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1.
Hormones (Athens) ; 19(4): 565-571, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32078734

RESUMO

PURPOSE: Platelet microparticles (PMPs), which are microvesicles shed from platelets, participate in inflammation, vascular homeostasis, and thrombosis. PMPs are increased in obese women with polycystic ovary syndrome (PCOS). Agents that modulate hormonal aspects of PCOS could affect the levels of PMPs. The aim of the present study was to evaluate the effects of oral contraceptives (OCPs), antiandrogen, and metformin use for 6 and 12 months on PMPs in normal-weight women with PCOS. METHODS: Forty-five women with PCOS and 13 healthy women were recruited. Biochemical, hormonal, and clinical parameters were recorded. Women with PCOS received treatment with OCPs, OCPs+antiandrogens, or metformin, depending on their main complaint or clinical/biochemical findings. PMPs were measured at baseline and after 6 and 12 months. RESULTS: At baseline, patients with PCOS had higher levels of PMPs than controls (p = 0.017), which increased after 6-month treatment with OCPs (p = 0.006). Subsequently, they decreased after 12-month treatment (p = 0.046). Metformin had no effect on PMP levels. CONCLUSION: In conclusion, PMP levels are increased in PCOS and further increase with OCP use. This effect could possibly contribute to the increased risk of venous thromboembolism associated with OCP use. However, further studies are needed to elucidate the exact role of PMPs in PCOS.


Assuntos
Antagonistas de Androgênios/farmacologia , Plaquetas/efeitos dos fármacos , Micropartículas Derivadas de Células/efeitos dos fármacos , Anticoncepcionais Orais Hormonais/farmacologia , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Quimioterapia Combinada , Feminino , Humanos , Avaliação de Resultados em Cuidados de Saúde , Adulto Jovem
2.
Ann Gastroenterol ; 32(3): 287-297, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31040627

RESUMO

BACKGROUND: Beta-blockers are used for prophylaxis of variceal bleeding. Our aim was to assess the efficacy and safety of carvedilol for primary or secondary prevention of variceal bleeding in patients with cirrhosis. METHODS: We searched Medline, Embase, CENTRAL and gray literature sources for randomized controlled trials (RCTs) comparing carvedilol with placebo or any active intervention. We synthesized data using random effects models. We summarized the strength of evidence using GRADE criteria. RESULTS: We included 13 trials with 1598 patients. Carvedilol was as efficacious as endoscopic variceal ligation (EVL) (4 RCTs, risk ratio [RR] 0.74, 95% confidence interval [CI] 0.37-1.49) or propranolol (3 RCTs, RR 0.76, 95%CI 0.27-2.14) for primary prevention of variceal bleeding. Likewise, carvedilol was as efficacious as EVL (3 RCTs, RR 1.10, 95%CI 0.75-1.61), non-selective beta-blockers (NSBBs) plus isosorbide-5-mononitrate (2 RCTs, RR 1.02, 95%CI 0.70-1.51) or propranolol (2 RCTs, RR 0.39, 95%CI 0.15-1.03) for secondary prevention of variceal bleeding. Carvedilol was associated with lower all-cause mortality compared to EVL (3 RCTs, RR 0.51, 95%CI 0.33-0.79). There was no difference in any other efficacy outcome. Finally, there were no significant differences in the safety profiles compared with EVL and NSBBs. Our confidence in the effect estimates for all outcomes was very low. CONCLUSION: Carvedilol is as efficacious and safe as standard-of-care interventions for the primary and secondary prevention of variceal bleeding.

