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1.
J Pharm Bioallied Sci ; 16(Suppl 1): S233-S235, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38595368

RESUMEN

Aim: This study was performed with the idea of assessing age and gender utilizing differences in osseous microanatomy in human jawbones. Materials and Methods: The study was conducted retrospectively among human jawbone samples. Various morphometric assessments such as trabecular width, marrow space, and their corelation were studied. In the samples, variations among osteon numbers, differences in the shapes of the osteocytes of jawbones, and amount of inflammation in the bony areas were recorded. Results: It was noted in this study that mean values of the diameter of the Haversian canal and vessel density had a noteworthy increase in female jawbone samples. The amount of osteocytes in both female and male bone samples was also statistically significant in terms of the correlation coefficient. Conclusion: We concluded that more sensitive identification of human remains, that is, age and gender analysis, can be performed by histomorphometric evaluation of bone remains.

2.
J Pharm Bioallied Sci ; 16(Suppl 1): S236-S238, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38595383

RESUMEN

Aim: The aim of the study is to know about the awareness of probiotics among undergraduate dental students. Materials and Methods: We conducted cross-sectional research where we had distributed a questionnaire consisting of ten open-ended questions, among 150 dental students through emails. The questions were based on the utilization of probiotics in dentistry. The data obtained was statistically analyzed with the help of Chi-square test. Results: In our study, we noted that most of the participants were aware of the term probiotics and had general ideas but were not fully aware of its pathogenesis. Around 83.2% of the participants were aware of probiotics and general concepts. We also noted that only 42.5% of the students agreed that probiotics can be used in the management of halitosis as well as periodontitis. Conclusion: We concluded that most of the dental students had a lack of awareness as well as were not familiar with the usage of probiotics in dentistry.

3.
J Trop Pediatr ; 70(1)2023 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-38116810

RESUMEN

BACKGROUND: Microbiological diagnosis of pediatric tuberculosis (TB) using conventional microbiological techniques has been challenging due to paucibacillary nature of the disease. Molecular methods using cartridge-based tests like Xpert, have immensely improved diagnosis. A novel next-generation cartridge test, Xpert Ultra, incorporates two additional molecular targets and claims to have much lower detection limit. We attempted to compare the two techniques in presumptive pediatric TB patients. OBJECTIVES: The aim of this study was to compare the diagnostic performance of Xpert MTB/Rif Ultra with Xpert MTB/Rif for the detection of pediatric TB. STUDY DESIGN: This is an observational comparative analytical study. METHODS: Children under 15 years of age with presumptive TB were enrolled. Appropriate specimens were obtained (sputum, induced sputum or gastric aspirate for suspected pulmonary TB, cerebrospinal fluid for suspected tubercular meningitis and pleural fluid for suspected tubercular pleural effusion), subjected to smear microscopy, mycobacterial culture, Xpert and Xpert ultra tests and other appropriate diagnostic investigations. RESULTS: Out of 130 enrolled patients, 70 were diagnosed with TB using a composite reference standard (CRS). The overall sensitivity of Xpert was 64.29% [95% confidence interval (CI) 51.93-75.93%] and that of Xpert Ultra was 80% (95% CI 68.73-88.61%) with 100% overall specificity for both. The sensitivity of Xpert and Xpert Ultra in pulmonary specimens (n = 112) was 66.67% and 79.37% and in extrapulmonary specimens (n = 18) was 42.86% and 85.71%, respectively. CONCLUSION: Our study found Ultra to be more sensitive than Xpert for the detection of Mycobacterium tuberculosis in children. Our findings support the use of Xpert Ultra as initial rapid molecular diagnostic test in children under evaluation for TB.


Asunto(s)
Antibióticos Antituberculosos , Mycobacterium tuberculosis , Tuberculosis Meníngea , Humanos , Adolescente , Niño , Rifampin/farmacología , Mycobacterium tuberculosis/genética , Antibióticos Antituberculosos/farmacología , Antibióticos Antituberculosos/uso terapéutico , Sensibilidad y Especificidad , Tuberculosis Meníngea/diagnóstico , Tuberculosis Meníngea/microbiología , Esputo/microbiología , Farmacorresistencia Bacteriana
4.
J Spinal Cord Med ; : 1-17, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37982811

