Effectiveness of gastrostomy for improving nutritional status and quality of life in patients with epidermolysis bullosa: a systematic review.

Individuals with epidermolysis bullosa (EB) may present with a broad spectrum of growth impairment and multiorgan disorders, with compromised nutritional status and quality of life. The provision of nutrients through a gastrostomy tube may minimize EB-related malnourishment but may also result in skin injuries and infections. In this systematic review we consider the current evidence about the effectiveness of gastrostomy in restoring nutritional status and improving quality of life in patients with EB. Seven studies (n = 146) met selection criteria and patients ranged in age from 6 weeks to 33 years of age. Although it is not a risk-free procedure, the placement of a gastrostomy tube is a feasible and safe alternative to provide nutritional support and to improve the quality of life of patients.

Unequal Impact of COL1A1 and COL1A2 Variants on Dentinogenesis Imperfecta.

Dentinogenesis imperfecta (DI) is the main orodental manifestation of osteogenesis imperfecta (OI) caused by COL1A1 or COL1A2 heterozygous pathogenic variants. Its prevalence varies according to the studied population. Here, we report the molecular analysis of 81 patients with OI followed at reference centers in Brazil and France presenting COL1A1 or COL1A2 variants. Patients were submitted to clinical and radiographic dental examinations to diagnose the presence of DI. In addition, a systematic literature search and a descriptive statistical analysis were performed to investigate OI/DI phenotype-genotype correlation in a worldwide sample. In our cohort, 50 patients had COL1A1 pathogenic variants, and 31 patients had COL1A2 variants. A total of 25 novel variants were identified. Overall, data from a total of 906 individuals with OI were assessed. Results show that DI was more frequent in severe and moderate OI cases. DI prevalence was also more often associated with COL1A2 (67.6%) than with COL1A1 variants (45.4%) because COL1A2 variants mainly lead to qualitative defects that predispose to DI more than quantitative defects. For the first time, 4 DI hotspots were identified. In addition, we showed that 1) glycine substitution by branched and charged amino acids in the α2(I) chain and 2) substitutions occurring in major ligand binding regions-MLRB2 in α1(I) and MLBR 3 in α2(I)-could significantly predict DI (P < 0.05). The accumulated variant data analysis in this study provides a further basis for increasing our comprehension to better predict the occurrence and severity of DI and appropriate OI patient management.

Pamidronate affects the mandibular cortex of children with osteogenesis imperfecta.

We hypothesized that mandibular cortical width (MCW) is smaller in children with osteogenesis imperfecta (OI) than in healthy children and that pamidronate can improve the cortical mandibular thickness. The aim of this study was to assess changes in the MCW on dental panoramic radiographs (DPRs) of children with normal bone mineral density (BMD) and with OI. We also compared the MCW of children with different types of OI regarding the number of pamidronate cycles and age at the beginning of treatment. MCW measurements were retrospectively obtained from 197 DPRs of 66 children with OI types I, III, and IV who were in treatment with a comparable dosage of cyclical intravenous pamidronate between 2007 and 2013. The control group had 92 DPRs from normal BMD children. Factorial analysis of variance was used to compare MCW measurements among different age groups and between sexes and also to compare MCW measurements of children with different types of OI among different pamidronate cycles and age at the beginning of treatment. No significant differences in results were found between male and female subjects in both OI and healthy children, so they were evaluated altogether (P > 0.05). There was an increase of MCW values related to aging in all normal BMD and OI children but on a smaller scale in children with OI types I and III. Children with OI presented lower mean MCW values than did children with normal BMD at the beginning of treatment (P < 0.05). A linear model estimated the number of pamidronate cycles necessary to achieve mean MCW values equivalent to those of healthy children. The thinning of the mandibular cortex depended on the number of pamidronate cycles, the type of OI, and the age at the beginning of treatment. DPRs could thus provide a way to identify cyclic pamidronate treatment outcomes in patients with OI.

Open clinical study of the efficacy and safety of terbinafine cream 1% in children with tinea corporis and tinea cruris.

