Genomic and non-genomic action of vitamin D on ion channels - Targeting mitochondria.

Recent studies revealed that mitochondria are not only a place of vitamin D3 metabolism but also direct or indirect targets of its activities. This review summarizes current knowledge on the regulation of ion channels from plasma and mitochondrial membranes by the active form of vitamin D3 (1,25(OH)2D3). 1,25(OH)2D3, is a naturally occurring hormone with pleiotropic activities; implicated in the modulation of cell differentiation, and proliferation and in the prevention of various diseases, including cancer. Many experimental data indicate that 1,25(OH)2D3 deficiency induces ionic remodeling and 1,25(OH)2D3 regulates the activity of multiple ion channels. There are two main theories on how 1,25(OH)2D3 can modify the function of ion channels. First, describes the involvement of genomic pathways of response to 1,25(OH)2D3 in the regulation of the expression of the genes encoding channels, their auxiliary subunits, or additional regulators. Interestingly, intracellular ion channels, like mitochondrial, are encoded by the same genes as plasma membrane channels. Therefore, the comprehensive genomic regulation of the channels from these two different cellular compartments we analyzed using a bioinformatic approach. The second theory explores non-genomic pathways of vitamin D3 activities. It was shown, that 1,25(OH)2D3 indirectly regulates enzymes that impact ion channels, change membrane physical properties, or directly bind to channel proteins. In this article, the involvement of genomic and non-genomic pathways regulated by 1,25(OH)2D3 in the modulation of the levels and activity of plasma membrane and mitochondrial ion channels was investigated by an extensive review of the literature and analysis of the transcriptomic data using bioinformatics.

GREM2 nucleotide variants and the risk of tooth agenesis.

OBJECTIVE: The etiology of tooth agenesis (TA) is multifactorial and still not fully understood. The aim of the study was to test whether variants of GREM2, encoding a bone morphogenetic protein (BMP) antagonist, are associated with the risk of this common dental anomaly in a Polish population. SUBJECTS AND METHODS: Direct sequencing of the GREM2 coding sequence including exon/intron boundaries was performed in 95 patients with both hypodontia and oligodontia. All identified GREM2 variants were then further tested in an independent group of patients (n = 163) and controls (n = 184). RESULTS: The previously described, functional GREM2 mutation (c.226C > G, p.Gln76Glu) was identified in two patients with hypodontia and associated dental anomalies, including taurodontism and microdontia. This mutation generating an allele with increased inhibitory activity was not detected in the control group. The second identified GREM2 variant, c.-1-21C > T (rs11806449), was not associated with the risk TA. The polymorphism allele frequency in both patients and controls was 0.21 (OR = 1.0, 95%CI: 0.76-1.46). The rs11806449 did not correlate either with the overall TA phenotype or hypodontia/oligodontia phenotypes. CONCLUSION: Our study confirmed that GREM2 is a candidate gene for tooth agenesis, which mutations can explain, however, only a small fraction of the genetic contribution to the pathogenesis of this anomaly.

Three types of ion channels in the cell membrane of mouse fibroblasts.

Patch clamp recordings carried out in the inside-out configuration revealed activity of three kinds of channels: nonselective cation channels, small-conductance K(+) channels, and large-conductance anion channels. The nonselective cation channels did not distinguish between Na(+) and K(+). The unitary conductance of these channels reached 28 pS in a symmetrical concentration of 200 mM NaCl. A lower value of this parameter was recorded for the small-conductance K(+) channels and in a 50-fold gradient of K(+) (200 mM/4 mM) it reached 8 pS. The high selectivity of these channels to potassium was confirmed by the reversal potential (-97 mV), whose value was close to the equilibrium potential for potassium (-100 mV). One of the features of the largeconductance anion channels was high conductance amounting to 493 pS in a symmetrical concentration of 200 mM NaCl. The channels exhibited three subconductance levels. Moreover, an increase in the open probability of the channels at voltages close to zero was observed. The anion selectivity of the channels was low, because the channels were permeable to both Cl(-) and gluconate - a large anion. Research on the calcium dependence revealed that internal calcium activates nonselective cation channels and small-conductance K(+) channels, but not largeconductance anion channels.

Comparison of dose-volume histograms and dose-wall histograms of the rectum of patients treated with intracavitary brachytherapy.

