Miracle-dz/UniFAR-FTUs huggingface dataset:
The application of nanosponges to cancer drug delivery

Introduction: The design of new nanocarriers as a strategy for the delivery of anti-cancer drugs offers a potential platform to overcome some limitations of current clinical treatments and to achieve targeted release into tumour tissues. Cyclodextrin-based nanosponges are a novel nanosized delivery system composed of hyper-cross-linked cyclodextrins connected in a three-dimensional network. They form porous nanoparticles with sizes lower than 500 nm, spherical shape and negative surface charge. They show a good capacity for incorporating small molecules, macromolecules, ions and gases within their structure. Area covered: This review will describe some applications of cyclodextrin-based nanosponges as carriers for anticancer drugs. Recent smart nanosponges, able to be responsive to an external stimulus, will be also discussed. In vitro and in vivo experimental results, obtained with currently used molecules, such as paclitaxel, doxorubicin, 5-fluorourcil and tamoxifen, will be shown. Expert opinion: Cyclodextrin-based nanosponges can be considered a challenging technology for the development of innovative formulations, suitable for various administration routes for anti-cancer drugs.
Recent advances in curcumin nanoformulation for cancer therapy

Introduction: Natural compounds are emerging as effective agents for the treatment of malignant diseases. Curcumin (diferuloylmethane), the active constituent of turmeric extract, has gained significant interest as a plant-based compound with anti-cancer properties. Curcumin is physiologically very well tolerated, with negligible systemic toxicity observed even after high oral doses administration. Despite curcumin’s superior properties as an anti-cancer agent its applications are limited due to its low solubility and physico-chemical stability, rapid systemic clearance and low cellular uptake. Areas covered: This review focuses on the development of curcumin nano-particle formulation to improve its therapeutic index through enhanced cellular uptake, localization to targeted areas and improved bioavailability. The feasibility of nano-formulation in delivering curcumin and the limitations and challenges in designing and administrating the nano-sized curcumin particles are also covered in this review. Expert opinion: Nanotechnology is a promising tool to enhance efficacy and delivery of drugs. In this context, formulation of curcumin as nano-sized particles could reduce the required therapeutic dosages and subsequently reduced its cell toxicity. These nanoparticles are capable to provide local delivery of curcumin targeted to specific areas and thereby preventing systemic clearance. In addition, using specific coating, better pharmacokinetic and internalization of nano-curcumin could be achieved. However, the potential toxicity of nano-carriers for curcumin delivery is an important issue, which should be taken into account in curcumin nano-formulation.
Extracellularly activatable nanocarriers for drug delivery to tumors

Introduction: Nanoparticles (NPs) for drug delivery to tumors need to satisfy two seemingly conflicting requirements: they should maintain physical and chemical stability during circulation and be able to interact with target cells and release the drug at desired locations with no substantial delay. The unique microenvironment of tumors and externally applied stimuli provide a useful means to maintain a balance between the two requirements. Areas covered: We discuss nanoparticulate drug carriers that maintain stable structures in normal conditions but respond to stimuli for the spatiotemporal control of drug delivery. We first define the desired effects of extracellular activation of NPs and frequently used stimuli and then review the examples of extracellularly activated NPs. Expert opinion: Several challenges remain in developing extracellularly activatable NPs. First, some of the stimuli-responsive NPs undergo incremental changes in response to stimuli, losing circulation stability. Second, the applicability of stimuli in clinical settings is limited due to the occasional occurrence of the activating conditions in normal tissues. Third, the construction of stimuli-responsive NPs involves increasing complexity in NP structure and production methods. Future efforts are needed to identify new targeting conditions and increase the contrast between activated and nonactivated NPs while keeping the production methods simple and scalable.
Carbon nanotubes part II: a remarkable carrier for drug and gene delivery

Introduction: Carbon nanotubes (CNT) have recently been studied as novel and versatile drug and gene delivery vehicles. When CNT are suitably functionalized, they can interact with various cell types and are taken up by endocytosis. Areas covered: Anti-cancer drugs cisplatin and doxorubicin have been delivered by CNT, as well as methotrexate, taxol and gemcitabine. The delivery of the antifungal compound amphotericin B and the oral administration of erythropoietin have both been assisted using CNT. Frequently, targeting moieties such as folic acid, epidermal growth factor or various antibodies are attached to the CNT-drug nanovehicle. Different kinds of functionalization (e.g., polycations) have been used to allow CNT to act as gene delivery vectors. Plasmid DNA, small interfering RNA and micro-RNA have all been delivered by CNT vehicles. Significant concerns are raised about the nanotoxicology of the CNT and their potentially damaging effects on the environment. Expert opinion: CNT-mediated drug delivery has been studied for over a decade, and both in vitro and in vivo studies have been reported. The future success of CNTs as vectors in vivo and in clinical application will depend on achievement of efficacious therapy with minimal adverse effects and avoidance of possible toxic and environmentally damaging effects.
Discovery of New Drugs Against Tuberculosis: History Guides

