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1.
Although the large use of diethylcarbamazine (DEC), as the major anti-filaricide drug, its mechanism of action remains a matter of controversy. Several authors defend the hypothesis that DEC has no direct effect on nematodes. This study demonstrated that infective larvae (L3) of Wuchereria bancrofti treated in vitro with DEC presented several behaviour and morphological changes. The first alteration produced by treatment for 2 h with 3, 5, 10 microg/ml of DEC was the reduction of motility. Larvae treated with 5, 10 microg/ml DEC showed severely affected organelles, formation of several vacuoles, mainly in neurocytes and in the muscle cells, and dissolution of cytoplasm. Some larvae showed extreme cellular disorganization with abundance of large and dense mitochondria and numerous large vacuoles containing residual organelles. Lamellar bodies, probably related to an assembly of hipodermal membranes, were also observed in some damaged larvae. Thus, undoubtedly in vitro treatment with concentrations of DEC similar to therapeutic conditions, which are 1-5 microg/ml (Hawking, 1979), had a direct effect on infective larvae of W. bancrofti by causing, primarily neuromuscular alterations with subsequent damage to organelles.  相似文献   

2.
BOLD-contrast functional magnetic resonance imaging (MRI) was used to assess the evolution of tumor oxygenation and blood flow after administration of four different anesthetics: pentobarbital (60 mg/kg), ketamine/xylazine (80/8 mg/kg), fentanyl/droperidol (0.078/3.9 mg/kg), and isoflurane (1.5%). Gradient echo sequences were carried out at 4.7 Tesla in a TLT tumor model implanted in the muscle of NMRI mice. In parallel experiments, tumor blood flow and tumor pO2 were measured using the OxyLite/OxyFlo probe system. A comparison was made with the changes occurring in the skeletal muscle (host tissue). The signal intensity was dramatically decreased in tumors after administration of anesthetics, except isoflurane. These results correlated well with measurements of oxygenation and blood perfusion. Isoflurane produced constant muscle pO2 and blood perfusion although large transient fluctuations in pO2 and blood flow were reported in some tumors. Our results emphasize the need for careful monitoring of the effects of anesthesia when trying to identify new therapeutic approaches that are aimed at modulating tumor hemodynamics.  相似文献   

3.
Light microscopy analyses of microfilariae of Wuchereria bancrofti treated with DEC revealed a striking loss of the microfilarial sheath. However, no effect was observed on microfilariae of Litomosoides chagasfilhoi treated with DEC. For quantitative analyses microfilariae of W. bancrofti were processed for SEM. Controls, which have not received DEC, had 29.8% of exsheathed microfilariae. Conversely, the number of exsheathed microfilariae increased as increased DEC concentrations: 5 μg/ml (75.9%), 10 μg/ml (80.1%), and 50 μg/ml (87.7%). After DEC treatment some of sheathed microfilariae showed a wrinkled surface, and in some microfilariae, sheaths were observed being liberated almost intact from the larvae surface. But, frequently residues of the lost sheath over the surface were also observed. No damage was observed in the microfilariae cuticle. The present work shows quantitative data on the loss of the microfilarial sheath of W. bancrofti after treatment with DEC. Since no loss of microfilarial sheath was observed in microfilariae of L. chagasfilhoi submitted to the same conditions, DEC may present different mechanisms of action for distinct filarial species.  相似文献   

