India is home to 60% of the total global visceral leishmaniasis (VL) population. Use of long-term oral (e.g. miltefosine) and parenteral drugs, considered the mainstay for treatment of VL, is now faced with increased resistance, decreased efficacy, low compliance and safety issues. The authors evaluated the efficacy and safety of an alternate treatment option, i.e. single infusion of preformed amphotericin B (AmB) lipid emulsion (ABLE) in comparison with that of liposomal formulation (LAmB).
Methods
In this multicentric, open-label study, 500 patients with VL were randomly assigned in a 3∶1 ratio to receive 15 mg/kg single infusion of either ABLE (N = 376) or LAmB (N = 124). Initial cure (Day 30/45), clinical improvement (Day 30) and long term definitive cure (Day 180) were assessed.
Findings
A total of 326 (86.7%) patients in the ABLE group and 122 (98.4%) patients in the LAmB group completed the study. Initial cure was achieved by 95.9% of patients in the ABLE group compared to 100% in the LAmB group (p = 0.028; 95% CI: −0.0663, −0.0150). Clinical improvement was comparable between treatments (ABLE: 98.9% vs. LAmB: 98.4%). Definitive cure was achieved in 85.9% with ABLE compared to 98.4% with LAmB. Infusion-related pyrexia (37.2% vs. 32.3%) and chills (18.4% vs. 18.5%) were comparable between ABLE and LAmB, respectively. Treatment-related serious adverse events were fewer in ABLE (0.3%) compared to LAmB (1.6%). Two deaths occurred in the ABLE group, of which one was probably related to the study drug. Nephrotoxicity and hepatotoxicity was not observed in either group.
Conclusions
ABLE 15 mg/kg single infusion had favorable efficacy and was well tolerated. Considering the demographic profile of the population in this region, a single dose treatment offers advantages in terms of compliance, cost and applicability.
AbstractDr. Armstrong's expert knowledge and vast experience with amphotericin B have allowed him to speak previously with authority on its merits and demerits. According to his assessment, amphotericin B is a valuable drug, marred by severe toxicity. I shall attempt to explain, in this short presentation, why liposomes as vehicles in which to administer amphotericin B have the potential to redress this agent's principal deficiency. 相似文献
Visceral Leishmaniasis (VL; also known as Kala-azar) is an ultimately fatal disease endemic in Bihar. A 2007 observational cohort study in Bihar of 251 patients with VL treated with 20 mg/Kg intravenous liposomal amphotericin B (Ambisome) demonstrated a 98% cure rate at 6-months. Between July 2007 and August 2012, Médecins Sans Frontières (MSF) and the Rajendra Memorial Research Institute (RMRI) implemented a VL treatment project in Bihar, India—an area highly endemic for Leishmania donovani—using this regimen as first-line treatment.
Methods and Principal Findings
Intravenous Ambisome 20 mg/kg was administered in four doses of 5 mg/kg over 4–10 days, depending on the severity of disease. Initial clinical cure at discharge was defined as improved symptoms, cessation of fever, and recession of spleen enlargement. This observational retrospective cohort study describes 8749 patients with laboratory-confirmed primary VL treated over a 5-year period: 1396 at primary healthcare centers, 7189 at hospital, and 164 at treatment camps. Initial clinical cure was achieved in 99.3% of patients (8692/8749); 0.3% of patients (26/8749) defaulted from treatment and 0.4% (31/8749) died. Overall, 1.8% of patients (161/8749) were co-infected with HIV and 0.6% (51/8749) with tuberculosis. Treatment was discontinued because of severe allergic reactions in 0.1% of patients (7/8749). Overall, 27 patients (0.3%) were readmitted with post Kala-azar dermal leishmaniasis (PKDL). Risk factors for late presentation included female sex, age >15 years and being from a scheduled caste.In 2012, a long-term efficacy survey in the same area of Bihar determined relapse rates of VL after 5 years'' intervention with Ambisome. Of 984 immunocompetent patients discharged between September 2010 and December 2011, 827 (84.0%) were traced in order to determine their long-term outcomes. Of these, 20 patients (2.4%) had relapsed or received further treatment for VL. Of those completing 6, 12, and 15 month follow-up, 0.3% (2/767), 3.7% (14/383), and 2.4% (4/164), respectively, had relapsed. The mean ±SD time-to-relapse was 9.6±3.0 months.
