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1.
J Family Med Prim Care ; 10(9): 3178-3184, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34760727

RESUMO

Pertinent perspectives for practical applications is advantageous professionalism. Congenital heart diseases (CHDs) are of varied types, severity, and complexity. Simple scientific approach along with sophistication is required for successful management at all levels. We gleaned important information from published evidence and authoritative resources and have put things in practical perspective. These include current prevention, care, correction, cure, and rehabilitation strategies for robust practices. Prospective prevention is with preconception counseling and addressing environmental factors. Fetal echocardiography and nondirective genetic counseling are important. Early detection and expert diligence is desirable. The suspicion is clinical. A number of clinical and investigative diagnostic modalities are available and should be utilized as guided by the clinical cues. Medical management includes general health maintenance, immunizations, monitoring, and complications treatment. Pediatric interventional cardiology is making rapid strides and treating many types of lesions. Understanding of procedure done is a prerequisite of follow-up care. Surgery is of curative, reparative, or palliative types. After surgical correction in early childhood long-term sequelae are rare. After reparative surgery some have life-long sequelae and some have significant late impairment. The number of postintervention/surgery survivors into adulthood is increasing. Microsurgical techniques are leading the way for precision and fewer complications. Follow-up care with "Ten Points Information and Action Plan (TP-IAP)" is suggested. The Armed Forces scenario involves frequent movements to difficult and harsh conditions. Special precautions for affected children needed. Cardiovascular health is enhanced by avoiding a sedentary lifestyle and obesity. Various intrinsic and extrinsic factors limiting functioning need to be suitably addressed.

2.
Pain ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34490850

RESUMO

ABSTRACT: Patients with chronic pain syndromes, such as those with painful peripheral neuropathy due to diabetes mellitus, have limited treatment options and suffer ongoing attrition of their quality of life. Safer and more effective treatment options are needed. One therapeutic approach encompasses phenotypic characterization of the neuropathic pain subtype, combined with the selection of agents that act on relevant mechanisms. ISC 17536 is a novel, orally available inhibitor of the widely expressed pain receptor, transient receptor potential ankyrin 1, which mediates nociceptive signaling in peripheral small nerve fibers. In this randomized, placebo-controlled, proof-of-concept trial, we assessed the safety and efficacy of 28-day administration of ISC 17536 in 138 patients with chronic, painful diabetic peripheral neuropathy and used quantitative sensory testing to characterize the baseline phenotype of patients. The primary end point was the change from baseline to end of treatment in the mean 24-hour average pain intensity score based on an 11-point pain intensity numeric rating scale. The study did not meet the primary end point in the overall patient population. However, statistically significant and clinically meaningful improvement in pain were seen with ISC 17536 in an exploratory hypothesis-generating subpopulation of patients with preserved small nerve fiber function defined by quantitative sensory testing. These results may provide a mechanistic basis for targeted therapy in specific pain phenotypes in line with current approaches of "precision medicine" or personalized pain therapeutics. The hypothesis is planned to be tested in a larger phase 2 study.

3.
J Family Med Prim Care ; 10(4): 1520-1524, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34123885

RESUMO

Radiation is important in health and disease. It is imperative to use properly and prevent misuse or overuse. Pertinent trends of increasing radiation in the environment need analysis. We gleaned important information, from published evidence and authoritative resources, for practicing safely and preventing harm. Science & technology progress is for the betterment of mankind, and all efforts should be made to prevent any untoward effects. Children and paediatric patients deserve special attention because of their vulnerability due to multiple reasons. Effective investigations & interventions in medical settings should be done based on best evidence. All those ordering radiological investigations should take into consideration the radiation exposure values & especially decide on clinical impact of the investigation. Prenatal exposure to radiation has risks. Computed Tomography is responsible for 24% of all radiation exposure. Dual-energy X-ray absorptiometry is useful for measuring changes in body tissue composition. Radiologists should tailor imaging individually. Radiotherapy is administered to more than half of all cancer patients. Acute toxicity alleviation and chronic toxicity consideration is important. Radiation emergencies can occur in isolation or as major catastrophe. Emergency life-support is needed. Decontamination along with using the ABCDE reduction approach components are elucidated. With increasing use of mobile phones the electro-magnetic fields produced by mobile phones use needs consideration. UV radiation overexposure prevention is with shade, clothing and hats. Applying sunscreen essential on those parts of the body that remain exposed like the face and hands. All the safety measures need popularization and continuous practice with precision & perfection.

