ß-Casomorphin: A complete health perspective.

ß-Casomorphin-7 (BCM-7) is a heptapeptide dietary molecule derived from the digestion of the ß-casein of dairy and dairy products. In this review, we have covered the extensive details about BCM and its derived peptides out of the gastrointestinal and enzymatic digestion of milk and milk products, its structure and properties, and its immunological aspects related to human health among infants and adults of both genders. We have left judgment about BCM's pros and cons to the reader by describing the details in a cyclopedic perspective. In addition, a section on the possible ways to detect BCMs from their sources using proteomics, genome-based techniques, such as PCR and aptamers, and other analytical techniques equip the reader to get an idea about the details of the diagnostics available and possible applications in future. Overall, this review will provide information to the end-users of milk and milk products to enable them to make their own decisions about BCMs.

Early exposure to environmental enrichment protects male rats against neuropathic pain development after nerve injury.

Because environmental elements modify chronic pain development and endogenous mechanisms of pain control are still a great therapeutic source, we investigated the effects of an early exposure to environmental enrichment (EE) in a translational model of neuropathic pain. Young male rats born and bred in an enriched environment, which did not count on running wheel, underwent chronic constriction injury (CCI) of sciatic nerve. EE abolished neuropathic pain behavior 14 days after CCI. Opioid receptors' antagonism reversed EE-analgesic effect. ß-endorphin and met-enkephalin serum levels were increased only in EE-CCI group. Blockade of glucocorticoid receptors did not alter EE-analgesic effect, although corticosterone circulating levels were increased in EE animals. In the spinal cord, EE controlled CCI-induced serotonin increase. In DRG, EE blunted the expression of ATF-3 after CCI. Surprisingly, EE-CCI group showed a remarkable preservation of sciatic nerve fibers compared to NE-CCI group. This work demonstrated global effects induced by an EE protocol that explain, in part, the protective role of EE upon chronic noxious stimulation, reinforcing the importance of endogenous mechanisms in the prevention of chronic pain development.

Architecting of a biodevice based on a screen-printed carbon electrode modified with the NiONP nanolayer and aptamer in BCM-7 detection.

In this study, an ultrasensitive and robust biodevice implemented on a screen-printed carbon electrode (SPCE) surface is introduced. The ß-casomorphin-7 (BCM-7) peptide as an early warning sign of autism disorder is distinguished in this system. The SPCE surface was directly electrodeposited with a nanolayer of the nickel oxide nanoparticles (NiONP). In next step, an Apt sequence as a capture of the BCM-7 was strongly attached on this surface. The embedded sensing interface offered some admirable characterizes to detect the BCM-7. The obtained DPV signals were reversely proportional to the concentrations of the BCM-7 through a stable binding reaction in two working linear ranges from 0.5 × 10-9-1.5 µmol l-. Also, an unrivaled limit of detection (LOD) value of 166.6 aM was achieved that is so superior by other reported methods in the BCM-7 sensing. This hand-held biodevice was satisfactorily tested for the BCM-7 detection in human urine and blood sample with an average recovery rate of ∼101.87 %. More importantly, this strategy is free from labeling steps, complex sample processing and interference from common biomolecules in blood or urine. Due to the inherent advantages of the SPCE and the NiONP, utilizing this facile sensing interface may be an ideal choice in constructing of the ultrasensitive biodevice with low cost for distinguishing of the autism disorder.

Designing of an ultrasensitive BCM-7 aptasensor based on an SPCE modified with AuNR for promising distinguishing of autism disorder.

