Phosphocitrate as a potential therapeutic strategy for crystal deposition disease.

The deposition of basic calcium phosphate and calcium pyrophosphate dihydrate crystals in articular tissues is probably an under-recognized event. Clinical observations indicate that exaggerated and uniquely distributed cartilage degeneration is associated with these deposits. Measurements of putative markers of cartilage breakdown suggest that these crystals magnify the degenerative process.

Do active cerebral neurons really use lactate rather than glucose?

Glucose has long been considered the substrate for neuronal energy metabolism in the brain. Recently, an alternative explanation of energy metabolism in the active brain, the astrocyte-neuron lactate shuttle hypothesis, has received attention. It suggests that during neural activity energy needs in glia are met by anaerobic glycolysis, whereas neuronal metabolism is fueled by lactate released from glia.

Biochemical mechanisms of action of Hypericum LI 160 in glial and neuronal cells: inhibition of neurotransmitter uptake and stimulation of extracellular signal regulated protein kinase.

We have investigated biochemical mechanisms that may underlie the antidepressant effects of Hypericum LI 160. We found that LI 160 inhibits uptake of serotonin and norepinephrine in cultures of rat cortical astrocytes. Observed differences in the kinetic parameters Km and Vmax as well as in the recovery of uptake after removal of Hypericum indicates that LI 160 does not affect serotonin and norepinephrine transport in the same manner.

Comparison of glucose and lactate as substrates during NMDA-induced activation of hippocampal slices.

It has been postulated that lactate released from astrocytes may be the preferred metabolic substrate for neurons, particularly during intense neuronal activity (the astrocyte-neuron lactate shuttle hypothesis). We examined this hypothesis by exposing rat hippocampal slices to artificial cerebrospinal fluid containing either glucose or lactate and either N-methyl-D-aspartate, which activates neurons without stimulating astrocytic glucose uptake, or alpha-cyano-4-hydroxycinnamate, which blocks monocarboxylate transport across plasma and mitochondrial membranes. When exposed to N-methyl-D-aspartate, slices lost synaptic transmission and K+ homeostasis more slowly in glucose-containing artificial cerebrospinal fluid than in lactate-containing artificial cerebrospinal fluid.

Hepatocellular carcinoma: an emerging problem with hepatitis C.

Hepatocellular carcinoma (HCC) is emerging as a major problem in the United States, primarily due to the development of liver cancer in patients with cirrhosis secondary to the hepatitis C virus. The diagnosis of HCC in patients with underlying cirrhosis can be achieved at an early stage if appropriate diagnostic measures are pursued by primary care physicians and gastroenterologists. African Americans are particularly vulnerable in developing HCC since their response to current therapy for chronic hepatitis C is less than optimal.

Rat hippocampal slices need bicarbonate for the recovery of synaptic transmission after anoxia.

The purpose of this study was to see how the nominal removal of bicarbonate (HCO(-)(3)) from the extracellular space of brain tissue influenced recovery of brain tissue from anoxia. Removal of HCO(-)(3) in HEPES-buffered artificial cerebrospinal fluid (aCSF) inhibited almost completely recovery of synaptic transmission in hippocampal slices after anoxia. Altered pH did not contribute to this finding because adjusting intracellular (pH(i)) and extracellular (pH(o)) pH to control levels did not reduce the effect of HCO(-)(3) removal.

Rectal Dieulafoy's lesion: report of a case and review of the literature.

Dieulafoy's lesion is an uncommon cause of gastrointestinal bleeding that occurs after rupture of an exposed submucosal artery. The vast majority of lesions are found in the stomach, but cases have been described in the esophagus, small intestine, colon, and rectum. We describe an elderly patient who presented with severe lower gastrointestinal bleeding caused by a rectal Dieulafoy's lesion.

Pseudo Sister Mary Joseph's nodule.

The Sister Mary Joseph's nodule is a significant finding in the physical examination. It is sometimes the only indication of an intra-abdominal metastatic malignancy. We report a patient who presented with an umbilical nodule that was discovered to be an omphalith.

Using hippocampal slices to study how aging alters ion regulation in brain tissue.

Aging alters ion regulation in brain tissue. This article describes methods useful for studying such age-related changes in the rat hippocampal slice preparation. Topics considered include (a) selection of appropriate age groups of rats for aging studies, (b) a description of methods for preparing and maintaining hippocampal slices, (c) measurement of intracellular pH with the H+-sensitive dye carboxy-SNARF-1, and (d) measurement of extracellular pH and K+ with cation-selective microelectrodes.

Paget's disease of bone: rheumatologic complications.

Pain is the most common reason people consult a physician when suffering from Paget's disease of bone. The most common reason for patients' pain is osteoarthritis, either directly or indirectly induced by Paget's disease. The physician should make a concerted effort to target the origin of the pain, because effective treatments for the two conditions seem to be different.

Aging and the effects of MK-801 on anoxic damage in rat hippocampal slices.

We examined whether age-related differences in N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity contribute to the increased vulnerability of the aged brain to anoxic damage. In both adult and aged hippocampal slices, NMDA receptor blockade with MK-801 did not affect the onset of anoxic depolarization. MK-801 improved the postanoxic recovery of synaptic transmission by the same percentage in both age groups.

The influence of glucose on intracellular and extracellular pH in rat hippocampal slices during and after anoxia.

In this study we investigated in rat hippocampal slices (1) how glucose availability affected tissue acidosis during and after anoxia, (2) whether the onset of anoxic depolarization was associated with a specific pH, (3) whether glycolysis was the major source of acidification before and during anoxic depolarization, and (4) whether improved recovery of synaptic function with elevated glucose levels was related to changes in tissue acidosis. Intracellular pH (pHi) and extracellular pH (pHo) were measured simultaneously before, during, and after anoxia in hippocampal slices bathed in 0, 5, 10, and 15 mM glucose. Slices exposed to 0 mM glucose were given 20 mM sodium lactate as a metabolic substrate.

