Dual antimicrobial and anticancer activity of a novel synthetic α-helical antimicrobial peptide.

Antimicrobial peptides (AMPs) are increasingly sought-after and researched antimicrobial agents due to its desired pharmacological properties and the continuous diminishing efficacy of antibiotics. In addition to this line of research, the aim of the present study is to determine the antimicrobial and anticancer activity of a de novo designed α-helical peptide. Circular dichroism showed 100% helical nature of the peptide in 10 mM SDS. Notably, the peptide exerted significant antimicrobial activity against the reference and antibiotic-resistant clinical isolates belonging to Pseudomonas sp. at a MIC and MBC of 2 and 8 µM, respectively. The progressive disruption and disturbance of cell membrane in the overall topography was observed in the scanning electron microscopy (SEM) micrographs of Pseudomonas aeruginosa ATCC 27853 treated with the peptide as compared to untreated control. The results of time-kill kinetics showed complete lysis at 3x MIC after 50 min of incubation of the microbe with the peptide. Moreover, the peptide did not lyse human RBCs even at the highest concentration of the peptide (10 mM) and retained its activity upon treatment at 0.5 mg/ml trypsin. Cancer cell lines, viz. A549 and MCF-7 were also found to be sensitive to peptide activity showing 50% reduction in survivability at 4 and 2 µM, respectively; however, L929 cells were unaffected. Drastic membrane permeability and necrotic mode of lysis of peptide-treated-A549 cells were affirmed by propidium iodide and live/dead cell staining. The results showed that the designed peptide could be an efficient drug molecule for clinical studies subjected to successful experiments on animal models.

Unusual progression of renal cell carcinoma with carcinomatosis peritoneii and Krukenberg tumour and alopecia with sunitinib therapy in young female.

BACKGROUND: Sunitinib is a multiple receptor tyrosine kinase inhibitor (TKI) used for the treatment of renal cell carcinoma (RCC). It increases the median survival considerably with minimum side effects. Alopecia is one of the rare side effects. Metastasis to the ovary is also rare. We report a case of RCC metastasizing to the ovary developing alopecia early on starting sunitinib. CASE PRESENTATION: A 22-year-old hypothyroid girl underwent right radical nephrectomy for T2N0 RCC. Histopathology was clear cell carcinoma. Six months later, she presented with right iliac fossa pain, imaging revealed metastasis to the ileocolic junction and the ovary, an exploratory laparotomy was carried out and, after debulking, the patient was started on sunitinib. Four weeks after the start of the  treatment, she developed alopecia. She was continued with sunitinib therapy till progression. CONCLUSIONS: The present case shows a rare metastasis to the ovary and early onset of rare adverse event of alopecia on starting sunitinib therapy. In the presence of confounding factors like hypothyroidism and dandruff, establishing this as an adverse reaction of sunitinib is difficult. This case had a unique metastatic spread with involvement of the bowel, ovary and peritoneal carcinomatosis. Use of adjuvant TKI's after resection of primary tumour in nonmetastatic setting may reduce metastatic rates and increase progression-free survival.

Analeptic agent from microbes upon cyanide degradation.

Microbes being the initial form of life and ubiquitous in occurrence, they adapt to the environment quickly. The microbial metabolism undergoes alteration to ensure conducive environment either by degrading the toxic substances or producing toxins to protect themselves. The presence of cyanide waste triggers the cyanide degrading enzymes in the microbes which facilitate the microbes to utilize the cyanide for its growth. To enable the degradation of cyanide, the microbes also produce the necessary cofactors and enhancers catalyzing the degradation pathways. Pterin, a cofactor of the enzyme cyanide monooxygenase catalyzing the oxidation of cyanide, is considered to be a potentially bioactive compound. Besides that, the pterins also act as cofactor for the enzymes involved in neurotransmitter metabolism. The therapeutic values of pterin as neuromodulating agent validate the necessity to pursue the commercial production of pterin. Even though chemical synthesis is possible, the non-toxic methods of pterin production need to be given greater attention in future.