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Background: Dual antiplatelet therapy with a P2Y12 inhibitor (e.g., clopidogrel and ticagrelor) and aspirin is recommended for at least one year after percutaneous coronary intervention (PCI) to prevent further myocardial infarction and stent thrombosis as the major adverse effects of PCI. Methods: This randomized clinical trial was conducted from October 2022 to March 2023. Patients who had undergone elective PCI were included in the study. Patients were randomized into two different groups. One group took ASA 80 mg and clopidogrel 75 mg once daily, while the other took ASA 80 mg once daily and ticagrelor 90 mg twice daily. After six months of close follow-up, patients were asked to score their dyspnea on a 10-point Likert scale. They were also asked about dyspnea on exertion, paroxysmal nocturnal dyspnea (PND), bleeding, and the occurrence of major adverse cardiovascular events (MACEs). Results: 223 patients were allocated to the clopidogrel group and 214 to the ticagrelor group. In the ticagrelor group, 95 patients (44.3%) reported dyspnea at rest, compared with only 44 patients (19.7%) in the clopidogrel group (P < 0.001). MACEs occurred in 7 patients (2.8%) in the ticagrelor group, compared with 16 (7.6%) in the clopidogrel group (P = 0.031). Eight patients (3.8%) reported bleeding with ticagrelor, as did seven (3.2%) with clopidogrel (P = 0.799). Conclusions: New-onset dyspnea was recorded more frequently with ticagrelor than clopidogrel, yet fewer MACEs occurred with ticagrelor (ClinicalTrials.gov number: NCT05858918).
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Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Humanos , Clopidogrel/efeitos adversos , Ticagrelor/uso terapêutico , Ticagrelor/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Hemorragia/epidemiologia , Aspirina/uso terapêutico , Dispneia/etiologia , Stents , Síndrome Coronariana Aguda/terapia , Resultado do TratamentoRESUMO
The kidney is a highly complex organ in the human body. Although creating an in vitro model of the human kidney is challenging, tremendous advances have been made in recent years. Kidney organoids are in vitro kidney models that are generated from stem cells in three-dimensional (3D) cultures. They exhibit remarkable degree of similarities with the native tissue in terms of cell type, morphology, and function. The establishment of 3D kidney organoids facilitates a mechanistic study of cell communications, and these organoids can be used for drug screening, disease modeling, and regenerative medicine applications. This review discusses the cellular complexity during in vitro kidney generation. We intend to highlight recent progress in kidney organoids and the applications of these relatively new technologies.
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Rim , Organoides , Humanos , Medicina Regenerativa/métodosRESUMO
This study characterized quinolone (Q) resistance determinants in a series of Klebsiella pneumoniae (n = 26) and Escherichia coli (n = 19) isolates of human and animal origin. The presence of plasmid-mediated quinolone resistance (PMQR) and carabpenemase genes was examined by PCR. The quinolone resistance-determining regions (QRDRs) of gyrA and parC genes were sequenced. Thirty-three isolates had ciprofloxacin MIC≥8 mg/l. About 34.6% and 10.5% of K. pneumoniae and E. coli isolates were ESBL producers respectively. The PMQR genes were detected in 77% (n = 35) of isolates. The oqxAB was the most prevalent PMQR gene being identified in all K. pneumoniae isolates, followed by aac(6')-Ib-cr (34.6%), qnrS (23%) and qnrB (7.7%). The most frequently detected gene among E. coli isolates was qnrS (36.8%) followed by aac(6')-Ib-cr (10.5%) and qepA (5.2%). All Q resistant isolates harbored amino acid substitutions in both GyrA and ParC QRDRs. High prevalence of PMQR genes among food-producing animal isolates is an issue of great concern.