Abstractly, in this study, an aptasensor is introduced based on a platform consisting of the gold nanorod (AuNR) on a screen printed carbon electrode (SPCE) surface. The aptasensor is applied for detection of the ß-casomorphin (BCM-7) as a promising biomarker of autism disorder. The NH2-Apt sequence is directly immobilized onto the AuNR/SPCE surface by formation of a chemisorption bond between the amine-Au groups. By incubation of the BCM-7 onto the aptasensor surface, the aptasensor directed against BCM-7 and cleverly formed a target/Apt complex to produce a measurable electrical current change. The aptasensor shows linearity over the range of 1 fmol L-1 to 25 nmol L-1 with a limit of detection (LOD) of 334 amol L-1. Furthermore, the function of the aptasensor in real samples such as human urine and plasma samples is evaluated. The achieved satisfactory results are mainly due to three main reasons including (1) the large specific surface area of the AuNR which forms a 3D network on the SPCE surface to capture more Apt sequences at the sensing interface, (2) utilizing Apt as the BCM-7 receptor with inherent unique properties to produce a synergetic effect with the AuNR, and finally, (3) effective using screen printing technology with the fantastic capability to less cost of the aptasensor preparation. There is hope that miniaturization of the proposed aptasensor may aid future efforts to detect autism symptoms as early as infancy under clinical conditions in real-world.

Role of Milk-Derived Opioid Peptides and Proline Dipeptidyl Peptidase-4 in Autism Spectrum Disorders.

Opioid peptides released during digestion of dietary proteins such as casein, were suggested to contribute to autism development, leading to the announcement of opioid excess hypothesis of autism. This paper examines role of enzyme proline dipeptidyl peptidase-4 (DPPIV; EC 3.4.14.5) and it is exogenous substrate, ß-casomorphin-7 (BCM7) in autism etiology. Our study included measurements of DPPIV and BCM7 concentrations in serum and urine, which were analyzed with ELISA assays and activity of DPPIV was measured by colorimetric test. The effect of opioid peptides from hydrolysed bovine milk on DPPIV gene expression in peripheral blood mononuclear cells (PBMC) in autistic and healthy children was determined using the Real-Time PCR (Polymerase Chain Reaction) method. Our research included 51 healthy children and 86 children diagnosed with autism spectrum disorder (ASD, ICDF84). We determined that the concentration of BCM7 in serum was significantly, 1.6-fold, higher in the ASD group than in controls (p < 0.0001). Concentration of DPPIV was found to also be significantly higher in serum from ASD children compared to the control group (p < 0.01), while we did not notice significant difference in enzymatic activity of serum DPPIV between the two study groups. We confirmed correlation according to the gender between analyzed parameters. The inspiration for this study emanated from clinical experience of the daily diet role in relieving the symptoms of autism. Despite this, we have concluded that milk-derived opioid peptides and DPPIV are potentially factors in determining the pathogenesis of autism; conducted studies are still limited and require further research.

Elevated endogenous opioids in obstructive jaundice: The possible skin mechanisms.

Obstructive jaundice disease is often accompanied by an increase in plasma endogenous opioids levels. Theses elevated endogenous opioids bring complications like pruritus, cardiac and vascular abnormalities in patients with cholestasis. However, little is known about the mechanism of increased endogenous opioids synthesis in cholestatic liver diseases. Different from the tradition view that the liver is the source of endogenous opioids peptides, recent researches give clues that skin may be another important organ in which endogenous opioid peptides were synthesized during cholestasis. Skin cells like keratinocytes, fibroblasts, macrophages and other inflammation cells had been reported to produce endogenous opioid peptides under certain physical and pathological conditions. In the course of obstructive jaundice, all these cells had the potential to be activated by different molecular mechanisms. And some cells like keratinocyte and inflammation cells had been proved to correlate with elevated plasma levels of enkephalin and beta-endorphin in patients with obstructive jaundice. Hence, we hypothesize that skin may be the site in which abundant endogenous opioid peptides been produced during the course of obstructive jaundice. These skin-cell related mechanisms should be further studied to resolve the puzzle of elevated peripheral opiate tone during obstructive jaundice.

Effects of transcranial direct current stimulation on pain, mood and serum endorphin level in the treatment of fibromyalgia: A double blinded, randomized clinical trial.