3.
J Clin Endocrinol Metab ; 104(5): 1623-1630, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30907957

RESUMO

BACKGROUND: Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method. RESULTS: We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials. CONCLUSIONS: This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas do Quadril/prevenção & controle , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Fraturas da Coluna Vertebral/prevenção & controle , Doenças Ósseas Metabólicas/tratamento farmacológico , Calcitonina/uso terapêutico , Moduladores de Receptor Estrogênico/uso terapêutico , Terapia de Reposição de Estrogênios , Feminino , Humanos , Metanálise em Rede , Norpregnenos/uso terapêutico , Pós-Menopausa , Vitamina D/uso terapêutico
4.
J Clin Endocrinol Metab ; 104(5): 1631-1636, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30907968

RESUMO

BACKGROUND: Several treatments are available to reduce the risk of fragility fractures associated with osteoporosis. The choice of treatment requires knowledge of patients' values and preferences. The aim of the present study was to summarize what is known about the values and preferences relevant to the management of osteoporosis in women. METHODS: We conducted a comprehensive search of several databases for studies reported in any language that had included women who had already started or were about to start any pharmacological therapy for osteoporosis. Pairs of reviewers independently selected the studies and extracted the data. The results were synthesized narratively. RESULTS: We included 26 studies reporting on 15,348 women (mean age, 66 years). The women considered the effectiveness and adverse events equally, followed by the convenience of taking the drug and its effect on daily routine (less frequent dosing was preferred, the oral route was preferred, and the injectable route was preferred over oral if given less frequently). The treatment cost and duration were less important factors for decision making. Fear of breast cancer and fear of resuming uterine bleeding were common reasons for not choosing estrogen therapy. Calcium and vitamin D were viewed as safe and natural. Across the studies, the preferences were not affected by age, previous drug exposure, or employment status. CONCLUSIONS: Women starting osteoporosis medications value effectiveness and side effects equally and prefer medications given less frequently. Injectable drugs appear acceptable if given less frequently. More research on patient values and preferences is needed to guide decision making in osteoporosis.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Preferência do Paciente , Tomada de Decisões , Feminino , Humanos
5.
Ann Gastroenterol ; 31(5): 572-582, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30174394

RESUMO

BACKGROUND: The aim of the study was to assess the efficacy and safety of tofacitinib and its impact on quality of life in patients with moderate-to-severe ulcerative colitis. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing tofacitinib with placebo or any active comparator. We searched Medline, Embase, the Cochrane Library and gray literature for articles published up to May 2017. We synthesized data using a fixed-effect model. We conducted subgroup analysis based on prior exposure to anti-tumor necrosis factor (TNF). We summarized the strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We included three trials with 1220 participants. Compared with placebo, tofacitinib was effective in inducing clinical remission (odds ratio [OR] 3.84, 95% confidence interval [CI] 2.29-6.44, I2: 41%, GRADE: moderate), clinical response (OR 2.95, 95%CI 2.21-3.95, I2: 0%, GRADE: high), mucosal healing (OR 2.70, 95%CI 1.81-4.03, I2: 0%, GRADE: high). Tofacitinib was effective in both anti-TNF-naïve and -experienced patients. Tofacitinib had a favorable effect on quality of life. There were no significant differences in the safety profile in terms of the incidence of any or serious adverse events compared to placebo. The risk for infections was increased (OR 1.51, 95%CI 1.05-2.19, I2: 0%, GRADE: moderate), but the incidence of serious infections did not differ between tofacitinib and placebo. CONCLUSION: In patients with moderate-to-severe ulcerative colitis, short-term treatment with tofacitinib is effective for induction of remission and improvement of quality of life.

