Ameliorative Effects of Zinc Oxide, in Either Conventional or Nanoformulation, Against Bisphenol A Toxicity on Reproductive Performance, Oxidative Status, Gene Expression and Histopathology in Adult Male Rats.

Bisphenol A (BPA) is a widely used endocrine disruptor that represents a significant risk to male reproductive function. Zinc (Zn) is vital for appropriate development of testes and to guarantee optimal testicular function and spermatogenesis. Our goal was to investigate if zinc oxide (ZnO), either in conventional or nanoformulation, could safeguard adult male rats' reproductive performance against the damaging effects of BPA. Signaling expression of CYP11A1 and Nrf-2 in the testis, testicular oxidant-antioxidant status, Bax/Bcl-2 apoptotic ratio, and histological examination of various reproductive organs were all evaluated. Twenty-eight adult male albino rats were divided randomly into 4 groups (7 animals each) including the control, BPA, conventional zinc oxide (cZnO) + BPA, and zinc oxide nanoparticles (ZnO-NPs) + BPA groups. The study was extended for 2 successive months. Our findings revealed strong negative effects of BPA on sperm cell characteristics such as sperm motility, viability, concentration and abnormalities. Additionally, BPA reduced serum levels of testosterone, triiodothyronine (T3), and thyroxine (T4). Also, it evoked marked oxidative stress in the testes; elevating malondialdehyde (MDA) and reducing total antioxidant capacity (TAC). BPA significantly downregulated testicular mRNA relative expression levels of CYP11A1 and Nrf-2, compared to control. Testicular apoptosis was also prompted by increasing Bax/ Bcl-2 ratio in testicular tissue. Histopathological findings in the testes, epididymis, prostate gland, and seminal vesicle confirmed the detrimental effects of BPA. Interestingly, cZnO and ZnO-NPs significantly alleviated all negative effects of BPA, but ZnO-NPs performed better. In conclusion, our findings point to ZnO, specifically ZnO-NPs, as a viable treatment for BPA-induced testicular dysfunction.

The protective effects of date seeds, in either conventional or nanoformulation, against bisphenol A-induced testicular toxicity: involvement of testicular expression of CYP11A1, Nrf-2 and Bax/Bcl-2 ratio.

Background: Bisphenol A (BPA), an endocrine-disrupting chemical (EDC), is ubiquitous in our environment and poses a significant threat to male fertility. Date seeds (DSs) are used in folk medicine due to their antioxidant activity. Aim: The purpose of this study was to assess the beneficial effects of DSs, whether in powder or nanoparticle form, against BPA-induced testicular oxidative challenges and apoptosis, aided by inspection of specific genes linked to fertility, oxidative stress and intrinsic mitochondrial pathway of apoptosis. Methods: Thirty-five adult male albino rats were equally divided into 5 groups including control, BPA, BPA + date seeds powder "DSP", BPA + date seed nanoparticle 1/10 (DSNP 1/10) and BPA + DSNP 1/20 groups. Results: TEM showed that the ball-mill method was effective to form DSNP with an average size of 20 nm. BPA significantly impaired sperm motility, morphology, viability and concentration. It also reduced serum testosterone levels and evoked marked oxidative stress in the testes. Additionally, serum levels of triiodothyronine and thyroxine were extremely reduced. Moreover, testicular mRNA relative expression levels of CYP11A1 and Nrf-2 were markedly downregulated. Testicular apoptosis was also promoted whereas Bax/Bcl-2 ratio was profoundly elevated. Histological pictures of the testes, epididymis, seminal vesicles and prostate confirmed the unfavorable effects of BPA. Surprisingly, we first demonstrated that DSs, specifically the nanoparticle form, strongly alleviated all of BPA's negative effects, with DSNP 1/20 achieving the best results. Conclusion: Therefore, DSNP in both doses could be regarded as an ideal candidate for abating the male reproductive challenges caused by BPA.

Effects of dietary boron supplementation on the testicular function and thyroid activity in male goats: Involvement of CYP17A1 gene.

