Finney and Jaboulay pyloroplasties for the treatment of benign gastric outlet lesions in dogs and cats: technique and outcome in 13 cases (2015-2024).

OBJECTIVES: To describe the use, complications and outcome of Finney or Jaboulay pyloroplasties for the treatment of benign gastric outlet lesions in dogs and cats. MATERIALS AND METHODS: The medical records of dogs and cats surgically treated with Finney or Jaboulay pyloroplasty for benign gastric outflow tract disease in three institutions between January 1, 2015 and August 31, 2023 were retrospectively reviewed. RESULTS: Eight dogs and five cats were diagnosed with benign obstructive or perforating gastric outlet lesions, including chronic hypertrophic pyloric gastropathy (n = 4), perforating pyloro-duodenal peptic ulcer (4), sub-obstructive pyloro-duodenal eosinophilic sclerosing fibroplasia (2) and antral or proximal duodenal obstructive mass (3). Nine cases were treated using hand-sewn Finney pyloroplasty and four cases were treated using stapled Jaboulay pyloroplasty. No major complications were recorded. Cases were followed for a median of 16.1 [11 to 29.6] months. At the last follow-up, the outcome was excellent in all cases, with no clinical signs recorded and no medical treatment required. CLINICAL SIGNIFICANCE: This case series suggests that Finney and Jaboulay pyloroplasties were safe and effective procedures for the surgical treatment of benign obstructive or perforating gastric outlet lesions in dogs and cats.

Feline ureteral rupture with para-ureteral urinomas following blunt trauma: clinical presentation and long-term outcome after treatment by urinary diversion for five cases from 2012 to 2019.

CASE HISTORY: Medical records were reviewed for cats that underwent surgical treatment of traumatic ureteral rupture (TUR) using urinary diversion procedures between 2012 and 2019. CLINICAL FINDINGS AND TREATMENT: Five cats had presented with injuries associated with road traffic accidents. These included three cats with abdominal hernias that required surgical management. At a median of 15 days after the accident, cats represented with lethargy, the presence of an abdominal mass or with lower urinary tract symptoms and in all cats contrast diagnostic imaging showed proximal unilateral TUR with associated para-ureteral urinoma. Four cats received subcutaneous ureteral bypass (SUB) device placement and one had ureteral anastomosis over a stent. Unilateral cyst-like retroperitoneal fluid consistent with para-ureteral urinoma was observed in all cats and a diffuse retroperitoneal haematoma was noticed in four cats. No immediate major complications occurred, and all cats had post-operative serum creatinine concentration within the reference interval. The cat that had received a ureteral stent subsequently required placement of a SUB following stent encrustation 15 months after surgery. Median follow-up time was 34 (min 28, max 58) months and renal function was normal in all cats at the last follow-up. CLINICAL RELEVANCE: Urinary diversion procedures provided long-term stable renal function following proximal TUR in these five cats. Delayed, subtle non-specific clinical signs subsequent to high-energy blunt trauma causing abdominal hernia and associated diffuse retroperitoneal haematoma, should raise suspicion of TUR. ABBREVIATIONS: AFAST: Abdominal focused assessment with sonography for trauma; SUB: Subcutaneous ureteral bypass; TUR: Traumatic ureteral rupture.

Treatment of urinary incontinence in a cat with genitourinary dysplasia using an urethral sphincter occluder.

A 2-year-old spayed female Maine Coon presented with urinary incontinence and recurrent urinary tract infection since 2 months of age. Clinical examination was unremarkable. Ultrasonography, CT and cystourethroscopy revealed urogenital abnormalities consistent with genitourinary dysplasia. Urethral pressure profilometry suggested urethral sphincter mechanism incompetence. Surgical placement of an artificial urethral sphincter occluder was performed. Mild decrease of urinary incontinence was observed 6 weeks postoperatively. Inflation of the occluder under urethral pressure profilometry was subsequently performed and resolved the incontinence. This is the first report to describe the use of urodynamic testing at the time of inflation of an artificial urethral sphincter occluder to adjust the degree of urethral occlusion.

