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.     

A new method for the termination of cervical pregnancy]

The authors described a 7 weeks old cervical pregnant case, whome was administered 250 mg methotrexate in infusion to eliminate the throphoblastic tissue. 3 days later the HCG was negative in the urine. After the dilatation of cervix by laminaria, the collapsed amniotic sac came from the cervix with minimal hemorrhage. They suggest the method is suitable to prevent the serious complications of cervical pregnancy.     

Primary Radiotherapy of Stage IIA/B–IIIB Cervical Carcinoma

BACKGROUND: Comprehensive literature on cervical cancer demonstrates, even today, the need for optimization of the timing of external-beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) in the treatment of stage IIA/B-IIIB cervical carcinoma. PATIENTS AND METHODS: 210 patients with carcinoma of the cervix were treated in the Municipal Center of Oncoradiology between January 1991 and December 1996 (FIGO IIA: n = 10, FIGO IIB: n = 113, and FIGO IIIB: n = 87). Two regimens were compared: sequential radiation therapy (SRT) with 4 x 8 Gy HDR-BT to point A followed by EBRT, and continuous radiation therapy (CRT) in which 5 x 6 Gy HDR-BT to point A, one session per week, was integrated into the EBRT. A total dose of 68-70 Gy to point A and 52-54 Gy to point B was given in EBRT with SRT, five fractions per week were applied. Four fractions per week were applied in CRT, i. e., no EBRT was performed on the day of HDR-BT. Total doses to points A and B were identical in both regimens. Overall treatment time (OTT) amounted to 56 days for SRT and 35 days for CRT. Median follow-up time was 3.4 (2.5-4.2) years. RESULTS: Progression-free 5-year-survival (PFS) was 71% in the CRT and 56% in the SRT group. Nevertheless, this difference was not statistically significant (p = 1.00), and the same was found in a subgroup analysis of the different tumor stages, showing, however, an unequivocal trend. Late bladder and rectal injuries occurred in 13% and 25%, respectively. Late rectal injuries were significantly more frequent with SRT than CRT (35 patients in the SRT and 18 patients in the CRT group; p = 0.037). This was due to the higher doses per fraction of HDR-BT in the SRT group. No difference was found regarding late bladder injuries (p = 0.837). CONCLUSION: For the patients included in this study, no advantage has been found so far in using CRT, i. e., shortening the OTT by weekly integration of HDR-BT into EBRT. Nevertheless, an obvious trend exists. The dose of 8 Gy per fraction of HDR-BT in the SRT regimen was obviously too high. To achieve a significant improvement in local control and disease-free survival (DFS) as well as overall survival (OS), the combination with modern chemotherapy regimens and regional deep hyperthermia may rather be the treatment option.     

CMSS-VEPs: Contrast modulated steady state visual evoked potentials: Its neuronal origin and clinical use

CMSS-VEPs are presented as a sensitive, non-invasive functional investigation technique of the visual function, applicable in clinical practice. New improvements of the technique are presented. The underlying neuronal mechanisms are discussed. The clinical use is illustrated in a case of optic neuritis.     

Effect of sleep on interictal spikes and distribution of sleep spindles on electrocorticography in children with focal epilepsy.

OBJECTIVE: To determine how sleep with central spindles alters the spatial distribution of interictal spike frequency in children with intractable focal seizures, and whether such children have spindles arising from the medial temporal region in addition to the frontal-central region. METHODS: Seventeen children (age: 7 months-17 years) were studied using extraoperative electrocorticography (ECoG). RESULTS: Overall spike frequency across the subdural electrodes was greater during sleep with central spindles compared to wakefulness. In 13 children showing at least 1 spike/min in an electrode, the spatial distribution of spike frequency was similar during wakefulness and sleep; in addition, the spike frequency was greater in the seizure onset zones compared to the non-onset areas, regardless of wakefulness or sleep. Spindles were identified in the medial temporal region during sleep with central spindles in all 17 children. CONCLUSION: Overall spike frequency may be increased by sleep with spindles, but the spatial distribution of spike frequency appears similar during wakefulness and sleep in children with intractable focal seizures. SIGNIFICANCE: Both awake and sleep ECoG may be useful to predict seizure onset zones in children with intractable focal epilepsy. Medial temporal spindles are present in some children with focal epilepsy.     

Modulation by a moving texture of cat area 18 neuron responses to moving bars

1. The influence of a moving texture on neuronal responses to a moving bar was tested in 103 area 18 neurons of anesthetized and paralyzed cats. The texture was a two-dimensional noise pattern, the bar moved at optimal speed, and its contrast was adjusted to yield 50% of the maximum response. 2. The moving texture exerted two different but related effects: it suppressed the response of area 18 neurons to the moving bar, and it modulated the direction selectivity of parastriate neurons. These effects were strongest when the texture moved at the same speed or faster than the bar. 3. Genuine suppressive effects of the moving texture were distinguished from lack of summation between bar and texture responses. Suppressive effects of either type were observed in 75% of the area 18 cells and occurred more frequently among C family cells, velocity tuned cells, and in layer 5 than in other groups of cells. 4. The modulation of direction selectivity was distinguished from pseudomodulation because of lack of summation of bar and texture responses. The direction selectivity of 35% of the area 18 cells was modulated by the moving texture. Six different relative direction selectivity (RDS) types were observed in area 18. 5. The neurons of which direction selectivity was modulated by the moving texture occurred predominantly in layers 2-3 and 6, suggesting that they represent a further stage of processing within area 18. 6. Many (75%) area 18 cells responded to the texture moving on its own. Most of these cells respond to isolated features ("grains") in the patterns rather than to the movement of the whole pattern. Cells responding to the movement of the whole pattern were generally C family cells, and their direction selectivity was not modulated by the moving texture. 7. These results are compared with those obtained under identical experimental conditions in area 17. Although suppressive effects are similar in both areas, RDS types are differently distributed in the two areas. 8. The possible origins of the interactions and their functional significance are discussed.     

Genetic basis of tobacco smoking: strong association of a specific major histocompatibility complex haplotype on chromosome 6 with smoking behavior

The genetic basis for addiction to tobacco smoking--particularly that of the perception of olfactory stimuli that may be important in reinforcing smoking addiction--is largely unknown. A cluster of genes for olfactory receptors is in close proximity to the MHC region on chromosome 6. Polymorphisms of MHC class III genes (RCCX modules, TNFA promoter polymorphisms) were determined in 101 healthy subjects and 232 coronary artery disease (CAD) patients from Hungary with defined tobacco smoking habits. A highly significant association between ever smoking (past + current smokers) and a specific MHC haplotype was observed (odds ratios = 2.14-4.13; P-values = 0.012 to <0.001). This haplotype is characterized by the presence of C4A null alleles and a solitary short C4B gene linked to the TNF2 allele of the promoter for TNFA gene. This haplotype occurred more frequently in the ever smokers than in the never smokers [odds ratio: 4.97 (1.96-12.62); P = 0.001], and such associations were stronger in women (odds ratio = 13.6) than in men (odds ratio = 2.79). An independent study of complement C4 protein polymorphism and smoking habits in Icelandic subjects (n = 351) yielded similar and confirmative results. Considering the documented link between olfactory stimuli and smoking in females, and the presence of a cluster of odorant receptor genes close to the MHC class I region, our findings implicate a potential role of the MHC-linked olfactory receptor genes in the initiation of smoking.