General side effects and challenges associated with anti-epilepsy medication: A review of related literature.

BACKGROUND: This study is coming against the background of people with epilepsy who are abandoning anti-epilepsy medication in developing countries, such as Zimbabwe. AIM: The aim of this article was therefore to review the general side effects and challenges associated with these anti-epilepsy medications. SETTING: The researchers reviewed literature related to the general side effects, psychological, social and economic challenges associated with anti- epilepsy medication. METHODS: To answer the research questions, the researchers used a narrative approach. RESULTS: Findings of the study reflected that the general side effects associated with anti- epilepsy medication include feelings of tiredness, stomach upset, dizziness or blurred vision, which usually happen during the first weeks of taking medicines. Psychologically, an individual with epilepsy may suffer cognitive problems that are associated with thinking, remembering, paying attention or concentrating and finding the right words to use. Socially, people with epilepsy experience social isolation, dependent behaviour, low rates of marriages, unemployment and reduced quality of life. Using anti-epilepsy medication is also associated with economic challenges. CONCLUSION: The researchers concluded that some people with epilepsy have discontinued using anti-epilepsy medications because of these side effects and challenges.

Elevation of both cyclooxygenase-2 and prostaglandin E2 receptor EP3 expressions in rat placenta after uterine artery ischemia-reperfusion.

Intrauterine growth restriction (IUGR) has a multifactorial pathogenesis and is an important cause of perinatal mortality. The relationship between fetal weight and placental blood flow in an animal model of IUGR has been investigated, showing that fetal growth is regulated by placental blood flow. The aim of the present study was to determine whether ischemia-reperfusion (I/R) injury stimulates the prostaglandin E2 (PGE2) system or the vascular endothelial growth factor (VEGF) system in the placenta of a rat IUGR model. COX-2 is reported to be involved in ischemic damage in many organs. There are 4 types of PGE2 receptor (EP1, EP2, EP3 and EP4). It is well known that EP1 and EP3 is associated with vasoconstriction. In the present study, vessels were occluded in the right uterine horn on day 17 of pregnancy in rats, and the clamps were removed after 30 min of ischemia. At 24h, 48 h, and 5 days after I/R injury, the live fetuses and placentas were obtained by cesarean section. This study revealed that I/R injury caused IUGR 5 days after the treatment. COX-2 expression and EP3 receptor expression were significantly elevated at 24h after I/R injury, but VEGF mRNA expression was not altered in the placenta from the ischemic horn compared with the non-ischemic horn. These results suggested that induction of the COX-2-EP3 system in the placenta may be one of the causes of IUGR induced by uterine ischemia, because the EP3 receptor and PGE2 are well known to mediate vasoconstriction in many organs.

Hemorrhagic infarction of fibroma. MR imaging appearance.

We experienced a case of hemorrhagic infarction of the ovarian fibroma and that indicated the characteristic following appearance: exhibiting a high signal intensity area observed at the periphery of mass on T1-weighted MRI (magnetic resonance imaging). It was thought that this appearance developed because hemorrhagic infarction was caused by subacute ovarian torsion. This is a useful finding for suspecting hemorrhagic infarction preoperatively.

Cyclic changes in expression of mRNA of vascular endothelial growth factor, its receptors Flt-1 and KDR/Flk-1, and Ets-1 in human corpora lutea.

OBJECTIVE: To evaluate the expression of mRNA of vascular endothelial growth factor (VEGF), its receptors Flt-1 and KDR/Flk-1, and Ets-1 in human corpora lutea. DESIGN: Prospective laboratory study. SETTING: University hospital in Japan. PATIENT(S): Women with regular menstrual cycles who underwent hysterectomy. INTERVENTION(S): Fifteen corpora lutea were obtained during hysterectomy (5 in the early luteal phase, 5 in the mid-luteal phase, and 5 in the late luteal phase). MAIN OUTCOME MEASURE(S): Expression of VEGF, Flt-1, KDR/Flk-1, and Ets-1 in human corpora lutea on northern blot analysis or immunohistochemistry. RESULT(S): Human corpora lutea in early luteal phase and mid-luteal phase had high VEGF mRNA expression. Expression of VEGF mRNA was significantly reduced in the late luteal phase. Immunohistochemistry showed that VEGF protein was expressed mainly in granulosa lutein cells and faintly in thecal lutein cells. Staining of VEGF protein was decreased in human corpora lutea in the late luteal phase. Expression of Flt-1 and KDR/Flk-1 mRNA was increased in the early luteal phase and mid-luteal phase and decreased in the late luteal phase. Immunohistochemistry showed that Flt-1 and KDR/Flk-1 proteins were expressed mainly in granulosa lutein cells and faintly in thecal lutein cells and endothelial cells in the early luteal phase and mid-luteal phase; their protein staining was reduced in the late luteal phase. Expression of Ets-1 mRNA changed similarly to VEGF and its receptor mRNA in human corpora lutea during the luteal phase. CONCLUSION(S): Levels of mRNA of VEGF and its receptors Flt-1 and KDR/Flk-1 in human luteal cells may be related to luteal function.

