High Risk Of Degeneration Research Articles

A natural composite hydrogel laden with mesenchymal stromal cells for osteochondral repair: Comparison between casting and 3D bioprinting

Synovial joints, and particularly the osteochondral unit, are prone to lesions, with high risk of degeneration towards osteoarthritis. Various treatment strategies have been developed, including surgical techniques and cellular therapies, but they all show limitations. In this context, tissue engineering approaches, particularly 3D bioprinting, are promising for generating osteochondral tissue substitutes for joint repair. In this work, two biofabrication techniques, casting and extrusion-based 3D bioprinting, of an optimized formulation of a gelatin/alginate/fibrinogen bioink loaded with murine mesenchymal stromal cells (MSCs) were compared for the generation of cartilage and bone substitutes. Cell viability, proliferation and differentiation were characterized. Both techniques showed similar results in terms of viability and proliferation, but only the 3D bioprinted constructs allowed for differentiation towards the chondrogenic or osteogenic lineage using specific culture media. Bioprinting of biphasic osteochondral constructs comprising a cartilage compartment on top of a bone compartment was also explored. The study highlights the potential of our natural composite hydrogel bioink and extrusion-based 3D bioprinting for the generation of osteochondral tissue substitutes. Although further optimizations are needed, the study laid the groundwork for future advancements in osteochondral tissue engineering.

Current Therapies in Superficial Malignant Tumors

This article is a review of diagnostic and therapeutic possibilities in common epibulbar malignant tumors, such as basal cell carcinoma, conjunctival lymphoma, squamous cell carcinoma and conjunctival melanoma. Most importantly, for every tumor patient there is a detailed anamnesis, split lamp examination and photo documentation. Further regular controls after therapy are required due to the risk of recurrences. Basal cell carcinoma is the most common tumor of the periocular skin, divided into three subtypes (nodular, superficial and morphea). The treatment consists of total excision with a sufficient safety margin.The most common tumor of the orbital and ocular adnexa are lymphoma. They can appear primary or secondary, as lymphatic system disease. The gold standard therapy is a percutaneous irradiation.Squamous cell carcinoma and its precancerous stages (CIN I-III) are frequently diagnosed on the conjunctiva. A complete tumor excision is required, but sometimes it is not possible due to large tumor growth. Therefore, an adjuvant therapy with mitomycin C eyedrops, brachytherapy with ruthenium plaque or proton radiotherapy is required.Conjunctival melanoma is a rare, but life-threatening disease. Melanosis with atypia has a high risk for degeneration and requires further treatment with mitomycin C eyedrops. In cases of malignant tumor growth, an excision with a non-touch technique and adjuvant therapy with brachy or proton irradiation should be applied.

Nerve excitability differences in slow and fast motor axons of the rat: more than just Ih.

The objective was to determine biophysical differences between fast and slow motor axons using threshold tracking and demonstrate confounds related to anesthetic. Nerve excitability of motor axons innervating the slow-twitch soleus (SOL) and fast-twitch tibialis anterior (TA) muscles was tested. The experiments were conducted with pentobarbital sodium (SP) anesthetic and compared with previous results that used ketamine-xylazine (KX). Nerve excitability indices measured with SP show definitive differences between TA and SOL motor axons that extend beyond previous reports. Nerve excitability indices sensitive to changes in Ih indicated an increase in SOL axons compared with TA axons [e.g., S3 t = 7.949 (df = 10), P < 0.001; hyperpolarizing threshold electrotonus (90-100 ms), t = 2.659 (df = 20); P = 0.01; hyperpolarizing I/V slope, t = 4.308 (df = 19); P < 0.001]. SOL axons also had a longer strength-duration time constant [t = 3.35 (df = 20); P = 0.003] and a longer and larger magnitude relative refractory period [RRP (ms) t = 3.53 (df = 12); P = 0.004; Refractoriness at 2 ms, t = 0.0055 (df = 9); P = 0.006]. Anesthetic choice affected many measures of peripheral nerve excitability with differences most apparent in tests of threshold electrotonus and recovery cycle. For example, recovery cycle with KX lacked a clear superexcitable and late subexcitable period. We conclude that KX had a confounding effect on nerve excitability results consistent with ischemic depolarization. Results using SP revealed the full extent of differences in nerve excitability measures between putative slow and fast motor axons of the rat. These results provide empirical evidence, beyond conduction velocity, that the biophysical properties of motor axons vary with the type of muscle fiber innervated. These differences suggest that fast axons may be predisposed to dysfunction during hyperpolarizing stresses, e.g., electrogenic sodium pumping following sustained impulse conduction.NEW & NOTEWORTHY Nerve excitability testing is a tool used to provide insight into the properties of ion channels in peripheral nerves. It is used clinically to assess pathophysiology of axons. Researchers customarily think of motor axons as homogeneous; however, we demonstrate there are clear differences between fast and slow axons in the rat. This is important for interpreting results with selective motor neuronopathy, like aging where fast axons are at high risk of degeneration.

