Anii fara ani

...pentru cei carora le place sa scrie

Mesajde jl_rona » Sâm Mai 23, 2009 10:29 pm

[color="Red"]Decreased melatonin production linked to light exposure[/color]

http://www.thefreelibrary.com/Decreased+melatonin+production+linked+to+light+exposure-a0143213709
“Love, work and knowledge are the wellsprings of our lives, they should also govern it.â€Â
jl_rona
Junior Member
 
Mesaje: 887
Membru din: Mar Mai 29, 2007 9:32 pm
Localitate: Bucuresti

Mesajde jl_rona » Sâm Mai 23, 2009 10:31 pm

Journal of Biological Rhythms, Vol. 14, No. 4, 281-289 (1999)
DOI: 10.1177/074873099129000696


Interactions between Light and Melatonin on the Circadian Clock of MiceSusan Benloucif
Monica I. Masana

Ken Yun

Margarita L. Dubocovich

Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611

Melatonin and light synchronize the biological clock and are used to treat sleep/wake disturbances in humans. However, the two treatments affect circadian rhythms differently when they are combined than when they are administered individually. To elucidate the nature of the interaction between melatonin and light, the present study assessed the effect of melatonin on circadian timing and immediate-early gene expression in the suprachiasmatic nucleus (SCN) when administered in the presence of light. Male C3H/HeN mice, housed in constant dark in cages equipped with running wheels, were treated with either melatonin (90 µg, sc) or vehicle (3% ethanol-saline) 5 min prior to exposure to light (15 min, 300 lux) at various times in the circadian cycle. Combined treatment resulted in lower magnitude phase delays of circadian activity rhythms than those obtained with light alone during the early subjective night and advances in phase when melatonin and light were administered during the subjective day (p < .001). The reduction in phase delays with combined treatment at Circadian Time (CT) 14 was significant when light exposure measured 300 lux but not at lower light levels (p < .05). When light preceded melatonin administration, the inhibition of phase delays attained significance only when the light exposure reached 1000 lux (p < .05). Neither basal nor light-induced expression of c-fos mRNA in the SCN was modified by melatonin administration at CT 14 or CT 22. Together, these results suggest that combined administration of melatonin and light affect circadian timing in a manner not predicted by summing the two treatments given individually. Furthermore, the interaction is not likely to be due to inhibition of photic input to the clock by melatonin but might arise from a photically induced enhancement of melatonin's actions on circadian timing.


Key Words: immediate-early genes • c-fos expression • circadian rhythms • melatonin • C3H/HeN mice • light • phase shifts

http://jbr.sagepub.com/cgi/content/abstract/14/4/281
“Love, work and knowledge are the wellsprings of our lives, they should also govern it.â€Â
jl_rona
Junior Member
 
Mesaje: 887
Membru din: Mar Mai 29, 2007 9:32 pm
Localitate: Bucuresti

Mesajde jl_rona » Sâm Mai 23, 2009 10:58 pm

Circadian Rhythms in the Suprachiasmatic Nucleus are Temperature-Compensated and Phase-Shifted by Heat Pulses In Vitro

Norman F. Ruby, D. Erik Burns, and H. Craig Heller
Department of Biological Sciences, Stanford University, Stanford, California 94305

ABSTRACT

Temperature compensation and the effects of heat pulses on rhythm phase were assessed in the suprachiasmatic nucleus (SCN). Circadian neuronal rhythms were recorded from the rat SCN at 37 and 31°C in vitro. Rhythm period was 23.9 ± 0.1 and 23.7 ± 0.1 hr at 37 and 31°C, respectively; the Q10 for tau was 0.99. Heat pulses were administered at various circadian times (CTs) by increasing SCN temperature from 34 to 37°C for 2 hr. Phase delays and advances were observed during early and late subjective night, respectively, and no phase shifts were obtained during midsubjective day. Maximum phase delays of 2.2 ± 0.3 hr were obtained at CT 14, and maximum phase advances of 3.5 ± 0.2 hr were obtained at CT 20. Phase delays were not blocked by a combination of NMDA [AP-5 (100 µM)] and non-NMDA [CNQX (10 µM)] receptor antagonists or by tetrodotoxin (TTX) at concentrations of 1 or 3 µM. The phase response curve for heat pulses is similar to ones obtained with light pulses for behavioral rhythms. These data demonstrate that circadian pacemaker period in the rat SCN is temperature-compensated over a physiological range of temperatures. Phase delays were not caused by activation of ionotropic glutamate receptors, release of other neurotransmitters, or temperature-dependent increases in metabolism associated with action potentials. Heat pulses may have phase-shifted rhythms by directly altering transcriptional or translational events in SCN pacemaker cells.

Key words: suprachiasmatic; circadian; temperature compensation; phase shift; phase response curve; single unit; electrophysiology; glutamate; tetrodotoxin; AP-5; CNQX


http://www.jneurosci.org/cgi/content/short/19/19/8630
“Love, work and knowledge are the wellsprings of our lives, they should also govern it.â€Â
jl_rona
Junior Member
 
Mesaje: 887
Membru din: Mar Mai 29, 2007 9:32 pm
Localitate: Bucuresti

Mesajde jl_rona » Sâm Iun 06, 2009 5:33 pm

Cytostatic action of cells of the immune system on tumor cells

Received: 20 September 1985

--------------------------------------------------------------------------

Without Abstract

Key Words cytostatic action - antitumor immunity

Research Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten'' í‰ksperimental''noi Biologii i Meditsiny, Vol. 101, No. 6, pp. 744–746, June, 1986.

Several types of cells of the immune system capable of producing lysis of tumor target cells exist.

