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1.
BMJ Case Rep ; 15(1)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996770

RESUMO

Postoperative fevers are common in hospitalised patients and warrant workup beyond the early post-op period. A 50-year-old man was admitted after sustaining a tibial plateau fracture. Fevers began 3 days after external fixation and persisted through a second surgery despite initial negative workup. Careful review of medications revealed enoxaparin as the instigating agent of a febrile drug reaction, and the fevers resolved after discontinuing the drug. On further questioning, it was discovered the patient had an allergy to pork, from which the main components of enoxaparin are typically derived. To our knowledge, this is the first reported enoxaparin-induced fever in the setting of a pork allergy. Enoxaparin-induced fevers should be considered in patients with unexplained post-op fever. Our case demonstrates the importance of analysing newly administered medications. Simple detailed history may significantly reduce patient morbidity and help to broaden differentials during investigation.


Assuntos
Febre de Causa Desconhecida , Hipersensibilidade , Carne de Porco , Carne Vermelha , Animais , Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/induzido quimicamente , Suínos
2.
Arch Soc Esp Oftalmol (Engl Ed) ; 97(1): 52-57, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35027147

RESUMO

We present the clinical case of a patient who developed a toxic optic neuropathy due to ethambutol in the context of a tuberculosis reactivation and who also had a personal history of multiple sclerosis. The objective is to highlight the importance of making a good differential diagnosis of this adverse effect and of knowing its main clinical, campimetric and tomographic manifestations and characteristics. Furthermore, since the reversibility of damage is still discussed in the literature, early diagnosis is essential. For this purpose, it is important to inform the patient of the possible symptoms and to carry out an ophthalmological examination and colour tests before starting treatment to assess whether there is progression.


Assuntos
Esclerose Múltipla , Doenças do Nervo Óptico , Antituberculosos/efeitos adversos , Etambutol/efeitos adversos , Humanos , Nervo Óptico , Doenças do Nervo Óptico/induzido quimicamente , Doenças do Nervo Óptico/diagnóstico
3.
Rev Med Liege ; 77(1): 8-12, 2022 Jan.
Artigo em Francês | MEDLINE | ID: mdl-35029334

RESUMO

The use of amphetamines and amphetamine derivatives such as ecstasy can cause serotonin toxic syndrome, an uncommon but potentially serious adverse effect. Although most of the reported cases evolve spontaneously and favourably, in rare cases, serious complications can occur leading to the death of the patient. We report the case of a 27-year-old man admitted to our emergency department for altered consciousness with hyperthermia at 42°C after illicit drug use. The patient developed severe multivisceral failure and disseminated intravascular coagulopathy despite maximalist management focused on cooling and multiorgan supportive therapy. The patient died within hours of admission. The diagnosis is essentially based on the patient history and clinical examination. The first treatment is to stop the toxic and then, to treat the symptoms and support possible organ failures.


La consommation d'amphétamines et de ses dérivés tels que l'ecstasy peut être responsable d'un syndrome toxique sérotoninergique, effet indésirable peu fréquent mais potentiellement redoutable. Bien que la plupart des cas rapportés évoluent spontanément favorablement, dans de rares cas, de graves complications peuvent survenir pouvant mener jusqu'au décès du patient. Nous rapportons le cas d'un homme de 27 ans, admis dans notre service des urgences pour altération de l'état de conscience avec hyperthermie à 42°C après consommation de drogues illicites. Le patient a développé une défaillance multiviscérale sévère ainsi qu'une coagulopathie intravasculaire disséminée malgré une prise en charge maximaliste centrée sur le refroidissement et le traitement supportif multi-organique. Le patient est décédé quelques heures après son admission. Le diagnostic du syndrome sérotoninergique est essentiellement basé sur l'anamnèse et l'examen clinique. La prise en charge comprend l'arrêt du toxique, le traitement des symptômes et le support des potentielles défaillances organiques.