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Infecções por Escherichia coli , Quinolonas , Animais , Antibacterianos/farmacologia , Galinhas , Farmacorresistência Bacteriana/genética , Escherichia coli , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/veterinária , Humanos , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Quinolonas/farmacologiaRESUMO
INTRODUCTION: Tigecycline (TGC) is one of the last-resort therapeutic agents for treating infections caused by extensively drug resistant Acinetobacter baumannii isolates. Although resistance to TGC is not common, non-susceptible A. baumannii (NSAB) isolates have been described. In the current study, we aimed to assess the molecular mechanisms mediating TGC non-susceptibility in 5 clinical isolates of A. baumannii with reduced susceptibility to TGC. METHODS: Susceptibility of isolates to TGC as well as various classes of antibiotics was evaluated by broth dilution and disk diffusion methods, respectively. The presence of tetX and tetX1 genes was investigated by PCR. The nucleotide sequences of adeR and adeS genes were assessed by PCR amplicon sequencing. To evaluate the association between reduced susceptibility to TGC and upregulation of AdeABC efflux pump, transcriptional level of adeB gene was quantified by RT-qPCR analysis. RESULTS: All 5 TGC-NSAB isolates had a TGC MIC of ≥4 mg/L and were resistant to all antimicrobials tested by disk diffusion method except for minocycline and doxycycline for which a susceptibility rate of 40% and 20% was observed, respectively. The tetX/X1 genes were not detected in any isolates. All TGC non-susceptible isolates harbored genetic alterations in the adeRS operon, including AdeS G186V, N268H, and D60N and AdeR A136V and V120I substitutions among, which G186V and D60N were predicted by PROVEAN tool analysis as inactivating alterations. Reduced TGC susceptibility was associated with upregulation of AdeABC efflux pump in all TGC non-susceptible isolates. CONCLUSION: It can be concluded from our results that reduced susceptibility to TGC in the studied isolates was mainly mediated by genetic alterations in the AdeRS system, which resulted in overexpression of AdeABC efflux pump. Emergence of TGC non-susceptibility among isolates that had not been previously exposed to TGC is an issue of great concern.
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Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Tigeciclina/farmacologia , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Infecções por Acinetobacter/diagnóstico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Fenótipo , Transcrição GênicaRESUMO
Fasciola hepatica is a well-known helminth parasite, with significant economic and public health importance all over the world. It has been known since more than 630 years ago and a considerable research work has been carried out on the life cycle of this important parasite. In the hepatic phase of the life cycle of F. hepatica, it is assumed that the young flukes, after about 6-7 weeks of migration in the liver parenchyma, enter into the bile ducts of the definitive hosts and become sexually mature. Even though the secretion of cysteine peptidases including cathepsin L and B proteases by F. hepatica may justify this opinion, because of several scientific reasons and based on the experimental studies conducted in different animals (reviewed in this article), the entry of parasites into the bile ducts, after their migration in the liver parenchyma seems to be doubtful. However, considering all the facts relating to the hepatic and biliary phases of the life cycle of F. hepatica, two alternative ideas are suggested: 1) some of the migrating juvenile flukes may enter into the bile ducts immediately after reaching the liver parenchyma while they are still very small, or 2) when newly excysted juvenile flukes are penetrating into the intestinal wall to reach the liver through the abdominal cavity, a number of these flukes may enter into the choleduct and reach the hepatic bile ducts, where they mature. According to the previously performed natural and experimental studies in different animals and human beings, the supporting and opposing evidences for the current opinion as well as the evidences that might justify the two new ideas are reviewed and discussed briefly. In conclusion, our present knowledge about the time and quality of the entry of F. hepaticas into the bile ducts, seems to be insufficient, therefore, there are still some dark corners and unknown aspects in this field that should be clarified.
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Ductos Biliares/parasitologia , Fasciola hepatica/crescimento & desenvolvimento , Fasciolíase/parasitologia , Estágios do Ciclo de Vida/fisiologia , Animais , Fasciola hepatica/fisiologia , Humanos , Fígado/parasitologia , Lymnaea/parasitologia , Fatores de TempoRESUMO
To date, a number of species of Haemogregarina have been described from different turtle hosts, mainly based on the morphology of the developmental stages detected in the host erythrocytes. The diversity and overlapping morphological features in the old and recent descriptions has led to considerable complications in the taxonomy of Haemogregarina spp. In this study, different stages of maturity and developing gamonts of a putative new species of Haemogregarina were detected in erythrocytes of the Caspian turtle Mauremys caspica (Gmelin) (Geoemydidae) originating from a southern province in Iran. Although some of the morphological characteristics were consistent with Haemogregarina stepanowi Danilewsky, 1885, some new observations were made, particularly in the gamont stage. The phylogenetic analysis based on 18S rDNA sequences revealed that the present isolate appears as basal to a large clade of Haemogregarina spp. with sequences available in the GenBank database. In accordance with the phylogenetic results, the present Iranian isolate showed a higher degree of interspecific divergence (up to 3.3%) compared to the data for the taxa available in the GenBank database. Thus, molecular data indicate that this isolate may represent a new species. However, further genetic analyses are needed as a complementary tool to the morphological characterisation in order to elucidate the phylogenetic relationships of Haemogregarina spp.
