Comparative effects of dexamethasone on placental and foetal organ weights and some linear body measurements in Yankasa sheep and Sahel goats

Dexamethasone is a potent synthetic glucocorticoid use in veterinary and human medicine. However, it causes intra uterine growth restriction (IUGR) and decreases birth weights in some animal species and humans, although each species respond differently. This study investigated the effects of dexamethasone on placental weights and some foetal parameters in Yankasa sheep and Sahel goats with known average gestational length of 148.35 ± 1.50 days and 148.33 ± 1.58 days respectively. Ten adult Sahel goats comprising 8 does and 2 bucks and 10 Yankasa Sheep comprising of 8 ewes and 2 rams were used for this study. Pregnancies were achieved by natural mating after synchronization. Repeated dexamethasone injections were intramuscularly given at 0.25mg/kg body weight on days 1, 3 and 5 during first trimester and days 51, 53 and 55 during second trimester. Foetuses were harvested at day 78 of gestation all through Caesarean section. Foetal weights, crown-rump lengths (CRL), height at withers, heart girth, abdominal circumference, weights of adrenal glands and placental weight were evaluated. Specimens from placentas and adrenal glands were collected for histological analysis. Results showed that the mean placental weights, placental efficiency and foetal body weights were significantly (P<0.05) decreased in dexamethasone treated sheep and goats compared to controls. There was no significant change in foetal adrenal glands and linear body measurements between dexamethasone treatment and control groups in both species except crown-rump lengths (CRL) which was significantly (P<0.05) reduced in Sheep foetuses. It was concluded that dexamethasone caused significant decrease in placental weights and placenta efficiency and hence placental- maternal- foetal transport of nutrient materials in both species and also caused decrease in foetal crown-rump-lengths in sheep but not in goats. This suggests that dexamethasone has some teratogenic effects and that Sheep are more susceptible to dexamethasone treatment compared to goats.Keywords: Dexamethasone, Foetuses, Placenta, Pregnancies, Sahel goats, Yankasa shee

Lipschitz operator ideals and the approximation property

[EN] We establish the basics of the theory of Lipschitz operator ideals with the aim of recovering several classes of Lipschitz maps related to absolute summability that have been introduced in the literature in the last years. As an application we extend the notion and main results on the approximation property for Banach spaces to the case of metric spaces. (C) 2015 Elsevier Inc. All rights reserved.P. Rueda acknowledges with thanks the support of the Ministerio de Economia y Competitividad (Spain) MTM2011-22417. E.A. Sanchez Perez acknowledges with thanks the support of the Ministerio de Economia y Competitividad (Spain) MTM2012-36740-C02-02.Achour, D.; Rueda, P.; Sánchez Pérez, EA.; Yahi, R. (2016). Lipschitz operator ideals and the approximation property. Journal of Mathematical Analysis and Applications. 436(1):217-236. https://doi.org/10.1016/j.jmaa.2015.11.050S217236436

The use of dexamethasone in animals: implication for fertility, pregnancy and extrapolation of the animal data to humans

Exposure to dexamethasone causes numerous changes in various biological systems including the reproductive system and this has huge implication on fertility and pregnancy. Maternal dexamethasone administration promotes foetal lung maturation and thermoregulation in premature foetuses. This indication makes dexamethasone a drug of choice in maternal and neonatal human and veterinary health care. In addition, dexamethasone is widely used in human and veterinary medicine as potent anti-inflammatory, immunosuppressive and analgesic drug in all age categories. Although the safety profile of short term dexamethasone treatment has been established, there has been growing concern about the long term effects of dexamethasone therapy and its implication on fertility and pregnancy in animals and humans. Most of the indications or uses in humans are extrapolated from animal data. This necessitates the need to provide review updates of current literature on dexamethasone use in humans and animals as there are many intrinsic differences between humans and animals. The review provides an overview of dexamethasone uses, its merits and demerits on animal pregnancy and fertility and implication on extrapolation of the animal data to humans. The review is based on a comprehensive literature search of relevant materials between 1969 and 2016 as well as authors’ personal manuscript/abstract files and citations of known references and discussed according to the multidisciplinary clinical experience of the authors. Although low-dose dexamethasone treatment has been used in veterinary and human clinics for many years and produced no severe effect on vital functions, repetitive high dose or long-term therapy may be associated with more serious sequelae on fertility and pregnancy. While no animal truly recapitulates human pregnancy and fertility, it is recommended that results from animal data be subjected to rigorous preclinical pharmacokinetic scaling processes to justify possible extrapolation to humans.Keywords: Animals, Dexamethasone, Fertility, Humans, Pregnanc

Phytochemistry of methanol seed extract of Abrus precatorius and its effect on spermatogenesis in rats