Assuntos
N-Metil-3,4-Metilenodioxianfetamina , Síndrome da Serotonina , Transtornos Relacionados ao Uso de Substâncias , Adulto , Serviço Hospitalar de Emergência , Febre , Humanos , Masculino , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Síndrome da Serotonina/induzido quimicamente , Síndrome da Serotonina/diagnóstico , Síndrome da Serotonina/terapia
4.
J Headache Pain ; 23(1): 1, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979902

RESUMO

BACKGROUND: Chronic migraine places a disabling burden on patients, which is extensively modeled by the nitroglycerin (NTG)-treated animal model. Although the NF-κB pathway is involved in an increase in CGRP levels and activation of the trigeminal system in the NTG model, the relationship between NTG and neuroinflammation remains unclear. This study aimed to optimize a chronic NTG rat model with hyperalgesia and the ethological capacity for estimating migraine therapies and to further explore the underlying mechanism of NTG-induced migraine. METHODS: Rats were administered different doses of NTG s.c. daily or every 2 d; 30 min and 2 h later, the mechanical threshold was tested. After 9 d, the rats were injected with EB or Cy5.5 for the permeability assay. The other animals were sacrificed, and then, brainstem and caudal trigeminal ganglion were removed to test CGRP, c-Fos and NOS activity; Cytokines levels in the tissue and serum were measured by ELISA; and NF-κB pathway and blood-brain barrier (BBB)-related indicators were analyzed using western blotting. Immunohistochemistry was performed to observe microglial polarization and IL-17A+ T cell migration in the medulla oblongata. RESULTS: NTG (10 mg/kg, s.c., every 2 d for a total of 5 injections) was the optimal condition, resulting in progressive hyperalgesia and migraine behavior. TNC neuroinflammation with increases in cytokines, CGRP and c-Fos and activation of the NF-κB pathway was observed, and these changes were alleviated by ibuprofen. Furthermore, NTG administration increased BBB permeability by altering the levels functional proteins (RAGE, LRP1, AQP4 and MFSD2A) and structural proteins (ZO-1, Occludin and VE-cadherin-2) to increase peripheral IL-17A permeation into the medulla oblongata, activating microglia and neuroinflammation, and eventually causing hyperalgesia and migraine attack. CONCLUSIONS: This study confirmed that NTG (10 mg/kg, s.c., every 2 d for a total of 5 injections) was the optimal condition to provoke migraine, resulting in mechanical hyperalgesia and observable migraine-like behavior. Furthermore, IL-17A crossed the blood-brain barrier into the medulla oblongata, triggering TNC activation through microglia-mediated neuroinflammation. This process was a novel mechanism in NTG-induced chronic migraine, suggesting that IL-17A might be a novel target in the treatment of migraine.


Assuntos
Transtornos de Enxaqueca , Nitroglicerina , Animais , Barreira Hematoencefálica , Modelos Animais de Doenças , Humanos , Interleucina-17 , Transtornos de Enxaqueca/induzido quimicamente , Nitroglicerina/toxicidade , Ratos
6.
Rev Alerg Mex ; 69 Suppl 1: s1-s14, 2022.
Artigo em Espanhol | MEDLINE | ID: mdl-34998305

RESUMO

Even though the SARS-CoV-2 pandemic represents a historical challenge, science has had an exponential development, and the current vaccination campaigns are proof of this. Unfortunately, along came misinformation and myths regarding their production and their adverse effects. For this reason, we have considered of utter importance to review anaphylaxis, one of the most feared vaccine adverse events.Anaphylaxis can be defined as a life-threatening acute and systemic allergic reaction, with a wide clinical spectrum, which can be explained by many immunological mechanisms, and whose diagnostic complexity demands the fulfillment of strict criteria. Though infrequent, any vaccine has the potential to trigger anaphylaxis. In the United States, for the new SARS-CoV-2 vaccines, rates from 1:200 000 (Pfizer-BioNTech) to 1:360 000 doses (Moderna) have been estimated. Vaccine adverse events can be mediated by hypersensitivity reactions, either allergic or not. Unlike a typical drug allergy, rarely is the active ingredient responsible for the reaction. Therefore, excipients must be considered during the approach to this problem. Vaccine associated anaphylaxis has to be referred to an allergist so as to guarantee the maximum benefit for the patient and improve the vaccines' security profile.


