Effects of haloperidol and domperidone on ventilatory roll off during sustained hypoxia in cats.

In a previous work, we showed that the adult cat demonstrates a ventilatory decline during sustained hypoxia (the "roll off" phenomenon) and that the mechanism responsible for this secondary decrease in ventilation lies within the central nervous system (J. Appl. Physiol. 63: 1658-1664, 1987). In this study, we sought to determine whether central dopaminergic mechanisms could have a role in the roll off. We studied the effects of haloperidol, a peripheral and centrally acting dopamine receptor antagonist, on the ventilatory response to sustained isocapnic hypoxia (end-tidal PO2 40-50 Torr, 20-25 min) in awake cats. In vehicle control cats (n = 5), sustained hypoxia elicited a biphasic respiratory response, during which an initial ventilatory stimulation is followed by a 24 +/- 6% (P less than 0.01) reduction. In contrast, in haloperidol- (0.1 mg/kg) treated cats (n = 5) the ventilatory roll off was virtually abolished (-1 +/- 1%; P = NS). We also measured ventilatory, carotid sinus nerve (CSN) and phrenic nerve (PhN) responses to sustained isocapnic hypoxia in anesthetized animals (n = 6) to explore the influence of haloperidol on peripheral and central response during the roll off. Control responses to hypoxia showed an initial increase in ventilation, PhN, and CSN activity, followed by a subsequent decline in ventilation and PhN activity of 17 +/- 3 and 17 +/- 5%, respectively (P less than 0.05). In contrast, CSN activity remained unchanged during the roll off. Administration of haloperidol (1 mg/kg) reduced the initial increment in ventilation, while the initial increase in CSN activity was augmented.(ABSTRACT TRUNCATED AT 250 WORDS)     

Entry of algal symbionts into oocytes of the coral Litophyton arboreum

On the Red Sea coral reefs Litophyton arboreum is a common octocoral whose endodermal cells are associated with endosymbiotic dinoflagellates (zooxanthellae). Colonies of this species are gonochoric and brood planulae which, upon release, are already associated with the algal symbionts. Algal cells within membrane-bound vacuoles are observed within the gastrovascular cavity of the polyps, adjacent to the oocytes and are gradually phagocytized by the follicular cells which surround the oocytes. During oogenesis, temporary gaps open in the mesoglea underlying the follicular cells. Symbionts within vacuoles, along with cytoplasm and various organelles derived from the follicular cells, are translocated through these gaps. Subsequently, groups of zooxanthellae accumulate at the perioocytic zone, flanked between the mesoglea and oocytic microvilli. At a later stage, prior to the commencement of the breeding season, symbionts pass through the oolemma and rest inside the periphery of the oocytes. It is proposed that early uptake of zooxanthellae by sexual progeny at the oocyte stage, indicates a highly specialized mode of interaction between this algal symbiont and its host.     

Urine metabolites are associated with glomerular lesions in type 2 diabetes

Introduction

Little is known about the association of urine metabolites with structural lesions in persons with diabetes.

Objectives

We examined the relationship between 12 urine metabolites and kidney structure in American Indians with type 2 diabetes.

Methods

Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan, and included a kidney biopsy at the end of the treatment period. Metabolites were measured in urine samples collected within a median of 6.5 months before the research biopsy. Associations of the creatinine-adjusted urine metabolites with kidney structural variables were examined by Pearson’s correlations and multivariable linear regression after adjustment for age, sex, diabetes duration, hemoglobin A_1c, mean arterial pressure, glomerular filtration rate (iothalamate), and losartan treatment.

Results

Participants (n?=?62, mean age 45?±?10 years) had mean?±?standard deviation glomerular filtration rate of 137?±?50 ml/min and median (interquartile range) urine albumin:creatinine ratio of 34 (14–85) mg/g near the time of the biopsy. Urine aconitic and glycolic acids correlated positively with glomerular filtration surface density (partial r?=?0.29, P?=?0.030 and r?=?0.50, P?<?0.001) and total filtration surface per glomerulus (partial r?=?0.32, P?=?0.019 and r?=?0.43, P?=?0.001). 2-ethyl 3-OH propionate correlated positively with the percentage of fenestrated endothelium (partial r?=?0.32, P?=?0.019). Citric acid correlated negatively with mesangial fractional volume (partial r=-0.36, P?=?0.007), and homovanillic acid correlated negatively with podocyte foot process width (partial r=-0.31, P?=?0.022).

Conclusions

Alterations of urine metabolites may associate with early glomerular lesions in diabetic kidney disease.