6.
Endocrine ; 54(3): 620-633, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27473096

RESUMO

We performed a systematic review and meta-analysis to assess the efficacy and safety of antigen-based immunotherapies in tertiary prevention of autoimmune diabetes. We searched for randomised controlled trials testing antigen-based immunotherapies in patients with recent-onset type 1 diabetes or latent autoimmune diabetes of adults in MEDLINE, COCHRANE and EMBASE databases, trial registries, conference proceedings and reference lists of pertinent records. Primary outcomes were fasting and stimulated C-peptide (after glucagon or mixed meal stimulation). Change in glycosylated haemoglobin (HbA1c), daily insulin needs and incidence of any or severe hypoglycaemic events or severe adverse events were secondary outcomes. Fifteen studies were included in the meta-analysis. Overall, there was no difference in fasting [weighted mean difference (WMD) 0.01 nmol/L; 95 % confidence interval (CI) -0.09, 0.11; I 2 = 73 %] or mixed meal stimulated C-peptide (WMD 0.02 nmol/L/min; 95 % CI -0.08, 0.12; I 2 = 50 %) compared with placebo. Glucagon stimulated C-peptide was maintained higher (WMD 0.13 nmol/L/min; 95 % CI 0.05, 0.21; I 2 = 0 %) in patients treated with Diapep277. Moreover, there was no change in daily insulin needs (WMD 0.02 IU/kg; 95 % CI -0.04, 0.09; I 2 = 51 %) or HbA1c (WMD -0.06 %; 95 % CI -0.35, 0.23; I 2 = 42 %) vs. placebo. Finally, there was no effect on the incidence of severe hypoglycaemic events or overall serious adverse events [risk ratio 0.94, 95 % CI 0.62, 1.41; I 2 = 0 % and 0.87; 95 % CI 0.53, 1.44; I 2 = 0 %, respectively). Antigen-based immunotherapies are not effective in preventing the progression of autoimmune diabetes in newly diagnosed patients.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Imunoterapia , Peptídeo C/sangue , Diabetes Mellitus Tipo 1/sangue , Glucagon , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Análise de Regressão
7.
Endocr Pract ; 22(4): 466-75, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26789343

RESUMO

OBJECTIVE: We conducted a systematic review and meta-analysis to synthesize the evidence about predictors that may affect biochemical remission and recurrence after transsphenoidal surgery (TSS), radiosurgery (RS), and radiotherapy (RT) in Cushing disease. METHODS: We searched multiple databases through December 2014 including original controlled and uncontrolled studies that enrolled patients with Cushing disease who received TSS (first-line), RS, or RT. We extracted data independently, in duplicates. Outcomes of interest were biochemical remission and recurrence. A meta-analysis was conducted using the random-effects model to estimate event rates with 95% confidence intervals (CIs). RESULTS: First-line TSS was associated with high remission (76% [95% CI, 72 to 79%]) and low recurrence rates (10% [95% CI, 6 to 16%]). Remission after TSS was higher in patients with microadenomas or positive-adrenocorticotropic hormone tumor histology. RT was associated with a high remission rate (RS, 68% [95% CI, 61 to 77%]; RT, 66% [95% CI, 58 to 75%]) but also with a high recurrence rate (RS, 32% [95% CI, 16 to 60%]; RT, 26% [95% CI, 14 to 48%]). Remission after RS was higher at short-term follow-up (≤2 years) and with high-dose radiation, while recurrence was higher in women and with lower-dose radiation. Remission was after RT in adults who received TSS prior to RT, and with lower radiation doses. There was heterogeneity (nonstandardization) in the criteria and cutoff points used to define biochemical remission and recurrence. CONCLUSION: First-line TSS is associated with high remission and low recurrence, while RS and RT are associated with reasonable remission rates but important recurrence rates. The current evidence warrants low confidence due to the noncomparative nature of the studies, high heterogeneity, and imprecision.


Assuntos
Adenoma Hipofisário Secretor de ACT/radioterapia , Adenoma Hipofisário Secretor de ACT/cirurgia , Adenoma/radioterapia , Adenoma/cirurgia , Hipersecreção Hipofisária de ACTH/radioterapia , Hipersecreção Hipofisária de ACTH/cirurgia , Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma Hipofisário Secretor de ACT/metabolismo , Adenoma/diagnóstico , Adenoma/metabolismo , Adulto , Biomarcadores/sangue , Feminino , Humanos , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipersecreção Hipofisária de ACTH/epidemiologia , Prognóstico , Recidiva , Indução de Remissão , Osso Esfenoide/cirurgia , Resultado do Tratamento
8.
Clin Gastroenterol Hepatol ; 13(1): 55-63.e5, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24993364

