Development, Characterization, and Evaluation of SLN-Loaded Thermoresponsive Hydrogel System of Topotecan as Biological Macromolecule for Colorectal Delivery.

BACKGROUND: Chemotherapeutic drugs cause severe toxicities if administered unprotected, without proper targeting, and controlled release. In this study, we developed topotecan- (TPT-) loaded solid lipid nanoparticles (SLNs) for their chemotherapeutic effect against colorectal cancer. The TPT-SLNs were further incorporated into a thermoresponsive hydrogel system (TRHS) (TPT-SLNs-TRHS) to ensure control release and reduce toxicity of the drug. Microemulsion technique and cold method were, respectively, used to develop TPT-SLNs and TPT-SLNs-TRHS. Particle size, polydispersive index (PDI), and incorporation efficiency (IE) of the TPT-SLNs were determined. Similarly, gelation time, gel strength, and bioadhesive force studies of the TPT-SLNs-TRHS were performed. Additionally, in vitro release and pharmacokinetic and antitumour evaluations of the formulation were done. RESULTS: TPT-SLNs have uniformly distributed particles with mean size in nanorange (174 nm) and IE of ~90%. TPT-SLNs-TRHS demonstrated suitable gelation properties upon administration into the rat's rectum. Moreover, drug release was exhibited in a control manner over an extended period of time for the incorporated TPT. Pharmacokinetic studies showed enhanced bioavailability of the TPT with improved plasma concentration and AUC. Further, it showed significantly enhanced antitumour effect in tumour-bearing mice as compared to the test formulations. CONCLUSION: It can be concluded that SLNs incorporated in TRHS could be a potential source of the antitumour drug delivery with better control of the drug release and no toxicity.

Analysis of performed paediatric oral and maxillofacial procedures under general anaesthesia over a two-year period in a North London NHS Trust.

Dental treatment remains one of the most common reasons for paediatric patients to undergo a general anaesthetic (GA). In addition to a wider scope of practice, oral and maxillofacial (OMF) surgeons are affiliated with this well-reported dentoalveolar surgical burden. Thus far much of the research has shown that the majority of these paediatric GAs are for the treatment of decayed teeth. The aim of this study was to evaluate reasons children in a North London region undergo GA procedures in an OMF department and this population's associated demographic factors. Patients treated by this OMF unit from 2016 to 2017 aged 0-16 were included. Retrospective data was obtained; including age, gender, and ASA physical status. Deprivation was calculated from postcodes using the Index of Multiple Deprivation. Chi squared statistical tests were applied. Data from 600 children undergoing 790 procedures were analysed. A similar number of males and females were treated. The most common age group were the 13-16-year-olds. A total of 89.5% of the patients were ASA I. The greatest surgical burden was simple orthodontic extractions, accounting for 24.4% of all OMF paediatric GA procedures. Deprivation impacted the prevalence of the extraction of carious teeth, soft tissue trauma, and orthodontic-related surgery. In the region studied, more paediatric patients are undergoing GA for orthodontic-related surgery than for the extraction of decayed teeth. The type of facial trauma experienced changes with the age of the child.

Pattern of Skin Diseases and Occupational Dermatoses among Paddy Field Workers in Kashmir Valley: A Cross-Sectional Study from North India.

INTRODUCTION: Paddy farming is one of the main occupations in Kashmir valley. The workers associated with paddy are exposed to variety of irritants such as manures, fertilizers, and pesticides, besides getting exposed to intense sunlight for long hours due to the nature of their work. All these factors can potentially either trigger skin diseases or can worsen them. AIM: The aim of this study was to find out the prevalence and pattern of various skin disorders among paddy field workers in Kashmir valley. MATERIALS AND METHODS: This was a cross-sectional descriptive study in which 600 workers engaged in paddy farming in different areas of Kashmir valley were screened. The diagnosis was made on clinical grounds and wherever deemed necessary, relevant investigations were carried out to establish the nature of the disease. RESULTS: A total of 600 workers were evaluated for the presence of skin disorders. Two hundred thirty workers (38.3%) were found to have skin lesions, while the rest, i.e. 370 (61.7%) were free from any skin problem. Out of the total skin lesions, infectious ones were seen in 40.4%, while non-infectious accounted for 59.6% cases. The main non-infectious disorders included melasma, followed by hand and foot eczemas, hyperkeratosis of palms and soles and callosities/cuts, while among the infectious group the major chunk was formed by bacterial infections followed by fungal, viral, and parasitic. Pitted keratolysis and intertrigo were the most common bacterial and fungal infections respectively. CONCLUSION: A large number of skin diseases were seen in paddy field workers, with some diseases showing an occupational nature.