BACKGROUND: Topical application of antifungal agents is considered the treatment of choice for dermatomycoses. Most of the available drugs are fungistatic, requiring long term treatment to prevent relapses. Terbinafine is a synthetic antifungal agent that, because of its fungicidal action, provides high cure rates and low relapse rates after short periods of treatment. METHODS: Ninety-seven children ages 2 to 15 years with a suspected diagnosis of tinea corporis and/or tinea cruris were enrolled in this open trial. After mycologic assessment to confirm diagnosis (culture and direct microscopy) terbinafine 1% cream was applied once daily during 1 week. Clinical and mycologic assessments were made at the baseline visit and on Days 7, 14 and 21. Efficacy assessment was based on 88 children (9 patients excluded by protocol violation). RESULTS: Therapy was considered effective in 92.0% (81 of 88) of patients (complete clinical and mycologic cure or mycologic cure with minimum signs and symptoms or clinical improvement, > or = 50%). Tolerability was assessed in 97 patients on an intention-to-treat basis. Adverse reactions were itching 3% (3 of 97), itching associated with erythema exacerbation 1% (1 of 97) and contact dermatitis 1% (1 of 97). CONCLUSION: Terbinafine 1% cream appears to be an effective and well-tolerated treatment for tinea corporis and tinea cruris in children.

Maternal tobacco use and substance abuse: reported prevalence rates and associations with the delivery of small for gestational age neonates.

OBJECTIVE: To determine the changes in reported prevalence rates of tobacco use and substance abuse in a population of pregnant women, as well as to evaluate the associations between such use and sociodemographic characteristics and the delivery of small for gestational age (SGA) neonates. METHODS: We studied 7741 women who delivered at Cedars-Sinai Medical Center from 1986-1990. Antenatal and delivery information was entered prospectively into the computerized perinatal data base. Subjects were classified according to tobacco use and substance abuse status. We defined SGA as a birth weight less than the tenth percentile for gestational age at delivery. Univariate and multivariate analyses were used to determine the associations between SGA and tobacco use, substance abuse, and sociodemographic characteristics. RESULTS: We found that the reported prevalence rates of tobacco use and substance abuse declined between 1986-1990 (10 versus 6% and 7 versus 2%, respectively; P < .001). Tobacco use and substance abuse were reported as being highest in black women (11 and 6%) and lowest in Asian and Hispanic women (4 and 3%), a significant difference (P < .001). Tobacco use and race-ethnicity were found to have the strongest independent associations with SGA. The incidence of SGA was highest in black women identified as tobacco users and substance abusers. CONCLUSIONS: The reported rates of tobacco use and substance abuse varied by year, race-ethnicity, and insurance status. There were significant associations between maternal tobacco use, substance abuse, and race-ethnicity and the incidence of SGA neonates.

Perinatal outcome in triplet versus twin gestations.

The present study was conducted to determine whether triplet pregnancies are associated with a significantly worse perinatal outcome than twin pregnancies. Maternal and neonatal outcome was evaluated in 15 triplet and twin pregnancies that were matched for maternal age, race, type of medical insurance, delivery mode, parity, and history of previous preterm delivery. Preterm labor occurred significantly more often in triplet than in twin gestations (80 versus 40%), as did preterm delivery (87 versus 26.7%). Triplets had a significantly lower mean birth weight (1720 versus 2475 g) and gestational age at delivery (33 versus 36.6 weeks). In addition, 53.3% of triplet pregnancies but only 6.7% of twin pregnancies had one or more neonates with intrauterine growth retardation. Discordancy also occurred more frequently in triplets than in twins (66.7 versus 13.3%). The mean averaged neonatal hospital stay was significantly higher in triplets (29 versus 8.5 days), and triplets had a fivefold increased risk of requiring neonatal intensive care as compared with twins. However, there were no significant differences between the groups in maternal morbidity or major neonatal complications such as respiratory distress syndrome or intraventricular hemorrhage. We believe that these data will be useful in counseling patients with respect to the anticipated perinatal outcome of triplet pregnancies.

The biophysical profile in labor.