Antileishmanial activity of a formulation of 2-n-propylquinoline by oral route in mice model.

2-n-propylquinoline is presently a drug-candidate for the treatment of visceral leishmaniosis in pre-clinical development. As this compound is in an oily state, it needs to be formulated and the objectives of this study are: to prepare a formulation; to demonstrate that the new salted formulation did not alter the activity of the active ingredient; and finally, that this activity was quite good compared to the reference oral drug, miltefosine. Therefore, a 2-n-propylquinoline formulation, as camphorsulfonic salt, was prepared and characterised. On the Leishmania donovani / Balb/c mice model, a treatment by oral route at 60 mmoles/kg/day for ten consecutive days with this formulation was compared to 2-n-propylquinoline alone and to miltefosine, the oral reference drug. The salt formulation did not alter the activity of the 2-n-propylquinoline. The formulation reduced the parasite burden of 76% compared to 89% for miltefosine (not significant). The characteristics of this formulation results in a suitable drugability of 2-n-propylquinoline for further studies.

Antifungal canthin-6-one series accumulate in lipid droplets and affect fatty acid metabolism in Saccharomyces cerevisiae.

The mechanism of action of antifungal canthin-6-one series was investigated in Saccharomyces cerevisiae. After a rapid uptake, a preferential accumulation of the drug within lipid droplets was observed. The antifungal action of canthin-6-one was found as reversible. Canthin-6-one did not exhibit affinity for sterols, and membrane ergosterol was not necessary for the antifungal activity since the MICs were similar on an ergosterol-deleted and the wild-type S. cerevisiae clones. Relative amount of unsaturated alkyl chain fatty acids was significantly enhanced suggesting a stimulation of desaturase enzyme systems. No synergistic effect was observed between canthin-6-one and amphotericin B, ketoconazole and caspofungine. Canthin-6-one should now be evaluated in vivo against fungal pathogens.

In vitro and in vivo antileishmanial efficacy of a new nitrilquinoline against Leishmania donovani.

The in vitro activity of a new analogue of 2-alkenylquinoline (2-nitrilquinoline or NQ) against Leishmania donovani was compared to oral reference drug miltefosine (HePC). IC(50) of NQ was found at 38.6 microM against promastigotes and 2.4 microM against intramacrophage amastigotes. In vivo evaluation in the L. donovani Balb/c mice model indicated that oral treatments at 12.5 and 25 mg/kg for 10 consecutive days significantly reduced the parasite burden in the liver by 68.9 and 68.5%, respectively. This activity was similar to those of HePC at 7.5 mg/kg for 10 days which reduced the parasite burden in liver by 72.5%. The present study shows the positive contribution of a nitril substitute being added into the alkenyl chain branched at the 2-position of the quinoline ring to the antileishmanial activity. In addition, any apparent toxicological disorder was observed during the experiments.

Larvicidal activity of Cybistax antisyphilitica against Aedes aegypti larvae.

The larvicidal activity against Aedes aegypti larvae of a stem wood hexane extract of Cybistax antisyphilitica was evaluated. Bioassay-guided fractionation of the crude extract, monitored by larvicidal assay, led to the isolation of a natural quinone identified as 2-hydroxy-3-(3-methyl-2-butenyl)-1.4-naphthoquinone (lapachol). This compound was quite potent against A. aegypti larvae (LC50 26.3 microg/ml).

Screening of New Caledonian and Vanuatu medicinal plants for antiprotozoal activity.

Sixty-seven extracts of 30 medicinal plants traditionally used in New Caledonia or Vanuatu by healers to treat inflammation, fever and in cicatrizing remedies were evaluated in vitro for their antiprotozoal activity against Leishmania donovani, Leishmania amazonensis and Trypanosoma cruzi. Among the selected plants, Pagiantha cerifera was the most active against both Leishmania species; four extracts were active against promastigotes of Leishmania donovani at EC(50) values inferior to 5 microg/ml. Garcinia pedicillata extract had an EC(50) value of 12.5 microg/ml against intracellular amastigotes of Leishmania amazonensis. Alone Amborella trichopoda reduced by more of 80% the trypomastigotes of Trypanosoma cruzi in the blood.

