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1.
Chem Biodivers ; 19(2): e202100532, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34929067

RESUMEN

MRSA infection is one of the alarming diseases in the current scenario. Identifying newer molecules to treat MRSA infection is of urgent need. In the present study, we have designed fluorinated thiazolidinone derivatives with various aryl/heteroaryl units at 5th position of the thiazolidinone core as promising anti-MRSA agents. All the compounds were screened for antibacterial activity against four bacterial strains. Among the tested compounds, the halogenated compounds with simple arylidene ring, (5Z)-5-[(3-chloro-2-fluorophenyl)methylidene]-2-[(1,3-thiazol-2-yl)amino]-1,3-thiazol-4(5H)-one (4b), (5Z)-5-[(4-chloro-2-fluorophenyl)methylidene]-2-[(1,3-thiazol-2-yl)amino]-1,3-thiazol-4(5H)-one (4c), (5Z)-5-[(3-fluoro-4-methylphenyl)methylidene]-2-[(1,3-thiazol-2-yl)amino]-1,3-thiazol-4(5H)-one (4f) and (5Z)-5-[(3,5-difluorophenyl)methylidene]-2-[(1,3-thiazol-2-yl)amino]-1,3-thiazol-4(5H)-one (4g) showed excellent activity with MIC 3.125-6.25 µg/mL against S. aureus and P. aeruginosa organism. Furthermore, these potent compounds were screened against MRSA strains, ESKAPE panel organism, and H37Rv mycobacterium strain. Compounds 4c (MIC 0.39 µg/mL), and 4f (MIC 0.39 and 0.79 µg/mL) displayed promising activity against MRSA strains (ATCC and clinical isolates, respectively). The most potent compounds, 4c and 4f eradicated the growth of bacterial colonies in a time-kill assay indicated that these are bactericidal in nature. The preliminary toxicity study of the potent molecules revealed that these compounds are non-hemolytic in nature as they did not induce lysis in human RBCs. In addition, the molecular docking and dynamics studies of compounds 4b, 4c, 4f and 4g were carried out on MurB protein of S. aureus (PDB code: 1HSK). Docking results demonstrated remarkable hydrogen bonding interaction with key amino acids ARG310, ASN83, GLY79 and π-π interactions with TYR149 which confirm the mode of action of the molecules.


Asunto(s)
Antibacterianos , Staphylococcus aureus , Antibacterianos/química , Antibacterianos/farmacología , Antituberculosos/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad
2.
Arch Pharm (Weinheim) ; 355(3): e2100342, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34923670

RESUMEN

As part of our effort to identify potent α-amylase inhibitors, in the present study, a novel series of fluorinated thiazolidinone-pyrazole hybrid molecules were prepared by the condensation of 3-(aryl/benzyloxyaryl)-pyrazole-4-carbaldehydes with fluorinated 2,3-disubstituted thiazolidin-4-ones. The structures of the newly synthesized compounds were confirmed by infrared, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and liquid chromatography-mass spectrometry data. All the compounds were screened for their α-amylase inhibitory and free radical scavenging activities by DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS methods. Among the tested compounds, compound 8g emerged as a promising α-amylase inhibitor with IC50 = 0.76 ± 1.23 µM, and it was found to be more potent than the standard drug acarbose (IC50 = 0.86 ± 0.81 µM). Compounds 8b and 8g showed strong free radical scavenging activity compared to the standard butylated hydroxyl anisole. The kinetic study of compound 8g revealed the reversible, classical competitive inhibition mode on the α-amylase enzyme. Molecular docking and dynamic simulations studies were performed for the most potent compound 8g, which displayed remarkable hydrogen bonding with the α-amylase protein (PDB ID: 1DHK).


