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1.
Int J Tuberc Lung Dis ; 28(4): 176-182, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38563339

RESUMEN

BACKGROUNDTanzanian TB guidelines recommend facility-based TB screening for symptomatic household contacts (HHCs) or those aged <5 years, but cost remains a major barrier. In this study, we evaluate the use of unconditional cash transfers (UCTs) to facilitate completion of HHC TB screening.METHODSIn this prospective interventional study, we enrolled index people diagnosed with TB (PWTB) within 8 weeks of TB treatment initiation from the TB clinic at Haydom Lutheran Hospital, Haydom, Tanzania, and surrounding TB dispensaries in rural Tanzania. The study provided at the time of enrollment an UCT up to 40,000 Tanzanian shillings (USD16.91) directly to heads of households with PWTB, covered medical costs from screening activities and provided three bi-weekly phone reminders to facilitate HHC TB screening. The primary outcome was TB screening completion for all HHCs compared to the same period of the preceding year.RESULTSWe enrolled 120 index PWTB, including 398 HHCs between July and December 2022. The median age for index PWTB was 35 years; 38% were females. Sixty-five (54%) households completed screening for all HHCs, compared to 7% during the same period of the preceding year.CONCLUSIONThese interventions may considerably improve completion of HHC TB screening in rural Tanzania..


Asunto(s)
Tuberculosis , Femenino , Humanos , Adulto , Masculino , Tuberculosis/terapia , Tanzanía/epidemiología , Estudios Prospectivos , Tamizaje Masivo , Composición Familiar
2.
Pharmaceutics ; 16(1)2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38258124

RESUMEN

Challenges to docetaxel use in prostate cancer treatment include several resistance mechanisms as well as toxicity. To overcome these challenges and to improve the therapeutic efficacy in heterogeneous prostate cancer, the use of multiple agents that can destroy different subpopulations of the tumor is required. Brusatol, a multitarget inhibitor, has been shown to exhibit potent anticancer activity and play an important role in drug response and chemoresistance. Thus, the combination of brusatol and docetaxel in a nanoparticle platform for the treatment of prostate cancer is expected to produce synergistic effects. In this study, we reported the development of polymeric nanoparticles for the delivery of brusatol and docetaxel in the treatment of prostate cancer. The one-factor-at-a-time method was used to screen for formulation and process variables that impacted particle size. Subsequently, factors that had modifiable effects on particle size were evaluated using a 24 full factorial statistical experimental design followed by the optimization of drug loading. The optimization of blank nanoparticles gave a formulation with a mean size of 169.1 nm ± 4.8 nm, in agreement with the predicted size of 168.333 nm. Transmission electron microscopy showed smooth spherical nanoparticles. The drug release profile showed that the encapsulated drugs were released over 24 h. Combination index data showed a synergistic interaction between the drugs. Cell cycle analysis and the evaluation of caspase activity showed differences in PC-3 and LNCaP prostate cancer cell responses to the agents. Additionally, immunoblots showed differences in survivin expression in LNCaP cells after treatment with the different agents and formulations for 24 h and 72 h. Therefore, the nanoparticles are potentially suitable for the treatment of advanced prostate cancer.