A pesar de la difícil situación que se enfrenta con la actual pandemia de COVID-19, la ciencia ha tenido un desarrollo exponencial. Si bien la inmunización contra esa enfermedad ha sido posible gracias a ello, desafortunadamente se ha acompañado de desinformación y mitos en torno a su fabricación y reacciones adversas. Por tal razón, es importante revisar una de las reacciones adversas a vacunas más temidas para el personal de salud y la población general, la anafilaxia. La anafilaxia se define como una reacción alérgica aguda y sistémica que puede poner en riesgo la vida; se asocia con distintos mecanismos inmunológicos, factores desencadenantes y manifestaciones clínicas. Su diagnóstico puede ser confuso, por lo que se han establecido diferentes criterios. Todas las inmunizaciones tienen el potencial de desencadenar anafilaxia, aunque este evento es poco frecuente. Respecto de las vacunas contra el coronavirus SARS-CoV-2, en Estados Unidos se ha reportado una tasa de anafilaxia de 1:200 000 para la vacuna Pfizer-BioNTech, y de 1:360 000 para la vacuna de Moderna. Al igual que un fármaco, las vacunas pueden presentar efectos adversos mediados por mecanismos de hipersensibilidad, pero a diferencia de lo que sucede con los medicamentos, el principio activo rara vez es el responsable; es más frecuente que las reacciones indeseadas se deban a los excipientes. La sospecha de una anafilaxia secundaria a su aplicación obliga a una oportuna referencia y a un correcto diagnóstico, tanto para el beneficio del paciente como para mejorar el perfil de seguridad de la vacuna.


Assuntos
Anafilaxia , COVID-19 , Vacinas , Anafilaxia/induzido quimicamente , Vacinas contra COVID-19 , Humanos , SARS-CoV-2 , Estados Unidos , Vacinas/efeitos adversos
7.
Zhonghua Jie He He Hu Xi Za Zhi ; 45(1): 47-52, 2022 Jan 12.
Artigo em Chinês | MEDLINE | ID: mdl-35000305

RESUMO

Objective: To investigate the clinicopathologic features and outcome of myositis in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors. Methods: The patients diagnosed with immune checkpoint inhibitor-related (ICI) myositis in the database of Respiratory Pathology Center of The First Affiliated Hospital, Guangzhou Medical University from June 2019 to December 2020 were retrospectively analyzed. We reported the muscle histology and main clinical manifestations of the patients in this study. Seven patients with advanced non-small cell lung cancer and ICI related myositis were examined; all of the patients were male, with a median age of 64 (range 42-79) years. Results: All seven patients developed myositis under therapy (three for pembrolizumab, three for sintilimab, and one for camrelizumab). Median delay between ICI initiation and myositis onset was 45 (range 15-176) days. Clinical manifestations were dominated by acute or subacute myalgia and limb weakness. Four patients had evidence of myocarditis. In all of the 7 patients, creatine kinase levels were elevated (median 2 354.4, range 468.6-19 709.2 U/L), while myositis-associated antibodies Ro-52 were positive in four patients. Muscle biopsy showed evident multifocal necrotic myofibers and infiltration of inflammation in two patients. Other patients only showed non-specific endomysial inflammation. Infiltration of inflammation mainly consisted of CD8+ T cells and CD68+ histocytes. After the identification of ICI related myositis, ICI treatment was withdrawn in all patients; 6 patients received corticosteroids therapy. All patients had shown marked clinical improvement. Conclusions: ICI myositis presents with remarkably homogeneous and unique clinicopathologic features, and half of the patients exhibit heightened risk for adverse cardiovascular events, which can be life-threatening if not treated in time. Timely identification of these patients, ICI withdrawal and rapid initiation of corticosteroids therapy can significantly improve patient outcome and/or save patients' lives.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Miosite , Adulto , Idoso , Linfócitos T CD8-Positivos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Miosite/induzido quimicamente , Estudos Retrospectivos
8.
J Med Food ; 25(1): 12-23, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35029511

