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OBJECTIVES: This study was undertaken to describe under real-life conditions the effects of acupuncture on symptomatic dyspepsia during pregnancy and to compare this with a group of patients undergoing conventional treatment alone. METHODS: A total of 42 conventionally treated pregnant women were allocated by chance into two groups to be treated, or not, by acupuncture. They reported the severity of symptoms and the disability these were causing in daily aspects of life such as sleeping and eating, using a numerical rating scale. The study also observed the use of medications. RESULTS: Six women dropped out (one in the acupuncture group and five in the control group). Significant improvements in symptoms were found in the study group. This group also used less medication and had a greater improvement in their disabilities when compared with the control group. CONCLUSIONS: This study suggests that acupuncture may alleviate dyspepsia during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to test the effects of acupuncture on insomnia in a group of pregnant women under real life conditions, and to compare the results with a group of patients undergoing conventional treatment alone (sleep hygiene). Methods: A total of 30 conventionally treated pregnant women were allocated at random Into groups with or without acupuncture. Seventeen patients formed the study group and 13 the control group. The pregnant women scored the severity of insomnia using a Numerical Rating Scale from 0 to 10. Women were followed up for eight weeks and interviewed live times, at two-week intervals. Results: Eight women dropped out. five in the study group and three in the control group. The study group reported a larger reduction on insomnia rating (5.1) than the control group (0.0), a difference which was statistically significant (P=0.0028). Average insomnia scores decreased by at least 50% over time in nine (75%) patients in the study group and in three (30%) of the control group. Conclusion: The results of this study suggest that acupuncture alleviates insomnia during pregnancy and further research is justified. [ABSTRACT FROM AUTHOR]

This study was undertaken to investigate the effects of acupuncture in low back and pelvic pain during pregnancy under real life conditions, as compared with patients undergoing conventional treatment alone. A total of 61 conventionally treated pregnant women were allocated randomly into two groups to be treated or not by acupuncture. Twenty-seven patients formed the study group and 34 the control group. They reported the severity of pain using a Numerical Rating Scale from 0 to 10, and their capacity to perform general activities, to work, and to walk. We also assessed the use of analgesic drugs. Women were followed up for eight weeks and interviewed five times, at two-week intervals. All women completed the study. In the study group the average pain during the study period showed a larger reduction (4.8 points) than the control group (-0.3 points) (P < 0.0001). Average pain scores decreased by at least 50% over time in 21 (78%) patients in the acupuncture group and in five (15%) patients in the control group (P < 0.0001). Maximum pain and pain at the moment of interview were also less in the acupuncture group compared with the control group. The capacity to perform general activities, to work and to walk was improved significantly more in the study group than in the control group (P < 0.05). The use of paracetamol was lower in the acupuncture group (P < 0.01). These results indicate that acupuncture seems to alleviate low back and pelvic pain during pregnancy, as well as to increase the capacity for some physical activities and to diminish the need for drugs, which is a great advantage during this period. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of the association of lopinavir and ritonavir administered during the whole period of rat pregnancy., Methods: 62 Wistar rats of the EPM-1 variant weighing about 200 g were randomly divided into five groups: two controls (Ctrl = stress control, n = 10; and Ctr2 = drug vehicle control, n = 10) and three experimental ones which were treated with an oral solution of lopinavir/ritonavir (Exp1 = 12.8/3.2 mg/kg b.w., n = 14; Exp2 = 38.4/9.6 mg/kg b.w., n = 14; Exp3 = 115.2/28.8 mg/kg b.w., n = 14) from 'day 0' up to the 20th day of pregnancy. Maternal body weight was recorded at the start of the experiment and on the 7th, 14th and 20th day thereafter. At term (20th day), upon laparotomy and hysterotomy, the rats were anesthetized and the amount of implantations, reabsorptions, living fetuses, placentae and intrauterine deaths were recorded. The collected fetuses and placentae were weighed and the concepts were examined under a stereoscope microscope for external malformations., Results: An apparent dose-unrelated lethal effect of the antiviral association on the pregnant rats was observed; notwithstanding, the body weight gain of the surviving rats had no changes, independent of the considered group. It was noted that the quantitative and qualitative intrauterine content of living term rats was indistinguishable from that of the controls., Conclusion: There was some degree of deleterious effects of the administration of the lopinavir/ritonavir association on pregnant rats; such effects eventually led to maternal death. However, neither the surviving rats showed toxicity nor did their concepts present any detectable change which could be related to the drug association.