RESUMO

BACKGROUND & AIMS: Guidelines advocate use of magnetic resonance imaging (MRI) to estimate concentrations of iron in liver, to identify patients with iron overload, and to guide titration of chelation therapy. However, this recommendation was not based on a systematic synthesis and analysis of the evidence for MRI's diagnostic accuracy. METHODS: We conducted a systematic review and meta-analysis to investigate the diagnostic accuracy of MRI in identifying liver iron overload in patients with hereditary hemochromatosis, hemoglobinopathy, or myelodysplastic syndrome; liver biopsy analysis was used as the reference standard. We searched MEDLINE and EMBASE databases, the Cochrane Library, and gray literature, and computed summary receiver operating curves by fitting hierarchical models. We assessed methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: Our final analysis included 20 studies (819 patients, total). Sensitivity and specificity values varied greatly, ranging from 0.00 to 1.00 and from 0.50 to 1.00, respectively. Because of substantial heterogeneity and variable positivity thresholds, we calculated only summary receiver operating curves (and summary estimate points for studies that used the same MRI sequences). T2 spin echo and T2* gradient-recalled echo MRI sequences accurately identified patients without liver iron overload (liver iron concentration > 7 mg Fe/g dry liver weight) (negative likelihood ratios, 0.10 and 0.05 respectively). However, these MRI sequences are less accurate in establishing a definite diagnosis of liver iron overload (positive likelihood ratio, 8.85 and 4.86, respectively). CONCLUSIONS: Based on a meta-analysis, measurements of liver iron concentration by MRI may be accurate enough to rule out iron overload, but not to definitely identify patients with this condition. Most studies did not use explicit and prespecified MRI thresholds for iron overload, therefore some patients may have been diagnosed inaccurately with this condition. More studies are needed of standardized MRI protocols and to determine the effects of MRI surveillance on the development of chronic liver disease and patient survival.


Assuntos
Terapia por Quelação/métodos , Monitoramento de Medicamentos/métodos , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/tratamento farmacológico , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Humanos , Radiografia
9.
Curr Vasc Pharmacol ; 12(3): 527-36, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23016964

RESUMO

Non-dipping is a common pattern of arterial hypertension and it is associated with increased cardiovascular risk. Use of ambulatory blood pressure monitoring, as suggested in recent guidelines, could further increase its prevalence among subjects with hypertension. In this review we discuss assessment, relevance and associated factors. Non-dipping could be addressed through chronotherapy, the use of specific classes of anti-hypertensives, such as renin-angiotensin blockers, or modification of associated factors. However, more data are needed in order to comprehensively estimate factors associated with non-dipping and how they could be modified.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Ritmo Circadiano , Hipertensão/fisiopatologia , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Risco
10.
Ann Intern Med ; 159(4): 262-74, 2013 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-24026259

RESUMO

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs. PURPOSE: To assess the efficacy and safety of SGLT2 inhibitors in adults with type 2 diabetes. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Library from inception through April 2013 without language restrictions; regulatory authorities' reports; and gray literature. STUDY SELECTION: Randomized trials comparing SGLT2 inhibitors with placebo or other medication for type 2 diabetes. DATA EXTRACTION: Three reviewers extracted or checked data for study characteristics, outcomes of interest, and risk of bias, and 3 reviewers summarized strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. DATA SYNTHESIS: Sodium-glucose cotransporter 2 inhibitors were compared with placebo in 45 studies (n = 11 232) and with active comparators in 13 studies (n = 5175). They had a favorable effect on hemoglobin A1c level (mean difference vs. placebo, -0.66% [95% CI, -0.73% to -0.58%]; mean difference vs. active comparators, -0.06% [CI, -0.18% to 0.05%]). Sensitivity analyses incorporating unpublished data showed similar effect estimates. Compared with other agents, SGLT2 inhibitors reduced body weight (mean difference, -1.80 kg [CI, -3.50 to -0.11 kg]) and systolic blood pressure (mean difference, -4.45 mm Hg [CI, -5.73 to -3.18 mm Hg]). Urinary and genital tract infections were more common with SGLT2 inhibitors (odds ratios, 1.42 [CI, 1.06 to 1.90] and 5.06 [CI, 3.44 to 7.45], respectively). Hypoglycemic risk was similar to that of other agents. Results for cardiovascular outcomes and death were inconclusive. An imbalance in incidence of bladder and breast cancer was noted with dapagliflozin compared with control. LIMITATION: Most trials were rated as high risk of bias because of missing data and last-observation-carried-forward methods. CONCLUSION: Sodium-glucose cotransporter 2 inhibitors may improve short-term outcomes in adults with type 2 diabetes, but effects on long-term outcomes and safety are unclear. PRIMARY FUNDING SOURCE: None.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Transportador 2 de Glucose-Sódio/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Medição de Risco , Viés de Seleção , Transportador 2 de Glucose-Sódio/efeitos adversos , Redução de Peso
11.
Eur J Obstet Gynecol Reprod Biol ; 159(2): 261-6, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21840110