3.
ACS Omega ; 9(2): 2615-2628, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38250376

RESUMEN

Glioblastoma (GBM) is the most aggressive and fatal brain tumor, with approximately 10,000 people diagnosed every year in the United States alone. The typical survival period for individuals with glioblastoma ranges from 12 to 18 months, with significant recurrence rates. Common therapeutic modalities for brain tumors are chemotherapy and radiotherapy. The main challenges with chemotherapy for the treatment of glioblastoma are high toxicity, poor selectivity, and limited accumulation of therapeutic anticancer agents in brain tumors as a result of the presence of the blood-brain barrier. To overcome these challenges, researchers have explored strategies involving the combination of targeting peptides possessing a specific affinity for overexpressed cell-surface receptors with conventional chemotherapy agents via the prodrug approach. This approach results in the creation of peptide drug conjugates (PDCs), which facilitate traversal across the blood-brain barrier (BBB), enable preferential accumulation of chemotherapy within the neoplastic microenvironment, and selectively target cancerous cells. This approach increases accumulation in tumors, thereby improving therapeutic efficiency and minimizing toxicity. Leveraging the affinity of the HAIYPRH (T7) peptide for the transferrin receptor (TfR) overexpressed on the blood-brain barrier and glioma cells, a novel T7-SN-38 peptide drug conjugate was developed. The T7-SN-38 peptide drug conjugate demonstrates about a 2-fold reduction in glide score (binding affinity) compared to T7 while maintaining a comparable orientation within the TfR target site using Schrödinger-2022-3 Maestro 13.3 for ligand preparation and Glide SP-Peptide docking. Additionally, SN-38 extends into a solvent-accessible region, enhancing its susceptibility to protease hydrolysis at the cathepsin B (Cat B) cleavable site. The SN-38-ether-peptide drug conjugate displayed high stability in buffer at physiological pH, and cleavage of the conjugate to release free cytotoxic SN-38 was observed in the presence of exogenous cathepsin B. The synthesized peptide drug conjugate exhibited potent cytotoxic activities in cellular models of glioblastoma in vitro. In addition, blocking transferrin receptors using the free T7 peptide resulted in a notable inhibition of cytotoxicity of the conjugate, which was reversed when exogenous cathepsin B was added to cells. This work demonstrates the potential for targeted drug delivery to the brain in the treatment of glioblastoma using the transferrin receptor-targeted T7-SN-38 conjugate.

4.
Pharmaceutics ; 15(11)2023 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-38004598

RESUMEN

Colorectal cancer (CRC) is one of the deadliest malignancies in the US, ranking fourth after lung, prostate, and breast cancers, respectively, in general populations. It continues to be a menace, and the incidence has been projected to more than double by 2035, especially in underdeveloped countries. This review seeks to provide some insights into the disease progression, currently available treatment options and their challenges, and future perspectives. Searches were conducted in the PubMed search engine in the university's online library. The keywords were "Colorectal Cancer" AND "disease process" OR "disease mechanisms" OR "Current Treatment" OR "Prospects". Selection criteria were original articles published primarily during the period of 2013 through 2023. Abstracts, books and documents, and reviews/systematic reviews were filtered out. Of over 490 thousand articles returned, only about 800 met preliminary selection criteria, 200 were reviewed in detail, but 191 met final selection criteria. Fifty-one other articles were used due to cross-referencing. Although recently considered a disease of lifestyle, CRC incidence appears to be rising in countries with low, low-medium, and medium social demographic indices. CRC can affect all parts of the colon and rectum but is more fatal with poor disease outcomes when it is right-sided. The disease progression usually takes between 7-10 years and can be asymptomatic, making early detection and diagnosis difficult. The CRC tumor microenvironment is made up of different types of cells interacting with each other to promote the growth and proliferation of the tumor cells. Significant advancement has been made in the treatment of colorectal cancer. Notable approaches include surgery, chemotherapy, radiation therapy, and cryotherapy. Chemotherapy, including 5-fluorouracil, irinotecan, oxaliplatin, and leucovorin, plays a significant role in the management of CRC that has been diagnosed at advanced stages. Two classes of monoclonal antibody therapies have been approved by the FDA for the treatment of colorectal cancer: the vascular endothelial growth factor (VEGF) inhibitor, e.g., bevacizumab (Avastin®), and the epidermal growth factor receptor (EGFR) inhibitor, e.g., cetuximab (Erbitux®) and panitumumab (Verbitix®). However, many significant problems are still being experienced with these treatments, mainly off-target effects, toxic side effects, and the associated therapeutic failures of small molecular drugs and the rapid loss of efficacy of mAb therapies. Other novel delivery strategies continue to be investigated, including ligand-based targeting of CRC cells.

