Formation of free choline in brain tissue during in vitro energy deprivation

Free choline and ATP contents were measured in Mongolian gerbil hippocampal slices (tissue) and incubation media (media) during exposure to 30 min of aglycemia, high potassium, anoxia, or ischemia. Changes in choline levels reflected the degree of energy reduction, lower ATP levels being associated with high choline (4-fold increase during exposure to high potassium and anoxia, and 11-fold increase during ischemia). Media (extracellular) choline was particularly affected and increased about twofold during relatively mild energy depletion (e.g., aglycemia), but tissue choline content was less sensitive to energy reduction. A plot of choline vs. ATP levels indicated a nonlinear correlation, and the sharp increase in choline occurred when ATP values fell to about 2.5 nmol/mg of protein. Inhibition of acetylcholine sterase by 10 microM physostigmine during ischemia did not prevent an increase in choline contents but rather enhanced them, indicating that acetylcholine hydrolysis was not the source of free choline. Formation of free choline was Ca2+ independent. These findings suggest the involvement of phospholipase D and phosphatidylcholine hydrolysis in free choline formation during energy stress. The extent of choline formation may be an indicator of the degree of membranal damage, which in turn reflects damage to the metabolic machinery of the cell.     

Bilateral naevus of Ota: a rare manifestation in a Caucasian

The naevus of Ota (naevus fusculocoeruleus ophthalmomaxillaris) was first described by the Japanese dermatologist M. T. Ota in 1939. It has a reported incidence of 0.2% to 1% in the Japanese population. It usually occurs in the skin innervated by the first or second branch of the trigeminal nerve. The naevus comprises dermal melanocytes and is congenital or acquired during adolescence. Commonly associated lesions include scleral melanocytosis and other ocular manifestations as well as lesions of the tympanic membrane, oral and intranasal mucosa and leptomeninges. Diseases associated with Ota's naevus in rare cases are open-angle glaucomas and melanoma. The naevus of Ota in Europeans is a rare manifestation. We report the very rare case of a bilateral naevus of Ota associated with enoral melanocytosis in a white European person.     

Postural stability by computerized posturography in minor head trauma

Mild head injuries are very common among young children. Often, these injuries are followed by a variety of subjective complaints termed posttraumatic syndrome. Posturography (balance test) was performed immediately after the trauma in 21 children who had sustained mild head injury. Significant difference in performance was observed in head-injured children in all subparts of the test as compared with a control group. We conclude that posturography may serve as a simple cost-effective method in qualifying the posttraumatic imbalance.     

Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine

To investigate the in vivo role of NMDA receptor stimulation in HIV-1-related CNS neurotoxicity, we evaluated the neuroprotective potential of the NMDA receptor antagonist memantine in transgenic mice which have gp120-induced CNS damage. Brains of mice treated chronically with memantine and of untreated controls were analysed for structural damage by laser scanning confocal microscopy of sections immunolabeled for microtubule-associated protein-2 (MAP-2) and synaptophysin. Qualitative and quantitative analysis of confocal images revealed that memantine treatment substantially decreased neuropathology in gp120 transgenic mice; this included statistically significant improvements in both dendritic and presynaptic terminal density. These results provide in vivo evidence that gp120 can activate neurotoxic pathways that can ultimately result in aberrant NMDA receptor stimulation and neuronal damage in the CNS. They also suggest that clinically tolerated NMDA receptor antagonists may be useful in the prevention of neuronal damage in HIV-1-infected patients.     

The relationship between receptor-effector unit heterogeneity and the shape of the concentration-effect profile: Pharmacodynamic implications

The apparent concentration-effect relationship is the ensemble of many effector units (such as individual cells or channels) that do not always exhibit a uniform stimulus-effect relationship. This concept is substantiated by many observations of heterogeneity in receptor-effector populations including hormone secreting cells, response to hormonal stimuli, activity pattern of second messengers, stimulus-evoked synaptic currents, and single ion channels. The relationship between drug concentration and magnitude of pharmacologic response is commonly described by the sigmoidalE _max model which was derived from the Hill equation. The sigmoidicity factor (N) in this model is assumed to be a pure mathematical parameter without physiological connotations. This work demonstrates that the numerical value ofN (measured empirically) is the product of two factors: (i) the degree of heterogeneity of the effector subunits, i.e., the elemental component that upon drug stimulus contributes its pharmacological effect independently and does not interact with other subunits (it could range from a single receptor up to a whole tissue), and (ii) value ofN ^*—the shape factor of the subunits' concentration-effect relationship. A special case of this approach occurs whenN ^*>5, which is an on-off case. HereN is determined by the distribution (density equation) of the subunit values. In case of heterogeneity of the microparameters of the effector subunits the apparentN will always have a lower value thanN ^*. According to this theory it can be concluded that without knowledge of the distribution of the microparameters no mechanistic interpretation can be deduced from the apparentN value. If in the futureN ^* can be determined by theoretical or experimental methods, the distribution function relatingN ^* toN can be calculated. The relevance of this theory is increased in view of the progress being made in advanced research techniques which may enable us to determine the concentration-effect relationship at the level of the individual effector unit.     

