Normal Saline Control Research Articles

Intramyocardial Injection of Plasmid Encoding Platelet Growth Factor Increases Epicardial-Mediated Post Infarction Myocardial Vascularization (Experimental Study)

Increasing incidence of ischemic diseases and limited resources for their treatment stimulate increased interest in studying the mechanisms of vascularization and finding new approaches for its promotion. One of these approaches is gene therapy aimed at activating the epicardium to produce the vascular precursor cells and microenvironment for the «assembly» of de novo vessels. The aim is to investigate the possibility of activating epicardial cells and post infarction cardiac vascularization by injecting a genetic construct encoding PDGFBB. Material and methods . A model of experimental myocardial infarction in a rat with subsequent intramyocardial injection of normal saline solution, control plasmid and plasmid encoding PDGFBB was used. The study of PDGFBB effect on epicardial cell activity was performed on the ex vivo model, as well as in vitro mesothelial cell culture. Results . Post infarction injection of plasmid encoding PDGFBB increases the density of the vascular network in the peri-infarct area as well as migration of pericytes to the injured zone. PDGFBB promotes activation of epicardial cell pool and expression of smooth muscle cell markers in them (shown on the ex vivo model), as well as stimulates activation of epithelial-mesenchymal transition (in vitro). Conclusion . Intramyocardial injection of a genetic construct encoding PDGFBB after an experimental myocardial infarction stimulated vascularization of the peri-infarction zone, which may have been partially due to the activation of the epicardial cell pool.

Immunogenicity and Efficacy Study on Newcastle Disease Vaccine Using Many Adjuvants and Chitosan Nanoparticles

To potentiate the immune responses of the Newcastle Disease vaccine, many adjuvants such as, Saponin, Paraffin oil, sunflower oil, Nigella Sativa oil, and Chitosan Nanoparticles “CHNPs”, were prepared with live and inactivated I-2 vaccines. The formulated vaccines were tested for their biological and physical characteristics, including sterility, safety, Immunogenicity protective efficacy, protein estimation for CHNPs, and the completion of the emulsification. The protein concentrations of pre and post encapsulation for CHNPs were 0.23g/100 ml and 0.065g/100 ml respectively. The encapsulation efficiency was 71.7%. To test the safety, immunogenicity and efficacy, a 180 white leghorn day-old-chicks divided randomly in to 9 groups of A, B, C, D, E, F, G, H, and I, a 20 chicks for each. Group A (Saponin + Iinactivated I-2), group B (Paraffin oil + Iinactivated I-2), group C (CH-NPs+ Inactivated I-2), group D (Saponin + Live + Inactivated), group E (Nigella Sativa oil+Live I-2), group F (Sunflower oil + Live I-2), group G (Saponin+Live I-2) each groups from A to G simultaneously and inrtaocularly (I/O) inoculated with 107 EID50 I-2 live vaccine. Group H (control group I) received only (Saponin+Inactivated), group I (control group II) received the placebo (Normal Saline) control group, in this group only 5 chicks out of 20 inoculated I/O with 106 EID50 of live I-2, and the remaining chicks were left unvaccinated. There was no evidence for bacterial growth for the tested and control groups, nor post vaccination reactions neither ND clinical signs observed (except for Nigella Sativa oil). Immunogenicity was estimated using ELISA test. The highest Abs mean titer was for group E While the lowest Abs mean titer was for group C. Mean values were analyzed using one way analysis of variance test (ANOVA). Mean Differences were considered to be statistically significant at P .05). Groups A, B, C, D, and H challenged via mixing with clinically ill chickens for 14 days. The highest protection level was 90% for group D, while the lowest protection 50% was for group B (Paraffin oil+ Inactivated).

Effects of conventional and herbal irrigants on microhardness and flexural strength of root canal dentin: An in vitro study.

