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INTRODUCTION: Leak following bariatric surgery continues to be associated with morbidity and rarely mortality. With improvement in surgical techniques and stapler design, leak rates have reduced drastically. Intra-operative high pressure Methylene blue leak test (HPMB) is one of the techniques employed to confirm integrity of anastomoses and staple lines. Despite this, evidence for its use remains limited. We evaluated the role of HPMB in detecting and preventing leaks. METHODS: A retrospective cohort of consecutive patients who underwent primary or revisional Laparoscopic Sleeve Gastrectomy (SG) or Laparoscopic Roux-en-Y Gastric bypass (RYGB) under the care of five surgeons in three centres across Birmingham, UK, between 2012 and 2016 were assessed. All patients had routine HPMB at the end of the procedure. Demographics, HPMB positivity, and post operative leaks were recorded. RESULTS: 924 patients underwent bariatric surgery: 696(75.3%) RYGB, and 225(24.3%) SG. 85(9.2%) were revisional procedures. Two HPMB were positive, which necessitated staple or suture line reinforcement with sutures intra-operatively. The patients had an uneventful recovery. 5 patients had postoperative leaks, all of whom had negative intraoperative HPMB: 3 SG patients; and 2 RYGB patients (gastro-jejunostomy anastomotic leaks). There was no statistically significant relationship between positive HPMB and anastomotic leak (Fishers exact test; p = 1). CONCLUSION: Despite routine use of methylene blue dye test in 924 patients, there were only two positive tests. Whilst HPMB may demonstrate technical failure, this study suggests that there is no role for its routine use in primary bariatric surgery. Discontinuation of this practice would reduce risk of anaphylaxis to the dye, cost, and intra-operative time.

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INTRODUCTION The superior mesenteric artery (SMA) syndrome, or Wilkie's syndrome, is a rare cause of postprandial epigastric pain, vomiting and weight loss caused by compression of the third part of the duodenum as it passes beneath the proximal superior mesenteric artery. The syndrome may be precipitated by sudden weight loss secondary to other pathologies, such as trauma, malignancy or eating disorders. Diagnosis is confirmed by angiography, which reveals a reduced aorto-SMA angle and distance, and contrast studies showing duodenal obstruction. Conservative management aims to increase intra-abdominal fat by dietary manipulation and thereby increase the angle between the SMA and aorta. Where surgery is indicated, division of the ligament of Treitz, anterior transposition of the third part of the duodenum and duodenojejunostomy have been described. METHODS We present four cases of SMA syndrome where the intention of treatment was laparoscopic duodenojejunostomy. The procedure was completed successfully in three patients, who recovered quickly with no short-term complications. A fourth patient underwent open gastrojejunostomy (complicated by an anastomotic bleed) when dense adhesions prevented duodenojejunostomy. CONCLUSIONS The superior mesenteric artery syndrome should be considered in patients with epigastric pain, prolonged vomiting and weight loss. Laparoscopic duodenojejunostomy is a safe and effective operation for management of the syndrome. A multi-speciality team approach including gastrointestinal, vascular and radiological specialists should be invoked in the management of these patients.

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Four new terpenes including, two sandaracopimaradiene diterpenoids, ent-8(14),15-sandaracopimaradiene-2alpha,18-diol, and ent8(14),15-sandaracopimaradiene-2beta,18-diol, and two lanostane triterpenoids, 23-hydroxy-5alpha-lanosta 7,9(11),24-triene-3-one, and 5alpha-lanosta-7,9(11),24-triene-3alpha,23-diol, were isolated from the methanolic extract prepared from the leaves of G. rhopalocarpa together with the known steroid stigmasterol and the coumarin, scopoletin. The isolates showed weak antiprotozoal activity against Leishmania donovani promastigotes, and Trypanosoma brucei brucei blood stream trypomastigotes, and were devoid of interesting activity towards Plasmodium falciparum. The isolates did not show significant cytotoxic activity against KB cells.

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Crude ethanol extracts of 18 medicinal plants from Sierra Leone, West Africa were examined for antiplasmodial activity against Plasmodium falciparum, using an in vitro microtest. Eleven of these extracts were also screened for in vitro antiamoebic activity against Entamoeba histolytica. Only one plant extract, Triclisia patens (Menispermaceae) showed significant antiplasmodial activity (IC(50) = 8 microg/mL). None of the plant extracts was effective against Entamoeba histolytica.

