antimony-sodium-gluconate and Acute-Disease

Electrical stimulation has been used as a mode of therapy for a number of clinical conditions. However, it has not been used for the treatment of cutaneous leishmaniasis (CL). For this purpose, we designed the "Baghdadin device". A total of 146 lesions of acute CL in 54 patients were treated by this device. Twenty-one lesions in the same patients were left untreated as controls. In addition, 36 lesions in 15 patients were treated with intralesional sodium stibogluconate. Treatment by the Baghdadin device consisted of weekly sessions of 10 minutes of direct current electrical stimulation. The intensity of the direct current ranged between 5 and 15 milliamperes, and the voltage was kept below 40 volts. Of the 146 lesions, 135 (92.5%) showed total clearance or marked improvement in 4-6 weeks time. Approximately 67% of the lesions needed only one or two sessions. Scarring was not observed after resolution. None of the untreated lesions showed any signs of improvement in 6 weeks. Of the lesions treated with sodium stibogluconate, 32 lesions (88.9%) showed total clearance or marked improvement, which was not significantly different from the results with the Baghdadin device.

Topics: Acute Disease; Administration, Topical; Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Electric Stimulation Therapy; Equipment Design; Female; Humans; Iraq; Leishmaniasis, Cutaneous; Male; Middle Aged; Treatment Outcome

A comparative clinical trial between two newly introduced intralesional treatments for acute leishmaniasis and the established treatment of intralesionally-administered pentavalent antimony compounds was performed. Treatments were allocated randomly to a total of 63 patients who received 2% zinc sulphate, 7% sodium chloride solutions or sodium stibogluconate intralesionally. A number of patients were left without treatment as controls. Patients were followed-up for 45 days, the results showing that the three treatments gave comparable cure rates by the end of the follow-up period. However, zinc sulphate gave a high cure rate (94.8%) usually with a single injection.

Topics: Acute Disease; Adolescent; Adult; Aged; Antimony Sodium Gluconate; Antiprotozoal Agents; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Middle Aged; Sodium Chloride; Treatment Outcome; Zinc Sulfate

Topics: Acute Disease; Alanine Transaminase; Antimony Sodium Gluconate; Chemical and Drug Induced Liver Injury; Glutathione Transferase; Humans; Infusions, Parenteral; Leishmaniasis, Cutaneous; Military Personnel; Paromomycin; Prospective Studies; United Kingdom

Cutaneous leishmaniasis represents a difficult disease to manage in endemic areas. Systemic treatment is hampered by both expense and compliance. Side effects may play a major role in this aspect as well.. The effectiveness of intralesional treatment of leishmaniasis was investigated. Seven hundred and ten patients were treated with injections of sodium stibogluconate intralesionally. The clinical diagnosis was confirmed by demonstrating the parasite in the smears obtained from the lesion. Fine insulin needle was used to infiltrate the lesion with sodium stibogluconate (0.5 to 1.0 mL).. Generally eight injections were sufficient, but some of the complicated lesions needed up to 24 injections. Sixty-two percent of patients were men. The majority of the study population (64%) were children below 15 years of age. The results showed that 72% of lesions healed completely, 23.9% showed some improvement, while 4.1% showed some deterioration. Lesions of the lips, cheeks, chin, and neck healed faster than lesions in other parts of the body. Side effects were mild and limited to pain at the site of the injection and hyperpigmentation in those who were treated by folk medicine.. Intralesional treatment is as effective as the standard systemic antimonials. It offers a less expensive alternative and a low side effects profile. Our findings confirmed the findings of earlier workers. It is recommended for treatment of cutaneous leishmaniasis in endemic areas.

Topics: Acute Disease; Adolescent; Adult; Antimony Sodium Gluconate; Child; Child, Preschool; Female; Humans; Injections, Intralesional; Leishmaniasis, Cutaneous; Male; Middle Aged; Treatment Outcome

Apparently for the first time, the peripheral blood monocytes of individuals with active visceral leishmaniasis (VL) have been found to show reduced expression of interferon gamma receptor-1 (IFNGR1). Since interferon gamma is the main cytokine responsible for defence against leishmanial parasites, it was thought possible that effective antileishmanial drugs may up-regulate IFNGR1. Confocal microscopy confirmed that monocytes from VL patients who had been treated, with sodium antimony gluconate (SAG), did display IFNGR1 up-regulation. To see if this effect could be mimicked in vitro, IFNGR1 expression was investigated using a human macrophage cell line (THP1), northern blotting and confocal microscopy. When the THP1 cells were treated with SAG or pentamidine, their expression of the receptor was increased. This drug-induced up-regulation was more intense if the macrophages were infected with Leishmania donovani than if they were left uninfected. The possibility that at least some antileishmanial drugs act by up-regulating IFNGR1 expression needs to be explored further. A good model for investigating the mechanisms of action of antileishmanial drugs might be based on the THP1 cell line.

