Lactation performance of Holstein cows treated with 2 formulations of recombinant bovine somatotropin in a large commercial dairy herd in Brazil.

The objectives of this controlled study were to compare the effects of 2 different formulations of recombinant bovine somatotropin (rbST) on milk yield, milk composition (fat and protein), milk somatic cell count, and body condition score (BCS) among dairy cattle in a large commercial herd. Regulatory approved 500-mg zinc sesame oil base rbST (ZSO-rbST; Elanco Animal Health, Greenfield, IN) and vitamin E lecithin base rbST (VEL-rbST; LG Life Sciences, Seoul, South Korea) formulations were administered per the manufacturers' recommendations every 14 d over 17 injection cycles starting at 57 to 70 d of lactation (90 cows per rbST group). Control cows (n = 60) received no rbST. Somatotropin-treated animals (VEL-rbST and ZSO-rbST combined) had increased average milk yield and protein percentage and lower average BCS compared with control cows. For primiparous cows, average milk yield was 37.75 kg/d with the ZSO-rbST treatment and 35.72 kg/d with the VEL-rbST treatment. For multiparous cows, average milk yield was 40.13 kg/d with the ZSO-rbST treatment and 38.81 kg/d with the VEL-rbST treatment. There were no differences in milk fat percentage between VEL-rbST and ZSO-rbST treatments, but milk protein content was greater with VEL-rbST treatment than with ZSO-rbST treatment. Nonetheless, cows treated with ZSO-rbST yielded more kilograms of fat and protein per day than cows treated with VEL-rbST. No significant differences in BCS were found between both rbST treatment groups. The differential increase in milk yield between cows treated with ZSO-rbST and VEL-rbST was driven by rbST response differences both within the 14-d cycle and throughout the 17 injection cycles. The cows treated with VEL-rbST demonstrated a more variable 14-d milk yield response curve, with more pronounced valleys between injections compared with the ZSO-rbST formulation. In addition, only the ZSO-rbST treatment was effective in modifying the lactation persistency compared with control cows. Compared with the VEL-rbST formulation, the ZSO-rbST formulation yielded more kilograms of milk, fat, and protein with less milk variation throughout the seventeen 14-d lactation cycles for both primiparous and multiparous cows.

Estimation of mouth level exposure to smoke constituents of cigarettes with different tar levels using filter analysis.

A nicotine part-filter method can be applied to estimate smokers' mouth level exposure (MLE) to smoke constituents. The objectives of this study were (1) to generate calibration curves for 47 smoke constituents, (2) to estimate MLE to selected smoke constituents using Japanese smokers of commercially available cigarettes covering a wide range of International Organization for Standardization tar yields (1-21mg/cigarette), and (3) to investigate relationships between MLE estimates and various machine-smoking yields. Five cigarette brands were machine-smoked under 7 different smoking regimes and smoke constituents and nicotine content in part-filters were measured. Calibration curves were then generated. Spent cigarette filters were collected from a target of 50 smokers for each of the 15 brands and a total of 780 filters were obtained. Nicotine content in part-filters was then measured and MLE to each smoke constituent was estimated. Strong correlations were identified between nicotine content in part-filters and 41 out of the 47 smoke constituent yields. Estimates of MLE to acetaldehyde, acrolein, 1,3-butadiene, benzene, benzo[a]pyrene, carbon monoxide, and tar showed significant negative correlations with corresponding constituent yields per mg nicotine under the Health Canada Intense smoking regime, whereas significant positive correlations were observed for N-nitrosonornicotine and (4-methylnitrosoamino)-1-(3-pyridyl)-1-butanone.

Impact of screening with thyroid ultrasonography in myasthenia gravis patients.