They include activated cells, such as macrophages, T killer cells, normal killer cells (NKC) and polynuclear lymphocytes.
{...}

It has been shown that tumor cells can remain for a long time in the body in a dormant state. These facts are evidence of the possible existence not only to cytotoxic, but also of cytostatic mechanisms of immunologic surveillance of tumor growth.

http://www.springerlink.com/content/wx804pp306416833/

Lysis (Greek λύσις, lysis from lyein = to separate) refers to the death of a cell by breaking of the cellular membrane, often by viral or osmotic mechanisms that compromise its integrity.

http://en.wikipedia.org/wiki/Lysis
“Love, work and knowledge are the wellsprings of our lives, they should also govern it.â€Â
jl_rona
Junior Member
 
Mesaje: 887
Membru din: Mar Mai 29, 2007 9:32 pm
Localitate: Bucuresti

Mesajde jl_rona » Sâm Iun 13, 2009 7:00 pm

[SIZE="5"]Prostaglandin involvement in hyperthermia induced by sleep deprivation: A pharmacological and autoradiographic study [/SIZE]

B.D. Palmaa, , , J.N. Nobregab, V.L. Gomesa, L.A. Esumia, M.L.V. Seabraa, S. Tufika and D.C. Hipolidea

aDepartment of Psychobiology, Universidade Federal de Sí£o Paulo, Sí£o Paulo, Brazil

bNeuroimaging Research Section, Centre for Addiction and Mental Health, Toronto, Canada

Received 19 June 2008;
accepted 9 December 2008.

Available online 16 December 2008.

Abstract

Aims

[color="Red"]Hyperthermia is a characteristic functional effect of sleep deprivation (SD). [/color]

[color="red"]We hypothesize here that prostaglandin E2 (PGE2) could be involved in hyperthermia induced by sleep deprivation.[/color]

Main methods

To address this issue we examined the effects of a selective cyclo-oxygenase-2 inhibitor (COX-2) agent on hyperthermia induced by SD in rats.

We also investigated binding to PGE2 receptors in hypothalamic brain areas of sleep-deprived rats using in vitro autoradiography. Male Wistar rats were deprived of sleep for 96 h using the platform technique.

Sleep deprived and control groups received saline or Celecoxib (20, 30 and 40 mg/kg; p.o.) daily during the SD period. Colonic temperature was measured daily.

Key findings

Results indicated that core temperature of sleep-deprived rats that receiving saline increased from the first to the fourth day of SD compared to baseline and to the respective control group.

However, the hyperthermia induced by SD was not blocked by COX-2 inhibitor at any dose. [3H]PGE2 binding did not differ significantly among the groups in any of a number of hypothalamic areas examined.

Significance

Although SD rats showed no response to the COX-2 inhibitor and no alterations in [3H]PGE2 binding, [color="red"]the possibility remains that other prostaglandin system and/or receptor subtypes may be altered by SD.[/color]

Keywords: Cyclooxygenase-2 (COX-2) inhibitor; Sleep; Temperature; Hypothalamus; Rat

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T99-4V59W39-3&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=8fb5caba4beb60b11245bb3cd2c0ea30

Copyright © 1993 Published by Elsevier Inc.

[SIZE="5"]Sodium diclofenac inhibits hyperthermia induced by paradoxical sleep deprivation: The possible participation of prostaglandins [/SIZE]

Maria de Lourdes Ventura Seabra, a and Sergio Tufika
aDepartment of Psychobiology, Escola Paulista de Medicina, Sí£o Paulo, SP, 04034-062, Brasil

Received 29 May 1992.
Available online 5 March 2003.

Abstract

[color="Red"]Sodium diclofenac inhibits hyperthermia induced by paradoxical sleep deprivation (PSD), which suggests the participation of prostaglandins. [/color]

The temperature of paradoxical sleep-deprived rats increased from the first to the fourth day of deprivation.

This hyperthermia was blocked on the second, third, and fourth days by daily administration, twice a day, of 10 mg/kg of sodium diclofenac, a potent prostaglandin synthesis inhibitor.

In the dose of 10 mg/kg, a decrease of temperature was observed only on the second and third days of PSD.

[color="red"]These data suggest the participation of prostaglandins in modulating the increase in temperature during PSD.[/color]

Keywords: Prostaglandins; Paradoxical sleep deprivation; Sodium diclofenac; Interleukin-1; Thermoregulation

Requests for reprints should be addressed to Maria de Lourdes Ventura Seabra at her present address: Departmento de Psicobiologia, Escola Paulista de Medicina, Rua Botucatu, 862, 10 andar, P.O. Box 20399, Sí£o Paulo, SP, 04034-062, Brasil.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0P-482RPY8-SJ&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=3c1a9228e60f407a8fce2adea037e685

WIKIPEDIA

During a woman's menstrual cycle, the endometrium thickens in preparation for potential pregnancy. After ovulation, if the ovum is not fertilized and there is no pregnancy, the built-up uterine tissue is not needed and thus shed.

[color="red"]Molecular compounds called prostaglandins are released during menstruation[/color], due to the destruction of the endometrial cells, and the resultant release of their contents.[1]

[SIZE="5"][color="red"]Release of prostaglandins and other inflammatory mediators in the uterus cause the uterus to contract.[/color] [/SIZE]

[color="red"]These substances are thought to be a major factor in primary dysmenorrhea[/color].[2]

http://en.wikipedia.org/wiki/Dysmenorrhea
“Love, work and knowledge are the wellsprings of our lives, they should also govern it.â€Â
jl_rona
Junior Member
 
Mesaje: 887
Membru din: Mar Mai 29, 2007 9:32 pm
Localitate: Bucuresti

Mesajde jl_rona » Sâm Iun 13, 2009 7:01 pm

R Soc Med. 1980 September; 73(9): 683. PMCID: PMC1438146

Copyright notice

Prostaglandins and Inflammation

Reviewed by D Geraint James

[color="red"]The prostaglandins have been recognized as mediators of inflammation for only a decade, but during this short span there has been an explosion of research in this field,[/color] starting with arachidonic acid and leading to thromboxane, prostacyclin, slow-releasing substances and metabolic switches from the cyclo-oxygenase to the lipoxigenase pathways.

Recent advances in this field are already spilling into the adjacent phase of macrophage activation, granuloma formation and atherosclerosis.

