RESUMEN
BACKGROUND: Alzheimer disease (AD) patients experience progressive neurological and cognitive decline attributed to neurodegeneration. Cerebral dopamine neurotrophic factor (CDNF) has been identified to protect and rescue neurons in various preclinical neurodegeneration models. The expression of this protein occurs in both the central nervous system and peripheral blood. Blood platelets exhibit several biochemical impairments similar to the brain tissues of patients with neurological disorders. This study examines CDNF mRNA expression in human blood platelets in healthy subjects and Alzheimer-probable patients. METHODS: Platelets were extracted from whole blood from patients. mRNA was extracted to synthesize cDNA and quantify CDNF gene expression from 21 Alzheimer-probable patients and 73 healthy age-matched control subjects using real-time qPCR. Grouping analysis of the data with regard to sex was conducted. RESULTS: CDNF mRNA expression was significantly decreased in Alzheimer-probable patients relative to the control subjects (P<0.05). Further analysis demonstrated reduced CDNF expression in male Alzheimer-probable patients compared with their age and sex-matched controls (P<0.05). However, no change in female subjects was observed. Interestingly, there is a lower level of CDNF expression in the female control group relative to the control male group (P<0.05). CONCLUSION: Alzheimer-probable male patients demonstrated significant reductions in CDNF expression, suggesting that CDNF plays a significant role in the pathogenesis of AD. In addition, it may assist in diagnosing male Alzheimer patients.
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Enfermedad de Alzheimer , Factores de Crecimiento Nervioso , Enfermedad de Alzheimer/genética , Plaquetas/metabolismo , Dopamina , Femenino , Humanos , Masculino , Factores de Crecimiento Nervioso/genética , Factores de Crecimiento Nervioso/metabolismo , ARN Mensajero/genéticaRESUMEN
BACKGROUND: Cerebral dopamine neurotrophic factor plays a critical role in repairing and maintaining healthy neurons in pathological conditions such as stroke. However, the association between cerebral dopamine neurotrophic factor expression and stroke has only recently been investigated in preclinical models and is rarely described in human studies. OBJECTIVES: The aims of this were to examine neurological alterations mirrored in human blood platelet cerebral dopamine neurotrophic factor gene expression. Cerebral dopamine neurotrophic factor is expressed in both the central nervous system and peripheral blood. Blood platelets are often used to model neuronal behavior because they exhibit biochemical impairments similar to brain tissues of patients with neurological disorders. METHODS: RNA was isolated from platelets and cDNA was synthesized to quantify cerebral dopamine neurotrophic factor gene expression of 36 stroke patients compared to 72 healthy aged-matched controls through real-time PCR. Further grouping analyses of data with regard to age, sex, and medication history were performed. RESULTS: Cerebral dopamine neurotrophic factor gene expression was significantly reduced in stroke patients relative to control subjects (Pâ¯=â¯.013). Subsequent analysis revealed a significant difference in expression between males and females within the control group (Pâ¯=â¯.026). Decreased cerebral dopamine neurotrophic factor expression was only observed in male stroke patients compared to their sex-matched controls (Pâ¯=â¯.008). Grouping stroke patients based on their medication history did not significantly alter cerebral dopamine neurotrophic factor gene expression. CONCLUSIONS: Further studies investigating cerebral dopamine neurotrophic factor expression could be directed towards the interplay of the central nervous system, hematopoietic derivatives, and utilizing cerebral dopamine neurotrophic factor as a therapeutic tool.
