Impact of Cuminaldehyde and Indomethacin Co-Administration on Inflammatory Responses in MIA-Induced Osteoarthritis in Rats.

Osteoarthritis (OA) remains a chronic incurable condition, presenting substantial challenges in treatment. This study explores a novel strategy by investigating the concurrent use of cuminaldehyde, a natural compound, with indomethacin in animal models of MIA-induced OA. Our results demonstrate that the co-administration of cuminaldehyde and indomethacin does indeed produce a superior effect when compared to these compounds individually, significantly enhancing therapeutic outcomes. This effect is evidenced by a marked reduction in pro-inflammatory cytokines IL-6 and IFN-γ, alongside a significant increase in the anti-inflammatory cytokine IL-10, compared to treatments with each compound alone. Radiographic analyses further confirm the preservation of joint integrity and a reduction in osteoarthritic damage, highlighting the association's efficacy in cartilage-reducing damage. These findings suggests that the association of cuminaldehyde and indomethacin not only slows OA progression but also offers enhanced cartilage-reducing damage and fosters the production of protective cytokines. This study underscores the potential benefits of integrating natural products with pharmaceuticals in OA management and stresses the importance of further research to fully understand the mechanisms underlying the observed potentiated effects.

The effect of low dose intra-articular S(+) ketamine on osteoarthritis in rats: an experimental study.

BACKGROUND: This study aimed to investigate the analgesic impact of S(+)-ketamine on pain behavior and synovial inflammation in an osteoarthritis (OA) model. METHODS: Animals were grouped as follows: OA-Saline (n = 24) and OA-Ketamine (n = 24), OA induced via intra-articular sodium monoiodoacetate (MIA); a Non-OA group (n = 24) served as the control. On the 7th day post OA induction, animals received either saline or S(+)-ketamine (0.5 mg.kg-1). Behavioral and histopathological assessments were conducted up to day 28. RESULTS: S(+)-ketamine reduced allodynia from day 7 to 28 and hyperalgesia from day 10 to 28. It notably alleviated weight distribution deficits from day 10 until the end of the study. Significant walking improvement was observed on day 14 in S(+)-ketamine-treated rats. Starting on day 14, OA groups showed grip force decline, which was countered by S(+)-ketamine on day 21. However, S(+)-ketamine did not diminish synovial inflammation. CONCLUSION: Low Intra-articular (IA) doses of S(+)-ketamine reduced MIA-induced OA pain but did not reverse synovial histopathological changes. IRB APPROVAL NUMBER: 23115 012030/2009-05.

Prejudice impairing quality of life in sickle cell disease patients in a developing country: faces of suffering

ABSTRACT Introduction: The perception of prejudice against, and stigmatization of, sickle cell disease (SCD) leads the patient to perceive a different treatment, due to the disease stigma and maybe related to a worse quality of life (QoL). Objectives: Describe and evaluate the perception of the prejudice against the disease and its impact on the quality of life of patients with sickle cell disease. Methods: This is a cross-sectional study conducted between March 2019 and February 2020, with patients diagnosed with SCD. Patients were questioned about the perception of prejudice in any kind of situation, choosing between "Yes" or "No", not differentiating situations related to prejudice. To assess the QoL and impact of the disease, the volunteers answered a version of the SF-36 questionnaire translated and validated into Brazilian Portuguese. Results: In this study, 113 patients with SCD were followed up, 92% were classified as HbSS and the rest, divided between HbSC and HbS-β-0. Regarding the SF-36, the worst scores were in the summary of the physical components (mean 48.19 ± 21.51) and the physical aspect had the lowest mean (30.75 ± €42.65). When questioned if they had already perceived any kind of prejudice, including the SCD, 32.74% answered "Yes". For this comparison, there was a significant difference in the summary of the physical and mental components, with worse QoL for those who had already suffered prejudice. Conclusion: Patients diagnosed with SCD who reported perception of prejudice had statistically significant worse QoL, revealing the negative impact, that might lead to sadness and social isolation.

Cuminaldehyde Effects in a MIA-Induced Experimental Model Osteoarthritis in Rat Knees.