4.
Single dose of diethylcarbamazine (DEC) used in control programs is effective in breaking the transmission of filariasis. In order to investigate the effect of aggressive therapy on Wuchereria bancrofti (Wb) microfilariae, DEC was given to 29 patients who were positive for the circulating filarial antigen (CFA) assay but did not have clinical manifestations of filariasis, at 6 mg/kg/day for 12 days and again six months later using the same dosing regimen. For each patient, microfilarial density and serum CFA were followed up for two years. Ultrastructural analyses on Wb microfilariae obtained after repeated treatment with DEC were also performed. Microfilaremia and antigenemia decreased significantly after 12 months but returned to the initial levels after 24 months. This could indicate, as shown by other authors, that aggressive repeated therapy with DEC alone is ineffective in eradicating adult W. bancrofti, particularly in infected but asymptomatic individuals. The objective of the present study was to analyze the microfilaremic and antigenemic behavior and ultrastructural changes caused by different DEC concentrations in vitro in Wb microfilariae obtained from individuals who were sensitive and refractory to treatment. After in vitro treatment of the microfilariae using 5 and 10 μg/ml of DEC for 1 h, ultrastructural analysis revealed low levels of cell damage compared with embryos obtained from individuals from a different area who had never received DEC treatment before. The results obtained suggest that microfilariae from patients who receive repeated aggressive therapy are less sensitive to DEC in vitro.  相似文献   

5.
Exposure of adult male mice to a magnetic resonance imaging (MRI) procedure has been shown to abolish the nocturnal analgesic responses observed following treatment with morphine. The field component(s) responsible for this inhibitory effect were examined by exposing mice to either the static, time-varying or rf magnetic field components associated with an MRI procedure. In the middle of the night portion of their day-night cycle, mice were exposed for 23.2 min to one of the above field components, intraperitoneally injected with morphine sulphate (10 mg/kg) and then exposed to the field conditions for another 23.2 min, after which analgesic responses were determined. Analgesia was quantitated by determining the length of time mice were content to be on a hot surface (50 degrees C) before they showed discomfort by licking their paws. It was observed that the time-varying magnetic field completely abolished, the rf field significantly reduced, while the static field component (0.15 T) had no evident effect on morphine-induced analgesia. These results indicate that the time-varying, and to a lesser extent the rf, fields associated with the MRI procedure inhibit morphine-induced analgesia in mice. These data also raise the possibility that exposure in humans to some of the magnetic field components associated with MRI may have clinically relevant effects on the actions of narcotic drugs such as morphine.  相似文献   

6.
19F Magnetic resonance spectroscopy was used to study the impact of the biochemical modulator thymidine (TdR) on the 5-fluorouracil (5FU) metabolism in the livers and radiation-induced fibrosarcoma (RIF-1) tumors of 5FU-treated C3H mice. The liver spectra measured after administration of 5FU (65 or 130 mg/kg IP) showed the 5 FU resonance and its catabolites alpha-fluoro-beta-ureidopropionic acid and alpha-fluoro-beta-alanine. At the latter dose, fluoronucleotide signal was also detected. The liver spectra of TdR-pretreated (500 mg/kg, IP) mice showed additional signals of fluoronucleotide and fluoronucleoside at both 5FU doses, while alpha-fluoro-beta-alanine was not detected. TdR pretreatment increased the half-life of 5FU in livers from 24 +/- 2 to 126 +/- 46 SEM min at the 5FU dose of 65 mg/kg and from 28 +/- 2 to 95 +/- 22 min at the 130 mg/kg dose (P less than .1 and P less than .01, respectively). TdR-pretreated mice had higher 5FU anabolite (fluoronucleotide + fluoronucleoside) levels in their RIF-1 tumors than nonpretreated mice that received the same 5FU doses (56 +/- 15 SEM vs. 0 arbitrary units at the 5FU dose of 65 mg/kg, and 88 +/- 21 vs. 10 +/- 3 arbitrary units at 130 mg/kg 5FU; P less than .0001). The percentage drop in tumor volume was enhanced in the mice that received TdR, from 27 +/- 4 SEM to 52 +/- 2 at the 5 FU dose of 65 mg/kg and from 24 +/- 3 to 65 +/- 4 at the 130-mg/kg dose (P less than .0001, both).  相似文献   