Aim:The aim of this in vitro study was to compare the effects of herbal irrigants with conventional irrigants on microhardness and flexural strength of root dentin.Materials and Methods:Sixty extracted permanent maxillary canines were selected. Decoronated roots were sectioned longitudinally into buccal and lingual segments to get 120 specimens. These were embedded in auto polymerizing acrylic resin and further grounded with fine emery papers under distilled water. Of these, 100 root segments without any defects were selected, further divided into four test groups and a control group according to the irrigants used (n = 20). Group 1: 2.5% Sodium hypochlorite, Group 2: Miswak stick extract, Group 3: Cashew leaves extract. Group 4: Mango leaves extract and Group 5: Normal saline (control). All specimens were treated with 5 ml of each irrigant for 10 minutes and rinsed immediately. Dentin microhardness was measured with a Vickers indenter, and the flexural strength test was done using a universal testing machine. The data were analyzed using one-way ANOVA and the intergroup comparison by student t-test.Results:The experimental groups showed a significant reduction in microhardness values when compared with the control group. Intragroup comparison among experimental groups, herbal irrigants showed the least reduction in microhardness values at cervical, middle, and apical thirds. When compared to the control group, the flexural strength values decreased significantly with experimental groups.Conclusion:Within the limitation of this study, it was concluded that herbal irrigants were least detrimental to root dentin microhardness when compared with conventional irrigant. But the flexural strength was equally reduced by both conventional and herbal irrigants.

The anti-breast cancer property of physcion via oxidative stress-mediated mitochondrial apoptosis and immune response

Context Physcion (Phy) exerts several pharmacological effects including anti-inflammatory, antioxidant, and antitumor properties. Objective This study investigates the cytotoxicity and its underlying mechanisms of Phy on breast cancer. Materials and methods Human breast cancer cell MCF-7 was treated with 5–400 µM Phy for 24 h, MCF-7-xenografted BALB/c nude mice and immunosuppressive mice model induced by cyclophosphamide were intraperitoneally injected with 0.1 mL/mouse normal saline (control group) and 30 mg/kg Phy every other day for 14 or 28 days, and pathological examination, ELISA and western blot were employed to investigate the Phy anti-breast cancer property in vitro and in vivo. Results In MCF-7 cells, Phy 24 h treatment significantly reduced the cell viability at dose of 50–400 µM and 24 h, with an IC50 of 203.1 µM, and 200 µM Phy induced 56.9, 46.9, 36.9, and 46.9% increment on LDH and caspase-3, −8 and −9. In MCF-7-xenograft tumour nude mice and immunosuppressive mice, 30 mg/kg Phy treatment inhibited tumour growth from the 8th day, and reduced Bcl-2 and Bcl-xL >50%, HO-1 and SOD-1 > 70% in tumour tissues of immunosuppressive mice. In addition, Phy reduced nuclear factor erythroid 2-related factor 2 > 30% and its downstream proteins, and enhanced the phosphorylation of nuclear factor-kappa B > 110% and inhibitor of NF-кB α > 80% in the tumour tissues of BALB/c mice. Discussion and conclusions This research demonstrated that Phy has an anti-breast cancer property via the modulation of oxidative stress-mediated mitochondrial apoptosis and immune response, which provides a scientific basis for further research on its clinical applications.

Nephroprotective effects of ethanolic root extract of Azima tetracantha lam in adenine-induced chronic kidney failure in Wistar rats.

OBJECTIVES: To evaluate the effects of ethanolic root Ethanolic extract of Azima tetracantha. Lam roots (EEATR) in adenine.induced chronic kidney failure in Wistar albino ratsTo assess the antioxidant activity of EEATR. MATERIALS AND METHODS:Thirty rats were selected and allocated to five groups with six animals in each group. Group 1 was given normal saline (control), Group 2 – adenine, 0.75% 40 mg/kg, Group 3 – adenine and 250 mg/kg of EEATR, Group 4 – adenine and 500 mg/kg EEATR, and Group 5 – EEATR 500 mg/kg. Saline, adenine, and EEATR were given orally once daily for 28 days. EEATR was given 60 min before adenine administration. Urine output, blood urea nitrogen (BUN), creatinine, albumin, and total proteins were estimated. The histopathological changes in the kidneys were examined, and antioxidant property of the extract was assessed in the renal tissue.RESULTS:Adenine treated rats had a reduction in urine output (‒45%), food intake (‒46%), body weight (‒28%), total proteins (‒66%) and albumin (‒59%) and an increase in creatinine (950%), BUN (73.6%), and kidney weight (43.75%). Histological examination of the kidneys showed capillary congestion, tubular damage, glomerular distortion, and many oxalate crystals. Rats co-administered with EEATR 250 and 500 mg/kg had marked improvement (P ≤ 0.0001%) in all the above parameters with a marked reduction in size and number of oxalate crystals in the kidney. In the anti-oxidant assays, EEATR exhibited significant antioxidant activity.CONCLUSION:EEATR was found to be an effective nephroprotective agent in adenine-induced chronic renal failure in Wistar albino rats.

