Afferent signalling from the acid-challenged rat stomach is inhibited and gastric acid elimination is enhanced by lafutidine

<p>Abstract</p> <p>Background</p> <p>Lafutidine is a histamine H₂receptor antagonist, the gastroprotective effect of which is related to its antisecretory activity and its ability to activate a sensory neuron-dependent mechanism of defence. The present study investigated whether intragastric administration of lafutidine (10 and 30 mg/kg) modifies vagal afferent signalling, mucosal injury, intragastric acidity and gastric emptying after gastric acid challenge.</p> <p>Methods</p> <p>Adult rats were treated with vehicle, lafutidine (10 – 30 mg/kg) or cimetidine (10 mg/kg), and 30 min later their stomachs were exposed to exogenous HCl (0.25 M). During the period of 2 h post-HCl, intragastric pH, gastric volume, gastric acidity and extent of macroscopic gastric mucosal injury were determined and the activation of neurons in the brainstem was visualized by c-Fos immunocytochemistry.</p> <p>Results</p> <p>Gastric acid challenge enhanced the expression of c-Fos in the nucleus tractus solitarii but caused only minimal damage to the gastric mucosa. Lafutidine reduced the HCl-evoked expression of c-Fos in the NTS and elevated the intragastric pH following intragastric administration of excess HCl. Further analysis showed that the gastroprotective effect of lafutidine against excess acid was delayed and went in parallel with facilitation of gastric emptying, measured indirectly via gastric volume changes, and a reduction of gastric acidity. The H₂receptor antagonist cimetidine had similar but weaker effects.</p> <p>Conclusion</p> <p>These observations indicate that lafutidine inhibits the vagal afferent signalling of a gastric acid insult, which may reflect an inhibitory action on acid-induced gastric pain. The ability of lafutidine to decrease intragastric acidity following exposure to excess HCl cannot be explained by its antisecretory activity but appears to reflect dilution and/or emptying of the acid load into the duodenum. This profile of actions emphasizes the notion that H₂receptor antagonists can protect the gastric mucosa from acid injury independently of their ability to suppress gastric acid secretion.</p

Mechanisms of Intragastric pH Sensing

Luminal amino acids and lack of luminal acidity as a result of acid neutralization by intragastric foodstuffs are powerful signals for acid secretion. Although the hormonal and neural pathways underlying this regulatory mechanism are well understood, the nature of the gastric luminal pH sensor has been enigmatic. In clinical studies, high pH, tryptic peptides, and luminal divalent metals (Ca2+ and Mg2+) increase gastrin release and acid production. The calcium-sensing receptor (CaSR), first described in the parathyroid gland but expressed on gastric G cells, is a logical candidate for the gastric acid sensor. Because CaSR ligands include amino acids and divalent metals, and because extracellular pH affects ligand binding in the pH range of the gastric content, its pH, metal, and nutrient-sensing functions are consistent with physiologic observations. The CaSR is thus an attractive candidate for the gastric luminal sensor that is part of the neuroendocrine negative regulatory loop for acid secretion

Toward a geography of black internationalism: Bayard Rustin, nonviolence and the promise of Africa

This article charts the trip made by civil rights leader Bayard Rustin to West Africa in 1952, and examines the unpublished ‘Africa Program’ which he subsequently presented to leading American pacifists. I situate Rustin’s writings within the burgeoning literature on black internationalism which, despite its clear geographical registers, geographers themselves have as yet made only a modest contribution towards. The article argues that within this literature there remains a tendency to romanticize cross-cultural connections in lieu of critically interrogating their basic, and often competing, claims. I argue that closer attention to the geographies of black internationalism, however, allows us to shape a more diverse and practiced sense of internationalist encounter and exchange. The article reconstructs the multiplicity of Rustin’s black internationalist geographies which drew eclectically from a range of Pan-African, American and pacifist traditions. Though each of these was profoundly racialized, they conceptualized race in distinctive ways and thereby had differing understandings of what constituted the international as a geographical arena. By blending these forms of internationalism Rustin was able to promote a particular model of civil rights which was characteristically internationalist in outlook, nonviolent in principle and institutional in composition; a model which in selective and uneven ways continues to shape our understanding of the period

Ultra-low-power hybrid light-matter solitons.

New functionalities in nonlinear optics will require systems with giant optical nonlinearity as well as compatibility with photonic circuit fabrication techniques. Here we introduce a platform based on strong light-matter coupling between waveguide photons and quantum-well excitons. On a sub-millimetre length scale we generate picosecond bright temporal solitons at a pulse energy of only 0.5 pJ. From this we deduce a nonlinear refractive index three orders of magnitude larger than in any other ultrafast system. We study both temporal and spatio-temporal nonlinear effects and observe dark-bright spatio-temporal polariton solitons. Theoretical modelling of soliton formation in the strongly coupled system confirms the experimental observations. These results show the promise of our system as a high speed, low power, integrated platform for physics and devices based on strong interactions between photons

Contextualising Apartheid at the End of Empire: Repression, ‘Development’ and the Bantustans

This article examines the global dynamics of late colonialism and how these informed South African apartheid. More specifically, it locates the programmes of mass relocation and bantustan ‘self-government’ that characterised apartheid after 1959 in relation to three key dimensions. Firstly, the article explores the global circulation of idioms of ‘development’ and trusteeship in the first half of the twentieth century and its significance in shaping segregationist policy; secondly, it situates bantustan ‘selfgovernment’ in relation to the history of decolonisation and the partitions and federations that emerged as late colonial solutions; and, thirdly, it locates the tightening of rural village planning in the bantustans after 1960 in relation to the elaboration of anti-colonial liberation struggles, repressive southern African settler politics and the Cold War. It argues that, far from developing policies that were at odds with the global ‘wind of change’, South African apartheid during the 1960s and 1970s reflected much that was characteristic about late colonial strategy