7.
Despite the reported enhanced electrochemical behavior of graphite anodes due to the addition of NaClO4 salts in to the electrolytes used in lithium battery applications, a detailed investigation upon the effect of addition of NaPF6 salt in an electrolyte containing 1 M LiPF6 in 1:1 V/V EC:DEC has resulted in inferior electrochemical behavior of graphite, i.e., quite contrast to the reported behavior of improved effects of addition of NaClO4 into 1 M LiClO4 solution, the addition of 0.22 mol dm−3 NaPF6 salt has been found to reduce the capacities of lithium-ion cells containing 1 M LiPF6 in 1:1 V/V EC:DEC. Towards this study, cells fabricated with and without the addition of 0.22 mol dm−3 NaPF6 in 1 M LiPF6 (1:1 V/V EC:DEC) were subjected to a systematic charging at a constant C/10 rate and discharging of cells at four different rates, viz., C/5, C/2 and C rates at the end of every 5 cycles. The observed results of the charge-discharge studies up to 15 cycles are discussed in this preliminary communication.  相似文献   

8.
Nanosilver has been widely used in medical biology; however, the distribution and interaction of nanosilver with cells is still unclear. There have been some reports demonstrating that nanoparticles can cross the blood-brain barrier (BBB). The present study investigated the accumulation of silver nanoparticles in the brain, and the effects of silver nanoparticles on BBB. Nanosilver and microsilver (62.8 mg/kg) particles were subcutaneously injected into rats. The rats were sacrificed at predetermined time points and the brains were obtained for ultrastructural observation and silver level detection. The results showed that silver nanoparticles could traverse the BBB and move into the brain in the form of particle. The silver nanoparticles can induce neuronal degeneration and necrosis by accumulating in the brain over a long period of time.  相似文献   

9.
The anticancer effect of thiacarpine, a synthetic analogue of the known cytotoxic alkaloid polycarpine isolated from the Pacific ascidian Polycarpa aurata, was investigated in vivo in experiments using mouse solid Ehrlich carcinoma tumor as the target. A high-resolution magnetic resonance imaging (MRI) technique using a MR tomograph "PharmaScan" US70/16 (Bruker, Ettlingen, Germany) was used for visualization and quantification of tumor size. Fluorescence microscopy and image analysis were applied to determine Ehrlich carcinoma cell chromatin condensing (apoptosis) and necrosis in Ehrlich carcinoma cells at the action of thiacarpine in in vitro experiments. The scan and size calculations of the tumor and some mouse organs were carried out during the experiments. Thiacarpine in a total dose of 100 mg/kg was found to exhibit the delay in growth of the mouse tumor. The antineoplastic effect of this compound was accompanied by an increase in the lifetime of experimental mice in comparison with the control group of animals. Our data show that the ability of thiacarpine to induce apoptosis in carcinoma cells may contribute to thiacarpine anticancer effects against mice solid Ehrlich carcinoma in vivo detected by MRI.  相似文献   

10.
Vardenafil citrate is a potent vasodilator used in the treatment of patients with erectile dysfunction. Its mechanism of action is based on the selective inhibition of phosphodiesterase-5 (PDE5), specific to guanosine 3′,5′-cyclic monophosphate (cGMP). Recently, chronic treatment with Vardenafil has been successfully used in cases of pulmonary hypertension and, despite being used in high doses for long periods, little is known about its effects on other systems. In the present study, female mice were treated daily with 5 mg/kg Vardenafil for 4 weeks, after which the ovaries were collected for morphological analyses and sera were collected for biochemical assays. This study found that treatment with Vardenafil decreased HDL serum levels and the number of antral follicles as well as induced lesser lipid content in luteal cells, suggesting that high levels of cGMP may affect follicle development.  相似文献   

11.
The chronic effects of kanamycin (KM) on hearing in the budgerigar were investigated by behavioral audiometry. The birds received a daily intramuscular injection of KM (100 mg/kg or 200 mg/kg) for 10 successive days, and absolute thresholds between pre- and post-treatment were compared. KM induced both transient and permanent low-frequency specific hearing loss; i.e., the elevation of threshold for frequencies below 1 kHz was greater than that for frequencies above 1 kHz. Moreover, the degree of hearing loss was dose dependent. The low-frequency selective effects of KM in the present study were contrary to the high-frequency specificity of aminoglycoside ototoxicity in mammals. To assess the effect of KM on auditory frequency resolution, critical ratios were estimated in pathological birds with low-frequency specific hearing loss. There was a linear relation between shift in critical ratio and shift in absolute threshold, suggesting that the increase in the critical ratio is due to a decrease in the efficiency of the detector mechanism rather than a change in the spectral resolving power of the birds.  相似文献   