OBJECTIVES: This study was conducted to screen thyroid abnormality evaluated with ultrasonography (US) in patients with myasthenia gravis (MG) and investigate further when malignancy is suspected. METHODS: Thyroid screening using US was conducted in 162 patients with MG. In cases where malignancy was suspected, further investigations were performed. RESULTS: Abnormal US findings were detected in 125 of 162 patients with MG (72 patients with nodules, 74 patients with cysts, 27 patients with diffuse findings such as enlargement, atrophy, a hypoechoic pattern or a heterogenous echoic pattern, and 28 patients with calcification). From among these 125 subjects, 30 patients underwent further examinations such as needle aspiration cytology. As a result, six patients (3.7% of 162 cases) were positive for papillary carcinoma. The size of the carcinoma in three patients was <10 mm, yet the stage of thyroid carcinomas was high (stage III or IVa) in all six cases. CONCLUSIONS: Our data suggest that the prevalence of thyroid carcinoma in cases of MG may be higher than that of the general population. Furthermore, in patients with MG, there is a possibility that the stage of the carcinoma is higher even when the carcinoma is of a very small size. Patients with MG, when diagnosed, should be advised to undergo US screening of the thyroid because most cases of thyroid carcinoma are highly curable.

Statistical properties of spectral fluctuations for a quantum system with infinitely many components.

Extending the idea formulated in Makino [Phys. Rev. E 67, 066205 (2003)], that is based on the Berry-Robnik approach [M. V. Berry and M. Robnik, J. Phys. A 17, 2413 (1984)], we investigate the statistical properties of a two-point spectral correlation for a classically integrable quantum system. The eigenenergy sequence of this system is regarded as a superposition of infinitely many independent components in the semiclassical limit. We derive the level number variance (LNV) in the limit of infinitely many components and discuss its deviations from Poisson statistics. The slope of the limiting LNV is found to be larger than that of Poisson statistics when the individual components have a certain accumulation. This property agrees with the result from the semiclassical periodic-orbit theory that is applied to a system with degenerate torus actions [D. Biswas, M. Azam, and S. V. Lawande, Phys. Rev. A 43, 5694 (1991)].

A unique case of limb-girdle muscular dystrophy type 2A carrying novel compound heterozygous mutations in the human CAPN3 gene.

A unique sib pair afflicted by limb girdle muscular dystrophy type 2A (LGMD2A) is described showing a slowly progressive autosomal recessive type of muscular dystrophy with onset in the third and fourth decades. The patients had early asymmetric muscle involvement characterized by prominent biceps brachii atrophy with sparing of the knee extensors. Additional findings included elevation of serum creatine kinase level, myopathic EMG changes and dystrophic type of pathology on muscle biopsy. Asymmetrical wasting of muscles in the extremities exhibited uniform and highly selective CT imaging patterns. RNA and DNA analyses confirmed novel compound heterozygous mutations (R147X/L212F) in the human CAPN3 gene.

Effect of streptozotocin-induced diabetes on epidermal growth factor receptors in rat liver plasma membrane.

The effect of streptozotocin-induced diabetes on 125I-labeled epidermal growth factor (EGF) binding was studied in microsomal membranes from rat liver. The binding of EGF in membranes from diabetic animals was significantly low, the value being about 60% of the control level. Scatchard analysis of the binding data clearly showed that the decrease in EGF binding was due to a decrease in the number of receptors. Treatment of diabetic animals with insulin restored EGF receptors to control levels, whereas the treatment with triiodothyronine had no effect. Serum EGF concentrations measured were almost the same among the control, diabetic, and insulin-treated diabetic groups. These results suggest that insulin deficiency in vivo causes a decrease in hepatic EGF receptors.

ADAMTS-1 is involved in normal follicular development, ovulatory process and organization of the medullary vascular network in the ovary.

