Antioxidant Properties and Protective Effects of Some Species of the Annonaceae, Lamiaceae, and Geraniaceae Families against Neuronal Damage Induced by Excitotoxicity and Cerebral Ischemia.

This study aimed to compare the antioxidant activities of extracts obtained from three plant families and evaluate their therapeutic effect on strokes. Ethanol extracts were obtained from either the leaf or the aerial parts of plants of the families Annonaceae (Annona cherimola, A. diversifolia, A. muricata, A. purpurea, and A. reticulata), Lamiaceae (Salvia amaríssima and S. polystachya), and Geraniaceae (Geranium niveum and G. mexicanum). Extracts were analyzed in terms of hydroxyl radical (OH•), peroxyl radical (ROO•), and superoxide anion (O2•-). The efficiency of the extracts to prevent neuronal death induced by excitotoxicity was tested with the tetrazolium assay, the O2•- scavenging capacity was evaluated with the dihydroethidium dye, and the protective effect of the extracts with the highest antioxidant activity was tested on a stroke experimental model. The extracts' IC50 values (µg/mL) of scavenging varied from 98.9 to 155.04, 4.5 to 102.4, and 20.2 to 118.97 for OH•, ROO•, and O2•-, respectively. In the excitotoxicity model, Annonaceae extracts were highly cytotoxic while Lamiaceae and Geraniaceae reduced intracellular O2•- production and protect neurons against oxidative stress. Salvia polystachya reduced cerebral damage, as well as improved survival and behavior after ischemia. Our results encouraged the use of plant extracts as natural antioxidants to minimize neuronal injury following stroke.

Resveratrol Prevents GLUT3 Up-Regulation Induced by Middle Cerebral Artery Occlusion.

Glucose transporter (GLUT)3 up-regulation is an adaptive response activated to prevent cellular damage when brain metabolic energy is reduced. Resveratrol is a natural polyphenol with anti-oxidant and anti-inflammatory features that protects neurons against damage induced in cerebral ischemia. Since transcription factors sensitive to oxidative stress and inflammation modulate GLUT3 expression, the purpose of this work was to assess the effect of resveratrol on GLUT3 expression levels after ischemia. Male Wistar rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by different times of reperfusion. Resveratrol (1.9 mg/kg; i. p.) was administered at the onset of the restoration of the blood flow. Quantitative-PCR and Western blot showed that MCAO provoked a substantial increase in GLUT3 expression in the ipsilateral side to the lesion of the cerebral cortex. Immunofluorescence assays indicated that GLUT3 levels were upregulated in astrocytes. Additionally, an important increase in GLUT3 occurred in other cellular types (e.g., damaged neurons, microglia, or infiltrated macrophages). Immunodetection of the microtubule-associated protein 2 (MAP2) showed that MCAO induced severe damage to the neuronal population. However, the administration of resveratrol at the time of reperfusion resulted in injury reduction. Resveratrol also prevented the MCAO-induced increase of GLUT3 expression. In conclusion, resveratrol protects neurons from damage induced by ischemia and prevents GLUT3 upregulation in the damaged brain that might depend on AMPK activation.

The MLN4924 inhibitor exerts a neuroprotective effect against oxidative stress injury via Nrf2 protein accumulation.

It was explored the cytoprotective and antioxidant effect of MLN4924, a specific inhibitor of Nedd8-activating enzyme (NAE), against hydrogen peroxide (H2O2)-induced damage in cerebellar granule neurons (CGNs). Primary cultures of CGNs were exposed to H2O2 after preincubation with MLN4924. The compounds were removed, and CGNs were incubated in culture medium for 24h in order to determine cell viability by 3-[4,5-dimethylthiazol-2-yl)]-2,5-diphenyl-tetrazolium bromide (MTT) and fluorescein diacetate (FDA) assays. It was demonstrated that MLN4924 remarkably attenuated H2O2-induced cell damage. Meanwhile reactive oxygen species (ROS) production was evaluated with the fluorescent probe dihydroethidium (DHE). Interestingly H2O2-induced ROS production was inhibited by pretreatment with MLN4924. MLN4924 treatment in CGNs resulted in nuclear factor E2-related factor 2 (Nrf2) protein accumulation. Intriguingly this effect was observed in the cytosolic and nuclear compartments of the CGNs. The cytoprotective effect of MLN4924 was associated with its ability to diminish ROS production induced by H2O2 and the accumulation of Nrf2 protein levels in the cytoplasm and nucleus of the CGNs.

