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The epididymis is divided into three regions including the caput, corpus and cauda. Gene expression profiles in different regions indicate the different functions of epididymis which are crucial for sperm maturation. In this study, three one-year-old rams was used as the experimental animal. Transcriptome sequencing technology was used to sequence mRNA in the caput, corpus and cauda of the epididymis. Based on the spatiotemporal-specific expression pattern in the epididymis, the mRNA expression profiles of the three parts of the epididymis were analysed. Region-specifically expressed genes were analysed by GO and KEGG analyses to screen the key genes involved in sheep sperm maturation. We obtained 129, 54 and 99 specifically expressed genes in the caput, corpus and cauda, respectively. And twenty specific expressed genes related to sperm maturation were used to construct functional networks. The heatmap showed that 6 genes of LCN protein family were highly expressed in the head of epididymis of sheep. We infer that sperm maturation is gradual in the epididymis and that there are significant differences in epididymal gene expression patterns between different species. This provides a data resource for analysing the regulatory mechanism of epididymis genes related to sperm maturation in rams. [ABSTRACT FROM AUTHOR]

Mg2+ is an important cation in our body. It is an essential cofactor for many enzymes. Despite many works, nothing is known about the protective effects of MgSO4 against hypoxia-induced lethality and oxidative damage in brain mitochondria. In this study, antihypoxic and antioxidative activities of MgSO4 were evaluated by three experimental models of induced hypoxia (asphyctic, haemic, and circulatory) in mice. Mitochondria protective effects of MgSO4 were evaluated in mouse brain after induction of different models of hypoxia. Antihypoxic activity was especially pronounced in asphyctic hypoxia, where MgSO4 at dose 600 mg/kg showed the same activity as phenytoin, which used as a positive control (P < 0.001). In the haemic model, MgSO4 at all used doses significantly prolonged latency of death. In circulatory hypoxia, MgSO4 (600 mg/kg) doubles the survival time. MgSO4 significantly decreased lipid peroxidation and protein carbonyl and improved mitochondrial function and glutathione content in brain mitochondria compared to the control groups. The results obtained in this study showed that MgSO4 administration has protective effects against lethality induced by different models of hypoxia and improves brain mitochondria oxidative damage. [ABSTRACT FROM AUTHOR]

Background: Children born extremely preterm are at heightened risk for intellectual and social impairment, including Autism Spectrum Disorder (ASD). There is increasing evidence for a key role of the placenta in prenatal developmental programming, suggesting that the placenta may, in part, contribute to origins of neurodevelopmental outcomes. Methods: We examined associations between placental transcriptomic and epigenomic profiles and assessed their ability to predict intellectual and social impairment at age 10 years in 379 children from the Extremely Low Gestational Age Newborn (ELGAN) cohort. Assessment of intellectual ability (IQ) and social function was completed with the Differential Ability Scales-II and Social Responsiveness Scale (SRS), respectively. Examining IQ and SRS allows for studying ASD risk beyond the diagnostic criteria, as IQ and SRS are continuous measures strongly correlated with ASD. Genome-wide mRNA, CpG methylation and miRNA were assayeds with the Illumina Hiseq 2500, HTG EdgeSeq miRNA Whole Transcriptome Assay, and Illumina EPIC/850 K array, respectively. We conducted genome-wide differential analyses of placental mRNA, miRNA, and CpG methylation data. These molecular features were then integrated for a predictive analysis of IQ and SRS outcomes using kernel aggregation regression. We lastly examined associations between ASD and the multi-omic-predicted component of IQ and SRS. Results: Genes with important roles in neurodevelopment and placental tissue organization were associated with intellectual and social impairment. Kernel aggregations of placental multi-omics strongly predicted intellectual and social function, explaining approximately 8% and 12% of variance in SRS and IQ scores via cross-validation, respectively. Predicted in-sample SRS and IQ showed significant positive and negative associations with ASD case–control status. Limitations: The ELGAN cohort comprises children born pre-term, and generalization may be affected by unmeasured confounders associated with low gestational age. We conducted external validation of predictive models, though the sample size (N = 49) and the scope of the available out-sample placental dataset are limited. Further validation of the models is merited. Conclusions: Aggregating information from biomarkers within and among molecular data types improves prediction of complex traits like social and intellectual ability in children born extremely preterm, suggesting that traits within the placenta-brain axis may be omnigenic. [ABSTRACT FROM AUTHOR]

Copyright of Journal of King Abdulaziz University: Science is the property of King Abdulaziz University, Scientific Publishing Centre and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Preeclampsia (PE) is a complication during pregnancy that is diagnosed by a new onset of hypertension and proteinuria. Although the pathogenesis of PE is not fully understood, a growing body of evidence indicates that oxidative stress and mitochondrial dysfunction might contribute to the progression of PE. Therefore, the aim of the present study was to determine the role of mitophagy in mitochondrial dysfunction and oxidative stress in PE, and to evaluate the role of DNA damage-regulated autophagy modulator 1 (DRAM1) in the development of PE. First, a mouse model of PE induced by hypoxia-inducible factor 1α was established, and high levels of oxidative stress, apoptosis and mitochondrial dysfunction were found in the placentas of PE mice. Additionally, the placentas of PE mice exhibited decreased mitophagy and significantly decreased DRAM1 expression. To further explore the role of DRAM1 in mitophagy, DRAM1 was overexpressed in the placental tissues of PE mice, and this overexpression effectively improved the symptoms of PE mice and significantly reduced blood lipid and urine protein levels. DRAM1 overexpression also improved mitochondrial function and reduced oxidative stress in the placentas of PE mice. In addition, the overexpression of DRAM1 improved mitochondrial fusion and fission, and enhanced mitophagy. Altogether, these results indicated a key role for DRAM1 in mitophagy that contributed to the regulation of PE. To the best of the authors' knowledge, the present study provided the first evidence of a role for DRAM1 in PE, and offered novel insight into the pathophysiological mechanisms of PE. [ABSTRACT FROM AUTHOR]