RESUMEN

CONTEXT: Antimicrobial Stewardship Programs (ASPs) are crucial to optimizing antibiotic use. ASPs are implemented in the Veterans Health Administration (VAs), but they do not target the needs of populations at high risk for resistant infections, such as spinal cord injury and disorder (SCI/D). OBJECTIVE: The goal of this study was to assess key ASP leader and SCI/D clinicians' perceived level of implementation and impact of 33 Antimicrobial Stewardship (AS) strategies. METHOD: SCI/D clinicians and ASP leaders across 24 VA facilities with SCI/D units were surveyed. Participants rated their perceived level of impact ("high", "mild", "low") and perceived level of implementation ("not", "partially", "fully") for 33 AS strategies in SCI/D units in VAs. Strategies were grouped into core elements which they support. We conducted a Fisher's exact test to assess differences between respondent perceptions based on role (SCI/D clinicians versus ASP leaders). RESULTS: AS strategy implementation varied across VA facilities. Of the AS strategies, pre-authorization was perceived to be highly impactful (78%) and fully implemented (82%). SCI/D clinicians and ASP leaders rated AS strategies differently such that SCI/D clinicians were less aware of implementation of AS strategies related to reporting requirements; further, SCI/D clinicians rated strategies which guide treatment duration and which limit C. difficile antibiotic exposure as more impactful than ASP leaders. Ratings for facility-wide and SCI/D unit ratings did not significantly differ for impact or implementation. CONCLUSION: Implementation practices varied across VA facilities. Future work should implement highly impactful AS strategies according to facility and unit needs.

5.
Am J Med ; 136(11): e218-e219, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37481024
6.
Am J Perinatol ; 2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37257487

RESUMEN

OBJECTIVE: Positive pressure ventilation (PPV) is crucial to the resuscitation of newborns. Although neonates often require PPV at birth, the optimal interface has not been determined. Both binasal prongs and face masks were deemed acceptable by the International Liaison Committee on Resuscitation in 2010 and have been utilized at our center since 2016; however, the choice is by provider preference. Previous studies have suggested that binasal prongs may be more effective than face masks at avoiding intubation in the delivery room. The objective of this study is to compare intubation rates of binasal prongs versus face masks for delivery room resuscitation of neonates born < 30 weeks' gestation. STUDY DESIGN: This retrospective study compares delivery room intubation rates by interface for neonates < 30 weeks' gestation born between August 2016 and April 2021 at our level IV neonatal intensive care unit. Exclusion criteria included diagnosis of congenital diaphragmatic hernia, no PPV required, or no resuscitation attempted. Data collected included interface device, demographics, maternal data, delivery room data, admission data, and discharge outcomes. The three interface groups (binasal prongs, face mask, face mask, and binasal prongs) were compared utilizing chi-square, analysis of variance with post hoc analysis, and logistic regression. RESULTS: Mean gestational ages and birthweights for the groups were 27.6 weeks and 1,126 g, 25.7 weeks and 839 g, and 27.1 weeks and 1,028 g, respectively. Neonates resuscitated with face masks were 9.9 times more likely to be intubated in the delivery room and 10.8 times more likely to be intubated at 6 hours of life compared with those resuscitated with binasal prongs after logistic regression analysis. CONCLUSION: The findings in our study support delivery room resuscitation with binasal prongs as a useful method in reducing the need for intubation both in the delivery room and at 6 hours of life. Further prospective studies are warranted. KEY POINTS: · The International Liaison Committee on Resuscitation recommends multiple interface options for neonatal resuscitation.. · Vermont Oxford Network endorses nasal interface for premature infants.. · Binasal prongs are associated with lower intubation rates..

