Sex pheromone of the queen butterfly: chemistry.

Two major components in the "hairpencil" secretion of the male of the queen butterfly (Danaus gilippus berenice) have been identified. One, a crystalline ketone (2,3-dihydro-7-methyl-1H-pyrrolizin-1-one), is known from another danaid butterfly. The other, a viscous terpenoid alcohol (trans, trans-3,7-dimethyldeca-2,6-dien-1,10-diol), is new; its structure is confirmed by an unambiguous synthesis.

Synthesis and analgetic activity of 1,2,3,4,5,6-hexahydro-1,6-methano-3-benzozocines.

1,2,3,4,5,6-Hexahydro-1,6-methano-3-benzazocine (1) has been synthesized via a four-step sequence from benzo-norbornadiene. This compound and its N-methyl derivative are more active than codeine in the mouse hot-plate antinociceptive assay and will not suppor morphine dependence in Rhesus monkeys.

Synthesis and pharmacological activity of 2,3,4,5,-tetrahydro-1,5-methano-1H-3-benzazepines.

2,3,4,5-Tetrahydro-1,5-methano-1H-3benzazepine (4) has been synthesized from 2,3-dioxobenzonorbornene. Oxidative cleavage of the diketone to cis-1,3-indandicarboxylic acid, followed by closure to the corresponding amhydride, conversion to the imide, and lithium aluminum hydride reduction, gave 4. Compound 4 and its N-derivatives show no analgesic activity in the mouse hot-plate assay and little antagonist activity in a tail-flick assay.

Synthesis and pharmacological properties of 1,2,3,4,5,6-hexahydro-1,6-methano-2-benzazocines.

1,2,3,4,5,6-Hexahydro-1,6-methano-2-benzazocine, 2'-methoxy-1,2,3,4,5,6-hexahydro-1,6-methano-2-benzazocine, and N-alkyl derivatives of 2'-hydroxy-1,2,3,4,5,6-hexahydro-1,6-methano-2-benzazocine have been synthesized in order to evaluate their analgesic activities. These compounds show only slight antinociceptive activities in the mouse hot-plate assay.

Synthesis and pharmacological activity of 6-aryl-2-azabicyclo[4.2.1]nonanes.

A series of 6-phenyl-, 6-(m-methoxyphenyl)-, and 6-(m-hydroxyphenyl)-2-azabicyclo[4.2.1]nonanes was synthesized by a sequence involving alkylation of an appropriate 2-arylcyclopentanone with an aminoalkyl substituent. Subsequent ring closure at the other alpha position on the cyclopentanone ring and Wolff-Kishner reduction afforded the title compound. Several derivatives of these materials showed activity in an antinociceptive assay comparable to codeine. Most analogues were either inactive or toxic.

Magnetic resonance-cholangiopancreatography in the diagnosis of biliopancreatic diseases.

BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is a new, noninvasive imaging technique for the visualization of the biliary ducts with cholangiographic images similar to those obtained with endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography. No contrast medium injection is used. The aim of this study was to assess the feasibility of MRCP versus ERCP in the diagnosis of biliary tract and pancreatic diseases. PATIENTS AND METHODS: One hundred and thirty-six patients were submitted to MRCP. They were referred to MR study according to four inclusion criteria: (1) evidence or suspicion of choledocholithiasis, (2) benign or malignant bile ducts stenosis, (3) follow-up of patients submitted to biliary-enteric anastomosis, and (4) chronic pancreatitis with Wirsung duct dilatation. The MRCP was performed with a 0.5T superconducting magnet (Philips Gyroscan T5). When neoplastic disease was detected, additional images on axial planes were acquired. MRCP allowed images of diagnostic value to be obtained in all the cases. RESULTS: In choledocholithiasis, MRCP showed 91.6% sensitivity, 100% specificity, and overall diagnostic accuracy 96.8%. Of 48 patients with stenotic lesions, 16 were correctly characterized as benign and 30 as malignant. Two cases of focal chronic pancreatitis were misdiagnosed as pancreatic head carcinoma. In the patients submitted to biliary-enteric anastomosis, MCRP was able to detect the dilatation of the intrahepatic ducts, the stenosis, and associated stones in all 8 positive cases. In the remaining 7 patients with mild signs of cholangitis, MCRP showed irregular aspects of the biliary tree in the main ducts. In the 11 patients with chronic pancreatitis, MCRP was able to depict the dilated Wirsung duct and the stenotic tract, although the fine details of the secondary ducts were not evaluated due to the low spatial resolution as compared with conventional films. CONCLUSIONS: MRCP can be considered a technique able to completely replace diagnostic ERCP. Further studies are necessary for a better evaluation of the potential advantages and disadvantages of this technique.