4.
Curr Drug Deliv ; 2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34126895

RESUMO

INTRODUCTION: Metformin, an anti-diabetic drug, has low bioavailability and a short biological half-life. Thus, bioavailability enhancement and prolonged release of the drug are highly desirable. In this regard, we aimed to developed gastroretentive nanoparticles made of jackfruit seed starch (JFSS) loaded with metformin. METHODS: The developed nanoparticles were optimized for various process variables and were further characterized. Nanoparticles exhibited good results with respect to particle size (244.3 to 612.4 nm), particle size distribution, shape, and drug entrapment efficiency (75.8 to 89.2 %) with sustained drug release for 24 h and a high buoyancy (89% for F7, formulation made of the highest concentration of Jackfruit seed starch prepared at 1000 RPM stirring speed). RESULTS: The hypoglycemic potential of these nanoparticles was tested in the nicotinamide streptozocin induced diabetic model; there was a significant reduction in blood glucose level (50 % reduction from 4 - 8 h, p < 0.01) for a prolonged period of time (up to 24 h) in comparison to diabetic control and plain metformin solution. CONCLUSION: The outcome of the study suggested that the developed formulations are suitable for gastro-retentive delivery of Metformin in a controlled manner appropriate for a single administration per day.

5.
Adv Med Educ Pract ; 12: 513-518, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34045915

RESUMO

Purpose: Advanced methodical learning and optimised learning leads to better-trained doctors. Such teaching typically comprises the illustration of features and access to facilities. This article explores the role of "Special clinics" in medical education. The role of sophisticated "Special clinics" is to provide vigour and vibrancy in treating and teaching as well as advancing the art and science of medicine. All this contributes towards the current evidence indicating benefits of reducing hospitalization. Methods: This article comprises an analysis of the guidance produced by leading medical education institutions. Findings are presented in the perspective of a relevant theoretical framework around "Special clinics", in light of the available evidence and personal experience. Results: The implementation and potential impacts of "Special clinics" are presented within the context of the "4SAs", a favoured teaching mnemonic: 1) Scientific Approach: medical education rules and regulations reflecting scientific reasoning in support of "Special clinics", 2) Setting Advantages: the mechanisms by which "Special clinics" are conducive to and contribute towards increasing the capacity to comprehensively treat complex disorders in the outpatient setting, avoiding hospitalization and its associated risks, as well as expenditure, 3) Sophistication Advantages: tools and techniques to ensure advanced clinical skills teaching including novel outpatient technologies, understanding the need for focussed study and practice, and exploiting the advantages of internationalization of medical education, and 4) Successes and Advancements: opportunities to observe experts providing specialist care of the highest standard. The use of a focussed approach aims to explore and advance frontiers of medical education. Conclusion: "Special clinics" will soon form a major component of the hospital workload and play a crucial role in medical education. They provide the advantage of condition-specific patient-centered care, the motivation for excellence. Clinical skills learnt by medical students in "Special clinics" will undoubtedly contribute to long-term improvements in the medical care.