7.
Int J Mycobacteriol ; 11(4): 394-399, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36510924

RESUMEN

Background: The etiological pattern of hemoptysis has evolved, with pulmonary tuberculosis (PTB) becoming less prevalent as a cause. There is a paucity of literature regarding the spectrum of diseases that present as hemoptysis and the data related to detailed clinical profile are lacking. Hence, this study is taken up to determine the clinical profile of hemoptysis and its correlation with radiological and microbiological findings. Methods: This was a 3-year observational prospective study of a total of 50 patients who presented with active hemoptysis. Data were recorded from these patients for assessing the clinical characteristics, radiological, and microbiological correlation. Results: The most common etiologies of hemoptysis identified in this study were PTB in 60% of the patients, aspergilloma in 14%, followed by bronchiectasis in 8%, pneumonia in 8%, carcinoma lung in 4%, and lung abscess in 1 (2%). Mild hemoptysis was present in 8% of patients, whereas 42% had moderate hemoptysis, 18% of patients had severe, and 32% had massive hemoptysis. Sixty percent of patients had recurrent hemoptysis, and the majority of the patients, i.e., 68% tested negative on sputum smear examination for acid-fast bacillus. In 60% of patients, no growth was obtained in the sputum cultures. The most common organisms isolated from sputum cultures of the rest of the patients were Pseudomonas in 14%, Klebsiella in 10%, Escherichia coli in 4%, Staphylococci in 4%, and Streptococcus pneumoniae in 4% of the cases. The majority of the patients were having consolidation and cavitary disease. A highly significant correlation was noted between the radiological findings of consolidation, mycetoma, cystic shadows, lung mass, and lung abscess and the etiology of hemoptysis (P = 0.000). Conclusion: Hemoptysis of any volume implies a life-threatening process, which mandates immediate evaluation and treatment. It is evident that the etiological spectrum of hemoptysis is continuously changing, and more sophisticated investigations, better imaging techniques, bronchoscopic tools, availability of newer techniques in the developing world, and changing patterns of diseases, all contribute to these changes. Identification of the etiology, and localization of the bleeding site, is essential for the efficient management of hemoptysis.


Asunto(s)
Bronquiectasia , Absceso Pulmonar , Enfermedades Pulmonares , Tuberculosis Pulmonar , Humanos , Estudios Prospectivos , Absceso Pulmonar/complicaciones , Hemoptisis/etiología , Bronquiectasia/complicaciones , Bronquiectasia/diagnóstico por imagen , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/diagnóstico por imagen , Enfermedades Pulmonares/complicaciones
8.
J Obstet Gynaecol India ; 72(Suppl 2): 418-420, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36457425
9.
Sci Total Environ ; 841: 156593, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-35690218

RESUMEN

The high prevalence and persistence of microplastics (MPs) in pristine habitats along with their accumulation across environmental compartments globally, has become a matter of grave concern. The resilience conferred to MPs using the material engineering approaches for outperforming other materials has become key to the challenge that they now represent. The characteristics that make MPs hazardous are their micro to nano scale dimensions, surface varied wettability and often hydrophobicity, leading to non-biodegradability. In addition, MPs exhibit a strong tendency to bind to other contaminants along with the ability to sustain extreme chemical conditions thus increasing their residence time in the environment. Adsorption of these co-contaminants leads to modification in toxicity varying from additive, synergistic, and sometimes antagonistic, having consequences on flora, fauna, and ultimately the end of the food chain, human health. The resulting environmental fate and associated risks of MPs, therefore greatly depend upon their complex interactions with the co-contaminants and the nature of the environment in which they reside. Net outcomes of such complex interactions vary with core characteristics of MPs, the properties of co-contaminants and the abiotic factors, and are required to be better understood to minimize the inherent risks. Toxicity assays addressing these concerns should be ecologically relevant, assessing the impacts at different levels of biological organization to develop an environmental perspective. This review analyzed and evaluated 171 studies to present research status on MP toxicity. This analysis supported the identification and development of research gaps and recommended priority areas of research, accounting for disproportionate risks faced by different countries. An ecological perspective is also developed on the environmental toxicity of contaminated MPs in the light of multi-variant stressors and directions are provided to conduct an ecologically relevant risk assessment. The presented analyses will also serve as a foundation for developing environmentally appropriate remediation methods and evaluation frameworks.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Adsorción , Ecosistema , Monitoreo del Ambiente , Humanos , Microplásticos/toxicidad , Plásticos/toxicidad , Contaminantes Químicos del Agua/análisis
10.
Gerontol Geriatr Educ ; 43(2): 239-249, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-32666906

RESUMEN

BACKGROUND: Although home care workers (HCWs) are increasingly caring for adults with heart failure (HF), many feel unprepared and lack HF training. To serve as the foundation for a future educational intervention, we aimed to elicit HCWs' HF educational needs. METHODS: We partnered with the largest healthcare union in the US to recruit 41 HCWs employed by 17 home care agencies. Using the nominal group technique, we asked HCWs to respond to three questions: When caring for an HF patient: (1) What information do you want? (2) What symptoms worry you? (3) What situations do you struggle with? Participants ranked their responses by priority. Data were consolidated by question. RESULTS: For question 1, participants ranked HF signs and symptoms most highly, followed by HF treatment and medications. For question 2, chest pain was most worrisome, followed by neurologic changes and shortness of breath. For question 3, participants struggled with encouraging patients to follow a heart-specific diet. CONCLUSIONS: HCWs expressed a need to learn more about signs and symptoms of HF and ways to assist patients with HF self-care. These findings can inform the development of an HF training program for HCWs that specifically addresses their expressed needs.