Unbalanced inflammatory reactions and oxidative stress are inseparably interconnected, and both may play crucial roles in the pathophysiological mechanisms of preeclampsia (PE). In the published previous studies, we have genotyped for SNPs that related to inflammation (rs2227485, rs153109, rs17855750, rs2027432, rs2275913, rs763780, rs4819554, and rs13015714) and oxidative stress (rs1695, rs4680, rs1800566, rs4807542, rs713041, rs7579, rs230813, rs1004467, rs3824755, and rs9932581) to investigate whether these polymorphisms were associated with susceptibility to PE in a Chinese Han population. In this present study, we collected these data of experimental and clinical from above studies for haplotype analysis of inflammation-related SNPs in 631 PE patients and 720 normal pregnancy and oxidative stress-related SNPs in 342 PE patients and 457 normal pregnancies for susceptibility to PE. The data of genotype distribution and allele frequency comparisons after correction for multiple comparisons (P/8 or P/10) showed 2 among the 8 candidate inflammation-related SNPs have significant differences (rs2027432 genotype χ2 = 407.377, p < 0.001, p < 0.00625). Moreover, the minor alleles of rs2027432 T (minor allele χ2 = 450.923, p < 0.001, p < 0.00625; OR = 21.439, 95%CI = 15.181-30.278) and rs4819554 G (minor allele χ2 = 163.465, p < 0.001, p < 0.00625; OR = 5.814, 95%CI = 4.380-7.719) were confirmed as risk allele of PE, respectively. Our analysis revealed rs2027432 (TT) of NLRP3 and rs4819554 (GG) of IL-17RA are risk factors for PE. However, no significant difference was found at the oxidative stress-related SNPs. In the candidate loci for oxidative stress, we also identified 3 SNP matches (rs4807542 and rs713041, rs230813 and rs75799, rs1004467 and rs3824755) that had high linkage disequilibrium (LD) with each other and were selected as a block (r2 = 0.98, r2 = 0.97, r2 = 0.97, r2 > 0.9), and the GT and GC haplotypes of rs4807542 and rs713041 in GPX4 showed significant differences between the PE and control groups (χ2 = 5.143, p = 0.0233, p < 0.05; χ2 = 6.373, p = 0.0116, p < 0.05). So, we inferred that polymorphisms of NLRP3 rs2027432 and IL-17RA rs4819554, which are related to inflammation, and the rs713041 variant of GPX4, which is related to oxidative stress, were associated with susceptibility to PE. The GT and GC haplotypes of rs4807542 and rs713041 in GPX4 may increase the risk of PE in the Chinese Han population. [ABSTRACT FROM AUTHOR]

Objective: To assess whether supplementation with Coenzyme Q10 (CoQ10) during pregnancy alleviate preeclampsia symptoms and the underlying mechanism in the rats with preeclampsia. Methods: Forty-five pregnant Wistar rats were equally divided into three groups randomly and received subcutaneous saline injection (control group, n = 15) or 200 mg/kg L-NAME injection to induce preeclampsia symptoms (PE group, n = 30). The PE rats were treated by distilled water (PE+DW group, n = 15) and CoQ10 (PE+CoQ10 group, n = 15) on day 15 to 21 of gestation randomly. Physiological characteristics such as urine volume, total urine protein, blood pressure, number and weight of pups were recorded. Fluorescent dye was used to detect mitochondrial membrane potential in placenta. Real-time fluorescent quantitative PCR was used to detect the expression of mitochondrial DNA(mtDNA) in placenta. Results: There was no statistic difference among all the three groups on day 10 of gestation in SBP and 24-h proteinuria (P > 0.05). Whereas, SBP and 24-h proteinuria were significantly higher in PE group than control group on day 15 and 21 of gestation (P < 0.05). SBP and 24-h proteinuria were significantly lower in PE+CoQ10 group than PE+DW group on day 21 of gestation (P < 0.05). The number and weight of normal pups were significantly lower in PE group than the control group (P < 0.05), which were most notably in distilled water group, and the number and weight of normal pups were markedly bigger in PE+CoQ10 group rats compared to PE+DW (P < 0.05). The PE+CoQ10 group showed a significantly higher in level of mitochondrial membrane potential than PE+DW group. The expression of mtDNA was significantly higher in the PE+CoQ10 group compared with PE+DW group (P < 0.05). Conclusions: CoQ10 can alleviate preeclampsia symptoms and enhance the function of mitochondria in the placenta. [ABSTRACT FROM AUTHOR]

Background/Aims: Magnesium, whose supplementation provides beneficial effects against oxidative stress-related conditions, has been here used to possibly protect Band 3 protein anion exchange capability and underlying signaling in an in vitro model of oxidative stress. Methods: Whole blood samples pre-exposed to 10 mM MgCl2, were treated for 30 min with H2O2 (300 µM, 600 µM and 1 mM) chosen as oxidant molecule. In a separate protocol, NEM (0.5,1 and 2 mM), a phosphatase inhibitor and thiol-alkilant agent, has been also applied. The rate constant for SO4= uptake, accounting for Band 3 protein anion exchange capability, has been measured by a turbidimetric method, while intracellular reduced glutathione (GSH) levels and membrane –SH groups mostly belonging to Band 3 protein were spectrophotometrically quantified after reaction with DTNB (5,5'-dithiobis-(2-nitrobenzoic acid). Expression levels of Band 3 protein, phosporylated Tyrosine (P-Tyr) and tyrosine kinase (Syk) involved in signaling have been also measured. Results: Our results show that Mg2+ prevented the reduction in the rate constant for SO4= uptake on H2O2-treated erythrocytes, not involving GSH levels and membrane -SH groups, unlike NEM, remaining both P-Tyr and Syk expression levels high. Conclusion: Hence, i) the measurement of the rate constant for SO4= uptake is a useful tool to evaluate Mg2+ protective effect; ii) the use of two different oxidant molecules shed light on Mg2+ effect which seems not to modulate phosphorylative pathways but would putatively stabilize membrane organization; iii) the use of Mg2+ in food supplementation can be reasonably supported to protect erythrocytes homeostasis in case of oxidative stress-related diseases. [ABSTRACT FROM AUTHOR]