5.
Front Genet ; 14: 1231536, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37732318

RESUMEN

Over the past few years, a number of studies have revealed that a significant number of men with prostate cancer had genetic defects in the DNA damage repair gene response and mismatch repair genes. Certain of these modifications, notably gene alterations known as homologous recombination (HRR) genes; PALB2, CHEK2 BRCA1, BRCA2, ATM, and genes for DNA mismatch repair (MMR); MLH1, MSH2, MSH6, and PMS2 are connected to a higher risk of prostate cancer and more severe types of the disease. The DNA damage repair (DDR) is essential for constructing and diversifying the antigen receptor genes required for T and B cell development. But this DDR imbalance results in stress on DNA replication and transcription, accumulation of mutations, and even cell death, which compromises tissue homeostasis. Due to these impacts of DDR anomalies, tumor immunity may be impacted, which may encourage the growth of tumors, the release of inflammatory cytokines, and aberrant immune reactions. In a similar vein, people who have altered MMR gene may benefit greatly from immunotherapy. Therefore, for these treatments, mutational genetic testing is indicated. Mismatch repair gene (MMR) defects are also more prevalent than previously thought, especially in patients with metastatic disease, high Gleason scores, and diverse histologies. This review summarizes the current information on the mutation spectrum and clinical significance of DDR mechanisms, such as HRR and MMR abnormalities in prostate cancer, and explains how patient management is evolving as a result of this understanding.

6.
J Hazard Mater ; 459: 132312, 2023 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-37604033

RESUMEN

Elevated non-volatile dissolved organic carbon (NVDOC) concentrations in groundwater (GW) monitoring wells under oil-contaminated hydrophobic soils originating from a pipeline rupture at the National Crude Oil Spill & Natural Attenuation Research Site near Bemidji, MN are documented. We hypothesized the elevated NVDOC is comprised of water-soluble photooxidation products transported from the surface to the aquifer. We use field and laboratory samples in combination with complementary analytical methods to test this hypothesis and determine the biological response to these products. Observations from optical spectroscopy and ultrahigh-resolution mass spectrometry reveal a significant correlation between the chemical composition of NVDOC leached from photochemically weathered soils and GW monitoring wells with high NVDOC concentrations measured in the aquifer beneath the contaminated soil. Conversely, the chemical composition from the uncontaminated soil photoleachate matches the NVDOC observed in the uncontaminated wells. Contaminated GW and photodissolution leachates from contaminated soil activated biological targets indicative of xenobiotic metabolism and exhibited potential for adverse effects. Newly formed hydrocarbon oxidation products (HOPs) from fresh oil could be distinguished from those downgradient. This study illustrates another pathway for dissolved HOPs to infiltrate GW and potentially affect human health and the environment.


Asunto(s)
Agua Subterránea , Petróleo , Humanos , Materia Orgánica Disuelta , Hidrocarburos , Receptores Citoplasmáticos y Nucleares , Suelo
7.
Biomed Pharmacother ; 165: 115151, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37473683

RESUMEN

Ovarian cancer is a highly lethal disease that affects women. Early diagnosis and treatment of women with early-stage disease improve the probability of survival. Unfortunately, the majority of women with ovarian cancer are diagnosed at advanced stages 3 and 4 which makes treatment challenging. While the majority of the patients respond to first-line treatment, i.e. cytoreductive surgery integrated with platinum-based chemotherapy, the rate of disease recurrence is very high and the available treatment options for recurrent disease are not curative. Thus, there is a need for more effective treatment options for ovarian cancer. Targeted drug conjugate systems have emerged as a promising therapeutic strategy for the treatment of ovarian cancer. These systems provide the opportunity to selectively deliver highly potent chemotherapeutic drugs to ovarian cancer, sparing healthy normal cells. Thus, the effectiveness of the drugs is improved and systemic toxicity is greatly reduced. In this review, different targeted drug conjugate systems that have been or are being developed for the treatment of ovarian cancer will be discussed.


