Mucosal irritation, adaptive cytoprotection, and adaptation to topical ammonia in the rat stomach

BACKGROUND: The urease-ammonia (NH4OH) system has been proposed to play a major role in the pathogenesis of the Helicobacter pylori-associated gastritis, but the mechanism of the mucosal damage has not been fully explained. This study was designed to examine possible adaptive cytoprotection and the adaptation of rat gastric mucosa to the irritant action of NH4OH and urease. METHODS AND RESULTS: Single application of NH4OH alone in various concentrations (15-500 mM) caused concentration-dependent mucosal damage starting with 30 mM and reaching a maximum at 250 mM NH4OH, similar to that obtained with 100% ethanol; it was accompanied by a decrease in gastric blood flow (GBF) to approximately 30% of the normal value. When the mucosa was first exposed to the low, non-damaging concentration (15 mM) of NH4OH and then insulted with 100% ethanol, the extent of ethanol damage was greatly attenuated as compared with that caused by ethanol alone. This adaptive cytoprotection was accompanied by the rise in GBF and reversed, in part, by the pretreatment with indomethacin, an inhibitor of prostaglandin (PG)-cyclooxygenase; with L-NAME, a blocker of NO-synthase; or with capsaicin deactivating the sensory nerves. Damaging concentrations of NH4OH (125 mM) caused widespread mucosal damage after the first application, but with repeated insults with 125 mM NH4OH a gradual reduction in the mucosal lesions, accompanied by enhanced mucosal cell proliferation and over-expression of epidermal growth factor (EGF) (using immunocytochemistry) and mRNA of EGF (using trans-reverse polymerase chain reaction), were observed. CONCLUSIONS: NH4OH alone damages gastric mucosa only at the concentration exceeding that found in H. pylori-infected stomachs, whereas at lower concentrations it acts as 'mild' irritant to induce adaptive cytoprotection. This adaptive cytoprotection appears to be mediated, in part, by endogenous PG, sensory nerves, and an arginine-NO-dependent pathway, and repeated applications of NH4OH induce gastric adaptation, probably mediated by enhanced expression of EGF and its receptors and by an increased cell proliferation.     

Clinicopathological profile of subacute hepatic failure

Sigmoid volvulus is an unusual cause of intestinal obstruction in children. We report two cases of sigmoid volvulus as a complication of segmental dilatation of the colon occurring in two girls (5 years old and 9 years old) previously treated for chronic constipation. In both cases the constipation had been recognised since the neonatal period mimicking a Hirschsprung's disease, a diagnosis which has been excluded after rectal biopsy. The delayed diagnosis of segmental dilatation of the sigmoid colon followed the volvulus. Segmental colonic resection resulted in both cases in the cure of the constipation.     

A STATISTICAL ANALYSIS OF A PACKED TOWER DEHUMIDIFIER

A dehumidifier is the heart of a liquid desiccant cooling system. In these systems, air is dehumidified using liquid desiccants and cooled with heat exchangers and/or evaporative coolers [I]. A Statistical Analysis Software (SAS) regression analysis was performed on experimental data from a packed tower desiccant dehumidifier tested at Texas Tech. The purpose of this analysis was to determine simple functional relationships for the liquid desiccant dehumidifier for use in computer models of liquid desiccant space cooling systems.

Six factors and four dependent variables were defined and four regression models were determined. These regression models were reduced to three factor models. The packed tower regression analysis showed Texas Tech's “Cost Effective Liquid Desiccant” (CELD) to be a well behaved stable desiccant solution.     

Surgery in South Africa

The practice of surgery in South Africa ranges from full-time service in state-funded and academic hospitals serving a largely indigent population to a private sector for medically insured patients. Surgical training occurs at eight medical schools, and specialist registration is obtained after 4 to 5 years with either a university-conferred degree or a fellowship from the College of Surgeons of South Africa. The wide spectrum of First- to Third-World diseases and the high incidence of trauma provide comprehensive experience for practical training. Surgical standards are uniformly high, matching and sometimes pioneering the very best of Western medicine. The health care system is undergoing radical change to correct the imbalances of the apartheid era. Academic institutions are under pressure, and with incipient major financial cutbacks, there is concern that the proud record of service, teaching, and research excellence may be compromised. To facilitate the mission of broadening health care services, diploma training in surgery for rural practitioners is being developed. Outreach programs and closer liaisons with surgical societies in sub-Saharan African countries have also been initiated.     

The effect of the gap paradigm on the latency of human smooth pursuit of eye movement

When a temporal gap is introduced between the extinction of a central fixation target and the illumination of an eccentric target (the gap paradigm), normal human subjects initiate saccadic eye movements towards the eccentric target at lower latency than when there is no gap. The aim of this study was to examine the latency of human smooth pursuit eye movements using a modified gap paradigm. Smooth pursuit latency was reduced in gap tasks, and the magnitude of reduction was related to the duration of the gap. The distribution of smooth pursuit latencies was also altered. It thus appears that human smooth pursuit latency is modulated in a similar manner to saccade latency in gap tasks.     

