Nitric oxide/cGMP signaling inhibits TSH-stimulated iodide uptake and expression of thyroid peroxidase and thyroglobulin mRNA in FRTL-5 thyroid cells.

OBJECTIVE: Nitric oxide (NO) induces morphological and functional alterations in primary cultured thyroid cells. The aim of this paper was to analyze the direct influence of a long-term exposition to NO on parameters of thyroid hormone biosynthesis in FRTL-5 cells. DESIGN: Cells were treated with the NO donor sodium nitroprusside (SNP) for 24-72 h. MAIN OUTCOME: SNP (50-500 micromol/L) reduced iodide uptake in a concentration-dependent manner. The inhibition of iodide uptake increased progressively with time and matched nitrite accumulation. SNP inhibited thyroperoxidase (TPO) and thyroglobulin (TG) mRNA expression in a concentration-dependent manner. SNP enhanced 3',5'-cyclic guanosine monophosphate (cGMP) production. 3',5'-cyclic adenosine phosphate (cAMP) generation was reduced by a high SNP concentration after 48 h. 8-Bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP), a cGMP analog, inhibited iodide uptake as well as TPO and TG mRNA expression. The cGMP-dependent protein kinase (cGK) inhibitor KT-5823 reversed SNP or 8-Br-cGMP-inhibited iodide uptake. Thyroid-stimulating hormone pretreatment for 24-48 h prevented SNP-reduced iodide uptake although nitrite levels remained unaffected. CONCLUSION: These findings favor a long-term inhibitory role of the NO/cGMP pathway on parameters of thyroid hormone biosynthesis. A novel property of NO to inhibit TPO and TG mRNA expression is supported. The NO action on iodide uptake could involve cGK mediation. The long-term inhibition of steps of thyroid hormonogenesis by NO could be of interest in thyroid pathophysiology.     

Clinical characteristics and outcome of diabetic patients with acute myocardial infarction. Data from the BLITZ-1 study.

BACKGROUND: The determinants of a worse outcome in diabetic patients after an acute myocardial infarction (AMI) are controversial. They include delayed hospital admission, worse clinical presentation and lesser efficacy of accepted therapeutic interventions. Therefore, to improve our knowledge, we aimed to describe the clinical characteristics, treatment options and short-term outcomes of diabetic patients in a survey of consecutive AMI subjects admitted to the Italian coronary care unit (CCU) network in the current era of reperfusion. METHODS: The BLITZ study prospectively enrolled patients with AMI, within 48 hours of symptom onset, admitted to 296 out of the 341 existing Italian CCUs from October 15 to 29, 2001. Diabetic status was recorded by collecting clinical history. In-hospital and post-discharge management and outcomes were collected up to 30 days from admission. RESULTS: Overall, 434 of 1959 enrolled patients (22%) had a clinical diagnosis of diabetes. Diabetic patients were older, more frequently women, had a worse coronary risk profile, and an unfavorable clinical presentation compared to non-diabetics. Among 1275 patients with ST-elevation AMI, diabetics (20%) received a similar proportion of any reperfusion therapy (61 vs 66%, p = 0.10), but significantly less primary percutaneous coronary angioplasty (9 vs 16%, p = 0.003). Diabetic patients were treated less often with oral beta-blockers than non-diabetics both during hospitalization (56 vs 64%, p = 0.003) and at discharge (54 vs 61%, p = 0.01). In contrast, in-hospital use of angiotensin-converting enzyme inhibitors (76 vs 67%, p = 0.0003), digitalis (10 vs 5%, p = 0.0005), and diuretics (54 vs 36%, p < 0.0001) was more frequent among diabetics. During their index admission, subjects with diabetes had higher in-hospital mortality (11 vs 6%, p = 0.0004), as well as higher rates of reinfarction (6 vs 2%, p = 0.0003), new congestive heart failure (28 vs 14%, p < 0.0001), cardiogenic shock (10 vs 5%, p = 0.0005) or recurrent angina (22 vs 16%, p = 0.0034). A similar pattern was observed at 30-day follow-up. At multivariate analysis, diabetic status was not confirmed to be an independent predictor of 30-day mortality. CONCLUSIONS: Although diabetic patients with AMI admitted to the Italian CCU network have a higher in-hospital and 30-day morbidity and mortality rates compared to non-diabetics, a clinical diagnosis of diabetes has no independent predictive value on short-term outcome.     

Molecular epidemiology of malaria in Cameroon. XIX. Quality of antimalarial drugs used for self-medication

Substandard and counterfeit pharmaceutical products are increasingly circulating and distributed around the world, in particular in less developed countries. These low-quality or counterfeit products often involve drugs that are in high demand for the prevention and treatment of highly prevalent diseases, such as antimalarial drugs in endemic countries. Self-medication for presumed malarial infections with drugs purchased from unofficial drug vendors is a common practice in Africa. The aim of the study was to investigate the quality of chloroquine, quinine, and sulfadoxine-pyrimethamine obtained from illegitimate sector in urban and rural areas in Cameroon and analyze the impact of these drugs on patients. We collected 284 samples of three antimalarial drugs from 132 different sources in 16 villages and cities throughout the country. We also collected antimalarial drugs that were used for self-medication by malaria-infected patients. Drug quality was assessed by a simple color reaction test and semi-quantitative thin-layer chromatography. Fifty (38%) of 133 chloroquine, 52 (74%) of 70 quinine, and 10 (12%) of 81 antifolates had either no active ingredient, an insufficient active ingredient, the wrong ingredient, or unknown ingredient(s). Self-medication with antimalarial drugs purchased from unofficial vendors is not a reliable strategy to diminish morbidity and mortality. These counterfeit drugs contribute to the spread of drug-resistant malaria parasites and may lead to increasing therapeutic failure and medical expense.     