To clarify the role of disintegrin-like and metalloproteinase with thrombospondin type I motifs-1 (ADAMTS-1) in ovarian function, we examined abnormalities in ovulatory processes, folliculogenesis and the vascular system of ADAMTS-1 null ovaries. First, when immature female mice were treated with pregnant mare serum gonadotropin (PMSG)/human chorionic gonadotropin (hCG), the number of ovulated oocytes was markedly decreased in ADAMTS-1 null mice in comparison to ADAMTS-1 (+/-) controls. The proportion of anovulated follicles to total mature follicles was significantly higher in ADAMTS-1 null females when compared with controls. The numbers of growing follicles at each stage were counted. The number of follicles at type 5b (late preantral) and later stages was markedly reduced in ADAMTS-1 null mice, irrespective of gonadotropin treatment (no gonadotropins, PMSG alone or PMSG/hCG). These data demonstrate that impairment of ovarian function to ovulate oocytes in ADAMTS-1 null mice occurs at two different levels: in the development of growing follicles and ovulatory processes. Furthermore, ADAMTS-1 null ovaries included a number of unusual atretic follicles that showed no sign of oocyte degeneration but lost the surrounding granulosa cell layers and were considered to be derived from type 4 or 5a follicles. These results suggest that ADAMTS-1 is important for follicular development beyond the type 4 and/or 5a and for maintaining normal granulosa cell layers in follicles. Finally, the number of large blood vessels in the medullar zone was significantly decreased in ADAMTS-1 null mice ovaries, suggesting that ADAMTS-1 is also involved in the organization of the medullary vascular network.

Ultrashort pulse-generation by saturable absorber mirrors based on polymer-embedded carbon nanotubes.

We demonstrate passive mode locking of solid-state lasers by saturable absorbers based on carbon nanotubes (CNT). These novel absorbers are fabricated by spin-coating a polymer doped with CNTs onto commercial dielectric laser-mirrors. We obtain broadband artificial saturable absorber mirrors with ultrafast recovery times without the use of epitaxial growth techniques and the well-established spin-coating process allows the fabrication of devices based on a large variety of substrate materials. First results on passive mode locking of Nd:glass and Er/Yb:glass lasers are discussed. In the case of Er/Yb:glass we report the to our knowledge shortest pulse generated in a self-starting configuration based on Er/Yb:bulk-glass: 68 fs (45 fs Fourier-limit) at 1570 nm wavelength at a pulse-repetition rate of 85 MHz.

Stage-specific cell-cycling of hematopoietic progenitor cells.

We studied the growth of hematopoietic progenitors at different progressive stages of differentiation and focused especially on changes in cell-cycling. Hematopoietic progenitors from 5-fluorouracil (5-FU)-treated mice were separated into three groups on the basis of differentiation, Stages I, II, and III, and have studied their cell-cycling. Primary marrow cells collected from 5-FU-treated mice were categorized as Stage I progenitors. Stages II and III progenitors are early and late progenies of Stage I progenitors, respectively. The rate of growth of hematopoietic progenitors supported by interleukin-3 (IL-3) and steel factor (SF) was estimated by sequential analysis of colony formation and studying replating efficiency of individual colonies. The time required for hematopoietic progenitors to go through the cell-cycle shortened as their stage of differentiation progressed. Similar results were obtained with other growth factor combinations. The analysis of DNA content of cells suggests that shortening of cell-cycling is mainly due to a decrease in the time of G1 phase of the cell-cycle. Our results demonstrate that in early hematopoiesis, the cell-cycling of hematopoietic progenitors accelerates as they differentiate.

Sex difference in epidermal growth factor receptor levels in rat liver plasma membrane.

The specific binding of [125I]epidermal growth factor [( 125I]EGF) to hepatic microsomal membranes was about 2-fold higher in adult male than in adult female rats. Scatchard analysis of the binding data showed that the sex difference in EGF binding was due to the difference in EGF receptor concentration rather than to a change in receptor affinity. From the developmental study, an apparent sex difference in EGF binding was observed from the pubertal period (4 weeks of age). Castration of adult male rats slightly, but significantly, decreased the EGF receptor level; and moreover, treatment of adult females with testosterone increased it only slightly. On the other hand, castration of neonatal male rats decreased the EGF receptor content almost to the female level. The decreased level of the receptor was completely restored by the combination of neonatal and pubertal treatments with testosterone. Neonatal or pubertal treatment alone of castrated animals had no significant effect on the decreased level of EGF receptors. These effects of testosterone were similarly observed when normal female rats were treated with the steroid. Moreover, hypophysectomy of the rats resulted in the marked decrease in EGF receptors only in the male animals. Treatment of hypophysectomized rats with either testosterone or T3 had no apparent effect on the EGF receptors. The membrane protein, cross-linked with [125I]EGF, had a mol wt of 170,000, and this protein (EGF receptor) was phosphorylated basally or by the addition of EGF. The rate of affinity labeling, or phosphorylation of EGF receptors, was in good agreement with the results of the EGF binding study. These results strongly suggest that the EGF receptor level in rat liver plasma membranes is in part regulated by the hypothalamopituitary unit and that neonatal androgens are essential for this regulation, probably through their effects on the hypothalamus.