There are five chapters covering metabolism of arachidonic acid; [color="red"]prostaglandins as mediators of acute and chronic inflammation and pain;[/color] effect of anti-inflammatory drugs on prostaglandin prodution; and the side-effects of these anti-inflammatory drugs.

Loss Of Sleep, Even For A Single Night, Increases Inflammation In The Body

ScienceDaily (Sep. 4, 2008) — [color="red"]Loss of sleep, even for a few short hours during the night, can prompt one’s immune system to turn against healthy tissue and organs.[/color]

A new article in the September 15th issue of Biological Psychiatry, by the UCLA Cousins Center research team, reports that [color="red"]losing sleep for even part of one night can trigger the key cellular pathway that produces tissue-damaging inflammation.[/color]

The findings suggest a good night’s sleep can ease the risk of both heart disease and autoimmune disorders such as rheumatoid arthritis.

Specifically, the researchers measured the levels of nuclear factor (NF)-κB, a transcription factor that serves a vital role in the body’s inflammatory signaling, in healthy adults. These measurements were repeatedly assessed, including in the morning after baseline (or normal) sleep, after partial sleep deprivation (where the volunteers were awake from 11 pm to 3:00 am), and after recovery sleep. In the morning after sleep loss, they discovered that activation of (NF)-κB signaling was significantly greater than after baseline or recovery sleep. It’s important to note that they found this increase in inflammatory response in only the female subjects.

These data close an important gap in understanding the cellular mechanisms by which sleep loss enhances inflammatory biology in humans, with implications for understanding the association between sleep disturbance and risk of a wide spectrum of medical conditions including cardiovascular disease, arthritis, diabetes, certain cancers, and obesity. John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, comments: “The closer that we look at sleep, the more that we learn about the benefits of sleeping. In this case, Irwin and colleagues provide evidence that sleep deprivation is associated with enhancement of pro-inflammatory processes in the body.â€Â
“Love, work and knowledge are the wellsprings of our lives, they should also govern it.â€Â
jl_rona
Junior Member
 
Mesaje: 887
Membru din: Mar Mai 29, 2007 9:32 pm
Localitate: Bucuresti

Mesajde jl_rona » Lun Iul 13, 2009 6:59 pm

Am postat pe blogul meu pozele de anul asta de la mare, pentru cine e interesat.
“Love, work and knowledge are the wellsprings of our lives, they should also govern it.â€Â
jl_rona
Junior Member
 
Mesaje: 887
Membru din: Mar Mai 29, 2007 9:32 pm
Localitate: Bucuresti

Mesajde jl_rona » Joi Oct 08, 2009 9:28 pm

[color="Red"]Endogenous substance P inhibits the expression of corticotropin-releasing hormone during a chronic inflammatory stress [/color]

Copyright © 1995 Published by Elsevier Science Inc.

H. S. Chowdreyxa*, P. J. Larsent, M. S. Harbuza, S. L. Lightmana and D. S. Jessopa,

a Department of Medicine, University of Bristol, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8Hw, U.K.

* School of Chemical and Life Sciences, University of Greenwich, London, U.K.

t Department of Medical Anatomy, The Panum Institute, University of, Copenhagen, Denmark


Revised 18 September 1995. Available online 5 April 2000.

Abstract
We have investigated the effects of a chronic inflammatory stress on substance P (SP) levels in the hypothalami of rats given adjuvant-induced arthritis (AA). Fourteen days after injection of . substance P concentrations in the paraventricular nucleus (PVN) and median eminence/arcuate nucleus were significantly increased. In AA rats injected intraperitoneally with the specific neurokinin-1 receptor antagonist RP67580, plasma ACTH and corticosterone concentrations were significantly elevated and corticotropin-releasing hormone (CRH) mRNA in the PVN was increased compared to the AA group which received saline alone. The increases in hypothalamic SP in AA, together with the data demonstrating that HPA axis activity is enhanced in AA following injection of a SP antagonist, are consistent with the hypothesis that SP is acting as an inhibitor of CRH expression in this model of chronic inflammatory stress.

Author Keywords: substance P; CRH; ACTH; corticosterone; RP67580

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T99-3YYTH4W-2N&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1040364663&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=085d8ea1a76009bf69d2d93c9300c9e5

[color="Red"]Corticotropin-releasing factor (CRF) and endocrine responses to stress: CRF receptors, binding protein, and related peptides.[/color]Turnbull AV, Rivier C.

Clayton Foundation Laboratory of Peptide Biology, Salk Institute, La Jolla, California 92037, USA.

Corticotropin-releasing factor (CRF) is a 41-amino acid neuropeptide, which is recognized as a critical mediator of complimentary, stress-related endocrine, autonomic, and behavioral responses in mammalian species. CRF belongs to a family of structurally related peptides including frogskin sauvagine and fish urotensin I. The effects of CRF and related peptides are mediated by two distinct receptors, which differ in their anatomical distribution, as well as in their pharmacological characteristics. In addition, CRF is bound with high affinity by a CRF binding protein (CRF-BP), which is a putative inhibitor of CRF action. CRF is probably not the sole endogenous ligand for CRF receptors or the CRF-BP, since a second mammalian member of the CRF family, urocortin, has recently been identified. This article describes recent findings with respect to CRF, its receptors, binding protein, and CRF-related peptides, which provide further insights into the role and mechanisms of CRF action in stress responses.

PMID: 9142133 [PubMed - indexed for MEDLINE]


[color="Red"]The neurosteroid tetrahydroprogesterone counteracts corticotropin-releasing hormone-induced anxiety and alters the release and gene expression of corticotropin-releasing hormone in the rat hypothalamus[/color].

Patchev VK, Shoaib M, Holsboer F, Almeida OF.
Department of Neuroendocrinology, Max Planck Institute for Psychiatry, Munich, Germany.