Long-Term Administration of Abacavir and Etravirine Impairs Semen Quality and Alters Redox System and Bone Metabolism in Growing Male Wistar Rats.

Highly active antiretroviral therapy (HAART) is used in HIV-infected patients. Alongside the prolongation of patients' life, adverse side effects associated with long-term therapy are becoming an increasing problem. Therefore, optimizing of HAART is extremely important. The study is aimed at evaluating the toxicity of abacavir and etravirine in monotherapy on the reproductive system, liver, kidneys, and bones in young, sexually mature, male rats. Thirty-six 8-week-old male Wistar rats randomized into three 12-animal groups received either normal saline (control), abacavir 60 mg/kg (AB group), or etravirine 40 mg/kg (ET group) once daily for 16 weeks. Semen morphology, oxide–redox state parameters (MDA, SOD, catalase, GPx, glutathione, GSH/GSSG ratio) in tissue homogenates (testes, liver, kidneys), and serum samples were studied. In bones, microcomputed tomography and a four-point bending test were performed. Total sperm count, sperm concentration, motility, and sperm morphology did not differ significantly in AB or ET groups compared to the control. In the flow cytometry of semen, an increased percentage of cells with denatured DNA was noticed for both tested drugs. However, no significant changes of oxide–redox state in testicular homogenates were found, except of increased SOD activity in the AB-receiving group. Additionally, ET significantly altered catalase and GPx in the liver and SOD activity in kidneys. Abacavir decreased catalase in the liver and GSH levels in kidneys. AB caused significant changes to bone microarchitecture (bone volume fraction, trabecular number, connectivity density, total porosity) and increased Young's modulus. Etravirine had a greater impact on macrometric parameters of bones (tibial index, mid-tibial diameter, femur length). After 4 weeks in the ET group, a lower 1,25-dihydroxyvitamin D3 serum concentration was found. The results showed that abacavir and etravirine disturb oxidative stress. An increase in the percentage of sperms with chromatin damage suggests decreased fertility in rats receiving the studied drugs. Both drugs affected bone formation in growing rats. Additionally, etravirine disturbed vitamin D metabolism.

Ginsenoside Rg2 alleviates myocardial fibrosis by regulating TGF-β1/Smad signalling pathway

Context Panax ginseng C.A. Meyer (Araliaceae) has cardioprotective effects. Ginsenosides are responsible for most of the pharmacological activities of ginseng. Objective This study investigates the effect of ginsenoside Rg2 on myocardial fibrosis in myocardial ischaemia rats. Materials and methods Male Wistar rats were divided into control, isoproterenol, ginsenoside Rg2 (5, 20 mg/kg) groups (n = 8). The rats were subcutaneously injected with isoproterenol (5 mg/kg) or normal saline (control group) once daily for 7 days. The animals were intragastrically treated with ginsenoside Rg2 or 0.5% CMC-Na (control and isoproterenol groups) daily for 28 days. At day 28, cardiac function, myocardial fibrosis, and TGF-β1/Smad signalling pathway were evaluated. Results Compared with myocardial ischaemic rats, ginsenoside Rg2 at doses of 5, 20 mg/kg abated partially the augment of LVEDP (8.9 ± 1.3 vs. 7.5 ± 0.7, 7.2 ± 1.0 mmHg) and the decreases of the LVSP (96.75 ± 13.2 vs. 118.3 ± 19.4, 124.3 ± 21.3 mmHg), the + dp/dt (2142.8 ± 309.3 vs. 2598.6 ± 404.0, 2661.5 ± 445.2 mmHg/s), and the -dp/dt (1996.3 ± 306.3 vs. 2476.6 ± 289.7, 2509.6 ± 353.1 mmHg/s). Ginsenoside Rg2 (9.2 ± 0.9%, 8.5 ± 0.8%) alleviated myocardial fibrosis when compared with the isoproterenol group (10.1 ± 1.0%), which was accompanied by suppressed TGF-β1/Smad signalling in heart tissues. Conclusions Ginsenosides from ginseng possess the property of alleviating myocardial fibrosis, improving cardiac function after myocardial ischaemia. Ginsenosides may be promising agents for improving the outcomes of patients with myocardial ischaemia.

