Search

1. The ionic permeability of Necturus maculosus small intestine epithelial cells was investigated using intracellular microelectrodes to measure membrane potential in intact tissue or by the single-electrode voltage-clamp technique in isolated cells. 2. The basolateral membrane of enterocytes appears to be K+ selective as demonstrated by the dependence of membrane potential and fractional serosal resistance measured in the intact epithelium on serosal K+ concentration. 3. Isolated cells had membrane potentials similar to those measured in the intact tissue. Voltage-clamp experiments in a physiological Ringer solution showed the presence of both large outward and inward currents. 4. Removal of Cl- from the bathing medium, linear subtraction or the use of a Cl- channel blocker revealed outwardly rectifying currents. The quasi-linear component was also revealed following K+ channel inhibition; it reversed near ECl, suggesting that the charge carrier was Cl-. 5. Outwardly rectifying currents could be kinetically resolved into two components. A fast component (tau for activation < 4 ms) accounted for 60-80% of the total current at positive potentials. A slowly activating component appeared at voltages positive to 50 mV with tau for activation of > 25 ms. 6. The slow outward current showed strong voltage dependence of both activation and relaxation, which were faster at more depolarized potentials. 7. Both fast and slow outward currents seem to be carried by K+ as they were blocked by Ba2+ and tetraethylammonium (TEA). Tail current analysis of the slow component indicated a reversal potential very similar to EK. 8. Fast outward currents were half-activated at about -40 mV whereas slow outward currents were only apparent at more positive potentials. It is proposed that the fast outward K+ current plays a role, together with Cl- currents, in determining the resting membrane potential of Necturus enterocytes.

International audience; BACKGROUND & AIMS: Acinar cells constitute 90% of the pancreas epithelium, are polarized, and secrete digestive enzymes. These cells play a crucial role in pancreatitis and pancreatic cancer. However, there are limited models to study normal acinar cell differentiation in vitro. The aim of this work was to generate and characterize purified populations of pancreatic acinar cells from embryonic stem (ES) cells. METHODS: Reporter ES cells (Ela-pur) were generated that stably expressed both beta-galactosidase and puromycin resistance genes under the control of the elastase I promoter. Directed differentiation was achieved by incubation with conditioned media of cultured fetal pancreatic rudiments and adenoviral-mediated co-expression of p48/Ptf1a and Mist1, 2 basic helix-loop-helix transcription factors crucial for normal pancreatic acinar development and differentiation. RESULTS: Selected cells expressed multiple markers of acinar cells, including digestive enzymes and proteins of the secretory pathway, indicating activation of a coordinated differentiation program. The genes coding for digestive enzymes were not regulated as a single module, thus recapitulating what occurs during in vivo pancreatic development. The generated cells displayed transient agonist-induced Ca(2+) mobilization and showed a typical response to physiologic concentrations of secretagogues, including enzyme synthesis and secretion. Importantly, these effects did not imply the acquisition of a mixed acinar-ductal phenotype. CONCLUSIONS: These studies allow the generation of almost pure acinar-like cells from ES cells, providing a normal cell-based model for the study of the acinar differentiation program in vitro.

To analyze the degree of compliance with a variety of internationally accepted standards defined for Total Parenteral Nutrition (TPN) quality control in our Surgery Department.Prospective study of patients treated with TPN over two years in the department of surgery of a university teaching hospital (n = 72). Assessment of quality was performed by measurements of compliance using 19 criteria. The criteria were divided into three groups according to characteristics of TPN standardisation: this must be "appropriate" to the nutritional requirements of the patient, "safe" in order to prevent complications and "accurate" in its daily programming. Corrective measures aimed at resolving the quality problem were applied to the deficient criteria over six months, paying particular attention to those criteria which had the highest percentage of errors in the study carried out using a Pareto analysis. During a third period of six months the information on all 19 criteria was gathered again and the improvement with regard to the standard values and to the compliance in the first period (using the value of z) was evaluated.The compliance with seven criteria was significantly below standard values: all those of the "appropriate" group, except the criteria "type of diet" and "composition of the diet", and the criteria "absence of complications" of the "safe" group, which was also the one with the highest number of grouped non-compliances. In the second period all the below standard criteria improved with compared to the first period. The criteria "time of fasting", "concordance" and "duration" were significantly improved. The criteria "time of fasting", "duration" and "latency" reached the standard. The rest of criteria that reached their standard in the first evaluation maintained the same results.Corrective measures introduced were effective since all the below standard criteria improved, including metabolic complications. Notwithstanding, it is necessary to continue in this line to improve the criteria still below standard.

This study compares the effect of an acceptance-based protocol (ACT) and a cognitive control—based (CONT) protocol on three measures of pain coping: tolerance, self-report, and believability. Specific methodological controls were employed to further isolate the role of the value of participating in a pain task, compared to previous investigations on the alteration of the function of aversive stimulation. Twenty participants were randomly assigned to one of the conditions (ACT vs. CONT), and a pre—post design was used. In the ACT condition, the protocol established a relation of coordination between the pain-related thoughts and the actions in the valued direction. In the CONT condition, the protocol established a relation of opposition between the same aspects. Results show an increase in pain tolerance and a reduction of self-reported pain at posttest for both conditions. However, ACT participants showed significantly lower believability of pain than did CONT participants. Conceptual and clinical implications are discussed.

Calcium-dependent potassium channels are implicated in electrolyte transport, cell volume regulation and mechanical responses in epithelia, although the pathways for calcium entry and their coupling to the activation of potassium channels are not fully understood. We now show molecular evidence for the presence of TRPV4, a calcium permeable channel sensitive to osmotic and mechanical stress, and its functional coupling to the large conductance calcium-dependent potassium channel (BK(Ca)) in a human bronchial epithelial cell line (HBE). Reverse transcriptase polymerase chain reaction, intracellular calcium imaging and whole-cell patch-clamp experiments using HBE cells demonstrated the presence of TRPV4 messenger and Ca(2+) entry, and outwardly rectifying cationic currents elicited by the TRPV4 specific activator 4alpha-phorbol 12,13-didecanoate (4alphaPDD). Cell-attached and whole-cell patch-clamp of HBE cells exposed to 4alphaPDD, and hypotonic and high-viscosity solutions (related to mechanical stress) revealed the activation of BK(Ca) channels subsequent to extracellular Ca(2+) influx via TRPV4, an effect lost upon antisense-mediated knock-down of TRPV4. Further analysis of BK(Ca) modulation after TRPV4 activation showed that the Ca(2+) signal can be generated away from the BK(Ca) location at the plasma membrane, and it is not mediated by intracellular Ca(2+) release via ryanodine receptors. Finally, we have shown that, unlike the reported disengagement of TRPV4 and BK(Ca) in response to hypotonic solutions, cystic fibrosis bronchial epithelial cells (CFBE) preserve the functional coupling of TRPV4 and BK(Ca) in response to high-viscous solutions.