Asunto(s)
Geriatría , Insuficiencia Cardíaca , Servicios de Atención de Salud a Domicilio , Escolaridad , Geriatría/educación , Insuficiencia Cardíaca/terapia , Humanos , Aprendizaje
11.
Int J Mycobacteriol ; 10(4): 475-477, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34916471

RESUMEN

Intestinal tuberculosis (TB) is a diagnostic challenge and can closely mimic Crohn's disease (CD) and colon cancer. These disease entities very closely resemble each other in symptomatology, imaging, appearance, and pathology. We present a case of colonic TB where the initial diagnostic workup was suggestive of CD. However, the detection of Mycobacterium tuberculosis in biopsy specimens confirmed the diagnosis.


Asunto(s)
Enfermedad de Crohn , Mycobacterium tuberculosis , Tuberculosis Gastrointestinal , Colon , Enfermedad de Crohn/diagnóstico , Humanos , Mycobacterium tuberculosis/genética , Tuberculosis Gastrointestinal/diagnóstico
12.
Int J Mycobacteriol ; 10(3): 341-343, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34494579

RESUMEN

Tuberculosis (TB) and sarcoidosis are multisystem, chronic granulomatous diseases. Although characterized by similar clinical manifestations, these disease entities vary significantly in etiologies and management. Sarcoidosis is an immunological disorder of unknown etiology, characterized by the presence of noncaseating granulomas in the tissues involved. TB is the infectious disease caused by Mycobacterium tuberculosis, characterized by granulomas with caseous necrosis. It is rare to have both the diseases concomitantly. We present the case of a 38-year-old male with microbiological confirmation of coexistent pulmonary TB and sarcoidosis.


Asunto(s)
Sarcoidosis , Tuberculosis Pulmonar , Tuberculosis , Adulto , Granuloma , Humanos , Masculino , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/diagnóstico
13.
Phys Rev E ; 103(5): L050601, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34134282

RESUMEN

In a supercooled liquid, the crossover temperature T_{c} separates a high-temperature region of diffusive dynamics from a low-temperature region of activated dynamics. A molecular-dynamics simulation of all-atom, flexible o-terphenyl [Eastwood et al., J. Phys. Chem. B 117, 12898 (2013)10.1021/jp402102w] is analyzed with advanced statistical methods to reveal the molecular features associated with this crossover. The simulations extend to an α-relaxation time of 14 µs (272.5 K), two orders of magnitude slower than at T_{c} (290 K). At T_{c} and below, a distinct state emerges that immediately precedes an orientational jump. Compared to the initial, tightly caged state, this jump-precursor state has a looser cage, with solid-angular excursions of 0.054-0.0125 × 4π sr. At T_{c} (290 K), rate heterogeneity is already the dominant cause of stretched relaxation. Exchange within the distribution of rates is faster than α relaxation at T_{c}, but becomes equal to it at the lowest temperature simulated (272.5 K). The results trend toward a recent experimental observation near the glass transition (243 K) [Kaur et al., Phys. Rev. E 98, 040603(R) (2018)10.1103/PhysRevE.98.040603], which saw exchange substantially slower than α relaxation. Overall, the dynamic crossover comprises multiple phenomena: the development of heterogeneity, an increasing jump size, an emerging jump-precursor state, and a lengthening exchange time. The crossover is neither sharp, nor a simple superposition of the high- and low-temperature regimes; it is a broad region that contains unique and complex phenomena.

14.
J Appl Gerontol ; 40(12): 1778-1785, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-32975471

RESUMEN

BACKGROUND: Many older adults receive help from both family caregivers and home care workers. We aimed to understand family caregivers' perspectives on home care workers. METHODS: This qualitative study took place at an academic medical center in New York, N.Y. We interviewed family caregivers of community-dwelling older adults about their experiences with home care workers. We analyzed transcripts thematically. RESULTS: We interviewed 17 family caregivers and identified four major themes: (a) home care workers provide functional and emotional support; (b) home care is logistically challenging; (c) finding the right fit between home care workers, older adults, and families is essential; and (d) home care workers and family caregivers coordinate care well beyond the initiation of home care. CONCLUSION: Despite its logistical challenges, home care benefits patients and family caregivers. Given the growing prevalence of caregiving, clinicians and family caregivers might benefit from training and support about working with home care workers.