Significance
This is the largest cohort of VL patients treated with 20 mg/kg Ambisome worldwide. The drug has high initial and long-term efficacy, and a low rate of adverse reactions when administered under field conditions in Bihar, India. Although challenging, its use as first line treatment in rural settings in Bihar is safe and feasible. 相似文献
The skin disorder Post Kala-Azar Dermal Leishmaniasis (PKDL) occurs in up to 10% of patients treated for visceral leishmaniasis (VL) in India. The pathogenesis of PKDL is not yet fully understood. Cases have been reported in India following therapy with most available treatments, but rarely in those treated with liposomal amphotericin B (Ambisome). Between July 2007 and August 2012 with the support of the Rajendra Memorial Research Institute (RMRI), Médecins Sans Frontières (MSF) supported a VL treatment programme in Bihar, India—an area highly endemic for Leishmania donovani—in which 8749 patients received 20 mg/kg intravenous Ambisome as first-line treatment. This study describes the characteristics of patients who returned to the MSF supported treatment programme with PKDL.
Methods and Principal Findings
Over a 5-year period, Ambisome was administered to 8749 patients with laboratory-confirmed VL (clinical signs, rK39 positive, with/without parasite confirmation) in four intravenous doses of 5 mg/kg to a total of 20 mg/kg, with a high initial-cure rate (99.3%) and low default rate (0.3%). All patients received health education highlighting the possibility and symptoms of developing PKDL, and advice to return to the MSF programme if these symptoms developed. This is an observational retrospective cohort study of the programme outcomes. Of the 8311 patients completing treatment for their first episode of VL, 24 (0.3%) returned passively to the programme complaining of symptoms subsequently confirmed as PKDL, diagnosed from clinical history, appearance consistent with PKDL, and slit-skin smear examination. Of the 24 patients, 89% had macular lesions, with a median time (interquartile range) to development of 1.2 (0.8–2.2) years following treatment. Comparison of the demographic and clinical characteristics of the VL patients treated with Ambisome who later developed PKDL, with those of the remaining cohort did not identify any significant risk factors for PKDL. However, the time to developing PKDL was significantly shorter with Ambisome than in a subset of patients presenting to the programme with PKDL following previous sodium stibogluconate treatment for VL.
Conclusions
In this large cohort of patients with VL in Bihar who were treated with 20 mg/kg Ambisome, PKDL following treatment appears to be infrequent with no predictive risk factors. The shorter median time to developing symptoms of PKDL compared with that after conventional VL treatments should be taken into account when counseling patients treated with regimens including Ambisome. 相似文献
A proportion of all immunocompetent patients treated for visceral leishmaniasis (VL) are known to relapse; however, the risk factors for relapse are not well understood. With the support of the Rajendra Memorial Research Institute (RMRI), Médecins Sans Frontières (MSF) implemented a program in Bihar, India, using intravenous liposomal amphotericin B (Ambisome) as a first-line treatment for VL. The aim of this study was to identify risk factors for VL relapse by examining the characteristics of immunocompetent patients who relapsed following this regimen.