Acute restraint stress reduces hippocampal oxidative damage and behavior in rats: Effect of S-allyl cysteine.

AIMS: This simple study was designed to investigate whether acute restraint stress can generate changes in behavioral tests and hippocampal endpoints of oxidative stress in rats, and if the antioxidant S-allyl cysteine (SAC) can prevent these alterations. MATERIALS AND METHODS: We evaluated motor activity, forced swimming and anxiety behavior, as well as the hippocampal levels of lipid peroxidation and the activities of glutathione-related enzymes in animals submitted to mild immobilization. The effect of SAC (100 mg/kg, i.p.), given to rats every day 30 min before starting the immobilization session, was also investigated. Immobilization (restraint) stress was induced for a period of 6 h per day for five consecutive days. KEY FINDINGS: Our results indicate that, under the tested conditions, acute restraint stimulates compensatory behavioral tasks (motor activity, anxiety and forced swimming) to counteract the stressing conditions prevailing, and selectively increased the levels of lipid peroxidation and the enzyme activities of glutathione-S-transferase (GST) and glutathione peroxidase (GPx) in the hippocampus also as adaptive responses. SAC exhibited preventive effects in the stressed group as it improved behavior, reduced lipid peroxidation and prevented the increase of GST and GPx activities, suggesting that this antioxidant blunted primary pro-oxidative stimuli induced by restraint stress. SIGNIFICANCE: Findings of this work also confirm that the use of antioxidants such as SAC can provide effective protection against the acute oxidative damage associated with anxiety produced by stressing conditions.

Macrophage migration inhibitory factor in obese and non obese women with polycystic ovary syndrome.

OBJECTIVE: To measure macrophage migration inhibitory factor (MIF) concentrations in obese and non-obese women diagnosed with polycystic ovary syndrome (PCOS). METHODS: Women diagnosed with PCOS and age-matched healthy controls with regular menses and normal ovaries on ultrasound examination were selected and divided into 4 groups (group A, PCOS and obese; group B, PCOS and non-obese; group C, obese controls; and group D, non-obese controls) based on body mass index (obese >30 kg/m2 and non-obese <25 kg/m2). Luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, sex hormone-binding globulin, serum glucose, insulin and MIF levels were measured. RESULTS: Obese and non-obese women with PCOS had higher luteinizing hormone, follicle-stimulating hormone, androstenedione, testosterone, and insulin levels as compared to the obese and non-obese control groups, respectively (P < .0001). Women with PCOS had significantly higher MIF levels (group A, 48.6 ± 9.9 mg/ml; group B, 35.2 ± 6.0 ng/ml) as compared to controls (group C, 13.5 ± 6.0 ng/ml; group D, 12.0 ± 4.3 ng/dl; P < .0001). A weak, positive and significant correlation was seen between fasting blood glucose and insulin levels in women with PCOS (P < .05). CONCLUSION: Significant differences exist in plasma MIF levels between obese and non-obese women with and without PCOS.

S-allylcysteine prevents cisplatin-induced nephrotoxicity and oxidative stress.

