BACKGROUND: Chronic nonspecific symptoms attributed to indoor nonindustrial work environments are common and may cause disability, but the medical nature of this disability is unclear. The aim was to medically characterize the disability manifested by chronic, recurrent symptoms and restrictions to work participation attributed to low-level indoor pollutants at workplace and whether the condition shares features with idiopathic environmental intolerance. METHODS: We investigated 12 patients with indoor air–related work disability. The examinations included somatic, psychological, and psychiatric evaluations as well as investigations of the autonomic nervous system, cortisol measurements, lung function, and allergy tests. We evaluated well-being, health, disability, insomnia, pain, anxiety, depression, and burnout via questionnaires. RESULTS: The mean symptom history was 10.5 years; for disabling symptoms, 2.7 years. Eleven patients reported reactions triggered mainly by indoor molds, one by fragrances only. Ten reported sensitivity to odorous chemicals, and three, electric devices. Nearly all had co-occurrent somatic and psychiatric diagnoses and signs of pain, insomnia, burnout, and/or elevated sympathetic responses. Avoiding certain environments had led to restrictions in several life areas. On self-assessment scales, disability showed higher severity and anxiety showed lower severity than in physician assessments. CONCLUSION: No medical cause was found to explain the disability. Findings support that the condition is a form of idiopathic environmental intolerance and belongs to functional somatic syndromes. Instead of endless avoidance, rehabilitation approaches of functional somatic syndromes are applicable.
Anxiety ; Autonomic Nervous System ; Depression ; Disability Evaluation ; Fungi ; Humans ; Hydrocortisone ; Hypersensitivity ; Lung ; Multiple Chemical Sensitivity ; Odors ; Rehabilitation ; Self-Assessment ; Sleep Initiation and Maintenance Disorders ; Weights and Measures

The study aimed to investigate the effect of inhibition of poly(ADP-ribose) polymerase-1 (PARP-1) activity on tau phosphorylation in HEK293/tau441 cells and its mechanism. HEK293/tau441 cells were treated with 3-aminobenzamide (3-AB), a PARP-1 inhibitor, at different doses (0.5, 1, 2, 4 mmol/L). After 24 h, the cell morphology was observed under phase contrast microscope, tau phosphorylation level in different sites (tau-1, tau-5, Thr231) and the activity of glycogen synthase kinase 3 (GSK-3) were detected by Western blotting. The results showed: (1) 3-AB at different doses failed to change the morphology of cells; (2) The 3-AB-induced decrease in activity of PARP-1 resulted in increase of unphosphorylation level in tau-1(Ser195/198/199/202) sites; (3) The phosphorylation of tau was decreased in Thr231 site, while the total tau was slightly changed after 3-AB treatment; (4) With the increased phosphorylation of GSK-3 at Ser9 site, the activity of GSK-3 was decreased after 3-AB treatment. The results suggest that the inhibition of PARP-1 by 3-AB could decrease tau phosphorylation in HEK293/tau441 cells probably through decreasing GSK-3 activity.
Benzamides ; pharmacology ; Depression, Chemical ; Glycogen Synthase Kinase 3 ; metabolism ; HEK293 Cells ; Humans ; Phosphorylation ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases ; metabolism ; tau Proteins ; metabolism

The aim of the present study was to investigate the role of hydrogen sulfide (H(2)S) in the proliferation of neonatal rat cardiac fibroblasts (NRCFs). Proliferation of NRCFs was induced by the presence of fetal bovine serum (FBS) or angiotensin II (Ang II) at various concentrations. The concentration-dependent effect of NaHS (donor of H(2)S) on NRCFs proliferation was examined. NRCFs proliferation was assessed by 5'-bromo-2'-deoxyuridine (BrdU) incorporation method. Reactive oxygen species (ROS) level was measured using the dye probe, 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The results showed that FBS- or Ang II-induced NRCFs proliferations were inhibited with the treatment of relatively high concentrations of NaHS (5 × 10(-5) mol/L, 1 × 10(-4) mol/L), but FBS-induced proliferation was increased by low concentration of NaHS (1 × 10(-5) mol/L). Two or 6 h of Ang II (1 × 10(-7) mol/L) treatment caused an increase of ROS level in NRCFs, while this increase was inhibited with NaHS (1 × 10(-4) mol/L) treatment. These results suggest that H(2)S is an inhibitor of cardiac fibroblast at a certain concentration range. This inhibitory effect may be mediated by a reduction in intracellular ROS production.
Angiotensin II ; pharmacology ; Animals ; Animals, Newborn ; Cell Proliferation ; drug effects ; Cells, Cultured ; Depression, Chemical ; Fibroblasts ; cytology ; Hydrogen Sulfide ; pharmacology ; Male ; Myocardium ; cytology ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism

Endothelial and neuronal nitric oxide synthases (eNOS and nNOS) are constitutively expressed in cardiomyocytes under the physiological condition, while inducible nitric oxide synthase (iNOS) is only expressed in cell stress. Nitric oxide (NO) derived from the constitutive isoforms of eNOS and nNOS plays four kinds of inhibitory effects on the myocardium: reducing the contractile frequency of cardiomyocyte, slightly attenuating cardiac contractility, accelerating relaxation and increasing distensibility of cardiomyocyte, and slightly inhibiting mitochondrial respiration and improving the efficiency of myocardial oxygen consumption. In conditions of enhanced cardiac reserve and cardiac hypertrophy, NO derived from eNOS, which forms a complex with a certain kind of receptor on the sarcolemma, modulates receptor-mediated signaling and generates an "accentuated antagonism" by moderate inhibition of cardiac contractility. NO derived from the complex of nNOS-ryanodine receptor (RyR) stabilizes RyR calcium release and increases the efficiency of Ca(2+) cycling in sarcoplasmic reticulum by the inhibitory effects. However, besides the above-mentioned inhibitions of NO derived from eNOS and nNOS, NO derived from iNOS generally prevents mitochondrial permeability transition pore opening by inhibiting mitochondrial respiration under the conditions of the myocardial ischemia-reperfusion injury and heart failure. Therefore, both in the physiological condition and in the pathological condition, NO exhibits a moderate inhibition in cardiac function, and eventually produces cardioprotection.
Animals ; Cardiotonic Agents ; Depression, Chemical ; Humans ; Mitochondria, Heart ; metabolism ; Mitochondrial Membrane Transport Proteins ; physiology ; Myocardial Contraction ; physiology ; Myocytes, Cardiac ; enzymology ; Nitric Oxide ; physiology ; Nitric Oxide Synthase ; metabolism ; Oxygen Consumption ; physiology ; Ryanodine Receptor Calcium Release Channel ; physiology

OBJECTIVETo investigate the protective effect and mechanism of baicalin on nerve tissue in rat with intracerebral hemorrhage (ICH).

METHODSRats were randomly divided into five groups: the sham-operated group, the ICH model group, and the three baicalin treated groups treated respectively with small, medium and large doses of baicalin. ICH rat model was established by injecting collagenase VII into caudate nucleus. Baicalin was given by peritoneal injection to the baicalin treated groups, and saline was given to the other two groups once a day started from 2 h after modeling. Animals were sacrificed in batches on the 1st, 3rd, 5th and 10th day of treatment to take their brains for detecting protease-activated receptor-1 (PAR-1) expression and cell apoptosis in brain tissue surrounding hematoma by Western blot and TUNEL method, respectively. And the water content of brain was estimated by dry-wet weight method.

RESULTSCompared with the model group, the PAR-1 expression and TUNEL-positive cells were significantly reduced in the baicalin treated groups; and brain edema was also significantly reduced (P<0.01).

CONCLUSIONSThe up-regulated PAR-1 expression after ICH in rats might play an important role in inducing cell apoptosis and brain edema. Baicalin shows significant protective effect on ICH rats, which may be related to its effects in inhibiting PAR-1 expression and decreasing apoptosis cells, so as to reduce brain edema.

Animals ; Apoptosis ; drug effects ; Brain ; metabolism ; pathology ; Cerebral Hemorrhage ; drug therapy ; Depression, Chemical ; Flavonoids ; pharmacology ; therapeutic use ; Male ; Phytotherapy ; Rats ; Rats, Wistar ; Receptor, PAR-1 ; metabolism

OBJECTIVETo observe the influences of Panax notoginsenosid(a compound of Chinese Traditional Medicine) on the spontaneous contraction of small intestine smooth muscle of rabbits in vitro and explore the mechanism.

METHODSThe influences of Panax notoginsenosid on the spontaneous contraction of small intestine in intacted rabbits(male or female) after the isothermal perfuse of small intestine in vitro were observed. Bay K8644 and nitro-L-arginine methylester (L-NAME) were added to the normal Tyrode's solution respectively before Panax notoginsenosid. In the Ca2+ free Tyrode's solution, rynodine was added before Panax notoginsenosid. The mechanism of Panax notoginsenosid was studied.