Methods and Principal Findings
This is an observational retrospective cohort study of all VL patients treated by the MSF program from July 2007 to August 2012. Intravenous Ambisome was administered to 8749 patients with VL in four doses of 5 mg/kg (for a total dose of 20 mg/kg) over 4–10 days, depending on the severity of disease. Out of 8588 patients not known to be HIV-positive, 8537 (99.4%) were discharged as initial cures, 24 (0.3%) defaulted, and 27 (0.3%) died during or immediately after treatment. In total, 1.4% (n = 119) of the initial cured patients re-attended the programme with parasitologically confirmed VL relapse, with a median time to relapse of 10.1 months. Male sex, age <5 years and ≥45 years, a decrease in spleen size at time of discharge of ≤0.5 cm/day, and a shorter duration of symptoms prior to seeking treatment were significantly associated with relapse. Spleen size at admission, hemoglobin level, nutritional status, and previous history of relapse were not associated with relapse.
Conclusions
This is the largest cohort of VL patients treated with Ambisome worldwide. The risk factors for relapse included male sex, age <5 and ≥45 years, a smaller decrease in splenomegaly at discharge, and a shorter duration of symptoms prior to seeking treatment. The majority of relapses in this cohort occurred 6–12 months following treatment, suggesting that a 1-year follow-up is appropriate in future studies. 相似文献
AbstractSeveral clinical trials are presently underway to study various liposomal formulations of antineoplastics and antimicrobial agents (1–3). Both liposomal amphotericin B (L-AmpB) and various liposome formulations have been used in the treatment of experimental systemic fungal infections (4–6) and leishmaniasis (7,8) in animals. In most reports, an enhanced therapeutic index was observed. A uniform reduction in the toxic effects usually attributed to AmpB was reported and, in some cases, an enhanced therapeutic efficacy was also attained. We recently reported on the use of L-AmpB in 46 patients with systemic fungal infections (9). of that number, 31 had leukemia, 2 had lymphoma, 11 had other diagnoses (5 had received intensive immunosuppressive therapy following a heart transplantation, 2 had multiple myeloma, and the rest had other malignancies); 2 patients had no underlying disease. Forty-one of these patients had been previously treated with conventional AmpB. the fungal diagnosis was candidiasis in 21 patients, aspergillosis in 19, agents of mucormycosis in 3, and other diagnoses in the rest. 相似文献
The present studies were designed to develop a formulation of amphotericin B in a lipid-based preparation as a microemulsion and to compare its toxicity with the commercial formulation Fungizone. The final product developed is a lyophilized amphotericin B, oil and surfactant blend for reconstitution in water to yield a microemulsion containing 5 mg/ml of the drug. Pseudoternary phase diagrams were constructed to identify areas of existence of microemulsion composed of Peceol (glyceryl monooleate) as oil phase and Mys 40 (polyethylene glycol 40 stearate) and Solutol HS 15 (polyethylene glycol 15 hydroxy stearate) as surfactants. Amphotericin B was co-evaporated with oil - surfactant mixture to produce a microemulsion pre-concentrate. The co-evaporate was diluted in water, filtered for sterilization and lyophilized to obtain the final product. The lyophilized as well as the reconstituted products were separately studied for stability and the latter was also characterized for various physicochemical aspects including droplet size of the dispersed phase, osmolarity and aggregation state of drug. The dispersion showed no evidence of precipitation of drug for 48 h, and resisted destabilization due to freeze-thaw cycles or centrifugation. The dispersed phase globules measured a mean size of 84 nm and uv-spectrophotometric studies indicated the presence of self-aggregated amphotericin B. The present formulation showed a 92% decrease in haemolysis of human RBC in vitro when compared with the commercially available Fungizone. The LD(50) in mice was estimated to be 3.4 mg/kg. The results indicate that the formulation holds promise for development as a safer and efficacious alternative for amphotericin B therapy. 相似文献