12.
This study investigated the effects of ultrasound treatment on the quality of salted Culter alburnus fish. The results showed that with the increasing ultrasound power, the structural degradation of muscle fibers was intensified, and the conformation of myofibrillar protein was significantly changed. The high-power ultrasound treatment group (300 W) had relatively higher thiobarbiturate reactive substance content (0.37 mg malondialdehyde eq/kg) and peroxidation value (0.63 mmol/kg). A total of 66 volatile compounds were identified with obvious differences among groups. The 200 W ultrasound group exhibited fewer fishy substances (Hexanal, 1-Pentene-3-ol, and 1-Octane-3-ol). Compared with control group, ultrasound groups (200, 300 W) contained more umami taste-related amino peptides such as γ-Glu-Met, γ-Glu-Ala, and Asn-pro. In the ultrasound treatment group, L-isoleucine and L-methionine, which may be used as flavor precursors, were significantly down-regulated, while carbohydrates and its metabolites were up-regulated. Amino acid, carbohydrate, and FA (fatty acyls) metabolism products in salted fish were enriched by ultrasound treatment, and those products might ultimately be related to the taste and flavor of salted fish.  相似文献   

13.
JAK/STAT通路抑制剂已被应用于多种疾病的临床试验,但其全身性用药对机体组织细胞功能活性的影响目前尚不明确.本研究运用基于核磁共振氢谱(1H NMR)的代谢组学方法分析了JAK/STAT通路抑制剂WP1066(20 mg/kg.bw,2天一次,持续2周)对C57BL/6小鼠血清代谢组的影响.首先采用1H NMR技术检测了WP1066处理组和对照组小鼠血清的代谢物,然后对所得的图谱数据进行了主成分分析(PCA)以及正交偏最小二乘法分析(OPLS).研究结果表明,抑制JAK/STAT通路可明显下调小鼠血清中的N-甲基烟酰胺(N-methylnicotinamide)水平,而上调顺乌头酸(cis-aconitate)、草酰乙酸(oxaloacetate)和乙酰胺(acetamide)水平,这些代谢物改变均与能量代谢密切相关.该结果提示代谢失衡相关指标可能作为JAK/STAT通路抑制剂治疗的临床监测参考指标.  相似文献   

14.
The current work features process parameters for the ultrasound (25 kHz)-assisted fabrication of polydopamine-shelled perfluorocarbon (PDA/PFC) emulsion droplets with bimodal (modes at 100–600 nm and 1–6 µm) and unimodal (200–600 nm) size distributions. Initial screening of these materials revealed that only PDA/PFC emulsion droplets with bimodal distributions showed photoacoustic signal enhancement due to large size of their optically absorbing PDA shells. Performance of this particular type of emulsion droplets as photoacoustic agents were evaluated in Intralipid®–India ink media, mimicking the optical scattering and absorbance of various tissue types. From these measurements, it was observed that PDA/PFC droplets with bimodal size distributions can enhance the photoacoustic signal of blood-mimicking phantom by up to five folds in various tissue-mimicking phantoms with absorption coefficients from 0.1 to 1.0 cm−1. Furthermore, using the information from enhanced photoacoustic images at 750 nm, the ultimate imaging depth was explored for polydopamine-shelled, perfluorohexane (PDA/PFH) emulsion droplets by photon trajectory simulations in 3D using a Monte Carlo approach. Based on these simulations, maximal tissue imaging depths for PDA/PFH emulsion droplets range from 10 to 40 mm, depending on the tissue type. These results demonstrate for the first time that ultrasonically fabricated PDA/PFC emulsion droplets have great potential as photoacoustic imaging agents that can be complemented with other reported characteristics of PDA/PFC emulsion droplets for extended applications in theranostics and other imaging modalities.  相似文献   