RESUMO

Acute pancreatitis is rare in pregnancy but it is associated with increased incidence of maternal and fetal mortality. It should be considered in the differential diagnosis of upper quadrant abdominal pain with or without nausea and vomiting. The commonest identified causes of acute pancreatitis in pregnancy are gallstones, alcohol and hypertriglyceridemia. The main laboratory finding is increased amylase activity. Appropriate investigations include ultrasound of the right upper quadrant and measurement of serum triglycerides and ionized calcium. Management of gallstone pancreatitis is controversial, although laparoscopic cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) are often used and may be associated with lower complication rates. In hypertriglyceridemia-induced acute pancreatitis ω-3 fatty acids and even therapeutic plasma exchange can be used. We also discuss preventive measures.


Assuntos
Pancreatite/etiologia , Pancreatite/terapia , Complicações na Gravidez/etiologia , Complicações na Gravidez/terapia , Consumo de Bebidas Alcoólicas/fisiopatologia , Animais , Feminino , Cálculos Biliares/fisiopatologia , Humanos , Hipertrigliceridemia/fisiopatologia , Pancreatite/fisiopatologia , Pancreatite/prevenção & controle , Pancreatite Necrosante Aguda/etiologia , Pancreatite Necrosante Aguda/fisiopatologia , Pancreatite Necrosante Aguda/prevenção & controle , Pancreatite Necrosante Aguda/terapia , Gravidez , Complicações na Gravidez/fisiopatologia , Complicações na Gravidez/prevenção & controle , Fatores de Risco
13.
Hematol Rep ; 3(3): e25, 2011 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-22593816

RESUMO

We report a case of a bone marrow aspiration and trephine biopsy (BMATB) associated haematoma in an 85-years old male without any predisposing risk factors. Six days after BMATB, he suffered from a massive thigh and buttock haematoma and a fall in haematocrit. It is important to know that BMATB can have complications aiding early recognition and therapy.

14.
Angiology ; 62(2): 163-6, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20682614

RESUMO

We assessed the effect of glucose and insulin on human monocytes. Monocytes were isolated from 16 healthy obese and 10 lean healthy participants. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp. Obese participants were subdivided into 2 subgroups: insulin sensitive (IS) and insulin resistant (IR). Monocyte oxidized low-density lipoprotein (oxLDL) phagocytosis was assessed pre and poststimulation in vitro with glucose or insulin. Experiments were repeated after incubation with a Na(+)/H(+) exchanger-1 inhibitor ([NHE-1]; cariporide) or rosiglitazone. Glucose increased oxLDL phagocytosis in all groups studied (at 1 or 3 hours incubation; P = .037-.002). Insulin increased oxLDL phagocytosis in all groups studied after 1-hour incubation (P = .027-.015) but not at 3 hours. Incubation with cariporide attenuated oxLDL phagocytosis except in the obese IS group. Rosiglitazone eliminated glucose- and insulin-induced increase in oxLDL phagocytosis in all studied groups. Glucose and insulin induce oxLDL phagocytosis.


