Correlation between psychosocial stresses, stress coping ability, pain intensity and degree of disability in patients with non-specific neck pain.

This study was conducted to find out which factor among stress inducing factors and stress coping factors that can affect patients with non-specific neck pain has more correlation with the intensity of neck pain and the degree of disability. This study is a cross-sectional correlational study. 100 patients diagnosed with non-specific neck pain participated in this study. The characteristics of the participants in this study are as follows. There were 56 men and 44 women, with an average age of 34.11 years, height of 169.91, and weight of 66.97 kg. The participant`s pain intensity was 5.18 and disability index was 21.44. In order to evaluate the pain intensity and disability level of patients with non-specific neck pain, Numeric Pain Rating SCALE (NPRS), and Neck Disability Index (NDI) were investigated, respectively. Depression, Anxiety, Stress Scale-21 (DASS-21), and Tampa Scale of Kinesiophobia (TSK) were used to evaluate stress inducing factors. Brief Resolution Scale (BRS), Latack Coping Scale (LCS), and Pain Self-Efficacy Questionnaire (PSEQ) were used to evaluate stress coping factors. Spearman correlation coefficients were used to determine the correlation between NPRS, NDI, and DASS-21, TSK, BRS, LCS, and PSEQ in patients with non-specific neck pain. As a results of this study, the NPRS was correlated with NDI and TSK. The NPRS and NDI were found to have a moderate correlation, but they were correlated with TSK, but showed a weak correlation. The NDI was found to be correlated with TSK, DASS, BRS, and PSEQ. In addition, NDI showed a weak correlation with TSK, BRS, and PSEQ, but the DASS showed a moderate correlation, showing the strongest correlation among the factors. These outcomes suggest that psychosocial factors, particularly stress-related factors such as depression, anxiety, and fear of movement, exert a more pronounced influence on pain intensity and disability in individuals with non-specific neck pain.

Association Between Hamstring Shortness and Asymmetry, Pain Intensity, Disability Index, and Compensatory Lumbar Movement in 60 Patients with Nonspecific Chronic Low Back Pain.

BACKGROUND The correlation between hamstring muscle shortening and nonspecific low back pain and compensatory lumbar movements is still controversial. The purpose of this study was to evaluate the association between hamstring shortness and asymmetry, pain intensity, the disability index, and compensatory lumbar movement in 60 patients with nonspecific chronic low back pain. MATERIAL AND METHODS Sixty patients with nonspecific low back pain participated in this study. The hamstring shortness and asymmetry, pain intensity, the disability index, and compensatory lumbar movement of the patients were assessed. The pain intensity was evaluated using a numeric pain rating scale (NPRS), active knee extension testing was performed to measure the length of the hamstring, and compensatory lumbar movement was assessed using a digital dual inclinometer. Correlation analysis was used for analysis of the obtained data. RESULTS The hamstring length showed a negative correlation with hamstring length asymmetry, NPRS, and disability index (P<0.05). The asymmetry of the hamstring length was positively correlated with NPRS, disability index, and compensatory lumbar rotation (P<0.05). Lumbar flexion was positively correlated with the hamstring muscle length (P<0.05). However, there was a negative correlation between the hamstring length asymmetry, NPRS, and disability index (P<0.05). There was no correlation between the compensatory lumbar rotation, hamstring length, or disability index. CONCLUSIONS Compensatory flexion movements, NPRS, and disability index in patients with nonspecific chronic low back pain were associated with hamstring shortness and asymmetry. These factors should be considered when planning physical therapy for patients with nonspecific low back pain.

Tat peptide-admixed elastic liposomal formulation of hirsutenone for the treatment of atopic dermatitis in NC/Nga mice.

BACKGROUND: The aim of the present study was to enhance a topical delivery of hirsutenone (HST), a naturally occuring immunomodulator, employing Tat peptide-admixed elastic liposomes (EL/T). METHODS: HST-loaded EL, consisting of phosphatidylcholine and Tween 80 (85:15 w/w%), were prepared using thin film hydration method. By adding Tat peptide to EL (0.16 w/w%), EL/T were formulated. The in vitro skin permeation of HST was examined using a Franz diffusion cell mounted with depilated mouse skin. Lesions for atopic dermatitis (AD) were induced by a topical application of diphenylcyclopropenone to NC/Nga mice. Therapeutic improvements of AD were evaluated by clinical skin severity scores. Immunological analyses on inducible nitric oxide synthase and cyclooxygenase-2 levels in the skin and interleukin (IL)-4, IL-13, immunoglobulin E, and eosinophil levels in the blood were also performed. RESULTS: EL systems were superior to conventional cream, revealing greater flux values in a permeation study. The addition of Tat peptide further increased the skin permeation of HST. In an efficacy study with AD-induced NC/Nga mice, an HST-containing EL/T formulation brought a significant improvement in both skin severity score and immune-related responses for the levels of nitric oxide synthase, cyclooxygenase-2, IL-4, IL-13, immunoglobulin E, and eosinophils. CONCLUSION: A novel EL/T formulation was successfully developed for topical delivery of HST to treat AD.

