This study evaluated the chronic effects of fluoxetine, a commonly prescribed SSRI antidepressant, on the peripheral and central levels of inflammatory cytokines including IL-1β, IL-6, TNF-α and ...IL-17 over a 4-interval in a rat model of chronic mild stress (CMS) which resembles the human experience of depression. Twenty-four Sprague-Dawley rats were randomly assigned to CMS+vehicle (n = 9), CMS+fluoxetine (n = 9) and the control (n = 6) groups. Sucrose preference and forced swim tests were performed to assess behavioral change. Blood samples were collected on day 0, 60, 90 and 120 for measurement of cytokine levels in plasma. On day 120, the brain was harvested and central level of cytokines was tested using Luminex. Four months of fluoxetine treatment resulted in changes in the sucrose preference and immobility time measurements, commensurate with antidepressant effects. The CMS+vehicle group exhibited elevated plasma levels of IL-1β, IL-17, and TNF-α on day 60 or 120. Rats treated with fluoxetine demonstrated lower IL-1β in plasma and brain after 90 and 120-day treatment respectively (p<0.05). There was a trend of reduction of IL-6 and TNF-α concentration. This study revealed the potential therapeutic effects of fluoxetine by reducing central and peripheral levels of IL-1β in the alleviation of depressive symptoms.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Depression is one of the most prevalent mental disorders associated with reductions in bone mineral density and increased fracture risk. Fluoxetine is a highly prescribed selective serotonin ...reuptake inhibitor (SSRI) in the treatment of depression and is reported to be a risk factor for fractures. The present study examined the effect of fluoxetine on bone microarchitecture and the mechanical properties under chronic mild stress (CMS), a rodent model of depression. Thirty-one 6–9 week-old rats were allocated to 4 groups: 1) CMS + fluoxetine group (
n
= 10), 2) fluoxetine-only group (
n
= 5), 3) CMS + placebo group (
n
= 10) and 4) control group (no CMS and treatment) (
n
= 6). After 16 weeks, bone microarchitecture of the distal femur was analyzed by µCT. Mechanical properties were assessed by the three-point bending test, and antidepressant efficacy was determined by sucrose preference and forced swimming tests. Significant correlations were found between volume of sucrose intake and bone volume/tissue volume (BV/TV) (
p
= 0.019) and elastic absorption energy (
p
= 0.001) in the fluoxetine only group. The fluoxetine-only group showed significantly higher in the second moment of area in y-direction (
p
= 0.0298), horizontal outer diameter (mm) (
p
= 0.0488) and average midshaft thickness (mm) (
p
= 0.00047) than control group. Comparing with the control group, there was a significant reduction in trabecular number (Tb.N) in the CMS + fluoxetine group (
p
= 0.026) but not the fluoxetine-only group (
p
> 0.05). Significant increases in trabecular separation were observed in the metaphysis of CMS + placebo (
p
= 0.003) and CMS + fluoxetine (
p
= 0.004) groups when compared to the control group but not in the fluoxetine-only group (
p
> 0.05). During the three-point bending test, the fluoxetine-only group demonstrated significantly higher structural strength than controls (
p
= 0.04). Micro computed tomography (µCT) slices showed loss of trabecular bone in the metaphysis region of the CMS + fluoxetine and CMS + placebo groups but not the fluoxetine-only and control groups. In an animal model of depression, the adverse effect on the bone microarchitecture was caused by CMS but not by fluoxetine. Without exposure to CMS, fluoxetine significantly increased the cross-sectional area, trabecular bone area, structural strength and osteoblasts / bone area as compared to control condition.
Background: Depressive disorder is treatable but costly, thus influencing quality of life of people. Aim: Determine direct and indirect costs incurred by depressive disorder in Singapore. Methods: A ...1-year prospective naturalistic study was conducted in a university mood disorder center between 2007 and 2008. Patients with primary International Classification of Disease-10 diagnosis of depressive disorder were recruited. Disease costs between mild, moderate and severe depression, and cost predictors were analyzed and determined. Results: Forty nine patients completed the study. Mean annual total costs per patient were US$7638. Indirect costs (81%) dominated the total costs. Approximately 50% of indirect costs were associated with loss of productivity and unemployment. Higher education level, higher mean Hamilton Rating Scale for Depression score and number of suicide attempts were independent variables associated with increased direct costs while mean Hamilton Rating Scale for Depression scale score was an independent variable for indirect costs. Conclusion: Medical cost saving strategies should focus on indirect costs.
