digoxin and Cataract

A case of a 62-year-old woman presenting with a 20-year history of vulvodynia previously unresponsive to medical treatment is described. The epidemiology, phenomenology and medical management of vulvodynia is reviewed. The case presentation illustrates the role of pregabalin in successful medical management of this chronic pain disorder, as well as the management of common psychiatric morbidities associated with this condition.

Topics: Amitriptyline; Analgesics; Anti-Ulcer Agents; Anticoagulants; Antidepressive Agents; Anxiety; Cardiotonic Agents; Cataract; Cataract Extraction; Cholecystectomy; Chronic Disease; Citalopram; Digoxin; Female; gamma-Aminobutyric Acid; Heart Failure; Humans; Hypertension; Hysterectomy; Lorazepam; Middle Aged; Mitral Valve Insufficiency; Omeprazole; Ovarian Neoplasms; Pain; Pregabalin; Sterilization, Tubal; Stomach Diseases; Vulvar Diseases

Both hypertension and cataract formation have been associated with reductions in sodium pump activity, possibly as a result of an endogenous inhibitor. The objective of the present study was to answer 4 closely related questions: (1) Is the lens sodium pump effectively inhibited by a labile, digitalis-like factor we have identified in the peritoneal dialysate from hypertensive patients in end-stage renal failure? (2) How does that inhibition compare to that induced by ouabain? (3) Does sodium pump isoform distribution determine the degree of lens sodium pump inhibition? (This question was precipitated by the unanticipated finding that the labile DLF was more effective in inhibiting lens sodium pump than was anticipated.) (4) Is sodium pump activity altered in lens in response to increased salt intake, a maneuver known to increase endogenous digitalis-like factor? We found that whereas ouabain produced equivalent or significantly less inhibition of lens Na(+), K(+)-ATPase from calf or rabbit, respectively, compared with brain, labile digitalis-like factor preferentially inhibited lens compared with brain. Analysis of whole-lens preparations from rabbit, calf, and normal human lens revealed substantial alpha2- and alpha3-isoforms of the sodium pump but little alpha1-isoform. Ouabain inhibition of whole-lens Na(+),K(+)-ATPase from rabbit and calf were comparable: for rabbit lens, K(i)=5.2x10(-7) mol/L; for calf lens, K(i)=1.0x10(-6) mol/L. Limited quantities of labile digitalis-like factor prohibited similar determinations; however, its concentration-activity profile paralleled that of ouabain. Na(+), K(+)-ATPase activity, measured in the 3 major anatomic regions of lens and normalized to nucleus, was greatest in epithelium (56. 9+/-17.9) compared with cortex (5.8+/-1.4) and nucleus (1.0+/-0.0; P=0.01). Immunohistochemistry of rabbit lens found abundant alpha2- and alpha3-isoforms in epithelium and limited alpha3 but undetectable alpha1 in cortex and nucleus. Finally, rats randomized to a high Na diet showed significantly reduced lens Na(+), K(+)-ATPase activity compared with those on a low Na diet, consistent with the effects of a sodium pump inhibitor. In conclusion, the present study suggests that digitalis-like factor may provide a link between hypertension and cataract formation.

Topics: Animals; Brain; Cardenolides; Cataract; Cattle; Digoxin; Enzyme Inhibitors; Humans; Immunohistochemistry; Isoenzymes; Lens, Crystalline; Ouabain; Rabbits; Rats; Rats, Sprague-Dawley; Saponins; Sodium-Potassium-Exchanging ATPase; Sodium, Dietary

Human cataractous lens nuclei extract inhibited, in a dose-dependent fashion, [3H]ouabain binding to rat brain synaptosomes and microsomal Na(+)- and K(+)-dependent adenosine triphosphate (Na+, K(+)-ATPase) activity and interacted with anti-digoxin antibodies. The compounds responsible for these activities, termed digitalis-like compounds (DLC), were also detected in bovine, rat, cat and rabbit, normal, transparent lenses, but the levels were only 0.7-5.4% of the average levels in the cataractous human lenses. DLC from the human cataractous lenses were purified by a procedure consisting of organic extractions and batch chromatography followed by filtration through a 3000 Da cut-off filter and subsequent separations using reverse-phase high-performance liquid chromatography. The presence of DLC in the different fractions obtained in the chromatograms was monitored by their ability to inhibit [3H]ouabain binding and Na+, K(+)-ATPase activity. Based on chemical ionization mass spectrometry together with ultraviolet spectrometry and biological characterization, it is suggested that new bufodienolides, 19-norbufalin and 19-norbufalin peptide derivatives are responsible for the endogenous DLC activity. It is proposed that these compounds may regulate Na+, K(+)-ATPase activity in the lens under some physiological and pathological conditions.

Topics: Animals; Antibodies; Blood Proteins; Bufanolides; Cardenolides; Cataract; Digitalis; Digoxin; Humans; Lens Nucleus, Crystalline; Mass Spectrometry; Microsomes; Molecular Weight; Ouabain; Plants, Medicinal; Plants, Toxic; Rats; Saponins; Sodium-Potassium-Exchanging ATPase

Topics: Aminophylline; Aspirin; Atropine; Cardiomyopathies; Cataract; Child, Preschool; Chloramphenicol; Chlorothiazide; Conjunctivitis; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Iatrogenic Disease; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Ophthalmic Solutions; Pre-Eclampsia; Pregnancy; Purpura, Thrombocytopenic; Substance-Related Disorders; Suppositories

Topics: Birth Weight; Cataract; Cesarean Section; Chloramphenicol; Digoxin; Drug-Related Side Effects and Adverse Reactions; Ductus Arteriosus, Patent; Female; Humans; Infant; Infant, Newborn; Penicillins; Pregnancy; Pregnancy Complications, Infectious; Rubella virus