Genital mycoplasma infection and spontaneous preterm birth outcome: a prospective cohort study.

OBJECTIVE: To assess the risk of spontaneous preterm birth (sPTB) associated with genital mycoplasma infection in asymptomatic women. DESIGN: Prospective cohort. SETTING: Public and private health services in Ribeirão Preto, SP, Brazil. POPULATION: A cohort of 1349 asymptomatic women with a singleton pregnancy at 20-25 weeks of gestation. METHODS: Participants completed a sociodemographic and clinical history questionnaire during the prenatal visit and provided cervicovaginal samples for the evaluation of Mycoplasma hominis (Mh), Ureaplasma spp. and bacterial vaginosis (BV). For gestational outcome, information about the delivery was assessed and sPTB was defined as a birth that occurred before 37 weeks of gestation. The association between variables and the risk of sPTB was evaluated using logistic regression analysis to estimate the odds ratios (ORs). MAIN OUTCOME MEASURES: Genital mycoplasma infection and prematurity. RESULTS: The prevalence of sPTB and genital mycoplasma was 6.8 and 18%, respectively. The infection was not a risk factor for sPTB (aOR 0.66, 95% CI 0.32-1.35), even when Mh and Ureaplasma spp. were found together (P = 0.83). Pregnant women with genital mycoplasma infections had greater BV (P < 0.0001), but this vaginal microbiota condition was not associated with sPTB (P = 0.35). Regarding the risk factors associated with sPTB, a previous history of sPTB (aOR 12.06, 95% CI 6.21-23.43) and a cervical length of ≤2.5 cm (aOR 3.97, 95% CI 1.67-9.47) were significant. CONCLUSIONS: Genital mycoplasma infection was not a risk factor for sPTB, even in the presence of other abnormal vaginal microbiota. TWEETABLE ABSTRACT: Genital mycoplasma infection was not a risk for sPTB, even when associated with bacterial vaginosis (BV).

Can increased resistance to uterine artery flow be a risk factor for adverse neurodevelopmental outcomes in childhood? A prospective cohort study.

A prospective cohort study was conducted to determine whether an increased uterine artery pulsatility index (UtA-PI) in the second trimester of pregnancy is a risk factor for neurodevelopmental outcomes in children 2-3 years of age. A group of pregnant women with a UtA-PI below the 90th percentile (P90) and a second group with a UtA-PI ≥ P90 in the second trimester were included in this study. The children of these women were evaluated during their second or third year of life using the Bayley III Screening Test. A total of 858 pregnancies with UtA-PI < P90 and 96 pregnancies with UtA-PI ≥ 90 were studied. The differences between the groups related to UtA-PI ≥ 90 were detected in relation to the variables of the Caucasian ethnicity, hypertension, newborn weight and stay in the intensive care unit after birth. However, adjusted neurodevelopmental outcomes did not differ between the groups: OR 0.53 (95% CI 0.27-1.04%). This study failed to demonstrate that the UtA-PI is a risk factor for adverse neurodevelopment in children.Impact statementWhat is already known on this subject? Early interventions in children at high risk for neurodevelopmental deficiency have proved to be beneficial. The complications associated with gestation and delivery negatively influence neurodevelopment. Several studies have shown that some adverse pregnancy outcomes such as preeclampsia, foetal growth restriction and foetal death can be predicted by increased resistance to flow in the uterine artery in the second trimester. However, there are no studies evaluating the association of the uterine artery with neurodevelopmental results.What do the results of this study add? This study concludes that neurodevelopment is influenced by multiple environmental and intrinsic factors and cannot be predicted by only one variable, such as the uterine artery blood flow. The brain has repair mechanisms to attenuate insults that occur during gestation and delivery.What are the implications of these findings for clinical practice and/or further research? This study was unable to demonstrate that blood flow in the uterine artery is a risk factor for neurodevelopment. Different, larger studies should be conducted by combining other factors with the uterine artery in an algorithm to allow the early identification of children at risk for neurodevelopmental impairment.

Low-dose curcuminoid-loaded in dextran nanobubbles can prevent metastatic spreading in prostate cancer cells.

