Jeff Wyatt

Uniquely hominid features of adult human astrocytes.

Defining the microanatomic differences between the human brain and that of other mammals is key to understanding its unique computational power. Although much effort has been devoted to comparative studies of neurons, astrocytes have received far less attention. We report here that protoplasmic astrocytes in human neocortex are 2.6-fold larger in diameter and extend 10-fold more GFAP (glial fibrillary acidic protein)-positive primary processes than their rodent counterparts. In cortical slices prepared from acutely resected surgical tissue, protoplasmic astrocytes propagate Ca2+ waves with a speed of 36 μm/s, approximately fourfold faster than rodent. Human astrocytes also transiently increase cystosolic Ca2+ in response to glutamatergic and purinergic receptor agonists. The human neocortex also harbors several anatomically defined subclasses of astrocytes not represented in rodents. These include a population of astrocytes that reside in layers 5–6 and extend long fibers characterized by regularly spaced varicosities. Another specialized type of astrocyte, the interlaminar astrocyte, abundantly populates the superficial cortical layers and extends long processes without varicosities to cortical layers 3 and 4. Human fibrous astrocytes resemble their rodent counterpart but are larger in diameter. Thus, human cortical astrocytes are both larger, and structurally both more complex and more diverse, than those of rodents. On this basis, we posit that this astrocytic complexity has permitted the increased functional competence of the adult human brain.

Efficacy of nonfetal human RPE for photoreceptor rescue: a study in dystrophic RCS rats.

This study determines the efficacy of nonfetal human retinal pigment epithelium (RPE) for photoreceptor rescue utilizing the dystrophic RCS rat as an animal model. Eyes from 10- and 49-year-old donors were obtained through the Rochester Eye and Human Parts Bank. The RPE was isolated by enzymatic treatment of the choroid-RPE with 2% dispase for 30 min at 37 degrees C. Mechanically dissociated RPE cells were injected at the superior hemisphere into the subretinal space of dystrophic RCS rats during the fourth postnatal week. Rats receiving vehicle injection served as sham controls. The animals were immunosuppressed with daily cyclosporine injections (10 mg/kg) and sacrificed 30 days posttransplantation for histologic evaluation of the RPE graft and its effect on photoreceptor survival. Transplantation of adult human RPE promoted the survival of photoreceptors in the dystrophic RCS rat. Morphometric analysis of the grafted superior hemisphere demonstrated a threefold increase in photoreceptor cell density (149.2 +/- 50 SD) compared to sham controls (39.7 +/- 31 SD) and the untouched inferior hemisphere (52.8 +/- 28 SD). RPE from the 49-year-old donor was as effective as RPE from the 10-year-old donor in promoting photoreceptor survival. The results of this study in RCS rats suggests that RPE from adult human donors of varied ages is suitable for transplantation and retains the capability to promote survival of photoreceptor cells. This finding opens the possibility of using nonfetal RPE cells in human retinal transplantation.

Correlates of Photoreceptor Rescue by Transplantation of Human Fetal RPE in the RCS Rat

This study uses a water maze paradigm as a tool to assess posttransplantation changes in behavior associated with a visual stimulus. A set of dystrophic RCS rats received bilateral injections of freshly isolated human fetal RPE cells into the subretinal space of the superior equatorial hemisphere. Five age-matched control dystrophic RCS rats received subretinal injections of vehicle. All animals were immunosuppressed. At 2 months posttransplantation, each rat was tested in the water escape apparatus. The rat used a single light source, randomly located on the edge of the tank, to locate a submerged platform, placed directly in front of the light. Each rat was timed and videotaped during 10 consecutive trials. The swimming paths and times for all rats were recorded and statistically analyzed. Subsequent to the water escape trials, the eyes were embedded for histologic analysis which included quantitative assessment of photoreceptor cells in predefined retinal regions. The water escape data indicated the differences between the sham and experimental groups changed significantly over time (P = 0.0017). Over time, the transplanted animals learned to use light as a clue (P < 0.0001), whereas the sham animals did not (P = 0.73). Transplanted eyes had a significantly greater mean number of photoreceptors in the superior, grafted region than seen in the inferior region of the same eyes and compared with either region of sham-injected eyes (P = 0.0023). Statistical analyses demonstrated a functional advantage for visually guided behavior in RCS rats transplanted with human fetal RPE cells and a statistically significant PRC rescue effect at 2 months after transplantation.

