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Similarity of A(3)-adenosine and swelling-activated Cl(-) channels in nonpigmented ciliary epithelial cells.

Chloride release from nonpigmented ciliary epithelial (NPE) cells is a final step in forming aqueous humor, and adenosine stimulates Cl(-) transport by these cells. Whole cell patch clamping of cultured human NPE cells indicated that the A(3)-selective agonist 1-deoxy-1-(6-[([3-iodophenyl]methyl)amino]-9H-purin-9-yl)-N-methyl-be ta-D-ribofuranuronamide (IB-MECA) stimulated currents (I(IB-MECA)) by approximately 90% at +80 mV. Partial replacement of external Cl(-) with aspartate reduced outward currents and shifted the reversal potential (V(rev)) from -23 +/- 2 mV to -0.0 +/- 0.7 mV. Nitrate substitution had little effect. Perfusion with the Cl(-) channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and niflumic acid inhibited the currents. Partial Cl(-) replacement with aspartate and NO(3)(-), and perfusion with NPPB, had similar effects on the swelling-activated whole cell currents (I(Swell)). Partial cyclamate substitution for external Cl(-) inhibited inward and outward currents of both I(IB-MECA) and I(Swell). Both sets of currents also showed outward rectification and inactivation at large depolarizing potentials. The results are consistent with the concept that A(3)-subtype adenosine agonists and swelling activate a common population of Cl(-) channels.

Adenosine↗

PGE(2), Ca(2+), and cAMP mediate ATP activation of Cl(-) channels in pigmented ciliary epithelial cells.

Purines regulate intraocular pressure. Adenosine activates Cl(-) channels of nonpigmented ciliary epithelial cells facing the aqueous humor, enhancing secretion. Tamoxifen and ATP synergistically activate Cl(-) channels of pigmented ciliary epithelial (PE) cells facing the stroma, potentially reducing net secretion. The actions of nucleotides alone on Cl(-) channel activity of bovine PE cells were studied by electronic cell sorting, patch clamping, and luciferin/luciferase ATP assay. Cl(-) channels were activated by ATP > UTP, ADP, and UDP, but not by 2-methylthio-ATP, all at 100 microM. UTP triggered ATP release. The second messengers Ca(2+), prostaglandin (PG)E(2), and cAMP activated Cl(-) channels without enhancing effects of 100 microM ATP. Buffering intracellular Ca(2+) activity with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'- tetraacetic acid or blocking PGE(2) formation with indomethacin inhibited ATP-triggered channel activation. The Rp stereoisomer of 8-bromoadenosine 3',5'-cyclic monophosphothioate inhibited protein kinase A activity but mimicked 8-bromoadenosine 3',5'-cyclic monophosphate. We conclude that nucleotides can act at >1 P2Y receptor to trigger a sequential cascade involving Ca(2+), PGE(2), and cAMP. cAMP acts directly on Cl(-) channels of PE cells, increasing stromal release and potentially reducing net aqueous humor formation and intraocular pressure.

Adenosine Triphosphate↗

[Effect of anti-hypertensive therapy with irbesartan on the absolute cardiovascular risk].

Blockade of the renin-angiotensin system with angiotensin converting enzyme inhibitors or with angiotensin receptor antagonists confers patients with arterial hypertension (AH) and associated risk factors, target organ lesion or cardiovascular disease with greater protection in morbidity and mortality terms. The objective of the present study was to evaluate the effect of irbesartan, an angiotensin II receptor antagonist, on the absolute cardiovascular risk in a cohort of hypertensive patients with moderate, high, or very high cardiovascular risk. This was a multicenter, prospective, observational, cohort study with 1974 patients (63 11 years; 47% males) with newly diagnosed essential AH or AH non-controlled with anti-hypertensive monotherapy, and moderate to very high cardiovascular risk. Irbesartan therapy at a dosage of 150300 mg was instituted as monotherapy or associated with hydrochlorothiazide, 12.5 mg. The clinical follow-up was 6 months. The evaluated parameters included the absolute cardiovascular risk, measured either quantitatively (Framingham algorithm) or qualitatively (low, moderate, high, and very high risk groups following the WHO/International Hypertension Society guidelines). Irbesartan therapy led to a significant (p = 0.0001) decrease in SBP (from 170.9 18.4 to 138.5 16.5 mmHg) and DBP (from 96.6 11 to 82 9 mmHg). The quantitative absolute cardiovascular risk decreased by 29.8% (from 12.14 8 to 8.65 6.2; p < 0.0001). The percentage of patients with very high cardiovascular risk decreased from 1.52% to 0.51% and that for patients with high cardiovascular risk from 92.77% to 88.32%. The latter patients changed to the moderate risk group. As a result, this moderate risk group increased from 5.71% to 11.17%. The adverse reaction rate was very low as only 2.2% of patients had some adverse reaction. In conclusion, irbesartan as monotherapy or associated with hydrochlorothiazide has been shown to be effective in reducing the absolute cardiovascular risk, which is obtained by a substantial decrease in arterial pressure and a good safety profile on the biochemical parameters. Tolerability was excellent, with a very low rate of adverse reactions.

