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To investigate the association between inflammatory biomarkers and overt hypothyroidism (OH). We measured inflammatory cytokines, interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) as well as cell-free DNA (cf-DNA) levels in 40 OH patients and 40 healthy controls. Total cholesterol, high and low density lipoprotein subfractions, triglyceride, fibrinogen, and D-dimer were recorded. Increased inflammatory profile was evidenced through significant elevations in the concentrations of all cytokines and cf-DNA levels in the OH group. Lipids and prothrombotic markers were also increased in hypothyroid subjects. A significant association between the inflammatory cytokines and lipid profile was observed. A multivariate analysis showed that this result was independent of the sex, age and BMI status of the subjects. Hypothyroidism is associated with proinflammatory state. Lipid abnormalities have a stronger influence on inflammation, increasing cardiovascular risk and atherosclerosis development in hypothyroidism.

Sulfate-reducing bacteria (SRB) are most likely involved in both the initiation and maintenance of inflammatory bowel disease (IBD); unfortunately present antibacterial chemotherapeutics used in the treatment of IBD have been ineffective. Thus, the antimicrobial activity of salicylamide derivatives against two different genera of intestinal SRB, Desulfovibrio and Desulfomicrobium, was investigated. Six 2-(phenylcarbamoyl)phenyl N-[(benzyloxy)carbonyl]alkanoates and three 2-hydroxy-N-[(2S)-1-oxo-1-(phenylamino)alkan-2-yl]benzamides showed MIC values in the range from 0.22 to 0.35 μM against Desulfovibrio piger Vib-7 and in the range from 0.27 to 8.52 μM against Desulfomicrobium sp. Rod-9, while MIC values of ciprofloxacin were 41.2 μM and 39.3 μM. The highest potency against the two strains was observed for 4-chloro-N-{(2S)-1-[(3,4-dichlorophenyl)amino]-3-methyl-1-oxobutan-2-yl}-2-hydroxybenzamide (MIC 0.22 μM and 0.27 μM). 4-Chloro-2-[(4-nitrophenyl)carbamoyl]phenyl (2S)-2-{[(benzyloxy)carbonyl]amino}-3-methylbutanoate showed high activity against D. piger Vib-7 (MIC = 0.26 μM), while 4-chloro-2-[(4-methylphenyl)carbamoyl]phenyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-2-yl)propanoate expressed high activity against Desulfomicrobium sp. Rod-9 (MIC = 0.31 μM). Structure-activity relationships are discussed.

The temporo-mandibular joint causes more problems than any other in the body and is the least understood with the high incidence of associated symptomatology remaining a major cause for concern. This lack of knowledge is partly due to the difficulties in acquiring information as it is not easy to access and practical and ethical constraints have ensured the almost complete absence of reliable in vivo data on joint loading and muscle forces. Whilst the issue of joint compression was debated throughout much of the twentieth-century, it is now considered that short-comings in the underlying biomechanical theory and analysis have contributed to this uncertainty and stifled progress, and that a reassessment of mandibular motion from a different perspective could resolve this.

Isolation of unexplored frontier molecules are needed to treat multidrug resistant pathogens especially Methicillin resistant Staphylococcus aureus (MRSA). A marine sponge endosymbiotic Streptomyces albus ICN33 produces an anti-MRSA metabolite is reported. The crude extract exhibited anti-MRSA activity and the active principle was isolated through fermentation and chromatographic techniques. A compound PVI331 with a molecular mass of 506 Da have been determined by high resolution mass spectrometry. LC-MS based dereplication analysis had revealed that the detected compound PVI331 as unknown. The antibacterial assay of the compound PVI331 showed remarkable antagonistic activity against MRSA and Escherichia coli. Minimum inhibitory concentrations were found to be 1 μg/ml against MRSA. Sub-inhibitory concentration of the compound PVI331 reduced the biofilm formation of Staphylococcus aureus ATCC25923 and increased the cell surface hydrophobicity index. Scanning electron microscopic observation of the sub-inhibitory concentration exposure revealed a wrinkled membrane surface and slight cellular damage shows the cell wall distracting property of the compound. Zebrafish embryo based toxicity assays exhibited 48 ± 2 μg/ml of LC₅₀ value and 30 μg/ml of compound as maximal non-lethal concentration which had demonstrated the positive relationship in safety index. This study highlighted the anti-MRSA property of Streptomyces albus ICN33 from a marine sponge.