Melatonin mitigates cadmium and aluminium toxicity through modulation of antioxidant potential in Brassica napus L.

Melatonin has emerged as an essential molecule in plants, due to its role in defence against metal toxicity. Aluminium (Al) and cadmium (Cd) toxicity inhibit rapeseed seedling growth. In this study, we applied different doses of melatonin (50 and 100 µm) to alleviate Al (25 µm) and Cd (25 µm) stress in rapeseed seedlings. Results show that Al and Cd caused toxicity in rapeseed seedling, as evidenced by a decrease in height, biomass and antioxidant enzyme activity. Melatonin increased the expression of melatonin biosynthesis-related Brassica napus genes for caffeic acid O-methyl transferase (BnCOMT) under Al and Cd stress. The genes BnCOMT-1, BnCOMT-5 and BnCOMT-8 showed up-regulated expression, while BnCOMT-4 and BnCOMT-6 were down-regulated during incubation in water. Melatonin application increased the germination rate, shoot length, root length, fresh and dry weight of seedlings. Melatonin supplementation under Al and Cd stress increased superoxide dismutase, catalase, peroxidase, ascorbate peroxidase, proline, chlorophyll and anthocyanin content, as well as photosynthesis rate. Both Cd and Al treatments significantly increased hydrogen peroxide and malondialdehyde levels in rapeseed seedlings, which were strictly counterbalanced by melatonin. Analysis of Cd and Al in different subcellular compartments showed that melatonin enhanced cell wall and soluble fractions, but reduced the vacuolar and organelle fractions in Al- and Cd-treated seedlings. These results suggest that melatonin-induced improvements in antioxidant potential, biomass, photosynthesis rate and successive Cd and Al sequestration play a pivotal role in plant tolerance to Al and Cd stress. This mechanism may have potential implications in safe food production.

Secukinumab for treatment of psoriasis: does secukinumab precipitate or promote the presentation of cutaneous T-cell lymphoma?

Secukinumab is an interleukin (IL)-17 monoclonal antibody inhibiting T-helper (Th)1-mediated immune response. It has proven high efficacy for moderate to severe psoriasis but data on its long-term toxicities are limited. We describe two patients who received secukinumab for clinically presumed psoriasis, but were subsequently diagnosed with mycosis fungoides (MF) following skin biopsies triggered by skin deterioration while on secukinumab. Previous studies suggested decreased numbers of regulatory T cells (Tregs) with increasing stage of MF, which may lead to the shift in the Treg/Th17 balance towards the Th17 pathway. Theoretically, the use of IL-17 monoclonal antibodies to inhibit Th17 pathway may lead to further immunosuppression and disease progression in cutaneous T-cell lymphoma (CTCL) by shifting the balance towards Tregs, although this hypothesis has not been proven. With uncertainty over the role of IL-17 and Treg/Th17 as well as diagnostic challenges in CTCL, we recommend that patients should have a confirmatory skin biopsy prior to the commencement of biologic therapy.

Hypopituitarism in a Dengue Shock Syndrome Survivor without known Pituitary Adenoma.

