Propofol blocks voltage-gated potassium channels in human T lymphocytes

The effect of propofol (PR) on voltage-gated potassium channels (KV) in human T lymphocytes (TL) was studied using the patch-clamp technique in the whole-cell configuration. PR was found to reversibly block the KV channels in a dose-dependent manner with a half-blocking concentration of approximately 40 microM. The decrease in the peak current caused by PR was voltage-independent. The activation time constant of the whole-cell potassium currents remained unaffected upon PR treatment, whereas both the rate and extent of the inactivation process were increased, indicating the "open channel block" mechanism. The PR half-blocking concentration was of the same order of magnitude as PR blood concentrations employed in anesthesia. Taking into account the extensive use of PR and the important role of KV channels in human TL, these results suggest a need for investigations into the effect of PR on TL cell-function regulation.     

Adhesions: pathogenesis and prevention-panel discussion and summary

This article summarizes the discussions of the faculty and chairpersons on four major topics on postsurgical adhesions examined at the symposium, "Adhesions: Pathogenesis and Prevention". These topics are: 1) clinical significance; 2) pathogenesis; 3) research status and directions; and 4) recommendations for reduction or prevention. Abdominal postsurgical adhesions develop following trauma to the mesothelium, which is damaged often by surgical handling and instrument contact, foreign materials such as sutures and glove dusting powder, desiccation, and overheating. Postoperative adhesions occur after most surgical procedures and can result in serious complications, including intestinal obstruction, infertility, and pain. A long-term and unpredictable problem, postoperative adhesions impact the surgical workload and hospital resources, resulting in considerable health care expenditures. Although understanding of the pathogenesis of adhesions has improved recently, the molecular mechanisms involved continue to be delineated. Adhesions result from the normal peritoneal wound healing response and develop in the first five to seven days after injury. Adhesion formation and adhesion-free re-epithelialization are alternative pathways, both of which begin with coagulation which initiates a cascade of events resulting in the buildup of fibrin gel matrix. If not removed, the fibrin gel matrix serves as the progenitor to adhesions by forming a band or bridge when two peritoneal surfaces coated with it are apposed. The band or bridge becomes the basis for the organization of an adhesion. Protective fibrinolytic enzyme systems of the peritoneum, such as the plasmin system, can remove the fibrin gel matrix. However, surgery dramatically diminishes fibrinolytic activity. The pivotal events determining whether the pathway taken is adhesion formation or re-epithelialization are therefore the apposition of two damaged surfaces and the extent of fibrinolysis. Research in postsurgical adhesion formation and prevention abounds in a variety of avenues of investigation, including: 1) identification on a molecular level of the components involved in adhesiogenesis and their interactions; 2) clarification of the role of fibrin and fibrinolysis in adhesion formation; 3) standardization of design in preclinical and clinical studies of adhesion formation and prevention; 4) delineation of the relationship between adhesion formation and adhesive complications; and 5) elucidation of efficient, site-specific methods of prophylactic drug delivery. Currently, it seems logical to focus preventive research on development of barriers, fibrinolytic drugs, and selected agents such as phospholipids. The major strategies for adhesion prevention or reduction are adjusting surgical practice and applying adjuvants. Surgeons should adjust their major practices by: 1) becoming aware of the potential adhesive complications of a procedure; 2) minimizing the invasiveness of surgery; and 3) minimizing surgical trauma, ischemia, exposure to intestinal contents, introduction of foreign material into the body, and the use of talc- or starch-containing gloves. Available adjuvants include a newly developed by hyaluronic acid-phosphate-buffered saline solution applied intraoperatively to protect peritoneal surfaces from indirect surgical trauma and three mechanical barriers. One of these, a bioresorbable membrane consisting of hyaluronic acid and carboxymethylcellulose, has demonstrated efficacy and safety in both general and gynecological surgery. The other two barriers, one made of expanded polytetrafluoroethylene and one developed from oxidized regenerated cellulose, are indicated only for use in gynecological surgery.     