The Visible and Infrared Thermal Imaging Spectrometer (VIRTIS) on board the ESA/Venus Express mission has technical specifications well suited for many science objectives of Venus exploration. VIRTIS will both comprehensively explore a plethora of atmospheric properties and processes and map optical properties of the surface through its three channels, VIRTIS-M-vis (imaging spectrometer in the 0.3-1 μm range), VIRTIS-M-IR (imaging spectrometer in the 1-5 μm range) and VIRTIS-H (aperture high-resolution spectrometer in the 2-5 μm range). The atmospheric composition below the clouds will be repeatedly measured in the night side infrared windows over a wide range of latitudes and longitudes, thereby providing information on Venus's chemical cycles. In particular, CO, H2O, OCS and SO2 can be studied. The cloud structure will be repeatedly mapped from the brightness contrasts in the near-infrared night side windows, providing new insights into Venusian meteorology. The global circulation and local dynamics of Venus will be extensively studied from infrared and visible spectral images. The thermal structure above the clouds will be retrieved in the night side using the 4.3 μm fundamental band of CO2. The surface of Venus is detectable in the short-wave infrared windows on the night side at 1.01, 1.10 and 1.18 μm, providing constraints on surface properties and the extent of active volcanism. Many more tentative studies are also possible, such as lightning detection, the composition of volcanic emissions, and mesospheric wave propagation. © 2007 Elsevier Ltd. All rights reserved.

International audience; Recent improvements in a comprehensive non-local thermodynamic equilibrium (non-LTE) model of CO 2 atmospheres has permitted a better understanding of a number of Venusian atmospheric measurements taken more than a decade ago by the "Near Infrared Mapping Spectrometer" (NIMS) on board the Galileo spacecraft during its Venus fly-by. Those data, containing a strong non-LTE component, showed a structure in the 4.3-mum spectral region which was challenging for non-LTE models so far. The model used in this work was refined after analysis of Martian CO 2 atmospheric emission taken by the "Planetary Fourier Spectrometer" (PFS) and the "Visible and Infrared Mineralogical Mapping Spectrometer" (OMEGA) instruments on board Mars Express. Here we show that both the limb and the nadir measurements of the Venus daylight atmosphere taken at 4.3-mum by NIMS can be fitted reasonably well with the revised model. This gives confidence in the usage of such model for the analysis of the Venus Express mission, in particular for the "Visible Infrared Thermal Imaging Spectrometer" (VIRTIS) instrument which will systematically observe these emissions. We present here non-LTE simulations for VIRTIS which demonstrate its capabilities and potential for detecting atmospheric emissions of CO and CO 2 under non-LTE, both in limb and nadir observations and we discuss briefly the perspectives to use them in order to improve our understanding of the physics of the upper atmosphere of Venus.

Primary mucinous epithelial tumors of the testis are extremely rare. Although isolated case reports and small series have been published, these interesting neoplasms are less well-known. We report a case of a primary intratesticular mucinous cystadenoma in an asymptomatic 44-year-old man. Right radical orchiectomy was performed because a malignant testicular tumor was suspected. We discuss the management of this uncommon testicular tumor based on the limited reports.

Airway epithelial cells are exposed to changes in the osmolality of their environment under physiological and pathological conditions. The cell regulatory volume decrease (RVD) response triggered by hypotonic stress requires the coordinated activity of Cl− and K+ channels. We have investigated the molecular nature of K+ channels mediating RVD response in human tracheal and bronchial epithelial cells. Our molecular, electrophysiological and pharmacological studies demonstrate the functional expression of calciumdependent K+ channels in human airways and their contribution to the RVD response. While the main swelling-activated K+ channel in tracheal cells is an intermediate conductance potassium channel (IK, KCNN4),1 in bronchial cells, a big conductance K+ channel (BK, KCNMA1) is the key player.2 Early work in murine small intestine have established a link between the cystic fibrosis transmembrane conductance regulator (CFTR) and volume regulation, suggesting the defective RVD response observed in murine intestinal crypts of cystic fibrosis (CF) mice is caused by the dysfunction of a calcium-dependent K+ channel.3, 4 Likewise, we have found that RVD response is impaired in both human CF tracheal1 and bronchial epithelial cells. Furthermore, we have shown that this defect in volume regulation is due to the lack of swelling-induced activation of the calciumdependent potassium channel mediating RVD response.1 Our results suggest that, at least in bronchial epithelial cells, the increase in intracellular Ca2+ necessary for potassium channel activation in response to hypotonicity, is achieved by an increased Ca2+ entry trough a swelling-activated cation channel. The molecular identity of this Ca2+ entry pathway might be related to TRPV4,2 a TRP channel that has been described as responsive to changes in extracellular osmolarity.5-7 Our more recent data also suggest the altered modulation of B (big conductance) K channels in response to cell swelling might be linked to alterations in regulation of the Ca2+ entry pathway in CF bronchial cells.

Received 13 July 2005; revised 16 December 2005; accepted 27 December 2005; published 27 January 2006. [1] Warming of the martian lower thermosphere (100–130 km) at north polar latitudes near the perihelion/winter solstice (Ls = 270) was recently observed. No analogous warming has been observed within the south polar thermosphere during its aphelion/winter season (Ls 90). Detailed global model simulations are required to investigate the physical processes driving these seasonal variations. New simulations are conducted for conditions approximating the atmosphere during these Mars Global Surveyor (MGS) and Odyssey (ODY) aerobraking periods. Strong northern winter polar warming features are calculated near 120 km, yielding nightside mean temperatures 10–15 K warmer than observed ODY values. No southern winter polar warming trend is simulated; however, nightside mean temperatures are 20– 30 K warmer than observed by MGS. The stronger interhemispheric circulation during northern winter is clearly driven by stronger insolation and dust heating near perihelion, resulting in subsidence and warmer temperatures in the northern polar night. Citation: Bougher, S. W., J. M. Bell, J. R. Murphy, M. A. Lopez-Valverde, and P. G. Withers (2006), Polar warming in the Mars thermosphere: Seasonal variations owing to changing insolation and dust distributions, Geophys. Res. Lett., 33, L02203, doi:10.1029/2005GL024059.

