Disrupted Balance of the Oxidant-Antioxidant System in the Pathophysiology of Female Reproduction: Oxidative Stress and Adverse Pregnancy Outcomes.

The significance of oxidative stress in the pathophysiology of male reproductive processes has been closely studied in the last two decades. Recently, it has become clear that oxidative stress can lead to numerous pathological conditions during female reproductive processes as well, contributing to the development of endometriosis, polycystic ovary syndrome and various forms of infertility. During pregnancy, physiological generation of reactive oxygen species (ROS) occurs in association with several developmental processes including oocyte maturation and implantation. An overproduction of ROS can lead to disturbances in fetal development and increases the risk for missed abortion, intrauterine growth restriction, pre-eclampsia, premature delivery and gestational diabetes. Our review focuses on the etiological role of the disrupted oxidant-antioxidant system during human gestation as it relates to adverse pregnancy outcomes.

How many brain metastases can be treated with stereotactic radiosurgery before the radiation dose delivered to normal brain tissue rivals that associated with standard whole brain radiotherapy?

INTRODUCTION: Clinical trial data comparing outcomes after administration of stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT) to patients with brain metastases (BM) suggest that SRS better preserves cognitive function and quality of life without negatively impacting overall survival. Here, we estimate the maximum number of BM that can be treated using single and multi-session SRS while limiting the dose of radiation delivered to normal brain tissue to that associated with WBRT. METHODS: Multiple-tumor SRS was simulated using a Monte Carlo - type approach and a pre-calculated dose kernel method. Tumors with diameters ≤36 mm were randomly placed throughout the contoured brain parenchyma until the brain mean dose reached 3 Gy, equivalent to the radiation dose delivered during a single fraction of a standard course of WBRT (a total dose of 30 Gy in 10 daily fractions of 3 Gy). Distribution of tumor sizes, dose coverage, selectivity, normalization, and maximum dose data used in the simulations were based on institutional clinical metastases data. RESULTS: The mean number of tumors treated, mean volume of healthy brain tissue receiving > 12 Gy (V12) per tumor, and total tumor volume treated using mixed tumor size distributions were 12.7 ± 4.2, 2.2 cc, and 12.9 cc, respectively. Thus, we estimate that treating 12-13 tumors per day over 10 days would deliver the dose of radiation to healthy brain tissue typically associated with a standard course of WBRT. CONCLUSION: Although in clinical practice, treatment with SRS is often limited to patients with ≤15 BM, our findings suggest that many more lesions could be targeted while still minimizing the negative impacts on quality of life and neurocognition often associated with WBRT. Results from this in silico analysis require clinical validation.

Multiple In-Mold Sensors for Quality and Process Control in Injection Molding.

The simultaneous improvement of injection molding process efficiency and product quality, as required by Industry 4.0, is a complex, non-trivial task that requires a comprehensive approach, which involves a combination of sensoring and information techniques. In this study, we investigated the suitability of in-mold pressure sensors to control the injection molding process in multi-cavity molds. We have conducted several experiments to show how to optimize the clamping force, switchover, or holding time by measuring only pressure in a multi-cavity mold. The results show that the pressure curves and the pressure integral are suitable for determining optimal clamping force. We also proved that in-channel sensors could be effectively used for a pressure-controlled SWOP. In the volume-controlled method, only the sensors in the cavity were capable of correctly detecting the end of the filling. We proposed a method to optimize the holding phase. In this method, we first determined the integration time of the area under the pressure curve and then performed a model fit using the relationship between the pressure integral and product mass. The saturation curve fitted to the pressure data can easily determine the gate freeze-off time from pressure measurements.

Machine Learning in Injection Molding: An Industry 4.0 Method of Quality Prediction.

One of the essential requirements of injection molding is to ensure the stable quality of the parts produced. However, numerous processing conditions, which are often interrelated in quite a complex way, make this challenging. Machine learning (ML) algorithms can be the solution, as they work in multidimensional spaces by learning the structure of datasets. In this study, we used four ML algorithms (kNN, naïve Bayes, linear discriminant analysis, and decision tree) and compared their effectiveness in predicting the quality of multi-cavity injection molding. We used pressure-based quality indexes (features) as inputs for the classification algorithms. We proved that all the examined ML algorithms adequately predict quality in injection molding even with very little training data. We found that the decision tree algorithm was the most accurate one, with a computational time of only 8-10 s. The average performance of the decision tree algorithm exceeded 90%, even for very little training data. We also demonstrated that feature selection does not significantly affect the accuracy of the decision tree algorithm.