BACKGROUND: Recent studies have shown that novel neuro-modulating techniques can have pain-relieving effects in the treatment of chronic pain. The aim of this work is to evaluate the effects of transcranial direct current stimulation (tDCS) in relieving fibromyalgia pain and its relation with beta-endorphin changes. MATERIAL AND METHODS: Forty eligible patients with primary fibromyalgia were randomized to receive real anodal tDCS or sham tDCS of the left motor cortex (M1) daily for 10 days. Each patient was evaluated using widespread pain index (WPI), symptom severity of fibromyalgia (SS), visual analogue scale (VAS), and determination of pain threshold as a primary outcome. Hamilton depression and anxiety scales (HAM-D and HAM-A) and estimation of serum beta-endorphin level pre and post-sessions were used as secondary outcome. All rating scales were conducted at the baseline, after the 5th, 10th session, 15 days and 1 month after the end of the sessions. RESULTS: Eighteen patients from each group completed the follow-up schedule with no significant difference between them regarding the duration of illness or the baseline scales. A significant TIME × GROUP interaction for each rating scale (WPI, SS, VAS, pain threshold, HAM-A, HAM-D) indicated that the effect of treatment differed in the two groups with higher improvement in the experimental scores of the patients in the real tDCS group (P = 0.001 for WPI, SS, VAS, pain threshold, and 0.002, 0.03 for HAM-A, HAM-D respectively). Negative correlations between changes in serum beta-endorphin level and the changes in different rating scales were found (P = 0.003, 0.003, 0.05, 0.002, 0002 for WPI, SS, VAS, HAM-A, and HAM-D respectively). CONCLUSION: Ten sessions of real tDCS over M1 can induce pain relief and mood improvement in patients with fibromyalgia, which were found to be related to changes in serum endorphin levels. ClinicalTrials.gov Identifier: NCT02704611.

The Effects of Ultraviolet Eye Irradiation on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice.

Ultraviolet (UV) eye irradiation denatures the cells of the intestine. This study examined the action of UVA and UVB on dextran sodium sulfate (DSS)-induced ulcerative colitis. We produced a mouse model of ulcerative colitis by administering DSS for 5 days and irradiated the eye with UVB or UVA for each day of the DSS treatment period. DSS-induced ulcerative colitis was deteriorated by the UVB eye irradiation. Conversely, the symptoms improved with UVA eye irradiation. The levels of adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), urocortin 2, interleukin (IL)-18, IL-6 and histamine in the blood increased after the UVB eye irradiation of DSS-treated mice (UVB/DSS-treated mice). In contrast, the ß-endorphin level in the blood of the UVA/DSS-treated mice increased and the levels of urocortin 2, tumor necrosis factor (TNF)-α and histamine decreased. Furthermore, in the colon, the expression of melanocortin-2 receptors (MC2R) increased in the UVB/DSS-treated mice, while the expression of µ-opioid receptors increased in the UVA/DSS-treated mice. When an ACTH inhibitor was administered, UVB eye irradiation caused the deterioration of DSS-treated ulcerative colitis, while the effect of UV eye irradiation disappeared with a µ-opioid receptor antagonist. These results suggested that UV eye irradiation plays an important role in DSS-induced ulcerative colitis.

Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows' milk.

BACKGROUND: Cows' milk generally contains two types of ß-casein, A1 and A2 types. Digestion of A1 type can yield the peptide ß-casomorphin-7, which is implicated in adverse gastrointestinal effects of milk consumption, some of which resemble those in lactose intolerance. This study aimed to compare the effects of milk containing A1 ß-casein with those of milk containing only A2 ß-casein on inflammation, symptoms of post-dairy digestive discomfort (PD3), and cognitive processing in subjects with self-reported lactose intolerance. METHODS: Forty-five Han Chinese subjects participated in this double-blind, randomized, 2 × 2 crossover trial and consumed milk containing both ß-casein types or milk containing only A2 ß-casein. Each treatment period was 14 days with a 14-day washout period at baseline and between treatment periods. Outcomes included PD3, gastrointestinal function (measured by smart pill), Subtle Cognitive Impairment Test (SCIT), serum/fecal laboratory biomarkers, and adverse events. RESULTS: Compared with milk containing only A2 ß-casein, the consumption of milk containing both ß-casein types was associated with significantly greater PD3 symptoms; higher concentrations of inflammation-related biomarkers and ß-casomorphin-7; longer gastrointestinal transit times and lower levels of short-chain fatty acids; and increased response time and error rate on the SCIT. Consumption of milk containing both ß-casein types was associated with worsening of PD3 symptoms relative to baseline in lactose tolerant and lactose intolerant subjects. Consumption of milk containing only A2 ß-casein did not aggravate PD3 symptoms relative to baseline (i.e., after washout of dairy products) in lactose tolerant and intolerant subjects. CONCLUSIONS: Consumption of milk containing A1 ß-casein was associated with increased gastrointestinal inflammation, worsening of PD3 symptoms, delayed transit, and decreased cognitive processing speed and accuracy. Because elimination of A1 ß-casein attenuated these effects, some symptoms of lactose intolerance may stem from inflammation it triggers, and can be avoided by consuming milk containing only the A2 type of beta casein. TRIAL REGISTRATION: ClinicalTrials.gov/NCT02406469.

