Avaliação dos efeitos da coenzima Q10 utilizada como coadjuvante local e/ou sistêmica ao tratamento mecânico da periodontite experimental em ratos tratados com nicotina / Evaluation of the effects of coenzyme Q10 as local and/or systemic adjuvant to mechanical treatment of experimental periodontitis in rats treated ith nicotine

O propósito do estudo foi avaliar a efetividade da raspagem e alisamento radicular (RAR) associado à coenzima Q10 (CQ10) administrada localmente e/ou sistemicamente no tratamento da periodontite experimental (PE) em ratos tratados sistemicamente com nicotina (NIC). 128 ratos (Wistar) foram divididos em oito grupos (n=16). Durante todo o período experimental, os animais receberam duas injeções subcutâneas diárias de 3mg/kg de hemissulfato de nicotina ou solução salina (SS) na região dorsal, com 12 horas de intervalo entre elas, começando nos 30 dias que antecederam à indução da PE. Após 15 dias da indução da PE, o protocolo de RAR foi realizado bem como o tratamento coadjuvante local e/ou sistêmico com CQ10, com e sem tratamento com a NIC, sendo: SS-PE-RAR e NIC-PE-RAR: irrigação subgengival com SS; SS-PE-RAR/Q10L e NIC-PE-RAR/Q10L: irrigação subgengival com 1ml solução de CQ10; SS-PE-RAR/Q10S e NIC-PE-RAR/Q10S: gavagem gástrica diária com 120 mg de CQ10; SS-PE-RAR/Q10LS e NIC-PE-RAR/Q10LS: irrigação subgengival com 1ml solução de CQ10 e gavagem gástrica diária com 120 mg de CQ10. As eutanásias foram realizadas 7 e 28 dias após tratamento. As peças coletadas foram processadas com desmineralização para as análises histopatológica, histométrica e imunoistoquímica para detecção de TRAP. Os dados foram submetidos ao teste paramétrico Anova two-way e pós-teste de Tukey. O nível de significância adotado foi de 5% (p≤0,05). Na análise histopatológica, pode-se observar que os grupos NIC-PE-RAR-Q10L E NIC-PE-RAR-Q10LS apresentaram tecidos periodontais com aspecto de normalidade, com preservação da inserção conjuntiva e de região de furca preservada aos 7 e 28 dias, de modo distinto do grupo NIC-PE-RAR e NIC-PE-RAR-Q10S em ambos os períodos. Na análise histométrica, pode-se observar maior porcentagem de osso na furca (POF) (p≤0,05) nos grupos NIC-PE-RAR-Q10L, NIC-PE-RAR-Q10S e NIC-PERAR-Q10LS em comparação com o grupo NIC-PE-RAR em ambos os períodos e também com o grupo SS-PE-RAR aos 28 dias. Pode-se observar menor número de células TRAP positivas (p≤0,05) no grupo NIC-PE-RAR-Q10L quando comparado aos grupos SS-PE-RAR E NIC-PE-RAR aos 7 dias e no grupo NIC-PE-RAR-Q10LS quando comparado aos mesmos grupos aos 28 dias. Conclui-se que RAR associado à CQ10 utilizada local e local/sistemicamente no tratamento da PE em ratos tratados sistemicamente com nicotina foram efetivas mostrando resultados favoráveis nas análises histopatológica, histométrica e imunoistoquímica(AU)

The aim of this study was to evaluate the effectiveness of scaling and root planing (SRP) combined with adjunctive local and/or systemic administration of coenzyme Q10 (CQ10) for the treatment of experimental periodontitis (EP) in rats systemically treated with nicotine (NIC). 128 Wistar rats were divided into 8 groups (n=16). Throughout the experiment, animals received two subcutaneous injections of either 3mg/kg nicotine hemissulfate or physiological saline solution (PSS) with 12 h interval between them. These injections were initiated 30 days prior EP induction. 15 days after EP induction, the protocol for SRP was performed together (or not) with local and/or systemic adjunctive CQ10 administration in animals treat with either NIC or PSS, as described: PSS-EP-SRP and NIC-EP-SRP: subgingival irrigation with PSS; PSS-EP-SRP/Q10L and NIC-EP-SRP/Q10L: subgingival irrigation with 1ml of CQ10 solution; PSS-EP-SRP/Q10S and NIC-EP-SRP/Q10S: daily gastric gavage with 120 mg of CQ10; PSS-EP-SRP/Q10LS and NIC-EP-SRP/Q10LS: subgingival irrigation with 1ml of CQ10 solution and daily gastric gavage with 120 mg of CQ10. The euthanasia was performed at 7 and 28 days after treatment. The specimens were collected and processed for histopathologic, histometric and immunochemical for of TRAP analyzes. The data were submitted to the two-way ANOVA and Tukey's post-test. The level of significance adopted was 5% (p≤0.05). In the histopathological analysis, it can be observed that the NIC-PE-RAR-Q10L and NIC-PE-RAR-Q10LS groups presented periodontal tissues with normal aspect, preserving the conjunctival insertion and furca region preserved at 7 and 28 days, differently from the NIC-PE-RAR and NIC-PE-RAR-Q10S groups in both periods. In histometric analysis, a higher percentage of bone in furca (PBF) (p≤0.05) can be observed in the NIC-PE-RAR-Q10L, NIC-PE-RAR-Q10S and NIC-PE-RAR-Q10LS groups compared to the NIC-PE-RAR group in both periods and also with the SS-PE-RAR group at 28 days. A lower number of TRAPpositive cells (p≤0.05) can be observed in the NIC-PE-RAR-Q10L group when compared to the SS-PE-RAR and NIC-PE-RAR groups at 7 days and in the NIC-PE-RAR-Q10LS group when compared to the same groups at 28 days. It was concluded that RAR associated with CQ10 used locally and locally/systemically in the treatment of EP in rats treated systemically with NIC were effective, showing favorable results in histopathological, histometric and immunohistochemical analyses(AU)