Effect of epidermal growth factor on collagen synthesis in osteoblastic cells derived from newborn mouse calvaria.

We investigated the effect of epidermal growth factor (EGF) on collagen and protein synthesis in clone MC3T30-E1, a cell line which retains osteoblast-like characteristics. EGF at concentrations of 2-50 ng/ml significantly the hydroxyproline content of the cell layer. These effects were completely abolished by the addition of anti-EGF rabbit serum. The addition of indomethacin did not affect these EGF-induced effects. Collagen fiber formation was also reduced by EGF; a fine and unstriated type of fibril was detected compared to the typical cross-striated fibrils seen in control cultures. EGF at concentrations of 2-50 ng/ml significantly decreased collagen synthesis in the cells, whereas protein synthesis was rather stimulated. Thus, the proportion of collagen to protein synthesized decreased markedly with increasing concentrations of EGF. Unrelated to its effect on collagen synthesis, EGF at concentrations of 0.4-50 ng/ml significantly increased the activity of prolyl hydroxylase, an enzyme involved in the biosynthesis of collagen. Since the plasma concentration of EGF in humans is sufficiently high to cause the observed effect, osteoblasts in vivo may be responsive to this peptide in the same manner as those observed in vitro.

Role of nitric oxide in the development of vascular alpha 1-adrenoreceptor desensitization and pressure diuresis in conscious rats.

We evaluated whether a minor impairment of the L-arginine-nitric oxide pathway would affect the desensitization of vascular alpha-adrenoreceptor and pressure diuresis induced by prolonged intravenous infusion of phenylephrine (an alpha-adrenoreceptor agonist) in conscious Wistar-Kyoto rats. We examined dose-pressor-response curves to phenylephrine after an intravenous infusion of phenylephrine (2.5 micrograms.kg-1.min-1) or saline for 9 hours with and without concomitant infusion of N omega-L-arginine methyl ester (L-NAME) given to partially inhibit the L-arginine-nitric oxide pathway. In addition, to evaluate the effect of plasma volume loss on the pressor response to phenylephrine, we evaluated the dose-pressor-response curves to phenylephrine after intravenous injection of furosemide (5 mg/kg) or infusion of phenylephrine (5 micrograms.kg-1.min-1) for 9 hours. The renin-angiotensin, vasopressin and autonomic nervous systems were blocked before the examination of dose-pressor responses. Prolonged infusion of phenylephrine (2.5 micrograms.kg-1.min-1) shifted the dose pressor-response curve to this agent rightward, with significantly increased log ED50 (the dose needed to reach 50% of the maximal response) to a similar extent in both L-NAME-treated (0.51 +/- 0.05 versus 0.93 +/- 0.07 microgram/kg) and -untreated (0.79 +/- 0.06 versus 1.08 +/- 0.03 micrograms/kg) rats. The log ED50 value after phenylephrine infusion (5 micrograms.kg-1.min-1) was significantly higher than that after furosemide injection (1.28 +/- 0.06 versus 1.02 +/- 0.01 micrograms/kg, respectively, P < .01), although the two treatments induced a similar loss of plasma volume. The slope in the linear relationship between the average change in mean arterial pressure during the 9-hour infusion period and the rate of urine excretion was significantly depressed in L-NAME-treated versus control rats (L-NAME: 0.057 mL.kg-1.h-1.mm Hg-1, control: 0.146 mL.kg-1.h-1.mm Hg-1, P < .05). In conclusion, a minor impairment of the L-arginine-nitric oxide pathway does not appear to interfere with the desensitization of vascular alpha-adrenoreceptor but does inhibit the pressure-diuresis response in conscious normotensive rats.

