Pilot study of an adult bowel management program for fecal incontinence.

OBJECTIVE: Bowel management programs are efficacious in pediatric patients with fecal incontinence or intractable constipation unresponsive to standard treatment. No studies have been done examining outcomes in adults. The objective of this study was to assess continence and quality of life outcomes in adults who have underwent bowel management program. METHODS: A retrospective review of patients 16 or older at the time they underwent a bowel management program for fecal incontinence or constipation was performed. Data collected included intake and follow-up stool and urinary continence, patient-reported outcomes measures (Cleveland Clinic Constipation Score, Baylor Continence Scale, Vancouver Symptom Score for Dysfunctional Elimination), and an age-adjusted health-related quality of life measure. RESULTS: The cohort included 38 patients with a median age of 19 years (range: 16-55) when they underwent our program. 50% of patients were female and the majority (33, 87%) were White. The most common diagnosis was anorectal malformation (16, 42%) followed by functional constipation (10, 27%). Stool continence rates improved after undergoing the program (52.7% prior to 87.6% at follow-up, p<0.01). There was significant improvement in the Baylor Continence Scale, Cleveland Clinic Constipation Score, and PedsQL (p<0.05). CONCLUSIONS: Adult patients who underwent a bowel management program for severe fecal incontinence or constipation show significant improvement in stool continence rates, patient-reported outcomes measures, and quality of life. A bowel management program (in-person or via telemedicine) is a feasible treatment strategy for adult patients who fail standard management of fecal incontinence or constipation and should be offered when appropriate. LEVEL OF EVIDENCE: III.

Antegrade continence enemas in children with functional constipation and dyssynergic defecation: Go or no go?

OBJECTIVE: To assess outcomes of children with functional constipation after antegrade continence enemas (ACEs) and determine if pre operative anorectal manometry (AMAN) findings, including dyssynergic defecation, are associated with outcomes. METHODS: A retrospective review of pediatric patients with functional constipation who received a Malone appendicostomy or cecostomy after failed medical management was conducted. Patients were included if they had AMAN data prior to their operation. Patients that underwent colonic resection were excluded. Demographics, clinical characteristics, manometry results, and post ACE outcomes were obtained. Descriptive statistics were performed. RESULTS: Thirty-nine patients were identified with median age at ACE of 8.9 years (IQR: 7.2-12.6) and median follow-up of 2.5 years (IQR: 1.8-3.2 years). Twenty patients (51%) were female and most (35, 92%) were White. All patients had severe constipation prior to ACE and 59% had fecal incontinence. Thirty-four patients (87%) received a Malone and 5 (13%) received a cecostomy. Post ACE, 35 (90%) were clean with daily flushes and 6 (15%) eventually successfully transitioned to laxatives only. Awake AMAN and balloon expulsion test were performed in 15 patients, with 14 (93%) displaying evidence of dyssynergic defecation. Twelve of 14 of patients (86%) with dyssynergia were clean with ACE at follow-up. because of the majority of patients being clean post ACE, there was limited power to detect predictors of poor outcomes. CONCLUSIONS: ACEs are successful treatment options for patients with severe constipation and fecal incontinence, including those with dyssynergic defecation. Larger studies are needed to identify factors predictive of poor outcomes. LEVEL OF EVIDENCE: III.