Purpose: To evaluate the morphological aspects in rats subjected to an association of the antiretroviral drugs zidovudine/lopinavir/ritonavir in different doses administered throughout the gestational period., Materials and Methods: Forty pregnant rats were randomly allocated into four groups: control (Ctrl) and experimental (Exp1, Exp2, and Exp3), which received zidovudine/lopinavir/ritonavir in the doses of 10/13.3/3.3, 30/39.9/9.9, and 90/119.7/29.7 mg/kg per day from the first to the 20th day of pregnancy, respectively. At term, the animals were euthanized and maternal and fetal organ samples were removed for morphological analysis., Results: No major changes were identified in the group treated with the lowest dosing compared with the control. In group Exp2, the authors found hepatocytes with eosinophilic cytoplasm, pyknotic nuclei, and vasodilation. The proximal convoluted tubules of maternal kidneys showed eosinophilic areas and hyperchromatic nuclei, as well as signs of vasodilation. In the group treated with the highest dose (Exp3); the morphological changes in the maternal kidneys and livers were similar and more pronounced than those found in Exp2. The maternal pancreas of groups Exp2 and Exp3 evidenced moderate and progressive signs of tissue damage. The morphological features of all fetal livers, kidneys, and pancreases were normal., Conclusion: High doses of zidovudine/lopinavir/ritonavir association during the entire rat pregnancy period can cause definite morphological changes in maternal liver, kidneys, and pancreas. On the other hand, the corresponding fetal organs were not affected.

Purpose: To evaluate the effects at term of a highly active antiretroviral drug association when administered for the whole period of rat pregnancy., Methods: Forty pregnant rats weighing about 200 g were randomly divided into four groups: a control group (Ctr = drug vehicle control, n=10) and three experimental groups, which were treated with an oral solution of zidovudine-stavudine (Explx = 10/1 mg/kg b.w., n=10; Exp3x = 30/3 mg/kg b.w., n=10; Exp9x = 90/9 mg/kg b.w., n=10) from "day 0" up to the 20th day of pregnancy. Maternal body weights were recorded at the start of the experiment and on the 7th, 14th and 20th day thereafter. At term (20th day) the rats were anesthetized and submitted to hysterotomy. Implantations, reabsorptions, living fetuses, placentae and intrauterine deaths were looked for and recorded. The collected fetuses and placentae were weighed and the concepts were examined by a stereoscopic microscope looking for external malformations., Results: No significant alterations due to the antiretroviral drug treatment could be detected regarding the number of implantations, fetuses, placentae, absorptions and malformations nor regarding maternal and fetal mortality., Conclusions: Administration of the association zidovudine/stavudine for the whole period of rat pregnancy did not interfere with the maternal, fetal and placental weight gain as well as abnormalities detectable by the employed methodology.

Purpose: To evaluate biochemical and morphological effects on rats submitted to three different doses of the association zidovudine and ritonavir administered throughout pregnancy., Methods: Forty pregnant EPM-1 Wistar rats weighing about 200 g were randomly divided into the control group (Ctr = drug vehicle control, n = 10) and three experimental ones which were treated with an oral solution of zidovudine/ritonavir (Exp1 = 10/20 mg/kg bw, n = 10; Exp2 = 30/60 mg/kg bw, n = 10; Exp3 = 90/180 mg/kg bw, n = 10) from 'day 0' up to the 20th day of pregnancy. At term (20th day) the rats were anesthetized. Blood and fetal and maternal organ samples (livers and kidneys) were taken for morphological and biochemical analyses., Results: Upon histological examinations fetal livers and kidneys appeared normal. In contrast the maternal samples revealed structural alterations. Maternal kidneys of the three experimental groups exhibited progressive and dose-dependent histological alterations; liver alterations were detected only in Exp3. Blood levels of AST and ALT were not significantly different from the control group but urea and creatinine levels were lower in groups Exp3 and Exp1., Conclusions: The administration of zidovudine plus ritonavir throughout rat pregnancy can cause morphological as well as functional changes in maternal kidneys.