OBJECTIVES: Cisplatin (CP) is an antineoplastic agent that induces nephrotoxicity and oxidative stress. S-allylcysteine (SAC) is a garlic-derived antioxidant. This study aims to explore whether SAC protects against CP-induced nephrotoxicity in rats. METHODS: In the first stage, the SAC protective dose was determined by measuring renal damage and the oxidative stress markers malondialdehyde, oxidized proteins and glutathione in rats injected with CP. In the second stage, the effect of a single dose of SAC on the expression of nuclear factor-erythroid 2-related factor-2 (Nrf2), protein kinase C beta 2 (PKCß2) and nicotinamide adenine dinucleotide phosphate oxidase subunits (p47(phox) and gp91(phox) ) was studied. In addition, the effect of SAC on oxidative stress markers and on the activity of catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in isolated proximal and distal tubules were evaluated. KEY FINDINGS: SAC (25 mg/kg) prevented the CP-induced renal damage and attenuated CP-induced decrease in Nrf2 levels and increase in PKCß2, p47(phox) and gp91(phox) expression in renal cortex and oxidative stress and decrease in the activity of CAT, GPx and GR in proximal and distal tubules. CONCLUSIONS: These data suggest that SAC provides renoprotection by attenuating CP-induced oxidative stress and decrease in the activity of CAT, GPx and GR.

Nordihydroguaiaretic acid induces Nrf2 nuclear translocation in vivo and attenuates renal damage and apoptosis in the ischemia and reperfusion model.

It has been shown that the pretreatment with nordihydroguaiaretic acid (NDGA), a lignan with direct and indirect antioxidant properties, protects against the ischemia-reperfusion (I/R)-induced renal oxidant damage. Although it has been shown that NDGA induces Nrf2 nuclear translocation in renal epithelial LLC-PK1 cells in culture, it is unknown if NDGA may induce Nrf2 translocation in vivo. In this work was explored if NDGA is able to induce in vivo Nrf2 nuclear translocation in kidneys of rats submitted to uni-nephrectomy (U-NX) or I/R injury. Four groups of male Wistar rats were used: U-NX, NDGA, I/R, and I/R+NDGA. NDGA was injected i.p. (10mg/kg/day) starting 48 h before I/R. Kidney samples were obtained at 3 h of reperfusion after to measure Nrf2 translocation. Additional groups of rats were studied at 24 h of reperfusion to measure histological damage and apoptosis. NDGA was able to induce Nrf2 translocation in vivo in kidneys of rats submitted to both U-NX and I/R injury and to protect against renal histological damage and apoptosis. It is concluded that the pretreatment of NDGA is able to induce in vivo nuclear Nrf2 translocation in kidney of rats suggesting that this may be involved in the renoprotection against I/R.

Sulforaphane attenuates gentamicin-induced nephrotoxicity: role of mitochondrial protection.

Sulforaphane (SFN), an isothiocyanate naturally occurring in Cruciferae, induces cytoprotection in several tissues. Its protective effect has been associated with its ability to induce cytoprotective enzymes through an Nrf2-dependent pathway. Gentamicin (GM) is a widely used antibiotic; nephrotoxicity is the main side effect of this compound. In this study, it was investigated if SFN is able to induce protection against GM-induced nephropathy both in renal epithelial LLC-PK1 cells in culture and in rats. SFN prevented GM-induced death and loss of mitochondrial membrane potential in LLC-PK1 cells. In addition, it attenuated GM-induced renal injury (proteinuria, increases in serum creatinine, in blood urea nitrogen, and in urinary excretion on N-acetyl- ß -D-glucosaminidase, and decrease in creatinine clearance and in plasma glutathione peroxidase activity) and necrosis and apoptosis in rats. The apoptotic death was associated with enhanced active caspase-9. Caspase-8 was unchanged in all the studied groups. In addition, SFN was able to prevent GM-induced protein nitration and decrease in the activity of antioxidant enzymes catalase and glutathione peroxidase in renal cortex. In conclusion, the protective effect of SFN against GM-induced acute kidney injury could be associated with the preservation in mitochondrial function that would prevent the intrinsic apoptosis and nitrosative stress.