Lysyl oxidase and MMP-2 expression in dehydroepiandrosterone-induced polycystic ovary in rats.

Polycystic ovary syndrome (PCOS) is characterized by cystogenesis; however, the cause of this cystogenesis is unknown. At ovulation, preovulatory collagenolytic activities in the ovarian follicles increase and various proteinases are needed to degrade the tissues surrounding the follicles. To clarify the roles of enzymes in collagen degradation of the follicular wall of polycystic ovary (PCO) in relation to the cystogenesis, we examined expression of lysyl oxidase (LOX), which initiates cross-link formation of the collagen and elastin in the extracellular matrix, and expression of matrix metalloproteinases (MMPs) in ovaries of model rats with PCO induced by dehydroepiandrosterone (DHEA) compared with MMP expression in control rats. DHEA treatment increased LOX mRNA expression to more than three times the control value (P: < 0.01). MMP-2 mRNA expression in control rats was threefold greater than that in the DHEA-induced group (P: < 0.05). Expression of both latent and active forms of MMP-2 in controls was more than twice that in the DHEA-induced group (P: < 0.05) as shown by Western blotting, and expression of the active form of MMP-2 was also twice as high in the controls as in the DHEA-treated group (P: < 0.05) as shown by zymography. Our results suggest that depression of MMP-2 activity and increased LOX expression may be one of the causes of the cystogenesis of PCO.

Expression of various matrix proteases and Ets family transcriptional factors in ovarian cancer cell lines: correlation to invasive potential.

OBJECTIVES: The aim of our study was to determine the important molecules responsible for the invasive activity of ovarian cancer cells. METHODS: We compared the biological characteristics, that is, growth rate, motility, and invasive activity, of five ovarian cancer cell lines with the gene expression of various matrix proteases (matrix metalloproteinase-1 [MMP-1], MMP-2, MMP-9, membrane-type MMP type 1 [MT1-MMP], MT2-MMP, MT3-MMP, urokinase plasminogen activator [uPA]), their inhibitors (tissue inhibitor of metalloproteinase type 1 [TIMP-1], TIMP-2, plasminogen activator inhibitor type 1, [PAI-1], and PAI-2), and the potential transcriptional regulators E1AF and Ets-1. RESULTS: There was no clear correlation in the growth rate, motility, and invasion, suggesting that there are independent properties for malignant potential in ovarian cancer cells. However, HTBOA, a poorly differentiated cancer cell line, exhibited highly invasive activity, rapid growth, and increased motility. This cell line also expressed both Ets transcriptional factors, E1AF and Ets-1, and many matrix-degrading enzymes. Three cell lines that expressed E1AF showed rapid cell growth. The highly invasive cell lines, HTBOA and HTOA (well-differentiated serous cystadenocarcinoma), produced either MMP-2 or MMP-1, and both cell lines expressed MT1-MMP and uPA. Furthermore, the active forms of pro-MMP-2 and pro-MMP-1 were detected in HTBOA and HTOA by zymography. CONCLUSION: We conclude that activated MMP-2 and MMP-1 are important in the invasive activity of these ovarian cancer cells.

Complete hydatidiform mole coexisting with a live fetus after gamete intrafallopian transfer. A case report.

BACKGROUND: Molar pregnancy with a coexisting live fetus is a rare occurrence. We report the only known case with a surviving coexistent fetus after gamete intrafallopian transfer (GIFT). CASE: After GIFT, a 28-year-old primary infertility patient was diagnosed as having a complete hydatidiform mole coexisting with a live fetus at 13 weeks of gestation. At 36 weeks of gestation, a cesarean section was performed due to elevated serum human chorionic gonadotropin (hCG) levels, and a male infant with a normal appearance and weighing 2,688 g was delivered. CONCLUSION: If the patient desires to try to carry the fetus to viability after counseling on the possible associated risks of malignancy, it is possible to achieve fetal viability if (1) there is decline in the serum hCG level after it peaks before the second trimester, (2) ultrasound reveals degeneration of the molar part, and (3) there are no complications of pregnancy.

The effects of growth hormone on corpus luteum of superovulated rats.

