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Biomedical subjects

C Porta

Publications and source records attributed to C Porta.

At least 19 recordsLinked to original sources
PubMed2006

Thrombosis-related complications and mortality in cancer patients with central venous devices: an observational study on the effect of antithrombotic prophylaxis.

BACKGROUND: Recent guidelines do not recommend antithrombotic prophylaxis (AP) to prevent catheter-related thrombosis in cancer patients with a central line. PATIENTS AND METHODS: This study assessed the management of central lines in cancer patients, current attitude towards AP, catheter-related and systemic venous thromboses, and survival. RESULTS: Of 1410 patients enrolled, 1390 were seen at least once in the 6-month median follow-up. Continuous AP, mainly low-dose warfarin, was given to 451 (32.4%); they were older, with a more frequent history of venous thromboembolism (VTE), and more advanced cancer. There was no difference in catheter-related thrombosis in patients given AP or not (2.8% and 2.2%, odds ratio 1.29, 95% confidence interval 0.64-2.6). The median time to first catheter-related complication was 120 days. Systemic VTE including deep and superficial thromboses and pulmonary embolism, were less frequent with AP (4% versus 8.2%, P = 0.005). Mortality was also lower (25% versus 44%, P = 0.0001). Multiple logistic regression analysis found only advanced cancer and no AP significantly associated with mortality. No major bleeding was recorded with AP. CONCLUSIONS: Current AP schedules do not appear to prevent catheter-related thrombosis. Systemic VTE and mortality, however, appeared lower after prophylaxis.

Catheterization, Central Venous↗
PubMed2005

Cardiovascular, cerebrovascular, and respiratory changes induced by different types of music in musicians and non-musicians: the importance of silence.

OBJECTIVE: To assess the potential clinical use, particularly in modulating stress, of changes in the cardiovascular and respiratory systems induced by music, specifically tempo, rhythm, melodic structure, pause, individual preference, habituation, order effect of presentation, and previous musical training. DESIGN: Measurement of cardiovascular and respiratory variables while patients listened to music. SETTING: University research laboratory for the study of cardiorespiratory autonomic function. PATIENTS: 12 practising musicians and 12 age matched controls. INTERVENTIONS: After a five minute baseline, presentation in random order of six different music styles (first for a two minute, then for a four minute track), with a randomly inserted two minute pause, in either sequence. MAIN OUTCOME MEASURES: Breathing rate, ventilation, carbon dioxide, RR interval, blood pressure, mid-cerebral artery flow velocity, and baroreflex. RESULTS: Ventilation, blood pressure, and heart rate increased and mid-cerebral artery flow velocity and baroreflex decreased with faster tempi and simpler rhythmic structures compared with baseline. No habituation effect was seen. The pause reduced heart rate, blood pressure, and minute ventilation, even below baseline. An order effect independent of style was evident for mid-cerebral artery flow velocity, indicating a progressive reduction with exposure to music, independent of style. Musicians had greater respiratory sensitivity to the music tempo than did non-musicians. CONCLUSIONS: Music induces an arousal effect, predominantly related to the tempo. Slow or meditative music can induce a relaxing effect; relaxation is particularly evident during a pause. Music, especially in trained subjects, may first concentrate attention during faster rhythms, then induce relaxation during pauses or slower rhythms.

Adult↗
PubMed2005

BBR 3438, a novel 9-aza-anthrapyrazole, in patients with advanced gastric cancer: a phase II study group trial of the Central European Society of Anticancer-Drug Research (CESAR).

BBR 3438, a member of the 9-aza-anthrapyrazole family designed to decrease anthracycline dependent cardiotoxicity and to improve efficacy provided high in vivo activity in gastric carcinoma xenograft models. The present study was carried out to assess the efficacy and safety of BBR 3438 applied at a dose of 50 mg/m(2) four-weekly as an 1-hour infusion to pretreated patients with gastric cancer. Twenty-seven patients received at least one administration of BBR 3438. Lymph nodes and liver were the most common sites of metastases. A total of 94 cycles were administered (median 2, range 1-6). The main toxicity consisted of (worst per patient [%]; NCIC CTC grades 1/2/3/4) neutropenia 7/7/19/52 (one case of febrile neutropenia), stomatitis 15/19/4/-, nausea 22/26/7/-, vomiting 19/7/7/-, alopecia 15/33/-/-. Neutrophil nadir (520/mul) was reached after a median 15 days. The median time to recovery to < or = grade 1 neutropenia was 13.5 days. The median average cumulative dose of BBR 3438 was 166.8 mg, and the median dose intensity was 48.8 mg/m(2). Left ventricular ejection function (LVEF) was monitored with multiple-gated angiography (MUGA). Median LVEF values at baseline and at the end of cycle 2 were 67.5% and 65%, respectively, and no patient showed a relevant decrease of LVEF. In 25 patients evaluable for response no remission was observed. Four patients (16%) had stable disease. Median time to progression was 51 days, median overall survival was 64 days. In all, the feasibility and tolerability of BBR 3438 applied 4-weekly at a dose of 50 mg/m(2) was confirmed and neither relevant LVEF decreases nor hints of cardiac toxicity were observed. In terms of antitumor activity, BBR 3438 was found to be ineffective in the treatment of gastric cancer.