The ring-A-reduced progesterone derivative 5 alpha-pregnan-3 alpha-ol-20-one (tetrahydroprogesterone) is synthesized under normal physiological conditions in the brain and is a potent modulator of the GABA receptor. This neurosteroid has significant sedative and anxiolytic properties. Corticotropin-releasing hormone plays a major role in stress-induced activation of the hypothalamo-pituitary-adrenal axis, and sustained hyperactivity of hypothalamic corticotropin-releasing hormone-producing neurons may be causally related to both, increased pituitary-adrenal secretion and behavioural symptoms observed in anxiety and affective disorders. We investigated the effect of tetrahydroprogesterone on corticotropin-releasing hormone-induced anxiety, the basal and methoxamine-stimulated release of corticotropin-releasing hormone from hypothalamic organ explants in vitro, and adrenalectomy-induced up-regulation of the gene expression of corticotropin-releasing hormone in the hypothalamic paraventricular nucleus in rats. At doses of 5 and 10 micrograms i.c.v., tetrahydroprogesterone counteracted the anxiogenic action of 0.5 microgram of corticotropin-releasing hormone. Tetrahydroprogesterone did not alter the basal release of corticotropin-releasing hormone in vitro, but suppressed the stimulatory effect of the alpha 1-adrenergic agonist methoxamine on this parameter. Measurements of the steady-state levels of mRNA coding for corticotropin-releasing hormone by quantitative in situ-hybridization histochemistry revealed that tetrahydroprogesterone was equipotent with corticosterone in preventing adrenalectomy-induced up-regulation of peptide gene expression. Systemic administration of tetrahydroprogesterone also restrained adrenalectomy-induced thymus enlargement. These results demonstrate that tetrahydroprogesterone has anxiolytic effects that are mediated through interactions with hypothalamic corticotropin-releasing hormone in both, genomic and non-genomic fashions.

http://www.ncbi.nlm.nih.gov/pubmed/7816204

AllopregnanoloneFrom Wikipedia, the free encyclopedia

[color="Red"]Allopregnanolone, also known as 3α,5α-tetrahydroprogesterone [/color]or THP, is an important neurosteroid in the human brain. It is a metabolite of progesterone and a barbiturate-like modulator of central gamma-aminobutyric acid (GABA) receptors that modify a range of behaviors, including the stress response.

The 5β epimer of this compound is known as pregnanolone, and has very similar properties to allopregnanolone. Both compounds are found endogenously and have similar hypnotic and anxiolytic effects.

http://en.wikipedia.org/wiki/Allopregnanolone
“Love, work and knowledge are the wellsprings of our lives, they should also govern it.â€Â
jl_rona
Junior Member
 
Mesaje: 887
Membru din: Mar Mai 29, 2007 9:32 pm
Localitate: Bucuresti

Mesajde jl_rona » Joi Oct 08, 2009 9:37 pm

Neuropsychopharmacology (1996) 15 533-540.

[color="Red"]The Neurosteroid Tetrahydroprogesterone Attenuates the Endocrine Response to Stress and Exerts Glucocorticoid-like Effects on Vasopressin Gene Transcription in the Rat Hypothalamus[/color]

V K Patchev MD, Ph.D, A H S Hassan B.V.Sc, Ph.D, F Holsboer MD, Ph.D and O F X Almeida Ph.D

From the Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Clinical Institute, Munich, Germany

Correspondence: V K Patchev, Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Clinical Institute, Kraepelinstr. 2, 80804 Munich, Germany. E-mail: patchev@mpipsykl.mpg.de

ABSTRACT

The neurosteroid tetrahydroprogesterone (5-pregnan-3-ol-20-one, allopregnanolone, THP), has been previously shown to counteract the anxiogenic effects of corticotropin-releasing hormone (CRH) and to interfere with noradrenergic and corticosteroid-mediated regulation of CRH release and gene transcription. Those observations indicated that, besides its sedative and analgesic activity, THP may also affect the neuroendocrine response to stress in a mode resembling that of corticosteroids. To examine this possibility, we compared the ability of THP, its precursor progesterone (P4), and the glucocorticoids dexamethasone (DEX) and corticosterone (CORT) to influence the pituitary-adrenal response to acute emotional stress and the adrenalectomy-induced increase in the gene transcription of the stress-related peptide arginine vasopressin (AVP) and of corticosteroid receptors (MR and GR) in the brain. Pretreatment of rats with a single dose of THP or P4 (50 g/kg) significantly attenuated the elevation of plasma adrenocorticotropin (ACTH) and serum corticosterone after emotional stress; both steroids were, however, less potent than a similar dose of DEX. Administration of 1 mg of THP, CORT, or P4 to adrenalectomized (ADX) rats attenuated the increase in AVP mRNA levels in the ventromedial subdivision of the hypothalamic paraventricular nucleus (PVN), as compared with vehicle-treated ADX rats. However, whereas CORT and P4 influenced the ADX-induced increase in the transcription of both types of corticosteroid receptors in the hippocampus, these were unaffected by THP. In contrast to the glucocorticoids, THP and P4 failed to decrease plasma ACTH levels in rats deprived of endogenous steroids. These results demonstrate that the neurosteroid THP and its precursor P4 resemble glucocorticoids in their suppression of the pituitary-adrenal response to emotional stress; however, THP influences the transcription of glucocorticoid-responsive genes in brain structures involved in the regulation of the hypothalamo-pituitary-adrenal system in a fashion that is quite distinct from that obtained with glucocorticoids. í“ American College of Neuropsychopharmacology

Keywords: Neurosteriods; Progesterone; Glucocorticoids; Vasopressin; Corticosteroid receptors; Stress

http://www.nature.com/npp/journal/v15/n6/abs/1380502a.html
“Love, work and knowledge are the wellsprings of our lives, they should also govern it.â€Â
jl_rona
Junior Member
 
Mesaje: 887
Membru din: Mar Mai 29, 2007 9:32 pm
Localitate: Bucuresti

Mesajde jl_rona » Joi Oct 08, 2009 9:41 pm

Clin Diagn Lab Immunol. 2002 July; 9(4): 852–857.
doi: 10.1128/CDLI.9.4.852-857.2002. PMCID: PMC120028