Current Therapies in Superficial Malignant Tumors

This article is a review of diagnostic and therapeutic possibilities in common epibulbar malignant tumors, such as basal cell carcinoma, conjunctival lymphoma, squamous cell carcinoma and conjunctival melanoma. Most importantly, for every tumor patient there is a detailed anamnesis, split lamp examination and photo documentation. Further regular controls after therapy are required due to the risk of recurrences.Basal cell carcinoma is the most common tumor of the periocular skin, divided into three subtypes (nodular, superficial and morphea). The treatment consists of total excision with a sufficient safety margin.The most common tumor of the orbital and ocular adnexa are lymphoma. They can appear primary or secondary, as lymphatic system disease. The gold standard therapy is a percutaneous irradiation.Squamous cell carcinoma and its precancerous stages (CIN I - III) are frequently diagnosed on the conjunctiva. A complete tumor excision is required, but sometimes it is not possible due to large tumor growth. Therefore, an adjuvant therapy with mitomycin C eyedrops, brachytherapy with ruthenium plaque or proton radiotherapy is required.Conjunctival melanoma is a rare, but life-threatening disease. Melanosis with atypia has a high risk for degeneration and requires further treatment with mitomycin C eyedrops. In cases of malignant tumor growth, an excision with a non-touch technique and adjuvant therapy with brachy or proton irradiation should be applied.

Modalités de fonctionnement d’un centre de suivi des femmes à haut risque de cancer du sein et de l’ovaire : une expérience à l’hôpital Tenon

High risk may be defined as either an absolute risk greater than 20 % or a relative risk greater than 4. Concerning breast and ovarian cancer, high risk patients include carriers of a constitutive deleterious mutation of BRCA1 or BRCA2 genes, patients with a significant family history of breast or ovarian cancer, and patients who have been diagnosed a benign breast lesion with a high risk of degeneration, i.e. atypical hyperplasia. Following up such patients relies on specific strategies. A center including a large panel of physicians involved in the various modalities for patients’ management (geneticians, radiologists, gynecologists, plastic surgeons, pathologists, endocrinologists, psychologists, medical oncologists) has been created at Tenon Hospital with this purpose. The collaboration of these different specialists with the referent physician of the patient allows for the definition and the implementation of a patient-centered follow-up continuously updated to take into account the different periods of a woman's life, according to best practices recommendations and the evolving state-of-the art.

Pathologic Characteristics of the Torn Human Meniscus

Background Acellular meniscus tissue is at a high risk for degeneration and retear. Information that would help surgeons predict, preoperatively, or intraoperatively which torn menisci had few viable cells could be useful in deciding which patients might be at increased risk for retear and failure of surgical repair. Hypothesis Patient age, length of time since injury, and tear type are predictors of the cellularity of meniscus tissue. Study Design Descriptive laboratory study. Methods Gross and histologic evaluation of torn meniscus tissue from 44 patients and 10 control menisci was performed. Results The patient factors of age, time since injury, and tear type all had significant effects on the pathologic characteristics of the torn meniscus. Patients older than 40 years had lower cellularity in the torn menisci than did patients younger than 40 years (P < .01). As time since injury increased, so did the rates of DNA fragmentation in the midsubstance of the meniscus and rates of Outerbridge II changes in the adjacent cartilage. Worse meniscal histologic scores were found in menisci with degenerative and radial tear types. Conclusion Patient age had a significant effect on the cellularity of the torn meniscus, with patients older than 40 years having significantly fewer meniscus cells than did those younger than 40 years. Further studies are needed to define the relative importance of the individual histologic findings in the clinical setting of meniscus tear and repair. Clinical Relevance In light of their decreased cellularity, menisci from patients older than 40 years may be more vulnerable to degeneration and retear after repair than are menisci of younger patients.

Differential expression of group I metabotropic glutamate receptors in human motoneurons at low and high risk of degeneration in amyotrophic lateral sclerosis

Glutamate excitotoxicity has been suggested to play a role in amyotrophic lateral sclerosis, since overstimulation of post-synaptic glutamate receptors by accumulated extracellular glutamate leads to motoneuron cell death. It is however unclear as to why some groups of motoneurons degenerate in this disease while other groups remain relatively intact even during terminal stages of the disease. Our previous studies in the rat showed differential expression of group I metabotropic glutamate receptors in motoneurons at low and high risk of degeneration in amyotrophic lateral sclerosis. Here we have extended this study to normal human brains. In situ hybridization showed that transcripts of both metabotropic glutamate receptor (mGluR) 1 and mGluR5 were expressed in motoneurons in both the resistant motor nucleus III and the vulnerable motor nucleus XII. Immunolabeling of mGluR1α and mGluR5 was found in both motoneurons and glia-like cells in all the motor nuclei and the ventral horn of the cervical spinal cord studied. Quantitative analysis of optical density measurements showed higher levels of mGluR1α protein expression but lower levels of mGluR5 protein expression in the vulnerable motoneuron pool (VII, XII and spinal cord) than in the resistant motoneuron pool (III, IV and VI). This differential expression of group I metabotropic glutamate receptor proteins within vulnerable motoneuron pools may predispose these neurons to degeneration as seen in amyotrophic lateral sclerosis.

