ABSTRACT
MicroRNAs (miRNAs) are an abundant class of small noncoding RNA molecules that play an important role in the regulation of gene expression at the posttranscriptional level. Due to their ability to simultaneously modulate the fate of different genes, these molecules are particularly well suited to act as key regulators during immune cell differentiation and activation, and their dysfunction can contribute to pathological conditions associated with neuroinflammation. Recent studies have addressed the role of miRNAs in the differentiation of progenitor cells into microglia and in the activation process, aiming at clarifying the origin of adult microglia cells and the contribution of the central nervous system (CNS) environment to microglia phenotype, in health and disease. Altered expression of several miRNAs has been associated with Alzheimer's disease, multiple sclerosis, and ischemic injury, hence strongly advocating the use of these small molecules as disease markers and new therapeutic targets. This review summarizes the recent advances in the field of miRNA-mediated regulation of microglia development and activation. We discuss the role of specific miRNAs in the maintenance and switching of microglia activation states and illustrate the potential of this class of nucleic acids both as biomarkers of inflammation and new therapeutic tools for the modulation of microglia behavior in the CNS.
Subject(s)
Central Nervous System/immunology , MicroRNAs/immunology , Microglia/immunology , Neurodegenerative Diseases/immunology , Biomarkers/metabolism , Cell Differentiation , Central Nervous System/drug effects , Central Nervous System/pathology , Cytokines/genetics , Cytokines/immunology , Gene Expression Regulation , Humans , Immunity, Innate/drug effects , Inflammation , Macrophage Activation , Macrophages/drug effects , Macrophages/immunology , Macrophages/pathology , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , Microglia/drug effects , Microglia/pathology , Neural Stem Cells/drug effects , Neural Stem Cells/immunology , Neural Stem Cells/pathology , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/pathology , Oligonucleotides, Antisense/pharmacologyABSTRACT
Brain disorders have been a health challenge and is increasing over the years. Early diagnosis and interventions are considered essential strategies to treat patients at risk of brain disease. Physical exercise has shown to be beneficial for patients with brain diseases. A type of exercise intervention known as whole-body vibration (WBV) exercise gained increasing interest. During WBV, mechanical vibrations, produced by a vibrating platform are transmitted, to the body. The purpose of the current review was to summarize the effects of WBV exercise on brain function and behavior in experimental studies with animal models. Searches were performed in EMBASE, PubMed, Scopus and Web of Science including publications from 1960 to July 2021, using the keywords "whole body vibration" AND (animal or mice or mouse or rat or rodent). From 1284 hits, 20 papers were selected. Rats were the main animal model used (75%) followed by mice (20%) and porcine model (5%), 16 studies used males species and 4 females. The risk of bias, accessed with the SYRCLE Risk of Bias tool, indicated that none of the studies fulfilled all methodological criteria, resulting in possible bias. Despite heterogeneity, the results suggest beneficial effects of WBV exercise on brain functioning, mainly related to motor performance, coordination, behavioral control, neuronal plasticity and synapse function. In conclusion, the findings observed in animal studies justifies continued clinical research regarding the effectiveness and potential of WBV for the treatment of various types of brain disorders such as trauma, developmental disorders, neurogenetic diseases and other neurological diseases.