6.
Am J Perinatol ; 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33975363

RESUMO

OBJECTIVE: This study aimed to determine if prolonged antibiotic use at birth in neonates with a negative blood culture increases the total cost of hospital stay. STUDY DESIGN: This was a retrospective study performed at a 60-bed level IV neonatal intensive care unit. Neonates born <30 weeks of gestation or <1,500 g between 2016 and 2018 who received antibiotics were included. A multivariate linear regression analysis was conducted to determine if clinical factors contributed to increased hospital cost or length of stay. RESULTS: In total, 190 patients met inclusion criteria with 94 infants in the prolonged antibiotic group and 96 in the control group. Prolonged antibiotic use was associated with an increase length of hospital stay of approximately 31.87 days, resulting in a $69,946 increase in total cost of hospitalization. CONCLUSION: Prolonged antibiotics in neonates with negative blood culture were associated with significantly longer hospital length of stay and increased total cost of hospitalization. KEY POINTS: · Prolonged antibiotic use at birth is associated with prolonged hospital stay.. · Prolonged antibiotic use at birth is associated with increased cost of hospitalization.. · Prolonged antibiotic use at birth is associated with increased days on total parenteral nutrition.. · Prolonged antibiotic use at birth is associated with increased subsequent courses of antibiotics..

7.
Neoreviews ; 22(5): e309-e319, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33931476

RESUMO

Tremendous advances have been made in the last 5 decades in the surgical management of congenital heart disease (CHD). Most infants affected by clinically significant CHD are at risk for developing heart failure (HF). Adult HF management is mostly evidence-based and our knowledge in this field has expanded significantly in the past decade. However, data on management approaches for HF in infants are limited. The indications and implications for various medications and interventions in patients with HF secondary to CHD are an upcoming area of interest. It is critical that we expand our ability to prevent, detect, and manage HF in the pediatric population.


Assuntos
Cardiopatias Congênitas , Insuficiência Cardíaca , Inibidores de Simportadores de Cloreto de Sódio e Potássio , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Lactente , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico
8.
Pediatric Health Med Ther ; 12: 151-159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790685

RESUMO

Purpose: Current recommendations for 'Febrile seizures' management include emergency first aid and treatment along with intermittent prophylaxis. Evidence of practices, efficacy, side-effects, and complications should lead to refined and rational management strategies. Patients and Methods: Study of cases referred and treated at a tertiary level hospital, providing referral services to a large state in India. Evidence sought for the research questions identified, these were (i) immediate treatment: First aid components and practices; response to drug treatment (ii) intermittent prophylaxis: effectiveness, compliance, and side-effects (iii) complications arising due to treatment side-effects: quantifying the number of cases of CNS infections missed as a result of alterations in consciousness levels due to benzodiazepines. Results: A total of 85 febrile seizure cases were studied. Full correct "First Aid" was provided by only 13 parents. Total 35 cases (41.18%) had seizures lasting more than 05 minutes. Emergency treatment for these included rectal diazepam in 14 cases with 57.14% success in terminating seizure, and intranasal midazolam in 21 cases with 71.43% success. The cases with persisting seizures were managed as status epilepticus treatment algorithm. Intermittent prophylaxis prevented recurrence of seizures in 90%, however side-effects were reported in 36.36%. There was no case of CNS infection missed. Conclusion: Safe and effective management strategy should include "Health education" for correct first aid and 'Protocols' for timely and correct emergency treatment by parents/pre-hospital teams/emergency duty doctors. Intermittent prophylaxis is effective but refinements needed to minimize side-effects. Vigilant clinical monitoring obviates the fear that treatment may mask CNS infection.

9.
J Perinatol ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686118

RESUMO

Echocardiogram (echo) is a commonly used noninvasive modality for the diagnosis of bronchopulmonary dysplasia associated pulmonary hypertension (BPD-PH). Though not considered the gold standard for the diagnosis of BPD-PH, it is an extremely valuable tool in the neonatal and pediatric population, especially when cardiac catheterization is not feasible. In addition to the traditional echo parameters that are used to assess the presence of BPD-PH, much attention has been recently placed on newer bedside echo measures, the so-called functional echo parameters, to aid and assist in the diagnosis. This review article provides a brief introduction to BPD-PH, describes the pitfalls of traditional echo parameters and details the newer echo modalities currently available for the diagnosis of neonatal PH.