High conductance, calcium- and voltage-activated potassium (BK, MaxiK) channels are widely expressed in mammals. In some tissues, the biophysical properties of BK channels are highly affected by coexpression of regulatory (beta) subunits. The most remarkable effects of beta1 and beta2 subunits are an increase of the calcium sensitivity and the slow down of channel kinetics. However, the detailed characteristics of channels formed by alpha and beta1 or beta2 are dissimilar, the most remarkable difference being a reduction of the voltage sensitivity in the presence of beta1 but not beta2. Here we reveal the molecular regions in these beta subunits that determine their differential functional coupling with the pore-forming alpha-subunit. We made chimeric constructs between beta1 and beta2 subunits, and BK channels formed by alpha and chimeric beta subunits were expressed in Xenopus laevis oocytes. The electrophysiological characteristics of the resulting channels were determined using the patch clamp technique. Chimeric exchange of the different regions of the beta1 and beta2 subunits demonstrates that the NH3 and COOH termini are the most relevant regions in defining the behavior of either subunit. This strongly suggests that the intracellular domains are crucial for the fine tuning of the effects of these beta subunits. Moreover, the intracellular domains of beta1 are responsible for the reduction of the BK channel voltage dependence. This agrees with previous studies that suggested the intracellular regions of the alpha-subunit to be the target of the modulation by the beta1-subunit.

The E65K polymorphism in the β 1 -subunit of the large-conductance, Ca 2+ -dependent K + (BK) channel, a key element in the control of arterial tone, has recently been associated with low prevalence of diastolic hypertension. We now report the modulatory effect of sex and age on the association of the E65K polymorphism with low prevalence of diastolic hypertension and the protective role of E65K polymorphism against cardiovascular disease. We analyzed the genotype frequency of the E65K polymorphism in 3924 participants selected randomly in two cross-sectional studies. A five-year follow-up of the cohort was performed to determine whether cardiovascular events had occurred since inclusion. Estrogen modulation of wild-type and mutant ion channel activity was assessed after heterologous expression and electrophysiological studies. Multivariate regression analyses showed that increasing age upmodulates the protective effect of the K allele against moderate-to-severe diastolic hypertension in the overall group of participants (odds ratio [OR], 0.35; P =0.006). The results remained significant when analyses were restricted to women (OR, 0.18; P =0.02) but not men (OR, 0.46; P =0.09). This effect was independent of the reported acute modulation of BK channels by estrogen. A five-year follow-up study also demonstrated a reduced age- and sex-adjusted hazard ratio of 0.11, 95% CI, 0.01 to 0.79 of K-carriers for “combined cardiovascular disease” (myocardial infarction and stroke) compared with EE homozygotes. Our study provides the first genetic evidence for the different impact of the BK channel in the control of human blood pressure in men and women, with particular relevance in aging women, and highlights the E65K polymorphism as one of the strongest genetic factors associated thus far to protection against myocardial infarction and stroke.

The objective of the study was to evaluate the nutritional status of the hospitalised elderly patients using the Mini Nutritional Assessment (MNA) and nutritional classic parameters, to estimate the prevalence of undernutrition among them and to value the correlation of undernutrition with epidemiological characteristics of the sample for determine the highest risk's group among the malnourished patients. A cross sectional survey was done among a sample of 200 elderly patients admitted to the USP San Carlos Hospital (Murcia, Spain) during a period of 3 months. Patients answered a questionnaire including demographic data and the MNA clinical tool. Lymphocyte concentration and albumin and transferrin serum levels were also collected. Statistical analyses were performed with the Student t and chi 2 tests. For the MNA, the Spearman's coefficient was employed. Mean age of the 200 patients was 80.72 SD 7.43 years. Mean weight was 63.41 SD 19.57 kg and mean height was 160.93 SD 8.36 cm, with a mean Body Mass Index of 24.27 SD 7.31. The serum values of albumin and transferrin and total lymphocytes in blood were 3.09 SD 0.5 g/l, 1.69 SD 0.37 mg/dl and 1412 mm3 respectively. Average score of the MNA was 15.9 SD 6.21 and, according to this scale, 50% (n=100) of the patients were malnourished. Correlation analyses resulted in significant association (p0.001) between values of undernutrition in the MNA and measurements under normality of the biochemical and immunological parameters. The patients who presents chronic diseases, advanced physical or mental deterioration and minor self-sufficiency are either malnourished or at high risk of being. The individualized nutritional evaluation must be performed routinely when the patient is admitted to the hospital for detect and treat early signs of malnutrition.

[1] The Martian general circulation model (GCM) at the Laboratoire de Meteorologie Dynamique (LMD) has been extended up to approximately 240 km and it is now the first GCM to fully simulate the Martian atmosphere from the ground up to the thermosphere. In this paper we summarize the processes that have been added and give a first simple study of the effects of parameterized orographic gravity waves on the zonal mean fields. This first study clearly emphasizes the coupling between the different atmospheric regions and notes the importance of having fully coupled models to simulate the atmosphere of Mars.

[1] A fast method to incorporate the UV heating and the photochemistry of the neutral upper atmosphere of Mars into general circulation models (GCMs) is presented. On the basis of more detailed one-dimensional (1-D) models, the scheme we propose makes use of a division of the UV spectrum in 36 subintervals of 20 nm average width. Photoabsorption coefficients are computed allowing for overlapping and are tabulated as a function of suitable column abundances. The photochemistry proposed includes 12 compounds and uses the approximation of photochemical equilibrium for the three fastest species, OH, O(1D), and HO2. The behavior of the fast scheme is shown against detailed 1-D calculations. The resulting acceleration is about a factor 200 in the UV heating, while in the photochemistry it is about a factor 100 at 120 km and much larger below. The proposed scheme has already been implemented into the GCM developed at the Laboratoire de Meteorologie Dynamique-CNRS in Paris (LMD), which therefore becomes the first single Martian GCM to cover the whole range of altitudes from the planet surface to the upper thermosphere. We present typical results of the Martian thermosphere obtained with the present scheme and the LMD-GCM, in order to illustrate its behavior and stability. In particular, we show the sensitivity of the Martian upper atmosphere's thermal structure to the local photochemistry. Comparisons with previous models are also presented, as first steps in an ongoing validation study, necessarily extensive for this kind of GCM, which will include more detailed comparisons with recent and future data from space missions.

Dentro de los defectos congénitos que afectan más frecuentemente al ser humano se encuentran las hendiduras labiales y palatinas, ocupando el segundo lugar en incidencia, sólo precedido por el pie equino varo.La prevalencia de las hendiduras labiales y/o palatinas en nuestro país es de 1 en cada 750 niños nacidos vivos, lo que equivale a la existencia de aproximadamente 150,000 individuos afectados en la República Mexicana. Sin embargo, nuestra experiencia nos ha demostrado que en determinadas regiones del país la presencia de estos casos es considerablemente mayor lo que elevaría el número de pacientes en forma considerable. Solamente en el Estado de Campeche con una población de 800,000 habitantes, tenemos registrados poco más de mil pacientes, aunque algunos de ellos se atienden en Campeche y son originarios de Yucatán, Quintana Roo o Tabasco. Esta patología se ha convertido en un verdadero problema de salud pública, sobre todo si consideramos que se requiere un tratamiento integral conformado por equipos multidisciplinarios ya que el tratamiento en estos pacientes va desde el nacimiento hasta la adolescencia tardía.