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Effects of non-caloric ultrashort wave on the expression of CoQ10 and C1GALT1C1 in rats with cerebral ischemia reperfusion injury / 中南大学学报(医学版)

OBJECTIVES@#To examine the changes of coenzyme Q10 (CoQ10) and β-galactosyl transferase specific chaperone 1 (C1GALT1C1) in brain of rats with ischemic injury at different time points and to explore the protective mechanism of ultrashort wave (USW) on ischemic brain injury.@*METHODS@#Fifty SD rats were randomly divided into 5 groups (=10 per group): a sham group (control group) and 4 experimental group (ischemia for 2 h). The 4 experimental groups were set as a model 1 d group, a USW 1 d group, a model 3 d group and a USW 3 d group, respectively. Five rats were randomly selected for 2,3,5-triphenyltetrazoliumchloride (TTC) staining in each experimental group, and the remaining 5 rats were subjected to Western blotting and real-time PCR. The percentage of cerebral infarction volume and the relative expression level of CoQ10 and C1GALT1C1 in the brain were examined and compared.@*RESULTS@#The infarct volume percentage after TTC staining was zero in the sham group. With the progress of disease and USW therapy, the infarct volume percentage was decreased in the experimental groups (all <0.05); Western blotting and real-time PCR showed that the relative expression level of CoQ10 in the sham group was the highest, while in the experimental groups, the content of CoQ10 showed a upward trend with the extension of disease and USW therapy, with significant difference (all <0.05). The relative expression level of C1GALT1C1 in the sham group was the lowest, but in the experimental groups, they showed a downward trend with the extension of disease and USW therapy, with significant difference (all <0.05).@*CONCLUSIONS@#Non-caloric USW therapy may upregulate the expression of CoQ10 to suppress the expression of C1GALT1C1 in rats, leading to alleviating cerebral ischemic reperfusion injury.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes / Estado antioxidante da coenzima Q10 e da vitamina E em crianças com diabetes tipo 1

Abstract Objective: The purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. Method: This case-control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. Results: Children with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p < 0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p < 0.05). The platelet redox status showed a negative correlation with the A1c % levels (r = −0.31; p = 0.022) and the duration of type 1 diabetes (r = −0.35, p = 0.012). Conclusion: Patients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress.

Resumo Objetivo: Avaliar o estado antioxidante da vitamina E no plasma e da coenzima Q10 no plasma e intracelular em crianças com diabetes tipo 1. Método: Este estudo caso-controle realizado em com 72 crianças com diabetes tipo 1 comparadas por idade, sexo e etnia de 58 crianças saudáveis. As crianças diabéticas foram divididas em dois grupos de acordo com sua hemoglobina glicosilada (A1c %): grupos de controle glicêmico bom e baixo. Todas as crianças foram submetidas a anamnese total, exame clínico e laboratorial para hemograma completo, A1c %, colesterol no plasma, triglicerídeos e níveis de vitamina E e níveis de coenzima Q10 no plasma, eritrócitos e plaquetas. Resultados: As crianças com baixo controle glicêmico mostraram nível de vitamina E no plasma significativamente maior, coenzima Q10, triglicerídeos, lipoproteína de baixa densidade, proporção da circunferência da cintura/estatura e níveis de colesterol e menor nível de lipoproteína de alta densidade e estado redox da coenzima Q10 em comparação aos com bom controle glicêmico e com o grupo de controle (p < 0,05). A coenzima Q10 no plasma mostrou correlação positiva com a duração da diabetes tipo 1, triglicerídeos, colesterol, vitamina E e A1c % e correlação negativa com a idade do grupo diabético (p < 0,05). O estado redox das plaquetas mostrou correlação negativa com os níveis de A1c % (r = -0,31; p = 0,022) e a duração da diabetes tipo 1 (r = -0,35, p = 0,012). Conclusão: Os pacientes com diabetes tipo 1, principalmente mal controlados, apresentaram aumento nos níveis de vitamina E no plasma e coenzima Q10 e redução no estado redox das plaquetas da coenzima Q10 que podem indicar aumento do estresse oxidativo.