Fullerenol C₆₀(OH)₂₄ nanoparticles (FNP) are promising radioprotectors in prevention of early and late ionizing radiation injury. The aim of this study was to compare the efficacy of FNP and amifostine (AMI) in protection of rats exposed to whole-body X-ray irradiation (7 or 8 Gy). Both compounds (FNP, 100 mg/kg ip; AMI, 300 mg/kg ip) were given 30 min before irradiation throughout the study. The general radioprotective efficacy of FNP and AMI were evaluated in rats irradiated with an absolutely lethal dose of X-rays (8 Gy) and their survival were monitored during the period of 30 days after irradiation. Both compounds were of comparable efficacy. Tissue-protective effects of tested compounds were assessed in rats irradiated with an sublethal dose of X-rays (7 Gy). For this purpose, the animals were sacrificed on the 7th and 28th day after irradiation. Their lung, heart, liver, kidney, small intestine and spleen were taken for histopathological and semiquantitative analysis. Careful examination of established tissue and vascular alteration revealed better radioprotective effects of FNP compared to those of AMI on the small intestine, lung and spleen, while AMI had better radioprotective effects than FNP in protection of the heart, liver and kidney. Results of this study confirmed high radioprotective efficacy of FNP in irradiated rats that was comparable to that of AMI, a well-known radioprotector.

Betahistine dihydrochloride, which is widely prescribed for the treatment of symptoms associated with Meniere's syndrome, is generally administered orally in solid or liquid formulations. There is a strong need of profound investigation of alternative routes of administration of betahistine to overcome difficulties related to oral administration. The aim of this study was to evaluate betahistine cytotoxicity and permeability in vitro and to assess the drug's relevance for incorporation in drug delivery systems for nasal administration. RPMI epithelial model was used to evaluate drug permeability in vitro. The cytotoxicity of betahistine was assessed by MTT test. Chitosan microspheres were used as a betahistine delivery system. RPMI 2650 formed a thick, impermeable cell layer on the apical side of the filter inserts and developed enough TEER values to confirm confluence. According to the obtained results, BET showed high permeability coefficients (Papp values in the range 2.3 × 10^-5 to 19 × 10^-5) and could, therefore, be successfully used in nasal drug delivery formulations. Also, BET exhibited a good safety profile regarding nasal epithelium toxicity. A dose-dependent reduction in cell viability was observed. The microspheres as drug delivery systems affected BET permeation profiles due to the presence of chitosan as an absorption enhancer.

Antimicrobial, antimycobacterial and antiviral activities of crude extracts, fractions and subfractions of Tabernaemontana catharinensis were evaluated. Best antimicrobial results occurred with the dichloromethane (DCM) and butanolic (NB) fractions against Staphylococcus aureus, Micrococcus sp., Enterococcus faecalis and Bacillus subtilis (minimal inhibitory concentration, MIC = 31.25-1000 μg/mL). Considering the Gram-negative bacteria, only NB fraction was effective against Proteus mirabilis and Aeromonas sp. (MIC = 62.5 μg/mL and 250 μg/mL, respectively). In addition, the fungi Candida albicans, Candida glabrata, Cryptococcus neoformans, Saccharomyces cerevisiae, Aspergillus flavus and Aspergillus fumigatus were particularly vulnerable for DCM fraction (MIC = 31.25-1000 μg/mL). The fractions and subfractions were effective against Mycobacterium smegmatis (MIC = 19.53-156.25 μg/mL). DCM (selectivity index - SI = 77.92), ethyl acetate (EA) (SI = 40.27) and NB (SI = 28.97) fractions from the leaves exhibited a potential antiviral activity toward Herpes Simplex Virus type 1 whereas DCM2 subfraction from leaves (SI = 12.28) and alkaloidal fraction (AF) (10.71) maintained this good activity. Steroids, terpenoids and phenolics compounds were identified by high-performance liquid chromatography with diode array detection (HPLC/DAD) and may be partially responsible for the antimicrobial and antiherpes activities observed. The results obtained in this study showed that T. catharinensis has antimicrobial and anti-herpetic activities and that these properties are reported for the first time for this species.

