The mechanism of exogenous adiponectin in the prevention of no-reflow phenomenon in type 2 diabetic patients with acute myocardial infarction during PCI treatment.

The article "The mechanism of exogenous adiponectin in the prevention of no-reflow phenomenon in type 2 diabetic patients with acute myocardial infarction during PCI treatment, by C.-J. Zhang, Y.-Z. Deng, Y.-H. Lei, J.-B. Zhao, W. Wei, Y.-H. Li, published in Eur Rev Med Pharmacol Sci 2018; 22 (7): 2169-2174-DOI: 10.26355/eurrev_201804_14751-PMID: 29687877" has been withdrawn from the authors due to some technical reasons (the authors still have not figured out how to address them). The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14751.

[Methods of repairing large soft tissue defect with latissimus dorsi myocutaneous flap and management of secondary wound in donor site].

Objective: To explore the methods of repairing large soft tissue defect with latissimus dorsi myocutaneous flap and the management of secondary wound in donor site. Methods: From June 2015 to June 2019, 30 patients with soft tissue defect caused by various reasons or hyperplastic scar were hospitalized in the First Medical Center of Chinese PLA General Hospital, including 10 males and 20 females, aged 25-64 years, with 18 cases of head soft tissue defects caused by the growth and rupture of tumor, 7 cases of hypertrophic scar in trunk and limbs, and 5 cases of facial and neck soft tissue defects caused by trauma. The area of primary wound after debridement or enlarged lesion resection was 14 cm×10 cm-18 cm×16 cm. Preoperative evaluation of 20 patients showed that the wound was relatively large, and the donor site could not be directly closed by suturing after resection of conventional single-lobe latissimus dorsi myocutaneous flap, so the bilobed latissimus dorsi myocutaneous flap with area of 14 cm×5 cm-18 cm×8 cm was cut to repair the wound, and the donor site was directly closed by suturing. Preoperative evaluation of 10 patients showed that the donor site could be directly closed by suturing after resection of conventional single-lobe latissimus dorsi myocutaneous flap, so that conventional single-lobe latissimus dorsi myocutaneous flap with area of 11 cm×9 cm-13 cm×10 cm was resected to repair the primary wound, resulting in big tension in donor site and secondary wound with area of 6 cm×4 cm-8 cm×6 cm that couldn't be directly sutured, which was repaired with donor site local flap with area of 7 cm×4 cm-9 cm×6 cm, and the second donor site was directly closed by suturing. Intraoperative end-to-end anastomosis was performed between the thoracodorsal arteries and veins of the latissimus dorsi myocutaneous flap and the arteries and veins of the primary recipient wound. The survival of latissimus dorsi myocutaneous flaps and local flaps were observed after surgery, and the appearance and function of the donor and recipient areas were observed during follow-up. Results: All the latissimus dorsi myocutaneous flaps and local flaps survived in the patients after surgery. Follow-up of 6-12 months showed that the latissimus dorsi myocutaneous flap was similar in color to the surrounding normal skin, with soft texture and good elasticity. The donor site of 20 patients repaired with bilobed latissimus dorsi myocutaneous flaps were only left with linear scars, among which 2 patients had hypertrophic scars and none had functional impairment. The donor site of 10 patients repaired with single-lobe latissimus dorsi myocutaneous flaps and donor site local flaps had good appearance, left with linear scar, irregular shape, but no local traction or dysfunction. Conclusions: When repairing a large soft tissue defect, the bilobed latissimus dorsi myocutaneous flap or the single-lobe latissimus dorsi myocutaneous flap combined with the local flap transfer in the donor site can be used after preoperative evaluation so that the donor site wound can be closed at one time while repairing the primary wound. The donor site has less scar, and both the recipient and donor sites have good appearance and function after surgery.

[Clinical application effects of portable visual retractor in superficial temporal fascia flap harvesting].

