El-Shaymaa El-Nahass

Kinetics and pathogenicity of equine herpesvirus-9 infection following intraperitoneal inoculation in hamsters.

The kinetics of infection and pathogenicity of equine herpesvirus-9 (EHV-9) was studied in a hamster model. Five-week-old Syrian hamsters and 5-day-old suckling hamsters were inoculated intraperitoneally with 10(5) and 4×10(4) plaque-forming units of EHV-9, respectively. EHV-9 antigens were detected by immunocytochemistry in the peritoneal macrophages, which may be the primary site of virus attachment and propagation at 6h post inoculation (hpi). At 12 hpi, viral antigen was observed in the abdominal nerves and ganglia (mainly the coeliac ganglia). Virus antigen was detected in the dorsal root (spinal) ganglia, in parts of the spinal cord (particularly the mid-lumbar area) and in the myenteric plexuses at 36, 48 and 72 hpi, respectively. At 96 hpi, virus antigen was detected in the most caudal part of the brain. Polymerase chain reaction conducted on samples of the blood, spinal cord and brain revealed EHV-9 DNA in the spinal cord at 36 hpi and in the blood at 48 hpi and for 4 days after this initial detection. It is suggested that after initial propagation in the abdominal macrophages, EHV-9 infected the abdominal ganglia or myenteric plexuses and then travelled to the brain via the peripheral nerves and spinal cord. Examination of other organs also revealed the presence of EHV-9, suggesting that the virus might infect tissues other than those of the nervous system.

Kinetics and pathogenicity of oral infection by equine herpesvirus-9 in mice and suckling hamsters.

The pathogenesis and kinetics of oral infection by equine herpesvirus (EHV)-9 were studied in mice and hamsters. After oral inoculation of 10(5) plaque-forming units (PFU) of virus, 1-week-old suckling hamsters showed varying severity of neurological disease from 72 hours post inoculation (hpi) and all of these animals had died by 96 hpi. Four-week-old ICR mice inoculated orally with 4 × 10(4)PFU of virus showed no clinical signs, but they developed erosive and ulcerative gastritis from 36 hpi. Varying degrees of encephalitis were seen in infected mice and hamsters, and the hamsters also developed myelitis by 96 hpi. Immunohistochemistry performed on whole body sections of suckling hamsters revealed the kinetics of spread of the virus to the central nervous system. EHV-9 antigen was detected initially in macrophages of the oral and lingual submucosa. At 36 hpi virus antigen was detected in the nerve fibres and pseudounipolar neurons of the trigeminal ganglion and at 96 hpi antigen was present in the myenteric plexuses of the intestine. Virus antigen was also detected in the liver, lungs and heart of affected animals. EHV-9 DNA was detected by polymerase chain reaction in the brain, blood and spinal cord of suckling hamsters at 36, 48 and 96 hpi. These findings show that EHV-9 may spread via the trigeminal nerve when mice and hamsters are inoculated orally with virus.

Effects of Equine Herpesvirus-9 Infection in Pregnant Mice and Hamsters

The pathogenicity of equine herpesvirus (EHV)-9, a new neurotropic equine herpesvirus isolated from gazelles, was assessed in pregnant rodents (mice and hamsters) following intranasal inoculation. The pregnant female mice and hamsters were inoculated with EHV-9 in the early or late trimesters. The inoculated animals exhibited mild to severe neurological signs and gave birth to dead or undersized fetuses. All three mice and four hamsters inoculated in the first trimester had varying degrees of placental abnormality, characterized by markedly dilated maternal blood sinusoids, atrophy of the trophoblast cells and necrosis of the middle layer of the trophoblast. There was also endometrial blood vessel congestion and necrosis and disorganization of the fetal capillaries in the mice and hamsters inoculated in the last trimester. EHV-9 antigen was detected in the brain of dams and the lungs of the fetuses and in the middle of the trophoblast layer of the placenta in hamsters inoculated in the first trimester. The placental lesions were milder in mice than in the hamsters. The mice and hamsters inoculated in the last trimester had more prominent lesions than the animals inoculated in the first trimester. These results suggest that EHV-9 can cause the death of the fetus or abortion and that these events may be secondary to placental vascular compromise.