Hypotensive and bradycardic effects of centrally administered vasopressin in stroke-prone spontaneously hypertensive rats.

The cardiovascular effects of centrally administered arginine vasopressin were studied in stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats. Arginine vasopressin was infused intracerebroventricularly into conscious rats at a rate of 2 pg/kg/min (4.6 microliter/hr) for 21 hours, and blood pressure and heart rate were monitored. Arginine vasopressin caused transient hypertension and tachycardia in Wistar-Kyoto rats, whereas it induced delayed hypotension and bradycardia in stroke-prone spontaneously hypertensive rats. The effects on the latter lasted for 24 to 72 hours after cessation of the infusion. Intravenous administration of arginine vasopressin at a rate of 2 pg/kg/min did not cause any change in blood pressure and heart rate in these rats. These results suggest that arginine vasopressin acts centrally to depress cardiovascular activities, at least in stroke-prone spontaneously hypertensive rats.

Role of vasopressin in neurocardiogenic responses to hemorrhage in conscious rats.

Vasovagal reflexes, such as hypotension and bradycardia, are induced by rapid hemorrhage and mimic neurocardiogenic reflexes in mammals. We examined the role of vasopressin in the neurocardiogenic responses to mild, rapid hemorrhage (1 mL/100 g for 30 seconds) and severe hemorrhage (1 mL/100 g body wt for 30 seconds repeated three times at 11-minute intervals) in homozygous Brattleboro and Long-Evans rats. Mild, rapid hemorrhage induced severe bradycardia and hypotension only in Long-Evans rats. Exogenous vasopressin (1.85 pmol/kg per minute for 1 hour) restored both the bradycardic and hypotensive responses in Brattleboro rats. DDAVP, a vasopressin V2-receptor agonist (0.19 pmol/kg per minute for 24 hours), did not affect the cardiovascular responses to hemorrhage in Brattleboro rats, although it maintained urine production within normal limits. However, OPC-31260 (21.6 mumol/kg IV), a vasopressin V2-receptor antagonist, attenuated both the hypotensive and bradycardic responses to hemorrhage in Long-Evans rats. A vasopressin V1-receptor antagonist attenuated bradycardia and delayed the recovery of arterial pressure after hemorrhage but did not affect the hypotension that occurred immediately after hemorrhage in Long-Evans rats. Methylatropine also attenuated both the bradycardic and hypotensive responses induced by hemorrhage, but propranolol had no effect on the cardiovascular responses to hemorrhage in Long-Evans rats. The recovery of arterial pressure after repeated hemorrhage was less adequate in Brattleboro rats than in Long-Evans rats. Our results suggest that the neurocardiogenic responses to hemorrhage, especially hypotension, may be related to vasodilation induced by a V2-receptor-mediated mechanism and by the vagal reflex, both of which are substantiated by the existence of vasopressin. The coexistence of V1- and V2-receptor mechanisms may be necessary for the hypotensive response to hemorrhage. We found that a V2-receptor antagonist attenuated the hypotension mediated by the so-called neurocardiogenic reflex.

Altered circadian blood pressure rhythm in patients with Cushing's syndrome.