Comparative evaluation of antimicrobial efficacy of Asphaline Temp, Triple antibiotic Paste and Ultracal XS against Enterococcus faecalis – An in vitro study

Aim: This study aimed to evaluate and compare the antimicrobial efficacy of asphaline temp, triple antibiotic paste (TAP), and Ultracal Xs against Enterococcus faecalis – An in vitro study.Materials and method: A hundred and twenty freshly extracted, single-rooted human permanent teeth were instrumented and autoclaved. Samples were inoculated with the pure culture of E. faecalis and incubated. After incubation, colony-forming units (CFUs) were recorded before medication. Each group was further divided into three subgroups containing ten samples each for days – 1 day, 5 days, and 7 days. Group A – Asphaline Temp; Group B – TAP; Group C – Calcium hydroxide; and Group D – Normal saline (Control). The various time interval bacterial (CFU) within the group were compared by the Analysis of Variance followed by Tukey's Post hoc test.Results: The greater antimicrobial effects were observed in the samples treated with Asphaline temp (P < 0.005). No statistical antimicrobial difference was found between Asphaline temp and TAP.Conclusion: Asphaline temp demonstrated significant antimicrobial effectiveness against E. faecalis.

Evaluation of Wound Healing Activity of an Ethanolic Extract of Anacardiumoccidentale Leaves in Wistar Rats

BACKGROUND -This study undertaken to screen a potential wound healing activity of an ethanolic extract of Anacardiumoccidentale(Ao)leaves in Wistar rats. MATERIALS AND METHODS-Excision wound of 500mm2created on the back of Wistar rats. A total of thirty adult Wistar rats were prescreened and divided into five groups of six rats each.Group I and II rats were treated by normal saline (control) and povidone-iodine (standard drug), respectively. Group III and IV with 0.5% and 2%of Anacardiumoccidentale ointment (test drugs), respectively, and Group V rats treated with anti-wound healer drug dexamethasone, i.m. + 2% Anacardiumoccidentale. All drugs were applied topically except Inj. dexamethasone. In the model of excision wound, the wound healing effect was determined by parameters such as the percentage of wound contraction, duration of epithelialization, and histopathological examination. RESULT-All drugs, povidone-iodine, 0.5%, and 2% of the Ao ointment treated group of rats showed a statistically significant increase (P&lt;0.05) in the % of wound contraction on 5th and 6thdays Vs.Control rats. In contrast,povidone-iodine, 2% Ao ointment and (dexamethasone + 2% Ao)treated rats decreased the period of epithelialization which was statistically significant (P&lt;0.05) compared to the control.However, the standard povidone-iodine treated rats showed a maximum increase in the percentage of wound contraction and minimum period of epithelialization, followed by a higher dose of 2% Ao extract. The plant extract 0.5% and 2% of Ao showeda significant increase inthe rate of wound contraction as compared to the standard drug povidone-iodine also. The combination of (2%Aoextract+dexamethasone) drug-treated rats decreased the rate of wound contraction on 5th, 9th days; whereas, povidone-iodine increased on all days, i.e., 5th, 9th, 13th and 17th days,which was statistically significant (p&lt;0.05) Vs.Normal saline. The povidone and 2% of Ao extract hastened the rate of wound healing activity, which was evident by maximum re-epithelialization and presence of the collagen fibers. CONCLUSION-In our study, the topical application of Anacardiumoccidentale leaf extract has shown promising wound healing activity; however, it failed to reverse the anti-wound healing property of steroids.

Cerium oxide nanoparticles elicit antitumourigenic effect in experimental breast cancer induced by N-methyl-N-nitrosourea and benzo(a)pyrene in female Wistar rats.

The use of cerium oxide nanoparticles [CeO2 NPs] in the biomedical field has continued to gain prominencedue to its potent antioxidant property. This study was designed to assess the antitumorigenic effect of CeO2 NPs in rats administered N-methyl-N-nitrosourea [NMU] and benzo(a)pyrene (BaP). Twenty four female Wistar rats were equally assigned into four groups and treated with normal saline (control), [NMU + BaP], [NMU + BaP+CeO2 NPs], and [NMU + BaP + vincristine]. Animals were pretreated with NMU and BaP three times (age 7, 10, and 13 weeks). Thereafter, vincristine and CeO2 NPs were administered twice and three times per week, respectively, for 13 weeks. Results showed that the administration of NMU and BaP increased serum nitric oxide [NO] and myeloperoxidase [MPO] by 220% and 132%, respectively, whereas the activities of aspartate and alanine aminotransferases and level of total bilirubin remained unchanged. Furthermore, mammary inflammatory [NO and MPO] and oxidative stress (LPO) markers were increased by 37%, 19%, and 24%, respectively. Mammary superoxide dismutase, catalase, reduced glutathione, and glutathione-S-transferase were significantly decreased in [NMU + BaP]-administered rats by 165%, 146%, 35%, and 36%, respectively. Immunohistochemistry showed downregulation of Bax, p53, and caspase-3, while histology revealed the presence of malignant epithelial cells with pyknotic nuclei and high nucleocytoplasm in [NMU + BaP]-administered rats. Treatment with CeO2 NPs attenuated oxidative stress, apoptosis, and inflammation and restored the cytoarchitecture of the tissue. Overall, CeO2 NPs show an antitumourigenic effect in experimental breast cancer by targeting pathways linked to inflammation and apoptosis.