The physiological effects of dietary boron (B) supplementation for farm animals specifically goat on male fertility are still scarce and need deep investigation. Thus, the current study was designed to investigate how adding B to the diet of male goats affected their testicular and thyroid activity. For that purpose, twelve male goats were divided randomly into two groups (six animals each); control group that was fed the basal diet and B group that was fed the basal diet containing 70 mg B/kg diet for 6 months. Serum samples were collected at different intervals, while testicular biopsies were obtained at the end of the experiment. The results showed that 6 months of dietary B supplementation resulted in a significant increment in serum B concentration. The results of repeated measure analysis showed that there were significant GROUP and TIME × GROUP interactions effects on blood testosterone levels (F = 119.408, p = .000 and F = 6.794, p = .013, respectively), demonstrating that compared with control, B supplementation caused a significant rise in serum testosterone levels over time. However, the mean animal body weights and the serum levels of triiodothyronine (T3) and thyroxine (T4) were kept comparable with the control ones at the different time points. The most striking finding is that B supplementation increased significantly the mRNA expression of the CYP17A1 which is essential for steroidogenesis (p < .001). In addition, a histological examination of testicular tissue corroborated our findings and demonstrated that B supplementation had a positive effect. As a result, B might be considered an excellent food supplement that could be safely added to the male goats' diet at the current dose to improve their reproductive capacity.

Developmental Programming: Physiological Impacts of Prenatal Melatonin Administration on Reproductive Capacity and Serum Triiodothyronine of Adult Female Offspring Rat Born to Moms Exposed to Bisphenol A During Pregnancy.

Gestational bisphenol A (BPA) exposure induced multiple programmed diseases in the adult offsprings. Thus, this study targeted exploring the physiological impacts of melatonin (MEL) as a reprogramming strategy against in utero BPA exposure on reproductive capacity of adult F1 female rat offspring. Forty adult pregnant albino female rats were divided equally into 5 groups (n = 8): group I (control), group II (low-dose BPA; 25 µg BPA/kg B.w.t.), group III (low-dose BPA + 10 mg MEL/kg B.w.t.), group IV (high-dose BPA; 250 µg/kg B.w.t.), and group V (high-dose BPA + MEL). Treatments were given daily by subcutaneous (s/c) injection from the fourth day of pregnancy until full term. After delivery, female offspring were selected, and on postnatal day 60, adult offspring were examined for estrus regularity and then were sacrificed at estrus to collect blood and tissue samples. Findings clarified that in utero BPA exposure (both doses) increased significantly (P < 0.05) the ovarian weights and the serum levels of estrogen but decreased that of triiodothyronine (T3) compared to control groups. Significant increasing of serum malondialdehyde (MDA) and decreasing of total antioxidant capacity (TAC) were also detected. Both doses of BPA disturbed remarkably the estrus cycles and caused marked aberrations in ovarian and uterine tissues. Interestingly, prenatal MEL co-treatment with BPA mitigated significantly all of these degenerative changes. Thus, this study first demonstrated that prenatal MEL therapy could be used as a potent reprogramming intervention against BPA-induced reproductive disorders in the adult F1 female rat offspring.

Investigation of a dynamic measurement methodology for fast detection of gross defects in regularly distributed nuclear material samples.

Non-Destructive Assay (NDA) techniques are widely used to verify Nuclear Materials (NM). Most of these techniques are static ones for which, the measuring device and the assayed samples are located at fixed positions during measurements. While assaying regularly distributed NM, attenuation and screening effects may contribute negatively to the accuracy of the results, especially for relatively high density materials. Another factor that may affect the accuracy is the allowable time of measurement. Detection of gross defects in such materials could be achieved more accurately and much faster by employing dynamic measurements. In this work, an investigation for a proposed Non-Destructive Dynamic (NDD) measuring system is presented. The system is assumed to detect gross defects in nuclear fuel assemblies of EK-10 type more accurately and faster than other traditional systems based on static measurements. Different scenarios were considered and studied using the MCNP5 Code. The results showed that the investigated method could be easily applied to detect gross defects in regularly-distributed NM samples.

Study on the performance of different uranium isotopic codes used in nuclear safeguards activities.

Accurate characterization of Nuclear Materials (NMs) for nuclear safeguards purposes requires studying the optimal conditions over a wide range of experimental conditions. Gamma spectroscopy is commonly used to measure the 235U enrichment in NMs bearing samples. Several commercials Codes such as the Multi Group Analysis (MGA++), the Multi Group Analysis for Uranium (MGAU) and the "Fixed energy, Response function Analysis with Multiple efficiencies" (PC/FRAM) are used to measure 235U enrichment. Many factors, such as sample enrichment, density, homogeneity, geometry, and container type may affect the results of measurement. This work studies the effect of these factors on the performance of each of the three codes to estimate uranium enrichment. The results are compared to determine the optimum conditions and best performance among the three codes for achieving the most accurate estimation of 235U enrichment in the measured samples.

The impact of using newborn bovine serum as fetal calf serum substitute in the in vitro bovine embryos production system.