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Eucoccidiida/classificação , Eucoccidiida/citologia , Filogenia , Tartarugas/parasitologia , Animais , DNA Ribossômico/genética , Eritrócitos/parasitologia , Água Doce , Irã (Geográfico) , Especificidade da EspécieRESUMO
Habronema muscae is a spirurid nematode that undergoes developmental stages in the stomach of equids, causing chronic catarrhal gastritis. Despite preceding investigations have developed polymerase chain reaction (PCR)-based assays for molecular diagnosis, we aimed to assess the applicability of cytochrome c oxidase subunit 1 (cox1) sequences to identify the H. muscae infection and to assess the level of intraspecific variations in this parasite obtained from affected horses in Southern Iran. According to the morphological characterizations, two different isolates of H. muscae were identified. Although the majority of the recovered specimens had normal characterizations of H. muscae, a number of parasites showed an abnormal feature as large, asymmetrical, and thick cuticular extensions was observed at their anterior end (head region) in gross and histologic examinations. Unexpectedly, molecular assay disclosed that both morphologically distinct samples were completely identical to each other based on cox1 sequence. Multiple alignment of the cox1 amino acid sequences showed that all polymorphism sites were silent. Also, phylogenetic analysis provided strong support that H. muscae form a sister group to Spirocerca lupi and Thelazia callipaeda.
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Doenças dos Cavalos/parasitologia , Infecções por Spirurida/veterinária , Spiruroidea/isolamento & purificação , Sequência de Aminoácidos , Animais , Sequência de Bases , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/genética , DNA de Helmintos/química , Mucosa Gástrica/parasitologia , Cavalos , Irã (Geográfico) , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase , Alinhamento de Sequência/veterinária , Infecções por Spirurida/parasitologia , Spiruroidea/anatomia & histologia , Spiruroidea/classificação , Spiruroidea/genéticaRESUMO
Many zoonotic parasitic diseases, including Toxocara cati, may be spread by stray cat populations. This study aimed to determine the prevalence of parasites by performing parasitological and histopathological examinations on stray cats in Shiraz, Iran. A total of 106 stray cats from different geographical areas of Shiraz, southern Iran, were examined for the presence of parasites. The overall prevalence was found to be 83.02% (88/106), and eight parasites were found. The parasites included three genera of cestodes [Joyeuxiella echinorhynoides (52.83%), Taenia taeniaeformis (21.70%), and Dipylidium caninum (1.89%)], three nematodes [Physaloptera praeputialis (23.59%), Toxocara cati (15.09%), and Rictularia sp. (1.89%)], one protozoa [Isospora spp. (6.60%)], and one arthropod [Ctenocephalides felis (5.66%)]. The prevalence did not significantly differ between males and females. It did appear, nevertheless, that the age of cats may be regarded as a risk factor for these parasitic infections. Histopathological examination revealed some parasite-induced lesions in the intestine and stomach, including hyperemia, hemorrhage, mucosal destruction and inflammation. The lung tissues showed some histopathological lesions such as hemorrhage, edema, emphysema and mild inflammation, and dormant larvae were found in one tongue sample. The results of the present study showed that parasitic infections and, more importantly, T. cati are relatively prevalent in stray cats, and the people living in this area are at serious risk of this zoonotic disease. The cats in this region need to be monitored, and specific preventive measures should be developed by public health officials.
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Doenças do Gato , Animais , Gatos , Irã (Geográfico)/epidemiologia , Doenças do Gato/parasitologia , Doenças do Gato/epidemiologia , Masculino , Feminino , Prevalência , Doenças Parasitárias em Animais/epidemiologia , Doenças Parasitárias em Animais/parasitologia , Parasitos/isolamento & purificação , Parasitos/classificaçãoRESUMO
Purpose: This study aimed to compare macular vascular changes one and three months after treatment with either panretinal photocoagulation (PRP) or intravitreal bevacizumab (IVB). Methods: A total of 62 eyes with very severe non-proliferative diabetic retinopathy or early proliferative diabetic retinopathy without center-involved diabetic macular edema, were included in this retrospective study. Thirty-nine eyes were allocated to the PRP group, while 23 eyes were treated with IVB. Optical coherence tomography angiography (OCTA) was performed to measure foveal avascular zone (FAZ) characteristics as well as the densities of superficial and deep capillary plexuses (SCP and DCP). Results: In the IVB group, the FAZ area and perimeter expanded at month one but returned to baseline level after three months. In the PRP group, however, the FAZ area and perimeter were rather steady. Changes in the FAZ area were significantly different between the treatment groups at month one (P = 0.02), but not at month three (P = 0.31). There was no significant difference in the change in FAZ circularity index between the two groups at each time point (P = 0.55 and P = 0.31). Similarly, changes in SCP density were not statistically significant between the two groups at both time points (all Ps > 0.05). A comparison of the two treatment arms based on the mean change in DCP density revealed a significant difference at month one, but not at month three (P = 0.01 and P = 0.49, respectively). Conclusion: Although bevacizumab and PRP have different short-term macular vascular responses, both therapies have the ability to normalize or stabilize vascular measures over time.
