In addition to some other functions, melanopsin-expressing retinal ganglion cells (RGCs) constitute the principal mediators of the circadian photoentrainment, a process by which the suprachiasmatic nucleus (the central clock of mammals), adjusts daily to the external day/night cycle. In the present study these RGCs were immunohistochemically labelled using a specific polyclonal antiserum raised against mouse melanopsin. A daily oscillation in the number of immunostained cells was detected in mice kept under a light / dark (LD) cycle. One hour before the lights were on (i.e., the end of the night period) the highest number of immunopositive cells was detected while the lowest was seen 4 h later (i.e., within the first hours of the light period). This finding suggests that some of the melanopsin-expressing RGCs “turn on” and “off” during the day/night cycle. We have also detected that these daily variations already occur in the early postnatal development, when the rod/cone photoreceptor system is not yet functional. Two main melanopsin-expressing cell subpopulations could be found within the retina: M1 cells showed robust dendritic arborization within the OFF sublamina of the inner plexiform layer (IPL), whilst M2 cells had fine dendritic processes within the ON sublamina of the IPL. These two cell subpopulations also showed different daily oscillations throughout the LD cycle. In order to find out whether or not the melanopsin rhythm was endogenous, other mice were maintained in constant darkness for 6 days. Under these conditions, no defined rhythm was detected, which suggests that the daily oscillation detected either is light-dependent or is gradually lost under constant conditions. This is the first study to analyze immunohistochemically the daily oscillation of the number of melanopsin-expressing cells in the mouse retina.
Chronic kidney disease (CKD) is characterized by loss of renal function. The pathological processes involved in the progression of this condition are already known, but the molecular mechanisms have not been completely explained. Recent reports have shown the intrinsic capacity of the kidney to undergo repair after acute injury through the reexpression of repairing proteins (Villanueva S, Cespedes C, Vio CP. Am J Physiol Regul Integr Comp Physiol 290: R861-R870, 2006). Stimulation with basic fibroblast growth factor (bFGF) could accelerate this process. However, it is not known whether bFGF can induce this phenomenon in kidney cells affected by CKD. Our aim was to study the evolution of renal damage in animals with CKD treated with bFGF and to relate the amount of repairing proteins with renal damage progression. Male Sprague-Dawley rats were subjected to 5/6 nephrectomy (NPX) and treated with bFGF (30 μg/kg, NPX+bFGF); a control NPX group was treated with saline (NPX+S). Animals were euthanized 35 days after bFGF administration. Functional effects were assessed based on serum creatinine levels; morphological damage was assessed by the presence of macrophages (ED-1), interstitial α-smooth muscle actin (α-SMA), and interstitial collagen through Sirius red staining. The angiogenic factors VEGF and Tie-2 and the epithelial/tubular factors Ncam, bFGF, Pax-2, bone morphogenic protein-7, Noggin, Lim-1, Wnt-4, and Smads were analyzed. Renal stem cells were evaluated by Oct-4. We observed a significant reduction in serum creatinine levels, ED-1, α-SMA, and Sirius red as well as an important induction of Oct-4, angiogenic factors, and repairing proteins in NPX+bFGF animals compared with NPX+S animals. These results open new perspectives toward reducing damage progression in CKD.
BackgroundThis double-blind, randomized trial compared dural puncture epidural analgesia (DPEA) for labor using 25-gauge and 27-gauge pencil point spinal needles. We hypothesized that both needle sizes would result in similar onset time (equivalence margin=2.5 min) and therefore designed the study as an equivalence trial.MethodsOne hundred and forty patients undergoing labor were randomized to DPEA with 25-gauge (n=70) or 27-gauge (n=70) pencil point spinal needles. After the placement of the epidural catheter, a bolus of 20 mL of bupivacaine 0.125% and fentanyl 2 µg/mL was administered to all subjects. Thereafter, patients received boluses of 12 mL of bupivacaine 0.125% every 2 hours as needed.A blinded investigator recorded the onset time (defined as the temporal interval required to achieve a pain score ≤1 on a 0–10 scale), S2 block, sensory block height (30 min after the initial bolus of local anesthetic), presence of motor block (30 min after the initial bolus of local anesthetic), number of top-up doses required during labor and incidence of postural headache.ResultsOut of the 140 recruited patients, 135 were retained for analysis. Compared with their 27-gauge counterparts, 25-gauge pencil point spinal needles provided a 1.6 min shorter DPEA onset (95% CI of the difference of the means: −3.2 to −0.1 min). However, there were no intergroup differences in terms of S2 block, sensory block height, motor block, number of top-up doses and incidence of postural headache.ConclusionDural puncture epidural analgesia with 25-gauge pencil point spinal needles provides a 1.6 min shorter onset time than DPEA with 27-gauge spinal needles. Although statistically significant, such a difference may not be clinically relevant. Further investigation is required to compare 25-gauge and 27-gauge spinal needles for DPEA in the setting of different local anesthetic infusion strategies.Trial registration number NCT03389945.
The amount of melanopsin protein per cell varies, depending on ambient light conditions. Periods of darkness or, more likely, the sequence of light and dark periods occurring under the daily cycles might be necessary for the normal development of the melanopsin system.
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