Osteoarthritis (OA) is a chronic degenerative disease that has a significant global impact. It is associated with aging and characterized by widespread joint destruction. Cuminaldehyde is a biologically active component of essential oils that has shown promise in the treatment of nociceptive and inflammatory diseases. This study investigated the effects of cuminaldehyde on an experimental model of osteoarthritis induced in rat knees. Cuminaldehyde was found to be as effective as indomethacin in reducing pain in all evaluated tests, including forced walking, functional disability of weight distribution on the legs, and spontaneous pain in animals with osteoarthritis. The knees of animals treated with cuminaldehyde had significantly higher radiographic and histopathological scores than those of animals that did not receive the treatment. Cuminaldehyde also modulated the production of pro-inflammatory cytokines. In vitro assays showed that cuminaldehyde preferentially inhibits COX-2 enzyme activity. In silico studies demonstrated that cuminaldehyde has satisfactory energy affinity parameters with opioid receptors and COX-2. These findings suggest that cuminaldehyde's anti-inflammatory activity is multifactorial, acting through multiple pathways. Its nociceptive activity occurs via central and peripheral mechanisms. Cuminaldehyde modulates the immune response of the inflammatory process and may be considered a leading compound for the development of new anti-inflammatory and analgesic drugs.

Prejudice impairing quality of life in sickle cell disease patients in a developing country: faces of suffering.

INTRODUCTION: The perception of prejudice against, and stigmatization of, sickle cell disease (SCD) leads the patient to perceive a different treatment, due to the disease stigma and may be related to a worse quality of life (QoL). OBJECTIVES: Describe and evaluate the perception of the prejudice against the disease and its impact on the quality of life of patients with sickle cell disease. METHODS: This is a cross-sectional study conducted between March 2019 and February 2020, with patients diagnosed with SCD. Patients were questioned about the perception of prejudice in any kind of situation, choosing between "Yes" or "No", not differentiating situations related to prejudice. To assess the QoL and impact of the disease, the volunteers answered a version of the SF-36 questionnaire translated and validated into Brazilian Portuguese. RESULTS: In this study, 113 patients with SCD were followed up, 92% were classified as HbSS and the rest, divided between HbSC and HbS-ß-0. Regarding the SF-36, the worst scores were in the summary of the physical components (mean 48.19 ± 21.51) and the physical aspect had the lowest mean (30.75 ±€42.65). When questioned if they had already perceived any kind of prejudice, including the SCD, 32.74% answered "Yes". For this comparison, there was a significant difference in the summary of the physical and mental components, with worse QoL for those who had already suffered prejudice. CONCLUSION: Patients diagnosed with SCD who reported perception of prejudice had statistically significant worse QoL, revealing the negative impact, that might lead to sadness and social isolation.

Anti-Candida albicans Activity of Ononin and Other Secondary Metabolites from Platonia Insignis MART.

Candida albicans is a human pathogen that is part of the healthy microbiome. However, it is often associated with opportunistic fungal infections. The treatment of these infections is challenging because prolonged exposure to antifungal drugs can culminate in fungal resistance during therapy, and there is a limited number of available drugs. Therefore, this study investigated the antifungal activity of ononin by in silico and in vitro assays, and in Tenebrio molitor as an alternative in vivo model of infection caused by C. albicans. Ononin is an isoflavone glycoside derived from formononetin that has various biological activities. According in silico evaluation, ononin showed the best electron affinity in molecular docking with CaCYP51, with a binding free energy of -10.89 kcal/mol, superior to that of the antifungal drugs fluconazole and posaconazole. The ononin + CaCYP51 complex formed hydrogen bonds with Tyr132, Ser378, Phe380, and Met508, as well as hydrophobic connections with Tyr118, Leu121, Phe126, Leu131, Ile304, and Leu309, and interactions with the heme group. Ononin exerted anti-Candida albicans activity, with MIC between 3.9 and 7.8 µg/mL, and inhibited young and mature biofilms, with a reduction in cell density and metabolic activity of 50 to 80%. The compound was not cytotoxic to sheep red blood cells at concentrations up to 1000 µg/mL. Larvae of the mealworm T. molitor were used as an alternative in vivo model of C. albicans infection. Ononin was able to prolong larval survival at concentrations of 0.5, 1, and 5 mg/kg, and was not toxic up to a concentration of 20 mg/kg. Moreover, ononin reduced the fungal charge in treated animals. In conclusion, our results suggest that ononin has anti-Candida albicans activity and is a potential candidate for the development of new therapeutic alternatives.