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Background: Colon carcinoma poses a significant health challenge globally, particularly in developed nations where sedentary lifestyles, poor dietary choices, and genetic factors play a crucial role in its prevalence. Chemotherapy, the primary treatment method, carries severe side effects that can jeopardize patients' lives. Herbal extracts such as Ocimum Basillicum extract have shown effectiveness against cancer cells. Additionally, nanoparticles can significantly enhance drug delivery efficacy in these scenarios. Aim: This article aims to investigate the impact of copper nanoparticles coated with Ocimum Bassilicum at chemoradiotherapy of Colon Carcinoma to hopefully create new treatment options with fewer side effects for patients. Methodology: CuO bio-NPs were produced by the addition of 15 mL of extract dropwise to 80 mL of a 5 mM Cu (OAc)2 aqueous solution, which was then refluxed for 2 h at 100 °C. The mixture gradually became darker brown in color as a result of the heating procedure. The production of CuO NPs and the hydrogen-donating activity of antioxidant phenols within the plant are signaled by surface plasmon resonance excitation, which is the cause of this. In the cell culture, LS174t colon cancer cells were treated with OB extract, CuNPs, and OB-coated CuNPs with and without different radiation levels in order to assess cell viability, through the MTT assay, and the pro-apoptotic BAX and anti-apoptotic BCL2 expressions, through qPCR assay. Results: The results demonstrate a decrease in cell viability and the expression of BCL2 and an increase in the expression of BAX especially when treated with OB-coated CuNPs and even furthermore when paired with radiation therapy. Conclusions: After doing the clinical trial studies, the recent nanoparticles can be used for the treatment of Colorectal carcinoma.
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Current methods of colon cancer treatment, especially chemotherapy, require new treatment methods due to adverse side effects. One important area of interest in recent years is the use of nanoparticles as drug delivery vehicles since several studies have revealed that they can improve the target specificity of the treatment thus lowering the dosage of the drugs while preserving the effectiveness of the treatment thus reducing the side effects. The use of traditional medicine has also been a favorite topic of interest in recent years in medical research, especially cancer research. In this research work, the green synthesis of Fe nanoparticles was carried out using Mentha spicata extract and the synthesized nanoparticles were identified using FT-IR, XRD, FE-SEM and EDS techniques. Then the effect of Mentha spicata, Fe nanoparticles, and Mentha spicata -loaded Fe nanoparticles on LS174t colon cancer cells, and our result concluded that all three, especially Mentha spicata -loaded Fe nanoparticles, have great cytotoxic effects against LS174t cells, and exposure to radiotherapy just further intensified these results. The in vitro condition revealed alterations in the expression of pro-apoptotic BAX and anti-apoptotic Bcl2, suggesting a pro-apoptotic effect from all three components, particularly the Mentha spicata-loaded Fe nanoparticles. After further clinical trials, these nanoparticles can be used to treat colon cancer.