Survival and early complications of preterm infants with birthweight less than 500 grams during a 10-year period in Hungary.

BACKGROUND: There are limited data available on the survival and early complications of preterm infants with less than 500 g birthweight. To estimate the outcomes for these infants, it is important for caregivers to be aware of perinatal factors that may affect survival. OBJECTIVES: We assessed the mortality and certain early complications of preterm infants born with less than 500 g in Hungary between 2006 and 2015. METHODS: We reviewed data of 486 infants from the database of the Hungarian Central Statistical Office and in parallel of 407 infants from the "NICU database." The study period was divided into two epochs: 2006-2010 and 2011-2015. RESULTS: The survival was 27.1% in the first epoch and 39.1% in the second epoch, and the incidence of early complications was slightly higher in the second epoch. In the surviving group (first and second epoch combined), gestational age (25.1 vs 23.7 weeks), birthweight (458 vs 447 g) antenatal steroid treatment (66.3% vs 52.3%), surfactant therapy (95.1% vs 84.3%), median Apgar scores (6 vs 3 and 8 vs 5 at 1 and 5 minutes, respectively) and proportion of caesarean delivery (89.3% versus 68.5%) were higher than in the non-surviving group (first and second epoch combined). The proportion of multiple births was lower in the surviving group (15.7% vs 33.4%). CONCLUSIONS: Survival of infants with less than 500 g improved between 2006-2010 and 2011-2015 in Hungary. The slightly higher occurrence of early complications might be associated with improving survival.

In-Mold Sensors for Injection Molding: On the Way to Industry 4.0.

The recent trend in plastic production dictated by Industry 4.0 demands is to acquire a great deal of data for manufacturing process control. The most relevant data about the technological process itself come from the mold cavity where the plastic part is formed. Manufacturing process data in the mold cavity can be obtained with the help of sensors. Although many sensors are available nowadays, those appropriate for in-mold measurements have certain peculiarities. This study presents a comprehensive overview of in-mold process monitoring tools and methods for injection molding process control. It aims to survey the recent development of standard sensors used in the industry for the measurement of in-mold process parameters, as well as research attempts to develop unique solutions for solving certain research and industrial problems of injection molding process monitoring. This review covers the established process monitoring techniques-direct temperature and pressure measurement with standard sensors and with the newly developed sensors, as well as techniques for the measurement of indirect process parameters, such as viscosity, warpage or shrinkage.

Trends in Mortality and Morbidity in Infants Under 500 Grams Birthweight: Observations from Our Neonatal Intensive Care Unit (NICU).

BACKGROUND In our previous study, some changes were presented in obstetric care and we studied the morbidity and mortality trends of infants with <500 grams birth weight. Several neonatal protocol changes occurred during the study period. The aim of this study was to analyze the changes in mortality and morbidity of premature infants in light of changing neonatal protocols. MATERIAL AND METHODS We performed a retrospective study of premature infants with <500 grams birth weight, born at our department between 2006 and 2015. We divided the study period into two 5-year epochs and compared mortality and morbidity rates. We calculated the duration of mechanical ventilation and non-invasive respiratory support, and also investigated the potential impact of the differences in clinical practice. RESULTS The survival rate was 30.8% during first epoch, which was significantly lower than the 70.4% survival rate during second epoch. There was no difference in the rate of complications between the 2 epochs. The total number of ventilator and non-invasive ventilation days was significantly lower in the second epoch. CONCLUSIONS We found significant differences in survival rates but no change in the incidence of morbidities between the 2 epochs. Therefore, although the number of neonates surviving with morbidities has increased, so did the number of those with intact survival. The increased survival of infants born with <500 grams birth weight is not associated with increased rate of morbidities. Protocol changes may have contributed to these findings; however, in a retrospective study it is not possible to separate the impact of individual changes.

[Placental gene activity of significant angiogenetic factors in the background of intrauterine growth restriction]. / A legjelentosebb angiogeneticus gének méhlepényi expressziójának változásai a méhen belüli növekedési visszamaradás hátterében.