: Treatment of tuberculosis was an obstacle for ages. In spite of good drugs, the disease is not under control. Thus, the need for more drugs existed. Searching for a new drug demands much investment on the time, money and human resources. There are many drugs with antitubercular action that are discovered and explored in the last century. The most common drug, Isoniazid, is now a frontrunner anti-tubercular drug. Like the same antitubercular effect of Trifluoperazine which is known since 1990s, but due to the lack of research its anti-tubercular potential is not yet explored completely.
Expression of stem cell-related genes in the endometrium and endometriotic lesions: a pilot study

Abstract Objective: To compare the expression of stem cell-related genes in the endometrium (END), superficial endometriosis (SE), and deep infiltrating endometriosis (DIE). Study design: We performed a prospective pilot study of six women suffering from SE and DIE who gave consent for laparoscopy surgery, endometrial biopsies, and participation in this study. Quantitative RT-PCR analysis of 84 stem cell-related genes was performed in 18 biopsy samples. Results: A total of 40 of 84 genes were expressed in SE and DIE, but were different from END as follows. Seven genes were over-expressed in SE and 33 genes were under-expressed in DIE compared with END. Two genes were only over-expressed in SE and three genes were only over-expressed in DIE. Six under-expressed genes were exclusively located in SE and one was only located in DIE. The remaining 31 genes were not different among the groups. There was no significant difference in gene expression between SE and DIE samples. Conclusion: Tissue of DIE and SE appears to have similar stem cell-related genes. Nevertheless, there are differences in gene expression between SE and DIE.
The impact of maternal hypothyroidism during pregnancy on neonatal outcomes: a systematic review and meta-analysis

Abstract The effects of maternal hypothyroidism on neonatal outcomes were not definitely confirmed. We conduct a systematic review of the literatures on the impact of maternal hypothyroidism on neonatal outcomes. We searched Pubmed, Embase and the Cochrane Controlled Trials Register databases complemented by manual searches in article references without language restrictions published from 1946 to April 2015. Nine trials are included. For preterm birth in pregnancies of hypothyroidism women, there is an increased tendency (RR 1.18; 95% CI 0.99 to 1.40; p = 0.06). The same result is seen relating to the low birth weight (RR 1.31; 95% CI 1.00 to 1.72; p = 0.05). Regarding small for gestational age there is no significant increase. Children who were born from mothers with hypothyroidism during pregnancy have increased birth weight (MD 32.35, 95% CI 7.46 to 57.24; p = 0.01). The impact of maternal hypothyroidism shows a trend of reduced risk of large for gestational age (RR 1.17; 95% CI 0.99 to 1.38; p = 0.06). Our review suggests that mothers with hypothyroidism during pregnancy are more likely to give birth to children with higher birth weight or LGA, and L-T4 supplementation should be recommended. The risk of preterm birth and low birth weight also tends to be higher in children with hypothyroidism mothers.
How different measures of cold weather affect chronic obstructive pulmonary disease (COPD) hospital admissions in London

Many COPD sufferers find that their symptoms become worse during colder weather, which can lead to an exacerbation resulting in hospital admission. This study investigates different measures of cold, assessing which most strongly relate to COPD admissions and whether they can be used to forecast risk of exacerbation. COPD admissions (ICD10 J40–J44) for the five Strategic Health Authorities (SHAs) in London and corresponding meteorological data were extracted for October–March 1997–2003. Correlations and regressions were used to compare the effects on admissions of: daily mean, maximum and minimum temperature; significant drops in temperature; weekly average maximum temperature; “cumulative cold”, summing the number of degrees the daily maximum temperature was below a threshold across a week; different windchill indices. All measures of cold showed significant negative correlations with COPD admissions. Daily relationships were weaker than weekly ones (R = −0.19, p<0.001 for daily maximum temperature, R = −0.36, p<0.001 for weekly average maximum temperature) but are most significant with an 8-day lag. Windchill had the strongest correlation with one-week lag (R = −0.397, p<0.001) accounting for 20% of the variation in admissions. “Cumulative cold” is also significant at p<0.001, ranging from R = 0.28 for a 3°C threshold to R = 0.36 for 18°C. Cold measures explain sufficient variation in COPD hospital admissions to be used in a forecast model of risk of exacerbation. The Met Office uses such a model in a health forecasting and anticipatory care service in England.
Use of polymerase chain reaction: Restriction fragment length polymorphism to detect acaricidal resistance to synthetic pyrethroids in Boophilus microplus ticks of South India

