Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy.

Effect of a cholesterol-rich diet on the metabolism of the free and esterified cholesterol components of a nanoemulsion that resembles LDL in rabbits

We have shown that the free cholesterol (FC) and the cholesteryl ester (CE) moieties of a nanoemulsion with lipidic structure resembling low-density lipoproteins show distinct metabolic fate in subjects and that this may be related to the presence of dyslipidemia and atherosclerosis. The question was raised whether induction of hyperlipidemia and atherosclerosis in rabbits would affect the metabolic behavior of the two cholesterol forms. Male New Zealand rabbits aged 4-5 months were allocated to a control group (N = 17) fed regular chow and to a 1 percent cholesterol-fed group (N = 13) during a 2-month period. Subsequently, the nanoemulsion labeled with ³H-FC and 14C-CE was injected intravenously for the determination of plasma kinetics and tissue uptake of the radioactive labels. In controls, FC and CE had similar plasma kinetics (fractional clearance rate, FCR = 0.234 ± 0.056 and 0.170 ± 0.038 h-1, respectively; P = 0.065). In cholesterol-fed rabbits, the clearance of both labels was delayed and, as a remarkable feature, FC-FCR (0.089 ± 0.033 h-1) was considerably greater than CE-FCR (0.046 ± 0.010 h-1; P = 0.026). In the liver, the major nanoemulsion uptake site, uptake of the labels was similar in control animals (FC = 0.2256 ± 0.1475 and CE = 0.2135 ± 0.1580 percent/g) but in cholesterol-fed animals FC uptake (0.0890 ± 0.0319 percent/g) was greater than CE uptake (0.0595 ± 0.0207 percent/g; P < 0.05). Therefore, whereas in controls, FC and CE have similar metabolism, the induction of dyslipidemia and atherosclerosis resulted in dissociation of the two forms of cholesterol.

Lipolysis of emulsion models of triglyceride-rich lipoproteins is altered in male patients with abdominal aorta aneurysm

Disorders of the lipid metabolism may play a role in the genesis of abdominal aorta aneurysm. The present study examined the intravascular catabolism of chylomicrons, the lipoproteins that carry the dietary lipids absorbed by the intestine in the circulation in patients with abdominal aorta aneurysm. Thirteen male patients (72 ± 5 years) with abdominal aorta aneurysm with normal plasma lipid profile and 13 healthy male control subjects (73 ± 5 years) participated in the study. The method of chylomicron-like emulsions was used to evaluate this metabolism. The emulsion labeled with 14C-cholesteryl oleate and ³H-triolein was injected intravenously in both groups. Blood samples were taken at regular intervals over 60 min to determine the decay curves. The fractional clearance rate (FCR) of the radioactive labels was calculated by compartmental analysis. The FCR of the emulsion with ³H-triolein was smaller in the aortic aneurysm patients than in controls (0.025 ± 0.017 vs 0.039 ± 0.019 min-1; P < 0.05), but the FCR of14C-cholesteryl oleate of both groups did not differ. In conclusion, as indicated by the triglyceride FCR, chylomicron lipolysis is diminished in male patients with aortic aneurysm, whereas the remnant removal which is traced by the cholesteryl oleate FCR is not altered. The results suggest that defects in the chylomicron metabolism may represent a risk factor for development of abdominal aortic aneurysm.

Afecções mais freqüentes do aparelho locomotor dos eqüídeos de tração no município de Belo Horizonte / Most frequent pathologies of the locomotor system in equids used for wagon traction in Belo Horizonte

Determinaram-se as enfermidades mais comuns do sistema músculo-esquelético dos animais de tração na cidade de Belo Horizonte. Foram utilizados 58 animais (42 eqüinos e 16 muares), sendo 31 machos e 27 fêmeas. O diagnóstico baseou-se no histórico e nos exames físico e radiológico. A freqüência observada para tenossinovite nos membros torácicos e pélvicos foi 55,2 por cento, para tendinite nos membros torácicos, 81,0 por cento, para tendinite nos membros pélvicos, 58,6 por cento, e para desmite do ligamento suspensório nos membros torácicos, 77,6 por cento. Para as lesões osteoarticulares, os resultados foram 13,8 por cento, 12,1 por cento, 27,6 por cento e 12,1 por cento de lesões osteoartríticas para a articulação interfalangeana distal dos membros torácicos e pélvicos e articulação interfalangeana proximal dos membros torácicos e pélvicos, respectivamente. Na articulação metacarpo-falangeana, a incidência foi 41,4 por cento e, nos membros pélvicos, 39,7 por cento. A incidência na articulação cárpica foi 62,1 por cento e, na articulação társica, 96,6 por cento. Os achados dos tecidos moles indicaram sobrecarga nos aparatos flexor e suspensório nesse tipo de atividade. Em ambos os casos, a atividade desenvolvida pelos animais parece ser a principal causa envolvida.