Effects of efavirenz and tenofovir on bone tissue in Wistar rats.

Clinical trials indicate an increased risk of osteoporosis and bone fractures in people infected with human immunodeficiency virus (HIV). The pathogenesis of bone disturbances in HIV-positive patients is unknown, but it is suggested that antiretroviral drugs may be involved. To assess the effects of efavirenz (EF) and tenofovir (T) on bone remodeling in rats. The study involved 36 male Wistar rats divided into 3 groups, receiving normal saline (control group - group C), efavirenz (group EF) or tenofovir disoproxil (group T). After 24 weeks of the study, the following observations were made: In blood serum of the EF group compared to group C, there were increased levels of tartrate-resistant acid phosphatase form 5b (TRAP) and inorganic phosphorus. In the densitometric examination, group T showed a lower total body (TB) bone mineral density (BMD) than group C. In the immunohistochemical assessment, group EF showed a higher intensity and extension of anti-tartrate resistant acid phosphatase antibodies (abTRAP) compared to group C. In the histopathological examination of the second lumbar vertebra (L2), group EF showed a lower bone surface/volume ratio (BS/BV) and higher trabecular thickness (Tb.Th) than the control group. In the histopathological examination of the femur, a lower bone surface/tissue volume (BS/TV) and lower trabecular number (Tb.N) were found in group T compared to in group C. A lower value of the Young's modulus was observed in the four-point bending trial in groups EF and T compared to group C. The results of this study indicate that EF affects bone microarchitecture and leads to impaired biomechanical properties of bones in rats. Additionally, the negative effect of T on bone tissue was confirmed.

Effect of Ultramicro Superparamagnetic Iron Oxide Nanoparticles on Cerebral Infarction in Mice.

To investigate the effect of Feraheme (ferumoxytol) intravenous injection on cerebral infarction volume and inflammatory response in mice with permanent middle cerebral artery occlusion. We randomly divided 30 CS7BL6J mice into sham operated group, normal saline control group, and Feraheme group with 10 mice in each group. The model of permanent occlusion of right middle cerebral artery was made via the modified suture method in the normal saline control group and the Feraheme group. After 24 h of establishment the model, the tail vein was injected with 18 mg/kg Feraheme in the sham operation group and Feraheme group, and the normal saline control group was injected with an equal volume of normal saline. Neurobehavioral scores were obtained 24 h (before injection of Feraheme or normal saline) and 48 h (before MRI) after the model was established. The volume of cerebral infarction was calculated according to T2 weighted imaging. Orbital blood was collected after nodal scanning to detect serum TNF-α, IL-1β, and IL-6 levels. Then, the brain tissues of mice were killed for HE staining and IBAL immunohistochemical staining. No significant differences in cerebral infarction volume and neurological function were observed between the normal saline control group and Feraheme group. The levels of TNF-α, IL-1β and IL-6 in the normal saline control group and Feraheme group were significantly higher than those in the sham operation group (P < 0.05), but there were no significant differences between the normal saline control group and Feraheme group. We showed that intravenous injection of 18 mg/kg Feraheme 24 h after cerebral ischemia does not affect the infarct volume and inflammatory response, suggesting that the dose of Feraheme can be used for molecular imaging studies of inflammatory response after cerebral ischemia.

