Comparison of the Myotoxic Effects of Levobupivacaine,Bupivacaine, and Ropivacaine: An Electron Microscopic Study

The aim of this study was to investigate the myotoxic effects of bupivacaine, ropivacaine, and levobupivacaine which were applied intramuscularly to rat skeletal muscle. Forty Wistar-Albino rats were divided into four groups. In the study, .5% bupivacaine (Group B), .5% ropivacaine (Group R), .5% levobupivacaine (Group L), or .9% normal saline (Group SF) was applied intramuscularly to the right gastrocnemius muscle of rats. The rats in each group were sacrificed on the second day after injection. Sections of muscle samples were stained with hematoxylin–eosin for light microscopic investigation and prepared for the evaluation of ultrastructural changes in the subcellular level with transmission electron microscopy. All three local anesthetic agents caused qualitatively similar skeletal muscle damage. The most observed muscle damage was in Group B, muscle damage of Group R was less than that of Group B, and the least damage was seen in Group L quantitatively. Electron microscopic examination of each group that caused cellular damage was qualitatively similar. The most subcellular damage was observed in the group receiving bupivacaine, less was seen in the ropivacaine group, and the least was observed in the levobupivacaine group. The results indicated that bupivacaine caused more myotoxic damage than the other two agents in the skeletal muscle of rats and that levobupivacaine caused less myotoxic damage than both bupivacaine and ropivacaine at the cell and tissue levels.     

Relationship between blood pressure and physical activity assessed with stable isotopes

Intrapopulation and interpopulation variation in blood pressure (BP) often reflects the joint effect of a complex set of risk factors, including lifestyle factors such as physical activity, diet, smoking and alcohol use. In this study, we set out to quantify the impact of habitual levels of physical activity on BP within and between three populations at contrasting levels of population risk of hypertension. Individuals were randomly sampled from communities in Nigeria (n=57), Jamaica (from Kingston, n=35) and the United States (from the Chicago area, n=32). Activity energy expenditure (AEE) (estimated from resting energy expenditure measured by indirect calorimetry and total expenditure measured with doubly labelled water) was used as an objective estimate of physical activity. In each of the three samples, there was a consistent negative correlation between BP and AEE. This negative association persisted after adjustment for age, sex and body fat (body mass index or percent fat mass). In multivariate models, adiposity was no longer a significant predictor of BP after accounting for low AEE. In conclusion these data suggest that habitual levels of physical activity may have a generalizable relationship with BP in populations with widely different social and environmental characteristics.     

Erythrocyte CD38 as a prognostic marker in cancer

Abstract

Background: Surface antigen CD38 which is a multifunctional protein with enzymatic and receptorial properties is involved in many processes of cell proliferation and activation. It is widely expressed within the hematopoetic system, and its expression is stimulated by proinflammatory cytokines. CD38-associated enzymatic activities in erythrocytes from cancer patients were investigated in this context.

Methods: Erythrocyte NAD glycohydrolase and ADP-ribosyl cyclase activities in normal individuals and cancer patients were compared and correlation of these activities to CEA values and anemia were determined. Changes in CD38-expression were followed by SDS-PAGE and Western blot analysis of erythrocyte membrane proteins.

Results: Erythrocyte NAD glycohydrolase and ADP-ribosyl cyclase activities were significantly increased in cancer, in parallel to enhancement of CD38 expression and in correlation with CEA values and anemia.

Conclusions: An increased expression of CD38 which may be due to action of proinflammatory cytokines produced in tumor–host reactions appears to account for the elevations in erythrocyte CD38-associated enzyme activities in cancer patients. The changes in these enzyme activities may provide a prognostic outlook in view of their apparently close correlation to tumor progressions.     

Wortmannin is a potent inhibitor of DNA double strand break but not single strand break repair in Chinese hamster ovary cells

Wortmannin, an inhibitor of p110 PI 3-kinase, also inhibitsDNA-dependent protein kinase, which is known to mediate DNAdouble strand break repair. It was recently demonstrated thatwortmannin sensitized cells to ionizing radiation (IR) (Priceand Youmell, Cancer Res., 56, 246–250, 1996). Wortmanninwas used to determine if the potentiation of IR-induced cytotoxicityin Chinese hamster ovary cells could be accounted for by aninhibition of DNA double strand break (DSB) repair. Wortmannin,at concentrations which were non-toxic per se (5 and 20 µM),increased IR cytotoxicity with dose enhancement factors at 10%survival of 2.7±0.28 (5 µM) and 5.3 ±0.86(20 µM). The effects of wortmannin on DSB levels wereassessed by neutral elution. The effects of wortmannin on thekinetics of DSB repair were evaluated over a 3 h time course.Wortmannin (50 µM) completely inhibited DSB repair overthis period, without having any effect on DSB levels itself.The concentration-dependent effects of wortmannin on DSB levelsshowed that inhibition of DSB repair was significant at 1 µM,and near-maximal at 20 µM. In marked contrast, it exertedno effect on the kinetics of single strand break (SSB) repairas assessed by alkaline elution, even at concentrations as highas 50 µM. There was an excellent correlation between theconcentration-dependence and exposure time of wortmannin requiredto enhance IR cytotoxicity and inhibit DSB repair. These dataimplicate inhibition of DNA-dependent protein kinase, and theconsequent inhibition of DSB repair, as the mechanism wherebywortmannin potentiates the cytotoxicity of IR.     

A common-source outbreak of Crimean-Congo haemorrhagic fever on a dairy farm

An outbreak of Crimean-Congo haemorrhagic fever (CCHF) on a dairy farm in the Orange Free State in 1984 is described. Forty-six cows were purchased from the western Cape Province in January 1984; 2 died from the tick-borne disease anaplasmosis in March and a labourer who helped butcher the carcasses became ill a few days later. Another cow died at the end of April and within 9 days 4 people who had come into contact with its blood became ill. Antibodies to CCHF virus were found in the sera of the 5 patients but not in other residents of the farm. Three patients recovered from a severe influenza-like illness without seeking medical attention; 1 patient, who was admitted to hospital, recovered from illness marked by haematemesis, epistaxis and amnesia and the 5th patient died of complications of surgery for brain haemorrhage. Antibody studies indicated that many of the cows became infected with CCHF after their arrival on the farm. It can be deduced that animals reared in tick-free, or relatively tick-free, circumstances, which are then moved to where they are subject to heavy parasitization by ticks, can acquire common tick-borne diseases of livestock plus CCHF infection simultaneously. In such circumstances there is a definite risk of human exposure to CCHF-infected blood or other tissues.     

Fatal human infection with rabies-related Duvenhage virus, South Africa

Duvenhage virus was isolated from a patient who died of a rabies-like disease after being scratched by a bat early in 2006. This occurred approximately 80 km from the site where the only other known human infection with the virus had occurred 36 years earlier.