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The need to explore the abundance of natural products cannot be overemphasized particularly in the management of various disease conditions. In traditional medical practice, Vernonia amygdalina has been widely adopted in the management of various inflammatory disorders. The objective of this investigation was to isolate the bioactive principles from the stem-bark and root of V. amygdalina and assess the anti-inflammatory (in vitro) activity of both the crude extracts and the isolated compounds. Following extraction with the methanol, the extract was subjected to gravity column chromatography and the resultant fractions was further purified to obtained pure compounds. The structural elucidation of the compounds were based on data obtained from 1H to 13C nuclear magnetic resonance (NMR) spectroscopies as well as fourier transform infrared (FT-IR). Using diclofenac as a control drug, the albumin denaturation assay was used to determine the in vitro anti-inflammatory activity of the extracts and isolates. Three distinct compounds characterized are vernoamyoside D, luteolin-7-α-o-glucuronide, and vernotolaside, a new glycoside. When compared to diclofenac, which has an IC50 of 167.8 µg/mL, luteolin-7-α-o-glucuronide, vernoamyoside D, and vernotolaside all showed significant inhibitions with respective IC50 values 549.8, 379.5, and 201.7 µg/mL. Vernotolaside is reported for the first time from the root. The assertion that the plant is used in traditional medicine for the management of inflammatory disorder is somewhat validated by the confirmation of the existence of the compounds with the biochemical actions. Further validation of the isolated compounds would be required in animal studies.
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BACKGROUND: Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) cause a wide variety of bacterial infections and coinfections, showing a complex interaction that involves the production of different metabolites and metabolic changes. Temperature is a key factor for bacterial survival and virulence and within the host, bacteria could be exposed to an increment in temperature during fever development. We analyzed the previously unexplored effect of fever-like temperatures (39 °C) on S. aureus USA300 and P. aeruginosa PAO1 microaerobic mono- and co-cultures compared with 37 °C, by using RNAseq and physiological assays including in vivo experiments. RESULTS: In general terms both temperature and co-culturing had a strong impact on both PA and SA with the exception of the temperature response of monocultured PA. We studied metabolic and virulence changes in both species. Altered metabolic features at 39 °C included arginine biosynthesis and the periplasmic glucose oxidation in S. aureus and P. aeruginosa monocultures respectively. When PA co-cultures were exposed at 39 °C, they upregulated ethanol oxidation-related genes along with an increment in organic acid accumulation. Regarding virulence factors, monocultured SA showed an increase in the mRNA expression of the agr operon and hld, pmsα, and pmsß genes at 39 °C. Supported by mRNA data, we performed physiological experiments and detected and increment in hemolysis, staphyloxantin production, and a decrease in biofilm formation at 39 °C. On the side of PA monocultures, we observed an increase in extracellular lipase and protease and biofilm formation at 39 °C along with a decrease in the motility in correlation with changes observed at mRNA abundance. Additionally, we assessed host-pathogen interaction both in vitro and in vivo. S. aureus monocultured at 39οC showed a decrease in cellular invasion and an increase in IL-8-but not in IL-6-production by A549 cell line. PA also decreased its cellular invasion when monocultured at 39 °C and did not induce any change in IL-8 or IL-6 production. PA strongly increased cellular invasion when co-cultured at 37 and 39 °C. Finally, we observed increased lethality in mice intranasally inoculated with S. aureus monocultures pre-incubated at 39 °C and even higher levels when inoculated with co-cultures. The bacterial burden for P. aeruginosa was higher in liver when the mice were infected with co-cultures previously incubated at 39 °C comparing with 37 °C. CONCLUSIONS: Our results highlight a relevant change in the virulence of bacterial opportunistic pathogens exposed to fever-like temperatures in presence of competitors, opening new questions related to bacteria-bacteria and host-pathogen interactions and coevolution.
