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.

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.

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.

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.

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.

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.

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.

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).

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.

The effect of bisbenzylisoquinoline alkaloids on Trypanosoma cruzi infections in mice.

Five bisbenzylisoquinoline (BBI) alkaloids, curine, cycleanine, isotet:andrine, limacine and pheanthine were tested for trypanocidal activity in C 3H He mice infected with Y or CL strain of Trypanosoma cruzi. The activity was compared with the baseline drug, benznidazole. Oral treatment was more effective with curine at 10 mg/kg or with cycleanine at 2 mg/kg daily for 10 days in mice infected with Y or CL strain. In these groups, the parasitemias were negative after 5-7 weeks after inoculation and mortality time 50 (MT(50)) was significantly higher than untreated mice. Benznidazole was effective in mice infected with CL strain but not in mice infected with Y strain. The other BBI showed a relative efficacy against both strains. The effect of BBI alkaloids could be due to a blocking of the Ca2+ channel for the regulation of T. cruzi infectivity to invade host cells or their selective immunosuppressive properties.

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.

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.

Activity of compounds isolated from Chilean lichens against experimental cutaneous leishmaniasis.

Three secondary metabolites isolated from Chilean lichens, (+) usnic acid, pannarine and 1'-chloropannarine, were tested against promastigotes forms of three strains of Leishmania ssp. Pannarine and 1'-chloropannarine exhibited in vitro activity at 50 micrograms/ml and (+) usnic acid at 25 micrograms/ml. BALB/c mice infected with Leishmania amazonensis were treated 4 weeks post-infection with (+) usnic acid by subcutaneous or oral routes for 15 days at 25 mg/kg or by five intralesional injections at interval of 4 days at 25 mg/kg of body weight. The reference drug, N-methylglucamine antimonate (Glucantime), was administered by subcutaneous injections (regimens of 28 mg of pentavalent antimony) for 15 days. The subcutaneous and oral treatments with (+) usnic did not produce any effect, but by intralesional administration we observed a significant effect that reduced by 43.34% the weight lesions and by 72.28% the parasites loads in infected footpads.

Leishmanicidal and trypanocidal activities of Bolivian medicinal plants.

Cutaneous and mucocutaneous leishmaniasis are endemic diseases in South America, especially in the subandean areas of the humid lowlands of Bolivia. Fourteen plants used topically in folk medicine to treat cutaneous leishmaniasis were collected in the tropical regions of colonization and in the rain forest occupied by Chimane Indians. Three of four plants used by the Chimane Indians exhibited an in vitro activity against three species of Leishmania. Two of ten plants used by the colonists showed an in vitro activity. We have also included results obtained with extracts from 53 Bolivian medicinal plants used for other diseases and from 43 plants collected with basis of chemotaxonomic criteria from all parts of Bolivia. All extracts were also screened in vitro against three strains of Trypanosoma cruzi (Trypanosomatidae), the causative agent of Chagas' disease.

Chemical constituents of essential oils of muña, Bolivian plants traditionally used as pesticides, and their insecticidal properties against Chagas' disease vectors.

The composition of essential oils from two muña, Bolivian medicinal plants, derived from Minthostachys andina and Hedomea mandonianum, were analyzed by gas chromatography/mass spectrometry. Major differences were observed in their chemical composition. Pulegone was the major component of H. mandonianum oil (44.6%) and M. andina oil (25.5%); menthone and isomenthone were around 33% of these oils. Differences were also observed in their insecticidal activity against the Chagas' disease vector, Rhodnius neglectus or Triatoma infestans bugs exposed on impregnated oil filter papers. While M. andina oil showed 30%-50% of mortality in both triatomine species after a period of 1 week, H. mandonianum oil did not show any insecticidal activity. Nevertheless, both species had insecticidal activity (33.3% and 50%) when oils were topically applied. The significance of these results is discussed in relation to the variability of the chemical composition and their potential use in Chasgas' disease vector control.