Subject(s)
Brain Diseases , Physical Conditioning, Animal , Animals , Brain Diseases/therapy , Female , Male , Mice , Physical Conditioning, Animal/physiology , Rats , Swine , Vibration/therapeutic useABSTRACT
Since clinical application of conventional cancer therapies is usually limited by drug resistance and toxic side effects, combination of chemotherapeutic agents with gene therapy appears as an attractive therapeutic strategy to overcome these issues. Being selectively expressed in tumor tissues, survivin is a promising target for the development of anticancer strategies aimed at eliminating tumor cells while sparing normal tissues. In this work, we achieved substantial protein knockdown in a number of human cell lines, namely, A549, HeLa and MCF-7 cells which overexpress survivin, after treatment with anti-survivin siRNAs, which was associated with a significant reduction of cell viability, when compared to treatment with control siRNAs. Interestingly, when the survivin-silencing approach was combined with a chemotherapeutic agent, an enhancement of the therapeutic effect was achieved. Treatment with anti-survivin siRNAs resulted in high levels of caspase 3/7 activation, and an enhancement of this effect was observed when survivin silencing was combined with vinblastine. In addition, we showed that for A549 and HeLa cells survivin silencing contributes to the reversion of cell resistance to doxorubicin. Overall, we demonstrate that the combination of a survivin-directed silencing strategy with chemotherapeutic agents constitutes a valuable approach for cancer treatment.
Subject(s)
Doxorubicin/pharmacology , Inhibitor of Apoptosis Proteins/metabolism , Antibiotics, Antineoplastic/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Blotting, Western , Caspase 3/metabolism , Caspase 7/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/genetics , Flow Cytometry , HeLa Cells , Humans , Inhibitor of Apoptosis Proteins/genetics , RNA, Small Interfering/genetics , RNA, Small Interfering/physiology , Reverse Transcriptase Polymerase Chain Reaction , Survivin , Vinblastine/pharmacologyABSTRACT
Central nervous system (CNS) diseases constitute a set of challenging pathological conditions concerning diagnosis and therapeutics. For most of these disorders, there is a lack of early diagnosis, biomarkers to allow proper follow-up of disease progression and effective therapeutic strategies to allow a persistent cure. The poor prognosis of most CNS diseases is, therefore, a global concern, especially regarding chronic age-related neurodegenerative disorders, which are already considered problems of public health due to the increasing average of life expectancy. The difficulties associated with the treatment of CNS diseases are owed, at least in part, to very specific characteristics of the brain and spinal cord, when compared to peripheral organs. In this regard, the CNS is physically and chemically protected by the blood-brain barrier (BBB), which, while maintaining essential brain homeostasis, significantly restricts the delivery of most therapeutic agents to the brain parenchyma. On the other hand, regenerative properties of the tissue are lacking, meaning that a CNS insult resulting in neuronal death is a permanent phenomenon. Approaches for transposing the BBB aiming to treat CNS diseases, relying on specific properties of nanosystems, have been reported for therapeutic delivery to CNS without interfering with the normal function of the brain. In this chapter, we address the latest advances concerning the principles of such approaches, employing lipid-based nanoparticles and cell-produced exosomes as drug and nucleic acid delivery systems, and summarize recent example of applications in the context of neurological diseases. Major achievements obtained in preclinical studies and the trends identified by these studies are emphasized to provide new prospects for further developments in this area, thus enabling us to move from the research realm to the clinical arena.
Subject(s)
Central Nervous System Diseases/drug therapy , Exosomes , Nanoparticles/therapeutic use , Nanotechnology/trends , Animals , Drug Delivery Systems , Humans , Lipids/administration & dosage , Nanoparticles/administration & dosageABSTRACT
Childhood obesity is an increasing problem at the global level and considered as a risk factor for obesity development and the associated co-morbidities in adult life. In this study, the occurrence of Bacteroides fragilis group, Clostridium spp., Bifidobacterium spp. and Escherichia coli in 84 faecal samples from 30 obese, 24 overweight and 30 lean children was verified by culture technique and quantitative determination by quantitative PCR. In addition, Lactobacillus spp. and Methanobrevibacter smithii were also analysed. A correlation between the body mass index (BMI) and these bacteria was sought. Bacteroides vulgatus, Clostridium perfringens and Bifidobacterium adolescentis were most prevalent in all samples evaluated by culture-method. The B. fragilis group were found at high concentrations in obese and overweight children when compared with the lean ones (p 0.015). The obese and overweight children harboured higher numbers of Lactobacillus spp. than lean children (p 0.022). The faecal concentrations of the B. fragilis group (r = 0.24; p 0.026) and Lactobacillus spp. (r = 0.44; p 0.002) were positively correlated with BMI. Bifidobacterium spp. were found in higher numbers in the lean group than the overweight and obese ones (p 0.042). Furthermore, a negative correlation between BMI and Bifidobacterium spp. copy number (r = -0.22; p 0.039) was observed. Our findings show some difference in the intestinal microbial ecosystem of obese children compared with the lean ones and a significant association between number of Lactobacillus spp. and B. fragilis group and BMI.
