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1.
J Pak Med Assoc ; 74(4): 797-799, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38751283

RESUMO

This case report discusses the diagnostic challenge of congenital lobar emphysema (CLE) in a three-month old infant with severe respiratory distress. The infant was initially misdiagnosed and managed as a case of pneumothorax. This case highlights the importance of CT scans as a diagnostic tool for early diagnosis and lifesaving management of CLE. It also signifies the need for adequate funds and infrastructure in the health care system especially in rural areas of developing countries like Pakistan.


Assuntos
Enfisema Pulmonar , Tomografia Computadorizada por Raios X , Humanos , Lactente , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/congênito , Pneumotórax/diagnóstico por imagem , Pneumotórax/diagnóstico , Masculino , Diagnóstico Diferencial
2.
J Contemp Dent Pract ; 24(5): 278-284, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38149804

RESUMO

AIM: Silver diamine fluoride (SDF) is a well-known caries preventive aid capable of arresting carious lesions and preventing secondary caries formation. Despite having the caries prevention potential, the clinical use of SDF is limited due to the tooth discoloration caused by SDF. The objective of this study was to evaluate the efficiency of natural antioxidants to inhibit SDF-induced tooth discoloration. MATERIALS AND METHODS: A total of 32 bovine teeth were polished to create a 6 mm circular window on the middle 1/3 (for enamel) or on the cervical 1/3 (for dentin) of the labial surface. Specimens were treated either with SDF alone or SDF followed by ascorbic acid (AA)/alpha lipoic acid (ALA)/7th generation bonding materials. The color parameters Lightness (L*), Chroma (C*), and Hue (H*) of the tooth window were measured at pretreatment, 1-hour, 1-week, and 1-month posttreatment using a digital color chromometer. RESULTS: Repeated measure ANOVA showed a significant tooth color alteration at 1-hour posttreatment. The L* and H* values dropped and C* value elevated significantly in 1-hour posttreatment measurement. All experimental groups showed significant tooth color alteration after treatment (p < 0.05) and were unable to reverse the discoloration even after 1-month period except the ALA group which did not show any significant (p > 0.05) color alteration compared with the pretreatment value. CONCLUSIONS: Within the limitation of the in vitro model and according to the results of this study, it can be concluded that ALA has the potential to prevent SDF-induced tooth discoloration; however, AA was unable to prevent the discoloration. CLINICAL SIGNIFICANCE: SDF induces discoloration of enamel and dentin can be reversed by applying Alpha lipoic acid immediacy after SDF application.


Assuntos
Cárie Dentária , Ácido Tióctico , Descoloração de Dente , Animais , Bovinos , Antioxidantes/farmacologia , Descoloração de Dente/induzido quimicamente , Descoloração de Dente/prevenção & controle , Descoloração de Dente/tratamento farmacológico , Ácido Tióctico/uso terapêutico , Fluoretos Tópicos , Cárie Dentária/prevenção & controle , Cárie Dentária/tratamento farmacológico , Compostos de Prata , Dentina
3.
Front Pharmacol ; 14: 1232088, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37663254

RESUMO

Introduction: Post-traumatic stress disorder (PTSD) is a chronic mental illness triggered by traumatic experiences such as wars, natural disasters, or catastrophes, and it is characterized by anxiety, depression and cognitive impairment. Diosgenin is a steroidal sapogenin with known neuroprotective and antioxidant properties. This study aimed to assess the pharmacological potential of diosgenin in a single prolonged stress (SPS) model of PTSD, plus other behavioral models along with any consequent alterations in brain neurochemistry in male mice. Methodology: SPS was induced by restraining animals for 2 h, followed by 20 min of forced swim, recuperation for 15 min, and finally, exposure to ether to induce anesthesia. The SPS-exposed animals were treated with diosgenin (20, 40, and 60 mg/kg) and compared with the positive controls, fluoxetine or donepezil, then they were observed for any changes in anxiety/depression-like behaviors, and cognitive impairment. After behavioral screening, postmortem serotonin, noradrenaline, dopamine, vitamin C, adenosine and its metabolites inosine and hypoxanthine were quantified in the frontal cortex, hippocampus, and striatum by high-performance liquid chromatography. Additionally, animal serum was screened for changes in corticosterone levels. Results: The results showed that diosgenin reversed anxiety- and depression-like behaviors, and ameliorated cognitive impairment in a dose-dependent manner. Additionally, diosgenin restored monoamine and vitamin C levels dose-dependently and modulated adenosine and its metabolites in the brain regions. Diosgenin also reinstated otherwise increased serum corticosterone levels in SPS mice. Conclusion: The findings suggest that diosgenin may be a potential candidate for improving symptoms of PTSD.

