Ischaemia is a common clinical event leading to local and remote injury. Evidence indicates that tissue damage is largely caused by activated neutrophils which accumulate when the tissue is reperfused. If the area of ischaemic tissue is large, neutrophils also sequester in the lungs, inducing non-cardiogenic pulmonary oedema. Ischaemia reperfusion injury is initiated by production of reactive oxygen species which initially appear responsible for the generation of chemotactic activity for neutrophils. Later, once adherent to endothelium, neutrophils mediate damage by secretion of additional reactive oxygen species as well as proteolytic enzymes, in particular elastase. Therapeutic options for limiting ischaemia reperfusion injury include inhibition of oxygen radical formation, pharmacological prevention of neutrophil activation and chemotaxis, and also the use of monoclonal antibodies which prevent neutrophil-endothelial adhesion, a prerequisite for injury.

The majority of women receiving treatment for breast cancer report menopausal symptoms, which negatively correlate, not only with their own, but also with their partner's quality of life. Most women experiencing hot flushes are not receiving treatment due to lack of both awareness and confidence in the existing treatment options.

Neutrophils have been implicated as central mediators in myocardial and skeletal muscle ischemia-reperfusion injury. This study tests whether these cellular elements and the chemoattractant leukotriene (LTB4) play a role in postischemic renal failure. Anesthetized rats underwent 45 min of left renal pedicle clamping. Five minutes after reperfusion, LTB4 levels were elevated to 1.42 ng/ml (P less than 0.05); thromboxane (Tx)B2 was 2,840 pg/ml, higher than 503 pg/ml in sham controls (P less than 0.05); renal artery blood flow was 67% of preclamping values at 1 min of reperfusion compared with 111% in sham (P less than 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P less than 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P less than 0.05); histology showed acute tubular necrosis (ATN). Neutrophil depletion by rabbit antiserum (n = 8) led during reperfusion to reduced LTB4 and TxB2 levels, 1.04 ng/ml and 1.043 pg/ml (P less than 0.05); increased renal blood flow of 174% (P less than 0.05); reduced creatinine levels of 1.8 mg/dl (P less than 0.05); and limited ATN. Pretreatment with diethycarbamazine prevented the increases in LTB4 and TxB2 (P less than 0.05), increased renal blood flow (P less than 0.05), minimized creatinine increase to 1.7 mg/dl (P less than 0.05), and reduced ATN. These data indicate that neutrophils and LTB4 play a role in ischemia-induced Tx synthesis and mediate postischemic renal injury.