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PubMed1998

Altered neuroimmunoendocrine communication during a condition of chronically increased brain corticotropin-releasing hormone drive.

Presently, it is clear that the brain, immune system, and endocrine system build a complex network of interactions at various levels. Inflammation, which may be regarded as a stressful challenge, initiates apart from immunological, autonomic, and neuroendocrine responses also profound behavioral (e.g., immobility, social disinterest) changes. Key mediators herein are corticotropin-releasing hormone (CRH) and cytokines, such as interleukin-1 beta (IL-1 beta). Currently, the behavioral changes, collectively termed sickness behavior, are thought to be adaptive responses to support the body's efforts to fight the infection. Using in vivo microdialysis and biotelemetry in freely moving animals, we have studied the monoaminergic circuits in the brain implicated in the regulation of physiological and behavioral responses to a peripheral inflammatory challenge (see also chapter of Linthorst and Reul in this volume). To expand our insight into the relationship between hypersecretion of CRH and physiological and behavioral abnormalities associated with stress-related disorders, a series of experiments was conducted with long-term centrally CRH-infused rats. These rats showed reduced body weight gain, decreased food intake, elevated plasma ACTH and corticosterone levels, thymus involution and immunosuppression, but, paradoxically, enhanced IL-1 beta mRNA expression in spleen macrophages. After a peripheral endotoxic challenge on the seventh day of treatment, the CRH-infused rats produced aberrant (i.e., blunted and/or delayed) HPA axis, fever, behavioral, and hippocampal serotonergic responses. However, endotoxin-induced plasma IL-1 and IL-6 bioactivities were significantly enhanced in these animals. The data show that chronically elevated central CRH levels as occurring during chronic stress result in defective central nervous system and immune system responses to an acute (inflammatory) challenge. These observations provide evidence that chronic CRH hypersecretion is an important factor in the etiology of stress-related disorders.

Animals↗

PubMed1997

Transgenic animals as new approaches in pharmacological studies.

Transgenic animals are becoming useful tools for pharmacological studies. The use of transgenic technology raises two types of questions, "How are transgenic animals made?" and "What types of pharmacological questions can be answered using transgenic technologies?" Answers to these questions are discussed in this review. The production of animals with specific genetic alteration can be achieved by two strategies. The first involves the simple addition of DNA sequences to the chromosomes. The second strategy is to select particular genetic loci for site-specific changes. There are two well-established procedures for simple introduction of DNA into an animal genome, pronuclear DNA injection and transduction using a retrovirus. In contrast, methods for targeting specific DNA sequences to definite sites in the chromosomes are evolving rapidly. Some of these procedures can be used in combination to make a different variety of gene alterations in animals. Pharmacological studies where transgenic technology has been extensively used are discussed, including studies in the cardiovascular system, the nervous system, the endocrine system, cancer, and toxicology.

Animals↗

PubMed1976

The spread of blood-borne metastases in malignant lymphomas of man.

An autopsy study was performed on 190 cases with Hodgkin's disease and on 134 cases with reticulum cell sarcomas. It was found that a cascade spread of metastases, as opposed to a random spread, was detectable in patients with Hodgkin's disease, but not in patients with reticulum cell sarcoma. Metastatic key-sites for both lymphomas are defined as those organs whose chance of being seeded by the primary tumor is the highest; these sites are the spleen, liver, bone marrow and lungs. This study could not demonstrate in Hodgkin's cases that metastases in the liver and bone marrow were spleen dependent, but rather it showed that the spleen, liver and bone marrow acted as three independent sources of generalized metastases. Explanations proposed to account for the different metastatic spread in Hodgkin's disease and reticulum cell sarcomas, included different intrinsic cellular characteristics of the two lymphomas. the different location of the primary tumor either because of nodal, or of extra nodal origin, or because the primary tumor was located either in the upper or in the lower torso or in both areas. Malignant cells in the kidney, central nervous system and endocrine system were either released by the spleen via the lungs, or released by the liver and the lungs, or they were bone marrow dependent. The cascade spread of metastases hold true only for Hodgkin's disease. In cases with reticulum cell sarcomas, metastases appeared to spread at random from the primary tumor throughout the body, with rare exceptions such as metastases in the central nervous system, which originated either in the liver or in the spleen, lungs, kidney and bones.

