Ciprofloxacin concentrations in serum, bone and bone marrow of rabbits

Ciprofloxacin concentrations were determined in serum, bone and bone marrow of rabbits. Four experimental groups of animals were examined: group A (n = 6) received a dosage of 60 mg/kg/day intramuscularly for 4 weeks, groups B (n = 6), C (n = 15) and D (n = 15) received dosages of 120 mg/kg/day subcutaneously for 2 days, 2 weeks, and 4 weeks, respectively. In the kinetic portion of the study, peak serum concentrations of ciprofloxacin measured at the 15 min sampling time were: 2.61 +/- 0.27 micrograms/ml in the 60 mg/kg/day group (group A) and 3.24 +/- 0.78 micrograms/ml in the 120 mg/kg/day group (group B). At necropsy, rabbits in group A had mean ciprofloxacin concentrations of 3.60 +/- 2.27 micrograms/ml in serum, 2.24 +/- 1.19 micrograms/g in marrow and 1.19 +/- 0.44 micrograms/g in bone. Rabbits in group B achieved mean levels of 4.02 +/- 1.23 micrograms/ml in serum, 2.48 +/- 0.79 micrograms/g in marrow, and 1.35 +/- 0.40 micrograms/g in bone. Rabbits in group C achieved mean levels of 5.65 +/- 2.16 micrograms/ml in serum, 3.74 +/- 1.33 micrograms/g in marrow and 1.92 +/- 0.94 micrograms/g in bone. Rabbits in group D achieved mean levels of 7.24 +/- 2.50 micrograms/ml in serum, 4.48 +/- 1.68 micrograms/g in marrow, and 1.93 +/- 0.54 micrograms/g in bone. Differences between mean values for the four experimental groups were not statistically significant.     

Effect of ciprofloxacin on subcutaneous abscesses induced with Staphylococcus epidermidis and a foreign body implant in the mouse

Subcutaneous abscesses were induced in mice with Staphylococcus epidermidis strain G19-85 and a foreign body implant. The MIC of ciprofloxacin for this strain was 0.25 microgram/ml. The ciprofloxacin dosage, 120 mg/kg/day, was divided into three injections, administered to the mice subcutaneously at 8 h intervals. Serum concentration kinetics in normal mice (n = 50) were determined. The peak serum level of ciprofloxacin was 3.18 micrograms/ml at the 15 min sampling time; the trough level was 0.53 micrograms/ml at 8 h. Abscesses were found in 96% (n = 49) of the untreated, infected control mice. Three modes of treatment with ciprofloxacin were tested: (1) four prophylactic injections of ciprofloxacin prior to infection reduced abscess formation to 64% (p less than or equal to 0.0002, n = 50). (2) Eleven therapeutic injections, initiated 4 days after infection, reduced abscess formation to 86% (p less than or equal to 0.17, n = 49). (3) One prophylactic injection prior to surgery and five therapeutic injections after infection reduced abscess formation to 43% (p less than or equal to 0.0001, n = 49). Culture results correlated with the abscess formation rates.     

Poly(ADP-ribose) degradation by glycohydrolase starts with an endonucleolytic incision

We have recently shown that poly(ADP-ribose) polymerase forms poly(ADP-ribose) by adding ADP-ribose residues to the polymerase-proximal end of an enzyme-bound nascent chain. In this light we have reexamined the mode of hydrolysis of enzyme-bound poly(ADP-ribose) by poly(ADP-ribose) glycohydrolase. When the substrate has been labeled by a pulse-chase protocol, soluble glycohydrolase releases a significant amount of labeled oligomer which can only come from the enzyme-distal (2') end of the polymer. This constitutes additional evidence for the proximal growth of chains. Oligomer is infrequently released from the proximal (1") end of enzyme-bound chains. Rather, the bulk of the poly(ADP-ribose) is digested directly to ADP-ribose monomers. We conclude that poly(ADP-ribose) glycohydrolase starts digestion with an endonucleolytic incision and then removes ADP-ribose residues processively in the 2'----1" direction. Therefore, in contrast to earlier models of polymer growth and hydrolysis, a single poly(ADP-ribose) chain may be extended at one end and simultaneously degraded at the other end. The balance between synthesis and degradation may control the quantity and distribution of polymer around the DNA break which occasions its synthesis.     

Nonenzymic adenosine 5'-diphosphate ribosylation of poly(adenosine diphosphate ribose)

Poly(adenosine 5'-diphosphate ribose) [poly(ADP-ribose]) is spontaneously ADP-ribosylated when it is incubated with nicotinamide adenine dinucleotide, especially in 0.5 M NaCl and at an alkaline pH. The ADP-ribose residues are monomeric and are attached to the middle of polymer chains. The linkage is similar to, and may be identical with, that of the branch points that are created in cells. RNA is also spontaneously ADP-ribosylated, but not DNA.     

Selection,linkage, and dominance in small populations

Summary Linkage, dominance, and selection interact significantly to alter the mean coefficient of inbreeding. The effect of one is not predictable without the other two. Close linkage between adjacent loci in the presence of intense selection caused a different response with overdominant gene action from with partial dominance. When selection was random, effects of linkage and dominance on the coefficient of inbreeding were nonexistent; but when selection was by either phenotype or genotype, linkage and dominance became important. Joint effects between linkage, dominance, and selection are illustrated in specific simulated populations.     

Problems of diabetics in prison.

Providing care for diabetics is difficult in prison. Six diabetic prisoners or former prisoners were seen whose care was difficult or unsatisfactory. Three had multiple admissions to hospital during their sentences with diabetic ketoacidosis that they induced themselves by not taking insulin. The motive seemed to be removal from prison to the fairly pleasant surroundings of the local hospital. A fourth prisoner required admission in a hyperglycaemic, hyperosmolar state that had gone unnoticed as he was thought to be "acting up." The two others had imperfect long term management of diabetes during their sentences. There is clearly room for improvement in diabetic services in British prisons, but manipulative behaviour on the part of some diabetic prisoners may remain a problem.     

Economic impact of a nationwide outbreak of salmonellosis: cost-benefit of early intervention.

The recognition and investigation of an outbreak of food poisoning in 1982 due to chocolate contaminated with Salmonella napoli enabled the food that carried the salmonella to be identified and four fifths of the implicated consignment of chocolate to be withdrawn. The economic benefits of prompt intervention in the outbreak have been assessed. The cost of the outbreak was over 0.5 pounds m. It is estimated that five deaths were prevented by the intervention and that 185 admissions to hospital and 29,000 cases of S napoli enteritis were avoided. This successful investigation yielded a 3.5-fold rate of return to the public sector and a 23.3-fold return to society on an investment in public health surveillance. A methodology is described that can be used to estimate the benefits of early intervention in outbreaks of foodborne illness and topics for further research are suggested. It is concluded that public health authorities and industry have much to gain by collaborating in the research into the design of cost effective programmes to prevent foodborne infections.