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Bioactivity-directed fractionation of the CHCl3-MeOH extract of the leaves of Celaenodendron mexicanum by means of the brine shrimp lethality test and chromatographic techniques led to the isolation of three carboxylic acid triterpenes, the new tirucalla-type triterpene, 3 alpha-hydroxytirucalla-7,24Z-dien-26-oic acid, 3-oxotirucalla-7,24Z-dien-26-oic acid, and epi-oleanolic acid, and three biflavonoids amentoflavone, podocarpusflavone A, and podocarpusflavone B. Four non-active compounds friedelin, maytensifolin B, 3 beta-hydroxyfriedelan-16-one, and celaenodendrolide were also obtained. epi-Oleanolic acid was the most active against brine shrimps with LC50 value of 23.3 microM. In addition, all isolates were tested for in vitro antiprotozoal and cytotoxic activities. 3-Oxotirucalla-7,24Z-dien-26-oic acid and epi-oleanolic acid showed the highest activity against Leishmania donovani promastigotes with IC50 values of 13.7 and 18.8 microM, respectively. Only 3-oxotirucalla-7,24Z-dien-26-oic acid showed activity against Trypanosoma brucei brucei bloodstream forms with IC50 value of 16.8 microM.

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Bioactivity-guided fractionation of Stephania dinklagei yielded six compounds including, two zwitterionic oxoaporphine alkaloids, N-methylliriodendronine, and 2-O,N-dimethylliriodendronine, two oxoaporphine alkaloids, liriodenine, and dicentrinone, one aporphine alkaloid, corydine, and one anthraquinone, aloe-emodin. Apart from corydine, the isolates have not been reported as constituents of S. dinklagei. N-Methylliriodendronine, and 2-O,N-dimethylliriodendronine are reported for the first time as natural products. All isolated compound were tested for antiprotozoal activity and cytotoxic activities in vitro. N-Methylliriodendronine was the most active against L. donovani amastigotes (IC50 = 36.1 microM). Liriodenine showed the highest activity against Leishmania donovani, and Plasmodium falciparum with IC50 values of 26.16 and 15 microM, respectively. Aloe-emodin was the only compound active (IC50 = 14 microM) against T. b. brucei.

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Twenty-one alkaloids have been assessed for activities against Plasmodium falciparum (multidrug- resistant strain K1) in vitro; 18 of these are reported for the first time. Two protoberberine alkaloids, dehydrodiscretine and berberine, were found to have antiplasmodial IC(50) values less than 1 M, while seven alkaloids-allocrytopine, columbamine, dehydroocoteine, jatrorrhizine, norcorydine, thalifendine, and ushinsunine-had values between 1 and 10 M. These results are discussed in the context of structure-activity relationships. Compounds were also assessed for antiamoebic and cytotoxic activities, but none was significantly active except for berberine, which was moderately cytotoxic.

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The lupane-type triterpene betulinic acid was isolated from an ethanol extract of the root bark of the Tanzanian tree Uapaca nitida Müll-Arg. (Euphorbiaceae). The in vitro antiplasmodial IC50 values of betulinic acid against chloroquine resistant (K1) and sensitive (T9-96) Plasmodium falciparum were found to be 19.6 micrograms/mL and 25.9 micrograms/mL, respectively. The in vitro activities of several related triterpenes were also evaluated. Betulin was found to be inactive at 500 micrograms/mL for both K1 and T9-96. Ursolic acid exhibited IC50 values of 36.5 micrograms/mL and 28 micrograms/mL, and oleanolic acid exhibited IC50 values of 88.8 micrograms/mL and 70.6 micrograms/mL against K1 and T9-96, respectively. When betulinic acid was tested for in vivo activity in a murine malaria model (P. berghei) the top dosage employed of 250 mg/kg/day was ineffective at reducing parasitaemia and exhibited some toxicity. Betulinic acid has not previously been evaluated for in vivo activity. This is believed to be the first compound to be isolated from U. nitida.

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Methanol extracts prepared from various parts of Alstonia scholaris, A. macrophylla and A. glaucescens, collected from Thailand, have been assessed for antiplasmodial activity against multidrug-resistant K1 strain of Plasmodium falciparum cultured in human erythrocytes. Pronounced antiplasmodial activity was exhibited by methanol extract of the root bark of A. macrophylla with an IC50 value of 5.7 micrograms/ml. Thirteen indole alkaloids were isolated from the active extract. These alkaloids and a semisynthetic bisindole O-acetylmacralstonine were subsequently tested against the K1 strain of P. falciparum. Pronounced antiplasmodial activity was observed mainly among the bisindole alkaloids, particularly villalstonine and macrocarpamine with IC50 values of 0.27 and 0.36 microM, respectively. The potent alkaloids were further tested against T9-96, the chloroquine-sensitive strain of P. falciparum. It has been found that the active alkaloids, in contrast to chloroquine, have significantly higher affinity to the K1 strain than to the T9-96 strain.

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Malaria and other protozoal diseases continue to pose serious health problems world-wide. Resistance of the malaria parasites, Plasmodium spp., to drugs such as chloroquine (and, more lately, quinine) occurs with increasing frequency and underlies the necessity to develop new agents for malaria chemotherapy; in the case of diseases caused by species of Leishmania and Trypanosoma there has always been a marked paucity of effective drugs, particularly those with a wide safety margin and minimal or no undesirable side effects. Novel drugs, are required to help alleviate morbidity and mortality and to contribute to the world-wide control of these diseases, in part by helping to reduce the reservoirs of infection. Reliance upon plants for the treatment of disease is high in the developing world and such plants offer a source of new molecules. Research centered upon Plasmodium has produced a number of findings which now prompt the formulation of important questions which may influence and focus the direction of phytotherapy research in the future.