4.
Heliyon ; 9(6): e17478, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37366526

RESUMO

The COVID-19 pandemic has inflicted millions of deaths worldwide. Despite the availability of several vaccines and some special drugs approved for emergency use to prevent or treat this disease still, there is a huge concern regarding their effectiveness, adverse effects, and most importantly, their efficacy against the new variants. A cascade of immune-inflammatory responses is involved with the pathogenesis and severe complications with COVID-19. People with dysfunctional and compromised immune systems display severe complications, including acute respiratory distress syndrome, sepsis, multiple organ failure etc., when they get infected with the SARS-CoV-2 virus. Plant-derived natural immune-suppressant compounds, such as resveratrol, quercetin, curcumin, berberine, luteolin, etc., have been reported to inhibit pro-inflammatory cytokines and chemokines. Therefore, natural products with immunomodulatory and anti-inflammatory potential could be plausible targets to treat this contagious disease. This review aims to delineate the clinical trials status and outcomes of natural compounds with immunomodulatory potential in COVID-19 patients along with the outcomes of their in-vivo studies. In clinical trials several natural immunomodulators resulted in significant improvement of COVID-19 patients by diminishing COVID-19 symptoms such as fever, cough, sore throat, and breathlessness. Most importantly, they reduced the duration of hospitalization and the need for supplemental oxygen therapy, improved clinical outcomes in patients with COVID-19, especially weakness, and eliminated acute lung injury and acute respiratory distress syndrome. This paper also discusses many potent natural immunomodulators yet to undergo clinical trials. In-vivo studies with natural immunomodulators demonstrated reduction of a wide range of proinflammatory cytokines. Natural immunomodulators that were found effective, safe, and well tolerated in small-scale clinical trials are warranted to undergo large-scale trials to be used as drugs to treat COVID-19 infections. Alongside, compounds yet to test clinically must undergo clinical trials to find their effectiveness and safety in the treatment of COVID-19 patients.

5.
Front Pharmacol ; 14: 1128496, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37033637

RESUMO

Background: Neuropathy is a prevalent and debilitating complication of poorly managed diabetes, contributing towards poor quality of life, amputation risk, and increased mortality. The available therapies for diabetic neuropathic pain (DPN) have limitations in terms of efficacy, tolerability and patient compliance. Dysfunction in the peripheral and central monoaminergic system has been evidenced in various types of neuropathic and acute pain. The objective of the present study was to investigate 1-methyl 1, 2, 3, 4-tetrahydroisoquinoline (1MeTIQ), an endogenous amine found in human brain with a known neuroprotective profile, in a model of streptozotocin (STZ) induced neuropathic pain. Methods: Diabetic neuropathy in male BALB/c mice was induced by intraperitoneal injection of a single dose of STZ (200 mg/kg). Upon development of DPN after 4 weeks, mice were investigated for mechanical allodynia (von Frey filament pressure test) and thermal hyperalgesia (tail immersion test). Ondansetron (1.0 mg/kg i.p.), naloxone (3.0 mg/kg i.p.) and yohimbine (2.0 mg/kg i.p.) were used to elucidate the possible mechanism involved. Postmortem frontal cortical, striatal and hippocampal tissues were dissected and evaluated for changes in levels of dopamine, noradrenaline and serotonin using High-Performance Liquid Chromatography (HPLC) with UV detection. Results: Acute administration of 1MeTIQ (15-45 mg/kg i.p.) reversed streptozotocin-induced diabetic neuropathic static mechanical allodynia (von Frey filament pressure test) and thermal hyperalgesia (tail immersion test), these outcomes being comparable to standard gabapentin. Furthermore, HPLC analysis revealed that STZ-diabetic mice expressed lower concentrations of serotonin in all three brain regions examined, while dopamine was diminished in the striatum and 1MeTIQ reversed all these neurotransmitter modifications. These findings suggest that the antihyperalgesic/antiallodynic activity of 1MeTIQ may be mediated in part via supraspinal opioidergic and monoaminergic modulation since they were naloxone, yohimbine and ondansetron reversible. Conclusion: It was also concluded that acute treatment with 1MeTIQ ameliorated STZ-induced mechanical allodynia and thermal hyperalgesia and restored brain regionally altered serotonin and dopamine concentrations which signify a potential for 1MeTIQ in the management of DPN.

