Chronic acalculous cholecystitis and biliary dysfunction: how does clinical diagnosis affect management?

Similar abdominal pain of biliary type in functional disorders of biliary tract and chronic acalculous cholecystitis causes objective difficulties to differentiate not only between each other, but also with other diseases of gastrointestinal tract. The clinical picture is so homogeneous and difficult to distinguish from cholelithiasis that some patients undergo unreasonable surgical interventions for CAC and FDBT. Individual publications pushing for such an aggressive strategy are sporadic and need to be clarified in larger studies. The first choice drugs for treatment of FDBT are spasmolytics; ursodeoxycholic acid drugs are used as adjuvant agents. In CAC, the initial therapy will be similar, but the treatment regimen can be expanded with targeted etiotropic (if the cause of cholecystitis is identified – giardiasis, opisthorchiasis, etc.) or empirical antimicrobial/antiparasitic therapy. The greatest interest today is caused by hymecromone – a drug with proven by both experimental and controlled studies combined choleretic, selective spasmolytic action, mediated effect of reducing bile lithogenicity and possible anti-inflammatory action. Hymecromone effectively relieves biliary pain without causing gallbladder contractions, which determines the possibility of its wide application both in CAC and FDBT, both in monotherapy and in combination with other agents, primarily with UDCA. In this article the issues of optimization of diagnostic and therapeutic strategy of management of patients with biliary pain to avoid unreasonable cholecystectomies in acalculous diseases of the biliary tract are considered.

A Probe into Prohealing Potential of Glyceryl Trinitrate

Wound healing is a complex, delicate process which consists of series of cellular and biochemical events leading to re-establishment of anatomical continuity. Anal fissure is a painful, chronic, non-healing wound. Its chronicity is due to spasm of anal sphincter and local ischemia. It is treated surgically by sphincterotomy to eliminate sphincter spasm. Therefore, Glyceryl trinitrate(GTN) has been used as a non-surgical alternative treatment due to its spasmolytic activity. The present study was undertaken to determine wound healing potential of GTN in wistar rats. 18 male wistar rats were divided in three groups, 6 rats per group Control (Normal saline), GTN, GTN Ointment base. A 500 mm2 excisional wound , circular in shape was created . The drugs were applied topically over the wound, one day after the wounding. Two parameters were studied viz; wound contraction and period of epithelization. Glyceryl trinitrate has shown statistically signfiicant difference in wound contraction compared to control on 10th day. Period of epithelization was not reduced significantly by Glyceryl trinitrate when compared to Control. Glyceryl trinitrate has wound healing potential apart from its spasmolytic action.

Spasmolytic Action of Preparations and Compounds from Hofmeisteria schaffneri

Hofmeisteria schaffneri is used in Mexican folk medicine for treating painful gastric complaints. Therefore, in this paper the smooth muscle relaxant effect of the essential oil, and an infusion of the whole plant were evaluated using the gastrointestinal transit test in mice. The results revealed that both preparations at 316 mg/kg inhibited gastrointestinal transit by 47.5 and 52.1%, respectively. The common component of the infusion and essential oil was 8,9-epoxy-10-acetoxythymol angelate (2), which inhibited the gastrointestinal transit by 53.4% at a dose of 31.6 mg/kg. An HPLC-UV method was developed and validated to quantify 2. The chromatographic conditions were: A LiChrospher® 100 RP-18 column (250 × 4 mm i.d., 5 μm) with a mobile phase composed of CH3CN-H2O, in a gradient run at a flow rate of 0.6 mL/min, using a wavelength of 215 nm. The method was linear, precise, accurate, and showed excellent recovery. According to the results, compound 2 can be used as a marker for the quality control procedures of the crude drug of H. schaffneri.

