A mechanistic derivation of the Monod bioreaction equation for a limiting nutrient.

We present a quasi-steady state mechanistic derivation of the Monod bioreaction equation based upon a conceptual model involving aqueous phase diffusive transport of substrate towards a spherical microbe; transport of the substrate across its surface membrane; and reaction depleting the substrate within the microbe. The resulting Monod coefficients [Formula: see text] and [Formula: see text] are dependent upon substrate-species pairs and the mass transfer properties of the system. Two substrate transport scenarios are investigated: (1) a constant rate model that is a function of a constant flux across the surface of the microbe; and (2) a linear rate model that is the product of a constant transport velocity and the concentration of substrate in contact with the surface of the microbe. The model is verified and parameterized using benzene, toluene, and phenol depletion and biomass growth data obtained from Reardon et al. (Biotechnol Bioeng: 385-400, 2000). Calibration results indicate a normalized surface to bulk concentration ratio of nearly unity in all simulations for benzene, toluene, and phenol when paired with P. putida F1, implying that the process is not aqueous phase diffusion limited.

Cell Enriched Autologous Fat Grafts to Follicular Niche Improves Hair Regrowth in Early Androgenetic Alopecia.

BACKGROUND: Adipose and adipose derived regenerative cells (ADRCs) play an increasing role in androgenetic alopecia. OBJECTIVES: The authors sought to evaluate the safety and feasibility of fat grafts enriched with ADRCs in early androgenetic alopecia. METHODS: Seventy-one patients were treated: 16 with Puregraft fat and 1.0 × 106 ADRCs/cm2 scalp; 22 with Puregraft fat and 0.5 × 106 ADRCs/cm2 scalp, 24 with Puregraft fat alone, and 9 with saline control. Treatments were delivered into the skin and subcutaneous layer of the scalp. A total of 40 cm2 of scalp was treated and macrophotography and global photography were obtained at baseline and at 6, 24, and 52 weeks. RESULTS: A total of 71 patients tolerated the procedures well. No unanticipated associated adverse events were reported. When evaluating all patients at 24 weeks, there were no statistical differences between any of the treatment groups with respect to nonvellus (terminal) hair counts or width. There were increases (mean change from baseline) in terminal hair count for the low-dose ADRC group in the Norwood Hamilton 3 subgroup at week 6 (13.90 ±â€…16.68), week 12 (11.75 ±â€…19.42), week 24 (16.56 ±â€…14.68), and week 52 (2.78 ±â€…16.15). For this subgroup, the difference in hair count between the low-dose ADRC group and no-fat saline control was statistically significant (P = 0.0318) at week 24. CONCLUSIONS: Puregraft fat and ADRCs are safe and well tolerated. In early male hair loss, this therapy demonstrated a statistically significant increase in terminal hair counts relative to the control population at 24 weeks and represents a promising approach for early androgenetic alopecia.

Reduction of diffusive contaminant emissions from a dissolved source in a lower permeability layer by sodium persulfate treatment.

Residual contamination contained in lower permeability zones is difficult to remediate and can, through diffusive emissions to adjacent higher permeability zones, result in long-term impacts to groundwater. This work investigated the effectiveness of oxidant delivery for reducing diffusive emissions from lower permeability zones. The experiment was conducted in a 1.2 m tall × 1.2 m wide × 6 cm thick tank containing two soil layers having 3 orders of magnitude contrast in hydraulic conductivity. The lower permeability layer initially contained dissolved methyl tert-butyl ether (MTBE) and benzene, toluene, ethylbenzene, and p-xylenes (BTEX). The treatment involved delivery of 10% w/w nonactivated sodium persulfate (Na2S2O8) solution to the high permeability layer for 14 days. The subsequent diffusion into the lower permeability layer and contaminant emission response were monitored for about 240 days. The S2O8(2-) diffused about 14 cm at 1% w/w into the lower permeability layer during the 14 day delivery and continued diffusing deeper into the layer as well as back toward the higher-lower permeability interface after delivery ceased. Over 209 days, the S2O8(2-) diffused 60 cm into the lower permeability layer, the BTEX mass and emission rate were reduced by 95-99%, and the MTBE emission rate was reduced by 63%. The overall treatment efficiency was about 60-110 g-S2O8(2-)delivered/g-hydrocarbon oxidized, with a significant fraction of the oxidant delivered likely lost by back-diffusion and not involved in hydrocarbon destruction.