Asunto(s)
Antineoplásicos , Neoplasias Ováricas , Humanos , Femenino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Resultado del Tratamiento , Quimioterapia Adyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antineoplásicos/uso terapéutico
8.
Pharmaceutics ; 15(5)2023 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-37242560

RESUMEN

Pancreatic cancer is fast becoming a global menace and it is projected to be the second leading cause of cancer-related death by 2030. Pancreatic adenocarcinomas, which develop in the pancreas' exocrine region, are the predominant type of pancreatic cancer, representing about 95% of total pancreatic tumors. The malignancy progresses asymptomatically, making early diagnosis difficult. It is characterized by excessive production of fibrotic stroma known as desmoplasia, which aids tumor growth and metastatic spread by remodeling the extracellular matrix and releasing tumor growth factors. For decades, immense efforts have been harnessed toward developing more effective drug delivery systems for pancreatic cancer treatment leveraging nanotechnology, immunotherapy, drug conjugates, and combinations of these approaches. However, despite the reported preclinical success of these approaches, no substantial progress has been made clinically and the prognosis for pancreatic cancer is worsening. This review provides insights into challenges associated with the delivery of therapeutics for pancreatic cancer treatment and discusses drug delivery strategies to minimize adverse effects associated with current chemotherapy options and to improve the efficiency of drug treatment.

9.
Anal Chem ; 94(42): 14537-14545, 2022 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-36215705

RESUMEN

We present a detailed molecular characterization of organophosphorus compounds in ambient organic aerosol influenced by wildfire smoke. Biomass burning organic aerosol (BBOA) is an important source of phosphorus (P) to surface waters, where even a small imbalance in the P flux can lead to substantial effects on water quality, such as eutrophication, algal blooms, and oxygen depletion. We aimed to exploit the ultrahigh resolving power, mass accuracy, and sensitivity of Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) to explore the molecular composition of an ambient BBOA sample collected downwind of Pacific Northwest wildfires. The 21-T FT-ICR MS yielded 10 533 distinct formulae, which included molecular species comprising C, H, O, and P with or without N, i.e., organophosphorus compounds that have long been quantified in wildfire smoke but have not yet been characterized at the molecular level. The lack of detailed molecular characterization of organophosphorus compounds in BBOA is primarily due to their inherently low concentrations in aerosols and poor ionization efficiency in complex mixtures. We demonstrate that the exceptional sensitivity of the 21-T FT-ICR MS allows qualitative analysis of a previously uncharacterized fraction of BBOA without its selective concentration from the organic matrix, exemplifying the need for ultrahigh-resolution tools for a more detailed and accurate molecular depiction of such complex mixtures.


Asunto(s)
Ciclotrones , Incendios Forestales , Análisis de Fourier , Humo , Compuestos Organofosforados , Espectrometría de Masas/métodos , Aerosoles , Fósforo , Oxígeno
10.
Polymers (Basel) ; 14(13)2022 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-35808648

RESUMEN

Passive targeting is the foremost mechanism by which nanocarriers and drug-bearing macromolecules deliver their payload selectively to solid tumors. An important driver of passive targeting is the enhanced permeability and retention (EPR) effect, which is the cornerstone of most carrier-based tumor-targeted drug delivery efforts. Despite the huge number of publications showcasing successes in preclinical animal models, translation to the clinic has been poor, with only a few nano-based drugs currently being used for the treatment of cancers. Several barriers and factors have been adduced for the low delivery efficiency to solid tumors and poor clinical translation, including the characteristics of the nanocarriers and macromolecules, vascular and physiological barriers, the heterogeneity of tumor blood supply which affects the homogenous distribution of nanocarriers within tumors, and the transport and penetration depth of macromolecules and nanoparticles in the tumor matrix. To address the challenges associated with poor tumor targeting and therapeutic efficacy in humans, the identified barriers that affect the efficiency of the enhanced permeability and retention (EPR) effect for macromolecular therapeutics and nanoparticle delivery systems need to be overcome. In this review, approaches to facilitate improved EPR delivery outcomes and the clinical translation of novel macromolecular therapeutics and nanoparticle drug delivery systems are discussed.