The present study reports the synthesis of polyethylene glycol (PEG) coated potassium ferrite nanoparticles. X-ray diffraction pattern revealed the formation of orthorhombic structure of KFeO₂ nanoparticles, along with additional characteristic peaks of PEG at 2θ ∼19° and 23°. The characteristic IR bands of PEG confirmed its coating thereby making the nanocomposite feasible for bio-conjugation. The coating of PEG on KFeO₂ nanoparticles, spherical formation, and reduced agglomeration of the nanocomposite were revealed by high resolution transmission electron microscope, transmission electron microscope and scanning electron microscope studies, respectively. In vibrating sample magnetometer analysis, the synthesized nanocomposite exhibited superparamagnetic behavior with magnetic saturation value of 5.78 emu/g and high biocompatibility below 250 μg/ml.

Chronic infections caused by Pseudomonas aeruginosa (P. aeruginosa) isolates are mainly related to resistance to antimicrobials and the production of certain virulence factors. The purpose of this study was twofold: to investigate the prevalence of virulence genes and to study the relationship between biofilm formation/alginate production/antibiotic resistance and the presence of genes associated with biofilm, alginate, flagella and exotoxin A in clinical isolates of P. aeruginosa.
Microtiter plate biofilm assay and Carbazole method were used to examine the biofilm formation and alginate production ability of the isolates, respectively. The genes, ppyR, pslA, pelA (biofilm formation), algD, algU, algL (alginate production), fliC (flagella) and exoA (exotoxin A) were detected by PCR.
Biofilm formation as well as alginate production ability was found in 47.1% of the clinical isolates. Based on PCR data, the frequency distribution of the genes in the clinical isolates was as follows: ppyR (99%), pslA (83.7%), pelA (45.2%), algU (90.4%), algL (73.1%), algD (87.5%), exoA (84.6%) and fliC (70.2%). Biofilm formation ability of the isolates was significantly correlated with the presence of the genes, pelA and fliC (statistically significant). In addition, 58.65% of the isolates were resistant to three or more different classes of antibiotics.

Silibinin is known to display high efficacy against cancer cells and for hepatic protection. Metformin, a well-known antidiabetic agent, has recently been reported to inhibit cancer. In the present study, we investigated the effect of metformin on silibinin-induced programmed cell death in cervical cancer cells (C-33A). MTT assay and Western blot assays were performed to quantify cell viability and the expression of signaling proteins, respectively. Combined treatment with metformin and silibinin decreased cell survival in synergistic manner in C-33A cells at a dose that did not affect nonmalignant cells (HUVECs). Silibinin and metformin increased PTEN and AMPK expression in C-33A cells, respectively. Combined treatment caused a greater increase in the expression of activated caspase-3 or AIF, indicating apoptosis. Combined treatment with silibinin and metformin may induce programmed cell death of human cervical cancer cells at a dose that does not affect HUVECs. This finding reveals a potential therapeutic strategy of cervical cancer.

Large screening programs of nasopharyngeal carcinoma (NPC) are still challenging due to the scarcity of the resources in higher prevalence parts of the world. In the present study, the development of a new low cost immunochromatography (ICG) strip test for screening of nasopharyngeal carcinoma is reported. A conjugate of gold nanoparticle-anti viral capsid antigen (VCA) immunoglobulin A (IgA) antibody was used as the detection probe. The test is based on a non-competitive immunoassay for rapid and reliable detection the serum specific IgA of Epstein-Barr virus (EBV) VCA. Patient serum samples were analyzed with the strip and compared with enzyme-linked immunosorbent assay (ELISA) and pathological evaluation. The obtained results from the ICG strips were well correlated with the two reference methods. An evaluation of stability, sensitivity and specificity suggested the strip suitable for NPC screening programs in high-risk peoples and also for the recurrence monitoring.