Safety and Tolerability of KIO-101 Eye Drops in Healthy Volunteers and Patients with Ocular Surface Disease-A Phase I Study.

PURPOSE: Inhibitors of dihydroorotate dehydrogenase (DHODH) have been found to be potent anti-inflammatory agents. Recently, a topical formulation (KIO-101 eye drops) of a DHODH inhibitor has been developed. The aim of the present study was to evaluate the safety and tolerability of KIO-101 eye drops in Healthy Volunteers (HVs) and patients with conjunctival hyperemia. METHODS: The study was carried out in a double-masked, placebo-controlled, randomized, parallel-group design with two parts. In part I, HVs received single and multiple instillations (four times daily for 12 consecutive days) of KIO-101 eye drops in ascending doses of 0.05%, 0.15%, and 0.30%, respectively. Part II was conducted in patients with conjunctival hyperemia who received 0.15% KIO-101 eye drops twice daily for 12 consecutive days. Ophthalmic and systemic safety examinations were performed on all participants. In part II, ocular hyperemia grading and an ocular surface disease index (OSDI) questionnaire were performed. RESULTS: 24 HVs participated in part I and 21 patients in part II. KIO-101 eye drops were well tolerated in all subjects. No serious adverse events (SAEs) occurred, and all AEs that were reported were transient and considered mild to moderate. In the highest dose cohort (0.30%), epistaxis occurred in two subjects after multiple instillations. In part II, after 12 days treatment with 0.15% KIO-101, conjunctival hyperemia decreased by -1.1 ± 0.27 points in the treatment and -0.6 ± 0.79 points in the placebo group (p = 0.0385). OSDI decreased from 47.9 ± 18.7 to 27.6 ± 19.13 points in the treatment group, while in the placebo group, a change from 41.3 ± 12.08 to 27.3 ± 18.63 points occurred. CONCLUSIONS: A 12-day treatment regimen with topical KIO-101 eye drops at low and mid doses was safe and well tolerated in both HVs and patients with conjunctival hyperemia. The obtained results point towards an early sign of reduction in conjunctival hyperemia.

Ranpirnase (OKG-0301), a Novel Ribonuclease, Demonstrates Antiviral Activity against Adenovirus in the Ad5/NZW Rabbit Ocular Replication Model.

Adenovirus ocular infections are common ocular viral infections seen worldwide, for which there is no approved antiviral therapy available. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA resulting in an inhibition of protein synthesis. The study goal was to determine the anti-adenoviral activity of topical formulations of ranpirnase (OKG-0301) on adenoviral replication in the Ad5/NZW rabbit ocular replication model. NZW rabbits were inoculated in both eyes with human adenovirus type 5 (HAdV5) after corneal scarification. A day later, topical therapy was initiated in both eyes with 0.03% OKG-0301, 0.003% OKG-0301, saline or 0.5% cidofovir. Eyes were cultured to determine HAdV5 eye titers over 2 weeks. OKG-0301 (0.03% and 0.003%) and 0.5% cidofovir decreased viral titers compared to saline. Furthermore, both OKG-0301 formulations and 0.5% cidofovir shortened the duration of the HAdV5 infection compared to saline. Both 0.03% OKG-0301 and 0.003% OKG-0301 demonstrated increased antiviral activity compared to saline in the Ad5/NZW rabbit ocular replication model. The antiviral activity of the OKG-0301 groups was similar to that of the positive antiviral control, 0.5% cidofovir. Ranpirnase (OKG-0301) may be a potential candidate for a topical antiviral for adenoviral eye infections. Further clinical development is warranted.

The use of adult stem cells in regenerative medicine.

The cellular component of the tissue engineering paradigm is arguably the most important piece of the complex task of regenerating or repairing damaged or diseased tissue. Critical to the development of clinical strategies is the need for reliable sources of multipotent cells that can be obtained with limited morbidity. The adult stem cell population may be well suited for this task. The next several years will bring many phase I and II studies using adult stem cells as the cellular foundation for engineered tissue constructs. Future research should be directed toward better characterization of this cell population, including identifying unique markers and mapping out lineage development. For now, the ideal source of adult stem cells remains uncertain, but as questions are answered, adult stem cell biology will likely transition from bench top to clinical reality.