Copyright © 2002, American Society for Microbiology
[color="red"]
Effects of Psychological Stress and Alprazolam on Development of Oral Candidiasis in Rats[/color]


M. J. Núñez, J. Balboa, P. Riveiro, D. Liñares, P. Mañá, M. Rey-Méndez, A. Rodrí­guez-Cobos, J. A. Suárez-Quintanilla, L. A. Garcí­a-Vallejo, and M. Freire-Garabal*

Neuroimmunology Laboratory, Department of Pharmacology, School of Medicine, University of Santiago de Compostela, 15705-Santiago de Compostela, Spain

*Corresponding author. Mailing address: Neuroimmunology Laboratory, Department of Pharmacology, School of Medicine, University of Santiago de Compostela, 15705-Santiago de Compostela, Spain. Phone: 34 600 942 256. Fax: 34 981 573 191. E-mail: fffregar@usc.es.
Received January 29, 2001; Revised May 16, 2001; Accepted April 23, 2002.
Top
Abstract
MATERIALS AND METHODS
RESULTS
DISCUSSION

REFERENCES

Abstract

Psychological stress has been found to suppress cell-mediated immune responses that are important in limiting the proliferation of Candida albicans.

Since anxiolytic drugs can restore cellular immunity in rodents exposed to stress conditions, we designed experiments conducted to evaluate the effects of alprazolam (1 mg/kg of body weight/day), a central benzodiazepine anxiolytic agonist, on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory stressor.

Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of C. albicans infection.

Application of stress and treatment with drugs (placebo or alprazolam) were initiated 7 days before C. albicans inoculation and lasted until the end of the experiments (day 15 postinoculation). Establishment of C. albicans infection was evaluated by swabbing the inoculated oral cavity with a sterile cotton applicator on days 2 and 15 after inoculation, followed by plating on YEPD (yeast extract-peptone-dextrose) agar. Tissue injury was determined by the quantification of the number and type (normal or abnormal) of papillae on the dorsal tongue per microscopic field. A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. Our results show that stress exacerbates C. albicans infection of the tongues of rats. Significant increases in Candida counts, the percentage of the tongue's surface covered with clinical lesions, the percentage of abnormal papillae, and the colonization of the epithelium by fungal hyphae were found in stressed rats compared to those found in the unstressed rats. Treatment with alprazolam significantly reversed these adverse effects of stress, showing that, besides the psychopharmacological properties of this anxiolytic drug against stress, it has consequences for Candida infection.
Top
Abstract
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES Candida albicans is an example of an opportunistic pathogen frequently isolated from the human mouth, yet few carriers develop clinical signs of candidiasis. The most common predisposing factors to oral candidiasis are immunosuppresive therapy, immunoincompetence, and immunodeficiencies, indicating that the host immune system provides a protective mechanism against superficial invasion by Candida.
Several lines of evidence indicate that cell-mediated immunity is important in limiting the proliferation of Candida; thus, this opportunistic human pathogen preferentially causes invasive and disseminated infections in patients with defective phagocytic defenses and serious mucocutaneous infection in patients with deficiencies in T-cell function. Phagocytes appear to protect the host from fungal colonization even in the absence of adaptive immune mechanisms, while as-yet-undefined T-cell-dependent factors seem necessary for the control of C. albicans on body surfaces (31).
In our previous research, we had observed adverse effects of stress on natural and specific immune responses that may predispose the host to more severe Candida infections (22). On the other hand, treatment with benzodiazepines (BZDs), such as alprazolam, was found to attenuate some of the effects of stress on the immune systems of rodents, such as T-cell depletion, the inhibition of the blastogenic and cytotoxic activities of spleen cells (14, 15, 18), impaired delayed type hypersensitivity (38), and defects in phagocytosis (21). We have already tested this drug in laboratory animal models of infection showing a correlation between the immunoprotective effect of alprazolam and the host resistance against bacteria (16) and viruses (19, 20). Despite other known or unknown mechanisms, central pharmacological effects regulating the release of neuroendocrine hormones, such us adrenalcorticotropic hormone (ACTH), should be involved, at least in part, in the effects of alprazolam on immunocompetence. Nevertheless, there is little data on the effects of this compound on the development of fungal infection. In order to further elucidate this relationship, we studied the effects of alprazolam on the development of oral candidiasis in rats exposed to a repeated auditory stressor.
Top
Abstract
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES MATERIALS AND METHODSAnimals.
Two-month-old male pathogen-free rats of the Sprague-Dawley strain (Interfauna Iberica, S.A., Barcelona, Spain) weighing 180 to 200 g were used. They were housed individually in filter-top cages and screened for the presence of C. albicans by plating oral swabs on YEPD (yeast extract-peptone-dextrose) agar (Sigma Chemical Co., St. Louis, Mo.) (17, 31). The cages were kept in a temperature-controlled (22 to 24°C) and humidity-controlled animal room, with an alternating light-dark cycle (lights on at 0600 and lights off at 1800) and with food (diet A.03; Panlab, Barcelona, Spain) and sterile water ad libitum.
Procedure.
Following verification that the rats were free of C. albicans, they were randomly divided into six experimental groups of four animals each according to the treatment they were to be submitted to: group 1, control (i.e., no stress or placebo); group 2, unstressed rats injected with placebo; group 3, unstressed rats injected with alprazolam; group 4, stressed rats with no treatment; group 5, stressed rats injected with placebo; group 6, stressed rats injected with alprazolam.
Stress procedure.
The rats were subjected to a broadband noise at 100 db daily for 5 s every minute during either a 1- or 3-h period (at random) around midnight, at the height of the diurnal activity cycle (32). All stressed rats were subjected to the same stress schedule. Unstimulated rats were exposed only to the normal activity of the animal room. Stress application started 7 days before C. albicans inoculation and lasted until the end of experiments (day 15 postinoculation).
Treatment with drugs.
“Love, work and knowledge are the wellsprings of our lives, they should also govern it.â€Â
jl_rona
Junior Member
 