Preventing recurrences and metastasis of prostate cancer after prostatectomy by administering adjuvant therapies is quite a controversial issue. In addition to effectiveness, absence of side effects and long term toxicity are mandatory. Curcuminoids (Curc) extracted with innovative techniques and effectively loaded by polymeric nanobubbles (Curc-NBs) satisfy such requirements. Curc-NBs showed stable over 30 d, were effectively internalized by tumor cells and were able to slowly release Curc in a sustained way. Significant biological effects were detected in PC-3 and DU-145 cell lines where Curc-NBs were able to inhibit adhesion and migration, to promote cell apoptosis and to affect cell viability and colony-forming capacity in a dose-dependent manner. Since the favourable effects are already detectable at very low doses, which can be reached at a clinical level, the actual drug concentration can be visualized and monitored by US or MRI, Curc-NBs can be proposed as an effective adjuvant theranostic tool.

Incorporation of Cró thermal water in a dermocosmetic formulation: cytotoxicity effects, characterization and stability studies and efficacy evaluation.

OBJECTIVE: Development of cosmetic formulations to provide a controlled release of hydrophilic active compounds from mineral medicinal waters constitutes an attractive challenge. The objective of this study was the development and the characterization of a dermocosmetic gel formulation with Cró thermal water, from Beira Interior of Portugal, as a major functional ingredient. METHODS: Concentrations of mineral chemical elements of Cró thermal water were previously determined by inductively coupled plasma-optical emission spectrometry or mass spectrometry and cytotoxicity assays using thermal water were carried out on normal human dermal fibroblasts (NHDF) cells. Then, the Cró thermal water was included (more than 90%) in a developed gel formulation that was characterized through rheological and texture analysis and submitted to stability assays during 30 days. The effects on the skin volunteers, namely skin pH, the degree of hydration, transepidermal water loss and skin relief, were evaluated through non-invasive biometric techniques. A gel formulation including purified water was used as a control. RESULTS: Cró thermal water is rich on several chemical elements in particular sodium, silica, potassium and calcium besides some trace elements, with important functions for the skin. NHDF cells adhered and proliferated in the presence of thermal water confirming the biocompatibility of the major component of the gel formulation. The developed gel formulation based on thermal water resulted in an improvement of textural parameters, comparing with the purified water-based one. Significant improvements in the cutaneous biometric parameters (degree of hydration, transepidermal water loss and skin relief) of volunteers were also registered for the gel formulation containing thermal water. CONCLUSION: This study demonstrated for the first time the potential benefits of Cró thermal water in a gel formulation to be used in cosmetic and dermatological applications.

OBJECTIF: Le développement de formulations cosmétiques permettant une libération contrôlée des substances actives hydrophiles à partir d'eaux médicinales minérales constitue un défi attractif. L'objectif de cette étude était le développement et la caractérisation d'une formulation de gel dermocosmétique avec l'eau thermale de Cró, de Beira Interior au Portugal, comme ingrédient fonctionnel majeur. MÉTHODES: Les concentrations en éléments chimiques minéraux de l'eau thermale de Cró ont étés préalablement déterminées par spectrométrie d'émission optique avec plasma couplé par induction ou spectrométrie de masse et des essais de cytotoxicité utilisant de l'eau thermale ont été réalisés sur des cellules de fibroblastes dermiques humains normaux (NHDF). Ensuite, l'eau thermale de Cró a été incluse (plus de 90%) dans une formulation de gel développée qui a été caractérisée par analyse rhéologique et texture et soumise à des tests de stabilité pendant 30 jours. Les effets sur la la peau des volontaires, à savoir le pH de la peau, le degré d'hydratation, la perte d'eau transépidermique et le relief cutané, ont été évalués à l'aide de techniques biométriques non invasives. Une formulation de gel comprenant de l'eau purifiée a été utilisée comme témoin. RÉSULTATS: L'eau thermale de Cró est riche en plusieurs éléments chimiques, en particulier le sodium, la silice, le potassium et le calcium, en plus de certains oligo-éléments, avec des fonctions importantes pour la peau. Les cellules NHDF ont adhéré et ont proliféré en présence d'eau thermale, confirmant la biocompatibilité du composant principal de la formulation du gel. La formulation de gel développée à base d'eau thermale a permis une amélioration des paramètres de texture comparée à celle à base d'eau purifiée. Des améliorations significatives des paramètres biométriques cutanés (degré d'hydratation, perte en eau transépidermique et relief cutané) des volontaires ont également été enregistrées avec la formulation en gel contenant de l'eau thermale. CONCLUSION: Cette étude a démontré pour la première fois les avantages potentiels de l'eau thermale de Cró dans une formulation de gel destinée aux applications cosmétiques et dermatologiques.