The pH buffering capacity of hippocampal slices from young adult and aged rats.

We examined the hypothesis that aging alters the capacity of brain tissue to buffer intracellular pH changes. Intracellular buffering power was determined in hippocampal slices from young adult and aged rats by raising the partial pressure of CO2. Changes in intracellular and extracellular pH in response to increases and decreases in CO2 were measured simultaneously with spectrophotometry and pH-sensitive microelectrodes.

Murine model of recurrent group G streptococcal cellulitis: no evidence of protective immunity.

Despite the well-known tendency of cellulitis due to beta-hemolytic streptococci to recur, little is known regarding the mechanisms of human immunity to this infection. We established cellulitis in mice by using a strain of group G streptococcus (1750) originally isolated from the bloodstream of a patient with acute cellulitis. This strain, which has been studied extensively in our laboratory, expresses M protein structurally and functionally analogous to that of group A streptococci, and we have cloned and sequenced the gene encoding this protein (emmMG1).

The influence of age of pH regulation in hippocampal slices before, during, and after anoxia.

Changes in intracellular and extracellular pH may influence the vulnerability of brain tissue to anoxic or ischemic damage. In the present study, we investigated whether the increased vulnerability of aged brain tissue to anoxic damage is associated with age-related alterations in pH regulation. We obtained evidence for altered pH regulation by measuring concurrent changes in intracellular and extracellular pH before, during, and after anoxia in hippocampal slices from young adult (6-8 months old) and aged (24-27 months old) rats.

Vasoactive intestinal peptide stimulates prostate-specific antigen secretion by LNCaP prostate cancer cells.

The secretion of prostate-specific antigen (PSA) by prostate cancer provides an important tool in the diagnosis and management of this disorder. While androgens are required for PSA synthesis, the neuroendocrine regulation of PSA secretion is less understood. Human prostate is extensively innervated with vasoactive intestinal peptide (VIP)-containing neurons, while both normal and malignant prostate cells contain VIP receptors.

Pseudoaneurysm of the superficial temporal artery.

Ours is the first report of pseudoaneurysm of the superficial temporal in a 90-year-old woman. Although falls with associated head and scalp injuries in the geriatric population are common, pseudoaneurysm of the superficial temporal artery is rarely reported, probably due to the generally protected course of the superficial temporal artery across the skull. Clinicians' familiarity with this entity is important for early diagnosis and intervention.

Expression and processing of peptidylglycine alpha-amidating monooxygenase messenger RNA in rat prostate.

The prostate gland contains neuroendocrine cells and amidated neuroendocrine peptides whose presence has been related to aggressive forms of prostate cancer. The enzyme peptidylglycine alpha-amidating monooxygenase (PAM) is critical to the bio-synthesis of amidated peptides and is commonly present in neuroendocrine cells. By northern blot hybridization analysis, PAM mRNA was detected in similar quantities in dorsolateral and ventral prostates of 3-month-old and 13-month-old rats.

Effects of lysophosphatidic acid, a novel lipid mediator, on cytosolic Ca2+ and contractility in cultured rat mesangial cells.

Lysophosphatidic acid (LPA), the smallest and structurally simplest phospholipid, has the potential to modulate cellular signaling in diverse tissues and cell types, including fibroblasts. In the present study, we assessed the effects of LPA on cultured rat glomerular mesangial cells. Quantitative changes of [Ca2+]i in response to LPA were measured in monolayers of mesangial cells loaded with the fluorescent Ca2+ indicator fura 2.

Neuroendocrine peptides stimulate adenyl cyclase in normal and malignant prostate cells.

Elevations of intracellular cAMP in human prostate cancer cells have been shown to increase invasiveness and to promote neuronal differentiation. Since neuroendocrine peptides capable of activating adenyl cyclase are present in prostatic nerves and epithelial neuroendocrine cells, we investigated normal and malignant human prostate cells for changes in intracellular cAMP in response to the prostatic peptides vasoactive intestinal peptide (VIP), calcitonin (CT), and calcitonin gene-related peptide (CGRP). Normal prostate epithelial cells and LNCaP prostate cancer cells exhibited, respectively, 6- and 30-fold increases in intracellular cAMP in response to VIP.

Sleep events among veterans with combat-related posttraumatic stress disorder.

Objective: Sleep disturbances are important features of posttraumatic stress disorder (PTSD); however, the published data characterizing PTSD sleep phenomena are limited. The authors report on the phenomenology and physiological correlates of symptomatic sleep events in PTSD.

Method: The study data included survey results that addressed sleep symptoms during the past month in combat veterans with and without PTSD (N = 58), sleep diary records of awakenings from combat veterans with PTSD hospitalized on an inpatient rehabilitation unit (N = 52), and overnight polysomnography recordings obtained from 21 medication-free combat veterans with PTSD and eight healthy comparison subjects not exposed to combat.

Clinical and immunological changes in AIDS patients following adoptive therapy with activated autologous CD8 T cells and interleukin-2 infusion.

Objectives: (1) To determine the safety and feasibility of repetitive reinfusions of activated autologous CD8 cells followed by low-dose continuous interleukin (IL)-2 infusion in patients with AIDS. (2) To study the relationships between clinical responses, surface marker phenotypic distributions and cytokine expression patterns of both cultured CD8 cells and lymphocytes in the peripheral blood compartment.

Design: Six adult patients with Centers for Disease Control and Prevention group IV HIV-1 disease ranging from mild to severe, were studied.