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.     

Predicted and Measured Muscle Forces after Recoveries of Differing Durations Following Fatigue in Functional Electrical Stimulation

Abstract: Using ³¹P nuclear magnetic resonance (NMR) spectroscopy, the bioenergetics of paralyzed muscles activated by functional electrical stimulation (FES) were studied in vivo during fatigue and recovery on paraplegic subjects. During the activation phase of the muscle, the muscle force was also monitored. The phosphorus metabolites were found to vary systematically during fatigue and to recover slowly to their rest state values after cessation of FES. During fatigue, a good correlation was found between the decaying force and each of the profiles of phos-phocreatine, inorganic phosphorus, and intracellular pH. A musculotendon 5 element model was proposed for the activated muscle to predict its force generation capacity. A fatigue recovery function, based on the metabolic profiles, was introduced into the model. This model allowed us to predict the force expected to be developed as a function of the time after recovery of given time durations. Validation experimental measurements of force were carried out and included recurrent fatigue tests, both in the initially un-fatigued state and at various times in the postfatigue stage of the muscle. Comparison of the predicted and measured forces indicated satisfactory agreement of the results. The developed model of muscle dynamics should help to design a strategy for reducing muscle fatigue under FES.     

Nodular regenerative hyperplasia: a controversial indication for orthotopic liver transplantation

Nodular regenerative hyperplasia of the liver is an uncommon cause of portal hypertension. Patients with nodular regenerative hyperplasia have signs and symptoms of portal hypertension, without evidence of hepatocellular failure or encephalopathy. We report the case of a 44-year-old woman with recurrent esophageal bleeding and refractory ascites who had a history of hemosiderosis, hepatitis C, and chronic renal allograft rejection. Our preoperative diagnosis was cirrhotic end-stage liver disease and end-stage renal disease for which the patient underwent combined hepatic and renal transplantation. Her portal hypertension symptoms resolved, and her renal function has been normal for 18 months of follow-up. Histologic examination of the liver revealed nodular regenerative hyperplasia, and a review of the literature regarding the surgical management of patients with nodular regenerative hyperplasia revealed that various shunting procedures are generally recommended. After the failure of medical management in patients with nodular regenerative hyperplasia, portosystemic shunting may be indicated before proceeding to hepatic transplantation.     

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.     

125I]His-neurokinin A binds selectively to NK2 receptors of the B-type in rat small intestine smooth muscle membranes.

The high-affinity, reversible binding of [125I]His-neurokinin A (NKA) to rat small intestine smooth muscle membranes was investigated. Endogenous neurokinin agonists, selective neurokinin analogues, both agonist and antagonist, were used to define the selectivity of the binding. Both the endogenous and selective neurokinin analogue agonists displayed orders of potency indicating that [125I]His-NKA was binding to NK2 receptors. The use of recently developed NK2-selective antagonists indicated that the NK2 receptors present in this preparation were similar to those described in hamster trachea preparations (NK2B), and not endothelium-denuded rabbit pulmonary artery (NK2A). The absence of NK2A receptors and the predominance of NK2B was confirmed by blocking experiments using MEN10376 and L659877. Low-affinity binding of NKA was also observed with this preparation, which was not sensitive to the NK2-selective agonist, [beta-Ala8]NKA4-10. This was shown not to be due to the presence of NK1 or NK3 receptors by using selective agonists for NK1 and NK3 to block any such receptors. (No evidence for the presence of these receptors was obtained during these blocking experiments.) Guanylylimidodiphosphate appears to discriminate between the high- and low-affinity binding sites for NKA. It was thus concluded that high-affinity binding of [125I]His-NKA to rat small intestine smooth muscle membranes was selective for NK2B receptors. No evidence was found for the binding of [125I]His-NKA to NK1, NK3 or NK2A receptors.