The circadian blood pressure rhythm was compared in patients with Cushing's syndrome, essential hypertension, and primary aldosteronism. In patients with essential hypertension or primary aldosteronism, a clear nocturnal fall in systolic and diastolic blood pressure and heart rate was observed. This fall was seen in untreated subjects as well as in patients receiving combined treatment with a calcium antagonist, diuretic, converting enzyme inhibitor, alpha-blocker and beta-blocker, or sympatholytic drug. In these groups, there was a positive correlation between heart rate and systolic or diastolic blood pressure. On the other hand, in patients with Cushing's syndrome, there was no nocturnal fall in blood pressure but in some patients a rise was observed. In all patients there was a nocturnal fall in heart rate. Thus, there was no significant correlation between heart rate and blood pressure in these patients. Exogenous glucocorticoid eliminated the normal nocturnal fall of blood pressure in patients with chronic glomerulonephritis or systemic lupus erythematosus. These results suggest that the changed circadian blood pressure pattern in patients with Cushing's syndrome is not due to antihypertensive treatment or to the mineralocorticoid excess accompanying this disease, but it is attributable to excess glucocorticoid or the associated disturbance in the adrenocorticotropic hormone-glucocorticoid system (or both). This conclusion also implies that the normal circadian rhythm of blood pressure may be regulated at least in part by the adrenocorticotropic hormone-glucocorticoid system.

Ambulatory blood pressure of adults in Ohasama, Japan.

We performed a cross-sectional study in a small town in northern Japan to evaluate the distribution, reference values, and daily variation in ambulatory blood pressure. A total of 705 subjects (229 men aged 61.3 +/- 13.4 years [mean +/- SD] and 476 women aged 57.5 +/- 13.3 years; 41.1% of the regional adult population, n = 1716), including those treated with antihypertensive drugs (n = 231, 66.5 +/- 9.5 years) as well as untreated subjects (n = 474, 55.0 +/- 13.5 years), participated in the study. Both ambulatory and screening blood pressures were measured in 659 subjects. Ambulatory blood pressure was measured with an automatic device (Colin ABPM-630). The 24-hour ambulatory blood pressure in the total population was 121.7 +/- 13.0/71.1 +/- 7.6 mm Hg (95th percentile value [95%] = 146/85 mm Hg). The corresponding value in the untreated subjects was 119.4 +/- 12.5/70.1 +/- 7.4 mm Hg (95% = 144/83 mm Hg). The 24-hour average ambulatory blood pressure was 118.0 +/- 11.1/69.4 +/- 6.8 mm Hg (95% = 139/81 mm Hg) in subjects identified as normotensive by their screening blood pressure (n = 448, 57.2 +/- 13.1 years) and 133.6 +/- 14.2/78.9 +/- 8.8 mm Hg in those identified as hypertensive by their screening blood pressure (n = 73, 63.1 +/- 10.6 years). Based on the mean+SD of the 24-hour ambulatory blood pressure in the normotensive subjects by their screening blood pressure (129/76 mm Hg), the 24-hour ambulatory blood pressures in 25 (34.2%) of these 73 hypertensive subjects by screening blood pressure were below this level. Nine (2%) of 448 normotensive subjects by screening blood pressure were above the mean+2 SDs (140/83 mm Hg) of the 24-hour ambulatory blood pressure in the normotensive group by screening blood pressure. Ambulatory and screening blood pressures increased with age. The age-dependent increase in ambulatory blood pressure was less apparent in men. The 24-hour average pulse rate decreased with age. The daily variation in ambulatory blood pressure (standard deviation) increased with age, whereas that of pulse rate decreased with age. Increases in blood pressure variation were observed in nighttime and daytime blood pressure values. The differences between day versus night ambulatory blood pressures decreased with age in men but not in women.(ABSTRACT TRUNCATED AT 400 WORDS)

Role of vasopressin in cardiovascular response to central cholinergic stimulation in rats.

The cardiovascular effects of centrally administered cholinomimetics were examined in conscious Long-Evans and Brattleboro rats. Carbachol (1 microgram/kg) or physostigmine (50 micrograms/kg) induced a long-lasting increase in blood pressure and a decrease in heart rate in Long-Evans rats whereas no bradycardia was observed in Brattleboro rats, and the pressor response was significantly less than that in Long-Evans rats. The cardiovascular responses to nicotine (30 micrograms/kg) in Brattleboro rats were not different from those in Long-Evans rats. Intravenous vasopressin antagonist, d(CH2)5Tyr(Me) arginine vasopressin, significantly attenuated the pressor response and eliminated the bradycardic response to carbachol in Long-Evans rats. However, the pressor response to carbachol in Brattleboro rats was still significantly less than that in Long-Evans rats treated with vasopressin antagonist. Intravenous phentolamine partially inhibited the pressor response to carbachol in Long-Evans rats and completely eliminated it in Brattleboro rats. Combined intravenous treatment with phentolamine and vasopressin antagonist completely eliminated the pressor response to carbachol in Long-Evans rats. Centrally administered methylatropine eliminated either the hypertensive or bradycardic response to carbachol in Long-Evans rats. These results indicate that the pressor and bradycardic response to carbachol or physostigmine is mediated by the central muscarinic receptor mechanism. Hypertensive response to intracerebroventricularly administered carbachol in normal rats is mediated both by an increase in central sympathetic outflow and in circulating vasopressin. The bradycardia seems to be mediated mainly by vasopressin.