Rabies Postexposure Prophylaxis, New York, 1995–2000

Bats are now the leading source of rabies postexposure prophylaxis.

The Intensity of the Pupillary Light Reflex Does Not Correlate with the Number of Retinal Photoreceptor Cells

The purpose of this study was to determine if the pupillary light reflex (PLR) can serve as an indicator of the number of photoreceptor cells present in the rat retina to a sufficient degree of precision to be useful for testing the functional effects of retinal transplantation. The PLR was measured as percentage constriction of normal Fischer 344 rats (n = 14) and compared to the PLR of light-damaged (1300 luxes/30 days exposure) Fischer rats (n = 13). Additionally, the PLR of RCS-rdy+ (congenic) rats (n = 8) was compared to the PLR or RCS dystrophic rats (n = 7). Three eyes from each group were randomly chosen for morphometry. The number of photoreceptor nuclear profiles per 60 microns of retinal length was counted at six predetermined loci and averaged. The mean PLR of Light-Damaged F344 group (64%) was significantly different from the mean PLR of the Normal F344 group (75%) (P = 0.003). However, the mean PLR of the RCS Dystrophic group (72%) did not differ from the mean PLR of the RCS Congenic group (71%) (P = 0.82). Morphometry revealed that the mean number of photoreceptor nuclear profiles within each group of animals was vastly different: Normal F344 = 138, Light Damaged F344 = 19, Congenic RCS = 93, and Dystrophic RCS = 1. No correlation was found between intensity of PLR and number of photoreceptors present (r = 0.11, P = 0.78).(ABSTRACT TRUNCATED AT 250 WORDS)

Morphometrics and pattern of growth in wild sifakas (Propithecus edwardsi) at ranomafana national park, madagascar

We summarize morphometric data collected over a period of 22 years from a natural population of rainforest sifakas (Propithecus edwardsi) at Ranomafana National Park, Madagascar, and we use those data to document patterns of growth and development. Individually identified, known‐age sifakas were successfully captured, measured, and released. We found that body segment lengths increased faster during growth than did body mass, with individuals attaining adult lengths earlier than adult mass. Females can begin reproducing before they are fully grown, but this may not be common. With the exception of hand length, we found no significant sex difference in any adult metric including body mass, chest, and limb circumferences, body segment lengths, and canine tooth height; however, body masses of individual females fluctuated more, independently of pregnancy, than did those of males. We found considerable interannual fluctuation in body mass with single individuals differing more within the same season in different years than from season to season in the same year. Such body mass fluctuation may be a consequence of eastern Madagascars variable and unpredictable environment in which rainfall during any selected month varies from year to year. Am. J. Primatol. 73:155–172, 2011.

PHARMACOKINETICS OF ORALLY ADMINISTERED TERBINAFINE IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS) FOR POTENTIAL TREATMENT OF ASPERGILLOSIS

Abstract The objective of this study was to determine the pharmacokinetic parameters of orally administered terbinafine hydrochloride based on 3, 7, and 15 mg/kg single- as well as multiple-dosage trials in order to calculate dosing requirements for potential treatment of aspergillosis in African penguins (Spheniscus demersus). Ten adult African penguins were used in each of these trials, with a 2-wk washout period between trials. Mean plasma concentrations of terbinafine peaked in approximately 4 hrs at 0.11 ± 0.017 µg/ml (mean ± SD) following administration of 3 mg/kg terbinafine, while 7 mg/kg and 15 mg/kg dosages resulted in peak plasma concentrations of 0.37 ± 0.105 and 0.33 ± 0.054 µg/ml, respectively. The volume of distribution increased with increasing dosages, being 37 ± 28.5, 40 ± 28.1, and 52 ± 18.6 mg/L for 3, 7, and 15 mg/kg doses, respectively. The mean half-life was biphasic with initial terminal half-life (t½) values of 9.9 ± 4.5, 17.2 ± 4.9 and 16.9 ± 5.4 hrs, for 3, 7, and 15 mg/kg doses, respectively. A rapid first elimination phase was followed by a slower second phase, and final elimination was estimated to be 136 ± 9.7 and 131 ± 9.9 hrs, for 7 and 15 mg/kg doses, respectively. Linearity was demonstrated for area under the curve but not for peak plasma concentrations for the three dosages used. Calculations based on pharmacokinetic parameter values indicate that a 15 mg/kg terbinafine q24h dosage regimen would result in steady-state trough plasma concentrations above the minimum inhibitory concentration (0.8–1.6 µg/ml), and this dosage is recommended as a potential treatment option for aspergillosis in penguins. However, additional research is required to determine both treatment efficacy and safety.

