Developmental toxicity of sodium fluoride measured during multiple generations.

Sodium fluoride (NaF) has been used to fluoridate drinking water in the United States since the mid 1940s. Because of the lack of reliable studies on the multigeneration effects of the compound, NaF (0, 25, 100, 175 or 250 ppm in drinking water) was given to rats continuously during three generations. Parental (F0) generation rats were treated for 10 weeks and mated within groups. At gestation day 20, caesarean sections were performed and eight F0 females per group and their litters (F1) were observed for implant status, fetal weight and length, sex and morphological development. The remaining F0 females (29-32 per group) were allowed to litter. F1 offspring (36 of each sex per group) were mated within groups, and caesarean sections were performed at gestation day 20. The F1 females and their litters (F2) were observed for implant status, fetal weight and length, sex and morphological development. In addition, F2 fetuses were evaluated for internal (soft-tissue) and skeletal development. Decreased fluid consumption for F0 and F1 dams at 175 and 250 ppm was attributed to decreased palatability of the solution. No dose-related effects in feed consumption or mean body weight gain were observed in either F0 or F1 females. Numbers of corpora lutea, implants, viable fetuses and fetal morphological development were similar in all groups. No dose-related anomalies in internal organs were observed in F2 fetuses. Ossification of the hyoid bone of F2 fetuses was significantly decreased at 250 ppm. Because of the decreased ossification of the hyoid bone, 250 ppm is considered the effect level.

A comparison of two time intervals for the ausculated acceleration test.

OBJECTIVE: Interest in an inexpensive, easy-to-administer antenatal screening test that did not rely on the use of electronic fetal monitoring led to development of the fetoscope administered auscultated acceleration test (AAT) in the late 1980s. More recent efforts have been directed toward providing those who may use the AAT with important information about the most effective and clinically appropriate AAT procedures. The purpose of this study was to determine the screening test validity performance of two AAT time intervals--6 minutes and 10 minutes. METHODS: Two auscultated acceleration tests (AAT6 and AAT10) were simultaneously performed using different time intervals on 205 women with high-risk pregnancies undergoing simultaneous nonstress tests (NSTS) who were referred to a tertiary care unit for antepartum testing. Standard measurements of screening test validity were calculated for each test in the prediction of selected perinatal outcomes. NST findings were included for comparative purposes. RESULTS: The AAT6 yielded an overall higher specificity as compared with the AAT10 at the expense of a slightly lower sensitivity for most perinatal outcomes; these differences were not significant at the .05 level. Relative risk ratios were similar for the AAT6 and AAT10 for both fetal distress and neonatal morbidity, with both AAT being a more effective predictor of neonatal morbidity than for fetal distress. Both tests yielded better sensitivity when compared with NST. CONCLUSIONS: Even though there was a nonsignificant trend toward higher sensitivities and lower specificities for the 10-minute AAT, this study showed that the differences in prediction of perinatal outcomes between the 6-minute and 10-minute AAT were minimal. In view of the added labor required for the 10-minute AAT in the absence of enhanced screening test validity, the 6-minute AAT is clinically preferred. This study has prompted new research questions for the continued development of the AAT as a low-technology fetal assessment technique with potential usefulness by midwives and their colleagues in a variety of settings worldwide.

Multigenerational evaluation of sodium fluoride in rats.

Since the mid 1940s, fluoride has been added to tap water in American communities in an effort to reduce the incidence of dental caries in the population. When the levels of fluoride in drinking water were tested and set, water was the only measurable source of fluoride for most communities. Now, adults and children ingest fluoride with foods and beverages prepared with fluoridated water, and they are exposed to fluoride-containing dental products. As a result, exposure to fluoride is greater than had been anticipated. In the early 1990s, the existing reproductive studies were reviewed in several reports and were considered to be inadequate to determine potential reproductive or developmental hazards. The effects of sodium fluoride ingestion at 0, 25, 100, 175 or 250 ppm in drinking water measured in rats throughout three generations are reported here. Feed and fluid consumption, body weights and clinical signs were recorded at regular intervals. Decreased fluid consumption observed at 175 and 250 ppm was attributed to decreased palatability and did not affect reproduction. No cumulative effects were observed in the three generations. Mating, fertility and survival indices were not affected. Organ-to-body-weight ratios and organ-to-brain weight ratios were not affected. Sodium fluoride up to 250 ppm did not affect reproduction in rats.

Testing the potential of flaxseed to affect spermatogenesis: morphometry.