Remote ischemic preconditioning does not increase circulating or effector organ concentrations of proopiomelanocortin derivates.

OBJECTIVES: The aim of the present study was to compare changes in circulating levels of proopiomelanocortin (POMC) derivates and lactate after remote ischemic preconditioning (IPC) and physical exercise. INTRODUCTION: Remote IPC (rIPC) is cardioprotective following acute myocardial infarction and major cardiac surgery. A blood-borne, transferable factor, released following not only rIPC but also vigorous exercise, mediates protection that is abolished by naloxone suggesting involvement of an opioid-receptor-dependent pathway. DESIGN: Eight healthy volunteers underwent rIPC by four cycles of 5-min inflation of a pneumatic tourniquet to 200 mmHg interrupted by 5 min of deflation. Subsequently, circulating plasma levels of POMC derivates, cortisol, and lactate were measured. After 3 days, the volunteers completed a vigorous exercise program, after which the same compounds were measured. RESULTS: While rIPC was not associated with any significant increase in circulating POMC derivates or lactate, exercise induced significant elevation of both compared with baseline. CONCLUSIONS: We were not able to demonstrate a detectable increase in circulating POMC derivates by a standard rIPC stimulus, suggesting that rIPC effect is not mediated by local or detectable central release of these derivates.

Aptamer-based sensing of ß-casomorphin-7.

ß-Casomorphin-7 (BCM-7), a seven amino acid peptide, is released during digestion of ß-casein A1 variant of milk which is speculated to be associated with certain diseases. Fifteen ssDNA aptamers having high affinity toward BCM-7 were identified from a 72 nt long random library after ten rounds of systematic evolution of ligands by exponential enrichment. Dissociation constant values of selected aptamers were in the range of 7.7-156.7 nM. Seq6 aptamer exhibited the lowest Kd value. Nine aptamers were evaluated for their binding toward BCM-7, BCM-9A1, and BCM-9A2 peptides, and binding was variable. SeqU5 exhibited the lowest binding with BCM-9A1 and BCM-9A2. Aptamer-coated gold nanoparticles (GNPs) resulted in color change of GNPs in the presence of BCM-7, thereby establishing recognition of BCM-7 by aptamers. The enzyme-linked aptamer-sorbent assay (ELASA) was evaluated as an assay of BCM-7 in biological fluids. BCM-7-peroxidase competed with BCM-7 in ELASA, performed with BCM-7 solution and BCM-7 spiked urine pretreated with urease, plasma, and ß-casein digest samples.

[Influence of enzymatic hydrolyzate of mussel meat on growth and some indicators of general adaptation syndrome in rats].

