RESUMO
In spite of its high effectiveness in the treatment of both leishmaniasis as well as a range of fungal infections, the free form of the polyene antibiotic amphotericin B (AmB) does not entertain the status of the most preferred drug of choice in clinical settings. The high intrinsic toxicity of the principal drug could be considered the main impedance in the frequent medicinal use of this otherwise very effective antimicrobial agent. Taking into consideration this fact, the pharma industry has introduced many novel dosage forms of AmB to alleviate its toxicity issues. However, the limited production, high cost, requirement for a strict cold chain, and need for parenteral administration are some of the limitations that explicitly compel professionals to look for the development of an alternate dosage form of this important drug. Considering the fact that the nano-size dimensions of drug formulation play an important role in increasing the efficacy of the core drug, we employed a green method for the development of nano-assemblies of AmB (AmB-NA). The as-synthesized AmB-NA manifests desirable pharmacokinetics in the treated animals. The possible mechanistic insight suggested that as-synthesized AmB-NA induces necrosis-mediated cell death and severe mitochondrial dysfunction in L. donovani promastigotes by triggering depolarization of mitochondrial membrane potential. In vivo studies demonstrate a noticeable decline in parasite burden in the spleen, liver, and bone marrow of the experimental BALB/c mice host. In addition to successfully suppressing the Leishmania donovani, the as-formed AmB-NA formulation also modulates the host immune system with predominant Th1 polarization, a key immune defender that facilitates the killing of the intracellular parasite.
RESUMO
BACKGROUND: Devic's syndrome or neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system associated with optic neuritis, myelitis involving 3 or more contiguous spinal cord segments, and seropositivity for NMO-IgG antibody. CASE: A 22-year-old African American woman P1G0 at 22 weeks of gestation presented with weakness for 1 week. The weakness initially started in the left lower extremity and then involved the other extremities. She also had horizontal diplopia, temporal headache, and arthralgias. On physical examination, she had a discoid rash behind the left ear, muscle strength 3/5 in the upper and 0/5 in the lower extremities, and hyporeflexia. She had lymphopenia, a highly positive antinuclear antibody, and SS-A/ SS-B antibodies. The magnetic resonance imaging of the patient showed abnormal cord signal within brain and cervical and thoracic spine. Salivary gland biopsy revealed mild lymphoplasmacytic inflammation. The NMO antibody was positive. A diagnosis of Devic's syndrome associated with probable systemic lupus erythematosus (SLE) was made. She was treated with pulse IV solumedrol and plasmapheresis for 4 days. The patient improved clinically with treatment, but the fetus developed bradycardia, which was treated with IV dexamethasone. DISCUSSION AND CONCLUSION: There is a debate about the relationship of NMO with autoimmune disorders, such as SLE or Sjogren syndrome. If clinically evident SLE or Sjogren or positive autoantibodies coexist with NMO signs and symptoms, the neurologic process could be an independent association due to NMO or may be a vasculitic complication of the systemic disease. Our case highlights these issues, difficulty in making a correct diagnosis, and choosing the appropriate management. Further case studies are needed to explore these important issues.