Spasmolytic Action of the Methanol Extract and Isojuripidine from Solanum asterophorum Mart. (Solanaceae) Leaves in Guinea-Pig Ileum

Solanum asterophorum Mart. (Solanaceae) is a shrub popularly known as “jurubeba-defogo” in the northeast of Brazil. In the present work, the methanol extract (SA-MeOH, 3-750 μg/mL) and isojuripidine (10-7 - 3 x 10-4 ᴍ), a steroidal alkaloid obtained from S. asterophorum Mart. leaves, inhibited phasic contractions induced by both 1 μᴍ histamine [IC50 = (225.8 ± 47.4) μg/mL and (3.5 ± 0.8) x 10-5 ᴍ] or 1μᴍ acetylcholine [IC50 = (112.5 ± 20.6) μg/mL and (2.3 ± 0.4) \ 10-5 ᴍ] in guinea-pig ileum, respectively. The extract and isojuripidine also relaxed the ileum (SA-MeOH, 1-750 μg/mL, and isojuripidine, 10-9 - 3 x 10-4 ᴍ) pre-contracted with 1 μᴍ histamine [EC50 = (101.1 ± 17.4) μg/mL and (1.2 ± 0.3) x 10-6 ᴍ] or 1 μm acetylcholine [EC50 = (136.8 ± 21.1) μg/mL and (1.9 ± 0.4) x 10-6 ᴍ] or 40 mᴍ KCl [EC50 = (149.4 d 19.5) μg/mL and (1.8 ± 0.7) x 10-6 ᴍ], respectively, in an equipotent and concentration-dependent manner. This effect is probably due to inhibition of calcium influx through voltage-operated calcium (Cav) channels. To confirm this hypothesis, we evaluated their effect on cumulative CaCl2 curves in depolarizing medium nominally without Ca2+. SA-MeOH (27, 243, 500, and 750 μg/mL) and isojuripidine (3 x 10-8, 10-6, 3 x 10-5, and 3 x 10-4 m) inhibited the contractions induced by CaCl2, in a concentrationdependent manner. The concentration-response curves to CaCl2, in the presence of SAMeOH and isojuripidine, were shifted downward in relation to a control curve in a nonparallel manner resulting in reduction of the maximum effect [Emax = (71.2 ± 9.2); (57.4 ± 9.2); (43.8 ± 3.4); (41.5 ± 2.4) and (90.6 ± 4.8); (74.7 ± 8.7); (66.4 ± 3.9); (31.3 ± 4.1)%, respectively]. SA-MeOH and isojuripidine present spasmolytic action in guinea-pig ileum due to a partially blockade of calcium influx through Cav channels.

Spasmolytic Action of Diplotropin, a Furanoflavan from Diplotropis ferruginea Benth., Involves Calcium Blockade in Guinea-Pig Ileum

Diplotropis ferruginea Benth. (Fabaceae) is a tree popularly known in Northeastern Brazil as “sucupira-preta”. In the present work, the isolation, identification and pharmacological activity of a furanoflavan-type flavonoid (2,3-trans-3,4-trans)-3,4,5,8-tetramethoxy-(6,7,2”,3”)-furanoflavan, which received the trivial name diplotropin is reported. The structure was determined by means of spectroscopic techniques, especially EIMS and 1D and 2D NMR. Diplotropin (10−8 −3 · 10−4 M) inhibited the phasic contractions induced by both acetylcholine (IC50 = 4.6±0.8 · 10−5 M) and histamine (IC50 = 2.3±1.1 · 10−5 M) in guinea-pig ileum. Diplotropin relaxed the ileum pre-contracted with KCl (EC50 = 3.9±1.1 · 10−6 M), acetylcholine (EC50 = 3.7±1.6 · 10−6 M) and histamine (EC50 = 4.4±1.4 · 10−5 M) in a concentration-dependent manner. As the maintenance of tonic contraction induced by these contractile agents involves Ca2+ influx through voltage-dependent Ca2+ channels, it is suggestive that this relaxation may be due to the blockade of Ca2+ influx through those channels. This hypothesis was confirmed by the observation that diplotropin antagonized (pD’2 = 4.83±0.37) CaCl2 induced contractions in Ca2+-free depolarizing medium (IC50 = 1.5±0.8 · 10−5 M).