This study was conducted to assess the effects of addition of 10% newborn bovine serum (NBS) in the maturation and culture media of bovine system on oocytes maturation and developed morula and blastocyst rates. For this purpose, 10% NBS was added to in vitro maturation (IVM) medium alone (Experiment I), in vitro culture (IVC) (Experiment II), and in IVM + IVC (Experiment III). In vitro bovine oocytes maturation and developmental rates of bovine embryos were then compared with control group where the basal maturation or culture media were supplemented with 10% fetal calf serum (FCS). Results revealed that maturation, cleavage, morula, and blastocyst formation rates of in vitro fertilized embryos were not significantly different in NBS and control groups in the 3 experiments. In conclusion, NBS is an efficient macromolecule in bovine system when added either to IVM or to IVC or to both stages. Thus, NBS could provide cheaper and more available treatment to be used as FCS substitute in the IVC system of bovines.

PCR-RFLP of bone morphogenetic protein 15 (BMP15/FecX) gene as a candidate for prolificacy in sheep.

Bone morphogenetic protein 15 (BMP15/FecX) gene is considered one of the major genes and a candidate marker for the reproduction in farm animals, especially sheep. The present study aimed to detect the genetic polymorphisms of BMP15 gene in sheep using PCR-RFLP technique. In the present study, 115 ewes were assigned into high and low prolificacy categories according to their reproductive history. In high prolific group (n = 20), ewes produced twins more than single births. In the low prolific type (n = 95), the ewes produced single births more than twins. DNA was extracted from blood samples of all ewes, subjected to PCR-RFLP analysis and confirmed by sequence analysis. The PCR products of 356 bp size were cut with HinƒI restriction enzyme. Three digested fragments of 70, 117 and 169 bp were obtained in both types of sheep. All animals were homozygous with CC genotype. In conclusion, the accessible findings did not detect any mutation in FecX gene in sheep, regardless their prolificacy. Therefore, further attempts are necessary to detect other SNP for BMP-15 gene in Egyptian sheep breeds.

Enhancing ex vivo expansion of cord blood-derived unrestricted somatic stem cells for clinical applications.

OBJECTIVES: To study effects of serum-containing medium (SCM) versus serum-free medium (SFM) and influence of seeding density, on rate of expansion of cord blood (CB) unrestricted somatic stem cells (USSCs), as a prerequisite for evaluating their therapeutic potential in ongoing clinical trials. MATERIAL AND METHODS: Isolation, propagation and characterization of USSCs from CB samples were performed and followed by their passage 3 culture in SCM and SFM, at cell densities of 5, 50, 500 and 5000 cells/cm(2) . RESULTS: The cells were CD44(+) , CD90(+) , CD73(+) , CD105(+) , CD34(-) , CD45(-) , and HLA-DR, with Oct4 & Sox2 gene expression; they were differentiated into osteoblasts and adipocytes. USSCs cultured in SCM had significantly higher population doubling levels (P < 0.01) than those cultured in SFM. Those cultured in SCM at 5 cells/cm(2) and those cultured in SFM at 50 cells/cm(2) had significantly higher population doubling (P < 0.01) levels than those cultured at higher cell densities. CONCLUSIONS: For scaling up of USSCs from 106 (?) to 1012 (?) in 6 weeks, culturing of CB-derived cells of early passage (≤P3) in SCM at low cell seeding density (5 cells/cm(2) ) is suggested for increasing cell count with lower passaging frequency, followed by culture of expanded USSCs at 50 cells/cm(2) in SFM, to avoid undesirable effects of bovine serum in clinical applications.

Primary health care in the Eastern Mediterranean Region: from Alma-Ata to Doha.

The celebration in Doha of the 30th anniversary of the Alma-Ata Declaration at the International Conference on Primary Health Care renewed the commitment of the Eastern Mediterranean Region to primary health care as the tool for better health. The principles agreed at Alma-Ata in 1978 apply as much now as they did before. The event provided an opportunity for the Eastern Mediterranean countries to define future directions to steer the health systems to integrate primary health care and harness the intersectoral approach.

Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients.