Predicting final lesion characteristics during MR-guided focused ultrasound pallidotomy for treatment of Parkinson's disease.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) ablation of the globus pallidus interna (GPi) is being investigated for the treatment of advanced Parkinson's disease symptoms. However, GPi lesioning presents unique challenges due to the off-midline location of the target. Furthermore, it remains uncertain whether intraprocedural MR thermometry data can predict final lesion characteristics. METHODS: The authors first performed temperature simulations of GPi pallidotomy and compared the results with those of actual cases and the results of ventral intermediate nucleus (VIM) thalamotomy performed for essential tremor treatment. Next, thermometry data from 13 MRgFUS pallidotomy procedures performed at their institution were analyzed using 46°C, 48°C, 50°C, and 52°C temperature thresholds. The resulting thermal models were compared with resulting GPi lesions noted on postprocedure days 1 and 30. Finally, the treatment efficiency (energy per temperature rise) of pallidotomy was evaluated. RESULTS: The authors' modeled acoustic intensity maps correctly demonstrate the elongated, ellipsoid lesions noted during GPi pallidotomy. In treated patients, the 48°C temperature threshold maps most accurately predicted postprocedure day 1 lesion size, while no correlation was found for day 30 lesions. The average energy/temperature rise of pallidotomy was higher (612 J/°C) than what had been noted for VIM thalamotomy and varied with the patients' skull density ratios (SDRs). CONCLUSIONS: The authors' acoustic simulations accurately depicted the characteristics of thermal lesions encountered following MRgFUS pallidotomy. MR thermometry data can predict postprocedure day 1 GPi lesion characteristics using a 48°C threshold model. Finally, the lower treatment efficiency of pallidotomy may make GPi lesioning challenging in patients with a low SDR.

Targeting of the dentato-rubro-thalamic tract for MR-guided focused ultrasound treatment of essential tremor.

BACKGROUND: Magnetic resonance-guided focused ultrasound ablation of the thalamic ventral intermediate nucleus is a safe and effective treatment for medically refractory essential tremor. However, indirect targeting of the ventral intermediate nucleus using stereotactic coordinates from normal neuroanatomy can be inefficient. We therefore evaluated the feasibility of supplementing this method with direct targeting of the dentato-rubro-thalamic tract. METHODS: We retrospectively identified four patients undergoing magnetic resonance-guided focused ultrasound ablation for essential tremor in which preoperative diffusion tractography imaging of the dentato-rubro-thalamic tract was fused with T2 weighted-imaging and utilized for intra-procedural targeting. The size and location of the dentato-rubro-thalamic tract and 24-hour lesion, as well as the center of the stereotactic coordinates, was evaluated. Finally, the amount of overlap between the dentato-rubro-thalamic tract and the lesion was calculated. RESULTS: The 24-hour lesion size was homogeneous in the cohort (mean 31.3 mm2, range 30-32 mm2), while there was substantial variation in the dentato-rubro-thalamic tract area (mean 14.3 mm2, range 3-24 mm2). The center of the stereotactic coordinates and dentato-rubro-thalamic tract diverged by more than 1 mm in mediolateral and anterposterior directions in all patients, while the dentato-rubro-thalamic tract and lesion centers were in close proximity (mean mediolateral separation 1 mm, range 0.1-2.2 mm; mean anteroposterior separation 0.75 mm, range 0.4-1.2 mm). There was greater than 50% coverage of the dentato-rubro-thalamic tract by the lesion in all patients (mean 82.9%, range 66.7-100%). All patients experienced durable tremor relief. CONCLUSION: Direct targeting of the dentato-rubro-thalamic tract using diffusion tractography imaging fused to T2 weighted-imaging may be a useful strategy for focused ultrasound treatment of essential tremor. Further investigation of the technique is warranted.

Effects of dietary Capsicum oleoresin on productivity and immune responses in lactating dairy cows.

