Gestational Diabetes Mellitus (GDM), Hypothyroidism,and Gene Variants (Keap1 Rs11085735) in Patients with Preeclampsia

Background:Preeclampsia is a multifactorial hypertensive disorder of pregnancy with multisystem involvement. Recent studies have demonstrated that preeclampsia is associated with increased placental oxidative stress at the cellular level. The nuclear factor erythroid-2-like 2 (Nrf2) / Kelch-like ECH-associated protein 1 (Keap1) signaling is an antioxidant pathway that plays an important role in protecting cells against oxidative stress. Here, we aimed to determine the possible association between the Keap1 variants and genetic susceptibility to preeclampsia.Methods:In a case-control study, 150 preeclampsia patients and 150 women with normal pregnancy from Northern Iran were selected to evaluate the genotypes of Keap1 (rs11085735) using the polymerase chain reaction (PCR)-restriction length polymorphism (RFLP) method.Results:A significant association between genotypes of Keap1 rs11085735 polymorphism with the renal function biomarkers and the risk of preeclampsia was not found. However, the aspartate aminotransferase (AST) level was higher in the presence of the Keap1 AA genotype compared to AC and CC genotypes. We found a significantly higher prevalence of gestational diabetes mellitus (GDM) in mild- and severe- preeclampsia and also hypothyroidism in severe preeclampsia compared to controls.Conclusion:We found an association between preeclampsia with GDM and hypothyroidism. Our findings suggest that the Keap1rs11085735 polymorphism may not be a risk factor for susceptibility to preeclampsia in our studied population; however, this polymorphism could affect the activity of AST.Key Words: Gestational diabetes mellitus, Hypothyroidism, Keap1 variants, Oxidative stress, Preeclampsia     

Modeling Nociception in Zebrafish: A Way Forward for Unbiased Analgesic Discovery

Acute and chronic pain conditions are often debilitating, inflicting severe physiological, emotional and economic costs and affect a large percentage of the global population. However, the development of therapeutic analgesic agents based primarily on targeted drug development has been largely ineffective. An alternative approach to analgesic development would be to develop low cost, high throughput, untargeted animal based behavioral screens that model complex nociceptive behaviors in which to screen for analgesic compounds. Here we describe the development of a behavioral based assay in zebrafish larvae that is effective in identifying small molecule compounds with analgesic properties. In a place aversion assay, which likely utilizes supraspinal neuronal circuitry, individually arrayed zebrafish larvae show temperature-dependent aversion to increasing and decreasing temperatures deviating from rearing temperature. Modeling thermal hyperalgesia, the addition of the noxious inflammatory compound and TRPA1 agonist allyl isothiocyanate sensitized heat aversion and reversed cool aversion leading larvae to avoid rearing temperature in favor of otherwise acutely aversive cooler temperatures. We show that small molecules with known analgesic properties are able to inhibit acute and/or sensitized temperature aversion.     

EFFECT OF MANIPULATION OF WATER AND NITROGEN SUPPLIES ON THE QUANTITATIVE PHENOLOGY OF LARREA TRIDENTATA (CREOSOTE BUSH) IN THE SONORAN DESERT OF CALIFORNIA

Two years of water and nitrogen augmentation experiments on Larrea tridentata (creosote bush) were carried out in a southern Californian warm desert wash plant community. Treatments consisted of control (C), water (W), water and soil nitrogen (W + SN), and soil nitrogen (SN). Quantitative phenological data and microclimatic measurements were collected prior to the onset of and during the growth period and treatments. Predawn and midday water potentials were lower in nonirrigated than irrigated individuals. Leaf conductance was higher in irrigated than in nonirrigated shrubs, with a maximum difference of 1 cm s^-1 observed in July 1984 under relatively low vapor pressure deficit conditions. Leaf production rates were significantly higher in the irrigated (W and W + SN) treatments than in the nonirrigated (C and SN) treatments in 1984. Addition of soil nitrogen caused no increased in vegetative growth rates in 1984. In 1985, a drier year, there was only minimal growth during the spring and summer growth periods in the nonirrigated treatments, while the W and W + SN treatments resulted in significantly higher leafand shoot growth rates. Growth rates in 1985 were significantly higher in the W + SN treatment than in the W treatment. Reproductive growth was higher in the nonirrigated than the irrigated treatments, with the lowest reproductive activity noted in the W treatment.     