Topics: Acute Disease; Adolescent; Adult; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Blotting, Northern; Cell Line; Child; Female; Humans; Interferon gamma Receptor; Leishmania donovani; Leishmaniasis, Visceral; Male; Microscopy, Confocal; Middle Aged; Monocytes; Pentamidine; Receptors, Interferon; Up-Regulation

PTPases are key signaling molecules and targets for developing novel therapeutics. We have studied the in vitro biological activity of PTPase inhibitor sodium stibogluconate (SS) on differentiation and proliferation of myeloid leukemia cell lines (NB4, HL-60 and U937). SS (250 microg/ml, 6 days) induced 87% of NB4 cells to reduce nitroblue tetrazolium (NBT), in comparison to the 90% induced by ATRA (1 microM, 6 days). SS treatment of NB4 cells resulted in an increase of CD11b expression and of a morphologically more mature population, coincident with growth arrest at S phase and increased cell death. The effect of SS on NB4 differentiation was irreversible and required continuous drug exposure. SS (400 microg/ml, 6 days) induced 60% and 55% of NBT-positive cells in HL-60 and U937 cell lines, which were augmented in the presence of GM-CSF (25 ng/ml) to levels (85% and 81%, respectively) comparable to those induced by ATRA. SS induced increased tyrosine phosphorylation of cellular proteins in the AML cell lines and inactivated SHP-1 PTPase in NB4 cells, consistent with SS functioning as a PTPase inhibitor in the leukemia cells. These results provide the first evidence of an anti-leukemia activity of SS as a PTPase inhibitor.

Topics: Acute Disease; Antimony Sodium Gluconate; Antineoplastic Agents; Antiprotozoal Agents; Cell Cycle; Cell Differentiation; Cell Division; Gene Expression Regulation, Leukemic; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Intracellular Signaling Peptides and Proteins; Leukemia, Myeloid; Nitroblue Tetrazolium; Oxidation-Reduction; Phosphorylation; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases; Tretinoin; Tumor Cells, Cultured; Tyrosine

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Antimony; Antimony Sodium Gluconate; Antiprotozoal Agents; Bone Marrow Cells; Erythroid Precursor Cells; Humans; Leishmaniasis, Visceral; Male

In this study, treatment efficacies of a nonionic surfactant vesicle formulation of sodium stibogluconate (SSG-NIV) and of several formulations of amphotericin B were compared in a murine model of visceral leishmaniasis. Treatment with multiple doses of AmBisome, Abelcet, and Amphocil (total dose, 12.5 mg of amphotericin B/kg of body weight) resulted in a significant suppression of parasite burdens in liver (P < 0.0005) and spleen (P < 0.0005) compared with those of controls, with Abelcet having the lowest activity. Only AmBisome and Amphocil gave significant suppression of parasites in bone marrow (compared to control values, P < 0.005). In the acute-infection model, single-dose treatments of SSG-NIV (296 mg of SbV/kg), SSG solution (296 mg of SbV/kg), or AmBisome (8 mg of amphotericin B/kg) were equally effective against liver parasites (compared to control values, P < 0.0005). SSG-NIV and AmBisome treatment also significantly suppressed parasites in bone marrow and spleen (P < 0.005), with SSG-NIV treatment being more suppressive (>98% suppression in all three sites). Free-SSG treatment failed to suppress spleen or bone marrow parasites. Infection status influenced treatment outcome. In the chronic-infection model, the AmBisome single-dose treatment was less effective in all three infection sites and the SSG-NIV single-dose treatment was less effective in the spleen. The results of this study suggest that the antileishmanial efficacy of SSG-NIV compares favorably with those of the novel amphotericin B formulations.