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Infecções por Pseudomonas , Infecções Estafilocócicas , Camundongos , Animais , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Virulência/fisiologia , Pseudomonas aeruginosa , Temperatura , Interleucina-6/metabolismo , Interleucina-6/farmacologia , Interleucina-8/metabolismo , Interleucina-8/farmacologia , Infecções por Pseudomonas/microbiologia , RNA Mensageiro/metabolismo , Biofilmes , Infecções Estafilocócicas/microbiologiaRESUMO
Allergen immunotherapies are often successful at desensitizing allergic patients but can require life-long dosing and suffer from frequent adverse events including instances of systemic anaphylaxis, leading to poor patient compliance and high cost. Allergen vaccines, in turn, can generate more durable immunological allergen desensitization with far fewer doses. However, like immunotherapies, allergen vaccines are often highly reactogenic in allergic patients, hampering their use in therapeutic settings. In this work, we utilize a peptide-based self-assembling nanofiber platform to design allergen vaccines against allergen B-cell epitopes that do not elicit systemic anaphylaxis when administered subcutaneously to allergic mice. We show that, in contrast to protein vaccines, nanofiber vaccines prevent leakage of allergen material into the vascular compartment, a feature that likely underpins their reduced systemic reactogenicity. Further, we show that our allergen vaccine platform elicits therapeutic IgG antibody responses capable of desensitizing allergic mice to allergen-induced Type I hypersensitivity reactions. Finally, we have demonstrated a proof-of-concept for the therapeutic potential of nanofiber-based peanut allergen vaccines directed against peanut allergen-derived epitopes.
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Anafilaxia , Vacinas , Humanos , Animais , Camundongos , Alérgenos , Dessensibilização Imunológica , Imunoglobulina GRESUMO
Background: The most common intracranial neoplasm worldwide is meningioma, followed by gliomas, and then pituitary adenomas. There are geographical differences in the pattern of occurrence of intracranial neoplasms.The purpose of this study is to establish the pattern of occurrence of different histological types of intracranial neoplasms with their age and sex distributions in our environment - Lagos, Nigeria.The histological patterns, age, and gender distributions of all the intracranial neoplasms diagnosed within the study period at the Department of Anatomic and Molecular Pathology, LUTH, Lagos, Nigeria were noted and analysed with SPSS version 23. Result: There were 296 patients (165 females, 131 males; mean age of 37.0 years) diagnosed with an intracranial neoplasm within the study period. The most frequently diagnosed intracranial neoplasm was meningioma (105 cases; 35%, median age of 42 years, male to female ratio of 1:2.2), followed by pituitary adenoma (78 cases; 26%, median age of 47 years, male to female ratio of 1.3:1), and then gliomas (71 cases; 24%, median age of 28, male to female ratio of 1:1.39). Conclusion: The result of the study shows pituitary adenoma to be more common than gliomas, unlike what is seen in Caucasians where the reverse is the case.
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Neoplasias Encefálicas , Glioma , Neoplasias Meníngeas , Meningioma , Neoplasias Hipofisárias , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Meningioma/epidemiologia , Neoplasias Hipofisárias/epidemiologia , Nigéria/epidemiologia , Universidades , Hospitais de Ensino , Neoplasias Encefálicas/epidemiologia , Glioma/epidemiologiaRESUMO
BACKGROUND: Access to health services during pregnancy, childbirth and the period after birth provides a substantial opportunity to limit cases of maternal mortality. In sub-Saharan Africa, the proportions of women who utilize health services remain below 70%. This study examined the factors associated with partial and adequate maternal health services utilization in Nigeria. METHODS: This paper used data from 2018 Nigeria Demographic and Health Survey (DHS) comprising 21,792 women aged 15-49 years who had given births within five years of the survey. The study focused on antenatal care attendance, place of birth and postnatal care using a combined model. Multinomial logistic regression was applied in the analysis. RESULTS: About 74% of the women attended antenatal care, 41% gave birth in health facilities and 21% attended postnatal care. While 68% of the women partially utilized health services, 11% adequately utilized the services. The odds of partially and adequately utilizing health services increased for ever married women, women with secondary or higher education, from richest households, living in urban area, having no problem either getting permission to visit health facility or reaching health facility. CONCLUSIONS: This study has revealed the factors associated with partial and adequate utilization of maternal health services in Nigeria. Such factors include education, household wealth, marital status, employment status, residence, region, media exposure, getting permission to use health service, unwillingness to visit health facility without being accompanied and distance to health facility. Efforts aimed at improving maternal health services utilization should place emphasis on these factors.