Gene-gene interactions in the NAMPT pathway, plasma visfatin/NAMPT levels, and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy.

Nicotinamide phosphorybosil transferase (NAMPT) polymorphisms affect visfatin/NAMPT levels and may affect the responsiveness to therapy in hypertensive disorders of pregnancy. We examined whether NAMPT polymorphisms (rs1319501 T>C and rs3801266 A>G), or haplotypes, and gene-gene interactions in the NAMPT pathway affect plasma visfatin/NAMPT levels and the response to antihypertensive therapy in 205 patients with preeclampsia (PE) and 174 patients with gestational hypertension. We also studied 207 healthy pregnant controls. Plasma visfatin/NAMPT levels were measured by ELISA. Non-responsive PE patients with the TC+CC genotypes for the rs1319501 T>C, and with the AG+GG genotypes for the rs3801266 A>G polymorphism had lower and higher visfatin/NAMPT levels, respectively. The 'C, A' haplotype was associated with response to antihypertensive therapy, and with lower visfatin/NAMPT levels in PE. Interactions among NAMPT, TIMP-1 and MMP-2 genotypes were associated with PE and with lack of response to antihypertensive therapy in PE. Our results suggest that NAMPT polymorphisms affect plasma visfatin/NAMPT levels in nonresponsive PE patients, and that gene-gene interactions in the NAMPT pathway not only promote PE but also decrease the response to antihypertensive therapy in PE.

Circulating microRNA expression profiles in pre-eclampsia: evidence of increased miR-885-5p levels.

OBJECTIVE: To validate and to compare the circulating microRNA (miR) expression profiles between pre-eclampsia and healthy pregnant women, to perform correlation analysis of the differently expressed miRs with clinical and biochemical parameters, and to verify the extracellular localisation of miRs in apoptotic bodies, microvesicles, and exosomes. DESIGN: A case-control study with a replication study. SETTING: Pregnant women attending maternity hospitals in Southeastern Brazil. POPULATION: Two obstetric white populations: a case-control study (19 pre-eclampsia and 14 healthy pregnant) and a replication study (eight pre-eclampsia and eight healthy pregnant). METHODS: PCR-array with 84 different miRs was performed in plasma from five pre-eclampsia and four healthy pregnant women. In the case-control study, differently expressed miRs were validated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and correlated with clinical and biochemical parameters. The plasma was then fractioned to study the extracellular localisation of miRs. MAIN OUTCOME MEASURES: Gene expression profiles of miRs. RESULTS: From PCR-array, three miRs (miR-376c-3p, miR-19a-3p, and miR-19b-3p) were found to be down-regulated and the miR-885-5p was found to be up-regulated in pre-eclampsia compared with healthy pregnant women. In the validation step, miR-885-5p was the only significantly different miR (fold-change = 5.0, P < 0.05), which was confirmed in the replication study (fold-change = 4.5, P < 0.05). Moreover, miR-885-5p was significantly correlated with the hepatic enzyme aspartate transaminase (r = 0.66; P = 0.0034) and it was mostly associated with the exosomes (32-fold higher than apoptotic bodies). CONCLUSIONS: miR-885-5p is increased in plasma from pre-eclampsia compared with healthy pregnant women, and it is released into circulation mainly inside exosomes. TWEETABLE ABSTRACT: miR-885-5p is increased in pre-eclampsia and is released into circulation mainly inside exosomes.

Tissue inhibitor of matrix metalloproteinase-1 polymorphism, plasma TIMP-1 levels, and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy.

Tissue inhibitor of metalloproteinase (TIMP)-1 is a major endogenous inhibitor of matrix metalloproteinase (MMP)-9, which may affect the responsiveness to therapy in hypertensive disorders of pregnancy. We examined whether TIMP-1 polymorphism (g.-9830T>G, rs2070584) modifies plasma MMP-9 and TIMP-1 levels and the response to antihypertensive therapy in 596 pregnant: 206 patients with preeclampsia (PE), 183 patients with gestational hypertension (GH) and 207 healthy pregnant controls. We also studied the TIMP-3 polymorphism (g.-1296T>C, rs9619311). Plasma MMP-9 and TIMP-1 levels were measured by ELISA. GH patients with the GG genotype for the TIMP-1 polymorphism had lower MMP-9 levels and MMP-9/TIMP-1 ratios than those with the TT genotype. PE patients with the TG genotype had higher TIMP-1 levels. The G allele and the GG genotype were associated with PE and responsiveness to antihypertensive therapy in PE, but not in GH. Our results suggest that the TIMP-1 g.-9830T>G polymorphism not only promotes PE but also decreases the responses to antihypertensive therapy.