Effect of intra-articular dexmedetomidine on experimental osteoarthritis in rats.

Pharmacological treatment of osteoarthritis is still inadequate due to the low efficacy of the drugs used. Dexmedetomidine via the intra-articular (i.a.) route might be an option for the treatment of osteoarthritis-associated pain. The present study assessed the analgesic and anti-inflammatory effects of dexmedetomidine administered via the i.a. route in different doses in an experimental model of rat knee osteoarthritis induced with monosodium iodoacetate. Rats were allocated to four groups with 24 animals in each group. The OA (osteoarthritis), DEX-1 (dexmedetomidine in dose of 1µg/kg) and DEX-3 (dexmedetomidine in dose of 3µg/kg) groups were subjected to induction of osteoarthritis through injection of monosodium iodoacetate (MIA) via the i.a. route on the right knee; the control group was not subjected to osteoarthritis induction. Clinical assessment was performed on day 0 (before osteoarthritis induction) and then on days 5, 10, 14, 21 and 28 after induction. Treatment was performed on day 7 via the i.a. route, consisting of dexmedetomidine in doses of 1 and 3 µg/kg, while group OA received 0.9% normal saline. The animals were euthanized on days 7, 14, 21 and 28. Samples of the synovial membrane were collected for histopathological analysis, and the popliteal lymph nodes were collected for measurement of cytokines (interleukin [IL] IL-6, tumor necrosis factor alpha [TNF-α]). Dexmedetomidine (1 and 3 µg/kg) significantly reduced the animals' weight distribution deficit during the chronic-degenerative stage of osteoarthritis and improved the pain threshold throughout the entire experiment. Histological analysis showed that dexmedetomidine did not cause any additional damage to the synovial membrane. The TNF-α levels decreased significantly in the DEX-3 group on day 28 compared with the OA group. Dexmedetomidine reduced pain, as evidenced by clinical parameters of osteoarthritis in rats, but did not have an anti-inflammatory effect on histological evaluation.

The analysis of alendronate action in bone fracture healing in rats.

INTRODUCTION: Osteoporosis is defined as a systemic skeletal disease characterized by reduced bone mass and degeneration of bone tissue microarchitecture which leads to bone fragility and fracture risk. Annually, 100 to 200 million people around the world are at risk for osteoporotic fractures. One way to prevent osteoporosis fracture is by using medications such as bisphosphonates. Alendronate is the most prescribed bisphosphonate in the world. The objective of this article is to evaluate the effect of alendronate on bone fracture healing. MATERIAL AND METHODS: 15 adult male rats that were 60 days old were used, divided into three groups: A or Control, B (non-osteoporotic bones plus alendronate application) and C (osteoporotic bones plus alendronate application). Osteoporotic bones were compared with non-osteoporotic bones that underwent bone window creation and administration of alendronate sodium. These bones were submitted to radiographic and histological analysis. RESULTS: All of Group A had complete bone healing, reaching the phase of bone remodeling. While in groups B and C, the rats were in the repair phase. CONCLUSIONS: The drug alendronate interferes with delayed fracture healing and delayed bone remodeling. The article advises that studies in humans are needed in order to assess whether the alendronate interferes with bone healing.

Cytotoxicity and Pro-Apoptotic, Antioxidant and Anti-Inflammatory Activities of Geopropolis Produced by the Stingless Bee Melipona fasciculata Smith.

Geopropolis is produced by some stingless bee species, such as Melipona fasciculata Smith, a native species from Brazil. This study aims to investigate the antioxidant and anti-inflammatory activities and cytotoxicity effects of geopropolis hydroethanolic extracts against lung (H460 and A549) and ovarian (A2780 and ES2) cancer cell lines and non-tumor (HUVEC) cell lines using chemical identification by LC/MS/MS analysis and in silico assays to determine which compounds are associated with bioactivity. The antioxidant activity of extracts and inhibitory activity against COX enzymes were assessed by in vitro assays; cytotoxicity effect was evaluated by the MTT assay; cell cycle was assessed by flow cytometry and apoptosis by Western blotting. The geopropolis extracts showed great radical scavenging potential, preferential inhibition of COX-2, decreased cancer cell viability, non-cytotoxic effects against the non-tumoral cell line, besides modulating the cell cycle and inducing cancer cell apoptosis through the activation of caspase-3 and PARP protein cleavage. The in silico study suggests that corilagin, typhaneoside, taraxerone and marsformosanone, identified by LC/MS/MS, can be associated with anti-inflammatory activity and cytotoxic effects. Thus, the current study suggests the potential of geopropolis concerning the research field of new pharmacological alternatives regarding cancer therapy.