Adult↗
PubMed2005

Cardiorespiratory interactions to external stimuli.

Respiration is a powerful modulator of heart rate variability, and of baro- or chemo-reflex sensitivity. This occurs via a mechanical effect of breathing that synchronizes all cardiovascular variables at the respiratory rhythm, particularly when this occurs at a particular slow rate coincident with the Mayer waves in arterial pressure (approximately 6 cycles/min). Recitation of the rosary prayer (or of most mantras), induces a marked enhancement of these slow rhythms, whereas random verbalization or random breathing does not. This phenomenon in turn increases baroreflex sensitivity and reduces chemoreflex sensitivity, leading to increases in parasympathetic and reductions in sympathetic activity. The opposite can be seen during either verbalization or mental stress tests. Qualitatively similar effects can be obtained even by passive listening to more or less rhythmic auditory stimuli, such as music, and the speed of the rhythm (rather than the style) appears to be one of the main determinants of the cardiovascular and respiratory responses. These findings have clinical relevance. Appropriate modulation of breathing, can improve/restore autonomic control of cardiovascular and respiratory systems in relevant diseases such as hypertension and heart failure, and might therefore help improving exercise tolerance, quality of life, and ultimately, survival.

Cardiovascular Physiological Phenomena↗
PubMed2004

Mutations in the coding region of the FOXL2 gene are not a major cause of idiopathic premature ovarian failure.

Premature ovarian failure (POF) is a heterogeneous disorder whose aetiology is still unknown. Recently, the autosomal FOXL2 gene, highly expressed in the adult ovary, has been correlated with the disorder. FOXL2 mutations, causing a truncation of the FOXL2 protein in the forkhead domain or in the poly-Ala tract lead to blepharophimosis-ptosis-epicanthus-inversus syndrome associated with POF (BPES I). Interestingly, in two out of 70 idiopathic POF patients, a 30 bp deletion (898-927del) and a missense mutation (1009T-->A) were identified. To further evaluate the correlation between POF and FOXL2 mutations, 120 phenotypically normal women affected by POF were analysed by direct sequencing of the FOXL2 coding region. The analysis did not reveal any mutation in the 240 analysed chromosomes, indicating that mutations in the FOXL2 coding region are rarely associated with non-syndromic POF.

Adult↗
PubMed2004

Impaired bone marrow hematopoietic progenitor cell function in rheumatoid arthritis patients candidated to autologous hematopoietic stem cell transplantation.

We have evaluated bone marrow morphology, percentage of bone marrow CD34(+) cells, proliferative activity of bone marrow precursors, clonogenic assay (BFU-E and CFU-GM) in short-term bone marrow cultures, and bone marrow cell apoptosis, together with serum TNF-alpha and IL-6, in 16 chronic, refractory RA patients, as well as in five healthy controls. Of 16 RA patients (68.7%), 11 showed a reduced bone marrow cellularity, while it was normal in all the controls. In RA patients, the median percentage of CD34(+) bone marrow cells, the median percentage of proliferating bone marrow myeloid precursors, and the median number of both BFU-E and CFU-GM colonies were significantly lower than observed in the controls. As far as TNF-alpha and IL-6 titers is concerned, the latter did not significantly differ from controls' values, while TNF-alpha titers were significantly lower in healthy controls. Finally, the median apoptotic index of early bone marrow myeloid cells of RA patients was significantly higher compared with controls. These observations may identify the biological risk factors for impaired mobilization and/or engraftment when RA patients are candidates for autologous hematopoietic stem cell grafting.