Beta-blockers for hemangiomas.

Infantile hemangiomas (IHs) are the most common tumors in infancy. Their typical natural history is characterized by an early rapid growth in the first months of life and by a slow spontaneous involution in the first years of life. Even though spontaneous regression of IHs could suggest therapeutic abstention, systemic treatment is the therapy of choice in many patients in which these situations occur: 1) rapid growth of IHs; 2) location of IHs in aesthetically critic areas; 3) recurrent hemorrhages, ulcerations or infections of IHs; 3) IHs interfering with important physiological functions (breathing, feeding, vision, hearing, etc.); 4) large or multicentric IHs that can cause heart failure. Since 2008, systemic administration of propranolol, an old non­selective ß­blocker, was found, serendipitously, to improve the treatment of IHs replacing older and more dangerous therapies like oral steroids, vincristine, interferon­alpha or vascular lasers. At present, oral propranolol has dramatically changed the approach of IHs because its efficacy is almost 100% and its action is rapid, without important side effects. The formal approval by FDA and EMA has been obtained in Spring 2014.

Multiple cutaneous and hepatic infantile hemangiomas having a successful response to propranolol as monotherapy at neonatal period.

Infantile hepatic hemangioma (IHH) is a common liver tumors of infancy with a higher incidence in females. Various treatments for infantile hepatic hemangioma such as systemic corticosteroids, interferon-alpha, vincristine and cyclophosphamide have been suggested, though no consensus exists about the first-choice treatment. Recent evidences suggest that propranolol, a nonselective ß-blocker, may be effective and safe as first-line therapy for infantile hepatic hemangioma. We report a case of female born at term with a weight of 2.450 g started to develop multiple cutaneous IHs at 10 days of age and presenting concomitant multiple cutaneous and hepatic infantile hemangiomas confirmed on magnetic resonance imaging. Propranolol, used as monotherapy, was started at 14 days of age at a dose of 2 mg/kg/day orally and maintained for 6 months. Patient was monitored in the hospital during first days of treatment with propranolol, and discharged after no side-effects were detected. Hepatic and cutaneous lesions had complete resolution in three months, although the fibro-fatty residuum of largest cutaneous nodule was still palpable at month 6. A further control after 6 months showed no recurrences. Our report case suggests that propranolol can be a safe and effective first-line therapy for neonates with concomitant multiple cutaneous and hepatic infantile hemangiomas.

Matrix metalloproteinase-9 polymorphisms affect plasma MMP-9 levels and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy.

Abnormal matrix metalloproteinase (MMP)-9 levels may have a role in hypertensive disorders of pregnancy. We examined whether MMP-9 genetic polymorphisms (g.-1562C >T and g.-90(CA)13-25) modify plasma MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 levels and the responses to antihypertensive therapy in 214 patients with preeclampsia (PE), 185 patients with gestational hypertension (GH) and a control group of 214 healthy pregnant (HP). Alleles for the g.-90(CA)13-25 polymorphism were grouped L (low) (< 21 CA repeats) or H (high) (≥ 21 CA repeats). Plasma MMP-9 and TIMP-1 concentrations were measured by enzyme-linked immunosorbent assay. Plasma MMP-9 concentrations were not affected by genotypes or haplotypes in HP and PE groups, except for the g.-90(CA)13-25 polymorphism: GH patients with the LH genotype for this polymorphism have higher MMP-9 levels than those with other genotypes. The T allele for the g.-1562C > T polymorphism and the H4 haplotype (combining T and H alleles) are associated with GH and lack of responsiveness to antihypertensive therapy in GH. The H2 haplotype (combining C and H alleles) was associated with lack of responsiveness to antihypertensive therapy in PE, but not in GH. In conclusion, our results show that MMP-9 genetic variants are associated with GH and suggest that MMP-9 haplotypes affect the responsiveness to antihypertensive therapy in hypertensive disorders of pregnancy.

Tumor lysis syndrome after propranolol therapy in ulcerative infantile hemangioma: rare complication or incidental finding?