The methanol seed extract of Abrus precatorius was studied for its acute toxicity and its effect on spermatogenesis in rats as well as its phytochemical constituents. The results of this investigation showed that the LD50 of the methanol seed extract following oral administration was above 5000 mg/kg showing low toxicity. Histological studies of the liver, kidneys and testes of the rats treated with the various oral doses (10 - 5000 mg/kg body weight) showed no remarkable changes in the hepatocytes, kidney cells and testes compared to the control. The effects on sperm cells did not show any significant increase in total sperm head counts. The Phytochemical analysis revealed the presence of pharmacologically active compounds such as reducing sugars, tannins, cardiac glycosides, terpenoids, saponins and flavonoids. In conclusion, the methanol seed extract of Abrus precatorius contain important phytochemical constituents possessing pharmacological activities and it is relatively safe but has no effects on sperm cell production.Keywords: Abrus precatorius, acute toxicity, phytochemical constituents, spermatogenesi

Histological changes following prolonged oral administration of sildenafil citrate in diabetics rats

Diabetes is a cluster of metabolic disorders reflected by abnormal hyperglycemia that causes chronic microvascular, macrovascular, and neuropathic diseases.Sildenafil citrate is widely used to dilate penile arteries, particularly in patient with erectile dysfunction which suggest that it may also dilate pulmonary arteries in patients with pulmonary hypertension. Objectives: The purpose of this study is to evaluate the effect of sildenafil citrate on heart and lung tissues of diabetic rats. Method: The study was performed using forty-two rats (42) weighing between 150-200 grams. The rats were grouped into 7 groups (A-G) of six (6) rats per 2 group. Wound area of 1.5 by 1.5 cm was created at the dorsal surface of each rat under sedation with ketamine and lignocaine. Type I diabetes was induced using a single dose of Alloxan monohydrate at dose rate of 130 mg/kg. Sildenafil citrate was administered at a dose rate of 50 mg/kg orally daily for 21 days and 10 international units of insulin was administered intraperitoneal to the control group once. At the end of 21 days lung and heart tissues were collected for histological studies. Results: The results revealed moderate thickening of interstitial demonstrated by congestion of blood vessels and oedema of the lungs. The heart muscles were swollen with loss of striation in myocardial fibers. Conclusion: Prolonged oral administration of sildenafil citrate caused appreciable pulmonary and cardiovascular damage to diabetic rats. Therefore, precautionary measures are needed when treating diabetic patients with pulmonary and cardiovascular diseases.&nbsp

Dexamethasone uses in humans and animals: public health and socio-economic implications

The importance of dexamethasone is demonstrated by its wide uses in human and veterinary medical practice. Unfortunately, dexamethasone use is prone to abuse. Health authorities have emphasized the importance of increasing knowledge of benefits and potential harmful effects of synthetic glucocorticoids use as a guide to responsible and judicious use of the pharmaceutical. This review provides an overview of the uses of dexamethasone and its consequences on public health visa vie socio–economy. Methodology: Source of Data: The review is based on literature searches using PubMed and MeSH and authors' personal manuscript/abstract files and citations of known references. Study selection: The selection of articles reflects the authors' opinion as to originality and importance in the context of the review. The review included human and some aspects of animal study. Data extraction: The electronic searches were scrutinized and full manuscripts of all quotes considered relevant to the study were obtained. All the articles whose abstracts were not available were excluded. Results: Dexamethasone is still one of the most prescribed medicines in human and veterinary medical practice despite over 4-decades of use and its attendant negative consequences. Recently non-medical uses of the drug are also on the increase which greatly contributed to the problems. Conclusion: Dexamethasone use has consequences on public health visa vie socio-economy. Its indispensability is not unconnected with its broad spectrum pharmacological actions and cost effectiveness. Due to rampant abuses and the attendant adverse effects of dexamethasone, it is recommended that the drug be enlisted as controlled drug

Aptamers that recognize drug-resistant HIV-1 reverse transcriptase

Drug-resistant variants of HIV-1 reverse transcriptase (RT) are also known to be resistant to anti-RT RNA aptamers. In order to be able to develop diagnostics and therapies that can focus on otherwise drug-resistant viruses, we have isolated two aptamers against a well-known, drug-resistant HIV-1 RT, Mutant 3 (M3) from the multidrug-resistant HIV-1 RT panel. One aptamer, M302, bound M3 but showed no significant affinity for wild-type (WT) HIV-1 RT, while another aptamer, 12.01, bound to both M3 and WT HIV-1 RTs. In contrast to all previously selected anti-RT aptamers, neither of these aptamers showed observable inhibition of either polymerase or RNase H activities. Aptamers M302 and 12.01 competed with one another for binding to M3, but they did not compete with a pseudoknot aptamer for binding to the template/primer cleft of WT HIV-1 RT. These results represent the surprising identification of an additional RNA-binding epitope on the surface of HIV-1 RT. M3 and WT HIV-1 RTs could be distinguished using an aptamer-based microarray. By probing protein conformation as a correlate to drug resistance we introduce an additional and useful measure for determining HIV-1 drug resistance

Comparative Analyses of SUV420H1 Isoforms and SUV420H2 Reveal Differences in Their Cellular Localization and Effects on Myogenic Differentiation