Asunto(s)
Antioxidantes , Inhibidores de Glicósido Hidrolasas , Pirazoles , alfa-Amilasas , Antioxidantes/química , Antioxidantes/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Simulación del Acoplamiento Molecular , Pirazoles/química , Pirazoles/farmacología , Relación Estructura-Actividad , alfa-Amilasas/antagonistas & inhibidores
3.
Am J Perinatol ; 38(5): 490-496, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-31683321

RESUMEN

OBJECTIVE: Hypoglycemia is a significant risk factor for perinatal brain injury and adverse outcomes, particularly in infants requiring resuscitation following hypoxic ischemic (HI) insult. We aimed to study blood glucose (BG) levels in physiologically stressed infants in the presence or absence of epinephrine (Epi) administration at resuscitation in the first 24 hours after birth. STUDY DESIGN: A retrospective chart review of all infants with heart rate (HR) < 100/min at 1 minute requiring positive pressure ventilation (PPV) at birth was performed. Infants were classified into two groups as follows: (1) PPV group: infants' HR improved with PPV only at resuscitation, and Epi group: infants received Epi at resuscitation for persistent bradycardia. Serial measurements of BG levels collected and glucose infusion rate (GIR) calculated at 24 hours. RESULTS: By design, infants in the Epi group had lower cord pH and higher base deficit. BG was significantly lower overtime in premature infants ≤32 weeks of gestation in the Epi group. The BG was markedly higher in near-term and term infants in the Epi group compared with the PPV group. Hypoglycemia was more common despite administration of higher GIR in premature infants ≤32 weeks of gestation. CONCLUSION: In the presence of physiological stress, premature infants are more at risk for hypoglycemia than term infants.


Asunto(s)
Asfixia Neonatal/terapia , Glucemia/análisis , Hipoglucemia/sangre , Resucitación/métodos , Asfixia Neonatal/sangre , Bradicardia/tratamiento farmacológico , Bradicardia/etiología , Epinefrina/administración & dosificación , Femenino , Humanos , Hipoglucemia/etiología , Recién Nacido , Recien Nacido Prematuro , Ventilación con Presión Positiva Intermitente , Masculino , Estudios Retrospectivos
4.
Am J Perinatol ; 38(12): 1320-1329, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-32485758

RESUMEN

OBJECTIVE: The effects of neonatal caffeine therapy in adults born preterm are uncertain. We studied the impact of neonatal caffeine on systemic blood pressure, vessel reactivity, and response to stress in adult mice. STUDY DESIGN: Mice pups were randomized to caffeine (20 mg/kg/d) or saline by intraperitoneal injection for 10 days after birth. We performed tail-cuff BP (8/12 weeks), urinary 8-hydroxydeoxyguanosine and fecal corticosterone (14 weeks), and vessel reactivity in aortic rings (16 weeks) in adult mice. RESULTS: No differences were noted in systolic, diastolic, and mean blood pressures between the two groups at 8 and 12 weeks of age. However, norepinephrine-induced vasoconstriction was substantially higher in aortic rings in CAF-treated male mice. More significant vasodilator responses to nitric oxide donors in aortic rings in female mice may suggest gender-specific effects of caffeine. Female mice exposed to caffeine had significantly lower body weight over-time. Caffeine-treated male mice had substantially higher fecal corticosterone and urinary 8-hydroxydeoxyguanosine at 14 weeks, suggestive of chronic stress. CONCLUSION: We conclude sex-specific vulnerability to the heightened vascular tone of the aorta in male mice following neonatal caffeine therapy. Altered vessel reactivity and chronic stress in the presence of other risk factors may predispose to the development of systemic hypertension in adults born preterm.


Asunto(s)
Presión Sanguínea/efectos de los fármacos , Cafeína/farmacología , Vasoconstricción/efectos de los fármacos , 8-Hidroxi-2'-Desoxicoguanosina/orina , Animales , Animales Recién Nacidos , Aorta/efectos de los fármacos , Cafeína/efectos adversos , Corticosterona/análisis , Heces/química , Femenino , Hipertensión/etiología , Masculino , Ratones , Norepinefrina/farmacología , Factores de Riesgo , Factores Sexuales , Estrés Fisiológico
5.
Biol Res ; 53(1): 51, 2020 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-33168088