[The role of surgery in the treatment of appendicular abscesses]. / Il ruolo della chirurgia nel trattamento degli ascessi appendicolari.

The management of appendiceal abscesses is still discussed and many different approaches are nowadays adopted. The aim of this study was to analyze retrospectively our experience with this disease to value the results of drainage of the abscess and appendectomy in one stage in presence of appendiceal abscesses. We studied 44 patients consecutively observed in our Department of General Surgery all submitted to drainage of the abscess and appendectomy for acute appendicitis with periappendiceal abscess. Preoperative ultrasonography showed an accuracy of 85.7% in detecting the presence of an abscess. Mean size of the abscesses were 5 cm (from a minimum of 3 cm to a maximum of 9 cm). The mean duration of surgical operation was 48 minutes (min 35'-max 95'), with a mean in-hospital stay of 6.2 days. Morbidity rate was 9% and was due in 75% of cases to wound infection and in 25% of cases to wound dehiscence. Neither major morbidity nor mortality were observed. In consideration of the results the authors conclude that even in presence of an appendiceal abscess, appendectomy with abscess drainage is not only a safe operation with a low morbidity rate but the procedure of choice allowing a significative reduction of hospitalization and health cost.

[Fistulectomy with closure by first intention in the treatment of perianal fistulae]. / La fistulectomia con chiusura per prima intenzione nel trattamento delle fistole perianali.

The authors report in a retrospective study their experience in the treatment of anal fistulas suggesting the total exercises of the fistula with primary closure of external and internal anal sphincters and rectal mucosa. In our department of surgery between 1987 and 1993, 36 patients (22 males and 14 females) with anal fistulas (17 intersphincteric, 15 trans-sphincteric and suprasphincteric) were treated with this technique. Postoperative in-hospital stay ranged between 2 and 5 days (mean 3.1) and surgical healing needed 12-15 days. A dehiscence of distal tract was observed in 3 cases (8.2%). in these cases secondary closure of the wound needed 24-28 days. All the patients controlled at follow-up (it lasted at least 1 year) did not show rectal incontinence for gas or stools. The authors conclude that total exeresis with primary closure is a safe procedure indicated in the treatment of anal fistula not associated to inflammatory bowel disease in consideration of earlier healing and minor costs.

[Trends in the incidence of acute appendicitis in Italy during the past 30 years]. / Andamento dell'incidenza dell'appendicite acuta in Italia negli ultimi 30 anni.

The incidence and mortality rate of acute appendicitis for the years 1955 and 1987 were calculated on the basis of data used by ISTAT. In 1955 the incidence was 5.7 per 1000 whereas in 1987 this had fallen to 3.7 per 1000. In both years examined there was a prevalence of females (in 1987 females accounted for 4.3 per 1000 in comparison to 3 per 1000 recorded for for males). In 1987 the lowest incidence was recorded in the over 60 years olds, whereas the highest incidence was in males between 1 and 14 years old (7.57 per 1000) and females between 15 and 24 years old (12.17 per 1000). Mortality diminished from 0.42% in 1955 to 0.05% in 1987. The highest rate of mortality was recorded in those patients over 60 years old (1.5%).

Imipenem/cilastatin (1.5 g daily) versus meropenem (3.0 g daily) in patients with intra-abdominal infections: results of a prospective, randomized, multicentre trial.