The impact of the 15-day consumption of enzymatic hydrolyzate of the mussels meat as a part of semi-synthetic diet on some stress biomarkers and apoptosis activity in various organs of growing male Wistar rats have been studied. Enzymatic hydrolyzate of the mussels meat (EMM) was obtained in pilot conditions using the enzyme preparation "Protozim". The animals of control group 1 (n = 8 with initial body weight of 179.4 ± 5.9 g) and experimental group 2 (n = 8, 176.3 ± 4.5 g) received a semi synthetic diet; the animals of the experimental group 3 (n = 8, 177.6 ± 4.0 g) received the same semi synthetic diet in which 50% of the casein was replaced by the peptides of EMM. On the penult day of the experiment animals of groups 2 and 3 were subjected to stress exposure by electric current on their paws (current 0.4 mA for 8 seconds) and were placed in metabolic cages for the collection of daily urine. At the 15th day of the study, all control and test animals were killed by decapitation under ether anesthesia and necropsied. The content of prostaglandin E2 and ß-endorphin in blood plasma was determined by ELISA test. The concentration of urine corticosterone was measured by HPLC. DNA damage and percentage of apoptotic cells (apoptotic index) were calculated in thymus by single-cell gel electrophoresis assay (Comet assay). The relative body weight increase of animals treated with EMM was significantly (p < 0.05) higher (68.2 ± 3.0%) than those in animals of groups 1 and 2 (57.2 ± 4.0 and 59.7 ± 2.8%, respectively). The apoptotic index in thymus cells of tested groups of animals (2 and 3) was significantly (p < 0.05) higher (1.13 ± 0.09 and 1.09 ± 0.01%) compared to intact animals of control group (1.04 ± 0.01%). Determination of ß-endorphin and prostaglandin E2 levels did not shown any significant differences between the groups. Significantly (p < 0.05) lower concentrations of corticosterone was found in the daily urine of stressed animals from group 3 (452 ± 78 ng/ml), treated with EMM, compared to stressed animals of group 2 that received a casein diet (834 ± 167 ng/ml). It has been shown that consumption of EMM with a high content of short and medium peptides has an impact on effectiveness of body weight gain of growing laboratory animals, and restrict the increase of corticosterone level in rats blood, which is typical for general adaptation syndrome.

[Effects of acupuncture combined general anesthesia on endorphin and hemodynamics of laparoscopic cholecystectomy patients in the perioperative phase].

OBJECTIVE: To observe the effects of different anesthesia ways on endorphin and hemodynamics of laparoscopic cholecystectomy patients in the perioperative phase. METHODS: A total of 90 laparoscopic cholecystectomy patients, 29 to 80 years old, were randomly assigned to Group A (treated with electroacupuncture at acupoints combined general anesthesia), Group B (treated with electroacupuncture at non-acupoints combined general anesthesia), and Group C (treated with general anesthesia) according to American Society of Anesthesiologists (ASA) I-II, 30 cases in each group. All patients were induced by 3 microg/kg Fentanyl (Fen), 2 mg/kg Propofol (Pro), and 0.1 mg/kg Vecuronium (Vcr). Bispectral index (BIS), being 40 -65, indicated the state of general anesthesia. The anesthesia was maintained by intravenous injecting Pro, interruptedly intravenous injecting Fen and Vcr. Each patient received patient controlled intravenous analgesia (PCIA) after operation. On these bases, patients in Group A received electrical acupuncture at bilateral Hegu (LI4), Neiguan (PC6), Quchi (Ll11), Zusanli (ST36), and Yanglingquan (GB34). Patients in Group B received electrical acupuncture at the points beside acupoints. The electroacupuncture was lasted from 15 -30 min before anesthesia induction to the end of the operation in Group A and B. The heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), cardiac output (CO), systemic vascular resistance index (SVRI), and acceleration index (ACI) were recorded before anesthesia induction, immediate before pneumoperitoneum, 5 min after pneumoperitoneum, excision of gallbladder, and at the end of operation. The time consumption from discontinuation to spontaneously breathing recovery, analeptic, and extubation were recorded. The blood samples (3 mL each time) were collected from the peripheral vein before anesthesia induction, 2 h after operation, the 1st day after operation, and the 3rd day after operation to detect the beta-endorphin (beta-EP) level. The visual analogue scale (VAS) were observed and recorded in the 3 groups at post-operative 4, 6, 8, 24, and 44 h, respectively. RESULTS: (1) Compared with before anesthesia induction in the same group, the CI, CO, ACI of all patients decreased significantly at 5 min after pneumoperitoneum and at excision of gallbladder (P < 0.01, P < 0.05). The HR, MAP, SVRI obviously increased in Group B and Group C at each time point (P < 0.05, P < 0.01). Less change happened in Group A. Compared with Group C, the increment of MAP was less in Group A at 5 min after pneumoperitoneum, showing statistical difference (P < 0.05). (2) The time consumption from discontinuation to analeptic and extubation was obviously shorter in Group A than in Group B and Group C (P < 0.05, P < 0.01). (3) The level of beta-EP on the 1st day of operation was significantly lower in Group A than in Group B (P < 0.05) and Group C (P < 0.01). (4) The VAS score at post-operative 44 h was significantly lower in Group A than in Group B and Group C (P < 0.05). CONCLUSIONS: Electroacupuncture at acupoints combined general anesthesia could maintain the stabilization of haemodynamics, and relieve the stress reaction after pneumoperitoneum and operation, and prolong it to early post-operative period, and strengthen the effects of post-operative analgesia. The post-operative recovery was fast, safe, and reliable.