BACKGROUND AND OBJECTIVE: Warfarin is a commonly used oral anticoagulant with a narrow therapeutic index and various genetic and clinical factors that influence interpatient variability in dose requirements. This study investigated the impact of genetic and nongenetic factors on warfarin dose requirements in Egyptians. METHODS: DNA was extracted from 207 patients taking warfarin for more than 2 months and genotyped for VKORC1 (3673 G>A), CYP2C9 *2*3*4*5*8, CYP4F2 (V33M; rs2108622), APOE (rs429358, rs7412), and CALU(rs339097) gene polymorphisms. Linear regression modeling was conducted to identify the genetic and nongenetic factors that independently influence warfarin dose requirements. RESULTS: VKORC1 3673 AA or GA genotype (P<0.0001), one or two variant alleles of CYP2C9 gene (P=0.0004), APOE ε2 haplotype (P=0.01), and increasing age (P<0.0001) were all associated with lower warfarin dose, whereas smoking (P=0.025) and pulmonary embolism (P=0.0059) showed association with higher warfarin doses. These factors explained 31% of the warfarin dose variability. This is the first independent confirmation of the association of the CALU rs339097 variant with higher warfarin dose requirement, although inclusion of this single nucleotide polymorphism in the multiple regression model failed to achieve significance (P=0.066). CYP4F2 (V33M) polymorphism was not significant (P=0.314), despite its high frequency in the studied population (42%). CONCLUSION: The study shows that VKORC1, CYP2C9 polymorphisms, APOE ε2 variant, and several clinical/demographic variables are important determinants of warfarin dose requirements in Egyptian patients. The percentage of variability explained by these factors is lower than in those of European ancestry, but similar to the variability explained in Asians and African ancestry.

Could the employment-based targeting approach serve Egypt in moving towards a social health insurance model?

The current health insurance system in Egypt targets the productive population through an employment-based scheme bounded by a cost ceiling and focusing on curative care. Egypt Social Contract Survey data from 2005 were used to evaluate the impact of the employment-based scheme on health system accessibility and financing. Only 22.8% of the population in the productive age range (19-59 years) benefited from any health insurance scheme. The employment-based scheme covered 39.3% of the working population and was skewed towards urban areas, older people, females and the wealthier. It did not increase service utilization, but reduced out-of-pocket expenditure. Egypt should blend all health insurance schemes and adopt an innovative approach to reach universal coverage.

Primary health care in the Eastern Mediterranean Region: from Alma-Ata to Doha

The celebration in Doha of the 30th anniversary of the Alma-Ata Declaration at the International Conference on Primary Health Care renewed the commitment of the Eastern Mediterranean Region to primary health care as the tool for better health. The principles agreed at Alma-Ata in 1978 apply as much now as they did before. The event provided an opportunity for the Eastern Mediterranean countries to define future directions to steer the health systems to integrate primary health carg and harness the intersectoral approach

Could the employment-based targeting approach serve Egypt in moving towards a social health insurance model?

The current health insurance system in Egypt targets the productive population through an employment-based scheme bounded by a cost ceiling and focusing on curative care. Egypt Social Contract Survey data from 2005 were used to evaluate the impact of the employment-based scheme on health system accessibility and financing. Only 22.8% of the population in the productive age range [19-59 years] benefited from any health insurance scheme. The employment-based scheme covered 39.3% of the working population and was skewed towards urban areas, older people, females and the wealthier. It did not increase service utilization, but reduced out-of-pocket expenditure. Egypt should blend all health insurance schemes and adopt an innovative approach to reach universal coverage

Radiological study of exposure levels in El Maghara underground coal mine.

Coal is largely composed of organic matter, but it is the inorganic matter in coal minerals and trace elements that have been cited as possible causes of health, environmental and technological problems associated with the use of coal. Some trace elements in coal are naturally radioactive. These radioactive elements include uranium (U), thorium (Th) and their numerous decay products, including radium (Ra) and radon (Rn). Although these elements are less chemically toxic than other coal constituents, such as arsenic, selenium or mercury, questions have been raised concerning the possible risk from radiation. In order to accurately address these questions and to predict the mobility of radioactive elements during the coal fuel cycle, it is important to determine the specific activity, distribution and form of radioactive elements in coal. The assessment of the radiation exposure from coal burning is critically dependent on the specific activity of radioactive elements in coal and in the fly ash that remains after combustion. The El-Maghara coal mine is the only producing coal mine in Egypt. It is located in the middle of the Sinai desert about 250 km north-east of Cairo, where a coal-fired power plant is intended to be built. In this study, a pre-operational radiological baseline of the site and the occupational radiation exposures due to radon progeny in the mine were determined. The specific activities of 226Ra, 232Th and 40K in soil and coal dust samples collected along the main gallery ranges were found to be 6-22.9, 9.6-47.3 and 77-489 Bq kg-1, respectively. Soil samples collected around the mine showed concentrations of 226Ra, 232Th and 40K in the ranges 2.7-20.2, 3.2-12.6 and 14.6-201 Bq kg-1, respectively. All of the mean values of radon progeny were lower than the action levels for working places recommended in the International Commission on Radiological Protection (ICRP) 65.