Subject(s)
Body Mass Index , Feces/microbiology , Gastrointestinal Microbiome , Brazil/epidemiology , Child , Child, Preschool , Female , Humans , Male , Metagenome , Metagenomics/methods , Microbiota , Obesity/epidemiology , Obesity/etiology , RNA, Ribosomal, 16S/genetics , Risk FactorsABSTRACT
The convenience of combining the measurement of antibodies to glutamic acid decarboxylase (GADA), protein tyrosine phosphatase (IA-2A), and autoantibodies to insulin (IAA) in diabetic patients was assessed. We analysed 71 type 1 and 115 adult-onset diabetic patients. The latter were grouped into three categories according to the time of evolution to insulin dependence. The main findings were as follows: (i) in type 1 diabetes, the combined analysis of GADA and IA-2A showed a sensitivity of 87.4% and was not appreciably improved by adding IAA; (ii) out of 31 adults who required insulin immediately or within the first two years of diagnosis, 41.9, 29.0, and 6.5% were positive for at least one, two or all three, and all three markers, respectively; GADA was the most prevalent (35.5%) and IA-2A the least represented (16.1%); (iii) 34 adult patients with slow evolution to insulin dependence showed a completely different profile: 5.9% were GADA positive and 23.5% were IAA positive and no double or triple positivity was observed as all patients were IA-2A negative; and (iv) 50 type 2 patients who had not required insulin treatment showed a low incidence of GADA (4%) as the only marker present. We conclude that a combined double-antigen test for GADA and IA-2A is a useful strategy for prospective screening of type 1 diabetes. However, in adults, the profile of individual markers discloses the course to insulin dependence. Therefore, it seems advisable to measure the markers separately, to allow a better classification of these patients, and help define their treatment.
Subject(s)
Autoantibodies/blood , Diabetes Mellitus, Type 2/immunology , Glutamate Decarboxylase/immunology , Insulin/immunology , Protein Tyrosine Phosphatases/immunology , Adolescent , Adult , Argentina , Biomarkers , Child , Diabetes Mellitus, Type 1/classification , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 2/classification , Female , Humans , Male , Middle Aged , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Radioligand AssayABSTRACT
OBJECTIVE: To characterize the type of malnutrition and to determine the usefulness of anthropometric indices in children with chronic liver disease (CLD). METHODS: 11 children (aged 5 - 105 mo) with CLD underwent anthropometric evaluation when they were clinically stable. The nutritional evaluation was made by the determination of Weight/Age (W/A), Height/Age (H/A) and Weight/Height (W/E) Z scores. The nutritional evaluation by Waterlow's method was also made. The fat and protein body deposits were estimated by triceps skinfold and midarm muscular circumference measurements. The analysis of the 24-hour recall was used to evaluate the quality and pattern of the feeding. RESULTS: The mean weight / age (W/A = -1.18) and height / age (H/A = - 1.26) Z scores were depressed under 1 SD, whereas mean weight / height (W/H) Z score was normal. The interpretation of the nutritional evaluation by Waterlow's method shows normal mean of the weight and almost normal mean of the height. Only three patients had normal triceps skinfold thickness (TSF) Z score, and the same occurred with five of them with the midarm muscular circumference. The quality and pattern of the feeding was adequate in only 4 patients. CONCLUSIONS: We conclude that chronic malnutrition is common in childhood CLD and that weight/height values underestimate the degree of acute malnutrition compared with TSF thickness, most likely because of the inflated patient weight caused by organomegaly. The reduction of the triceps skinfold thickness best reflected the nutritional impairment of the patients. The quality of feeding of the patients was mostly inadequate.