The science behind animal-assisted therapy.

Animal-assisted therapy is a complementary medicine intervention, typically utilizing dogs trained to be obedient, calm, and comforting. Several studies have reported significant pain relief after participating in therapy dog visits. Objective reports of reduced pain and pain-related symptoms are supported by studies measuring decreased catecholamines and increased endorphins in humans receiving friendly dog visits. Mirror neuron activity and disease-perception through olfactory ability in dogs may also play important roles in helping dogs connect with humans during therapeutic encounters. This review will explore a variety of possible theories that may explain the therapeutic benefits that occur during therapy dog visits.

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.

The exogenous opioid peptides and DPPIV serum activity in infants with apnoea expressed as apparent life threatening events (ALTE).

Casein-derived peptides have been suggested to play a role in sudden infant death syndrome (SIDS). In this study, we have determined the content of bovine ß-casomorphin-7 (bBCM-7) and the activity of dipeptidyl peptidase-IV (DPPIV) in sera of infants with apparent life threatening events (ALTE syndromes, 'near miss SIDS'). We have found that the sera of some infants after an apnoea event contained more ß-casomorphin-7 than that of the healthy infants in the same age. In all the children after an apnoea event, however, a lowered DPPIV was detected. We suspect that the low activity of that peptidase may be responsible for opioid-induced respiratory depression, induced by bBCM-7 in the general circulation.

Study on endocronological effects of radon speleotherapy on respiratory diseases.

BACKGROUND: Radon, as a radioactive noble gas of natural origin, is generally present in the atmosphere of caves during the speleotherapeutic treatment of different diseases. However, the role of radon in the therapeutic effect is not fully clarified yet. Endocrine parameter levels may be influenced by radon-like endocrine levels in balneotherapeutic treatments (bath treatment). For this reason changes of these parameters were examined in this study. PATIENTS AND METHOD: A total of 81 speleotherapy patients were involved in the survey. They spent four hours daily in Tapolca Cave, five days a week, for two weeks. In this study, the thyreoiedea stimulating hormone, free triiodine-tironin, free thyroxine, prolactine, cortisol, dehydroepiandrosterone sulphate, adrenocorticotropic hormone, and beta endorphine levels of the body were examined before and after the treatment. RESULTS: After statistical analysis of the data a significant decrease of cortisol levels of patients was found, which was not directly correlated with radon concentration. In the case of thyroid hormones, there were no significantly detectable changes of the hormone levels except for low radon concentration levels a significant decrease in the free thyroxine and the thyreoiedea stimulating hormone level of male patients was observed. CONCLUSION: Speleotherapy has an effect on the level of endocrine hormones; however, no direct correlation with differences in radon level was found. For patients whose endocrine levels fell outside the normal endocrine parameter values, more striking changes in endocrine hormone levels were seen, but changes of these parameters could not be statistically analyzed due to the small number of cases.

Naltrexone effect on physiological and subjective response to a cold pressor task.

In this double-blind, cross-over study physiological (i.e. blood pressure, heart rate, plasma catecholamine concentrations, plasma cortisol concentrations) and subjective (i.e. McGill Pain Questionnaire, positive affect, distress) response to a cold pressor task was assessed in 19 subjects 1 h after the administration of 50 mg naltrexone and after placebo. Significant differences in plasma catecholamine concentrations were found. Plasma epinephrine concentrations increased during the 1 h period after naltrexone administration but remained largely unchanged after placebo administration. A significant treatment x period effect was also found for plasma norepinephrine concentrations. No significant differences were found for other measures assessed. Further research is necessary to determine the subpopulations in which these effects are of greatest magnitude and the long term safety implications of these effects.