ABSTRACT
Slack (Slo 2.2), a member of the Slo potassium channel family, is activated by both voltage and cytosolic factors, such as Na(+) ([Na(+)](i)) and Cl(-) ([Cl(-)](i)). Since the Slo family is known to play a role in hypoxia, and since hypoxia/ischemia is associated with an increase in H(+) and CO(2) intracellularly, we hypothesized that the Slack channel may be affected by changes in intracellular concentrations of CO(2) and H(+). To examine this, we expressed the Slack channel in Xenopus oocytes and the Slo 2.2 protein was allowed to be inserted into the plasma membrane. Inside-out patch recordings were performed to examine the response of Slack to different CO(2) concentrations (0.038%, 5%, 12%) and to different pH levels (6.3, 6.8, 7.3, 7.8, 8.3). In the presence of low [Na(+)](i) (5 mM), the Slack channel open probability decreased when exposed to decreased pH or increased CO(2) in a dose-dependent fashion (from 0.28+/-0.03, n=3, at pH 7.3 to 0.006+/-0.005, n=3, P=0.0004, at pH 6.8; and from 0.65+/-0.17, n=3, at 0.038% CO(2) to 0.22+/-0.07, n=3, P=0.04 at 12% CO(2)). In the presence of high [Na(+)](i) (45 mM), Slack open probability increased (from 0.03+/-0.01 at 5 mM [Na(+)](i), n=3, to 0.11+/-0.01, n=3, P=0.01) even in the presence of decreased pH (6.3). Since Slack activity increases significantly when exposed to increased [Na(+)](i), even in presence of increased H(+), we propose that Slack may play an important role in pathological conditions during which there is an increase in the intracellular concentrations of both acid and Na(+), such as in ischemia/hypoxia.
Subject(s)
Acidosis/metabolism , Hypercapnia/metabolism , Nerve Tissue Proteins/physiology , Potassium Channels/physiology , Animals , Carbon Dioxide/pharmacology , Chlorides/pharmacology , Electrophysiology , Hydrogen-Ion Concentration , Oocytes/metabolism , Patch-Clamp Techniques , Plasmids/genetics , Potassium Channels, Sodium-Activated , RNA, Complementary/biosynthesis , RNA, Complementary/genetics , Rats , Xenopus laevisABSTRACT
Temperature sensitive liposome entrapped adriamycin was injected into the hepatic artery of Wistar rats bearing implanted hepatic tumor. Two hours after the injection, the liver was heated to 42 degrees C and maintained at that temperature for 6 minutes using a local hyperthermia. The variation in the pattern of the concentration of the liposomal drug in circulation, and the drug distribution in tissues were investigated. Results indicated that adriamycin was released from the liposomes with the drug concentration peaking in circulation at 30 minutes after heating. Following the hyperthermia treatment, the total amount of drug in the liver decreased, while that in the tumor and urine increased. The 14C labeled liposome track test showed that a parallel relationship between the lipid and the drug was maintained for 8 hours after the hepatic injection, and physiological environment was a determinant of change and existence of liposomal carrier. However, the drug encapsulated in the liposomes can be controlled by hyperthermia to target the tumor. Therapeutic experiments showed that in the group treated with the hepatic artery-injected liposome plus hyperthermia control, the liver tumor growth of the rats administered at 7 days after W256 carcinosarcoma implantation on liver was notably inhibited and the life-span of the animal was greatly extended compared with those of aqueous administration groups and iv injected liposome group.
Subject(s)
Carcinoma 256, Walker/drug therapy , Doxorubicin/administration & dosage , Animals , Doxorubicin/blood , Doxorubicin/therapeutic use , Drug Carriers , Hepatic Artery , Hyperthermia, Induced , Injections, Intra-Arterial , Liposomes , Male , Neoplasm Transplantation , Rats , Rats, Inbred StrainsABSTRACT
This paper summarizes the work done to control lead poisoning in the People's Republic of China. The work can be divided into the following four phases: (i) health surveillance of lead workers, (ii) health standard setting, (iii) research for early detection indicators, and (iv) improvement of the work conditions and health surveillance of "undeserved" groups. In 1949 prevention started with the initiation of the health surveillance of lead workers. Since then health surveillance has been used to supplement environmental monitoring in the early detection of lead poisoning, and the prevalence of lead poisoning has decreased. This activity has also helped to identify the needs for improvement in technological control. The next step has been the promulgation of health standards. The current standard for lead gives the maximum allowable concentration in air as 0.03 mg/m3 for lead fume and 0.05 mg/m3 for lead dust. Research on indicators for the early detection of lead has improved the quality of prevention. It has recently led to the addition of zinc protoporphyrin to the list of indicators in use. Finally the work conditions and surveillance of workers that had earlier been considered "underserved," particularly workers in agriculture and small industries in rural areas, are being improved.
Subject(s)
Lead Poisoning/prevention & control , Lead , Occupational Diseases/prevention & control , Occupational Health Services/trends , China , Humans , Maximum Allowable Concentration , Occupational Diseases/chemically induced , Population SurveillanceABSTRACT
The authors recommend the application of silver nitrate solution for the treatment of yellow phosphorus skin burns instead of the traditionally used copper sulfate solution. The latter may cause copper poisoning if absorbed through damaged skin. Silver nitrate treatment has been successfully applied in 13 cases of phosphorus burns.