Adaptive changes in sigma and phencyclidine receptors during the long-term use of haloperidol and raclopride in rats

The experiments on male albino rats have shown that 15 days haloperidol (0.5 mg/kg) and raclopride (1 mg/kg) treatment, but not acute administration, causes the increase of density of sigma receptors in the brain. The number of phencyclidine receptors was also elevated, but this increase was not statistically evident. The behavioral effects of ketamine (5 mg/kg) were evidently decreased after long-term haloperidol and raclopride treatment. The motor stimulation and stereotyped behavior induced by apomorphine (0.15 mg/kg) were increased only after treatment of haloperidol, but not raclopride. It seems probable that repeated neuroleptic (haloperidol and raclopride) treatment causes the hyposensitivity of sigma and phencyclidine receptors, despite the increase of their number. It is possible that this change is related to the depolarization inactivation of dopamine neurons caused by repeated neuroleptic administration.     

Differential changes in GPR55 during microglial cell activation

We examined how lipopolysaccharide (LPS) and interferon gamma (IFN-γ), known to differentially activate microglia, affect the expression of G protein-coupled receptor 55 (GPR55), a novel cannabinoid receptor. We found that GPR55 mRNA is significantly expressed in both primary mouse microglia and the BV-2 mouse microglial cell line, and that LPS down-regulates this message. Conversely, IFN-γ slightly decreases GPR55 mRNA in primary microglia, while it upregulates this message in BV-2 cells. Moreover, the GPR55 agonist, lysophosphatidylinositol, increases ERK phosphorylation in BV-2 stimulated with IFN-γ, in correlation with the increased amount of GPR55 mRNA. Remarkably, these stimuli-induced changes in GPR55 expression are similar to those observed with CB₂-R, suggesting that both receptors might be involved in neuroinflammation and that their expression is concomitantly controlled by the state of microglial activation.     

Hemostatic changes induced by exercise during oral contraceptive use

Exercise-induced changes in hemostatic measurements were studied in 25 women. Twelve of the subjects were not using oral contraceptives and the remainder were using Demulen (ethynodiol diacetate (1 mg) and ethinyl estradiol (0.05 mg)). Exercise on a treadmill induced similar changes in both groups, but during the use of Demulen the levels of fibrinogen and plasminogen were higher, antithrombin level was lower, and the recalcified clotting and dilute whole blood lysis times were shorter in group 2 than in the corresponding samples obtained from the nonpill users.     

Generating pluripotent stem cells: Differential epigenetic changes during cellular reprogramming

Pluripotent stem cells hold enomous potential for therapuetic applications in tissue replacement therapy. Reprogramming somatic cells from a patient donor to generate pluripotent stem cells involves both ethical concerns inherent in the use of embryonic and oocyte-derived stem cells, as well as issues of histocompatibility. Among the various pluripotent stem cells, induced pluripotent stem cells (iPSC)-derived by ectopic expression of four reprogramming factors in donor somatic cells-are superior in terms of ethical use, histocompatibility, and derivation method. However, iPSC also show genetic and epigenetic differences that limit their differentiation potential, functionality, safety, and potential clinical utility. Here, we discuss the unique characteristics of iPSC and approaches that are being taken to overcome these limitations.     

Effects of haloperidol on ventilation during isocapnic hypoxia in humans

Pedersen, Michala E. F., Keith L. Dorrington, and Peter A. Robbins. Effects of haloperidol on ventilation during isocapnic hypoxia in humans. J. Appl. Physiol.83(4): 1110-1115, 1997.Exposure to isocapnic hypoxia produces anabrupt increase in ventilation [acute hypoxic ventilatoryresponse (AHVR)], which is followed by a subsequent decline[hypoxic ventilatory depression or decline (HVD)]. In cats, both anesthetized and awake,haloperidol has been reported to increase AHVR and almost entirelyabolish HVD. To investigate whether this occurs in humans, theventilatory responses of 15 healthy young volunteers to 20 min ofisocapnic hypoxia (end-tidal PO₂ = 50 Torr) were assessed at 1, 2, and 4.5 h after placebo (control) andafter oral haloperidol (Seranace, 0.05 mg/kg) on different days. Threesubjects were unable to complete the study because of akathisia. AHVRwas significantly greater with haloperidol compared with control(P < 0.01, analysis of variance).However, no significant change in HVD was found [control HVD = 9.3 ± 1.6 (SD) l/min, haloperidol HVD = 9.9 ± 2.1 l/min;P = not significant, analysis ofvariance]. We conclude that combined central and peripheraldopamine-receptor antagonism in humans with haloperidol produces asimilar pattern of change to that reported previously with theperipheral antagonist domperidone. We have been unable to show inhumans a decrease in HVD by the centrally acting drug as observed incats.

