Acrylonitrile Potentiates Noise-Induced Hearing Loss in Rat

Acrylonitrile, one of the 50 most commonly produced industrial chemicals, has recently been identified as a promoter of noise-induced hearing loss (NIHL). This agent has the potential to produce oxidative stress through multiple pathways. We hypothesize that acrylonitrile potentiates NIHL as a consequence of oxidative stress. The objectives of this study were to characterize acrylonitrile exposure conditions that promote permanent NIHL in rats and determine the ability of this nitrile to produce auditory dysfunction by itself. Additionally, we sought to determine whether a spin-trap agent that can form adducts with ROS would protect against the effects of acrylonitrile. Acrylonitrile administration produced significant elevation in NIHL detected as a loss in compound action potential sensitivity. The effect was particularly robust for high-frequency tones and particularly when acrylonitrile and noise were given on repeated occasions. Acrylonitrile by itself did not disrupt threshold sensitivity. Administration of the spin-trap agent phenyl-N-tert-butylnitrone (PBN), given to rats prior to acrylonitrile and noise, did block the elevation of NIHL by acrylonitrile. However, PBN at the dose and time interval given was ineffective in protecting auditory function in subjects exposed to noise alone. The results suggest that oxidative stress may play a role in the promotion of NIHL by acrylonitrile.     

Sak/Plk4 and mitotic fidelity

Sak/Plk4 differs from other polo-like kinases in having only a single polo box, which assumes a novel dimer fold that localizes to the nucleolus, centrosomes and the cleavage furrow. Sak expression increases gradually in S through M phase, and Sak is destroyed by APC/C dependent proteolysis. Sak-deficient mouse embryos arrest at E7.5 and display an increased incidence of apoptosis and anaphase arrest. Sak(+/-) mice are haploinsufficient for tumor suppression, with spontaneous tumors developing primarily in the liver with advanced age. During liver regeneration following partial hepatectomy, Sak(+/-) hepatocytes display a delay in reaching the first M phase, multipolar spindles, disorganized tissue morphology and loss of acuity for cyclin B1 expression. Similarly, Sak(+/-) MEF cells proliferate slowly, and show a high incidence of centrosome hyper-amplification. We suggest that Sak provides feedback to cell cycle regulators, and thereby precision to the switch-like transitions of centrosome duplication and exit-from-mitosis. Sak binds to p53, and studies are underway to provide a molecular context for the Sak-p53 interaction. Animal models of haploinsufficiency and more comprehensive models of cell cycle regulation should contribute to improvements in cancer risk assessment and novel therapies.     

Inguinal Herniation of Urinary Bladder on F-18 Sodium Fluoride (NaF) PET-CT

Inguinal herniation of urinary bladder is uncommon and usually an incidental finding in asymptomatic patients. In some of these patients, residual urine volume and consequently, urinary tracer activity can be higher in the herniated bladder than the native bladder, in which case interpretation can be challenging on conventional planar imaging. We describe an interesting case of physiological activity in a herniated bladder simulating a “tear-drop”. This case serves an important reminder that whilst F-18 NaF PET-CT has a similar spectrum of urinary activity to conventional bone scintigraphy; morphological correlation on hybrid imaging is invaluable in ensuring the physiological nature of uptake.     

Genomic integrity of the Y chromosome sequence‐tagged‐sites in infertile and Down syndrome Jordanian males

The long arm of the Y chromosome contains nonoverlapping regions termed azoospermia factor (AZF) with great influence on male fertility. Microdeletions at these regions minimise the males' ability to father offsprings. In this preliminary study, we attempted to screen the presence or absence of twenty Y chromosome's sequence‐tagged sites (STS) associated with fertility in infertile and Down syndrome (DS) males. Genomic DNA from 35 fertile, 74 infertile and 22 karyotyped DS males was extracted and amplified in multiplex polymerase chain reaction (PCR) containing 20 primer pairs that amplify Y‐specific STS that cover functional regions associated with AZF and spermatogenesis‐related genes. Our results indicated the integrity of the Y chromosome at the 20 fertility markers for both the fertile and Down syndrome males. However, the results of the infertile males showed the presence of microdeletions at these Y‐specific STS. Three samples showed Y chromosome microdeletion when blood and seminal fluid genomic DNA were assayed, while two samples showed microdeletion only when seminal fluid genomic DNA was assayed. The current study demonstrated that the molecular genetic aspect of infertility should be given proper attention when dealing with infertility cases. Furthermore, our results indicate the importance of genetic counselling in managing infertility cases.     

Evaluation of the in vivo genotoxicity of liposomal formulation for delivering anticancer estrogenic derivative (ESC8) in a mouse model

The genotoxic potential of glucocorticoid receptor (GR)-targeted liposomal formulations of the anticancer drug molecule ESC8 was studied in vivo. A methodical literature review discovered no previous studies on the genotoxicity of ESC8. Genotoxicity was assessed in both male and female mice by various assay systems, such as comet assay, chromosomal aberrations and micronuclei assay, which detect different abnormalities. Eleven groups of male mice and eleven groups of female mice, containing six animals per group, were used in the present study: group I served as vehicle control; group II received the positive control (cyclophosphamide 40 mg/kg; CYP); and animals in group III to XI received free drug (ESC8), DX liposome and drug-associated DX liposomal formulation (DXE), respectively, dissolved in 5% solution of glucose at a drug-dose of 1.83, 3.67 and 7.34 mg/kg, respectively. Same drug treatments were followed for the female mice groups. The obtained data revealed the safety of DXE, which did not show substantial genotoxic effects at different dose levels. In contrast, the positive control, CYP, exhibited highly substantial irregular cytogenetic variations in comparison with the control group in different assays.     

