Evidence for dual modulation of pepsinogen secretion using isoproterenol, carbachol, CCK-8, forskolin, 8 bromo-cAMP, and A23187 probes

The cellular mechanisms by which pepsinogen (PNG) secretion is controlled are not understood. The aim of this study was to explore whether modulation of PNG secretion is mediated by cAMP or calcium-calmodulin (C-C). PNG secretion in isolated rabbit gastric fundic glands (IGG) was tested, using agents believed to act via cAMP or C-C. IGG were stimulated for 30 minutes with histamine (H) 10(-5) M, isoproterenol (I) 10(-5) M, carbachol (C) 10(-5) M, cholecystokinin-octapeptide (CCK-8) 10(-7) M, forskolin (F) 10(-5) M, 8 bromo-cAMP (8B) 10(-3) M, and A23187 (A) 10(-6) M. PNG levels were determined by spectrophotometric assay of hemoglobin digestion products. PNG amounts secreted were (mean per cent above basal levels of total IGG PNG units +/- SEM): H, -0.02 +/- 0.30%; I, 3.5 +/- 0.9%; C, 5.1 +/- 2.2%; CCK-8, 5.3 +/- 1.5%; F, 10.6 +/- 3.8%; 8B, 13.8 +/- 4.5%; A, 2.1 +/- 1.1%. All secretagogues except H stimulated PNG release significantly above basal levels (p less than 0.05). A primary histaminergic mechanism for pepsinogen secretion is unlikely. Since two other adenylate cyclase activators, isoproterenol and forskolin and the 3':5'-cyclic adenosine monophosphate analog 8-bromo cAMP stimulated pepsinogen secretion, cAMP-dependence is probable. Since carbachol, CCK-8, and A23187, which are believed to act via calcium-calmodulin, also stimulated pepsinogen secretion, this system, too, presumably plays a substantial role. Thus the data support a dual 3':5'-cyclic adenosine monophosphate/calcium-calmodulin modulation of pepsinogen secretion.     

What can be expected from the sub-trigonal injection of phenol in the treatment of idiopathic instability of the bladder?

Sub-trigonal phenol injection ensures a satisfactory response in about 50% of patients with detrusor instability. When oral anticholinergic treatment is poorly tolerated or ineffective, this minimally invasive technique has been found, in our series of 11 patients, to be a useful adjunct, at least temporarily.     

Neutropenic enterocolitis in adults with acute leukemia

Neutropenic enterocolitis has been previously described only by case reports and literature reviews. Of 499 adults with acute leukemia seen over a 23-year period (1962 to 1985), 13 cases (2.6%) of neutropenic enterocolitis have been reported. Eleven of these 13 patients were profoundly neutropenic (mean white blood cell count, 472/cu mm) and developed abdominal symptoms during either initial induction or relapse of acute leukemia. Histologic confirmation was available in ten cases, five cases after surgical resection and five cases at autopsy after nonoperative management. Three patients with isolated ileocecal inflammation without infarction at the time of surgery were successfully managed without resection. Five patients treated with surgery died four to 64 weeks postoperatively (mean survival, 21.6 weeks) of nonsurgical complications of leukemia. Three patients were still alive, one patient 42 months after right hemicolectomy and two patients five months after exploration only. All five patients managed medically died an average of 1.4 days (range, zero to four days) after the onset of abdominal pain. Survival in patients with acute leukemia who develop neutropenic enterocolitis is determined by early recognition and appropriate surgical exploration that can be expected to yield an acceptable operative mortality.     