An open-label prospective, randomized, parallel multicentre study was undertaken to compare the efficacy and tolerability of 1.5 g/day intravenous imipenem/cilastatin with 3 g/day intravenous meropenem in the treatment of intra-abdominal infections. A total of 287 patients were enrolled: 201 patients, divided between the 2 treatment groups, were evaluable. Clinical outcome, bacteriological outcome, untoward microbiological effects, and clinical and laboratory adverse experiences were evaluated. 98% of patients receiving imipenem/cilastatin therapy were cured, with 96% showing eradication of infection. 95% of those on meropenem were cured, with 98% showing eradication. These differences in clinical and bacteriological outcome between the 2 treatments were not statistically significant. Two patients receiving imipenem/cilastatin and 5 receiving meropenem had untoward microbiological effects. There was a 0.7% frequency (1/139 patients) of possibly or probably drug-related clinical or laboratory adverse experiences with imipenem/cilastatin and a 2.7% frequency (4/148) with meropenem. The mean time to defervescence was significantly less for patients in the imipenem/cilastatin treatment group than for those receiving meropenem. This study shows that 1.5 g/day of imipenem/cilastatin is equivalent to 3.0 g/day meropenem in clinical and bacteriological outcome, as well as in incidence of side effects.

In vivo study of xibornol on phagocyte functions.

Polymorphonuclear leukocytes (PML) represent the first step of defense against bacteria and fungi. Since many antimicrobial drugs have been reported to inhibit phagocyte function, we tested the interference of xibornol, a new antimicrobial agent, on phagocyte functions, in order to evaluate its possible use in chronic respiratory diseases. In the patients treated with xibornol (500 mg every 8 h for 7 days) we did not find any modification in phagocytosis frequency (PMF), phagocytosis index (PHI), nitroblue tetrazolium (NBT), reduction frequency (NRF), microbicidal activity and neutrophil mobility of PML, before, during and after the end of therapy.

Structural factors influencing the biodegradation of imides.

Comparative studies on the biodegradability of amides and imides are presented. Low-molecular-weight imides of varying chain lengths (4, 6, 7, 8, 18, and 20 carbons) were biodegrable. N-alkyl substitution of amides and imides resulted in non-biodegrable derivatives when the amide portion was greater than two carbons in length. N-alkyl-substituted derivatives of acetamide or diacetamide, however, were biodegrable. Several soil isolates, including Aspergillus niger and species of Flavobacterium and Alcaligenes, were capable of growth with imides as sole N or C sources.

Structure of 5-hydroxy-5-phenyl-7-azatricyclo[7.4.0.02,7]trideca-2,9(1), 10,12-tetraen-8-one by the consistent electron density approach.

C18H15NO2, Mr = 277.3, monoclinic, P21/n, a = 7.408 (2), b = 22.311 (7), c = 8.613 (2) A, beta = 103.53 (3) degrees, V = 1384 (1) A3, Z = 4, Dx = 1.33 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.94 cm-1, F(000) = 594, T = 293 K, 2229 unique diffractometer data, 963 with I greater than 3 sigma(I), R = 0.050. Structure solution was by the consistent electron density approach which combines the concepts of the OMIT map and density modification procedures. The benzolactam portion of the molecule is highly planar; most bond lengths and angles have typical values.

Structure of 3-methyl-1,2,3,4,5,6-hexahydro-1,6-methano-3-benzazocinium hydrogen oxalate.

C13H18N+.C2HO4-, Mr = 277.3, orthorhombic, P2(1)2(1)2(1), a = 5.752 (1), b = 15.502 (2), c = 15.910 (2) A, V = 1418.6 (6) A3, Z = 4, Dx = 1.298 g cm-3, Mo K alpha (lambda = 0.71069 A), mu = 1.01 cm-1, F(000) = 592, T = 295 K. Final R = 0.035, wR = 0.042 for 1003 reflections with I greater than 3 sigma(I). The compound is an ammonium hydrogen oxalate. Both O atoms of the ionized carboxyl group act as acceptors in the formation of two hydrogen bonds: (a) an N--H...O bond linking the cation and anion with N...O and H...O distances of 2.722 (4) and 1.78 (5) A and (b) a strong O--H...O bond linking a chain of oxalate ions along a with O...O and H...O distances of 2.578 (4) and 1.59 (6) A. The relative stereochemistry of the heterocyclic and aromatic rings in the cation is similar to that in morphine.