10.
Curr Drug Deliv ; 18(5): 654-668, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33106142

RESUMO

BACKGROUND: Low bioavailability of anti-diabetic drugs results in the partial absorption of the drug as they are mainly absorbed from the stomach and the lower part of the GIT. Drug bioavailability of anti-diabetic drugs can be significantly increased by prolonging gastric retention time through gastro-retentive dosage form such as floating microspheres. OBJECTIVE: The study was aimed to develop and characterize resin based floating microspheres of Repaglinide and Metformin for superior and prolonged maintenance of normoglycaemia in type-2 diabetes mellitus. METHODS: Repaglinide and metformin were complexed with amberlite resin; later resin complexed drug was encapsulated in Ethylcellulose floating microspheres. Floating microspheres were characterized for morphology, particle size, IR spectroscopy, DSC, in vitro release and buoyancy studies. Further, floating microspheres were tested for in vivo blood glucose reduction potential in Streptozocin- induced diabetic mice. RESULTS: Floating microspheres had a spherical shape and slightly rough surface with the entrapment efficiency in a range of 49-78% for metformin and 52-73% for repaglinide. DSC studies revealed that no chemical interaction took place between polymer and drugs. Floating microspheres showed good buoyancy behavior (P<0.05) and prolonged drug release as compared to plain drug (P<0.05). The blood glucose lowering effect of floating microspheres on Streptozocin induced diabetic rats was significantly greater (P<0.05) and prolonged (˃12h) and normoglycaemia was maintained for 6hr. CONCLUSION: Floating microspheres containing drug resin complex were able to prolong drug release in an efficient way for a sustained period of time; as a result, profound therapeutic response was obtained.

11.
Pancreatology ; 21(1): 74-80, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33262050

RESUMO

BACKGROUND: Malnutrition and bone disease are common in adults with chronic pancreatitis (CP). We studied the nutritional status and bone mineral density (BMD) of children with CP and the factors predicting them. METHODS: CP children were prospectively evaluated with a detailed questionnaire, anthropometry, 25-hydroxy vitamin D, fecal elastase and BMD [total body less head (TBLH), spine and hip] by dual energy x-ray absorptiometry. Body mass index (BMI) Z score of -1 to -1.9, -2 to -2.9 and <-3 was taken as mild, moderate and severe malnutrition respectively. Low BMD and osteoporosis were defined as per International Society for Clinical Densitometry. RESULTS: 83 children (46 boys, 14[4.3-21]years) with CP were enrolled. Majority had Cambridge IV (51,62.2%) or III (15,18.3%) changes. 34(41%) had undernutrition (mild-37.3%, moderate-2.4%, severe-1.2%). Overweight and obesity were present in 3.6% and 1.2% cases. BMI had a significant correlation with haemoglobin, serum albumin, percentage body fat and BMD. A majority had low fecal elastase (69 [84.1%], <100 µg/g) and vitamin D deficiency (70[84.3%],<20 ng/ml). 9 cases had a history of fractures. 14/75(18.6%) cases had low TBLH-BMD and this group had a lower BMI (-1.3[-1.9 to 0.34] vs 0.8 [-2.1 to 5.50; p = 0.03) than patients with normal BMD. There was no difference in age, disease duration, vitamin D, fecal elastase and Cambridge grade between normal and low BMD. CONCLUSIONS: 41% CP children have undernutrition with a majority having mild undernutrition. Nearly 20% have low BMD, with osteoporosis in none. Subjects with low BMI have lower BMD and percentage body fat.