Cisplatin, first (platinum) compound to be evolved as an anticancer agent, has found its important place in cancer chemotherapy. However, the dose-dependent toxicities of cisplatin, namely nephrotoxicity, ototoxicity, peripheral neuropathy, and gastrointestinal toxicity hinder its widespread use. Liposomes can reduce the toxicity of cisplatin and provide a better therapeutic action, but the low lipid solubility of cisplatin hinders its high entrapment in such lipid carrier. In the present investigation, positively charged reactive aquated species of cisplatin were complexed with negatively charged caprylate ligands, resulting in enhanced interaction of cisplatin with lipid bilayer of liposomes and increase in its encapsulation in liposomal carrier. Prepared cisplatin liposomes were found to have a vesicular size of 107.9 ± 6.2 nm and zeta potential of −3.99 ± 3.45 mV. The optimized liposomal formulation had an encapsulation efficiency of 96.03 ± 1.24% with unprecedented drug loading (0.21 mg cisplatin / mg of lipids). The in vitro release studies exhibited a pH-dependent release of cisplatin from liposomes with highest release (67.55 ± 3.65%) at pH 5.5 indicating that a maximum release would occur inside cancer cells at endolysosomal pH. The prepared liposomes were found to be stable in the serum and showed a low hemolytic potential. In vitro cytotoxicity of cisplatin liposomes on A549 lung cancer cell line was comparable to that of cisplatin solution. The developed formulation also had a significantly higher median lethal dose (LD50) of 23.79 mg/kg than that of the cisplatin solution (12 mg/kg). A promising liposomal formulation of cisplatin has been proposed that can overcome the disadvantages associated with conventional cisplatin therapy and provide a higher safety profile.Key Words: cisplatin, complexation, cytotoxicity, LD50, liposome相似文献
AbstractLiposomal hepatitis B vaccine was prepared by encapsulating recombinant 22-nm hepatitis B surface antigen (HBsAg) particles derived from a Chinese hamster ovary (CHO) cell line in multilammelar lipid vesicles (MLV) composed of 9:1 dimyristoyl phosphatidyl-choline/dimyristoyl phosphatidylglycerol. The CHO-derived HBsAg particles reveal 6 bands in polyacrylamide gel electrophoresis related to the presence of 3 peptides (S, M, & L). Four different methods were used to prepare the MLV vaccine, each resulting in freeze-dried powder which upon hydration gave MLV of a similar mean size, 4.5 μm. The humoral response to these 4 liposomal vaccines in mice was dependent on the method of preparation, but for all of them it was better than the response to alum-based vaccine (especially at a low dose of antigen). Comparison of vaccination using “naked” HBsAg particles, particles adsorbed to alum, and particles encapsulated in liposomes demonstrated that at low dose of antigen the liposomal vaccine was superior in eliciting humoral response. Encapsulation in liposomes did not improve specific cytotoxic T lymphocyte (CTL) response. The alum in the vaccine completely eliminates CTL response, though it improved the humoral response by increasing the linear range in the antigen dose-response curve (increasing the antibody titer at high antigen dose). A similar response profile was obtained with recombinant yeast (Hansenula) 22-nm particles composed of a single non-glycosylated (p24) peptide and lipids. The similarity in the response to the mammalian cell and yeast derived vaccine suggests that the physical nature of the vaccine, more than the exact composition, determines the balance between humoral and CTL responses. 相似文献
The aim of this study was to determine amphotericin B (AmB) permeation across lipid bilayer membranes mounted on Transwell® and to observe the phagocytosis of the AmB and the AmB-lipid formulations by alveolar macrophage (AM) cell lines using a fluorescence microscope. The lipid bilayer membranes were prepared from phospholipid and ergosterol as well as phospholipid and cholesterol in a ratio (67:33 mol%). AmB-lipid formulations were prepared from AmB incorporated with four lipid derivatives during a lyophilization process. In vitro cytotoxicity studies were carried out on kidney cells by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The levels of nitric oxide production by AMs exposed to these AmB-lipid formulations were determined by the Griess reaction. Phagocytosis of the AmB-lipid formulations was carried out using AM cells. The lipid bilayer membranes and AmB-lipid formulations were successfully prepared. In vitro cytotoxicity results showed less toxicity to kidney cells than pure AmB, and a 1,000-fold less production of nitric oxide by NR8383 cell lines was obtained when compared to lipopolysaccharide. Permeation results were two- to fivefold higher than for pure AmB in the ergosterol containing lipid bilayer and two- to fourfold higher than AmB in the cholesterol containing compositions, both of which were enough to kill the fungi according to their MICs and MFCs. AM phagocytosed the AmB-lipid formulations. We suggest that these products especially the AmB-sodium deoxycholate sulfate are potential candidates for targeting AM cells for the treatment of invasive pulmonary aspergillosis. 相似文献