16 páginas, 2 figuras, 1 tabla.-- El documento en word es la versión post-print., Atherosclerosis and associated coronary heart disease events have lower prevalence in women than in men, especially during young adult years. Although multiple lines of evidence suggest that estrogens contribute to this difference, the efficacy of hormone replacement therapy for the prevention of cardiovascular disease in postmenopausal women is controversial. The protective action of estrogen in the cardiovascular system appears to be mediated indirectly by an effect on serum lipoprotein and triglyceride profiles and on the expression of coagulant and fibrinolytic proteins, and by a direct effect on the vessel wall itself. Estrogen has both rapid effects involving alteration of membrane ionic permeability and activation of membrane-bound enzymes and increases in endothelial cell nitric oxide synthase activity, as well as longer-term effects on gene expression that are mediated, at least in part, by the ligand-activated transcription factors, estrogen receptor (alfa) and (beta) . Compounds with pure antiestrogenic activity and selective estrogen receptor modulators that regulate estrogen receptor function in a tissue-specific manner have been developed in an attempt to achieve the cardioprotective effects of estrogens while minimizing the undesirable risks associated with hormone replacement therapy (e.g., endometrial and breast cancer). In this review, we will discuss recent developments on the mechanisms of estrogen action in the cardiovascular system. The results of clinical trials testing the long-term efficacy of hormone replacement therapy for the treatment of cardiovascular disease will also be discussed., Supported in part by grants from the Ministry of Science and Technology of Spain and Fondo Europeo de Desarrollo Regional (grants 1FD97-1035-C02-01 and 02, and SAF2001-2358), Fondo de Investigación Sanitaria (F.I.S.) (grant FIS 01/0917, and Red de Enfermedades Cardiovasculares C03/01), Generalitat de Catalunya, and Human Frontiers Science Program. S. M. Sanz-González received salary support from the F.I.S.

Hypertension is the most prevalent risk factor for cardiovascular diseases, present in almost 30% of adults. A key element in the control of vascular tone is the large-conductance, Ca(2+)-dependent K(+) (BK) channel. The BK channel in vascular smooth muscle is formed by an ion-conducting alpha subunit and a regulatory beta(1) subunit, which couples local increases in intracellular Ca(2+) to augmented channel activity and vascular relaxation. Our large population-based genetic epidemiological study has identified a new single-nucleotide substitution (G352A) in the beta(1) gene (KCNMB1), corresponding to an E65K mutation in the protein. This mutation results in a gain of function of the channel and is associated with low prevalence of moderate and severe diastolic hypertension. BK-beta(1E65K) channels showed increased Ca(2+) sensitivity, compared with wild-type channels, without changes in channel kinetics. In conclusion, the BK-beta(1E65K) channel might offer a more efficient negative-feedback effect on vascular smooth muscle contractility, consistent with a protective effect of the K allele against the severity of diastolic hypertension. This work was supported by the Human Frontiers Science Organization, the Ministerio de Ciencia y Tecnología (Spain), Red HERACLES (Fondo de Investigaciones Sanitarias, Spain), Comissió Interdepartamental de Recerca i Innovació Tecnològica, de la Generalitat de Catalunya per a la Promoció de la Recerca Universitaria, and Fondo Nacional de Investigaciones Científicas y Tecnológicas (Chile)

1424-3903/$ e see front matter http://dx.doi.org/10.1016/j.pan.2012.07.010 A 43-year-old womanwith a history of cesarean and right oophorectomy presented with dyspepsia and epigastric discomfort attributed to a carcinoid gastric tumor. Physical examinationwas normal. Subsequent Computed Tomography (CT) demonstrated a 17mm, nonenhancing well-circumscribed mass in the head of the pancreas, composed entirely of fat. Abdominal endoscopic ultrasonography (US) showed a round, solid, hypoechoic mass within pancreas; there was no biliary tract or pancreatic duct obstacle. An endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) confirmed the diagnosis (mature fat cells with no atypia). Pancreatic lipomas are uncommon mesenchymal tumors accounting for 1e2% of all pancreatic neoplasms. In most cases, symptoms are not specific and the diagnosis is usually made by non-invasive imaging, CT and/or Magnetic Resonance Imaging. CT characteristically depicts lipomas as homogeneus, well-defined mass with a few scattered vessels and thin septums with no central or peripheral contrast enhancement or any extravisceral continuation

Cell line models of colonic electrolyte transport have been extensively used despite lacking some of the characteristics of native tissue. While native colonic crypts absorb or secrete NaCl, immortalized cell lines only retain the secretory phenotype. In the present study we have characterized functionally and molecularly, vectorial fluid and electrolyte transport in the morphologically differentiated human colonic cell line LIM1863. LIM1863 cells form morphologically differentiated organoids resembling native human colonic crypts, which secrete fluid and electrolytes across the apical membrane into a centrally located lumen. Net fluid secretion was evaluated by means of morphometric measurement of lumens formed in LIM organoids in response to known secretagogues. Pharmacological profiling of the channels and transporters involved in fluid and electrolyte transport showed that net fluid transport requires Cl- uptake across the basolateral membrane through a Na(+)-K(+)-2Cl- cotransporter (NKCC1) and its subsequent exit across an apical cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. Similar to the native colon, net Cl- secretion in the LIM1863 cell line is activated by cAMP-mediated agonists. Carbachol, a Ca(2+)-mediated agonist, does not induce net Cl- secretion but modulates the cAMP-activated response. Expression of chloride channels (CFTR and the Ca(2+)-dependent Cl- channel, ClCa1), potassium channels (KCNN4 and KCNQ1), epithelial Na+ channel (ENaC) alpha, beta and gamma subunits and ion transporters (NKCC1; anion exchanger, AE2; Na+/H+ exchangers, NHE1-3) was detected by RT-PCR and Western blot in the case of ENaC. Based on this evidence we propose that LIM1863 cells provide a unique model for studying CFTR-dependent Cl- secretion in a morphologically differentiated human colonic crypt cell line that also expresses ENaC.

The cell membrane large conductance voltage-dependent chloride channel (Maxi Cl- channel) has been recorded in different cell types following excision of membrane patches or stimulation by antiestrogens under whole-cell recording conditions. However, both its molecular nature and relevance to cell physiology await elucidation. Its electrophysiological properties resemble those of the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane. This observation has led to the controversial hypothesis that VDAC could be the molecular correlate of the plasma membrane Maxi Cl- channel. We have investigated the cellular localization of VDAC and its relationship with the antiestrogen-activated Maxi Cl- current in C1300 neuroblastoma cells. The presence of a plasma membrane VDAC was demonstrated by immunoblotting of membrane fractions with monoclonal antibodies against the VDAC and by reverse transcription-PCR using primers that hybridize to a VDAC sequence coding for an N-terminal leader peptide required for its plasma membrane sorting. Besides, VDAC colocalized with markers of plasma membrane lipid rafts (cholera toxin beta subunit) but not caveolin-1. Transfection of C1300 cells with an antisense oligonucleotide directed against the specific membrane leader sequence of VDAC markedly reduced both VDAC immunostaining and antiestrogen-activated Maxi Cl- currents, suggesting that VDAC forms the plasma membrane Maxi Cl- channel or a part thereof.