15.
BACKGROUND: alpha-Galactosylceramide (alpha-GalCer) can be presented by CD1d molecules of antigen-presenting cells, and is known to induce a potent NKT cell-dependent cytotoxic response against tumor cells. However, the main effector cells in alpha-GalCer-induced antitumor immunity are still controversial. METHODS: In order to elucidate the cell phenotype that plays the most important role in alpha-GalCer-induced antitumor immunity, we purified and analyzed tumor-infiltrating leukocytes (TILs) from liver metastatic nodules of a colon cancer cell line (Colon26), comparing alpha-GalCer- and control vehicle-treated mice. Flow cytometry was performed to analyze cell phenotype in TILs and IFN-gamma ELISA was performed to detect antigen-specific immune response. RESULTS: Flow cytometry analysis showed a significantly higher infiltration of NK cells (DX5+, T cell receptor alphabeta (TCR)-) into tumors in alpha-GalCer-treated mice compared to vehicle-treated mice. The DX5+TCR+ cell population was not significantly different between these two groups, indicating that these cells were not the main effector cells. Interestingly, the CD8+ T cell population was increased in TILs of alpha-GalCer-treated mice, and the activation level of these cells based on CD69 expression was higher than that in vehicle-treated mice. Moreover, the number of tumor-infiltrating dendritic cells (DCs) was increased in alpha-GalCer-treated mice. IFN-gamma ELISA showed stronger antigen-specific response in TILs from alpha-GalCer-treated mice compared to those from vehicle-treated mice, although the difference between these two groups was not significant. CONCLUSIONS: In alpha-GalCer-induced antitumor immunity, NK cells seem to be some of the main effector cells and both CD8+ T cells and DCs, which are related to acquired immunity, might also play important roles in this antitumor immune response. These results suggest that alpha-GalCer has a multifunctional role in modulation of the immune response.  相似文献   

16.
Acetaminophen (APAP) toxicity is responsible for approximately half of all cases of acute liver failure in the United States. The mouse model of APAP toxicity is widely used to examine mechanisms of APAP toxicity. Noninvasive approaches would allow for serial measurements in a single animal to study the effects of experimental interventions on the development and resolution of hepatocellular necrosis. The following study examined the time course of hepatic necrosis using small animal magnetic resonance imaging (MRI) following the administration of 200 mg/kg ip APAP given to B6C3F1 male mice. Mice treated with saline served as controls (CON). Other mice received treatment with the clinical antidote N-acetylcysteine (APAP+NAC). Mouse liver pathology was characterized using T1- and T2-weighted sequences at 2, 4, 8 and 24 h following APAP administration. Standard assays for APAP toxicity [serum alanine aminotransaminase (ALT) levels and hematoxylin and eosin (H&E) staining of liver sections] were examined relative to MRI findings. Overall, T2 sequences had a greater sensitivity for necrosis and hemorrhage than T1 (FLASH) images. Liver injury severity scoring of MR images demonstrated increased scores in the APAP mice at 4, 8 and 24 h compared to the CON mice. APAP+NAC mice had MRI scores similar to the CON mice. Semiquantitative analysis of hepatic hemorrhage strongly correlated with serum ALT. Small animal MRI can be used to monitor the evolution of APAP toxicity over time and to evaluate the response to therapy.  相似文献   