6.
Front Pharmacol ; 14: 1135497, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37033640

RESUMO

Purpose: Chronic unpredictable stress (CUS) induces long-term neuronal and synaptic plasticity with a neurohormonal disbalance leading to the development of co-existing anxiety, depression, and cognitive decline. The side effects and delayed onset of current clinically used antidepressants has prompted a quest for antidepressants with minimum drawbacks. Fraxetin is a natural coumarin derivative with documented antioxidant and neuroprotective activity though its effects on stress are unknown. This study therefore aimed to investigate any possible acute effect of fraxetin in behavioral tests including a CUS paradigm in correlation with brain regional neurochemical changes. Methods: Mice were subjected to a series of mild stressors for 14 days to induce CUS. Furthermore, behavioral performance in the open field test, forced swim test (FST), Y-maze and elevated plus-maze were evaluated. Postmortem frontal cortical, hippocampal and striatal tissues were analyzed via high-performance liquid chromatography (HPLC) for neurochemical changes. Result: Acute administration of fraxetin (20-60 mg/kg, orally) decreased depression-like behavior in the FST and behavioral anxiety in both the open field test and elevated plus-maze. Memory deficits induced during the CUS paradigm were markedly improved as reflected by enhanced Y maze performance. Concurrent biochemical and neurochemical analyses revealed that only the two higher fraxetin doses decreased elevated serum corticosterone levels while diminished serotonin levels in the frontal cortex, striatum and hippocampus were reversed, though noradrenaline was only raised in the striatum. Concomitantly, dopamine levels were restored by fraxetin at the highest dose exclusively in the frontal cortex. Conclusion: Acute treatment with fraxetin attenuated CUS-induced behavioral deficits, ameliorated the increased corticosterone level and restored altered regional neurotransmitter levels and this may indicate a potential application of fraxetin in the management of anxiety and depression modeled by CUS. However, further studies are warranted regarding the chronic effects of fraxetin behaviorally and neurochemically.

7.
Biol Res ; 55(1): 40, 2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36572914

RESUMO

BACKGROUND: Cartilaginous disorders comprise a wide range of diseases that affect normal joint movement, ear and nose shape; and they have great social and economic impact. Mesenchymal stem cells (MSCs) provide a promising regeneration alternative for treatment of degenerative cartilaginous disorders. This study aimed to compare therapeutic potential of different types of laser activated MSCs to promote auricular cartilage regeneration. Twelve adult rabbit allocated equally in four groups, all animals received a surgical mid auricular cartilage defect in one ear; Group I (Positive control) injected sub-perichondrially with phosphate-buffered saline (PBS), Group II (ADMSC-transplanted group) injected adipose-derived MSCs (ADMSCs), Group III (BMMSCs-transplanted group) received bone marrow-derived MSCs (BMMSCs), and Group IV (EMSC-transplanted group) received ear MSCs (EMSCs) in the defected ear. The auricular defect was analyzed morphologically, histopathologically and immunohistochemically after 4 weeks. In addition, a quantitative real-time polymerase chain reaction was used to examine expression of the collagen type II (Col II) and aggrecan as cartilage growth factors. RESULTS: The auricles of all treatments appeared completely healed with smooth surfaces and similar tissue color. Histopathologically, defective areas of control positive group, ADMSCs and EMSCs treated groups experienced a small area of immature cartilage. While BMMSCs treated group exhibited typical features of new cartilage formation with mature chondrocytes inside their lacunae and dense extracellular matrix (ECM). In addition, BMMSC treated group showed a positive reaction to Masson's trichrome and orcein stains. In contrary, control positive, ADMSC and EMSC groups revealed faint staining with Masson's trichrome and Orcein. Immunohistochemically, there was an intense positive S100 expression in BMMSCs (with a significant increase of area percentage + 21.89 (P < 0.05), a moderate reaction in EMSCs (with an area percentage + 17.97, and a mild reaction in the control group and ADMSCs (area percentages + 8.02 and + 11.37, respectively). The expression of relative col II and aggrecan was substantially highest in BMMSCs (± 0.91 and ± 0.89, respectively). While, Control positive, ADMSCs and EMSCs groups recorded (± 0.41: ± 0.21, ± 0.6: ± 0.44, ± 0.61: ± 0.63) respectively. CONCLUSION: BMMSCs showed the highest chondrogenic potential compared to ADMSCs and EMSCs and should be considered the first choice in treatment of cartilaginous degenerative disorders.


