The chondrocyte channelome: A narrative review

Chondrocytes are the main cells in the extracellular matrix (ECM) of articular cartilage and possess a highly differentiated phenotype that is the hallmark of the unique physiological functions of this specialised load-bearing connective tissue. The plasma membrane of articular chondrocytes contains a rich and diverse complement of membrane proteins, known as the membranome, which defines the cell surface phenotype of the cells. The membranome is a key target of pharmacological agents and is important for chondrocyte function. It includes channels, transporters, enzymes, receptors, and anchors for intracellular, cytoskeletal and ECM proteins and other macromolecular complexes. The chondrocyte channelome is a sub-compartment of the membranome and includes a complete set of ion channels and porins expressed in these cells. Many of these are multi-functional proteins with “moonlighting” roles, serving as channels, receptors and signalling components of larger molecular assemblies. The aim of this review is to summarise our current knowledge of the fundamental aspects of the chondrocyte channelome, discuss its relevance to cartilage biology and highlight its possible role in the pathogenesis of osteoarthritis (OA). Excessive and inappropriate mechanical loads, an inflammatory micro-environment, alternative splicing of channel components or accumulation of basic calcium phosphate crystals can result in an altered chondrocyte channelome impairing its function. Alterations in Ca²⁺ signalling may lead to defective synthesis of ECM macromolecules and aggravated catabolic responses in chondrocytes, which is an important and relatively unexplored aspect of the complex and poorly understood mechanism of OA development.     

Cough and paradoxical vocal fold motion

OBJECTIVES: The differential diagnosis and treatment of patients with chronic cough, paradoxical vocal fold motion, and disordered breathing can be a challenge to most practicing otolaryngologists. Tracheobronchial (ie, asthma, bronchitis, and tracheal stenosis), laryngeal (ie, vocal fold paralysis and neoplasms), and rhinologic (ie, allergies and rhinosinusitis) etiologies are commonly diagnosed and treated effectively. However, occasionally one is faced with patients who are refractory to medical treatment and have no obvious rhinologic, laryngeal or pulmonary cause. STUDY DESIGN AND SETTING: We conducted a review of the literature. METHODS: We present a thorough review of the current medical literature exploring the complex neurologic mechanisms involved in the production of cough and the relationship between gastroesophageal reflux disease, vagal neurapathy, and paradoxical vocal fold motion. RESULTS: The diagnosis and successful treatment of chronic cough can be complex. It requires a thorough understanding of the neurologic mechanisms behind cough excitation and suppression. Successful treatment strategies include aggressive management of the patient's reactive airway disease, gastroesophageal reflux disease, and, in select cases, paradoxical vocal fold motion. This may involve a well-coordinated effort among pulmonologists, otolaryngologists, gastroenterologists, and speech pathologists. CONCLUSION: Gastroesophageal reflux disease, vagal neuropathy, and paradoxical vocal fold motion are additional causes of chronic cough and disordered breathing that need to be considered, in the absence of obvious laryngotracheal and/or rhinologic pathology. A high index of suspicion is essential in making the diagnosis and formulating an effective multidisciplinary treatment plan for these patients.     

Leptin, lipid and lipid metabolism-related hormones in chronic renal failure in Arabia

SUMMARY: In patients with chronic renal failure (CRF), hyperleptinaemia has been widely reported, but the exact mechanisms leading to elevated leptin levels are unclear. Impaired renal clearance of leptin and the influence of other hormones may be important. In this study, we measured serum leptin levels in 150 patients on haemodialysis, peritoneal dialysis or in the predialysis phase of CRF. Furthermore, we measured plasma levels of insulin, growth hormone (GH) and insulin-like growth factor 1 (IGF-1), as well as plasma levels of triacylglycerols and total low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol. We observed significantly elevated levels of leptin, particularly in female patients, and leptin was shown to correlate significantly with insulin, total and LDL-cholesterol and log triacylglycerols. Leptin was inversely correlated with GH concentrations, but was not correlated with IGF-1 levels. Despite the multiple correlations established between leptin levels and other variables, only hyperinsulinaemia in CRF seems to be important as a determinator of leptin levels.     

Displaced acetabular fractures

Displaced acetabular fractures occur primarily in young adults involved in high energy trauma and can lead to disabling posttraumatic arthritis. An initial roentgenographic evaluation with accurate delineation of all fracture lines provides the key to decisions about whether to give closed or open treatment. When open treatment is indicated, a surgical approach can be chosen that will almost always lead to reduction without the necessity of a second approach. The authors have found that the Kocher-Langenbeck, ilioinguinal, and extended iliofemoral approaches are the most useful. A fracture table and specialized reduction instruments aid fracture reduction and fixation. Satisfactory operative reduction of the fracture is the factor that correlates best with a satisfactory clinical result. The rate of satisfactory operative reductions improved gradually over the first 50 operations of a prospective study of 121 displaced acetabular fractures. Overall, there were 80% satisfactory clinical results in this series. Complications included a 3% infection rate and a 5% incidence of nerve palsy. Open reduction and internal fixation are indicated for the majority of displaced fractures. However, closed treatment can produce satisfactory results in selected patients.     

Buserelin in premenstrual syndrome.

Buserelin, a luteinizing hormone releasing hormone agonist was administered nasally in doses of 900 micrograms daily to inhibit the ovarian cycle. Of 16 patients recruited, ten completed the treatment. Daily symptoms were measured on the Visual Analogue Scale and Trigg's trend analysis utilized for the analysis. The peak severity of symptoms (ESAmax) and the maximum global scores (Gmax) reduced on buserelin treatment. The minimum global scores (Gmin) and the minimum score for each symptom (ESAmin) increased, suggesting worsening of underlying symptoms. The difference between ESAmax and ESAmin (ESAdelta) and Gmax and Gmin (Gdelta) were calculated to determine the degree of symptom change. The delta scores for symptoms of depression, bloatedness and breast symptoms, and Gdelta were significantly reduced (p less than 0.05) on buserelin, whilst the latter significantly worsened in the follow-up months. Side-effects may limit the place of buserelin in the long-term treatment of premenstrual syndrome, although combination of additional hormonal treatment may facilitate long-term treatment.