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A new benzoquinone (1-hydroxybenzoisochromanquinone) and benz [g]isoquinoline-5, 10-dione have been isolated from the woody parts of Psychotria camponutans, as a result of bioactivity-guided fractionation. The compounds were characterized by UV, IR, EI-mass, 1H-, and 13C-NMR, and HETCOR NMR spectroscopy. Both compounds, together with acetylbenzoisochromanquinone, showed in vitro strong activity against brine shrimp, KB cells, and chloroquine-resistant P. falciparum.

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Crithidia fasciculata was used to replace murine peritoneal wash cells as feeder cells for the adaptation of Plasmodium falciparum isolates to continuous culture in vitro, thus avoiding the need to sacrifice animals. Fourteen of 17 malaria parasite isolates in one study, and 12 of 12 isolates in a second study, were successfully adapted to continuous culture in the presence of C. fasciculata, while only 5 of 17 parallel control isolates in the first study, and 2 of 12 isolates in the second study, were adapted in the absence of any feeder cells. Biochemical assays were performed to investigate various hypotheses put forward to explain the mode of action of feeder cells. No effect of C. fasciculata feeder cells was observed on lactate removal, osmotic pressure, or glucose or amino acid content of the malaria culture media. This feeder cell system was shown to reduce the pH of the malaria culture medium. Neither this feeder system nor another system, murine peritoneal macrophages, had any effect on the cysteine content of the culture medium. C. fasciculata was shown to reduce the redox potential of the culture medium, as were other malaria growth enhancers including cysteine and glutathione. This effect on the redox potential of the culture medium is proposed to be a possible mode of action for the feeder cell systems studied.

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Twenty-four bisbenzylisoquinoline alkaloids were screened for antiplasmoidal, antiamoebic, and cytotoxic activities by use of in vitro microtests. Eight of the alkaloids had antiplasmodial activity, with a 50% inhibitory concentration (IC50) of less than 1 microM against a multidrug-resistant strain of Plasmodium falciparum (chloroquine had an IC50 of 0.2 microM). The three alkaloids most active against Entamoeba histolytica, aromoline, isotrilobine, and insularine, had IC50s of 5 to 11.1 microM (metronidazole had an IC50 of 1.87 microM). None of the 24 bisbenzylisoquinoline alkaloids exhibited significant cytotoxicity against the KB cell line, the most toxic being berbamine, with an IC50 of 17.8 microM (the IC50 of podophyllotoxin was 0.008 microM). Bisbenzylisoquinoline alkaloids merit further investigation as potential novel antimalarial agents.

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The bitter and related constituents have been isolated fromVernonia amygdalina (Compositae), a plant ingested by wild chimpanzees possibly suffering from parasite-related diseases in the Mahale Mountains National Park, Tanzania. Isolated from the plant were four known sesquiterpene lactones, seven new steroid glucosides, and two aglycones of the glucosides. The sesquiterpene lactones showed significant in vitro antischistosomal, plasmodicidal, and leishmanicidal activities. Antischistosomal activity was also found for the major steroid glucoside, vernonioside B1. A trend in the glucosides to show significant antischistosomal, plasmodicidal, and amebicidal activities when the sugar moiety was removed, was observed. Vernodalin, judged as the most significant constituent for antiparasitic activities in vitro, was tested for in vivo antischistosomal effect. It was, however, highly toxic to the cercaria-infected mouse. Chimpanzees have been only rarely observed to ingest anything but the pith of the young stem. The occurrence of vernonioside B1 and its aglycone vernoniol B1, the major constituents among the steroid-related constituents, were detected at significant levels in the pith. However, vernodalin was abundant only in the leaves and bark. Thus, chimpanzees at Mahale were hypothesized to control parasite-related diseases by ingesting the young pith of this tree containing steroid-related constituents.

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A review of the literature on Alstonia species indicates that evidence in support of their effectiveness in the treatment of malaria is controversial. The antiprotozoal activity of the major alkaloid present in Alstonia species, echitamine, was assessed in vitro against Plasmodium falciparum and Giardia intestinalis. Echitamine displayed little antiplasmodial activity, but two quinoline alkaloids from A. coriacea (corialstonine and corialstonidine) were found to have some activity against P. falciparum although this was approximately 10 times less than that of quinine. None of the three Alstonia alkaloids was active against G. intestinalis. These results are discussed in the context of previously published data.

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An aqueous decoction of the root bark of Uapaca nitida Müll-Arg. is currently used locally at the Benedictine Mission at Peramiho in Tanzania to treat malaria. We have now demonstrated that extracts of root bark and leaves of this tree are active against the multidrug-resistant K1 strain of Plasmodium falciparum in vitro. An ethanolic extract of root bark showed activity against P. berghei in mice but at a dose which also showed toxic effects. The use of this plant in treating malaria appears to be novel and further studies would be of value.

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