Quantitative information was collected on male reproductive effects of maternal and postnatal dietary exposure to flaxseed (20 or 40%), flaxmeal (13 or 26%) or standard NIH AIN-93 feed (0% flaxseed control). Measurements were made on the testes of F1 generation males rats (1) whose mothers were exposed to the diets designated above, and (2) who, after weaning, were placed on the same diet as their mothers for an additional 70 days. The seminiferous tubules comprised 86%, 84%, 84%, 84% and 85% of the total testis volume while the interstitial space comprised 12%, 14%, 14%, 14%, 13% of the total testis volume for the 0% flaxseed/flaxmeal, 20% flaxseed, 13% flaxmeal, 40% flaxseed and 26% flaxmeal groups, respectively. Statistically significant decreases in the absolute volume of the seminiferous tubules were observed in the 20% and 40% flaxseed-treated groups when these groups were compared to controls. Borderline statistically significant differences were also observed when Sertoli cell nucleolar number per tubular cross-section were compared in the 13% flaxmeal and 20% flaxseed treatment groups. These effects were not considered biologically significant because other parameters of male reproductive function appeared normal. Overall, the quantitative information obtained suggests that exposure to flaxseed/flaxmeal at the doses used in the present study does not adversely affect testis structure or spermatogenesis in the rat.

The effect of maternal exposure to flaxseed on spermatogenesis in F(1) generation rats.

Pregnant Sprague-Dawley rats were exposed to a flaxseed (20 or 40%), flaxmeal (13 or 26%) or standard NIH AIN-93 (0% flaxseed control) diet throughout gestation and until their offspring were weaned. After weaning, F(1) generation males were placed in the same diet treatment groups as their mothers for 70 days. Statistically significant differences were not observed between either low-dose or high-dose flaxseed and flaxmeal-treated animals and the 0% flaxseed control animals for testis weights, homogenization resistant spermatid counts, daily sperm production rates, epididymal weights, seminal vesicle weights, seminiferous tubule fluid testosterone concentrations and the percentage of sperm abnormalities. The following statistically significant differences were observed when treated groups and the 0% flaxseed control groups were compared: (1) increases in serum LH in the 20% and 40% flaxseed treatment groups and in serum LH and testosterone in the 26% flaxmeal treatment group; (2) increases in the cauda epididymal weight from the 20% and 40% flaxseed groups; (3) increases in cauda epididymal sperm numbers/g epididymis from the 20% and 40% flaxseed and the 13% and 26% flaxmeal treatment groups; (4) a decrease in prostatic weight from the 20% flaxseed and 13% and 26% flaxmeal treatment groups. Prostate weight in the 40% flaxseed treatment group was lower but not statistically significantly different than the 0% flaxseed control group. Histological effects on spermatogenesis were not observed in either the control group, flaxmeal or the flaxseed treated groups.

The effect of vomitoxin (Deoxnivalenol) on testicular morphology, testicular spermatid counts and epididymal sperm counts in IL-6KO [B6129-IL6 [TmlKopf] (IL-6 gene deficient)] and WT [B6129F2 (wild type to B6129-IL6 with an intact IL-6 gene)] mice.

The potential of vomitoxin (VT) to affect testicular morphology and testicular and epididymal sperm counts was assessed in three strains of mice: IL-6KO [B6129-IL6 (tmlKopf) (IL-6 gene deficient)], WT [B6129F2 (wild type to B6129-IL6 with an intact IL-6 gene)] and B6C3F1 mice in a 90-day feeding study. The treated mice received VT at a concentration of 10 ppm in their diet. The body weight of VT-treated animals was significantly reduced compared with control animals. Slight changes, not statistically significant, were observed in relative testis weight and testicular spermatid counts. Histological changes were not apparent in the testes of VT-treated animals. The diameter of the seminiferous tubules, the height of the seminiferous epithelium and the number of Sertoli cell nucleoli per cross-sectioned seminiferous tubule in the VT-treated groups were not significantly different from their respective untreated controls. The IL-6KO and B6C3F1 VT-treated mice had significantly reduced cauda epididymal weights compared with their respective controls. These changes were not attributed to decreased sperm counts and this finding suggests that VT may exert an adverse affect on the epididymis.

Light microscopic observations on the reproductive tract of the male sand rat, Psammomys obesus.