Background: Boophilus microplus is an important ectoparasite of livestock. Apart from transmitting diseases, heavy tick burden can decrease production and damage hides. The synthetic pyrethroids which are advantageous over other acaricides for treatment of this infestation are now losing their efficacy due to development of resistant strains of ticks. Materials and Methods: Boophilus microplus ticks with a previous history of acaricidal treatment especially synthetic pyrethroids (SP) such as cypermethrin, deltamethrin and flumethrin were randomly collected from different pockets of four Southern States of India namely Tamil Nadu, Kerala, Karnataka, Andhra Pradesh, and Puducherry from cattle. Deoxyribonucleic acid extracted from pooled adult B. microplus tick from each State was subjected to polymerase chain reaction-restriction fragment length polymorphism to detect point mutation in carboxyl esterase gene. Results: A product size of 372 bp was obtained for cattle tick samples collected from all over Southern States of India. Conclusions: B. microplus ticks found in Southern part of India are not resistant to commonly used SP.
Self-nano-emulsifying drug delivery systems: an update of the biopharmaceutical aspects

Introduction: Thirty percent of top marketed drugs in the USA and 70% of all new drug candidates are lipophilic and exhibit poor water solubility. With such physicochemical properties, the oral bioavailability of these compounds lacks dose proportionality, is very limited and extremely erratic. Different lipid-based formulations have been explored in the past few decades to improve the oral delivery of such compounds. In recent years, the most popular approach is their incorporation into self-emulsifying drug delivery systems (SEDDS), with particular emphasis on self-nano-emulsifying drug delivery systems (SNEDDS). Areas covered: This review offers an updated overview of SNEDDS application from the biopharmaceutical point of view. The focus of this review deals with the potential of SNEDDS utilization to overcome absorption barriers following oral administration of lipophilic drugs. This includes a comprehensive description of the primary mechanisms by which lipids and lipophilic excipients, used to formulate SNEDDS, could affect drug absorption, bioavailability and disposition following oral administration. Expert opinion: The utilization of SNEDDS to augment the oral bioavailability of poorly water-soluble drugs goes beyond improvement in drug’s solubility, as was initially presumed. In fact, SNEDDS have a potential to increase oral bioavailability by multi-concerted mechanisms such as reduced intra-enterocyte metabolism by CYP P450 enzymes, reduced P-glycoprotein (P-gp) efflux activity and hepatic first-pass metabolism bypass via lymphatic absorption. This unique biopharmaceutical point of view, presented in this review, contributes to the understanding of proper drug candidate selection and of the approach in SNEDDS formulation design.
Brain–blood ratio: implications in brain drug delivery

Introduction: The brain–blood ratio is an important model correlating the brain-targeting ability of neurotherapeutics with the CNS pharmacokinetics, which need to be presented before the scientific community for exploration of its scientific worth. The purpose of this article is to bring this key concept and its precise discussion to the attention of the researchers. Areas covered: Three major points are discussed herein: First, the significance of brain–blood ratio with respect to investigational neurotherapeutics, and carrier systems and correlation of its research findings with the brain targeting efficiency. Second, the various factors influencing the brain–blood ratio. Third, the various strategies for enhancing the brain–blood ratio. In addition, the benchmark criteria for CNS-likeness of drug molecules and the correlation of brain–blood ratio with brain targeting ability of neurotherapeutics have been tabulated. Expert opinion: The brain–blood ratio (also referred to as the brain–plasma ratio) represents one of the tools available today for estimation of CNS pharmacokinetics. It is preferred over other complicated techniques (in situ brain perfusion and microdialysis) due to its ease of use and practicality. We are optimistic that the brain–blood ratio offers an excellent way of evaluating brain-targeting efficiency of neurotherapeutics effectively. In our opinion, it is a very fundamental aspect of brain bioavailability and needs to be presented in a precise way.
Bedside point of care toxicology screens in the ED: Utility and pitfalls

Exposure to drugs and toxins is a major cause for patients’ visits to the emergency department (ED). For most drugs-of-abuse intoxication, ED physicians are skeptical to rely on results of urine drug testing for emergent management decisions. This is partially because immunoassays, although rapid, have limitations in sensitivity and specificity and chromatographic assays, which are more definitive, are more labor intensive. Testing for toxic alcohols is needed, but rapid commercial assays are not available. ED physicians need stat assays for acetaminophen, salicylates, co-oximetry, cholinesterase, iron, and some therapeutic drugs that could be used as agents of self-harm. In this review, we look at the potential limitations of these screening tests and suggest improvements and innovations needed for better clinical utilization. New drugs of abuse should be sought and assays should be developed to meet changing abuse patterns.
Impact of acetazolamide use in severe exacerbation of chronic obstructive pulmonary disease requiring invasive mechanical ventilation