Objective: To explore the clinical application effects of portable visual retractor in superficial temporal fascia flap harvesting. Methods: From January 2010 to June 2019, 27 patients meeting the inclusion criteria and planning to perform operation of superficial temporal fascia flap harvesting were admitted to the Department of Plastic and Reconstructive Surgery of the First Clinical Medical Center of the People's Liberation Army General Hospital. The patients were divided into traditional surgical method group [6 males and 3 females, aged (34±14) years], cold light source retractor group [6 males and 4 females, aged (35±16) years], and portable visual retractor group [7 males and 1 female, aged (30±14) years] according to way of superficial temporal fascia flap harvesting. The superficial temporal fascia flaps of patients in traditional surgical method group were resected by traditional way of resection, and the superficial temporal fascia flaps of patients in cold light source retractor group and portable visual retractor group were resected at assistance of cold light source retractor and portable visual retractor, respectively. Length of incision, operation time, intraoperative blood loss volume, postoperative drainage volume, and postoperative complication of patients in 3 groups were observed and recorded. Data were processed with Fisher's exact probability test, one-way analysis of variance, least significant difference test, Kruskal-Wallis H test, and Bonferroni correction. Results: The length of incision of patients in visual retractor group was (3.6±0.8) cm, significantly shorter than (12.6±1.6) cm in traditional surgical method group and (5.8±0.9) cm in cold light source retractor group (P<0.05). The incision length of patients in traditional surgical method group was significantly longer than that in cold light source retractor group (P<0.05). The operation time of patients in visual retractor group was 24.0 (23.3, 25.8) min, significantly shorter than 35.0 (30.5, 36.5) min in traditional surgical method group and 28.5 (26.8, 30.5) min in cold light source retractor group (H=16.5, 9.8, P<0.05). The operation time of patients in traditional surgical method group was significantly longer than that in cold light source retractor group (H=6.6, P<0.05). The intraoperative blood loss volume was (26±3) mL of patients in visual retractor group, significantly less than (34±4) mL in traditional surgical method group and (30±6) mL in cold light source retractor group (P<0.05). The intraoperative blood loss volume of patients in traditional surgical method group was significantly more than that in cold light source retractor group (P<0.05). The postoperative drainage volumes of patients in visual retractor group, cold light source retractor group, and traditional surgical method group were (33±4), (34±6), and (31±7) mL, respectively, and there were no significantly statistical differences in postoperative drainage volumes among patients in the three groups (F=0.3, P>0.05). There were no severe complications such as ischemia and necrosis of superficial temporal fascia flaps in patients of the three groups. One patient in cold light source retractor group had subcutaneous hematoma after operation, which was improved by removing stitches and hematoma. Conclusions: Superficial temporal fascia flap harvesting at the assistance of portable visual retractor has the advantages of clear visual field, simple operation, short operation time, small incision, and less intraoperative blood loss.

Modulative effects of lncRNA TCONS_00202959 on autonomic neural function and myocardial functions in atrial fibrillation rat model.

OBJECTIVE: Atrial fibrillation (AF) is a typical cardiac arrhythmia. The autonomic nervous system can modulate the myocardial system with complicated mechanisms. Long non-coding RNA (lncRNA) is involved in myocardial diseases, and lncRNA TCONS_00202959 is down-regulated in AF. However, the detailed effects of AF on automatic functions or cardiomyocytes are not well known yet. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were randomly divided into control group, AF group (which was prepared by injecting the acetylcholine-CaCl2 solution) and treatment group (receiving lentiviral transfection of lncRNA TCONS_00202959 on AF rats). Real Time-quantitative PCR (RT-PCR) was used to measure the expression of lncRNA TCONS_00202959. Atrial effective refractory period (AERP) and AF induction rate were measured, along with heart rate variability (HRV) analysis to reveal autonomic nervous function. The expression of tyrosine hydroxylase (TH) and choline acetyltransferase (CHAT) was analyzed in atrial tissues. RESULTS: The expression of lncRNA TCONS_00202959 was decreased in the AF group compared to the control group (p < 0.05), which also had shortened AERP and elevated AF induction rate. The analysis of the autonomic nervous function revealed lower standard deviation of NN intervals (SDNN), SDNN of atrial (SDANN), root mean square of successive differences (RMSSD) and SDNN intervals in all 5-min segments (SDNNindx), plus elevated power ratio of low frequency (LF)/high frequency (HF). TH expression was increased whilst CHAT expression was decreased (p < 0.05). The treatment group showed enhanced expression of lncRNA TCONS_00202959, elongated AERP plus decreased AF induction rate. The treatment rats also had higher SDNN, SDANN, RMSSD and SDNNindx, lower LF/HF ratio, decreased TH expression and increased CHAT expression (p < 0.05 compared to the AF group). CONCLUSIONS: AF rats had decreased expression of lncRNA TCONS_00202959, which can help to prevent AF pathogenesis by suppressing cardiac autonomic nervous function.

