Dexamethasone partially reduces and 2% saline-treatment abolished electroacupunture analgesia: these findings implicate pituitary endorphins.

Dexamethasone, a cortisol analogue which inhibits ACTH and endorphin release in a negative feedback system, partially reduces electroacupuncture analgesia (EAA) in mice. In addition, mice forced to drink 2% saline for 3 days (this reduces pituitary endorphin levels) had a complete loss of EAA. These two experiments support our previous finding that hypophysectomy abolishes EAA. Altogether, these results implicate pituitary endorphins in EAA.     

前列腺Ⅰ号抗炎镇痛作用以及抗前列腺炎的实验研究

采用热板法和扭体法观察前列腺Ⅰ号抗炎、镇痛以及抗大鼠实验性前列腺炎的作用。采用小鼠耳廓二甲苯制炎法观察抗炎作用,前列腺炎模型采用向大鼠前列腺组织内注入角叉菜胶的方法。结果显示前列腺Ⅰ号能减少小鼠扭体反应数,延长小鼠热板法引起的痛反应潜伏期,对小鼠耳廓肿胀有明显的抑制作用,前列腺炎模型试验中,前列腺液检查卵磷脂小体明显增加,白细胞数降低。因此前列腺Ⅰ号具有明显的抗炎、镇痛以及抗前列腺炎的作用。     

钙离子对小鼠电针镇痛和吗啡镇痛影响的相似性

本工作以小鼠为对象研究了脑 Ca~(2 )水平与吗啡及电针镇痛的相互关系。脑室内注射杆菌肽和亮-脑啡肽能增强电针镇痛,后者可被腹腔注射 Ca~(2 )对抗。用多巴胺受体激动剂阿朴吗啡和拮抗剂氟派啶预处理并不改变 Ca~(2 )对电针镇痛的对抗作用,这表示脑内多巴胺类似不直接参与 Ca~(2 )对抗电针镇痛的作用。Ca~(2 )对抗电针镇痛和吗啡镇痛的时程十分相似。所有的结果表明,吗啡镇痛与电针镇痛的机理很可能是相同的。     

Unique behavioral effects of beta endorphin and their relationship to thermoregulation and hypothalamic function.

Intraventricular (ivt) injections of sub-cataleptic doses of β endorphin in rats were observed to result in wet-dog shakes. Subsequent to the wet-dog shakes, copious salivation accompanied by a clonic, seizure-like state was occasionally observed to occur. This sialogogic effect of β endorphin was blocked by naloxone and diminished by injections of thyrotropin releasing hormone. None of these behaviors were observed following ivt injection of morphine in equi-antinociceptive doses. Furthermore, hypophysectomy was observed to attenuate or block these behaviors. Both the wet-dog shakes and “sialogogic seizures” were demonstrated to be dependent upon dose as well as ambient temperature. It appears possible that the occurrence of initial wet-dog shakes may result in the elevated body temperature which then precipitates excess salivation. Since both β endorphin induced wet-dog shakes and salivation were shown to be correlated with alterations in temperature, it is possible that these effects of β endorphin indicate a physiological role for that peptide in thermoregulation.     

Methamphetamine mortality to emotional stimuli administered in the form of affective communication

Methamphetamine induced mortality in physically stressed and non-physically stressed mice was investigated by employing a communication box in which shocked mice communicated their distress to unshocked mice in neighboring boxes. Intraperitoneal administration of methamphetamine 30 mg/kg caused greater mortality in both the shocked “sender” mice and the unshocked “responder” mice than in control when maintained at 27 ± 1 °C. Forty-eight hours after injection, the “sender”, “responder” and control mice showed mortality of 80, 60 and 10 %, respectively. This result indicates that the mortality of methamphetamine may be potentiated not only by physical stress but also by non-physical stress.     

Chronic inflammation in mice exposed to the long-term un-entrainable light–dark cycles

Shift work is indispensable in our modern society; therefore, measures for maintaining the health of shift workers are urgently required. In this prospective study observing the effects of different types of scheduled light–dark shift conditions in wild-type mice, we reared mice for 630 days under two chronic jet lag conditions with distinct programs of light and darkness: an 8-h phase delay every 7 days (delay, n = 14) or an 8-h phase advance every 4 days (advance, n = 34). “Delay” represents a mild condition in which mice are entrained, whereas “Advance” represents a condition of circadian rhythm disorder in which mice are not entrained. Our results showed that the 26.5% (9/34) mice reared under the “Advance” shift condition died or were sacrificed by humane endpoint throughout the experiment, whereas the first death under “Delay” condition occurred on day 611. The mortality rate of the mice reared under “Advance” condition was higher than the mice under “Delay” condition [HR (95% CI) 4.26 (0.54–33.6)]. In “Advance” mice of shorter lifespan, which showed splenomegaly and increased myeloid cells in bone marrow, which indicates that chronic inflammation existed in those mice. Although this study is still preliminary, these findings suggest that prolonged severe circadian rhythm disorder may result in the induction of chronic inflammation and tend to result in a shorter lifespan. Further studies are needed to understand why and how circadian rhythm disorder increases the risk of various dysfunction of physiology and diseases.

