Safety and effectiveness of amphotericin B deoxycholate for the treatment of visceral leishmaniasis in Uganda

Between September 2003 and April 2004, the supply of antimonial drugs to Amudat Hospital, in north-eastern Uganda, was interrupted and all cases of visceral leishmaniasis presenting at the hospital could only be treated with amphotericin B deoxycholate (AmB). This allowed the safety and effectiveness of the AmB to be evaluated, in comparison with an historical cohort of patients treated, at the same hospital, with meglumine antimoniate (Sb-V). Demographic and clinical data were collected before and after treatment. Adverse effects were recorded passively in all the subjects, and actively, using a standardized questionnaire, in a sub-group of the patients given AmB. The in-hospital case-fatality 'rates' were 4.8% [95% confidence interval (CI) =2.4%-8.8%] among the 210 patients treated with AmB and 3.7% (CI=1.4%-7.9%) among the 161 patients treated with Sb-V (P>0.20). Adverse effects requiring treatment interruption were rare in both cohorts. Treatment failures (i.e. non-responses or relapses) were observed in 2.9% (CI= 1.2%-6.4%) of the patients treated with AmB and 1.2% (CI=0.1%-4.4%) of the patients treated with Sb-V (P>0.20). For the treatment of visceral leishmaniasis in Uganda, AmB therefore had a similar effectiveness and safety profile to that of meglumine antimoniate.

Antimoniais empregados no tratamento da leishmaniose: estado da arte

Antimony preparations are the drugs of choice for the treatment of leishmaniasis over 90 years, a disease that currently affects 12 million people worldwide. Its introduction was based on 19th century concepts of therapeutic effects of metal salts as arsenicals and other metals, most of them abandoned due to toxic effects or better drugs. In the last three decades, there was a great improvement in the knowledge of cell biology and immunology of those infections, but chemotherapy has not been improved in the same strength. The structure and mechanism of action of the two pentavalent antimonial drugs of choice, meglumine antimoniate and sodium stibogluconate, are not well known and the contamination of those pharmaceutical by toxic contaminants have been verified.

Combination of pulsed corona discharge with TiO2 photocatalysis: verification of hypothesis

The oxidation potential of pulsed corona discharge concerning aqueous impurities is limited in respect to certain refractory compounds. This may be enhanced in combination of the discharge with catalysis/photocatalysis as developed in homogeneous gas-phase reactions. The objective of the work consists of testing the hypothesis of oxidation potential enhancement in combination of the discharge with TiO2 photocatalysis applied to aqueous solutions of refractory oxalate. Meglumine acridone acetate was included for meeting the practical needs. The experimental research was undertaken into oxidation of aqueous solutions under conditions of various target pollutant concentrations, pH and the pulse repetition rate with plain electrodes and the electrodes with TiO2 attached to their surface. The results showed no positive influence of the photocatalyst, the pollutants were oxidized with the rate identical within the accuracy of measurements. The possible explanation for the observed inefficiency may include low UV irradiance, screening effect of water and generally low oxidation rate in photocatalytic reactions. Further studies might include combination of electric discharge with ozone decomposition/radical formation catalysts.

Distribution of liposome-encapsulated antimony in dogs

The achievement of complete cure in dogs with visceral leishmaniasis is currently a great challenge, since dogs are the main reservoir for the transmission of visceral leishmaniasis to humans and they respond poorly to conventional treatment with pentavalent antimonials. In order to improve the efficacy of treatment, we developed a novel formulation for meglumine antimoniate based on the encapsulation of this drug in freeze-dried liposomes (LMA). The aim of the present study was to evaluate the biodistribution of antimony (Sb) in dogs following a single intravenous bolus injection of LMA. Four healthy male mongrel dogs received LMA at 3.8 mg Sb/kg body weight and were sacrificed 3, 48 and 96 h and 7 days later. Antimony was determined in the blood, liver, spleen and bone marrow. In the bone marrow, the highest Sb concentration was observed at 3 h (2.8 µg/g wet weight) whereas in the liver and spleen it was demonstrated at 48 h (43.6 and 102.4 µg/g, respectively). In these organs, Sb concentrations decreased gradually and reached levels of 19.1 µg/g (liver), 28.1 µg/g (spleen) and 0.2 µg/g (bone marrow) after 7 days. Our data suggest that the critical organ for the treatment with LMA could be the bone marrow, since it has low Sb levels and, presumably, high rates of Sb elimination. A multiple dose treatment with LMA seems to be necessary for complete elimination of parasites from bone marrow in dogs with visceral leishmaniasis.