Birth is an event that exposes the newborn baby to a high concentration of free radicals (reactive oxygen species (ROS)/reactive nitrogen species (RNS)), which can contribute to several diseases. The balanced equilibrium between ROS/RNS and the antioxidant system of the newborn is a key factor in preventing a plethora of diseases. The antioxidant system involves endogenous and exogenous molecules, from vitamins (A, E, C) to enzymes (glutathione peroxidase, superoxide dismutase), metals (copper, zinc, and selenium) and other molecules (coenzyme Q₁₀, melatonin) that can act in a synergistic manner to deactivate free radicals. A competent antioxidant system of the baby is strongly dependent on the intake of free radical deactivating molecules from feeding, either maternal or formula milk, with several studies pointing that breast milk has more powerful antioxidant effects on lowering the infant's oxidative status. An improved understanding of the antioxidant molecules, their mechanism of action, and the relationships between them, are key factors to comprehend all the potential benefits of human breastfeeding in this matter. The purpose of this review is to describe different research efforts and methodologies of evaluation of TAS in human milk, and to evaluate and summarize the contribution of different antioxidant molecules.

Intercellular interactions are able to influence the biological properties of many types of tumors including malignant melanoma. Differentiation pattern of melanoma cells is significantly influenced by the melanoma-associated fibroblasts but the information about interaction of these cells with other important element of melanoma microenvironment, resp. with keratinocytes, is limited. In this, study we tested the effect of fibroblasts isolated from malignant melanoma on phenotype of normal human keratinocytes, especially on their expression of vimentin, a cytoskeletal protein weakly expressed in normal human keratinocytes. The co-culture with normal dermal fibroblasts was used for comparison. The results demonstrated the high expression of vimentin in keratinocytes co-cultured with melanoma-associated fibroblasts compared with those co-cultured with normal dermal fibroblasts. These data suggest participation of melanoma-associated fibroblasts-keratinocyte crosstalk in formation of melanoma niche.

Electrogastrography (EGG) is a non-invasive method for the assessment of gastric myoelectrical activity. Porcine EGG is comparable with human one. There are no data on the impact of moderate to high doses of atropine on EGG, neither in humans nor experimental pigs. The purpose of this study was to evaluate the effect of different doses of atropine on EGG in experimental pigs.
Six fasting pigs entered the study three times in a random order. The baseline EGG recording lasted 20 min, followed by a 105-min EGG trial recording. Intramuscular atropine 1.5 mg (part 1), 3.0 mg (part 2) and 4.5 mg (part 3) was administrated after the baseline EGG.
Atropine doses of 1.5 and 3.0 mg revealed a similar pattern in the EGG power course. After an initial increase (at the first 15-min interval), the areas of amplitudes decreased back to values comparable with basal levels and subsequently increased significantly again to the maximum at 105 min. The EGG power was quite different after the administration of 4.5 mg of atropine. Areas of amplitudes decreased gradually to the minimum values at 105 min after atropine administration.
In conclusion, different dose-dependent changes in the EGG pattern were found after moderate to high doses of atropine.

Ocimum sanctum L. (OS) leaves have been shown to have a potential for lipid-lowering action. The present study was conducted to evaluate the anti-hyperlipidaemic ability of the EO extracted from OS leaves in rats fed with a high cholesterol (HC) diet. EO of OS leaves was extracted using the hydrodistillation method and its chemical composition was further determined by GC-MS. The results showed that phenylpropanoid compounds (eugenol and methyl eugenol) were the major components of the EO. There were no significant differences in body weight gain, food intake, and heart weight in all groups of rats. The HC diet apparently raised the serum total cholesterol, LDL-C and atherogenic index without significant effect on serum triglyceride, whereas it decreased the HDL-C level. The EO significantly decreased serum total cholesterol, LDL-C, triglyceride and atherogenic index whereas no significant effect on HDL-C was observed. EO depressed a high level of liver total cholesterol and triglyceride whereas no significant effect on both lipids excreted in faeces was found. It can be concluded that the EO extracted from OS leaves contributes to a lipid-lowering action in HC rats. Its anti-hyperlipidaemic action is predominantly due to the suppression of liver lipid synthesis. Phenylpropanoid compounds, the main composition of EO are possibly responsible for the lipid-lowering effect.

Huperzine A (Hup A) is a reversible AChE inhibitor that crosses the blood-brain barrier. It is presently approved for, or is in a course of clinical trials for, the treatment of Alzheimer's disease. This compound has also been successfully tested for the pretreatment of organophosphate poisoning. Organophosphate nerve agents are potent irreversible inhibitors of acetylcholinesterase in the central and also in the peripheral compartment. In this study Hup A in a higher dose (500 μg/kg) was tested as a prophylaxis against a high, mainly centrally acting, nerve agent (soman). According to the results obtained, Hup A in this dosage was not able to protect AChE against soman in both the peripheral and central compartments. The effect of Hup A and soman was found to be additive and all animal subjects died.