12.
Diabetes Ther ; 12(1): 133-142, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33314000

RESUMO

The ongoing global pandemic of the coronavirus disease 2019 (COVID-19) has placed a severe strain on the management of chronic conditions like diabetes. Optimal glycemic control is always important, but more so in the existing environment of COVID-19. In this context, timely insulinization to achieve optimal glycemic control assumes major significance. However, given the challenges associated with the pandemic like restrictions of movement and access to healthcare resources, a simple and easy way to initiate and optimize insulin therapy in people with uncontrolled diabetes is required. With this premise, a group of clinical experts comprising diabetologists and endocrinologists from India discussed the challenges and potential solutions for insulin initiation, titration, and optimization in type 2 diabetes mellitus (T2DM) during the COVID-19 pandemic and how basal insulin can be a good option in this situation owing to its unique set of advantages like lower risk of hypoglycemia, ease of training, need for less monitoring, better adherence, flexibility of using oral antidiabetic drugs, and improved quality of life compared to other insulin regimens. The panel agreed that the existing challenges should not be a reason to delay insulin initiation in people with uncontrolled T2DM and provided recommendations, which included potential solutions for initiating insulin in the absence or restriction of in-person consultations; the dose of insulin at initiation; the type of insulin preferred for simplified regimen and best practices for optimal titration to achieve glycemic targets during the pandemic. Practical and easily implementable tips for patients and involvement of stakeholders (caregivers and healthcare providers) to facilitate insulin acceptance were also outlined by the expert panel. Simplified and convenient insulin regimens like basal insulin analogues are advised during and following the pandemic in order to achieve glycemic control in people with uncontrolled T2DM.

13.
J Family Med Prim Care ; 9(9): 4648-4655, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33209778

RESUMO

Context: Adolescent health information within new global health initiatives is advocated. Global School-based Student Health Survey (GSHS) is among young people 13 to17 years. Early prevention and promotion is beneficial. Aim: To find health behaviors and protective factors at different adolescence physiological stages. Settings and Design: School-based survey in an Army Public School. Methods and Materials: The study parameters were dietary behaviors, hygienic practices, mental health, physical activity, and protective factors. A total of 1232 adolescents were surveyed. Early adolescence (10-13 years) participants were 760 and middle adolescence (14-17 years) were 472. Male: female ratio was 1.819:1. Statistical Analysis: Calculation of percentage ± Standard error using standard methods. Results: The study reveals interesting trends. There is a disparity between body mass index (BMI) findings and effort direction for weight. There is a sharp rise in girls making efforts to lose weight from early to middle adolescence (27.8% and 40.7%, respectively). Hygienic practices are marginally short of 100%. Worry causing the inability to sleep at night most of the time or always reported by 9.2-18.7%. There is a sharp rise in the number of girls feeling this from early to middle adolescence (9.8%-18.7%). Adolescents spending three or more hours per day doing sitting activities are 25.6-38.6%. This is rising from early to middle adolescence, and sharply in girls. Protective factors are trending towards the positive side. Conclusions: First, for advancements of adolescents' health, top priorities are (i) Popularizing importance of ideal BMI, (ii) Betterment of mental health for a smooth transition across stages and being proactive for preventing worsening, (iii) Promoting physical activity early and sustaining efforts, especially amongst girls. Second, the 'GSHS Questionnaire' needs to be modified for fruits and vegetable consumption to how many servings/what part of plate and include questions for details of physical activity likings of girls.