Evaluation of the analgesic activity of an aqueous extract of the seeds of Nigella sativa Linn in albino rats

Background: Many herbs and plant products have been claimed to have a significant analgesic action. However, not much work has been reported on the pharmacological evaluation of such plant-based products for the analgesic effects claimed in traditional medicine. Aim and Objective: The study aimed to assess the analgesic potential of the aqueous extract of Nigella sativa Linn (NSL) in albino rats by the hot plate and tail-flick method and to compare it with the standard drug indomethacin. Materials and Methods: Four groups of randomly divided albino rats were made. Group 1 was given oral normal saline (0.1 mg/kg) (control group). Group 2 was given indomethacin 25 mg/kg orally (standard group). Groups 3 and 4 (test groups) were administered NSL 300 mg/kg body weight (BW) and 600 mg/kg BW orally, respectively. The hot plate and tail-flick method were used to screen for analgesic potential. Results: Our study revealed a uniform increase in reaction time in both test groups which received NSL. Maximum analgesic activity was noted at 120 min. NSL has good analgesic activity in comparison with the control. However, indomethacin has significantly better activity than NSL at both doses. NSL at 600 mg/kg BW has analgesic activity comparable to indomethacin only at 20 min. Conclusion: NSL has analgesic potential, but comparatively, indomethacin is a more potent analgesic drug.

The Effect of Epinephrine Sprayed on the Papilla on Prevention of Post–Endoscopic Retrograde Cholangiopancreatography Pancreatitis (PEP); a Double-Blind Randomized Control Trial

Acute pancreatitis is the most common and serious complication of Endoscopic Retrograde Cholangiopancreatography (ERCP). The use of effective medicines with low side effects should be considered in the process of RCP due to acute pancreatitis prevention. Therefore, we investigate the effects of epinephrine sprayed on the papilla in this study. This randomized clinical trial was performed on 343 patients referred to the ERCP Department of Imam Reza Hospital and Apadana Clinic, Mashhad, Iran. About 10 ml of diluted epinephrine (case group) or normal saline (control group) were sprayed on the papilla before diagnostic ERCP. Afterward, the two groups were assessed in terms of post-ERCP pancreatitis. The data were analyzed using Statistical Package for the Social Sciences (SPSS) software, version 20. The level of significance was considered to be 0.05. The overall results of this study indicated that post-ERCP pancreatitis occurred in 4.95% of the patients. Mild pancreatitis was diagnosed in five patients of the case group and three patients of the control group, respectively. Moderate pancreatitis was diagnosed in three patients of the case group and three patients of the control group. Only one patient in the case group and two patients in the control group were shown to have severe pancreatitis. Moreover, there was no significant difference between the incidence of pancreatitis between the two groups (P&gt;0.05). With regard to the findings of this study, it appears that the topical application of epinephrine is not effective in preventing post-ERCP pancreatitis.

Permethrin exposure affects neurobehavior and cellular characterization in rats' brain.

This study investigated the neurotoxic effects of permethrin on the cerebellum, hippocampus and prefrontal cortex of Wistar rats and its effects on some behavioral patterns. Fifteen adult male Wistar rats were grouped into three categories: Group A received 0.1 mL normal saline (control), and Groups B and C received mixed feed with 500 mg/kg and 1,000 mg/kg of 0.6% permethrin, respectively, for 14 days. The animals were assessed for memory, anxiety and exploratory locomotion and thereafter anesthetized and transcardially perfused with normal saline and 4% paraformaldehyde (PFA). Cerebellum, hippocampus and prefrontal cortex were excised from the whole brain and processed for tissue histology, histochemistry and immunohistochemistry. Oxidative status and lipid peroxidation were also assessed using catalase, glutathione peroxidase, superoxide dismutase and malondialdehyde as biomarkers. Results revealed dose-dependent decrease in body weights but increase in cerebellar and prefrontal weights, depletion of endogenous antioxidant markers, cognitive deficits, reduced locomotor activities, degenerative changes in the microarchitecture at high doses and presence of chromatolytic cells at both low and high doses of permethrin. Astrocytes were activated while synaptophysin expression was downregulated. Permethrin causes dose-dependent neurotoxicity on the morphology, neurochemistry and oxidative status of different brain regions, and these could affect behavioral performance and other neurologic functions.