RESUMO

Previously, we demonstrated that extracts of the ripe fruit (rPM) and unripe fruit (uPM) of Prunus mume (Siebold) Siebold & Zucc. and citric acid have a laxative effect, which is at least partially mediated by the increase in fecal parameters as seen in the low-fiber diet-induced constipation model rats. This study aims at investigating the laxative effects of citric acid-enriched aqueous extracts of rPM, uPM, and its active compounds, such as citric acid and malic acid, on loperamide-induced constipation rat models. Animal studies were conducted with loperamide-induced constipation animal models. The results showed that rPM and citric acid, the major organic acid compounds, significantly improved stool parameters (number, weight, and water content of the stools) generated in loperamide-induced constipation rats, without adverse effects of diarrhea. The gastrointestinal (GI) motility was activated fully in the rPM- and citric acid-treated rats than in rats treaded with loperamide alone. In addition, when rPM and citric acid were added to RAW264.7 cells and used to treat loperamide-induced constipation model rats, the secretion of prostaglandin E2 (PGE2) increased significantly in cells and tissue. Furthermore, rPM and citric acid decreased the expression of the aquaporin 3 (AQP3) in the rat colons. Our results demonstrated that rPM and citric acid, the major organic acid compound in rPM, can effectively promote defecation frequency and regulate PGE2 secretion and AQP3 expression in the colon, providing scientific evidence to support the use of rPM as a therapeutic application.


Assuntos
Laxantes , Prunus , Animais , Aquaporina 3 , Ácido Cítrico/uso terapêutico , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Loperamida , Prostaglandinas/uso terapêutico , Prostaglandinas E/uso terapêutico , Ratos
9.
Clin Neuropharmacol ; 45(1): 7-8, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35029863

RESUMO

BACKGROUND: Vortioxetine is a novel multimodal antidepressant for the treatment of major depressive disorders and is widely used in clinical practice. Vortioxetine has a safe profile. However, there are case reports of other adverse effects in the literature. In this article, a case of amenorrhea due to vortioxetine is presented. CASE: The patient is 36 years old, married, female, and is an anesthesiologist. She applied to the psychiatric outpatient clinic with symptoms of major depression. Vortioxetine was initiated at 10 mg/d and then gradually increased to 20 mg/d. She had regular menstruation until now. However, she did not menstruate after taking vortioxetine. The patient used vortioxetine for 3 months and never had a period. Pregnancy test and other tests to investigate organic etiology were normal. Two weeks after discontinuation of vortioxetine, the patient had a menstrual period. CONCLUSIONS: Further research is needed on the relationship and possible mechanisms between vortioxetine and amenorrhea.


Assuntos
Transtorno Depressivo Maior , Adulto , Amenorreia/induzido quimicamente , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Humanos , Vortioxetina/uso terapêutico
10.
Clin Neuropharmacol ; 45(1): 9-10, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35029864

RESUMO

BACKGROUND: Clozapine has been shown to be an effective and well-tolerated treatment for Parkinson disease (PD) psychosis as well as for refractory tremor in PD. Doses used are generally less than one tenth those used in treating schizophrenia. While the risk of leukopenia and agranulocytosis are reported to be independent of dose, that belief is based on the use of doses used in refractory schizophrenia. There are no published data on the risk of agranulocytosis in patients taking extremely low doses of clozapine. CASE REPORT: This 87-year-old man with diabetes and PD experienced a granulocyte count drop from normal, 3900, at dose initiation, to 0, at the ninth week of treatment taking clozapine 12.5 mg twice daily for refractory tremor. He recovered without developing an infection. CONCLUSIONS: This is the first known reported case of agranulocytosis due to clozapine used at an extremely low dose. This report underscores the importance of blood monitoring, even at extremely low doses, although the exact risk remains unknown.


Assuntos
Agranulocitose , Antipsicóticos , Clozapina , Esquizofrenia , Idoso de 80 Anos ou mais , Agranulocitose/induzido quimicamente , Agranulocitose/tratamento farmacológico , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Humanos , Contagem de Leucócitos , Masculino , Esquizofrenia/tratamento farmacológico
11.
J Headache Pain ; 23(1): 8, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35033010