Placental vascular endothelial growth factor A (VEGF-A) gene and endoglin gene are both overexpressed in placental samples obtained from pregnancies with intrauterine growth restriction compared to normal pregnancies. In the background of these changes a mechanism can be supposed, in which the increased endoglin activity in intrauterine growth restriction (IUGR) leads to impaired placental circulation through an antioangiogenetic effect. This results in the development of placental vascular dysfunction and chronic fetal hypoxia. It is chronic hypoxia that turns on VEGF-A as a compensatory mechanism to improve fetal vascular blood supply by promoting placental blood vessel formation. Although the maternal serum placental growth factor (PlGF) level is a potential predictor for both IUGR and praeeclampsia, placental PlGF gene activity may be less of an active in the regulation of placental circulation in IUGR pregnancies during the later stages of gestation. Orv. Hetil., 2017, 158(16), 612-617.

Role of Apoptosis in the Development of Uterine Leiomyoma: Analysis of Expression Patterns of Bcl-2 and Bax in Human Leiomyoma Tissue With Clinical Correlations.

To describe gene expression patterns of the apoptotic regulatory genes Bcl and Bax in human uterine leiomyoma tissue. To investigate the relationship between alterations of gene expression patterns and several relevant clinical parameters. We obtained samples from 101 cases undergoing surgery for uterine leiomyoma for gene expression analysis of the Bcl-2 and Bax genes. Gene expression was quantified using RT-PCR technique. In the leiomyoma group, the Bcl-2 gene was significantly overexpressed compared with the control group although there was no such difference in the gene expression of Bax. Gene activity of Bcl-2 positively correlated with the tumor number in individual uterine leiomyoma cases. Although there was no significant correlation between the length of the cumulative lactation period before the development of uterine leiomyoma and Bcl-2 gene expression in the leiomyoma tissue, we observed a trend for a shorter cumulative lactation period to be associated with overexpression of the Bcl-2 gene. Overexpression of the antiapoptotic Bcl-2 gene appeared to be a factor in the development of uterine leiomyoma, whereas gene activity of the proapoptotic Bax gene did not seem to play a role in the process.

[Importance of nerve-sparing surgical technique in the treatment of deep infiltrating endometriosis]. / Az idegkímélo mutéti technika jelentosége a mélyen infiltráló endometriosis sebészetében.

INTRODUCTION: Traditional surgeries performed in cases of deep infiltrating endometriosis lead to impaired quality of life. AIM: To summarize the postoperative outcome and to compare the rate of postoperative complications after different therapeutic approaches applied in deep infiltrating endometriosis. METHOD: The authors analized the articles published between March 31, 2004 and March 31, 2015, in the database http://www.pubmed.org using the following keywords: endometriosis, deep infiltrating, nerve sparing, surgery. RESULTS: Non-nerve sparing surgery resulted in temporary urinary dysfunction in 19.1-38.5% of patients, while it occurred in 0.61-33.3% of patients after nerve-sparing surgery. Non-nerve sparing surgical technique resulted in an average of 121 days of need for self-catheretisation. When nerve-sparing surgeries were performed the duration of self-catheterisation varied between 7 to 39.8 days. After nerve sparing surgeries, permanent bladder dysfunction was not detected in any case. CONCLUSIONS: Because of the successful treatment of the patients symptoms and the lower postoperative complication rate, nerve-sparing surgical technique leads to a significant improvement of the quality of life.

[RADIOSURGERY OF INTRACEREBRAL CAVERNOMAS--CURRENT HUNGARIAN PRACTICE]. / AZ INTRACEREBRALIS CAVERNOMÁK SUGÁRSEBESZETE--HOL TART MAGYARORSZÁG?

