Differential contribution of clinical amounts of acetaldehyde to skeletal and cardiac muscle dysfunction in alcoholic myopathy

Acute intoxication due to alcohol consumption has been known to elicit reversible skeletal and cardiac muscle dysfunction, or "alcoholic myopathy and cardiomyopathy". Sometimes, irreversible muscle damage can be induced after heavy alcohol drinking. Many researchers have proposed that acetaldehyde, the major oxidised product of alcohol, may be a primary factor underlying alcohol-induced muscle dysfunction. Because acetaldehyde is rapidly metabolised to acetate by aldehyde dehydrogenase (ALDH) mainly in the liver, blood concentration of acetaldehyde is maintained at a low level even after heavy alcohol intoxication. In alcoholics, blood acetaldehyde level is relatively high, probably due to hepatic inhibition of ALDH activity. Several mM of acetaldehyde have been used for studies of cardiac muscle contraction, the intracellular calcium transient, and the L-type calcium channel. In skeletal muscle, the calcium release channel/ryanodine receptor activity has been reported to be inhibited by exposure to 1 mM acetaldehyde. However, these observations were made using potentially lethal concentrations of acetaldehyde, so the hypothesis that acetaldehyde plays a crucial role on alcoholic myopathy is questionable. In this review, we will summarise the effect of alcohol and its major oxidised product, acetaldehyde, on skeletal and heart muscles and propose a toxic contribution of clinical concentrations of acetaldehyde to alcoholic myopathy. In addition, this review will include briefly the effect of acetaldehyde on diabetic cardiomyopathy.     

Hypouricemia in severely disabled children II: influence of elemental enteral nutrition on the serum uric acid levels

The previous study showed that both valproic acid (VPA) and a bedridden state decreased the serum uric acid level, and VPA-induced renal tubular dysfunction was suspected to be one cause of hypouricemia in severely disabled children. However, it was uncertain what factor of bedridden state influences the uric acid level in severely disabled children. Among many factors of a bedridden state that might influence the uric acid level, we examined the influence of elemental nutrition on the serum uric acid level in severely disabled children because many severely disabled children with marked hypouricemia receive elemental nutrition. Thirty-one severely disabled children were included in this study, who were divided into two groups-group A: 11 patients with elemental nutrition; group B: 20 patients with non-elemental nutrition. The laboratory data in both groups were analyzed statistically, using the t-test. The uric acid level was significantly decreased in group A compared with group B (p < 0.01) without elevation of urinary excretion of uric acid. Other laboratory data, except phosphate and potassium, did not differ between the two groups significantly. An elemental diet may be one factor that decreases the uric acid level in severely disabled children.     

Diagnosing dry eye using a blue-free barrier filter

PURPOSE: To investigate the benefit of the blue-free barrier filter (BF filter) in diagnosing dry eye. DESIGN: Nonrandomized clinical comparison. METHODS: Fifty-three eyes with Sj?gren syndrome (n = 42) or keratoconjunctivitis sicca (n = 11) were enrolled. Fluorescein staining was performed in temporal and nasal conjunctiva, and staining was scored with (BF score) and without the filter (FL score) from 0 to 3. Rose bengal staining was also scored (RB score) similarly. RESULTS: With FL scores of 0, 1, or 2, the BF score was significantly higher: 0.85 +/- 0.37 (P =.031), 1.74 +/- 0.65 (P =.001), and 2.65 +/- 0.48 (P =.001), respectively; with a FL score of 3, the BF score was 3 at all sites. The BF score was superior to the FL score in 66.6% of cases when the FL score was 0 and 1 and in 65.2% when the FL score was 2, but not when the FL score was 3. When the RB score was 0, 1, or 2, the BF score was higher: 1.88 +/- 0.92, 1.78 +/- 0.79, and 2.57 +/- 0.50, respectively (P =.001 for all); when the RB score was 3, the BF score was 2.97 +/- 0.16. The BF score was superior to the RB score in 75.5% of cases when the RB score was 0 and 1 and in 57.8% when the FL score was 2, but not in cases with a RB score of 3. CONCLUSIONS: The BF filter detects damaged conjunctival epithelium stained with fluorescein. Using the filter was beneficial in mild-to-moderate cases, not in severe cases. The BF filter allows diagnosis of dry eye even at the initial stage that is undetectable by conventional observation.     

Iliopsoas abscess accompanied by epidural abscess--a case report

A 55-year-old man was admitted to a hospital with pain of the low back as well as the left leg, and fever. He was suspected of suffering from the lumbar disc herniation because of the presence of Lasegue's sign on the first physical examination. Abdominal computed tomography, however, revealed the swelling of the left iliopsoas muscle. Iliopsoas abscess accompanied epidural abscess was confirmed by subsequent magnetic resonance imaging (MRI). Antibiotic therapy was started for the successive 8 days. The fever resolved, but the pain persisted. The abscess extending from the iliopsoas muscle to the epidural space was still seen on the MRI 20 days after the completion of the antibiotic therapy, and he still complained of the pain of his low back and left leg. Therefore, we conducted epidural puncture under fluoroscopic guidance. Approximately 3 ml of pus was aspirated from the epidural space. Then, his complains decreased remarkably. Iliopsoas abscess should be taken into account in case of a patient with pain on the low back and leg and also inflammatory signs such as fever and leucocytosis.     