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Neuroinflammation facilitates seizure acquisition and epileptogenesis in developing brain. Yet, the studies on impact of neuroinflammation on mature brain epileptogenesis have led to inconsistent results. Hippocampus is particularly vulnerable to damage caused by ischemia, hypoxia and trauma, and the consequent neuroinflammation, which can lead in turn to epilepsy. Lipopolysaccharide (LPS) is extensively used in experimental studies to induce neuroinflammation. In this study, effect of acute and chronic intra-CA1 infusion of LPS on amygdala-kindled seizures and epileptogenesis was examined in mature rats. LPS (5 µg/rat) inhibited evoked amygdala afterdischarges and behavioral seizures. Anticonvulsant effect of LPS was observed 0.5 h after administration and continued up to 24 h. This effect was accompanied by intra-hippocampal elevation of nitric oxide (NO), interleukin1-ß, and tumor necrosis factor-α and was prevented by microglia inhibitor, naloxone, NO synthase inhibitor, Nω-nitro-L-arginine methyl ester, cyclooxygenase inhibitor, piroxicam, and interleukin1-ß receptor antagonist, interleukin1-ra. Moreover, daily intra-hippocampal injection of LPS significantly retarded kindling rate. In order to further elucidate the effect of LPS on synaptic transmission and short-term plasticity, changes in field excitatory postsynaptic potentials and population spikes were measured in stratum radiatum and stratum pyramidale of LPS-treated kindled rats. LPS impaired baseline synaptic transmission in hippocampal Schaffer collateral-CA1 synapse and reduced the magnitude of paired-pulse facilitation. Our results suggest that direct suppression of presynaptic mechanisms in Schaffer collateral-CA1 synapses, as well as the inflammatory mediators released by LPS in the hippocampus, is involved in antiepileptic effect of LPS.
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Hipocampo/fisiologia , Excitação Neurológica/fisiologia , Lipopolissacarídeos/administração & dosagem , Convulsões/prevenção & controle , Convulsões/fisiopatologia , Animais , Hipocampo/efeitos dos fármacos , Injeções Intraventriculares , Excitação Neurológica/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
BACKGROUND: We aimed to determine the effects of systemic therapy with autologous adipose tissue derived mesenchymal stem cells (AD-MSCs) on different parameters of peritoneal function and inflammation in peritoneal dialysis (PD) patients. METHODS: We enrolled nine PD patients with ultrafiltration failure (UFF). Patients received 1.2±0.1×106 cell/kg of AD-MSCs via cubital vein and were then followed for six months at time points of baseline, 3, 6, 12, 16 and 24 weeks after infusion. UNI-PET was performed for assessment of peritoneal characteristics at baseline and weeks 12 and 24. Systemic and peritoneal levels of tumor necrosis factor α (TNF-α), interleukin-6(IL-6), IL-2 and CA125 (by ELISA) and gene expression levels of transforming growth factor beta (TGF-ß), smooth muscle actin (ð¼-SMA) and fibroblast-specific protein-1 (FSP-1) in PD effluent derived cells (by quantitative real-time PCR) were measured at baseline and weeks 3, 6, 12, 16 and 24. RESULTS: Slight improvement was observed in the following UF capacity indices: free water transport (FWT, 32%), ultrafiltration - small pore (UFSP, 18%), ultrafiltration total (UFT, 25%), osmotic conductance to glucose (OCG, 25%), D/P creatinine (0.75 to 0.70), and Dt/D0 glucose (0.23 to 0.26). There was a slight increase in systemic and peritoneal levels of CA125 and a slight decrease in gene expression levels of TGF-ß, α-SMA and FSP-1 that was more prominent at week 12 and vanished by the end of the study. CONCLUSION: Our results for the first time showed the potential of MSCs for treatment of peritoneal damage in a clinical trial. Our results could be regarded as hypothesis suggestion and will need confirmation in future studies.
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Fibrose Peritoneal , Humanos , Projetos Piloto , Soluções para Diálise/metabolismo , Fator de Crescimento Transformador beta , Glucose/metabolismoRESUMO
Linguatula serrata is an important zoonotic parasite with worldwide distribution. The objective of the present study was to investigate the molecular characterization and phylogenetic analysis of nymphal stage of L. serrata from camels, goats and sheep in Iran. The mesenteric lymph nodes were collected from various ruminants including goats, sheep and camels at Isfahan and Shiraz slaughterhouses and the nymphs were identified using morphological characteristics. After DNA extraction, the 18 S rRNA and Cox1 genes were amplified by polymerase chain reaction. The sequencing of the genes was conducted using specific primers and a capillary DNA analyzer. The comparison of amplified sequences with existing data confirmed the presence of L. serrata with 99.6-100% nucleotide sequence similarity. Based on 18 S rRNA and Cox1 sequences, two isolates collected from sheep revealed 100% and 99.9% sequence identity, respectively. Also, three isolates from camel had 99.64-100% and 99.7-100% homology. Two isolates from sheep had 100% identity in their 18SrRNA gene and were categorized together, but showed 99.9% similarity in the Cox1 gene, not clustering together. Phylogenetic analysis of the Cox1 gene classified nearly all the isolates into L. arctica clade. It can be concluded that 18 S rRNA and Cox1 genes sequencing can be a proper method for the analysis of phylogenetic relationships of L. serrata among different hosts in different parts of Iran, possibly helpful for infection control and prevention.