Purpose: To evaluate at term the effects of a highly active antiretroviral (HAAR) drug association administered during the entire period of rat pregnancy., Methods: Three groups (n = 10 each) of adult pregnant rats were treated with an oral solution of HAAR (Exp 1 = 10/5/20 mg/kg b.w.; Exp 2 = 30/15/60 mg/kg b.w.; Exp 3 = 90/45/180 mg/kg b.w.) from day "0" up to the 20th day of pregnancy. A fourth group served as a control. At term (20th day) the rats were killed under deep anesthesia and the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded., Results: The highest HAAR doses caused lower maternal weight gain, lower litter weights, and lower placental weights compared to the control group., Conclusions: HAAR during the entire period of rat pregnancy can reduce maternal body weight gain and lower term placental weight.

The purpose of the study was to evaluate at term, the effects of the association of zidovudine/ritonavir administered during the entire period of rat pregnancy. Forty pregnant EPM-1 Wistar rats were divided randomly into four groups: one control (drug vehicle control, n=10) and three experimental treated with an oral solution of zidovudine/ritonavir (Exp 1 = 10/20 mg/kg bw, n = 10; Exp 2 = 30/60 mg/kg bw, n=10; Exp 3 = 90/180 mg/kg bw, n=10) from day 0 up to day 20 of pregnancy. Maternal body weights were recorded at the start of the experiment and at the 7th, 14th and the 20th day thereafter. At term (20th day) the rats were anesthetized and, upon laparotomy and hysterotomy, the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded. The collected fetuses and placentae were weighed, and the concepts were examined under a stereoscopic microscope for external malformations. The maternal body gain and the mean fetal weight at term were both significantly lower (p < 0.01 and p < 0.0001, respectively) in the experimental groups compared to the control. The recorded resorptions were higher in Exp 2 and Exp 3 groups than in the control group. The other parameters were not affected. The exposure of pregnant rats at term to a 1:2 association of zidovudine plus ritonavir resulted in a significant reduction in maternal body weight gain and increased rate of fetal resorption.

Since indinavir is currently used in combination with other antiretroviral agents, there is a scarcity of studies in the literature on its single-drug perinatal safety. Thus, we decided to examine the gross maternal and fetal effects of indinavir administered alone during the entire period of rat pregnancy. Forty pregnant animals were assigned at random to four groups (C = control) treated with the drug vehicle (distilled water); the experimental groups were treated with indinavir as follows: E1 = 40 mg/kg; E2 = 120 mg/kg; E3 = 360 mg/kg from "zero" up to the 20th day of gestation. Drug or vehicle were administered daily by gavage. Each group consisted of ten animals. At term-pregnancy, the rats were deeply anesthetized and blood samples were collected for alanine aminotransferase (ALT) and aspartate aminotransferase (AST), creatinine and urea determinations. Fragments of maternal and fetal livers and kidneys were taken and routinely processed for histopathological study. Serum ALT activity in the E2 group was significantly higher (p < 0.01) than that of the other groups. The concentration of creatinine in blood was lower in the E2 and E3 groups than in group E1 (p < 0.01), whereas blood urea in group E3 was significantly lower than in the other groups (p < 0.01). Morphological (light microscopy) studies revealed that no significant effects of the drug could be detected regarding either maternal or fetal organs of the E1 and E2 groups. However, the maternal hepatocytes in the E3 group showed heterochromatic nuclei. In addition, there was some fatty infiltration, congested sinusoids and portal dilation. Maternal kidneys in the E2 and E3 groups revealed vascular dilation around the convoluted tubules. Regarding the biochemical determinations, the alterations observed were mild, without biological relevance, thus indicating that the treatment with indinavir during the entire gestation was essentially devoid of hepatic or renal effects which could result in altered metabolic parameters. It is concluded that indinavir was well tolerated in therapeutic and even in 9-fold higher doses. Notwithstanding, discrete morphological alterations occurred in the maternal compartment, but with no functional expression that could indicate deleterious effects on mothers and/or fetuses.