Pseudomixoma peritoneal / Pseudomyxoma peritonei

El pseudomixoma peritoneal es una condición relativamente rara y poco comprendida en la cual la mucina se acumula en la cavidad peritoneal. En forma clásica se caracteriza por una colección difusa gelatinosa abdominal (jelly belly) con implantes mucinosos en la superficie peritoneal. Se presenta un caso de pseudomixoma mucinoso que se originó de un cistadenoma mucinoso de ovario en una mujer de 56 años de edad, con antecedentes de dolor en hipogastrio, náuseas y vómitos. La ecografía pélvica reveló la presencia de una tumoración sólido-quística ecogénica que salía desde el anexo derecho y líquido libre con ecogenicidad mixta en el abdomen. Se realizó laparotomía ginecológica, aspiración del líquido mucinoso e histerectomía, encontrándose cistadenoma mucinoso de ovario y liquido peritoneal mucinoso compatible con pseudomixoma peritoneal.

Pseudomyxoma peritonei is a relatively rare and poorly understood condition in which mucin accumulates within the peritoneal cavity. Classically, it is characterized by diffuse intra-abdominal gelatinous collections ("jelly belly") with mucinous implants on peritoneal surfaces. A case of pseudomyxoma peritonei originated from a mucinous cystadenoma of the ovary is presented in a 56-year-old woman with history of hypogastric pain and abdominal distension, nausea and vomiting. Pelvic ultrasound scan revealed a solid-cystic echogenic mass arising from the right adnexa and free fluid of mixed echogenicity in the abdomen. Gynecological laparotomy, aspiration of mucinous fluid and hysterectomy were performed revealing mucinous cystadenoma of the ovary and mucoid peritoneal fluid compatible with pseudomyxoma peritonei.

Compresa quirúrgica retenida posterior a cesárea electiva / Retained textiloma after elective cesarean section

La compresa quirúrgica retenida o textiloma es el resultado de un error quirúrgico poco frecuente y evitable. Se ha reportado que la incidencia es 1 por cada 1 000 a 15 000 cirugías intraabdominales. La compresa quirúrgica retenida puede causar graves complicaciones que llevan hasta la muerte. Se presenta el caso de una paciente de 26 años quien llegó por dolor abdominal. Tenía un antecedente quirúrgico de cesárea 20 meses antes. Durante la laparotomía, se encontró una compresa quirúrgica retenida a 25 centímetros de la válvula ileocecal, que fue resecada en bloque. Aunque rara en la práctica diaria, se debe considerar la retención de compresas intraperitoneales en pacientes que se presentan con síntomas abdominales complejos posteriores a una cirugía abdominal previa.

Retained surgical swab or textiloma is an infrequent but avoidable result of surgical error. The reported incidence is 1 in 1 000 to 15 000 intraabdominal surgeries. A retained surgical swab may cause serious complications and may lead to death. We present the case of a 26 year-old woman who was seen for abdominal pain. Her surgical history included a cesarean section 20 months ago. During laparotomy, a retained surgical sponge located 25 centimeters from the ileocecal valve was found and resected en bloc. Although rare in daily practice, a retained intraperitoneal swab body should be considered in patients with complex abdominal symptoms following a history of abdominal surgery.

Linfangioma mesentérico quístico de intestino delgado simulando tumoración ovárica / Mesenteric cystic lymphangioma of small bowel mimicking ovarian tumor

Resumen El linfangioma quístico, caracterizado por proliferación de los espacios linfáticos, es una lesión infrecuente en pacientes adultos. Menos del 1% de todos los linfangiomas corresponden a linfangiomas del intestino delgado. La presentación clínica es diversa, variando desde un quiste abdominal asintomático, diagnosticado de forma incidental, a un cuadro de abdomen agudo. Se presenta un caso de linfangioma mesentérico quístico del intestino delgado en una mujer de 30 años y quien consultó por dolor abdominal y vómitos. La ecografía y la tomografía computada abdominal mostraron un quiste con múltiples septos en el cuadrante inferior derecho simulando un tumor de ovario. En la laparotomía se encontró un tumor quístico, lobulado y marrón, procedente del mesenterio del intestino delgado. A la paciente se le realizó resección de la tumoración y del intestino delgado adyacente con reconstrucción del tránsito intestinal. La evaluación histológica confirmó el diagnóstico de linfangioma mesentérico quístico.