The content of nitrite admixture in preparations of dinitrosyl iron complexes (DNIC) with glutathione synthesized by treatment of aqueous solutions of Fe²⁺ + glutathione with gaseous NO (complex 1) or by mixing solutions of S-nitrosoglutathione (GS-NO) with solutions of Fe²⁺ + glutathione (complex 2) was determined using the Griess method and HPLC as well as from the level of HNO₂ formed upon interaction of gaseous NO with acidified distilled water. In both preparations, DNIC were predominantly represented by the binuclear form (B-DNIC). In complex 1, the appearance of nitrite in DNIC solutions was induced by nitrogen dioxide present in gaseous NO; its interaction with NO gives an adduct, which is further hydrolyzed to nitrite in aqueous solutions. In complex 2, the presence of nitrite admixture could appear in the presence of nitrite non-incorporated into GS-NO synthesized by mixing glutathione and nitrite in acid media. The per cent content of nitrite (with respect to the total content of complex 1) was 6%, whereas in complex 2 it was as low as 0.4%. Such a low level of nitrite contamination in the course of conventional synthesis of DNIC with glutathione does not make any significant contribution to their biomedical (e.g., hypotensive or vasodilator) activity.

The ability to detect pathogenic and physiologically relevant molecules in the body with high sensitivity and specificity offers a powerful opportunity in the early diagnosis and treatment of diseases. Early detection and diagnosis can be used to greatly reduce the cost of patient care associated with the advanced stages of many diseases. However, despite their widespread clinical use, these techniques have a number of potential limitations. For example, a number of diagnostic devices have slow response times and are burdensome to patients. Furthermore, these assays are expensive and cost the health care industry billions of dollars every year. Therefore, there is a need to develop more efficient and reliable sensing and detection technologies. A biosensor is commonly defined as an analytical device that uses a biological recognition system to target molecules or macromolecules. Biosensors can be coupled to a physiochemical transducer that converts this recognition into a detectable output signal. Typically biosensors are comprised of three components: (1) the detector, which identifies the stimulus; (2) the transducer, which converts this stimulus to a useful output; and (3) the signal processing system, which involves amplification and display of the output in an appropriate format. The goal of this combination is to utilize the high sensitivity and selectivity of biological sensing for analytical purposes in various fields of research and technology. We review here some of the main advances in this field over the past few years, explore the application prospects, and discuss the issues, approaches, and challenges, with the aim of stimulating a broader interest in developing biosensors and improving their applications in medical diagnosis.

To evaluate parallel circadian rhythms in salivary and serum cortisol concentrations during 48-h period, sampling was performed in six clinically healthy dogs of various breeds housed under natural photoperiod in spring (sunrise 05:20, sunset 20:20). Saliva and blood samples were taken every 3 h for a 48-h period to determine the daily changes in salivary and serum cortisol concentrations. The relationship between salivary and serum cortisol level was determined as well. In the two-day period of monitoring, salivary and serum cortisol concentrations showed the same trend. Their levels started to increase at sunrise and reached their peak in the middle of the photophase. Both parameters showed a high robustness of rhythm. A positive correlation between salivary and serum cortisol concentration was observed during the day 1 and 2. Acrophase and robustness of rhythm showed no statistically significant difference between salivary and serum cortisol concentrations. We can claim that salivary cortisol, a measure of free cortisol, follows the circadian rhythm of serum cortisol. Therefore, saliva sampling is a valid and non-invasive technique useful in chronomedicine to estimate free cortisol.