Uranium bioassay and radioactive dust measurements at some uranium processing sites in Egypt--health effects.

The safety of radiation workers in the uranium mining industry requires close and continuous monitoring of their working conditions. In this study, external radiation surveillance, radioactive dust monitoring and the bioassay of uranium were carried out in some processing sites. As dust represents one of the most important sources of radiation exposure in mills and mines, dust monitoring and bioassays were performed for a sample of workers on the production lines. The concentration of uranium in air ranged from 22.6 x 10(-7) to 11.1 x 10(-5) Bq cm-3, and the exposure levels ranged from 1 to 80 microSv h-1. Laser fluorimetric determination of uranium in urine samples showed concentrations in the range 8.4-29.2 micrograms L-1. Renal function parameters, such as serum creatinine and urea, and hematological parameters were determined in an attempt to correlate them with radiation exposure and the health status of the workers. Urine specimens collected from workers at the ore crushing and separation site showed elevated concentrations of uranium (up to 29.2 micrograms L-1) and a strong correlation between these concentrations and the registered serum creatinine. The mean uranium excretion in the investigated group was more than 20 times the occupational exposure decision level for urine uranium of 0.8 microgram L-1.

Depleted uranium: an overview of its properties and health effects.

There has been much debate about the use of depleted uranium in the Gulf War and its health effects on United States and European war veterans. However, studies on the impact of this radioactive substance on the residents of the surrounding Gulf region are far from adequate. Depleted uranium introduces large quantities of radioactive material that is hazardous to biological organisms, continues to decay for millennia and is able to travel tens of kilometres in air. If depleted uranium were used in the Gulf War, its impact on the health of people in the area would have been considerable. This review of depleted uranium--its origin, properties, uses and effects on the human environment and health--aims to trigger further research on this subject.

Depleted uranium: an overview of its properties and health effects

There has been much debate about the use of depleted uranium in the Gulf War and its health effects on United States and European war veterans. However, studies on the impact of this radioactive substance on the residents of the surrounding Gulf region are far from adequate. Depleted uranium introduces large quantities of radioactive material that is hazardous to biological organisms, continues to decay for millennia and is able to travel tens of kilometres in air. If depleted uranium were used in the Gulf War, its impact on the health of people in the area would have been considerable. This review of depleted uranium-its origin, properties, uses and effects on the human environment and health-aims to trigger further research on this subject

Going beyond the curriculum to promote medical education and practice in Saudi Arabia.

The foundation of health starts as early as undergraduate medical education. Medical education in the Kingdom has always been successful in promoting the medical profession and population health. The current issue in the Kingdom is quality assurance in all organizations including the health field. Thus emerges the value of evaluating the efficiency and effectiveness of the current system in meeting health needs and expectations. The aim of this paper was to analyze the current situation in order to design a frame for the direction of promotion of medical education and practice that best meets health needs and expectations. In fact, medical practice is a multidisciplinary process that is showing continuously changing theories. It has a broad scope of serving the whole community and improving the quality of life of all population categories. The huge quantity of information, needed to be retained by medical professionals, necessitates the move away from traditional methods of education to more practical and comprehensive programs of study. Most of the recent reform in medical education, in the Kingdom, has focused on curriculum and disregarded the education process. The requisite for the education process is a complete model of community-based health care, education and research. This study proposes a design aiming to enhance medical education and promote the medical profession, through developing the quality of medical professionals, that will foster growth of their activity and productivity, moving them into the community where clinical practice and experience are more relevant to the true health situation.

Characteristics of NORM in the oil industry from eastern and western deserts of Egypt.

Naturally occurring radionuclides (NORs) from the 232Th- and 238U-series, which are omnipresent in the earth's crust, can be concentrated by technical activities, particularly those involving natural resources. Although, a great deal of work has been done in the field of radiation protection and remedial action on uranium and other mines, recent concern has been devoted to the hazard arising from naturally occurring radioactive materials (NORM) in oil and gas facilities. NORM wastes associated with oil and gas operations from scale deposits, separated sludge and water at different oil fields in the eastern and western deserts were investigated. Concentrations of the uranium, thorium, and potassium (40K) series have been determined from high-resolution gamma-ray spectrometry. Total uranium content of samples was determined using laser fluorimetry. The levels of radioactivity were mainly due to enhanced levels of dissolved radium ions. Only minute quantities of uranium and thorium were present. The disequilibrium factor for 238U/226Ra has been determined.