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1.
Pak J Pharm Sci ; 37(1(Special)): 245-255, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38747276

RESUMO

Aripiprazole (ARI), an antipsychotic having low solubility and stability. To overcome this, formation of binary and ternary using inclusion complexes of Methyl-ß-cyclodextrin (MßCD) /Hydroxy propyl beta cyclodextrin (HPßCD) and L-Arginine (ARG)/ Lysine (LYS) are analyzed by dissolution testing and phase stability study along with their complexation efficacy and solubility constants made by physical mixing. Inclusion complexes with ARG were better than LYS and prepared by solvent evaporation and lyophilization method as well. They are characterized by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (AT-FTIR), X-ray powder diffractometry (XRD), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM) and Thermal gravimetric analysis (TGA). The bond shifting in AT-FTIR confirmed the molecular interactions between host and guest molecules. The SEM images also confirmed a complete change of drug morphology in case of ternary inclusion complexes prepared by lyophilization method for both the polymers. ARI: MßCD: ARG when used in the specific molar ratio of 1:1:0.27 by prepared by lyophilization method has 18 times best solubility while ARI:HPßCD:ARG was 7 times best solubility than pure drug making MßCD a better choice than HPßCD. Change in the molar ratio will cause loss of stability or solubility. Solvent evaporation gave significant level of solubility but less stability.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina , Arginina , Aripiprazol , Varredura Diferencial de Calorimetria , Lisina , Solubilidade , beta-Ciclodextrinas , Aripiprazol/química , Arginina/química , beta-Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina/química , Lisina/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , Liofilização , Antipsicóticos/química , Estabilidade de Medicamentos , Microscopia Eletrônica de Varredura , Composição de Medicamentos , Química Farmacêutica/métodos
2.
Int J Mol Sci ; 24(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36982742

RESUMO

Methamphetamine, a highly addictive central nervous system (CNS) stimulant, is used worldwide as an anorexiant and attention enhancer. Methamphetamine use during pregnancy, even at therapeutic doses, may harm fetal development. Here, we examined whether exposure to methamphetamine affects the morphogenesis and diversity of ventral midbrain dopaminergic neurons (VMDNs). The effects of methamphetamine on morphogenesis, viability, the release of mediator chemicals (such as ATP), and the expression of genes involved in neurogenesis were evaluated using VMDNs isolated from the embryos of timed-mated mice on embryonic day 12.5. We demonstrated that methamphetamine (10 µM; equivalent to its therapeutic dose) did not affect the viability and morphogenesis of VMDNs, but it reduced the ATP release negligibly. It significantly downregulated Lmx1a, En1, Pitx3, Th, Chl1, Dat, and Drd1 but did not affect Nurr1 or Bdnf expression. Our results illustrate that methamphetamine could impair VMDN differentiation by altering the expression of important neurogenesis-related genes. Overall, this study suggests that methamphetamine use may impair VMDNs in the fetus if taken during pregnancy. Therefore, it is essential to exercise strict caution for its use in expectant mothers.


Assuntos
Estimulantes do Sistema Nervoso Central , Metanfetamina , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Camundongos , Animais , Neurônios Dopaminérgicos/metabolismo , Metanfetamina/toxicidade , Metanfetamina/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Mesencéfalo/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Trifosfato de Adenosina/metabolismo , Diferenciação Celular
3.
Acta Biochim Pol ; 70(2): 325-334, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37257151

RESUMO

Extensive pesticides (herbicides) use is negatively disturbing the environment and humans. Pesticide bioremediation with eco-friendly techniques bears prime importance. This study aimed to isolate and characterize three different herbicides (metribuzin, clodinafop- propargyl, MCPA (2-methyl, 4 chlorophenoxyacetic acids) and Bromoxynil) degrading bacterial strains from agricultural fields of Punjab University, Pakistan. Among the 12 bacterial isolates, 5 were metribuzin degrading, 3 were clodinafop propargyl degrading and, 4 were MCPA and Bromoxynil degrading bacteria. Morphological, microscopic, and molecular characterization revealed that the majority of these bacterial strains were gram-negative and belonged to Bacillus and Pseudomonas genera. The isolates A6, B3, and C1 were subjected to respective herbicide degradation and the data was confirmed through GC-MS analysis. The effect of herbicide concentrations, pH, and temperature on bacterial growth was determined at OD600. The strain A6 degraded 14.8% metribuzin out of the provided concentration of 50 ppm by following the deamination pathway. While the isolates B3 and C1 degraded 23.2% and 33.9% clodinafop, MCPA and bromo-xynil, respectively, at a spiking concentration of 50ppm. The clodinafop, MCPA and Bromoxynil were metabolized into less toxic products i.e., dicarboxylic acids and 2-methyl phenol respectively, and metabolized via decarboxylation and dehalogenation mechanism. The present study evaluates the herbicides degrading bacterial strains that could potentially be used for bioremediation of agricultural contaminated sites.


Assuntos
Ácido 2-Metil-4-clorofenoxiacético , Herbicidas , Praguicidas , Poluentes do Solo , Humanos , Ácido 2-Metil-4-clorofenoxiacético/metabolismo , Biodegradação Ambiental , Solo , Bactérias/metabolismo , Microbiologia do Solo , Poluentes do Solo/metabolismo
4.
Pak J Biol Sci ; 24(8): 913-919, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34486359

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neuro developmental disorder. Traditionally ADHD was considered a childhood disorder but recent evidence confirms that ADHD can also occur in adulthood. The prevalence of ADHD worldwide is around 5% in children and 3% in adults. ADHD affects patients throughout their lives by causing failures in education as well as in occupations, which increase the risk of accidents and criminality. The disorder has no single cause, which reflects the heterogeneity of ADHD. Understanding the genetic and molecular changes associated with familial/heritable ADHD development is challenging, due to the lack of relevant models of ADHD and the difficulty of collecting brain samples. The current review will highlight upon the genetic diversity of ADHD and summarize some recent relevant studies. Knowledge about the ADHD's variants might be useful for a new ADHD genetic research.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Variação Genética , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Encéfalo/fisiologia , Criança , Predisposição Genética para Doença , Humanos , Adulto Jovem
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