Assuntos
Cartilagem da Orelha , Células-Tronco Mesenquimais , Animais , Coelhos , Agrecanas/metabolismo , Condrócitos , Matriz Extracelular , Células Cultivadas , Diferenciação Celular
8.
Environ Toxicol Pharmacol ; 94: 103911, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35724857

RESUMO

Plastic products are widely used in different applications. Thus, exposure of human and other organisms to these products may affect their biological system. The current study was conducted to investigate the potential deleterious effect of Polysterene nanoparticles (PS-NPs) on the liver and to state the cellular and molecular mechanisms associated with exposure to PS-NPs.30 male rats were divided randomly and equally into 3 groups; control (distilled water), low dose (3 mg/kg/day) and high dose (10 mg/kg/day) exposed group via oral gavage for 5 successive weeks. PS-NPs caused elevation in ALT, AST and MDA, upregulation of apoptosis-related genes and significant decrease in GSH and mRNA expression for antioxidant-related genes (Nrf-2 and GPx). Moreover, alterations in hepatic tissue architecture and positive caspase-3 expression was noticed in a dose- dependent manner. Collectively, PS-NPs can induce hepatoxicity in rats in a dose dependent manner, so the health risk of PS-NPs should not be ignored.


Assuntos
Hepatopatias , Nanopartículas , Animais , Apoptose , Hepatócitos/metabolismo , Humanos , Fígado , Hepatopatias/metabolismo , Masculino , Nanopartículas/toxicidade , Estresse Oxidativo , Poliestirenos/toxicidade , Ratos
9.
Environ Sci Pollut Res Int ; 29(55): 83797-83809, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35771327

RESUMO

Atrazine (ATZ) is a widely used herbicide; however, it has deleterious effects. The current study aimed to investigate the potential toxic effect of ATZ as a neuroendocrine disruptor on the cerebellum and thyroid gland and on the liver as a detoxifying organ. We examined the ability of ATZ to induce oxidative stress and subsequent apoptosis in these organs. Moreover, we investigated the potential protective effect of Acacia nilotica, because of its potent antioxidant activity. Thus, our study was carried out on 40 adult male albino rats that were divided equally into 4 groups (10 rats/each group). The first group received distilled water, while the second group received ATZ dissolved in corn oil at 200 mg/kg body weight/day by stomach gavage. The third group was treated orally by ATZ (200 mg/kg body weight/day) plus Acacia nilotica (400 mg/kg/day). Group IV received Acacia nilotica only at a dose (400 mg/kg/day). After successive 30 days of the experiment, blood and tissue samples were collected from all groups. Our findings revealed the ability of ATZ to induce toxic effects was observed microscopically in the form of degenerated neurons and vacuolated neuropil of the cerebellum, degenerated hepatocytes, and vacuolation of the follicular cells of the thyroid gland. Furthermore, ATZ significantly elevated AST, ALT, and ALP serum levels and TB concentration, while decreased GSH. DNA fragmentation% and activated caspase-3 expression significantly increased after ATZ exposure. Interestingly, Acacia nilotica administration was able to partially protect the examined organs against the toxic effect of ATZ exposure.


Assuntos
Acacia , Atrazina , Ratos , Animais , Acacia/química , Atrazina/toxicidade , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo , Peso Corporal
10.
Environ Sci Pollut Res Int ; 29(20): 30697-30711, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34994930