RESUMEN

BACKGROUND: Hyperoxia at resuscitation increases oxidative stress, and even brief exposure to high oxygen concentrations during stabilization may trigger organ injury with adverse long-term outcomes in premature infants. We studied the long-term effects of short-term perinatal oxygen exposure on cell cycle gene expression and lung growth in adult mice. METHODS: We randomized mice litters at birth to 21, 40, or 100%O2 for 30 min and recovered in room air for 4 or 12 weeks. Cell cycle gene expression, protein analysis, and lung morphometry were assessed at 4 and 12 weeks. RESULTS: The principal component analysis demonstrated a high degree of correlation for cell cycle gene expression among the three oxygen groups. Lung elastin was significantly lower in the 100%O2 groups at 4 weeks. On lung morphometry, radial alveolar count, alveolar number, and septal count were similar. However, the mean linear intercept (MLI) and septal length significantly correlated among the oxygen groups. The MLI was markedly higher in the 100%O2 groups at 4 and 12 weeks of age, and the septal length was significantly lower in the 100%O2 groups at 12 weeks. CONCLUSION: Short-term exposure to high oxygen concentrations lead to subtle changes in lung development that may affect alveolarization. The changes are related explicitly to secondary crest formation that may result in alteration in lung elastin. Resuscitation with high oxygen concentrations may have a significant impact on lung development and long-term outcomes such as BPD in premature infants.


Asunto(s)
Hiperoxia/patología , Pulmón/patología , Oxígeno/efectos adversos , Animales , Elastina/metabolismo , Femenino , Pulmón/crecimiento & desarrollo , Ratones , Estrés Oxidativo , Embarazo
6.
BMC Pulm Med ; 19(1): 138, 2019 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-31362742

RESUMEN

BACKGROUND: Caffeine therapy for apnea of prematurity reduces the incidence of bronchopulmonary dysplasia (BPD) in premature neonates. Several mechanisms, including improvement in pulmonary mechanics underly beneficial effects of caffeine in BPD. As vascular development promotes alveologenesis, we hypothesized that caffeine might enhance angiogenesis in the lung, promoting lung growth, thereby attenuating BPD. METHODS: C57Bl/6 mice litters were randomized within 12 h of birth to room air (RA) or 95%O2 to receive caffeine (20 mg/kg/day) or placebo for 4 days and recovered in RA for 12wks. The lung mRNA and protein expression for hypoxia-inducible factors (HIF) and angiogenic genes performed on day 5. Lung morphometry and vascular remodeling assessed on inflation fixed lungs at 12wks. RESULTS: Caffeine and hyperoxia in itself upregulate HIF-2α and vascular endothelial growth factor gene expression. Protein expression of HIF-2α and VEGFR1 were higher in hyperoxia/caffeine and angiopoietin-1 lower in hyperoxia. An increase in radial alveolar count, secondary septal count, and septal length with a decrease in mean linear intercept indicate an amelioration of hyperoxic lung injury by caffeine. An increase in vessel surface area and a significant reduction in smooth muscle thickness of the pulmonary arterioles may suggest a beneficial effect of caffeine on vascular remodeling in hyperoxia, especially in male mice. CONCLUSIONS: Postnatal caffeine by modulating angiogenic gene expression early in lung development may restore the pulmonary microvasculature and alveolarization in adult lung.


Asunto(s)
Cafeína/farmacología , Hiperoxia/complicaciones , Lesión Pulmonar/tratamiento farmacológico , Neovascularización Fisiológica , Alveolos Pulmonares/efectos de los fármacos , Angiopoyetina 1/metabolismo , Animales , Animales Recién Nacidos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Displasia Broncopulmonar/tratamiento farmacológico , Displasia Broncopulmonar/metabolismo , Modelos Animales de Enfermedad , Pulmón/patología , Lesión Pulmonar/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Alveolos Pulmonares/metabolismo , Distribución Aleatoria , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo
7.
J Perinat Med ; 47(9): 986-990, 2019 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-31586967