14.
J Microencapsul ; 37(8): 609-623, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32985297

RESUMO

AIM: This study was aimed to develop Eudragit S100-coated, pH-awakened microbeads (MBs) encapsulating folic acid (FA)-modified tristearin solid lipid nanoparticles (SLNs) loaded with oxaliplatin (OP). Afterward, these formulations were evaluated (in vitro and in vivo) for their potential against colorectal cancer (CRC). METHODS: The SLNs were synthesised by employing the solvent diffusion technique and then they were entrapped in the MBs. The prepared uncoupled and coupled SLNs (SLN-OP and FA-SLN-OP, respectively) were examined for in vitro cytotoxicity effect against COLO-205. Gamma-scintigraphy study was used for determining biodistribution (in vivo) of drug in different organs through MBs. RESULTS: Outcomes for FA-SLN-OP revealed more cytotoxicity (50% inhibitory concentration [IC50] = 6.8 µg/ml) against COLO-205 cells (in vitro) than OP solution (IC50 = 8.0 µg/ml) and SLN-OP (IC50= 7.5 µg/ml). MBs were also investigated in vivo using Gamma-scintigraphy study. After 48 h study, 99mTc-EuB-FA-SLN-OP confirmed an elevated level of drug in the colonic tumour, which was found significantly (p< 0.0001) higher than that of 99mTc-EuB-SLN-OP. CONCLUSIONS: In conclusion, developed MBs formulation (99mTc-EuB-FA-SLN-OP) suggested promising results against therapy of CRC using dual targeting (i.e. ligand-directed and pH-awakened) approach.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Microesferas , Nanopartículas/química , Oxaliplatina/administração & dosagem , Ácidos Polimetacrílicos/química , Tecnécio/química , Animais , Antineoplásicos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Fólico/química , Raios gama , Humanos , Concentração de Íons de Hidrogênio , Concentração Inibidora 50 , Ligantes , Lipídeos/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Cintilografia , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Triglicerídeos/química
15.
Ther Adv Endocrinol Metab ; 11: 2042018820937217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32647562

RESUMO

Objective: To assess the real-world management practices of subjects with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM) in India. Methods: This cross-sectional study was conducted between 7 March 2016 and 15 May 2016 in India as part of the seventh wave (2016) of the International Diabetes Management Practices Study (IDMPS). Adult subjects with T1DM or T2DM visiting physicians during a 2-week recruitment period were included. Results: A total of 55 physicians included 539 subjects who met eligibility criteria. Of 495 subjects with T2DM, 303 were treated with oral glucose lowering drugs (OGLDs) only, 158 were treated with OGLD + insulin, and 27 received insulin only. Among 44 subjects with T1DM receiving insulin, 13 (29.5%) were also treated with OGLD therapy. The most commonly used insulin regimens were basal alone (69/184; 37.5%) and premixed alone (63/184; 34.2%) in subjects with T2DM, and basal + prandial insulin (24/44; 54.5%) in subjects with T1DM. Proportions of subjects achieving glycemic targets were low [glycated haemoglobin (HbA1c) <7%: T1DM = 7.3% (3/44), T2DM = 25.2% (106/495); as targeted by the treating physician: T1DM = 31.8% (14/44), T2DM = 32.1% (59/185); global target: T1DM = 4.8% (2/42) and T2DM = 1.7% (8/482)]. In subjects with T2DM, HbA1c <7% was noted in 11/22 subjects receiving insulin only and 76/260 receiving only OGLDs. Lack of experience in self-managing insulin dosing, poor diabetes education and failure to titrate insulin dosages were the main reasons for non-achievement of glycemic targets. Conclusion: Timely insulinization, education and empowerment of people with diabetes may help improve glycemic control in India.

16.
Curr Drug Deliv ; 17(6): 448-469, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32394836

RESUMO

Eudragit® polymer has been widely used in film-coating for enhancing the quality of products over other materials (e.g., shellac or sugar). Eudragit® polymers are obtained synthetically from the esters of acrylic and methacrylic acid. For the last few years, they have shown immense potential in the formulations of conventional, pH-triggered, and novel drug delivery systems for incorporating a vast range of therapeutics including proteins, vitamins, hormones, vaccines, and genes. Different grades of Eudragit® have been used for designing and delivery of therapeutics at a specific site via the oral route, for instance, in stomach-specific delivery, intestinal delivery, colon-specific delivery, mucosal delivery. Further, these polymers have also shown their great aptitude in topical and ophthalmic delivery. Moreover, available literature evidences the promises of distinct Eudragit® polymers for efficient targeting of incorporated drugs to the site of interest. This review summarizes some potential researches that are being conducted by eminent scientists utilizing the distinct grades of Eudragit® polymers for efficient delivery of therapeutics at various sites of interest.