Antibacterial effects of sodium tripolyphosphate against Porphyromonas species associated with periodontitis of companion animals

Porphyromonas species are closely associated with companion animal periodontitis which is one of the most common diseases in dogs and cats and leads to serious systemic diseases if left untreated. In this study, we evaluated the antimicrobial effects and mode of action of sodium tripolyphosphate (polyP3, Na5P3O10), a food additive with proven safety, using three pathogenic Porphyromonas species. The minimum inhibitory concentrations (MICs) of polyP3 against Porphyromonas gulae, Porphyromonas cansulci, and Porphyromonas cangingivalis were between 500 and 750 mg/L. PolyP3 significantly decreased viable planktonic cells as well as bacterial biofilm formation, even at sub-MIC concentrations. PolyP3 caused bacterial membrane disruption and this effect was most prominent in P. cangingivalis, which was demonstrated by measuring the amount of nucleotide leakage from the cells. To further investigate the mode of action of polyP3, high-throughput whole-transcriptome sequencing was performed using P. gulae. Approximately 30% of the total genes of P. gulae were differentially expressed by polyP3 (> 4-fold, adjusted p value < 0.01). PolyP3 influenced the expression of the P. gulae genes related to the biosynthesis of thiamine, ubiquinone, and peptidoglycan. Collectively, polyP3 has excellent antibacterial effects against pathogenic Porphyromonas species and can be a promising agent to control oral pathogenic bacteria in companion animals.

Prophylaxis with melatonin for primary stabbing headache in pediatrics: a case report / Profilaxis con melatonina para cefalea punzante primaria en pediatría: reporte de caso

Abstract Introduction: Primary stabbing headache (or "ice pick headache") is an alteration characterized by brief jabs (short stabs of pain, lasting ~3 seconds), which appear spontaneously, irregularly, and affecting unilaterally or bilaterally. Indomethacin has traditionally been used as the main therapeutic option. However, this drug is ineffective in a considerable percentage of patients and can generate multiple adverse effects that occur at therapeutic doses. Clinical case: A 7-year-old male patient with primary stabbing headache of mild to moderate intensity, lasting 3 to 4 seconds, without relevant history, with normal neurodevelopment, neurological examination and neuroimaging; no triggers were identified. It was started therapeutic trial with Coenzyme Q10; however, no improvement in the symptoms was identified. Treatment and outcomes: A therapeutic management was carried out with Melatonin, which led to complete remission of the symptoms; without adverse effects in the posterior follow-up months. Clinical and scientific relevance: There is little information regarding effective and safe treatments for primary stabbing headache in children. The present case identifies Melatonin as an innovative, effective and safe therapeutic alternative in the treatment of primary stabbing headache in children. This is a significant advance in the understanding of primary stabbing headache in the pediatric population. Conclusion: Melatonin may be an effective and safe therapeutic option for the treatment of primary stabbing headache in pediatric patients. It is necessary to deepen its research, in order to establish its use in a clinical practice guide.

Resumen Introducción: La cefalea punzante primaria, es una alteración que se caracteriza por punzadas breves (∼3 segundos), que aparecen espontáneamente, de forma irregular y afectación unilateral o bilateral. Tradicionalmente se ha utilizado Indometacina como opción terapéutica principal. Sin embargo, este medicamento es inefectivo en un porcentaje considerable de pacientes y puede generar múltiples efectos adversos que se presentan a dosis terapéuticas. Caso clínico: Paciente masculino de 7 años de edad con cefalea punzante primaria de intensidad leve a moderada con una duración entre 3 y 4 segundos sin antecedentes relevantes, con neurodesarrollo, examen neurológico y de neuroimagen normales; no se identificaron desencadenantes. Se inició prueba terapéutica con Coenzima Q10, sin embargo no se identificó mejoría en los síntomas. Tratamiento y resultados: Se realizó un manejo terapéutico con Melatonina que conllevó a remisión completa de la sintomatología y sin efectos adversos en los meses posteriores de seguimiento. Relevancia clínica y científica: Existe poca información respecto a tratamientos efectivos y seguros para cefalea punzante primaria en niños. El presente caso identifica la Melatonina como una alternativa terapéutica innovadora, efectiva y segura en el tratamiento de la cefalea punzante primaria en niños. Lo anterior constituye un avance significativo en la comprensión de la cefalea punzante primaria en la población pediátrica. Conclusión: La melatonina puede ser una opción terapéutica efectiva y segura para el tratamiento de la cefalea punzante primaria en pacientes pediátricos. Se requiere ahondar en su investigación para establecer su uso en una guía de práctica clínica.

Therapeutic effects of proanthocyanidin and coenzyme Q10 on nitrogen mustard-induced ocular injury / Efeitos terapêuticos da proantocianidina e da coenzima q10 em lesão ocular induzida por mostarda de nitrogênio

ABSTRACT Purpose: Nitrogen mustard (NM) is a devastating casualty agent in chemical warfare. There is no effective antidote to treat NM-induced ocular injury. We aimed to assess the effects of proanthocyanidin (PAC) and coenzyme Q10 (CoQ10) on NM-induced ocular injury. Methods: Eighteen male rats were divided into the following 4 groups: NM, NM + PAC, NM + CoQ10, and control. The 3 NM groups received a single dose of NM (0.02 mg/μL) on the right eye to induce ocular injury. The control group received saline only. Thirty minutes after the application of NM, the NM + PAC group received PAC (100 mg/kg) via gastric gavage, while the NM + CoQ10 group received CoQ10 (10 mg/kg) via intraperitoneal injection. PAC and CoQ10 were administered once a day for 5 consecutive days. The rats were then sacrificed. Macroscopic images of the eyes were examined and eye tissues were collected for histology. Results: The treatment groups were compared to the control group with regard to both corneal opacity and lid injury scores. The findings were not significantly different for both the NM + PAC and NM + CoQ10 groups. In both the NM + PAC and NM + CoQ10 groups, the histological changes seen in the NM group demonstrated improvement. Conclusions: Our results indicate that PAC and CoQ10 treatments have therapeutic effects on NM-induced ocular injury in a rat model. PAC and CoQ10 may be novel options in patients with NM-induced ocular injury.