The mechanism of exogenous adiponectin in the prevention of no-reflow phenomenon in type 2 diabetic patients with acute myocardial infarction during PCI treatment.

OBJECTIVE: To investigate the mechanism of exogenous adiponectin in the prevention of no-reflow phenomenon in type 2 diabetic (T2DM) patients with acute myocardial infarction (AMI) during percutaneous coronary intervention (PCI) treatment. PATIENTS AND METHODS: 66 patients were randomly divided into control group and observation group, 33 cases in each group. According to the percutaneous coronary intervention (PCI) emergency treatment principle, patients from the control group were treated with an intracoronary injection of adenosine combined with a micro-pump intravenous infusion of tirofiban. Patients from the observation group were injected with exogenous adiponectin in addition to the adenosine and tirofiban treatments. RESULTS: There were no significant differences in gender, age, location of the target lesion, degree of stenosis, stent implantation number, length and the inner diameter between control and observation group (p > 0.05). Lower frequent of slow blood flow and no-reflow and shorter interventional procedures were observed in observation group compared with those of control group (p < 0.05). Moreover, the increase of plasma creatine kinase (CK-MB) in patients of observation group was lower than that of the patients in control group (p < 0.05). In addition, the levels of troponin-I (cTnI), IL-6, TNF- α, endothelin-1 (ET-1), vascular endothelial adhesion molecular I (VCAM-1) and bax/Bcl-2 were significantly lower in observation group than those in control (p < 0.05). Furthermore, the occurrence of major adverse cardiac events (MACE) during a 12-month follow-up was significantly lower in the observation group than that of control (p < 0.05). CONCLUSIONS: Exogenous adiponectin further reduced the no-reflow phenomenon during PCI treatment of the patients with T2DM combined with AMI. The function of exogenous adiponectin is associated with the reduced myocardial and endothelial cell injury and the inhibited inflammation and apoptosis. The application of exogenous adiponectin can significantly improve the clinical outcomes.

[Analysis of life-threatening complications during perioperative period in patients undergoing radical cystectomy with orthotopic neobladder].

OBJECTIVE: To investigate the factors influencing life-threatening complications during perioperative period in patients undergoing traditional cystectomy with orthotopic neobladder. METHODS: To retrospectively analyze the clinical data of 206 cases who underwent radical cystectomy with orthotopic neobladder. Logistic regression analysis was used to analyze the significance of the factors such as age, amount of bleeding, pathological stage, effective supplement of albumin, cardiovascular disease, diabetes mellitus, operation duration, intestinal preparation, etc., on the occurrence of severe complications. RESULTS: Among the 206 patients who underwent radical cystectomy with orthotopic neobladder, 22 cases (10.7%) had life-threatening complications (intestinal fistula, hemorrhagic shock, severe infection) during the perioperative period, and 9 cases died (mortality rate 4.4%). Logistic regression analysis showed that the elderly age, long operation duration, lack of effective supplement of albumin, diabetes mellitus are independent factors influencing the occurrence of life-threatening complications during the perioperative period of radical cystectomy with orthotopic ileal neobladder (P<0.05 for all), and are risk factors positively correlated with the severe complications. CONCLUSION: The elderly age, long operation duration, lack of effective supplement of albumin, and diabetes mellitus are risk factors of the occurrence of life-threatening complications during the perioperative period in patients undergoing radical cystectomy with orthotopic ileal neobladder, therefore, attention should be paid to this issue.

Effect of siRNA targeting EZH2 on cell viability and apoptosis of bladder cancer T24 cells.

We investigated the effect of siRNA targeting enhancer of EZH2 on cell proliferation, invasion, migration, and apoptosis of human bladder cancer T24 cells. An siRNA-expressing plasmid targeting the EZH2 gene was transfected into T24 cells. Quantitative polymerase chain reaction and Western blot analysis were used to detect EZH2 expression at the mRNA and protein levels, respectively. Proliferation, invasion, and migration of T24 cells were examined in vivo using MTT, wound healing, and transwell chamber migration assays, respectively. Annexin V-fluorescein isothiocyanate/propidium iodide flow cytometric analysis was performed to determine cell apoptosis levels. Expression of EZH2 in T24 cells was suppressed at the mRNA and protein levels. Following transfection for 48 h, growth was inhibited by 37.9%, which was markedly lower than that in the negative control group (P < 0.05). Following a wound-healing assay for 24 h, transfected cell migration distance was 1.37 ± 0.12, which was markedly less than the horizontal migration distance of negative control group cells (P < 0.01). In addition, the cell invasion ability of EZH2- siRNA group cells decreased by 67% compared with negative control group cells (P < 0.01). Following transfection for 48 h, early- and late-stage apoptosis rates for T24 cells were 22.8 and 3.60%, respectively, which were higher than in the negative control group (P < 0.01). EZH2 gene silencing effectively suppressed the proliferation, invasion, and migration abilities of human bladder cancer cells, promoting apoptosis.