RESUMO

BACKGROUND: Astrocytic activation might play a significant role in the central sensitization of chronic migraine (CM). However, the temporal characteristics of the astrocytic activation in the trigeminal nucleus caudalis (TNC) and the molecular mechanism under the process remain not fully understood. Therefore, this study aims to investigate the duration and levels change of astrocytic activation and to explore the correlation between astrocytic activation and the levels change of cytokines release. METHODS: We used a mice model induced by recurrent dural infusion of inflammatory soup (IS). The variation with time of IS-induced mechanical thresholds in the periorbital and hind paw plantar regions were evaluated using the von Frey filaments test. We detected the expression profile of glial fibrillary acidic protein (GFAP) in the TNC through immunofluorescence staining and western blot assay. We also investigated the variation with time of the transcriptional levels of GFAP and ionized calcium binding adapter molecule 1 (Iba1) through RNAscope in situ hybridization analysis. Then, we detected the variation with time of cytokines levels in the TNC tissue extraction and serum, including c-c motif chemokine ligand 2 (CCL2), c-c motif chemokine ligand 5 (CCL5), c-c motif chemokine ligand 7 (CCL7), c-c motif chemokine ligand 12 (CCL12), c-x-c motif chemokine ligand 1 (CXCL1), c-x-c motif chemokine ligand 13 (CXCL13), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), macrophage colony-stimulating factor (M-CSF), interleukin 1beta (IL-1ß), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 17A (IL-17A). RESULTS: Recurrent IS infusion resulted in cutaneous allodynia in both the periorbital region and hind paw plantar, ranging from 5 d (after the second IS infusion) to 47 d (28 d after the last infusion) and 5 d to 26 d (7 d after the last infusion), respectively. The protein levels of GFAP and messenger ribonucleic acid (mRNA) levels of GFAP and Iba1 significantly increased and sustained from 20 d to 47 d (1 d to 28 d after the last infusion), which was associated with the temporal characteristics of astrocytic activation in the TNC. The CCL7 levels in the TNC decreased from 20 d to 47 d. But the CCL7 levels in serum only decreased on 20 d (1 d after the last infusion). The CCL12 levels in the TNC decreased on 22 d (3 d after the last infusion) and 33 d (14 d after the last infusion). In serum, the CCL12 levels only decreased on 22 d. The IL-10 levels in the TNC increased on 20 d. CONCLUSIONS: Our results indicate that the astrocytic activation generated and sustained in the IS-induced mice model from 1 d to 28 d after the last infusion and may contribute to the pathology through modulating CCL7, CCL12, and IL-10 release.


Assuntos
Transtornos de Enxaqueca , Núcleos do Trigêmeo , Animais , Sensibilização do Sistema Nervoso Central , Hiperalgesia/induzido quimicamente , Camundongos , Dor
12.
Am J Case Rep ; 23: e934410, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35034948

RESUMO

BACKGROUND Chronic acetaminophen toxicity has been known to cause an anion gap metabolic acidosis (AGMA) due to accumulation of 5-oxoproline metabolites. This diagnosis requires a high index of suspicion when evaluating a patient with AGMA as occasional acetaminophen use is very common among patients, whom oftentimes are not entirely truthful about the extent of ingestion and have multiple comorbid conditions complicating diagnosis.  CASE REPORT A 68-year-old male with multiple medical comorbidities presented to the emergency room with recurrent generalized weakness. On all occasions the patient denies focal weakness or infectious symptoms. The patient also denies ingestions other than his routine prescribed medications, including acetaminophen 325mg as needed, which he describes taking "a couple times" a day. His prior visits were notable for profound anion-gap metabolic acidosis, hypernatremia, acute kidney injury, and positive urine ketones. As the patient's blood urea nitrogen (BUN), blood sugar, liver function tests, lactic acid, and serum osmolality were normal, the patient received a diagnosis of "starvation ketosis" and received supportive care each time. Further investigation at his final admission revealed an extremely elevated 5-oxoproline level revealing a delayed diagnosis of chronic acetaminophen toxicity CONCLUSIONS This report emphasizes the need for a high index of suspicion related to chronic acetaminophen toxicity and other ingestions contributing to a metabolic acidosis in at-risk populations, even when routine history is unrevealing. Furthermore, severe acidosis should prompt more extensive investigation when out of proportion to obvious routine etiologies.