Increased visfatin expression has been shown to increase gene expression, which promotes cell survival and increases SirT1 activity thereby promoting angiogenesis. Previous studies have shown that oral squamous cell carcinomas (OSCCs) express high levels of activated signal transducer and activator of transcription 3 (Stat3). Since visfatin expression is increased by Stat3, we hypothesized that visfatin protein may be highly expressed in OSCCs. Immunohistochemistry was the technique used to examine the expression of visfatin in 19 OSCCs and 4 hyperplastic lesions. The results indicated that visfatin was detected in the cytoplasm and nuclei of the OSCCs and epithelial hyperplasia as well as in the stromal tissues of patients with OSCC and oral hyperplasia. Furthermore, co-expression of visfatin and proliferating cell nuclear antigen proteins was noted in verrucous epithelial hyperplasia, and co-expression of visfatin and CD68 in the inflammatory cells of the stromal region was noted in the OSCCs. In addition, enzyme-linked immunosorbent assay showed that plasma visfatin concentrations were significantly increased in the patients with OSCC and oral hyperplasia compared to those of the control subjects. In conclusion, visfatin expression and concentrations were higher in OSCCs and oral hyperplasia, suggesting that visfatin may play a role in the pathogenesis of oral cancers.

Avidity is an important feature of antibodies associated with their pathogenic effects. Anticardiolipin antibodies (aCLs) are the most commonly examined antiphospholipid antibodies, however, their avidity has been investigated only marginally. The aim of the study was to compare the avidity of the antibodies specifically bound to the cardiolipin-coated microtitrate wells with those bound to the wells bearing no cardiolipin in various conditions. We analysed 22 serum samples with high, medium and low levels of aCL IgG. The avidity of aCL IgG was determined in serially diluted sera by the ELISA method in the presence of increasing urea concentrations (from 2 to 8 mol/L) as a chaotropic agent. The serum dilution 1:50 and 1:100 and the concentrations of urea 6 mol/L and 8 mol/L seemed to be suitable for the determination of aCL avidity. The avidity of antibodies specifically bound to the cardiolipin and those bound to the cardiolipin-free wells significantly differed in their avidity. The simultaneous determination of higher-avidity aCL and lower-avidity polyspecific antibodies, whose presence complicates the ELISA methods by an increase of the background signal, might limit the shortcomings of some ELISA methods.

Epigallocatechin-3-gallate (EGCG) is widely used as a weight controlling supplement. Concerns about its safety evoked after cases of hepatotoxicity occurred upon its use. The underlying factors that could be involved in EGCG associated hepatotoxicity are not fully studied. In this study, we investigated the possible impact of lipopolysaccharide (LPS), as an inflammagen, on the effect of EGCG on hepatocytes. HepG2 cells were treated with different concentrations of EGCG (100, 200, 500 μM), with and without LPS (10 nM)-presensitization of the cells. Viability of HepG2 cells decreased with the increased concentrations of EGCG; the viability was even lesser in LPS-presensitized cells. Oxidative stress (Ox.LDL and CXCL16), the expression of nuclear retinoic receptors (RAR, RXR) and the biomarkers of hepatocellular injury (TNFα, TGFβ1) were all relatively higher in LPS-presensitized cells compared to non-sensitized cells upon treatment with EGCG. Sensitization of HepG2 cells with LPS alone did not affect the viability or any of the other biomarkers considered in this study. In conclusion, EGCG alone can be harmful to liver at high concentrations and this effect may become more pronounced under the influence of an inflammagen.

Melanins are polymorphous and multifunctional biopolymers with a relatively high concentration of free radicals. EPR spectroscopy was used to study o-semiquinone free radicals in model eumelanins synthesized from 3,4-dihydroxyphenylalanine (DOPA) and tyrosine in the presence of tyrosinase, and melanins isolated from A-375 and G-361 human melanoma malignum cells exposed to two compounds: 5,7-dimethoxycoumarin (DMC) and valproic acid (VPA). Changes were determined in the concentrations of free radicals in the individual melanins from tumour cells treated with DMC and VPA. A strong decrease in the concentrations of free radicals characterizes melanins isolated from tumour cells treated together with DMC and VPA. Slow spin-lattice relaxation processes were noted in the melanins tested with homogeneous broadened EPR spectra. The EPR technique may be useful not only for the elucidation of free radicals in melanins from A-375 and G-361 cells treated with VPA and DMC but it could also be applied to establish the relationship between melanin type and the malignancy of melanoma malignum.

