Time-dependent effect of chlorhexidine surgical prep.

Despite continued advances in preoperative preventive measures and aseptic technique, surgical site infections remain a problem. The purpose of this study was to evaluate the time-dependent effectiveness of chlorhexidine, a common surgical preparation solution, at various concentrations. Agar plates containing a Mueller-Hinton medium were inoculated with Staphylococcus aureus (lux) bacteria. The bacteria are genetically engineered to emit photons, allowing for quantification with a photon-counting camera system. Standardized amounts of aqueous chlorhexidine at three different concentrations (group 1:4%; group 2:2%; group 3:0.4%) were applied to the agar plates and comparisons in bacterial reduction were made. After 2 min of contact time, groups 1 and 2 had similar reductions in bacterial load with 30% bacterial load remaining in each group (P=0.512), whereas group 3 had a significantly higher bacterial load (33%) when compared to both groups 1 and 2 (1 vs 3, P<0.0001; 2 vs 3, P=0.0002). The bacterial load in all three groups continued to decrease out to the final time point (1h) with group 1 having the least amount of bacterial load remaining, 9% (P<0.0001) and group 3 with the highest bacterial load remaining, 19% (P<0.0001). This study demonstrates two key results: first, dilution of chlorhexidine correlates directly with its bactericidal activity; second, its effectiveness is directly related to its contact time. Based on the results of this study, the authors recommend using 4% chlorhexidine for surgical site preparation and allowing a minimum of 2 min of contact time prior to making the skin incision.

Pharmacological studies on relaxation of spastic primate cerebral arteries in subarachnoid hemorrhage.

Chronic cerebral vasospasm was induced in 16 monkeys by direct placement of a clot of autologous blood over the arteries of the circle of Willis on the right side. The middle cerebral arteries (MCA's) on the clot side all showed angiographic vasospasm, which was maximal 7 days after subarachnoid hemorrhage. Animals were sacrificed at this time and vascular responses to acetylcholine (ACh), histamine, and the calcium ionophore A23187 were studied in MCA rings from the clot (spastic) side and the non-clot (control) side. In control preparations with an intact endothelium, which had been precontracted by prostaglandin F2 alpha (PGF2 alpha), histamine and A23187 produced significant relaxation. The same concentrations of histamine and A23187 did not relax vascular tissues in which the endothelium had been mechanically removed. Acetylcholine did not produce a significant endothelium-dependent relaxation of primate MCA rings, but did relax rings of primate common carotid artery. Pretreatment with chlorpheniramine (an H1-receptor antagonist) prevented histamine-induced relaxation; however, cimetidine (an H2-receptor antagonist) had no inhibitory action. It thus seems that histamine mediates relaxation of intact MCA's mostly by an H1-receptor-mediated release of endothelium-derived relaxing factor (EDRF). Relaxations induced by histamine and A23187 in MCA's from the clot side were substantially reduced. Moreover, the small component of ACh-induced relaxation was also abolished. Endothelium-independent relaxation induced by glyceryl trinitrate (GTN) occurred in arteries from both the control and the clot sides. Constrictions induced by KC1 and PGF2 alpha were reduced on the clot side of the MCA's. These results suggest that subarachnoid hemorrhage influences both the generation of EDRF and the constriction of affected arteries. The small contraction which was elicited in spastic arteries was fully relaxed by GTN.

Some pharmacological activities of novel adenine-related compounds isolated from a marine sponge Agelas mauritiana.

Agelasimine A and agelasimine B, two novel compounds related to adenine, have been isolated from the orange sponge, Agelas mauritiana, and have been tested for a variety of biological activities. Both compounds inhibited proliferation of cultured L1210 leukemia cells at nanomolar concentrations with accumulation in the G1 stage of the cell cycle. However, no prolongation of life was observed in mice bearing P388 leukemia treated with these compounds. In the rat isolated aorta, micromolar concentrations of agelasimines were very effective in inhibiting contractions elicited by potassium chloride but had little or no effect on responses for prostaglandin F2 alpha and had modest effects on the responses to noradrenaline and significant effects on 5-hydroxytryptamine. Agelsamines A and B appeared to be equipotent in causing relaxation in rabbit jejunum and bovine coronary artery, and they also inhibited nucleoside transport into rabbit erythrocytes in micromolar concentrations.

Oxalic acid decreases calcium absorption in rats.

Calcium absorption from salts and foods intrinsically labeled with 45Ca was determined in the rat model. Calcium bioavailability was nearly 10 times greater for low oxalate kale, CaCO3 and CaCl2 than from CaC2O4 (calcium oxalate) and spinach (high in oxalates). Extrinsic and intrinsic labeling techniques gave a similar assessment of calcium bioavailability from kale but not from spinach.

Effects of nimodipine on in vitro contractility of cerebral arteries of dog, monkey, and man.

Cerebrovascular spasm in the cynomolgus monkey does not appear to be modified by nimodipine. It is possible that cerebral arteries from this species are unusually resistant to the action of calcium antagonists. To test this hypothesis, parallel studies on the in vitro response of cerebral arteries from monkey, dog, and man have been carried out. Rings of basilar or middle cerebral artery were tested with potassium chloride, noradrenaline, 5-hydroxytryptamine, prostaglandin F2 alpha, and hemoglobin. The responses were then reexamined in the presence of various concentrations of nimodipine. There is a significant variation among species in sensitivity to nimodipine, the vessels from the monkey being more resistant to nimodipine than those from other species. There is, as expected, a considerable difference in the ability of nimodipine to block the different agonists. Responses to potassium chloride are blocked by low concentrations of nimodipine in all species, whereas noradrenaline and 5-hydroxytryptamine are more resistant. It is noteworthy that, in all species tested, hemoglobin and prostaglandin F2 alpha were antagonized poorly even by higher concentrations of nimodipine. If these agonists play a major role in the development of vasospasm and subsequent delayed ischemia, it may be that the calcium antagonists exert a beneficial effect by some mechanism other than dilation of spastic arteries.

Temperature and histamine receptor function--what is really happening?

Early studies suggested that a low temperatures there was a transition of receptor type from an H1 to an H2 receptor when the temperature was reduced from 37 degrees C to temperatures below 20 degrees C. These original observations were based on the development of sensitivity of guinea-pig ileum to the H2 antagonist metiamide as the temperature was reduced. More recently, evidence from a number of laboratories has cast doubt on the existence of a simple H1-H2 receptor transition, but there is abundant evidence that there are major changes in the response of a variety of smooth muscle preparations to histamine at reduced temperatures. The evidence in regard to alterations in histamine response at low temperatures is reviewed, some new evidence presented, and a model which is consistent with most of the observations is suggested.

Detection of endothelium in cerebral blood vessels.

An increasing body of evidence implies that the results of pharmacological studies of blood vessels may depend on the presence of an intact layer of endothelial cells inside the blood vessels. This is often inadvertently removed during the early part of the experiment and it is thus necessary to have some means of determining whether the endothelium is intact or has suffered extensive damage. Previous reports describe a stain that will enable the endothelial cells to be visualized, however we find that in the cerebral vasculature this approach is unsatisfactory in that it provides a gross underestimate of the amount of intact endothelium. A modification of the original procedure is described that provides results that correspond well with those of scanning or transmission electron microscopy.