Design, synthesis, analgesic, anti-inflammatory activity of novel pyrazolones possessing aminosulfonyl pharmacophore as inhibitors of COX-2/5-LOX enzymes: Histopathological and docking studies

A series of newly synthesized 4-aryl-hydrazonopyrazolones were designed and their structures were confirmed by spectral and elemental analyses. All synthesized compounds were evaluated for their in vitro COXs, 5-LOX inhibition, in vivo analgesic and anti-inflammatory activities. Compounds 5d, 5f and 5i were found to be the most potent COX-2/5-LOX inhibitors with superior COX-2 selectivity index values (SI = 5.29-5.69) to reference standard celecoxib (SI = 3.52). Four compounds; 5b, 5c, 5d and 5f showed excellent anti-inflammatory activity (% edema inhibition = 72.72-54.54%) and perfect ED50 values (ED50 = 0.044-0.104 mmol/kg) relative to celecoxib (ED50 = 0.032 mmol/kg). To explore the most active compounds, ulcerogenic effect on stomach in comparison with indomethacin and celecoxib in addition to histopathological investigations were performed. Compound 5f showed better gastric profile (UI = 2.33) than celecoxib (UI = 3.00). Also, 5f caused 50% increase in thermal pain threshold close to reference drug indomethacin (53.13%). Docking study of all the target compounds into COX-2 and 5-LOX active sites was performed to rational their anti-inflammatory activities.

Moringa oleifera Leaves Extract Protects Titanium Dioxide Nanoparticles-Induced Nephrotoxicity via Nrf2/HO-1 Signaling and Amelioration of Oxidative Stress

The efficacy of Moringa oleifera leaf extract (MO) in alleviating nephrotoxicity induced by titanium dioxide nanoparticles (TiO2 NPs) was studied. Rats were divided into four groups. Group I received distilled water. Group II received TiO2NPs. Group III received both TiO2NPs suspension beside MO. Group IV received MO only. Kidney KIM-1, NF-кB TNF-α, and HSP-70 expression were significantly upregulated while both Nrf2 and HO-1were significantly downregulated in TiO2NPs-treated rats. MO decreases expression of KIM-1, NF-кB, TNF-α, and HSP-70. In addition, MO has markedly upregulated the expression of Nrf2 and HO-1. In conclusion, MO can inhibit nephrotoxicity by suppressing oxidative stress and inflammation. These effects are suggested to be mediated by activating Nrf2/HO-1.The biochemical analysis and histopathological finding reinforced these results. These data support the antioxidant properties’ nutraceutical role of MO against TiO2NPs-induced toxicity.

Forensic Image Analyses of Skin and Underlying Muscles as a Tool for Postmortem Interval Delimitation: Histopathologic Examination

Abstract One of the biggest challenges for forensic pathologists is to diagnose the postmortem interval (PMI) delimitation; therefore, the aim of this study was to use a routine histopathologic examination and quantitative analysis to obtain an accurate diagnosis of PMI. The current study was done by using 24 adult male albino rats divided into 8 groups based on the scarification schedule (0, 8, 16, 24, 32, 40, 48, and 72 hours PMI). Skin specimens were collected and subjected to a routine histopathologic processing. Examination of hematoxylin-eosin–stained sections from the skin, its appendages and underlying muscles were carried out. Morphometric analysis of epidermal nuclear chromatin intensities and area percentages, reticular dermis integrated density, and sebaceous gland nuclei areas and chromatin condensation was done. Progressive histopathologic changes could be detected in epidermis, dermis, hypodermis, underlying muscles including nerve endings, and red blood cells in relation to hours PMI. Significant difference was found in epidermal nuclear chromatin intensities at different-hours PMI (at P < 0.001). The highest intensity was detected 40 hours PMI. Quantitative analysis of measurements of dermal collagen area percentages revealed a high significant difference between 0 hours PMI and 24 to 72 hours PMI (P < 0.001). As the PMI increases, sebaceous gland nuclei and nuclear chromatin condensation showed a dramatic decrease. Significant differences of sebaceous gland nuclei areas between 0 hours and different-hours PMI (P < 0.001) were obtained. A combination between routine histopathologic examination and quantitative and morphometric analysis of the skin could be used to evaluate the time of death in different-hours PMI.

Pathological findings in equine herpesvirus 9-induced abortion in rats.

Pregnant rats were infected experimentally with equine herpesvirus (EHV)-9, a new neurotropic equine herpesvirus serologically similar to EHV-1, during the first and third trimesters. The inoculated dams had mild to severe neurological signs and gave birth to dead fetuses or undersized pups. Rats inoculated during the first and last trimesters had varying degrees of encephalitis as well as abnormalities of the placentas in the form of marked dilation of maternal blood sinusoids and varying degrees of atrophy and necrosis of the trophoblast cells of the labyrinth, the spongiotrophoblasts and the giant cell layer. Virus antigen was detected by immunohistochemistry in the brain and the trophoblast cells of labyrinth, the spongiotrophoblasts and giant cell layer of the placenta in rats inoculated during the first trimester. Virus antigen was detected in fetuses from rats inoculated in the first and last trimesters. Virus DNA was amplified by polymerase chain reaction from the placenta and fetuses of inoculated rats. EHV-9 may induce fetal death and abortion in pregnant dams, possibly caused by direct EHV-9 infection of the placenta and/or fetus as well as the secondary effect of vascular injury.