Conformation of a biologically active C-terminal hexapeptide analog of the pheromone biosynthesis activating neuropeptide by NMR spectroscopy.

The solution conformation of a biologically active C-terminal hexapeptide analog of the pheromone biosynthesis activating neuropeptide Tyr-D-Phe-Ser-Pro-Arg-Leu-NH2 has been studied by NMR spectroscopy. A beta-turn conformation was identified from the NOE connectivities observed for the peptide in a mixed solvent of water and DMSO, indicating that this is the biologically active conformation of the peptide. This study also suggests that the use of such an aqueous-like solvent mixture allows the observation of a preferred conformation for small linear peptides in the presence of conformational averaging.

Effector Th-1 cells with cytotoxic function in the intestinal lamina propria of patients with Crohn's disease.

A large body of evidence points to a pivotal relationship between Th-1 cells and mucosal inflammation in Crohn's disease (CD). The aim of the present study was to assess whether CD is associated with specific functional activity of lamina propria T lymphocytes (LPT), particularly purified CD4, such as cytotoxic activity and specific cytokine-secreted profile. The results showed that CD4 LPT in patients displayed a chronically activated memory-like surface phenotype and, when compared to controls, had a significantly enhanced antibody-redirected cytotoxicity. Interestingly, the ratio of perforin expression in CD4 LPT was higher compared to controls, and a redirected lysis of human RBC mediated by a CD4 subset of intestinal lamina propria was evident, suggesting a cytolytic pore-forming mechanism. Moreover, a unique Th-1 cytokine profile pattern in the CD4 cells from CD was defined. These effector cells produced 12 times more IFN-gamma, two times more TNF-alpha, and three times less IL-4 than controls. In contrast, no increase in IL-2 was detected, while IL-5 was undetectable. Our studies suggest that these preexisting in vivo activated CD4 LPT may play an important role in the inflammatory process in CD, thus directly contributing to the intestinal lesions.

NMR-studies of triiodothyropropionic acid in ethanol-HCl.

The barrier to rotation in the N-acetyl methyl ester of the thyroxine was found to be 8.6 kcal mol-1. Previous experiments determining the barrier to rotation in triiodothyropropionic acid in HCl-ethanol were shown to be in error.

MR cholangiography (MRC) in the evaluation of CBD stones before laparoscopic cholecystectomy.

BACKGROUND: The aim of our work was to evaluate the predictive value of MR cholangiography (MRC) in detecting CBD stones before laparoscopic surgical treatment. METHODS: MRC was performed as a unique preoperative imaging modality in 45 selected patients (16 male; 29 female; age range: 28-72; mean age: 54.4) before laparoscopic cholecystectomy. MRC imaging was obtained with a 3D Turbo Spin-Echo sequence (TR = 3000 ms, TE = 700 ms, Echo Train Length--128) with an acquisition time of 5 min 48 s. Diagnostic confirmation was obtained in all the cases at i.o. cholangiography. When a stone was detected it was removed by transcystic or transcholedochal approach. RESULTS: Eighteen of the 45 patients (40%) had CBD stones. MRC correctly evaluated 16 out of 18 stones, with a resulting sensitivity of 88.9%, specificity 100%, positive predictive value 100%, negative predictive value 90%, and accuracy 95.6%. CONCLUSIONS: Despite the good results of MRC, it cannot be proposed as a screening technique to be performed in all patients submitted to laparoscopic cholecystectomy due to high cost and the limited amount of MR equipment. In conclusion, only selected patients should be submitted to MRC before laparoscopic cholecystectomy.