Tumor necrosis factor (TNF alpha) in lymphadenopathy and bone marrow involvement: histopathological and serological study.

Serum samples were collected from 40 patients with enlarged lymph nodes. Lymph node and bone marrow biopsies were performed and processed as usual. Tumor necrosis factor-alpha (TNF alpha) was determined in the sera by factor test human TNF alpha ELISA kit. Histopathological studies of lymph node and bone marrow biopsies were evaluated. The data obtained from this study showed that bone marrow was involved in only 5 patients and their TNF showed the lowest level in this study with a mean level 50 pg/ml. The highest level of TNF occurred in cases with granulomatous lymphadenitis (124 pg/ml) followed by reactive lymphadenitis (105 pg/ml). It can be considered that TNF reflects the immune status of the patient and its study in the serum can be of help in evaluating the progress of the disease. An extended study is need to evaluate the role of TNF-alpha as a prognostic marker in malignancy.     

A Null mutation in the vasopressin V2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus in the Hopewell kindred

Congenital nephrogenic diabetes insipidus (DIR) Is a rare X-linkedhereditary disorder in which the renal collecting duct Is unresponsiveto arginine vasopressin; thus, the urine is consistently hypotonicto plasma. Recently, the association between the V2 receptorgene (AVPR2) and DIR has been proven. We have determined thegene sequence of four family members, from three generations,of a large North American family with CNDI who were originallypart of the study used to formulate the Hopewell hypothesis.It had been proposed that a single DIR gene defect was Introducedto North America by a member of an Ulster Scot kindred arrivingon the ship Hopewell In 1761. DNA sequencing of the AVPR2 hasIdentified a single base transversion from G     

Neurodegeneration in the Central Nervous System of apoE-Deficient Mice

Apolipoprotein E (apoE) is involved in the development and regeneration of the central nervous system (CNS). ApoE may also be necessary to maintain the integrity of the synapto-dendritic complexity. We analyzed the synaptic alterations in the CNS of apoE-deficient (knockout) mice during the aging process. In apoE-deficient homozygous mice, there was an age-dependent 15 to 40% loss of synaptophysin-immunoreactive nerve terminals and microtubule-associated protein 2-immunoreactive dendrites in the neocortex and hippocampus, when compared to controls. Dendritic alterations were observed as early as 4 months of age. Ultrastructural analysis revealed extensive dendritic vacuolization and disruption of the endomembrane system and cytoskeleton in apoE-deficient homozygous mice. Further immunocytochemical studies of the neuronal cytoskeleton showed that in apoE-deficient mice there was a decrease in the immunoreactivity of α and β tubulin (but not kinesin) in the cell bodies and processes. These results support the contention that apoE might play an important role in maintaining the stability of the synapto-dendritic apparatus and that altered or deficient functioning of this molecule could underlie the synaptic and cytoskeletal alterations in Alzheimer's disease.     

The Evaluation of Routine Andrological Parameters in Human Semen/Auswertung der Routine-Parameter der Andrologie am Sperma

A study was carried out to evaluate the andrological parameters in 540 human semen specimens divided into groups according to sperm counts. The parameters were: motility percentage and grade, percentage of viability and of morphologically normal sperm and immature cells. The Duncan multiple range test and the Kruskal-Wallis test with multiple comparison of ranks were used in the statistical analyses. Of particular interest, among other our findings, were the significant differences obtained by comparing the group with sperm counts up to 5 x 10(6) per ml semen and that with counts ranging from 5.1 to 10 x 10(6) per ml semen. This was true for all parameters with the exception of semen volume. Comparison of the oligozoospermic groups (up to 20 x 10(6)/ml) with those having higher sperm counts also showed significant differences. There was a trend towards improvement of the examined parameters with the increase in sperm density, but with a remarkable heterogeneity particularly within the oligozoospermic groups. In all groups motility, viability and morphological normality of sperm showed a positive correlation with each other. "Normal values" of the parameters studied could be derived from scatterplot charts over the entire range of sperm counts and from the statistical evaluation of the grouped material.