Channeling Vision: CaV1.4-A Critical Link in Retinal Signal Transmission.

Voltage-gated calcium channels (VGCC) are key to many biological functions. Entry of Ca2+ into cells is essential for initiating or modulating important processes such as secretion, cell motility, and gene transcription. In the retina and other neural tissues, one of the major roles of Ca2+-entry is to stimulate or regulate exocytosis of synaptic vesicles, without which synaptic transmission is impaired. This review will address the special properties of one L-type VGCC, CaV1.4, with particular emphasis on its role in transmission of visual signals from rod and cone photoreceptors (hereafter called "photoreceptors," to the exclusion of intrinsically photoreceptive retinal ganglion cells) to the second-order retinal neurons, and the pathological effects of mutations in the CACNA1F gene which codes for the pore-forming α1F subunit of CaV1.4.

Cone dystrophy and ectopic synaptogenesis in a Cacna1f loss of function model of congenital stationary night blindness (CSNB2A).

Congenital stationary night blindness 2A (CSNB2A) is an X-linked retinal disorder, characterized by phenotypically variable signs and symptoms of impaired vision. CSNB2A is due to mutations in CACNA1F, which codes for the pore-forming α1F subunit of a L-type voltage-gated calcium channel, Cav1.4. Mouse models of CSNB2A, used for characterizing the effects of various Cacna1f mutations, have revealed greater severity of defects than in human CSNB2A. Specifically, Cacna1f-knockout mice show an apparent lack of visual function, gradual retinal degeneration, and disruption of photoreceptor synaptic terminals. Several reports have also noted cone-specific disruptions, including axonal abnormalities, dystrophy, and cell death. We have explored further the involvement of cones in our 'G305X' mouse model of CSNB2A, which has a premature truncation, loss-of-function mutation in Cacna1f. We show that the expression of genes for several phototransduction-related cone markers is down-regulated, while that of several cellular stress- and damage-related markers is up-regulated; and that cone photoreceptor structure and photopic visual function - measured by immunohistochemistry, optokinetic response and electroretinography - deteriorate progressively with age. We also find that dystrophic cone axons establish synapse-like contacts with rod bipolar cell dendrites, which they normally do not contact in wild-type retinas - ectopically, among rod cell bodies in the outer nuclear layer. These data support a role for Cav1.4 in cone synaptic development, cell viability, and synaptic transmission of cone-dependent visual signals. Although our novel finding of cone-to-rod-bipolar cell contacts in this mouse model of a retinal channelopathy may challenge current views of the role of Cav1.4 in photopic vision, it also suggests a potential new target for restorative therapy.

Insulin-like growth factor-I and its binding proteins in colostrum compared to measures in serum of Holstein neonates.

Colostral insulin-like growth factor-I (IGF-I) may be beneficial in the development of gastrointestinal tracts of bovine neonates. Thus, the purpose of this study was to examine relationships among concentrations of IGF-I and IGF-binding proteins (IGFBP) in colostrum used at two initial feedings and serum concentrations of IGF-I, IGFBP, total protein, gamma glutamyltransferase (GGT), and immunoglobulin G at 0 and 48 h after birth in Holstein neonates. Calves (n = 22) were separated from dams immediately after birth. Blood samples were taken before initial feeding and at 48 h after birth. Calves were fed 2 L of colostrum twice and milk replacer thereafter. Linear regression of serum IGF-I at 48 h and colostral IGF-I revealed a significant positive relationship (R2 = 0.204). Serum IGFBP-3 at 48 h and colostral IGFBP-3 also had a positive relationship (R2 = 0.143). However, linear regression of colostral IGF-I on the difference in serum IGF-I at 48 and 0 h was not significant. Calves were assigned to group 1 (0-h serum IGF-I < 10 ng/ml; n = 11) or group 2 (0-h serum IGF-I > or = 10 ng/ml; n = 11) for further analysis. There were no differences in serum IGF-I or IGFBP-2, -3, -4, and -5 concentrations at 48 h between groups 1 and 2. Correlation coefficients revealed negative relationships of serum IGF-I at 0 h to the difference between serum IGF-I at 48 and 0 h (r = -0.824), as well as birth weight of the calf to the amount of GGT at 48 h (r = -0.604). Females had lower birth weights than males, but sex of calf did not affect serum measures. At 0 h, but not 48 h, total serum protein was correlated to serum GGT concentrations (r = 0.573). From indirect evidence, absorption of colostral IGF-I and IGFBP-3 into systemic circulation may occur, but relative importance compared to endogenous sources is uncertain.

Propionibacteria fed to dairy cows: effects on energy balance, plasma metabolites and hormones, and reproduction.

