A randomized trial of Boswellia in association with betaine and myo-inositol in the management of breast fibroadenomas.

OBJECTIVE: Breast fibroadenoma is a common finding in young women and actually accounts for the majority of benign breast lumps. Fibroadenoma does not require any treatment unless clinical symptoms (mostly mastalgia) or histological markers of cancer risk (atypia) impose specific medical or surgical intervention. In symptomatic fibroadenoma, anti-estrogenic treatments provided evidence of success. Yet, these therapies are often associated with relevant side effects that lead to drug treatment discontinuation. Additionally, in such cases, relapse is a frequent issue. Therefore, an optimal strategy is still warranted. Boswellia, betaine and myo-inositol have already been proved to modulate different pathways - inflammatory, metabolic, oxidative and endocrine processes - in a wide array of human tissues. Based on that background, we hypothesized that these substances can effectively synergize in inducing the regression of fibroadenoma. PATIENTS AND METHODS: We included 64 patients ≤ 30 years of age with fibroadenoma. The patients were randomized into two groups. The experimental group was treated with an association of Boswellia, betaine, myo-inositol, B-group vitamins and N-acetylcysteine for 6 months; otherwise, the placebo group was treated only with B-group vitamins and N-acetylcysteine. Patients were monitored at the enrollment and the end of the study for evaluating the clinical response. RESULTS: A significant clinical improvement was observed in the experimental arm. Fibroadenoma median volume reduction averaged 17.86% in the experimental group and 5.96% in the placebo group. Moreover, 14 out of 36 (38.88%) patients showed a reduction of fibroadenoma volume compared to 5/28 (17.85%) observed in the placebo group (p = 0.005). CONCLUSIONS: A supplementation with Boswellia, betaine and myo-inositol reduces fibroadenoma dimension in young women. No relevant side effects have been recorded.

An association of boswellia, betaine and myo-inositol (Eumastós) in the treatment of mammographic breast density: a randomized, double-blind study.

OBJECTIVE: Mammographic breast density is a recognized risk factor for breast cancer. The causes that lead to the proliferation of the glandular breast tissue and, therefore, to an increase of breast density are still unclear. However, a treatment strategy to reduce the mammary density may bring about very relevant clinical outcomes in breast cancer prevention. Myo-inositol is a six-fold alcohol of cyclohexane, has already been proved to modulate different pathways: inflammatory, metabolic, oxidative and endocrine processes, in a wide array of human diseases, including cancer and the genesis of mammary gland and breast diseases, like fibrosis, as well as metabolic and endocrine cues. Similarly, boswellic acid and betaine (three-methyl glycine) both inhibit inflammation and exert protective effects on breast physiology. Based on this scientific background, we hypothesized that a combination including, boswellic acid, betaine and myo-inositol would be able to reduce breast density working on different pathways. PATIENTS AND METHODS: In this study, seventy-six premenopausal women were randomly assigned to the placebo and the experimental drug arms (Eumastós) for six months. RESULTS: After 6 months of treatment, statistically significant difference between the two groups was recorded on the breast density reduction (60% vs. 9%), using mammographic as well as ultrasound examination. CONCLUSIONS: Preliminary data collected here with support the starting assumptions, that the association comprising boswellic acid, betaine and myo-inositol significantly reduces mammary density, providing the first evidence for a new and safe approach for the management of mammographic density treatment.

Sex differences in regional specialisation across the placental surface.

There may be regional specialisation in structure and function across the placental surface. In Riyadh, Saudi Arabia, the length and the breadth of the placental surface at birth were highly correlated, but the breadth was more closely associated with the size of the baby. To replicate this we studied 321 pregnant Saudi women in the town of Baish. We measured the size of the newborn babies and their placentas. The association of the length and breadth of the placental surface on the baby's body size differed in boys and girls. Among boys the breadth had a stronger association with all birth measurements except crown-heel length. This was similar to the findings in Riyadh. Placental surface length was related to crown-heel length. For each centimetre in surface length, crown-heel length increased by 0.27 cm (95% CI 0.09-0.44, p = 0.004). Among girls placental surface breadth was related to crown-heel length, whereas surface length was related to birth weight, head and thigh circumferences. For each centimetre in surface breadth, crown-heel length increased by 0.33 cm (0.13-0.53, p = 0.001). We conclude that, within Saudi Arabia, there are both geographical and sex differences in regional specialisation across the placental surface. In the adverse circumstances of Baish, linked to the mothers' short stature, boys were smaller at birth than girls. Boys may have compensated for under-nutrition by increasing the depth of spiral artery invasion rather than by recruiting additional spiral arteries. Girls may have had more effective regional specialisation across the placental surface.