RESUMEN

Objective To describe the clinical characteristics and risk factors in infants with subcutaneous fat necrosis (SFN) following therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). Methods A case-control study was performed by a retrospective chart review of infants with moderate or severe HIE admitted to a level IV regional perinatal center and who underwent whole-body cooling. Results A total of 14 (8.1%) of 171 infants with moderate or severe HIE who underwent whole-body cooling developed SFN during hospitalization. There were more females [71% (10/14)] and large-for-gestational age (LGA) infants [28% (4/14)] in the SFN group vs. 36% females (57/157) and 8% LGA infants (13/157) in the group without SFN (P-values of 0.009 and 0.015, respectively). The mean lowest platelet count was lower 108 ± 55 109/L vs. 146 ± 62 109/L and the mean highest calcium level was higher 11.3 ± 2.5 vs. 10.6 ± 0.8 mg/dL in infants with SFN vs. infants without SFN, respectively (P-values of 0.0078 and 0.006, respectively). Distribution of skin lesions followed distinctive patterns representing the areas with direct contact with the cooling blanket. One infant developed severe, life-threatening hypercalcemia that required aggressive management, including diuretics, corticosteroids and bisphosphonates. Conclusion Although SFN is a rare complication of therapeutic hypothermia, it can be a life-threatening condition if complicated by severe hypercalcemia. Infants who undergo therapeutic hypothermia for HIE need regular skin examinations to evaluate for SFN. If SFN is identified, monitoring of serum calcium levels to prevent life-threatening hypercalcemia is recommended.


Asunto(s)
Necrosis Grasa/etiología , Hipotermia Inducida/efectos adversos , Hipoxia-Isquemia Encefálica/terapia , Grasa Subcutánea/patología , Estudios de Casos y Controles , Necrosis Grasa/diagnóstico , Necrosis Grasa/patología , Femenino , Humanos , Hipoxia-Isquemia Encefálica/complicaciones , Recién Nacido , Masculino , Estudios Retrospectivos , Factores de Riesgo
8.
Pediatr Surg Int ; 34(7): 735-742, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29808281

RESUMEN

BACKGROUND: Congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia, cardiac dysfunction and pulmonary hypertension. Inhaled nitric oxide (iNO) and milrinone are commonly used pulmonary vasodilators in CDH. We studied the hemodynamic effects of iNO and milrinone in infants with CDH. METHODS: A retrospective chart review was performed of all CDH infants admitted to two regional perinatal centers and infants classified into three groups: No-iNO group; iNO-responders and iNO-nonresponders. Oxygenation and hemodynamic effects of iNO and milrinone were assessed by blood gases and echocardiography. RESULTS: Fifty-four percent (39/72) of infants with CDH received iNO and 31% of these infants (12/39) had complete oxygenation response to iNO. Oxygenation response to iNO was not associated with a decrease in right ventricular pressures (RVP) or ECMO use. Four infants (33%) in the iNO-responder group and eight infants (30%) in the iNO-nonresponder group received milrinone. Milrinone lowered RVP and improved ejection fraction (EF). Response to iNO was associated with improved oxygenation to milrinone and increased survival following ECMO (67 vs. 20% among nonresponders). CONCLUSIONS: Response to inhaled nitric oxide in combination with milrinone may be associated with improved oxygenation and better survival after ECMO in infants with CDH.


Asunto(s)
Anomalías Múltiples/tratamiento farmacológico , Hernias Diafragmáticas Congénitas/complicaciones , Hernias Diafragmáticas Congénitas/cirugía , Enfermedades Pulmonares/tratamiento farmacológico , Pulmón/anomalías , Milrinona/administración & dosificación , Óxido Nítrico/administración & dosificación , Vasodilatadores/administración & dosificación , Administración por Inhalación , Análisis de los Gases de la Sangre , Oxigenación por Membrana Extracorpórea , Femenino , Hernias Diafragmáticas Congénitas/terapia , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/terapia , Recién Nacido , Enfermedades Pulmonares/complicaciones , Masculino , Estudios Retrospectivos
9.
Pediatr Res ; 82(2): 349-355, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28288148