     

Humoral endorphin: A new endogenous factor with opiate-like activity

Humoral (H) endorphin, a novel endogenous opioid ligand detected in brain, blood and cerebrospinal fluid was tested in a series of opiate sensitive assays. H-endorphin displaced radiolabeled enkephalin from its specific bindings sites and inhibited the electrically evoked contraction of the guinea pig ileum and mouse vas deferens. When injected to unanesthesized animals, humoral endorphin induced analgesia in rats and mydriasis in mice. The activity of H-endorphin both $\text{in}\text{vitro}$ and $\text{in}\text{vivo}$ attests to its opioid nature. However, while its antinociceptive effect was blocked by naloxone, mydriasis induced by H-endorphin was resistant to the effect of the opiate antagonist. Similarly, intermediate concentrations of naloxone inhibited the effect of H-endorphin on the guinea pig ileum while its effect on the mouse vas deferens was completely refractory to naloxone. The physiological function of humoral endorphin in various naturally occuring states that show similar paradoxical interactions with naloxone is discussed.     

Prolonged hypalgesia following "acupuncture" in monkeys

After learning to escape painful electrical stimulation of one leg, Cebus albifrons monkeys were presented with a random schedule of five intensities, and they consistently responded with minimal latencies to the higher intensities during control sessions. Preceding different sets of experimental sessions, the monkeys received mild electrical stimulation between loci below the knees that were intended to correspond to acupuncture points. following the majority of these “acupuncture treatments” significant elevations of escape latencies were observed at the higher stimulus intensities. The decreased reactivities to noxious stimuli were often delayed in onset following the end of “acupuncture treatments,” and substantial alterations of escape behavior were detected up to 70 hours post-treatment. Regardless of the relevance of this finding to acupuncture, it represents an unusually enduring alteration of pain sensitivity following stimulation of the body surface in a situation free from suggestive influences.     

Studies on the mechanism of transplantation tolerance: I. Do suppressor cells play a role in the induction and maintenance of neonatal transplantation tolerance?

Neonatal transplantation tolerance was induced in CBA (H-2^k) mice to A (H-2^a) mice by injection of (CBA × A)F₁ spleen cells. Animals carrying an A-skin test allograft for more than 4 months without any visible sign of rejection were considered to be permanently tolerant. Permanently tolerant CBA mice were given normal syngeneic spleen cells to abrogate the state of tolerance. Abrogation of tolerance was greatly facilitated by antithymocyte serum (ATS) treatment of tolerant mice prior to the normal syngeneic cell transfer. Survival of A allografts on normal, adult, ATS-treated CBA mice was significantly prolonged (and in many cases “adult” tolerance was achieved) by transfer of spleen cells of syngeneic mice made permanently tolerant at neonatal age. The possible role of the F₁-cell “contamination” in the tolerance-inducing effect of the transferred “tolerant” spleen cells was excluded. The results indicate that ATS-sensitive suppressor cells play a definite role in the induction, maintenance, and transfer of neonatally induced transplantation tolerance.     

Digitalis receptor desensitization in rat ventricle: Ouabain produces two inotropic effects

In rat ventricular strips at 35° and 37°C, at 1 Hz and 3 Hz stimulation rate and in Krebs-Henseleit and Tyrode solution, cumulative dose/response curves of ouabain revealed two apparent positive inotropic effects, a “low-dose” effect with a half maximal increase in contractile force (ED₅₀) of 0.5 μM ouabain representing about 30% of the total inotropy and a “high-dose” effect of 19 to 35 μM ouabain representing about 70% of total inotropy. The overall or combined ED₅₀ was 16 μM ouabain. The “low-dose” effect was not prevented by α or β adrenergic blockade, by reserpinization, or by histamine H₂ antagonist. However, when the tissue preparations were washed for 60 to 120 min after completion of the first dose/response experiment, a second dose/response curve with ouabain revealed an absence or disappearance of the “low-dose” effect and a normal “high-dose” effect. The “low-dose” effect is apparently related to pretreatment with ouabain. We refer to this phenomenon as “desensitization”.     