Intergenerational effects of in utero exposure to Ramadan in Tunisia.

UNLABELLED: We have reported that changes in the lifestyle of pregnant women during Ramadan affect more than one generation. In a series of newborn babies in Saudi Arabia, those whose mothers had been in utero during Ramadan differed from those whose mothers had not been in utero during Ramadan. These were unexpected findings and require replication. METHODS: We examined body size at birth in 1,321 babies (682 boys and 639 girls) born in Gafsa, a small city in Tunisia. RESULTS: Babies whose mothers had been in utero during Ramadan were smaller and thinner, and had smaller placentas, than those whose mothers had not been in utero during Ramadan. After adjustment for sex, the babies were 93 g lighter (95% confidence interval, 32-153, P=0.003) than those whose mother had not been in utero during Ramadan, their mean ponderal index was 0.52 kg/m(3) lower (0.24-0.79, P<0.001) and their placental weight was 21 g lower (5-37, P=0.01). The findings did not differ by trimester of maternal exposure to Ramadan. They were similar in boys and girls and in primiparous and multiparous mothers CONCLUSION: This study provides further evidence that changes in lifestyle during Ramadan have intergenerational effects.

An ultrastructural study of oogenesis and cell dynamics during cocoon shell secretion in the subterranean freshwater planarian Dendrocoelum constrictum (Platyhelminthes, Tricladida).

The ultrastructure of the ovary and the female atrium during cocoon formation was investigated in the subterranean freshwater planarian Dendrocoelum constrictum. In the peripheral portion of the ovary, the oogonia are recognized as undifferentiated germ cells, which are morphologically similar to neoblasts that have a high nucleus/cytoplasm ratio. Oocyte maturation is characterized by a marked growth of the cytoplasm because of the accumulation of cytoplasmic organelles and inclusions. The Golgi complexes begin to increase within the ooplasm and produce vesicles with an electron-dense content that fuse to produce larger spherical globules with homogeneous and electron-dense material. In the mature oocyte, the spherical globules migrate toward the cortical ooplasm, forming a continuous monolayer. We confirm that these spherical globules, which represent cortical granules rather than eggshell globules, vary in size up to 2µm and their electron-dense content shows concentric thin bands. After leaving the ovary through the oviduct, the mature and fertilized oocytes reach the female atrium where they are packaged with thousands of vitelline cells in the cocoon shell. Based on our ultrastructural analysis, we demonstrate that the wall of the cocoon shell is composed of two layers, each of which has a different origin. The shell granules extruded from the vitelline cells are involved in the secretion of the inner layer of the cocoon shell, whereas the outer layer of the cocoon shell is synthesized by the epithelial cells in the genital atrium.

The breadth of the placental surface but not the length is associated with body size at birth.

Studies of pregnancies complicated by preeclampsia led to the suggestion that the surface of the placenta is aligned along two axes, measured by its breadth and length. It was hypothesised that tissue along the breadth serves as a nutrient sensor, responding to the mother's nutritional state and fetal nutritional demands, while tissue along the length has different functions. To develop this hypothesis we measured the breadth and length of the placental surface in 401 neonates born in the King Khalid Hospital, Riyadh, Saudi Arabia, and related these measurements to the baby's body size. The breadth and length of the placental surface were highly correlated (coefficient = 0.7). Nevertheless, in a simultaneous regression with both measurements, only the breadth was associated with neonatal body size. There were strong trends of increasing birth weight, ponderal index, and the circumferences of the head, chest, abdomen and thigh with increasing placental breadth. In contrast no measurement of baby's body size was related to placental length. Birth weight increased by 125 g per cm increase in placental breadth (95% confidence interval 88 to 162, p < 0.001) but only by 20 g per cm increase in placental length (-13 to 53, p = 0.2). The corresponding figures for head circumference were 0.28 cm (0.17-0.39, p < 0.001) and 0.03 (-0.07 to 0.14, p = 0.5). The associations between placental breadth and neonatal body size were strongest if the mother's height was below the median (157 cm). The associations between a larger breadth of the placental surface and a larger baby are consistent with the hypothesis that tissue along the breadth plays a key role in nutrient transfer from mother to baby. Mothers who are short in stature are known to have lower rates of protein turnover in pregnancy. In these circumstances the ability of the placenta to transfer amino acids to the fetus may be critical.