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Myianoetus is a Histiostomatidae mites that are phoretic on flies. The relation between flies and phoretic mites is considered to be of potential value in forensic studies, as the development of flies associated with decomposing human remains. So, they may useful in determining the time of death of an individual. This study represents the first records of Myianoetus muscarum deutonymph phoretic on adult Musca domestica in Iran. Further studies are needed to find any relation between phoretic mites and flies.
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Dípteros , Ácaros , Humanos , Animais , Irã (Geográfico)RESUMO
The present study aimed to investigate the effects of 8-week of coenzyme Q10 (CoQ10) supplementation alone or combined with concurrent training (CT) on functional capacity, serum brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in multiple sclerosis (MS) patients. Our hypothesis is that CT promotes improvements in the studied outcomes with higher results for the combination of CT and CoQ10. Randomized placebo-controlled trial. Twenty-eight patients with MS were randomly divided into 4 groups: CT+placebo, CT+CoQ10, CoQ10 and placebo. CT involved two resistance training sessions and one aerobic training session per week. CoQ10 was supplemented with 200 mg daily. Serum levels of BDNF, NGF and functional tests [timed up and go (TUG), 6-min walk (6MW), chest press, lateral pull down, leg extension, and lying leg curls one repetition maximum] were measured before and after the intervention period. CT+placebo and CT+CoQ10 significantly improved performance in TUG, 6MW, chest press, lateral pull down, leg extension, and lying leg curls, with superior results to both CoQ10 and placebo groups. Changes in TUG for CT+placebo were significantly higher than CT+CoQ10 (p<0.05). There were no significant differences in NGF and BDNF among the four groups (p >0.05). CT improves physical abilities in patient with MS, regardless CoQ10 supplementation. CT should be recommended for MS patients to increase functional capacity, but there seems to be no benefit in supplementing CoQ10.
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Traumatic brain injury (TBI), characterized by acute neurological impairment, is associated with a higher incidence of neurodegenerative diseases, particularly chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD), whose hallmarks include hyperphosphorylated tau protein. Recently, phosphorylated tau at Thr231 has been shown to exist in two distinct cis and trans conformations. Moreover, targeted elimination of cis P-tau by passive immunotherapy with an appropriate mAb that efficiently suppresses tau-mediated neurodegeneration in severe TBI mouse models has proven to be a useful tool to characterize the neurotoxic role of cis P-tau as an early driver of the tauopathy process after TBI. Here, we investigated whether active immunotherapy can develop sufficient neutralizing antibodies to specifically target and eliminate cis P-tau in the brain of TBI mouse models. First, we explored the therapeutic efficacy of two different vaccines. C57BL/6 J mice were immunized with either cis or trans P-tau conformational peptides plus adjuvant. After rmTBI in mice, we found that cis peptide administration developed a specific Ab that precisely targeted and neutralized cis P-tau, inhibited the development of neuropathology and brain dysfunction, and restored various structural and functional sequelae associated with TBI in chronic phases. In contrast, trans P-tau peptide application not only lacked neuroprotective properties, but also contributed to a number of neuropathological features, including progressive TBI-induced neuroinflammation, widespread tau-mediated neurodegeneration, worsening functional deficits, and brain atrophy. Taken together, our results suggest that active immunotherapy strategies against pathogenic cis P-tau can halt the process of tauopathy and would have profound clinical implications.
