[Predictor of clinical response to subcutaneous immunotherapy with dust mites in polysensitized allergic rhinitis patients].

Objective: To evaluate the efficacy of 1-year subcutaneous immunotherapy (SCIT) with dust mites in polysensitized allergic rhinitis (AR) patients and to analyze the serological markers associated with clinical response. Methods: A retrospective analysis of data from 69 polysensitized AR patients who completed 1-year SCIT with dust mites from Oct 2020 to Mar 2022 in Shandong Provincial ENT Hospital was conducted. The median patient age was 21 years, including 41 males and 28 females. The changes in symptoms and serum IgE, IgG4 assessed before and after treatment were evaluated. The differences in serological markers between effective and ineffective groups were analyzed. Multivariate regression analysis was used to investigate the predictors of clinical response. SPSS 22.0 software was used for data processing. Results: After immunotherapy, there was a significant reduction in symptom scores and a substantial improvement in the quality of life of polysensitized AR patients (all P<0.001). Dust mite specific IgG4 (sIgG4) significantly increased and dust mite specific IgE (sIgE)/sIgG4 significantly decreased (all P<0.05). sIgE, total IgE (tIgE), sIgE/tIgE and sIgE/sIgG4 were significantly lower in ineffective group than those in effective group (all P<0.05). The clinical response of SCIT related only to dust mite sIgE (r=0.29, P=0.036), and sIgE≥53.86 kU/L had the best sensitivity (77.78%) and specificity (57.89%) to predict effective SCIT in polysensitized AR patients. Conclusions: One-year dust mite SCIT is effective for polysensitized AR patients. Pre-treatment serum dust mite sIgE≥53.86 kU/L may play a role in predicting clinical response of dust mite SCIT in polysensitized AR patients.

Nitric oxide inhibits Ca(2+) mobilization through cADP-ribose signaling in coronary arterial smooth muscle cells.

The present study was designed to determine whether the cADP-ribose-mediated Ca(2+) signaling is involved in the inhibitory effect of nitric oxide (NO) on intracellular Ca(2+) mobilization. With the use of fluorescent microscopic spectrometry, cADP-ribose-induced Ca(2+) release from sarcoplasmic reticulum (SR) of bovine coronary arterial smooth muscle cells (CASMCs) was determined. In the alpha-toxin-permeabilized primary cultures of CASMCs, cADP-ribose (5 microM) produced a rapid Ca(2+) release, which was completely blocked by pretreatment of cells with the cADP-ribose antagonist 8-bromo-cADP-ribose (8-Br-cADPR). In intact fura 2-loaded CASMCs, 80 mM KCl was added to depolarize the cells and increase intracellular Ca(2+) concentration ([Ca(2+)](i)). Sodium nitroprusside (SNP), an NO donor, produced a concentration-dependent inhibition of the KCl-induced increase in [Ca(2+)](i), but it had no effect on the U-46619-induced increase in [Ca(2+)](i). In the presence of 8-Br-cADPR (100 microM) and ryanodine (10 microM), the inhibitory effect of SNP was markedly attenuated. HPLC analyses showed that CASMCs expressed the ADP-ribosyl cyclase activity, and SNP (1-100 microM) significantly reduced the ADP-ribosyl cyclase activity in a concentration-dependent manner. The effect of SNP was completely blocked by addition of 10 microM oxygenated hemoglobin. We conclude that ADP-ribosyl cyclase is present in CASMCs, and NO may decrease [Ca(2+)](i) by inhibition of cADP-ribose-induced Ca(2+) mobilization.

Altered [Ca2+]i mobilization in diabetic cardiomyocytes: responses to caffeine, KCl, ouabain, and ATP.

To study the mechanisms mediating intracellular calcium transients involved in diabetic cardiac dysfunction, changes in intracellular calcium concentration ([Ca2+]i) in response to stimulation by caffeine, ouabain, KCl and ATP were studied in single cardiomyocytes (quiescent or electrically-stimulated) isolated from streptozotocin (STZ) diabetic rats. [Ca2+]i was measured by fluorescence microscopy using fura-2. Peak [Ca2+]i response to caffeine (20 mM) and decline of [Ca2+]i (-peak d[Ca2+]i/dt) were decreased in diabetic myocytes. Insulin treatment corrected these depressed [Ca2+]i responses. The data suggest a reduced sarcoplasmic reticulum (SR) calcium content and a depressed Na-Ca exchange activity in diabetic myocytes. Insulin deficiency may play a causal role in these changes. The maximum [Ca2+]i increase in response to ouabain was reduced in diabetic cells while the sensitivity of diabetic myocytes to ouabain was increased. This may be a result of depressed Na-K ATPase and elevated [Na+]i as previously reported. The KCl (12.5-50 mM)-induced [Ca2+]i increase was enhanced in diabetic cells. Caffeine (20 mM) and dichlorobenzamil (DCB, 10 microM) blocked this [Ca2+]i transient to a smaller degree in diabetic cells, but nitrendipine effects were similar in diabetic and control cells. These effects may be due to the increased L-channel activity and altered features, such as different responses to Ca-channel blockers, in diabetes which has previously been reported. The maximum response of [Ca2+]i to exogenous ATP was increased in diabetic cells while the sensitivity remained unchanged. The mechanisms underlying this enhanced response may be similar to the KCl-induced [Ca2+]i changes in diabetes.

[Effects of L-arginine on pulmonary circulation and cerebral blood flow in acute and chronic hypoxic rats].

The effects of L-arginine (L-Arg) on pulmonary circulation and cerebral blood flow in acute and chronic hypoxic rats and their mechanism were studied. The results showed that bolus injection of L-Arg 400mg.kg-1 did not inhibit acute hypoxic pulmonary vasoconstriction (HPV), while 800mg.kg-1 could inhibit HPV. Neither of these two doses of L-Arg was found to have any influence on the change in cerebral blood flow during acute hypoxia. Long-term administration of L-Arg (300mg.kg-1/d) could attenuate chronic hypoxic pulmonary hypertension, the increase in pulmonary vascular resistance and right ventricular hypertrophy, and the HPV as well. It did not influence the cerebral blood flow. Since the inhibitor of NO synthetase, NG-nitro-L-arginine methyl ester, could antagonize the effect of L-Arg, it is suggested that an increase in the synthesis of NO might contribute to the effect of L-Arg.