Nitric oxide as a mediator of the laxative action of magnesium sulphate.

1. Magnesium sulphate was studied for its effects on diarrhoea, fluid secretion, gastrointestinal transit and nitric oxide (NO) synthase activity in rats. 2. At a dose of 2 g kg-1 orally magnesium sulphate produced diarrhoea that was delayed in onset and intensity in a dose-related manner by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). This was prevented by the NO precursor, L-arginine and the NO donating compound, isosorbide-5-mononitrate (IMN). 3. Nitric oxide synthase activity was stimulated in gut tissue from rats given magnesium sulphate and this was inhibited by L-NAME. Dexamethasone (1 mg kg-1, i.p.), an inhibitor of inducible NO synthase, had no effect on magnesium sulphate-induced diarrhoea. 4. Magnesium sulphate stimulated fluid and electrolyte accumulation in the intestinal lumen; these effects were prevented by L-NAME but not D-NAME. 5. Gastrointestinal transit of a non-absorbable marker (charcoal suspension) was increased by oral magnesium sulphate from a mean value of 54.1% to 72.9% (P < 0.01), and this was prevented by pretreatment with L-NAME. 6. The results demonstrate that oral magnesium sulphate produces diarrhoea in rats by increasing the accumulation of fluid in the intestinal lumen and enhancing flow from the proximal to distal intestine. The mechanism involves release of NO, probably through stimulation of the constitutive form of NO synthase. Whether or not the effects of magnesium sulphate are due to an osmotic action or an intrinsic effect of the magnesium or sulphate ions cannot be determined from these experiments.     

Sensory and motor deficits of central nervous system origin

The sensory and motor deficits of the CNS are varied, depending on the etiologic factors and the structures involved. Nevertheless, the clinical picture is predictable, provided one has an adequate knowledge of the neuroanatomy and the functions of the different fiber tracts, nuclei, and other specific regions of the brain and spinal cord. The purpose of this section is to provide an overall view of the sensory and motor deficits of the CNS, which will enable the clinician to treat these patients in a more objective and effective manner. Etiologically, the diseases affecting the CNS can be grouped under the following categories: congenital, traumatic, inflammatory, neoplastic, and degenerative. Congenital conditions usually manifest in infancy and childhood. Examples are hydrocephalus, spina bifida, and Arnold-Chiari malformation. There are a host of other conditions, but the discussion in this article is confined to the more common entities. Traumatic conditions such as cerebral concussion, contusion, laceration, hematomas--extradural, subdural, or intracerebral--and spinal cord injuries can occur in any age group, though their incidence is higher during the more active period of life (20 to 35 years). Automobile accidents are by far the most common etiologic factor for the traumatic lesions. Others, such as falls, gunshot and stab wounds, and so forth account for the remainder. Among the inflammatory conditions, three conditions are important: brain abscess, meningitis, and transverse myelitis. Though brain abscess develops by direct extension from an adjacent focus of infection, often it forms as a result of metastatic infection, chiefly from lung abscess or bronchoectasis. It behaves more like an intracranial space occupying lesion. Of the various types of meningitis, meningococcal meningitis is the commonest. Transverse myelitis may be caused by viruses or bacteria. The clinical picture resembles that of spinal cord injury. Neoplasms of the brain and spinal cord present a wide and varied spectrum. They may be benign or malignant. Meningioma and neurofibroma are essentially benign lesions. Malignant tumors can be primary or secondary. Gliomas and specifically astrocytomas are the commonest primary malignant tumors. The commonest sites of metastatic tumors are lung, breast, kidney, and gastrointestinal tract. The clinical picture will depend on the location of the tumor and the structures pressed upon or infiltrated. Any age group can be affected. Many of the malignant tumors are slowly and relentlessly progressive. Complete surgical extirpation where possible, followed by radiation therapy, is the treatment of choice. Chemotherapy has not been of much benefit.(ABSTRACT TRUNCATED AT 400 WORDS)     

A novel 37-Kd adhesive membrane protein from cloned murine bone marrow stromal cells and cloned murine hematopoietic progenitor cells

The adhesion of hematopoietic progenitor cells to bone marrow stromal cells is critical to hematopoiesis and involves multiple effector molecules. Stromal cell molecules that participate in this interaction were sought by analyzing the detergent-soluble membrane proteins of GBI/6 stromal cells that could be adsorbed by intact FDCP-1 progenitor cells. A single-chain protein from GBI/6 cells having an apparent molecular weight of 37 Kd was selectively adsorbed by FDCP-1 cells. This protein, designated p37, could be surface-radiolabeled and thus appeared to be exposed on the cell membrane. An apparently identical 37- Kd protein was expressed by three stromal cell lines, by Swiss 3T3 fibroblastic cells, and by FDCP-1 and FDCP-2 progenitor cells. p37 was selectively adsorbed from membrane lysates by a variety of murine hematopoietic cells, including erythrocytes, but not by human erythrocytes. Binding of p37 to cells was calcium-dependent, and was not affected by inhibitors of the hematopoietic homing receptor or the cell-binding or heparin-binding functions of fibronectin. It is proposed that p37 may be a novel adhesive molecule expressed on the surface of a variety of hematopoietic cells that could participate in both homotypic and heterotypic interactions of stromal and progenitor cells.     

Investigation of intestine function during acute viral hepatitis using combined sugar oral loads.

One fifth of all cases of A virus hepatitis (AVH) have symptoms of gastroenteritis at the onset. This study investigated the mediated intestinal absorption of D-xylose (D-xyl) and 3-o-methyl-D-glucose (3-omG) and the non-mediated permeation of lactulose (Lacl, mol wt 342) and L-rhamnose (L-rh, mol wt 164) during acute and remission phases of AVH. Ten patients with AVH were given an oral load containing these sugars (5 g D-xyl: 2.5 g 3-omG, 1 g L-rh, 5 g lacl in 250 ml water) once during the acute phase and again during remission. The same load was given once to a group of 22 healthy controls. The mean concentration of D-xyl in urine and the ratio of D-xyl to 3-omG in plasma and urine were normal in both the AVH phases, ruling out intestinal malabsorption even in the acute phase. This study showed a significant increase in non-mediated permeation to Lacl, but not to L-rh, during the acute phase. These data indicate that the barrier function of the intestine is compromised in AVH infection while the absorptive function is not. An abnormally low concentration of D-xyl and 3-omG in plasma at one hour was found in all patients during the acute phase. This finding cannot be explained by alterations in intestinal absorption, but could be accounted for by increased space distribution of the sugars because of increased diffusion into tissue cells and/or expansion of the extracellular space by fluid retention.