Biological components in a standardized derivative of bovine colostrum.

Products of different origin, time of collection, and activities fall under the general term of colostrum and, therefore, great variability in composition as well as in the concentration of its components has been reported in the literature. In the present study, we describe the standardization of a bovine colostrum derivative and the characterization of its bioactive components. Evaluation of the most representative agents (lactoferrin, transferrin, IL-2, IFN-γ, tumor necrosis factor, IgG, and IgA) showed that a marked decrease in active components occurs after the first few hours. Bovine colostrum was, therefore, collected up to the fifth hour after delivery from Holstein cows, in the presence of preservatives, and immediately frozen. A protocol of centrifugation, filtration, and lyophilization was then applied to pools of colostrum from at least 30 cows to obtain a stable, sterile, standardized product. Preservatives were removed by dialysis. Evaluation of the active biological components of colostrum showed that the final product of colostrums contained significant and reproducible amounts of bioactive factors, including cytokines, immunomodulating factors, growth factors, and immunoglobulins. The final product appeared, therefore, as a sterile, pyrogen-free, standardized derivative of bovine colostrum with a high concentration of bioactive components.

Effectiveness of electroacupuncture analgesia compared with opioid administration in a dog model: a pilot study.

BACKGROUND: Although opioid analgesics are the usual drugs to treat post-surgical pain, acupuncture has also been demonstrated to relieve various pain syndromes. The present pilot study aims to investigate the efficacy of electroacupuncture compared with a conventional opioid compound, butorphanol, for postoperative pain treatment in dogs undergoing elective ovariohysterectomy. METHODS: Twelve dogs were randomly allocated into two groups. Dogs received either electroacupuncture stimulation (16 and 43 Hz) at Shen Shu, Chang Shu, He Gu, Tai Yuan, Zu San Li, Yang Ling Quan, and Bai Hui acupoints, while control dogs were treated with butorphanol. Cardiovascular and respiratory parameters were recorded for both groups during operation. Plasma ß-endorphin concentrations were evaluated before surgery (baseline) and up to 24 h later. For each dog, pain was measured according to a dedicated subjective pain scoring system. RESULTS: Plasma ß-endorphin levels in dogs receiving electroacupuncture increased significantly against baseline values after 1 and 3 h after surgery. Moreover, the end-tidal isoflurane concentration needed for second ovary traction was significantly lower in acupuncture-treated dogs than control animals. All animals having electroacupuncture experienced prolonged analgesia, over 24 h at least, while four out of six dogs treated with butorphanol needed post-surgical ketorolac and tramadol supplementation to their pain relief. CONCLUSIONS: The results obtained from the present investigation showed some evidence for electroacupuncture as an alternative technique to provide postoperative analgesia in dogs.

Hypothalamic beta-endorphin concentrations are decreased in animals models of autoimmune disease.

Complex interactions between the neuroendocrine and the immune systems are present in autoimmune diseases. The central opioid peptide beta-endorphin (BE) has been shown to modulate peripheral immune responses in normal animals. In the present study we analyze the hypothalamic concentrations of this peptide in two models of spontaneous autoimmune disease, the MRL [corrected] lpr/lpr mouse, that develops a lupus-like autoimmune disease, and the obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis. In both instances, hypothalamic concentrations of BE are significantly lower than normal controls. In MRL [corrected] lpr/lpr mice, BE is already lower at 1 month of age, when no clinical sign of the disease is yet present. Similarly, low levels of BE are observed in OS chickens before the onset of thyroiditis, i.e., already at the embryonic stage. Moreover, a further decrease of BE is observed in OS chickens in correspondence with the first signs of thyroid mononuclear infiltration. Considering the immunosuppressive effects exerted by central BE, these results are suggestive of the fact that in autoimmune disease prone animals the low hypothalamic concentrations may be one of several factors predisposing for the development of autoimmune disease.

Presence of a reduced opioid response in interleukin-6 knock out mice.

Cytokines are known to influence neuronal functions. The purpose of this study was to investigate the putative role of the cytokine interleukin-6 (IL-6) in the pathways involved in opioid-mediated responses, by using IL-6-deficient mice. We reported that with a thermal stimulus IL-6-knock-out (IL-6KO) mice presented nociceptive thresholds similar to those measured in their controls. However, they showed a reduced analgesic response both to the restraint stress and to the administration of low doses of morphine. Hypothalamic levels of the opioid peptide beta-endorphin were significantly higher in IL-6KO mice than they were in their controls. The development of tolerance to the analgesic effect of morphine was more rapid in IL-6-deficient mice than in wild-type controls. Binding experiments showed that the number of opioid receptors in the midbrain, but not in the hypothalamus, decreased in IL-6KO mice. Autoradiographic binding analysis revealed that the density of mu receptors diminished while the delta-opioid receptors did not. These results suggest that IL-6 is necessary for a correct development of neuronal mechanisms involved in the response to both endogenous and exogenous opiates.