Adult↗
PubMed2003

Response to first-line chemotherapy and long-term survival in patients with multiple myeloma: results of the MM87 prospective randomised protocol.

In this study we evaluated whether a good response to conventional chemotherapy, i.e. a significant tumour reduction, is a prerequisite for improved survival in multiple myeloma (MM). Between January 1987 and March 1990, 341 consecutive previously untreated patients with MM received chemotherapy within the prospective, multicentre, randomised Protocol MM87. Of these, 258 patients were evaluable for both response and long-term survival and 244 (94.6%) have died. The median survival of all patients was 40 months (6-162 months). The median survival did not differ between patients who had complete response (CR) (50 months (9-162 months)), partial response (PR) (46 months (8-147 months)) or stable disease (SD) (41 months (7-135 months)). The median survival was shorter (13.6 months (6-135 months)) (P<0.0001) in patients whose disease progressed while they were receiving first induction chemotherapy. Causes of death were more frequently (P=0.04) related to MM in patients who had progressive disease (PD) than in patients who had a CR or PR or SD. The main clinical and laboratory characteristics were similar in the four groups. These data indicate that patients who maintain SD during first-line chemotherapy have a prognosis similar to that of patients who attain a response. Only patients whose disease progresses have a distinctly worse outcome.

Analysis of Variance↗
PubMed2003

Mininvasive abdominal aortic surgery. Early recovery and reduced hospitalization after multidisciplinary approach.

AIM: Clinical experience in gastrointestinal surgery demonstrated that a multimodal approach can improve the outcome and reduce the length of hospital stay. In this paper we investigate the impact of a multimodal clinical program, based on mininvasive surgery, epidural anesthesia and early feeding and mobilization, on postoperative morbidity and hospitalization after abdominal aortic surgery. METHODS: A 2-armed study was designed. All patients undergoing abdominal aortic surgery between May 2000 and April 2001 were enrolled in a multidisciplinary clinical program including thoracic epidural anesthesia and analgesia, left sub-costal minilaparotomy without evisceration, encouragement to feed and mobilize soon after surgery (Multidisciplinary group: n=82). For comparison purposes, a retrospective analysis was conducted using the data of all patients operated on between January and December 1997, receiving standard anesthesia care and a standard surgical and nursing program (Standard group: n=64). RESULTS: In the Multidisciplinary group we observed significantly better pain relief (p<0.01), earlier restoration of ambulation (p<0.01), earlier feeding (p<0.01) and passage of stools (p<0.01). The incidence of complications was significantly lower in the Multidisciplinary group: pulmonary (0% vs 14.1%), cardiac (2.4% vs 9.4% ) and gastrointestinal (0% vs 10.9%). None of the patients in the Multidisciplinary group required admission to Intensive Care. Median postoperative hospitalization was 3 days in the Multidisciplinary group compared to 9 days in the Standard group (p<0.01). CONCLUSION: These results suggest that a multidisciplinary intervention with review of the traditional surgical care program would enhance recovery, decrease morbidity and hospitalization after abdominal aortic surgery.

Aged↗
PubMed2002

Mutation analysis of the inhibin alpha gene in a cohort of Italian women affected by ovarian failure.

BACKGROUND: Premature ovarian failure (POF) is a secondary hypergonadotrophic amenorrhoea affecting 1-3% of females, whose aetiology is almost unknown. However, inhibin alpha gene (INHalpha) has recently been indicated as candidate in POF pathogenesis. METHODS: We analysed patients affected by POF (n = 157) for the missense mutation (769G-->A transition) in the exon 2 of the INHalpha gene. The same analysis was carried out on early menopause (EM) (n = 36) and primary amenorrhoea (n = 12) patients. RESULTS: The incidence of the mutation was significantly more frequent within both POF (7/157, 4.5%) (Fisher's exact test, P = 0.030) and primary amenorrhoea (3/12, 25%) (Fisher's exact test, P < 0.001) patients, compared with the control population of women (0/100), who experienced physiological menopause. No mutation was found in EM patients. Furthermore, the likelihood of finding the mutation was statistically significant in familial (5/65; 7.7%) (Fisher's exact test, P < 0.01) but not in sporadic (2/92; 2.2%) (Fisher's exact test, P = not significant) POF, compared with the control group. The analysis of pedigrees showing the inheritance of the 769G-->A mutation and POF strengthens the concept of the disease heterogeneity, since the POF phenotype was not always associated with the mutation. Moreover, a higher prevalence of the C allele of a single nucleotide polymorphism (129C-->T), located in the 5'-UTR of the INHalpha gene, was observed in POF patients (80.3%) than in the control group (66.7%) (Fisher's exact test, P = 0.014). CONCLUSION: These data strengthen the concept of the INHalpha gene as a candidate for ovarian failure.

