Distal Lateral Subungual Onychomycosis Owing to <Emphasis Type="Italic">Tritirachium oryzae</Emphasis>: A Bystander or Invader?

The genus Tritirachium is a mitosporic fungus which inhabits in soil and decaying plant material and also a notable insect pathogen. Human infections with Tritirachium species though rare were previously reported to cause corneal ulcers, otomycosis, onychomycosis, and dermatomycosis of the scalp and hence may be considered as a potential pathogen. Here we report a case of distal lateral subungual onychomycosis involving right great toenail in a 22-year-old female, wherein direct potassium hydroxide preparations, fungal cultures, and molecular sequencing of the isolate established Tritirachium oryzae as the etiological agent. Antifungal susceptibility performed by the microbroth technique of CLSI revealed increased MICs to amphotericin B and low MICs to azoles and echinocandins. The case was managed with surgical nail avulsion followed by topical application of 2% ketoconazole cream resulting regrowth of normal nail. To the best of our knowledge, this is the first report of non-dermatophytic mold T. oryzae causing onychomycosis in India.     

Rapid quantitative analysis of monoclonal antibody heavy and light chain charge heterogeneity

An alternative method to traditional 2-dimensional gel electrophoresis (2D-PAGE) and its application in characterizing the inherent charge heterogeneity of chromatographically isolated monoclonal antibody heavy and light chains is described. This method, referred to as ChromiCE, utilizes analytical size-exclusion chromatography (SEC), performed under reducing and denaturing conditions, followed by imaged capillary isoelectric focusing (icIEF) of the chromatographically separated heavy and light chains. Under conditions suitable for the subsequent icIEF analysis, the absolute and relative SEC elution volumes of the heavy and light chains were found to be highly pH dependent, a phenomenon that can be exploited in optimizing chromatographic separation. Compared to 2D-PAGE, the ChromiCE method substantially decreases the time and labor needed to complete the analysis, improves reproducibility, and provides fully quantitative assessment of charge heterogeneity. The ChromiCE methodology was applied to a set of diverse monoclonal antibodies to demonstrate suitability for quantitative charge variant analysis of heavy and light chains. A typical application of ChromiCE in extended characterization and stability studies of a purified antibody is shown.     

Suppression of insulin aggregation by heparin

The aggregation of insulin near its isoelectric point and at low ionic strength was suppressed in the presence of heparin. To understand this effect, we used turbidimetry and stopped-flow to study the pH- and ionic strength ( I)-dependence of the aggregation of heparin-free insulin. The results supported the role of interprotein electrostatic interactions, contrary to the commonly held view that such forces are minimized at pH = pI. Electrostatic modeling of insulin (DelPhi) revealed that attractive interactions arise from the marked charge anisotropy of insulin near pI. We show how screening of the interprotein attractions by added salt lead to maximum aggregation near I = 0.01 M, corresponding to a Debye length nearly equal to the diameter of the insulin dimer, consistent with a dipole-like protein charge distribution. This analysis is also consistent with suppression of aggregation by heparin, a strong polyanion that by binding to the positive domain of one protein, inhibits its interaction with the negative domain of another.     

Mycosis of the Plantar Surface of Foot Owing to Nondermatophyte Mold Nodulisporium griseobrunneum Mimicking a Tinea Pedis

Nondermatophyte molds (NDM) and dematiaceous molds are less frequently implicated as the etiological agents of tinea-like infections of the foot. Among the etiological agents, Hendersonula toruloidea (now, Nattrassia mangiferae), Scytalidium hyalinum, Alternaria species (spp.), and Fusarium spp. are infrequently associated with foot mycoses. Nodulisporium (N.) spp. is a mitosporic NDM, which has been implicated in human infections like cerebral phaeohyphomycosis and allergic fungal sinusitis. Here, we report N. griseobrunneum in a 9-year-old female with mycosis of the plantar surface of foot mimicking a tinea pedis. Potassium hydroxide mount of skin specimen demonstrated dichotomous branching septate hyphae. Fungal culture and molecular sequencing established N. griseobrunneum as the etiological agent. Antifungal susceptibility testing revealed lower MICs to all seven drugs tested including itraconazole (ITR). The patient was treated with ITR and topical terbinafine. To the best of our knowledge, this is the first communication depicting molecular confirmation of the etiologic agent and antifungal susceptibility data of the mycosis of the plantar surface of foot owing to N. griseobrunneum from India.