RESUMO Objetivo: A mostarda de nitrogênio (MN) é um agente de guerra química devastador. Não existe um antídoto eficaz para tratar lesões oculares induzidas por MN. Nosso objetivo foi avaliar os efeitos da proantocianidina (PAC) e da coenzima Q10 (CoQ10) na lesão ocular induzida por MN. Métodos: Dezoito ratos machos foram divididos em 4 grupos: MN, MN + PAC, MN + CoQ10 e Controle. Três grupos receberam uma dose única de MN (0,02 mg/μL) destilada no olho direito para gerar lesão ocular. Os animais do grupo controle receberam apenas solução salina. Trinta minutos após a aplicação de MN nos animais, o grupo MN + PAC recebeu PAC (100 mg/kg) por gavagem gástrica, enquanto a CoQ10 (10 mg/kg) foi administrada ao grupo MN + CoQ10 por meio de injeção intraperitoneal. A administração de PAC e de CoQ10 foi realizada uma vez por dia, durante 5 dias consecutivos. Os ratos foram, então, sacrificados. Imagens macroscópicas dos olhos foram examinadas e tecidos oculares foram coletados para histologia. Resultados: Os grupos de tratamento foram comparados ao grupo de controle quanto à opacidade da córnea e quanto aos escores de lesão da cobertura da córnea. Os resultados foram insignificantes para ambos os grupos. Ambos, o grupo MN+PAC e o grupo MN+CoQ10, apresentaram melhoras das alterações histológicas observadas no grupo MN. Conclusões: Nossos resultados indicam que os tratamentos com PAC e com CoQ10 têm efeitos terapêuticos sobre lesões oculares induzidas por MN em um modelo em ratos. A proantocianidina e a CoQ10 podem ser uma nova opção nesses casos.

A utilização da coenzima Q10 adjunta à terapia periodontal básica na periodontite crônica / The use of coenzyme Q10 accompanies basic periodontal therapy in chronic periodontitis

A porção inflamatória da resposta imunoinflamatória é mediada por moléculas oxidativas que causam degradação de colágeno e danos às células periodontais. Uma disbiose nessa resposta leva a periodontite. Essas moléculas oxidativas podem ser neutralizadas pela coenzima Q10 (CoQ10), sendo um composto produzido pelo corpo, e apresenta duas formas moleculares, na forma oxidada chamada de Ubiquinona e na reduzida denominada de Ubiquinol. O Ubiquinol é a molécula que confere propriedade antioxidante a esse composto. O objetivo desse estudo é apresentar uma revisão de literatura sobre o uso adjunto da CoQ10 na terapia periodontal básica de pacientes com periodontite crônica. Para tal, foi realizada uma revisão de literatura de ensaios clínicos controlados de pacientes com diagnóstico de periodontite crônica cujo tratamento consistia em raspagem e alisamento radicular (RAR) e CoQ10 adjunta (grupo teste) em comparação a RAR isolado ou associado a um placebo (grupo controle). Os parâmetros periodontais avaliados foram índice de placa (IP), índice gengival (IG), profundidade de bolsa (PB) e nível clínico de inserção (NIC). Foram obtidos 5 estudos e 3 deles não relataram respostas estatisticamente significantes para nenhum parâmetro periodontal avaliado. Entretanto, nos outros dois estudos verificaram-se melhoras estatisticamente significantes para IG e IP após 3 meses e 4 semanas respectivamente utilizando-se CoQ10 adjunta. Após análise dos resultados, pode-se concluir que o uso da CoQ10 adjunta à terapia periodontal básica em paciente com periodontite crônica apresentou melhoras estatisticamente significantes, somente para IG, quando usada em forma de suplementação oral e somente IP quando usada em gel intrabolsa. (AU)

The inflammatory portion of the immune-inflammatory response is mediated by oxidative molecules, which cause collagen degradation and damage to periodontal cells. A dysbiosis in this response leads to periodontitis. These oxidative molecules can be neutralized by coenzyme Q10 (CoQ10), which is a compound produced by the body, and has two molecular forms, in the oxidized form called Ubiquinone and in the reduced form called Ubiquinol. Ubiquinol is the molecule that confers the antioxidant property to this compound. The purpose of this study is to present a literature review on CoQ10 adjunctive use in basic periodontal therapy of patients with chronic periodontitis. A literature review of controlled clinical trials of patients diagnosed with chronic periodontitis, whose treatment consisted of scaling and root planing (SRP) and adjunct CoQ10 (test group) compared to SRP alone or with a placebo associated. The periodontal parameters evaluated were: plaque index (PI) and gingival index (GI), pocket depth (PD) and clinical attachment level (CAL). Five studies were obtained, of which 03 did not report statistically significant responses for any periodontal parameter evaluated. The other two studies showed statistically significant improvements in GI after 3 months of use, and PI after 4 weeks using CoQ10, respectively. After analyzing the results, it can be concluded that the use of CoQ10 adjunct to basic periodontal therapy in patients with chronic periodontitis showed statistically significant improvements, only for GI, when used as oral supplementation, and only PI when applied in intrapocket gel. (AU)