RESUMEN

Background: At birth, the release of surfactant from alveolar type II cells (ATIIs) is stimulated by increased activity of the beta-adrenergic/adenylyl cyclase/cyclic 3'-5' adenosine monophosphate-signaling cascade. Atrial natriuretic peptide (ANP) stimulates surfactant secretion through natriuretic peptide receptor A (NPR-A). ANP inhibits adenylyl cyclase activity through its binding to NPR-C. We wished to further understand the role of the NPR-C in perinatal transition. Methods: We studied ATII expression of NPR-C in fetal and newborn sheep using immunohistochemistry, and surfactant secretion in isolated ATIIs by measuring 3[H] choline release into the media. Results: ANP induced surfactant secretion, and, at higher doses, it inhibits the stimulatory effect of the secretagogue terbutaline. ATII NPR-C expression decreased significantly after birth. Premature delivery also markedly decreased ANP and NPR-C in ATIIs. Co-incubation of terbutaline (10-4 M) with ANP (10-6 M) significantly decreased 3[H] choline release from isolated newborn ATII cells when compared with terbutaline alone; this inhibitory effect was mimicked by the specific NPR-C agonist, C-ANP (10-10 M). Conclusion: ANP may act as an important epithelial-derived inhibitor of surfactant release in the fetal lung, and downregulation of ANP and NPR-C following birth may sensitize ATII cells to the effects of circulating catecholamines, thus facilitating surfactant secretion.


Asunto(s)
Pulmón/metabolismo , Péptido Natriurético Tipo-C/metabolismo , Ovinos/embriología , Animales , Animales Recién Nacidos , Inmunohistoquímica , Toxina del Pertussis/farmacología , Surfactantes Pulmonares/metabolismo , Terbutalina/farmacología
10.
Pediatr Int ; 59(8): 891-897, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28452098

RESUMEN

BACKGROUND: Fetal hypoxia from intrapartum events can lead to absent heart rate (HR) or bradycardia at birth requiring aggressive neonatal resuscitation. Neonatal resuscitation guidelines do not differentiate bradycardia (HR <100 beats/min) from absent HR at birth. Given that HR is the primary determinant of resuscitation, we hypothesize that infants with no HR at 1 min would require more extensive resuscitation with worse clinical outcome than infants with bradycardia at 1 min. METHODS: A retrospective analysis was performed in infants born between 1 January 2000 and 31 December 2015 with no HR at 1 min (defined as Apgar score [AS] = 0 at 1 min; absent HR [AHR] group) or bradycardia at 1 min (AS = 1 at 1 min). Patient demographics, resuscitation characteristics and clinical outcomes were analyzed in both the groups. RESULTS: Apgar score was significantly lower in the AHR group over time. The AHR group had significantly higher rates of intubation, chest compression (CC) and i.v. epinephrine (i.v. epi); resulting in longer duration of CC, time to HR > 100 beats/min and duration of resuscitation. Systematic hypotension and death were higher in the AHR group. On logistic regression, CC and cord pH were significantly correlated with AS = 0 at 1 min. Gestational age, birthweight, AS at 5 min, cord pH and first blood gas pH after resuscitation were related to overall mortality. CONCLUSIONS: Infants with AHR at 1 min did worse than infants with bradycardia. Education focused on effective positive pressure ventilation and early use of i.v. epinephrine is essential for successful resuscitation of the depressed newborn.