RESUMO

Atrazine (ATZ) is herbicide that has been widely used for different crops. This extensive use has resulted in severe deleterious effects in different species. In this work, we investigated the potentially harmful effect of atrazine herbicide on the brain and submandibular salivary gland. Our investigation was carried out on 20 adult male albino rats that were equally divided into two groups. The first group received distilled water as control, while the second group received ATZ at 200 mg/kg body weight/ day via stomach gavage for 30 successive days of the experiment; the oral LD50 for ATZ is 3090 mg/kg. Our findings revealed the ability of ATZ to cause damage to the cerebrum, hippocampus, and submandibular salivary gland. This damage resulted from the induced oxidative stress, which was indicated by a significant elevation in malondialdehyde (MDA) concentration, DNA fragmentation, tumor necrotic factor-alpha (TNF-α) expression, with a significant decrease in reduced glutathione (GSH) level and reduction of B cell lymphoma 2 (BCL2), dopamine receptor D1 (Drd1), cAMP-responsive element-binding protein 1 (Creb1) genes expression after ATZ exposure. Moreover, degeneration of cells, cytoplasmic vacuolation, congestion of blood vessels, a strong immune reaction to caspase 3, and negligible immune expression of a glial fibrillary acidic protein (GFAP) were also noticed in the ATZ-treated group. We concluded that ATZ induces oxidative stress and has a toxic and apoptotic effects on the cerebrum, hippocampus, and salivary gland of adult male albino rats.


Assuntos
Atrazina , Herbicidas , Animais , Atrazina/toxicidade , Encéfalo/metabolismo , Herbicidas/toxicidade , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo , Ratos
11.
Environ Sci Pollut Res Int ; 29(1): 936-948, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34345985

RESUMO

Fipronil (FIP) is a highly effective insecticide that has been used in agriculture and veterinary medicine. Its neurotoxic effect to insects and to non-target organisms, after nonintentional exposure, was reported. Many studies were conducted to evaluate FIP effects on mammals. However, slight is known about its effect on the brain stem and diencephalon. The current study was designed to investigate the ability of FIP to induce oxidative stress as a molecular mechanism of FIP neurotoxicity that resulted in apoptosis and neural tissue reactivity in these regions. Ten adult male rats received 10 mg/kg of FIP technical grade by oral gavage, daily for 45 days. Brain stem and diencephalon were processed to examine oxidative stress-induced macromolecular alteration (MDA, PCC and DNA fragmentation). Also, the histopathological assessment and immunoreactivity for caspase-3 (active form), iNOS and GFAP were performed on the thalamus, hypothalamus and medulla oblongata. Our results revealed that FIP significantly raised MDA, PCC and DNA fragmentation (p ≤ 0.05). In addition, significantly increased immunoreactivity to GFAP, iNOS and caspase-3 (active form) in the FIP-treated group was noticed (p ≤ 0.05). Moreover, alterations in the histoarchitecture of the neural tissue of these regions were observed. We conclude that FIP can induce oxidative stress, leading to apoptosis and tissue reaction in brain stem and diencephalon.


Assuntos
Apoptose , Tronco Encefálico/patologia , Diencéfalo/patologia , Estresse Oxidativo , Pirazóis/toxicidade , Animais , Apoptose/efeitos dos fármacos , Tronco Encefálico/efeitos dos fármacos , Diencéfalo/efeitos dos fármacos , Inseticidas/toxicidade , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos
12.
Int J Biol Macromol ; 191: 792-802, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34597692

RESUMO

Melamine and its analogues are illegally added to raise the apparent protein content in foods. The elevated concentrations of these compounds cause adverse effects in humans and animals. In this contribution, the protective effects of the synthesized starch-stabilized selenium nanoparticles (Se-NPs@starch) on melamine-induced hepato-renal toxicity have been systematically investigated. The Se-NPs@starch were characterized by X-ray photoelectron spectroscopy (XPS) analysis, energy dispersive spectroscopy (EDS) mapping analysis, TEM, and FT-IR. Starch plays a crucial role in the stabilization and dispersion of Se NPs, as noticed from the TEM and EDS investigations. Furthermore, the atomic ratio of Se distribution over the starch surface is approximately 1.67%. The current study was conducted on four groups of adult male rats, and the oral daily treatments for 28 days were as follows: group I served as control, group II received Se-NPs@starch, group III was exposed to melamine, while group IV was treated with melamine and Se-NPs@starch. The results reveal a significant alteration in the histoarchitecture of both hepatic and renal tissues induced by melamine. Furthermore, elevated liver and kidney function markers, high malondialdehyde, and increased expression levels of apoptosis-related genes besides a reduction in GSH and expression levels of antioxidant genes were observed in the melamine-exposed group. Interestingly, the administration of the Se-NPs@starch resulted in remarkable protection of rats against melamine-induced toxicity through increasing the antioxidant capacity and inhibiting oxidative damage. Collectively, this study provides affordable starch-stabilized Se-NPs with potent biological activity, making them auspicious candidates for prospective biomedical applications.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Nanopartículas/química , Selênio/química , Amido/química , Triazinas/toxicidade , Animais , Apoptose , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Nanopartículas/uso terapêutico , Estresse Oxidativo , Ratos
13.
Acta Histochem ; 123(6): 151764, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34352653