Low-molecular weight heparins (LMWH) are anticoagulants that have shown anti-inflammatory activity in several experimental models. Hot water burn inflammatory model accurately simulates human clinical situations allowing its use for nociception test and evaluation of anti-inflammatory drugs. The present study aims to evaluate the enoxaparin pretreatment on local and systemic inflammation biomarkers in the animal burn model. Inflammation was induced by submersing the rat left hind paw in water at 60o C for 60 s. C-reactive protein (CRP) and thrombin–antithrombin complex (TAT) were estimated by immunosorbent assay, fibrinogen (Fg) by the gravimetric method and paw oedema by orthogonal digital photography. Highest values of paw oedema, CRP and TAT were observed at 4 h post-burn while Fg peak occurs at 12 h post-burn; enoxaparin pretreatment decreased oedema (− 32.1%), and concentration of TAT (− 66.7%), PCR (− 37.9%) and Fg (− 8%). This study shows that enoxaparin has local and systemic anti-inflammatory effects and should be considered as a potential adjuvant drug for the treatment of burns. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the changes in plasma membrane Ca2+-ATPase (PMCA) and sarcoendoplasmic reticulum CA2+-ATPase (SERCA-2) according to the antepartal magnesium sulfate (MgSO4) administration in the placentas from pregnancies with pre-eclampsia (PE) or fetal growth restriction (FGR). Pregnant women were classified as follows: (group 1) pregnancies without PE or FGR (n=16), (group 2) pregnancies with PE or FGR but without MgSO4 administration (n=14), and (group 3) pregnancies with PE or FGR and with MgSO4 administration (n=28). We observed the localization of PMCA and SERCA-2 in placentas and compared its expression among 3 groups. And we observed its expression in BeWo cells following treatment with MgSO4 and CoCl2 PMCA staining was more observed in the basal membrane, whereas SERCA-2 staining was observed predominantly under the microvillous membrane. SERCA-2 expression was significantly increased in group 3 compared with that in group 1. Considering the gestational age at delivery, PMCA expression was increased in group 2 and group 3 compared with that in group 1 after 36 weeks of gestation. SERCA-2 was increased in group 3, but not in group 2 compared with that in group 1 after 36 weeks of gestation. In BeWo cells, MgSO4 treatment increased PMCA and SERCA-2 expression. PMCA expression was influenced by gestational age at delivery, and SERCA-2 expression was increased in the presence of PE and antepartal MgSO4 administration. This indicates that antepartal MgSO4 administration has a greater influence on SERCA-2 than PMCA. [ABSTRACT FROM AUTHOR]

Copyright of Parasite (1252607X) is the property of EDP Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Canadian Journal of Physiology & Pharmacology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Endogenous digitalis-like factor(s), originally proposed as a vasoconstrictor natriuretic hormone, was discovered in fetal and neonatal blood accidentally because it cross-reacts with antidigoxin antibodies (ADAs). Early studies using immunoassays with ADA identified the digoxin-like immuno-reactive factor(s) (EDLF) in maternal blood as well, and suggested it originated in the feto-placental unit. Mammalian digoxin-like factors have recently been identified as at least two classes of steroid compounds, plant derived ouabain (O), and several toad derived bufodienolides, most prominent being marinobufagenin (MBG). A synthetic pathway for MBG has been identified in mammalian placental tissue. Elevated maternal and fetal EDLF, O and MBG have been demonstrated in preeclampsia (PE), and inhibition of red cellmembrane sodium, potassium ATPase (Na, K ATPase (NKA)) by EDLF is reversed by ADA fragments (ADA-FAB). Accordingly, maternal administration of a commercial ADA-antibody fragment (FAB) was tested in several anecdotal cases of PE, and two, small randomized, prospective, double-blind clinical trials. In the first randomized trial, ADA-FAB was administered post-partum, in the second antepartum. In the post-partum trial, ADA-FAB reduced use of antihypertensive drugs. In the second trial, there was no effect of ADA-FAB on blood pressure, but the fall in maternal creatinine clearance (CrCl) was prevented. In a secondary analysis using the pre-treatment maternal level of circulating Na, K ATPase (NKA) inhibitory activity (NKAI), ADA-FAB reduced the incidence of pulmonary edema and, unexpectedly, that of severe neonatal intraventricular hemorrhage (IVH). The fall in CrCl in patients given placebo was proportional to the circulating level of NKAI. The implications of these findings on the pathophysiology of the clinical manifestations PE are discussed, and a new model of the respective roles of placenta derived anti-angiogenic (AAG) factors (AAGFs) and EDLF is proposed. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Zoology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Magnesium is the fourth most abundant cation in the body. It has several functions in the human body including its role as a cofactor for more than 300 enzymatic reactions. Several studies have shown that hypomagnesemia is a common electrolyte derangement in clinical setting especially in patients admitted to intensive care unit where it has been found to be associated with increase mortality and hospital stay. Hypomagnesemia can be caused by a wide range of inherited and acquired diseases. It can also be a side effect of several medications. Many studies have reported that reduced levels of magnesium are associated with a wide range of chronic diseases. Magnesium can play important therapeutic and preventive role in several conditions such as diabetes, osteoporosis, bronchial asthma, preeclampsia, migraine, and cardiovascular diseases. This review is aimed at comprehensively collating the current available published evidence and clinical correlates of magnesium disorders. [ABSTRACT FROM AUTHOR]

C11-BODIPY 581/591 is a fluorescent probe that has been successfully used to evaluate lipid peroxidation in different species, but it has not been completely studied in the dog. Thus, the aim of the present study was to assess lipid peroxidation of dog spermatozoa using C11-BODIPY 581/591 and compare different positive controls of the technique. Twenty-four ejaculates were collected from 8 adult male dogs. Routine seminal characteristics were evaluated in raw semen. Lipid peroxidation evaluation was performed as described in other species. Samples were divided in three aliquots, exposed to UV radiation, incubated with hydrogen peroxide or left without treatment (control). Lipid peroxidation was significantly greater only in UV-exposed samples than in the control ones (91 ± 6% vs. 8.3 ± 3.5%, p ˂ .01). In conclusion, C11-BODIPY 581/591 is useful to evaluate lipid peroxidation of dog spermatozoa and UV radiation is a good promoter of membrane oxidation, so irradiated samples can be used as a positive control of this technique., (© 2021 Wiley-VCH GmbH.)

Epinephrine, a key stress hormone, is known to affect ion transport in the colon. Stress has been associated with alterations in colonic functions leading to changes in water movements manifested as diarrhea or constipation. Colonic water movement is driven by the Na+-gradient created by the Na+/K+-ATPase. Whether epinephrine acts via an effect on the Na+/K+-ATPase hasn’t been studied before. The aim of this work was to investigate the effect of epinephrine on the Na+/K+-ATPase and to elucidate the signaling pathway involved using CaCo-2 cells as a model. The activity of the Na+/K+-ATPase was assayed by measuring the amount of inorganic phosphate released in presence and absence of ouabain, a specific inhibitor of the enzyme. Epinephrine, added for 20 minutes, decreased the activity of the Na+/K+-ATPase by around 50%. This effect was found to be mediated by α2 adrenergic receptors as it was fully abolished in the presence of yohimbine an α2-blocker, but persisted in presence of other adrenergic antagonists. Furthermore, treatment with Rp-cAMP, a PKA inhibitor, mimicked epinephrine’s negative effect and didn’t result in any additional inhibition when both were added simultaneously. Treatment with indomethacin, PP2, SB202190, and PD98059, respective inhibitors of COX enzymes, Src, p38MAPK, and ERK completely abrogated the effect of epinephrine. The effect of epinephrine did not appear also in presence of inhibitors of all four different types of PGE2 receptors. Western blot analysis revealed an epinephrine-induced increase in the phosphorylation of p38 MAPK and ERK that disappeared in presence of respectively PP2 and SB2020190. In addition, an inhibitory effect, similar to that of epinephrine’s, was observed upon incubation with PGE2. It was concluded that epinephrine inhibits the Na+/K+-ATPase by the sequential activation of α2 adrenergic receptors, Src, p38MAPK, and ERK leading to PGE2 release. [ABSTRACT FROM AUTHOR]

