scholarly journals Chondromalacia patellae: current options and emerging cell therapies

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Weitao Zheng ◽  
Hanluo Li ◽  
Kanghong Hu ◽  
Liming Li ◽  
Mingjian Bei

AbstractChondromalacia patellae (CMP), also known as runner’s knee, typically occurs in young patients, which is characterized by anterior knee pain (AKP) that is associated with visible changes in patellar cartilage. The initial pathological changes include cartilage softening, swelling, and edema. CMP is caused by several factors, including trauma, increased cartilage vulnerability, patellofemoral instability, bony anatomic variations, abnormal patellar kinematics, and occupation hazards. CMP may be reversible or may progress to develop patellofemoral osteoarthritis. Quadriceps wasting, patellofemoral crepitus, and effusion are obvious clinical indications. Additionally, radiological examinations are also necessary for diagnosis. Magnetic resonance imaging (MRI) is a non-invasive diagnostic method, which holds a promise in having the unique ability to potentially identify cartilage lesions. Modalities are conventionally proposed to treat cartilage lesions in the PF joint, but none have emerged as a gold standard, neither to alleviated symptoms and function nor to prevent OA degeneration. Recently, researchers have been focused on cartilage-targeted therapy. Various efforts including cell therapy and tissue emerge for cartilage regeneration exhibit as the promising regime, especially in the application of mesenchymal stem cells (MSCs). Intra-articular injections of variously sourced MSC are found safe and beneficial for treating CMP with improved clinical parameters, less invasiveness, symptomatic relief, and reduced inflammation. The mechanism of MSC injection remains further clinical investigation and is tremendously promising for CMP treatment. In this short review, etiology, MRI diagnosis, and treatment in CMP, especially the treatment of the cell-based therapies, are reviewed.

2021 ◽  
Vol 12 ◽  
Author(s):  
Mariam Moalla ◽  
Wajdi Safi ◽  
Maab Babiker Mansour ◽  
Mohamed Hadj Kacem ◽  
Mona Mahfood ◽  
...  

Introduction/AimsMaturity-Onset Diabetes of the Young (MODY) is a monogenic non-autoimmune diabetes with 14 different genetic forms. MODY-related mutations are rarely found in the Tunisian population. Here, we explored MODY related genes sequences among seventeen unrelated Tunisian probands qualifying the MODY clinical criteria.Materials and MethodsThe GCK and HNF1A genes were systematically analyzed by direct sequencing in all probands. Then, clinical exome sequencing of 4,813 genes was performed on three unrelated patients. Among them, 130 genes have been reported to be involved in the regulation of glucose metabolism, β-cell development, differentiation and function. All identified variants were analyzed according to their frequencies in the GnomAD database and validated by direct sequencing.ResultsWe identified the previously reported GCK mutation (rs1085307455) in one patient. The clinical features of the MODY2 proband were similar to previous reports. In this study, we revealed rare and novel alterations in GCK (rs780806456) and ABCC8 (rs201499958) genes with uncertain significance. We also found two likely benign alterations in HNF1A (rs1800574) and KLF11 (rs35927125) genes with minor allele frequencies similar to those depicted in public databases. No pathogenic variants have been identified through clinical exome analysis.ConclusionsThe most appropriate patients were selected, following a strict clinical screening approach, for genetic testing. However, the known MODY1-13 genes could not explain most of the Tunisian MODY cases, suggesting the involvement of unidentified genes in the majority of Tunisian affected families.


2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.


Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 931
Author(s):  
Chiao-Hsu Ke ◽  
Chia-Hui Hsu ◽  
Yu-Ling Lin ◽  
Wei-Hsiang Huang ◽  
Hsin-Pei Weng ◽  
...  

Osteoarthritis (OA) is a common degenerative disorder and is accompanied by numerous pain symptoms. With increased age, individuals develop a chronic inflammatory status, and pro-inflammatory cytokines as well as mediators contribute to the progression of OA. However, no desirable remedies have been completely able to inhibit OA progression or safely provide effective symptomatic relief. Natural component extracts or dietary-derived compounds are widely used for anti-inflammatory diseases. Curcumin and freshwater clam extract (FCE) have been proven as functional foods that are able to regulate immune systems. This study demonstrated that curcumin and FCE had synergistic effects on alleviating the progression of OA by assuaging inflammation and repairing the cartilage within the joints. After consumption of curcumin and FCE, the severity of synovitis was quantified by the infrapatellar fat pad inflammation scoring system and the Osteoarthritis Research Society International (OARSI) scoring system. Significant improvement and articular cartilage regeneration were noted. Moreover, once the inflammation within the joints was reduced, the animals redistributed their body weight on the OA-induced hindlimb. In summary, curcumin and FCE possess desirable anti-inflammatory and repair functions, suggesting their potential as alternative remedies in the management of OA or other inflammatory diseases.