Effects of Atorvastatin Calcium on the Survival of Ultra-long Dorsal Random Skin Flaps in Rats

To investigate the effects of atorvastatin calcium (ATR) on the survival of ultra-long dorsal random skin flaps in rats. Thirty SD rats were divided into five groups ( n=6) according to the random number table: normal saline control group (CON group), ATR 10 mg/kg group (P10 group), ATR 20 mg/kg group (P20 group), ATR 30 mg/kg group (P30 group), and ATR 40 mg/kg group (P40 group). After pretreatment with ATR or 0.9% saline for 3 days, an ultra-long dorsal random skin flaps with size of 8 cm×2 cm was made on the back of each rat and replanted in situ. After the operation, the ATR or saline treatment lasted for 3 d. Seven days after operation, the appearance of skin flaps was observed with naked eyes, the survival rate of skin flaps was calculated. The pathological changes in the surviving areas of skin flaps were observed by HE staining, the number of microvessels in skin flaps was observed by immunohistochemistry staining, the mRNA expressions of vascular endothelial growth factor ( VEGF) and basic fibroblast growth factor ( bFGF) were tested by quantitative real-time PCR, and the contents of superoxide dismutase, nitrogen monoxide and malonaldehyde were tested by enzyme linked immunosorbent assays (ELISA). On the 7 thday after operation, the skin flap of the CON group showed a large area of necrosis, and the necrotic part formed crusts. Crusts were hard and inelastic, and a large amount of tissue fluid exudated. The fascial layer showed dark purple. No exudation of tissue fluid was observed in the flaps of P10, P20, P30 and P40 groups. The scab shell fell off naturally and the fur grew normally. HE staining of CON group showed that a large number of inflammatory cell infiltration, epidermal loss and necrosis in skin flaps, but the pathological changes in skin flaps were significantly improved after treatment with ATR. Compared with the CON group, the survival rate of skin flaps, the number of microvessels in skin flaps and the levels of VEGF mRNA, bFGF mRNA, SOD, NO in skin flaps also increased with the dose of ATR, which reached a peak at 30 mg/kg ATR ( P<0.05). However, the level of MDA in skin flaps decreased with the dose of ATR, which reached the lowest at 30 mg/kg ATR ( P<0.05). ATR can enhance the survival of ultra-long dorsal random skin flaps in rats, which may be related to promoting microangiogenesis and inhibiting inflammatory and oxidative stress.

Hemodynamic Assessment and In vivo Catabolism of Adenosine 5'-triphosphate in Doxorubicin or Isoproterenol-induced Cardiovascular Toxicity.

Previous studies have shown that catabolism of adenosine 5'-triphosphate (ATP) in systemic blood is a potential surrogate biomarker for cardiovascular toxicity. We compared the acute toxicity of high doses of doxorubicin (DOX) and isoproterenol (ISO) on hemodynamics and ATP catabolism in the systemic circulation. sprague Dawley (SD) rats (n = 8 - 11) were each given either a single dose of 30 mg/kg ISO, or a twice-daily dose of 10 mg/kg of DOX or 4 doses of normal saline (control) by subcutaneous injection. Blood samples were collected up to 6 hours for measuring concentrations of ATP and its catabolites. Hemodynamics was recorded continuously. The difference was considered significant at p < 0.05 (ANOVA). Mortality was 1/8, 5/11, and 0/11 for the DOX, ISO, and control groups, respectively. Systolic blood pressure was significantly lower in the DOX and ISO treated rats than in control measured at the last recorded time (76 ± 9 for DOX vs. 42 ± 8 for ISO vs. 103 ± 5 mmHg for control, p < 0.05 for all). Blood pressure fell gradually after the final injection for both DOX and control groups, but abruptly after ISO, followed by a rebound and then gradual decline till the end of the experiment. Heart rate was significantly higher after ISO, but there were no differences between the DOX and control rats (p > 0.05). RBC concentrations of ADP and AMP, and plasma concentrations of adenosine and uric acid were significantly higher in the ISO group. In contrast, hypoxanthine concentrations were significantly higher in the DOX treated group (p < 0.05). Acute cardiovascular toxicity induced by DOX and ISO may be measured by changes in hemodynamics and breakdown of ATP and adenosine in the systemic circulation, albeit a notable qualitative and quantitative difference was observed.

Aldh2 gene reduces oxidative stress in the bladder by regulating the NF-κB pathway in a mouse model of ketamine-induced cystitis.