The primary aim of this study was to investigate the effects of ortanique peel polymethoxylated flavones extract (PMF^ort) on antioxidant enzymes activities and lipid peroxide levels in organs of hypercholesterolemic and normal rats. Thirty Sprague-Dawley rats were fed high cholesterol diets supplemented with 1.5% PMF^ort and niacin respectively for 49 days. Hypercholesterolemic rats fed PMF^ort had significant reductions in malondialdehyde levels in the liver and brain compared to untreated hypercholesterolemic control rats. This reduction also occurred in the brain of the rats fed niacin. The activities of catalase, glutathione reductase, transferase and peroxidase were significantly reduced in the spleen, brain and liver of hypercholesterolemic rats fed PMF^ort compared to control. The activities of these enzymes were only reduced in the brain and liver of rats fed niacin. The results would suggest that PMF^ort modulates hypercholesterolemia-associated organ injury and oxidative stress in rat organs. PMF^ort could therefore be a suitable candidate of natural origin for prophylactic and therapeutic treatment of hypercholesterolemia-associated oxidative stress and organ injury.

The appearance of heterochromatin is generally accepted as a useful tool for the evaluation of the cell state including pathology; however, information on the heterochromatin DNA condensation state expressed by the image optical density in interphase nuclear regions and mitotic chromosomes with silent genes is very limited. Since human proliferating myeloblasts are a very convenient model, they were studied in the bone marrow of leukemic patients and established cell cultures using computer assisted image densitometry at the single cell level after heterochromatin visualization by a simple but sensitive cytochemical procedure for demonstration of DNA. As was expected, a high DNA image optical density was noted in central heterochromatin regions in contrast to the nuclear periphery at the nuclear envelope. Similarly, a high nuclear DNA image optical density was also expressed in mitotic chromosomes. Thus the possibility exists that the large heterochromatin DNA condensation expressed by the large image optical density in central nuclear regions, as in mitotic chromosomes, is related to silent gene locations. The similar width of mitotic chromosomes and chromatin fibrils in the heterochromatin regions in the interphase nuclei supports that explanation. The chromatin DNA fibrils in the central heterochromatin nuclear regions of interphase cells might just represent masked silent chromosomal segments. Such a conclusion is in harmony with "classical" cytology in the first part of the last century, which suggests the chromosome continuity from the mitotic division to the interphase where each chromatin region ("Kernbezirk") actually represents a chromosomal territory.

Impaired daily rhythms in vertebrate physiology occur with age. Particularly, age-related changes in melatonin and serotonin rhythms and hypercortisolemia have been reported to be linked to age-related disorders. This study was aimed at assessing the effect of a Jerte Valley cherry-based nutraceutical product (patent no ES 2342141 B1), which contains high levels of tryptophan, serotonin, and melatonin, on the serum melatonin, serotonin, corticosterone, and total antioxidant capacity (TAC) levels in young and old ring doves (Streptopelia risoria) and rats (Rattus norvegicus) as representatives of animals with diurnal and nocturnal habits, respectively. The animals consumed the cherry product for 10 days. Serum melatonin, serotonin, corticosterone, and TAC were measured with commercial ELISA kits. The consumption of the cherry product induced a significant increase in the circulating levels of melatonin and serotonin, as well as in the serum TAC and a significant decrease in the circulating levels of corticosterone in both species and groups of age as compared to their respective values in the control groups. The consumption of a Jerte Valley cherry-based nutraceutical product may help to counteract the decrease in melatonin and serotonin and the increase in oxidative stress, suggesting a potential health benefit especially in aged populations where these parameters have been found to be altered.

Proteins MPT63 and MPT83 which are common for both Mycobacterium tuberculosis and Mycobacterium bovis, due to their high immunogenicity, are thought to play a promising role in the development of immunodiagnostic reagents and vaccines. To enhance the antigenic and immunogenic properties of these proteins, fragments of the mpt83 and mpt63 genes were fused in tandem. In this article we present an effective method for the MPT63-MPT83 fusion product purification by metal-affinity chromatography and in vitro refolding. Our results demonstrate that the antigenic properties of the recombinant proteins obtained are comparable to their native analogues. The anti-rMPT63 and anti-rMPT83 sera were found to be highly reactive against the rMPT63-MPT83 fusion protein, which suggests that the fusion protein retains the antigenic properties of the parent proteins. Our results may potentially contribute to the development of improved diagnostic tools or vaccines against human and/or cattle tuberculosis.