This study investigated the effect of Capsicum oleoresin in granular form (CAP) on nutrient digestibility, immune responses, oxidative stress markers, blood chemistry, rumen fermentation, rumen bacterial populations, and productivity of lactating dairy cows. Eight multiparous Holstein cows, including 3 ruminally cannulated, were used in a replicated 4×4 Latin square design experiment. Experimental periods were 25 d in duration, including a 14-d adaptation and an 11-d data collection and sampling period. Treatments included control (no CAP) and daily supplementation of 250, 500, or 1,000 mg of CAP/cow. Dry matter intake was not affected by CAP (average 27.0±0.64 kg/d), but milk yield tended to quadratically increase with CAP supplementation (50.3 to 51.9±0.86 kg/d). Capsicum oleoresin quadratically increased energy-corrected milk yield, but had no effect on milk fat concentration. Rumen fermentation variables, apparent total-tract digestibility of nutrients, and N excretion in feces and urine were not affected by CAP. Blood serum ß-hydroxybutyrate was quadratically increased by CAP, whereas the concentration of nonesterified fatty acids was similar among treatments. Rumen populations of Bacteroidales, Prevotella, and Roseburia decreased and Butyrivibrio increased quadratically with CAP supplementation. T cell phenotypes were not affected by treatment. Mean fluorescence intensity for phagocytic activity of neutrophils tended to be quadratically increased by CAP. Numbers of neutrophils and eosinophils and the ratio of neutrophils to lymphocytes in peripheral blood linearly increased with increasing CAP. Oxidative stress markers were not affected by CAP. Overall, in the conditions of this experiment, CAP did not affect feed intake, rumen fermentation, nutrient digestibility, T cell phenotypes, and oxidative stress markers. However, energy-corrected milk yield was quadratically increased by CAP, possibly as a result of enhanced mobilization of body fat reserves. In addition, CAP increased neutrophil activity and immune cells related to acute phase immune response.

In vitro and in vivo antimutagenic effects of DIG, a herbal preparation of Berberis vulgaris, Taraxacum officinale and Arctium lappa, against mitomycin C.

DIG, a liquid herbal preparation made from a mixture of diluted mother tinctures of Berberis vulgaris, Taraxacum officinale and Arctium lappa, was assessed for its antimutagenic properties against mitomycin C. The micronucleus assay on Chinese hamster ovary (CHO)-K1 cells was used to evaluate the in vitro anticlastogenic activity of DIG compared to those of separately diluted mother tinctures. The micronucleus assay was performed on mouse erythrocytes and the comet assay was performed on mouse liver, kidney, lung, brain and testicles to assess the protective effects of DIG (0.2 and 2 % at libitum) against an intraperitoneal injection of mitomycin C (1 mg Kg(-1)) in mice. DIG exerted a powerful anticlastogenic activity, under both pretreatment and simultaneous treatment conditions as assessed by the micronucleus assay in CHO-K1 cells. Its protective activity was greater than that observed for each mother tincture. DIG reduced micronuclei levels in mouse erythrocytes and suppressed >80 % of DNA strand breaks in the liver, kidney, lung, brain and testicles of mice exposed to mitomycin C.

Immune and production responses of dairy cows to postruminal supplementation with phytonutrients.

This study investigated the effect of phytonutrients (PN) supplied postruminally on nutrient utilization, gut microbial ecology, immune response, and productivity of lactating dairy cows. Eight ruminally cannulated Holstein cows were used in a replicated 4×4 Latin square. Experimental periods lasted 23 d, including 14-d washout and 9-d treatment periods. Treatments were control (no PN) and daily doses of 2g/cow of either curcuma oleoresin (curcumin), garlic extract (garlic), or capsicum oleoresin (capsicum). Phytonutrients were pulse-dosed into the abomasum of the cows, through the rumen cannula, 2 h after feeding during the last 9 d of each experimental period. Dry matter intake was not affected by PN, although it tended to be lower for the garlic treatment compared with the control. Milk yield was decreased (2.2 kg/d) by capsicum treatment compared with the control. Feed efficiency, milk composition, milk fat and protein yields, milk N efficiency, and 4.0% fat-corrected milk yield were not affected by treatment. Rumen fermentation variables, apparent total-tract digestibility of nutrients, N excretion with feces and urine, and diversity of fecal bacteria were also not affected by treatment. Phytonutrients had no effect on blood chemistry, but the relative proportion of lymphocytes was increased by the capsicum treatment compared with the control. All PN increased the proportion of total CD4(+) cells and total CD4(+) cells that co-expressed the activation status signal and CD25 in blood. The percentage of peripheral blood mononuclear cells (PBMC) that proliferated in response to concanavalin A and viability of PBMC were not affected by treatment. Cytokine production by PBMC was not different between control and PN. Expression of mRNA in liver for key enzymes in gluconeogenesis, fatty acid oxidation, and response to reactive oxygen species were not affected by treatment. No difference was observed due to treatment in the oxygen radical absorbance capacity of blood plasma but, compared with the control, garlic treatment increased 8-isoprostane levels. Overall, the PN used in this study had subtle or no effects on blood cells and blood chemistry, nutrient digestibility, and fecal bacterial diversity, but appeared to have an immune-stimulatory effect by activating and inducing the expansion of CD4 cells in dairy cows. Capsicum treatment decreased milk yield, but this and other effects observed in this study should be interpreted with caution because of the short duration of treatment.