Ionic radiocontrast inhibits endothelium-dependent vasodilation of the canine renal artery in vitro: possible mechanism of renal failure following contrast medium infusion

To determine if radiocontrast impairs vascular relaxation of the renal artery, segments (4-5 mm in length) of canine renal artery were suspended in vitro in organ chambers to measure isometric force (95% O2/5% CO2, at 37ºC). Arterial segments with and without endothelium were placed at the optimal point of their length-tension relation and incubated with 10 µM indomethacin to prevent synthesis of endogenous prostanoids. The presence of nonionic radiocontrast (iohexol, Omnipaque 350, 1 ml in 25 ml control solution, 4% (v/v)) did not alter endothelium-dependent relaxation to acetylcholine in rings precontracted with both norepinephrine and prostaglandin F2alpha (N = 6). When the rings were precontracted with prostaglandin F2alpha, the presence of ionic contrast did not inhibit the relaxation of the arteries. However, in canine renal arteries contracted with norepinephrine, the presence of ionic radiocontrast (diatrizoate meglumine and diatrizoate sodium, MD-76, 1 ml in 25 ml control solution, 4% (v/v)) inhibited relaxation in response to acetylcholine, sodium nitroprusside (N = 6 in each group), and isoproterenol (N = 5; P < 0.05). Rings were relaxed less than 50% of norepinephrine contraction. Following removal of the contrast, vascular relaxation in response to the agonists returned to normal. These results indicate that ionic radiocontrast nonspecifically inhibits vasodilation (both cAMP-mediated and cGMP-mediated) of canine renal arteries contracted with norepinephrine. This reversible impairment of vasodilation could inhibit normal renal perfusion and act as a mechanism of renal failure following radiocontrast infusion. In the adopted experimental protocol the isoproterenol-induced relaxation of renal arteries precontracted with norepinephrine was more affected, suggesting a pivotal role of the cAMP system.

Surgical treatment of gynaecomastia in a Saanen goat

Background: Gynaecomastia in male goats is characterized by abnormal development of the mammary gland. Enlarged udder may be observed cranially to the scrotum, which can occasionally reach the size of the testicles. The udder may carry functional glands and impair the animal's reproductive performance and welfare. The case of a successful surgical treatment of gynaecomastia in a high reproductive performance Saanen buck-goat is reported in the present study.Material, Methods & Results: The animal was admitted presenting significant augmentation of the mammary glands, which was clinically diagnosed as gynaecomastia. The male goat owned optimal phenotypic characteristics for the Saanen breed, which had been producing high performance descendents. The mammary glands had been impairing the goat's locomotion and sexual performance. Manual milking resulted in great amount of milk secretion. The animal presented anorexia and impaired sexual performance. After clinical and laboratorial evaluation, the animal was submitted to radical mastectomy. An elliptic skin incision was performed around each mammary gland. Subcuticular blunt dissection was accomplished to isolate the mammarian tissue from the abdominal muscular layer and the spermatic chord. The excised mass was sampled for histological assessment. Subcuticular layer and skin closure was carried in a routine fashion. Hygienization of the surgical wound was performed with 2,5% PVP-I solution for ten days. Additionally, an association of penicillin G benzathine and streptomycin, and fluxinin meglumine were also given. The surgical procedure was successfully accomplished without any peroperative complication. The excised mass was sampled for anatomic/histological assessment. Macroscopically, the left mammary gland presented 22 cm in length, 12 cm wide and 26 cm in diameter. The right gland presented 16 cm in length, 7 cm wide and 13,5 cm in diameter. The microscopic assessment revealed hyperplasia of the glandular ducts. No abnormalities resembling malignant mammary neoplasms or degeneration were observed. At the end of the treatment, the animal was completely recovered. The animal convalesced satisfactorily and surgical wound healed completely within the first 10 days post-op. The goat was not culled and returned to normal reproductive activity. Within 12 months of follow-up, the animal was able to produce high milk yield performance progenies.Discussion: This case report presented relevant aspects of the surgical management of gynaecomastia, especially to veterinary practitioners dealing with milk goats. Gynaecomastia is not as common as other reproductive disorders in domestic animals. In opposition to the findings of the present study, other trials revealed that gynaecomastia usually does not affect fertility, libido, ejaculate parameters and sexual performance of goats. However, it is important to consider that neoplasic disorders such as mammary adenocarcinoma may be present, even though these are rare complications. Last but not least, the decision making on mastectomy in the present study was crucial in order to reestablish the animal's welfare and its functionality in the farms reproduction program.

Tratamento da leishmaniose cutanea difusa (LCD) com a associacao antimoniato-N-metilglucamina (Glucantime®) e sulfato de paramomicina (Gabbrox®)

Diffuse cutaneous leishmaniasis (DCL) is a rare form of tegumentary leishmaniasis (TL) and 350 cases have been reported world wide. Presently in Brazil, there were 31 cases reported corresponding to 8.9% of the world cases. The state of Maranhao contributed with ten cases (32.3%) of national reports. Recently the authors had opportunity to follow two new cases of DCL, both from the countryside of that state totaling 12 cases. The parasite Leishmania L. amazonensis was incriminated in the disease, confirming the available data as being the unique species to produce DCL in this state. The therapy associating meglumine anthimoniate with paramomicine sulphate (Gabbrox®) during 90 days, showed good tolerance and favorable response, being another option for fills form of DCL that constituted a challenge to science so far.