Reduced sperm motility (asthenospermia) and resulting infertility arise from deletion of the Plasma Membrane Ca2+-ATPase 4 ( Pmca4) gene which encodes the highly conserved Ca2+ efflux pump, PMCA4. This is the major Ca2+ clearance protein in murine sperm. Since the mechanism underlying asthenospermia in PMCA4's absence or reduced activity is unknown, we investigated if sperm PMCA4 negatively regulates nitric oxide synthases (NOSs) and when absent NO, peroxynitrite, and oxidative stress levels are increased. Using co-immunoprecipitation (Co-IP) and Fluorescence Resonance Energy Transfer (FRET), we show an association of PMCA4 with the NOSs in elevated cytosolic [Ca2+] in capacitated and Ca2+ ionophore-treated sperm and with neuronal (nNOS) at basal [Ca2+] (ucapacitated sperm). FRET efficiencies for PMCA4-eNOS were 35% and 23% in capacitated and uncapacitated sperm, significantly ( p < 0.01) different, with the molecules being <10 nm apart. For PMCA4-nNOS, this interaction was seen only for capacitated sperm where FRET efficiency was 24%, significantly ( p < 0.05) higher than in uncapacitated sperm (6%). PMCA4 and the NOSs were identified as interacting partners in a quaternary complex that includes Caveolin1, which co-immunoprecipitated with eNOS in a Ca2+-dependent manner. In Pmca4−/− sperm NOS activity was elevated twofold in capacitated/uncapacitated sperm (vs. wild-type), accompanied by a twofold increase in peroxynitrite levels and significantly ( p < 0.001) increased numbers of apoptotic germ cells. The data support a quaternary complex model in which PMCA4 co-ordinates Ca2+ and NO signaling to maintain motility, with increased NO levels resulting in asthenospermia in Pmca4−/− males. They suggest the involvement of PMCA4 mutations in human asthenospermia, with diagnostic relevance. [ABSTRACT FROM AUTHOR]

Leishmania amazonensis promastigotes are known to express furosemide (Lasix®)-sensitive P-type membrane Na+-ATPase. In the present study, furosemide activity was studied in intracellular amastigotes and infected BALB/c mice to investigate its efficacy in cutaneous leishmaniasis (CL). Intracellular parasites, but not macrophages, were found to be sensitive to killing by furosemide (IC50 = 87 µmvs CC50 ≫ 1000 µm, respectively). Although furosemide did not induce nitric oxide production or intracellular pH changes in infected macrophages, it led to a significant reactive oxygen species (ROS) burst. Freshly isolated tissue parasites expressed a high degree of Na+-ATPase activity that decreased with culture, indicative of a higher enzyme expression in amastigotes than in promastigotes. Both intraperitoneal and oral treatment of L. amazonensis-infected mice with furosemide dosages equivalent to that prescribed as a diuretic significantly reduced the parasite's growth compared with the situation in untreated mice. Combination with oral furosemide increased the efficacy and safety of intraperitoneal treatment with sodium stibogluconate (SSG). To summarize, furosemide control of intracellular leishmanial growth by means of parasite Na+-ATPase inhibition, and macrophage ROS activation may help explain its sole and SSG-combined therapeutic effect against murine CL. [ABSTRACT FROM PUBLISHER]

The Catsper channel is a sperm-specific, Ca2+ -permeable, pH-dependent, and low voltage-dependent channel that is essential for the hyperactivity of sperm flagellum, chemotaxis towards the egg, capacitation and acrosome reaction. All of these physiological events require calcium entry into sperm cells. Remarkably, Catsper genes are exclusively expressed in the testis during spermatogenesis, and are sensitive to ion channel-induced pH change, such as NHEs, Ca2+ATPase, K+ channel, Hv1 channel and HCO3 - transporters. Furthermore, the Catsper channel is regulated by some physiological stimulants, such as progesterone, cyclic nucleotides (e.g., cAMP, cGMP), zona pellucida (ZP) glycoproteins and bovine serum albumin (BSA). All of these factors normally stimulate Ca2+ entry into sperm through the Catsper channel. In addition, the Catsper channel may be a potential target for male infertility treatment or contraception. This review will focus on the structure, functions, regulation mechanisms and medicinal targets of the Catsper channel. [ABSTRACT FROM AUTHOR]

