Effect of Ala-Glu-Asp-Gly peptide on life span and development of spontaneous tumors in female rats exposed to different illumination regimes

The effects of Ala-Glu-Asp-Gly peptide (Epithalon) on the life span and development of spontaneous tumors were studied in female rats exposed to standard, natural for North-Western Russia, and constant illumination. The mean life span of animals exposed to constant or natural illumination decreased by 13.5 and 25.5%, the maximum by 9 and 7 months, respectively, and spontaneous tumors developed much more rapidly than in animals living under conditions of the standard light regimen. Epithalon (0.1 μg daily 5 times a week from the age of 4 months) did not change the life span of rats living under conditions of standard day/night regimen, while in rats exposed to the natural and constant light it promoted prolongation of the maximum life span by 95 and 24 days, respectively. Epithalon prolonged the mean life span of the last 10% of rats exposed to natural and constant illumination, treated with Epithalon, by 137 and 43 days, respectively. This peptide exhibited virtually no effect on the development of spontaneous tumors in rats exposed to standard and constant illumination, but significantly inhibited their development in rats exposed to natural light. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 12, pp. 676–681, December, 2007     

Sexual and olfactory preference in noncopulating male rats

In some species including rats, mice, gerbils, and rams, apparently normal males fail to copulate when repeatedly tested with receptive females. These animals are called "noncopulators (NC)," and the cause of this behavioral deficit is unknown. It has been shown that NC rats do not have hormonal alterations or deficits in the mechanisms that control penile function. The present study was designed to examine (Experiment 1) whether NC male rats prefer receptive females to sexually active males. In addition, the olfactory preference for bedding soiled from estrous or for anestrous bedding was investigated. These tests were performed in NC and copulating (C) male rats when the subjects were intact, gonadectomized (GDX), or GDX and treated with high doses of testosterone propionate (TP). Our results demonstrate that NC rats do not display sexual behavior even after high TP treatment. While C male rats have a clear preference for receptive females as opposed to a sexually active male, NC rats do not. In all hormonal conditions, the preference shown by NC rats for estrous bedding was significantly reduced in comparison to that seen in C rats. TP treatment in NC rats did not modify either partner or odor preference. In Experiment 2, we evaluated if NC rats are feminized and if it could be easier to induce feminine-like behavior by hormone treatment with estradiol benzoate (EB) or with EB plus progesterone (P) (EB+P). Odor preference for estrous or male bedding under these hormonal conditions was also compared. No differences between NC and C rats were found in feminine sexual behavior. In the olfactory test, we found that NC rats prefer odors from receptive females as opposed to male odors, but this preference is reduced compared to that of C rats. Males treated with EB or EB+P show no preference for female odors. These results demonstrate that treatment with EB or EB+P does not increase feminine sexual behavior in NC rats.     

Effect of dehydroepiandrosterone on avoidance behavior of adult male rats

We studied the effect of repeated intraperitoneal treatment with dehydroepiandrosterone in doses of 0.1 and 0.7 mg/kg on conditioned-response activity and behavior of adult male rats. The effect of dehydroepiandrosterone on learning was estimated in conditioned active and passive avoidance response paradigms. Chronic administration of dehydroepiandrosterone in low and high doses had no effect on retention of conditioned passive avoidance response in adult male rats 24 h after learning. However, chronic administration of dehydroepiandrosterone in low dose impaired acquisition of the conditioned active avoidance response. It should be emphasized that chronic administration of dehydroepiandrosterone in high dose did not modulate acquisition and retention of this reaction. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 63–67, July, 2004 This work was supported by the Regional Social Foundation for Russian Medicine.     

Hprt mutant frequencies in splenic T-cells of male F344 rats exposed by inhalation to propylene

Propylene is a major industrial intermediate and atmospheric pollutant to which humans are exposed by inhalation. In this study, 6-week-old male F344 rates were exposed to 0, 200, 2000, or 10,000 ppm propylene by inhalation for 4 weeks (6 h/day, 5 days/week), and mutant frequencies were determined in the Hprt gene of splenic T-lymphocytes. Twenty milligrams of cyclophosphamide monohydrate (CPP)/kg bw, given on the penultimate day of propylene exposure, was used as a positive control mutagen. Rats (n = 8/group) were necropsied for isolation of T-cells 8 weeks after the last dose, a sampling time that produced peak spleen Hprt mutant frequencies (Mfs) in a preliminary mutant manifestation study using CCP treatment. Hprt Mfs were measured via the T-cell cloning assay, which was performed without knowledge of the animal treatment groups. Mean Hprt Mfs were significantly increased over control values (mean Mf = 5.24 +/- 1.55 (SD) x 10(-6)) in CPP-treated rats (10.37 +/- 4.30 x 10(-6), P = 0.007). However, Hprt Mfs in propylene-exposed rats were not significantly increased over background, with mean Mfs of 4.90 +/- 1.84 x 10(-6) (P = 0.152), 5.05 +/- 3.70 x 10(-6) (P = 0.895), and 5.95 +/- 2.49 x10(-6) (P = 0.500) for animals exposed to 200, 2000, or 10,000 ppm propylene, respectively. No significant increase in F344 rat or B6C3F1 mouse cancer incidence was reported in the National Toxicology Program carcinogenicity studies of propylene across this same exposure range. Taken together, these findings support the conclusion that inhalation exposure of rats to propylene does not cause mutations or cancer.     