11.
J Fr Ophtalmol ; 44(1): 41-47, 2021 Jan.
Artículo en Francés | MEDLINE | ID: mdl-33158610

RESUMEN

PURPOSE: The goal of this study was to compare the intraocular pressure (IOP) values obtained with each of the tonometry methods as well as to study the effect of corneal pachymetry on the measurements obtained by each method. MATERIAL AND METHODS: We carried out a cross-sectional, descriptive, analytical, prospective study in the ophthalmology department of a multispecialty clinic in Abidjan (Ivory Coast) from April 2018 to August 2018. Patients aged 15 and over were included in the study. Over this period, IOP was measured by Goldman Applanation Tonometer (HaagStreit, AT 900, Switzerland) and air-puff Tonopachymeter (Nidek, NT 530 P, Japan), which also permitted measurement of central optical corneal pachymetry. The data analyzed focused on socio-demographic characteristics, ophthalmologic history, tonometry, and central corneal pachymetry. The comparison of the values obtained by both devices and the effect of central corneal thickness (CCT) on tonometry were analyzed using EpiDataAnalysis V2.2.2.183 software. RESULTS: We examined 318 eyes of 159 patients whose mean age was 40±12.57 years, range 16 to 82 years. The gender ratio was 1. A past ophthalmologic history was noted in 79.2% of patients. The mean IOP by Goldmann applanation tonometry was 12.75±3.17mmHg, and that by non-contact air-puff tonometry was 13.83±3.80mmHg. The mean central corneal thickness was 530.50±32.61µm. The difference between IOP measured by non-contact tonometry and that measured by contact tonometry was statistically significant, with P=0.00. There was no statistically significant relationship between central corneal pachymetry and contact tonometry (P=0.80). However, there was a statistically significant relationship between non-contact tonometry and central pachymetry (P=0.00). The values obtained with the air-puff tonometer are more affected by central corneal thickness. CONCLUSION: The values obtained by Goldmann applanation tonometry are not equivalent to those obtained by non-contact air-puff tonopachymetry.


Asunto(s)
Córnea , Tonometría Ocular , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Côte d'Ivoire , Estudios Transversales , Humanos , Presión Intraocular , Manometría , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Adulto Joven
12.
Environ Res ; 191: 110114, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32866496

RESUMEN

Ultrahigh resolution mass spectrometry is widely used for nontargeted analysis of complex environmental and biological mixtures, such as dissolved organic matter, due to its unparalleled ability to provide accurate mass measurements. Accurate and efficient characterization of these mixtures is critical to being better able to evaluate their effect on human health and climate. This characterization requires accurate mass signals free from isobaric interferences, instrument noise, and mass measurement biases, allowing for molecular formula identification. To address this need, an open source post-processing pipeline for ultrahigh resolution mass spectra of environmental complex mixtures software was developed. MFAssignR contains functions that perform noise estimation, 13C and 34S polyisotopic mass filtering, mass measurement recalibration, and molecular formula assignment as part of a consistent data processing environment. Novel applications of mass defect analysis were used in the functions for noise estimation and isotope pair identification. Using formula extensions, exact mass measurements are converted to unambiguous molecular formulas via data dependent pathways, reducing a priori decisions. Optional molecular formula ambiguity and multiple non-oxygen heteroatoms are provided for custom user applications, including isotopically labeled reactive species, halogen-containing species, or tandem ultrahigh resolution mass spectrometry. This represents uncommon flexibility for an open-source software package. To evaluate the performance of MFAssignR, it was used to characterize a sample of biomass burning influenced organic aerosol and the results were compared to those from other available methods of molecular formula assignment and noise estimation. The differences between the methods are described here. Overall, the inclusion of a full pipeline of data preparation functions and the data-dependent ambiguity reductions in MFAssignR render excellent results and make MFAssignR well-suited for the consistent and efficient analysis of environmental complex mixtures. MFAssignR is publicly available via GitHub.