Assuntos
Acidose , Analgésicos não Narcóticos , Cetose , Acetaminofen/efeitos adversos , Equilíbrio Ácido-Base , Acidose/induzido quimicamente , Idoso , Humanos , Cetose/induzido quimicamente , Cetose/diagnóstico , Masculino
13.
Molecules ; 27(1)2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35011506

RESUMO

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. Anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time, it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of most active compounds was confirmed using lipopolysaccharide (LPS)-treated blood to mimic the conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5-15.2 times as compared to LPS-treated blood.


Assuntos
Anticoagulantes/farmacologia , Compostos Azo/química , Coagulação Sanguínea/efeitos dos fármacos , Hemorragia/tratamento farmacológico , Pirimidinas/química , Animais , Anticoagulantes/química , Hemorragia/induzido quimicamente , Lipopolissacarídeos/toxicidade , Masculino , Coelhos , Ratos
14.
Biomed Res Int ; 2022: 1522426, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35013710

RESUMO

Several therapeutic regimens for COVID-19 have been studied, such as combination antiviral therapies. We aimed to compare outcome of two types of combination therapies atazanavir/ritonavir (ATV/r) or lopinavir/ritonavir (LPV/r) plus hydroxychloroquine among COVID-19 patients. 108 patients with moderate and severe forms of COVID-19 were divided into two groups (each group 54 patients). One group received ATV/r plus hydroxychloroquine, and the other group received hydroxychloroquine plus LPV/r. Then, both groups were evaluated and compared for clinical symptoms, recovery rates, and complications of treatment regimens. Our findings showed a significant increase in bilirubin in ATV/r-receiving group compared to LPV/r receivers. There was also a significant increase in arrhythmias in the LPV/r group compared to the ATV/r group during treatment. Other findings including length of hospital stay, outcome, and treatment complications were not statistically significant. There is no significant difference between protease inhibitor drugs including ATV/r and LPV/r in the treatment of COVID-19 regarding clinical outcomes. However, some side effects such as hyperbilirubinemia and arrhythmia were significantly different by application of atazanavir or lopinavir.


Assuntos
Sulfato de Atazanavir/uso terapêutico , COVID-19/tratamento farmacológico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Idoso , Antivirais/uso terapêutico , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/fisiopatologia , Bilirrubina/análise , COVID-19/metabolismo , Combinação de Medicamentos , Quimioterapia Combinada/métodos , Feminino , Hospitalização/tendências , Humanos , Hidroxicloroquina/uso terapêutico , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Resultado do Tratamento
15.
Int J Nanomedicine ; 17: 1-14, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35023915

RESUMO

Introduction: The charcoal processed product of Armeniacae Semen Amarum (ASA), ASA Carbonisata (ASAC), has long been used for its anti-inflammatory effects. However, the material basis and mechanism of action of ASAC remain unclear. Aim: To explore the anti-inflammatory effects of Armeniacae Semen Amarum Carbonisata-derived carbon dots (ASAC-CDs). Methods: The physicochemical properties of ASAC-CDs including morphology, optical properties, functional groups were characterized by a series of methods, mainly including electron microscopy, optical technology and X-ray photoelectron spectroscopy. The anti-inflammatory effect of ASAC-CDs was evaluated and confirmed using acute lung injury (ALI) induced by lipopolysaccharides (LPS) in rats. Results: The ASAC-CDs ranged from 1.5 to 5.5 nm in diameter, with a quantum yield of 3.17%. ASAC-CDs alleviated LPS-induced inflammation, as demonstrated by reducing the levels of IL-6, IL-1ß and TNF-α and increasing the contents of IL-10 in rat serum. More interestingly, ASAC-CDs reduce the content of MDA and MPO and increase the activity of SOD and the content of GSH, indicating the antioxidant activity of ASAC-CDs. Conclusion: These results demonstrate the remarkable anti-inflammatory effects of ASAC-CDs against ALI induced by LPS, which provide an important basis for the application of ASAC-CDs in clinical anti-pneumonia, and lay an experimental foundation for the research and development of novel nano-drugs.