RESUMO

Fipronil (FIP) insecticide is extensively used in agriculture, public health and veterinary medicine. Although it is considered as a neurotoxin to insects (target organisms) and exhibits neurological signs upon vertebrates (non-target organisms) exposure, slight is known about its potential neurotoxic effects and its molecular mechanisms on vertebrates. The current study is designed to assess oxidative stress as a molecular mechanism of FIP neurotoxicity subordinated with apoptosis and neural tissue reactivity. Ten adult male albino rats received 10 mg/kg body weight fipronil technical grade by oral gavage daily for 45 days (subacute exposure). Brain neural tissue regions (hippocampus, cerebellum and caudate putamen) were processed to examine oxidative stress induced cellular macromolecular alterations as MDA, PCC and DNA fragmentation. Besides, TNF-α and Bcl-2 gene expression and immunoreactivity for caspase-3 (active form), iNOS and GFAP were evaluated. Also, histopathological assessment was conducted. We found that FIP significantly raised MDA, PCC and DNA fragmentation (p ≤ 0.05). Also, it significantly upregulated TNF-α and non-significantly down-regulated Bcl-2 gene expression (p ≤ 0.05). Further, significant increased immunoreactivity to GFAP, iNOS and caspase-3 (active form) in these brain neural tissue regions in FIP treated group was noticed (p ≤ 0.05). Histopathological findings, including alterations in the histological architecture and neuronal degeneration, were also observed in these brain regions of FIP treated group. In conclusion, we suggest the ability of FIP to induce oxidative stress mediated macromolecular alterations, leading to apoptosis and tissue reaction in these brain regions which showed variable susceptibility to FIP toxic effects.


Assuntos
Apoptose/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Tecido Nervoso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pirazóis/efeitos adversos , Animais , Caspase 3/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/biossíntese , Masculino , Tecido Nervoso/patologia , Óxido Nítrico Sintase Tipo II/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Pirazóis/farmacologia , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/biossíntese
14.
Recent Pat Anticancer Drug Discov ; 16(2): 161-186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34132186

RESUMO

BACKGROUND: Over recent years, there has been an increasing focus on the repurposing of existing, well-known medications for new, novel usage. One such drug is metformin, typically utilized in the management of diabetes, which demonstrates a positive relationship between its administration and lower cancer morbidity and mortality. Based on this finding, numerous studies and clinical trials have been conducted to examine the potential usage of metformin as an anticancer agent. OBJECTIVE: This article aims to summarize metformin's anticancer effects through reviewing its literatures and patents, with a focus on its potential to be repurposed for cancer therapy. METHODS: Various databases were examined using keywords, 'Metformin' and 'Cancer'. Research articles were collected through the PubMed database, clinical trials were obtained from the Clinical Trials database, and patents were collected through the Google Patents database. RESULTS: Metformin shows antineoplastic activity in various models. These anticancer properties appear to synergize with existing chemotherapeutics, which allows a reduction in drug dosage without losing potency while minimizing adverse effects. Numerous patents on metformin have been filed which claim various combination therapies, delivery methods, and uses for cancer therapy, displaying an increasing interest in metformin's anticancer potential. CONCLUSION: Preclinical studies, along with early phase clinical trials, have examined the antitumor properties of metformin on a variety of cancers. Metformin's anticancer effects are well documented, demonstrating a great promise in improving current cancer therapies. However, there is a significant lack of late phase clinical trials, specifically those involving nondiabetic cancer patients, and therefore further research in this area is required.