Assuntos
Glucose/farmacologia , Insulina/farmacologia , Lipoproteínas LDL/metabolismo , Monócitos/efeitos dos fármacos , Obesidade/metabolismo , Fagocitose/efeitos dos fármacos , Adolescente , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Técnicas de Cultura de Células , Feminino , Guanidinas , Humanos , Hipoglicemiantes/farmacologia , Masculino , Monócitos/metabolismo , Obesidade/patologia , Projetos Piloto , Rosiglitazona , Sulfonas , Edulcorantes/farmacologia , Tiazolidinedionas , Adulto Jovem
15.
Angiology ; 62(1): 38-45, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20682615

RESUMO

We assessed the effect of epinephrine on human monocytes. Monocytes were isolated from 16 healthy obese and 10 lean healthy subjects. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp. Obese subjects were subdivided into 2 sub-groups, insulin sensitive (IS) and insulin resistant (IR). Monocyte properties [attachment to laminin 1, migration through laminin 1, oxidized-low density lipoprotein (oxLDL) phagocytosis] were assessed pre- and post-stimulation in vitro with epinephrine. Experiments were repeated after incubation with a Na(+)/H( +) exchanger-1 inhibitor (NHE-1) (cariporide). Epinephrine increased monocyte attachment to laminin in lean and obese IR subjects through involvement of NHE-1, PKC, NO synthase, NADPH oxidase and actin polymerization. In contrast, epinephrine did not affect monocyte migration. Epinephrine increased oxLDL phagocytosis in all groups studied. Incubation with cariporide attenuated oxLDL phagocytosis. Epinephrine induces monocyte dysfunction which may be atherogenic.


Assuntos
Epinefrina/farmacologia , Resistência à Insulina , Monócitos/efeitos dos fármacos , Monócitos/fisiologia , Obesidade/sangue , Magreza/sangue , Adolescente , Adulto , Feminino , Humanos , Masculino , Projetos Piloto , Adulto Jovem
16.
Open Cardiovasc Med J ; 4: 181-8, 2010 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-21160910

RESUMO

BACKGROUND: Sodium/hydrogen exchanger-1 (NHE-1) contributes to maintaining intracellular pH (pHi). We assessed the effect of glucose, insulin, leptin and adrenaline on NHE-1 activity in human monocytes in vitro. These cells play a role in atherogenesis and disturbances in the hormones evaluated are associated with obesity and diabetes. METHODS AND RESULTS: Monocytes were isolated from 16 healthy obese and 10 lean healthy subjects. NHE-1 activity was estimated by measuring pHi with a fluorescent dye. pHi was assessed pre- and post-incubation with glucose, insulin, leptin and adrenaline. Experiments were repeated after adding a NHE-1 inhibitor (cariporide) or an inhibitor of protein kinase C (PKC), nitric oxide synthase (NOS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, phosphoinositide 3-kinases (PI3K) or actin polymerization. Within the whole study population, glucose enhanced NHE-1 activity by a processes involving PKC, NOS, PI3K and actin polymerization (p = 0.0006 to 0.01). Insulin-mediated activation of NHE-1 (p = <0.0001 to 0.02) required the classical isoforms of PKC, NOS, NADPH oxidase and PI3K. Leptin increased NHE-1 activity (p = 0.0004 to 0.04) through the involvement of PKC and actin polymerization. Adrenaline activated NHE-1 (p = <0.0001 to 0.01) by a process involving the classical isoforms of PKC, NOS and actin polymerization. There were also some differences in responses when lean and obese subjects were compared. Incubation with cariporide attenuated the observed increase in NHE-1 activity. CONCLUSIONS: Selective inhibition of NHE-1 in monocytes could become a target for drug action in atherosclerotic vascular disease.

17.
Expert Opin Investig Drugs ; 19(12): 1545-56, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21047280

RESUMO

IMPORTANCE OF THE FIELD: The sodium/hydrogen exchanger-1 (NHE-1/SLC9A1) is a ubiquitous plasma membrane protein whose main role is maintenance of intracellular pH and volume. NHE-1 plays a role in atherogenesis; however, its clinical relevance has not yet been established. AREAS COVERED IN THIS REVIEW: We herein review the contribution of NHE-1 in atherogenesis (namely its effect on endothelial cells, monocytes, smooth muscle cells and platelets). WHAT THE READER WILL GAIN: Studies have shown that NHE is involved in atherogenesis-related properties of isolated monocytes. We also consider the relationship between NHE-1 and vascular risk factors such as obesity, diabetes mellitus, hypertension, dyslipidemia and inflammation. TAKE HOME MESSAGE: Even though clinical trials with certain NHE-1 inhibitors have had discouraging results, NHE-1 cannot be excluded as a potential future therapeutic target for the prevention and/or treatment of atherosclerosis.