RESULTSPanax notoginsenosid reduced the amplitude of contraction of small intestine smooth muscle in rabbits in a does-depended manner. Bay K8644 and L-NAME could completely block the inhibition of Panax notoginsenosid on the contraction of small intestine smooth muscle. Panax notoginsenosid inhibited significantly the intracellular calcium-depended contraction induced by rynodine in the Ca2+ free Tyrode's solution.

CONCLUSIONPanax notoginsenosid inhibits significantly the contraction of small intestine smooth muscle of rabbits in vitro. The mechanism may be related to increase NO concentration in small intestine smooth muscle so that inhibit extracellular Ca2+ inflowing via cell membrane and intracellular Ca2+ releasing via sarcoplasmic reticulum.

Animals ; Calcium ; metabolism ; Depression, Chemical ; Drugs, Chinese Herbal ; pharmacology ; Female ; In Vitro Techniques ; Intestine, Small ; physiology ; Male ; Muscle Contraction ; drug effects ; Muscle, Smooth ; metabolism ; physiology ; Nitric Oxide ; metabolism ; Panax notoginseng ; chemistry ; Rabbits

OBJECTIVE: To investigate the effect of mevastatin (Mev) on the expression of peroxisome-proliferator-activated receptor-gamma (PPAR-gamma) mRNA and differentiation of Thyroid-associated ophthalmopathy (TAO) derived orbital preadipocytes in vitro. METHODS: Orbital adipose tissues were obtained from TAO patients undergoing orbital decompression surgery. The orbital preadipocytes cultured from the orbital adipose tissues were divided into Group A (a control group) and Group B (an intervention group). Group B was subdivided into Group B1-B5, all groups were stimulated to differentiate into mature adipocytes with cocktail differentiation medium.The entire course of differentiation was 10 d. The differentiation of orbital preadipocytes in Group A was induced with routine inducer,while at in Group B1,B2, and B3 was interfered with 5 micromol/L (B1), 10 micromol/L(B2),20 micromol/L (B3) mevastatin respectively during the whole process of differentiation. The differentiation of orbital preadipocytes in Group B4 and B5 was interfered with 10 micromol/L mevastatin day 4 (B4) or day 8 (B5) of the differentiation process until the entire course was over. Intracellular fat accumulation in differentiated adipocytes was determined by oil red O staining. The value of optical absorption was measured at 492 nm with enzyme-linked immunosorbent assay. The expression of PPAR-gamma mRNA was detected by reverse transcription polymerase chain reaction. RESULTS: The light absorption value (A) and PPAR-gamma mRNA expression of differentiated cells in Group A,B1,B2,and B3 decreased successively,and there was significant difference in any of the 2 groups among Group A, B1 and B2, and B3 (P<0.05). The value A and PPAR-gamma mRNA expression of differentiated cells in Group A, B4, and B2 decreased successively, and the difference in any of the 2 groups among these 3 groups was significant. However, there were no significant difference between Group A and B5. CONCLUSION Mevastatin inhibits the differentiation of TAO derived orbital preadipocytes by blocking PPAR-gamma mRNA expression. The degree of inhibition is not only concentration-dependent but also associated with the stage of differentiation. The earlier the differentiation, the stronger the inhibition.
Adipocytes ; pathology ; Adipose Tissue ; pathology ; Cell Differentiation ; drug effects ; Cells, Cultured ; Depression, Chemical ; Graves Ophthalmopathy ; pathology ; Humans ; Lovastatin ; analogs & derivatives ; pharmacology ; Orbit ; PPAR gamma ; antagonists & inhibitors ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism

AIMTo investigate the effect of Honeysuckle flower (HF) and Scutellaria Baicalensis Georgi (SBG) on contraction and electric activity of small intestine smooth muscle in rabbit and the underlying mechanisms.

METHODSUsing organ bath technique to observe the effect of HF and SBG on contractive and electric activity of small intestine smooth muscle in rabbit.

RESULTSHF and SBG significantly decreased the amplitude, frequency and area under the curve of contractive, as well as electric activity in a dose-depended manner. IC50 of the contractive amplitude was 6.30 g/L and 1.56 g/L by Logit Loglinear analysis. The inhibitive effect of HF and SBG on contractive activity could be partly decreased by beta-receptor blocker Propranolol, NO synthase inhibitor L-NAME, and K+ channel blocker Glibenclamide. Also HF and SBG inhibited acetylcholine-induced both intracellular and extracellular calcium-depended contraction significantly.