The most common conditions of the musculoskeletal system of draft equidae in the city of Belo Horizonte were determined. Fifty-eight animals (42 horses and 16 mules) were randomly examined, being 31 males and 27 females. Diagnosis was based on history, clinical and radiological examinations. The frequency observed for tenosynovitis in the fore and hindlimbs was 55.2 percent, 81.0 percent, for tendinitis in the forelimbs, 58.6 percent for tendinitis in the himblimbs, and 77.6 percent for suspensory ligament desmitis in the forelimbs. The results showed 13.8%, 12.1 percent, 27.6 percent and 12.1 percent of osteoarthritic lesions for distal interphalangeal joint of fore and hindlimbs and proximal interphalangeal joint of fore and hindlimbs, respectively. In the fetlock joints of the forelimbs, the incidence was 41.4 percent, and 39.7 percent in the hindlimbs. The incidence increased in the carpal joints, reaching 62.1 percent and it was even higher in the tarsal joints, reaching 96.6 percent. Findings in soft tissues indicated an overloading of both suspensory and flexor apparatus. Osteoarthritis was a common finding in draft equine, especially in tarsal joint. In both cases, the activity developed by those animals seems to be the main related cause.

In vitro cytotoxicity of the LDE-daunorubicin complex in acute myelogenous leukemia blast cells

Acute myelogenous leukemia (AML) blast cells show high-affinity degradation of low-density lipoprotein (LDL), suggesting an increased expression of cellular LDL receptors. LDE is a lipid microemulsion easily synthesized in vitro which is known to mimic the metabolic pathway of LDL. We used LDE as a carrier for daunorubicin and assayed the cytotoxicity of the complex using AML blast cells since RT-PCR analysis showed that AML cells express LDL receptor mRNA. The LDE:daunorubicin complex killed 46.7 percent of blast cells and 20.2 percent of normal bone marrow cells (P<0.001; Student t-test). Moreover, this complex destroyed AML blast cells as efficiently as free daunorubicin. Thus, LDE might be a suitable carrier of chemotherapeutic agents targeting these drugs to neoplastic cells and protecting normal tissues

Etofibrate but not controlled-release niacin decreases LDL cholesterol and lipoprotein (a) in type IIb dyslipidemic subjects

Etofibrate is a hybrid drug which combines niacin with clofibrate. After contact with plasma hydrolases, both constituents are gradually released in a controlled-release manner. In this study, we compared the effects of etofibrate and controlled-release niacin on lipid profile and plasma lipoprotein (a) (Lp(a)) levels of patients with triglyceride levels of 200 to 400 mg/dl, total cholesterol above 240 mg/dl and Lp(a) above 40 mg/dl. These patients were randomly assigned to a double-blind 16-week treatment period with etofibrate (500 mg twice daily, N = 14) or niacin (500 mg twice daily, N = 11). In both treatment groups total cholesterol, VLDL cholesterol and triglycerides were equally reduced and high-density lipoprotein cholesterol was increased. Etofibrate, but not niacin, reduced Lp(a) by 26 percent and low-density lipoprotein (LDL) cholesterol by 23 percent. The hybrid compound etofibrate produced a more effective reduction in plasma LDL cholesterol and Lp(a) levels than controlled-release niacin in type IIb dyslipidemic subjects

Priapismo en niños con enfermedad de células falciformes: reporte de un caso / Priapism in children with sickle cell disease: case report

El priapismo es una entidad rara en la infancia,frecuentemente asociada a enfermedad de células falciformes.En pacientes con pocas horas de evolución,el manejo conservador generalmente es efectivo.Se presenta el caso de un niño de 5 años de edad con un cuadro clínico de 24 horas de evolución en quien el tratamiento clínico conservador durante 12 horas no logró la detumescencia del pene.Posteriormente fue practicada sin éxito la compresíon del pene,previa infiltración de bupivacaina al 0,5 por ciento en su base,por lo que fue necesario aspiración e irrigación de los cuerpos cavernosos con suero fisiológico en 3 oportunidades diferentes.Luego del tratamiento refirió porla madre presencia de erecciones