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Serviços de Saúde Materna , Feminino , Gravidez , Humanos , Estudos Transversais , Nigéria , Aceitação pelo Paciente de Cuidados de Saúde , Cuidado Pré-NatalRESUMO
OBJECTIVES: Syncope at age 65+ is associated with increased mortality, irrespective of cause. Syncope rules were designed to aid in risk-stratification but were only validated in the general adult population. Our objective was to determine if they can be applied to a geriatric population in predicting short-term adverse outcomes. METHODS: In this single-center retrospective study, we evaluated 350 patients aged 65+ presenting with syncope. Exclusion criteria included confirmed non-syncope, active medical condition, drug or alcohol-related syncope. Patients were stratified into high or low risk based on Canadian Syncope Risk Score (CSRS), Evaluation of Guidelines in Syncope Study (EGSYS), San Francisco Syncope Rule (SFSR), and Risk Stratification of Syncope in the Emergency Department (ROSE). Composite adverse outcomes at 48-hour and 30-day included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), return emergency department visit, hospitalization, or medical intervention. We assessed each score's ability to predict the outcomes using logistic-regression and compared performances using receiver-operator curves. Multivariate analyses were performed to study the associations between recorded parameters and outcomes. RESULTS: CSRS outperformed with AUC of 0.732 (95% CI: 0.653-0.812) and 0.749 (95% CI: 0.688-0.809) for 48-h and 30-day outcomes, respectively. Sensitivities for CSRS, EGSYS, SFSR, and ROSE for 48-hour outcomes were 48%, 65%, 42% and 19%; and for 30-day outcomes were 72%, 65%, 30% and 55%, respectively. Atrial fibrillation/flutter on EKG, congestive heart failure, antiarrhythmics, systolic blood-pressure < 90 at triage, and associated chest pain highly correlated with 48-h outcomes. An EKG abnormality, heart disease history, severe pulmonary hypertension, BNP > 300, vasovagal predisposition, and antidepressants highly correlated with 30-day outcomes. CONCLUSIONS: Performance and accuracy of four prominent syncope rules were suboptimal in identifying high-risk geriatric patients with short-term adverse outcomes. We identified some significant clinical and laboratory information that may play a role in predicting short-term adverse events in a geriatric cohort.
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Background: Staphylococcus aureus and Pseudomonas aeruginosa cause a wide variety of bacterial infections and coinfections, showing a complex interaction that involves the production of different metabolites and metabolic changes. Temperature is a key factor for bacterial survival and virulence and within the host, bacteria could be exposed to an increment in temperature during fever development. We analyzed the previously unexplored effect of fever-like temperatures (39°C) on S. aureus USA300 and P. aeruginosa PAO1 microaerobic mono- and co-cultures compared with 37°C, by using RNAseq and physiological assays including in-vivo experiments. Results: In general terms both temperature and co-culturing had a strong impact on both PA and SA with the exception of the temperature response of monocultured PA. We studied metabolic and virulence changes on both species. Altered metabolic features at 39°C included arginine biosynthesis and the periplasmic glucose oxidation in S. aureus and P. aeruginosa monocultures respectively. When PA co-cultures were exposed at 39°C they upregulated ethanol oxidation related genes along with an increment in organic acid accumulation. Regarding virulence factors, monocultured SA showed an increase in the mRNA expression of the agr operon and hld, pmsα and pmsß genes at 39°C. Supported by mRNA data, we performed physiological experiments and detected and increment in hemolysis, staphylxantin production and a decrease in biofilm formation at 39°C. On the side of PA monocultures, we observed increase in extracellular lipase and protease and biofilm formation at 39°C along with a decrease in motility in correlation with changes observed at mRNA abundance. Additionally, we assessed host-pathogen interaction both in-vitro and in-vivo . S. aureus monocultured at 39°C showed a decrease in cellular invasion and an increase in IL-8 -but not in IL-6- production by A549 cell line. PA also decreased its cellular invasion when monocultured at 39°C and did not induce any change in IL-8 or IL-6 production. PA strongly increased cellular invasion when co-cultured at 37°C and 39°C. Finally, we observed increased lethality in mice intranasally inoculated with S. aureus monocultures pre-incubated at 39°C and even higher levels when inoculated with co-cultures. The bacterial burden for P. aeruginosa was higher in liver when the mice were infected with co-cultures previously incubated at 39°C comparing with 37°C. Conclusion: Our results highlight a relevant change in the virulence of bacterial opportunistic pathogens exposed to fever-like temperatures in presence of competitors, opening new questions related to bacteria-bacteria and host-pathogen interactions and coevolution.