Terapia biológica em artrite reumatoide: novas perspectivas no controle e remissão / Biological therapy in rheumatoide arthritis: new perspectives in control and remission

O tratamento das doenças autoimunes sofreu grande avanço nos últimos anos. A artrite reumatoide, de etiologia desconhecida, porém com uma desregulação do sistema imunológico relacionada à sua eclosão e evolução, é hoje passível de tratamento, visando à remissão tanto clínica quanto das lesões estruturais. Além dos anti-inflamatórios e analgésicos utilizados para alívio dos sintomas, várias outras drogas, rotuladas de modificadoras do curso da doença (DMCDs), que visam controlar este distúrbio imunológico expresso pela atividade de diversos mediadores inflamatórios, estão contribuindo para a melhoria da qualidade de vida e do prognóstico dos pacientes.

Autoimmune diseases, as rheumatoid arthritis (RA) had a strong development in their treatment last years. Over the past years, the knowledge about the pathophysiological mechanism of RA has advanced dramatically, with the development of new classes of drugs and the implementation of different strategies of treatment and follow-up. Beside this new drugs, the associated use of the anti-inflammatory drugs, corticoids, sintetic or traditionals disease-modifying antirheumatic drugs allow control or suppress the disease activity giving a better quality of life and prognosis to the patients.

Genotoxic and clastogenic activity of saponins extracted from Nauclea bark as assessed by the micronucleus and the comet assays in Chinese Hamster Ovary cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Bark extracts of Nauclea latifolia, Nauclea diderrichii, Nauclea pobeguinii and Nauclea vandergutchii are used in traditional medicine in West and South Africa for the treatment of fevers, diarrhea and malaria. AIM OF THE STUDY: To estimate the possible long-term toxicity and genotoxicity of plant extracts (dichloromethane, methanol, water/methanol, water) and saponins. MATERIALS AND METHODS: The clastogenicity of plant extracts and saponins was assessed by the micronucleus assay performed on Chinese Hamster Ovary cells. The DNA-damaging activity of saponin mixture was assessed by the comet assay on Chinese Hamster ovary cells. RESULTS: Hydromethanolic extracts from Nauclea latifolia, Nauclea diderrichii and Nauclea pobeguinii exhibited a significant clastogenic/aneugenic activity without S9 mix. The hydromethanolic extract from Nauclea diderrichii was the most clastogenic/aneugenic fraction with a Minimal Active Concentration (MAC) of 23.1 µgm L(-1). It was submitted to a separation step leading to six main saponins identified as quinovic acid glycosides (saponins A, D, E, G, J, K). None of the isolated saponins exerted a significant clastogenic/aneugenic activity by the micronucleus assay, however a mixture made with equal quantities of each of the six saponins exhibited a direct genotoxic/clastogenic activity as assessed by both the micronucleus assay and the comet assay on Chinese Hamster Ovary cells. CONCLUSION: Saponins present in the hydromethanolic extracts of Nauclea induced synergistic in vitro DNA-damage and chromosome mutations in mammalian cells. This genotoxic activity was probably due to the capacity of Nauclea saponins to reduce cell defense against oxidative stress through the inhibition of glutathione-S-transferase activity.

