Regulation by phosphodiesterase isoenzymes of non-adrenergic non-cholinergic contraction in guinea-pig isolated main bronchus.

1. We have investigated the role of phosphodiesterase isoenzymes in modulating electric field stimulation (EFS), substance P and capsaicin-induced contraction of the guinea-pig isolated main bronchus. 2. Non-adrenergic non-cholinergic contractile responses were elicited by EFS (3 Hz, 20 s) in the guinea-pig isolated main bronchus in the presence of the non-selective muscarinic antagonist, atropine (0.1 microM), the non-selective beta-adrenoceptor antagonist, propranolol (1 microM), the neutral endopeptidase inhibitor, thiorphan (10 microM) and the cyclo-oxygenase inhibitor, indomethacin (5 microM). The type III, type III/IV, type IV and type V phosphodiesterase isoenzyme inhibitor, SKF 94836, benzafentrine, Ro-20-1724 and zaprinast respectively, significantly attenuated the contractile response to EFS. The IC50 (95% confidence limits) value for SKF 94836, benzafentrine, Ro-20-1724 and zaprinast was 8.3 microM (0.89-78); 0.7 microM (0.1-4.5); 0.5 microM (0.2-1.2) and 13 microM (2-87) respectively. 3. The phosphodiesterase isoenzyme inhibitors, SKF 94836, Ro-20-1724 and zaprinast, partially attenuated the contractile response to substance P (10 nM). Benzafentrine significantly inhibited the contractile response to substance P, yielding an IC50 value of 1.9 microM (0.9-3.8). 4. The phosphodiesterase isoenzyme inhibitor, Ro-20-1724 (0.1-100 microM) failed to reduce significantly the contractile potency of capsaicin (P > 0.05). In contrast, SKF 94836 (1 microM), benzafentrine (10 microM) and zaprinast (100 microM) significantly reduced the contractile potency of capsaicin (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

马兜铃酸的倍半萜的酯类化合物VI.绵毛马兜铃中马兜铃酸萜酯I的结构鉴定

从绵毛马兜铃(Aristolocha mannisima Hance)中分得一个马兜铃酸倍半萜的酯类化合物,经红外、紫外、高分辩质谱和多种一维和二维核磁共振谱鉴定,确定了其骨架结构及顺反构型,命名为马兜铃酸萜酯I。     

Intraoperative ultrasonography (IOUS) during laparoscopic cholecystectomy

Background: The purpose of this study was to evaluate the usefulness of intraoperative ultrasonography (IOUS), a new method of imaging the biliary tree and related structures, during laparoscopic cholecystectomy. Method: An IOUS probe (Aloka, Tokyo, Japan) with a 7.5-MHz linear-array transducer was used during cholecystectomy in 124 patients with symptomatic cholelithiasis (45 men, 79 women; mean age, 48±14 years). Results: The examination of the common bile duct (CBD) was excellent in 117 patients but unsatisfactory in 7 cases (5.6%) at the level of the head of the pancreas. In 5 patients, IOUS showed unsuspected choledocholithiasis: a subsequent intraoperational cholangiogram confirmed this. In five cases IOUS was able to help the surgeon to localize a Calot area obscured by inflammation. Postoperatively, one patient had an injury of the cystic duct stump: a nasobiliary tube resolved the bile leakage after 7 days. Another patient was submitted to postoperative endoscopic retrograde cholangiopancreatography (ERCP) for a choledocholithiasis recognized by a trans-cystic-tube cholangiography: the stone was suspected but not demonstrated either by laparoscopic IOUS or by intraoperative cholangiography. During the follow-up period, one patient had an episode of acute pancreatitis. ERCP showed a small stone wedged in the sphincter of Oddi. Conclusions: IOUS may be a real alternative to cholangiography during laparoscopic cholecystectomy since it is safer and offers a complete examination of the biliary tree. It has some disadvantages which can solved by additional experience.     