Assuntos
Lesão Pulmonar Aguda , Medicamentos de Ervas Chinesas , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/prevenção & controle , Animais , Carbono , Lipopolissacarídeos , Ratos , Sêmen
16.
Environ Pollut ; 296: 118772, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34974090

RESUMO

The association between polycyclic aromatic hydrocarbons (PAHs) exposure and hearing loss is rarely assessed. We aimed to evaluate the relationship of polycyclic aromatic hydrocarbons (PAHs) exposure and hearing loss among US adults and adolescents, and to explore the mediating role of systemic inflammation in the associations. Participants from the National health and Nutrition Examination Surveys (NHANES, 2001-2016) were included. Multiple logistic regression models were used to explore the associations between PAH metabolites and hearing loss. A total of 4200 adults and 1337 adolescents were included in the present analysis. For adults, we found positive association between urinary PAH metabolites and hearing loss, including total, speech-frequency and high-frequency hearing loss. The odds ratios (ORs) and 95% confidence intervals (CIs) for each one-unit increase in the log-transformed level of 3-Hydroxyfluorene (3-OHFlu), 2-Hydroxyfluorene (2-OHFlu) and 2 & 3-Hydroxyphenanthrene (2&3-OHPh) with total hearing loss were 1.17 (1.04-1.31), 1.24 (1.07-1.43), and 1.18 (1.03-1.37), respectively. For adolescents, urinary PAH metabolites were positively associated with total and speech-frequency hearing loss, not with high-frequency. The ORs and 95% CIs for each one-unit increase in the log-transformed level of 3-OHFlu, 2-OHFlu and total urinary PAH metabolites with total hearing loss were 1.34 (1.06-1.68), 1.48 (1.13-1.93), and 1.33 (1.04-1.72), respectively. Each one-unit increase in the log-transformed level 2-OHFlu (ß = 0.112, 95%CI = 0.018-0.206) and 2&3-OHPh (ß = 0.145, 95%CI = 0.037-0.253) were positively associated with C-reactive protein (CRP) among adolescents, but not among adults. No mediating effect for CRP on the association of urinary PAH metabolites with hearing loss was found (all P > 0.05). 3-OHFlu and 2-OHFlu are associated with increased prevalence of hearing loss among adults and adolescents. Systemic inflammation does not mediate the associations. Further studies should be conducted to verify the results.


Assuntos
Perda Auditiva , Hidrocarbonetos Policíclicos Aromáticos , Adolescente , Adulto , Biomarcadores , Perda Auditiva/induzido quimicamente , Perda Auditiva/epidemiologia , Humanos , Inflamação , Inquéritos Nutricionais
17.
Trials ; 23(1): 23, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34998423

RESUMO

BACKGROUND: It is well known that obstructive jaundice could affect the pharmacodynamics of some anesthetics, and the sensitivity of some anesthetics would increase among icteric patients. Remimazolam is a new ultra-short-acting intravenous benzodiazepine sedative/anesthetic, which is a high-selective and affinity ligand for the benzodiazepine site on the GABAA receptor. However, no study has reported the pharmacodynamics of remimazolam in patients with obstructive jaundice. We hypothesize that obstructive jaundice affects the pharmacodynamics of remimazolam, and the sensitivity of remimazolam increases among icteric patients. METHODS/DESIGN: The study will be performed as a prospective, controlled, multicenter trial. The study design is a comparison of remimazolam requirements to reach a bispectral index of 50 in patients with obstructive jaundice versus non-jaundiced patients with chronic cholecystitisor intrahepatic bile duct stones. Remimazolam was infused at 6 mg/kg/h until this endpoint was reached. DISCUSSION: Remimazolam could be suitable for anesthesia of patients with obstructive jaundice, because remimazolam is not biotransformed in the liver. Hyperbilirubinemia has been well-described to have toxic effects on the brain, which causes the increasing of sensitivity to some anesthetics, such as desflurane, isoflurane, and etomidate. Furthermore, remimazolam and etomidate have the same mechanism of action when exerting an anesthetic effect. We aim to demonstrate that obstructive jaundice affects the pharmacodynamics of remimazolam, and the dose of remimazolam when administered to patients with obstructive jaundice should be modified. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100043585 . Registered on 23 February 2021.