Sex differences in birth size and intergenerational effects of intrauterine exposure to Ramadan in Saudi Arabia.

OBJECTIVES: In Europe, boys and girls have different body proportions at birth. We examined newborn babies in Saudi Arabia to determine the sex differences and whether fetal growth differed if the mother was in utero during Ramadan. METHODS: We examined body size at birth among 967 babies (479 boys and 488 girls) born in Unizah, a small city in Saudi Arabia. RESULTS: Large head circumference was the strongest single predictor of male sex. In a simultaneous regression, female sex was predicted by small head circumference (P < 0.001), low birth weight (P = 0.002), and large chest circumference (P = 0.008). The mothers of boys were heavier in pregnancy than the mothers of girls and had a higher body mass index, 31.7 kg/m(2) compared to 30.2 (P < 0.001). The mothers of girls, however, were taller than the mothers of boys, 158.6 cm compared to 157.4 (P = 0.001). Compared to babies whose mothers were not in utero during Ramadan boys whose mothers were in mid gestation during Ramadan were 1.2 cm longer (P = 0.005) while girls had a 0.4 week shorter gestation period (P = 0.04). CONCLUSION: Our findings are consistent with other evidence that boys are more ready than girls to trade off visceral development in utero to protect somatic and brain growth. They also support the hypothesis that boys are more responsive to their mother's current diet than girls, who respond more to their mother's life time nutrition and metabolism. They provide the first evidence that changes in the life style of pregnant women during Ramadan affect more than one generation.

Secular increase in placental weight in Saudi Arabia.

BACKGROUND: Ramadan is an annual period of day-time fasting during which people in Saudi Arabia, including pregnant women, change their diets and physical activity. We recently reported that among babies who were in the second or third trimester of gestation during Ramadan placental growth slowed. We also found that, over the four years of the study, placental weight increased by 29 g per year. We have now extended our data collection in order to examine this trend in more detail. METHODS: We studied the birth records of 17 660 singletons born in King Saud Hospital, Unizah, Saudi Arabia, over a ten year period. The records included birth weight, placental weight and gestational age. RESULTS: During the first six years of the study period mean placental weight rose by more than 100 g while mean birth weight was unchanged. This secular increase in placental weight was accompanied by a change in the placenta's response to Ramadan. During the first half of the study period babies who were in their second or third trimester of gestation during Ramadan had reduced placental weight (475 g and 476 g compared with 484 g, p < 0.001 for both). During the second half of the study period babies who were in their first trimester of gestation during Ramadan had reduced placental weight (533 g compared with 539 g, p = 0.03). CONCLUSIONS: We suggest that the secular increase in placental weight reflects changes in maternal body composition. These have altered placental responses to the dietary changes during Ramadan. The biological processes underlying these responses are not known.

Changes in placental size during Ramadan.

BACKGROUND: Placental growth responds to maternal influences. Ramadan is an annual period of day-time fasting during which people in Saudi Arabia, including pregnant women, change their diets and physical activity. Little is known about the effects of this altered lifestyle on placental development. METHODS: We studied the birth records of 7083 babies born over a four-year period to Saudi nationals in Unizah, a small city 350km to the north of Riyadh, the capital city of Saudi Arabia. The records included birth weight, placental weight and gestational age. RESULTS: Mean birth weight was similar to European values but the mean placental weight and ratio of placental weight to birth weight were lower. Among babies who were in the second or third trimester of gestation during Ramadan the mean placental weight and ratio were below those of babies who were not in utero during Ramadan. Among boys the mean placental ratios were 14.4 percent (second trimester) and 14.5 percent (third trimester) compared with 14.9 percent (p=<0.001 and 0.002). The corresponding figures for girls were 14.8 and 14.6 percent compared with 15.1 percent (p=0.02 and <0.001). CONCLUSIONS: In Saudi Arabia placentas respond to mothers' limited ability to deliver nutrients to them. Placental growth slows but efficiency is increased so that fetal growth is sustained, albeit with a reduced reserve capacity. The lifestyle changes associated with Ramadan further slow placental growth. Ramadan may influence placental growth through dietary changes other than day-time fasting. Changes in placental growth during Ramadan could be associated with altered fetal programming, and may therefore have long-term implications for the health of the next generation.