Asunto(s)
Mezclas Complejas , Programas Informáticos , Humanos , Isótopos , Espectrometría de Masas en Tándem
13.
BMC Res Notes ; 10(1): 519, 2017 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-29078819

RESUMEN

OBJECTIVE: Burkitt's lymphoma (BL) is a common aggressive non-Hodgkin's lymphoma in East and Central Africa among children. Persistent infections with Epstein Barr virus or Plasmodium falciparum are associated with immune hyperstimulation. It is hypothesised that inadvertent cytokine responses to infections indirectly or directly influence B cell neoplastic transformation through c-myelocytomatosis (c-myc) gene translocation. We sought to describe cytokines in children and adolescents with BL. Participants were recruited from western Kenya with parental consent, diagnosis confirmed using histology and consensus panel of immunohistochemistry antibodies. T helper1/2/17A and transforming growth factor-ß1 (TGF-ß1) cytokines were estimated using cytometric bead array in plasma. Complete blood counts (CBC) were determined by Beckman Coulter®. RESULTS: Out of 104 enrolled participants, 32% were confirmed BL and 68% grouped as non-BL. Mean (pg/ml) levels of cytokines in BL and non-BL were: interleukin (IL)-6 100.3 and 39.4 p = 0.152; IL-10 11.5 and 12.5 p = 0.363; IL-17A 17.8 and 64.9 p = 0.094 respectively. Expressions of interferon-γ, IL-2 and tumour necrosis factor-α were low and TGF-ß1 undetectable in both groups. Mean CBC differed between the two groups before and after chemotherapy, WBC being significantly so. Interleukin-6, IL-17A and IL-10 responses to infections in the study area may be associated with pathogenesis and be potential therapeutic targets.


Asunto(s)
Linfoma de Burkitt/metabolismo , Citocinas/metabolismo , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/genética , Preescolar , Femenino , Humanos , Inmunohistoquímica , Kenia , Masculino
14.
Trop Med Health ; 45: 19, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28794686

RESUMEN

BACKGROUND: Tumors commonly are infiltrated by leukocytes, or tumor infiltrating leukocytes (TILs). It remains unclear, however, if the density and type of individual TILs has a direct or simply correlative role in promoting poor prognosis in breast cancer patients. Breast cancer in Kenyan women is aggressive with presentation at a young age, with advanced grade (grade III), large tumor size (>2.0 cm), and poor prognosis. We previously observed that the tumors were predominantly estrogen receptor positive (ER+) but also included both a high percentage of triple negative tumors and also increased immune cell infiltration within the tumors. We used breast tumor tissues from each patient to make tissue microarrays that were then stained for leukocyte and myeloid markers including CD4, CD8, CD20, CD25, CD68, and CD163 using immunohistochemical techniques. The immune cell infiltration into the cancer tissue included increased numbers of macrophages (CD68+), helper T cells (CD4+), and CD25+ lymphocytes compared to benign tissue. RESULTS: This study characterized the grade, molecular subtypes, and proliferation index of these tumors and determined if TIL density was enriched across any of these factors. We analyzed 49 malignant patient tissue samples for this study. The patient population had a mean age of 51.9 years. The tumors analyzed were heterogeneous by grade: grade I (6%), grade II (47%), and grade III (39%). Most patients presented with large tumors (>2.0 cm) (69%). We classified the tumors into molecular subtypes based on clinical marker expression. Based on this analysis, the molecular subtype distribution was heterogeneous with luminal B (41%), basal/triple negative (TN) (37%), luminal A (14%) and HER2 (8%) breast cancer subtypes. While the basal/TN subtype had a much higher proliferative index (Ki-67+) than did the other molecular subtypes, we did not see a significant correlation between TIL density and either subtype or tumor grade. Therefore, TIL density is independent of molecular subtype and grade. CONCLUSION: This study identified a Kenyan patient cohort that develops large, high-grade tumors primarily of the luminal B and basal molecular subtypes. After analyzing the TILs within these tumors, we found that immune cell infiltration of these tumors correlated with increased proliferation but not grade or molecular subtype. Future research is required to determine if the aberrant recruitment of TILs to tumors contributes to cancer progression and response to cancer treatments.

15.
Mol Pharm ; 12(12): 4175-87, 2015 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-26524196

RESUMEN

RNA interference (RNAi) is triggered by oligonucleotides that are about 21-23 nucleotides long and are capable of inducing the destruction of complementary mRNA. The RNAi technique has been successfully utilized to target HIV replication; however, the main limitation to the successful utilization of this technique in vivo is the inability of naked siRNA to cross the cell membrane by diffusion due to its strong anionic charge and large molecular weight. This review describes current nonviral nanotechnological approaches to deliver anti-HIV siRNAs for the treatment of HIV infection.


