Treatment of ovarian cysts by laparoscopic surgery: a retrospective study of 40 cases

The ovarian cysts treatment has taken advantage of the improvement made on the operating laparoscopy, that gives progressively better results than those of the laparotomy. On the one hand, laparoscopic surgery reduces the traditional surgery constraints by giving an exact histologic diagnosis and a radical cyst treatment. On the other hand, it prevents against inherent recurrence related to a sample puncture, and en the same time diminish adhesion risks. The laparoscopy can treat all kind of histologic benign ovarian cysts. We report the first experience of the Maternité Universitaire des Orangers in treating ovarian cysts by laparoscopic surgery.     

Neurokinin A-induced guinea pig gallbladder contraction: Potential mechanism of action

The present study was performed to examine the mechanism of action of neurokinin A (NKA) on guinea pig gallbaldder smooth muscle. Muscle strips were prepared and mounted in 10 mL tissue bath containing Krebs' solution under 1 g tension. NKA induced a concentration-dependent increase in gallbladder muscle tension and reached a maximal response at 1 μM. The EC₅₀ value was approximately 30nM. Preincubation of the muscle strips with neurotoxins, tetrodotoxin (1 μM), or omega-conotoxin (0.1 μM) had no effect on the NKA contractile response. NKA-induced gallbladder contractions were insensitive to cyclooxygenase inhibitors (5 μM) piroxicam and indomethacin. In contrast, the calcium channel blockers verapamil and diltiazem (0.1–1 μM) significantly blocked the contractile response to NKA. The intracellular calcium chelator BAPTA/AM had no significant effect on NKA activity. The removal of extracellular calcium, however, completely abolished the contractile response of NKA. These data suggest that NKA has a direct contractile effect on guinea pig gallbladder smooth muscle, which is independent of prostaglandin release. The primary source of calcium involved in mediating the NKA contractile response is the extracellular pool, suggesting that NKA might act via activation of L-type voltage-operated calcium channels to mediate its action. © 1992 Wiley-Liss, Inc.     

The discovery of a new structural class of cyclin-dependent kinase inhibitors, aminoimidazo[1,2-a]pyridines

The protein kinase family represents an enormous opportunity for drug development. However, the current limitation in structural diversity of kinase inhibitors has complicated efforts to identify effective treatments of diseases that involve protein kinase signaling pathways. We have identified a new structural class of protein serine/threonine kinase inhibitors comprising an aminoimidazo[1,2-a]pyridine nucleus. In this report, we describe the first successful use of this class of aza-heterocycles to generate potent inhibitors of cyclin-dependent kinases that compete with ATP for binding to a catalytic subunit of the protein. Co-crystal structures of CDK2 in complex with lead compounds reveal a unique mode of binding. Using this knowledge, a structure-based design approach directed this chemical scaffold toward generating potent and selective CDK2 inhibitors, which selectively inhibited the CDK2-dependent phosphorylation of Rb and induced caspase-3-dependent apoptosis in HCT 116 tumor cells. The discovery of this new class of ATP-site-directed protein kinase inhibitors, aminoimidazo[1,2-a]pyridines, provides the basis for a new medicinal chemistry tool to be used in the search for effective treatments of cancer and other diseases that involve protein kinase signaling pathways.     

β2-Adrenoceptors mediate inhibition of carbachol-induced contraction and cAMP generation in isolated smooth muscle cells from rabbit gastric antrum

The regulation of inhibition of carbachol-induced contraction by β-adrenoceptors of rabbit gastric antrum has been investigated. A functional assay using isolated smooth muscle cells (ISMC) was used to study the effect of β-adrenergic agonists and antagonists on carbacholcontracted ISMC and cAMP generation. The nonselective β-adrenergic agonist isoproterenol caused concentration-related inhibition of carbachol-induced contraction associated with a significant increase in cellular cAMP. The EC₅₀ for the effect of isoproterenol on cell inhibition of carbachol-induced contraction was closely related to the EC₅₀ for cAMP formation; the two curves were superimposable, indicating a positive correlation between the biological activity (inhibition of carbachol-induced contraction) and the intracellular event (cAMP formation) caused by the activation of β-adrenoceptors. The Kinetic studies demonstrate that maximum inhibition of carbachol-induced contraction and a parallel elevation of intracellular cAMP content were reached at 30 sec of incubation with isoproterenol. The β₂-selective receptor agonist terbutaline induced inhibition of carbachol-induced contraction of carbachol-contracted ISMC and cAMP generation. However, the relatively β₁-selective receptor agonist norepinephrine had no significant effect. Propranolol, a nonselective β- adrenoceptor antagonist (β₁ and β₂) caused a significant inhibition of the carbacholβ₂ induced contraction and rise in cAMP induced by isoproterenol and terbutaline, while the β₁-selective adrenergic receptorantagonist metoprolol, even at higher concentration, was inactive. These data demonstrate that there is a correlation between inhibition of carbachol-induced contraction and cAMP generation upon activation of the β₂-adrenoreceptors in the ISMC of rabbit gastric antrum. © 1992 Wiley-Liss, Inc.     

Liposarcoma of the thumb

Liposarcoma is the most common malignant deep soft-tissue tumor in adults. however, primitive cutaneous liposarcoma is very rare. We report the observation of a patient who presents a liposarcoma of the thumb.     

Pyrrolizidine esters and amides as 5-HT4 receptor agonists and antagonists

A series of pyrrolizidine esters, amides, and ureas was prepared and tested for 5-HT(4) and 5-HT(3) receptor binding, 5-HT(4) receptor agonism in the rat tunica muscularis mucosae (TMM) assay, and for 5-HT(3) receptor-mediated functional antagonism in the Bezold-Jarisch reflex assay. Several pyrrolizidine derivatives were identified with high affinity for the 5-HT(4) receptor, including benzamide 12a (SC-53116), a potent and selective 5-HT(4) partial agonist that exhibits efficacy in promoting antral contractions and activity in promoting gastric emptying in canine models. Also discovered were 5-HT(4) receptor antagonists, including imidazopyridine amide 12h (SC-53606), which is a potent and selective 5-HT(4) receptor antagonist with a pA(2) value of 8.13 in the rat TMM assay. N-Methyl indole ester 13d was identified as a potent 5-HT(4) antagonist with a pA(2) value of 8.93. High selectivity was observed for these pyrrolizidine derivatives versus other monoamine receptors, including 5-HT(1), 5-HT(2), D(1), D(2), alpha(1), alpha(2), and beta receptors.