Objective: To study the morphological and biochemical effects on liver, pancreas and kidney of pregnant rats and their fetuses subjected to stavudine treatment., Methods: Forty animals were distributed in four groups E1, E2, E3, and C (control) and received by gavage once a day 1, 3 or 9 mg/kg of stavudine in 2 mL distilled water, from days 1 to 20 of pregnancy. After this period, the animals were sacrificed; blood samples were collected for further determinations of AST, ALT, creatinine, urea, glucose and amylase. Samples of liver, kidneys and pancreas of every rat and of the corresponding fetuses were taken and examined under light microscopy., Results: The maternal livers of groups E1, E2 and E3 displayed progressive morphological alterations without corresponding changes in serum AST and ALT activity. Maternal kidney histology and function were similar in all groups. Maternal pancreas of groups E2 and E3 evidenced moderate and progressive signs of tissue damage without functional repercussion. All fetal livers, kidneys and pancreas presented normal morphology., Conclusions: High doses of stavudine produced signs of mild to moderate maternal hepatic and pancreatic toxicity at the morphological level. This was not followed by changes in biochemical parameters, most conceivably due to the functional reserve of these organs.

Purpose: To evaluate the effects of L-arginine oral supplementation in spontaneously hypertensive pregnant rats (SHR)., Methods: Thirty SHR and ten Wistar-EPM-1 virgin female rats were used in the study. Before randomization, females were caged with males of the same strain (3:1). Pregnancy was confirmed by sperm-positive vaginal smear (Day 0). Wistar-EPM-1 rats served as counterpart control (C-1). SHR rats were randomized in 4 groups (n=10): Group Control 2, non-treated rats; Group L-Arginine treated with L-arginine 2%; Group Alpha-methyldopa treated with Alpha-methyldopa 33 mg/Kg; Group L-Arginine+Alpha-methyldopa treated with L-arginine 2%+Alpha-methyldopa 33 mg/Kg. L-arginine 2% solution was offered ad libitum in drinking water and Alpha-methyldopa was administered by gavage twice a day during the length of pregnancy (20 days). Blood pressure was measured by tail-cuff plethysmography on days 0 and 20. Body weight was measured on days 0, 10 and 20. Results were expressed as mean +/-SD (Standard Deviation). One-Way ANOVA/Tukey (or Kruskal-Wallis/Dunn, as appropriate) was used for group comparisons. Statistical significance was accepted as p<0.05., Results: There was no significant weight gain in isolated L-arginine treated SHR. Mean blood pressure decreased in L-arginine-treated SLR compared with untreated-SHR rats., Conclusion: L-arginine oral supplementation reduces blood pressure in spontaneously hypertensive rats during pregnancy.

Objective: To develop a bovine protocol for training in preimplantation genetic diagnosis (PGD) using PCR., Design: Randomized study., Setting: Human reproduction PCR laboratory., Patient(s): Cow ovaries obtained from slaughterhouses., Intervention(s): The ovaries were punctured and the oocytes were matured and submitted to in vitro fertilization. On the third day after fertilization, the embryos were biopsied and 1-2 blastomeres removed. A blastomere and the rest of the embryo were submitted to PCR for sex determination., Main Outcome Measure(s): Establishment of a possible training protocol., Result(s): A total of 50 embryos and 50 biopsied blastomeres were submitted to DNA amplification for sexing. Of the 50 embryos, 41 (82%) achieved successful DNA amplification and 9 (18%) did not. Of the 50 biopsies, 31 (62%) amplified and 19 (38%) did not. In 27 (65.9%) of the 41 embryos with DNA amplification, sex was identified as female and in 14 (34.1%) as male. In 40 cases (80%) amplification and sex determination were successful in both embryos and blastomeres. Sex was identical in all these cases., Conclusion(s): This training model seems to be useful in identifying mistakes and difficulties and improving the professional's performance in the various stages of preimplantation genetic diagnosis.