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Studies have implicated oxidative stress-sensitive signaling in the pathogenesis of stress-induced male infertility. However, apart from oxidative stress, gonadotropin inhibitory hormone (GnIH) plays a major role. The present study provides a detailed review of the role of GnIH in stress-induced male infertility. Available evidence-based data revealed that GnIH enhances the release of corticosteroids by activating the hypothalamic-pituitary-adrenal axis. GnIH also mediates the inhibition of the conversion of thyroxine (T4) to triiodothyronine (T3) by suppressing the hypothalamic-pituitary-thyroidal axis. In addition, GnIH inhibits gonadotropin-releasing hormone (GnRH), thus suppressing the hypothalamic-pituitary-testicular axis, and by extension testosterone biosynthesis. More so, GnIH inhibits kisspeptin release. These events distort testicular histoarchitecture, impair testicular and adrenal steroidogenesis, lower spermatogenesis, and deteriorate sperm quality and function. In conclusion, GnIH, via multiple mechanisms, plays a key role in stress-induced male infertility. Suppression of GnIH under stressful conditions may thus be a beneficial prophylactic and/or therapeutic strategy.
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Sistema Hipotálamo-Hipofisário , Infertilidade Masculina , Masculino , Humanos , Sistema Hipófise-Suprarrenal , Sêmen , Gonadotropinas , Infertilidade Masculina/etiologia , FertilidadeRESUMO
Urinary tract infections (UTIs) are a major public health problem affecting millions of individuals each year. Recurrent UTIs are managed by long-term antibiotic use, making the alarming rise of antibiotic resistance a substantial threat to future UTI treatment. Extended antibiotic regimens may also have adverse effects on the microbiome. Here, we report the use of a supramolecular vaccine to provide long-term protection against uropathogenic Escherichia coli, which cause 80% of uncomplicated UTIs. We designed mucus-penetrating peptide-polymer nanofibers to enable sublingual (under the tongue) vaccine delivery and elicit antibody responses systemically and in the urogenital tract. In a mouse model of UTI, we demonstrate equivalent efficacy to high-dose oral antibiotics but with significantly less perturbation of the gut microbiome. We also formulate our vaccine as a rapid-dissolving sublingual tablet that raises response in mice and rabbits. Our approach represents a promising alternative to antibiotics for the treatment and prevention of UTIs.
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Infecções por Escherichia coli , Nanofibras , Infecções Urinárias , Vacinas , Camundongos , Coelhos , Animais , Infecções por Escherichia coli/prevenção & controle , Infecções Urinárias/prevenção & controle , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
Airway smooth muscle contraction is one of the primary factors involved in the initiation and progression of asthma which in turn is regulated by increased cytosolic Ca2+ concentration from intracellular stores and through transmembrane ion channels. Calcium-independent factors such as reactive oxygen species (ROS) generation, nitric oxide (NO) depletion and cyclooxygenase (COX) pathways also contribute to tracheal smooth muscle contraction. Studies on copper toxicity suggest significance of this essential micronutrient overdose in acute respiratory disorders, allergic asthma and ciliary motion in tracheal explants. However, the mechanism of copper caused hypercontraction upon direct exposure to tracheal smooth muscle is largely unknown. In this study we investigate the effect of copper exposure on isolated tracheal rings and relative contributions of various factors in acetylcholine-induced contractions. Results obtained suggest that rise in intracellular calcium concentration via voltage-operated Ca2+ channel (VOCC), store-operated Ca2+ channel (SOCC), stretch-activated channels (SAC) and TRP channel (transient receptor potential channel) activation is the major factor in copper-mediated hypercontraction. ROS generation or COX-dependent pathways do not appear to significantly contribute to Cu2+ caused hypercontraction.