     

Genotype Selection to Rapidly Breed Congenic Strains

Congenic strains can now be constructed guided by the transmission of DNA markers. This allows not only selection for transmission of a desired, donor-derived differential region but also selection against the transmission of unwanted donor origin genomic material. The additional selection capacity should allow congenic strains to be produced in fewer generations than is possible with random backcrosses. Here, we consider modifications of a standard backcross breeding scheme to produce congenic mice by the inclusion of genotype-based selective breeding strategies. Simulation is used to evaluate the consequences of each strategy on the number of chromosomes that contain unwanted, donor-derived genetic material and the average length of this unwanted donor DNA for each backcross generation. Our prototypic strategy was to choose a single mouse to sire each generation using criteria designed to select against the transmission of chromosomes, other than the one containing the replacement genomic region, that contain any donor origin sequence at all. This chromosome elimination strategy resulted in an average of 16.4 chromosomes free of donor DNA in mice of the third backcross (N(3)) generation. A strategy based solely on positive selection for the replacement region required six backcross generations to achieve the same results.     

Novel, developmentally specific control of Ds transposition in maize

Plants form their gametes late in somatic development and, as a result, often pass somatic mutations on to their progeny. Classic examples of this process are the germinal revertants of unstable, Ac/Ds transposon-induced kernel mutations in maize: frequent and early reversion events during somatic development are generally correlated with a high frequency of revertant gametes. We have characterized a Ds allele of the maize waxy(wx) gene, wx-m5:CS7, for which the correlation between somatic and germinal reversion frequencies no longer holds. The ability of wx-m5:CS7 (CS7) to produce revertant gametes is suppressed ∼100-fold in comparison with a second Ds allele, wx-m5:CS8 (CS8), which has an identical insertion at Wx and the same frequent and early somatic reversion pattern in endosperm. The excision of Ds from wx is not reduced 100-fold in the somatic tissues of CS7 plants as compared with CS8 plants. Suppressed formation of CS7 revertant gametes is independent of the Ac transposase source and is heritably passed to the embryos of progeny kernels; however, frequent and early somatic reversion is observed again in endosperms of these progeny kernels. This suppression appears to be caused by a dominant mutation in a trans-acting product that can suppress the germinal reversion of other Ds-induced alleles as well; the mutation is tightly linked to Wx but is not in the CS7 Ds itself. Taken together, the data suggest a novel mode of developmental control of Ac/Ds elements by the host plant, suppressing element excision in the shoot meristem. Received: 16 December 1996 / Accepted: 4 March 1997     

Role of endogenous female hormones in hypoxic chemosensitivity

Tatsumi, Koichiro, Cheryl K. Pickett, Christopher R. Jacoby,John V. Weil, and Lorna G. Moore. Role of endogenous female hormones in hypoxic chemosensitivity. J. Appl.Physiol. 83(5): 1706-1710, 1997.Effective alveolar ventilation and hypoxicventilatory response (HVR) are higher in females than in males andafter endogenous or exogenous elevation of progesterone and estrogen.The contribution of normal physiological levels of ovarian hormones toresting ventilation and ventilatory control and whether their site(s) of action is central and/or peripheral are unclear.Accordingly, we examined resting ventilation, HVR, and hypercapnicventilatory responses (HCVR) before and 3 wk after ovariectomy in fivefemale cats. We also compared carotid sinus nerve (CSN) and centralnervous system translation responses to hypoxia in 6 ovariectomized and 24 intact female animals. Ovariectomy decreased serum progesterone butdid not change resting ventilation, end-tidalPCO₂, or HCVR (allP = NS). Ovariectomy reduced theHVR shape parameter A in the awake(38.9 ± 5.5 and 21.2 ± 3.0 before and after ovariectomy, respectively, P < 0.05) andanesthetized conditions. The CSN response to hypoxia was lower inovariectomized than in intact animals (shape parameterA = 22.6 ± 2.5 and 54.3 ± 3.5 in ovariectomized and intact animals, respectively,P < 0.05), but central nervous system translation of CSN activity into ventilation was similar inovariectomized and intact animals. We concluded that ovariectomy decreased ventilatory and CSN responsiveness to hypoxia, suggesting that the presence of physiological levels of ovarian hormones influences hypoxic chemosensitivity by acting primarily at peripheral sites.

     

Identification of Quantitative Trait Loci Controlling Levels of Radiation-Induced Thymocyte Apoptosis in Mice

Thymocyte apoptosis levels are higher in C57BL/6J mice than in C3Hf/Kam mice. Low-dose irradiation increases the numbers of thymocytes undergoing apoptosis, but the strain difference persists. We mapped three loci controlling radiation-induced thymocyte apoptosis levels in F2 intercross progeny of these strains. The strongest association of a genomic region with an apoptosis level occurred in a region of chromosome 11 known to harbor a locus (or loci) important in the pathogenesis of several rodent models of autoimmune disease. Additional loci influencing radiation-induced thymocyte apoptosis were identified on chromosomes 9 and 16. The genetic polymorphisms underlying these loci may have an evolutionary role in fine-tuning the apoptotic response in T cells and may be important in the etiology of lymphoproliferative disorders and autoimmunity.