CONCLUSIONHF and SBG obviously inhibit the contractive and electric activity of small intestine smooth muscle of rabbit. The mechanisms are related to several pathways.

Action Potentials ; drug effects ; Animals ; Depression, Chemical ; Drugs, Chinese Herbal ; pharmacology ; Female ; Flowers ; chemistry ; In Vitro Techniques ; Intestine, Small ; physiology ; Lonicera ; chemistry ; Male ; Muscle Contraction ; drug effects ; Muscle, Smooth ; physiology ; Rabbits ; Scutellaria baicalensis ; chemistry

AIMTo investigate the effects of endothelin-1 (ET-1) and nitric oxide (NO) on lipopolysaccharide(LPS)-induced myocardial dysfunction, and explore the related underlying mechanisms.

METHODSExperimental septic model was established by intraperitoneal injection of LPS (10 mg x kg(-1)). The study was carried out on the isolated rat hearts to determine the roles of ET-1 and NO in the effect of LPS on the cardiac contractility and on the isolated rat ventricular myocytes model to observe the [Ca2+]i homeostasis in cardiac myocytes.

RESULTS(1) The levels of serum NO2-/NO3- and plasma ET-1 were markedly increased by LPS treatment for 4 hours. (2) LPS induced the decrease in rate-pressure product (RPP), and increase in left ventricular end-diastolic pressure (LVEDP) in the isolated perfused rat hearts. Pretreatment with either aminoguanidine (AMG) (100 mg x kg(-1), i.p.) or BQ-123 (1 mg x kg(-1), i.p.) partially attenuated LPS-induced myocardial depression. When these two drugs were simultaneously given, myocardial depression elicited by LPS was almost abolished. (3) LPS significantly decreased the amplitude of caffeine induced [Ca2+]i transients compared to the control cells. The activity of SR Ca22+ -ATPase was significantly decreased in the cardiac myocytes from LPS-treated rats. Single pretreatment with either AMG or BQ-123 did not attenuate the impairment of SR Ca2+ -ATPase induced by LPS.

CONCLUSIONET-1 and NO mediate myocardial dysfunction in hearts isolated and decrease [Ca2+]i transients in cardiac myocytes from LPS-treated rats. But neither ET-1 nor NO participates in the impairment of SR Ca2+ -ATPase induced by LPS.

Animals ; Depression, Chemical ; Endothelin-1 ; physiology ; Lipopolysaccharides ; toxicity ; Male ; Myocardial Contraction ; drug effects ; physiology ; Nitric Oxide ; physiology ; Rats ; Rats, Sprague-Dawley ; Shock, Septic ; chemically induced ; physiopathology

OBJECTIVETo evaluate the effect of Xinkeshu Tablet (XKS) on heart rate variability (HRV) in patients with coronary heart disease (CHD).

METHODSSixty patients with their diagnosis of CHD confirmed by coronary angiography were randomized into two groups equally. Besides the conventional treatment for CHD, XKS and Metoprolol were given respectively to patients in the treated group and the control group for 8 weeks. Symptoms and 24 h dynamic ECG were observed before and after treatment.

RESULTSEpisode of angina pectoris decreased obviously in both groups after treatment, from 8.8 +/- 3.2 times per week (the same hereafter) to 4.4 +/- 2.1 in the treated group (P<0.05), and from 8.4 +/- 3.1 to 3.9 +/- 2.0 in the control group (P <0.05). HRV analysis showed that after treatment the average heart rate lowered from 85.44 +/- 2.89 beat/min to 77.32 +/- 2.17 beat/min in the treated group and from 83.80 +/- 4.30 beat/min to 76.70 +/- 2.93 beat/min in the control group (both P < 0.05), showing no significant difference in extent of lowering between groups (P > 0.05). The time-domain indexes elevated in both groups, showing no statistical difference between groups (P >0.05). As for the frequency-domain indexes, low frequency (LF), high frequency (HF) and total power raised, while LF/HF and very low frequency lowered in both groups, but the changes were more significant in the treated group (P <0.05).

CONCLUSIONXKS could improve HRV in patients of CHD and reduce the episode of angina pectoris in them.

Cardiovascular Agents ; pharmacology ; therapeutic use ; Coronary Disease ; drug therapy ; Depression, Chemical ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Heart Rate ; drug effects ; Humans