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Contração Muscular , Músculo Liso , Acetilcolina , Animais , Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , RatosRESUMO
Engineered nanoparticles are known to boost membrane performance in membrane technology. Hitherto, tunable properties that lead to improved hydrophilicity due to increased surface oxygen functionalities upon oxidation of petrol soot have not been fully exploited in membrane filtration technology. Herein, the integration of oxidized petrol soot nanoparticles (PSN) into polyethersulfone ultrafiltration membranes produced via phase inversion technique for dye removal in wastewater is reported. The nanoparticles, as well as the composite membranes, were characterized with diverse physicochemical methods, particularly TEM, SEM, BET, AFM, contact angle, etc. The effect of varying the ratio of PSN (0.05-1.0 wt %) on the properties of the composite membrane was evaluated. The composite membranes displayed increased hydrophilicity, enhanced pure water flux, and antifouling properties relative to the pristine membrane. For example, the obtained pure water flux increased from 130 L·m-2·h-1 for base membrane to 265 L·m-2·h-1 for the best composite membrane (M4). The best flux recovery ratio (FRR) observed for the membranes containing PSN was ca. 80% in contrast to 49% obtained with the pristine membrane indicative of the positive influence of PSN on membrane antifouling behavior. Furthermore, the PSN composite membranes displayed relatively selective anionic dye rejection of Ë95% for Congo red and between 50-71% for methyl orange compared with 42-96% rejection obtained for cationic methylene blue dye with increasing PSN content. The successful fabrication of polyethersulfone-PSN composite membranes by a simple blending process opens a novel route for the preparation of economical, functional, and scalable water purification membranes capable of addressing the complex issue of water remediation of organic azo dyes.
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Existing studies show a consensus on the importance of women's household decision-making autonomy. However, the studies also show mixed findings of the association between the variable and intimate partner violence (IPV). In this study, moderating effects of husband's controlling and domineering attitudes on the association between women's household decision-making autonomy and husband-perpetrated physical, sexual, and emotional violence were investigated. Data used in the study were drawn from an existing database of a 2013 cross-sectional Demographic and Health Survey (DHS) of nationally representative sample (N = 19,360) of Nigerian married women. Participants were interviewed on measures of women's autonomy, husband's attitudes, and husband-perpetrated violence. Results revealed that women who exercised high household decision-making autonomy significantly experienced more physical (b = .31, t = 11.78, p < .001), sexual (b = .05, t = 3.59, p < .01), and emotional (b = .17, t = 9.76, p < .001) violence if they reported relationship with husbands who endorsed high controlling and domineering attitudes. The results represent an extension over existing research and have implications on how husband's attitudes could improve women's autonomy and reduce their IPV experience in various intervention settings.
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Violência por Parceiro Íntimo , Cônjuges , Atitude , Estudos Transversais , Feminino , Humanos , Violência por Parceiro Íntimo/prevenção & controle , Nigéria , Fatores de RiscoRESUMO
Husband's controlling and domineering attitudes have been shown to contribute to women's intimate partner violence experience in Nigeria. Some scholars have suggested that women's safer sex negotiation may create additional opportunity for incurring partner violence. The purpose of the current study was to test the possibility that married women's tendency to negotiate safer sex would contribute significant additional proportions of the variance in their experience of physical, sexual, and emotional violence. Using nationally representative data from a sample of married women in Nigeria (N = 19,360), three separate hierarchical regression analyses were performed to examine the contributions of husband's controlling and domineering attitudes and tendency to negotiate safer sex to the three types of violence experience. Regression analyses revealed that women whose husbands endorsed more controlling and domineering attitudes experienced more physical, sexual, and emotional violence. Furthermore, women with higher tendency to negotiate safer sex experienced more of all the forms of violence. After accounting for the influence of husband's controlling and domineering attitudes, regression analyses revealed that women's tendency to negotiate safer sex accounted for significant additional contributions of the variance in physical, sexual, and emotional violence experience. The additional contributions suggest that specific interventions may be needed for improving women's negotiation skills to reduce husband perpetrated violence risk.
