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.     

Medical care of persons aged 25-84 years with acute myocardial infarction in Kaunas in 1996 (ischemic heart disease register data)

AIM: To evaluate peculiarities of medical care provided for patients with acute myocardial infarction (AMI) depending on sex and age in Kaunas in 1996. METHODS: Kaunas community-based ischemic heart disease register conducted according to the WHO MONICA Project methodology was the source of the data. RESULTS: Number of diagnosed acute myocardial infarctions among Kaunas population aged 25-84 years in 1996 was 1269. Only 28 day AMI survivors were considered in the present study (n=626). During first 4 hours from onset of chest pain male patients sought for medical assistance as frequently as female AMI patients: 38.1% and 34.0%, respectively. A mobile team provided first medical aid in 62.3% of cases. Thrombolytics were used in each 11th men and in 3% of women. Percutaneous coronary angioplasty was carried out in 4.9 and 1.2% of men and women, respectively. Coronary angiography and angioplasty were more often performed in men (13.1 and 4.9%, respectively) than in women (2.7 and 1.2, respectively).     

Prediction of improvement in left ventricular function during a 1-year follow-up after acute myocardial infarction by the degree of acute resolution of electrocardiographic changes

Background and Purpose

Reperfusion therapy results in better left ventricle (LV) function in cases of successful myocardial reperfusion; however, insufficient reperfusion or reocclusion of the infarct-related artery is associated with LV dysfunction. This study was proposed to determine whether the rate of ECG stage dynamics, after mechanical, thrombolytic, or spontaneous recanalization, is a predictor of improvement in LV function.

Methods

Twenty-seven consecutive patients, observed for 1 year, were divided into group A (11, change rate of ≥2 ECG stages per 2 days), group B (13, no rapid change), and cases with reocclusion (3).

Results

Clinical and radiographic signs of heart failure tended to decrease in group A but tended to increase in other cases. Echocardiographic dyssynergic score decreased, and LV ejection fraction increased only in group A: 4.3 ± 1.2 vs 2.7 ± 1.5, P = .04, and 42.0 ± 4.8 vs 46.0 ± 8.3, P = .049, respectively; in group B, the values were 3.4 ± 2.4 vs 3.4 ± 2.2 and 44.0 ± 6.9 vs 43.8 ± 9.3, respectively.

Conclusions

Rapid ECG stage changes predict follow-up improvement in LV function.     

Link between monthly rates of four subtypes of acute myocardial infarction and their corresponding cosmophysical activity parameters

The aim of this study was (1) to examine the relation between the monthly rate of acute myocardial infarction (AMI) and three cosmophysical activity parameters: solar activity (SA), geomagnetic activity (GMA), and cosmic rays activity (CRA) levels; (2) to study whether different subtypes of AMI: ST-elevation MI (STEMI), non-ST-elevation (NSTEMI), Q-wave (Q-waveMI) and non-Q-wave (NQ-wave MI) are linked with monthly cosmophysical indices or with the daily level (I degrees-IV degrees) of GMA. METHODS: For the first question, we studied for 204 consecutive months (1983-1999) 16,683 patients (including 10405 males) with AMI who were included in the Kaunas Registry and for the second, 3824 AMI patients (2342 males), 72-month data. Cosmophysical data were obtained from the Apatity Neutron Monitoring Station of the Russian Academy of Science. RESULTS: According to neutron monitoring data, total AMI and all its subtypes significantly correlated with monthly levels of CRA and inversely correlated with SA and GMA indices (r = 0.32-0.45; p = 0.0007-0.0001). No significant correlation was found between AMI subtypes and the daily level (I degrees-IV degrees) of GMA. All cosmophysical parameters were stronger in female patients. CONCLUSION: The monthly rates of all subtypes of AMI were significantly correlated with CRA and inversely correlated with SA and GMA, more strongly in female patients. We presume that the environmental factors studied here affect the general patho-physiological components of AMI, and that different subtypes are a consequence of the localization and extent of the process.     

The counterphobic defense in children

The clinical data for this study were derived from the case histories of five children who consistently used the counterphobic defense either alone or in combination with phobic attitudes. The children's manifestations of this defense appeared in both verbal and nonverbal behavioral patterns. The choice of defensive style was found related to at least three factors: an early history of trauma, especially separation, parental encouragement of toughness, and essentially a counterphobic family style.     

New insights into bacterial persistence in reactive arthritis

Persistence of arthritis-triggering bacteria can cause chronization of reactive arthritis (ReA). In the evaluation of bacterial persistence in ReA, the persistence of both the triggering bacteria and also of the other bacteria residing in the foci of chronic infection, are important. Two forms of bacterial persistence, cell wall-deficient bacteria (L-forms) and bacterial biofilms, are characterized, and the possible links between these forms and ReA are revealed. Data showing the possibility of bacterial ReA triggers to enter the cell wall-deficient state and to persist in bacterial biofilms, and evidence, suggesting that cell wall-deficient bacteria and bacterial biofilms are involved in the foci of chronic infection, are discussed. The understanding of the properties of microbes when they exist in cell wall-deficient state and bacterial biofilms may expand our knowledge on the clinical value of persisting microorganisms in ReA. In conclusion, both modes of persistence, cell wall-deficient state of bacteria and bacterial biofilms, deserve rheumatologists' attention, as their investigation, applying modern standardized methods, may contribute to the elaboration of new beneficial schemes of antibacterial ReA therapy.     

Le « channelome » du chondrocyte. Revue narrative

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