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/genética , Infecciones por VIH/terapia , ARN Interferente Pequeño/genética , Animales , Sistemas de Liberación de Medicamentos/métodos , Humanos , Nanopartículas/administración & dosificación , Nanotecnología/métodos , Interferencia de ARN/fisiología
16.
J Pharm Sci ; 103(8): 2546-55, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24961596

RESUMEN

The macromonomer method was used to prepare cross-linked, paclitaxel-loaded polylactide (PLA)-polyethylene glycol (stealth) nanoparticles using free-radical dispersion polymerization. The method can facilitate the attachment of other molecules to the nanoparticle surface to make it multifunctional. Proton nuclear magnetic resonance and Fourier transform infrared spectra confirm the synthesis of PLA macromonomer and cross-linking agent. The formation of stealth nanoparticles was confirmed by scanning and transmission electron microscopy. The drug release isotherm of paclitaxel-loaded nanoparticles shows that the encapsulated drug is released over 7 days. In vitro cytotoxicity assay in selected breast and ovarian cancer cell lines reveal that the blank nanoparticle is biocompatible compared with medium-only treated controls. In addition, the paclitaxel-loaded nanoparticles exhibit similar cytotoxicity compared with paclitaxel in solution. Confocal microscopy reveals that the nanoparticles are internalized by MCF-7 breast cancer cells within 1 h. Preliminary biodistribution studies also show nanoparticle accumulation in tumor xenograft model. The nanoparticles are suitable for the controlled delivery of bioactive agents.


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Preparaciones de Acción Retardada/química , Nanopartículas/química , Paclitaxel/administración & dosificación , Poliésteres/química , Animales , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/farmacología , Mama/efectos de los fármacos , Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Humanos , Células MCF-7 , Ratones Desnudos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Ovario/efectos de los fármacos , Ovario/patología , Paclitaxel/farmacocinética , Paclitaxel/farmacología
17.
Drug Dev Ind Pharm ; 40(11): 1547-56, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24059281

RESUMEN

PURPOSE: Nanoparticle size is important in drug delivery. Clearance of nanoparticles by cells of the reticuloendothelial system has been reported to increase with increase in particle size. Further, nanoparticles should be small enough to avoid lung or spleen filtering effects. Endocytosis and accumulation in tumor tissue by the enhanced permeability and retention effect are also processes that are influenced by particle size. We present the results of studies designed to optimize cross-linked biodegradable stealth polymeric nanoparticles fabricated by dispersion polymerization. METHODS: Nanoparticles were fabricated using different amounts of macromonomer, initiators, crosslinking agent and stabilizer in a dioxane/DMSO/water solvent system. Confirmation of nanoparticle formation was by scanning electron microscopy (SEM). Particle size was measured by dynamic light scattering (DLS). D-optimal mixture statistical experimental design was used for the experimental runs, followed by model generation (Scheffe polynomial) and optimization with the aid of a computer software. Model verification was done by comparing particle size data of some suggested solutions to the predicted particle sizes. RESULTS AND CONCLUSION: Data showed that average particle sizes follow the same trend as predicted by the model. Negative terms in the model corresponding to the cross-linking agent and stabilizer indicate the important factors for minimizing particle size.


Asunto(s)
Nanopartículas/química , Poliésteres/química , Sistemas de Liberación de Medicamentos , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Propiedades de Superficie , Tecnología Farmacéutica
18.
Artículo en Inglés | MEDLINE | ID: mdl-24146518