Androgen receptor coregulators NOCR1, TIF2, and ARA70 may account for the hydroxyflutamide insensitivity of prostate cancer cells.

INTRODUCTION: Prostate cancer cells can switch from an androgen-dependent state to an androgen-independent state after a continuous androgen ablation therapy. However, the molecular mechanisms underlying this switch are still unclear. Therefore, we explored the change in androgen receptor (AR)-related gene expression during this transition in a novel cell model. MATERIAL AND METHODS: Prostate cancer cells were continuously treated with competitive androgen receptor inhibitor hydroxyflutamide for 1.5 years, which yielded an flutamide-insensitive LNCaP subline, LNCaP-flu, as confirmed by MTT assays, flow cytometry, and electron microscopy. We analyzed the differences in gene expression in LNCaP-flu cells and LNCaP cells using gene chips and follow-up RT-PCR. RESULTS: Over 2,428 genes were differentially expressed between these cell lines: 1,194 were down-regulated and 1,234 were up-regulated. Three genes in particular were considered related to the androgen-dependent transition: NCOR1, TIF2 (NCOA2), and ARA70 (NCOA4). There were no apparent changes in expression of the androgen receptor or prostate-specific antigen. CONCLUSION: ARs and associated coregulators play a central role in the flutamide-insensitive transition of prostate cancer cells. Although AR expression does not change during this transition, the change in AR coregulators may be a critical factor in the development of antiandrogen insensitivity.

[Clinical research on the relationship between the orthondontic treatment and the temporomandibular joint noises].

The sign of the temporomandibular joint(TMJ) noise was assessed through the comparison among seventy orthodontic patients before and after orthondontic treatment. The results showed, after orthondontic treatment the TMJ noise was less than before, no significant correlation was found between TMJ noise and the orthondontic treatment with or without tooth extraction.

Effects and interactions of opioids on plasma exudation induced by cigarette smoke in guinea pig bronchi.

The effects of opioids on cigarette smoke-induced plasma exudation were investigated in vivo in the main bronchi of anesthetized guinea pigs, with Evans blue dye as a plasma marker. Acute inhalation of cigarette smoke increased plasma exudation by 216% above air control values. Morphine, 0.1-10 mg/kg but not 30 mg/kg, inhibited the exudation but had no significant effect on substance P-induced exudation. Both 10 and 30 mg/kg of morphine increased exudation in air control animals, an effect inhibited by antihistamines but not by a tachykinin neurokinin type 1-receptor antagonist. Naloxone inhibited all morphine responses. Cigarette smoke-induced plasma exudation was inhibited by a mu-opioid-receptor agonist (DAMGO) but not by agonists at delta (DPDPE)- or kappa (U-50488H)-receptors. None of these agonists affected exudation in air control animals. DPDPE prevented the inhibition by DAMGO of cigarette smoke-induced plasma exudation, and the combination of DAMGO and DPDPE increased exudation in air control animals. Prevention of inhibition and the combination-induced increase were inhibited by antihistamines or the mast cell-stabilizing drug sodium cromoglycate. U-50488H did not alter the response to either DAMGO or DPDPE. We conclude that, in guinea pig main bronchi in vivo, mu-opioid-receptor agonists inhibit cigarette smoke-induced plasma exudation via a prejunctional mechanism. Plasma exudation induced by mu- and delta-receptor interactions is due to endogenous histamine release from mast cells.

Involvement of hydroxyl radicals in neurogenic airway plasma exudation and bronchoconstriction in guinea-pigs in vivo.