Molecular testing of <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> contaminating tissue allografts recovered from deceased donors

Microbiological screening of tissue allografts is crucial to prevent the transmission of bacterial and fungal infections to transplant recipients. Klebsiella was the most prevalent and resistant contaminating microorganism observed in our setting in the Iranian Tissue Bank. This study was conducted to determine the presence of extended-spectrum β-lactamase (ESBL) genes, antimicrobial resistance patterns of Klebsiella pneumoniae isolates, and their clonal relationships in allograft materials. K. pneumoniae contaminating bone and other tissue allografts recovered from deceased donors were identified and ESBL isolates were detected using a phenotypic confirmatory method. Antimicrobial susceptibility testing was carried out using the disk diffusion method. Distribution of ESBL genes and molecular typing were performed using polymerase chain reaction (PCR) and Repetitive-element (rep-PCR) methods. Of 3828 donated tissues, 51 (1.3%) were found contaminated by K. pneumoniae isolates. Compared to tissue allografts from brain-dead, heart-beating tissue donors, allografts from donors with circulatory cessation were associated with a higher risk of K. pneumoniae contamination [odds ratio (OR), 1.2 (CI 95% 0.9–2.3) (P value < 0.001)]. Half of the isolates produced ESBL, and the rate of susceptibility to cephalosporins was 51%. Among isolates, 22 (43.1%) harbored CTX-M, 31 (60.8%) SHV, and 9 (17.6%) harbored TEM types. The rep-dendrogram indicated that clones having identical or related strains with a similar antibiotype were isolated in the same period. This study provides evidence that a single clone of K. pneumoniae contaminated tissue allografts recovered from many different donors. A single clone found on tissues from several donors suggests contamination of tissues from a single source such as the tissue recovery process and environment. Genomic DNA testing and clonality of contaminating bacteria using molecular methods can focus the epidemiologic investigation on the tissue allograft recovery process including a search for contamination of the tissue recovery room environment, recovery staff, recovery equipment, reagents, solutions and supplies.     

Phenolic compounds profiling in shake flask and bioreactor system cell cultures of <Emphasis Type="Italic">Scrophularia striata</Emphasis> Boiss

Variation in levels of phenolic acids and flavonoids in Scrophularia striata Boiss. cells cultured in both shake flask and bioreactor in vitro systems, was studied at different growth phases. Four phenolic acids (cinnamic, salicylic, coumaric, and caffeic acid), one stilbenoid (resveratrol), and seven flavonoids (diosmin, rutin, kaempferol, catechin, myricetin, quercetin, and luteolin) were analyzed by high-performance liquid chromatography with photodiode array detection. Production of phenolics in the bioreactor was higher than in shake flasks. Catechin was the most abundant flavonoid in both culture systems, while quercetin, which was detected only in the bioreactor, was the lowest amount represented (32.82 μg g^?1 DW). Resveratrol accumulation in bioreactor cultures was 59.84-fold higher than that in shake flasks. Moreover, hierarchical clustering analysis based on Pearson’s correlation coefficient confirmed a positive correlation between the growth phase and some metabolites. The flavonoid accumulation increased with the cells’ physiological age in the bioreactor. Principal component analysis showed that the time course of induction of phenolic acids, flavonoids, and a stilbenoid (resveratrol) was significantly correlated. These findings highlight the capacity of S. striata for large-scale production of desired phenolics using a bioreactor system.     

Carbon isotopic composition of legumes with photosynthetic stems from mediterranean and desert habitats

The carbon isotopic compositions of leaves and stems of woody legumes growing in coastal mediterranean and inland desert sites in California were compared. The overall goal was to determine what factors were most associated with the carbon isotope composition of photosynthetic stems in these habitats. The carbon isotope signature (d13C) of photosynthetic stems was less negative than that of leaves on the same plants by an average of 1.51 ± 0.42 ;pp. The d13C of bark (cortical chlorenchyma and epidermis) was more negative than that of wood (vascular tissue and pith) from the same plant for all species studied on all dates. Desert woody legumes had a higher d13C (less negative) and a lower intercellular CO2 concentration (Ci ) (for both photosynthetic tissues) than that of woody legumes from mediterranean climate sites. Differences in the d13C of stems among sites could be entirely accounted for by differences among site air temperatures. Thus, the d13C composition of stems did not indicate a difference in whole-plant integrated water use efficiency (WUE) among sites. In contrast, stems on all plants had a lower stem Ci and a higher d13C than leaves on the same plant, indicating that photosynthetic stems improve long-term, whole-plant water use efficiency in a diversity of species.