Laser-assisted microvascular anastomosis of human adult and placental arteries with expanded polytetrafluoroethylene microconduit

Laser-assisted microvascular anastomoses can be performed more quickly than sutured anastomoses, yet manifest similar patency rates and tensile strength. This study was undertaken to determine if in vitro laser-assisted microvascular anastomoses could be created between human adult arteries (anterior tibial arteries), human placental arteries, and expanded polytetrafluoroethylene microconduits. A CO2 laser was applied in single or continuous bursts with a matrix of variables encompassing power P = 80 to 160 mW, spot size SS = 150 to 500 microns, and exposure time EXP = 1.0-second continuous exposure (n = 2 each composite setting). The endpoints measured to assess the ability to laser-weld vessels were morphologic appearance by scanning electron microscopy and bursting strength. Scanning electron microscopy revealed apparent fusion of human placental arteries and human adult arteries to expanded polytetrafluoroethylene microconduits at settings of P = 130 mW, SS = 300 microns, and EXP = 1.0 second, though bursting pressure at all settings was less than 10 mmHg. Laser-assisted microvascular anastomoses of human placental artery to human placental artery and human adult artery to human adult artery were successful at this setting, though bursting pressures of anastomoses incorporating placental vessels were significantly weaker than those created with adult tissue. The relative weakness of laser-assisted microvascular anastomoses incorporating placental arteries might be explained by qualitative or quantitative differences in vessel wall collagen, as seen in fetal tissue, and deserves further characterization.     

Variability in the oral bioavailability of all-trans-retinoic acid

BACKGROUND: Orally administered all-trans-retinoic acid (all-trans-RA) can induce complete remission in a high proportion of patients with acute promyelocytic leukemia. A previous pharmacokinetic study in patients with acute promyelocytic leukemia raised the possibility that the absorption of orally administered all-trans-RA is a saturable process that would have significant clinical impact on dosing strategies. PURPOSE: This study was specifically designed to examine the saturability of all-trans-RA absorption by measuring the effect of doubling the oral dose of all-trans-RA on plasma drug concentration in patients receiving long-term oral therapy. METHODS: Six patients with solid tumors received oral doses of 10-mg gelatin capsules of all-trans-RA. Patients were studied on 2 consecutive days after they received 28 days of all-trans-RA administered as two daily 78-mg/m2 doses. The study assigned the patients to two groups. Three patients took a 156-mg/m2 dose on day 28 and a 78-mg/m2 dose on day 29; the other three patients took the lower dose on day 28 and the double dose on day 29. Blood samples for the determination of all-trans-RA plasma concentration were obtained at 30-minute intervals starting just prior to drug administration and continuing for a total of 7 hours. The plasma concentration of all-trans-RA was measured by high-performance liquid chromatography. RESULTS: Plasma concentrations following an oral dose of all-trans-RA were highly variable, with peak concentrations ranging from 0.07 to 1.2 microM for the 78-mg/m2 dose level. Doubling the dose from 78 to 156 mg/m2 increased plasma concentration in all six patients, but the increase was unpredictable and not related to dose, ranging from less than a 1.2-fold to more than a 10-fold increase. CONCLUSION: The current study does not support the hypothesis that the gastrointestinal absorption of all-trans-RA involves a saturable process but instead suggests that absorption is highly variable among patients. This wide interpatient variability suggests that pharmacokinetic drug monitoring may have an important role in the management of patients receiving all-trans-RA.     

Lanthanide inhibition of 5′-nucleotidase in the phosphodiesterase assay of calmodulin

Previous studies from this group reported the ability of some lanthanide-calmodulin complexes to activate the enzyme 3′,5′-cyclic nucleotide phosphodiesterase. The same studies, however, also showed inhibition at higher lanthanide concentrations. This study shows that part of the apparent inhibition is due to lanthanide inhibition of 5′-nucleotidase, one of the enzymes used in the assay. The other enzyme used, 3′,5′-cyclic nucleotide phosphodiesterase, does not appear to be inhibited by the lanthanides, nor do the other experimental techniques used in the assay. The results of this study are important because this assay is widely used to evaluate the ability of various metals to replace calcium in calmodulin.     

Chemistry of pseudomonic acid. Part 16. Aryl and heteroaryl ketone derivatives of monic acid

The synthesis, antibacterial activities, murine pharmacokinetic and infection model data for a range of aryl and heteroaryl ketone derivatives of monic acid (2a) are reported. The best results were found for the 3-furyl and 2-methoxy thiazol-5-yl analogues.