Reliability of using random urine samples for "spot" determination of fractional excretion of electrolytes in cats

OBJECTIVE: To determine whether the "spot" method of determining fractional excretion (FE) of electrolytes in cats is accurate. ANIMALS: 5 clinically normal young adult female cats. PROCEDURE: Cats were acclimated to metabolism cages, and 2 consecutive 72-hour collections of urine were made to determine FE of total calcium, potassium, total magnesium, sodium, and phosphorus by conventional methods, using endogenous creatinine clearance as an estimate of glomerular filtration rate. During collections, small samples of urine were obtained by cystocentesis at 8 AM, 3 PM, and 9 PM for determination of FE of the electrolytes by use of the "spot" method. RESULTS: Values from "spot" determinations were highly variable, compared with 72-hour values, with a high percentage falling outside the range of mean +/- 2 SD for 72-hour FE values. CONCLUSIONS AND CLINICAL RELEVANCE: The "spot" method for determining FE is not precise, and if used, caution and judgement should be exercised in interpretation of the results.     

Development and validation of a geriatrics knowledge test for primary care residents

This study reports the development and preliminary validation of an instrument to measure geriatrics knowledge of primary care residents. A 23-item test was developed using questions selected from the American Geriatrics Society's Geriatrics Review Syllabus. Ninety-six internal medicine and family practice residents, 14 geriatrics fellows, and 11 geriatrics faculty members participated in the study. Findings support the reliability (Cronbach's alpha = 0.66) and validity (content and "known groups") of this short test. Predictive validity and sensitivity of the test to changes in knowledge will have to be further explored as residents progress through their training.     

Neurotic disturbances, depression and anxiety disorders in the population living in the vicinity of overhead high-voltage transmission line 400 kV. Epidemiological pilot study

Numerous reports suggest a relationship between the increased incidence of depressive and neurotic symptoms in humans and the exposure to extremely low frequency electromagnetic field (EMF) at the place of residence. Our study was conducted in one of the Cracow suburbs with low socio-economic status, adjacent to an easement containing two 400 kV high-voltage transmission lines (distance up to 50 m from the line). The population investigated comprised 70 persons (35 males and 35 females). This group was exposed to EMF from 1986. A control group (n = 37), non-exposed to EMF, was also tested. The EMF intensity was measured by special devices. The following assessments instruments were used: Anamnestic Data Questionnaire, Neurotic Symptoms Questionnaire "O" Spielberger Self-Rating Questionnaire, and Beck-Self-Rating Scale. The measurements of the electric field levels taken at the front walls of investigated buildings averaged much higher than normal values of safety exposure. Our investigation showed the increased psychopathological values in all clinical tests. The difference between the group exposed to EMF and the control population was statistically significant. The results of our study did not support a possible cause-and-effect relationship between EMF and psychopathology observed. Some other factors (noise) can be responsible for the data obtained. The hypothesis that EMF produced by external electric power lines may enhance the occurrence of neurotic symptoms and depression, requires further clinical and experimental investigations.     

Resonance ultrasonic measurements of microscopic gas bubbles

The positive identification and location of stationary or moving bubbles in human tissue is a persisting problem in the study and management of dysbarism. Since bubbles are resonant scatterers of ultrasound, while structures such as red-cell clumps and tissue interfaces are not, it is possible in principle to identify bubbles uniquely and to determine their position and size. A pulsed, ultrasonic echo-ranging system was expressly designed to exploit the principle of bubble resonance, and was evaluated for bubble identification and location in two experiments. Echos from bubbles in a water bath were computer-processed to reveal a distinct "line-narrowing" in the Fourier domain, which is diagnostic of gas bubbles. An increase in echo signal from a dog's jugular vein upon distal bubble injecton was obtained as evidence for in vivo bubble detection. We conclude that the exploitation of the bubble resonance principle can offer a safe, noninvasive technology for micro-bubble identification, location, and size determination in many tissues. This technology appears capable of measuring stationary bubbles in tissue spaces or impacted in blood vessels as well as those moving in the vascular system.     