On 1 March 2002 the Envisat research satellite has been launched successfully into its sun-synchronous orbit. One of its instruments for atmospheric composition sounding is the Michelson Interferometer for Passive Atmospheric Sounding, a limb-scanning mid-infrared Fourier transform spectrometer. Different scientific objectives of data users require different approaches to data analysis, which are discussed. A strategy on how to validate the involved algorithms and relevant strategies is presented.

Activity of the antioestrogen-activated maxi-Cl(-) channel has been recorded in different cell types, including fibroblasts, vascular smooth muscle, endothelial and neuroblastoma cells. Its electrophysiological properties resemble those of the voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane, a channel of particular relevance to the physiology and pathophysiology of mitochondria. The hypothesis that VDAC could be the molecular correlate of the plasma membrane maxi-Cl(-) channel has been debated over the last few years, with the lack of clear evidence for the presence of VDAC in the plasma membrane constituting the main argument of the detractors. In the present study, we investigated the cellular localisation of VDAC in NIH3T3 fibroblasts. The presence of a plasma membrane VDAC was demonstrated by immunoblotting of membrane fractions with monoclonal antibodies against the VDAC and by RT-PCR using primers that hybridise to a VDAC sequence coding for a N-terminal leader peptide required for its plasma membrane sorting. In addition, confocal microscopy studies showed the colocalisation of VDAC with caveolin-1. As expected, VDAC also localised to mitochondria. Colocalisation studies with TOM-20, a protein also present in the outer mitochondrial membrane, showed that VDAC proteins localised only to peripheral and not to perinuclear mitochondria.

Malignant atrophic papulosis is an uncommon vasculopathy affecting multiple systems and frequently associated with a poor prognosis. We describe a 56-year-old patient with this rare disorder whose death was the result of intestinal involvement. Clinical diagnostic features of malignant atrophic papulosis as well as the main therapeutic approaches suggested in the literature are presented herein.

The cell regulatory volume decrease (RVD) response triggered by hypotonic solutions is mainly achieved by the coordinated activity of Cl− and K+ channels. We now describe the molecular nature of the K+ channels involved in the RVD response of the human bronchial epithelial (HBE) cell line 16HBE14o−. These cells, under isotonic conditions, present a K+current consistent with the activity of maxi K+ channels, confirmed by RT-PCR and Western blot. Single-channel and whole cell maxi K+ currents were readily and reversibly activated following the exposure of HBE cells to a 28% hypotonic solution. Both maxi K+ current activation and RVD response showed calcium dependency, inhibition by TEA, Ba2+, iberiotoxin, and the cationic channel blocker Gd3+ but were insensitive to clofilium, clotrimazole, and apamin. The presence of the recently cloned swelling-activated, Gd3+-sensitive cation channels (TRPV4, also known as OTRPC4, TRP12, or VR-OAC) was detected by RT-PCR in HBE cells. This channel, TRPV4, which senses changes in volume, might provide the pathway for Ca2+ influx under hypotonic solutions and, consequently, for the activation of maxi K+channels.

Amyloid beta-peptide (Abeta) fibril deposition on cerebral vessels produces cerebral amyloid angiopathy that appears in the majority of Alzheimer's disease patients. An early onset of a cerebral amyloid angiopathy variant called hereditary cerebral hemorrhage with amyloidosis of the Dutch type is caused by a point mutation in Abeta yielding Abeta(Glu22--Gln). The present study addresses the effect of amyloid fibrils from both wild-type and mutated Abeta on vascular cells, as well as the putative protective role of antioxidants on amyloid angiopathy. For this purpose, we studied the cytotoxicity induced by Abeta(1-40 Glu22--Gln) and Abeta(1-40 wild-type) fibrils on human venule endothelial cells and rat aorta smooth muscle cells. We observed that Abeta(Glu22--Gln) fibrils are more toxic for vascular cells than the wild-type fibrils. We also evaluated the cytotoxicity of Abeta fibrils bound with acetylcholinesterase (AChE), a common component of amyloid deposits. Abeta(1-40 wild-type)-AChE fibrillar complexes, similar to neuronal cells, resulted in an increased toxicity on vascular cells. Previous reports showing that antioxidants are able to reduce the toxicity of Abeta fibrils on neuronal cells prompted us to test the effect of vitamin E, vitamin C, and 17beta-estradiol on vascular damage induced by Abeta(wild-type) and Abeta(Glu22--Gln). Our data indicate that vitamin E attenuated significantly the Abeta-mediated cytotoxicity on vascular cells, although 17beta-estradiol and vitamin C failed to inhibit the cytotoxicity induced by Abeta fibrils.

The whole-cell mode of the patch-clamp technique has been used to monitor ionic currents in T84 colonic carcinoma cells. The cells were stimulated by either a cAMP cocktail, ionomycin or hypotonicity. Sizeable currents with distinct kinetics were observed after the stimulation with the different agonists. These kinetically distinct Cl- currents also presented a differential sensitivity to the anti-oestrogen Tamoxifen and to the halide I-. Tamoxifen only inhibits the volume activated Cl- current without affecting the other two. Substitution of extracellular Cl- by I- shifted the reversal potential towards more negative values both in the hypotonicity and ionomycin activated Cl- currents. The cAMP activated current responded to the Cl- substitution by I- with a blockade of both outward and inward currents, in addition to the displacement of the zero current level towards positive values. Thus, the use of these two simple tools, I- and tamoxifen, allows the distinction of Cl- channels in epithelial cells.

Objectives: The aim of this research has been to evaluate: (a) the frequency of the use of non-standard terms in medical prescriptions; (b) the proportion of “new drugs of irrelevant therapeutic value” or medication of low therapeutic utility (LTU); and (c) the use of Generic Pharmaceutical Specialties (GPS). Materials and methods: Descriptive transversal observational study with analytical components over the hospital discharge reports issued in a year. The main variables of the results were: a) the proportion of prescriptions with abbreviations, symbols or expressions of non-recommended doses in the discharge report, b) the frequency of prescriptions of pharmaceutical specialties without the relevant contribution (NRPS), c) the proportion of LTU medication in the hospital discharge reports , d) the frequency of GPS or, if they are not available, the Common International Denomination (CID) of the active ingredient in the discharge reports , and e) the mean cost per prescribed medication in the hospital discharge report . Results: A total of 854 discharge reports have been studied containing 4,055 medical prescriptions. A considerable number (38.8%) of the medical prescriptions in the discharge report have used abbreviations and non-recommended symbols for dose expression. The prescription of new drugs of irrelevant therapeutic value reached 2.8% while the prescription of pharmaceutical products of LTU was 2.1%. Only 13.8% of the prescriptions were carried out as an active ingredient. The mean cost per prescription was 17.3 euros ( SD = 31.34). Conclusions: Appropriateness in the prescription of medication at hospital discharge is considered to be not satisfactory and our results are consistent with other previously published reports. However, there are frequent errors in the prescription of medication and given the demonstrated relationship between errors and possible adverse effects, it is necessary to introduce programs to raise awareness about the importance of the introduction of safe practices in the medical prescriptions of the hospital discharge report.