New Mutation of Coenzyme Q Monooxygenase 6 Causing Podocyte Injury in a Focal Segmental Glomerulosclerosis Patient / 中华医学杂志(英文版)

Background@#Focal segmental glomerulosclerosis (FSGS) is a kidney disease that is commonly associated with proteinuria and the progressive loss of renal function, which is characterized by podocyte injury and the depletion and collapse of glomerular capillary segments. The pathogenesis of FSGS has not been completely elucidated; however, recent advances in molecular genetics have provided increasing evidence that podocyte structural and functional disruption is central to FSGS pathogenesis. Here, we identified a patient with FSGS and aimed to characterize the pathogenic gene and verify its mechanism.@*Methods@#Using next-generation sequencing and Sanger sequencing, we screened the causative gene that was linked to FSGS in this study. The patient's total blood RNA was extracted to validate the messenger RNA (mRNA) expression of coenzyme Q monooxygenase 6 (COQ6) and validated it by immunohistochemistry. COQ6 knockdown in podocytes was performed in vitro with small interfering RNA, and then, F-actin was determined using immunofluorescence staining. Cell apoptosis was evaluated by flow cytometry, the expression of active caspase-3 was determined by Western blot, and mitochondrial function was detected by MitoSOX.@*Results@#Using whole-exome sequencing and Sanger sequencing, we screened a new causative gene, COQ6, NM_182480: exon1: c.G41A: p.W14X. The mRNA expression of COQ6 in the proband showed decreased. Moreover, the expression of COQ6, which was validated by immunohistochemistry, also had the same change in the proband. Finally, we focused on the COQ6 gene to clarify the mechanism of podocyte injury. Flow cytometry showed significantly increased in apoptotic podocytes, and Western blotting showed increases in active caspase-3 in si-COQ6 podocytes. Meanwhile, reactive oxygen species (ROS) levels were increased and F-actin immunofluorescence was irregularly distributed in the si-COQ6 group.@*Conclusions@#This study reported a possible mechanism for FSGS and suggested that a new mutation in COQ6, which could cause respiratory chain defect, increase the generation of ROS, destroy the podocyte cytoskeleton, and induce apoptosis. It provides basic theoretical basis for the screening of FSGS in the future.

Eficacia y seguridad de coenzoma Q10, carnitina y riboflavina en pacientes con enfermedades mitocondriales / Efficacy and safety of coenzyme Q10, carnitine and riboflavin in patients with mitochondrial diseases

INTRODUCCIÓN: Antecedentes: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad de la coenzima Q10, carnitina y riboflavina respecto a su uso en pacientes con enfermedades mitocondriales. Aspectos Generales: Las mitocondrias son organelas complejas de doble membrana que cuentan con un ADN propio, heredado de la madre. Subojetivo es producir energia a partir de los nutrientes en fora de calor y ATP, mediante la respiración. El proceso por el cual se produce la energía es conocido como fosforilación oxidativa y se lleva a cabo en la cadena respiratoria de las mitocondrias, también llamada cadena transportadora de electrones. Tecnologia Sanitária de Interés: Coenzima Q10: La coenzima Q10, también conocida como ubiquinona, es una quinona soluble en grasas , sintetizada en la mitocondria y que se encuentra presente en la membranas celulares. La coenzima Q'0 endógena es producida por el organismo como parte de la vía de producción del colestereol, mientras que la exógena es ingerida por la dieta como ubiquinona (forma oxidada) y ubuquinol (forma reducida). Esta molécula se encuentra presente en todas las células del organismo, en mayor concentración en el tejido del cerebro, corazón, riñones, e hígado. Carnitina: La carnitina, presente en el organismo y en los alimentos como I-carnitina, es un aminoácido sintetizado en el tejido muscular, renal y hepático a partir de los aminoácidos l-lisina yl-metionina. Existen fuentes exógenas de l-carnitina como las carnes rojas, el pescado, el pollo e la leche. Esta molécula cumple una función importante en el metabolismo de ácidos grasos, ya que promueve la utilización de la grasa almacenada en el organismo como fuente de energia. Especificamente, la L-carnitina es un transportador de lípidos que permite el ingreso de las cadenas de ácidos grasos a la matriz mitocondrial para ser convertidos en energía a través del proceso de la beta-oxidación. Riboflavina: La riboflavina (vitamina B2) es una vitamina hidrosolubre que se encuentra la manera natural en los alimentos de origen animal y vegetal, y puede ser producida también por la microbiota intestinal. Esta vitamina se absorve en el intestino delgado proximal y, cuando es consumida en exceso, es excretada por la orina y/o almacenada en concetraciones reducidas en el hígado, riñones, y corazón. METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda de literatura científica en relación a la eficacia y seguridad del uso de la coenzima Q10, carnitina y riboflavina en pacientes con enfermedades mitocondriales (EM). Sedio preferencia a guías de práctica clínica, revisiones sistemáticas con o sin meta-análisis y ensayos clínicos aleatrorizados. RESULTADOS: Sinopsis de la Evidencia: Se realizó la busqueda bibliográfica y de evidencia científica que sustente el uso de coenzima Q10, carnitina y riboflavina en pacientes con diganóstico de enfermedades mitocondriales (EM). CONCLUSIONES: En la presente evaluación de tecnología sanitária se presenta a la evidencia recabada sobre el beneficio de la coenzima Q10, carnitina y riboflavina en pacientes con enfermedades mitocondriales. La evidencia encontrada que evalúa el uso de estos compuestos en pacientes con enfermedades mitocondriales es escasa. Se ha identificado evidencia proveniente de tres ensayos clínicos y un estudio obervacional. Ninguno de los estudios evaluó los tres suplementos en conjunto como una sola intervención. El Instituto de evaluación en Salud e Investigación-IETSI, aprueba el uso de la coenzima Q10, carnitina y riboflavina en pacientes con enfermedades mitocondriales. El presente Dictamen Preliminar tiene una vigencia de dos años a partir de la fecha de publicación.

Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects / Coenzima Q10 e marcadores pró-inflamatórios em crianças com síndrome de Down: aspectos clínicos e bioquímicos

Abstract: Objective: Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. Methods: Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. Results: Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014). Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p = 0.002), while coenzyme Q10 was significantly decreased (p = 0.002). Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. Conclusion: Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

Resumo: Objetivo: Foram relatadas evidências de estresse oxidativo em indivíduos com a síndrome de Down. Há um interesse cada vez maior na contribuição do sistema imunológico na síndrome de Down. O objetivo deste estudo é avaliar a coenzima Q10 e marcadores pró-inflamatórios selecionados, como interleucina 6 e o fator de necrose tumoral α, em crianças com a síndrome de Down. Métodos: Foram inscritas neste estudo de caso-controle 86 crianças (5-8 anos) de duas instituições públicas. No momento da amostragem, os pacientes e os controles não sofriam de doença aguda ou crônica e não recebiam terapia ou suplementos. Foram medidos os níveis de interleucina 6, fator de necrose tumoral α, coenzima Q10, glicemia de jejum e quociente de inteligência. Resultados: Foram incluídas em oito meses (janeiro-agosto 2014) 43 crianças com síndrome de Down e 43 controles. Em comparação com o grupo de controle, os pacientes com síndrome de Down mostraram aumento significativo na interleucina 6 e no fator de necrose tumoral α (p = 0,002), ao passo que a coenzima Q10 apresentou significativa redução (p = 0,002). Além disso, o índice de massa corporal e a glicemia de jejum eram significativamente maiores nos pacientes. Houve uma correlação significativamente positiva entre os níveis de coenzima Q10 e do quociente de inteligência, bem como entre a interleucina 6 e o fator de necrose tumoral α. Conclusão: Os níveis de interleucina 6 e o fator de necrose tumoral α em crianças mais novas com síndrome de Down podem ser usados como biomarcadores, refletem o processo neurodegenerativo neles. A coenzima Q10 pode ter um papel como bom suplemento em crianças com síndrome de Down para melhorar os sintomas neurológicos.

Development and validation of stability indicating liquid chromatographic (RP-HPLC) method for estimation of ubidecarenone in bulk drug and formulations using quality by design (QBD) approach

ABSTRACT A novel, accurate, precise and economical stability indicating Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) method, was developed and validated for the quantitative determination of ubidecarenone (UDC) in bulk drug, UDC marketed formulation and UDC loaded cubosomes (CBMs) nanocarriers through Response surface methodology (RSM) design with three factors and three levels was performed to optimize the chromatographic variables followed by forced degradation studies of UDC were performed to detect degradation peak. RP-HPLC separation was achieved using mobile phase consisting of Acetonitrile:Tetrahydrofuran:Deionised water in the ratio 55:42:3 and a flow rate of 1.0 mL/min was optimized with a standard retention time (Rt) of 2.15 min, through experiment. The method was found linear in the concentration range of 5-100 µg/mL with a regression coefficient of 0.999. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 3.04 µg/mL and 9.11 µg/mL, respectively.

The efficacy and safety of coenzyme Q10 in preventing the progression of early Parkinson's disease: A meta-analysis

INTRODUCTION: Coenzyme Q10, also known as Ubiquinone, is a substance now being used as a dietary supplement in many countries including the Philippines. It has also been the focus of several researches as treatment for several diseases including Parkinson's Disease. Several studies have shown that Coenzyme Q10 inhibits mitochondrial dysfunction in Parkinson's Disease, hence delaying its progression.OBJECTIVES: The objective of this study is to assess and summarize the available evidence on the efficacy and safety of Coenzyme Q10 administration in the prevention of the progression of early Parkinson's Disease.METHODS: This is meta-analysis of randomized controlled trials on the use of Coenzyme Q10 in Parkinson's Disease. A literature search in several databases was conducted for relevant studies. Three randomized controlled trials met the inclusion criteria. The efficacy of Coenzyme Q10 were measured using the total and the component scores of the Unified Parkinson Disease Rating Scale on follow-up. On the other hand, safety were measured using the withdrawal rate and the associated adverse reactions during the therapy of CoQ10. The Review Manager Software was utilized for the meta-analysis.RESULTS: Compared to Placebo, treatment of CoQ10 did not show any significant difference in the mean scores of the UPDRS mental and ADL scores. Interestingly, the UPDRS motor score showed a significant difference between Coenzyme Q10 and placebo, but no significant difference when a subgroup analysis between high-dose (-4.03 [-15.07-7.01], p-value 0.47, I2 67%, P for heterogeneity 0.08) and low-dose Coenzyme Q10 (0.53 [-0.89-1.94], p-value 0.47, I2 34%, P for heterogeneity 0.22) was done. Overall, there was no significant difference in the total UPDRS score (0.68 [-0.61-1.97], p-value 0.30, I2 0%, P for heterogeneity 0.70). The anxiety, back pain, headache, sore throat, nausea, dizziness and constipation.CONCLUSION: Contrary to some animal and human studies, this meta-analysis showed that the use of CoQ10 results to non-significant improvement in all components of the UPDRS scores as opposed to placebo. However, the use of CoQ10 is tolerated and seems to be safe but further studies are needed to validate this finding.