Amphibian secretions for drug discovery studies: A search for new antiparasitic and antifungal compounds

The antiparasitic and antifungal activities of nine amphibian skin secretions were studied in different in vitro models. Seven secretions presented a considerable antiprotozoan activity and one showed promising results against Candida sp. These results can be the basis for the development of new drugs, especially for neglected parasitic diseases. © 2007 Bentham Science Publishers Ltd.

Avaliação hematológica de cães naturalmente infectados por Leishmania (Leishmania) chagasi submetidos a tratamento com antimoniato de meglumina

The present research was carried out aiming to assess the hematological response of dogs with visceral leishmaniasis submitted to treatment. For this, seven animals naturally infected by Leishmania sp. were submitted to a treatment with 75 mg/kg meglumine antimoniate subcutaneously, 12-12h/3 weeks. In all animals, a complete blood count and bone marrow aspiration biopsy were carried out for a descriptive evaluation at up to seven moments: before the treatment, 30, 60, 90, 120, 150 and 180 days after the start of the treatment. Before the beginning of the experiment hematological alterations were observed in four of the seven dogs (57.1%), among them, nonregenerative anemia, lymphopenia, lymphocytosis and monocytosis. During the course of the experiment the occurrence of leukocytoses, such as left shift neutrophilia and eosinophilia, were observed in some of the animals. Before the beginning of the treatment (M1), the occurrence of erythrocytic hypoplasia was detected by bone marrow cytology in two of the dogs (28.6%). This was reversed through an increase in the amount of erythroid progenitor cells after the administration of meglumine antimoniate. Thus, it can be concluded that the treatment led to normalization of the hematological alterations and recovery of the bone marrow.

Avaliação clínica e parasitológica de cães naturalmente infectados por Leishmania (Leishmania) chagasi submetidos a tratamento com antimoniato de meglumina e alopurinol

Aiming to assess the efficacy of the treatment, to verify the occurrence of possible disease relapses and to search for the presence of parasites after the treatment, seven dogs naturally infected by Leishmania sp., were submitted to a treatment with meglumine antimoniate and allopurinol. For this, lymph node and bone marrow aspiration biopsies were carried out at seven moments. After the end of the six-month observation period all dogs were submitted to euthanasia. Then, spleen and liver imprints and in vitro cultures were carried out to search for amastigote forms of the parasite. All animals presented remission of the symptoms and during all the observation period no dog presented relapse of the disease, although amastigote forms of the parasite were observed in two of the animals at the end of the experiment. Thus, it was possible to conclude that the treatment promotes clinical healing but it does not eliminate the parasites completely.

Attitude of Brazilian veterinarians in the recognition and treatment of pain in horses and cattle

Objective: The objective of this study was to assess the use of analgesics, describe the attitudes of Brazilian veterinarians towards pain relief in horses and cattle and evaluate the differences due to gender, year of graduation and type of practice. Study design: Prospective survey. Methods: Questionnaires were sent to 1000 large animal veterinarians by mail, internet and delivered in person during national meetings. The survey investigated the attitudes of Brazilian veterinarians to the recognition and treatment of pain in large animals and consisted of sections asking about demographic data, use of analgesic drugs, attitudes to pain relief and to the assessment of pain. Descriptive statistics were used to analyze frequencies. Simple post hoc comparisons were performed using the chi-square test. Results: Eight hundred questionnaires were collected, but 87 were discarded because they were incomplete or blank. The opioid of choice for use in large animals was butorphanol (43.4%) followed by tramadol (39%). Flunixin (83.2%) and ketoprofen (67.6%) were the most frequently used NSAIDs by Brazilian veterinarians. Respondents indicated that horses received preoperative analgesics for laparotomy more frequently (72.9%) than cattle (58.5%). The most frequently administered preoperative drugs for laparotomy in horses were flunixin (38.4%) and xylazine (23.6%), whereas the preoperative drugs for the same surgical procedure in cattle were xylazine (31.8%) and the local administration of lidocaine (48%). Fracture repair was considered the most painful surgical procedure for both species. Most veterinarians (84.1%) believed that their knowledge in this area was not adequate. Conclusions and clinical relevance: Although these Brazilian veterinarians thought that their knowledge on recognition and treatment of pain was not adequate, the use of analgesic in large animals was similar in Brazil to that reported in other countries. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Avaliação hematológica, bioquímica e parasitológica de cães, naturalmente acometidos por leishmaniose visceral, submetidos a diferentes protocolos de tratamento

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Síntese e caracterização so polímero supramolecular à base de óleo de semente de mamão (Carica papaya L.) maleinizado-meglumina

Pós-graduação em Química - IQ

Síntese e caracterização de adutos óleo de rícino maleinizado-meglumina como potenciais carreadores de fármacos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Estudo da técnica de venografia dos dígotos de vacas

Pós-graduação em Medicina Veterinária - FMVZ