1. Cigarette smoke induces plasma exudation in the airways of rodents by activation of capsaicin-sensitive 'sensory-efferent' nerves. The response is mediated predominantly by substance P (SP) and the magnitude of exudation is regulated by neutral endopeptidase (NEP). The component(s) of the smoke responsible for the activation of the nerves may be reactive oxygen radicals. We investigated the effect of the hydroxyl radical scavenger dimethylthiourea (DMTU), a regulator of superoxide anion, superoxide dismutase (SOD), and a regulator of hydrogen peroxide, catalase, on plasma exudation (measured using Evans blue dye) induced by cigarette smoke in guinea-pig main bronchi in vivo. The effect of DMTU on plasma exudation and non-cholinergic bronchoconstriction (measured as pulmonary insufflation pressure, PIP) induced by electrical stimulation of the vagus nerves was also assessed. Interaction between hydroxyl radicals and NEP was assessed with the NEP inhibitor phosphoramidon. 2. In each of the experiments, cigarette smoke increased plasma exudation by approximately 200% above air-exposed controls. Acute administration of DMTU (1.5 g kg-1, i.v. for 20 min) significantly reduced cigarette smoke-induced plasma exudation by 69%. In contrast, neither SOD (240,000 u kg-1, i.v.) nor catalase (400,000 u kg-1, i.v.) significantly affected the exudative response. 3. Chronic pretreatment with DMTU (1.25 g kg-1 over 4 days) significantly reduced bronchial plasma exudation induced by cigarette smoke by 72%. Phosphoramidon (1.5 mg kg-1, i.v.) completely reversed the inhibition by DMTU of cigarette smoke-induced plasma exudation. 4. Vagal stimulation increased plasma exudation by approximately 200% and PIP by approximately 250%. Acute treatment with DMTU had no significant inhibitory effect on these responses, whereas chronic pretreatment inhibited them by approximately 80%. Phosphoramidon reversed the inhibition by chronic DMTU. 5. SP (1 nmol kg-1) increased plasma exudation by approximately 250%, a response which was not inhibited by either acute or chronic DMTU. 6. We conclude that hydroxyl radicals, rather than superoxide anion or hydrogen peroxide, are involved in the induction of neurogenic plasma exudation and bronchoconstriction induced by cigarette smoke or by electrical stimulation of the vagus nerves. These radicals also affect the activity of NEP. Acute DMTU may affect directly the neural actions of hydroxyl radicals contained in the cigarette smoke. Chronic pretreatment with DMTU may inhibit the neurogenic airway responses by effects on tachykinin biosynthesis and/or axonal transport.

Mechanisms and modulation of airway plasma exudation after direct inhalation of cigarette smoke.

We characterized plasma exudation induced by direct inhalation of cigarette smoke in anesthetized, artificially ventilated guinea pigs, using Evans blue dye as a plasma marker, and investigated the neurogenic mechanisms underlying the response. Cigarette smoke increased plasma exudation in the lower trachea, main bronchi, and proximal intrapulmonary airways in a dose-related manner. Exudation was rapid in onset and was maintained for 0.5 to 2 h, depending upon airway level. Exudation was not reduced after removal of the particular phase of the smoke, nor by atropine, phentolamine, propranolol, hexamethonium, antihistamines, or bilateral vagotomy. Nicotine, at a dose calculated to approximate that in the plasma of cigarette-exposed animals, did not increase airway plasma exudation. Cigarette smoke-induce exudation was blocked by capaicinization or by a substance P antagonist and was potentiated by phosphoramidon but not by captopril. Nedocromil sodium or morphine (0.1 mg/kg each intravenously) partially inhibited cigarette smoke-induced exudation but had no effect on the response to substance P. Inhibition by morphine, but not that by nedocromil sodium, was reversed by naloxone. Thus, direct inhalation of cigarette smoke induces a dose-related, long-lasting increase in airway plasma exudation that is due to vapor-phase activation of sensory-efferent nerves, release of sensory neuropeptides that mediate the exudative response via interaction with substance P receptors, and regulation by neutral endopeptidase. The inhibitory effect of nedocromil and morphine on cigarette smoke-induced airway plasma exudation occurs through inhibition of neurotransmission.

Inhibition of neurogenic plasma exudation and bronchoconstriction by a K+ channel activator, BRL 38227, in guinea pig airways in vivo.

Intravenous administration of a K+ channel activator, BRL 38227, inhibited cigarette smoke-induced plasma exudation in guinea pig airways in vivo in a dose-dependent manner with an approximate ED50 of 6 microgram/kg. BRL 38227 also inhibited vagally induced plasma exudation and bronchoconstriction but did not inhibit substance P-induced plasma exudation or neurokinin A-induced bronchoconstriction. K+ channels modulate neurotransmission in the airways and K+ channel activators may have therapeutic potential in bronchial diseases including asthma and chronic bronchitis.