Coenzyme Q10 defects may be associated with a deficiency of Q10-independent mitochondrial respiratory chain complexes

BACKGROUND: Coenzyme Q10 (CoQ10 or ubiquinone) deficiency can be due either to mutations in genes involved in CoQ10 biosynthesis pathway, or to mutations in genes unrelated to CoQ10 biosynthesis. CoQ10 defect is the only oxidative phosphorylation disorder that can be clinically improved after oral CoQ10 supplementation. Thus, early diagnosis, first evoked by mitochondrial respiratory chain (MRC) spectrophotometric analysis, then confirmed by direct measurement of CoQ10 levels, is of critical importance to prevent irreversible damage in organs such as the kidney and the central nervous system. It is widely reported that CoQ10 deficient patients present decreased quinone-dependent activities (segments I + III or G3P + III and II + III) while MRC activities of complexes I, II, III, IV and V are normal. We previously suggested that CoQ10 defect may be associated with a deficiency of CoQ10-independent MRC complexes. The aim of this study was to verify this hypothesis in order to improve the diagnosis of this disease. RESULTS: To determine whether CoQ10 defect could be associated with MRC deficiency, we quantified CoQ10 by LC-MSMS in a cohort of 18 patients presenting CoQ10-dependent deficiency associated with MRC defect. We found decreased levels of CoQ10 in eight patients out of 18 (45 %), thus confirming CoQ10 disease. CONCLUSIONS: Our study shows that CoQ10 defect can be associated with MRC deficiency. This could be of major importance in clinical practice for the diagnosis of a disease that can be improved by CoQ10 supplementation.

Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of the polyglutamine domain of the ataxin-3 (ATX3) protein. MJD/SCA3 is the most frequent autosomal dominant ataxia in many countries. The mechanism underlying MJD/SCA3 is thought to be mainly related to protein misfolding and aggregation leading to neuronal dysfunction followed by cell death. Currently, there are no effective treatments for patients with MJD/SCA3. Here, we report on the potential use of lithium carbonate and coenzyme Q10 to reduce cell death caused by the expanded ATX3 in cell culture. Cell viability and apoptosis were evaluated by MTT assay and by flow cytometry after staining with annexin V-FITC/propidium iodide. Treatment with lithium carbonate and coenzyme Q10 led to a significant increase in viability of cells expressing expanded ATX3 (Q84). In addition, we found that the increase in cell viability resulted from a significant reduction in the proportion of apoptotic cells. Furthermore, there was a significant change in the expanded ATX3 monomer/aggregate ratio after lithium carbonate and coenzyme Q10 treatment, with an increase in the monomer fraction and decrease in aggregates. The safety and tolerance of both drugs are well established; thus, our results indicate that lithium carbonate and coenzyme Q10 are good candidates for further in vivo therapeutic trials.

Mitochondria-targeted antioxidant Mitoquinone protects post-thaw human sperm against oxidative stress injury / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the potential protective effect of the mitochondria-targeted antioxidant Mitoquinone (MitoQ) on post-thaw human sperm.</p><p><b>METHODS</b>Semen samples were collected from 60 normal fertile men, each divided into six parts of equal volume to be incubated at 37 °C in normal saline (G0, control) or in the extender with 2 nmol/L (G1), 20 nmol/L (G2), 200 nmol/L (G3), 2 µmol/L (G4), and 20 µmol/L of MitoQ (G5). After one hour of incubation, the samples were subjected to computer-assisted semen analysis (CASA) for sperm motility, flow cytometry for reactive oxygen species (ROS), thiobarbituric acid assay for the concentration of malondialdehyde (MDA), and MitoTracker fluorescent staining and flow cytometry for the sperm mitochondrial membrane potential (MMP). Then, the semen were cryopreserved with none (B0), 200 nmol/L (B1), and 2 µmol/L of MitoQ (B2), followed by detection of the changes in the ROS, MDA, and MMP of the post-thaw sperm.</p><p><b>RESULTS</b>The percentage of progressively motile sperm and total rate of sperm motility were significantly higher in G3 ([30.8 ± 10.2]% and [70.6 ± 9.0]%) and G4 ([32.7 ± 13.5]% and [70.3 ± 11.9]%) than in G0 ([17.6 ± 5.0]% and [54.9 ± 11.5]%) (P < 0.05). The level of ROS dropped markedly with the increased concentration of MitoQ, 86.5 ± 31.6 in G3, 93.6 ± 42.0 in G4, and 45.1 ± 15.0 in G5, as compared with 160.8 ± 39.7 in G0 (P < 0.05). The content of MDA was remarkably lower in G3 ([0.9 ± 0.5] µmol/mg) and G4 ([0.9 ± 0.5] µmol/mg) than in G0 ([1.9 ± 1.1] µmol/mg) (P < 0.05), but not in G5 ([1.7 ± 0.7] µmol/mg), which was even higher than in G3 and G4 (P < 0.05). The MMP showed a significant reduction in G5 (1156 ± 216) in comparison with G0 (1701 ± 251) (P < 0.05) but exhibited no remarkable difference between G0 and G1 (1810 ± 298), G2 (1995 ± 437), G3 (1950 ± 334), or G4 (1582 ± 314). The percentage of progressively motile sperm and total rate of sperm motility after freezing-thawing were significantly decreased as compared with those of the fresh semen (P < 0.01), but both were remarkably higher in B1 ([3.2 ± 2.3]% and [ 43.0 ± 9.5]%) than in B0 ([0.8 ± 0.6]% and [26.5 ± 11.4]%) (P < 0.05). The ROS level was significantly lower in B1 and B2 than in B0 (34.6 ± 12. 3 and 37.0 ± 10.5 vs 56.9 ± 14.3, P < 0.05), and so was the MDA content ([1.4 ± 0.5] and [1.4 ± 0.6] µmol/mg vs [2.6 ± 1.0] µmol/mg, P < 0.05), but the MMP was markedly higher in B1 and B2 than in B0 (1010.0 ± 130.5 and 880.6 ± 128.6 vs 721.1 ± 24.8, P < 0.05).</p><p><b>CONCLUSION</b>Addition of MitoQ to the freezing extender at 200 nmol/L may effectively improve the quality of human sperm and MitoQ is a good protective addictive for human sperm cryopreservation.</p>