To determine whether the biophysical profile would be a valuable intrapartum addition to fetal heart rate monitoring in predicting umbilical arterial acid-base status at delivery, 95 patients at term had serial studies during labor and umbilical artery blood gas analysis. There was no significant association between biophysical profile score and cord blood pH, nor was there a difference in scores between the acidemic and nonacidemic groups. Of the five components of the initial biophysical profile, only a nonreactive nonstress test (NST) was associated with both pH 7.20 or less (P = .019) and metabolic acidemia (P = .016). None of the individual variables of the final examination correlated with a pH of 7.20 or less. However, a nonreactive NST was associated with metabolic acidemia (P = .03), as was the presence of breathing (P = .03). Of the ten infants with pH 7.20 or less, eight had an initial and five had a final biophysical profile score of 8 or higher. Of the five whose pH was less than 7.15, four had an initial and three a final score of 8 or more. Finally, of the five with metabolic acidemia, four had an initial and two a final score of 8 or higher. Half of the acidemic fetuses had final biophysical profile scores of 8 or higher, suggesting that this score in labor is not reliable to rule out acidemia at delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Cigarette smoking during pregnancy: acute effects on uterine flow velocity waveforms.

OBJECTIVE: To determine the acute effects of smoking during pregnancy on selected characteristics of the flow velocity waveform of the uterine artery. METHODS: We studied 19 chronic smokers at a mean (+/- standard error) gestational age of 28 +/- 1 weeks. After informed consent was given, the uterine artery was located using ultrasound imaging with color flow mapping. The characteristic waveform was imaged by pulsed Doppler ultrasonography. Maternal heart rate and blood pressure and the systolic-diastolic ratio (S/D) and resistance index of the uterine artery were measured before (-10 and -1 minutes), during (+5 and +10 minutes), and after (+20 and +30 minutes) smoking two standard cigarettes in succession. RESULTS: Maternal heart rate increased 27%, systolic blood pressure increased 8%, and diastolic blood pressure increased 19% with smoking (P < .001). The uterine artery S/D and resistance index decreased from 2.33 to 2.02 and from 0.55 to 0.49, respectively (P < .001). CONCLUSION: The acute effects of smoking on maternal systemic hemodynamics probably influence the flow velocity waveform of the uterine artery and preclude any definitive interpretation of acute changes in downstream resistance.

Gangliosides on intestinal microcirculation and animal survival during reperfusion.

This study investigated the effect of gangliosides (Gang) on small bowel microcirculation and animal survival after normothermic intestinal ischemia-reperfusion injury. Five adult male EPM-1 Wistar rats in each of three groups received FK506 (0.2 mg/kg), Gang (3 mg/kg), or vehicle (at same volume) either 24 or 12 hours prior to the experiment. The animals were anesthetized intramuscularly with ketamine (60 mg/kg) and xylazine (10 mg/kg) and hydrated with 80 mL/kg of prewarmed saline solution delivered subcutaneously before the ischemic insult and 40 mL/kg at 1 hour after reperfusion. Under anesthesia, they underwent a laparotomy with clamping of the superior mesenteric artery (SMA) at its origin for 75 minutes. Microcirculation was evaluated with a laser Doppler flowmeter, 5 minutes before ischemia (baseline) and reperfusion (ischemia), and 20, 40, and 60 minutes after reperfusion. Animal survival was observed up to 24 hours. Small bowel flow measured before ischemia was considered to be the baseline level (100%). After SMA occlusion a significant reduction in microcirculatory tissue perfusion to about 8% was observed in all groups. At 20, 40, and 60 minutes of reperfusion treatment with Gang (77%, 81%, and 100%) or FK506 (70%, 85%, and 98%) promoted better recovery of the intestinal microcirculation when compared to the control group (45%, 72%, and 75%). Concerning animal survival there was no difference between groups (just one animal from each group, Gang and FK506, survived up to 24 hours). Based on our data we conclude that Gang and FK506 improve intestinal microcirculation in ischemia-reperfusion injury but do not change animal survival after severe ischemia.

[Madurella grisea eumycetoma. Presentation of a case]. / Eumicetoma por Madurella grisea. Relato de caso.