The correlation between dose values from dose-volume histograms (DVHs) and dose values from dose-wall histograms (DWHs) of the rectum tissue of patient with uterine cervix cancer was determined. The minimum dose in 2 cm3 in the high-dose region of the DVH is a good estimate of the dose in the rectum wall.

[Clinical characteristics of migraine in children according to the age]. / Obraz kliniczny migreny u dzieci w zaleznosci od wieku.

We investigated 100 children with migraine admitted to the Developmental Neurology Department, Medical University of Gdansk between 1988-1997. The diagnosis was made on IHS Criteria (1988). There were 53 children with migraine with aura and 47--without aura. The children were divided into three groups according to the onset of migraine attacks (3-16 years of age). To reveal the relation between clinical manifestation of migraine and the age, statistical analysis was made. The results showed that a higher frequency of migraine with aura was observed in the oldest group of children. Boys were more predisposed to develop migraine earlier. The headaches most often were pulsatile and located in the forehead, rarely-lateralized. There was no relation between location of headache, age, sex and type of migraine. In 63% of children the duration of headache was above 2 hours, in 37%--from few minutes to 2 hours. Vomiting was noticed in two thirds of patients, phonophobia and photophobia were observed in 20 children with migraine without aura and in 5 children with migraine with aura. The frequency of migraine attacks was higher in migraine without aura. Aura symptoms were mainly sensory and visual. CT and MRI were negative.

[Prevalence of COPD in Gdansk sea port workers]. / Czestosc wystepowania przewleklej obturacyjnej choroby pluc wsród pracowników portowych.

UNLABELLED: The purpose of the study was to evaluate prevalence of COPD in sea-port workers who has been employed with handling phosphoric compounds, sulphur compounds and grain. Smoking habits has been also analysed. Study group consists of 238 persons working in Gdansk sea-port. Protocol of the study has included: medical history, detailed description of work place, smoking habit analysis and spirometric study. As a spirometric parameters FEV1, FVC, FEV1%VC, PEF, MEF25%VC, MEF50%VC and MEF75%VC has been assessed. In study group 106 persons worked with phosphoric compounds handling, 42 persons with sulphuric compounds handling and 90 persons with grain handling. COPD had been diagnosed in 55 persons--43 smokers and 12 non-smokers. Mean values of FEV1% in groups with equal 10-20 years time-work has been compared. Typical COPD features has been present in 37 persons--25 smokers and 12 non-smokers. COPD has been defined based on medical history, physical examination and no response o FEV1 after bronchodilatator application (Berodual). CONCLUSION: Smoking habits in Gdansk sea-port workers has been more important factor in COPD development than work place toxicities.

[A case of binocular blindness in small cell lung cancer]. / Przypadek obuocznej slepoty w przebiegu drobnokomórkowego raka pluca.

A was reported case of binocular blindness associated with small cell lung cancer. Most probably this complication was a clinical manifestation of the paraneoplastic syndrome. No tumor response was induced with chemotherapy and patient died due to tumor progression.

[The influence of passive smoking on the respiratory tract]. / Wplyw biernego palenia papierosów na uklad oddechowy.

The harmful effects of passive smoking are well known and proved. A cause-and-effect relationship between involuntary inhalation of cigarette smoke and increased number of various respiratory diseases either in children or in adults is now clearly established. Many publications indicate that the respiratory consequences of passive smoking in humans may include nonmalignant disease in addition to lung cancer. It has been observed that children exposed to cigarette smoke have more frequently asthma and other wheezing diseases. An influence of the passive smoking on the pulmonary function tests has been also widely examined. A functional disorders especially of bronchioles have been detected. Since adverse effects of passive smoking on human health are proved there is a necessity to enable life in the environment free from cigarette smoke.

[Thoracoscopy]. / Wziernikowanie jamy oplucnej.

The purpose of the work is presentation of own experience in the use of thoracoscopy in patients with pathological pleural changes. In the years 1989-1991 in the Chair and Department of Pulmonology and Tuberculosis, Medical Academy in Gdansk, 20 thoracoscopies were performed with simultaneous taking of material for histopathological examination. In 15 patients from this group the diagnosis was made confirming the aetiology of pleural pathological changes. It should be stressed that in the group of patients with suspected malignancy, the diagnosis was confirmed in 100% of cases. Thoracoscopy is a useful diagnostic procedure during which aimed pleural biopsy may be performed.