Assuntos
Aterosclerose/etiologia , Aterosclerose/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Animais , Aterosclerose/patologia , Proteínas de Transporte de Cátions/química , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Humanos , Concentração de Íons de Hidrogênio , Hipertensão/complicações , Hipertensão/metabolismo , Hipertensão/patologia , Inflamação/complicações , Inflamação/metabolismo , Inflamação/patologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Trocador 1 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/química
18.
Curr Med Res Opin ; 26(10): 2517-20, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20843163

RESUMO

Ezetimibe, an inhibitor of cholesterol intestinal absorption, is a lipid lowering agent with potential pleiotropic actions. Ezetimibe in combination with a statin is effective in decreasing low density lipoprotein cholesterol(LDL-C), lowering triglyceride and raising high density lipoprotein cholesterol levels. Ezetimibe plus statin achieve LDL-C targets in a greater proportion of patients than statin monotherapy. Ezetimibe also seems to improve renal function, insulin resistance and inflammatory markers. These actions are useful in patients with diabetes. Ezetimibe is a well-tolerated and effective (in terms of achieving LDL-C targets) option inpatients with hyperlipidemia with or without diabetes. This editorial will discuss several properties of ezetimibe, with special reference to diabetes.


Assuntos
Anticolesterolemiantes/uso terapêutico , Azetidinas/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Anticolesterolemiantes/farmacologia , Azetidinas/administração & dosagem , Azetidinas/farmacologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus/sangue , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Ezetimiba , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sinvastatina/administração & dosagem
20.
J Am Coll Nutr ; 29(1): 41-5, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20595644

RESUMO

BACKGROUND: Obesity is a rapidly expanding epidemic in Western societies, with rates of more than 30% across Europe, and it is associated with an increased risk of metabolic disturbances. Previous reports have documented an association of reduced physical activity and abstinence from the traditional Mediterranean diet (MD) with increased mortality rate and prevalence of obesity in a population of Greek subjects. OBJECTIVE: The aim of the present study was to evaluate and analyze the dietary habits in a population of Greek overweight and obese subjects and to investigate the potential associations between those patterns and the prevalence of metabolic syndrome components. METHODS: The study recruited 226 consecutive adult (30 men, 169 women) overweight or obese (body mass index >25 kg/m(2)) individuals attending the Metabolic Diseases Unit. Medical history, dietary history, and anthropometric parameters were recorded during the first visit. Fasting blood samples were collected for biochemistry assaying. RESULTS: According to the nutrient intake history and Mediterranean Diet Scale (MDS), participants were divided into 3 groups: those adhering to the MD and those not following the MD, who were further subdivided into the high-carbohydrate (HC) and high-fat (HF) diet groups according to the source of maximum energy intake. Adherence to the MD was associated with a lower prevalence of metabolic syndrome (27.3%, 69.2%, and 60.4% in MD, HC, and HF respectively, p = 0.006), lower low-density lipoprotein cholesterol (p = 0.009, MD vs. HF), and lower postchallenge glucose values (p = 0.028, MD vs. HF). CONCLUSIONS: Adherence to the MD seems to be declining among Greek overweight and obese subjects, a phenomenon that is associated with an increase in the prevalence of the metabolic syndrome.


Assuntos
Glicemia/metabolismo , LDL-Colesterol/sangue , Dieta Mediterrânea , Dieta , Comportamento Alimentar , Síndrome Metabólica/prevenção & controle , Obesidade/dietoterapia , Adulto , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Feminino , Grécia/epidemiologia , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Obesidade/metabolismo , Prevalência
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