The cystic fibrosis transmembrane conductance regulator (CFTR) protein has the ability to function as both a chloride channel and a channel regulator. The loss of these functions explains many of the manifestations of the cystic fibrosis disease (CF), including lung and pancreatic failure, meconium ileus, and male infertility. CFTR has previously been implicated in the cell regulatory volume decrease (RVD) response after hypotonic shocks in murine small intestine crypts, an effect associated to the dysfunction of an unknown swelling-activated potassium conductance. In the present study, we investigated the RVD response in human tracheal CF epithelium and the nature of the volume-sensitive potassium channel affected. Neither the human tracheal cell line CFT1, expressing the mutant CFTR-ΔF508 gene, nor the isogenic vector control line CFT1-LC3, engineered to express the βgal gene, showed RVD. On the other hand, the cell line CFT1-LCFSN, engineered to express the wild-type CFTR gene, presented a full RVD. Patch-clamp studies of swelling-activated potassium currents in the three cell lines revealed that all of them possess a potassium current with the biophysical and pharmacological fingerprints of the intermediate conductance Ca 2+ -dependent potassium channel (IK, also known as KCNN4). However, only CFT1-LCFSN cells showed an increase in IK currents in response to hypotonic challenges. Although the identification of the molecular mechanism relating CFTR to the hIK channel remains to be solved, these data offer new evidence on the complex integration of CFTR in the cells where it is expressed.

Volume regulation is essential for normal cell function. A key component of the cells' response to volume changes is the activation of a channel, which elicits characteristic chloride currents (ICl, Swell). The molecular identity of this channel has been controversial. Most recently, ClC-3, a protein highly homologous to the ClC-4 and ClC-5 channel proteins, has been proposed as being responsible for ICl, Swell (1). Subsequently, however, other reports have suggested that ClC-3 may generate chloride currents with characteristics clearly distinct from ICl, Swell. Significantly different tissue distributions for ClC-3 have also been reported, and it has been suggested that two isoforms of ClC-3 may be expressed with differing functions. In this study we generated a series of cell lines expressing variants of ClC-3 to rigorously address the question of whether or not ClC-3 is responsible for ICl, Swell. The data demonstrate that ClC-3 is not responsible for ICl, Swell and has no role in regulatory volume decrease, furthermore, ClC-3 is not activated by intracellular calcium and fails to elicit chloride currents under any conditions tested. Expression of ClC-3 was shown to be relatively tissue-specific, with high levels in the central nervous system and kidney, and in contrast to previous reports, is essentially absent from heart. This distribution is also inconsistent with the previous proposed role in cell volume regulation.

The cell volume regulatory response following hypotonic shocks is often achieved by the coordinated activation of K(+) and Cl(-) channels. In this study, we investigate the identity of the K(+) and Cl(-) channels that mediate the regulatory volume decrease (RVD) in ciliated epithelial cells from murine trachea. RVD was inhibited by tamoxifen and 1,9-dideoxyforskolin, two agents that block swelling-activated Cl(-) channels. These data suggest that swelling-activated Cl(-) channels play an important role in cell volume regulation in murine tracheal epithelial cells. Ba(2+) and apamin, inhibitors of K(+) channels, were without effect on RVD, while tetraethylammoniun had little effect on RVD. In contrast, clofilium, an inhibitor of the KvLQT/IsK potassium channel complex potently inhibited RVD, suggesting a role for the KvLQT/IsK channel complex in cell volume regulation by tracheal epithelial cells. To investigate further the role of KvLQT/IsK channels in RVD, we used IsK knock-out mice. When exposed to hypotonic solutions, tracheal cells from IsK(+/+) mice underwent RVD, whereas cells from IsK(-/-) failed to recover their normal size. These data suggest that the IsK potassium subunit plays an important role in RVD in murine tracheal epithelial cells.

Antarctic polar descent and planetary wave activity in the upper stratosphere and lower mesosphere are observed in ISAMS CO data from April to July 1992. CO-derived mean April-to-May upper stratosphere descent rates of 15 K/day (0.25 km/day) at 60 S and 20 K/day (0.33 km/day) at 80 S are compared with descent rates from diabatic trajectory analyses. At 60 S there is excellent agreement, while at 80 S the trajectory-derived descent is significantly larger in early April. Zonal wavenumber 1 enhancement of CO is observed on 9 and 28 May, coincident with enhanced wave 1 in UKMO geopotential height. The 9 May event extends from 40 to 70 km and shows westward phase tilt with height, while the 28 May event extends from 40 to 50 km and shows virtually no phase tilt with height.

A review is presented of CO 2 and CO in the middle atmosphere. Knowledge of their abundances is important for understanding the thermal budget and transport processes of the middle atmosphere, and for its remote sounding. For both CO and CO 2 , several techniques have been used to measure their abundance. Significant improvements have occurred over the last two decades with high quality satellite data now available from the Atmospheric Trace Molecule Spectroscopy (ATMOS) and Improved Stratospheric and Mesospheric Sounder (ISAMS) experiments. The CO 2 observations are well explained by models that account for diffusive separation, but a small overestimate above 95 km still remains. TIME-GCM calculations suggest a large depletion in the polar winter, down to near the stratopause which is as yet unconfirmed but which could be significant for remote sensing. The CO observations confirm the basic features of the seasonal and latitudinal variability predicted by dynamical models, particularly the enhancements in polar winter. However, the models underpredict the mesospheric CO abundance at mid-latitudes by a factor of 1.5-3 and fail to reproduce the strong latitudinal and vertical gradients in the polar regions. A reduction in the OH abundance from standard chemical models may partially solve this discrepancy. Finally, a comparison of simultaneously measured CO 2 and CO in the upper mesosphere/lower thermosphere with models suggests an eddy diffusion coefficient about 2-3 times smaller than those currently used.

Maxi-K channels consist of a pore-forming α subunit and a regulatory β subunit, which confers the channel with a higher Ca 2+ sensitivity. Estradiol bound to the β subunit and activated the Maxi-K channel ( hSlo ) only when both α and β subunits were present. This activation was independent of the generation of intracellular signals and could be triggered by estradiol conjugated to a membrane-impenetrable carrier protein. This study documents the direct interaction of a hormone with a voltage-gated channel subunit and provides the molecular mechanism for the modulation of vascular smooth muscle Maxi-K channels by estrogens.