The anatomy of the reproductive tract of the male sand rat, Psammomys obesus, was examined by light microscopy. Histologically, the reproductive tract is similar to other rodent species. Seminiferous tubules in the 1-month-old sand rat do not contain a tubular lumen but Sertoli cells, spermatogonia and spermatocytes are present. A full complement of germ cells is present in the seminiferous tubules by 2.5 months and spermatogenesis is well established. The interstitial space is not well defined until 2.5 months when cell types typical of most rodent species are observed. The epididymis is not noticeably segmented into lobules. An epididymal lumen is not observed until 2.5 months. Cauda epididymal sperm are not observed in the 1 or 2.5-month-old animals and cauda epididymal sperm counts from the 7.5 and 12.5-month-old animals are highly variable. The epididymis, proximal and middle regions of the vas deferens, seminal vesicles and prostate display morphological and histological characteristics similar to other rodent species. The distal end of the vas deferens is not expanded to form an ampulla.

Testing the potential of sodium fluoride to affect spermatogenesis: a morphometric study.

This study provides quantitative information on the effect of sodium fluoride (NaF) on the testes of F1 generation male rats exposed in utero and during lactation to NaF at one of four concentrations (25, 100, 175, 250 ppm). At weaning, the F1 generation males were exposed to NaF in their drinking water for 14 weeks, after which time testicular tissues were perfusion-fixed with glutaraldehyde and observed after being embedded in plastic. The seminiferous tubules comprised 89%, 87%, 88%, 88% and 88% of the total testis volume while the interstitial space occupied 9.3%, 11.2%, 10.2%, 9.8% and 9.9% of the total testis volume for the 0, 25, 100, 175 and 250 ppm NaF treatment groups, respectively. Statistically significant differences between control and NaF-treated rats were not observed with respect to absolute volume of the seminiferous tubules, interstitial space, Leydig cells, blood vessels boundary layer, lymphatic space, macrophages, tubular lumen or absolute tubular length and absolute tubular surface area, mean Sertoli cell nucleoli number per tubular cross-section, mean seminiferous tubule diameter and the mean height of the seminiferous epithelium. A statistically significant decrease in the absolute volume and volume percent of the lymphatic endothelium was observed in the 175 and 250 ppm NaF-treated groups and in the testicular capsule in the 100 ppm NaF-treated groups. The significance of this finding is unknown at the present time. Overall, the quantitative information obtained suggests that exposure to NaF at the doses used in the present study does not adversely affect testis structure or spermatogenesis in the rat.

Effects of fumonisin B1 in pregnant rats. Part 2.

The developmental toxicity of purified fumonisin B1 (FB1), a mycotoxin from the common corn fungus Fusarium moniliforme, was examined in Charles River rats. Pregnant rats were dosed orally on gestation days 3-16 at 0, 6.25, 12.5, 25 or 50 mg FB1/kg body weight/day. FB1 was not teratogenic at the doses tested. At 50 mg/kg, maternal toxicity (inappetence, emaciation, lethargy, death, resorption of entire litters) and foetal toxicity (increased number of late deaths, decreased foetal body weight, decreased crown rump length, increased incidence of hydrocephalus, increased incidence of skeletal anomalies) were seen. The foetal toxicity observed at 50 mg/kg may be related to maternal toxicity. Histopathological evaluation of tissues from dams of control and all treated groups revealed dose-related toxic changes in kidney and liver tissues. Acute toxic tubular nephrosis was seen in kidneys from all treated groups. Hepatocellular cytoplasmic alteration and individual cellular necrosis of the liver was seen in the two high-dose groups. Sphinganine (Sa) and sphingosine (So) were measured in day-17 adult and foetal tissues. Dose related increases in Sa/So ratios were seen in maternal liver, kidney, serum and brain, but there was no effect on foetal liver, kidney and brain. These data suggest that FB1 does not cross the placenta and further suggest that the observed foetal toxicity is a secondary response to maternal toxicity.

Effects of fumonisin B1 in pregnant rats.

Fumonisin B1 (FB1), the major mycotoxin from Fusarium moniliforme, has been implicated as a causative agent in several animal and human diseases. Despite animal toxicity studies and human epidemiological studies of FB1, knowledge of its reproductive effects is scarce. In this study, one of a series of proposed studies that will allow extrapolation to humans, pregnant rats were given oral doses of 0, 1.875, 3.75, 7.5 or 15 mg FB1/kg on gestation days 3 16. Caesarean sections were performed on day 17 or 20, and maternal condition, implantation efficiency, foetal viability and foetal development were measured. Dose-related decreases in overall feed consumption and body weight gain were seen, but only the feed consumption decrease at 15 mg/kg, and the decreased body weight gain at 15 mg/kg on days 0-17 were statistically significant. Foetal body weights at day 17 were similar in control and treated groups; but in day-20 foetuses, female weight and crown-rump length were significantly decreased at 15 mg/kg. FB1 was not teratogenic at the doses tested, and no dose-related effects were seen in either skeletal or soft-tissue development. In day-17 animals, maternal and foetal brain, liver and kidney tissues, and maternal serum were preserved to study the levels of sphinganine (Sa), sphingosine (So), and the Sa/So ratios. Dose-related increases were seen in Sa/So ratios in maternal livers, kidneys and serum. Sa/So ratios of maternal brains were not affected, nor were those of foetal kidneys, livers or brains.