Quantitative proton magnetic resonance spectroscopy detects abnormalities in dorsolateral prefrontal cortex and motor cortex of patients with frontotemporal lobar degeneration.

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease of the frontal and temporal neocortex. The single most common pathology underlying FTLD is neuronal degeneration with ubiquitin-positive but tau-negative inclusions consisting of Tar DNA binding proteins (TDP-43). Inclusions containing TDP-43 in neurons are also the most common pathology underlying motor neuron disease (MND). The present study tested the hypothesis that abnormal metabolite patterns within the dorsolateral prefrontal cortex (DLPFC) as well as the motor cortex (MC) may be observed in FTLD patients without motor disorders, using proton magnetic resonance spectroscopy ((1)H MRS). Twenty-six FTLD patients with cognitive damage and ten controls underwent multivoxel (1)H MRS. Absolute concentrations of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI) were measured from the DLPFC, the MC and the parietal cortex (PC, an internal control). Statistical analyses were performed for group differences between FTLD patients and controls. Comparisons were also made across brain regions (PC and DLPFC; PC and MC) within FTLD patients. Significant reductions in NAA and Cr along with increased Cho and mI were observed in the DLPFC of FTLD patients compared to controls. Significantly lower NAA and higher Cho were also observed in the MCs of patients as compared to controls. Within the FTLD patients, both the MC and the DLPFC exhibited significantly decreased NAA and elevated Cho compared to the PC. However, only the DLPFC had significantly lower Cr and higher mI. Abnormal metabolite pattern from the MC supports the hypothesis that FTLD and MND may be closely linked.

In vitro antifungal and antileishmanial activities of steroidal saponins from Allium leucanthum C. Koch -- a Caucasian endemic species.

Five steroidal saponins were isolated for the first time in the flower of Allium leucanthum C.Koch. In vitro antifungal and antileishmanial activities of pure compounds as well as crude extract, spirostanoid and furostanoid fractions were evaluated. Spirostanol saponins (25R),5alpha- spirostan -3beta,6beta- diol 3-0-{beta-D-glucopyranosyl-(1-->2)- 0-[beta-D-xylopyranosyl-(1-->3)]- 0-beta-D- glucopyranosyl -(1-->4)-beta-D- galactopyranoside } compound 3 were more antifungal active especially with a MCF ranging from 6,25 to 12,5 microg/ml on the most yeast stains tested. Spirostanol fraction was more active on amastigote forms of leishmania with IC(50) 0,9 microg/ml.

Effects of Leontice smirnowii tuber monodesmosides and crude extract in carrageenan- and histamine-induced acute inflammation model of rats.

Leontice smirnowii is a member of the Berberidaceae family. We have recently reported the 1,1-diphenyl-2-picryl-hydrazyl radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, reducing power and metal chelating activities of L. smirnowii products. In the current study we investigated the possible effects of the crude extracts of L. smirnowii (CELS) and the monodesmoside's purified extract (MPE) of L. smirnowii in the carrageenan- and histamine-induced acute inflammation models in rats. The experiment revealed that CELS and MPE have anti-inflammatory effects, dose dependently in carrageenan-induced acute inflammation. On the other hand, their proinflammatory effects were surprisingly observed, especially in low doses, in the histamine-induced acute inflammation model. Summarizing these data, we may state that CELS and MPE exert their anti-inflammatory effects via non-histaminergic pathways.

Screening of antiradical and antioxidant activity of monodesmosides and crude extract from Leontice smirnowii tuber.

