Pathophysiology and etiology of Alzheimer's disease

Morphologic, neurochemical, and physiologic alterations in the brain constitute the biologic correlates of aging and of progressive, irreversible deterioration in mental function and personality characteristics of Alzheimer's disease.     

A bioenergetic basis for peripheral nerve fiber dissociation

The selective vulnerability of myelinated axons in lesions of peripheral nerve is incompletely understood and appears somewhat at variance with the energy conservation attached to saltation in these fibers. We evaluated the relative energy requirement of resting A and C fibers in rabbit vagus nerve by measuring the amplitude of the components of the compound action potential at 5-10 min intervals during incubation in Ringer-bicarbonate solutions containing 0-20 mM glucose. In nerves in which the perineurial sheath was retained intact the A components remained at control amplitude with 20 mM glucose but, after a plateau period, declined increasingly rapidly with 5, 2, 1, 0.5 and 0 mM glucose. 2mM glucose sufficed to maintain control amplitude of the C fiber component. In desheathed nerves the A component remained at control amplitude with 5 mM glucose but declined increasingly rapidly with 2, 1, 0.5 and 0 mM glucose; 0.5 mM glucose sufficed to maintain control amplitude to C fibers. The depressed potentials generally recovered incompletely after transfer to glucose 5 mM (desheathed) or 20 mM (sheathed); however, the partial recovery was more rapid and more nearly complete in the C fiber group than in the A fiber group (P less than 0.05). The data demonstrate that resting A fibers are much more susceptible to energy lack in vitro than resting C fibers. This suggests that deprivation of energy may be a factor in the preferential destruction of large fibers, termed fiber dissociation, which characterized several syndromes of chronic pain.     

Mitochondrial disease: beyond etiology unknown

Mitochondrial dysfunction is now recognized as a relatively common cause of degenerative disease in children. Mutations in either the mitochondrial or the nuclear genome that cause errors in the synthesis of enzymes essential for energy production and metabolism lead to a wide variety of pediatric problems, including developmental delays, sensorimotor impairment, seizures, diabetes, and organ failure. This article reviews the role of mitochondria in health and illness, discusses the clinical aspects of mitochondrial dysfunction, describes the experiences of three children with mitochondrial disease, and presents nursing strategies for affected families.     

A case of mitochondrial disease with severe left ventricular hypertrophy

A 35-year-old woman was admitted for progressive dyspnea with lower limb edema. Transthoracic echocardiography showed severe left ventricular hypertrophy (LVH) and heart failure with preserved ejection fraction (HFPEF). Electron microscopy of an endomyocardial biopsy sample revealed a high density of mitochondria of abnormal size and shape. We report a case of mitochondrial disease with severe LVH and HFPEF.     

The etiology of ABO hemolytic disease of the newborn

The etiology of ABO hemolytic disease of the newborn is complex because of the natural presence of anti-A and/or anti-B in individuals who do not possess the A and/or B antigen. Although only IgG anti-A and anti-B can cross the placenta, these antibodies are found in the circulation of most newborn infants born to blood group O mothers. The A and B antigens are much weaker on the red blood cell of newborn infants than of adults. This relatively weak reactivity constitutes a major protective factor against maternal antibodies which have crossed the placental barrier. However, much variation was found in the strength or the reactivity of the A antigen among infants born at term. This variation was large enough to account for the poor quantitative relationship between maternal antibody levels and the ensuing hemolytic process in the infant. Thus, the variation in antigen strength among newborns constitutes an unpredictable factor in the etiology of ABO hemolytic disease. Infants with a relatively weak A antigen can tolerate a moderately high level of circulatory anti-A without any untoward effects, while in the presence of the same antibody level, infants with a relatively strong A antigen, a portion of the red blood cells will be destroyed.     

Parkinson's disease: the disease concept, etiology and diagnostic bases

Parkinson's disease (PD) is caused by degeneration of nigral dopaminergic neurons. This results in dysfunction of the basal ganglia, thereby exhibiting movement disorders. The four cardinal signs of PD include bradykinesia, rigidity, resting tremor and postural instability. In the majority of patients with PD, the four cardinal signs are ameliorated by levodopa. In addition to anti-parkinson medication, surgery of the basal ganglia for PD has been applied. Local electrical stimulation of particular nuclei of the basal ganglia (deep brain stimulation) for PD has also proved to give satisfactory outcome. Both genetic and environment factors are considered to contribute to the initiation of PD. Some mutations of particular genes (e.g., alpha-synuclein) are found to link to parkinsonian families.     

The clinicomethodological aspects of the etiology of coronary artery disease

Having analyzed more than 150 original papers dedicated to the study of cardial pathology risk factors from clinical (specific) and methodological (philosophic) points of view, the authors put forward a hypothesis of the etiology of diseases (by the example of coronary artery disease) as a "critical mass" of these risk factors. Reasoning from it, the authors suggest the ways of using this statement by large quantitative evaluation of clinical data, and application of mathematic modeling to the diagnostics and prognostics of cardial pathology in each particular case.     

A bioenergetic explanation for the selective vulnerability of renal medullary tubules to hypoxia

1. In order to explain the vulnerability of medullary thick ascending limb of Henle's loop (mTAL) during hypoxia, adenosine 5'-triphosphate (ATP) content was measured in isolated rat mTAL cells during control conditions and chemically induced hypoxia and compared with those in medullary collecting duct (MCD) cells. 2. Basal ATP levels in mTAL and MCD were estimated as 3.6 and 2.1 mmol/l, respectively. Antimycin A (5 mumol/l) decreased the ATP content by 41% of the control value in the mTAL cells, but failed to reduce that of the MCD cells. Administration of sodium cyanide (5 mmol/l) drastically depleted ATP in the mTAL cells within 5 min (2-3% of control). On the other hand, ATP levels in MCD cells were sustained for at least 60 min after cyanide administration (64% of control). 3. When tubules were made permeable to sodium by the addition of nystatin, the effects of chemical hypoxia on the cell ATP levels were intensified in both segments, and this was partially blocked by pretreatment with ouabain, or by lowering the sodium concentration of the medium. 4. Higher doses of nystatin in mTAL caused a reduction in ATP levels even under control conditions, but its effect was prevented in low sodium medium. 5. The present study suggests that cell ATP levels can be altered by sodium, potassium-dependent adenosine triphosphatase activity, and that due to their high sodium-transporting activity, mTAL cells are more sensitive to reductions in ATP levels during hypoxia than are MCD cells.