Asunto(s)
Servicios de Atención de Salud a Domicilio , Auxiliares de Salud a Domicilio , Anciano , Cuidadores , Familia , Humanos , Vida Independiente , Investigación Cualitativa
15.
J Gen Intern Med ; 35(6): 1721-1729, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32026253

RESUMEN

BACKGROUND: Readmission rates are high among heart failure (HF) patients who require home health care (HHC) after hospitalization. Although HF patients who require HHC are often sicker than those who do not, HHC delivery itself may also be suboptimal. OBJECTIVE: We aimed to describe the workflow of HHC among adults discharged home after a HF hospitalization, including the roles of various stakeholders, and to determine where along these workflow challenges and opportunities for improvement exist. DESIGN AND PARTICIPANTS: In this qualitative study, we used purposeful sampling to approach and recruit a variety of key stakeholders including home health aides, nurses, HF patients, family caregivers, physicians, social workers, home care agency leaders, and policy experts. The study took place in New York, NY, from March to October 2018. APPROACH: Using a semi-structured topic guide, we elicited participants' experiences with HHC in HF through a combination of one-on-one interviews and focus groups. Data were recorded, transcribed, and analyzed thematically. We also asked selected participants to depict in a drawing their understanding of HHC workflow after hospitalization for HF patients. We synthesized the drawings into a final image. KEY RESULTS: Study participants (N = 80) described HHC for HF patients occurring in 6 steps, with home health aides playing a main role: (1) transitioning from hospital to home; (2) recognizing clinical changes; (3) making decisions; (4) managing symptoms; (5) asking for help; and (6) calling 911. Participants identified challenges and opportunities for improvement for each step. CONCLUSIONS: Our findings suggest that HHC for HF patients occurs in discrete steps, each with different challenges. Rather than a one-size-fits-all approach, various interventions may be required to optimize HHC delivery for HF patients in the post-discharge period.


Asunto(s)
Insuficiencia Cardíaca , Servicios de Atención de Salud a Domicilio , Adulto , Cuidados Posteriores , Insuficiencia Cardíaca/terapia , Humanos , New York , Alta del Paciente , Flujo de Trabajo
16.
Am J Clin Oncol ; 42(11): 870-883, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31592804

RESUMEN

OBJECTIVES: Cancer patients with comorbid diabetes have a 50% increased risk of all-cause mortality compared with cancer patients without diabetes. Less attention to diabetes management (glucose control, medication adherence, and diabetes self-management behaviors) during active cancer treatment is hypothesized as an explanation for worse outcomes among diabetic cancer patients. The objective of this systematic review is to determine and quantify how a cancer diagnosis impacts diabetes management. METHODS: Quantitative and qualitative studies evaluating diabetes management among patients were identified by searching 4 databases: MEDLINE, EMBASE, The Cochrane Library, and Web of Science. Two independent reviewers extracted data and summarized results from eligible studies. Study quality was formally assessed. RESULTS: Thirty-six studies met all inclusion criteria. We observed heterogeneity across studies in terms of study design, sample size, cancer site, type of diabetes management evaluated, and quality. Numerous articles discussed that overall, glucose control, medication adherence, and diabetes self-management behaviors declined following a cancer diagnosis. However, findings were inconsistent across studies. CONCLUSIONS: Although the effects of a cancer diagnosis on diabetes management are mixed, when results across studies were synthesized together, diabetes management appeared to generally decline after a cancer diagnosis. Declines in diabetes management seem to be primarily due to shifts in the priority of care from diabetes management to cancer. A next critical step in this line of work is to identify patient and provider level predictors of better or worse diabetes management to design and test interventions aimed at improving effective diabetes management for cancer patients.