Components of the major urinary protein complex of inbred mice: Determination of NH2-terminal sequences and comparison with homologous components from wild mice

The major urinary protein (MUP) complex of normal inbred laboratory mice (Mus musculus musculus) is a family of three electrophoretically distinguishable components, designated 1, 2, and 3 in order of increasing anodal mobility at pH 5.5. Components 1 and 2 are under the control of a single genetic locus; the MUP complex of a given inbred strain consists of component 1 or 2 plus component 3. In this study, the urinary protein of two subspecies of Asian wild mice, Mus musculus molossinus (originally trapped in Japan) and Mus musculus castaneus (originally trapped in Thailand), was examined electrophoretically and ultracentrifugally. The MUP complex of male M. m. molossinus and M. m. castaneus sedimented at approximately the same rate as that of M. m. musculus (s ₂₀ =2.0?2.2S). It consisted of a “fast” (i.e., more anodal than component 3) and an “intermediate” component plus one or more “origin” (i.e., less anodal than component 1) components. The “fast” and “origin” components were isolated chromatographically, and NH₂-terminal sequences spanning the first 36 residues were determined. Comparison with the NH₂-terminal sequences determined for components 1, 2, and 3 isolated from the urine of BALB/c or C57BL/6 mice revealed, except for a single replacement at position 6 in the “origin” component of M. m. molossinus, no differences among the 1, 2, “origin”, and “fast” components. Component 3 was highly homologous but differed from component 1 at nine positions; its residue at position 6 was the same as that of the M. m. molossinus “origin” component.     

Tissue Culture Studies in Bovine Leukosis

By examining cover slips stained at regular intervals the development of primary lymph node tissue cultures from 2 cases of juvenile bovine leukosis and 2 “normal” foetuses was studied. Secondly, comparisons were made between cell lines prepared from 23 bovines — “normal” animals and foetuses, cases of adult leukosis, juvenile leukosis and skin leukosis — with respect to susceptibility to infection with interferon sensitive viruses (VSV and PRV) and/or growth rate in the presence of sera from “normal” and leukotic animals. Nuclear budding, nuclear fragmentation, lymphocyte adsorption and giant cell formation were observed — though to a much greater extent in cultures prepared from the leukosis animals — in all 4 cases studied. No indications of different susceptibility for the test virus infections appeared between cell lines prepared from “normal” and leukotic animals. The growth rate of the cell lines seemed similar irrespective of the kind of serum used.     

Suppression of nociceptive reactions in mice under low-intensity microwave irradiation of acupuncture points

We studied nociceptive responses to subcutaneous injections of formalin and electrical stimulation of the limbs in control mice and in mice whose acupuncture points (AP) were subjected to low-intensity microwave irradiation. In the latter animals, nociceptive reactions were significantly weaker than those in the control mice. The analgesic effect depended on what AP was selected and irradiated and on the duration and timing of microwave irradiation. In different experimental series, the duration of a formalin injection-induced nociceptive behavioral reaction decreased by 23.3–59.6%. The threshold of vocalization responses to stimulation on an electrified floor increased by 25.8±28.0%. The results demonstrate that a technique of analgesia by influencing the AP with microwave irradiation of a nonthermal intensity is rather effective.     

脚内核在电针镇痛及兴奋尾壳核镇痛中的作用

用行为学和电生理学的方法 ,探讨脚内核在电针镇痛及兴奋尾壳核镇痛中的作用。脚内核微量注射红藻氨酸 7d后 ,电针对辐射热引起的大鼠缩腿潜伏期无明显影响 ,电针或兴奋尾壳核对丘脑束旁核神经元的伤害性反应亦无明显影响。与正常对照组电针或兴奋尾壳核产生的抑制作用相比有显著性差异 (P <0 .0 5 ) ;与脚内核微量注射生理盐水 7d后 ,电针可提高大鼠缩腿潜伏期 ,及电针或兴奋尾壳核对束旁核神经元伤害性反应的抑制作用相比 ,有显著性差异 (P <0 0 5 )。上述结果提示 ,脚内核在电针及兴奋尾壳核镇痛中发挥重要作用     

Persistently low natural killer cell activity and circulating levels of plasma beta endorphin: risk factors for infectious disease

Beta endorphin levels were quantitated in plasma samples obtained from normal subjects (n = 81, 37% males and 63% females, age range 18-45 years) as a component of a prospective study examining the relationship of illness morbidity to natural killer cell activity and psychological indices of stress. The present study was designed to test whether beta endorphin levels contributed additionally to the explanation of illness outcome variance. In the larger study, persistently low NK (LNK) activity was associated prospectively with higher illness morbidity. The findings reported here suggest that the observed LNK activity might be affected by circulating levels of plasma beta endorphin, as lower endorphin levels predicted the LNK pattern, which in turn, predicted higher illness morbidity.     