5' Untranslated Regions↗
PubMed2002

Widespread cardiovascular autonomic dysfunction in primary amyloidosis: does spontaneous hyperventilation have a compensatory role against postural hypotension?

OBJECTIVE: To investigate the possible causes of abnormal blood pressure control in light chain related (primary, AL) amyloidosis. DESIGN: Cardiovascular, autonomic, and respiratory response to passive tilting were investigated in 51 patients with primary amyloidosis (mean (SEM) age 56 (2) years) and in 20 age matched controls. Spontaneous fluctuations in RR interval, respiration, end tidal carbon dioxide, blood pressure, and skin microcirculation were recorded during supine rest and with tilting. The values were subjected to spectral analysis to assess baroreflex sensitivity and the autonomic modulation of cardiac and vascular responses. SETTING: Tertiary referral centre. RESULTS: Autonomic modulation of the heart and blood pressure was nearly absent in the patients with amyloidosis: thus baroreflex sensitivity and the low frequency (0.1 Hz) fluctuations in all cardiovascular signals were severely reduced (p < 0.01 or more), as were respiratory fluctuations in the RR interval, and no change was observed upon tilting. Despite reduced autonomic modulation, blood pressure remained relatively stable in the amyloid group from supine to tilting. End tidal carbon dioxide was reduced in the amyloid patients (p < 0.001) indicating persistent hyperventilation; the breathing rate correlated inversely with the fall in blood pressure on tilting (p < 0.05). CONCLUSIONS: In primary amyloidosis, pronounced abnormalities in arterial baroreflexes and cardiovascular autonomic modulation to the heart and the vessels may be partly compensated for by hyperventilation at a slow breathing rate.

Amyloidosis↗
PubMed2002

Cowpea mosaic virus: from the presentation of antigenic peptides to the display of active biomaterials.

The potential of cowpea mosaic virus (CPMV), a plant icosahedral virus, for the presentation of foreign peptides and proteins is reported. The most prominent feature at the virus surface is a region of the smaller of the two coat proteins (S) which has been extensively used for the insertion of foreign peptides. Given the availability of the three-dimensional structure of the native virus and the amenability of foreign peptide-expressing CPMV chimeras to crystallisation, immunological data can be correlated with the conformational state of the foreign insert. The latter is influenced by proteolysis which occurs within the foreign inserts. In an effort to offer an alternative context for peptide expression, extensive exploration of a second region of the S protein is reported with respect to tolerance to small insertions. Moreover, to make CPMV suitable for a wider spectrum of presentation, a technique was developed to allow surface coupling of a peptide which can serve as the anchoring point for a range of proteins. This new approach is also widely applicable for the direct chemical cross-linking of peptides and full-length protein domains to the viral capsid.

Amino Acid Sequence↗
PubMed2001

SV40 replication in human mesothelial cells induces HGF/Met receptor activation: a model for viral-related carcinogenesis of human malignant mesothelioma.

Recent studies suggested that simian virus 40 (SV40) may cause malignant mesothelioma, although the pathogenic mechanism is unclear. We found that in SV40-positive malignant mesothelioma cells, the hepatocyte growth factor (HGF) receptor (Met) was activated. In human mesothelial cells (HMC) transfected with full-length SV40 DNA (SV40-HMC), Met receptor activation was associated with S-phase entry, acquisition of a fibroblastoid morphology, and the assembly of viral particles. Coculture experiments revealed the ability of SV40-HMC to infect permissive monkey cells (CV-1), HMC, and murine BNL CL cells. Cocultured human and murine SV40-positive cells expressed HGF, showed Met tyrosine phosphorylation and S-phase entry, and acquired a spindle-shaped morphology (spBNL), whereas CV-1 cells were lysed. Cocultured HMC inherited from SV40-HMC the infectivity, as they induced lysis in cocultured CV-1 cells. Treatment with suramin or HGF-blocking antibodies inhibited Met tyrosine phosphorylation in all large T antigen (Tag)-positive cells and reverted the spindle-shaped morphology of spBNL. This finding indicated that Met activation and subsequent biological effects were mediated by an autocrine HGF circuit. This, in turn, was causally related to Tag expression, being induced by transfection with the SV40 early region alone. Our findings suggest that when SV40 infects HMC it causes Met activation via an autocrine loop. Furthermore, SV40 replicates in HMC and infects the adjacent HMC, inducing an HGF-dependent Met activation and cell-cycle progression into S phase. This may explain how a limited number of SV40-positive cells may be sufficient to direct noninfected HMC toward malignant transformation.