Mesaje: 887
Membru din: Mar Mai 29, 2007 9:32 pm
Localitate: Bucuresti

Mesajde jl_rona » Joi Oct 08, 2009 9:41 pm

Alprazolam (Upjohn, Kalamazoo, Inc.) was intraperitoneally injected at a dose of 1 mg/kg of body weight in a volume of 1 ml of 1% water solution of carboxymethylcellulose per kg of body weight as a vehicle. Mice in the placebo group were intraperitoneally injected with 1 ml of diluent per kg of body weight. Drugs were administered daily at 9:30 a.m. during all periods of stress application.
Surgical hyposalivation.
As in humans, xerostomia in rats facilitates the establishment and persistence of C. albicans infection in the mouth; therefore, it constitutes a suitable animal model for the study of oral candidiasis (25). Sialoadenectomy in rats causes intense xerostomia, but the minor salivary glands, the main producers of mucin, an important barrier for mucosal permeability and a major source of immunoglobulin A, were preserved. In our experiment, xerostomia was surgically provoked in all rats 1 month before treatment with drugs and stress application were initiated. The rats were anesthetized with 44 mg of ketamine (Ketolar; Parke-Davis, Barcelona, Spain) per kg of body weight and 1 mg of diazepam (Valium; Roche, Madrid, Spain) per kg of body weight (40). The parotid salivary ducts of the animals were ligated, and the submandibular and sublingual salivary glands were surgically removed according to procedures previously described (7, 30, 31).
Source and culture of C. albicans.
The C. albicans organisms used to inoculate the rats were obtained from a patient with erythematous oral candidiasis (17). The Candida strains were grown on YEPD agar plates at room temperature (35). The isolated organisms were identified as C. albicans by a germ tube test and chlamydospore production as described by Schaar et al. (36).
Inoculation of C. albicans.
The C. albicans organisms isolated were prepared for inoculation by suspending colonies in sterile buffered saline and were washed twice by centrifugation before being resuspended in normal saline. The concentration of organisms was adjusted to 3 í— 108/ml by optical density at 300 nm (3). The tongues of the animals were swabbed on 2 successive days with a cotton-tipped applicator saturated with 0.1 ml of fresh inoculum (31).
Quantification of C. albicans cells.
Establishment of C. albicans infection was evaluated by swabbing the inoculated oral cavity with a sterile cotton applicator, followed by plating on YEPD agar (25, 31). Samples were collected 2 days after inoculation and at the end of experiment. The cotton applicator was immediately immersed in 0.99 ml of sterile isotonic saline to obtain a dilution of 10−2, and it was agitated for 2 min. This dilution was considered to be 10−2. Dilutions up to 10−5 (0.1 ml) were cultured in duplicate in Sabouraud's dextrose agar at 37°C for 48 h. Candida colonies were counted in plates exhibiting between 30 and 300 colonies. Plates with less than 30 colonies in the 10−2 dilution were considered to have 101 cells (25).
Clinical lesions.
At the end of the experimental period, all animals were sacrificed by asphyxiation in a CO2 atmosphere and were then decapitated. The dorsal tongue was photographed in situ at a magnification of í—10 (3). Clinical lesions were measured with a digital imaging system (Técnicas Médicas MAB, Barcelona, Spain) and expressed as the percentage of the surface area of the tongue (percent area) that was covered with the lesions.
Tissue handling.
The tongues from the rats were hemidissected in the sagittal plane, with half of the lesion immersed in 10% buffered formalin for routine processing and the other half placed in 2.5% glutaraldehyde with 0.1 M Sorensen's phosphate buffer at 4°C (3).
Light microscopy.
Both hematoxylin and eosin and periodic acid-Schiff stains were used. C. albicans infection was assessed with a digital imaging system according to evidence of lesions and hyphal colonization on the dorsal tongue (3, 33). Tissue injury was determined by quantification of the number and type (normal, atrophic, and hypertropic) of papillae per microscopic field (magnification, í—46). A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. In this scale, the absence of colonization was given a score of 0, while maximal colonization, in excess of 50 hyphae, could be seen in each high-power field (magnification, í—400) was assigned a score of 4. The scores given were 1 for 1 to 5 hyphae, 2 for 6 to 15 hyphae, and 3 for 16 to 50 hyphae. The specimens were examined by one of us, who was blind as to the source. Three high-power fields per sample were examined for the light microscopy experiments.
Scanning electron microscopy preparation.
Following fixation for 24 h, the tissue was rinsed three times in buffer and postfixed in 1% phosphate-buffered osmium tetroxide (pH 7.4) for 1 h. After two buffer rinses, the specimens were dehydrated in ascending concentrations of ethanol, followed by critical point dehydration in a Denton DCP-1 critical point drying apparatus with liquid CO2. The tissue samples were affixed on aluminum stubs with silver conductive paint and were sputter-coated with gold-palladium by using a Hummer VI sputter-coating apparatus (Anatech Electronics, Garfield, N.J.). Specimens were viewed with a Zeiss 910 electron microscope (Zeiss, Oberkochen, Germany) operated at 20 kV (2).
Statistical analysis.
Statistical analysis of the quantitation of C. albicans cells in oral tissue was performed by one-way analysis of variance, followed by Bonferroni's t test. The percentage of areas of clinical lesions was analyzed by Student's t test (25). The Wilcoxon signed-rank sum test for paired comparisons and the Kruskal-Wallis test for multiple comparisons were used to determine the degree of colonization of the epithelium by fungal hyphae (33). Differences were considered significant at P < 0.05.
Top
Abstract
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES RESULTSC. albicans counts at 2 and 15 days after inoculation (Table 1), as well as the percent area of clinical lesions in the dorsal tongue (Table 2), were increased in stressed rats compared with those in unstressed animals (differences, P < 0.05). A decrease in the total number of papillae and an increase in the percentage of abnormal (atrophic and hypertrophic) papillae (Fig. (Fig.1)1) were observed in stressed animals (differences, P < 0.01). On the semiquantitative scale of colonization of the epithelium by fungal hyphae, stressed rats (Fig. (Fig.2)2) scored higher than untreated controls (differences, P < 0.05). Neither placebo nor alprazolam significantly affected those parameters in unstressed rats (P > 0.05), with the only exception that placebo increased the degree of colonization of the epithelium in unstressed animals. In contrast, treatment with alprazolam significantly (P < 0.05) reversed the adverse effects of stress in all parameters assayed.
TABLE 1.
C. albicans counts from tongues of rats