Solid dispersion formulations of megestrol acetate with copovidone for enhanced dissolution and oral bioavailability.

In order to enhance the dissolution profile and oral bioavailability of megestrol acetate (MA), solid dispersions of MA (MASDs) were formulated with copovidone and crystal sugar as a hydrophilic polymeric carrier and an inert core bead, respectively. Solvent evaporation method and fluidized bed coating technique were employed. MASDs were categorized as crystalline solid dispersion by the characterization of differential scanning calorimetry and X-ray diffraction. The mass-median diameters of MASDs were in a range of 1.4 to 2.6 µm. Based on drug to polymer ratio, MASD (1:1) and (1:2) were considered as optimized formulations, resulting in a smooth-surfaced homogeneously coated layer with enhanced dissolution rate. Dissolution of MASD was gradually increased up to 15 min, after which it reached a plateau. For the initial period, dissolution rates were in the decreasing order of MASD (1:2) ≥ MASD (1:1) > MASD (1:3) > MASD (1:5) > MASD (1:0.5) > MA powder. In the comparative pharmacokinetic study with Megace OS, a reference drug product, MASD (1:1) showed improved bioavailability of over 220% with 2-fold higher C(max) and 30% faster T(max). We conclude that MASD (1:1) is a good candidate for the development of oral solid dosage forms.

Acrolein, an I-κBα-independent downregulator of NF-κB activity, causes the decrease in nitric oxide production in human malignant keratinocytes.

Acrolein, a reactive electrophilic α, ß-unsaturated aldehyde, is known to be an alkylating chemical carcinogen. The effect of acrolein on the activation of NF-κB in human malignant epidermal keratinocytes was examined to elucidate the molecular mechanism associated with this NF-κB-acrolein regulation and its consecutive sequence, nitric oxide (NO) production. Acrolein significantly downregulated the cellular NF-κB activity up to 60% compared with control as well as the lipopolysaccharide (LPS)-induced NO production in a dose response manner at concentrations of 10~30 µM. To investigate the regulatory mechanism associated with this NF-κB-acrolein downregulation, the relative level of phosphorylation of I-κBα (serines-32 and -36), a principle regulator of NF-κB activation, represented by acrolein, was quantified. Acrolein inhibited NF-κB activity without altering cellular levels of the phosphorylated and nonphosphorylated forms of I-κBα, implying that the downregulatory effect of acrolein on cellular NF-κB activity in human skin cells is an I-κBα-independent activation pathway. The results suggests that acrolein causes the decrease in nitric oxide production as an I-κBα-independent downregulator of NF-κB activity in human malignant keratinocytes, and acrolein-induced carcinogenesis may be associated with the modulation of cellular NF-κB activity.

N-nitroso-N-methylurea and N-nitroso-N-ethylurea induce upregulation of cellular NF-kappa B activity through protein kinase C-dependent pathway in human malignant keratinocytes.

The upregulatory mechanism of cellular NF-kappaB activity by carcinogens, N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU) in human malignant keratinocytes was investigated. To elucidate the role of protein kinase C (PKC) in the upregulation of NF-kappaB by NMU and NEU, two known PKC inhibitors, staurosporine and H-7 were studied. Treatment of cells with PKC inhibitors decreased NF-kappaB activity in a dose responsive manner at concentrations of 20 approximately 200 nM. Staurosporine (160 nM) and H-7 (200 nM) downregulated the cellular NF-kappaB activation up to 20 and 60% compared to the NF-kappaB activity that was upregulated by NMU (5 microM) and NEU (5 microM), respectively. These results indicated that the PKC activity was responsible for the upregulation of NF-kappaB activity. The level of phosphorylation of I-kappaBalpha, the predominant form of the I-kappaB family represented by NMU and NEU, was quantified. The relative amount of I-kappaBalpha phosphorylation (serines-32 and -36) determined using the cellular activation of signaling ELISA assay method showed that NMU (5 microM) and NEU (5 microM) increased the amount of I-kappaBalpha phosphorylation up to 17 and 10% compared to the control, respectively. The results demonstrate the upregulatory effect of NMU and NEU on cellular NF-kappaB activity in human keratinocytes via the protein kinase C-mediated pathway.

The chemopreventive effect of retinoids on cellular NF-kappaB activity induced by NMU and NEU in human malignant keratinocytes.