In vitro inhibition of a polymorphic human liver P-450 isozyme by narcotic analgesics

Genetically determined differences in the ability of individuals to oxidize certain drugs by hepatic P-450 processes has gained increasing attention. The so-called debrisoquin hydroxylase, which is defective in approximately 5-10% of whites, is known to be of major importance for the metabolism of several drugs. The possible relation of this isozyme to the metabolism of narcotics eliminated by oxidative biotransformation has not been studied. Several narcotics were screened for in vitro interaction with this P-450 isozyme. This was accomplished by testing for competitive inhibition by narcotics of the 2-hydroxylation of desmethylimipramine in a human liver microsomal preparation. Alfentanil, fentanyl, and dextropropoxyphene were found to competitively inhibit this pathway demonstrating an interaction with this polymorphic isozyme. No interaction was found for codeine, meperidine, methadone, morphine, or nalbuphine. These results suggest that a genetic defect may be important for elimination clearance by metabolism for dextropropoxyphene, alfentanil, and fentanyl and that in vivo investigation is warranted.     

Immunohistochemical localization of vanilloid receptor subtype 1 (TRPV1) in the guinea pig respiratory system

Transient receptor potential vanilloid-1 (TRPV1) containing nerves are implicated in cough and bronchoconstriction although the significance of their documentation on non-neuronal cells is unclear. We have investigated the anatomical distribution and location of TRPV1 in an animal species often utilized in models of cough and airway inflammation. The distribution and localization of TRPV1 immunoreactivity in the lung was studied using confocal microscopy. Double labelling were carried out using the panaxonal marker, protein gene product 9.5 (PGP) and the neuropeptide substance P. TRPV1 was localized to fine axons within the epithelium of the trachea, however this represented only a fraction of the total axonal innervation of the epithelium. TRPV1 immunoreactive axons were also found in and around subepithelial regions of the airways, including smooth muscle and blood vessels and within the lower airways, found in the vicinity of bronchi and bronchioles, and in and around alveolar tissue. TRPV1 in the epithelium of the trachea was co-localized with substance P containing axons, although TRPV1 immunoreactive neuropeptide negative axons were also discernible. We found evidence for TRPV1 localization to axons throughout the respiratory tract. The distribution was heterogeneous and represented a fraction of the total neuronal innervation of the airways. No TRPV1 was found localized to airway epithelial cells. TRPV1 was often co-localized with the sensory neuropeptide substance P but there was evidence of TRPV1 positive neurones that did not express substance P. This suggests a role for TRPV1 in the airway that is independent of sensory neuropeptides.     

Non-Hodgkin's lymphoma and hepatitis C virus: a case-control study from northern and southern Italy

HCV has been associated with NHL, but the evidence from case series and case-control studies is not totally consistent. Between 1999 and 2002, we conducted a hospital case-control study on the association between HCV, HBV and NHL in 2 areas of Italy where HCV infection is relatively frequent. Cases (n = 225, median age 59 years) were consecutive patients with a new diagnosis of NHL admitted to local specialized and general hospitals. Controls (n = 504, median age 63 years) were patients with a wide spectrum of acute conditions admitted to the same hospitals as cases. HCV prevalence was 19.6% among NHL cases and 8.9% among controls (adjusted OR = 2.6, 95% CI 1.6-4.3). The ORs for HCV were similar for low-grade and intermediate-/high-grade B-cell NHL (3.2 and 2.4, respectively) as well as for nodal and extranodal NHL (2.7 and 2.6, respectively). Positivity for HBsAg was found in 3.8% of cases and 0.9% of controls (OR = 4.1, 95% CI 1.2-14.4). An elevated OR was also found for history of hepatitis C (OR = 4.7, 95% CI 2.3-9.5). History of blood transfusion before 1990 was associated with HCV positivity among controls but not with NHL risk. In conclusion, HCV infection was associated with an increase in NHL risk, and the fraction of NHL cases attributable to HCV was 12.4% (range 6.3-18.5%).