Ethanol plays a detrimental role in the development of the brain. Multiple studies have shown that ethanol inhibits insulin-like growth factor I receptor (IGF-IR) function. Because the IGF-IR contributes to brain development by supporting neural growth, survival, and differentiation, we sought to determine the molecular mechanism(s) involved in ethanol's effects on this membrane-associated tyrosine kinase. Using multiple neuronal cell types, we performed Western blot, immunoprecipitation, and GST-pulldowns following acute (1-24 h) or chronic (3 weeks) treatment with ethanol. Surprisingly, exposure of multiple neuronal cell types to acute (up to 24 h) ethanol (50 mM) enhanced IGF-I-induced phosphorylation of extracellular regulated kinases (ERKs), without affecting IGF-IR tyrosine phosphorylation itself, or Akt phosphorylation. This acute increase in ERKs phosphorylation was followed by the expected inhibition of the IGF-IR signaling following 3-week ethanol exposure. We then expressed a GFP-tagged IGF-IR construct in PC12 cells and used them to perform fluorescence recovery after photobleaching (FRAP) analysis. Using these fluorescently labeled cells, we determined that 50 mM ethanol decreased the half-time of the IGF-IR-associated FRAP, which implied that cell membrane-associated signaling events could be affected. Indeed, co-immunoprecipitation and GST-pulldown studies demonstrated that the acute ethanol exposure increased the recruitment of p52-Shc to the Grb2-Shc complex, which is known to engage the Ras-Raf-ERKs pathway following IGF-1 stimulation. These experiments indicate that even a short and low-dose exposure to ethanol may dysregulate function of the receptor, which plays a critical role in brain development. J. Cell. Physiol. 232: 1275-1286, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The common cuttlefish (Sepia officinalis), a dominant species in the north-east Atlantic ocean and Mediterranean Sea, is potentially subject to hypoxic conditions due to eutrophication of coastal waters and intensive aquaculture. Here we initiate studies on the biochemical response to an anticipated level of hypoxia. Cuttlefish challenged for 1 h at an oxygen level of 50% dissolved oxygen saturation showed a decrease in oxygen consumption of 37% associated with an 85% increase in ventilation rate. Octopine levels were increased to a small but significant level in mantle, whereas there was no change in gill or heart. There were no changes in mantle free glucose or glycogen levels. Similarly, the hypoxic period did not result in changes in HSP70 or polyubiquinated protein levels in mantle, gill, or heart. As such, it appears that although there was a decrease in metabolic rate there was only a minor increase in anaerobic metabolism as evidenced by octopine accumulation and no biochemical changes that are hallmarks of alterations in protein trafficking. Experiments with isolated preparations of mantle, gill, and heart revealed that pharmacological inhibition of protein synthesis could decrease oxygen consumption by 32 to 42% or Na+/K+ ATPase activity by 24 to 54% dependent upon tissue type. We propose that the decrease in whole animal oxygen consumption was potentially the result of controlled decreases in the energy demanding processes of both protein synthesis and Na+/K+ ATPase activity. [ABSTRACT FROM AUTHOR]

Objective: To compare serum ferritin (SF) concentrations and other hematological parameters between patients with preeclampsia (PE) and normal pregnant women of the same gestational period who received supplemental iron during pregnancy. Methods: Prospective, comparative, observational pilot study that included 31 women with PE and 30 healthy pregnant women, at 20 weeks’ of gestation. Ferritin, iron and complete blood cell count were compared between groups. Results: In comparison with controls, preeclamptic patients had a higher weight, body mass index, and arterial pressure. Serum ferritin and serum iron were higher in patients with PE (median: 36.5 μg/l vs. 20.9 μg/l and 103.9 μg/dl vs. 90.8 μg/dl) with a significant difference (P = 0.019 andP = 0.345). SF values >40 μg/l correlated with PE (r = 0.281;P = 0.032). A platelet count less than 100 × 109/l was higher in the PE group than in the control group (13% vs. 3%,P = 0.354). Conclusion: Higher SF levels, despite being within normal range, were associated with PE. The incidence of thrombocytopenia was higher in preeclamptic women, however, the remaining hematological parameters were similar in both groups. [ABSTRACT FROM AUTHOR]

During pregnancy, the placenta is a site of active oxygen metabolism that continuously generates oxidative stress ( OS). Overproduction of reactive oxygen species and reactive nitrogen species can destroy normal placental functions. Therefore, the feto-placental unit generates abundant antioxidants to keep OS under control. Properly controlled oxidative species have been proven to serve as indispensable cellular signal messengers by regulating gene expression and downstream cellular activities. OS also plays an important immunoregulatory role during pregnancy. Oxidative disorder and immune disturbances are associated with adverse pregnancy outcomes such as spontaneous abortion, preeclampsia and intrauterine growth restriction. In this review, we introduce recent studies revealing basal functions and regulatory roles of placental OS in metabolism and immunity. The relationships between OS- and pregnancy-related disorders are also discussed. [ABSTRACT FROM AUTHOR]

An 8 weeks feeding trial was conducted to investigate the effect of dietary cerium (Ce) and its complex with chitosan oligosaccharide ( COS-Ce) on growth performance and cadmium (Cd) accumulation of turbot, Scophthalmus maximus L. under Cd stress. The basal diet (Diet 0) was formulated without Cd and cerium as the control. Seven other experimental diets (Diets 1-7) were formulated with supplementation of 50 mg Cd2+/kg feed, 50 mg Cd2+/kg and 50 mg Ce3+/kg feed, 50 mg Cd2+/kg and 100 mg Ce3+/kg feed, 50 mg Cd2+/kg and 200 mg Ce3+/kg feed, 50 mg Cd2+/kg and 50 mg COS-Ce/kg feed, 50 mg Cd2+/kg and 100 mg COS-Ce/kg feed, and 50 mg Cd2+/kg +200 mg COS-Ce/kg feed. Results of the present study showed that, compared with the control group, the condition factor in fish fed the diet with 50 mg Cd2+/kg feed (Diet 1) was significantly lower, whereas the Cd concentration in liver and kidney of fish fed the diet with 50 mg/kg Cd2+ (Diet 1) was significantly higher ( P < 0.05). The high Cd accumulation of fish fed diets with sole 50 mg/kg Cd (Diet 1) could be significantly decreased by 51.72% after supplementation of 200 mg COS-Ce/kg in the diet (Diet 7). These results suggested that elevated COS-Ce could effectively protect against dietary Cd accumulation in turbot. [ABSTRACT FROM AUTHOR]

Cd2+ has been associated with decreased sperm motility in individuals exposed to this element, such as smokers. Among other factors, this lowered motility could be the result of inhibition exerted by Cd2+ on the activity of the sperm ATPases associated with sperm motility. In this study, we evaluated the plasma membrane Ca2+-ATPase and the axonemal dynein-ATPase activities as well as sperm motility, in the presence of different free Cd2+ concentrations in the assay media. It was found that spermatozoa incubated for 5 h in a medium containing 25 nm free Cd2+ showed a significant inhibition of progressive motility, reaching values even lower at higher Cd2+ concentrations. In addition, it was found that the activity of the plasma membrane Ca2+-ATPase reached maximal inhibition at 50 nm free Cd2+, with a K50% inhibition of 18.3 nm free Cd2+. The dynein-ATPase activity was maximally inhibited by 25 nm free Cd2+ in the assay medium, with a K50% inhibition of 11.3 nm Cd2+. Our results indicate that the decreased activity of the sperm ATPases might have a critical importance in the biochemical mechanisms underlying the decreased sperm motility of individuals exposed to Cd2+. [ABSTRACT FROM AUTHOR]