Avaliação dos efeitos a curto prazo de programas de conscientiização e de terapia com pravastatina em indivíduos de alto risco para doença cardiovascular provenientes de consultórios particulares / The evaluation of short term effects of awareness programs and pravastatin therapy on subjects from private clinics at high risk for cardivascular disease

OBJETIVO - Avaliar a eficácia de programas de conscientização (PC) sobre o controle de fatores de risco (FR) para doença cardiovascular (DCV). MÉTODOS - Pacientes hipercolesterolêmicos de alto risco para DCV foram divididos em 2 frupos durante 16 semanas. O grupo A(n=180, 54,4ñ10,0 anos, 55 'por cento' homens) recebeu orientação verbal e escrita sobre controle de FR, e o grupo B (n=180, 54,4ñ10,9 anos, 45 'por cento' homens) apenas orientação verbal. Todos os participantes receberam 10mg/dia de pravastatina por 12 semanas. Avaliaram-se o peso, pressão arterial, o colesterol total (CT) e fraçöes, triglicérides, índices I e II de Castelli (CT/HDL-C e LDL-C/HDL-C) e escores de Framingham. RESULTADOS - No basal, A diferiu de B no HDL-C (40,0ñ11,0 vs 43,0ñ11,0mg/dl, p=0,013) e no índice I (8,2ñ3,0 vs 7,6ñ2,3, p=0,008). Após 16 semanas as variaçöes 'porcentagem' foram maiores em A do que B no CT (-28,0 vs -25,0, p<0,05), LDL-C (-29,0 vs -27,6, p<0,05), HDL-C (+13,7 vs +10,8, p<0,05) e índice I (-39,0 vs -33,0; p<0,05). A pravastatina potencializou os efeitos da dieta sobre os lípides. CONCLUSÄO - O PC parece ser mais eficaz a curto prazo, em reduzir os FR para DCV do que a orientação apenas verbal.

Clearance of a chylomicron-like emulsion from plasma is delayed in patients with coronary artery disease

To determine whether the metabolism of chylomicrons and their remmants is related to atherogenesis, a triglyceride-rich emulsion known to mimic chylomicron behavior in plasma and labeled with 1-14C-cholesteryl oleate was injected intravenously into 11 normolipidemic patients (triglycerides: 133 + or - 60 mg/dl; total cholesterol: 207 + or - 20 mg/dl; LDL: 143 + or - 20 mg/dl; VLDL: 27 + or - 13 mg/dl; and HDL cholesterol: 41 + or - 11 mg/dl; apo AI: 1.27 + or - 0.54 g/l and apo B: 1.42 + or - 0.31 gl) with atherosclerotic coronary artery disease and into 11 control subjects (triglycerides: 109 + or - 32 mg/dl; total cholesterol: 190 + or - 38 mg/dl; LDL: 125 + or - 29 mg/dl; VLDL: 22 + or - 6 mg/dl; and HDL cholesterol: 44 + or - 9 mg/dl; apo AI: 1.09 + or - 0.28 g/land apo B: 1.09 + or - 028 g/l) without the disease. The emulsion (69 percent triolein, 23 percent lecithin, 6 percent cholesteryl oleate and 2 percent cholesterol) was injected intravenously at approximately 9:00 a.m., after a 12-h fast. The clearance of the emulsion label from plasma, expressed as fractional clearance rate (FCR), was lower in coronary artery disease compared to controls (0.019 + or - 0.005/min vs 0.036 + or - 0.018/min, respectively, P<0.05). These results indicate that the rate of removal of chylomicron remmants is slower in patients with coronary artery disease

Lipoprotein (a) in subjects with or without coronary artery disease: relation to clinical history and risk factors

Lipoprotein (a) [Lp(a)] is an atherogenic lipoprotein resembling low-density lipoprotein (LDL) but with an additional apoprotein (apo), apo(a). To determine whether plasma Lp(a) levels can influence the clinical presentation and extent of coronary artery disease (CAD), Lp(a), plasma lipids and apolipoproteins were determined in 203 Caucasian subjects with CAD and in 66 subjects without CAD, all confirmed by cinecoronariography. CAD patients were divided into groups according to their clinical history. The extent of the disease was evaluated by a scoring system. Lp(a) was elevated in CAD patients compared to subjects without CAD. However, there was no difference between patients that had myocardial infarction as the first manifestation of the disease and those who had only angina pectoris for at least two years. Plasma lp(a) levels were correlated with extent of the disease. Among patients with CAD, Lp(a) was higher in females. Lp(a) was also studied separately in 29 Black subjects, Lp(a) was higher than in Caucasians but there was no difference between subjects with and without CAD. Among the other risk factors studied, only plasma apo B levels and smoking were correlated with CAD