Longevity of exercising male rats: effect of an antioxidant supplemented diet

Food restriction increases maximal life span in rodents. Male rats that exercise in voluntary running wheels do not have an increase in maximal longevity despite a relative caloric deficit. In contrast, sedentary rats that are food restricted so as to cause the same caloric deficit have an extension of maximal longevity. It seemed possible that exercise-induced oxidative stress might prevent a maximum life span-extending effect of a caloric deficit to manifest itself. This study was done to determine if antioxidants would allow a maximal longevity-extending effect of exercise to manifest itself in male rats. The antioxidant diet had no effect on longevity of the runners (Antiox., 951±158 days versus control 937±171 days), or of the sedentary controls (875±127 versus 858±152 days). As in previous studies, wheel running modestly increased average longevity (≈9%), but had no effect on maximal life span. The finding that antioxidants had no effect on longevity of the wheel runners supports the interpretation that the caloric deficit induced by exercise in male rats does not have a life-extending effect that is countered by oxidative tissue damage.     

Effect of delta sleep-inducing peptide on electrophysiological parameters of sleep in rats during abstinence from alcohol

Laboratory for the Search and Study of Methods of Prevention and Treatment of Drug Addictions, Research Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Val'dman). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 9, pp. 281–283, September, 1990.     

燃煤型氟中毒对雄性大鼠生殖内分泌激素的影响

 摘要 目的：研究燃煤型氟中毒对雄性大鼠生殖内分泌的影响。方法：将105只雄性SD大鼠随机分为7组：对照组、低氟组、中氟组、高氟组、低氟加营养组、中氟加营养组、高氟加营养组。各染毒组喂饲含不同比例的燃煤型氟中毒病区煤烘玉米的饲料,复制燃煤型氟中毒动物模型。分别于染毒90d、120d和180d三阶段以股动脉放血法处死动物,查看氟斑牙,测尿氟,用RIA法测定大鼠睾丸内T,血清T、E2、LH、FSH 、GnRH、PRL。结果：建成氟中毒动物模型。与对照组相比,各染毒组大鼠血清T、E2、PRL水平随染毒时间延长和染氟剂量增加逐渐降低（p<0.05或p<0.01）; LH、FSH均水平随染毒时间延长和染毒剂量增加逐渐增高（p<0.05或p<0.01）;与对照组相比,而各染毒组GnRH水平随染毒时间延长逐渐降低（p<0.05或p<0.01）,而不同剂量的染毒组之间,随染氟剂量增加逐渐升高（p<0.05或p<0.01）。相同染氟剂量加营养组性激素水平均有所改善（p<0.05或p<0.01）。结论：燃煤型氟中毒对雄性大鼠生殖内分泌有明显的影响作用,染氟剂量越多、染毒时间越长,影响越重,降低摄氟量及提高饮食营养可改善其影响。     

Role of testosterone secretion and penile reflexes in sexual behavior and sperm competition in male rats: a theoretical contribution

A number of experiments have documented that when male rats are exposed to female rats they undergo a marked increase in the secretion of luteinizing hormone and testosterone. This response can be conditioned to other, previously neutral, stimuli associated with mating. Recent work has highlighted the remarkable sensitivity of penile reflexes to fluctuations in blood concentration of testosterone. Other work has pointed to the function of penile reflexes in seminal plug removal and deposition. It is hypothesized that penile reflexes are potentiated by the increase in testosterone that occurs in response to sexually relevant cues and that the potentiated reflexes play a role in sperm competition during multi-male mating encounters. The sperm competition centers around a male rat's ability to dislodge seminal plugs left in the vagina by other males and to deposit his own plug as tightly as possible to resist dislodgement by another.     