Assuntos
Antineoplásicos/farmacologia , Metformina/farmacologia , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Reposicionamento de Medicamentos , Sinergismo Farmacológico , Humanos , Hipoglicemiantes/farmacologia , Metformina/administração & dosagem , Metformina/efeitos adversos , Patentes como Assunto
15.
16.
Acta Histochem ; 123(2): 151682, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33465564

RESUMO

Methotrexate (MTX) has been used for treatment of autoimmune diseases, inflammatory disorders as rheumatic arthritis, and different types of cancers. However, it has shown adverse effects on vital organs. The current study was conducted to investigate the toxic effect of MTX on the hippocampus, cerebellum, liver and kidneys of adult male albino rats. MTX was injected weekly at 5 mg/kg body weight via I/P injection for 6 weeks. At the end of the experiment, histopathological, immunohistochemical and biochemical evaluation were performed on the hippocampus, cerebellum, liver, and kidney tissues of the sacrificed rats. We observed that methotrexate induced neural tissue damage in the hippocampus and cerebellum, degeneration of hepatocytes, congestion of the central vein and blood sinusoids of the liver, distortion in the renal corpuscles and necrosis of the renal tubule. Immunohistochemical findings revealed strong positive expression of Caspase-3, PCNA and GFAP. Biochemical studies revealed significant elevation in the serum levels of AST and ALT, in addition to high serum concentrations of creatinine and urea. Also, MTX injection increased MDA, while it decreased GSH, SOD and AChE levels. We conclude the ability of MTX to induce oxidative stress that results into apoptosis and tissue injury, leading to neurotoxicity, hepatotoxicity, and nephrotoxicity.


Assuntos
Cerebelo/metabolismo , Hipocampo/metabolismo , Rim/metabolismo , Fígado/metabolismo , Metotrexato/farmacologia , Animais , Apoptose/efeitos dos fármacos , Cerebelo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Imuno-Histoquímica , Técnicas In Vitro , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos
17.
Int J Ment Health Syst ; 15(1): 11, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468192

RESUMO

BACKGROUND: In many low resource settings, the provision of government mental health care services is limited to specialized psychiatry units in urban hospital care facilities, where the most common treatment for common mental disorders (CMDs) is pharmacotherapy, occasionally with adjunct nonspecific psychological support. We aimed to evaluate the effectiveness of adding a low intensity, psychological intervention, Problem Management Plus (PM+) for CMDs into routine care in a specialized mental health care facility in Pakistan. METHODS: A two arm, single-blind individual randomized controlled trial (RCT) was carried out with adults (N = 192), referred for psychological support by psychiatrists. The study participants were randomized (1:1) to PM + plus Treatment as Usual (TAU) (n = 96) or TAU only (n = 96). The primary outcomes were symptoms of anxiety and depression, measured by the Hospital Anxiety and Depression Scale (HADS) and functional impairment as measured by WHO Disability Assessment Schedule (WHODAS 2.0) at 20 weeks after baseline. RESULTS: The analysis was done on intention-to-treat principle. The linear mixed model analysis showed that at 20 weeks after baseline, there was a significant reduction in symptoms of anxiety and depression (mean [SD], 16.23 [8.81] vs 19.79 [7.77]; AMD, - 3.10; 95% CI, - 0.26 to - 5.76); p = 0.03 and improvement in functioning (mean [SD], 22.94 [9.37] vs 27.37 [8.36]; AMD, - 4.35; 95% CI, - 1.45 to - 7.24); p = 0.004 in PM + plus TAU versus TAU arm. The follow-up rate was 67% at primary end-point. CONCLUSIONS: Specialized care facilities in LMICs may consider adding brief, evidence-based psychological treatments for CMDs to their routine care. Trial Registration Australian New Zealand Clinical Trials Registry, ACTRN12616000381482. Registered March 23, 2016. Retrospectively registered, https://www.anzctr.org.au/Default.aspx/ ACTRN12616000381482.