17.
The use of zinc oxide nanoparticles (ZnO NPs) in numerous products is increasing, although possible negative implications of their long-term consumption are not known yet. Our aim was to evaluate the chronic, 6-week oral exposure to two different concentrations of ZnO NPs on isolated rat hearts exposed to ischemic-reperfusion injury and on small intestine morphology. Wistar rats of both sexes (n = 18) were randomly divided into three groups: (1) 4 mg/kg ZnO NPs, (2) 40 mg/kg ZnO NPs, and (3) control. After 6 weeks of treatment, the hearts were isolated, the left ventricular pressure (LVP), the coronary flow (CF), the duration of arrhythmias and the lactate dehydrogenase release rate (LDH) were measured. A histological investigation of the small intestine was performed. Chronic exposure to ZnO NPs acted cardiotoxic dose-dependently. ZnO NPs in dosage 40 mg/kg maximally decreased LVP (3.3-fold) and CF (2.5-fold) and increased the duration of ventricular tachycardia (all P < 0.01) compared to control, whereas ZnO NPs in dosage 4 mg/kg acted less cardiotoxic. Goblet cells in the small intestine epithelium of rats, treated with 40 mg ZnO NPs/kg, were enlarged, swollen and numerous, the intestinal epithelium width was increased. Unexpectedly, ZnO NPs in both dosages significantly decreased LDH. A 6-week oral exposure to ZnO NPs dose-dependently increased heart injuries and caused irritation of the intestinal mucosa. A prolonged exposure to ZnO NPs might cause functional damage to the heart even with exposures to the recommended daily doses, which should be tested in future studies.  相似文献   

18.
To seek a promising candidate electrolyte at elevated temperature for lithium manganese oxide (LiMn2O4)/Li cells, the electrochemical performance of 0.7 mol L?1 LiBOB (lithium bis(oxalate)borate)-SL (sulfolane)/DEC (diethyl carbonate) (1:1, in volume) electrolyte was studied at 55 °C. The Mn dissolution in electrolyte was analyzed by inductively coupled plasma (ICP) analysis. AC impedance measurement and scanning electron microscopy (SEM) analysis were used to analyze the formation of the surface film on the LiMn2O4 electrode. The results demonstrate that the LiBOB-SL/DEC electrolyte can slow down the dissolution and erosion of Mn ions, and decrease the interface impedance. Moreover, the LiBOB-SL/DEC electrolyte could obviously improve the capacity retention, the operating voltage (4.05 V), and the rate performance of LiMn2O4/Li cells.  相似文献   

19.
Chinchillas were treated with kanamycin sulfate (150--200 mg/kg/day) to produce high-frequency hearing loss extending to about 4.0 kHz. Thresholds and psychophysical tuning curves (PTCs) were obtained before and after treatment, utilizing a shuttlebox avoidance procedure, and cochlear hair cells were evaluated under phase contrast microscopy. Hair cell loss resulting from kanamycin treatment varied from restricted lesions of the outer hair cells (OHCs) in the cochlear base, with no loss of inner hair cells (IHCs), to more extensive lesions involving both OHCs and IHCs. Threshold shift of at least 40 dB was always associated with OHC loss. PTCs obtained from frequency regions exhibiting 40--50 dB of threshold shift were normal in shape. With threshold shift in excess of 50 dB, PTCs were progressively distorted, with truncation of the tip segment and in some cases increased sensitivity of the tail segment. The results suggest that the threshold of optimally functional IHCs after kanamycin-induced OHC loss is about 40 dB higher than normal. Threshold shift in excess of 40 dB may represent IHC damage. IHCs are capable of transducing the fine-frequency information necessary for generating normally sharp PTCs in the absence of OHCs. However, with threshold shift in excess of approximately 50 dB, this frequency resolution is increasingly compromised.  相似文献   

20.
An electrohydrodynamic (EHD) atomization from a point-to-plate system, with a wet porous point as a corona electrode, has been studied. And the atomized water droplets from the wet porous point, as well as the water droplet traces, the water droplet charge-to-mass ratios, and the water droplet number concentrations, were investigated. It was observed that the wet porous point can atomize abundant amounts of water droplet, 2.8, 2.6 and 2.2 mg/min for negative, AC and positive corona, respectively. The migrated water droplet traces were observed. The positive wet porous point atomized very fine water droplets than those obtained with the negative wet porous point. Moreover, the water droplets atomized from the AC corona showed granular-like larger traces. A weak corona discharge can atomize water droplets very effectively. On the other hand, an intensive corona discharge can eject more water droplets. As a result with the wet porous point, the maximum corona-current-based and corona-power-based water droplet atomization yields of YC = 3.34, 3.32 and 3.25 μg/μAs and YP = 0.35, 0.40 and 0.27 mg/Ws have been obtained for the negative, AC and positive corona discharges.  相似文献   

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