Surface modification of liposomes with targeting ligands is known to improve the efficacy with reduced untoward effects in treating infective diseases like visceral leishmaniasis (VL). In the present study, modified ligand (ML), designed by modifying polysaccharide with a long chain lipid was incorporated in liposomes with the objective to target amphotericin B (Amp B) to reticuloendothelial system and macrophages. Conventional liposomes (CL) and surface modified liposomes (SML) were characterized for size, shape, and entrapment efficiency (E.E.). Amp B SML with 3% w/w of ML retained the vesicular nature with particle size of ～205 nm, E.E. of ～95% and good stability. SML showed increased cellular uptake in RAW 264.7 cells which could be attributed to receptor-mediated endocytosis. Compared to Amp B solution, Amp B liposomes exhibited tenfold increased safety in vitro in RAW 264.7 and J774A.1 cell lines. Pharmacokinetics and biodistribution studies revealed high t1/2, area under the curve (AUC)0–24, reduced clearance and prolonged retention in liver and spleen with Amp B SML compared to other formulations. In promastigote and amastigote models, Amp B SML showed enhanced performance with low 50% inhibitory concentration (IC50) compared to Amp B solution and Amp B CL. Thus, due to the targeting ability of ML, SML has the potential to achieve enhanced efficacy in treating VL. 相似文献
The present pilot study investigating the minimum dose for short-course single and double-dose treatment of kala-azar with an apparently new liposomal formulation of amphotericin B, Fungisome, led to identification of immunological components for early detection of success and/or failure to cure.
Methods
Patients were treated with 5, 7.5 (single-dose) and 10 mg/kg body weight (5 mg/kg double-dose) of Fungisome. Immunological investigations involving plasma cytokines and antigen-specific lymphoproliferation and cytokine responses from PBMCs were carried out before, 1 week after Fungisome treatment, at the time of relapse, and again after conventional amphotericin B treatment.
Results
At 1-month follow-up all the patients showed 100% initial cure. However, total doses of 5, 7.5 and 10 mg/kg Fungisome showed 60%, 50% and 90% cure, respectively, at 6-months posttreatment. Patients successfully cured demonstrated downregulation of IL-12 and IL-10 in plasma, and two-fold or more elevation of IFN-γ, IL-12 and TNF, and significant down-regulation of IL-10 and TGF-β in culture supernatants 1-week posttreatment irrespective of drug-dose. A differential immune profile, involving insignificant decline in IL-10 and IL-12 in plasma and negligible elevation of IFN-γ, IL-12 and TNF, and persistence of IL-10, despite decline in TGF-β in culture supernatants, in apparently cured individuals, corresponded with relapse within 6-months of treatment.
Conclusion
Immunological investigations revealed significant curative and non-curative immunomodulation 1-week posttreatment, correlating with successful cure and relapse, respectively. Although immune-correlation was dose-independent, almost consistent curative response in patients treated with the highest dose 10 mg/kg reflected a definitive impact of the higher-dose on the immune response.
Visceral Leishmaniasis (VL; also known as kala-azar) is an ultimately fatal disease endemic in the Indian state of Bihar, while HIV/AIDS is an emerging disease in this region. A 2011 observational cohort study conducted in Bihar involving 55 VL/HIV co-infected patients treated with 20–25 mg/kg intravenous liposomal amphotericin B (AmBisome) estimated an 85.5% probability of survival and a 26.5% probability of VL relapse within 2 years. Here we report the long-term field outcomes of a larger cohort of co-infected patients treated with this regimen between 2007 and 2012.