Environmental stimulation reduces learning deficits in experimental cretinism

Behavioral deficits in adult rats exposed perinatally to thiouracil were substantially reduced or elimated by a 5-week period of "superenriched" postweaning rearing conditions before testing. This treatment resulted in remediation of hypothyroid rats' deficits in maze learning, maze retention, and resistance to extinction of bar-pressing; the facilitative effect persisted for more than 4 months. These behavioral results were consistent with neurohistological findings from studies of early thyroid deficiency and postweaning environmental stimulation in rats.     

Evaluation of Biolog for identification of members of the family Micrococcaceae

The Biolog Identification System (Biolog, Inc., Hayward, Calif.) was challenged at two separate laboratories with 113 coded isolates, including 33 type strains of staphylococci, 5 strains of Micrococcus spp., and 1 strain of Stomatococcus mucilaginosus. Test parameters between the sites were controlled as much as possible. Discrepancies were arbitrated by using conventional biochemicals. Overall accuracies (correct to the species level) upon initial testing were 47.7 and 59.3%, respectively, at the two laboratories. After repeat testing of isolates generating "no identification" responses or errors, the overall accuracies increased to 69.0 and 74.3% at the two sites, respectively, revealing no significant difference in the final results at the two laboratories (78 of 113 versus 84 of 113; P > 0.05). Error rates were 7.1% at one site and 9.7% at the other. The Biolog is not yet accurate enough to serve as a primary method for identifying staphylococci.     

The influence of the oncogenes NRAS and MYC on the radiation sensitivity of cells of a human melanoma cell line

Activation of certain oncogenes may alter the sensitivity of cells to ionizing radiation. We studied the effect of oncogene activation on the radiation sensitivity of cells of a human melanoma cell line. The cell line IGR39D was transfected with the MYC oncogene, the proto-oncogene NRAS, NRAS activated by a point mutation (61-arginine) or a combination of mutated NRAS and MYC. Single-dose experiments showed a decreased survival after transfection with MYC, wild-type NRAS or mutated NRAS. Co-transfection with MYC and mutated NRAS decreased survival up to 4 Gy, whereas at higher doses no shift in radiosensitivity was seen. Flow cytometry data indicated that differences in radiosensitivity could be explained at least in part by a difference in the distribution of cells in the phases of the cell cycle. After transfection of cells with either NRAS or MYC, the number of cells in G1 phase decreased with a concomitant increase of cells in the G2/M phase. When the cell line transfected with activated NRAS was manipulated so that the distribution of the cells in the phases of the cell cycle resembled th at of the parental line at the time of irradiation, the survival of the cells was improved. Similar experiments with the cell line containing MYC did not result in an alteration of the distribution of the cells in the cycle, or the survival after single-dose fractions, suggesting the presence of a distinct mechanism for influencing radiation sensitivity. Both NRAS and MYC transfection decrease the radiation sensitivity of human melanoma cells, but the underlying mechanisms seem different. In conclusion, transfection with NRAS or MYC alone increases radiation sensitivity while transfection of cells containing NRAS with MYC restores resistance at higher doses.     

Exacerbation of methamphetamine-induced neurochemical deficits by melatonin

Methamphetamine (METH), administered in large, repeated doses, compromises the dopaminergic and serotonergic systems as indicated by prolonged suppression of tyrosine hydroxylase and tryptophan hydroxylase activity and concurrent decreases in the content of dopamine and 5-hydroxytryptamine. Because dopamine is necessary for these dopaminergic and serotonergic deficits we postulated that dopamine and/or its reactive metabolites are responsible for these degenerative alterations. Because we previously demonstrated that in vitro reducing conditions reverse the decrease in tryptophan hydroxylase activity, we reasoned that melatonin, a purported endogenous antioxidant, may alter this response. Rats were treated with METH and/or melatonin and trytophan hydroxylase activity and 5-hydroxytryptamine content were assessed; tyrosine hydroxylase activity and dopamine content were also measured. Not only did melatonin not prevent METH-induced deficits in serotonergic and dopaminergic parameters, but coadministration of melatonin with METH actually enhanced most of the monoaminergic effects of METH. This enhancing effect could not be attributed to alteration of body temperature. Because METH abuse causes insomnia and melatonin is promoted in some countries for insomnia, the implications of the interaction between these two drugs could be clinically important.