RESUMO
We observed multisystem inflammatory syndrome in 2 older adults in the United States who had received mRNA coronavirus disease vaccine soon after natural infection. We identified 5 similar cases from the Vaccine Adverse Events Reporting System. The timing of vaccination soon after natural infection might have an adverse effect on the occurrence of vaccine-related systemic inflammatory disorders.
Assuntos
COVID-19 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Idoso , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , SARS-CoV-2 , Estados Unidos , Vacinação/efeitos adversosRESUMO
The antimalarial agent fosmidomycin is a validated inhibitor of the nonmevalonate isoprenoid biosynthesis (methylerythritol 4-phosphate [MEP]) pathway in the malaria parasite, Plasmodium falciparum. Since multiple classes of prenyltransferase inhibitors kill P. falciparum, we hypothesized that protein prenylation was one of the essential functions of this pathway. We found that MEP pathway inhibition with fosmidomycin reduces protein prenylation, confirming that de novo isoprenoid biosynthesis produces the isoprenyl substrates for protein prenylation. One important group of prenylated proteins is small GTPases, such as Rab family members, which mediate cellular vesicular trafficking. We have found that Rab5 proteins dramatically mislocalize upon fosmidomycin treatment, consistent with a loss of protein prenylation. Fosmidomycin treatment caused marked defects in food vacuolar morphology and integrity, consistent with a defect in Rab-mediated vesicular trafficking. These results provide insights to the biological functions of isoprenoids in malaria parasites and may assist the rational selection of secondary agents that will be useful in combination therapy with new isoprenoid biosynthesis inhibitors.
Assuntos
Plasmodium falciparum/metabolismo , Proteínas de Protozoários/metabolismo , Terpenos/metabolismo , Proteínas rab5 de Ligação ao GTP/metabolismo , Androstadienos/farmacologia , Antimaláricos/farmacologia , Vias Biossintéticas/efeitos dos fármacos , Células Cultivadas , Resistência a Medicamentos , Transporte de Elétrons/efeitos dos fármacos , Eritritol/análogos & derivados , Eritritol/metabolismo , Eritrócitos/parasitologia , Fosfomicina/análogos & derivados , Fosfomicina/farmacologia , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/crescimento & desenvolvimento , Prenilação de Proteína , Transporte Proteico/efeitos dos fármacos , Esquizontes/efeitos dos fármacos , Esquizontes/crescimento & desenvolvimento , Esquizontes/metabolismo , Fosfatos Açúcares/metabolismo , Vesículas Transportadoras/metabolismo , Ubiquinona/metabolismo , Vacúolos/efeitos dos fármacos , Vacúolos/metabolismo , Vacúolos/ultraestrutura , WortmaninaRESUMO
Mucopolysaccharidosis VII (MPS VII) is due to mutations within the gene encoding the lysosomal enzyme ß-glucuronidase, and results in the accumulation of glycosaminoglycans. MPS VII causes aortic dilatation and elastin fragmentation, which is associated with upregulation of the elastases cathepsin S (CtsS) and matrix metalloproteinase 12 (MMP12). To test the role of these enzymes, MPS VII mice were crossed with mice deficient in CtsS or MMP12, and the effect upon aortic dilatation was determined. CtsS deficiency did not protect against aortic dilatation in MPS VII mice, but also failed to prevent an upregulation of cathepsin enzyme activity. Further analysis with substrates and inhibitors specific for particular cathepsins suggests that this enzyme activity was due to CtsB, which could contribute to elastin fragmentation. Similarly, MMP12 deficiency and deficiency of both MMP12 and CtsS could not prevent aortic dilatation in MPS VII mice. Microarray and reverse-transcriptase real-time PCR were performed to look for upregulation of other elastases. This demonstrated that mRNA for complement component D was elevated in MPS VII mice, while immunostaining demonstrated high levels of complement component C3 on surfaces within the aortic media. Finally, we demonstrate that neonatal intravenous injection of a retroviral vector encoding ß-glucuronidase reduced aortic dilatation. We conclude that neither CtsS nor MMP12 are necessary for elastin fragmentation in MPS VII mouse aorta, and propose that CtsB and/or complement component D may be involved. Complement may be activated by the GAGs that accumulate, and may play a role in signal transduction pathways that upregulate elastases.