Peripheral mononeuropathy affects hypothalamic and splenocyte beta-endorphin levels but not immune function in the rat.

Beta-endorphin and substance P levels were measured in the hypothalamus of rats 14 days after chronic constriction injury of right sciatic nerve. Furthermore, beta-endorphin concentrations in splenocytes, phytoemoagglutinin-induced proliferation of splenocytes, and natural killer activity were assessed. We observed a significant increase of beta-endorphin and substance P hypothalamic levels, and a significant decrease of beta-endorphin concentrations in the immune cells. In contrast, the peripheral mononeuropathy did not affect the immune function. This study presents a picture of central and peripheral peptide changes consistent with a painful condition, but different from what previously observed in rats which underwent peripheral nerve deafferentation or stressful conditions.

Sex-related effects on behaviour and beta-endorphin of different intensities of formalin pain in rats.

The effects of two intensities of formalin pain on behaviour and beta-Endorphin (beta-EP) concentration in the brain and pituitary were studied in male and female rats. The animals were familiarized with the Hole-Board apparatus for 3 days, and then, after a subcutaneous injection of formalin (50 microliter, 0.1 or 10%) or Sham-injection (Control) in the hindpaw, they were tested in the Hole-Board for 60 min. Licking, Flexing and Paw-Jerk of the injected limb were recorded. beta-EP concentration was determined in the hypothalamus (HYP), the periaqueductal gray matter (PAG), the anterior pituitary (AP) and the neurointermediate lobe (NIL). Licking and Flexing durations were greater in females than males only with formalin 10%. Sex differences in beta-EP concentration between the Control groups were found in all tissues except the HYP; beta-EP levels were higher in females in the PAG and NIL, but greater in the AP in males. beta-EP concentration increased in males in the HYP and NIL with formalin 10%; in females, a decrease was found in the HYP with formalin 0.1%. The present results suggest that: (a) there are differences between males and females in the responses to formalin pain, and the nature (pattern and duration) of the sex differences varies according to the pain intensity; (b) there are differences in beta-EP concentration between the two sexes in control animals, and male and female rats also exhibit differences in the modifications of beta-EP in response to formalin-induced pain.

Psychoimmunoendocrine aspects of panic disorder.

Immunological, neuroendocrine and psychological parameters were examined in 14 psychophysically healthy subjects and in 17 panic disorder patients before and after a 30-day course of alprazolam therapy. T lymphocyte proliferation in response to the mitogen phytohemagglutinin, lymphocyte beta-endorphin (beta-EP) concentrations, plasma ACTH, cortisol and beta-EP levels were examined in basal conditions and after corticotropin-releasing hormone (CRH) stimulation. Cortisol inhibition by dexamethasone (DST) and basal growth hormone (GH) and prolactin levels were also examined. Depression, state or trait anxiety, anticipatory anxiety, agoraphobia, simple and social phobias, severity and frequency of panic attacks were monitored by rating scales. The immune study did not reveal any significant difference between patients and controls, or any effect of alprazolam therapy. The hormonal data for the two groups were similar, except for higher than normal basal ACTH and GH plasma levels, lower than normal ratios between the ACTH and cortisol responses to CRH, and blunted DST in some patients. All the impairments improved after alprazolam therapy, in parallel with decreases in anxiety and in severity and frequency of panic attacks.

Chronic intrathecal cannulation affects hypothalamic opioids depending on the technique employed.

Previous studies have shown that chronic intrathecal cannulation can interfere with the homeostasis of central opioid peptides. These results show that beta-endorphin and Met-enkephalin concentrations did not change in the hypothalamus of rats bearing a chronic cannula inserted between C8-T1 up to L3 and fixed to the processes transversus T1. These results suggest that chronically cannulated rats can be considered as normal when studying hypothalamic beta-endorphin or Met-enkephalin concentrations, and used in physiological studies, depending on the technique employed.

Traditional acupuncture increases the content of beta-endorphin in immune cells and influences mitogen induced proliferation.

We measured beta-endorphin concentrations in peripheral blood mononuclear cells and mitogen-induced T-lymphocyte proliferation in patient who underwent treatment with traditional acupuncture. Traditional acupuncture increased both the concentrations of the opioid in the immune cells and lymphocyte proliferation. Our data are consistent with the hypothesis that traditional acupuncture modulates immune responses in man.

Chronic intrathecal cannulation affects hypothalamic beta-endorphin and met-enkephalin concentrations.