     

Differential blood flow changes between the future dominant and subordinate follicles precede diameter changes during follicle selection in mares

Diameter deviation during a follicular wave is characterized by the continued growth of the developing dominant follicle and reduced growth and regression of the subordinate follicles. This study considered the hypothesis that reduced blood flow in the future largest subordinate follicle precedes the beginning of diameter deviation. The hypothesis was tested by quantifying the daily changes in blood-flow velocities and blood-flow area within the wall of follicles before and during diameter deviation in mares (n = 7). The blood-flow end points were quantified daily by transrectal color Doppler ultrasonography. Follicles were identified retrospectively by rank as F1 (largest) and F2 according to the maximum attained diameter. Follicles were grouped into nine F1 diameter ranges of 3.0 mm each (equivalent to 1 day's growth) centered on 6.5, 9.5, 12.5, 15.5, 18.5, 21.5, 24.5, 27.5, and 30.5 mm. Diameter deviation began in the 24.5-mm group, as indicated by a smaller (P < 0.05) difference between F1 and F2 in the 24.5-mm group than in the 27.5-mm group. Based on a similar approach, peak systolic velocity and time-averaged maximum velocity of blood flow began to deviate between F1 and F2 in the 18.5-mm group (P < 0.04) and blood flow area began to deviate in the 21.5-mm group (P < 0.009). Thus, differential blood flow area between F1 and F2 began an average of 3.0 mm (equivalent to 1 day) and differential blood-flow velocities began an average of 6.0 mm before the beginning of diameter deviation. The results demonstrated that deviation between F1 and F2 in the blood flow of the follicle walls occurred 1 or 2 days before deviation in follicle diameter during follicle selection in mares.     

Diurnal changes in the duration of mitosis in rats]

The colchicine method was applied to the study of the 24-hour changes in the duration of mitosis in 45-day rats. The average diurnal duration of mitosis in the pancreatic epithelium, the liver and the epidermis of adult animals was almost half of that in the 7-day-old rats. Diurnal variations of the mitotic index in the investigated tissues could be due both to the variation in the mitotic rate and to that of the duration of mitosis.     

Differential changes in the synthesis and steady-state levels of thylakoid proteins during bean leaf senescence

During senescence of primary bean leaves (Phaseolus vulgaris), there are differential changes in the rates at which thylakoid proteins are synthesized. In particular, synthesis of the 32 kD herbicide-binding protein continues throughout senescence, whereas formation of the and subunits of ATPase, the 68 kD photosystem I reaction center polypeptide, cytochrome f, cytochrome b₆ and the structural apoprotein of the lightharvesting chlorophyll protein complex (LHCP) declines. Pulse-chase experiments with intact leaves indicated rapid degradation of the 32 kD protein, which is consistent with its known rapid rate of turnover. This degradation was light-dependent and inhibited by DCMU, and the kinetics of degradation were similar for young and senescent membranes. In Coomassie-stained gels, the 68 kD reaction center polypeptide of photosystem I, the and subunits of ATPase and the LHCP were the dominant proteins for all ages of membranes. Western blot analysis indicated that cytochrome f and cytochrome b₆ are selectively depleted during senescence. The data have been interpreted as indicating that translational disruptions in both the cytoplasmic and chloroplastic compartments may contribute to the decline in photosynthetic electron transport in the senescing leaf.     

Validating the use of wrist-level light monitoring for in-hospital circadian studies

This clinical methods comparison study describes the difference between light levels measured at the wrist (Actiwatch-L) and at the eye (Daysimeter) in a postoperative in-patient population. The mean difference between the two devices was less than 10 lux at light levels less than 5000 lux. Agreement between the devices was found to decrease as eye-level light exposure increased. Measurements at eye level of 5000 lux or more corresponded to a difference between the devices of greater than 100 lux. Agreement between the eye- and wrist-level light measurements also appears to be influenced by time of day. During the day, the measurement differences were on average 50 lux higher at eye level, whereas at night they were on average 50 lux lower. Although the wrist-level monitor was found to underestimate light exposure at higher light levels, it was well tolerated by participants in the clinical setting. In contrast, the eye-level monitor was cumbersome and uncomfortable for the patients to wear. This study provides light-exposure data on patients in real conditions in the clinical environment. The results show that wrist-level monitoring provides an adequate estimate of light exposure for in-hospital circadian studies.     