A cDNA fragment (FaPR4) encoding a class I pathogenesis-related protein 4 (PR-4) from Ficus awkeotsang was obtained by PCR cloning. Plant PR-4s were grouped into class I and II, differing by the ...presence of ChtBD and hinge. The predicted mature FaPR4 comprises N-terminal chitin-binding domain (ChtBD), hinge, Barwin domain and C-terminal extension. FaPR4-C, an N-terminal truncated form of FaPR4, was designed to mimic the structural feature of class II PR-4s. FaPR4 and FaPR4-C were over-expressed in yeast Pichia pastoris, and both recombinants exhibited RNase and anti-fungal activities. To our knowledge, it is the first report that FaPR4, a member of class I PR-4s has RNase activity as class II. FaPR4 possesses better anti-fungal activities toward Fusarium oxysporum and Sclerotium rolfsii than FaPR4-C. Heat-treated FaPR4 remained RNase and anti-fungal activities; while heat-treated FaPR4-C lost those activities. Therefore, ChtBD of FaPR4 may not only contribute to its anti-fungal but also improve the thermal stability of protein. It also implied the correlation of RNase activity with anti-fungal activity of FaPR4-C. Furthermore, FaPR4 was detected to have weak but significant chitinase activity, and its chitinase activity was reduced after heat treatment. The chitinase activity by FaPR4-C was much lower than FaPR4.
► FaPR4 coding for a class I PR-4 from jelly fig achenes was obtained by PCR. ► FaPR4 and FaPR4-C represent class I and II PR-4, each were expressed in yeast. ► FaPR4, heat-treated FaPR4 and FaPR4-C showed RNAase activity. ► FaPR4, heat-treated FaPR4 and FaPR4-C exhibited anti-fungal activity. ► First report indicates that a class I PR-4 has RNase activity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This review addresses the importance of psychoneuroimmunology (PNI) studies in understanding the role of acute and chronic psychological stressors on the immune system and development of coronary ...artery disease (CAD). Firstly, it illustrates how psychological stressors change endothelial function and lead to chemotaxis. Secondly, acute psychological stressors lead to leukocytosis, increased natural killer cell cytotoxicity and reduced proliferative response to mitogens while chronic psychological stressors may lead to adverse health effects. This will result in changes in cardiovascular function and development of CAD. Thirdly, acute and chronic psychological stressors will increase haemostatic factors and acute phase proteins, possibly leading to thrombus formation and myocardial infarction. The evidence for the effects of acute and chronic psychological stress on the onset and progression of CAD is consistent and convincing. This paper also highlights potential research areas and implications of early detection of immunological changes and cardiovascular risk in people under high psychological stress.
The association between selective serotonin reuptake inhibitor (SSRI) treatment and lower bone mineral density (BMD) remains controversial, and further research is required. This study aimed to ...compare the BMD, levels of bone formation and bone metabolism markers in medicated premenopausal Singaporean women with major depressive disorder (MDD) and matched healthy controls. We examined 45 women with MDD who received SSRI treatment (mean age: 37.64 ± 7) and 45 healthy controls (mean age: 38.1 ± 9.2). BMD at the lumbar spine, total hip and femoral neck were measured using dual-energy X-ray absorptiometry. We also measured bone formation markers, procollagen type 1 N-terminal propeptide (P1NP) and bone metabolism markers, osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa-Β ligand (RANKL). There were no significant differences in the mean BMD in the lumbar spine (healthy controls: 1.04 ± 0.173 vs. MDD patients: 1.024 ± 0.145,
= 0.617, left hip (healthy controls: 0.823 ± 0.117 vs. MDD patients: 0.861 ± 0.146,
= 0.181) and right hip (healthy controls: 0.843 ± 0.117 vs. MDD patients: 0.85 ± 0.135,
= 0.784) between healthy controls and medicated patients with MDD. There were no significant differences in median P1NP (healthy controls: 35.9 vs. MDD patients: 37.3,
= 0.635), OPG (healthy controls: 2.6 vs. MDD patients: 2.7,
= 0.545), RANKL (healthy controls: 23.4 vs. MDD patients: 2178.93,
= 0.279) and RANKL/OPG ratio (healthy controls: 4.1 vs. MDD patients: 741.4,
= 0.279) between healthy controls and medicated patients with MDD. Chronic SSRI treatment might not be associated with low BMD in premenopausal Singaporean women who suffered from MDD. This finding may help female patients with MDD make an informed decision when considering the risks and benefits of SSRI treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Aim: To assess the frequency of, and factors associated with, depression and anxiety in Singaporean patients with rheumatoid arthritis (RA).
Method: One hundred RA patients were recruited in a ...cross‐sectional study. Socio‐demographics, severity of anxiety and depression, disease activity, levels of serological markers and health‐related quality of life were analyzed.