Purpose: To analyse the impact of acetazolamide (ACET) use in severe acute decompensation of chronic obstructive pulmonary disease requiring mechanical ventilation and intensive care unit (ICU) admission . Patients and Methods: Retrospective pair-wise, case-control study with 1:1 matching. Patients were defined as cases when they had received acetazolamide (500 mg per day) and as controls when they did not received it. Patients were matched according to age , severity on admission (pH, PaO 2 /FiO 2 ratio) and SAPSII score. Our primary endpoint was the effect of ACET (500 mg per day) on the duration of mechanical ventilation. Our secondary endpoints were the effect of ACET on arterial blood gas parameters, ICU length of stay (LOS) and ICU mortality. Results: Seventy-two patients were included and equally distributed between the two studied groups. There were 66 males (92%). The mean age (± SD) was 69.7 ± 7.4 years ranging from 53 to 81 years . There were no differences between baseline characteristics of the two groups. Concomitant drugs used were also not significantly different between two groups. Mean duration of mechanical ventilation was not significantly different between ACET(+) and ACET(-) patients (10.6 ± 7.8 days and 9.6 ± 7.6 days, respectively; P = 0.61). Cases had a significantly decreased serum bicarbonate, arterial blood pH, and PaCO 2 levels . We did not found any significant difference between the two studied groups in terms of ICU LOS. ICU mortality was also comparable between ACET(+) and ACET(-) groups (38% and 52%, respectively; P = 0.23). Conclusion: Although our study some limitations, it suggests that the use of insufficient acetazolamide dosage (500 mg/d) ACET (500 mg per day) has no significant effect on the duration of mechanical ventilation in critically ill COPD patients requiring invasive mechanical ventilation. Our results should be confirmed or infirmed by further studies.
Computational science in drug metabolism and toxicology

Computational scientific tools involving construction and testing of models, screening and data mining for drug and chemical induced toxicities and metabolism have significantly grown in experimental use to help guide product development and assist by enhancing certain areas of regulatory decision making. This themed issue of the journal entitled Computational Science in Drug Metabolism & Toxicology contains state-of-the-art review articles and perspectives covering a diversity of in silico approaches. Computational science tools have a strong potential for expediting our further understanding of drug metabolism and toxicity and are continually being developed and validated. The reader will gain an understanding of the current state of in silico tools and modeling approaches aimed at reducing these liabilities. In addition, how these tools are tested and developed for use in drug safety to support drug development efforts and a review of how they are used to predict genotoxic liabilities are covered in this issue. Computational science tools when properly validated and used judiciously can lend themselves as enablers to support drug safety assessment in investigative and applied settings.
Transplante autólogo de células mononucleares da medula óssea em úlcera de córnea experimental em cães

Bone marrow (BM) mononuclear cells (MC) are a great subject in tissual regeneration. The main stem cell source to the eye is the limbus. Theses cells replace injured corneal cells, however, if the limbal stem cells are not functional, a limbal deficiency with concomitant conjunctivalization takes place. This pathological condition can be caused for several reasons, in which alkali burns are the most common. To conduct a research about transplanted BM MC presence, the cells homing and to histopathologically compare the treated and sham group, an experimental corneal ulcer model associated with MC autotransplant was used. Sixteen, male or female, stray dogs suffered experimental corneal ulceration with sodium hydroxide soaked filter discs. After the lesions, animals were submitted to subconjunctival autotransplant of previously marked BM MC. The evaluation was made by immunofluorescence on the sixth day after lesions creation and histopathology was conducted 15 days after the same procedure, when it was possible to observe that the MC grafted in the injured area, the cells did not execute the homing process and, despite the inflammatory decrease, they did not help the corneal epithelial healing process in a short term evaluation. Thus, future studies about MC transplantations in corneal ulcers are indicated.
Effect of preeclampsia on insulin sensitivity

Objective: The objective of this study is to investigate whether preeclampsia is associated with exacerbation of insulin resistance. Materials and Methods: The study was conducted over a period of 7 months from November 2011 to May 2012, in a tertiary care hospital attached to a medical college. A total of 14 pregnant women in the third trimester with preeclampsia were recruited for this study and 14 well-matched normotensive women in the third trimester were taken as control. 15 g, 50% dextrose load was given intravenously and blood sampling was carried out for glucose and insulin levels up to 3 h afterward. Minimal model analysis of glucose and insulin levels was performed to arrive at results. Results: No significant changes in mean age, body mass index, gestation, serum lipid and progesterone, cortisol and androgen concentrations were recognized. No significant difference was found between the glucose decay curves and between the glucose clearance rate K, in the two groups (preeclamptic vs. normotensive: 2.1 ± 0.2 vs. 2.2 ± 0.3; P = 0.48). Therefore, there was a small but prolonged decrease in the insulin response of women with preeclampsia compared with women in the normotensive group. Conclusion: Preeclampsia per se is not a risk factor for development of insulin resistance.