Methylation of histone H4 on lysine 20 plays critical roles in chromatin structure and function via mono- (H4K20me1), di- (H4K20me2), and trimethyl (H4K20me3) derivatives. In previous analyses of histone methylation dynamics in mid-gestation mouse embryos, we documented marked changes in H4K20 methylation during cell differentiation. These changes were particularly robust during myogenesis, both in vivo and in cell culture, where we observed a transition from H4K20me1 to H4K20me3. To assess the significance of this change, we used a gain-of-function strategy involving the lysine methyltransferases SUV420H1 and SUV420H2, which catalyze H4K20me2 and H4K20me3. At the same time, we characterized a second isoform of SUV420H1 (designated SUV420H1_i2) and compared the activity of all three SUV420H proteins with regard to localization and H4K20 methylation.Immunofluorescence revealed that exogenous SUV420H1_i2 was distributed throughout the cell, while a substantial portion of SUV420H1_i1 and SUV420H2 displayed the expected association with constitutive heterochromatin. Moreover, SUV420H1_i2 distribution was unaffected by co-expression of heterochromatin protein-1α, which increased the targeting of SUV420H1_i1 and SUV420H2 to regions of pericentromeric heterochromatin. Consistent with their distributions, SUV420H1_i2 caused an increase in H4K20me3 levels throughout the nucleus, whereas SUV420H1_i1 and SUV420H2 facilitated an increase in pericentric H4K20me3. Striking differences continued when the SUV420H proteins were tested in the C2C12 myogenic model system. Specifically, although SUV420H1_i2 induced precocious appearance of the differentiation marker Myogenin in the presence of mitogens, only SUV420H2 maintained a Myogenin-enriched population over the course of differentiation. Paradoxically, SUV420H1_i1 could not be expressed in C2C12 cells, which suggests it is under post-transcriptional or post-translational control.These data indicate that SUV420H proteins differ substantially in their localization and activity. Importantly, SUV420H2 can induce a transition from H4K20me1 to H4K20me3 in regions of constitutive heterochromatin that is sufficient to enhance myogenic differentiation, suggesting it can act an as epigenetic ‘switch’ in this process

Identifying potential survival strategies of HIV-1 through virus-host protein interaction networks

Background: The National Institute of Allergy and Infectious Diseases has launched the HIV-1 Human Protein Interaction Database in an effort to catalogue all published interactions between HIV-1 and human proteins. In order to systematically investigate these interactions functionally and dynamically, we have constructed an HIV-1 human protein interaction network. This network was analyzed for important proteins and processes that are specific for the HIV life-cycle. In order to expose viral strategies, network motif analysis was carried out showing reoccurring patterns in virus-host dynamics.Results: Our analyses show that human proteins interacting with HIV form a densely connected and central sub-network within the total human protein interaction network. The evaluation of this sub-network for connectivity and centrality resulted in a set of proteins essential for the HIV life-cycle. Remarkably, we were able to associate proteins involved in RNA polymerase II transcription with hubs and proteasome formation with bottlenecks. Inferred network motifs show significant over-representation of positive and negative feedback patterns between virus and host. Strikingly, such patterns have never been reported in combined virus-host systems.Conclusions: HIV infection results in a reprioritization of cellular processes reflected by an increase in the relative importance of transcriptional machinery and proteasome formation. We conclude that during the evolution of HIV, some patterns of interaction have been selected for resulting in a system where virus proteins preferably interact with central human proteins for direct control and with proteasomal proteins for indirect control over the cellular processes. Finally, the patterns described by network motifs illustrate how virus and host interact with one another

Shiga Toxin Binding to Glycolipids and Glycans

Background: Immunologically distinct forms of Shiga toxin (Stx1 and Stx2) display different potencies and disease outcomes, likely due to differences in host cell binding. The glycolipid globotriaosylceramide (Gb3) has been reported to be the receptor for both toxins. While there is considerable data to suggest that Gb3 can bind Stx1, binding of Stx2 to Gb3 is variable. Methodology: We used isothermal titration calorimetry (ITC) and enzyme-linked immunosorbent assay (ELISA) to examine binding of Stx1 and Stx2 to various glycans, glycosphingolipids, and glycosphingolipid mixtures in the presence or absence of membrane components, phosphatidylcholine, and cholesterol. We have also assessed the ability of glycolipids mixtures to neutralize Stx-mediated inhibition of protein synthesis in Vero kidney cells. Results: By ITC, Stx1 bound both Pk (the trisaccharide on Gb3) and P (the tetrasaccharide on globotetraosylceramide, Gb4), while Stx2 did not bind to either glycan. Binding to neutral glycolipids individually and in combination was assessed by ELISA. Stx1 bound to glycolipids Gb3 and Gb4, and Gb3 mixed with other neural glycolipids, while Stx2 only bound to Gb3 mixtures. In the presence of phosphatidylcholine and cholesterol, both Stx1 and Stx2 bound well to Gb3 or Gb4 alone or mixed with other neutral glycolipids. Pre-incubation with Gb3 in the presence of phosphatidylcholine and cholesterol neutralized Stx1, but not Stx2 toxicity to Vero cells