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Violência por Parceiro Íntimo , Sexo Seguro , Estudos Transversais , Feminino , Humanos , Negociação , Nigéria , Fatores de RiscoRESUMO
Primary vaginal leiomyosarcoma (VLMS) is an extremely rare variant of primary vaginal cancers with very poor prognosis irrespective of the stage at presentation and the type of treatment received. It is easily recurrent and has a high propensity for haematogenous spread especially to the lungs. We present the case of a 34-year-old Para 1 + 1 (1 alive) woman with recurrent vaginal mass of 8 years duration after two surgical excisions without histological evaluation. She had examination under anaesthesia and a wide local excision of the vaginal mass. Histological examination of the mass revealed poorly differentiated VLMS with positive surgical margins and she was commenced on adjuvant chemo-radiation. Histological evaluation remains the hallmark for diagnosing rare malignancies like VLMS, which unfortunately is not a standard practice in some resource-constraint settings.
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Although there are several reports on the toxic actions of sodium diclofenac (DF), there is dearth information on its effect on the male reproductive system. Therefore, the study investigated the effects of DF and melatonin in male rats. Twenty rats were used in this study, which lasted for 6 weeks. The control group (vehicle treated) received normal saline (0.1â¯ml/day, p.o.). In the experimental groups, DF was administered during the first (group 2) and last (group 3) three weeks of the study. However, in group 4, melatonin was administered for 3 weeks, after 3 weeks of treatment with DF. DF and melatonin were administered at 1 and 10â¯mg/kg b.w./day (p.o.) respectively. The results showed that unlike melatonin, DF had no effect on gonadotrophins; however, it caused significant decreases in GNRH and testosterone, but a significant increase in prolactin. Melatonin attenuated the pro-antioxidant and pro-inflammatory effects of DF, which caused significant decreases in SOD, TAC, CAT, but significant elevations in LDH, MDA, uric acid and CRP. Moreover, the hormone reversed the adverse effect of DF on sperm count, sperm motility and sperm morphology. There were slight evidence of the precipitation of imbalance in lipid metabolism by DF and the antidyslipidaemic action of melatonin. Compared to DF, DF recovery showed more adverse effects on prolactin, testosterone, LDH, MDA, UA, CRP, semen parameters (except sperm motility), TC, LDL-c, HDL-c and phospholipid. The histological results agreed with the biochemical assays. In conclusion, the reproductive toxicity effects of DF seem to escalate after withdrawal; however, these effects could be attenuated by treatment with melatonin.
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Reports on the coexistence of diabetes mellitus and osteoarthritis in human subjects dated back to the 1960s. However, there is no account in literature on the co-manifestation of these disease conditions in experimental animals. In our previous study, we reported for the first time, the effects of pharmacological agents on glucoregulatory indices, lipid profile, and inflammatory markers in experimental diabetic-knee osteoarthritic rat. However, in the present study, the effects of salmon calcitonin (Sct), and/or omega-3 fatty acids (N-3) were further investigated on other biomarkers. Forty-nine rats of seven animals per group were used for this study. Diabetes was induced by the administration of streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg). Thereafter, knee osteoarthritis was induced by the intra-articular injection of 4 mg of sodium monoiodoacetate in 40 µl of saline. Nine days after the inductions, treatments started, and they lasted for 4 weeks. N-3 was administered at 200 mg/kg/day, while Sct was administered at 2.5 and 5.0 IU/kg/day. The results of the study indicated that the induced diabetes-knee osteoarthritis caused significant alterations in all the observed biomarkers. Sct showed a dose-specific effect and an additive action with N-3 in reducing malondialdehyde and lactate dehydrogenase, and in elevating total bilirubin and total antioxidant capacity. However, it largely demonstrated a nondose-specific effect and nonadditive action with N-3 on superoxide dismutase, catalase, glutathione peroxidase, total alkaline phosphatase, c-telopeptide of type-I collagen, collagen type-2 alpha 1, and hematological indices. In conclusion, the combined administration of Sct and N-3 proffer better therapeutic effects than the single therapy; therefore, they could be used in the management of diabetic-osteoarthritic condition.