Expression and function of activin receptors in human endometrial adenocarcinoma cells

Menstrual cycle-dependent expressions of activin A in normal human endometrial tissues have been reported. Expression of activin receptor mRNAs and increased activin A production were also observed in human endometrial adenocarcinoma tissues, suggesting that activin A might enhance cell proliferation and inhibit apoptotic signaling in endometrial cancer cells. In this study, we have examined the effects of activin A on cell proliferation, anticancer drug-induced apoptosis and Fas-mediated apoptosis in 3 differentiated human endometrial adenocarcinoma cell lines, namely HEC-1, HHUA and Ishikawa. Flow cytometric analyses revealed moderate expressions of all 4 types of activin receptor subunits on the cell surfaces of the 3 cell lines. The proliferations of the 3 endometrial cancer cells were completely unaffected by activin A, whereas it suppressed the cell proliferation of a human ovarian endometrioid adenocarcinoma cell line, OVK-18, in a dose-dependent manner. Moreover, activin A did not affect the apoptotic changes in the 3 endometrial adenocarcinoma cells treated with 4 different anticancer drugs, namely CDDP, paclitaxel, etoposide and SN38. The apoptotic changes in HHUA cells treated with anti-Fas IgM were also unaffected by activin A. These results indicate that the increased activin A production in human endometrial adenocarcinoma tissues in vivo may not stimulate carcinoma cell proliferation or inhibit apoptotic signaling in carcinoma cells. Insensitivity to the usual growth suppression signals induced by activin A might be one of the mechanisms of immortality of human endometrial adenocarcinoma cells.     

Dopamine receptors and dopamine-sensitive adenylate cyclase in canine caudate nucleus. Characterization and solubilization

The activities of dopamine-sensitive adenylate cyclase and [³H] dopamine binding showed a similar subcellular distribution in the canine caudate nucleus, and were present primarily in the synaptic membrane fractions. Binding of [³H]dopamine to the crude synaptic membranes was rapid, saturable and reversible in the presence of 2 mM ATP with a rate constant of 2.5 × 10⁵ M^?1 min^?1 and 0.63 min^?1for the forward and reverse reactions respectively. The equilibrium dissociation constant (K_d) for the binding was about 1.5 μM, almost identical to the K_a of adenylate cyclase for dopamine to stimulate half-maximally. Binding of [³H]dopamine in the absence of ATP exhibited a negative cooperativity, with two K_d values (0.11 μM and 8.1 μM), which was abolished by addition of 2 mM ATP. The major role of ATP appears to enhance the association of [³H]dopamine to the membranes. [³H]Dopamine binding in the presence of 2 mM ATP and dopamine-sensitive adenylate cyclase in the membranes were affected in a similar manner by catecholamines, some antidepressants and a variety of neuroleptics, with the exception of some phenothiazine derivatives such as chlorpromazine and fluphenazine. Propranolol and cocaine, an uptake inhibitor at neuronal membranes, did not inhibit either activity. Dopamine sensitivity of the pariculate adenylate cyclase tended to be increased by the addition of 0.001% Lubrol PX in the incubation but was greatly impaired by more than 0.005% Lubrol PX. The synaptic membranes were solubilized with 2% Lubrol PX in the presence of NaF from the particulate fractions. This solubilization procedure preserved well not only fluoride sensitivity but also dopamine responsiveness of adenylate cyclase in the supernatant fluid.     

Mechanism of immune interferon production in vitro: interaction between immune interferon-producing cells and antigenic cells.

Various processes of in vitro immune interferon production by sensitized spleen cells stimulated with allogeneic cells were investigated. When L cells, an interferon-inducing antigen, were fixed with methyl alcohol or paraformaldehyde, the ability to induce immune interferon disappeared. In this immune interferon production system, the majority of sensitized spleen cells adhered to target cells within 1 h of cocultivation. Adherence of immune interferon-producing cells to target cells was observed only when L cell-sensitized spleen cells were cocultured with L cells or with mouse embryo cells derived from C3H mice. Fixation of antigenic cells with methyl alcohol or paraformaldehyde significantly reduced cell adherence. When L cells alone or sensitized spleen cells alone were pretreated separately with cytochalasin D, neither cell type could bind to partner cells. Specific adherence did not take place at 4 degrees C, nor in the presence of dinitrophenol or sodium azide. Continuous protein synthesis in both cells was not required for immune cell adherence. Divalent cations, Ca2+ or Mg2+, were required for this immune specific adherence to take place. However, once stable adherence was established, treatment with cytochalasin D, ethylenediaminetetraacetic acid, or sodium azide, or simple reduction of temperature, did not disrupt the binding. Interaction between immune interferon-producing cells and antigenic cells can be subdivided into two phases according to the requirement for divalent cations: (i) lymphocytes and antigenic cells interact transiently, and divalent cations are required to maintain the binding; (ii) lymphocytes and antigenic cells form a stable interaction, and deprivation of divalent cations does not disrupt the binding. Colchicine showed an inhibitory effect in the period after cell-to-cell adherence. Colchicine did not inhibit the release of interferon. On the other hand, vinblastine, another antimicrotubule agent inhibited the secretion of immune interferon. Since interferon synthesis was not stopped immediately after addition of cycloheximide, continued protein synthesis of sensitized spleen cells was not required for interferon secretion. The present study showed that adherence of immune interferon-producing cells to antigenic cells was a complex phenomenon involving a series of successive events.