One case of mycetoma produced by Madurella grisea localised on the foot of a house wife is reported. The identification of the strain was made through the following features: aspect of the grains, micro e macromorphology in Sabouraud agar and capacity of assimilation of the sugars. This is the fifth case of mycetoma by Madurella grisea reported from Brasil.

Avaliação da atividade antimicrobiana de extratos de Eugenia anomala e Psidium salutare (Myrtaceae) frente à Escherichia coli e Listeria monocytogenes / Evaluation of the antimicrobial activity of extracts of Eugenia anomala and Psidium salutare (Myrtaceae) against the Escherichia coli and Listeria monocytogenes

RESUMO As doenças transmitidas por alimentos ocorrem principalmente devido à ingestão de alimentos contaminados por microrganismos patogênicos, dentre eles a Escherichia coli e Listeria monocytogenes. Uma das alternativas estudadas para minimizar a contaminação de alimentos é o emprego de plantas, ou seus extratos, como agentes antimicrobianos de origem natural em produtos alimentícios. Desta forma o objetivo do presente estudo é fornecer dados científicos a respeito de duas plantas nativas do RS ainda não estudadas, Eugenia anomala e Psidium salutare, visando potencial emprego como agente antimicrobiano natural em alimentos. Para tanto, avaliou-se a atividade antimicrobiana de extratos de E. anomala e P. salutare contra E. coli e L. monocytogenes através da determinação da concentração inibitória mínima (CIM) pelo método de microdiluição em caldo, a capacidade antioxidante dos extratos por meio do método de redução do radical DPPH e a citotoxicidade in vitro empregando células CHO-K1. Os resultados obtidos mostraram que os extratos de acetato de etila e etanólico de ambas as espécies possuem ação antioxidante muito alta, de 94,08% e 93,86%, respectivamente. Apenas o extrato hexânico de P. salutare apresentou ação antimicrobiana moderada (CIM = 312,5 µg/mL). Todos os extratos apresentaram ação citotóxica sendo que os maiores percentuais foram do extrato clorofórmico de E. anomala (77,05%) e hexânico de P. salutare (76,79%), na concentração de 100 µg/mL. Assim, o presente estudo demonstrou que as espécies vegetais estudadas apresentam potencial para emprego como agente antimicrobiano destes microrganismos.

ABSTRACT The foodborne diseases occur mainly due to the ingestion of food contaminated by pathogenic microorganisms, including Escherichia coli and Listeria monocytogenes. One of the alternatives studied to minimize contamination of food is the use of plants or their extracts as antimicrobial agents naturally occurring in food products. The objective of this study is to provide scientific data on two native plants of RS have not studied Eugenia anomala and Psidium salutare for a potential use as a natural antimicrobial agent in food. To this end, we evaluated the antimicrobial activity of extracts of E. anomala and P. salutare against E. coli and L. monocytogenes by determining the minimum inhibitory concentration (MIC) by the broth microdilution method, the antioxidant capacity of the extract for means DPPH radical reduction method and in vitro cytotoxicity using CHO-K1 cells. The results showed that the ethyl acetate and ethanolic extracts of both species have very high antioxidant activity, of 94.08% and 93.86%, respectively. Only the hexane extract of P. salutare showed a moderate antimicrobial activity (MIC = 312.5 mg/mL). Moreover, all extracts showed cytotoxic action of which the highest percentages were the chloroform extract of E. anomala (77.05%) and hexane P. salutare (76.79%) at a concentration of 100 mg/mL. Thus, the present study showed that plant species have potential for use as an antimicrobial agent against these microorganisms.