Methods and Principal Findings
Intravenous AmBisome (20–25 mg/kg) was administered to 159 VL/HIV co-infected patients (both primary infections and relapses) in four or five doses of 5 mg/kg over 4–10 days. Initial cure of VL at discharge was defined as improved symptoms, cessation of fever, improvement of appetite and recession of spleen enlargement. Test of cure was not routinely performed. Antiretroviral treatment (ART) was initiated in 23 (14.5%), 39 (24.5%) and 61 (38.4%) before, during and after admission respectively. Initial cure was achieved in all discharged patients. A total of 36 patients died during follow-up, including six who died shortly after admission. Death occurred at a median of 11 weeks (IQR 4–51) after starting VL treatment. Estimated mortality risk was 14.3% at six months, 22.4% at two years and 29.7% at four years after treatment. Among the 153 patients discharged from the hospital, 26 cases of VL relapse were diagnosed during follow-up, occurring at a median of 10 months (IQR 7–14) after discharge. After accounting for competing risks, the estimated risk of relapse was 16.1% at one year, 20.4% at two years and 25.9% at four years. Low hemoglobin level and concurrent infection with tuberculosis were independent risk factors for mortality, while ART initiated shortly after admission for VL treatment was associated with a 64–66% reduced risk of mortality and 75% reduced risk of relapse.
Significance
This is the largest cohort of HIV-VL co-infected patients reported from the Indian subcontinent. Even after initial cure following treatment with AmBisome, these patients appear to have much higher rates of VL relapse and mortality than patients not known to be HIV-positive, although relapse rates appear to stabilize after 2 years. These results extend the earlier findings that co-infected patients are at increased risk of death and require a multidisciplinary approach for long-term management. 相似文献
AbstractFree and liposomal formulations of caprylated TNF-SAM2, a TNF mutant, were evaluated in both a canine model for TNF-induced hypotension and in the murine Meth A sarcoma model for efficacy. The liposomal formulations consisted of caprylated TNF-SAM2 either bound to the outer leaflet of small unilamellar vesicles (SUVs) or encapsulated in multilamellar vesicles (MLVs). Whereas systemic administration of parental TNF-a to anesthesized mongrel dogs resulted in acute shock with a precipitous fall in systemic arterial pressure (SAP), the SUV-TNF-SAM2 resulted in no net hypotension. Both the free and liposomal-TNF-SAM2 elicited a hyperdynamic response with tachycardia and elevated cardiac output and SAP, which was not observed with parental TNF-a. Two tail-vein injections of these formulations were administered 4–5 days apart to BALB/c mice in which Meth A sarcoma cells were previously implanted subcutaneously or intradermally. Free TNF-SAM2 at 4 × 10 U/mouse caused highly significani tumor control compared to PBS on days 5 and 12; however, substantial toxicity (-24% lethality; was observed at this level. The liposomal formulations of caprylated TNF-SAM2 demonstratec significant tumor control at all dose levels (up to 8 × 10 U/mouse) on day 12 (p<0.025) wit! either no or reduced lethality (0–15%); the tumor responses were comparable to those with fret TNF-SAM2. We conclude that the liposomal caprylated-TNF-SAM2 formulations exhibit; therapeutic index superior to that of free parental TNF-a or free TNF-SAM2. 相似文献
We report nanomicelles of amphotericin B (AmB) using various molar ratios of AmB and sodium deoxycholate sulfate (SDCS) for inhalation with improved stability, solubility, bioactivity, and safety. The particle sizes of all aerosolized formulations are expressed as mass median aerodynamic diameter (0.9–1.6 μm), fine particle fraction (70.3–86.5%), and geometric standard deviation (1.4–2.1) which indicated their sizes are appropriate for use as an inhaler. In vitro cytotoxicity studies conducted using respiratory and kidney cell lines demonstrated that the marketed Fungizone® was toxic to macrophage and embryonic kidney cells and cell viability decreased from 96 to 48% and from 97 to 67%, respectively when the AmB equivalent concentration was increased from 1 to 16 μg/mL. However, AmB-SDCS formulations showed no evidence of toxicity even up to 8 μg/mL compared to Fungizone®. Minimum inhibitory and fungicidal concentrations were significantly reduced against Cryptococcus neoformans, and Candida albicans. Also, antileishmanial activity significantly improved for AmB-SDCS formulations. There was an evidence of phagocytosis of the AmB-SDCS formulation by alveolar macrophages NR 8383. Molecular modeling studies suggested the role of hydrogen bonding in stabilization of the AmB-SDCS complex. This study indicated that AmB-SDCS nanomicelles can be used to design a safe and cost-effective AmB for inhalation.