Anti-Inflammatory and Antinociceptive Activity of Pollen Extract Collected by Stingless Bee Melipona fasciculata.

The stingless bee, Melipona fasciculata Smith (Apidae, Meliponini), is a native species from Brazil. Their products have high biotechnological potential, however there are no studies about the biological activities of pollen collected by M. fasciculata. In this context, the present study investigated the chemical composition, anti-oxidant, anti-inflammatory, and analgesic activities of hydroethanolic pollen extracts collected by M. fasciculata in three cities in Maranhão State, Brazil. We verified the antioxidant activity of the extracts and inhibitory activity against the cyclooxygenase enzyme using in vitro assays and in allowed to select the extract with higher efficiency to be used on in vivo assays. In these trials, the selected extract showed high anti-inflammatory activity as well as nociceptive effects at central and peripheral level, suggesting that this extract acts on inhibition of histamine release and decreased synthesis of prostaglandins and the in-silico study suggested that polyphenols and acids fatty acids in the extract may be associated with these activities. The results of the present study report the high biological potential of pollen extract and we conclude that the pollen collected by M. fasciculata can be considered as the object of research for new pharmacological alternatives.

Effects of Extract of Arrabidaea chica Verlot on an Experimental Model of Osteoarthritis.

The aim of this study was to analyze the analgesic potential of Arrabidaea chica extract (EHA) as an alternative to osteoarthritis (OA) treatment. Thus, the extract was initially evaluated by the cyclooxygenase inhibition test. The analgesic effect of the extract, in vivo, was also verified in a model of OA induced by sodium monoiodoacetate (2 mg). EHA was administered to rats at doses of 50, 150, and 450 mg/kg between 3 and 25 days after OA induction. The animals were clinically evaluated every 7 days, euthanized at 29 days, and the liver, spleen, kidney and knee collected for histopathological analysis. The chemical composition of EHA was identified by HPLC-MS and the identified compounds submitted to molecular docking study. The results showed that the extract promoted cyclooxygenase inhibition and produced significant improvements in disability, motor activity, hyperalgesia, and OA-induced allodynia parameters, in addition to improvements in the radiological condition of the knees (but not observed in the histopathological study). Chemically the extract is rich in flavonoids. Among them, we evidence that amentoflavone showed very favorable interactions with the enzyme COX-2 in the in silico analysis. Thus, it is concluded that A. chica has important analgesic properties for the treatment of OA.

Therapeutic Use of Scoparia dulcis Reduces the Progression of Experimental Osteoarthritis.

Pain is recognized as one of the main symptoms in knee osteoarthritis and is the main reason why patients seek medical attention. Scoparia dulcis has been popularly used to relieve discomfort caused by various painful conditions. The objective of the study is to evaluate the analgesic and anti-inflammatory effect of the crude extract of S. dulcis, in an experimental model of osteoarthritis. The experiment was performed with Wistar rats divided into 4 groups with 5 animals each: healthy, saline, crude extract, and meloxicam groups. Knee osteoarthritis was induced by intra-articular injection of sodium mono-iodoacetate. First, clinical parameters of pain were assessed at days 0, 5, 10, 15, and 20 after induction. Second, the potential cyclooxygenase inhibition was evaluated, and the cytokines of the synovial fluid were quantified. An in silico test and Molecular Docking tests were performed. A histopathological evaluation was made on articular cartilage with safranin O staining. The results showed that a 15-day treatment with crude extract reduced edema, spontaneous pain, peripheral nociceptive activity, and proinflammatory cytokines in the synovial fluid. The highest inhibition of cyclooxygenase 2 in the crude extract occurred at 50 µg/mL. The crude extract of S. dulcis presents therapeutic potential for the treatment of osteoarthritis due to its anti-inflammatory and anti-nociceptive action.

Antihypertensive Effect of Syzygium cumini in Spontaneously Hypertensive Rats.