Cardiovascular depression and stabilization by central vasopressin in rats.

The role of endogenous vasopressin in cardiovascular homeostasis was examined using vasopressin-deficient rats (Brattleboro) (n = 194) and their parent strain, Long-Evans rats (n = 181). Mean arterial pressure (blood pressure) and heart rate were measured every 4 seconds with or without infusion of drug solution for 21 hours, and mean values and their standard deviations (lability) were calculated. Blood pressure in Brattleboro rats (116 +/- 1.1 mm Hg, mean +/- SEM) was significantly higher than that in Long-Evans rats (96 +/- 0.7 mm Hg, p less than 0.001), whereas heart rates (381 +/- 3.3 and 375 +/- 2.9 beats/min, respectively) were similar. The lability of blood pressure and heart rate in Brattleboro rats (9.2 +/- 0.1 mm Hg and 42.3 +/- 0.7 beats/min) was also greater than that in Long-Evans rats (6.7 +/- 0.1 mm Hg, p less than 0.001 and 38.4 +/- 0.8 beats/min, p less than 0.01, respectively). In Brattleboro rats, intravenous vasopressin (0.1 ng/kg/min or 0.6 ng/kg/min) did not affect blood pressure, although it did reduce heart rate and decreased lability of blood pressure and heart rate. Intracerebroventricular (central) infusion of vasopressin (2 pg/kg/min) in Brattleboro rats induced initial hypertension and tachycardia followed by long-lasting hypotension and bradycardia, whereas in Long-Evans rats it induced only hypertension and tachycardia. In both strains, central vasopressin dramatically decreased the lability of blood pressure and heart rate. Neither intravenous (0.2 ng/kg/min) nor central desmopressin (2 pg/kg/min or 0.2 ng/kg/min), a V2 renal receptor agonist, changed any of these parameters in Brattleboro rats, although both diminished urinary volume. Neither intravenous (50 ng/kg/min) nor central (3.3 pg/kg/min) d(CH2)5-Tyr(Me)-arginine vasopressin, a vasopressin V1 receptor antagonist, modulated any of these parameters in Long-Evans rats. These results suggest that endogenous as well as exogenous vasopressin acts centrally as a cardiovascular inhibitor and stabilizer through a receptor mechanism other than V1 or V2 receptor mechanisms.

Cytotoxic fragment of amyloid precursor protein accumulates in hippocampus after global forebrain ischemia.

We developed an antibody specific to beta-amyloid precursor protein (beta APP) fragments possessing the exact amino terminus of the beta-amyloid peptide and examined its induction in postischemic hippocampus. In control hippocampus, this APP fragment was lightly observed in pyramidal neurons of CA sectors and dentate granule cells. Transient forebrain ischemia enhanced accumulation of the APP fragment in CA1 pyramidal neurons. Seven days after the ischemia, while the APP fragment was still observed in dentate granule cells and CA3 neurons, it disappeared in dead CA1 neurons. While astrocytes did not show in any immunoreactivity throughout the experiment, those in the CA1 sector showed moderate immunoreactivity 7 days after the ischemia. The APP fragment has a cytotoxic effect on cultured neurons. These results suggest that the accumulation of the cytotoxic APP fragment in CA1 neurons may play a role in the development of delayed neuronal death after the ischemic insult.