Measurements of IR emissions from CO at 4.6 mu m in the middle atmosphere were recorded for nearly one year, from September 1991 to July 1992 by the Improved Stratospheric and Mesospheric Sounder (ISAMS) on board the Upper Atmosphere Research Satellite (UARS). These have been used to retrieve carbon monoxide abundances and study their distribution and variability in the middle atmosphere. Observations of carbon monoxide in this atmospheric region and from transitions of the same vibrational-rotational band were also carried out, using the solar occultation technique with fine altitude resolution, by the high resolution interferometer ATMOS during the ATLAS-1 mission (late March and early April 1992). Comparisons between these simultaneous emission and absorption experiments have been performed in order to improve and validate both data sets. Some of the first results and conclusions are presented and discussed. (C) 1999 COSPAR. Published by Elsevier Science Ltd.

The nonsteroidal antioestrogen tamoxifen has been shown to block a number of voltage-gated cation-selective channels but its effect on ligand-gated cation-selective channels has not been studied. We have investigated the action of tamoxifen and the related derivative toremifene on ligand-gated cationic nicotinic acetylcholine and 5-HT3 receptor channels. Tamoxifen and toremifene both inhibited cationic currents of adult-type human muscle nicotinic acetylcholine receptors expressed in Xenopus oocytes with similar IC50 values of 1.2 +/- 0.03 microM (nH = 0.84 +/- 0.02) and 1.2 +/- 0.1 microM (nH = 1.1 +/- 0.1), respectively. Tamoxifen could also block native 5-HT3 receptors in NG108-15 neuroblastoma/glioma hybrid cells with IC50 = 0.81 +/- 0.15 microM and nH of 1.3 +/- 0.3. The characteristics of block by tamoxifen at the 5-HT3 receptor were voltage- and use-independent. The inhibition of the 5-HT-evoked currents were not overcome by increasing concentrations of 5-HT consistent with a noncompetitive mechanism of block.

In most cell types volume regulatory mechanisms involve the activation of ionic pathways in order to restore the original volume of the cells. In response to a hyposmotic external solution the cell will activate pathways which will result in the net efflux of K+ and Cl− (Hoffmann et al. 1993). This volume regulatory mechanism is referred to as regulatory volume decrease (RVD). Although many studies have documented and characterized swelling-activated ionic pathways (for reviews see Hoffmann et al. 1993; Strange et al. 1996), very little is known about which pathway(s) is important in RVD. Furthermore, since the mechanism for sensing volume changes is also unknown it may be that different stimuli which result in cell swelling will be sensed by different mechanisms and hence activate different RVD pathways. It has been difficult to resolve these possibilities, not least because the molecular identity of many of the membrane channels and transporters involved is still unknown. An outwardly rectifying swelling-activated Cl− current has been well characterized in many cell types including the T84 human adenocarcinoma cell line (Worrell et al. 1989; Solc & Wine, 1991; Valverde et al. 1993). This current has been termed volume-sensitive osmolyte and anionic current (VSOAC; Strange et al. 1996) or ICl(swell) (Sheppard & Valverde, 1997). These currents are typically characterized by a time-dependent decay at depolarizing voltages and the anion permeability sequence I− > Br− > Cl− > F− (Diaz et al. 1993). Pharmacological studies have found this current to be sensitive to 1,9-dideoxyforskolin (DDFSK) and 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS) (Diaz et al. 1993), and tamoxifen (Valverde et al. 1993). It has been suggested that this current is important in RVD and, in a recent report by Valverde et al. (1996), it was demonstrated that the activity of this current can be correlated with the ability to effect RVD in Chinese hamster ovary (CHO) cells. However, no demonstration of the association of this current with RVD in epithelial cells has been presented as yet. ClC-2, a member of the ClC family of voltage-gated Cl− channels, has also been suggested to play a role in volume regulation (Grunder et al. 1992). ClC-2 currents are characterized by an inward rectification and a time-dependent activation at hyperpolarizing voltages. Pharmacological studies have shown ClC-2 currents to be partially blocked by diphenylamine-2-carboxyl acid and DIDS (Thiemann et al. 1992). Ubiquitous expression in all cell types tested implies that ClC-2 must play a role in a universal and necessary function for all cells (Thiemann et al. 1992). ClC-2 channels expressed in Xenopus oocytes generate inwardly rectifying Cl−-selective currents which have been shown to increase with large hyperpolarizing voltages as well as after exposure to hyposmotic shock (Grunder et al. 1992). The human homologue hClC-2 has been identified and cloned from the human T84 adenocarcinoma cell line (Cid et al. 1995), and a hyperpolarization-activated ClC-2-like current has been characterized (Fritsch & Edelman, 1996) in this cell line. This current showed the same biophysical characteristics and pharmacology as had been previously described for rat ClC-2 expressed in Xenopus oocytes (Thiemann et al. 1992). In addition, the currents were shown to be inhibited by Cd2+ (Fritsch & Edelman, 1996) and modulated by cell swelling (Fritsch & Edelman, 1997). Although both ICl(swell) and ClC-2 currents can be activated or modulated, respectively, by cell swelling it is unclear whether they play a role in the mechanisms involved in RVD after hyposmotic shock in epithelial cells. Moreover, the fact that hyposmotic stress elicits Cl− secretion in T84 cells (McEwan et al. 1993) makes the channels involved in such responses good candidates for manipulation in those epithelia affected in cystic fibrosis. To determine the Cl− conductance(s) involved in RVD after hyposmotic stimulation we monitored RVD in T84 cells in the presence of selective blockers of ICl(swell) (tamoxifen, DDFSK) or ClC-2 currents (Cd2+).

1Whole-cell, swelling-activated Cl− currents, ICl(swell), were characterized in Chinese hamster ovary (CHO) cells and found to exhibit time-dependent inactivation at depolarizing potentials, tamoxifen and dideoxyforskolin sensitivity, and an anion permeability sequence: SCN− > I− > Br− > Cl− > F− > gluconate−. 2CHO cells permanently transfected with either the human MDR1 or mouse mdr1a cDNAs demonstrated an increased rate of activation of ICl(swell) compared with parental cells or those permanently transfected with the mouse mdr1b cDNA. However, no differences in the magnitude of the currents were observed at steady state. 3Pretreatment with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) did not affect ICl(swell) in MDR1 or mdr1a permanently transfected CHO cells. In contrast, pretreatment with TPA reduced ICl(swell) in MDR1(G185V)-expressing transfected NIH3T3 fibroblasts. Subsequently, the CHO cell lines were shown to contain significantly reduced levels of protein kinase C (PKC), suggesting that PKC concentrations might be limiting in these cell lines, at least under whole-cell patch clamp conditions. 4Addition of purified PKC to the pipette solution, followed by a pretreatment with TPA, reduced the rate of ICl(swell) activation in human Pgp- and mouse Pgp1a-expressing CHO cells to the levels observed in parental and mouse Pgp1b-expressing cells. This confirms that PKC is limiting in these cells under whole-cell, patch clamp conditions. Furthermore, these results suggest that PKC-mediated phosphorylation of human Pgp and mouse Pgp1a disengages the influence which these Pgps have on ICl(swell). 5These studies also demonstrate a functional distinction between the two mouse homologues, Pgp1a and Pgp1b. Although both can function as drug efflux pumps, only Pgp1a can act like human Pgp to influence ICl(swell).