RESUMEN

Mistletoes of the Loranthaceae and Viscaceae are hemiparasitic plants and their preparations in the form of injectable extracts, infusions, tinctures, fluid extracts or tea bags are widely used in various cultures in almost every continent to treat or manage various health problems including hypertension, diabetes mellitus, inflammatory conditions, irregular menstruations, menopause, epilepsy, arthritis, cancer, etc. The medicinal values of some species of Mistletoes (Loranthaceae) growing in the West African sub-region have been reviewed along with some considerations of their chemistries and local uses. These have been compared with Mistletoes (Loranthaceae and Viscaceae) growing elsewhere in Europe and Asia. This review has attempted to update our knowledge on the values of these hemi-parasites which belong to the genera - Globimetula, Phragmanthera, Agelanthus and Tapinanthus, and which have, for years, been seen as only devastating and notorious plants. They are also seen as epiphyting economic, ornamental and medicinal plants. The hemi-parasitic plants (Mistletoes) are not well understood as very little is known about their biology (taxonomy, host/plant relationship, ecology, toxicology, physiological characteristics, etc.) and chemistry (chemical constituents' profile). Some pharmacological studies carried out on the various crude alcoholic extracts and purified fractions have, however, revealed that mistletoes showed hypotensive, hypoglycaemic, antilipidaemic, anti-oxidative, anti-inflammatory, antimicrobial, etc. effects and were non-toxic in experimental animals at the doses used. The findings showed that mistletoes can be very useful as medicinal agents in ameliorating health problems such as diabetes mellitus, hypertension, arthritis, pain, cancer and a host of other ailments if properly studied and developed.


Asunto(s)
Etnofarmacología , Loranthaceae/química , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Humanos , Extractos Vegetales/farmacología
19.
J Contemp Dent Pract ; 6(3): 86-94, 2005 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-16127476

RESUMEN

This aim of this study was to determine the antibacterial activity in extracts obtained from various Nigerian chewing sticks. Aqueous extracts from seventeen chewing sticks and the fruit of C. ferruginea, one fruit used in oral hygiene in Nigeria, were screened for antibacterial activity against type cultures of Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. Eleven of the test extracts showed activity against at least two of these referenced organisms. Minimum inhibitory concentrations (MIC) of these eleven extracts against clinical isolates from orofacial infection were determined. All the extracts demonstrated activity against Staphylococcal and Streptococcal isolates. Over half of the extracts were active against Enterobacteriaceae and obligate anaerobic isolates, including Prevotella melaninogenica, Porphyromonas gigivalis, Fusobacterium nucleatum, and Peptostreptococcus prevotii. Extracts of the Vitellaria paradoxa root, Bridellia ferruginea stem and twigs, Garcinia cola stem, Terminalia glaucescens root, Morinda lucida root, and Cnestis ferruginea fruit showed appreciable activity against all classes of bacterial isolates. The extracts of these plants may serve as sources for chemotherapeutic agents for the management of orofacial infections.


Asunto(s)
Bacterias Anaerobias/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Cepillado Dental/instrumentación , Connaraceae , Pruebas de Sensibilidad Microbiana , Nigeria
20.
J Ethnopharmacol ; 87(1): 67-72, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12787956

RESUMEN

The antioxidant activities of three prenylated flavonoids from Dorstenia mannii (6,8-diprenyleriodictyol, dorsmanin C and dorsmanin F) were compared to the common, non-prenylated flavonoid, quercetin. The prenylated flavonoids were found to be potent scavengers of the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), and are more potent than butylated hydroxy toluene (BHT), a common antioxidant used as a food additive. The prenylated flavonoids also inhibited Cu(2+)-mediated oxidation of human low density lipoprotein (LDL). Dose-response studies indicated that the prenylated flavonoids were effective inhibitors of lipoprotein oxidation with IC50 values <1 microM and had similar inhibitory potency compared to quercetin, but was not directly related to Cu binding. Unlike quercetin, they did not show any pro-oxidant activity at high doses in the Cu(2+)-mediated lipoprotein oxidation system. The medicinal action of Dorstenia mannii may be related to the high concentration of potent antioxidant prenylated flavonoids in this species.


Asunto(s)
Antioxidantes/química , Flavonoides/química , Moraceae/química , África , Antioxidantes/aislamiento & purificación , Compuestos de Bifenilo , Hidroxitolueno Butilado/química , Flavonoides/aislamiento & purificación , Depuradores de Radicales Libres/química , Picratos/química , Quercetina/química , Factores de Tiempo
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