Assuntos
Doenças da Aorta/etiologia , Ativação do Complemento , Dilatação Patológica/etiologia , Mucopolissacaridose VII/complicações , Animais , Aorta/metabolismo , Aorta/patologia , Aorta/fisiopatologia , Doenças da Aorta/metabolismo , Doenças da Aorta/fisiopatologia , Catepsinas/deficiência , Proteínas do Sistema Complemento/genética , Proteínas do Sistema Complemento/metabolismo , Elastina/metabolismo , Perfilação da Expressão Gênica , Terapia Genética , Glucuronidase/biossíntese , Glucuronidase/sangue , Glucuronidase/genética , Glicosaminoglicanos/metabolismo , Masculino , Metaloproteinase 12 da Matriz/deficiência , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mucopolissacaridose VII/fisiopatologia , Mucopolissacaridose VII/terapia , Análise de Sequência com Séries de Oligonucleotídeos , Elastase Pancreática/genética , Elastase Pancreática/metabolismo , Transdução de Sinais , Extratos de Tecidos , Regulação para CimaRESUMO
BACKGROUND: The lateral retinacular nerve (LRN) is a branch of the superior lateral genicular nerve (SLGN) and is believed to contribute to anterolateral knee pain. The precise anatomical pathway of the LRN, however, has not been demonstrated as it relates to the performance of targeted nerve block procedures. OBJECTIVE: To describe the anatomical landmarks for localization of the LRN to facilitate diagnostic and therapeutic nerve blocks in the treatment of chronic anterolateral knee pain. DESIGN: Descriptive study. SETTING: Anatomy dissection laboratory in an academic institution. METHODS: Twenty lower extremities were dissected in 12 cadavers. The sciatic nerve was identified, and its branch to the posterior aspect of the knee, the SLGN, was dissected. The SLGN dissection was continued distally to identify its first branch, the LRN. Two measurements were taken from the branch point on the lateral knee deep to the distal biceps tendon in alignment with the fibular head. A validation study completed in 4 knees was performed as follows: 1 mL of colored dye was injected at the first and second measurements. The cadaveric knee was then dissected to assess the accuracy. MAIN OUTCOME MEASUREMENTS: Localization of the branch point of the LRN from the SLGN via dissection and then direct assessment of injected dye at the measurement points via dissection. RESULTS: The branch point of the LRN from the SLGN was, on average, 5.5 ± 0.66 cm (with a range of 4.5-7.0 cm) proximal to the lateral tibiofemoral joint line in line with the head of the fibula and 2.6 ± 0.62 cm (2.0-4.5 cm) proximal to the tip of the lateral femoral epicondyle. On assessment of the 2 measurements, the measurement 5.5 cm proximal to the lateral joint line accurately targeted the branch point in 100% (4/4) of the knees, whereas the measurement 2.6 cm proximal the tip of the lateral femoral epicondyle accurately targeted the branch point in 75% (3/4) of the knees. CONCLUSION: The results of this study provide 2 dependable landmarks and a description of the path of the LRN, making it possible to accurately target the LRN to diagnose and alleviate lateral knee pain.
Assuntos
Articulação do Joelho/anatomia & histologia , Articulação do Joelho/inervação , Bloqueio Nervoso/métodos , Nervos Periféricos/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Pontos de Referência Anatômicos , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
As first-year medical students, we were excited, but nervous, to start the anatomy course. We were prepared to dedicate ourselves to the physical demands of dissection, and the hours of memorizing names and relations of countless anatomic features. We expected to leave the anatomy course with a comprehensive understanding of the human body that we would apply to our future studies and careers. We were not prepared, however, for the experience we had with our cadaver, Lucy.* Lucy was a small woman, but as we learned, she had endured a lot, physically and medically, in her 83 years of life. She had a pacemaker. She had coronary artery disease and a triple bypass procedure. She also had severe peripheral artery disease and had undergone at least one extraordinary surgical graft procedure to maintain blood flow into her lower extremities. The surprise of discovering a small piece of an axillobifemoral bypass graft and then continuing to uncover it, region by region, throughout the anatomy course, brought our dissection experience and our connection to Lucy to a more profound level than we could ever have anticipated. *The name Lucy was chosen as a pseudonym to protect the identity of the cadaver.
RESUMO
Peripheral artery disease (PAD) occurs when plaque accumulates in the arterial system and obstructs blood flow. Narrowing of the abdominal aorta and the common iliac arteries due to atherosclerotic plaques restricts blood supply to the lower limbs. Clinically, the lower limb symptoms of PAD are intermittent claudication, discoloration of the toes, and skin ulcers, all due to arterial insufficiency. Surgical revascularization is the primary mode of treatment for patients with severe limb ischemia. The objective of the surgical procedure is to bypass a blockage in an occluded major vessel by constructing an alternate route for blood flow using an artificial graft. This article presents information on aortoiliac reconstruction, with an emphasis on axillobifemoral bypass grafting.
RESUMO
OBJECTIVE: To summarize the past 10 years of published research concerning the 2% of American children younger than 18 years old who are adoptees. METHOD: Review recent literature on developmental influences, placement outcome, psychopathology, and treatment. RESULTS: Adoption carries developmental opportunities and risks. Many adoptees have remarkably good outcomes, but some subgroups have difficulties. Traditional infant, international, and transracial adoptions may complicate adoptees' identity formation. Those placed after infancy may have developmental delays, attachment disturbances, and posttraumatic stress disorder. Useful interventions include preventive counseling to foster attachment, postadoption supports, focused groups for parents and adoptees, and psychotherapy. CONCLUSIONS: Variables specific to adoption affect an adopted child's developmental trajectory. Externalizing, internalizing, attachment, and posttraumatic stress disorder symptoms may arise. Child and adolescent psychiatrists can assist both adoptive parents and children.
Assuntos
Adoção , Família/psicologia , Criança , Humanos , Apego ao ObjetoRESUMO
Having up-to-date knowledge of the variability in facial artery topography is an essential starting point in performing certain surgical and radiological procedures on the head and neck (e.g. oromucosal reconstruction flaps, transarterial embolization). We report a unique case with: (1) the left facial artery truncating as an atypical inferior labial artery, (2) the left anterolateral face being perfused by unusual arterial collaterals derived from the right superior labial, left infraorbital and left dorsal nasal arteries, (3) the transverse facial artery not being one of the perfusing collaterals, and (4) the right submental artery piercing the mylohyoid muscle and entering the oral cavity. The embryologic basis of this atypical vascular pattern is discussed. Discovery of a highly atypical facial artery highlights the importance of performing a thorough pre-operative vascular evaluation to prevent iatrogenic injuries and complications before any surgical or therapeutic procedure.