Leontice smirnowii is a member of the Berberidaceae family. In the current study we investigated the possible antiradical and antioxidant activity of the monodesmosides (MLS) and crude extract (CELS) of Leontice smirnowii using different antioxidant tests: 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging, scavenging of superoxide anion radical-generated non-enzymatic system, ferric thiocyanate (FTC) method, reducing power, hydrogen peroxide scavenging and metal chelating activities. Experiment revealed that MLS and CELS have an antioxidant effect concentration-dependently. Total antioxidant activity was performed according to FTC method. At the 30mug/ml concentration, the inhibition effects of MLS and CELS on peroxidation of linoleic acid emulsion were found to be 95.3% and 95.6%, respectively. On the other hand, percentage inhibition of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), alpha-tocopherol and trolox were found to be 98.2%, 98.5%, 84.0% and 87.9% inhibition of peroxidation of linoleic acid emulsion, respectively, at the same concentration. In addition, MLS and CELS had effective DPPH radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, reducing power and metal chelating activities. Also, these various antioxidant activities were compared with BHA, BHT, alpha-tocopherol and trolox which were accepted as references antioxidants.

Amyotrophic lateral sclerosis: diffusion-tensor and chemical shift MR imaging at 3.0 T.

PURPOSE: To prospectively determine whether diffusion-tensor magnetic resonance (MR) imaging in conjunction with two-dimensional chemical shift imaging can assist in identifying upper motor neuron involvement and whether disease severity and duration can be predicted based on imaging parameters in patients with amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained for this HIPAA-compliant study. Fifteen patients with ALS (12 men, three women; mean age, 57.3 years) with clinical evidence of upper motor neuron involvement and 10 healthy control subjects (five men and five women; mean age, 49.4 years) were studied. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured from the corticospinal tracts at the level of the internal capsule. Average N-acetylaspartate (NAA)/creatine-phosphocreatine (Cr) and NAA/choline-containing compounds (Cho) ratios were calculated from the precentral gyrus. Student t test, multiple linear regression analysis, and Spearman correlation coefficients were employed to quantify relationships between imaging and clinical parameters. RESULTS: Patients with ALS exhibited significantly reduced FA values and NAA/Cr and NAA/Cho ratios compared with values in control subjects (P<.05) for both affected and nonaffected sides of the brain. ADC was elevated significantly in the affected side (P<.05) and was an independent predictor of disease duration after adjusting for age; however, FA values and NAA/Cr ratios for the affected side were even stronger predictors of disease duration. Moderate but statistically significant correlation was found between the FA values for the affected side and the ALS Functional Rating Scale Revised (ALSFRS-R) score (r=0.51, P<.05). The NAA/Cr ratio also correlated with both the ALSFRS-R and upper motor neuron scores (r=0.50 and 0.54, respectively; P<.05). CONCLUSION: Diffusion-tensor and two-dimensional chemical shift MR imaging spectroscopy can be used to identify upper motor neuron involvement and predict disease duration in patients with ALS.

Acute anti-inflammatory activity of four saponins isolated from ivy: alpha-hederin, hederasaponin-C, hederacolchiside-E and hederacolchiside-F in carrageenan-induced rat paw edema.

The anti-inflammatory potential of alpha-hederin (monodesmoside) and hederasaponin-C from Hedera helix, and hederacolchisides-E and -F (bidesmosides) from H. colchica was investigated in carrageenan-induced acute paw edema in rats. Saponins and indomethacin were given orally in concentrations of 0.02 and 20mg/kg body wt. For the first phase of acute inflammation, indomethacin was found as the most potent drug. Alpha-hederin and hederasaponin-C were found ineffective, while hederacolchisides-E and -F showed slight anti-inflammatory effects on the first phase. For the second phase of acute inflammation, indomethacin and hederacolchiside-F were determined as very potent compounds. alpha-hederin was found ineffective for the second phase, either. Despite hederasaponin-C and -E were found effective in the second phase of inflammation, they were not found as effective as indomethacin and hederacolchiside-F. As a conclusion, hederasaponin-C, -E and -F, may exert their anti-inflammatory effects by blocking bradykinin or other inflammation mediators. The latter affect may occur via affecting prostaglandin pathways. Regarding the structure activity relationship, it is likely that sugars at C3 position and Rha7-Glcl-6Glc moiety at C28 position are essential for the acute anti-inflammatory effect.