Bone Marrow Diseases↗

PubMed1979

Fasting therapy for psychosomatic disorders in Japan.

It has been well known in Japan that fasting therapy has an excellent effect on various kinds of psychosomatic diseases. From 1967 to 1977 the therapy was carried out on about 382 cases of psychosomatic diseases in our clinic with an efficacy rate of 87%. The following diseases were considered as suitable indications for the therapy; irritable colon, behavioral disturbance of eating, functional disorders of the G-I tract, neurocirculatory asthenia, labile hypertension, variable psychosomatic symptoms of puberty, conversion hysteria and many kinds of neurosis with somatic complaints. The mechanism of effectiveness of the therapy is discussed from the psychological and biological aspects. It is concluded that the regulating mechanisms of the autonomic nervous system and endocrine system may change the whole functioning of the body including the brain, resulting in a spontaneous deconditioning of maladaptive bodily and mental behavior and an improved homeostatic adjustment to life.

Electroencephalography↗

PubMed1983

Anaesthesia and the kidney.

Applied anatomy and physiology of the kidney are briefly reviewed. This includes an account of renal blood flow, glomerular filtration rate, juxtaglomerular apparatus, renal autoregulation and intra-renal blood flow distribution, tubular transport mechanisms, solute handling in proximal tubule, function of loop of Henle and distal tubule system. This section concludes with a summary of changes in tubule fluid along the length of the nephron. Acute effects of anaesthesia are reviewed in detail. Indirect effects include those on circulatory and sympathetic nervous systems, autoregulation, endocrine systems such as those involving anti-diuretic hormone, adrenaline and noradrenaline, renin-angiotensin and aldosterone. Direct effects of anaesthesia on renal function have now been confirmed both in vitro and in vivo. Delayed direct nephrotoxicity of anaesthetics relates predominantly to methoxyflurane (MOF) and its metabolism to inorganic fluoride. Other factors are MOF dose, genetics, age, enzyme induction, obesity, other nephrotoxic drugs. Clinical implications are presented. Enflurane nephrotoxicity is rare but aetiologic factors are similar to the foregoing. Isoflurane and halothane are not nephrotoxic. A consideration of the influence of anaesthetic management on the incidence and severity of postoperative acute renal failure concludes the review.

Anesthesia↗

PubMedDate not supplied

An immunocytochemical study of endocrine cells in the gut of a stomachless teleost fish, grass carp, Cyprinidae.

Nineteen different antisera raised against mammalian hormones were used to identify the occurrence and distribution of endocrine cells in the gut of grass carp (Ctenopharyngodon idellus). Positive reactions were obtained in gut epithelium with antisera gastrin, glucagon, gastric inhibitory peptide, leucine enkephalin, substance P, and bovine pancreatic polypeptide. No immunoreactive product was formed using antisera against somatostatin, 5-hydroxytryptamine, insulin, avian pancreatic polypeptide, motilin, cholecystokinin, secretin, neurotensin, vasoactive intestinal polypeptide, bombesin, neuron-specific enolase, prochymosin, and pepsinogen. The exact distribution mapping of six kinds of immunoreactive endocrine cells throughout the gut of grass carp (C. idellus) is presented. The morphological characteristics of immunoreactive endocrine cells is described. Their distribution characteristics and possible modes of secretion and function are discussed. Finally, the possible relationship between the transplantation of these cells in the gastro-entero-pancreatic endocrine system is discussed.

Animals↗

PubMed1981

The adrenoleukomyeloneuropathy complex: expression in four generations.

Varying combinations of leukodystrophy, myeloneuropathy, peripheral neuropathy, and primary Addison disease were identified in 14 members of four generations of a kindred of 49 persons. Of these, 26 persons from three generations were evaluated clinically. We propose that adrenoleukomyeloneuropathy (ALMN) is a rare, progressive, presumably biochemical disorder of uncertain inheritance. ALMN is expressed clinically by dysfunction of the central nervous system, peripheral nervous system, and endocrine system. We stress that suspicion of this disorder be high in evaluating uncertain neurologic disorders, and that identification of one manifestation of this complex should alert the clinician to the possibility of a different expression of the same complex in other family members.