Abstract Cystic lymphangioma, characterized by proliferation of lymphatic spaces, is an infrequent lesion in adult patients. Less than 1% of all lymphangiomas correspond to small-bowel lymphangiomas. Clinical presentation can be diverse ranging from incidental abdominal cysts to an acute abdomen. We report a case of small bowel mesenteric cystic lymphangioma in a 30 years-old woman who presented with abdominal pain and vomiting. The abdominal ultrasound and computed tomography scan showed a cystic multiseptated mass at the right lower quadrant mimicking an ovarian tumor. Laparotomy found a lobulated, brown, cystic tumor from the small bowel mesentery. The patient underwent resection of the tumor and the adjacent small intestine with reconstruction of the intestinal transit. The histological study confirmed diagnosis of mesenteric cystic lymphangioma.

Recurrencia colónica tardía de adenocarcinoma endometrial / Late colonic recurrence of endometrial adenocarcinoma

La tasa de recurrencia del carcinoma endometrial después de la cirugía más radioterapia es baja y la mayoría de los casos ocurren dentro de los primeros 3 años. La cúpula vaginal es el sitio más común de recurrencia. La recurrencia del cáncer endometrial al colon es muy rara. Se presenta el caso de una mujer de 69 años que presentaba dolor en fosa ilíaca izquierda, anorexia y pérdida de peso de 5 meses de evolución, con antecedentes de histerectomía abdominal total y ooforosalpingectomía bilateral por carcinoma endometrial estadio IA hacía 7 años. La colonoscopia reveló constricción circunferencial en el tercio medio del colon transverso, sospechosa de compresión extrínseca. La tomografía computada no reveló si la tumoración se originaba en el colon sigmoides o lo rodeaba. Durante la laparotomía, se observó enfermedad macroscópica que afectaba colon transverso y mesenterio del intestino delgado, con estenosis vascular. Se realizó la resección intestinal de las porciones afectadas y omentectomía total, sin dejar enfermedad residual macroscópica durante el procedimiento. El análisis inmunohistoquímico reveló adenocarcinoma endometrial pobremente diferenciado. La paciente se recuperó sin complicaciones y fue tratada con quimioterapia adyuvante.

The recurrence rate of endometrial carcinoma after surgery plus radiotherapy is low and, in most cases, it occurs within the first 3 years of treatment. The vaginal vault is the most common site of recurrence. Recurrence of endometrial cancer to the colon is very rare. We report a 69-year-old woman who presented with right iliac fossa pain, anorexia and weight loss for five months. She had a history of total abdominal hysterectomy and bilateral oophorosalpingectomy for stage IA endometrial carcinoma 7 years ago. Colonoscopy revealed a mid-sigmoid colon stricture suspicious of external compression. A CT scan did not reveal if the tumor was arising from the sigmoid colon or abutting it. During laparotomy, we found macroscopic disease involving transverse colon and small bowel mesentery with an ischemic stricture was found. Bowel resection and total omentectomy were performed leaving no residual macroscopic disease. Immunohistochemistry analysis revealed a poorly-differentiated endometrial adenocarcinoma. Patient recovered without complications and was treated with chemotherapy.

Curcumin prevents Cr(VI)-induced renal oxidant damage by a mitochondrial pathway.