This study evaluated the in vivo potential antihypertensive effect of hydroalcoholic extract of Syzygium cumini leaves (HESC) in normotensive Wistar rats and in spontaneously hypertensive rats (SHR), as well as its in vitro effect on the vascular reactivity of resistance arteries. The hypotensive effect caused by intravenous infusion of HESC (0.01-4.0 mg/kg) in anesthetized Wistar rats was dose-dependent and was partially inhibited by pretreatment with atropine sulfate. SHR received HESC (0.5 g/kg/day), orally, for 8 weeks and mean arterial pressure, heart rate, and vascular reactivity were evaluated. Daily oral administration of HESC resulted in a time-dependent blood pressure reduction in SHR, with a maximum reduction of 62%. In the endothelium-deprived superior mesenteric arteries rings the treatment with HESC reduced by 40% the maximum effect (E max⁡) of contraction induced by NE. The contractile response to calcium and NE of endothelium-deprived mesenteric rings isolated from untreated SHR was reduced in a concentration-dependent manner by HESC (0.1, 0.25, and 0.5 mg/mL). This study demonstrated that Syzygium cumini reduces the blood pressure and heart rate of SHR and that this antihypertensive effect is probably due to the inhibition of arterial tone and extracellular calcium influx.

Análise de prontuários de pacientes com câncer de mama em tratamento com bisfosfonatos: fator de risco para manifestações orais e osteonecrose induzida / Analysis of medical records of patients with breast cancer on treatment with bisphosphonates: risk factor for oral manifestations and induced osteonecrosis

JUSTIFICATIVA E OBJETIVOS: A terapêutica do câncer de mama (CM) merece ser avaliada com cuidado antes de ser prescrita, pois dentre as opções, existem os bisfosfonatos que mostram relação com a indução a osteonecrose dos maxilares.O objetivo deste estudo foi verificar o uso de bisfosfonato na terapêutica anticâncer e a sua relação com osteonecrose induzida através da análise de prontuários de portadoras do câncer de mama. MÉTODOS: Estudo longitudinal com dados coletados de pacientes que com diagnóstico de câncer de mama entre 2007 e 2008, internadas no Hospital Aldenora Belo, referência neste tipo de tratamento em São Luis/MA, usuárias de bisfosfonato há mais de um ano, sendo a amostra formada por 31 mulheres.RESULTADOS: Das 31 pacientes em tratamento que compuseram a amostra (20,6%), 3 (1,99%) vieram a óbito, 13 (8,63%) desistiram e 15 (9,96%) continuaram, com maioria pertencentes a faixa etária superior aos 40 anos e usuárias de pamidronato por via venosa, sendo, este dois fatores, por si só, fatores de risco.Observou-se apenas um caso de destruição óssea craniofacial com comprovada associação entre idade e uso prolongado do fármaco.CONCLUSÃO: Constatou-se que o pamidronato nunca é o fármaco de primeira escolha, seus efeitos colaterais são significantes.Quanto à osteonecrose induzida, não há nenhum caso confirmado nos prontuários, visto que o diagnóstico é complexo (acompanhamento clínico e radiográfico) além do Cirurgião Dentista não fazer parte da equipe multidisciplinar do hospital.

BACKGROUND AND OBJECTIVES: The treatment of breast cancer (BC) must be carefully evaluated before being prescribed, since there are, among the options, bisphosphonates that show a relation with the induction of osteonecrosis of the jaw. The aim of this study was to investigate the use of bisphosphonates in anticancer therapy, and its relationship to induced osteonecrosis by analyzing medical records of patients with breast cancer. METHODS: A longitudinal study with data collected from patients diagnosed with breast cancer between 2007 and 2008, admitted at Hospital Aldenora Belo, a reference in this type of treatment in the city of São Luis, in the state of Maranhão,who were bisphosphonate users for over a year, with the sample being comprised of 31 women. RESULTS: Of the 31 patients treated in the sample (20.6%), 3 (1.99%) died, 13 (8.63%) quit and 15 (9.96%) continued, with most of them aged over 40 years, and users of intravenous pamidronate, these two factors alone being risk factors. There was one case of craniofacial bone destruction with proven association with age and prolonged use of the drug. CONCLUSION: It was found that pamidronate is never the first-choice drug, its side effects are significant. Regarding induced osteonecrosis, there is no confirmed case in the records, since the diagnosis is complex (clinical and radiographic monitoring) and also because the Dentist is not part of the multidisciplinary team at the hospital.