New components of transdisciplinary spectra or known components in new variables in us, matching those around us, are being mapped. Their hardly trivial interactions associated with the good and bad around us - from religiosity to crime and war - are being rendered measurable, for the eventual development of countermeasures to the diseases of societies and nations. Internal cycles not only underlie life itself and underlie our evolving genetics at all levels of organization; they also constitute the essential control and reference information in all transdisciplinary science. In preparing for travel to Mars and other missions in space that may take more than a year, let us do what is immediately practicable. Transyears may have very small amplitudes yet are associated with sudden cardiac death in some terrestrial locations; if they should play a role in these electrical incidents of the heart, among others like myocardial infarction and stroke, they will jeopardize lengthy missions in extraterrestrial space, away from hospitals.
The likelihood of stroke or cardiac death can be immediately reduced by chronobiologically assessing blood pressure and heart rate variability and by optimizing the efficacy of timed treatment rather than relying on an unacceptable and often inaccurate spotcheck and treating by convenience rather than pertinence. Needed are: detection of nocturnal abnormality when medication may no longer be effective (or is too effective) neither seen during office visits by day; detection of circadian hyper-amplitude-tension (CHAT) associated with a risk of stroke and kidney disease greater than other risks (including "hypertension" when all risks are assessed concomitantly); detection of CHAT as high risk among normotensives who may not need anti-hypertensive medication; individualized inferential statistical testing to determine whether a drug or non-drug intervention such as autogenic training (relaxation) is effective and for how long (detecting any initial and later success or failure), some of which conditions otherwise are not found without chronobiology; individualization of treatment timing, since the same dose of the same medication can further lower the subject's blood pressure average and circadian amplitude when the timing of daily administration is optimized, as ascertained by sequential testing and parameter tests.
Thus, we save lives by monitoring and assessing, and if need be treating, vascular disease risk through chronobiologically interpreted 24-hour or preferably longer (24-hour/7-day) blood pressure and heart rate variability. Abnormalities in the variability of blood pressure and heart rate, impossible to find during a conventional office visit (the latter aiming at the fiction of a "true" blood pressure), can raise cardiovascular disease risk in the next six years from 4% to 100%.

Selective congruence, namely a pairing of various biospheric cycles of certain frequencies with different environmental ones and further selectivity of phase behavior at the given frequency characterize an ultradian to infradian, prominently circadian transdisciplinary spectrum. Diseases documented among others to be influenced by the cosmos range from individuals' strokes to populations' crime and terrorism, conditions studied by chronomics as time structures (chronomes). Methods of investigation include the extended cosinor allowing for the added estimation of the period with a measure of uncertainty, as well as global and gliding spectral windows complemented by chronobiologic serial sections. These methods estimate, each of them with uncertainties, changes as a function of time in weather on earth and in space on the one hand and in human personal and broader affairs on the other. They further map features of these time structures that may change as a function of time in a logically consistent way. Associations of several biological time series with physical environmental variables are presented herein, as are methods used for their investigation and a statistical assessment of their congruence.

Arterial hypertension is a polygenic disease and about 50 candidate genes have been analysed. We followed the size of the heart sections and the endothelial function in juvenile hypertensives according to the polymorphisms in the genes for angiotensin converting enzyme (I/D), endothelin 1 (Lys198/Asn) and endothelin 1 converting enzyme (Thr341/Ile).
We observed 44 juvenile hypertensives and 94 controls of the same age. An echocardiographic examination was carried out during standard examinations. The endothelial function was analysed with the use of ultrasound with high acuity after revoking a reactive hyperaemia. The genotypisations were performed using the polymerase chain reaction and restriction analysis. Statistical analyses were carried out using the BMDP statistical software.
There were no differences between controls and hypertensives in alleles frequency. The hypertensives differed from the control group in the endothelial function (statistically significant). The hypertensives homozygotes D/D and the heterozygotes Lys198/Asn had a larger left ventricle (statistically significant); the hypertensives with the Thr341/Ile had a larger left ventricle septum (statistically significant) and back wall of the left ventricle (statistically significant) than the controls with the same genotype.
We concluded that the genes for ACE, endothelin 1 and endothelin 1 converting enzyme have an influence on the size of the heart sections and on the endothelial function of the juvenile hypertensives.