ABSTRACT
OBJECTIVE: To evaluated the effect of short-term oral supplementation in the nutritional status of 14 patients with cystic fibrosis in 19 hospital admissions. METHODS: All patients received standard pulmonary therapy, and to 13 patients (Group I = GI) a high-fat oral supplement was offered besides the standard diet. The control group (GII) received the same diet except for the supplement. Anthropometric measurements, quantitative assessment of energy intake and serum biochemical parameters were determined on admission and prior to discharge from hospital. RESULTS: There was no difference in the weight gain between groups (median: GI=+1000 g; GII=+550 g), nor in the variations of height, skinfolds and body fat. Z scores were calculated (mean-/+SD: weight/age, GI=-2.19-/+1.0, GII=-2.57-/+1.1; height/age, GI=-1.73-/+1.4, GII=-2.06-/+1.4 ), showing that those patients had chronic severe malnutrition, with no changes in Z Score in this period. The diet offered to the patients provided the RDA for calories only in the supplemented group, and this value was significantly higher compared to the non-supplemented group (mean -/+ SD : GI= 146-/+20% RDA; GII=105-/+13%RDA). The energy intake was significantly higher in group I (mean-/+SD: GI=126-/+22%RDA; GII= 81-/+27%RDA), and it increased significantly by the end of admission in this group. The biochemical assessment revealed low levels of prealbumin in both groups on admission (mean-/+SD: GI=11-/+10mg/dl; GII=8-/+8 mg/dl), with significant increase only in group I (mean-/+SD: GI=23-/+15 mg/dl; GII=8-/+11 mg/dl). No variations in the levels of triglycerides were observed, but the cholesterol levels increased significantly in both groups. CONCLUSIONS: Although the weight gain was similar in both groups, prealbumin increased only in the supplemented group. This group had a higher energy intake than the non-supplemented one, and it reached the RDA for calories.
ABSTRACT
Avian mycoplasmosis causes great economic losses to the poultry industry, and one of the major agents involved is Mycoplasma synovie (MS). Serum from commercial poultry breeders (n = 2781) was tested for MS by serum plate agglutination (SPA), hemagglutination inhibition (HI), and enzyme-linked immunosorbent assay (ELISA). From 2,781 samples tested, 736 (26.46%) were positive in SPA. From 712 SPA-positive sera, 30 samples (4.21%) were positive in HI, and 150 samples (21.06%) were positive in ELISA. Copositivity between ELISA and HI was 90%, and conegativity was 82.0%. Agreement between HI and ELISA was rejected by McNemar's test (P ≤ .001), and Kappa coefficient showed a weak correlation between the two techniques (k = 0.25; 0.21 ≤ k < 0.40). Weak statistical correlation was observed between all serological tests (SPA, HI, and ELISA), and they should only be used for initial screening for MS.
ABSTRACT
Excitotoxicity is one of the main features responsible for neuronal cell death after acute brain injury and in several neurodegenerative disorders, for which only few therapeutic options are currently available. In this work, RNA interference was employed to identify and validate a potential target for successful treatment of excitotoxic brain injury, the transcription factor c-Jun. The nuclear translocation of c-Jun and its upregulation are early events following glutamate-induced excitotoxic damage in primary neuronal cultures. We present evidence for the efficient knockdown of this transcription factor using a non-viral vector consisting of cationic liposomes associated to transferrin (Tf-lipoplexes). Tf-lipoplexes were able to deliver anti-c-Jun siRNAs to neuronal cells in culture, resulting in efficient silencing of c-Jun mRNA and protein and in a significant decrease of cell death following glutamate-induced damage or oxygen-glucose deprivation. This formulation also leads to a significant c-Jun knockdown in the mouse hippocampus in vivo, resulting in the attenuation of both neuronal death and inflammation following kainic acid-mediated lesion of this region. Furthermore, a strong reduction of seizure activity and cytokine production was observed in animals treated with anti-c-Jun siRNAs. These findings demonstrate the efficient delivery of therapeutic siRNAs to the brain by Tf-lipoplexes and validate c-Jun as a promising therapeutic target in neurodegenerative disorders involving excitotoxic lesions.