We report the role of mitochondria in the protective effects of curcumin, a well-known direct and indirect antioxidant, against the renal oxidant damage induced by the hexavalent chromium [Cr(VI)] compound potassium dichromate (K(2)Cr(2)O(7)) in rats. Curcumin was given daily by gavage using three different schemes: (1) complete treatment (100, 200, and 400 mg/kg bw 10 days before and 2 days after K(2)Cr(2)O(7) injection), (2) pretreatment (400 mg/kg bw for 10 days before K(2)Cr(2)O(7) injection), and (3) posttreatment (400 mg/kg bw 2 days after K(2)Cr(2)O(7) injection). Rats were sacrificed 48 h later after a single K(2)Cr(2)O(7) injection (15 mg/kg, sc) to evaluate renal and mitochondrial function and oxidant stress. Curcumin treatment (schemes 1 and 2) attenuated K(2)Cr(2)O(7)-induced renal dysfunction, histological damage, oxidant stress, and the decrease in antioxidant enzyme activity both in kidney tissue and in mitochondria. Curcumin pretreatment attenuated K(2)Cr(2)O(7)-induced mitochondrial dysfunction (alterations in oxygen consumption, ATP content, calcium retention, and mitochondrial membrane potential and decreased activity of complexes I, II, II-III, and V) but was unable to modify renal and mitochondrial Cr(VI) content or to chelate chromium. Curcumin posttreatment was unable to prevent K(2)Cr(2)O(7)-induced renal dysfunction. In further experiments performed in curcumin (400 mg/kg)-pretreated rats it was found that this antioxidant accumulated in kidney and activated Nrf2 at the time when K(2)Cr(2)O(7) was injected, suggesting that both direct and indirect antioxidant effects are involved in the protective effects of curcumin. These findings suggest that the preservation of mitochondrial function plays a key role in the protective effects of curcumin pretreatment against K(2)Cr(2)O(7)-induced renal oxidant damage.

Titanium dioxide nanoparticles impair lung mitochondrial function.

Titanium dioxide nanoparticles (TiO(2) NPs) are used in an increasing number of human products such as cosmetics, sunscreen, toothpaste and paints. However, there is clear evidence about effects associated to TiO(2) NPs exposure, which include lung inflammation and tumor formation and these effects are related to reactive oxygen species (ROS) formation. The ROS generation could be attributed to a mitochondrial dysfunction. Even though, it has been shown that TiO(2) NPs exposure can induce some alterations in mitochondria including cytochrome c release to cytosol, change in mitochondrial permeability and decrease of mitochondrial membrane potential (ΔΨ(m)), there is no information about the changes in mitochondrial function induced by TiO(2) NPs. We hypothesized that TiO(2) NPs effects are associated with mitochondrial dysfunction and redox unbalance. To test our hypothesis we isolated mitochondria from lung tissue of rats and exposed them to 10(g TiO(2) NPs (particle size<25nm)/mg protein for 1h. Our results showed that TiO(2) NPs decreases NADH levels and impairs ΔΨ(m) and mitochondrial function accompanied by ROS generation during mitochondrial respiration.

Procalcitonina Plasmática en mujeres obesas y no obesas con Síndrome de Ovarios Poliquísticos / Plasma Procalcitonin in obese and non obese women with Polycystic Ovary Syndrome

Objetivo: Determinar las concentraciones plasmáticas de procalcitonina, marcador de inflamación de bajo grado, en mujeres obesas y no obesas con diagnóstico de síndrome de ovarios poliquísticos (SOPQ). Métodos: Se seleccionaron mujeres con diagnóstico de SOPQ y controles sanas, de edades similares, con menstruaciones regulares y ovarios normales por ecografía, que fueron divididas en cuatro grupos (grupo A: SOPQ obesas; grupo B: SOPQ no obesas; grupo C: controles obesas y grupo D controles no obesas) de acuerdo al índice de masa corporal (obesas > 30 Kg/m² y no obesas < 25 kg/m²). Se analizaron las concentraciones de hormona luteinizante (LH), hormona foliculoestimulante (FSH), androstendiona, testosterona, globulina fijadora de hormonas sexuales, glucosa sérica, insulina y procalcitonina. Resultados: Las mujeres con SOPQ obesas y no obesas presentaron concentraciones más elevadas de LH, FSH, testosterona, androstendiona e insulina comparado con las mujeres del grupo control de obesas y no obesas respectivamente (p< 0,0001). Se observó que las mujeres con SOPQ presentaron concentraciones significativamente más altas de procalcitonina (grupo A: 0,026±0,003 ng/mL y grupo B: 0,024±0,002 ng/mL) comparado con los controles (grupo C: 0,015±0,001 ng/mL y grupo D: 0,012±0,001 ng/dL; p< 0,0001). Se observó que las concentraciones de procalcitonina presentaban una correlación positiva y significativa con los valores de insulina en ayunas en las mujeres con SOPQ (p< 0,0001). Conclusión: Las concentraciones plasmáticas de procalcitonina son significativamente mayores en las mujeres con SOPQ obesas y no obesas comparado con las mujeres controles. La procalcitonina podría ser útil como marcador de inflamación de bajo grado en el SOPQ.