BACKGROUND AND PURPOSE: Radiosurgery is an increasingly popular treatment option especially for deep eloquent intracerebral cavernomas that are often too risky for surgical removal, but their re-bleed carries significant risk for persisting neurological deficit. Gamma-radiation based radiosurgery has been being available since 2007 in Hungary in Debrecen. Our aim is to summarize our experience accumulated during the first five years of treatment and to compare it to the international experience. PATIENT SELECTION AND METHODS: We retrospectively analyzed 51 cavernomas in 45 patients treated between 2008 and 2012 in terms of localization, natural history, and the effect of radiosurgery on re-bleed risk and epilepsy, and its side effects. RESULTS: We treated 26.5% deep eloquent (brainstem, thalamic/basal ganglia) and 72.5% superficial hemispheric cavernomas. The median presentation age was 25 years (13-60) for deep, and 45 years (6-67) for superficial cavernomas. They were treated median of 1 year after presentation. 64.5% of deep cavernomas bled before treatment, the annual risk of first hemorrhage was 2%/lesion, re-bleed risk 21.7%, with 44% persisting morbidity. 13.5% of superficial cavernomas bled prior to treatment, the risk of first bleed was 0.3%, there was no re-bleed, and 35% caused epilepsy. We used GammaART-6000TM rotating gamma system for treatment, marginal dose was 14 Gy (10-16), and treatment volume 1.38-1.53 cm3. Re-bleed risk of deep eloquent lesions fell to 4% during the first two years after treatment and to 0% thereafter, and no hemorrhage occurred from superficial lesions after treatment. Persisting morbidity in deep lesions came from adverse radiation effect in 7% and from re-bleed in 7%, and there was no persisting side effect in superficial cavernomas. 87.5% of cases of epilepsy resistant to medical therapy improved. Radiological regression was found in 37.5% and progression in 2% after treatment. CONCLUSIONS: Radiosurgery of cavernomas is safe and effective. Early preventive treatment for deep cavernomas carrying high surgical risk is justified. Moreover, for superficial lesions that are surgically easily accessible radiosurgery also appears to be an attractive alternative.

Hypofractionated radiation therapy for early stage breast cancer: outcomes, toxicities, and cost analysis.

A French prospective randomized trial comparing whole breast radiotherapy with 45 Gy in 25 fractions versus 23 Gy in four fractions demonstrated equivalent 5-year local control and survival. On the basis of this data, we offer the hypofractionated regimen to women who refuse to undergo standard radiotherapy. We report our outcomes and a cost analysis. Between 2000 and 2012, 84 patients participated in this IRB-approved study and underwent whole breast radiation to 23 Gy in four fractions. Local control and survival were analyzed using the Kaplan-Meier method. Acute toxicities and overall long-term cosmetic results were assessed. Costs were estimated from 2012 Medicare reimbursement data and compared to costs from standard courses of 25 and 16 fractions. All 84 patients are included in this report. Median age was 83 (range 42-98). Most patients had stage I (80%), hormone receptor positive (90%) breast cancer. Fifty-eight patients (69%) were treated prone and 26 (31%) supine. At a median follow-up of 3 years, one local recurrence has occurred, of ductal carcinoma in situ histology. Among the 13 patients deceased, two died of metastatic breast cancer. Five-year actuarial local control is 99%, breast cancer-specific survival is 98%, and overall survival is 79%. Toxicities were limited to grade 1 dermatitis in 32 patients (38%) and grade 2 fatigue in three (4%). Sixty-three patients (75%) reported good or excellent cosmetic outcome at their last follow-up. Collected Medicare reimbursement was $4,798 for the hypofractionated course. Compared to the projected reimbursement of standard regimens, $10,372 for 25 fractions and $8,382 for 16 fractions, it resulted in a difference of $5,574 and $3,584, respectively. At a follow-up of 3 years, this hypofractionated regimen appears to be a promising approach, primarily for elderly women who are unable to undergo longer treatment courses but have indications for whole breast radiotherapy.

[Epigenetic mechanisms in physiologic and pathologic pregnancies]. / Epigenetikai mechanizmusok élettani és kóros terhességben.

Epigenetic factors are nowadays in the focus of scientific interest in medicine including obstetrics. The environment in utero and early neonatal life may induce a permanent response in the fetus and the newborn leading to enhanced susceptibility to later diseases. There is now growing evidence that the effects of developmental programming may also manifest themselves in the next generations without further suboptimal exposure. The so-called fetal programming may also highlight a tight connection between pathological conditions in pregnancy, environmental factors and the development of chronic diseases in adulthood. Investigation of epigenetic factors may yield new possibilities for the prevention of chronic diseases affecting a significant part of the population.

[Epigenetic background of the most common non-oncologic gynecological diseases]. / A leggyakoribb nem onkológiai eredetu nogyógyászati kórképek epigenetikai háttere.

Epigenetic effects influence the function of genes regulating the main physiological mechanisms. Some of these environmental factors may reduce or inhibit the function of these genes. The environmental effects on gene function may result in a change of the DNA structure leading to non-heritable phenotype changes. Epigenetic factors play an important etiological role in the development of numerous diseases in obstetrics and gynecology. Uterine fibroids probably have a complex etiological background including epigenetic mechanisms. The multifactorial aetiology of endometriosis suggests key roles for immunological and hormonal factors in the development of the diseases. These mechanisms are influenced by epigenetic factors, which may serve as therapeutic targets in the future. The possible in utero origin of polycystic ovary syndrome determines the main directions of research concerning epigenetic factors in the etiological background, with the hope of eventual prevention and/or treatment in the preconceptional period as well as during pregnancy care.