Screening of some New Caledonian and Vanuatu medicinal plants for antimycobacterial activity.

Twenty plants, belonging to sixteen families, used in traditional New Caledonian and Vanuatu medicine for treatment of symptoms potentially related to tuberculosis (cough, fever or inflammation) were screened for antimycobacterial activity. We also screened an original endemic plant, Amborella trichopoda, only member of the monogeneric family Amborellaceae and considered the most primitive living angiosperm. In total, 55 extracts were evaluated for inhibitory activity against Mycobacterium bovis BCG strain at a concentration of 100 microg/ml. Methanolic and dichloromethane extracts of Amborella trichopoda, Codiaeum peltatum, Myristica fatua, and essential oils Myoporum crassifolium showed an activity at this concentration. Methanolic extract of Amborella trichopoda fruits presented a significant activity with a minimal inhibitory concentration included between 1 and 2.5 microg/ml. In the same conditions, this activity was comparable with those of the reference drugs pyrazynamide and ethambutol, at 20 and 2.5 microg/ml, respectively.

Leishmanicidal activity of two canthin-6-one alkaloids, two major constituents of Zanthoxylum chiloperone var. angustifolium.

The crude alkaloidal extract of Zanthoxylum chiloperone stem bark exhibited in vitro activity against various strains of Leishmania ssp. at 100 microg/ml. Two active major constituents were isolated and identified as canthin-6-one and 5-methoxycanthin-6-one. The effect of these compounds was also tested in an in vivo assay using BALB/c mice infected with Leishmania amazonensis. The mice were treated for 5 weeks postinfection with these alkaloids by oral (14 days) or intralesional route (4 days) at 10 mg/kg daily. The reference drug, N-methylglucamine antimonate was administered by subcutaneous injections at 100 mg/kg for 10 days. Intralesional administration of canthin-6-one reduced the parasite burden but not significantly when it was compared with the untreated group, while the reference drug reduced by 91% the parasite loads in the lesion.

Experimental treatment of chronic Trypanosoma cruzi infection in mice with 2-n-propylquinoline.

It was reported previously that 2-n-propylquinoline was active against the epimastigote form of Trypanosoma cruzi. The effects of oral treatments with benznidazole and 2-n-propylquinoline were evaluated in Balb/c mice infected with T. cruzi chronically. The reference drug and 2-n-propylquinoline were administered 60 days post-infection for 30 days at 25 mg/mL. At 35 days post-treatment, the serological tests (ELISA) of the 2-n- propylquinoline-treated mice were significantly different from the controls (p = 0.01) and the benznidazole-treated mice (p = 0.03), while this was not the case at 85 days post-treatment. These results are encouraging for continuing the investigation of other analogues of 2-n-propylquinoline in experimental chronic Chagas' disease.

Actividad antipacudica y potenciación de lacloroquina con alcaloides aporfinicos in vitro / In vitro antimalarial activity and chloroquine potentiating action of aporphine alkaloids

