We previously reported a new effective therapy, continuous intrathecal amphotericin B (AMB), for the treatment of cryptococcal meningitis, which had fewer side effects and complications than conventional intrathecal AMB. In this study, the pharmacokinetics of continuous intrathecal administration and conventional intrathecal AMB were compared in rabbits, providing a pharmacokinetic basis for the use of continuous intrathecal AMB therapy. The AMB concentration in the cerebrospinal fluid (CSF), sampled via an inserted cisterna magna catheter, was determined by a liquid chromatography-tandem mass spectrometry assay. The results revealed significant pharmacokinetic differences between the two groups. In the continuous intrathecal group (0.15 mg/kg/24 h), the concentration of AMB peaked 7.01 g/ml at 4 h and then decreased to a stable level of 1.0 to 1.34 g/ml, with no neurological impairments, while in the conventional intrathecal group (0.015 mg/kg), the drug concentration reached a peak of 3.41 g/ml at 1 h and then decreased progressively, with fever and neurological impairments, including convulsion and paralysis. The pharmacokinetic results indicated that the continuous intrathecal AMB is a more effective and safe therapy than the conventional intrathecal AMB, with comparatively rational pharmacokinetics and fewer neurological impairments. Cryptococcal meningitis (CM), caused by Cryptococcus neoformans or Cryptococcus gattii varieties, is a life-threatening opportunistic fungal infection in both human immunodeficiency virus (HIV)-positive and HIV-negative patients. The key management principles include therapy for CM with antifungal agents, as well as control of the underlying disease (15). The challenges in the treatment of CM correlate with its long course of disease, high relapse rate, and unsatisfactory therapeutic efficacy. The 3-month mortality rate during management of acute CM is approximately 20% despite access to advanced medical care (3). Moreover, the advent of the azoles has not led to cure. Emphasis was placed on the combined use of antifungal agents such as polyenes, flucytosine, and fluconazole in new guidelines for the management of CM (15,21). Amphotericin B (AMB), a major member of the polyenes, remains a first-line option for empirical therapy in the treatment of CM (15). However, its poor penetration into cerebrospinal fluid (CSF) limits its effect against CM (14). Many clinicians prefer intrathecal AMB as a part of the CM treatment regimen in order to clear infection more completely and rapidly. Conventional intrathecal AMB might increase the drug concentration in CSF and improve therapeutic efficacy, but the toxicities associated with AMB given intrathecally have limited its clinical application (9, 18). Taking account of this, it is necessary to investigate new therapeutic options in the treatment of CM.We previously reported a new therapy, continuous intrathecal AMB, for the treatment of CM (5, 11, 24). The results of our pharmacokinetics study revealed that the AMB concentrations with co...
According to the reality, an online monitoring and fault diagnosis system of the main hoist for Mine was designed in this article. The system adopts the signal acquisition and processing, fault diagnosis, Web visualization, network real-time database and other related technologies, Real-time monitoring the current, voltage, temperature, speed, vibration and other parameters of the main elevators to Achieve the goals that Increasing efficiency by downsizing, protecting the safe operation of equipment, reducing the maintenance costs.
The influence of Cr on corrosion behavior of P110 steel was studied in the simulated CO2 environment. The result demonstrated that the Cr cant change the effect of temperature on P110 steel. The corrosion rates of the two kinds of materials reached the peak at 90°C. The temperature has dual effects on corrosion, which caused the adhesive and productivity of corrosion product formed up 90°C are better than that formed below 90°C; The adding of Cr in the P110 steel can prohibit the local corrosion to occur.
The buttress thread connection was used in deep well or ultra-deep well widely because of its high joint efficiency. Pullout failure scarcely happen on buttress premium thread connection with great joint strength and good sealing property. Direct evidences about connection dropout couldn’t get in most cases by reason of casing string had fallen into well or casing string had been concreted in formation by cement. Now the difficulty of analysis on pullout is higher and higher. A buttress premium thread casing joint had pulled out at mill end of coupling in a straight well and dropout casing string couldn’t get out of the well. Research on this pullout case was carried out combining relative theories with tests. Macroscopic analysis and dimension measurement were done for dropout coupling. The material’s physical and chemical properties were checked. Thread inspection and full-scale tests were done for two casing simples that are same lot with pullout. Metallograph analysis was carried out on load flank and guide flank in box thread of pullout coupling and same lot new coupling. The results showed that dropout failure was ascribe to inadequate make-up torque at mill end of pullout coupling and complex downhole condition and improper handling in the oil field. On the other hand joint’s strength decline on the effect of unsuitable heat treatment to coupling and greatly uneven black crested pin thread around circumference. The pertinence measures were laid down at the end of this passage.
The fracture failure research on a drilling jar’s top joint was carried out on basis of correlative theories and tests. Macroscopic analysis, dimension measurement and nondestructive testing were done for failure joint. The material’s chemical and physical properties were tested. The drilling strings assembly was analyzed specially and the bending strength ratio between top joint and adapter joint was calculated detailedly. The results showed that the drilling jar’s joint was broken because of fatigue induced by irrational drilling strings assembly and improper matching between top joint and adapter joint. The joint’s fatigue life was reduced further because material’s impact toughness is less than standard value.
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