Differential expression of Group I metabotropic glutamate receptors in motoneurons at low and high risk for degeneration in ALS.

Glutamate excitotoxicity has been suggested to play a role in amyotrophic lateral sclerosis (ALS), yet it remains unclear why some groups of motoneurons (MNs) are more vulnerable to degeneration than others. Our aim was to compare, in normal adult rats, the expression of Group I metabotropic glutamate receptors (mGluR1 and mGluR5) in MNs normally affected in ALS (XII and spinal MNs) with those which are spared (III and IV MNs). RT-PCR analysis of tissue punches taken from III and XII motor nuclei revealed mRNA for both 'a' and 'b' splice variants of the mGluR1 and mGluR5 receptor subtypes, with expression of the 'a' variant dominant for both receptor subtypes in III and XII nuclei. Immunolabeling for mGluR1a protein was strong in vulnerable (XII and spinal) but negligible in the resistant (III and IV) MNs. Immunoreactivity for mGluR5 was not detected in the cell bodies or proximal dendrites of any MN pool examined. Greater expression of mGluR1a receptor protein within vulnerable MN pools may predispose these neurons to neurodegeneration as seen in ALS.

GluR2 AMPA Receptor Subunit Expression in Motoneurons at Low and High Risk for Degeneration in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder that results in selective degeneration of most, but not all, groups of motoneurons. The greater susceptibility of vulnerable motoneurons to glutamate excitotoxicity and neurodegeneration has been hypothesized to result from their lower expression of the GluR2 AMPA receptor subunit under control conditions, which renders these receptors permeable to calcium. To address the question of whether there is differential expression of the GluR2 subunit in motoneurons, we compared in normal adult rats expression of GluR2 mRNA and protein within two cranial motor nuclei that are either resistant (III; oculomotor nucleus) or vulnerable (XII; hypoglossal nucleus) to degeneration in ALS. RT-PCR analysis of tissue punched from III and XII motor nuclei detected mRNA for all AMPA subunits (GluR1-R4). In situ hybridization demonstrated no significant difference in GluR2 mRNA expression between III and XII nuclei. Immunohistochemical examination of GluR2 (and GluR4) protein levels demonstrated a similar pattern of the subunit expression in both motor nuclei. This equivalent expression of GluR2 mRNA and protein in motoneurons that differ in their vulnerability to degeneration in ALS suggests that reduced expression of GluR2 is not a factor predisposing motoneurons to degeneration.

Calcium binding proteins in motoneurons at low and high risk for degeneration in ALS

Recent reports challenge the hypothesis that expression of calcium binding proteins contributes to the greater resistance of some motoneurons to degeneration in amyotrophic lateral sclerosis (ALS). We therefore re-examined, using immunohistochemistry, the expression of calbindin, calretinin and parvalbumin in vulnerable (hypoglossal, XII; and cervical spinal) and resistant (oculomotor, III) motoneurons of adult rats. Calbindin immunoreactivity was lacking in motor nuclei but strong in the dorsal horn. Calretinin was expressed in spinal, but not III or XII, motoneurons. Parvalbumin immunoreactivity, tested with a polyclonal antibody, was intense in spinal and III, but not XII, motoneurons; however, no staining in the ventral horn was observed with a monoclonal antibody. Differential expression of calretinin and parvalbumin within vulnerable motoneurons suggests that immunoreactivity for these proteins is not a reliable marker for resistance to degeneration in ALS.

Late results of mitral valve replacement with Carpentier-Edwards high profile bioprosthesis in young adults

Carpentier-Edwards (C/E) high profile supra-annular porcine bioprostheses were implanted in 163 patients between September 1982-February 1987 in the mitral position due to rheumatic disease. The patients' ages ranged between 15 and 58 years (mean: 36.5 +/- 11.5). One hundred-two of the patients (62.5%) were female. The hospital mortality was 9.8% (16/163). The total cumulative follow-up period was 1093 patient-years (p-y) with a mean of 7.3 +/- 3.5 p-y (range 6 months-12 years). Linearised occurrence rates of the late complications were as follows: Thromboembolism 0.82%/p-v, anticoagulant-related bleeding 1.0%/p-y, prosthetic valve endocarditis 0.09%/p-y. Actuarial survival rates for 5 and 12 years were 87% +/- 6% and 76% +/- 9%, respectively, with 95% confidence limits. Freedom from structural deterioration was 92% +/- 5% for 5 years and 44% +/- 11% for 12 years. Freedom from all valve-related complications was 81% +/- 7 for 5 years and 26% +/- 9 for 12 years. In conclusion, this prosthesis provides satisfactory clinical performance in young population despite the high risk of degeneration with good prognosis and better tolerability of reoperation.