Results: Twenty‐six percent presented with anxiety, 15% with depression and 11% with both. Univariate regression showed that age (P = 0.039), Disease Activity Scale (DAS‐28) (P < 0.001), number of medications (P < 0.001) and rheumatoid factor (RF) (P < 0.001) were positively associated with severity of depression, while income (P = 0.001), education (P = 0.029), self‐perceived social support (P = 0.007), Short form 12 (SF‐12) physical health (P < 0.001) and SF‐12 mental health (P < 0.001) were negatively associated with severity of depression. After adjustment for confounding factors in multivariate regression, income (β = −0.347, P = 0.018), RF (β = 0.304, P = 0.043) and SF‐12 mental health (β = −0.501 P = 0.001) remained significantly associated with depression. Univariate regression showed that DAS‐28 (P = 0.009), number of medications (P = 0.004) and RF (P = 0.043) were positively associated with anxiety, while income (P = 0.022), self‐perceived social support (P = 0.04), SF‐12 physical health (P < 0.001) and SF‐12 mental health (P < 0.001) were negatively associated with anxiety. After adjustment for confounding factors, no factors remained significantly associated with anxiety.
Conclusion: Low income, high levels of RF and poor mental health were associated with depression in RA. Our findings may help to formulate depression screening strategies. Further research is required to identify the role of RF in depression.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Seed storage proteins of plants commonly comprise several groups of multiple isoforms encoded by gene families. From about 300 expressed sequence tag (EST) clones in maturing jelly fig (Ficus ...awkeotsang Makino) achenes, gene families encoding precursor polypeptides of two storage protein classes, including six 11S globulin isoforms and two 2S albumin isoforms, were identified. Complete sequences encoding the precursor polypeptides of these eight storage proteins were obtained by sequencing the pertinent EST clones that contained full-length cDNA fragments. Matrix-assisted laser desorption/ionization mass spectrometry analysis confirmed the presence of these storage protein isoforms in the extract of jelly fig achenes resolved in SDS-PAGE. The amino acid compositions of the deduced storage proteins indicated that achene proteins in jelly fig are nutritive, for both isoforms of 2S albumin are sulfur-rich, and one of them is also rich in tryptophan.
Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) is regarded as a nutritive food source as well as herbal medicine. The food nutrition is a consequence of its high protein content and superior amino ...acid composition. From ca. 200 expressed sequence tag (EST) sequences in maturing adlay grains, clones encoding precursor polypeptides of 10 seed storage proteins in the prolamin family, including 8 α-coixin isoforms, 1 δ-coixin, and 1 γ-coixin, were identified. Full-length cDNA fragments encoding these 10 coixins were obtained by PCR cloning. Mass spectrometric analyses confirmed the presence of these 10 coixins in the extract of adlay grain. Calculated amino acid compositions indicate that all 10 coixins are rich in glutamine (>20% in α-coixin isoforms, 13.3% in δ-coixin, and 31.2% in γ-coixin). The 8 α-coixin isoforms are low in methionine, cysteine, and lysine (on average, 0.8, 0.6, and 0.1%, respectively). However, the δ-coixin is a sulfur-rich protein (18.2% methionine and 9.1% cysteine), and the γ-coixin is a nutritive protein composed of 2.0% methionine, 6.6% cysteine, 2.6% lysine, and 8.9% histidine. The company of δ-coixin and γ-coixin with α-coixin isoforms enhances the nutritional value of alday grain for human consumption.
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IJS, KILJ, NUK, PNG, UL, UM, UPUK
Jelly curd used for a popular summer drink in Taiwan is prepared by extracting the pericarpial portion of jelly fig (Ficus awkeotsang Makino) achenes. The two most abundant proteins found in jelly ...curd have been identified as a pectin methylesterase and a chitinase. A method was developed to purify the next abundant protein by 40% ammonium sulfate precipitation and flowing through Mono Q chromatography. In sodium dodecyl sulfate−polyacrylamide gel electrophoresis analyses, the purified protein migrated as a polypeptide of 20 kDa in the absence of β-mercaptoethanol but split into a minor polypeptide of 20 kDa and a major polypeptide of 27 kDa in the presence of this reducing agent. Two cDNA fragments encoding precursor polypeptides of two putative thaumatin-like protein isoforms were obtained by polymerase chain reaction cloning and subsequently overexpressed in Escherichia coli to generate recombinant proteins for antibody preparations. Immunological detection and mass spectrometric analyses indicated that the two split polypeptides were thaumatin-like protein isoforms encoded by the two cloned cDNA fragments. Keywords: Achene; jelly fig (Ficus awkeotsang); mass spectrometric analyses; pericarp; thaumatin-like protein
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