Atrial natriuretic peptide and its mRNA in heart and brain of vasopressin-deficient Brattleboro rats

To understand the secretion and synthesis of atrial natriuretic peptide we measured immunoreactive atrial natriuretic peptide from plasma, heart tissues and brain areas, and ANP mRNA was determined from heart auricles and ventricles of vasopressin-deficient Brattleboro rats (DI) and from desmopressin treated Brattleboro rats (DI + DDAVP). Long-Evans rats (LE) served as controls. DI + DDAVP rats were given for 3 days sc. injections of 0.5/g l-desamino-8-D-arginine vasopressin in 1 ml. saline twice a day. The rats were housed in single metabolic cages and urinary output and water intake were measured daily. All the body and organ weight parameters were similar in the three groups when the rats were killed. No change was seen in the plasma ANP level between the groups. The right ventricle of DI + DDAVP rats had significantly (P < 0.05) higher concentration of ANP than LE rats (15.8 + 4.4 vs. 3.4 + 0.6 ng mg“¹ tissue). The left ventricle of DI and DI+DDAVP had significantly (P < 0.05) lower amounts of ANP mRNA than LE rats (0.5 ± 0.2 vs. 1.3 + 0.2 and 0.5 + 0.1 vs. 1.3 + 0.2 arbitrary units). In the hypothalamus, the ANP concentration was significantly (P < 0.05) lower both in DI and in DI + DDAVP rats than in LE rats (9.3 ±1.3 vs. 14.5 ±±1.6 and 6.1+0.6 vs. 14.5 ± 1.6 pg mg^-1 tissue). To conclude, although the water intake and urinary output of DI rats were changed towards normal with desmopressin treatment, the heart ventricular and hypothalamic ANP did not parallel the change. Desmopressin increased the ANP concentration in the right ventricle of DI rats. Thus the correction of the complete vasopressin deficiency-does not appear to associate with synthesis or release of atrial natriuretic peptide in heart or hypothalamus.     

Testosterone induced mounting behavior in adult female rats born in litters of different female to male ratios

Female rats can show mounting behavior towards isosexual or heterosexual conspecifics. The present experiments were designed to study whether the prenatal presence of male fetuses would affect display of this mounting behavior in adulthood. Therefore mounting behavior, after gonadectomy and during continuous treatment with testosterone propionate (TP) was studied in female rats which were born in litters without male siblings (“all female” litters) and in litters with a variable number of male siblings. Litter composition at birth did not affect display of adult mounting behavior during protracted tests (a total of 6 tests during 8 weeks of treatment with TP). The data indicate that TP induced mounting behavior in adulthood occurs independent of the prenatal presence of male fetuses. If mounting behavior in adulthood has to be “organized” by prenatally present androgen (the current way of thinking), then the present data indicate that female rat fetuses provide themselves with these hormones. It would then seem inappropriate to judge adult mounting behavior as a sign of “masculinization” of the rat brain.     

Vasoactive intestinal peptide in rats with focal cerebral ischemia enhances angiogenesis

We studied the effect of vasoactive intestinal peptide (VIP) on angiogenesis in the ischemic boundary area after focal cerebral ischemia. Adult male Sprague–Dawley rats underwent middle cerebral artery occlusion for 2 h. A single dose of VIP was given via i.c.v. injection at the beginning of reperfusion. Immunohistochemistry and Western blotting were performed to assay angiogenesis and brain levels of vascular endothelial growth factor (VEGF) protein, respectively. In addition, the expression of VEGF and its receptors (flt-1 and flk-1), as well as endothelial proliferation, was measured using rat brain microvascular endothelial cells. Immunohistochemical analyses revealed significant (P<0.05) increases in the numbers of bromodeoxyuridine (BrdU) positive endothelial cells and microvessels at the boundary of the ischemic lesion in rats treated with VIP compared with rats treated with saline. Western blotting analysis showed that treatment with VIP significantly (P<0.05) raised VEGF levels in the ischemic hemisphere. In addition, treatment with VIP increased flt-1 and flk-1 immunoreactivity in endothelial cells. In vitro, incubation with VIP significantly (P<0.01) increased the proliferation of endothelial cells and induced the expression of VEGF, flt-1 and flk-1 in endothelial cells. The stimulatory effect of VIP on the proliferation of endothelial cells was significantly (P<0.01) inhibited by SU5416, a selective inhibitor of VEGF receptor tyrosine kinase. Our data suggest that treatment with VIP enhances angiogenesis in the ischemic brain, and this effect may be mediated by increases in levels of VEGF and its receptors.     

微波硫灯、热辐射灯、日光灯和LED灯对雄性抑郁大鼠生殖功能的影响

目的探讨微波硫灯、热辐射灯、日光灯和LED灯对雄性抑郁大鼠生殖系统的影响。方法采用慢性、温和、不可预见性刺激(CUMS)方法建立抑郁大鼠模型。对模型大鼠分别给予微波硫灯、热辐射灯、日光灯和LED灯连续光照45 d后,摘取大鼠生殖器官测定其脏器系数比;ELISA检测血清中睾酮(T)、雌二醇(E2)、孕酮(PROG)及催乳素(PRL)含量;HE染色检测睾丸组织形态学变化,Western blot检测睾丸组织中褪黑素受体(Mel 1a)、胆固醇侧链裂解酶(P450scc)以及3β-羟类固醇脱氢酶(3β-HSD)的蛋白表达。结果与对照组相比,抑郁模型大鼠体质量增长缓慢,睾丸、附睾及精囊腺脏器系数均明显降低(P0.05),血清中T、E2、PRL及PROG水平显著下降(P0.05),睾丸间质充血严重,生精小管萎缩,细胞排列分散,Mel 1a、3β-HSD和P450scc表达下调(P0.05)。微波硫灯照射可以上调T、E2、PRL和PROG的水平以及Mel 1a、3β-HSD和P450scc的表达(P0.05),减轻睾丸组织病理学改变。结论微波硫灯照射可以改善雄性抑郁大鼠的睾丸结构及功能。     