Gene expression patterns of insulin-like growth factor 2 in human uterine fibroid tissues: a genetic study with clinical correlations.

BACKGROUND/AIMS: We investigated insulin-like growth factor 2 (IGF-2) gene activity in human uterine fibroid tissue. Results of the genetic testing were correlated with clinical data. METHODS: We obtained samples from patients treated for uterine fibroid and from patients undergoing hysterectomy due to other indications (control group). The examined group (with fibroid) contained 101 cases, while the control group was similar with 110 patients. Gene expression values were determined using the standard PCR technique. Clinical data were available from the computer database of the department. RESULTS: IGF-2 gene expression was significantly higher in the fibroid group. There was no correlation between increase in gene activity and the number of tumors. History of previous uterine fibroid did not seem to predict IGF-2 gene activity in the current fibroid tumor tissue. IGF-2 gene expression did not correlate with cumulative duration of lactation following prior pregnancies. CONCLUSION: IGF-2 gene activity is significantly increased in leiomyoma tissue compared to normal myometrium. Familial aggregation of uterine fibroids is not significantly associated with increased IGF-2 gene activity; other genes may have a stronger etiological role. It appears that the genetic factors potentially important in the development of familiar uterine leiomyoma are not related to the IGF-2 gene.

[Prenatal diagnosis of central nervous system malformations]. / A központi idegrendszer fejlodési rendellenességeinek praenatalis diagnosztikája.

The prenatal diagnosis of fetal malformations have been the subject of numerous publications in the literature. This has dramatically increased in the last 15 years, mainly due to the advent of high-resolution ultrasound. In addition adequate guidelines issued by professional organizations have encouraged the universal approach to the imaging of fetal anatomy as well as malformations. One of the most significant groups of the fetal anomalies is the central nervous system malformation. Due to its prevalence and severity the praenatal diagnostics of central nervous system malformations got basic significance. In this review we attempted to summarize the recent informations concerning the prenatal diagnostics of the central nervous system anomalies.

Breast radiotherapy in the prone position primarily reduces the maximum out-of-field measured dose to the ipsilateral lung.

PURPOSE: To quantify the potential advantages of prone position breast radiotherapy in terms of the radiation exposure to out-of-field organs, particularly, the breast or the lung. Several dosimetric studies have been reported, based on commercial treatment planning software (TPS). These TPS approaches are not, however, adequate for characterizing out-of-field doses. In this work, relevant out-of-field organ doses have been directly measured. METHODS: The authors utilized an adult anthropomorphic phantom to conduct measurements of out-of-field doses in prone and supine position, using 50 Gy prescription dose intensity modulated radiation therapy (IMRT) and 3D-CRT plans. Measurements were made using multiple MOSFET dosimeters in various locations in the ipsilateral lung, the contralateral lung and in the contralateral breast. RESULTS: The closer the organ (or organ segment) was to the treatment volume, the more dose sparing was seen for prone vs supine positioning. Breast radiotherapy in the prone position results in a marked reduction in the dose to the proximal part of the ipsilateral lung, compared with treatment in the conventional supine position. This is true both for 3D-CRT and for IMRT. For IMRT, the maximum measured dose to the lung was reduced from 4 to 1.6 Gy, while for 3D-CRT, the maximum measured lung dose was reduced from 5 to 1.7 Gy. For the proximal part of the ipsilateral lung, as well as for the contralateral lung and the contralateral breast, there is little difference in the measured organ doses whether the treatment is given in the prone or the supine-position. CONCLUSIONS: The decrease in the maximum dose to the proximal part of the ipsilateral lung produced by prone position radiotherapy is of potentially considerable significance. The dose-response relation for radiation-induced lung cancer increases monotonically in the zero to 5-Gy dose range, implying that a major decrease in the maximum lung dose may result in a significant decrease in the radiation-induced lung cancer risk.

Automated beam placement for breast radiotherapy using a support vector machine based algorithm.