This experimental study aimed to evaluate the safety of nelfinavir when administered in normal up to high doses during the entire period of rat pregnancy. The renal and liver compartments of both mothers and fetuses were studied. For this purpose, three groups of pregnant rats were treated with nelfinavir (E1 = 40 mg/kg; E2 = 120 mg/kg; E3 = 360 mg/kg; no. = 10 in every group) from "zero" up to the 20th day of gestation. These doses were divided into two daily administrations by gavage. Controls (no. = 10) received distilled water in the same schedule. At term-pregnancy, the rats were deeply anesthesized and blood samples were collected for alanine and aspartate aminotransferases, creatinine and urea determinations. Fragments of maternal and fetal livers and kidneys were taken and processed for histopathological study. In all groups blood transaminases were within the normal limits, as were the levels of creatinine and urea, thus indicating that the treatment with nelfinavir during the entire gestation was essentially devoid of liver or kidney effects which could result in altered metabolic parameters. Morphological (light microscopy) studies revealed that no significant effects of the drug could be detected regarding either maternal or fetal organs of the E1 and E2 groups. However, the maternal hepatocytes in the E3 group showed heterochromatic nuclei. In addition, there was some fatty infiltration, congested sinusoids and portal dilatation. It is concluded that only doses of nelfinavir used during the entire gestation in doses well above the usual human doses could be considered to be potentially hepatotoxic for the pregnant rat.

This study was undertaken to investigate the effects of acupuncture in low back and pelvic pain during pregnancy under real life conditions, as compared with patients undergoing conventional treatment alone. A total of 61 conventionally treated pregnant women were allocated randomly into two groups to be treated or not by acupuncture. Twenty-seven patients formed the study group and 34 the control group. They reported the severity of pain using a Numerical Rating Scale from 0 to 10, and their capacity to perform general activities, to work, and to walk. We also assessed the use of analgesic drugs. Women were followed up for eight weeks and interviewed five times, at two-week intervals. All women completed the study. In the study group the average pain during the study period showed a larger reduction (4.8 points) than the control group (-0.3 points) (P < 0.0001). Average pain scores decreased by at least 50% over time in 21 (78%) patients in the acupuncture group and in five (15%) patients in the control group (P < 0.0001). Maximum pain and pain at the moment of interview were also less in the acupuncture group compared with the control group. The capacity to perform general activities, to work and to walk was improved significantly more in the study group than in the control group (P < 0.05). The use of paracetamol was lower in the acupuncture group (P < 0.01). These results indicate that acupuncture seems to alleviate low back and pelvic pain during pregnancy, as well as to increase the capacity for some physical activities and to diminish the need for drugs, which is a great advantage during this period.

Objective: Stavudine is an inhibitor of HIV reverse transcriptase and acts as a chain terminator during DNA synthesis. The aim of the study presented here was to evaluate the effects of stavudine during rat pregnancy., Methods: Female rats were randomly divided into four treatment groups: GI (treated with the drug vehicle); GII; GIII; and GIV (treated with 1, 3 or 9 mg/kg of stavudine, respectively) (n = 25 pregnant rats for every group). Rats were treated by gavage once daily. The treatment period extended from day 0 until the 20th day of pregnancy. Body weights were recorded weekly during this period. At term, the rats were sacrificed, and the implantation sites and number of fetuses and resorptions were recorded. The fetuses were evaluated for external abnormalities under a stereomicroscope., Results: No differences in body weight gain between the groups were observed. The mean number of implantations per dam in stavudine-treated groups was higher than in the control group (P < 0.05); however, only GIII presented an increase in the mean number of resorptions compared to the other groups (P < 0.01). The resorption/implantation rate was higher in the GII group and lower in the GIV group as compared to the other groups. Neither the mean fetal weights nor the placental weights differed significantly among the groups. No external anomalies were observed at dissection in rat fetuses, placentae or uteri., Conclusion: Rat pregnancy outcome seems to be affected by stavudine, mainly with respect to the mechanisms of intrauterine concept survival.