Acupuncture analgesia in rats and its changes under the effect of morphine and naloxone

It was established in chronic experiments on rats that electric acupuncture of the acupuncture point noticeably decreases pain reaction to electric stimulation of the tail. Morphine given in a subanalgetic dose (5 mg/kg) potentiated acupuncture analgesia, while 5 mg/kg of naloxone completely abolished it. Potential mechanisms of analgesia realization during electric acupuncture are discussed.     

EXPECTATIONS AND STABILITY OF PREFERENCE CHOICE

When identical milk samples are presented, only 30% of participants respond with a “no preference” rating. Stability of the “no preference” rating was studied under a variety of conditions, having consumer panelists rate both identical and different pairs of milk samples with varying fat content. The proportion of participants choosing the “no preference” option, when the samples in the pair were identical, was largely consistent despite manipulation of pretest conditions and changes in test questions and answer formats. However, when the milk preference test was preceded by a same/different test, and those responding “same” were assumed to have no preference, the percent of “no preference” was two to three times larger for identical test samples (60–69%). Thus by branching the question, the “false preference” choice for identical milks was lowered. Among those responding “different” to identical milks, the false‐alarm rate increased to 91%, suggesting that perception of (spurious or momentary) differences is driving at least part of the preference choice.     

Feline Toxoplasmosis from Acutely Infected Mice and the Development of Toxoplasma Cysts*

SYNOPSIS. The development of Toxoplasma cysts was studied in mice inoculated with tachyzoites by several routes. After 1–30 days of infection, murine tissues were examined microscopically, and portions or whole carcasses were fed to mice and cats. The feces of the cats were examined for oocyst shedding. Cyst-like structures containing distinct PAS-positive granules were first seen after 3 days of infection with tachyzoites, and became numerous by 6 days. Argyrophilic walls were first seen after 6 days, and became numerous by 16 days of infection with tachyzoites. Prepatent periods to oocyst shedding (PPO) were either “short” (3–10 days) or “long” (19–48 days). The “short” PPO was found only in cats that had ingested mice infected for 3 days or longer, and was related to the development of PAS-positive granules in T. gondii, and to high, 60–100%, oral infectivity rates for cats. The “long” PPO followed the ingestion of mice infected for only 1–2 days, and was related to tachyzoites without distinct PAS-positive granules and low, 32% or less, infectivity for cats. The “long” PPO followed also the ingestion of oocysts and the parenteral inoculation of tachyzoites, bradyzoites, or sporozoites. Using the “short” PPO as a criterion for detecting cysts in tissues, it was shown that (a) numerous cysts developed in mice 5 days after inoculation with tachyzoites, 7–9 days after inoculation with cysts, and 9–10 days after inoculation with oocysts, and (b) cysts developed faster and more frequently in the brain and muscle than in lungs, liver, spleen, and kidneys of mice inoculated with tachyzoites.     

Cellular events in tolerance. VII. Decrease in tolerant spleens of PFC precursors stimulated in vitro by specific antigen or mitogen.

Spleen cells from adult mice rendered tolerant to the fluorescein (FL) hapten (as FL-sheep γ-globulin) were analyzed at limiting dilution for the numbers of precursors stimulatable either by specific antigen (FL-polymerized flagellin; FL-POL) or by a polyclonal B-cell activator (E. coli lipopolysaccharide; LPS). As expected, the number of PFC presursors activated by FL-POL was reduced more than fourfold in the spleens of FL-tolerant mice compared to normal controls. In contrast, LPS was able to trigger equivalent numbers of “FL-specific” PFC precursors in both normal and tolerant spleens. However, the clones stimulated by LPS were predominantly the “low-avidity” precursors in FL-tolerant spleens as shown by plaque inhibition studies. In addition, after FL-gelatin enrichment of normal or tolerant spleen cells, which contain equal numbers of antigen-binding cells, we found that purified cells from tolerant mice were in fact reduced in the numbers of clonable precursors upon LPS stimulation. Two other B-cell mitogens, POL and PPD, also failed to activate PFC precursors from FL-gelatin-purified tolerant spleen cells. Our results suggest that some high-avidity clones may be functionally deleted even in adult B-cell tolerance as previously noted for neonatal tolerance.