Asunto(s)
Bradicardia/terapia , Reanimación Cardiopulmonar/métodos , Paro Cardíaco/terapia , Puntaje de Apgar , Bradicardia/diagnóstico , Bradicardia/mortalidad , Reanimación Cardiopulmonar/estadística & datos numéricos , Femenino , Paro Cardíaco/diagnóstico , Paro Cardíaco/mortalidad , Humanos , Recién Nacido , Modelos Logísticos , Masculino , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
11.
Am J Perinatol ; 34(5): 428-440, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27627792

RESUMEN

Background Inhaled nitric oxide (iNO) is being increasingly used in preterm infants < 34 weeks with hypoxemic respiratory failure (HRF) and/or pulmonary hypertension (PH). Objective To evaluate the risk factors, survival characteristics, and lung histopathology in preterm infants with PH/HRF. Methods Retrospective chart review was conducted to determine characteristics of 93 preterm infants treated with iNO in the first 28 days and compared with 930 matched controls. Factors associated with survival with preterm HRF and smooth muscle actin from nine autopsies were evaluated. Results Preterm neonates treated with iNO had a higher incidence of preterm prolonged rupture of membrane (pPROM ≥ 18 hours), oligohydramnios and delivered by C-section. In infants treated with iNO, antenatal steroids (odds ratio [OR],3.7; confidence interval [CI], 1.2-11.3; p = 0.02), pPROM (OR, 1.001; CI, 1.0-1.004; p = 0.3), and oxygenation response to iNO (OR, 3.7; CI, 1.08-13.1; p = 0.037) were associated with survival. Thirteen infants with all three characteristics had 100% (13/13) survival without severe intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL) compared with 48% survival (12/25, p = 0.004) and 16% severe IVH/PVL without any of these factors. Severity of HRF correlated with increased smooth muscle in pulmonary vasculature. Conclusion Preterm infants with HRF exposed to antenatal steroids and pPROM had improved oxygenation with iNO and survival without severe IVH/PVL. Precisely targeting this subset may be beneficial in future trials of iNO.


Asunto(s)
Hipertensión Pulmonar/tratamiento farmacológico , Enfermedades del Prematuro/tratamiento farmacológico , Óxido Nítrico/uso terapéutico , Insuficiencia Respiratoria/tratamiento farmacológico , Vasodilatadores/uso terapéutico , Actinas/metabolismo , Administración por Inhalación , Estudios de Casos y Controles , Hemorragia Cerebral Intraventricular/etiología , Femenino , Rotura Prematura de Membranas Fetales/etiología , Edad Gestacional , Humanos , Hipertensión Pulmonar/patología , Hipoxia/etiología , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/patología , Leucomalacia Periventricular/etiología , Masculino , Músculo Liso Vascular/metabolismo , Óxido Nítrico/administración & dosificación , Oxígeno/sangre , Selección de Paciente , Atención Prenatal , Factores Protectores , Arteria Pulmonar/metabolismo , Venas Pulmonares/metabolismo , Insuficiencia Respiratoria/complicaciones , Insuficiencia Respiratoria/patología , Estudios Retrospectivos , Esteroides/uso terapéutico , Tasa de Supervivencia , Vasodilatadores/administración & dosificación
12.
Bioorg Khim ; 41(2): 249-56, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26165132

RESUMEN

A new series of N-Aryl-2-(5H-[1,2,4]triazino[5,6-b]indol-3-ylsulfanyl)acetamides were synthesized by condensation of tricyclic compound 2,5-dihydro-3H-[1,2,4]triazino[5,6-b]indole-3-thione with chloro N-phenylacetamides. The tricyclic compound was obtained by condensation of Isatin with thiosemicarbazide. Chloro N-phenylacetamides were obtained from different substituted anilines. Their structures were characterized by IR, 1H NMR, LC-MS and elemental analyses. Newly synthesized compounds were screened for antimicrobial, antidepressant and anticonvulsant activities. Preliminary results indicated that most of the compounds showed lesser MIC value than the standard drug used when tested for antimicrobial activity. Some of the compounds were endowed with very good antidepressant and anticonvulsant activity.