Testing the potential of sodium fluoride to affect spermatogenesis in the rat.

The potential of sodium fluoride (NaF) to affect spermatogenesis and endocrine function was assessed in P and F1 generation male rats. Male and female experimental rats received sodium fluoride in their drinking water at one of four concentrations (25, 100, 175, 250 ppm). P generation male and female rats were exposed to sodium fluoride in their drinking water for 10 wk and then males were mated to females within the same treatment groups. Reproductive tissues were collected from P generation male rats after approximately 14 wk of treatment. Pregnant females (P) were exposed to sodium fluoride via their drinking water through gestation and lactation. F1 generation weanling male rats remained within the same treatment groups as their parents. F1 generation male rats were exposed to sodium fluoride in their drinking water for 14 wk, at which time reproductive tissues were collected. Dose-related effects were not observed within the P and F1 treatment groups in testis weights, prostate/seminal vesicle weights, non-reproductive organ weights, testicular spermatid counts, sperm production per gram of testis per day, sperm production per gram of testis, LH, FSH or serum testosterone concentrations. Histological changes were not observed in testicular tissues from either the P or F1 generation. We conclude that prolonged exposure to sodium fluoride in drinking water at the doses administered in this study does not adversely affect spermatogenesis or endocrine function in the P and F1 generation male rats.

Depot medroxyprogesterone. Management of side-effects commonly associated with its contraceptive use.

Depot medroxyprogesterone acetate is one of the most popular, effective methods of contraception used in the United States. Many women experience unpleasant side effects from this method, including episodic vaginal bleeding, hair loss, depression, and weight gain. This Clinical Practice Exchange describes the treatment strategies for these side-effects used by nurse-midwives from a variety of settings and locales. Contraceptive use can be more acceptable for many women if they are better able to cope with unpleasant side effects of the method. This Clinical Practice Exchange provides knowledge to enhance client coping.

PIP: In this clinical practice exchange, nurse-midwives in a variety of settings and US regions describe their treatment strategies for addressing the side effects associated with depot medroxyprogesterone acetate (DMPA). Although DMPA is a safe, effective, long-acting method of hormonal contraception, this injectable has been linked with side effects such as weight gain, menstrual changes, headache, dizziness, acne, abdominal bloating, breast swelling, depression, reduced libido, and alopecia. Approximately one-third of DMPA acceptors discontinue use by the end of the first year and half discontinue by the end of the second year, primarily because of these side effects. Nurse-midwives report that adolescents who are unable to take the pill consistently and breast-feeding women are ideal candidates for DMPA use. Constant vaginal bleeding, the most troublesome side effect, can be treated through use of ibuprofen, oral estrogen, or oral DMPA. Potential or actual weight gain can be averted through life-style changes such as reduced dietary fats and increased exercise. Unanticipated pregnancies can be avoided by administering the initial DMPA injection within 5 days after the onset of menses. Pre-acceptance anticipatory counseling, along with regular support and encouragement, increase user satisfaction with DMPA.

Nutritional concerns in women's primary care.

The midwife needs to be aware of current guidelines for nutritional monitoring, including those in Healthy People 2000, to provide primary care screening for nutritional factors that affect the health status of women. This article reviews the relationship between dietary habits and specific health concerns, including cardiovascular disease, obesity, osteoporosis, cancer, and diabetes; special attention is paid to high-risk groups. It also examines the relationship between improved nutritional status and the reduction of the major causes of morbidity in women.

Public health approaches to community-based needs. Boston's infant mortality crisis as a case study.

In light of a 10-year infant mortality crisis in Boston, a comprehensive public health approach was undertaken in which an extensive community-based needs assessment was used to develop a citywide maternal and child health improvement agenda. On the basis of the needs assessment, recommendations were made calling for community-based perinatal initiatives and midwifery services as critical elements in care for underserved communities and enhancement of perinatal services. A case description of one perinatal initiative illustrates the challenges of public health practice and describes a practice setting in which midwives provided leadership and guidance by using an interdisciplinary team approach in the implementation of a community empowerment project.