Objective: To determine plasma concentrations of procalcitonina, marker of low-grade inflammation, in obese and non-obese women with diagnosis of polycystic ovary syndrome (PCOS). Methods: Women with diagnosis of PCOS and age-matched healthy controls, with regular menstruations and normal ultrasound ovaries were selected and divided in four groups (group A: PCOS and obese; group B: PCOS and non-obese; group C: obese controls and group D: non-obese controls) according to body mass index (obese > 30 Kg/m² and non-obese < 25 kg/m²). Concentrations of luteinizing hormone, follicle-stimulating hormone, androstenodione, testosterone, sex hormone-binding globulin, serum glucose, insulin and procalcitonin were measured. Results: Obese and non-obese women with PCOS had higher luteinizing hormone, follicle stimulating hormone, androstenodione, testosterone, and insulin levels as compared to women in the obese and non-obese control group, respectively (p< 0.0001). Women with PCOS had significantly higher procalcitonin levels (group A 0.026±0.003 ng/mL and group B: 0.024±0.002 ng/mL) as compared with controls (group C: 0.015±0.001 ng/mL and group D: 0.012±0.001 ng/dL; p< 0.0001). We observed that procalcitonin concentrations presented a positive and significant correlation with fasting insulin in PCOS women (p< 0.0001). Conclusion: Plasma procalcitonin concentrations were significantly higher in obese and non-obese women with PCOS compared with normal controls. Procalcitonin could be useful as a marker of low-grade inflammation in PCOS.

The antithrombotic effect of the aminoestrogen prolame (N-(3-hydroxy-1,3,5(10)-estratrien-17B-YL)-3-hydroxypropylamine) is linked to an increase in nitric oxide production by platelets and endothelial cells.

OBJECTIVE: Women under hormone replacement therapy carry an increased risk of venous thromboembolism (VTE), mostly during the first year. Despite great efforts devoted to hormone therapy research, VTE remains a major drawback of estrogenic therapy, and the search for new compounds continues. We have synthesized and evaluated prolame, an aminoestrogen with anticoagulant properties. The aim of our work was to elucidate the anticoagulant mechanism of prolame. METHODS: We studied the effects of prolame on nitric oxide (NO) synthesis in cultured endothelial cells and platelets using flow cytometry, on NO metabolites using a modified Griess method, on NO formation in vivo using electron paramagnetic resonance spectroscopy, on participation of nuclear estrogen receptors using flow cytometry, and on endothelial NO synthase (eNOS) mRNA expression using RT-PCR. We also studied the impact of prolame-treated endothelial cells (EC) on ADP-induced platelet aggregation, as well as the ability to prevent occlusive thrombi in an in vivo mice thrombosis model. RESULTS: (a) Prolame induces NO production in ECs, platelets, and in a mouse model in vivo. (b) The NO-elevating effect of prolame can only be partially attributed to the nuclear estrogen receptors (ERs) since endothelial nitric oxide synthase (e-NOS) is slightly induced (37%) in ECs treated with prolame. (c) Platelets become 60% less responsive to aggregation induced by 10muM ADP when in suspension with prolame-treated ECs. (d) Prolame reduces the formation of thrombi in an in vivo thrombosis model. CONCLUSIONS: Prolame could be a preferred alternative to other estrogens because of its reduced thromboembolic risk.