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Cartilagem , Animais , Antioxidantes , Biomarcadores , Calcitonina , Ácidos Graxos Ômega-3 , RatosRESUMO
BACKGROUND: Fungal lipase dependent processes are important for their pathogenicity. Lipases can therefore be explored as direct target of promising herbal antifungals. OBJECTIVE: We explored Aspergillus niger lipase as a direct target of eugenol through spectroscopic techniques and compare results with Bovine Serum Albumin and lysozyme to comment on selectivity of eugenol towards lipase. METHODS: In vitro activity assays of lipase are used to determine concentration ranges. UV-Visible, Fluorescence and Circular dichroism spectroscopy were employed to determine binding constant, stoichiometric binding sites and structural changes in Lipase, BSA and lysozyme following incubation with varying concentrations of eugenol. RESULTS: In activity assays 50% inhibition of lipase was obtained at 0.913 mmoles/litre eugenol. UV-vis spectroscopy shows formation of lipase-eugenol, Bovine Serum Albumin-eugenol and lysozyme-eugenol complex well below this concentration of eugenol. Eugenol binding caused blue shift with Bovine Serum Albumin and lysozyme suggestive of compaction, and red shift with lipase. Negative ellipticity decreased with lipase but increased with Bovine Serum Albumineugenol and lysozyme-eugenol complexes suggesting loss of helical structure for lipase and compaction for Bovine Serum Albumin and lysozyme. Binding of eugenol to lipase was strong (Ka= 4.7 x 106 M-1) as compared to Bovine Serum Albumin and lysozyme. The number of stoichiometric eugenol binding sites on lipase was found to be 2 as compared to 1.37 (Bovine Serum Albumin) and 0.32 (lysozyme). Docking results also suggest strong binding of eugenol with lipase followed by Bovine Serum Albumin and lysozyme. CONCLUSION: Eugenol is found to be effective inhibitor and disruptor of secondary and tertiary structure of lipase, whereas its binding to Bovine Serum Albumin and lysozyme is found to be weak and less disruptive of structures suggesting selectivity of eugenol towards lipase.
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Eugenol/química , Proteínas Fúngicas/antagonistas & inibidores , Lipase/antagonistas & inibidores , Aspergillus niger/enzimologia , Sítios de Ligação , Proteínas Fúngicas/química , Lipase/química , Simulação de Acoplamento Molecular , Muramidase/química , Ligação Proteica , Conformação Proteica , Soroalbumina Bovina/química , Espectrofotometria/métodos , Especificidade por Substrato , TermodinâmicaRESUMO
This study investigated the predictability of physical activity (PA) and body weight status (BWS) on health-related quality of life (HRQoL) of patients with hypertension. A cross-sectional study involved 250 patients with hypertension (≥140/90≤179/109 mmHg) selected from government hospitals in Osun State, Nigeria. Purposive sampling technique was used to select participants. Socio-demographic characteristics and cardiovascular parameters were recorded. PA and HRQoL were assessed using the International Physical Activity Questionnaire and Short Form health survey questionnaire respectively. Sufficient PA equals ≥150 min/wk while BWS was defined using body mass index classification. Data were analyzed using descriptive and inferential statistics. Alpha level was set at P<0.05. Of all participants, 63.6% reported sufficient PA and 78.4% was either overweight or obese. The HRQoL of participants become poorer in all domains with higher body weight. The HRQoL including role limitation due to physical health (RLdPhp) and emotional problems (RLdEmp) had worst scores. Participants in the categories of normal and overweight/obese with sufficient PA demonstrated higher (better) HRQoL in all domains than those with insufficient PA (P<0.05). When adjusted for body weight, significant differences were found in all domains of HRQoL except in RLdPhp, RldEmp, and bodily pain (P>0.05). There were significant correlations between PA and all domains of HRQoL except in RldEmp, emotional well-being and bodily pain (P>0.05). Regression models established PA as a significant predictor of HRQoL. Sufficient PA is a better predictor of HRQoL among patients with hypertension irrespective of BWS. Regular PA is recommended for improving HRQoL among patients with hypertension.