Avaliação de indicadores biológicos na validação de processos de esterilização de isoladores por peróxidos de hidrogênio / Assessment of biological indicators in the validation of isolator decontamination with hydrogen peroxide

Os isoladores permitem a aplicação de descontaminação por gases, resultando em ambiente estéril. Esta característica, adicionada a possibilidade de não interferência humana no processo, torna o emprego dos isoladores consideravelmente vantajosa quando comparada com a performance dos processos em salas limpas convencionais. A descontaminação empregando peróxido de hidrogênio é vantajosa em relação a outros métodos disponíveis uma vez que é de fácil remoção após aplicação; sendo água e oxigênio seus produtos de degradação, apresenta boa compatibilidade com materiais usualmente empregados nas áreas produtivas; e seu custo é relativamente baixo. O propósito deste estudo foi demonstrar que o Geobacillus stearothermophilus (ATCC 12980) é o microrganismo mais resistente quando comparado com microrganismos isolados presentes em áreas produtivas, assim como avaliar o melhor material a servir de suporte durante a validação do processo de descontaminação das superfícies internas do isolador e externas de materiais presentes. Bacillus sp., Micrococcus luteus, Corynebacterium sp., Staphylococcus sp. e Penicilium sp. foram os microrganismos que apresentaram maior incidência na área produtiva. Aço inoxidável é o material mais adequado a ser usado como suporte para o emprego do peróxido de hidrogênio, por ser inerte e o principal componente dos isoladores e por não demonstrar incompatibilidade com o agente esterilizante. Os resultados obtidos nesta etapa do estudo demonstraram que o Geobacillus stearothermophilus é o microrganismo mais resistente para ser utilizado na avaliação da eficácia do peróxido de hidrogênio quando comparado com aqueles microrganismos encontrados na flora normal. Adicionalmente, o melhor suporte é o aço inoxidável, significando que os indicadores biológicos comercialmente disponíveis neste material são a melhor opção para este propósito.

Isolators allow decontamination gases to be employed to create a sterile processing environment. This feature, added to the potential removal of human interference in the process, makes the use of isolators rather advantageous, compared to performing aseptic processes in conventional clean rooms. Decontamination with vaporized hydrogen peroxide (VHP) offers several advantages over other available methods, as it decomposes to water and oxygen and is thus easy to remove after use, is highly compatible with materials usually employed in production areas and it is relatively cheap. The aims of this study were to prove that Geobacillus stearothermophilus (ATCC 12980) is more resistant than microorganisms isolated from the normal production area flora and to determine the best material to serve as a support during validation of the decontamination of the inner surfaces of isolators and outer surfaces of materials inside them. Bacillus sp., Micrococcus luteus, Corynebacterium, Staphylococcus sp. and Penicillium sp. were the microorganisms of highest incidence among those identified in the production area. Stainless steel is the best material to be used as a support for the VHP treatment of specimens, as it is inert and the main component of isolators and showed no incompatibility with this sterilizing agent. The results obtained in this phase of the experiment proved that Geobacillus stearothermophilus is the most resistant microorganism with which to challenge the effectiveness of hydrogen peroxide, when tested against species of the normal flora. Secondly, the best support material is stainless steel, showing that the commercial bioindicators available on the market with this support material are scientifically proved to be the best choice for this purpose.

Plasma levels of atrial natriuretic peptide in normal and hypertensive pregnancies: a meta-analysis.

OBJECTIVE: Our goals were (1) to use meta-analysis to determine whether pregnancy and the puerperium are accompanied by alterations in plasma atrial natriuretic peptide levels when compared with the nonpregnant state and (2) to evaluate the additional effects of hypertensive disease during pregnancy on plasma atrial natriuretic peptide levels. STUDY DESIGN: Articles measuring atrial natriuretic peptide levels during pregnancy were reviewed. Data from articles meeting inclusion criteria were abstracted, and a meta-analysis was performed with the use of the maximum likelihood methods of Jennrich and Schluchter (Biometrics 1986;42:805-20). RESULTS: The mean atrial natriuretic peptide level in nonpregnant control subjects was 28.7 pg/ml (95% confidence interval 22.5 to 36.7). The mean plasma atrial natriuretic peptide level rose 41% to 40.5 pg/ml (95% confidence interval 31.7 to 51.8) in the third trimester (p < 0.0001). It was 71.1 pg/ml (95% confidence interval 51.2 to 98.7) or 148% greater than the mean nonpregnant level during the first week post partum (p < 0.0001). Compared with levels in pregnant control subjects, plasma atrial natriuretic peptide levels increased 52% to 52.1 pg/ml (95% confidence interval 32.9 to 82.5) in women with gestational hypertension (p < 0.005) and 130% to 78.8 pg/ml (95% confidence interval 52.3 to 118.8) in women with preeclampsia (p < 0.0001). Chronic hypertension did not significantly alter atrial natriuretic peptide levels. CONCLUSIONS: The 41% increase in atrial natriuretic peptide levels in the third trimester suggests that atrial stretch receptors sense the expanded blood volume as normal to moderately increased. The rise in atrial natriuretic peptide during the first week post partum is consistent with known hemodynamic changes and suggests that atrial natriuretic peptide may be involved in the postpartum diuresis. The marked increase in plasma atrial natriuretic peptide levels observed in preeclampsia is not likely to result from elevated arterial pressures alone but may reflect underlying factors unique to this disease process.