The Levels of Cortisol and Oxidative Stress and DNA Damage in Child and Adolescent Victims of Sexual Abuse with or without Post-Traumatic Stress Disorder

OBJECTIVE: The aim of this study was to investigate whether cortisol and oxidative stress levels and DNA damage differ between individuals who developed PTSD or not following a sexual trauma. METHODS: The study included 61 children aged between 5 and 17 years who sustained sexual abuse (M/F: 18/43). The patients were divided into two groups: patients with PTSD and patients without PTSD based, based on the results of a structured psychiatric interview (K-SADS-PL and CAPS-CA). Cortisol, glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q, 8-Hydroxy-2-Deoxyguanosine (8-OHdG) were all evaluated by the ELISA method. RESULTS: Our evaluation revealed a diagnosis of PTSD in 51% (n=31) of victims. There was no significant difference between the groups with or without PTSD in terms of cortisol, GPx, SOD, coenzyme Q, and 8-OHdG levels. There was no correlation between CAPS scores and GPx, SOD, coenzyme Q, and 8-OHdG levels between patients with or without PTSD. In patients with PTSD, both cortisol and 8-OHdG levels decreased with increasing time after trauma, and there was no significant correlation with cortisol and 8-OHdG levels in patients without PTSD. CONCLUSION: Although the present study did not find any difference between the groups in terms of 8-OHdG concentrations, the decreases in both cortisol and 8-OHdG levels with increasing time after trauma is considered to indicate a relationship between cortisol and DNA damage.

Adherence to standard precautions from the standpoint of the Health Belief Model: the practice of recapping needles / Adesão às precauções padrão sob o prisma do Modelo de Crenças em Saúde: a prática de reencapar agulhas

The aim of this study was to applythe Health Belief Model to explain the adherence to the recommendation not to recap needles by dentists and dental assistants of the public health system in a municipality in the State of São Paulo. A questionnaire validated and adapted for the oral health area was used, which included variables related to the frequency of recapping and health beliefs using Likert-type scales. The relationship between beliefs and adherence to the recommendation not to recap needles was obtained by regression analysis. Of all the professionals in this study (n=79), the majority (83.5%) reported recapping needles at least once in the last month. Through regression analysis, it was observed that the relationship between the beliefs described by the model and the attitude whether or not to follow the recommendation not to recap needles was explained by a lower perception of psychological barriers and a greater perception of stimuli not to recap needles. The conclusion reached is that the acceptance of recommendations to prevent working accidents with biological material was explained by some dimensions of the Health Belief Model, enabling discussion about reformulation of training offered to professionals of the public health system.

Objetivou-se neste estudo aplicar o Modelo de Crenças em Saúde a fim de explicar a adesão à recomendação de não reencapar agulhas por cirurgiões-dentistas e auxiliares de saúde bucal da rede pública de um município paulista. Utilizou-se um questionário validado e adaptado para a área de saúde bucal, que contemplava variáveis relativas à frequência do reencape e crenças em saúde, por meio de escalas tipo Likert. A relação entre as crenças e a adesão à recomendação de não reencapar agulhas foi obtida por meio da análise de regressão. Da amostra de profissionais obtida por adesão ao estudo (n = 79), a maioria (83,5%) relatou ter reencapado agulhas pelo menos alguma vez no último mês. Por meio da análise de regressão, foi observado que a relação entre as crenças descritas pelo modelo e a atitude de aderir ou não à recomendação de não reencapar agulhas foi explicada por uma menor percepção de barreiras psicológicas e por uma maior percepção de estímulos para não reencapar agulhas. Conclui-se que a aceitação das recomendações para prevenir acidentes do trabalho com material biológico foi explicado por algumas dimensões do Modelo de Crenças em Saúde, possibilitando a discussão sobre a reformulação de capacitações oferecidas para profissionais do sistema público de saúde.