A 33-day-old female with an ulcerated infantile hemangioma (IH) undergoing oral therapy with propranolol 2 mg/kg per day developed hyperkalemia and hyperphosphatemia 24 h after starting medication. No electrocardiographic or clinical abnormalities secondary to the electrolyte changes were noticed. A laboratory tumor lysis syndrome (TLS) was diagnosed after excluding other causes of electrolyte imbalance in the diagnostic workup. No treatment was required to reverse the TLS condition, and the propranolol therapy was continued as the electrolyte alterations were only mild. One month later, the IH was remarkably reduced in size and no longer ulcerated. Maintenance of propranolol was extended for a total of 6 months. Parallel to the gradual involution of the IH, serum potassium and phosphorus levels returned within normal levels. We suggest that TLS may be a rare complication of ulcerated IH treated with propranolol. Clinicians must be aware and order appropriate screening tests for TLS in patients at risk.

[A new location of angiokeratoma circumscriptum]. / Une nouvelle localisation de l'angiokératome circonscrit næviforme.

BACKGROUND: Angiokeratomas are papular telangiectasias having a common histology of ectasia of the superficial dermal vessels surmounted by a hyperkeratotic epidermis. PATIENTS AND METHODS: The patient was a 9-year-old girl born of non-consanguineous parents after a well-followed pregnancy with problem-free delivery at term. From birth, she had a tumefaction of the left side of the nose and the left half of the upper lip that gradually increased in size without obstructing the nasal orifice and bled easily. Examination revealed the presence of tumefaction of the left nostril and the left half of the upper lip projecting towards the contralateral side especially in the nose. It was soft and painless, with the presence at the surface of dull red keratotic papules of 1 to 2 mm in diameter. Examination of the nasal mucosa revealed the same appearance of papules. DISCUSSION: Angiokeratoma circumscriptum is a rare congenital malformation, the rarest of five types. Since its initial description in 1890, few cases have been reported. However, female predominance has been noted with a male/female sex ratio of 1/3. It appears to be due to a genetic mutation that is probably autosomal, but the site of which is still unknown. In view of the special features of this case, several diagnoses were suggested, including Rendu Osler's disease, superficial lymphangioma and verrucous angioma. CONCLUSION: The particularity of this case is that it includes the first description of this site, which posed a therapeutic problem, especially concerning the choice of laser type to be used.

Variability on the energy properties of charcoal and charcoal briquettes for barbecue.

In recent years there has been a strong increase in interest in the world of barbecues and outdoor cooking in high-income countries. Referring to FAO data, an exponential growth in imports of charcoal was observed in Europe and North America. Italy is one of the major European consumers and importers. On the market it is possible to find material with different characteristics and origins. However, analysis aimed at ascertaining the quality of the material are poorly performed. This research aimed to analyze the energy properties of charcoal commonly available on the Italian market. Twenty-four bags of charcoal and charcoal briquettes were analyzed. Eighteen samples represent the products most easily found on the market, in stores and on websites. In addition, six samples were supplied directly by the producer/importing company. The samples were grouped according to the continent of origin of the material (Europe, North-Central America and South America). Charcoal briquette samples were included together in a group. Referring to the ISO 17225-1 standard, the moisture content, ash content, heating value, volatile matter and fixed carbon were determined. Except for the moisture content, the results of the tests performed on all parameters show a strong variability both between different groups and within the same group. In detail, the European charcoal samples show characteristics more suitable for their use in barbecues. These have the highest values of fixed carbon and heating value and, at the same time, low values of ash and volatile matter. On the contrary, charcoal briquettes have less suitable characteristics for barbecue. The work also highlighted some gaps in the reference standard relating to laboratory analyses. To ensure careful control of the qualitative characteristics of the products on the market, it is necessary to promote the creation of a quality brand.

Effective energy exploitation from horse manure combustion.