Asunto(s)
Antiinfecciosos , Anticonvulsivantes , Antidepresivos , Animales , Antiinfecciosos/síntesis química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Anticonvulsivantes/síntesis química , Anticonvulsivantes/química , Anticonvulsivantes/farmacología , Antidepresivos/síntesis química , Antidepresivos/química , Antidepresivos/farmacología , Bacterias/crecimiento & desarrollo , Evaluación Preclínica de Medicamentos , Masculino , Ratones
13.
J Indian Prosthodont Soc ; 14(1): 120-3, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24605009

RESUMEN

True Anophthalmos is an extremely rare condition and can cause psychological problems due to not only the absence of an eye but also from the disfigurement of the orbital socket and the eyelids. The present case shows the multidisciplinary approach in the treatment of a patient with anophthalmos. He needed an ocular plastic surgery for correct prosthesis insertion. The disfigurement caused by the loss of ocular content when restored with prosthesis maintains the facial symmetry there by improves the esthetics as well as anatomic and physiological function.

14.
Children (Basel) ; 10(6)2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37371221

RESUMEN

The incidence of preterm births is increasing globally, with increasing survival into adulthood [...].

15.
Children (Basel) ; 10(6)2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37371279

RESUMEN

We are delighted to present an editorial for the Special Issue 'Advances in Healthcare for Neonates' [...].

16.
ACS Omega ; 8(49): 47187-47200, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38107948

RESUMEN

A crucial role in the regulation of DNA replication is played by the highly conserved CDC kinase. The CDC7 kinase could serve as a target for therapeutic intervention in cancer. The primary heterocyclic substance is pyrazole, and its derivatives offer great potential as treatments for cancer cell lines. Here, we synthesized the two pyrazole derivatives: 4-(2-(4-chlorophenyl)hydrazinyl)-5-methyl-2-tosyl-1H-pyrazol-3(2H)-one (PYRA-1) and 4-(2-(2,4-difluorophenyl)hydrazinyl)-5-methyl-2-tosyl-1H-pyrazol-3(2H)-one (PYRA-2). The structural confirmation of both the compounds at the three-dimensional level is characterized using single crystal X-ray diffraction and density functional theory. Furthermore, the in silico chemical biological properties were derived using molecular docking and molecular dynamics (MD) simulations. PYRA-1 and PYRA-2 crystallize in the P-1 (a = 8.184(9), b = 14.251(13), c = 15.601(15), α = 91.57(8), ß = 97.48(9), 92.67(9), V = 1801.1(3) 3, and Z = 2) and P21/n (a = 14.8648(8), b = 8.5998(4), c = 15.5586(8), ß = 116.47(7), V = 1780.4(19) 3, and Z = 4), space groups, respectively. In both PYRA-1 and PYRA-2 compounds, C-H···O intermolecular connections are common to stabilize the crystal structure. In addition, short intermolecular interactions stabilizes with C-H···π and π-π stacking. Crystal packing analysis was quantified using Hirshfeld surface analysis resulting in C···H, O···H, and H···H contacts in PYRA-1 exhibiting more contribution than in PYRA-2. The conformational stabilities of the molecules are same in the gas and liquid phases (water and DMSO). The docking scores measured for PYRA-1 and PYRA-2 with CDC7 kinase complexes are -5.421 and -5.884 kcal/mol, respectively. The MD simulations show that PYRA-2 is a more potential inhibitor than PYRA-1 against CDC7 kinase.

17.
Children (Basel) ; 9(12)2022 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-36553286

RESUMEN

Advances in perinatal and neonatal care have led to improved survival of preterm infants into adulthood. However, the shift in focus to long-term health in adults born preterm requires a clear understanding of the impact of prematurity on developing organ systems and the development of adult-oriented disease. A less well-recognized area of risk for surviving preterm infants is their cardiometabolic health. Epidemiologic evidence has linked preterm birth to the development of systemic hypertension, type 2 diabetes, metabolic syndrome, heart failure, and ischemic heart disease. Of more significant concern is that the risk of cardiometabolic disorders is higher in adults born preterm compared to full-term infants. The interconnected nature of the cardio-pulmonary system means worsening morbidity and mortality in adults born preterm. Addressing the problems of adults born preterm holistically would help promote cardiovascular health, wellness, and quality of life over their lifetime. Recognizing that adults born preterm are a unique subset of the population is a challenge in the current healthcare environment. Addressing issues relevant to adults born preterm in the clinically and research domain, using technology to characterize cardiopulmonary physiology and exercise tolerance, developing screening tools for early diagnosis and treatment, and robust follow-up of these infants with access to longitudinal data would improve both the quality and longevity of life in adults born preterm.