Asunto(s)
Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Hipoglucemiantes/uso terapéutico , Cumplimiento de la Medicación/estadística & datos numéricos , Neoplasias/epidemiología , Centros Médicos Académicos , Comorbilidad , Diabetes Mellitus/diagnóstico , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Neoplasias/diagnóstico , Neoplasias/terapia , Pronóstico , Medición de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento
17.
J Educ Health Promot ; 8: 45, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30993138

RESUMEN

INTRODUCTION: Oral health is an important component of general health. The World Health Organization has highly recommended the integration of oral health promotion into general health care. In majority of the cases, patients visit their physicians with simultaneous oral and systemic complaints, and primary oral complaints are more frequently encountered. Therefore, primary care physicians can play an expanded role within oral health care to raise the overall health of the patients. AIM: This study aimed to assess the knowledge and awareness of family physicians regarding oral health. MATERIALS AND METHODS: An observational (cross-sectional) study was conducted among 250 family physicians who are practicing in Tricity. A self-structured questionnaire (close-ended) prepared by a panel of oral health experts in English language (close-ended) was administered to the study participants. The questionnaire which was divided into two parts, A and B, contained 15 questions on knowledge and awareness regarding oral health. Categorization of knowledge scores was done at three levels: low, medium, and high. Statistical analysis was performed using analysis of variance and Student's t-test. RESULTS: Males comprised 72.8% (182) of the study population and 55.2% (138) of the participants were doing combined practice (academic and private both). Low knowledge scores were reported in 47.2% (118) of the participants whereas only 22.4% (56) of participants had a high score. The mean knowledge score according to educational level and working profile was statistically significant (P < 0.05). CONCLUSION: The results of our study showed a considerable lack of knowledge among family physicians regarding connection of oral health with general health. Therefore, there is an urgent need to increase their knowledge by various continued medical education and training programs.

18.
J Biol Chem ; 294(22): 8806-8818, 2019 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-30996005

RESUMEN

Aß1-42 is involved in Alzheimer's disease (AD) pathogenesis and is prone to glycation, an irreversible process where proteins accumulate advanced glycated end products (AGEs). Nϵ-(Carboxyethyl)lysine (CEL) is a common AGE associated with AD patients and occurs at either Lys-16 or Lys-28 of Aß1-42. Methyglyoxal is commonly used for the unspecific glycation of Aß1-42, which results in a complex mixture of AGE-modified peptides and makes interpretation of a causative AGE at a specific amino acid residue difficult. We address this issue by chemically synthesizing defined CEL modifications on Aß1-42 at Lys-16 (Aß-CEL16), Lys-28 (Aß-CEL28), and Lys-16 and -28 (Aß-CEL16&28). We demonstrated that double-CEL glycations at Lys-16 and Lys-28 of Aß1-42 had the most profound impact on the ability to form amyloid fibrils. In silico predictions indicated that Aß-CEL16&28 had a substantial decrease in free energy change, which contributes to fibril destabilization, and a increased aggregation rate. Single-CEL glycations at Lys-28 of Aß1-42 had the least impact on fibril formation, whereas CEL glycations at Lys-16 of Aß1-42 delayed fibril formation. We also tested these peptides for neuronal toxicity and mitochondrial function on a retinoic acid-differentiated SH-SY5Y human neuroblastoma cell line (RA-differentiated SH-SY5Y). Only Aß-CEL16 and Aß-CEL28 were neurotoxic, possibly through a nonmitochondrial pathway, whereas Aß-CEL16&28 showed no neurotoxicity. Interestingly, Aß-CEL16&28 had depolarized the mitochondrial membrane potential, whereas Aß-CEL16 had increased mitochondrial respiration at complex II. These results may indicate mitophagy or an alternate route of metabolism, respectively. Therefore, our results provides insight into potential therapeutic approaches against neurotoxic CEL-glycated Aß1-42.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Amiloide/metabolismo , Fragmentos de Péptidos/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/síntesis química , Péptidos beta-Amiloides/toxicidad , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Glicosilación , Humanos , Lisina/análogos & derivados , Lisina/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Fragmentos de Péptidos/síntesis química , Fragmentos de Péptidos/toxicidad , Agregado de Proteínas , Conformación Proteica en Lámina beta , Estabilidad Proteica , Oxígeno Singlete/metabolismo
19.
Chem Commun (Camb) ; 53(60): 8459-8462, 2017 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-28702630

RESUMEN

Advanced lipid peroxidation end-products (ALEs) accumulate with ageing and oxidative stress-related diseases. Despite their potential therapeutic value, there are no suitably protected ALE building blocks reported in the literature to enable their site-specific incorporation into synthetic peptides. The synthesis of an Fmoc-protected ALE building block, N∈-(3-methylpyridinium)lysine (MP-lysine) and its incorporation into collagen model peptides is reported.


Asunto(s)
Materiales Biomiméticos/química , Colágeno/química , Productos Finales de Glicación Avanzada/química , Peroxidación de Lípido , Péptidos/química
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