We investigated the exploitation of horse manure for energy recovery by combustion. First, the impact of the waste origin and management (storage conditions) was evaluated in terms of elemental analysis, moisture content, heating value, and ash melting temperature. Besides some carbon loss over the time, horse manure origin and management policy do not impact its profitable exploitation by combustion. More relevant, the ignition tests disproved the current industrial opinion that combustion of manure alone is difficult, without the addition of auxiliary fuel, like wood shavings. It has been demonstrated through ignition tests that the major limitation in manure combustion is just the high moisture content (approx. 60% w.b.). The study focused on overcoming the detrimental effect of the large moisture content, and specifically its removal efficiency. The latter requires the understanding of manure permeability which is determined by the bedding material and the stable management. Here we provide indications of the impact of the manure composition and its sample size on the efficiency of moisture removal, whose energy impact must be minimized for an effective energy recovery. The energy balance confirms that the total removal of 62% w.b. moisture reduces by 23% the potential energy content of the manure; this drying penalty on energy is largely offset by the dramatic improvement in reactivity of the residual solid fuel.

Design and optimization of an experimental maintenance system for yellow clam broodstock Amarilladesma mactroides (Reeve, 1854).

The yellow clam is a sand-burrowing bivalve that inhabits the dissipative beaches from southern Brazil to the north coast of Argentina. In the last decades, populations of this species have been impacted by mass mortality events, overfishing and other anthropogenic activities. The production of juveniles in captivity would allow feasibility studies to be carried out to restore the natural stock as well as the production in aquaculture systems. Given the scarcity of studies on the maintenance of this species in captivity, a culture system and a management protocol were developed and tested. Wild-caught clams (total length ≥50 mm) were used in a series of 14 day-long trials. Survival was higher in clams that were allowed to bury into the sand. A permanent ink marker covered with a thin layer of a quick-hardening adhesive proved to be a reliable method to tag clams. The maintenance of yellow clams in this system resulted in high survival and growth, increases in the condition factor and oocyte diameter, and a relative advancement of gonadal development.

Is soft drink consumption associated with gestational hypertension? Results from the BRISA cohort.

It is still unknown whether excessive consumption of sugar-sweetened beverages may be linked to gestational hypertensive disorders, other than preeclampsia. This study investigated the association between soft drink consumption and hypertension during pregnancy, analyzing the relationship from the perspective of counterfactual causal theory. Data from pregnant women of the BRISA cohort were analyzed (1,380 in São Luis and 1,370 in Ribeirão Preto, Brazil). The explanatory variable was the frequency of soft drink consumption during pregnancy obtained in a prenatal interview. The outcome was gestational hypertension based on medical diagnosis, at the time of delivery. A theoretical model of the association between soft drink consumption and gestational hypertension was constructed using a directed acyclic graph. Marginal structural models (MSM) weighted by the inverse of the probability of soft drink consumption were also employed. Using Poisson regression analysis, high soft drink consumption (≥7 times/week) was associated with gestational hypertension in São Luís (RR=1.48; 95%CI: 1.03-2.10), in Ribeirão Preto (RR=1.51; 95%CI: 1.13-2.01), and in the two cohorts combined (RR=1.45; 95%CI: 1.16-1.82) compared to lower exposure (<7 times/week). In the MSM, the association between high soft drink consumption and gestational hypertension was observed in Ribeirão Preto (RR=1.63; 95%CI: 1.21-2.19) and in the two cohorts combined (RR=1.51; 95%CI: 1.15-1.97), but not in São Luís (RR=1.26; 95%CI: 0.79-2.00). High soft drink consumption seems to be a risk factor for gestational hypertension, suggesting that it should be discouraged during pregnancy.

eNOS haplotypes affect the responsiveness to antihypertensive therapy in preeclampsia but not in gestational hypertension.

Variations of the endothelial nitric oxide synthase (eNOS) gene have been associated with hypertensive disorders of pregnancy. We examined whether eNOS polymorphisms affect the therapeutic responses of women with gestational hypertension (GH) or preeclampsia (PE). We studied 304 hypertensive pregnant women (152 GH and 152 PE), who were stratified according to clinical and laboratorial parameters of therapeutic responsiveness. We compared the frequencies of three eNOS genetic polymorphisms (T-786C, Glu298Asp and b/a intron 4) in responsive and nonresponsive PE and GH patients. We found no significant differences in genotype or allele distributions when responsive and nonresponsive groups were compared (both PE or GH; all P>0.05). However, the eNOS haplotype distribution differed in PE (but not in GH)-responsive and -nonresponsive groups (P=0.0003). The 'C-Glu-a' and 'T-Asp-a' hapotypes were associated with responsiveness and nonresponsiveness to therapy, respectively (both P<0.001), thus suggesting that eNOS haplotypes affect the responsiveness to antihypertensive therapy in PE.