In general, growth hormone acts as a factor promoting cell proliferation in the positive direction and suppresses apoptosis. No report has described growth hormone (GH)-induced structural luteolysis. The present studies showed that GH induced structural luteolysis in rats after the induction of functional luteolysis by treatment with bromocriptine, and that apoptotic cells were present among luteal cells during structural luteolysis as shown by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling. Zymography showed that the activity of matrix metalloproteinase (MMP)-2 increased during GH-induced structural luteolysis. The expression of c-myc protein of luteal cells was significantly decreased, but proliferating cell nuclear antigens (PCNA) were conversely increased during structural luteolysis, as shown by Western blot analysis. We propose that an excessive increase in PCNA and a marked decrease in c-myc protein of luteal cells lead to a disorder in the signals concerned with DNA synthesis, causing mitotic catastrophe and inducing apoptosis in luteal cells, and that structural luteolysis may be triggered. GH-induced apoptosis in structural luteolysis therefore highly depends on the cell cycle. There are thought to be two mechanisms of GH-induced structural luteolysis. One is apoptosis, and the other is destruction of extracellular matrix by MMP.

Gonadotropin-releasing hormone agonist has the ability to induce increased matrix metalloproteinase (MMP)-2 and membrane type 1-MMP expression in corpora lutea, and structural luteolysis in rats.

Gonadotropin-releasing hormone (GnRH) and its agonist analog (GnRHa) are well known to have luteolytic effects. We previously reported that prolactin (PRL) stimulated matrix metalloproteinase (MMP)-2 activity to degrade collagen type IV as a mechanism of structural luteolysis. The effects of GnRHa treatment on developed corpora lutea are unknown. In this study we assessed the effect of GnRH on MMP expression and induction of structural involution of developed corpora lutea of superovulated rats using GnRHa. Pregnant mare serum gonadotropin-human chorionic gonadotropin (hCG)-synchronized ovulation and luteinization were induced in immature female rats, followed by daily treatment with GnRHa from 5 days after hCG treatment. GnRHa-induced involution of corpora lutea was evident 3 days after the treatment, as shown by their markedly smaller size (60% of the control weight). Nine days after hCG injection, serum progesterone and 20alpha-dihydroprogesterone concentrations were as low as those associated with structural luteolysis. These findings revealed that GnRHa has the ability to induce structural luteolysis in superovulated rats in the same way that PRL does. To gain information on mechanisms of luteal involution induced by GnRHa, we performed gelatin zymography. This showed a significant increase in the active form of MMP-2 in the luteal extract of GnRHa-treated rats (more than twofold that of the control). Activation of pro-MMP-2 by membrane type-MMP (MT-MMP) is reported to be a rate-limiting step for catalytic function. Another function of MT-MMP is to degrade collagen types I and III. The plasma membrane fraction of corpora lutea of GnRHa-treated rats activated pro-MMP-2 of fetal calf serum, resulting in a marked shift of the 68-kDa band to the 62-kDa band in the zymogram. A Northern hybridization study also revealed simultaneous significant increases in expression of MMP-2 mRNA and MT1-MMP mRNA in corpora lutea of GnRHa-treated rats (more than threefold the control level). In summary, hormonal and histological features of corpora lutea of GnRHa-treated superovulated rats correspond to those of structural luteolysis. GnRHa stimulated the expression of MMP-2 and MT1-MMP in developed corpora lutea associated with involution. These findings support the conclusion that MMP-2, activated by MT1-MMP, and MT1-MMP itself, remodel the extracellular matrix during structural luteolysis induced by GnRHa.

Effects of estradiol and an aromatase inhibitor on progesterone production in human cultured luteal cells.

The human corpus luteum produces both estradiol and progesterone. It is well known that there are both autocrine and paracrine systems for the regulation of the corpus luteum and that estradiol regulates the progesterone production of the corpora lutea of some other species. To assess the direct effects of estrogen on human luteal function, we performed cell culture experiments. A low concentration of estradiol, almost equal to the amount of estradiol produced by human cultured luteal cells, directly stimulated progesterone production. 4-Cyclohexylaniline, an aromatase inhibitor, significantly reduced both progesterone production and estradiol production. Levels of estradiol higher than the levels that cultured human luteal cells themselves produced significantly reduced basal progesterone production and also significantly reduced human chorionic gonadotropin (hCG), forskolin and dibutyryl-cyclic AMP-stimulated progesterone production. According to these data, high doses of estradiol produced a luteolytic action which widely inhibited the steroidogenesis process. In conclusion, our results indicated that estradiol in part regulates progesterone production physiologically and blocks progesterone production in a pharmacological or pathological state in the human corpus luteum.