The efficacy of orally dosed ketamine and ketamine/medetomidine compared with intramuscular ketamine in rhesus macaques (Macaca mulatta) and the effects of dosing route on haematological stress markers.

Background  This study compared the efficacy of two orally‐dosed (PO) anaesthetic regimens for chemical immobilization in rhesus macaques (Macaca mulatta), versus the standard protocol of intramuscular (TM) ketamine. In addition, the effects of dosing route on haematological stress markers were evaluated.

Water escape performance of adult RCS dystrophic and congenic rats: a functional and histomorphometric study

The dystrophic Royal College of Surgeons (RCS) rat undergoes photoreceptor degeneration due to a hereditary defect in the retinal pigment epithelium. The congenic rat remains unaffected. Although the retinal degeneration is well characterized, few functional studies of this strain are available. We wished to compare the visual function of congenic and dystrophic RCS rats using a water escape paradigm that tested their ability to find a submersed, randomly placed platform using a light source as a clue. Three different behavioral experiments were sequentially performed on all animals: Experiment 1--The Light and Platform test measured the time to swim from the center of the pool to a platform located under a light clue. Each animal was given 10 trials. Experiment 2--The No Light with Platform test was performed as above except no light clue was used. Experiment 3--The Light and No Platform test was performed with a light clue but without a platform. The animal was allowed to swim for 2 min. All trials were videotaped. After the final experiment, the animals were sacrificed and a histomorphometric analysis of their retinas were performed. Expt. 1--The time to find the platform using light as a clue was greater for the dystrophic than for the congenic rats. Expt. 2--In the absence of light clue, there was no significant difference in performance between the congenic and dystrophic animals. Expt. 3--In the absence of a platform, a significantly greater amount of time was spent in the area indicated by the light clue by the congenic animals as compared to the dystrophic. Morphometric analysis revealed a mean number of 133 photoreceptor nuclear profiles/90 microns of retina for congenic rats as compared to 0.14 for dystrophic rats. This simplified version of the Morris water maze permits quantitative evaluation of visually-guided behavior in an important model of retinal degeneration.

Comparison of in vitro toxicological effects of biomass smoke from different sources of animal dung

Worldwide, over 4 million premature deaths each year are attributed to the burning of biomass fuels for cooking and heating. Epidemiological studies associate household air pollution with lung diseases, including chronic obstructive pulmonary disease, lung cancer, and respiratory infections. Animal dung, a biomass fuel used by economically vulnerable populations, generates more toxic compounds per mass burned than other biomass fuels. The type of animal dung used varies widely depending on local agro-geography. There are currently neither standardized experimental systems for dung biomass smoke research nor studies assessing the health impacts of different types of dung smoke. Here, we used a novel reproducible exposure system to assess outcomes related to inflammation and respiratory infections in human airway cells exposed to six different types of dung biomass smoke. We report that dung biomass smoke, regardless of species, is pro-inflammatory and activates the aryl hydrocarbon receptor and JNK transcription factors; however, dung smoke also suppresses interferon responses after a challenge with a viral mimetic. These effects are consistent with epidemiological data, and suggest a mechanism by which the combustion of animal dung can directly cause lung diseases, promote increased susceptibility to infection, and contribute to the global health problem of household air pollution.