Aldehyde dehydrogenase 2 (aldh2) serves an important role in the development of organ injury. Therefore, the present study investigated the effects of aldh2 on the oxidative stress response in a mouse model of ketamine-induced cystitis (KIC). A total of 60 8-week-old male Institute of Cancer Research wild-type (WT) mice and 45 aldh2 knock-out (KO) mice were randomized to receive low-dose ketamine (30 mg/kg), high-dose ketamine (60 mg/kg) or normal saline (controls). At 4, 8 and 12 weeks post-injection, bladder tissues were harvested and used to investigate the protective mechanisms of aldh2 on bladder function. The results demonstrated that aldh2 KO mice exhibited significant weight loss following chronic ketamine injection compared with that in WT mice. Furthermore, ketamine treatment increased the urination rate (P<0.05), pathological score (P<0.05), levels of the oxidative stress product malondialdehyde (P<0.05) in addition to reducing the expression of the anti-oxidative stress enzyme superoxide dismutase (P<0.05) and glutathione-SH (P<0.05). Oxidative stress in aldh2 KO mice was also found to significantly enhance the expression of proteins associated with the NF-κB signaling pathway, which promoted the expression of inducible nitric oxide synthase (P<0.05) and cyclooxygenase-2 (P<0.05) further. Finally, aldh2 KO mice demonstrated higher severity of fibrosis in the submucosal and muscular layers of the bladder. In conclusion, the present study suggests that aldh2 serves a protective role in preventing inflammation and fibrosis in KIC.

Involvement of Mitophagy in Aluminum Oxide Nanoparticle-Induced Impairment of Learning and Memory in Mice.

Aluminum oxide nanoparticles (nano-aluminum) have been known to be widespread in the environment for decades. Exposure to nano-aluminum may impair learning and memory, but the potential mechanism has not yet been elucidated. In neurons, efficient clearance of damaged mitochondria through mitophagy plays an important role in mitochondrial energy supply, neuronal survival, and health. However, abnormal mitophagy induces accumulation of damaged mitochondria, which induces cellular dysfunction, contributing to the impairment of learning and memory. It is currently unclear whether nano-aluminum interferes with the function of nerve cells through mitophagy, leading to learning and memory disorders. Institute of Cancer Research (ICR) female mice were randomly divided into four groups, and treated with normal saline (control) and 50nm nano-aluminum at concentrations of 25, 50, and 75mg/kg for 30days. Our results showed that exposure to nano-aluminum impaired the spatial learning and memory of mice. Superoxide dismutase levels decreased, whereas the levels of malondialdehyde increased. Moreover, there were significant pathological changes in the ultra-structure and function of mitochondria. Finally, expression of autophagy-related proteins LC3-II and Beclin-1 was upregulated and p62 expression decreased, but the expression of apoptotic and necrosis-related proteins had no significant difference among groups. Our results suggest that learning and memory impairment induced by nano-aluminum could be related to mitophagy.

Cystoscopy with antibiotic irrigation during pelvic reconstruction and minimally invasive gynecologic surgery: A double-blind randomized controlled trial.

After pelvic reconstructive surgery, the risk of postoperative urinary tract infection (UTI) is significant; intraoperative cystoscopy may contribute to this risk. Intravesical antibiotics are used in the ambulatory setting and may be applied to the surgical arena. Our objective was to evaluate the efficacy of antibiotic irrigation during intraoperative cystoscopy to prevent postoperative UTI. This double-blind randomized controlled trial enrolled 216 women undergoing cystoscopy with elective surgery for pelvic organ prolapse, stress urinary incontinence, or laparoscopic gynecologic surgery at an academic medical center 2016-2019. Participants were randomized to cystoscopic irrigation fluid type: normal saline (control) or 200,000 U polymyxin B + 40 mg neomycin solution in normal saline (antibiotic). Patients and providers who treated UTIs were blinded. The primary outcome was treatment of UTI within 6 weeks postoperatively, defined as positive culture or treatment for a symptomatic UTI. χ2 and multivariable logistic regression analyses were performed. We enrolled 216 women: 111 control (51.4%) and 105 antibiotic (48.6%). Mean age was 51.6 years. Groups were well matched in medical comorbidities and surgery type. Primary vaginal surgery was most common (n = 127, 58.8%). Overall, 10.7% of patients developed a postoperative UTI with no difference in incidence between groups: 9.9% of control (n = 11, 95% confidence interval [CI]: 4.0%-16.0%) versus 11.4% of antibiotic subjects (n = 12, 95% CI: 5.0%-18.0%), on χ2 (p = .718) and logistic regression analysis (adjusted odds ratio, 1.3; CI: 0.53-3.16; p = .569). When cystoscopy is performed during elective pelvic surgery, use of antibiotic irrigation does not impact the rate of postoperative UTI.