Animals↗
PubMed2001

Modulatory effects of respiration.

Respiration is a powerful modulator of heart rate variability, and of baro- and chemoreflex sensitivity. Abnormal respiratory modulation of heart rate is often an early sign of autonomic dysfunction in a number of diseases. In addition, increase in venous return due to respiration may help in maintaining blood pressure during standing in critical situations. This review examines the possibility that manipulation of breathing pattern may provide beneficial effects in terms not only of ventilatory efficiency, but also of cardiovascular and respiratory control in physiologic and pathologic conditions, such as chronic heart failure. This opens a new area of future research in the better management of patients with cardiovascular autonomic dysfunction.

Arrhythmia, Sinus↗
PubMed2001

Sequential intrahepatic and systemic fluoropyrimidine-based chemotherapy for metastatic colorectal cancer confined to the liver. A phase II study.

PURPOSE: Several trials have suggested that intrahepatic chemotherapy increases the likelihood of response in advanced colon cancer patients, but has no significant impact on survival due to the development of extrahepatic metastases. We report our experience of combined hepatic intraarterial and systemic chemotherapy in advanced colorectal cancer patients. METHODS: A group of 35 patients received intrahepatic FUDR (0.3 mg/kg per day for 14 days by continuous infusion), followed, after 1 week's rest, by systemic 5-FU and L-leucovorin (370 and 100 mg/m2 per day, respectively, both for 5 consecutive days). After another week off therapy, the combined intrahepatic and systemic regimen was repeated and cycles continued until disease progression. RESULTS: Of 32 assessable patients, 17 (53.1%) had an objective response, while 8 (25%) had disease stabilization. Median time to progression (TTP) was 32 weeks (range 8-104 weeks), while the median overall survival was only 39 weeks (range 9-109 weeks). Incomplete liver perfusion was the only variable that showed a significant correlation with a poorer survival (P = 0.046, log-rank test). CONCLUSIONS: Our results are in agreement with previous data suggesting a relative efficacy of such a treatment approach for advanced colon cancer patients. More thorough investigations are warranted, especially as an adjuvant treatment for selected high-risk patients.

Adult↗
PubMed2001

Inhibitors of the Cl-/HCO3- exchanger activate an anion channel with similar features in the epithelial cells of rabbit gallbladder: patch-clamp analysis.

The stilbene- and dipyridamole-sensitive Cl-conductance (GCl), non-additively activated by some inhibitors of the Cl-/HCO3- exchanger (hydrochlorothiazide, phlorizin, phenylglyoxal) after the exchanger inhibition in the apical plasma membrane of rabbit gallbladder epithelium, has been investigated by patch-clamp technique with cell-attached and inside-out configurations. No Cl- channels were observed under basal conditions or after treatment with 2.5 x 10(-4) mol/l 8-Br-cAMP or hydrochlorothiazide (HCTZ) on the cytosolic side. Conversely, with 2.5 x 10(-4) mol/l HCTZ or 2 mmol/l phlorizin in the pipette, a non-rectifying Cl- channel with about 5 pS conductance and 0.3-0.4 voltage-independent open probability was observed; it was inhibited by 10(-4) - 5 x 10(-4) mol/l SITS, 10(-4) mol/l furosemide or 0.6 x 10(-4) mol/l dipyridamole; the effects of HCTZ and phlorizin were not additive. Open probability increased from 0 (after seal formation) to a maximum of 0.3-0.4 reached in 7-9 min. Similar results were obtained with both configurations. With the cell-attached configuration, HCTZ added to the bath did not activate Cl- channels in the patch. The channel was shown to exclude cations, to be selective for Cl-, but also conductive for gluconate (PGluc/PCl = 0.18). On this basis, it is concluded that: (1) GCl, activated either by HCTZ or phlorizin, has the same underlying anion channels, (2) the channels can be activated only on the external side of the membrane, also in the absence of cytoplasm, without cellular mediations or effects at a distance along the membrane, (3) the channels are inhibited by the same drugs which inhibit the very small intrinsic anion conductance of the exchanger, (4) they are either related to a slow conversion of inhibited exchangers into channels or, less probably, they are parallel to the exchanger and slowly activated by intra-membrane (or membrane-bound) mediators in their turn activated by near, inhibited exchangers.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Inhibitors of the Cl-/HCO3- exchanger activate an apical anion conductance with similar features in the epithelial cells of rabbit gallbladder: analysis in intact epithelium.