Subject(s)
Drug Carriers/chemistry , Gene Silencing/drug effects , Neurons/drug effects , Neuroprotective Agents/administration & dosage , Proto-Oncogene Proteins c-jun/genetics , RNA, Small Interfering/administration & dosage , Transferrin/chemistry , Animals , Blotting, Western , Cell Culture Techniques , Cell Survival/drug effects , Cells, Cultured , Cholesterol/chemistry , Drug Compounding , Fatty Acids, Monounsaturated/chemistry , Glutamic Acid/toxicity , Humans , Immunohistochemistry , Kainic Acid/toxicity , Liposomes , Mice , Mice, Inbred C57BL , Neurons/metabolism , Neurons/pathology , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Protein Transport , Proto-Oncogene Proteins c-jun/antagonists & inhibitors , Quaternary Ammonium Compounds/chemistry , RNA, Small Interfering/pharmacology , RNA, Small Interfering/therapeutic use , Reverse Transcriptase Polymerase Chain Reaction , Seizures/drug therapy , Seizures/metabolism , Seizures/pathologySubject(s)
Ethics Committees , Biological Science Disciplines , Ethics , Human Rights , Humans , PortugalABSTRACT
Although RNAi-based gene silencing holds a great potential for treatment of neurological disorders, its application to the CNS has been restricted by low levels of tissue distribution and cellular uptake. In this work we report that cationic lipid-based vectors can enhance siRNA delivery to neurons both in vitro and in vivo. DOTAP:Chol liposomes associated with transferrin (Tf) and complexed with siRNAs (Tf-lipoplexes) were delivered to primary cultures of luciferase-expressing cortical neurons. Confocal microscopy studies revealed efficient cellular uptake of Cy3-labelled siRNAs after Tf-lipoplex delivery, which was reduced but not completely inhibited by blocking the Tf-receptor with excess Tf. Gene silencing was also evaluated after delivery of anti-luciferase or anti-c-Jun siRNAs. Our results demonstrate that Tf-lipoplexes achieve up to 50% luciferase and c-Jun knockdown, 48 h after transfection, without significant cytotoxicity. Similar results were observed in vivo, where a 40% reduction of luciferase activity was found in the striatum of luciferase mice. In addition, fluorescence microscopy studies showed extensive local distribution and internalization of Tf-lipoplex-associated Cy3-siRNAs without tissue toxicity. Overall, our results demonstrate that Tf-lipoplexes can mediate efficient gene silencing in neuronal cells, both in vitro an in vivo, which may prove useful in therapeutic approaches to neuronal protection and repair.