Pregunta de investigación: ¿Los alcaloides aporfínicos tiene una actividad intrinseca antipalúdica, pueden potencializar la acitivad de la cloroquina y revertir la resitencia de Plasmodium falciparum?. OBjetivos: Determinar la actividad antipaludica intrinseca de 12 alcaloides aporfínicos, Determinar el nivel de su efecto, establecer si tiene efecto y de maduracion o ponteciación, sinergismo aditivo o de antagonismo con la cloroquina, Determinar qué alcaloide pueden provocar reversión de la resistencia a la cloroquina, Estudiar un posible mecanismo de acción. Lugar:IINSAD, IBBA. Métodos: Cultivo de estadios eritrocitarios de Plasmodium falciparum, evaluación de la actividad antipalúdica in vitro de los alcaloides aporfinicos usando varios métodos. Resutlados: Los alcaloides evaluados son menos acativos que la cloroquia sola, todos los alcaloides mostraron un claro efecto acumulativo, especialmente Glaucina fumarato, Los alcaloides asimilobina, isoboldina HCI, coridina y actinodafnia conbinados con lacloroquina mostraron un efecto antagónico hacia esta droga, losalcaloides nuciferina HCI, pachyconfina, cassiticina, presentan un efecto de potenciación a la cloroquina. Glaucina fumarato, lautotetanina e isocorytuberina mostraron un sinergismo aditivo a la cloroquina, Nuceferina HCI revierte la resisstencia de la cloroquina a 0.5ug/ml, pachyconfina a la concentraion de 2 ug/ml y cassyticina a 1 ug/ml, se evidenció que los alcaloides aorfinicos no perturban el mecanismo de transporte creado por los parásitos intraeritrocitarios. Conclusión: Los 12 alcaloides aporfinicos, no presentan una actividad mayor que la cloroquina, pero nuciferina HCI, pachyconfina y cassyticina convinados con esta 4 aminoquinolina, pueden potencializar su actividad y revertir la resitencia de cepas cloroquina-resistentes, la modalidad de acción de estos alcaloides es de tipo acumulativo y no perturban el mecanismo de transporte creado por los parásitos intraeritrocitarios.

Cohibins C and D, two important metabolites in the biogenesis of acetogenins from Annona muricata and Annona nutans.

Two new annonaceous acetogenins, cohibins C (1a) and D (1b), have been isolated by extensive chromatography of a hexane extract of Annona muricata seeds and a cyclohexane extract of Annona nutans root bark. Their structures have been established on the basis of spectral evidence (NMR, MS) and confirmed by chemical transformation into a pair of monotetrahydrofuran (mono-THF) acetogenins. The role of these compounds in the biogenesis of mono-THF acetogenins is discussed.

Bisbenzylisoquinoline alkaloids from Guatteria boliviana (Annonaceae).

Together with known alkaloids, five new bisbenzylisoquinoline derivatives were isolated from the stem bark of Guatteria boliviana (Annonaceae), puertogalines-A 1 and -B 2, (+)-guatteboline 3, philogaline 4 and (-)-antioquine 5. Their structures were elucidated by spectrometric methods and their antiparasitic activity was evaluated in vitro on Leishmania sp., Trypanosoma cruzi and Plasmodium falciparum. Their cytotoxic activity was also measured in KB cell line.

Efficacy of the bisbenzylisoquinoline alkaloids in acute and chronic Trypanosoma cruzi murine model.

We have shown previously that daphnoline and cepharanthine are active against Trypanosoma cruzi and inhibited trypanothione reductase. The effects of oral treatments with daphnoline, cepharanthine and benznidazole were examined in Balb/c mice infected with T. cruzi acutely and chronically. In acute infections, parasitaemia was significantly reduced in the daphnoline-treated mice compared with controls and benznidazole-treated mice. The parasitological cure rate was increased in mice treated with daphnoline. Fifty days after infection, the negative serological response in both models was significantly different for the three tested drugs. Daphnoline showed the highest negative serological rate (48%). In chronically infected mice treated with daphnoline, we were unable to detect parasites in 70% of mice. The results obtained of oral treatment of daphnoline suggest that this bisbenzylisoquinoline may be useful in the treatment of acute and chronic Chagas' disease. This was not seen with cepharanthine, an excellent trypanothione reductase inhibitor.

Stability of commercial solutions of 5-fluorouracil for continuous infusion in an ambulatory pump.