PURPOSE: To develop an automated beam placement technique for whole breast radiotherapy using tangential beams. We seek to find optimal parameters for tangential beams to cover the whole ipsilateral breast (WB) and minimize the dose to the organs at risk (OARs). METHODS: A support vector machine (SVM) based method is proposed to determine the optimal posterior plane of the tangential beams. Relative significances of including/avoiding the volumes of interests are incorporated into the cost function of the SVM. After finding the optimal 3-D plane that separates the whole breast (WB) and the included clinical target volumes (CTVs) from the OARs, the gantry angle, collimator angle, and posterior jaw size of the tangential beams are derived from the separating plane equation. Dosimetric measures of the treatment plans determined by the automated method are compared with those obtained by applying manual beam placement by the physicians. The method can be further extended to use multileaf collimator (MLC) blocking by optimizing posterior MLC positions. RESULTS: The plans for 36 patients (23 prone- and 13 supine-treated) with left breast cancer were analyzed. Our algorithm reduced the volume of the heart that receives >500 cGy dose (V5) from 2.7 to 1.7 cm(3) (p = 0.058) on average and the volume of the ipsilateral lung that receives >1000 cGy dose (V10) from 55.2 to 40.7 cm(3) (p = 0.0013). The dose coverage as measured by volume receiving >95% of the prescription dose (V95%) of the WB without a 5 mm superficial layer decreases by only 0.74% (p = 0.0002) and the V95% for the tumor bed with 1.5 cm margin remains unchanged. CONCLUSIONS: This study has demonstrated the feasibility of using a SVM-based algorithm to determine optimal beam placement without a physician's intervention. The proposed method reduced the dose to OARs, especially for supine treated patients, without any relevant degradation of dose homogeneity and coverage in general.

Gene expression patterns of the Bcl-2 and Bax genes in preterm birth.

OBJECTIVE: The apoptotic genes Bax and Bcl-2 are both involved in the pathogenesis of preterm delivery in conjunction with additional factors. We characterized gene expression patterns of these apoptotic regulatory genes as well as relevant environmental factors. DESIGN: A gene expression study with evaluation of clinical data. SETTING: Semmelweis University, Budapest, Hungary. SAMPLE: Human placental samples from 104 preterm and 140 full-term pregnancies. METHODS: Gene tests were performed using real-time PCR to assess gene expression patterns of Bax and Bcl-2 in human placental samples. Clinical data were collected from our computerized database. MAIN OUTCOME MEASURES: Apoptotic gene expression pattern and clinical information against the background of preterm delivery. RESULTS: In placental samples from preterm delivery pregnancies, expression of the Bcl-2 gene was unchanged, whereas the Bax gene was overexpressed. Placental gene expression of Bax in preterm delivery was dependent on gestational age with gestational weeks 28-32 and 32-36 associated with overexpression, and no overexpression in gestational weeks 24-28. Preterm delivery began with premature rupture of membranes in 70.2% and spontaneous uterine activity in 29.8%. CONCLUSIONS: The Bax gene was overexpressed in preterm delivery, whereas expression of the Bcl-2 gene remained unchanged. After the 28(th) gestational week, apoptosis appears to be a key factor in the pathogenesis of preterm delivery.

[The role of homocysteine and methylenetetrahydrofolate reductase, methionine synthase, methionine synthase reductase polymorphisms in the development of cardiovascular diseases and hypertension]. / A homocisztein és a metilén-tetrahidrofolát-reduktáz, metionin-szintáz, valamint a metionin-szintáz-reduktáz génpolimorfizmusok szerepe a cardiovascularis megbetegedésekben és a magas vérnyomás kialakulásában.

Cardiovascular diseases (CVDs) are the leading causes of death in the developed countries. Elevated homocysteine level is as an independent risk factor of CVDs. The C677T and A1298C variants of methylenetetrahydrofolate reductase gene (MTHFR) have been shown to influence folate and homocysteine metabolisms. However, the relationship between MTHFR polymorphisms and hyperhomocysteinemia has not been well established yet. The gene variants were also reported to be associated with CVDs. In addition, the C677T polymorphisms may play a role in the development of hypertension. Recent research evidence has suggested that MTHFR variants might be independently linked to CVDs and hypertension, because of the involvement of the MTHFR enzyme product (5-methyl-tetrahydrofolate /5-MTHF) in the regulation of endothelial functions. Further research is required to investigate the association between gene polymorphisms of folate-metabolizing enzymes and CVDs, and to identify the possible role of the relevant gene variants in the molecular pathogenesis of hyperhomocysteinemia.