Subject(s)
Central Nervous System/metabolism , Drug Delivery Systems/methods , Gene Silencing , Neurons/metabolism , RNA, Small Interfering/administration & dosage , Animals , Brain/metabolism , Cell Nucleus/metabolism , Cell Survival , Cells, Cultured , Cholesterol/chemistry , Cytoplasm/metabolism , Fatty Acids, Monounsaturated/chemistry , Gene Expression , JNK Mitogen-Activated Protein Kinases/genetics , JNK Mitogen-Activated Protein Kinases/metabolism , Lipids/chemistry , Liposomes/chemistry , Liposomes/toxicity , Luciferases/genetics , Luciferases/metabolism , Mice , Mice, Inbred C57BL , Mice, Transgenic , Microscopy, Confocal , Microscopy, Fluorescence , Neurons/drug effects , Quaternary Ammonium Compounds/chemistry , RNA, Small Interfering/genetics , Transfection , Transferrin/chemistry , Transferrin/genetics , Transferrin/metabolismABSTRACT
BACKGROUND: RNA interference provides a powerful technology for specific gene silencing. Therapeutic applications of small interfering RNA (siRNA) however require efficient vehicles for stable complexation, protection, and extra- and intracellular delivery of these nucleic acids. Here, we evaluated the potential of transferrin (Tf)-associated liposomes for siRNA complexation and gene silencing. METHODS: Cationic liposomes composed of DOTAP : Cholesterol associated with or without transferrin (Tf) were complexed with siRNA at different lipid/siRNA charge ratios. Complexation and protection of siRNA from enzymatic degradation was assessed with the PicoGreen intercalation assay and gel electrophoresis. Cellular internalization of these siRNA Tf-lipoplexes was detected by confocal microscopy. Luciferase assay, immunoblot and fluorescence-activated cell sorting (FACS) analysis were used to evaluate reporter gene silencing in Huh-7 hepatocarcinoma and U-373 glioma cells. c-Jun knockdown in HT-22 cells was evaluated by quantitative real-time polymerase chain reaction (RT-PCR). Cytotoxicity of the siRNA complexes was assessed by Alamar blue, lactate dehydrogenase and MTT assays. RESULTS: Complexation of siRNA with the cationic liposomes in the presence of Tf results in the formation of stable particles and prevents serum-mediated degradation. Confocal microscopy showed fast cellular internalization of the Tf-lipoplexes via endocytosis. In the GFP glioma cells Tf-lipoplexes showed enhanced gene silencing at minimum toxicity in comparison to Tf-free lipoplexes. Targeting luciferase in the hepatocarcinoma cell line resulted in more than 70% reduction of luciferase activity, while in HT-22 cells 50% knockdown of endogenous c-Jun resulted in a significant protection from glutamate-mediated toxicity. CONCLUSIONS: Cationic liposomes associated with Tf form stable siRNA lipoplexes with reduced toxicity and enhanced specific gene knockdown activity compared to conventional lipoplexes. Thus, such formulations may constitute efficient delivery systems for therapeutic siRNA applications.
Subject(s)
Genetic Therapy/methods , Liposomes/chemistry , Neoplasms/therapy , RNA Interference , RNA, Small Interfering/administration & dosage , Transferrin/metabolism , Cations , Cell Line, Tumor , Fatty Acids, Monounsaturated/chemistry , Fluorescence , Gene Transfer Techniques , Genes, Reporter , Genetic Vectors/chemistry , Green Fluorescent Proteins/antagonists & inhibitors , Green Fluorescent Proteins/genetics , Humans , JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , JNK Mitogen-Activated Protein Kinases/genetics , Lipids/chemistry , Liposomes/metabolism , Quaternary Ammonium Compounds/chemistry , RNA, Small Interfering/chemistry , RNA, Small Interfering/therapeutic use , Transferrin/chemistryABSTRACT
1. Our objective was to evaluate the toxic effects of aflatoxin B1 (AFB1) and fumonisin B1 (FB1), administered singly or in combination to broilers. 2. Feeds were prepared with concentrations equal to 0, 50 and 200 microg AFB1/kg, and/or 0, 50 and 200 mg FB1/kg, and offered to broiler chicks from 8 to 41 d of age. The experimental design was totally randomised, in a 3 x 3 factorial arrangement with 9 treatments and 12 birds per treatment. Animals were vaccinated against Newcastle disease on d 14 of life and killed at 41 d. 3. Compared with controls, all mycotoxin-treated groups at 41 d had lower body weight and weight gain, and higher relative heart weight. The relative weight of the liver increased only in birds fed diets containing 200 mg FB1, singly or in combination with AFB1. 4. At 35 d, all groups receiving mycotoxin-treated rations had reduced geometrical mean antibody titres, with birds from groups fed combinations of AFB1 and FB1/kg having even lower values, when compared to the other groups. 5. Histological changes were observed only in liver from birds fed mycotoxin-contaminated rations, and in kidneys of birds fed the diet containing 200 microg AFB1 and 200 mg FB1/kg. Main alterations included vacuolar degeneration and cell proliferation of bile ducts in the liver, and hydropic degeneration in renal tubules in the kidneys. 6. We concluded that AFB1 and FB1 in combination have primarily additive effects on body weight, liver structure and immunological response of broilers at the concentrations used.