To determine the effect of feeding Propionibacteria on energy balance, milk yield, and composition, metabolites and hormones of early-lactating dairy cows, multiparous Holstein cows were individually fed a total mixed ration from -2 to 12 wk postpartum with no addition (control, n = 10) or with an additional 17 g of Propionibacteria culture daily (Treated, n = 9). Daily feed intake and milk production were recorded. Plasma cholesterol, nonesterified fatty acids (NEFA), leptin, insulin, glucose, insulin-like growth factor-I (IGF-I), IGF-binding proteins (IGFBP), and progesterone concentrations were measured up to twice weekly. Cows fed supplemental Propionibacteria had improved energy balance at wk 1 of lactation and had lower DMI per kg of body weight than control cows on wk 3 to 7, 10, and 12. Cows fed Propionibacteria had a greater percentage of milk protein and solids-not-fat and plasma NEFA concentrations than did control cows only at wk 1 of lactation. Treatment did not affect milk production or percentage of milk fat and lactose. Leptin levels were greater in treated than control cows throughout the study. Plasma glucose, insulin, cholesterol, IGFBP-3, and IGF-I concentrations were not affected by feeding Propionibacteria, but those variables increased with week postpartum. Plasma IGFBP-2 and IGFBP-5 levels decreased with week postpartum. Measures of reproductive and ovarian function did not differ between Propionibacteria-treated and control cows. Feeding Propionibacteria culture to transition and early lactating dairy cows may hold potential for improved milk protein production and metabolic efficiency during early lactation, without affecting reproductive function.

[Acute amoxapine poisoning with rhabdomyolysis and acute renal insufficiency]. / Intoxication aiguë à l'amoxapine avec rhabdomyolyse et insuffisance rénale aiguë.

Acute renal failure and rhabdomyolysis are reported in a 33 year old man who had taken 6 g of amoxapine. Different possible levels for the toxic action of amoxapine are discussed and compared with literature data.

Validation of real-time ultrasound technology for predicting fat thicknesses, longissimus muscle areas, and composition of Brangus bulls from 4 months to 2 years of age.

Sixty Brangus bulls were evaluated live using two real-time ultrasound instruments and four technicians to estimate longissimus muscle area (LMA) and 12th rib fat thickness (FT) every 4 mo beginning at 4 and 12 mo of age, respectively, and continuing until 24 mo of age. Ten bulls were slaughtered every 4 mo to determine actual LMA and FT, 9-10-11th rib chemical composition, yield grade (YG) factors, and empty body weight (EBW). Live animal traits were used to predict 9-10-11th rib composition, YG, and EBW. Scanned mean FT was accurate (P less than .05) at 16 mo and was not different (P = .09) from the actual mean FT (95% of the time the error in estimation was less than or equal to .33 cm). Scanned mean LMA was accurate (P less than .05) at 12 mo (95% of the time the error in estimation was less than or equal to 20.0 cm2). Absolute differences between scanned and actual mean FT and LMA were different (P less than .05) from zero for the main effects of month, operator and(or) interpreter, and instrument. Increased level of operator skill did not improve the accuracy of FT or LMA measurements, whereas increased level of skill of the interpreter of scans did improve the accuracy of LMA estimations. There was no difference (P greater than .05) between ultrasound instruments in accuracy of estimating FT or LMA. The most accurate prediction of YG occurred at 12 mo and incorporated LW, hip height (HH), and ultrasound LMA (R2 = .95, SD = .14). The most accurate prediction of EBW occurred at 16 mo and incorporated LW, HH, and ultrasound FT (R2 = .99, SD = 6.65 kg), whereas the most accurate equation for combined slaughter periods incorporated LW, HH, and ultrasound LMA (R2 = .99, SD = 20.71 kg). We conclude that scanning of LMA at 12 mo and of FT at 12 or 16 mo were sufficiently accurate to characterize groups of bulls; however, some individual measurements were quite inaccurate. Measurements at other months should not be considered accurate for either individuals or groups of bulls. Yield grade and EBW can be accurately estimated from live animal and ultrasound measurements, which may be useful in identifying Brangus cattle with superior cutability and may eliminate the need for serial slaughter in research projects.

An evaluation of the Haema-Count MK-40 blood counting system.

The Haema-Count MK-40, a semiautomated blood counting system, determines hemoglobin, erthrocyte count, leukocyte count, and hematocrit values of blood cell suspensions prepared with a small automatic pipetter-diluter. It is similar to the MK-3, which the authors previously evaluated, but has automatic coincidence correlation and a modified prime and rinse cycle. Its performance was compared with those of standard methods, i.e., the single-channel Coulter Counter and manual cyanmethemoglobin and microhematocrit methods. Precisions for hemoglobin determinations and for leukocyte and erythrocyte counts were equal to those of the reference (comparative) methods. Patients comparisons for those determinations had only small intermethod variability and small clinically insignificant biases. The hematocrit channel was the least precise. With a modified method of calibration, the authors obtained patient comparisons without statistically significant bias from the microhematocrit. Calibration was stable for all channels during the course of the study.