A procedure to obtain long-lasting fluorescence in formaldehyde fixed tissues.

The authors made a study of the small intestine by immunofluorescence in 5% phosphate-buffered formaldehyde fixed tissues, using the Nairn (1976) technique associated with Evans blue (Fry and Wilkinson 1963). The ability of the sections to fluoresce has been maintained after a storage time of more than 4 years. Similar very good results were obtained when skin biopsies from pemphigus foliaceus patients were fixed in formaldehyde for two h and afterwards washed in 30% sucrose solution for 12 to 18 h.

Effect of hemodialysis on uterine and umbilical artery Doppler flow velocity waveforms.

A case of a pregnant woman with membranous glomerulonephropathy requiring hemodialysis is described. During hemodialysis the patient underwent Doppler flow studies of the uterine and umbilical arteries. In spite of avoidance of hypotension and major fluid shifts, hemodialysis was accompanied by a significant increase in the systolic/diastolic ratio of the proximal uterine artery. There was no significant change in the umbilical artery systolic/diastolic ratio.

Plasma atrial natriuretic peptide levels during the rat estrous cycle, pregnancy, and puerperium.

The rat has been used as a model for studying the changes that occur in maternal blood volume and renal function during pregnancy. The role, if any, that atrial natriuretic peptide plays in regulating these changes is unknown, and little information is available on atrial natriuretic peptide levels at different stages of gestation in the rat. In this study we measured plasma atrial natriuretic peptide levels by radioimmunoassay in the rat at each stage of the estrous cycle, during the last 2 weeks of pregnancy, and in the early postpartum period. Atrial natriuretic peptide levels did not change during the estrous cycle. Atrial natriuretic peptide levels were low on days 10 to 15 of gestation but rose to become significantly higher than nonpregnant levels on days 16 to 18. On day 21 shortly before delivery, levels were similar to nonpregnant values. Postpartum, atrial natriuretic peptide levels rose immediately and remained elevated for the next 48 hours. These findings suggest that factors other than blood volume may mediate plasma atrial natriuretic peptide levels during pregnancy and the postpartum period.

Atrial natriuretic factor: the effects of pregnancy and a high-salt diet on atrial levels.

The chronic and relatively acute changes in blood volume that occur during pregnancy and post partum may be associated with alterations in the content of atrial natriuretic factor in the atria. We measured the concentration of atrial natriuretic factor in the right and left atria of virgin, pregnant, and postpartum Sprague-Dawley rats by radioimmunoassay as well as the concentration of atrial natriuretic factor in the atria and plasma of term pregnant rats on a high-salt diet. Neither right nor left atrial concentrations of atrial natriuretic factor were elevated during pregnancy in animals on a normal diet, but both were increased during the first 2 days after delivery. Term pregnant rats on a high-salt diet showed a small increase in atrial natriuretic factor levels in the left atria only, without any change in plasma atrial natriuretic factor levels. We conclude that relatively acute changes in fluid and electrolyte balance are more likely than chronic ones to be associated with alterations in atrial natriuretic factor concentrations in the atria.

Atrial natriuretic peptide metabolism during pregnancy in the rat.