Subject(s)
Aflatoxin B1/toxicity , Body Weight/drug effects , Fumonisins/toxicity , Mycotoxicosis/immunology , Poultry Diseases/immunology , Animal Feed , Animals , Antibodies, Viral/blood , Chickens , Kidney/pathology , Liver/pathology , Male , Newcastle Disease/prevention & control , Random Allocation , Viral Vaccines/immunologyABSTRACT
The development of efficient systems for in vivo gene transfer to the central nervous system (CNS) may provide a useful therapeutic strategy for the alleviation of several neurological disorders. In this study, we evaluated the feasibility of nonviral gene therapy to the CNS mediated by cationic liposomes. We present evidence of the successful delivery and expression of both a reporter and a therapeutic gene in the rodent brain, as evaluated by immunohistochemical assays. Our results indicate that transferrin-associated cationic liposome/DNA complexes (Tf-lipoplexes) allow a significant enhancement of transfection activity as compared to plain complexes, and that 8/1 (+/-) Tf-lipoplexes constitute the best formulation to mediate in vivo gene transfer. We demonstrated that Tf-lipoplex-mediated nerve growth factor transgene expression attenuates the morphological damages of the kainic acid-induced lesion as assessed by 2,3,5-triphenyltetrazolium chloride (TTC) vital staining. These findings suggest the usefulness of these lipid-based vectors in mediating the delivery of therapeutic genes to the CNS.
Subject(s)
Brain Injuries/therapy , Genetic Therapy/methods , Nerve Growth Factor/genetics , Transfection/methods , Animals , Brain/metabolism , Brain Chemistry , Brain Injuries/metabolism , Corpus Striatum , Gene Expression , Immunohistochemistry/methods , Injections , Kainic Acid , Liposomes , Male , Models, Animal , Nerve Growth Factor/analysis , Rats , Rats, Wistar , Transferrin/genetics , Transferrin/metabolismABSTRACT
Few studies have tried to characterize the efficacy of parenteral support of critically ill infants during short period of intensive care. We studied seventeen infants during five days of total parenteral hyperalimentation. Subsequently, according to the clinical conditions, the patients received nutritional support by parenteral, enteral route or both up to the 10th day. Evaluations were performed on the 1st, 5th, and 10th days. These included: clinical data (food intake and anthropometric measurements), haematological data (lymphocyte count), biochemical tests (albumin, transferrin, fibronectin, prealbumin, retinol-binding protein) and hormone assays (cortisol, insulin, glucagon). Anthropometric measurements revealed no significant difference between the first and second evaluations. Serum albumin and transferrin did not change significantly, but mean values of fibronectin (8.9 to 16 mg/dL), prealbumin (7.7 to 18 mg/dL), and retinol-binding protein (2.4 to 3. 7 mg/dL) increased significantly (p < 0.05) from the 1st to the 10th day. The hormonal study showed no difference for insulin, glucagon, and cortisol when the three evaluations were compared. The mean value of the glucose/insulin ratio was of 25.7 in the 1st day and 15. 5 in the 5th day, revealing a transitory supression of this hormone. Cortisol showed values above normal in the beginning of the study. We conclude that the anthropometric parameters were not useful due to the short time of the study; serum proteins, fibronectin, prealbumin, and retinol-binding protein were very sensitive indicators of nutritional status, and an elevated glucose/insulin ratio, associated with a slight tendency for increased cortisol levels suggest hypercatabolic state. The critically ill patient can benefit from an early metabolic support.