Angiotensin Receptor Antagonists↗

[Graves' disease in preschool children].

Graves' disease, which is the main cause of hyperthyroidism in the pediatric age group, is very rare in pre-school children. We describe the cases of four girls, aged less than 6 years old, out of a total of 30 patients diagnosed with Graves' disease between 1985 and 2004. Investigations were motivated by tachycardia, chronic diarrhea, language development delay or thyroid nodules detected by cervical ultrasonography. In three of the four patients height and bone age were advanced. In all patients goiter was small or absent. None of the patients had ophthalmic disease. In all patients free T3 and T4 were elevated and thyroid-stimulating hormone was suppressed. Three patients were positive for thyroid-stimulating immunoglobulins (the method was not available for the oldest case). Two patients showed complete resolution after 5 years of treatment with carbimazole. The remaining two patients are still under treatment and no adverse effects have been documented.

Child, Preschool↗

[Utility of extended release indapamide in the treatment of hypertension in at risk elderly: extended release study].

INTRODUCTION: It is estimated that more than 65% of the elderly population in Spain is hypertensive. This study aimed to evaluate the safety and efficacy of extended release indapamide in hypertensive patients over 60 years of age, having high cardiovascular risk and the factors that influence this effect. MATERIAL AND METHODS: Prospective study made in 944 patients with essential HBP and age > 60 years (55.9% women) in whom treatment with extended release indapamide in single drug therapy or in combination was indicated, whether as a new drug or due to lack of efficacy of the previous therapy. The action scope was hospital out-patient clinics of Internal Medicine and follow-up time of the patients was 6 months. RESULTS: Extended release indapamide causes a significant decrease (p < 0.05) of systolic blood pressure (SBP) (21.3 mmHg) and diastolic blood pressure (DBP) (10.8 mmHg). No significant differences were found between the results in monotherapy or combined therapy. A total of 52.7% of the patients included had 3 or more cardiovascular risk factors (RF) or had target organ lesion (TOL) and 41.1% had an associated cardiovascular disease (CVD). Those patients with greater baseline SBP and DBP were those having a greater decrease in BP. On the other hand, patients with 1 or 2 RF showed a greater decrease of the SBP in comparison with patients with 3 or more RF, TOL or associated CVD. The adverse reactions rate was 2.8%. CONCLUSIONS: Extended release indapamide is an effective drug in the elderly population having high cardiovascular risk and is well tolerated.

Aged↗

[Treatment and control of cardiovascular risk in primary care in Spain. The PREVENCAT study].

BACKGROUND AND OBJECTIVE: The PREVENCAT study was designed to estimate the control of the main cardiovascular risk factors (CVRF) and their treatment in a sample of population having the diagnoses of hypertension (HT), type 2 diabetes mellitus (DM2) or hypercholesterolemia (HC) who was attended by primary care physicians in Spain. PATIENTS AND METHOD: Cross-sectional study in patients with HT, DM2 and/or HC, who were consecutively recruited. We describe the treatments for HT, DM2 and HC and analyze and the association between several potential predictors and the control of these CVRF. RESULTS: 2,649 patients were included in the study. 95% of HT patients were under treatment, as were 84% of DM2 and 71.4% of HC patients; most common drugs were diuretics, sulphonylureas and statins, respectively. Monotherapy was more frequent than combined therapy for hypertension treatment. The frequency of HT and DM2 treatment was similar among the subgroups defined by the presence or absence of the other two diagnoses. However, HC treatment was more common in the presence of DM2 (p = 0.001). Age, previous cardiovascular disease (CVD), DM2, obesity and sedentarism were all predictors of poor blood pressure control despite drug treatment. Age, previous CVD, HT and sedentarism were predictors of poor HC control. CONCLUSIONS: CVRF treatment was high although heterogeneous and not based on the best available evidence. DM2, previous CVD and obesity were associated with insufficient blood pressure control.