PURPOSE: Retinoids have been shown to be effective in suppressing tumor development when chemical carcinogens such as N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU) were used to induce mammary tumors in a variety of animal models. However, the molecular mechanisms associated with the retinoid-mediated chemopreventive process, as linked to transcription factor NF-kappaB activation, for chemoprevention have not been elucidated. The purpose of this study was to determine the implications of NF-kappaB activation on the chemopreventive role of retinoids and their effect on cellular NF-kappaB activity that's induced by known alkylating chemical carcinogens such as NMU and NEU in human transfectant squamous cell carcinoma (SCC-13) cells. MATERIALS AND METHODS: The activity of NF-kappaB, as regulated by chemical carcinogens and retinoids, was determined in cultured human SCC-13 keratinocytes that were transfected with the pNF-kappaB-SEAP-NPT plasmid; this permitted the expression of the secretory alkaline phosphatase (SEAP) reporter gene in response to the NF-kappaB activity, and the plasmid contained the neomycin phosphotransferase (NPT) gene, which confers resistance to geneticin. The reporter enzyme activity was measured using a fluorescence detection assay method. RESULTS: All-trans retinoic acid and 13-cis retinoic acid induced a reduction of NF-kappaB activity up to 64% and 65%, respectively, compared to the control. For the treatment of the human transfectant cells with chemical carcinogens, all-trans retinoic acid (5 mM) and 13-cis retinoic acid (5 mM) downregulated the cellular NF-kappaB activation up to 83% and 85% compared to the NF-kappaB activity that was upregulated by NMU (5microM) and NEU (5microM), respectively. CONCLUSION: These results suggest that the chemopreventive effect of retinoids may be mediated by the downregulated activation of NF-kappaB and that retinoids are implicated in the activation of NF-kappaB in human skin cells.

Site-specific mutagenesis in human cells by bulky exocyclic amino-substituted guanine and adenine derivatives.

PURPOSE: 7-Bromomethylbenz[a]anthracene is a well-known mutagen and carcinogen. The aim of this study is to determine the mutagenic potency of its two major DNA adducts [N(2)-(benz[a]anthracen-7-ylmethyl)-2'-deoxyguanosine (b[a]a(2)G) and N(6)-(benz[a]anthracen-7-ylmethyl)-2'-deoxyadenosine (b[a]a(6)A)] and the simpler benzylated analogs [N(2)-benzyl-2'-deoxyguanosine (bn(2)G) and N(6)-benzyl-2'-deoxyadenosine (bn(6)A)] in Ad293 human cells and to compare to their mutagenicity in human cells and E. coli. MATERIALS AND METHODS: The shuttle vector pGP50 is capable of replicating in E. coli and human cells. Modified nucleotides were positioned in the plasmid pGP50 in a manner similar to pGP10 as described (8). Adenovirus transformed human embryonic kidney cells (line 293) were transfected with a shuttle vector containing an adduct. Two days later, the plasmids were recovered and treated with DpnI to remove unreplicated DNA. DH10B E. coli were transformed with the plasmids. Bacteria were cultured with the media containing X-gal, IPTG and ampicillin. Bacteria transformed by the plasmid with the adduct-induced mutation in the initiation codon of lacZ' form white colonies whereas bacteria transformed by the plasmid without mutation form blue colonies. RESULTS: In the human cell site-specific mutagenesis system, bn(2)G exhibited weak mutagenicity and bn(6)A was not mutagenic, although b[a]a(2)G or b[a]a(6)A produced 8% and 7% mutant colonies, respectively. At the site of the adduct, b[a]a(2)G induced the G-->T transversion mutation while b[a]a(6)A produced the A-->G transition mutation. CONCLUSION: These data indicate that bulkier b[a]a(2)G and b[a]a(6)A exhibit significantly greater mutagenicity in human cells than in E. coli.

Upregulation of cellular NF-kappa B activity by alkylating carcinogens in human epidermal keratinocytes.

Effect of alkylating carcinogens, i.e., N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU), as well as the simpler alkylating agents, methyl iodide and ethyl iodide, on the activation of NF-kappaB was evaluated in human epidermal squamous cell carcinoma (SCC-13) keratinocytes in order to investigate the possible correlation of cellular NF-kappaB activity with chemical carcinogenesis. The activities of NF-kappaB induced by chemical carcinogens were determined in human SCC-13 keratinocytes transfected with pNF-kappaB-SEAP-NPT plasmid, permitting expression of the secretory alkaline phosphatase (SEAP) reporter gene in response to the NF-kappaB activity and contains the neomycin phosphotransferase (NPT) gene conferring resistance to the geneticin. In this cell-based assay system, all alkylating carcinogens significantly upregulated the cellular NF-kappaB activations in a time- and dose-dependent manner until 72 h, at concentrations of 0.5-5 microM. These results suggest that carcinogenicity by alkylating chemicals may be associated with the modulation of cellular NF-kappaB activity in human skin cells.