PURPOSE: The stability of 5-fluorouracil (FU) Roche solutions in a portable infusion pump under prolonged "in-use" conditions (32 degrees C, in the dark) was studied, especially with respect to the formation of the cardiotoxic compounds fluoroacetaldehyde (Facet) and fluoromalonic acid semialdehyde (FMASAld). METHODS: The solutions, prepared according to three protocols frequently used at the Anticancer Centre in Toulouse, were analysed by 19F NMR immediately after preparation (T0) and after 2, 3 or 10 days (TF) in the pump. RESULTS: The commercial solution already contained 64 fluorinated "impurities", among them fluoride ion (F-), FMASAld and Facet. The concentration of FU did not change significantly between T0 and TF, whatever the protocol. The levels of F- had not increased significantly after 2 or 3 days, but had increased by about 50% after 10 days. The increases in FMASAld levels were low (12-28%) albeit significant in the three protocols. The levels of Facet had increased by a factor of about 2 after 2 or 3 days, and by a factor of > 3 after 10 days. The levels of the other fluorinated compounds were constant during the first 2 or 3 days, but had increased by about 30% after 10 days. FU Dakota lyophilizates, analysed immediately after reconstitution, contained neither FMASAld nor Facet. After 2 days at 25 degrees C, low levels of FMASAld were present but Facet could still not be detected. CONCLUSION: This study showed that special attention must be paid to the risk of increasing concentrations of highly toxic FMASAld and Facet when FU is administered via a pump for long periods of time. It would be preferable not to exceed 3 days of treatment when patients receive FU from a portable infusion pump. This underlines the interest in using a lyophilized formulation of FU in clinical practice.

Synthesis and in vitro antiprotozoal activity of thiophene ring-containing quinones.

A series of quinones (3a-i, 4-9, 11) and aromatic compounds (2a, 2d, 2g) containing the thiophene ring were tested in vitro against the trypomastigote form of Trypanosoma cruzi and the promastigote forms of Leishmania. The quinones 3a-i, 4, 5a, b, 6 and 9 having the thiophene ring fused to a quinone nucleus were the most active members of the series. The electron affinities of the benzo[b]thiophene-4,7-quinones 3, evaluated by their LUMO energies and halfwave potentials, are reported.

Antiprotozoal activity of aporphine alkaloids isolated from Unonopsis buchtienii (Annonaceae).

On a preliminary screening, substantial leishmanicidal activity was observed for the petroleum ether and alkaloidal extracts of the stem bark of Unonopsis buchtienii, the alkaloids and sterols isolated from these were studied. Of the alkaloids, liriodenine exhibited the highest activity against Leishmania major and L donovani (IC100 = 3.12 micrograms/mL). On the other hand, O-methylmoschatoline and the petroleum ether extract without alkaloids showed an interesting in vitro activity against Trypanosoma brucei with an IC100 of 6.25 micrograms/mL. The highest cytotoxic activities were found with the petroleum ether extracts without alkaloids and with all alkaloids isolated (IC50 < 9 micrograms/mL for Vero cell line).

Acetogenins and other compounds from Rollinia emarginata and their antiprotozoal activities.

Bioactivity-directed fractionation of the MeOH extract of the stem barks of Rollinia emarginata resulted in the isolation of six compounds, four acetogenins, rolliniastatin-1, sylvaticin, squamocin, and rollidecin B, one lignan, lirioresinol B, and an oxoaporphine, liriodenin. Their structures were determined by spectroscopic analysis and their in vitro leishmanicidal and trypanocidal properties are reported.

Trypanocidal bisbenzylisoquinoline alkaloids are inhibitors of trypanothione reductase.

Eleven bisbenzylisoquinoline (BBIQ) alkaloids were studied for in vitro trypanocidal activity against trypomastigote forms of the Y strain of Trypanosoma cruzi. The inhibitory activity of these compounds against trypanothione reductase (TR), a target enzyme for chemotherapy against Chagas disease, was also studied. Six BBIQ alkaloids (antioquine, cepharanthine, daphnoline, limacine, cycleanine and (-) curine) displayed a 50% lethal concentration (LC50) against T. cruzi of less than 100 microM. Daphnoline and curine, with LC50 values of 10 microM, are attractive for further investigation as potential anti-Chagasic drugs. Kinetic analyses suggested the BBIQ alkaloids are mixed inhibitors of TR. These compounds are reasonably potent inhibitors of TR; the best TR inhibitor, cepharanthine, had an IC50 of 15 microM, which is in the same order of magnitude as its LC50 against T. cruzi. The similar magnitudes of the IC50 and LC50 values suggest that inhibition of TR could contribute to the trypanocidal activity exhibited by the BBIQ alkaloids.