In the apical plasma membrane of rabbit gallbladder epithelium, hydrochlorothiazide (HCTZ), besides its inhibiting action on Na+-Cl- symport and some side-effects, opens a SITS-sensitive Cl- conductance (Gcl), resulting in depolarization of the membrane due to a cell-to-lumen Cl- backflux. Some previous indications suggest that GCl is someway related to the Cl-/HCO3- exchanger. Thus the actions on the apical membrane of HCTZ and two inhibitors of the exchanger mainly studied in erythrocytes, namely phlorizin and phenylglyoxal (PG), have been compared. The transapical Cl- influx was measured radiochemically and the anion exchange fraction identified. The apical and transepithelial membrane potentials (Vm, Vm), the apical/basolateral membrane resistance ratio (Rm/Rs) and the transepithelial resistance (Rep) were measured with conventional microelectrodes and the changes in apical electromotive force and conductance were calculated. It has been shown that: (1) 2.5 x 10(-4) mol/l HCTZ abolishes Cl-/HCO3- exchange in a few seconds, (2) exchanger inhibition by HCTZ is direct and not mediated by carbonic anhydrase inhibition, (3) 2 mmol/l phlorizin and 4 mmol/l PG also inhibit the exchanger in a few seconds or at least rapidly and in parallel activate a depolarization of 6-7 mV, like HCTZ, (4) dose/response curves of the three drugs for depolarization activation and anion exchange inhibition overlap, (5) depolarization time courses are similar for the three drugs, (6) a decrease in the Rm/Rs ratio occurs in the presence of the three drugs, with a significant change in apical electromotive force when the luminal Cl- concentration is reduced, all this indicating the appearance of a substantial, quantifiable GCl which is absent in the absence of incubation with the drugs, (7) GCl values are similar, regardless of the drug which generates them, (8) the effects of the three drugs are not additive, and (9) stilbenes and dipyridamole abolish GCl (but not DPC) as well as the basal intrinsic conductance of the exchanger. On this basis it is concluded that some inhibitors of the Cl-/HCO3- exchanger either turn it into an anion channel or, less probably, activate a parallel GCl, as a consequence of the exchanger inhibition.

Animals↗
PubMed2001

Diphenylamine-2-carboxylic acid (DPC), Usually an inhibitor of Cl- and non-selective cation channels, inhibits Cl-/HCO3- exchange and opens Cl- and cation conductances in rabbit gallbladder epithelium.

In the apical plasma membrane of rabbit gallbladder epithelium various drugs (hydrochlorothiazide, phlorizin, phenylglyoxal) inhibit Cl-/HCO3- exchange and probably enhance the almost negligible intrinsic anion conductance of the exchanger. By radiochemical measurements of apical Cl- influx, the anion exchange is shown here to be directly and immediately inhibited by diphenylamine-2-carboxylic acid (DPC) too. Using conventional microelectrode techniques in intact tissue, DPC, with same dose/response curve, is shown to activate an apical anion conductance (GCl) that has similar properties and amplitude to the GCl activated by the other exchange inhibitors so far tested; the actions are not additive. Patch-clamp methods (cell-attached and excised inside-out patch configurations) reveal that GCl is due to anion channels that are non-rectifying, cytoplasm independent, sensitive to stilbene and dipyridamole and have conductance of a few picosiemens. All this strengthens the correlation between inhibition of anion exchange and the activation of GCl and channels with features similar to those of the almost negligible intrinsic anion conductance of the exchanger. Among the drugs tested, the effects of DPC and hydrochlorothiazide are even more similar, such that even their dose/response curves overlap. Moreover, both drugs also directly activate some verapamil-sensitive Ca2+ channels and consequently apamin-sensitive, Ca2+-activated K+ channels. Thus DPC, usually an inhibitor of Cl- and non-selective cation channels, is shown here to be capable of activating Cl- and cation conductances.

Animals↗