OBJECTIVE: Our purpose was to determine whether plasma clearance rates and production rates of atrial natriuretic peptide 99-126 are altered during pregnancy in the rat. STUDY DESIGN: Twelve virgin and 12 late-pregnant chronically instrumented, conscious, unrestrained Sprague-Dawley rats were studied. Mean arterial pressure, heart rate, and plasma atrial natriuretic peptide levels were measured before and during a 40-minute continuous infusion of atrial natriuretic peptide (10 ng/kg/min). RESULTS: Control mean arterial pressure was 106 +/- 5 mm Hg in virgin rats versus 97 +/- 4 mm Hg in pregnant rats. Atrial natriuretic peptide infusion did not significantly affect mean arterial pressure in either group of animals but decreased heart rate in virgin rats. Basal plasma atrial natriuretic peptide levels were significantly higher in virgin than in pregnant rats (107 +/- 10 vs 78 +/- 7 pg/ml, respectively, p < 0.05). Atrial natriuretic peptide infusion significantly increased plasma levels in both groups to similar (183 +/- 19 and 154 +/- 14 pg/ml, virgin vs pregnant rats). Calculated plasma clearance rates were similar in virgin and pregnant rats (166 +/- 27 vs 155 +/- 17 ml/kg/min). Estimated production rates of atrial natriuretic peptide were higher in virgin then in pregnant rats (15.1 +/- 1.4 vs 11.4 +/- 1.1 ng/kg/min, p < 0.05). CONCLUSIONS: Plasma atrial natriuretic peptide levels are lower in chronically instrumented near-term pregnant rats compared with levels in virgin rats. This is not related to differences in plasma atrial natriuretic peptide clearance rates but rather to a decrease in production rates in late pregnancy.

Long-term nitric oxide blockade in the pregnant rat: effects on blood pressure and plasma levels of endothelin-1.

OBJECTIVE: Abnormalities in the production of nitric oxide and endothelin-1 have been implicated in the development of preeclampsia. We postulated that long-term nitric oxide synthase inhibition with L-nitro-arginine methyl ester would induce sustained hypertension, a rise in plasma levels of endothelin-1, and fetal growth restriction. STUDY DESIGN: Conscious virgin and pregnant Sprague-Dawley rats received infusions of vehicle or L-nitro-arginine methyl ester (2.5 mg/kg/hr) for 11 days. Mean arterial pressure was assessed serially. On day 21 of gestation (or equivalent in virgin rats) plasma was collected for endothelin-1 levels; pup weight and litter size were determined. Data were analyzed with analysis of variance and regression techniques. RESULTS: Mean arterial pressure was constant in virgin control rats (n = 7) but declined in pregnant control rats (n = 11) as gestation advanced. Nitric oxide synthase inhibition in virgin (n = 10) and pregnant (n = 11) rats caused sustained elevations in mean arterial pressure (165 +/- 7 vs 100 +/- 3 mm Hg, L-nitro-arginine methyl ester vs control virgin rats, p < 0.0001; 149 +/- 5 vs 91 +/- 2 mm Hg, L-nitro-arginine methyl ester vs control pregnant rats, p < 0.0001). L-nitro-arginine methyl ester induced a rise in plasma endothelin-1 levels in virgin (4.4 +/- 0.1 vs 3.5 +/- 0.1 pg/ml, L-nitro-arginine methyl ester vs control, p < 0.0001) and pregnant rats (3.0 +/- 0.1 vs 2.6 +/- 0.1 pg/ml, L-nitro-arginine methyl ester vs control, p < 0.0001). Pregnant rats had lower endothelin-1 levels than did virgin rats (p < 0.0001). Mean arterial pressure and endothelin-1 were significantly correlated in pregnant rats. L-nitro-arginine methyl ester decreased pup weight (2.4 +/- 0.4 vs 3.7 +/- 0.2 gm/pup/litter, L-nitro-arginine methyl ester vs control, p < 0.01) and litter size (6.6 +/- 1.3 vs 10.2 +/- 0.9 pups/litter, L-nitro-arginine methyl ester vs control, p < 0.05). CONCLUSIONS: Long-term nitric oxide synthase blockade causes sustained hypertension, elevated levels of endothelin-1, and fetal growth restriction. Although the endocrine and pressor effects are not unique to pregnancy, this model clearly induces some of the changes seen in preeclampsia and may be useful for studying specific interventions.