Subject(s)
Critical Illness , Nutrition Assessment , Parenteral Nutrition , Anthropometry , Blood Glucose , Enteral Nutrition , Female , Follow-Up Studies , Humans , Hydrocortisone/blood , Infant , Infant, Newborn , Insulin/blood , Male , Respiratory Distress Syndrome, Newborn/diet therapy , Severity of Illness Index , Statistics, NonparametricABSTRACT
OBJECTIVES: A nutritional evaluation of infants born from HIV seropositive mothers was carried out during their follow up and diagnostic investigation. The energy balance (EB) of infected and noninfected children were compared. METHODS: The energy balance (intake energy, fecal energy, and resting energy expenditure) was prospectively determined by indirect calorimetry, considering 13 infants (6 girls and 7 boys) between 1 and 6 months of age, born from HIV positive mothers. This was made in two opportunities: before and after the diagnosis of the disease. A full nutritional assessment, including clinical examination and anthropometric measures (weight, height and skinfold thickness), was also determined in these two opportunities. After the definite diagnosis, the infants were finally assembled in 2 different groups: infected (5 in 13) and noninfected (8 in 13). The children were monthly submitted to clinical evaluations and orientation, during all the study. RESULTS: By analyzing the anthropometric measures of the two groups, it was observed that the infected group had malnutritional manifestations since the first evaluation. The resting energy expenditure (kcal/kg/dia) of the infected group was higher than that of the noninfected group: 64.5-/+16.8 vs 48.0-/+5.7 (p<0.05) at the first evaluation and 68.0-/+11.7 vs 51.8-/+3.1 (p<0.05) at the second, respectively. CONCLUSION: The higher resting energy expenditure of the children in the infected group might be the cause of the protein energy malnutrition during the asymptomatic phase when the diagnosis was uncertain.
ABSTRACT
O interesse pelos bioensaios frente à larvas de Aedes aegypti e Culex quinquefasciatus deve-se ao fato de que estas espécies estão distribuídas por todo o território nacional, sendo portanto uma atividade realizada por inúmeros pesquisadores do Brasil. Os óleos essenciais de Syzigium aromaticum (L.) Merr. & Perry, Lippia sidoides Cham.,e Hyptis martiusii Benth.,foram testados no combate ao transmissor da dengue e da filariose. As larvas de terceiro estádio foram expostas em triplicatas a diferentes concentrações (1000, 500, 250, 100, 50, 25 e 10 ppm). As análises foram observadas após dez minutos do início do tratamento, e mostraram resultados bastante significativos, com potencialidade de mortalidade de até 100 por cento das larvas testadas, indicando acentuados efeitos tóxicos de alguns constituintes voláteis presentes nos óleos. Para os óleos de S. aromaticum, L. sidoides e H. martiusii foram constatadas, frente à Aedes aegypti, valores respectivos de CL50 de 21,4; 19,5 e 18,5 ppm e frente ao Culex quinquefasciatus, 14,5; 16,6 e 27,5 ppm, respectivamente.
The interest for a biological assay against larvae of Aedes aegypti and Culex quinquefasciatus is due to the fact that these species are distributed by the whole national territory, being therefore an activity carried out by countless researchers of Brazil. The essential oils of Syzigium aromaticum, Hyptis martiusii and Lippia sidoides were tested in the combat of the transmitter of the dengue and of the filariosis, using larvae of third stadium were exposed in triplicate to different concentrations (1000, 500, 250, 100, 50, 25 and 10 ppm). The larvicidal activity was observed after ten minutes of the beginning of the treatment, in the end showed very significant results, with mortality potentials of up to 100 percent of the tested larvae, indicating accentuated toxical effects in some representatives of the volatile compounds present in the oils. For the oils of S. aromaticum, L. sidoides and H. martiusii DL50 of 1,0; 1,0 and 8,0 ppm, respectively, were observed.