No abstract

Selective stimulation of the PGE2 signal through EP2 receptors by a specific agonist promoted regeneration of cartilage tissues with a physiological osteochondral boundary, suggesting the potential usefulness of this small molecule for the treatment of injured articular cartilages.

1 We examined eects of g-aminobutyric acid (GABA) on vasoconstriction and noradrenaline (NA) release induced by electrical renal nerve stimulation (RNS) in the isolated pump-perfused rat kidney. 2 RNS (1 and 2 Hz for 2.5 min each, 0.5-ms duration, supramaximal voltage) increased renal perfusion pressure (PP) and renal NA eux. GABA (3, 10 and 100 mM) attenuated the RNSinduced increases in PP by 10 ± 40% (P50.01) and NA eux by 10 ± 30% (P50.01). GABA did not aect exogenous NA (40 and 60 nM)-induced increases in PP. 3 The selective GABA B agonist baclofen (3, 10 and 100 mM) also attenuated the RNS-induced increases in PP and NA eux, whereas the RNS-induced responses were relatively resistant to the selective GABA A agonist muscimol (3, 10 and 100 mM). 4 The selective GABA B antagonist 2-hydroxysaclofen (50 mM), but not the selective GABA A antagonist bicuculline (50 mM), abolished the inhibitory eects of GABA (10 mM) on the RNSinduced responses. 5 The selective a 2 -adrenoceptor antagonist rauwolscine (10 nM) enhanced the RNS-induced responses. GABA (3, 10 and 100 mM) potently attenuated the RNS-induced increases in PP by 40 ± 60% (P50.01) and NA eux by 20 ± 50% (P50.01) in the presence of rauwolscine. 6 Prazosin (10 and 30 nM) suppressed the RNS-induced increases in PP by about 70 ± 80%. Neither rauwolscine (10 nM) nor GABA (10 mM) suppressed the residual prazosin-resistant PP response. 7 These results suggest that GABA suppresses sympathetic neurotransmitter release via presynaptic GABA B receptors, and thereby attenuates adrenergically induced vasoconstriction in the rat kidney.

Summary:A 16-year-old boy developed bronchiolitis obliterans (BO) 10 years after BMT for myelodysplastic syndrome. Although the patient complained of almost no dyspnea on exertion, he had mild hypercapnea with a markedly reduced forced expiratory volume of 0.32 l. Chest Xrays showed occasional bilateral minimal pneumothoraces, which is in accordance with the existence of multiple small bullae found on the pleural surface at videoassisted thoracic surgery. Histologic examination of the biopsied lung revealed BO. This case indicates that BO in adolescence following BMT and possible chronic GVHD may be masked because of lung immaturity at BMT, and BO after BMT may be associated with multiple pleural bullae. Keywords: bronchiolitis obliterans; BMT; pneumothorax; GVHD Bronchiolitis obliterans (BO) is a localized inflammatory process of the bronchioles featuring fibrotic obliteration of the lumen. BO is a characteristic pulmonary complication which occurs usually within a few years after BMT. [1][2][3] We report a patient with asymptomatic BO and bilateral pneumothoraces caused by multiple bullae after BMT. Case reportA 16-year-old male was referred to our outpatient clinic because of abnormal shadows after a routine chest radiogram despite no respiratory symptoms (Figure 1a). At the age of 6, he had been diagnosed with myelodysplastic syndrome, for which he had received an allogeneic BMT from his HLA-matched sister after a preparative regimen with a total of 12 Gy TBI in six fractions and CY at a dose of

We examined modulation by nitric oxide (NO) of sympathetic neurotransmitter release and vasoconstriction in the isolated pump-perfused rat kidney. Electrical renal nerve stimulation (RNS; 1 and 2 Hz) increased renal perfusion pressure and renal norepinephrine (NE) efflux. Nonselective NO synthase (NOS) inhibitors [N(omega)-nitro-L-arginine methyl ester (L-NAME) or N(omega)-nitro-L-arginine], but not a selective neuronal NO synthase inhibitor (7-nitroindazole sodium salt), suppressed the NE efflux response and enhanced the perfusion pressure response. Pretreatment with L-arginine prevented the effects of L-NAME on the RNS-induced responses. 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), which eliminates NO by oxidizing it to NO(2), suppressed the NE efflux response, whereas the perfusion pressure response was less susceptible to carboxy-PTIO. 8-Bromoguanosine cGMP suppressed and a guanylate cyclase inhibitor [4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one] enhanced the RNS-induced perfusion pressure response, but neither of these drugs affected the NE efflux response. These results suggest that endogenous NO facilitates the NE release through cGMP-independent mechanisms, NO metabolites formed after NO(2) rather than NO itself counteract the vasoconstriction, and neuronal NOS does not contribute to these modulatory mechanisms in the sympathetic nervous system of the rat kidney.