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Lesões Encefálicas Traumáticas , Doenças Neurodegenerativas , Tauopatias , Animais , Camundongos , Encéfalo/metabolismo , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/terapia , Lesões Encefálicas Traumáticas/metabolismo , Modelos Animais de Doenças , Imunoterapia Ativa , Camundongos Endogâmicos C57BL , Proteínas tau/metabolismo , Tauopatias/terapia , Tauopatias/complicações , Tauopatias/metabolismoRESUMO
Background: Although statins decrease mortality in coronary artery disease, the effect of high-dose statins and duration of therapy post-percutaneous coronary intervention (PCI) is not well addressed. Aim: To determine the effective dose of statin to prevent major adverse cardiovascular events (MACEs), such as acute coronary syndrome, stroke, myocardial infarction, revascularisation and cardiac death, after PCI in patients with chronic coronary syndrome. Methods: In this randomised, double-blind clinical trial, all chronic coronary syndrome patients with a recent history of PCI were randomly divided into two groups after 1 month of high-dose rosuvastatin therapy. Over the next year, the first group received rosuvastatin 5 mg daily (moderate intensity), while the second received rosuvastatin 40 mg daily (high intensity). Participants were evaluated in terms of high-sensitivity C-reactive protein and MACEs. Results: The 582 eligible patients were divided into group 1 (n=295) and group 2 (n=287). There was no significant difference between the two groups in terms of sex, age, hypertension, diabetes, smoking, previous history of PCI or history of coronary artery bypass grafting (p>0.05). There were no statistically significant differences in MACE and high-sensitivity C-reactive protein after 1 year between the two groups (p=0.66). Conclusion: The high-dose group had lower LDL levels. However, given the lack of association between high-intensity statins and MACEs in the first year after PCI among chronic coronary syndrome patients, the use of moderate-intensity statins may be as effective as high-intensity statins, and treatment based on LDL targets may suffice.
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Hypertension is a highly prevalent disease with serious cardiovascular and renal complications. Many studies have demonstrated a weak correlation between the consumption of calcium (or calcium plus vitamin D) and blood pressure, suggesting that calcium supplements might reduce blood pressure. However, the results to date remain controversial. In this study, we assessed the effect of calcium and vitamin D supplementation on the blood pressure of postmenopausal women with hypertension as a population group in which the use of calcium supplements is prevalent. This triple-blind randomized clinical trial enrolled 98 women of postmenopausal age with hypertension in 2019. The study period was 8 weeks with close follow-up. We used 24-h ambulatory blood pressure monitoring to record the initial and final blood pressure in all participants. The changes in both the mean systolic (p = 0.047) and diastolic blood pressure (p = 0.015) were suggestive of an increase in blood pressure after consuming calcium and vitamin D supplements. Among patients who had been using calcium channel blockers, calcium and vitamin D supplementation caused a notable increase compared to baseline systolic (p = 0.019) and diastolic blood pressures (p = 0.001). The present results differ from those of previous studies. This suggests that calcium supplementation for postmenopausal women with hypertension requires the close observation of blood pressure to prevent any further increase, especially in women who are being treated with calcium channel blockers (clinicaltrial.gov registration: NCT04618952).
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Hipertensão , Vitamina D , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Cálcio , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Hipertensão/tratamento farmacológico , Pós-Menopausa , Vitamina D/uso terapêuticoRESUMO
BACKGROUND: Dyslipidemia is a prominent cause of cardiovascular disease as it leads to inflammation and plaque deposition within arteries. Treatment includes lifestyle modifications and lipid-lowering medications. We aimed to assess the therapeutic effects of red yeast rice (RYR) alongside statin therapy. METHODS: This triple-blind randomized clinical trial involved 92 dyslipidemia patients and was performed in 2019. Standard laboratory tests were used to assess the serum LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), total cholesterol, triglyceride (TG), and high sensitivity C-reactive protein (hs-CRP) levels. Subsequently, patients randomly received one daily RYR or placebo tablet for 1 month beside routine single statin therapy. Subsequently, blood tests were repeated and compared against the baseline. Liver function tests were also requested. RESULTS: Total cholesterol significantly (P = 0.019) decreased in the treatment group (- 10.2 mg/dL) compared with the placebo group (- 1.3 mg/dL). HDL cholesterol decreased by 2.19 mg/dL in the treatment group but increased by 0.53 mg/dL in the treatment group (P = 0.083). LDL cholesterol declined in both placebo (- 5.09) and treatment (- 0.73) groups (P = 0.187). TG increased by about 7 mg/dL in the treatment group but fell by roughly 1 mg/dL in the placebo group (P = 0.386). Hs-CRP increased by 0.28 mg/dL in the treatment group but decreased by 0.09 mg/dL in the placebo group (P = 0.336). CONCLUSIONS: We found that adding RYR (Lesstat®) to statin medications significantly decreases total cholesterol. However, no significant effect was seen on other lipid profile components or Hs-CRP. Finally, we showed that RYR is safe to add to statins considering liver function (clinicaltrials.gov: NCT05095480).