Assuntos
Ácidos Polimetacrílicos/administração & dosagem , Administração Oral , Sistemas de Liberação de Medicamentos , Humanos , Ácidos Polimetacrílicos/química
17.
Proc Natl Acad Sci U S A ; 117(20): 10958-10969, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32366656

RESUMO

Necrotizing enterocolitis (NEC) is an inflammatory bowel necrosis of premature infants and an orphan disease with no specific treatment. Most patients with confirmed NEC develop moderate-severe thrombocytopenia requiring one or more platelet transfusions. Here we used our neonatal murine model of NEC-related thrombocytopenia to investigate mechanisms of platelet depletion associated with this disease [K. Namachivayam, K. MohanKumar, L. Garg, B. A. Torres, A. Maheshwari, Pediatr. Res. 81, 817-824 (2017)]. In this model, enteral administration of immunogen trinitrobenzene sulfonate (TNBS) in 10-d-old mouse pups produces an acute necrotizing ileocolitis resembling human NEC within 24 h, and these mice developed thrombocytopenia at 12 to 15 h. We hypothesized that platelet activation and depletion occur during intestinal injury following exposure to bacterial products translocated across the damaged mucosa. Surprisingly, platelet activation began in our model 3 h after TNBS administration, antedating mucosal injury or endotoxinemia. Platelet activation was triggered by thrombin, which, in turn, was activated by tissue factor released from intestinal macrophages. Compared to adults, neonatal platelets showed enhanced sensitivity to thrombin due to higher expression of several downstream signaling mediators and the deficiency of endogenous thrombin antagonists. The expression of tissue factor in intestinal macrophages was also unique to the neonate. Targeted inhibition of thrombin by a nanomedicine-based approach was protective without increasing interstitial hemorrhages in the inflamed bowel or other organs. In support of these data, we detected increased circulating tissue factor and thrombin-antithrombin complexes in patients with NEC. Our findings show that platelet activation is an important pathophysiological event and a potential therapeutic target in NEC.


Assuntos
Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/patologia , Doenças do Recém-Nascido/metabolismo , Trombina/metabolismo , Animais , Animais Recém-Nascidos , Plaquetas/metabolismo , Modelos Animais de Doenças , Humanos , Recém-Nascido , Inflamação/metabolismo , Enteropatias/patologia , Intestinos/lesões , Intestinos/patologia , Macrófagos/metabolismo , Camundongos , Trombocitopenia/metabolismo
18.
Neoreviews ; 21(3): e165-e178, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32123121

RESUMO

Failure of the normal transition from in utero to ex utero physiology leads to "persistent" pulmonary hypertension of the newborn (PPHN). PPHN is frequently associated with low systemic blood pressure and low cardiac output because of increased right ventricular afterload and myocardial dysfunction. The general management of newborns with PPHN is geared toward maintenance of normothermia, normal serum electrolytes, normal intravascular volume, correction of acidosis, adequate sedation/analgesia, adequate ventilation and oxygenation with optimal lung recruitment, and avoidance of hyperoxia. Inotropic and vasoactive agents are commonly initiated early to increase cardiac output, maintain adequate systemic blood pressure, and enhance oxygen delivery to the tissue. Unfortunately, there is not much evidence on the choice, timing of initiation, dosing, monitoring, and titrating of vasoactive agents in this patient population. In this review, we will discuss the pathophysiology of PPHN and review the use of inotropic, lusitropic, and vasoactive agents in the management of PPHN, with particular attention to milrinone.