18.
Drug Des Devel Ther ; 14: 4511-4518, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149549

RESUMO

INTRODUCTION: Physical, chemical, thermal injuries along with infectious diseases lead to acute pain with associated inflammation, being the primary cause of hospital visits. Moreover, neuropathic pain associated with diabetes is a serious chronic disease leading to high morbidity and poor quality of life. OBJECTIVE: Earlier multiple sulphonamides have been reported to have an antinociceptive and antiallodynic profile. 4-Fluoro-N-(4-sulfamoylbenzyl) Benzene Sulfonamide (4-FBS), a synthetic sulfonamide with reported carbonic anhydrase inhibitory activity, was investigated for its potential effects in mice model of acute and diabetic neuropathic pain. METHODS AND RESULTS: 4-FBS was given orally (p.o.) one hour before the test and then mice were screened for antinociceptive activity by using the tail immersion test, which showed significant antinociceptive effect at both 20 and 40 mg/kg doses. To explore the possible mechanisms, thermal analgesia of 4-FBS was reversed by the 5HT3 antagonist ondansetron 1mg/kg intraperitoneally (i.p.) and by the µ receptor antagonist naloxone (1 mg/kg i.p.), implying possible involvement of serotonergic and opioidergic pathways in the analgesic effect of 4-FBS. Diabetes was induced in mice by a single dose of streptozotocin (STZ) 200 mg/kg i.p. After two weeks, animals first became hyperalgesic and progressively allodynic in the fourth week, which was evaluated through behavioral parameters like thermal and mechanical tests. 4-FBS at 20 and 40 mg/kg p.o. significantly reversed diabetes-induced hyperalgesia and allodynia at 30, 60, 90, and 120 minutes. CONCLUSION: These findings are significant and promising while further studies are warranted to explore the exact molecular mechanism and the potential of 4-FBS in diabetic neuropathic pain.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Dor/tratamento farmacológico , Administração Oral , Analgésicos/administração & dosagem , Analgésicos/química , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Diabetes Mellitus Experimental/induzido quimicamente , Neuropatias Diabéticas/induzido quimicamente , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hiperalgesia/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Estreptozocina , Relação Estrutura-Atividade
19.
Indian J Anaesth ; 64(8): 704-709, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32934405

RESUMO

BACKGROUND AND AIMS: Various methods have been used to check vocal cord movements as a routine before awakening the patient at the end of thyroidectomy to rule out recurrent laryngeal nerve (RLN) palsy; out of which, fibreoptic-assisted visualisation via laryngeal mask airway (LMA) being the most desirable. METHODS: Thirty patients of either sex, aged 18-65 years, American Society of Anaesthesiologists (ASA) grade I/II, scheduled for thyroidectomy under general anaesthesia (GA) were included and were randomised to receive either fibreoptic assisted (FB) or LMA CTrach-assisted (CT) visualisation of laryngeal structures at the end of thyroidectomy. The primary outcome was grade of view of laryngeal structures and secondary outcomes were time taken to achieve optimal view of laryngeal structures, ease of visualisation, hemodynamic parameters, and complications. RESULTS: In the fibreoptic group, we obtained comparable optimal laryngeal view i.e., grade 1 and 2 in all (100%) patients in comparison to 14 (93.33%) in LMA CTrach group. The "time taken to achieve the optimal view" was significantly lower in the CTrach group when compared to Fibreoptic group (220.67 ± 95.98 vis-a-vis 136.67 ± 68.98). The ease of visualisation of laryngeal structures was comparable (P = 0.713) and the baseline haemodynamic parameters were comparable between the 2 groups and at various designated intervals. In total, 6.66% and 26.66% patients in group FB and CT group, respectively, required manoeuvres. However, difference was statistically significant (P < 0.05). CONCLUSION: Both Fibreoptic-assisted and LMA CTrach-assisted visualization of laryngeal structures in thyroidectomy are equally efficacious in terms of the optimal laryngeal view obtained and ease of visualisation. However, the time taken to achieve optimal laryngeal view was lesser with LMA CTrach.

20.
Am J Public Health ; 110(S2): S215-S218, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32663077

RESUMO

A health care system and a Medicaid payer partnered to develop an educational intervention and payment redesign program to improve timely postpartum visits for low-income, high-risk mothers in New York City between April 2015 and October 2016. The timely postpartum visit rate was higher for 363 mothers continuously enrolled in the program than for a control group matched by propensity score (67% [243/363] and 56% [407/726], respectively; P < .001). An innovative partnership between a health care system and Medicaid payer improved access to health care services and community resources for high-risk mothers.


Assuntos
Custo Compartilhado de Seguro/métodos , Medicaid/economia , Cuidado Pós-Natal/estatística & dados numéricos , Adulto , Feminino , Humanos , Programas de Assistência Gerenciada , Motivação , Cidade de Nova Iorque , Educação de Pacientes como Assunto/métodos , Cuidado Pós-Natal/economia , Pobreza , Gravidez , Gravidez de Alto Risco , Centros de Atenção Terciária , Estados Unidos
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