An analysis of the measurements taken by the improved stratospheric and mesospheric sounder (ISAMS) in its carbon monoxide wideband channel around 4.6 μm at daytime is presented. The radiances show a good signal to noise ratio up to the lower thermosphere (about 120 km) and have been shown to be mainly due to emission from the weak CO2 4.3 μm isotopic and hot bands. They exhibit a very clear dependence with the solar illumination at tangent heights above about 60 km, where they have been found to be almost exclusively determined by the solar elevation. Below about 50 km they are dominated by the variations of the kinetic temperature. The measurements have been analyzed in the 50–100 km range by using a detailed non local thermodynamic equilibrium (LTE) model of the CO2 states emitting in the 4.3 μm spectral region and the GENLN2 line-by-line radiance code. A large number (up to 32) of CO2 isotopic and hot bands emit significantly in this spectral region. The N2O(ν3 = 1) and two O3(ν1 + ν3) bands also give contributions in the stratosphere and lower mesosphere. The CO(1→0) band is of relative importance only in the lower thermosphere. The absolute radiances as well as the solar zenith angle dependence are well reproduced by the model. The dependence on the solar zenith angle is due to the absorption of solar radiation in the CO2 near-infrared bands. A sensitivity study of the radiances was also conducted. The major conclusions are (1) the inclusion of the excitation of N2(1) from the electronic energy of O(1D) was required to explain the radiances in the lower mesosphere; (2) the value for the rate of the vibrational exchange between CO2(ν1,ν2,1) and N2(1) is very similar to the laboratory measurements and to that used in the analysis of the Spectral Infrared Rocket Experiment (SPIRE) 4.3 μm CO2 atmospheric limb radiances; and (3) the CO2 volume mixing ratio (vmr) in the 70–100 km region is significantly smaller than that measured in rocket experiments and similar to that deduced from the atmospheric trace molecule spectroscopy (ATMOS) absorption measurements. A reanalysis of the SAMS 4.3 μm limb radiance measurements has also been conducted with the same non-LTE model and the GENLN2 line-by-line radiance code. The values for the parameters derived from the ISAMS data also explain the SAMS measurements very satisfactorily.

An update of the CO2 non local thermodynamic equilibrium (LTE) radiative transfer model of Lopez-Puertas et al. [1986a,b] is presented. The major improvements are (1) a revision of the modified Curtis matrix method; (2) a significant extension of the CO2 vibrational levels and bands (the current version includes 76 states and 129 transitions); and (3) a revision of the excitation mechanisms and collisional parameters. The major differences with previous results are discussed.

Publisher Summary This chapter discusses the association of P-glycoprotein (Pgp) with swelling-activated chloride channels. Channel properties vary among cell types, suggesting that there may be several distinct channels, not all of which are affected by Pgp. Factors that influence channel regulation can differ among cell types and Pgp modulates the rate of channel activation. The multidrug resistance Pgp is an adenosine triphosphate (ATP)-dependent transporter that pumps hydrophobic molecules out of cells. In humans, Pgp is encoded by the MDR1 gene. In rodents, the equivalent of the MDR1 gene is duplicated: the products of the mdr1a and mdr1b genes share >80% sequence identity. When overexpressed, Pgp can confer resistance of cells and tumors to a wide variety of cytotoxic agents including chemotherapeutic drugs.

Hemiplegic migraine (HM) is a rare and severe subtype of autosomal dominant migraine, characterized by a complex aura including some degree of motor weakness. Mutations in three genes (CACNA1A, ATP1A2 and SCN1A) have been detected in familial and in sporadic cases. This genetically and clinically heterogeneous disorder is often accompanied by permanent ataxia, epileptic seizures, mental retardation, and chronic progressive cerebellar atrophy.

Purpose: There is a strong possibility that many problems associated with local anaesthetics go undocumented. We describe an epidural catheter complication and its consequence. Clinical

Chloride channels play important functions in different aspects of cell physiology including volume regulation, transepithelial ion transport and stabilization of membrane potential. In recent years the molecular identity of the chloride channels defective in cystic fibrosis and myotonia congenita has been elucidated, highlighting the importance of anion-selective channels in cell and tissue function. Concurrently, several proteins have been identified as chloride channels along with proteins that possess channel regulatory behavior. Novel interactions with more potent pharmacological compounds have been reported with different chloride channels. This burgeoning field of interest is reviewed.

Satellites are a relatively new tool for investigating atmospheric chemical processes and their products. The precision and, in particular, the space and time coverage, now being achieved is immensely useful, and often essential, where global-scale phenomena like the variability of the stratospheric ozone layer are under study. The IR remote-sensing method using pressure modulator radiometry has recently been extended to the mapping of trace species. The technique is described, and its capabilities demonstrated with some selected new results from the improved stratospheric and mesopheric sounder (ISAMS) on the upper atmosphere research satellite (UARS). ISAMS was designed to study nitrogen-catalysed ozone chemistry, plus transport and other processes involving water vapour, methane and carbon monoxide, in the middle atmosphere. Its primary products are fields of temperature and composition, including all of the important members of the active nitrogen family, water, methane, carbon monoxide, ozone, aerosols and ice clouds. In the new data, all of these show large variations with time, height and latitude. The results have not yet been fully analysed, but early indications are that they confirm some models based on theoretical predictions and earlier, more limited, data, while in other cases they show that the situation is more complex than had been assumed. Sophisticated studies of the radiative–chemical–dynamical system in the stratosphere using satellite data and computer models are now in progress. In the future, even more advanced sensors now being built will obtain improved spatial resolution in the stratosphere, and map the global budgets of tropospheric trace gases as well.

The discovery of a severe pulmonary airleakage (PAL) associated with bi-level positive airway pressure (BiPAP) is a truly strange clinical finding, even for a very experienced specialist in pulmonary medicine. We present a woman who developed pneumomediastinum, pneumoperitoneum, retropneumoperitoneum and subcutaneous emphysema while being treated with BiPAP for hypoxic respiratory failure associated with pneumonia. The pulmonary barotrauma completely resolved after discontinuation of BiPAP. PAL following spontaneous BiPAP is benign and self-limited.