TABLE 2.
Percent area of clinical lesion

FIG. 1.
Percentage of normal papillae in the tongues of rats. The results are the means ± standard deviations of four animals. Values were analyzed by using Student's t test. , differences between stressed and unstressed rats significant at (more ...)
“Love, work and knowledge are the wellsprings of our lives, they should also govern it.â€Â
jl_rona
Junior Member
 
Mesaje: 887
Membru din: Mar Mai 29, 2007 9:32 pm
Localitate: Bucuresti

Mesajde jl_rona » Joi Oct 08, 2009 9:43 pm

FIG. 2.
Semiquantitative scale to assess degree of colonization of epithelium by fungal hyphae. In this scale, the absence of colonization was given a score of 0, while maximal colonization, in which an excess of 50 hyphae could be seen in each high-power field (more ...)

Clinically evident lesions and inflammatory changes of the underlying connective tissue were observed 15 days after C. albicans inoculation. The latter were found in all experimental groups, but they were more evident in stressed rats. Animals showed macroscopic focal patchy atrophy of the dorsal tongue papillae. Light microscopy showed localized dense zones of hyphal penetration of the keratin layer in the giant conical papillae and filiform papillae of the dorsal tongue. Microabscesses in the keratin and the superficial spinous layers were observed in association with hyphal invasion. The underlying connective tissue showed a mild chronic inflammatory cell infiltrate. Those papillae that supported the Candida growth appeared shorter and blunter than the surrounding uninfected papillae.
Scanning electron microscopy (Fig. (Fig.3)3) of the dorsal tongues showed a higher loss of papillae in the giant conical and filiform areas of the specimens together with an increase in the size of the flat central portion of the lesion in stressed rats in comparison with unstressed animals. This adverse effect of stress was also reduced by the administration of alprazolam.
FIG. 3.
Scanning electron microscopy (Fig. (Fig.3)3) of the dorsal tongues of rats from control (A), stressed plus placebo treated (B), and stressed plus alprazolam-treated (C) rats. A higher loss of papillae in the giant conical and filiform areas of (more ...)

Top
Abstract
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES DISCUSSIONOur results show that stress exacerbates C. albicans infection of the tongues of rats. Significant increases in Candida counts, the percent area of clinical lesions, the percent abnormal papillae, and the colonization of the epithelium by fungal hyphae were found in stressed rats compared with those found in unstressed animals. Treatment with alprazolam partially reversed those adverse effects of stress on the development of oral candidiasis. Alprazolam was found to reverse many of the effects of stress on C. albicans infection of the tongues of rats, including Candida counts, the percent area of clinical lesions, the percent abnormal papillae, and the colonization of the epithelium by fungal hyphae.
Clinical and experimental observations indicate that the opportunistic proclivities of this fungus vary considerably, depending on the nature of the immunological defect of the victim. Patients with qualitative or quantitative defects of phagocytes are mainly prone to the invasive form of this mycosis (10, 11, 37). In contrast, defective T-cell-mediated immunity has been specifically associated with thrush and other forms of candidiasis limited to mucocutaneous surfaces (11, 12, 24, 26). Krause and Schaffner (28) demonstrated that cyclosporine, a relatively selective suppressor of T-cell-mediated immunity and NK cell activity, promoted the formation of thrushlike lesions on cyst surfaces and impeded the elimination of C. albicans from such lesions, but it had no effect on systemic candidiasis induced by intravenous inoculation.
Our results are in line with the previous literature on the stress-induced modulation of the immune system. Changes in murine splenic cytotoxic activities, mediated by NK cells and cytotoxic T lymphocytes have been reported (10-12, 24, 26, 32, 37). Stress also interferes with the activity of phagocytosis and T-cell-dependent antibody responses (21, 28).
The mechanism by which stress inhibits the cellular immune response has been widely studied. A molecular basis for bidirectional communication between the immune and neuroendocrine systems has been described previously (5). Cell-to-cell communication between the immune and the neuroendocrine systems is primarily mediated by hormones and neuropeptides that reach lymphoid organs and cells through the vascular system or directly through the autonomic connections between nerve endings and lymphoid organs (1, 8). Receptor sites are present in lymphoid cells for many hormones and neurotransmitters (6, 39). A number of molecules produced by cells of the nervous system such as ACTH, PRL, opioid peptides, GH, TSH, dynorphin, dopamine, and others have been shown to have the ability to modulate immune functions.
On the other hand, humoral factors generated by the immune system, such as thymic peptides and lymphokines, modulate neuroendocrine functions. In addition, in the course of lymphocyte activation, lymphoid cells may produce hormonal substances identical to those produced by the hypophysis, such as ACTH, TSH, GH, PRL, gonadotrophin, and β-endorphin (6).
At least one of the neuroendocrine responses to stress, such as the rise in plasma corticosterone concentrations via ACTH secretion, has an easily demonstrable destructive effect on specific cells and tissues that are required for optimal immune defense (4, 34). In our previous studies, we observed a stress-induced increase in ACTH levels proportional to the decrease in T-cell populations (15). Nevertheless, in these studies, we observed that adrenalectomized mice showed a lower pattern of immunosuppression in comparison with sham-operated mice. So, this led us to believe that other neuropeptides and neurotransmitters could be involved in the immunosuppressive response to stress.