Transfer of phospholipids and cholesterol from triglyceride-rich emulsions to HDL in rats treated with alloxan, propylthiouracil or ethanol

1. The transfer of lipids that constitute the surface of lipoprotein particles, phospholipids and unesterified cholesterol, from chylomicrons and VLDL to other lipoproteins, mainly HDL, was examined. 2. Emulsions known to mimic the metabolism of chylomicrons labeled with [3H]-phosphatidylcholine, [14C]-cholesterol or [3H]-triolein were injected through a cannula implanted into the carotid artery of male Wistar rats weighing 280-350 g. Plasma clearance of the radioactively labeled emulsion lipid constituents and transfer of surface lipids from the emulsions to native HDL and LDL were measured in plasma samples collected at 2-min intervals during 10 min. 3. The transfer was measured in rats with alloxan-induced diabetes (single intraperitoneal dose, 140 mg/kg body weight) or with propylthiouracil-induced hypothyroidism (0.1 per cent v/v in drinking water for 30 days), or given ethanol (20 per cent in drinking water) for a period of 30 days, and in control rats. 4. The entry of emulsion phospholipids into the HDL fraction was not affected by the different treatments (controls: 9.3 +/- 0.6 per cent of injected radioactivity, N = 8; diabetes: 12.5 +/- 2.4 per cent , N = 9; hypothyroidism: 10.9 +/- 0.9 per cent , N = 13; ethanol: 7.8 +/- 0.9 per cent , N = 5). However, phospholipid transfer to the LDL fraction was increased in diabetes (10.0 +/- 2.3 per cent ) and hypothyroidism (12.1 +/- 1.3 per cent ) compared to controls (6.7 +/- 0.9 per cent ). Transfer of unesterified cholesterol from the emulsions to LDL and HDL was increased in both diabetic and hypothyroid rats (controls, LDL: 1.6 +/- 0.6 per cent , HDL: 2.5 +/- 0.6, N = 5; diabetes, LDL: 5.3 +/- 1.2, HDL: 8.4 +/- 2.1 N = 5; hypothyroidism, LDL: 4.0 +/- 0.6, HDL: 3.6 +/- 0.4, N = 8). In ethanol-treated rats, transfer of surface lipids was similar to controls

Increased plasma removal of microemulsions resembling the lipid phase of low-density lipoproteins (LDL) in patients with acute myeloid leukemia: a possible new strategy for the treatment of the disease

A microemulsion of lipid composition resembling low-density lipoprotein (LDL), but devoid of apolipoproteins and labeled with [14C]-cholesteryl oleate was injected into 16 healthy subjects and into 15 patients with acute myeloid leukemia (AML). Removal from plasma of the lipid label was higher in the leukemic group compared to healthy subjects in terms of fractional clearance rate (0.185 +/- 0.205 and 0.080 +/- 0.030 h-1, respectively, P < 0.03). When the emulsion was again injected into 10 of the AML patients after complete hematological remission, the fractional clearance rate of cholesteryl ester was reduced to one third of the value observed prior to treatment (0.061 +/- 0.038 h-1) and was not different from that obtained for the healthy subjects. Also, in untreated AML patients, serum LDL-cholesterol levels inversely correlated with the values of fractional clearance rate of the microemulsion. This correlation was no longer observed after treatment. These data suggest that the LDL-like microemulsion was selectively taken up by the neoplastic cells presumably by interaction with LDL receptors. Therefore, microemulsions may function as potential carriers for anticancer drugs that are targeted to tumor cells for patients with acute myeloid leukemia. Unlike native LDL, microemulsions are suitable for utilization in routine clinical practice

Invaginacao colo-colica cronica. Apresentacao de um caso. / Chronic colonic intussusception. Report of a case

Os autores apresentam um caso de invaginacao colo-colica-cronica (30 dias), devido a um polipo juvenil do colo descendente. Tecem comentarios sobre a incidencia, quadro clinico, radiologico e tratamento desta patologia