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Plaquetas/metabolismo , Factores de Crecimiento Nervioso/sangre , Accidente Cerebrovascular/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , Regulación hacia Abajo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Crecimiento Nervioso/genética , ARN Mensajero/sangre , Factores Sexuales , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/genética , Adulto JovenRESUMEN
INTRODUCTION: Tetracycline molecules comprise a group of broad-spectrum antibiotics whose primary mechanism of action is the inhibition of protein synthesis through the binding of the bacterial ribosome. In addition, tetracyclines inhibit matrix metalloproteases (MMPs), a family of zinc-dependent proteases that contribute to tissue remodeling, inflammation, and angiogenesis and are overexpressed in certain pathophysiologies such as diabetic foot ulcers (DFUs). OBJECTIVE: This study aims to develop a liquid chromatography and mass spectrometry (LC-MS/MS) doxycycline quantification methodology to facilitate the development of a stable topical doxycycline hyclate (DOXY) formulation as well as evaluate the topical DOXY formulation for the efficacy in MMP-9 inhibition in vitro and in a clinical application of diabetic lower extremity wounds. MATERIALS AND METHODS: A simple quantification method utilizing LC-MS/MS was used to develop a topical DOXY formulation, a sample of which was analyzed in stability testing. The formulation was evaluated in vitro for MMP-9 activity using a commercial assay and compared with internal kit controls as well as in a clinical setting for wound healing. RESULTS: Two formulations of 2% (w/w) DOXY demonstrated acceptable stability (±10% target concentration) for 70 days when stored at 4°C. Using an in vitro assay of MMP-9 enzyme activity, the 2% DOXY formulation imparted a ~30% decrease in MMP-9 inhibitory potential as compared with the control drug alone (IC50 values 62.92 µM and 48.27 µM, respectively). This topical product was evaluated for clinical utility in a patient with a DFU, and preliminary data suggest this intervention may promote wound healing. CONCLUSIONS: In summary, novel DOXY formulations may be stable and biologically active tools amenable to complex wound care.
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Antibacterianos/farmacología , Compuestos Cromogénicos/farmacología , Pie Diabético/tratamiento farmacológico , Doxiciclina/administración & dosificación , Doxiciclina/farmacología , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Cicatrización de Heridas/efectos de los fármacos , Administración Tópica , Antibacterianos/administración & dosificación , Cromatografía Liquida , Compuestos Cromogénicos/administración & dosificación , Pie Diabético/patología , Femenino , Humanos , Espectrometría de Masas , Inhibidores de la Metaloproteinasa de la Matriz/administración & dosificación , Persona de Mediana Edad , Resultado del Tratamiento , Cicatrización de Heridas/fisiologíaRESUMEN
BACKGROUND: Chronic Venous Disease is characterized by morphological abnormalities of the venous system. Affected limbs are classified in increasing clinical severity with the Clinical Etiological Anatomical and Pathological system from C0 to C6. Limbs assessed at C3 through C6 meet the criteria of Chronic Venous Insufficiency. Chronic Venous Insufficiency of the Lower Limbs is a very common pathology affecting approximately ~40% of the world's population. This study observes the use of the LivRelief Varicose Vein Cream, a Natural Health Product that is licensed for sale by Health Canada, for use in the treatment of varicose veins. METHODS: An open label, single arm interventional, pilot study was conducted to determine the feasibility of recruitment and data collection in this population. To accomplish this, the cream was provided to all enrolled subjects. Subsequently, objective and subjective measures were performed at baseline and after 6 weeks of at-home use. Recruitment and data collection targets of at least 70% were established and the data collected at both timepoints were compared and analyzed using a paired t-test. Results were also reported as proportions where appropriate. RESULTS: A total of 32 subjects were enrolled. The pre-defined feasibility objectives for recruitment and data collection were met with the enrolment of 97% of all screened patients and the collection of 94% of all scheduled data. The most significant therapeutic improvement was seen in the results of the Venous Clinical Severity Score where 66% of the treated legs experienced a decrease in severity after 6 weeks of treatment. P values were <0.0001 and 0.0003 for the left and right leg, respectively. CONCLUSION: It is feasible to recruit and collect data with the chosen outcome assessments within this population. Preliminary results suggest that the product could improve some of the clinical symptoms associated with the presence varicose veins. These results warrant further exploration in a longer, randomized and placebo-controlled study. TRIAL REGISTRATION: Clinicaltrial.gov: NCT03653793.