The effects of alprazolam, an anxiolytic drug with high affinity for central BZD receptors on the pathogenicity of this opportunistic fungus could be attributed, at least in part, to its well-known protective effects against the immunosuppressive response to the type of stress assayed here. The recovery of the immune state of the victim could decrease the pathogenicity of this opportunistic fungus. In this regard, in our previous studies, we demonstrated that alprazolam reversed the suppressive effects of stress on the activity of phagocytosis, T-cell populations, the blastogenic response of spleen cells, murine splenic cytotoxic activities, mediated by NK cells and CTL. Fride et al. (23) found that low doses (0.02 to 1.0 mg/kg) of alprazolam significantly increased the NK cell activity, mixed leukocyte reactivity, and mitogen-induced lymphocyte proliferation in unstressed mice.
The mechanism of action of BZDs on the immune system remains to be defined. A dual approach has been described at the present time. First, central pharmacological effects related to the central type BZD receptors that facilitate inhibitory GABA neurotransmission in the central nervous system may regulate the release of neuroendocrine hormones involved in the immune response to stress. The ability of alprazolam to decrease the stress-induced increase of ACTH levels (29) has been demonstrated to play a important role in the immunoprotective effects of this drug. Nevertheless, significant immunoenhancing effects of alprazolam were also appreciated in stressed adrenalectomized rats (15), suggesting that the modulatory effect of this BZD agonist on other neurohormones like opioid peptides, PRL, melatonin, TSH, or GH could also be involved (13).

A second aspect of the effects of BZDs is the existence of a BZD receptor with high affinity on immune cells that express the so-called peripheral specificity for BZDs (41). Nevertheless, alprazolam is described in the literature as strict central type ligand of the BZD receptor (29). Alprazolam has potent PAF antagonist properties (27) that seem to affect T-cell, B-cell, and macrophage responses under in vitro conditions (9).

One could ask whether secondary (nonimmune or biochemical) effects of the drug treatment might account for the final observations and whether or not stress might break down the state of tolerance normally associated with Candida infection (as opposed to acting solely as an immunopotentiator). Although these considerations should be taken into account, our previous data concerning the immunomodulatory effects of alprazolam under stress conditions (14, 15, 18, 21, 38) lead us to consider immune changes as the main factor involved on the effects of stress and alprazolam on the evolution of oral candidiasis in rats.

A second question concerns the biological significance of our results.

Although our data at present show stress may leave the subject vulnerable to the action of C. albicans and provide evidence of a protective effect of alprazolam on the development of oral candidiasis in rats, the biological significance and health relatedness of these findings should be assessed. In this respect, differences between untreated stressed rats and placebo- or alprazolam-stressed rats are statistically significant, but in some parameters, they are not striking. Moreover, there is a relationship between differences obtained in different determinations, but there is not a mathematical correlation as expected.

The large number of interactions at molecular, cellular, and functional levels between the nervous system and the immune system characterizing the operational compositions and expressions of the neuroimmune network make complex isolation of the pathways in which stress and alprazolam may be involved in the regulation of the host defense mechanisms against infection.

Nevertheless, the literature has provided evidence that stress-induced immunosuppression and alprazolam-induced immunoprotection are in a relationship with susceptibility to bacteria (16), virus (20), and, as a conclusion of the present investigation, Candida infection.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=120028
“Love, work and knowledge are the wellsprings of our lives, they should also govern it.â€Â
jl_rona
Junior Member
 
Mesaje: 887
Membru din: Mar Mai 29, 2007 9:32 pm
Localitate: Bucuresti

Mesajde jl_rona » Vin Oct 09, 2009 11:27 pm

[color="Red"]Regulation of progesterone production in human term trophoblasts in vitro by CRH, ACTH and cortisol (prednisolone) [/color]

Udo Jeschke1 , Ioannis Mylonas1, Dagmar-Ulrike Richter2, Ingo Hí¶cker2, Volker Briese2, Antonis Makrigiannakis3 and Klaus Friese1

(1) 1st Department of Obstetrics and Gynaecology, Ludwig-Maximilians-University of Munich, Maistrasse 11, 80337 Munich, Germany
(2) Department of Obstetrics and Gynecology, University of Rostock, Rostock, Germany
(3) Department of Obstetrics & Gynocology, Medical School, University of Crete, Heraklion, 71110, Greece

Received: 13 December 2004 Accepted: 11 January 2005 Published online: 16 April 2005

Abstract Background:

In most mammals, onset of labor is accompanied with progesterone withdrawal.

[color="red"]In humans, cortisol blockade of progesterone is a possible mechanism involved in the initiation of labor.[/color]

Therefore, aim of the study was to clarify the effect of CRH, ACTH and cortisol (prednisolone) on the release of progesterone by term trophoblast cells in vitro. Methods: Cytotrophoblast cells were prepared from human term placentas by standard dispersion of villous tissue followed by a percoll gradient centrifugation step. Trophoblasts were incubated with CRH, ACTH as well as with prednisolone Results: The release of progesterone is decreased in CRH- and ACTH-treated trophoblast cell cultures compared to untreated trophoblast cells. Addition of prednisolone in varying concentrations leads to an increase of trophoblast progesterone production. Conclusions: The results suggest that CRH and ACTH directly modulate the endocrine function of trophoblasts in culture by downregulating progesterone production. Prednisolone on the other hand showed a stimulating effect on progesterone production in term trophoblast cells in vitro. Because blockade of progesterone is a possible mechanism involved in initiation of labor, we may speculate that CRH and ACTH are directly involved in the auto- or paracrine regulation of this procedure.
Keywords CRH - ACTH - Prednisolone - Progesterone production - Trophoblast cells

http://www.springerlink.com/content/hg9txt426r9q2821/

A short luteal phase (is the period that starts at ovulation and ends on the day before the next period) that lasts less than 10 days also indicates low levels of progesterone.

http://www.buzzle.com/articles/low-progesterone.html
“Love, work and knowledge are the wellsprings of our lives, they should also govern it.â€Â
jl_rona
Junior Member
 
Mesaje: 887
Membru din: Mar Mai 29, 2007 9:32 pm
Localitate: Bucuresti

Anterior

Înapoi la Scrieri, ganduri si jurnale

Cine este conectat

Utilizatorii ce navighează pe acest forum: Niciun utilizator înregistrat şi 2 vizitatori

cron