Effects of two novel tachykinin antagonists, FK224 and FK888, on neurogenic airway plasma exudation, bronchoconstriction and systemic hypotension in guinea-pigs in vivo.

1. We compared the effects of two novel tachykinin receptor antagonists, FK888 (selective at the tachykinin NK1 receptor) and FK224 (dual antagonist at NK1 and NK2 tachykinin receptors) on stimulus-evoked airway plasma exudation, bronchoconstriction and systemic hypotension in guinea-pigs in vivo. Plasma exudation was induced by substance P (SP), synthetic tachykinin receptor agonists, platelet activating factor (PAF), electrical stimulation of the cervical vagus nerves or by inhalation of cigarette smoke. Changes in airway tone and in carotid artery blood pressure (BP) were induced by synthetic tachykinin agonists, PAF and vagal stimulation. 2. Both FK224 and FK888 dose-dependently inhibited SP-induced plasma exudation in the lower trachea and main bronchi (ID50 values respectively of 1.1 and 0.1 mumol kg-1 in lower trachea, and of 0.5 and 0.1 mumol kg-1 in main bronchi) with complete inhibition at both airway levels at 10 mumol kg-1 for FK224 and at 2 mumol kg-1 for FK888. 3. The NK1-selective tachykinin receptor agonist, [Sar9,Met(O2)11]substance P ([Sar]SP), induced plasma exudation, a response which was blocked by both FK888 and FK224. The NK2-selective agonist, [beta-Ala8]neurokinin A-(4-10) ([beta-Ala]NKA), did not induce plasma exudation: neither FK888 nor FK224 affected this lack of response to [beta-Ala]NKA. 4. [beta-Ala]NKA induced bronchoconstriction, a response which was blocked by FK224 but which was completely unaffected by FK888. [Sar]SP induced a small but significant bronchoconstriction which was completely inhibited by both tachykinin antagonists. 5. In animals pretreated with capsaicin to deplete sensory neuropeptides, PAF induced both plasma exudation and bronchoconstriction. Neither response to PAF was inhibited by either FK888 or FK224.6. Both FK888 and FK224 inhibited plasma exudation induced by vagus nerve stimulation or by cigarette smoke, with FK888 more potent than FK224.7. FK224 inhibited non-cholinergic bronchoconstriction induced by vagal stimulation, whereas FK888,at doses inhibiting vagally-induced plasma exudation, did not.8. Decreases in BP induced by SP or [Sar]SP were blocked by both FK888 and FK224. In contrast,neither antagonist had any significant inhibitory effect on the decrease in BP induced by vagal stimulation (in the presence of atropine) or PAF. [beta-Ala]NKA did not decrease BP and neither tachykinin antagonist had any significant effect on this lack of response.9. We conclude that in guinea-pig airways, plasma leakage induced by endogenous tachykinins is mediated predominantly via NK1-receptors, whereas bronchoconstriction is mediated predominantly via NK2-receptors. In addition, SP-evoked decreases in BP are also mediated via NK1 receptors, whereas the contribution of endogenous tachykinins to vagally-induced decreases in BP appears to be minimal.Development of selective tachykinin receptor antagonists will be important in understanding the involvement of tachykinins in airway physiology and pathophysiology, whereas potent dual tachykinin receptor antagonists such as FK224 may have greater therapeutic potential in certain airway diseases in which tachykinins have been implicated in pathogenesis, including asthma and chronic bronchitis associated with cigarette smoking.

Regulation of NANC neural bronchoconstriction in vivo in the guinea-pig: involvement of nitric oxide, vasoactive intestinal peptide and soluble guanylyl cyclase.