Downregulation of NF-kappaB activation in human keratinocytes by melanogenic inhibitors.

BACKGROUND: Exposure of skin cells, particularly keratinocytes to various nuclear factor-kappaB (NF-kappaB) activators (e.g. tumor necrosis factor-alpha, interleukin-1, lipopolysaccharides, and ultraviolet light) leads to phosphorylation and degradation of the inhibitory protein, IkappaB. Liberated NF-kappaB is translocated into the nucleus where it can change or alter expression of target genes, resulting in the secretion of extracellular signaling molecules including melanotrophic factors affecting melanocyte. OBJECTIVE: In order to demonstrate the possible role of NF-kappaB activation on the synthesis of melanotrophic factors from the keratinocytes, the activities of NF-kappaB induced by melanogenic inhibitors (MIs) were determined in human HaCaT keratinocytes transfected with pNF-kappaB-SEAP-NPT plasmid. Transfectant cells released the secretory alkaline phosphatase (SEAP) as a transcription reporter in response to the NF-kappaB activity and contain the neomycin phosphotransferase (NPT) gene for the dominant selection marker for geneticin resistance. METHODS: MIs such as niacinamide, kojic acid, hydroquinone, resorcinol, arbutin, and glycolic acid were preincubated with transfectant HaCaT cells for 3 h and then ultraviolet B (UVB) was irradiated. NF-kappaB activation was measured with the SEAP reporter gene assay using a fluorescence detection method. RESULTS: Of the MIs tested, kojic acid (IC(50)=60 microM) was found to be the most potent inhibitor of UVB-upregulating NF-kappaB activation in transfectant HaCaT cells, which is followed by niacinamide (IC(50)=540 microM). Pretreatment of the transfectant HaCaT cells with the MIs, especially kojic acid and niacinamide, effectively lowered NF-kappaB binding measured by electrophoretic mobility shift assay. Furthermore, these two inhibitors remarkably reduced the secretion level of IL-6, one of melanotrophic factors, triggered by UV-radiation of the HaCaT cells. CONCLUSION: These observations suggest that MIs working at the in vivo level might act partially through the modulation of the synthesis of melanotrophic factors in keratinocyte.

Site-Specific Mutagenesis in Escherichia coli by Bulky Exocyclic Amino-Substituted Guanine and Adenine Derivatives in Double-Stranded or Gapped Plasmids.

PURPOSE: 7-Bromomethylbenz[alpha]anthracene is a known mutagen and carcinogen. The mutagenic potency of its two major DNA adducts, i.e., N2-(benz[alpha]anthracen-7-ylmethyl)-2'-deoxyguanosine (b[alpha]a2G) and N6-(benz[alpha]anthracen-7-ylmethyl)-2'-deoxyadenosine (b[alpha]a6A), as well as the simpler benzylated analogs, N2-benzyl-2'-deoxyguanosine (bn2G) and N6-benzyl-2'-deoxyadenosine (bn6A), were determined in E. coli. MATERIALS AND METHODS: Double-stranded and gapped plasmid vectors were used to determine the mutagenicity of b[alpha]a2G, b[alpha]a6A, bn2G and bn6A in E. coli. The four, suitably protected, bulky exocyclic amino-substituted adducts were incorporated into 16-base oligodeoxyribonucleotides, in place of normal guanine or adenine residues, which form part of the ATG initiation codon for the lacZ' alpha-complementation gene. The site-specifically modified oligodeoxyribonucleotides were then incorporated into double-stranded plasmids, which contained uracil residues in the complementary strand in the vicinity of the initiation codon. The uracil residues lead to the creation of a gap in the complementary strand due to the actions of E. coli uracil-DNA glycosylase and AP endonuclease. Following the transfection of these plasmid vectors into E. coli strain GP102, a lacZ alpha complementing version of the parent strain AB1157, their propensity to induce mutation was investigated. RESULTS: The percentages of mutant colonies produced by the four modified nucleosides, in both the double-stranded and gapped plasmid vectors, were not significantly different from those produced by the unmodified plasmids. The mutagenicities of the b[alpha]a2G and b[alpha]a6A were extremely low, and a totally unexpected result, whereas, those of the bn2G and bn6A were undetectable. CONCLUSION: In this E. coli site-specific mutagenesis system, these bulky aralkylated adducts exhibited no significant mutagenicities, either with or without SOS induction.