Assuntos
Cardiotônicos/farmacologia , Milrinona/farmacologia , Síndrome da Persistência do Padrão de Circulação Fetal/tratamento farmacológico , Síndrome da Persistência do Padrão de Circulação Fetal/fisiopatologia , Vasoconstritores/farmacologia , Humanos , Recém-Nascido
19.
Diabetes Ther ; 11(3): 621-632, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32009224

RESUMO

AIM: To develop an evidence-based expert group consensus document on the best practices and simple tools for titrating basal insulins in persons with type 2 diabetes mellitus (T2DM). BACKGROUND: Glycemic control is suboptimal in a large proportion of persons with T2DM, despite insulin therapy, thereby increasing the risk of potentially severe complications. Early initiation of insulin therapy and appropriate dose titration are crucial to achieving glycemic targets. Attitudes and practices among healthcare professionals (HCPs) and perceptions about insulin therapy among persons with diabetes contribute largely to suboptimal glycemic control. Improving HCP-patient communication, encouraging the use of additional educational tools, and providing support for the titration process to increase confidence, both at the initiation visit and at home, facilitate the optimization of dose titration. In Indian settings, specific guidelines and a consensus statement are lacking on the optimal insulin initiation dose, frequency of dose titration, and basal insulin profile needed to achieve optimal titration. In clinical practice, physicians and persons with diabetes often do not adhere to the titration algorithms that currently exist for the purpose of achieving optimal titration as they perceive these to be very cumbersome. In this context, a group of experts met at an advisory board meeting and arrived at a consensus on best practices for the titration of basal insulin in persons withT2DM in India, using the modified Delphi methodology. REVIEW RESULTS: After a review of evidence and further discussions, the expert group provided recommendations on insulin initiation dose, ideal period for titration in practice, titration regimen for use in practice, basal insulin profile for titration, and choosing a self-monitoring blood glucose schedule for titration. CONCLUSIONS: In the management of T2DM, insulin can be effectively titrated by following a few simple recommendations. The use of second-generation basal insulin aids in mitigating the risk of hypoglycemic events. The implementation of a simplified titration regimen is crucial to achieving glycemic targets and long-term treatment goals.

20.
Int J Biol Macromol ; 151: 830-844, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32061847

RESUMO

To achieve an enhanced anticancer effect of drug to treat colorectal cancer, a dual-targeted (i.e., ligand-tailored and pH-triggered) multiparticulate system has been designed to deliver drug directly into the colon domain. In this regard, folic acid-grafted solid lipid nanoparticles (SLNs) bearing irinotecan were encapsulated in microbeads of alginates. Afterward, these microbeads were coated with enteric polymer (i.e., Eudragit S100) to make them pH-responsive. COLO-205 cells were used to determine in vitro cytotoxicity potential of various formulations. Findings for IHT loaded FA-coupled SLNs suggested significantly (p < 0.05) higher cytotoxic effect against COLO-205 cells (in vitro) as compared to drug solution and uncoupled SLNs. Further, the microbeads incorporating SLNs were evaluated for drug release in various simulated gastrointestinal fluids (i.e., pH, 1.2, 4.5, 7.4, and 6.8). Findings confirmed the release of the drug in the intestinal region only (i.e., pH > 7.0). In therapeutic experiments (in vivo), the optimized radiolabeled microbeads (99mTc-EuBIRSLN3 and 99mTc-EuBIRSLNF3) were administered via oral route to Balb/c mice. The results suggested that FA-coupled microbeads (99mTc-EuBIRSLNF3) distributed higher (19.62 ± 0.78%) amount of drug (i.e., 99mTc-IHT/g of tissue) as compared to uncoupled microbeads (99mTc-EuBIRSLN3, 7.63 ± 0.49%) in the colon tumor after 48 h, which confirmed its targeting ability to the tumor in the colon region. Further, 99mTc-EuBIRSLNF3 showed significantly (p < 0.01) higher antitumor effect against HT-29 cells bearing Balb/c mice over uncoupled microbeads and advocated their potential for enhanced antitumor efficacy for the treatment of colorectal cancer.


Assuntos
Alginatos/química , Antineoplásicos/administração & dosagem , Ácido Fólico/química , Concentração de Íons de Hidrogênio , Microesferas , Animais , Linhagem Celular Tumoral , Neoplasias do Colo , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Lipídeos , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Nanopartículas/química
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