Abciximab therapy improves 1-month survival rate in unselected patients with acute myocardial infarction undergoing routine infarct artery stent implantation

Background The impact of abciximab therapy on mortality in unselected patients with acute myocardial infarction (AMI) undergoing routine primary infarct-related artery (IRA) stent implantation is not yet defined, and previous randomized studies have produced conflicting results. Methods A strategy of IRA stenting alone as opposed to IRA stenting plus abciximab was compared in a series of 561 consecutive unselected patients with AMI. Abciximab tretament was strongly encouraged for all patients. The contraindication for abciximab therapy was a high risk of major bleeding as assessed by the operator before mechanical intervention. Results Of 561 patients, 348 patients underwent abciximab therapy and 213 underwent primary IRA stenting alone. The 1-month overall mortality rate was 2.9% in the abciximab group and 10.8% in the stent alone group (P < .001). The relative reduction in mortality rate was 73% for patients overall, 77% in the subset of patients aged ≤70 years (mortality rate, 1.2% vs 5.2%, P = .020), 57% in patients aged >70 years (7.7% vs 18%, P = .043), 63% in patients with cardiogenic shock (17% vs 46%, P = .022), and 77% in patients without cardiogenic shock (1.3% vs 5.6%, P = .002). Multivariate analyses on the basis of all patients, and on the subset of patients aged ≤70 years, showed that abciximab therapy was independently related to the risk of death at 1 month. No differences were seen between groups in the procedural success rate (99.1% vs 98.1%) or in the incidence rates of nonfatal reinfarction (0.3% vs 1.9%) or repeat target vessel revascularization (1.7% vs 1.9%). Conclusion The results of this study strongly support the use of abciximab therapy in nonselected patients with AMI undergoing routine IRA stent implantation. The mechanism of the clinical benefit of abciximab was not related to the patency of the IRA. (Am Heart J 2002;144:315-22.)     

Evaluación multimodal de la degeneración estructural de válvulas percutáneas en el seguimiento a largo plazo

Introduction and objectivesWe assessed the long-term hemodynamic performance of transcatheter heart valve (THV) by paired transthoracic echocardiography (TTE), and the incidence, characteristics and factors associated with THV structural valve degeneration (SVD).MethodsA total of 212 patients who underwent transcatheter aortic valve replacement and had a potential follow-up > 5 years with at least 1 TTE ≥ 1-year postprocedure were included. All patients had a TTE at 1 to 5 years and 36 had another one at 6 to 10 years. SVD was defined as subclinical (increase > 10 mmHg in mean transvalvular gradient +  decrease > 0.3 cm² in valve area and/or new-onset mild or moderate aortic regurgitation) and clinically relevant (increase > 20 mmHg in mean transvalvular gradient + decrease > 0.6 cm² in valve area and/or new-onset moderate-to-severe aortic regurgitation). Fifteen patients had a transesophageal echocardiography at the time of SVD diagnosis, and 85 an opportunistic computed tomography examination at 1 (0.5-2) years.ResultsTransvalvular mean gradient increased and valve area decreased over time (P < .01). At 8 years of follow-up, SVD occurred in 30.2% of patients (clinically relevant: 9.3%). Transesophageal echocardiography revealed thickened and reduced-mobility leaflets in 80% and 73% of SVD cases, respectively. No baseline or procedural factors were associated with SVD. THV underexpansion (3.5%) or eccentricity (8.2%) had no impact on valve hemodynamics/SVD at follow-up.ConclusionsA gradual THV hemodynamic deterioration occurred throughout a 10-year period, leading to SVD in ～30% of patients (clinically relevant in < 10%). Leaflet morphology/mobility were frequently impaired in SVD cases, but THV geometry did not influence valve hemodynamics or SVD.     

Insulin-like growth factor (IgF)-I,IgF binding protein-3, and prostate cancer: correlation with gleason score

Introduction

Non-androgenic growth factors are involved in the growth regulation of prostate cancer (PCa).

Objective

This is the first Brazilian study to correlate, in a population of patients operated for PCa, PSA, total testosterone, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) with Gleason score and to compare with a control group with benign prostate hyperplasia (BPH).

Materials and Methods

This retrospective single-center study included 49 men with previously diagnosed PCa and 45 with previously diagnosed BPH. PSA, testosterone, IGF-I, IGFBP-3 were determined in both groups.

Results

PSA and IGFBP-3 levels were significantly higher in the PCa group as compared to the BPH group (p<0.001 and p=0.004, respectively). There was a significant difference when we compared the PSA before surgery (p<0.001) and at the inclusion in the study (p<0.001) and IGFBP3 (0.016) among patients with Gleason <7, ≥7 and BPH. In the PCa group, PSA, testosterone, IGF-I and IGFBP-3 levels were comparable between Gleason <7 and ≥7.

Conclusions

Our data suggest that in localized PCa, the quantification of PSA and, not of IGF-1, may provide independent significant information in the aggressiveness. IGFBP-3 could be a biochemical marker of disease control in PCa patients.