There is a growing demand for durable advanced wound dressings for the management of persistent infections after deep burn injuries. Herein, we demonstrated the preparation of durable antimicrobial nanofiber mats, by taking advantage of strong interfacial interactions between polyhydroxy antibiotics (with varying number of OH groups) and gelatin and their in-situ crosslinking with polydopamine (pDA) using ammonium carbonate diffusion method. Polydopamine crosslinking did not interfere with the antimicrobial efficacy of the loaded antibiotics. Interestingly, incorporation of antibiotics containing more number of alcoholic OH groups (N ≥ 5) delayed the release kinetics with complete retention of antimicrobial activity for an extended period of time (20 days). The antimicrobials-loaded mats displayed superior mechanical and thermal properties than gelatin or pDA-crosslinked gelatin mats. Mats containing polyhydroxy antifungals showed enhanced aqueous stability and retained nanofibrous morphology under aqueous environment for more than 4 weeks. This approach can be expanded to produce mats with broad spectrum antimicrobial properties by incorporating the combination of antibacterial and antifungal drugs. Direct electrospinning of vancomycin-loaded electrospun nanofibers onto a bandage gauze and subsequent crosslinking produced non-adherent durable advanced wound dressings that could be easily applied to the injured sites and readily detached after treatment. In a partial thickness burn injury model in piglets, the drug-loaded mats displayed comparable wound closure to commercially available silver-based dressings. This prototype wound dressing designed for easy handling and with long-lasting antimicrobial properties represents an effective option for treating life-threatening microbial infections due to thermal injuries.

Corneal stromal dystrophies are a group of genetic disorders that may be caused by mutations in the transforming growth factor β-induced (TGFBI) gene which results in the aggregation and deposition of mutant proteins in various layers of the cornea. The type of amino acid substitution dictates the age of onset, anatomical location of the deposits, morphological features of deposits (amyloid, amorphous powder or a mixture of both forms) and the severity of disease presentation. It has been suggested that abnormal turnover and aberrant proteolytic processing of the mutant proteins result in the accumulation of insoluble protein deposits. Using mass spectrometry, we identified increased abundance of a 32 amino acid-long peptide in the 4th fasciclin-like domain-1 (FAS-1) domain of transforming growth factor β-induced protein (amino acid 611–642) in the amyloid deposits of the patients with lattice corneal dystrophies (LCD). In vitro studies demonstrated that the peptide readily formed amyloid fibrils under physiological conditions. Clinically relevant substitution (M619K, N622K, N622H, G623R and H626R) of the truncated peptide resulted in profound changes in the kinetics of amyloid formation, thermal stability of the amyloid fibrils and cytotoxicity of fibrillar aggregates, depending on the position and the type of the amino acid substitution. The results suggest that reduction in the overall net charge, nature and position of cationic residue substitution determines the amyloid aggregation propensity and thermal stability of amyloid fibrils.

A new method has been developed for the simultaneous measurement of inulin and PAH clearance in small laboratory animals (rats). A double-chambered Teflon capsule (capacity: 3 ml) is implanted intraperltuneally. One of the chambers is filled with inulin solution and the other with PAH solution. Both solutions are iso-osmotie. The open ends of the capsule are sealed with double dialysis membranes. Sufficiently high serum and urine levels of both substances can thus be maintained for 72 h. By adapting suitable methods, it proved possible to estimate inulin and PAH in 500 #1 of blood or urine. The advantage of the method is that it can be used for renal clearance tests in small conscious animals, able to move freely within their cages without anaesthesia or intravenous infusions.The feasibility of the technique was tested by monitoring the behaviour of various parameters of renal function after administration of the following nephrotoxic agents: puromycin aminonucleoside, 100 mg/kg s.c.; uranyl nitrate, 2 mg/kg s.c.; mercuric chloride, I mg/kg i.p. The following factors were measured or calculated: urine output, GFR, fractional water reabsorption, PAH clearance, serum urea concentration and clearance, reabsorbed/secreted urea (percentage of filtered urea), Na + clearance and fractional Na + reabsorption, urine glucose concentration, glucose clearance and fractional reabsorption, and urine protein concentration. After the dose of aminonucleoslde there was a significant rise in plasma urea together with significant protelnuria reaching their peak on the eighth day. Uranyl nitrate poisoning caused an approximately 25% reduction in GFR, a drastic reduction in PAH clearance, a definite rise in plasma urea and a reduction in fractional glucose reabsorption from 99 to 55%, all these changes reaching their maximum on the sixth day. After mercuric chloride poisoning the changes reached their peak on the third day; GFR was reduced by approximately 60% and at the same time fractional water reabsorption fell from 97 to 90%. PAH clearance was reduced to 25% of normal and urea concentration rose to 231 mg/100 ml -an extremely high level. Fractional glucose reabsorption was 70.9~ as Part of this work was presented at the 18th and 19th Spring Meetings of the German Pharmacological Society in Mainz, 1977 and1978. compared with 99.7% in the controls. From these results it is apparent that the renal lesion induced by aminonueleoside is situated exclusively in the glomeruli, while the damage caused by uranyl acetate is entirely or almost entirely eonfined to the tubules. The nephrotoxle action of mercuric chlorlde involves both glomerular and tubular functions. However, such an interpretation disregards the fact, established by histological examination, that in mercuric chloride poisoning a large proportion of the proximal tubuli are consistently blocked with cell debris. Under the light microscope the glomerull appear to be intact so that the reduction in GFR cannot be ascribed to glomerular damage, but must be the result of ...

The high mortality associated with invasive fungal infections, narrow spectrum of available antifungals, and increasing evolution of antifungal resistance necessitate the development of alternative therapies. Host defense peptides are regarded as the first line of defense against microbial invasion in both vertebrates and invertebrates. In this work, we investigated the effectiveness of four naturally occurring pore-forming antimicrobial peptides (melittin, magainin 2, cecropin A, and mastoparan B) against a panel of clinically relevant pathogens, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida glabrata. We present data on the antifungal activities of the four pore-forming peptides, assessed with descriptive statistics, and their cytocompatibility with cultured human cells. Among the four peptides, mastoparan B (MB) displayed potent antifungal activity, whereas cecropin A was the least potent. We show that MB susceptibility of phylogenetically distant non-candida albicans can vary and be described by different intrinsic physicochemical parameters of pore-forming α-helical peptides. These findings have potential therapeutic implications for the design and development of safe antifungal peptide-based drugs.

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