1. We investigated the effect of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and the peptidase alpha-chymotrypsin on non-adrenergic, non-cholinergic (NANC neural) bronchoconstriction induced by electrical stimulation of the vagus nerves and by capsaicin in anaesthetized guinea-pigs in vivo using pulmonary insufflation pressure (PIP) as an index of bronchial tone. We also investigated the contribution of soluble guanylyl cyclase (SGC) to NANC neural relaxant mechanisms. 2. In the presence of atropine and propranolol, electrical stimulation of the vagus nerves induced a frequency-dependent increase in PIP above baseline of 67% at 2.5 Hz, of 128% at 5 Hz and of 230% at 10 Hz. L-NAME (1-50 mg kg-1, i.v.), at doses inducing increases in systemic blood pressure, dose-relatedly potentiated NANC bronchoconstriction. At 10 mg kg-1 i.v., L-NAME significantly (P < 0.05) potentiated NANC bronchoconstriction by a further 106% at 2.5 Hz and a further 147% at 5 Hz but did not potentiate the increase in PIP at 10 Hz. L-NAME did not induce bronchoconstriction in sham-stimulated control animals. D-NAME did not potentiate NANC bronchoconstriction. Raising systemic blood pressure with phenylephrine did not potentiate vagally-induced bronchoconstriction (2.5 Hz). 3. The NO precursor L-arginine, but not D-arginine, (100 mg kg-1, i.v.) significantly reversed the potentiation by L-NAME of NANC bronchoconstriction. L-Arginine alone significantly inhibited neurogenic bronchoconstriction at 10 Hz (by 74%); the inhibition of 25% at 2.5 Hz was not significant. 4. L-NAME did not significantly affect the increases in PIP induced by intravenous substance P. neurokinin A (NKA) or capsaicin. 5. The inhibitor of SGC, methylene blue (10 mg kg', i.v.) potentiated (by 110-140%) NANC neural bronchoconstriction induced by lower frequencies of nerve stimulation and reversed the reduction in PIP induced by the SGC activator, sodium nitroprusside (SNP, 1.05 mg kg- 1, i.v.). SNP significantly (P <0.05) reduced by 65% the bronchoconstriction induced by nerve stimulation at 10 Hz. Methylene blue did not effect baseline PIP in sham-stimulated controls. The airway effects of methylene blue and SNP were not associated with their cardiovascular effects. 6. a-Chymotrypsin (2 units kg-', i.v.) significantly potentiated vagally-induced bronchoconstriction by a further 63% at 2.5 Hz, by a further 95.6% at 5 Hz but did not potentiate the increase in PIP at 10 Hz. alpha-Chymotrypsin also potentiated (by 116%) capsaicin-induced bronchoconstriction. Vasoactive intestinal peptide (VIP, 10 ig kg-' i.v. infused over min) significantly reduced by 70% the increase in PIP induced by NKA (0.1 .Lmol kg-' i.v., infused over 30 s). 7. The combination of a-chymotrypsin (2 units kg-', i.v.) and L-NAME (5 mg kg-', i.v.) significantly potentiated NANC bronchoconstriction by a further 304% at 2.5 Hz, an increase in PIP which was greater than that induced by either a-chymotrypsin or L-NAME alone (P <0.05). 8. We conclude that endogenous NO and a bronchodilator peptide, possibly VIP, released in association with nerve stimulation, as well as activation of soluble guanylyl cyclase, regulate the magnitude of NANC neurogenic bronchoconstriction in guinea-pigs in vivo.

Inhibition of neurogenic plasma exudation in guinea-pig airways by CP-96,345, a new non-peptide NK1 receptor antagonist.

A new non-peptide tachykinin antagonist, CP-96,345, inhibited airway plasma exudation induced in guinea-pigs by i.v. substance P in a dose-dependent manner with dose-ratios in the main bronchi of 5 at 1 nmol kg-1 and 19 at 100 nmol kg-1. At 100 nmol kg-1, CP-96,345 completely inhibited plasma exudation induced by either electrical stimulation of the cervical vagus nerves or i.v. capsaicin, indicating inhibition of the effects of endogenous tachykinins, but did not inhibit the bronchoconstrictor response to neurokinin A, suggesting selectivity for NK1 receptors. CP-96,345 may be useful in examining the role of endogenous tachykinins in vivo.

[Combined surgery and radiotherapy of glioblastoma multiforme--report of 73 cases].

A retrospective analysis of 73 patients with glioblastoma multiforme treated with surgery plus radiotherapy (63 cases) or surgery alone (10 cases) showed that the 5-year survival was 16% versus 0% and the median survival time was 14 versus 5 months. The median survival time in patients receiving postoperative radiotherapy was almost 3 times as long as that in patients treated with surgery alone. The difference in survival was insignificant between patients treated with a local extended field and those with whole brain plus local irradiation. The age, sex, course of disease, extent of operation and dose of irradiation are the factors influencing prognosis.