Uterine smooth muscle cells remain quiescent throughout most of gestation, only generating spontaneous action potentials immediately prior to, and during, labor. This study presents a method that combines transcriptomics with biophysical recordings to characterise the conductance repertoire of these cells, the ‘conductance repertoire’ being the total complement of ion channels and transporters expressed by an electrically active cell. Transcriptomic analysis provides a set of potential electrogenic entities, of which the conductance repertoire is a subset. Each entity within the conductance repertoire was modeled independently and its gating parameter values were fixed using the available biophysical data. The only remaining free parameters were the surface densities for each entity. We characterise the space of combinations of surface densities (density vectors) consistent with experimentally observed membrane potential and calcium waveforms. This yields insights on the functional redundancy of the system as well as its behavioral versatility. Our approach couples high-throughput transcriptomic data with physiological behaviors in health and disease, and provides a formal method to link genotype to phenotype in excitable systems. We accurately predict current densities and chart functional redundancy. For example, we find that to evoke the observed voltage waveform, the BK channel is functionally redundant whereas hERG is essential. Furthermore, our analysis suggests that activation of calcium-activated chloride conductances by intracellular calcium release is the key factor underlying spontaneous depolarisations. [ABSTRACT FROM AUTHOR]

Background: Women at risk of preterm delivery receive magnesium sulfate (MgSO4) in the pre-delivery phase to reduce their child's risk of neurodevelopmental complications associated with preterm birth. However, the mechanisms underpinning its placental vascular role remain uncertain. Methods: The aim of this study was to examine MgSO4 action on vascular tone in male and female human placental vessels from term and preterm deliveries. Vessels were obtained from placental biopsy following birth at term (37-41 weeks) or preterm gestation (<36 weeks of gestation). The vessels were mounted on a pressure myograph, pre-constricted with synthetic endoperoxide prostaglandin PGH2 (U46619) (0.1-100 μmol/l), and percentage of relaxation was calculated following incubation with bradykinin. Experiments were carried out in the presence of MgSO4 (0.2 mmol/l), NΨ-nitro-L-arginine methyl ester (L-NAME) (0.1 mmol/l), indomethacin (10 μmol/l), Ca2+-activated K+ channel blocker TRAM-34 (1 μM) and apamin (3 μM) to assess mechanisms of vascular function. Vascular [calcium ions (Ca2+)] was analysed using a colorimetric calcium assay. Results: Vasodilation in vessels from preterm males was significantly blunted in the presence of MgSO4 when compared to preterm female and term male and female vessels. Overall, MgSO4 was observed to differentially modulate placental vascular tone and vascular calcium concentrations in a sex-specific manner. Conclusions: As MgSO4 regulates human placental blood flow via specific pathways, foetal sex-specific MgSO4 treatment regimes may be necessary. In an era of increasing awareness of individualised medicine, sex-specific effects may be of importance when developing strategies to optimise care in high-risk patients. [ABSTRACT FROM AUTHOR]

The present study evaluated various sodium and potassium concentrations in hatchery water to determine which proportions would be optimal for Macrobrachium rosenbergii larviculture. Using a closed RAS system (60-L), experiments were conducted in two stages. In the first stage, larval quality parameters were compared among triplicate treatments of sodium (2000, 3000, 4000 and 5000 mg L−1) and potassium (100, 150, 200 and 250 mg L−1). During the second stage, these same parameters were compared from interactions of the two best concentrations determined in the first stage. Initial larval density was fixed at 100 larvae L−1 and larval quality parameters such as larval stage index ( LSI), larval condition index ( LCI), larvae dry weight, survival (%), LC50-24 h for formalin stress and time of the first postlarvae ( PL) appearance were measured. Results showed that during the early larval period time LSI, LCI and survival parameters were affected only by potassium and the interaction with sodium was not significant. At a later period of the larval development, interactions between both sodium and potassium were measurable for LSI ( P < 0.05) while the interactions on LCI and survival were not significant. Measurable differences among the combined treatments 4000 mg L−1 sodium and 150 mg L−1 potassium resulted in the best performance for M. rosenbergii larviculture. This concentration also provided the highest final survival to PL metamorphosis (40.6 ± 2.5%) which was at least 10% higher than the other treatments. [ABSTRACT FROM AUTHOR]

Ca2+-Mg2+-ATPase is a membrane-bound enzyme and is responsible for regulating cytosolic free calcium.In vitroandin vivoeffects of cadmium were studied on Ca2+-Mg2+-ATPase activity in plasma membrane/mitochondrial fraction ofPenaeus monodonpost larvae.In vitrostudies revealed a concentration-dependent decrease in enzyme activity with an IC50value of 11.02 µM.In vivoexperiments were conducted by exposing the post larvae to 1/10th (0.12 ppm) and 1/5th (0.24 ppm) of LC50values of cadmium for 30 days. Both ATPase activity and metal accumulation were estimated in post larvae exposed to 0.12 and 0.24 ppm of cadmium at different intervals of 24 h, 48 h, 96 h, 10 days and 30 days. ATPase activity showed a gradual decrease in post larvae on exposure to both the sub-lethal concentrations with respect to their controls and the decrease was significant (p < .05) from 96 h onwards in post larvae exposed to 0.24 ppm and 10 days onwards on exposure to 0.12 ppm of cadmium. However, the effect of cadmium was higher in 1/5th than 1/10th sub-lethal concentration and also time-dependent. These enzyme studies were found to correlate with metal accumulation in post larvae at both the exposure concentrations. Disruption of calcium homeostasis might be one of the possible mechanisms of cadmium toxicity in these organisms. [ABSTRACT FROM PUBLISHER]

A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F2t-isoprostane were significantly higher in preeclamptic patients relative to the control (3.05 vs. 2.00 ng/mg creatinine). Surprisingly enough, plasma levels of 25-hydroxyvitamin D3 in both study groups were below the clinical reference range with no significant difference between the groups. In vitro study performed on isolated placental mitochondria and placental cell line showed that suicidal self-oxidation of cytochrome P450scc may lead to structural disintegration of heme, potentially contributing to enhancement of oxidative stress phenomena in the course of preeclampsia. As placental cytochrome P450scc pleiotropic activity is implicated in the metabolism of free radical mediated arachidonic acid derivatives as well as multiple Vitamin D3 hydroxylations and progesterone synthesis, we propose that Vitamin D3 might act as a competitive inhibitor of placental cytochrome P450scc preventing the production of lipid peroxides or excess progesterone synthesis, both of which may contribute to the etiopathogenesis of preeclampsia. The proposed molecular mechanism is in accord with the preliminary clinical observations on the surprisingly high efficacy of high-dose Vitamin D3 supplementation in prevention and treatment of preeclampsia. [ABSTRACT FROM AUTHOR]