Mutagenicity, insecticidal and trypanocidal activity of some Paraguayan Asteraceae.

The insecticidal, moulting inhibition and trypanocidal effects of crude extracts of 7 Paraguayan Asteraceae were evaluated on Triatoma infestans and bloodstream forms of Trypanosoma cruzi, respectively. Both mutagenicity and toxicity were evaluated by sister chromatid exchange (SCE) in human peripheral lymphocyte culture and by the lethality test of Artemia salina. The ethanolic extracts from Chromolaena christieana (stem and bark), Achyrocline satureoides (leaves and flowers) and Mikania cordifolia (root and stem), at a concentration of 250 micrograms/ml, showed the highest percentage of lysis on bloodstream forms of Trypanosoma cruzi. The extracts of Chromolaena christieana and Achyrocline satureoides also presented high mutagenic and toxic capacity when they were evaluated by the SCEs assay and Artemia salina test, respectively. Insecticidal activity was only observed in the hexane extract of flowers of Achyrocline satureoides (45% of mortality), when 0.05 microgram of crude concentration was applied on Triatoma infestans. The ethanolic extracts of stem from Mikania cordifolia and Vernonia brasiliana inhibited the moulting of Triatoma infestans when it was compared with their controls. Since no ethnobotanical information on these plants has been found related to similar use in Paraguay, our findings suggest, for the first time, the potential anti-trypanocidal and moulting inhibition of these Asteraceae.

Biological and chemical studies of Pera benensis, a Bolivian plant used in folk medicine as a treatment of cutaneous leishmaniasis.

The stem barks of Pera benensis are employed by the Chimane Indians in the Bolivian Amazonia as treatment of cutaneous leishmaniasis caused by the protozoan Leishmania braziliensis. The chloroform extracts containing quinones were found active against the promastigote forms of Leishmania and the epimastigote forms of Trypanosoma cruzi at 10 micrograms ml-1. The activity guided fractionation of the extract by chromatography afforded active compounds. Their structures were elucidated, by spectral and chemical studies, as known naphthoquinones, plumbagin, 3,3'-biplumbagin, 8-8'-biplumbagin, and triterpene, lupeol. The activity in vitro of each compound was evaluated against 5 strains of Leishmania (promastigote), 6 strains of Trypanosoma cruzi (epimastigote) and the intracellular form (amastigote) of Leishmania amazonensis. The baseline drugs used were Glucantime and pentamidine (Leishmania spp.), nifurtimox and benznidazole (T. cruzi). Plumbagin was the most active compound in vitro. This study has demonstrated that Pera benensis, a medicinal plant used in folk medicine, is an efficient treatment of cutaneous leishmaniasis.

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.

[Active antihelminitic alkaloids: active in vitro against Leishmanic Tropica the protozoa involved in leishmaniasis]. / Activité antiparasitaire d'alcaloïdes bisbenzylisoquinoleiques. I: Activité in vitro sur des promastigotes de trois souches de Leishmania.

Leishmaniasis caused by protozoan Leishmania ssp., is an endemic parasitic disease in Central and South America. The chemotherapeutic agents against Leishmania ssp. (pentavalent antimony compounds, pentamidine and amphothericine B) are toxic and expensive products. Basing on the Bolivian folk medicine, we tried to find new active principles. Fourteen isoquinoline alkaloids, especially bisbenzylisoquinoline alkaloids extracted from Annonaceae, Berberidaceae, Hernandiaceae and Menispermaceae, demonstrate highly effective activity against this protozoan. Among them gyrocarpine, daphnandrine and obaberine seem to be of particular interest. The therapeutic effect was studied by biological assays on culture forms in vitro three strains of Leishmania, L. donovani, L. braziliensis (cutaneous and mucocutaneous leishmaniasis), L. mexicana amazonensis (cutaneous) and L. donovani (visceral leishmaniasis).