Beta-endorphin concentrations decrease and met-enkephalin concentrations increase in the hypothalamus of rats bearing a chronic intrathecal cannula. The modification of the concentrations of beta-endorphin is already present on day 1 after surgery, whereas met-enkephalin is affected starting on day 6, and both peptides are still modified on day 10. These results indicate that chronically cannulated rats are not to be considered normal animals.

Effect of chronic morphine on plasma and brain beta endorphin and methionine enkephalin in pregnant rats and in their fetuses or newborn.

Normal or pregnant rats were treated orally for 21 days or throughout pregnancy with water or increasing doses of morphine and killed on days 7, 14, and 21 of pregnancy and 1 day post partum. At these time intervals, plasma, pituitary, and hypothalamic concentrations of beta-endorphin and methionine enkephalin were measured in normal and pregnant rats. Moreover, pituitary and hypothalamic concentrations of the two peptides were also measured in fetuses and newborn. Plasma beta-endorphin and methionine enkephalin increased significantly during pregnancy without any specific effect of morphine. Pituitary concentrations of beta-endorphin were not modified either by pregnancy or morphine treatment, while methionine enkephalin concentrations increased on days 7 and 11 of pregnancy, in both water- and morphine-treated rats. The pattern of the two peptides in the hypothalamus is completely superimposable to the one present in the pituitary with the exception of an increase of beta-endorphin on day 21 of pregnancy, which is more evident in control animals. Consistently with our observations in human newborn and the neurological dysfunctions we observed in them, the concentrations of both the peptides are significantly increased in the hypothalamus of fetuses and newborn of morphine-treated mothers, while in the pituitary only beta-endorphin concentrations are increased.

Brain and spinal cord neuropeptides in adjuvant induced arthritis in rats.

The concentrations of brain and spinal cord beta-endorphin, met-enkephalin, dynorphin and substance P were measured in rats bearing the Freund adjuvant induced arthritis. Beta-endorphin brain concentrations decreased gradually in time with a nadir on day twenty-one, when arthritis was at its maximum, and were back to normal by day thirty-five, when arthritis was no more evident. Met-enkephalin concentrations increased in brain areas and in the lumbar spinal cord and returned to normal with the same time pattern, while dynorphin and substance P concentrations did not change. These data indicate that peripheral lesions can induce important changes in brain concentrations of some opioid peptides involved in the modulation of pain.

Diclofenac and pirprofen modify pituitary and hypothalamic beta-endorphin concentrations.

We provide evidence that both Diclofenac and Pirprofen, two cyclooxygenase inhibitors with a potent analgesic effect both in the experimental animal and in man, induce a significant and long lasting decrease in pituitary beta-endorphin concentrations, together with an increase of the hypothalamic concentrations of the peptide. We suggest that this effect might participate in the potent analgesic effect of the two compounds, that exceeds the one expected by drugs of this class.

Antiepileptic agents affect hypothalamic beta-endorphin concentrations.

beta-Endorphin, Met-enkephalin, substance P, and somatostatin concentrations were evaluated in the hypothalami of rats treated either acutely or chronically (15 days) with sodium valproate, diphenylhydantoin, phenobarbital, or ethosuximide. All of these drugs, with the exception of ethosuximide, induced significant decreases in beta-endorphin concentrations after acute treatment, while only sodium valproate induced a decrease after chronic treatment. The acute and chronic effects of sodium valproate were also produced by aminooxyacetic acid, an inhibitor of gamma-aminobutyric acid (GABA) transaminase, while another GABA transaminase inhibitor, ethanolamine-O-sulphate, and THIP, a GABA receptor agonist, were effective after acute administration. Metenkephalin, substance P, and somatostatin concentrations were never affected by the drugs used. The present results, indicating that antiepileptic agents specifically decrease beta-endorphin concentrations, seem to correlate well with the capacity of these agents to blunt the epileptic activity of the peptides tested. Moreover, our data suggest that GABA may be involved in the anticonvulsant-induced reduction of beta-endorphin concentrations.

Teaching self-hypnosis to patients with chronic pain.

For the past twenty years hypnotherapy and self-hypnosis have been utilized as valid tools for the successful management of severe protracted pain. Control often has been achieved in cases where other modalities of pain management had been inadequate. Hypnosis properly applied can bring some degree of improvement to 90 percent of patients. More remarkable degree of pain relief is achievable in the 25 percent of patients who have high hypnotic "talent," and with very limited expenditure of time and effort. The author discusses basic theories of pain, pain-control pain-control and hypnosis, and he clarifies the effects of physiological, biochemical, and psychological variables which can affect the procedures and the results. Presentation of a clinical case with quoted excerpts of verbalization serves to illustrate the most important points.