We characterize the kinetic properties of a gill (Na, K)-ATPase from the pelagic marine seabob Xiphopenaeus kroyeri. Sucrose density gradient centrifugation revealed membrane fractions distributed mainly into a heavy fraction showing considerable (Na, K)-ATPase activity, but also containing mitochondrial FF- and Na- and V-ATPases. Western blot analysis identified a single immunoreactive band against the (Na, K)-ATPase α-subunit with an M of ≈110 kDa. The α-subunit was immunolocalized to the intralamellar septum of the gill lamellae. The (Na, K)-ATPase hydrolyzed ATP obeying Michaelis-Menten kinetics with V = 109.5 ± 3.2 nmol Pi minmg and K = 0.03 ± 0.003 mmol L. Mg (V = 109.8 ± 2.1 nmol Pi minmg, K = 0.60 ± 0.03 mmol L), Na (V = 117.6 ± 3.5 nmol Pi minmg, K = 5.36 ± 0.14 mmol L), K (V = 112.9 ± 1.4 nmol Pi minmg, K = 1.32 ± 0.08 mmol L), and NH (V = 200.8 ± 7.1 nmol Pi minmg, K = 2.70 ± 0.04 mmol L) stimulated (Na, K)-ATPase activity following site-site interactions. K plus NH does not synergistically stimulate (Na, K)-ATPase activity, although each ion modulates affinity of the other. The enzyme exhibits a single site for K binding that can be occupied by NH, stimulating the enzyme. Ouabain (K = 84.0 ± 2.1 µmol L) and orthovanadate (K = 0.157 ± 0.001 µmol L) inhibited total ATPase activity by ≈50 and ≈44 %, respectively. Ouabain inhibition increases ≈80 % in the presence of NH with a threefold lower K, suggesting that NH is likely transported as a K congener. [ABSTRACT FROM AUTHOR]

Vesicle preparations from cell plasma membranes, red blood cells in particular, are extensively used in transport and enzymic studies and in the fields of drug delivery and drug-transport interactions. Here we investigated the role of spectrin-actin, the main components of the red cell cortical cytoskeleton, in a particular mechanism of vesicle generation found to be relevant to the egress process of Plasmodium falciparum merozoites from infected red blood cells. Plasma membranes from red blood cells lysed in ice-cold media of low ionic strength and free of divalent cations spontaneously and rapidly vesiculate upon incubation at 37 °C rendering high yields of inside-out vesicles. We tested the working hypothesis that the dynamic shape transformations resulted from changes in spectrin-actin configuration within a disintegrating cytoskeletal mesh. We showed that cytoskeletal-free membranes behave like a two-dimensional fluid lacking shape control, that spectrin-actin remain attached to vesiculating membranes for as long as spontaneous movement persists, that most of the spectrin-actin detachment occurs terminally at the time of vesicle sealing and that naked membrane patches increasingly appear during vesiculation. These results support the proposed role of spectrin-actin in spontaneous vesiculation. The implications of these results to membrane dynamics and to the mechanism of merozoite egress are discussed. [ABSTRACT FROM AUTHOR]

Incubation of boar spermatozoa in a capacitation medium with oligomycin A, a specific inhibitor of the F0 component of the mitochondrial ATP synthase, induced an immediate and almost complete immobilisation of cells. Oligomycin A also inhibited the ability of spermatozoa to achieve feasible in vitro capacitation (IVC), as measured through IVC-compatible changes in motility patterns, tyrosine phosphorylation levels of the acrosomal p32 protein, membrane fluidity and the ability of spermatozoa to achieve subsequent, progesterone-induced in vitro acrosome exocytosis (IVAE). Both inhibitory effects were caused without changes in the rhythm of O2 consumption, intracellular ATP levels or mitochondrial membrane potential (MMP). IVAE was accompanied by a fast and intense peak in O2 consumption and ATP levels in control spermatozoa. Oligomycin A also inhibited progesterone-induced IVAE as well as the concomitant peaks of O2 consumption and ATP levels. The effect of oligomycin on IVAE was also accompanied by concomitant alterations in the IVAE-induced changes on intracellular Ca2+ levels and MMP. Our results suggest that the oligomycin A-sensitive mitochondrial ATP-synthase activity is instrumental in the achievement of an adequate boar sperm motion pattern, IVC and IVAE. However, this effect seems not to be linked to changes in the overall maintenance of adequate energy levels in stages other than IVAE. [ABSTRACT FROM AUTHOR]

Background: Signs of severe oxidative stress are evident in term placentae of infants born to mothers with preeclampsia (PE), but it is unclear whether this is a cause or consequence of the disease. Here fibroblast lines were established from umbilical cords (UC) delivered by mothers who had experienced early onset PE and from controls with the goal of converting these primary cells to induced pluripotent stem cells and ultimately trophoblast. Contrary to expectations, the oxidative stress responses of these non-placental cells from PE infants were more severe than those from controls. Methods and Findings: Three features suggested that UC-derived fibroblasts from PE infants responded less well to oxidative stressors than controls: 1) While all UC provided outgrowths in 4% O2, success was significantly lower for PE cords in 20% O2; 2) PE lines established in 4% O2 proliferated more slowly than controls when switched to 20% O2; 3) PE lines were more susceptible to the pro-oxidants diethylmaleate and tert-butylhydroquinone than control lines, but, unlike controls, were not protected by glutathione. Transcriptome profiling revealed only a few genes differentially regulated between PE lines and controls in 4% O2 conditions. However, a more severely stressed phenotype than controls, particularly in the unfolded protein response, was evident when PE lines were switched suddenly to 20% O2, thus confirming the greater sensitivity of the PE fibroblasts to acute changes in oxidative stress. Conclusions: UC fibroblasts derived from PE infants are intrinsically less able to respond to acute oxidative stress than controls, and this phenotype is retained over many cell doublings. Whether the basis of this vulnerability is genetic or epigenetic and how it pertains to trophoblast development remains unclear, but this finding may provide a clue to the basis of the early onset, usually severe, form of PE. [ABSTRACT FROM AUTHOR]