Decreased GABABR expression and increased neuronal cell death in developing rat brain after PTZ-induced seizure

The objective of this study was to evaluate the PTZ-induced seizures effects on GABA_B receptor (R) expression and to observe its neurodegenerative effect in hippocampal part of developing rat brain. In the present study, high dose of pentylenetetrazol (PTZ 40 mg/kg) was injected in developing rats of age 5 weeks having average weight of 60–65 g for 4 days. Further, baclofen (B 3 mg/kg i.p) agonist and phaclofen (P 30 μg/rat) antagonist of GABA_BR were injected along with PTZ. Western blot analysis was used to elucidate expression of GABA_BR protein upon PTZ, baclofen and phaclofen exposure in the developing rat brain. Furthermore, PTZ-induced apoptotic neurodegeneration was also observed through the release of caspase-3 antibody and propidium iodide (PI) staining using confocal microscopy. Seizure was confirmed using electroencephalography (EEG) data obtained from the Laxtha EEG-monitoring device in the EEG recording room and EEG was monitored 5–15 min after PTZ injection. The results of the present study showed that PTZ-induced seizure significantly decreased GABA_BR expression and induced neuronal apoptosis in cortical and hippocampal part of brain. While, baclofen reverse the effect of PTZ by increasing the expression of GABA_BR as compared to the PTZ- , PTZ plus B- and PTZ plus P-treated groups. Our findings indicated that PTZ-induced seizure showed not only decrease in GABA_BR expression but also cause neuronal apoptosis in the developing rat brain.     

Serum immunoglobulin E levels in human immunodeficiency virus‐infected children with pneumonia

Elevated serum immunoglobulin E (IgE) levels have been reported in association with human immunodeficiency virus (HIV) infection in adults, but there is little information in children. The aim of the present study was to compare serum IgE levels in HIV‐positive and ‐negative children hospitalized with pneumonia in South Africa and to investigate whether IgE may be useful as a marker of specific infections or prognosis in HIV‐infected children. History, examination, blood tests, and induced sputum or bronchoalveolar lavage were carried out. Of 122 children [45% female, median age 8 months (3–20 months)], 81 were infected with HIV. A history of allergy or asthma was present in three children (two of whom were HIV positive). Serum IgE was higher in HIV‐infected children [83 (33–147) vs. 29 (6–113) IU/l; p = 0.011] as was immunoglobulin G (IgG) [49 (37–63) vs. 27.5 (23–34) g/l; p < 0.001]. CD4 lymphocytes [600 (330–1210) vs. 1900 (1500–3030) cells/µl], percentage CD4 cells [13.6 (9.4–20.3) vs. 40.1 (31.1–44.9)] and CD4 : CD8 ratio [0.3 (0.2–0.4) vs. 2 (1.4–2.8)] were lower in HIV‐positive children (p < 0.001 for all). Bacteremia occurred in 12 (10%) children; other specific pathogens identified included Mycobacterium tuberculosis in eight (7%) and Pneumocystis carinii in nine (7%). There was no correlation with CD4 count, CD4 : CD8 ratio, or the presence of specific pathogens, and IgE level. In‐hospital mortality (11%) did not correlate with IgE levels. HIV‐infected children with pneumonia have higher serum IgE compared with seronegative patients. In HIV‐positive children, IgE levels did not correlate with the degree of immunosuppression or with outcome.     

Dual Inhibition of Ca+2 Influx and Phosphodiesterase Enzyme Provides Scientific Base for the Medicinal Use of Chrozophora prostrata Dalz. in Respiratory Disorders

The crude ethanolic extract of Chrozophora prostrata (Cp.Cr) was tested using in vivo and ex vivo assays for its possible bronchodilatory effects in order to validate its medicinal use in respiratory disorders, like asthma and cough. Cp.Cr exhibited dose‐dependent inhibition of carbachol (CCh)‐induced bronchospasm in anesthetized rats, similar to aminophylline. When tested on guinea‐pig tracheal preparations, Cp.Cr caused relaxation of both CCh (1 μM) and high K⁺ (80 mM)‐induced contractions with comparable potencies, similar to papaverine, a dual inhibitor of phosphodiesterse (PDE) and Ca⁺² influx. Pre‐treatment of the tracheal tissues with Cp.Cr resulted in potentiation of the inhibitory effect of isoprenaline on CCh‐induced contractions, like that caused by papaverine indicative of PDE inhibitory activity, which was confirmed when Cp.Cr concentration dependently (1 and 3 mg/mL) increased intracellular cAMP levels of the tracheal preparations, like papaverine. Cp.Cr shifted concentrationresponse curves of Ca⁺² constructed in guinea‐pig tracheal preparation towards right with suppression of the maximum response, similar to both verapamil and papaverine. These data indicate bronchodilator activity of Chrozophora prostrata mediated possibly through dual inhibition of PDE and Ca⁺² influx, thus, showing therapeutic potential in asthma with effect enhancing and side‐effect neutralizing potential Copyright © 2016 John Wiley & Sons, Ltd.