Acetaminophen (paracetamol) is an analgesic-antipyretic drug virtually devoid of typical anti-inflammatory activity and hence free of some of the side-effects of aspirin and related agents (e.g. gastric erosion and bleeding complications). The worldwide use of paracetamol as a household analgesic, including during pregnancy, prompted us to investigate its potentially deleterious effects in that setting. Pregnant rats were treated with paracetamol (150, 500 or 1,500 mg/kg, once a day by gavage) from the first day up to term pregnancy. In the group treated with the lowest doses, no histological changes were noticed in maternal and fetal livers or kidneys when examined under light or electron microscopy. With the higher doses, however, various dose-dependent effects of paracetamol were observed, namely necrotic areas of the liver seen with light microscope and further confirmed by electron microscopy. The kidneys revealed degeneration and necrotic foci under light microscopy with ultrastructural derangements. Electronmicrographs of the liver revealed hepatocytes bearing translucent bodies as a consequence of a dilated smooth endoplasmic reticulum. There were signs of necrosis both in the hepatocytes (lysis of mitochondria and presence of lipid droplets) and renal tissue (mitochondrial cytolysis in convoluted tubules). Our data point out the fact that both maternal and fetal tissues can be adversely affected by paracetamol.

In view of the very important role played by ritonavir in the prevention of maternal-fetal HIV-vertical transmission, the aim of this experimental study was to evaluate its possible effects on several important obstetric parameters. Ritonavir was administered daily to three groups of pregnant rats (E1 = 20 mg/kg; E2 = 60 mg/kg; E3 = 180 mg/kg; n = 10 in every group) from 'zero' up to the 20th day of pregnancy. Controls (n = 10) were injected with the drug vehicle (propyleneglycol) in the same schedule. We evaluated the effects on fetal and maternal weight gain, placental weight, number of implantations and resorptions, malformations, fertility rate, and maternal and fetal death rates. Body weight gain of the E3 group was significantly lower than that of the other groups, most likely due to a toxic effect of the highest dose of ritonavir. Ritonavir did not affect the number of implantations. Group E3 had five resorptions and some reduction in fertility. The mortality rate was significantly affected by ritonavir (2/10 maternal deaths in E2 and 4/10 in E3). On the other hand, no alterations were observed in the fetuses, a finding which could be due at least in part to the protective action of placental P-glycoprotein.

The worldwide use of acetylsalicylic acid (ASA) as an analgesic-antipyretic drug, including during pregnancy, prompted us to investigate its potentially deleterious effects in that condition. Pregnant rats were treated with ASA (1, 10 or 100 mg/kg once a day) from the first day up to term pregnancy. No histological changes were noticed in maternal and fetal livers or kidneys when examined under light microscopy, but some definite dose-dependent effects of ASA were observed on electron microscopy examination. In livers and kidneys of pregnant rats treated with the highest doses of ASA we observed cytoplasmic derangement, mitochondrial cristolysis and abnormally shaped rough endoplasmic reticulum. Similarly, in foetal livers and kidneys from this group we observed degenerative cytoplasmic vacuoles and ballooned mitochondria with cristae derangement and myelin figures. Our data point out the fact that both maternal and foetal tissues can be importantly affected by ASA at the ultrastructural level, without overt signs of toxicity.

Female rats received 1.25 mg/kg body weight of N-2-cyano-ethylamphetamine. HCl (Fenproporex chlorhydrate) by oral route, once daily from the 5th to the 21st day of pregnancy, and compared to untreated pregnant rats, showed an increased total lipid content in maternal blood and fetal hearts; liver and heart have had total lipids decrease, while in placenta and fetal livers they were not observed significant differences.