Assuntos
Icterícia Obstrutiva , Anestésicos Intravenosos , Benzodiazepinas , Humanos , Hipnóticos e Sedativos/efeitos adversos , Icterícia Obstrutiva/induzido quimicamente , Icterícia Obstrutiva/diagnóstico , Icterícia Obstrutiva/tratamento farmacológico , Estudos Multicêntricos como Assunto , Estudos Prospectivos
18.
Korean J Radiol ; 23(1): 60-67, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34983094

RESUMO

OBJECTIVE: To categorize multiparametric MRI features of Bacillus Calmette-Guérin (BCG)-related granulomatous prostatitis (GP) and discover potential manifestations for its differential diagnosis from prostate cancer. MATERIALS AND METHODS: The cases of BCG-related GP in 24 male (mean age ± standard deviation, 66.0 ± 9.4 years; range, 50-88 years) pathologically confirmed between January 2011 and April 2019 were retrospectively reviewed. All patients underwent intravesical BCG therapy followed by a MRI scan. Additional follow-up MRI scans, including diffusion-weighted imaging (DWI), were performed in 19 patients. The BCG-related GP cases were categorized into three: A, B, or C. The lesions with diffusion restriction and homogeneous enhancement were classified as type A. The lesions with diffusion restriction and a poorly enhancing component were classified as type B. A low signal intensity on high b-value DWI (b = 1000 s/mm²) was considered characteristic of type C. Two radiologists independently interpreted the MRI scans before making a consensus about the types. RESULTS: The median lesion size was 22 mm with the interquartile range (IQR) of 18-26 mm as measured using the initial MRI scans. The lesion types were A, B, and C in 7, 15, and 2 patients, respectively. Cohen's kappa value for the inter-reader agreement for the interpretation of the lesion types was 0.837. On the last follow-up MRI scans of 19 patients, the size decreased (median, 5.8 mm; IQR, 3.4-8.5 mm), and the type changed from A or B to C in 11 patients. The lesions resolved in four patients. In five patients who underwent prostatectomy, caseous necrosis on histopathology matched with the non-enhancing components of type B lesions and the entire type C lesions. CONCLUSION: BCG-related GP demonstrated three imaging patterns on multiparametric MRI. Contrast-enhanced T1-weighted imaging and DWI may play a role in its differential diagnosis from prostate cancer.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Prostatite , Neoplasias da Bexiga Urinária , Idoso , Idoso de 80 Anos ou mais , Vacina BCG/efeitos adversos , Imagem de Difusão por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico por imagem , Prostatite/induzido quimicamente , Prostatite/diagnóstico por imagem , Estudos Retrospectivos
19.
An Acad Bras Cienc ; 94(1): e20191476, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35018996

RESUMO

The aim of present study, to evaluate the genotoxic potential of 1-(4-(3,3-dimethyl-1,6-dioxo-2,3,4,6,11,13-hexahydro-1H-indazolo[1,2b] phthalazine-13yl)phenyl)-2-phenylazetidine-3-yl-acetate which was synthesised assuming that it may be a pharmaceutical raw material and found to inhibit human carbonic anhydrase I, II isozymes. To determine the genotoxic potential of this phthalazine substituted ß-lactam compound, chromosomal aberration (CA) and micronucleus (MN) tests were implemented in human peripheral blood lymphocytes. In these tests, lymphocyte cultures were treated with four concentrations (30, 15, 7.5, 3.75 µg/mL) of test compound and simultaneously with negative control (sterile distilled water), solvent control (DMSO) positive control (MMC). According to our results, CA frequencies were significantly increased in two high applied concentrations (30, 15 µg/mL) compared with negative and solvent control. MN frequencies were significantly increased in three applied concentrations (30, 15, 7.5 µg/mL) except lowest concentration (3.75 µg/mL) compared with solvent control. Mitotic indices were also affected by treatment with test compound. The obtained results provide evidence to demonstrate that new phthalazine substituted ß-lactam derivative can exert genotoxic and cytotoxic effects in peripheral human lymphocytes especially at high concentrations.


Assuntos
Micronúcleos com Defeito Cromossômico , beta-Lactamas , Células Cultivadas , Aberrações Cromossômicas/induzido quimicamente , Dano ao DNA , Relação Dose-Resposta a Droga , Humanos , Linfócitos , Testes para Micronúcleos , Ftalazinas/toxicidade , beta-Lactamas/toxicidade
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