Increases in morphologically abnormal sperm in rats exposed to Co60 irradiation

We have investigated the effects of testicular exposure to different doses of Co⁶⁰ radiation on sperm morphology in F-344 rats. The results indicate that from 150rad to 500 rad gamma irradiation causes statistically significant, dose-related increases in 1) the percent of morphologically aberrant sperm and 2) the frequency of tailless sperm. Both of these effects were detectable in sperm which were derived from treated spermatid, spermatocytes, and spermatogonial cells. These data indicate that the development of a sperm morphology assay in rats is feasible.     

人类心房利钠肽基因在自发性高血压大鼠体内表达及其对血压的影响

目的研究人类心房利钠肽（hANP）基因在自发性高血压大鼠（SHRs）体内表达、持续时间和对血压的影响。方法 12只8周龄雄性SHRs,随机分为两组,于左腿股四头肌注射pcDNA3.1-hANP质粒的为实验组,在同一部位注射pcDNA3.1空质粒的为对照组,每周测量大鼠尾动脉收缩压,及利用放射免疫方法监测血中hANP水平。结果转基因后第1周起与对照组比较,实验组血压开始下降,两组动物一直相差（13±3.1）mmHg（P〈0.05）,其作用可持续10周;且放射免疫方法监测实验组血中hANP水平较高;RT-PCR和Western印迹杂交技术检测显示实验组hANP基因在肌肉组织中高效表达,对照组则未见表达。结论肌肉注射法将hANP基因导入SHRs,hANP基因可在肌肉组织中高效表达,且hANP可释放入血,降低SHRs的血压,显示了hANP基因对高血压患者治疗的可能性。     

Circadian temperature and wake rhythms of rats exposed to prolonged continuous illumination

The purpose of this study was to simultaneously measure temperature and sleep in the rat under continuous illumination in an attempt to reveal properties of the underlying circadian oscillators. At first, the circadian rhythms of temperature and wake free-ran in parallel. Within weeks or months, circadian arrhythmicity developed in most animals. Both circadian rhythms eventually damped out, even at fairly low light intensities. The circadian rhythm of wake was weaker and disintegrated sooner than the circadian rhythm of temperature. Although the data did not rule out control by separate circadian oscillators, one for temperature and one for wake, a single oscillator model was sufficient to explain this phenomenon. Ultradian variations with a period of about 2–5 hr were superimposed upon the circadian rhythms. When the circadian rhythms damped out, the ultradian variations remained. The ultradian bursts of wake preceded the ultradian bursts of temperature, suggesting a causal relationship. On the other hand, the circadian rhythm of temperature could not be dependent on the circadian rhythm of wakefulness, because the temperature rhythm could persist while the wake rhythm was absent.     

Effect of the hydra peptide morphogen on posthypoxic disorders in rats exposed to prenatal hypoxia

Lipid peroxidation in the lungs and blood are activated while DNA synthesis in the tracheal epithelium and hepatocytes is inhibited during the first five days of postnatal life in rat pups after severe prenatal hypoxia. Intraperitoneal injection of the undecapeptide pGlu-Pro-Pro-Glu-Glu-Ser-Lys-Val-Ile-Leu-Phe, a peptide morphogen isolated from the hydra, before hypoxia normalizes lipid peroxidation in the lungs and blood of the five-day-old pups. A compensatory activation of DNA synthesis occurs in tracheal epithelium and hepatocytes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 3, pp. 269–272, March, 1997.     

Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging

A 12-year randomized clinical study of epithalamine (pineal gland peptide preparation) was carried out in elderly patients with coronary disease and accelerated aging of the cardiovascular system. Long-term treatment with epithalamine decreased the functional age and degree of cardiovascular aging; exercise tolerance increased. After 12 years the number of elderly subjects dead in the group treated by epithalamine was 28% lower than in the control group, despite the same basic therapy. Cardiovascular mortality was 2-fold lower in patients treated by epithalamine; the incidence of cardiovascular failure and respiratory diseases was 2-fold lower in this group. Long-term treatment with epithalamine was associated with a geroprotective effect on the long-term life prognosis in elderly subjects with accelerated aging. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 9, pp. 328–332, September, 2006