Cartilage ◽  
2020 ◽  
pp. 194760352095450
Author(s):  
Jesus Medina ◽  
Ignacio Garcia-Mansilla ◽  
Peter D. Fabricant ◽  
Thomas J. Kremen ◽  
Seth L. Sherman ◽  
...  

Objective The purpose of this study was to describe the current practice trends for managing symptomatic cartilage lesions of the knee with microfracture among ICRS (International Cartilage Regeneration & Joint Repair Society) members. Design A 42-item electronic questionnaire was sent to all ICRS members, which explored indications, surgical technique, postoperative management, and outcomes of the microfracture procedure for the treatment of symptomatic, full thickness chondral and osteochondral defects of the knee. Responses were compared between surgeons from different regions and years of practice. Results A total of 385 surgeons answered the questionnaire. There was a significant difference noted in the use of microfracture among surgeons by region ( P < 0.001). There was no association between the number of years in practice and the self-reported proportion of microfracture cases performed ( P = 0.37). Fifty-eight subjects (15%) indicated that they do not perform microfracture at all. Regarding indication for surgery, 56% of surgeons would limit their indication of microfracture to lesions measuring 2 cm2 or less. Half of the surgeons reported no upper age or body mass index limit. Regarding surgical technique, 90% of surgeons would recommend a formal debridement of the calcified layer and 91% believe it is important to create stable vertical walls. Overall, 47% of surgeons use biologic augmentation, with no significant difference between regions ( P = 0.35) or years of practice ( P = 0.67). Rehabilitation protocols varied widely among surgeons. Conclusions Indications, operative technique, and rehabilitation protocols utilized for patients undergoing microfracture procedures vary widely among ICRS members. Regional differences and resources likely contribute to these practice pattern variations.


1995 ◽  
Vol 4 (4) ◽  
pp. 393-400 ◽  
Author(s):  
Olle Lindvall

Cell transplantation is now being explored as a new therapeutic strategy to restore function in the diseased human central nervous system. Neural grafts show long-term survival and function in patients with Parkinson's disease but the symptomatic relief needs to be increased. Cell transplantation seems justified in patients with Huntington's disease and, at a later stage, possibly also in demyelinating disorders. The further development in this research field will require systematic studies in animal experiments but also well-designed clinical trials in small groups of patients.


2013 ◽  
Vol 25 (1) ◽  
pp. 42-45
Author(s):  
AFMA Chowdhury ◽  
A Alam ◽  
UK Sarkar ◽  
AA Mahmud ◽  
U Habiba ◽  
...  

Dental trauma is common in young patients with immature teeth. When necrosis of pulp follows in such a tooth, apexification of the root is the most recognized and accepted treatment of choice. Calcium hydroxide paste is the most popular material used to induce the apical hard tissue barrier which may be composed of different tissues. Hertwig’s epithelial root sheath and (or) its remnants, the cell rests of Malassez may contribute to the apical closure. In the presented case, careful multidisciplinary treatment approach helped to regain esthetic and function. After 27 months the tooth showed every sign of success. DOI: http://dx.doi.org/10.3329/medtoday.v25i1.16071 Medicine Today 2013 Vol.25(1): 42-45