Invasive fungal infections in liver transplant recipients are associated with elevated morbidity and mortality and pose a challenge to the treating physicians. Despite of lacking clinical data, the use of antifungal combination therapy is often considered to improve response rates in an immunocompromised patient population. We herein report a case of refractory invasive candidiasis in a liver transplant recipient treated successfully with a combination of isavuconazole und high-dose liposomal amphotericin B. The antimycotic combination treatment was able to clear a bloodstream infection with C. glabrata and led to regression of bilomas among tolerable side effects. The use of the above-mentioned antifungal combination therapy in a liver transplant recipient has not been reported previously. This case highlights the efficacy and safety of antifungal combination therapy in immunocompromised patients with refractory invasive candidiasis.
This study reports a physicochemical stability evaluation of a previously reported liposomal prilocaine (PLCLUV) formulation () before and after steam sterilization as well as its local toxicity evaluation. Prilocaine (PLC) was encapsulated into extruded unilamellar liposomes (LUVs) composed by egg phosphatidylcholine:cholesterol:alfa-tocopherol (4:3:0.07, mole?%). Laser light-scattering analysis (p?>?0.05) and thiobarbituric acid reaction (p?>?0.05) were used to evaluate the liposomes physical (size) and chemical (oxidation) stability, respectively. The prilocaine chemical stability was followed by 1H-nuclear magnetic resonance. These tests detected no differences on the physicochemical stability of PLC or PLCLUV, sterilized or not, up to 30 days after preparation (p?>?0.05). Finally, the paw edema test and histological analysis of rat oral mucosa were used to assess the possible inflammatory effects of PLCLUV. PLCLUV did not evoke rat paw edema (p?>?0.05), and no significant differences were found in histological analysis, when compared to the control groups (p?>?0.05). The present work shows that PLCLUV is stable for a 30-day period and did not induce significant inflammatory effects both in the paw edema test and in histological analysis, giving supporting evidence for its safety and possible clinical use in dentistry. 相似文献
We report a 38-year-old woman presenting with febrile neutropenia, acute myeloid leukemia (AML) and invasive mucormycosis. Bone marrow aspirate was characteristic of AML minimally differentiated (WHO classification 2008). Flow cytometric immunophenotyping analysis showed blasts positive for CD7, CD33, CD34, CD71, CD117, HLA-DR, MPO, and TdT, with normal karyotype (46, XX), and the absence of the FLT3-ITD and NPM1 mutations. The patient’s management included chemotherapy with cytarabine and idarubicin, and treatment with liposomal amphotericin B, deferasirox, hyperbaric oxygen therapy, and antibiotics. Nowadays, she is in complete hematological remission, and CT images of control are normal. Invasive mucormycosis is an uncommon and severe condition, which involves diagnosis and treatment challenges. Clinical features and predisposing factors should be highlighted in order to enhance the suspicion index, contributing to early diagnosis and disease control. Our aim is to report classical features of this uncommon condition and to emphasize usual management challenges. 相似文献