Background: Several studies have correlated protein restriction associated with other nutritional deficiencies with the development of cardiovascular and renal diseases. The driving hypothesis for this study was that Ang II signaling pathways in the heart and kidney are affected by chronic protein, mineral and vitamin restriction. Methodology/Principal Findings: Wistar rats aged 90 days were fed from weaning with either a control or a deficient diet that mimics those used in impoverished regions worldwide. Such restriction simultaneously increased ouabain-insensitive Na+-ATPase and decreased (Na++K+)ATPase activity in the same proportion in cardiomyocytes and proximal tubule cells. Type 1 angiotensin II receptor (AT1R) was downregulated by that restriction in both organs, whereas AT2R decreased only in the kidney. The PKC/PKA ratio increased in both tissues and returned to normal values in rats receiving Losartan daily from weaning. Inhibition of the MAPK pathway restored Na+-ATPase activity in both organs. The undernourished rats presented expanded plasma volume, increased heart rate, cardiac hypertrophy, and elevated systolic pressure, which also returned to control levels with Losartan. Such restriction led to electrical cardiac remodeling represented by prolonged ventricular repolarization parameters, induced triggered activity, early after-depolarization and delayed after-depolarization, which were also prevented by Losartan. Conclusion/Significance: The mechanisms responsible for these alterations are underpinned by an imbalance in the PKC- and PKA-mediated pathways, with participation of angiotensin receptors and by activation of the MAPK/ERK1/2 pathway. These cellular and molecular alterations culminate in cardiac electric remodeling and in the onset of hypertension in adulthood. [ABSTRACT FROM AUTHOR]

Besides infection with drug-resistant parasites, therapeutic failure in leishmaniasis may be caused by altered drug pharmacokinetics, re-infection, and host immunologic compromise. Our aim has been to evaluate if relapses that occur in patients suffering from diffuse cutaneous leishmaniasis (DCL) associate with changes in the fitness of infecting organisms. Therefore, in isolates from patients suffering DCL, we correlated glucose uptake and plasma membrane potential and compared the results with those obtained from reference strains. The data demonstrate that Leishmania parasites causing DCL incorporate glucose at an efficient rate, albeit without significant changes in the plasma membrane potential as their corresponding reference strains. The isolate that did not change its accumulation rate of glucose compared to its reference strain expressed a less polarized membrane potential that was insensitive to mitochondrial inhibitors, suggesting a metabolic dysfunction that may result in glycolysis being the main source of ATP. The results constitute a proof of concept that indicates that parasites causing DCL adapted well to drug pressure and expressed an increased fitness. That is, that in Leishmania mexicana and Leishmania amazonensis, parasites isolated from DCL patients, a strong modification of the parasite physiology might occur. As consequences, the parasites adapted well to drug pressure, increased their fitness, and they had an efficient glucose uptake rate albeit not significant changes in membrane potential as their corresponding reference strains. Further validation of the concepts herein established and whether or not the third isolate corresponds with a drug-resistant phenotype need to be demonstrated at the genetic level. [ABSTRACT FROM AUTHOR]

The physiological roles of ANG-(3-4) (Val-Tyr), a potent ANG II-derived peptide, remain largely unknown. The present study 1)investigates whether ANG-(3-4) modulates ouabain-resistant Na+-ATPase resident in proximal tubule cells and 2) verifies whether its possible action on pumping activity, considered the fine tuner of Na+ reabsorption in this nephron segment, depends on blood pressure. ANG-(3-4) inhibited Na+-ATPase activity in membranes of spontaneously hypertensive rats (SHR) at nanomolar concentrations, with no effect in Wistar- Kyoto (WKY) rats or on Na+-K+-ATPase. PD123319 (10-10 M) and PKA(5-24) (10-6 M), an AT2 receptor (AT2R) antagonist and a specific PKA inhibitor, respectively, abrogated this inhibition, indicating that AT2R and PKA are central in this pathway. Despite the lack of effect of ANG-(3-4) when assayed alone in WKY rats, the peptide (108 M) completely blocked stimulation of Na+-ATPase induced by 10-10 M ANG II in normotensive rats through a mechanism that also involves AT2R and PKA. Tubular membranes from WKY rats had higher levels of AT2R/AT1R heterodimers, which remain associated in 10-10 M ANG II and dissociate to a very low dimerization state upon addition of 10-8 M ANG-(3-4). This lower level of heterodimers was that found in SHR, and heterodimers did not dissociate when the same concentration of ANG-(3-4) was present. Oral administration of ANG-(3-4) (50 mg/kg body mass) increased urinary Na+ concentration and urinary Na+ excretion with a simultaneous decrease in systolic arterial pressure in SHR, but not in WKY rats. Thus the influence of ANG-(3-4) on Na+ transport and its hypotensive action depend on receptor association and on blood pressure. [ABSTRACT FROM AUTHOR]

Inflammation in the male genitourinary tract has been associated with the release of pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and elevated reactive oxygen species, which affects spermatozoa capacitation, motility, and the acrosome reaction, along with functions regulated by the concentration of cytoplasmic Ca2+ ([Ca2+]cyto). Though Ca2+ signaling is of particular significance in sperm, the effect of IFN-γ intracellular calcium on these cells is still unknown. The present study evaluated the effect of IFN-γ on the [Ca2+]cyto and Ca2+ permeability on human sperm. A cell suspension loaded with fura-2 was incubated with or without IFN-γ (from 0 to 2000 pg/ml) for 0, 30, 60, and 120 minutes, and the [Ca2+]cyto was measured. The permeability to Ca2+ was evaluated by the change of the intracellular concentration following an extracellular Ca2+ pulse. IFN-γ at low concentrations (≤500 pg/ml) did not affect the [Ca2+]cyto and Ca2+ permeability of sperm. At a high concentration (2000 pg/ml), IFN-γ did not alter the [Ca2+]cyto, but significantly decreased the magnitude and velocity of Ca2+ entry into the cell. This effect was dependent on incubation time and IFN-γ concentration. This alteration induced by IFN-γ was prevented by the simultaneous incubation of sperm with the antioxidant butylhydroxytoluene (BHT). In conclusion, in vitro, IFN-γ modifies Ca2+ sperm membrane permeability, probably via lipid peroxidation. IFN-γ in high concentration, as observed in inflammation/infection, can affect [Ca2+]cyto regulation and alter sperm fertilizing capacity. [ABSTRACT FROM AUTHOR]

Maternal-to-fetal transfer of nutrient and other substances occurs across the placental barrier ( PB) which is made up of endothelial cells ( EC) on the fetal side and the syncytiotrophoblast ( STB) on the maternal side. Numerous studies were conducted to explore the transport characteristics across the STB layer, which is also considered as the major resistance for maternal-to-fetal exchange of materials. In contrast the layer of EC has received very little attention if at all. A recently developed viable co-culture model of the PB revealed significant resistance of the EC layer for maternal-to-fetal transfer of glucose. This argues for a major contribution of the EC to overall transplacental transfer of nutrients. Accordingly, it is recommended to fill the void of knowledge and expand our understanding on the role of the feto-placental endothelium for transplacental transport characteristics. [ABSTRACT FROM AUTHOR]