Effect of intratesticular injection of sodium fluoride on spermatogenesis.

The potential of sodium fluoride to affect spermatogenesis in the rat was assessed by intratesticular injection. Experimental rats' left testis was injected with sodium fluoride (50, 175 and 250 ppm) in vehicle (0.9% physiological saline); control testes were injected with vehicle. The right testis served as a non-injected control. Testicular tissues collected 'at' and 'distal to' the injection site and from the non-injected control testes were evaluated microscopically 24 hr and 1, 2 and 3 wk post-injection. Testicular tissues obtained at and distal to the injection site in all fluoride-injected groups resembled tissues collected from corresponding areas in the controls. Seminiferous tubule damage observed in both the vehicle-injected control testes and the fluoride-injected testes but not in the non-injected testes was attributed to injection trauma. Polymorphonuclear leucocyte infiltration was observed 24 hr post injection only at the injection site in the vehicle- and fluoride-injected groups. Leydig cells were unaffected. Leucocyte infiltration with seminiferous tubule damage was not considered to be a fluoride treatment-related effect because it was observed in both vehicle- and fluoride-injected testes. The results demonstrate that the rat is not adversely affected by direct exposure to fluoride at levels 200 times greater than those under normal conditions.

Primary care for women. Cultural competence in primary care services.

The assessment of cultural competence in providing primary care services for women is addressed. Emphasis is placed on the ways in which cultural competency attainment can ensure the availability of key primary care components to all women, especially those from certain vulnerable populations and those who have specific primary health care needs. A cultural competence continuum is described that will assist providers in an assessment of their own cultural competency levels, as well as those of the service settings in which they practice. Six scenarios are provided, describing experience at each level of the continuum that may hinder the development and delivery of effective primary care service interventions. Examples of ways in which nurse-midwives can provide leadership in the area of cultural competence in women's primary care are also included.

Developmental toxicity of orange B when given to rats by gavage.

The pyrazolone dye Orange B was given by gavage to pregnant Osborne-Mendel rats throughout gestation. Dose levels of 0, 15, 30, 100, 200, 400, or 700 mg/kg body weight were given daily. On gestation day 20, the females were killed and cesarean sections were performed. Feed consumption and maternal weight gain were not affected. No dose-related changes were seen in maternal clinical findings, implantations, fetal viability, or fetal size (weight and length). No compound-related effects were seen in sternebral development. No dose-related effect was seen in the incidence of skeletal variations in fetuses or in the number of litters containing fetuses with skeletal variations. Skeletal development, as measured by the average number of ossified vertebrae, was similar in all groups. No compound-related effects were seen in soft-tissue development.

Primary care for women. An overview of the role of the nurse-midwife.

The nurse-midwife's past, present, and future roles in the primary care of women are explored using a recent Institute of Medicine report on primary care as a framework for discussion. Primary care, the scope of services, and the role of the primary care clinician are described, and specific strategies for a primary care emphasis in basic nurse-midwifery education are addressed. The nurse-midwife's future roles in collaborative practice for the primary care of women and the need for continuing education opportunities in primary care are also discussed.

Developmental effects and mineral interactions in rats fed textured vegetable protein.

The teratogenic effects of feeding a diet based on textured vegetable protein to Long-Evans rats were studied along with maternal and fetal mineral interactions and their relationship to diet composition. Pregnant rats were fed purified diets containing 18% protein as casein (CAS), textured vegetable protein (TVP, from defatted soy flour) with 18 mg Zn/kg, or TVP diet with 100 mg Zn/kg. A fourth group was fed diet NIH-31. The animals received their diets throughout pregnancy and were sacrificed on day 20 of gestation. Fetuses were examined for developmental effects, and mineral levels were determined in maternal and fetal tissues by inductively coupled argon plasma-atomic emission spectrometry. Females fed the casein diet or diet NIH-31 had normal weight gains throughout pregnancy and their progeny exhibited normal development. The animals on the TVP-containing diet with 18 mg Zn/kg had decreased food consumption and body weights, and their fetuses exhibited developmental anomalies as well as reductions in size and weight. These developmental alterations may be the result of decreased zinc levels in the fetal tissues, caused by reduced bioavailability of the trace element in the maternal diet. Significant increases in tissue iron accompanied the low zinc levels. No developmental effects were found in animals receiving the high Zn-TVP diet, and mineral data from these animals were not significantly different from the casein group.