2021 ◽  
pp. 56-57
Author(s):  
Jakra Priyanka ◽  
Mishra Meenu ◽  
Soni Kamini

Introduction:Avascular necrosis is also known as aseptic, osteonecrosis and ischaemic necrosis of bone. There are a multitude of risk factors but over 80% of cases are attributed to glucocorticoid treatment or alcohol excess. Avascular Necrosis of femoral head is the most common type of necrosis, because the artery supplying to neck of femur is very narrow which easily gets injured. In modern medicine there is no specic treatment rather than surgery. In Ayurveda avascular necrosis can be correlated with Asthimajjagatvata. Aim: To assess the efcacy of Dashmooladi Majja Sneha in the management of avascular necrosis. The objective of the treatment includes the preservation of structure and function of hip joint with symptomatic relief. Materials & Methods:The present case study is upon a 32 year old, diagnosed case of avascular necrosis of femoral head with complaints of pain in bilateral sacroiliac joint since one and half years which was associated with difculty in doing normal daily activities such as walking, sitting, squatting along with change in the gait, at the Panchakarma OPD of Govt. Ayurvedic hospital Bhopal. The patient of idiopathic AVN of femoral head was treated with Dashmooladi Majja Sneha, Brihatvata Chintamani Rasa, Amritaristha, Panchtikta Ghrita Guggulu and Shastik Shali Pind Swedan have done as per the classical method for 30 days. Assessment was done after treatment and follow up after 15 days for 2months. Observations: The Ayurvedic therapies and oral medicines yielded complete symptomatic relief from pain, general debility and improvement in the gait. Conclusion: On the basis of the results obtained it can be concluded that Dashmooladi Majja Sneha, Shastik Shali Pind Swedan and some oral medicines can be used as an effective treatment in the management of Avascular Necrosis.


2020 ◽  
Vol 21 (19) ◽  
pp. 7424
Author(s):  
Nicholas J. Chandler ◽  
Melissa J. Call ◽  
Matthew E. Call

The impressive success of chimeric antigen receptor (CAR)-T cell therapies in treating advanced B-cell malignancies has spurred a frenzy of activity aimed at developing CAR-T therapies for other cancers, particularly solid tumors, and optimizing engineered T cells for maximum clinical benefit in many different disease contexts. A rapidly growing body of design work is examining every modular component of traditional single-chain CARs as well as expanding out into many new and innovative engineered immunoreceptor designs that depart from this template. New approaches to immune cell and receptor engineering are being reported with rapidly increasing frequency, and many recent high-quality reviews (including one in this special issue) provide comprehensive coverage of the history and current state of the art in CAR-T and related cellular immunotherapies. In this review, we step back to examine our current understanding of the structure-function relationships in natural and engineered lymphocyte-activating receptors, with an eye towards evaluating how well the current-generation CAR designs recapitulate the most desirable features of their natural counterparts. We identify key areas that we believe are under-studied and therefore represent opportunities to further improve our grasp of form and function in natural and engineered receptors and to rationally design better therapeutics.


2019 ◽  
Vol 15 (4) ◽  
pp. 20190059 ◽  
Author(s):  
Katharina Riebel ◽  
Karan J. Odom ◽  
Naomi E. Langmore ◽  
Michelle L. Hall

Historically, bird song has been regarded as a sex-specific signalling trait; males sing to attract females and females drive the evolution of signal exaggeration by preferring males with ever more complex songs. This view provides no functional role for female song. Historic geographical research biases generalized pronounced sex differences of phylogenetically derived northern temperate zone songbirds to all songbirds. However, we now know that female song is common and that both sexes probably sang in the ancestor of modern songbirds. This calls for research on adaptive explanations and mechanisms regulating female song, and a reassessment of questions and approaches to identify selection pressures driving song elaboration in both sexes and subsequent loss of female song in some clades. In this short review and perspective we highlight newly emerging questions and propose a research framework to investigate female song and song sex differences across species. We encourage experimental tests of mechanism, ontogeny, and function integrated with comparative evolutionary analyses. Moreover, we discuss the wider implications of female bird song research for our understanding of male and female communication roles.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 152 ◽  
Author(s):  
Nina Hanke ◽  
Claudia Kunz ◽  
Meinolf Thiemann ◽  
Harald Fricke ◽  
Thorsten Lehr

The protein therapeutic and CD95L inhibitor asunercept is currently under clinical investigation for the treatment of glioblastoma and myelodysplastic syndrome. The purpose of this study was to predict the asunercept pharmacokinetics in children and to give dose recommendations for its first use in pediatric glioblastoma patients. A physiologically-based pharmacokinetic (PBPK) model of asunercept in healthy and diseased adults was successfully developed using the available clinical Phase I and Phase II study data. This model was then extrapolated to different pediatric populations, to predict the asunercept exposure in children and to find equivalent starting doses. Simulation of the asunercept serum concentration-time curves in children between 1–18 years of age shows that a dosing regimen based on body weight results in a similar asunercept steady-state exposure in all patients (pediatric or adult) above 12 years of age. For children between 1–12 years, higher doses per kg body weight are recommended, with the highest dose for the very young patients. Translational PBPK modeling is strongly encouraged by regulatory agencies to help with the initial dose selection for pediatric trials. To our knowledge, this is the first report of pediatric PBPK to support the dose selection of a therapeutic protein before its administration to children.


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