In vivo and in vitro electrophysiological experiments were performed on the rat dorsal vagal complex (DVC, i.e. nucleus of the tractus solitarius, NTS, and dorsal motor nucleus of the vagus, DMV) to examine the effects of corticotropin releasing hormone (CRF) on the central components of the vago‐vagal reflex control of gastric function. When applied to gastrointestinal projecting DMV neurones, CRF (10‐300 nm) induced a concentration‐dependent membrane depolarization, an increase in action potential firing rate and decrease in amplitude of the action potential afterhyperpolarization (P < 0.05). Pretreatment with the non‐selective CRF antagonist, astressin (0.5‐1 μM) or the selective CRF2 receptor antagonist, astressin 2B (500 nm) attenuated the CRF‐induced increase in firing rate but did not alter basal discharge rate. CRF (30‐300 nm) increased the amplitude of excitatory postsynaptic currents (EPSCs) evoked by stimulation of the NTS (P < 0.05). An alteration in the paired pulse ratio indicated the EPSC's increase occurred due to actions at presynaptic sites. In the in vivo anaesthetized rat preparation, bilateral microinjections (20 fmol in 20 nl for each site) of CRF in the DVC decreased gastric motility in rats pretreated with the muscarinic agonist, bethanecol (P < 0.05). The effects of CRF were abolished by systemic administration of the NOS inhibitor, L‐NAME, or by bilateral vagotomy. We concluded that CRF had both a direct and an indirect excitatory effect on DMV neurones via activation of CRF2 receptors and the decrease in gastric motility observed following microinjection of CRF in the DVC is due to the activation of an inhibitory non‐adrenergic non‐cholinergic input to the gastrointestinal tract.
Using whole cell patch clamp in thin brain stem slices, we tested the effects of cholecystokinin (CCK) on identified gastric-projecting neurons of the rat dorsal motor nucleus of the vagus (DMV). Perfusion with the sulfated form of CCK octapeptide (CCK8s, 30 pM-300 nM, EC50 approximately 4 nM) induced a concentration-dependent inward current in 35 and 41% of corpus- and antrum/pylorus-projecting DMV neurons, respectively. Conversely, none of the fundus-projecting DMV neurons responded to perfusion with CCK8s. The CCK8s-induced inward current was accompanied by a 65 +/- 17% increase in membrane input resistance and reversed at 90 +/- 4 mV, indicating that the excitatory effects of CCK8s were mediated by the closure of a potassium conductance. Pretreatment with the synaptic blocker TTX (0.3-1 microM) reduced the CCK8s-induced current, suggesting that a portion of the CCK8s-induced current was mediated indirectly via an action on presynaptic neurons apposing the DMV membrane. Pretreatment with the selective CCK-A receptor antagonist lorglumide (0.3-3 microM) attenuated the CCK8s-induced inward current in a concentration-dependent manner, with a maximum inhibition of 69 +/- 12% obtained with 3 microM lorglumide. Conversely, pretreatment with the selective CCK-B antagonist triglumide did not attenuate the CCK8s-induced inward current; pretreatment with triglumide (3 microM) and lorglumide (1 microM) attenuated the CCK8s-induced current to the same extent as pretreatment with lorglumide alone. Immunohistochemical experiments showed that CCK-A receptors were localized on the membrane of 34, 65, and 60% of fundus-, corpus-, and antrum/pylorus-projecting DMV neurons, respectively. Our data indicate that CCK-A receptors are present on a subpopulation of gastric-projecting neurons and that their activation leads to excitation of the DMV membrane.
Patients awaiting hip-replacement because of osteoarthritis were more likely to be restricted in their physical and social life than adults in the general population, but mental state and vitality appear unimpaired in this group. This contrasts with findings from other chronic pain disorders. Manual social class is not linked to being on a waiting list for osteoarthritic hip replacement but does add to the burden on health status, particularly social functioning in those with osteoarthritis of the hip.
Previous evidence suggests that substance P (SP) activates subpopulations of neurons within the dorsal motor nucleus of the vagus (DMV). In this study we aimed at identifying these subpopulations in relation to their gastrointestinal projection organs or vagal branches and characterizing pharmacologically the SP response. Using whole cell patch-clamp recordings from identified gastrointestinal-projecting vagal motoneurons, we found that SP induced an inward current in all neuronal groups except for cecum-projecting cells. The lowest percentage of SP-responding neurons was found in fundus-projecting cells, where SP also had a concentration-response curve that was shifted to the left (P < 0.05). Independently from the projections, the SP response was reduced by sendide and MEN 10,376 and mimicked by a combination of [Sar(9)-Met(O(2))(11)]SP and alpha-neurokinin. SP and alpha-neurokinin also increased the frequency, but not the amplitude, of postsynaptic currents. In conclusion, we demonstrated that SP induces both pre- and postsynaptic effects on DMV neurons via activation of neurokinin NK(1) and NK(2) receptors. The magnitude of the SP response was correlated to the peripheral target organ.
Lateral unicompartment knee replacements are performed infrequently in the United Kingdom. This study evaluates the experience of two knee surgeons in a District General Hospital for all lateral unicompartmental arthroplasties performed between October 2007 and August 2011. Two different implants were used in this time period, the Oxford domed and the Zimmer fixed-bearing system. Twenty-seven procedures were completed in this time span (15 Oxford domed and 12 Zimmer fixed bearing), all of which once completed were followed up and 21 patients completed an Oxford knee score. Average Oxford knee scores were 36.6 (95 % CI 29.0-44.2) for the Oxford domed prosthesis and 28.6 (19.8-37.5) for the Zimmer fixed-bearing prosthesis (p = 0.15). One patient with an Oxford domed prosthesis required revision for bearing dislocation. The follow-up Oxford knee scores support the use of this technique as an alternative to total knee replacement but with no significant difference in functional outcome. Our results, however, may encourage a more cautious approach to the use of a mobile-bearing prosthesis in favour of a fixed-bearing prosthesis.
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