Acute and chronic antiinflammatory profile of the ivy plant, Hedera helix, in rats.

Hedera helix is a plant well-known as ivy or English ivy, and a member of the Araliaceae family. In the present study, we tested the possible antiinflammatory effects of a crude saponin extract (CSE) and a saponin's purified extracts (SPE) of Hedera helix in carrageenan- and cotton-pellet-induced acute and chronic inflammation models in rats. Both the CSE and SPE of Hedera helix were found to have antiinflammatory effects. The most potent drug screened was indomethacin (89.2% acute antiinflammatory effect), while the most potent extract screened was the CSE of Hedera helix at 100 and 200 mg/kg body wt. doses with 77% acute antiinflammatory effects. For testing chronic antiinflammatory (antiproliferative) effects, the cotton-pellet-granuloma test was conducted. Indomethacin was found to be the most potent drug in the chronic phase of inflammation, with 66% effect. The SPE of Hedera helix was more potent than the CSE in its chronic antiinflammatory effect (60% and 49%, respectively).

In vitro antileishmanial activity of three saponins isolated from ivy, alpha-hederin, beta-hederin and hederacolchiside A(1), in association with pentamidine and amphotericin B.

The in vitro antileishmanial activity of three saponins isolated from ivy, alpha-hederin, beta-hederin and hederacolchiside A(1), was investigated on parasites of the species Leishmania mexicana, in their promastigote and amastigote forms compared with their toxicity versus human monocytes. The results showed that saponins exhibited a strong antiproliferative activity on all stages of development of the parasite but demonstrated a strong toxicity versus human cells. Association of subtoxic concentrations of saponins with antileishmanial drugs such as pentamidine and amphotericin B demonstrated that saponins could enhance the efficiency of conventional drugs on both the promastigote and the amastigote stages of development of the parasite. The results demonstrated moreover that the action of saponins on promastigote membrane was cumulative with those of amphotericin B.

Rapid high-performance liquid chromatography analysis for the quantitative determination of oleuropein in Olea europaea leaves.

Olea europaea (Oleaceae) leaves of 14 different cultivars have been studied by a new isocratic HPLC method. Qualitative and quantitative determinations of principal compounds were established for each cultivar. Oleuropein concentration was determined for each sampled tree, using coumarin as internal standard. Bid el Haman, Chemlali, Meski, Cailletier, Tanche, a Verdale-Picholine hybrid, and Lucques, in particular, had high oleuropein concentrations and could be useful sources for industrial extractions.

Antileishmanial activity of three saponins isolated from ivy, alpha-hederin, beta-hederin and hederacolchiside A1, as compared to their action on mammalian cells cultured in vitro.

The in vitro antileishmanial activity of three saponins isolated from ivy, alpha-hederin, beta-hederin and hederacolchiside A1, was investigated on Leishmania infantum. The assessment of possible targets (membrane integrity, membrane potential, DNA synthesis and protein content) was performed in both Leishmania promastigotes and human monocytes (THP1 cells). Results observed in Leishmania showed that the saponins exhibited a strong antiproliferative activity on all stages of development of the parasite by altering membrane integrity and potential: hederacolchiside A1 appeared to be the most active compound against both promastigotes and amastigotes. Results observed in THP1 cells demonstrated that the saponins exerted also a potent antiproliferative activity against human monocytes, by producing a significant DNA synthesis inhibition. The ratio between antileishmanial activity on amastigotes and toxicity to human cells suggested that the saponins could be considered as possible antileishmanial drugs.