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BACKGROUND: There is a continuous search for a better therapy in osteoarthritis (OA) management. Therefore, this study investigated the effects of salmon calcitonin (Sct) and/or omega-3 fatty acids (N-3) relative to diclofenac sodium (DF) in induced knee osteoarthritic male Wistar rats. METHODS: The 40 rats that were used in this study were divided into 8 groups (n=5 rats), viz: Normal control; OA control; OA+N-3; OA+Low dose of Sct (Sct.Lw); OA+High dose of Sct (Sct.Hi); OA+N-3+SCt.Lw; OA+N-3+Sct.Hi; and, OA+DF. OA was induced with 4 mg of sodium monoiodoacetate in 40 µL of saline. The solution was injected into the left knee joint space of anaesthetised rats. Sct was administered at 2.5 and 5.0 IU/kg b.w. (im), whereas N-3 and DF were administered at 200 and 1 mg/kg b.w. (p.o.), respectively. Treatments commenced 9 days after the induction of OA, and they lasted for 28 days. RESULTS: Sct and/or N-3 significantly reduced c-telopeptide of type 1 collagen (CTX-1), collagen type 2 α-1 (C2M), malondialdehyde (MDA), uric acid (UA), and interleukin-6 (IL-6), but, significantly increased superoxide dismutase (SOD) after OA induction. Both therapies had additive effects on C2M, MDA, SOD, and catalase (CAT), but, non-additive actions on UA, IL-6, and CTX-1. Like the Sct and N-3, DF significantly reduced CTX-1, C2M, UA, and IL-6. However, it had no significant effect on SOD and MDA, even though it significantly reduced CAT activity. None of the therapies had significant effect on total alkaline phosphatase activity, except N-3+Sct.Lw. CONCLUSIONS: The combined, and sometimes the single administration of Sct and N-3 proved to be better therapies in OA management than DF.
Assuntos
Calcitonina/uso terapêutico , Diclofenaco/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Fosfatase Alcalina/sangue , Animais , Colágeno Tipo I/sangue , Colágeno Tipo II/sangue , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Interleucina-6/sangue , Ácido Iodoacético , Masculino , Malondialdeído/sangue , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/induzido quimicamente , Osteoartrite do Joelho/enzimologia , Ratos , Superóxido Dismutase/sangue , Ácido Úrico/sangueRESUMO
Clinical evidences on the coexistence of diabetes mellitus (DM) and osteoarthritis (OA) dated back to the 1960s. Therefore, the study investigated the effects of induced DM and/or knee osteoarthritis (KOA) on some biochemical and haematological parameters in adult male Wistar rats. Twenty rats were used for this study. They were randomly divided into 4 groups (N=5 rats) which included: Normal control; Osteoarthritic (OA) control; Diabetic control; and, Diabetic+Osteoarthritic (D+OA) control. DM was induced in overnight fasted rats by the administration of streptozotocin (65mg/kg b.w., i.p.) 15min after the administration of nicotinamide (110mg/kg, b.w., i.p.). However, KOA was induced by the intra-articular injection of 4mg of sodium monoiodoacetate in 40µl of normal saline. In the D+OA group, KOA was induced about 12h after the induction of DM. The rats were left untreated for four weeks. Afterwards, the experiment was terminated. The results showed that both DM and OA featured hypercortisolism and dyslipidaemia. The additive effects of both conditions were observed on the lipid profile and some haematological indices in the D+OA group. Unlike DM, OA had mild adverse effects on the haematological profile. Nevertheless, it significantly contributed to hyperglycaemia in the D+OA group, even though it had no significant effect on the insulin resistance. However, the hypocalcaemic and glycogenolytic effects of DM were negated by OA. In conclusion, the coexistence of DM and OA presents a greater challenge on the biochemical and haematological profiles than the individual disease. But, this prediction could sometimes be annulled by the intervention of endogenous homeostatic mechanisms.