Adolescent↗

PubMed2003

The effects of whole body vibration on humans: dangerous or advantageous?

The effects of whole body vibration (WBV) have been studied extensively in occupational medicine. In particular, it has been shown that when the body undergoes chronically to whole body vibrations spinal degeneration is likely to be one of the deleterious outcomes. Low back pain has been shown to be the leading major cause of industrial disability in the population under the age of 45 years and has been linked to whole body vibration exposure encountered in some industrial settings. Whole body vibration has been recently purposed as an exercise intervention suggesting its effectiveness in increasing force-generating capacity in lower limbs and low back. It has also been reported to be an effective non-pharmacological intervention for patients with low back pain. Relatively short exposure to whole body vibration has been also shown to increase the serum levels of testosterone and growth hormone. The combined effects on the neuromuscular system and endocrine system seem to suggest its effectiveness as a therapeutic approach for sarcopenia and possibly osteoporosis. Due to the danger of long-term exposure to whole body vibration, it is important to develop safe exercise protocols in order to determine exercise programs for different populations.

Exercise Therapy↗

PubMed2003

Highlights of the biology of endocrine tumours of the gut and pancreas.

Originating from cells of the diffuse endocrine system the endocrine tumours of the gut and the pancreatic tract are rare entities characterized by a common phenotypic aspect and producing several bioactive substances including growth factors. Two major categories are identified: well-differentiated and poorly differentiated tumours. The clinical behaviour varies ranging from benign to low grade malignant for well-differentiated tumours/carcinomas to high grade malignant for poorly differentiated carcinomas. The two major categories of well-differentiated and poorly differentiated tumours display distinct phenotypes and genetic backgrounds possibly supporting distinct histogenesis. Genetic abnormalities associated with either induction or progression of tumours may vary depending on the site of origin.

Biomarkers, Tumor↗

PubMed2026

Mechanic evaluation of Jisheng Shenqi Wan on calcium oxalate kidney stones: an integrated network pharmacology and metabolomics.

OBJECTIVE: To understand the efficacy of Jisheng Shenqi Wan (JSSQW, ) in treating calcium oxalate kidney stones (KS) and to investigate the mechanism of JSSQW action by combining network pharmacology with metabolomics analysis based on ultra-high performance liquid chromatography combined with tandem electrostatic field orbital trap high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS). METHODS: The chemical components of JSSQW absorbed into rat blood were identified by UHPLC-Q/Orbitrap HRMS. The identified components were introduced into the Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine platform to screen for target genes, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and disease enrichment analysis. A KS rat model was generated using the oxalic acid precursor method to examine the efficacy of JSSQW for treating KS. Serum metabolomics was used to monitor changes in endogenous substances in KS rats after JSSQW intervention. RESULTS: Twenty-three chemicals from JSSQW were identified in the blood of JSSQW gavage-administered rats. KEGG enrichment analysis predicted the top 20 signaling pathways affected by these 23 chemicals. Disease enrichment analysis showed that the target genes of these 23 chemicals were enriched in diseases of the urinary system and endocrine system, including kidney stones. In a KS rat model, JSSQW inhibited the aggregation of calcium oxalate crystals, reduced renal tubular injury, lowered the renal index, and improved biochemical indicators (blood creatinine, blood urea nitrogen). Serum metabolomics identified 25 differential metabolites that responded to JSSQW treatment. They were mainly lipids, with phosphatidylethanolamine and phosphorylcholine and their derivatives accounting for the highest proportion. Metabolic pathway analysis showed that the changes in differential metabolites were related to multiple metabolic pathways, especially sphingolipid metabolism and sphingolipid signaling pathways. CONCLUSIONS: JSSQW can inhibit the aggregation of calcium oxalate crystals in the kidneys, reduce tubular injury, and improve kidney function in KS rats. Its mechanism of action may be related to regulating disordered metabolites and metabolic pathways, especially glycerol phospholipid metabolism, sphingolipid metabolism, and sphingolipid signaling.

Drugs, Chinese Herbal↗

PubMed2005

Physiological responses induced by pleasant stimuli.