Effect of temperature on blood flow and metabolism in a neurovascular island skin flap

Using the buttock flap in 29 white Yorkshire pigs, blood flow and O2 consumption were measured at dermal temperatures between 35 degrees C and 15 degrees C. Flow was measured with an electromagnetic flowmeter and O2 consumption was calculated as the product of blood flow and the difference in flap A-VO2. Baseline flow was 6.6 +/- .9 (SE) ml/100 g/min at 35 degrees C and 3.1 +/- .02 (SE) ml/10 g/min at 15 degrees C. Blood flow through the flap stopped completely at a dermal temperature of 14 degrees C. Oxygen consumption was 0.16 +/- .02 (SE) ml/100 g/min at 35 degrees C and 0.04 +/- 0.01 (SE) ml/100 g/min at 15 degrees C. At 20 degrees C blood flow was 4.3 ml/100 g/min and metabolism was .04 ml/100 g/min. In other words, blood flow was 65% of baseline, while O2 consumption was only 25% of baseline. The therapeutic effect of local cooling at 20 degrees C deserves further investigation. The cessation of flow at 14 degrees C may be caused by increased plasma viscosity.     

Laminar organization of the main olfactory bulb of Podarcis hispanica: an electron microscopic and Golgi study

In this study, the lamination pattern of the main olfactory bulb (MOB) of P. hispanica has been described using EM and Golgi-impregnation techniques. Six layers could be distinguished from the external surface to the ventricles: olfactory nerve layer (ONL), glomerular layer (GL), external plexiform layer (EPL), mitral layer (ML), internal plexiform layer (IPL), and granular cell layer (GCL). In ONL unmyelinated axonic bundles from the olfactory mucosa are seen. The GL is defined by the presence of terminal ramifications of the mitral primary dendrites and by axonic terminals of the olfactory nerve. The EPL is a dendritic articulation layer between the mitral and granule cells, where a great density of dendrodendritic synaptic contacts has been found. The ML is defined by the large mitral cell somata, and the IPL by myelinated axonic bundles that run rostro-caudally. Finally, the GCL is characterized by the presence of granule cells. Using the Golgi-impregnation method, five different neuronal types have been described. In the glomerular layer, a small cell population is located; these neurons seem the periglomerular cells described in mammals. The second type corresponds to the mitral cell population and the morphological features of these cells resemble to those of mammals. The three remaining types constitute the granule cell population; this population is characterized by a great morphological heterogeneousness. However, these types have been differentiated according to their dendritic tree morphology and location of the cell body. A morphological gradient depending on the distance of cell body for each type to the ependymal layer, has been observed. In EM, four different types of neuronal cell bodies according to their location and ultrastructure have been defined. The laminar organization of the MOB of Podarcis is similar to that in all vertebrates. The results for the fine structure and dendritic tree morphology have revealed a high similarity between these reptiles and mammals.     

Electrophysiologic effects of halothane and quinidine on canine Purkinje fibers: evidence for a synergistic interaction

The authors studied possible interactions between halothane and quinidine on the action potentials of canine Purkinje fibers superfused with Tyrode's solution. Using standard microelectrode techniques and a physiologic pacing rate (2 Hz), halothane in concentrations from 0.5% to 2% decreased the action potential duration to 50% repolarization (ADP50). Total ADP (APD100), in contrast, increased after 1% and 2% halothane. Resting membrane potential (RMP) and action potential amplitude (APamp) increased after 0.5% halothane, but returned to control with higher halothane levels. Conduction time (CT) increased at each halothane level. Pacing at faster (3 Hz) or slower (1 Hz) rates did not markedly alter the effects of halothane. Quinidine 1 X 10(-5)M decreased the phase O upstroke (Vmax) and prolonged APD100 and CT. When halothane was added, RMP and APamp decreased, Vmax decreased further, and APD100 and CT were markedly prolonged. This resulted in conduction block or inexcitability, especially at faster pacing rates (3 Hz). Synergistic interactions between halothane and quinidine were found on RMP, APamp, APD100, and CT. Effects on Vmax, APD50, and action potential duration to 90% repolarization (APD90) were additive. It is concluded that quinidine and halothane act synergistically to decrease action potential amplitude, lower RMP, and prolong conduction. Severe depression of conduction often progressed to conduction block or inexcitability when halothane, 2%, was administered during superfusion with therapeutic concentrations of quinidine.