18.
RSC Adv ; 12(7): 3809-3827, 2022 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-35425455

RESUMEN

Owing to its presence in several biological processes, Sirt1 acts as a potential therapeutic target for many diseases. Here, we report the structure-based designing and synthesis of two distinct series of novel Sirt1 inhibitors, benzimidazole mono-peptides and amino-acid derived 5-pyrazolyl methylidene rhodanine carboxylic acid. The compounds were evaluated for in vitro enzyme-based and cell-based Sirt1 inhibition assay, and cytotoxic-activity in both liver and breast cancer cells. The tryptophan conjugates i.e.13h (IC50 = 0.66 µM, ΔG bind = -1.1 kcal mol-1) and 7d (IC50 = 0.77 µM, ΔG bind = -4.4 kcal mol-1) demonstrated the maximum efficacy to inhibit Sirt1. The MD simulation unveiled that electrostatic complementarity at the substrate-binding-site through a novel motif "SLxVxP(V/F)A" could be a cause of increased Sirt1 inhibition by 13h and 13l over Sirt2 in cell-based assay, as compared to the control Ex527 and 7d. Finally, this study highlights novel molecules 7d and 13h, along with a new key hot-spot in Sirt1, which could be used as a starting lead to design more potent and selective sirtuin inhibitors as a potential anticancer molecule.

19.
Pediatr Rep ; 13(2): 289-301, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-34205900

RESUMEN

The COVID-19 pandemic has affected maternal and infant health globally both directly from infection with the SARS-CoV-2 virus and indirectly from changes in health care resulting from social, economic, and health care policies unique to each country. The developing countries have to share the disproportionate burden on maternal and infant health. In this review, we discuss the uncertainties resulting from SARS-CoV-2 infection in pregnancy, vertical transmission of the virus, and its effects on breastfeeding of the newborn. The problems of families and communities caring for mothers with COVID-19 and its impact on breastfeeding in newborns are discussed. The challenges posed by the pandemic have forced us to think and devise innovative solutions, including telemedicine help for antenatal counseling, breastfeeding education, and lactation support. Optimal utilization of resources and technology to find creative solutions at the individual and the community level will help in facilitating maternal-infant bonding soon after birth. Appropriate health care policies to support pregnant and lactating mothers will go a long way in meeting healthy child development goals.

20.
Children (Basel) ; 8(6)2021 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-34200043

RESUMEN

Coronavirus disease 2019 (COVID-19), a condition associated with SARS-CoV-2, typically results in mild infection in infants and children. However, children with risk factors such as chronic lung disease and immunosuppression have higher risk of severe illness from COVID-19. We report a case of a 27-week-gestation extremely premature infant born to a mother with COVID-19 infection. The infant, initially treated for surfactant deficiency, developed worsening hypoxic respiratory failure on the fifth day of life requiring escalating ventilatory support, an elevated level of C-reactive protein, thrombocytopenia, and an elevated level of d-dimer. The infant was positive for SARS-CoV-2 by RT-PCR from Day 1 to Day 42 of his life. The infant responded to a seven-day course of dexamethasone with a gradually decreasing oxygen requirement and could be extubated to non-invasive ventilation by the end of the fifth week after birth. The infant is currently on home oxygen by nasal cannula. Prolonged shedding of the virus may be a unique feature of the disease in premature infants. Extreme prematurity, immature lungs, and an immunocompromised status may predispose these infants to severe respiratory failure and a prolonged clinical course. Instituting appropriate COVID-19 protocols to prevent the spread of the disease in the neonatal intensive care unit (NICU) is of utmost importance. Infection with SARS-CoV-2 may have implications in the management of extremely premature infants in the NICU.

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