The specific physiological responses induced by pleasant stimuli were investigated in this study. Various physiological responses of the brain (encephaloelectrogram; EEG), autonomic nervous system (ANS), immune system and endocrine system were monitored when pleasant stimuli such as odors, emotional pictures and rakugo, a typical Japanese comical story-telling, were presented to subjects. The results revealed that (i) EEG activities of the left frontal brain region were enhanced by a pleasant odor; (ii) emotional pictures related to primitive element such as nudes and erotic couples elevated vasomotor sympathetic nervous activity; and (iii) an increase in secretory immunoglobulin A (s-IgA) and a decrease in salivary cortisol (s-cortisol) were induced by rakugo-derived linguistic pleasant emotion. Pleasant emotion is complicated state. However, by considering the evolutionary history of human being, it is possible to assess and evaluate pleasant emotion from certain physiological responses by appropriately summating various physiological parameters.

Autonomic Nervous System↗

PubMed1998

Pharmacokinetics of drugs used in critically ill adults.

Critically ill patients exhibit a range of organ dysfunctions and often require treatment with a variety of drugs including sedatives, analgesics, neuromuscular blockers, antimicrobials, inotropes and gastric acid suppressants. Understanding how organ dysfunction can alter the pharmacokinetics of drugs is a vital aspect of therapy in this patient group. Many drugs will need to be given intravenously because of gastrointestinal failure. For those occasions on which the oral route is possible, bioavailability may be altered by hypomotility, changes in gastrointestinal pH and enteral feeding. Hepatic and renal dysfunction are the primary determinants of drug clearance, and hence of steady-state drug concentrations, and of efficacy and toxicity in the individual patient. Oxidative metabolism is the main clearance mechanism for many drugs and there is increasing recognition of the importance of decreased activity of the hepatic cytochrome P450 system in critically ill patients. Renal failure is equally important with both filtration and secretion clearance mechanisms being required for the removal of parent drugs and their active metabolites. Changes in the steady-state volume of distribution are often secondary to renal failure and may lower the effective drug concentrations in the body. Failure of the central nervous system, muscle, the endothelial system and endocrine system may also affect the pharmacokinetics of specific drugs. Time-dependency of alterations in pharmacokinetic parameters is well documented for some drugs. Understanding the underlying pathophysiology in the critically ill and applying pharmacokinetic principles in selection of drug and dose regimen is, therefore, crucial to optimising the pharmacodynamic response and outcome.

Adult↗

PubMed1997

Neurohumoral mechanisms in rheumatoid arthritis.

The observation that following stroke or peripheral nerve injuries the development of rheumatoid arthritis is either prevented or ameliorated in the affected limb was the first observation of the involvement of the neurological system in the pathogenesis of the disease. Much subsequent work has established that there are intimate and intricate associations between the central nervous system, the endocrine system and immuno-inflammatory mechanisms. The predominant interaction is through the hypothalamic-pituitary adrenal axis which mediates the secretion of corticotrophin releasing hormone which then stimulates the pituitary to release ACTH. A subsequent stimulation of the adrenal cortex leads to glucocorticoid release with their known potent anti-inflammatory effects. Many factors can interact within the central nervous system to modify this pathway. Of particular relevance is the observation that the hypothalamic-pituitary adrenal axis may be defective in rheumatoid arthritis. This has implications not only in terms of pathogenesis but also in the way in which glucocorticoids are used for the treatment of rheumatoid arthritis.

Arthritis, Rheumatoid↗

PubMed1986

The effect of auricular electroacupuncture on the neuronal activity of the thalamic and hypothalamic neurons of the rat.

Acupuncture has many physiological effects on pain control, instinctual behavior, autonomic nervous system and endocrine system. However, the mechanism of how acupuncture can affect these functions is not well known. The electrophysiological study was done using anesthetized rats to examine the effect of auricular electroacupuncture. 122 neurons of the thalamus and hypothalamus were examined. 20% of the neurons in the thalamus responded either by increasing firing rate or decreasing to auricular electroacupuncture. Some thalamic neurons responded by increasing to the nociceptive stimulation and by decreasing to acupuncture stimulation. These effects might explain some part of the analgesic effect of acupuncture. 14% of the neurons of the hypothalamus, mainly in the dorsomedial hypothalamic nucleus and around the mammillothalamic tract, responded to acupuncture. The neurons in the lateral hypothalamic area and the ventromedial hypothalamic nucleus did not respond. These results suggest the indirect effect on instinctual behavior, especially on feeding behavior, of acupuncture.

