dalechampia sp. 1. During the dry season, the type Ludwigia sp. was the most frequent, followed by Dalechampia sp. 2. The high frequency of Dalechampia and Ludwigia species in the larval food, observed in both habitats and in the two seasons could be considered relevant for T. diversipes, suggesting highly selective diet based primarily on two plant species unrelated, but similar in size of pollen grains.

Thyroid hormone enhances transected axonal regeneration and muscle reinnervation following rat sciatic nerve injury.

Improvement of nerve regeneration and functional recovery following nerve injury is a challenging problem in clinical research. We have already shown that following rat sciatic nerve transection, the local administration of triiodothyronine (T3) significantly increased the number and the myelination of regenerated axons. Functional recovery is a sum of the number of regenerated axons and reinnervation of denervated peripheral targets. In the present study, we investigated whether the increased number of regenerated axons by T3-treatment is linked to improved reinnervation of hind limb muscles. After transection of rat sciatic nerves, silicone or biodegradable nerve guides were implanted and filled with either T3 or phosphate buffer solution (PBS). Neuromuscular junctions (NMJs) were analyzed on gastrocnemius and plantar muscle sections stained with rhodamine alpha-bungarotoxin and neurofilament antibody. Four weeks after surgery, most end-plates (EPs) of operated limbs were still denervated and no effect of T3 on muscle reinnervation was detected at this stage of nerve repair. In contrast, after 14 weeks of nerve regeneration, T3 clearly enhanced the reinnervation of gastrocnemius and plantar EPs, demonstrated by significantly higher recovery of size and shape complexity of reinnervated EPs and also by increased acetylcholine receptor (AChRs) density on post synaptic membranes compared to PBS-treated EPs. The stimulating effect of T3 on EP reinnervation is confirmed by a higher index of compound muscle action potentials recorded in gastrocnemius muscles. In conclusion, our results provide for the first time strong evidence that T3 enhances the restoration of NMJ structure and improves synaptic transmission.

A collagen-poly(lactic acid-co-ɛ-caprolactone) hybrid scaffold for bladder tissue regeneration.

Scaffold materials should favor cell attachment and proliferation, and provide designable 3D structures with appropriate mechanical strength. Collagen matrices have proven to be beneficial scaffolds for tissue regeneration. However, apart from small intestinal submucosa, they offer a limited mechanical strength even if crosslinking can enhance their mechanical properties. A more cell-friendly way to increase material strength is to combine synthetic polymer meshes with plastic compressed collagen gels. This work describes the potential of plastic compressed collagen-poly(lactic acid-co-ɛ-caprolactone) (PLAC) hybrids as scaffolds for bladder tissue regeneration. Human bladder smooth muscle and urothelial cells were cultured on and inside collagen-PLAC hybrids in vitro. Scaffolds were analyzed by electron microscopy, histology, immunohistochemistry, and AlamarBlue assay. Both cell types proliferated in and on the hybrid, forming dense cell layers on top after two weeks. Furthermore, hybrids were implanted subcutaneously in the backs of nude mice. Host cell infiltration, scaffold degradation, and the presence of the seeded bladder cells were analyzed. Hybrids showed a lower inflammatory reaction in vivo than PLAC meshes alone, and first signs of polymer degradation were visible at six months. Collagen-PLAC hybrids have potential for bladder tissue regeneration, as they show efficient cell seeding, proliferation, and good mechanical properties.

The role of matrix metalloproteinase mmp-9 in peripheral neural system regeneration

Multiple lines of evidence show that matrix metalloproteinases (MMPs) are involved in the peripheral neural system degenerative and regenerative processes. MMP-9 was suggested in particular to play a role in the peripheral nerve after injury or during Wallerian degeneration. Interestingly, our previous analysis of Lpin1 mutant mice (which present morphological signs of active demyelination and acute inflammatory cell migration, similar to processes present in the PNS undergoing Wallerian degeneration) revealed an accumulation of MMP-9 in the endoneurium of affected animals. We therefore generated a mouse line lacking both the Lpin1 and the MMP-9 genes in order to determine if MMP-9 plays a role in either inhibition or potentiation of the demyelinating phenotype present in Lpin1 knockout mice. The inactivation of MMP-9 alone did not lead to defects in PNS structure or function. Interestingly we observed that the double mutant animals showed reduced nerve conduction velocity, lower myelin protein mRNA expressions, and had more histological abnormalities as compared to the Lpin1 single mutants. In addition, based on immunohistochemical analysis and macrophage markers mRNA expression, we found a lower macrophage content in the sciatic nerve of the double mutant animals. Together our data indicate that MMP-9 plays a role in macrophage recruitment during postinjury PNS regeneration processes and suggest that slower macrophage infiltration delays regenerative processes in PNS.