Amphotericin B Nano-Assemblies Circumvent Intrinsic Toxicity and Ensure Superior Protection in Experimental Visceral Leishmaniasis with Feeble Toxic Manifestation.

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.

Clival Defect with Primary CSF Rhinorrhea: A Very Rare Presentation with Challenging Management.

BACKGROUND: Primary spontaneous cerebrospinal fluid (CSF) rhinorrhea due to clival defect is an extremely rare presentation, and only 6 cases have been reported in the literature so far17. CASE DESCRIPTION: We present a unique case of a 64-year-old woman who presented with a 2-year history of ongoing CSF rhinorrhea. She had similar episode at the age of 40 years and suffered from meningitis. She underwent magnetic resonance imaging, computed tomography cisternogram, as well as computed tomography of the brain, which showed clival defect with CSF leak into the sphenoid sinus. She underwent transsphenoidal repair of the clival defect with concurrent lumbar drain insertion for CSF drainage. She returned a few months later with recurrent CSF rhinorrhea and meningitis. She was administered broad-spectrum antibiotics and underwent septal reconstruction of clival defect. CONCLUSIONS: Timely endoscopic transnasal, transsphenoidal repair of CSF leaks is the gold standard practice and could prevent devastating complications including repeated episodes of meningitis.

Neurotropic cutaneous malignant melanoma with contiguous spread to spinal cord, an extremely rare presentation.

Neurotropic melanoma (NM) is a rare variant of cutaneous melanomas. Compared with conventional melanoma, NM is more locally aggressive with an increased tendency for local recurrence but less likely for nodal or distant metastases. The often amelanotic, benign appearance may lead to treatment issues such as late presentation, diagnostic delay, misdiagnosis, insufficient surgical margins, and recurrence with resulting poor outcome. To our knowledge, this is the first case report of NM with contiguous spread to the spinal cord. We present a case report of a 73-year-old male with gradual decline in mobility over the period of few months. He deteriorated very rapidly whilst inpatient with progressive myelopathy, loss of sphincter function and dysphonia with dysphagia due to involvement of lower cranial nerves. The neurotropic nature of the disease and prevalence in the head and neck region results in perineural and neural invasion with resulting neuropathies. Patient underwent posterior cervical decompression and resection of the higher cervical intramedullary spinal cord NM lesion. He recovered well with improvement of his limb weakness as well as bulbar function. Wide local excision (WLE) with adjuvant radiotherapy where indicated remains the current practice for treatment, with chemotherapy predominately being reserved as a salvage treatment for patients with disseminated disease.

Malignant paraganglioma, a rare presentation with foot drop: a case report.

Paragangliomas (or extra-adrenal paragangliomas) are rare neuroendocrine tumors that arise from the extra-adrenal autonomic paraganglia, small organs consisting mainly of neuroendocrine cells that are derived from the embryonic neural crest and have the ability to secrete catecholamines. This is in contrast to pheochromocytomas, where tumors occur in the adrenal gland. Malignant paraganglioma is a very rare presentation. We present a case report of a 56-year-old woman with acute foot drop with no previous significant background history. To the best of our knowledge, the current case represents the first case of malignant paraganglioma with acute foot drop presentation.