Acupuncture Therapy↗

PubMed1988

The role of trigeminal nerve in acupuncture.

The purpose of this work is to expose the topographoanatomical and functional aspects of trigeminal nerve (TN) on the view of somatotopic representation of acupuncture microsystems, the interaction among the central nervous system, the endocrine system and the immune system via the endorphins and enkephalins. In order to establish the structural and functional relationships between the TN, acupuncture points and zones on the head and neck regions; the following has been done: 1) Identification of number of acupuncture points and zones, comparing with other localization; 2) the analysis of volume of diagnostic and therapeutic indications of about 20,000 patients treating and 662 patients operated by acupuncture; and 3) the analysis of sensory somatotopic cortical representation of the TN. Our research confirmed the role of TN in acupuncture microsystems and we expect it to play this role in the future also.

Acupuncture Therapy↗

PubMed1979

Arteriohepatic dysplasia: a benign syndrome of intrahepatic cholestasis with multiple organ involvement.

Arteriohepatic dysplasia (Alagille's syndrome) is presumed to be one of the familial intrahepatic cholestatic syndromes, all of which present with neonatal jaundice or failure to thrive, or both. We report the findings in five patients with this syndrome, four of whom have been followed into adulthood. In addition to hepatic dysfunction, patients had abnormalities of the cardiovascular system, eyes, bones, central nervous system, kidney, endocrine system, and habitus. Analysis of these cases allows a more complete characterization of this syndrome and shows that the cholestasis improves, although the abnormalities of the hands and face become more pronounced, with age. Patients with arteriohepatic dysplasia display the variability in expression seen in many autosomal-dominant conditions. New findings in the eye and spine provide markers specific for this syndrome and serve to differentiate it from other forms of cholestatic liver disease.

Adolescent↗

PubMed1992

Neurobiology and inflammatory arthritis.

As diagrammed in Figures 1 and 2, the central and peripheral nervous systems, the endocrine system, and immune and inflammatory systems are extensively integrated. The boundaries defining these systems are both anatomically and molecularly blurred. This realization has been driven by the ongoing revolution in molecular biology. Normally the deleterious effects of excessive or persistent inflammation are prevented by homeostatic neuroendocrine feedback loops. Conversely, dysfunction in these counter-regulatory responses may lead to important clinical phenomena such as autoimmunity and chronic inflammation in association with behavioral alterations such as fatigue, depressed mood, and loss of libido. Continued research into the neurobiology of inflammation appears likely to explain some of the fundamental abnormalities in diseases such as RA and lead to new, more effective therapies.

Arousal↗

PubMed2001

[A study of the relationship among interleukin-8, cortisol and idiopathic preterm labor].

OBJECTIVE: To assess the effect of interleukin-8 and cortisol on the onset of idiopathic preterm labor (PL). METHODS: In 35 women with preterm labor and 17 controls, maternal serum and urine samples were collected. Interleukin-8 concentration was measured by enzyme-linked immunosorbant assay, serum cortisol level was measured by radioimmunoassay. RESULTS: The concentration of interleukin-8 in maternal serum and urine and cortisol in serum were significantly higher in PL group than those in the control [(0.26 +/- 0.13) microg/L vs (0.16 +/- 0.08) microg/L, (0.16 +/- 0.15) x 10(-2) g/mol Cr vs (0.04 +/- 0.02) x 10(-2) g/mol Cr, (765.83 +/- 408.55) microg/L vs (512.41 +/- 142.65) microg/L; P < 0.05, P < 0.01, P < 0.01, respectively]. A strong correlation was found ammong interleukin-8 and cortisol concentration in maternal serum in PL (r = 0.448; P < 0.05). CONCLUSIONS: There is a strong relationship between interleukin-8 and cortisol in the onset of preterm labor. Immune system and endocrine system might be involved in the mechanisms of idiopathic preterm labor.

Case-Control Studies↗