Influence of substance P on the behavioral changes induced by haloperidol in rats

Locomotor activity and grooming behavior of rats were recorded for a period of 30 min following intraventricular injections of substance P(SP) in doses of 0.60 and 2.50 microgram/rat. The lower dose of the peptide significantly increased locomotion for 10 min and time spent grooming for 25 min. The effects of the same two doses of SP on the hypokinesia induced by various pharmacological treatments modifying catecholaminergic systems were then examined. SP did not affect the behavioral depression produced by alpha-methyl-para-tyrosine (250 mg/kg), FLA-63 (25 mg/kg) and phenoxybenzamine (20 mg/kg). However, SP, in dose of 0.60 microgram/rat, systematically reversed the decrease in locomotor activity induced by a relatively small dose of haloperidol, 0.1 mg/kg. The dame dose of the peptide significantly counteracted the rigidity but not the hypokinesia and catalepsy resulting from the previous administration of a higher dose of haloperidol, 3 mg/kg. The results support the hypothesis that SP may exert direct or indirect function in motor behavior, possible via a modulatory action on brain dopaminergic systems.     

Differential changes of fat-soluble vitamins and pollutants during lactation in northern elephant seal mother-pup pairs

We investigated the changes of vitamins A and E as well as PCBs and DDTs during lactation in northern elephant seal (Mirounga angustirostris) mother-pup pairs. On average, milk vitamin A concentrations were 6 times higher during late lactation than during early lactation, a pattern that differs dramatically from terrestrial mammals. Vitamin A concentrations also significantly increased in the inner blubber throughout lactation, whereas they remained constant in the outer blubber. Similar dynamics were observed for PCBs and DDTs in maternal blubber and milk. Blubber appears to be an important storage site for vitamin A and organochlorines in seals and a direct transfer of those molecules to the mammary gland may occur. The dynamics of vitamin A, PCBs and DDTs differed from those of vitamin E. There was a significant drop in milk vitamin E concentrations between early and late lactation, which is the usual pattern observed in terrestrial mammals. The dynamics of vitamin E in the blubber layers also differed from those of vitamin A, suggesting different mechanisms of mobilization and transfer into the milk.     

Natriuria during immersion of brief duration

During immersion in sitting position to the neck of 10 normal adult males, natriuria is significantly increased even after pretreatment with captopril (2 mg X kg-1, p.o.). Inhibition of the renin-angiotensin-aldosterone cascade does not completely block the mechanisms causing natriuria during immersion.     

Differential changes in the steady state levels of thylakoid membrane proteins during senescence in Cucumis sativus cotyledons

Chloroplast structure and function is known to alter during foliar senescence. Besides, the alterations in the structural organisation of thylakoid membranes changes in the steady state levels of thylakoid membrane proteins occur due to leaf ageing. We monitored temporal changes in some of the specific proteins of thylakoid membrane protein complexes by western blotting in the Cucumis sativus cotyledons as a function of the cotyledon age. We observed that the levels of D1 and D2 proteins of photosystem II started declining at the early stages of senescence of Cucumis cotyledons and continued to decline with the progress of cotyledon age. Similarly the level of Cyt f of Cyt b6/f complex declined rapidly with progress of senescence in these cotyledons. The reaction centre proteins of photosystem I were relatively found to be more stable than that of photosystem II reaction centre proteins reflecting possibly the disorganisation of photosystem II prior to photosystem I. The 33 kDa extrinsic protein (MSP) of oxygen evolving complex, the LHCII apoprotein and the beta-subunit of ATPsynthase showed the declined levels with the progress of cotyledon age. However, the extents of loss of these proteins were not as high as the reaction centre proteins of photosystem II and the Cyt f. These results provide that during senescence, proteins of thylakoid membranes degrade in a specific temporal sequence and thereby affect the temporal photochemical functions in Cucumis sativus cotyledons.