Topics: Acute Disease; Amphotericin B; Animals; Antimony Sodium Gluconate; Antiprotozoal Agents; Chronic Disease; Female; Leishmaniasis, Visceral; Male; Mice; Mice, Inbred BALB C; Surface-Active Agents

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Antimony Sodium Gluconate; Antiprotozoal Agents; Female; Humans; Leishmaniasis, Visceral; Pancreatitis

To determine the utility of the serum concentrations of interleukin 6 (IL-6) as a marker of disease activity and therapeutic efficacy in visceral leishmaniasis (VL), IL-6 levels were measured in 19 patients with active VL from Sudan before and after treatment. IL-6 levels were 30 +/- 6 pg/ml during the active phase of the disease, decreased to levels around the detection limit of the assay (2 pg/ml) directly after successful antimony therapy, and remained low or undetectable for up to 6 months in persistently cured patients (P < 0.005 versus baseline). In 2 patients who had a relapse of VL, IL-6 was elevated at the time the relapse was diagnosed. Two patients with post-kala-azar dermal leishmaniasis did not have detectable IL-6 in their circulation. Sequential measurements of serum IL-6 levels may be useful for monitoring therapeutic efficacy in patients with VL.

Topics: Acute Disease; Adolescent; Adult; Antimony Sodium Gluconate; Antiprotozoal Agents; Biomarkers; Child; Child, Preschool; Female; Humans; Interleukin-6; Leishmaniasis, Visceral; Male; Middle Aged

Acute pancreatitis is an adverse effect of the treatment with antimonial drugs which is infrequently described in patients with HIV infection and visceral leishmaniasis (VL). Twenty-two percent of the patients having this treatment had acute pancreatitis (7 cases) in the authors' center. In all the cases, severe immunosuppression was present with pancreatitis appearing following the administration of 3,400 to 15,300 mg of stibogluconate. The pancreatitis was slight in the 7 cases with no complications of note and with no symptoms observed in three cases. The maximum values of amylasemia ranged from 976 to 2,568 U/l, from 1,055 to 5,860 U/l for lipasemia, and from 1,970 to 25,520 U/l for trypsinemia. These values returned to normal from 15 days to 2 months after suppression of the drug. Stibogluconate was readministered in three patients due to VL recurrence with a further acute pancreatitis being observed. The authors conclude that acute pancreatitis is a relatively infrequent complication of antimonial treatment for VL in patients with HIV infection and believe that a maximum dose of 850 mg/day should not be surpassed.

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Antimony Sodium Gluconate; Antiprotozoal Agents; Clinical Enzyme Tests; Female; HIV-1; Humans; Leishmaniasis, Visceral; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Pancreatitis; Recurrence

Topics: Acute Disease; Adult; Amphotericin B; Antimony Sodium Gluconate; Female; HIV Infections; Humans; Leishmaniasis, Visceral; Pancreatitis

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Amylases; Animals; Antimony Sodium Gluconate; Humans; Leishmania infantum; Leishmaniasis, Visceral; Male; Necrosis; Pancreas; Pancreatitis

BALB/c mice with an acute or chronic Leishmania donovani infection were treated with intravenous sodium stibogluconate solution and the parasite suppressions determined in the spleen, liver and femur bone marrow. Antimony concentrations in these and other tissues were determined by hydride generation-atomic absorption spectrophotometry. There was little correlation between tissue antimony levels one hour after treatment and drug efficacy. It would appear that the peak tissue antimony concentration achieved soon after dosing, rather than the lower concentrations which are readily sustained in most tissues, is the most important factor in the antileishmanial activity of stibogluconate. A high peak antimony concentration occurred in the liver, where parasites were significantly suppressed, and was not observed in the two other sites of infection, where the parasites were apparently less susceptible to stibogluconate therapy.

Topics: Acute Disease; Animals; Antimony; Antimony Sodium Gluconate; Chronic Disease; Female; Leishmania donovani; Leishmaniasis, Visceral; Mice; Mice, Inbred BALB C

One hundred and thirty lesions of cutaneous leishmaniasis in 60 patients were treated with intralesional injections of Pentostam and 30 lesions were left untreated as controls. The injections were given at 8-day intervals and the patients followed-up for 42 days. One hundred and four lesions (80%) needed one injection only, 20 (15.4%) needed two and six (4.6%) needed three injections. One hundred and twenty three of the treated lesions (94.6%) showed a good clinical response with complete healing or marked improvement within the follow-up period. None of the control lesions showed marked improvement or complete healing. Scarring was minimal or absent following healing of treated lesions. The only side-effect was some localized pain following the injection. We recommend intralesional Pentostam as a safe and effective method of treating acute cutaneous leishmaniasis.

Topics: Acute Disease; Adolescent; Adult; Antimony Sodium Gluconate; Child; Female; Gluconates; Humans; Injections; Leishmaniasis; Male; Middle Aged