Adult↗

[Strategies for effective control of arterial hypertension in Spain. Consensus document].

Blood pressure (BP) control is inadequate among treated hypertensive patients in Spain. Control rates are lower than 40% of all treated patients and the cause of this problem is multifactorial. Despite the fact that possible solutions to this problem have been repeatedly suggested by expert groups along the last 10 years, BP control rates are still low. This fact have a negative impact on cardiovascular morbidity and mortality of patients with hypertension. The aim of the present document has been to achieve a consensus on effective specific measures in order to improve hypertension control rates in Spain. These measures involve health care professionals (physicians, nurses, pharmaceutics), health care authorities and patients. The document summarizes the consensus conference of several scientific societies involved in cardiovascular medicine in five group of measures: a) improvement of the methodology of office BP measurement; b) improvement of compliance to treatment by patients; c) clarification of pressure targets to be achieved in hypertensive patients; d) optimization of life style modifications and pharmacological treatment of hypertension; and e) continuous medical education. The document emphasize life style changes as a crucial aspect to be implemented in all patients. These changes have a beneficial impact on pressure reduction, contribute to a better control of associated cardiovascular risk factors, and increase the effectiveness of antihypertensive drugs. Health care professionals should base their clinical practice on the recommendations of guidelines in order to modify their therapeutic attitudes in patients whose targets have not been achieved.

Antihypertensive Agents↗

[Quality indicators in Hypertension Care Units: indicators of structure in the QUALIHTA study].

AIM: To evaluate the minimum-required indicators of quality of care in Hypertension Units at two levels of delivered care (secondary and tertiary) in Spain. METHODS: A total of 51 quality indicators were included (N) in order to evaluate: architectural resources (8), material resources (12 on devices and 22 on supportive services) and human resources (9), which were presented as a formulary to the head of the corresponding Hypertension Unit. As a measure of the indicator, the accomplishment (yes/no) was registered. RESULTS: Data from 61 participating centers were collected and included in the analysis: 42 (68,9%) centers of tertiary level and 19 (31,1%) of secondary level. The degree of compliance of the different quality indicators in the global sample is (range): architecture, 60%-100%; material resources, 83.3%-100% (devices); 57.4-100% auxiliary services; 51.7% with respect to human resources and 69-100% with respect to continuing education and the dedication of the personnel. As expected, the differences between care levels were observed mainly in the availability of auxiliary services. CONCLUSIONS: The Hypertension Units in Spain comply with a series of structural indicators of care quality at an acceptable level. The degree of compliance in certain aspects of human resources, mainly percent of dedication, number and continuing education could be improved. The evaluation of these aspects of care quality could allow the Scientific Societies to define the recommendation in order to deliver the best quality of care in hypertension.

Cross-Sectional Studies↗

Monoclonal antibodies against Der s 1, a major allergen of Dermatophagoides siboney.

Six stable clones secreting murine monoclonal antibodies (Mabs) against Der s 1 were obtained. The binding of Mabs showed cross-reactivity with Dermatophagoides farinae, as determined by enzyme-linked immunosorbent assay (ELISA). In a Western blot assay, antibodies reacted with a 24-kD protein considered to represent the major allergen Der s 1. The repertoire of antigenic sites on Der s 1 was studied using a panel of Mabs. Epitope specificity of the Mabs was determined by both competitive inhibition and sandwich ELISA assays. The results defined six different, non-overlapping and non-repeated antigenic sites on the allergen molecule. Der s 1 allergen from Dermatophagoides siboney extracts was purified by Mab affinity chromatography, this procedure gave 43% recovery of >90% pure allergen. The purified allergen had capacity to bind specific human IgE and demonstrated an allergenic activity of up to 77% of total D. siboney extract. An Mab-ELISA was developed using Mabs directed against different epitopes on Der s 1. This assay could detect up to 1 ng/ml of Der s 1 and Der f 1 in allergen preparations.

Allergens↗