Dengue infection is endemic in South East Asia and parts of the Americas. Dengue hemorrhagic fever is characterized by vascular permeability, coagulation-disorders and thrombocytopenia, which can culminate in hypotension i.e. dengue shock syndrome. Hypopituitarism arising as a complication of dengue is extremely rare. Hemorrhagic pituitary apoplexy of pre-existing pituitary adenomas has been rarely reported in dengue. We describe an uncommon case of hypopituitarism in a dengue shock syndrome survivor without known pituitary adenoma. A 49 years old nulliparous lady (from Kuala Lumpur, Malaysia) presented with typical symptoms of hypocortisolism. Postural hypotension was evident with normal secondary sexual characteristics. Further history revealed that she survived an episode of dengue shock syndrome 6 years ago where premature menopause developed immediately after discharge, and subsequently insidious onset of multiple hormonal deficiencies indicative of panhypopituitarism. There were no neuro-ophthalmological symptoms suggestive of pituitary apoplexy during hospitalization for severe dengue. Magnetic resonance imaging of the pituitary 6 years later revealed an empty sella. Autoimmune screen and anti-thyroid peroxidase antibodies were negative. We describe a rare possible causative association of severe dengue with panhypopituitarism without known pituitary adenoma, postulating pituitary infarction secondary to hypotension (mimicking Sheehan's syndrome), or a direct viral cytopathic effect. Subclinical pituitary apoplexy secondary to asymptomatic pituitary hemorrhage however cannot be excluded. Future research is required to determine the need for and timing of pituitary axis assessment among dengue shock syndrome survivors.

Gene polymorphisms, tobacco exposure and oral cancer susceptibility: a study from Gujarat, West India.

Polymorphic variability in the enzymes involved in biotransformation of tobacco-related pro-carcinogens plays an important role in modulating oral cancer susceptibility. CYP1A1*2A, CYP1A1*2C, GSTM1 and GSTT1 polymorphisms were determined in 122 oral carcinoma cases and 127 controls from Gujarat, West India using PCR-based methods. The results revealed that the polymorphic variants of CYP1A1 gene did not show association towards oral cancer risk. The GSTM1 and GSTT1 null genotypes were found to be over-represented in patients than controls, suggesting a moderate increase in risk of oral cancer. The oral cancer risk was significantly increased in the patients having either alone or concurrent deletion of GSTM1 and GSTT1. The results also suggested significant association between tobacco habits, especially chewing, variant genotypes of CYP1A1, GSTM1 and GSTT1 and oral cancer risk. Our data have provided evidence that GST polymorphism modified the susceptibility to oral cancer and individuals with variant genotypes of the three genes with tobacco habits are at significant risk of developing oral cancer.

Benign mediastinal teratoma with intrapulmonary and bronchial rupture presenting with recurrent hemoptysis.

Mediastinal teratomas are usually asymptomatic tumors, located most commonly in the anterior mediastinum. Very rarely, such tumors may rupture into the tracheobronchial tree, lung, pleura or pericardium. Computed Tomography (CT) is helpful in the diagnosis and differentiation of ruptured and unruptured tumors. We report a case of ruptured anterior mediastinal teratoma in a 20-year-old female presenting with recurrent hemoptysis and cough; thus, mimicking a lung malignancy or tuberculosis. CT demonstrated a heterogeneous fat containing lesion in the anterior mediastinum with extension into the lingular lobe. Subsequent fine needle aspiration cytology (FNAC) yielded plenty of anucleate squames and debris, and a clear cut diagnosis could not be made. Total excision of the tumor was performed and histopathology of the surgically excised mass confirmed the CT diagnosis.

Carbon availability triggers the decomposition of plant litter and assimilation of nitrogen by an ectomycorrhizal fungus.

The majority of nitrogen in forest soils is found in organic matter-protein complexes. Ectomycorrhizal fungi (EMF) are thought to have a key role in decomposing and mobilizing nitrogen from such complexes. However, little is known about the mechanisms governing these processes, how they are regulated by the carbon in the host plant and the availability of more easily available forms of nitrogen sources. Here we used spectroscopic analyses and transcriptome profiling to examine how the presence or absence of glucose and/or ammonium regulates decomposition of litter material and nitrogen mobilization by the ectomycorrhizal fungus Paxillus involutus. We found that the assimilation of nitrogen and the decomposition of the litter material are triggered by the addition of glucose. Glucose addition also resulted in upregulation of the expression of genes encoding enzymes involved in oxidative degradation of polysaccharides and polyphenols, peptidases, nitrogen transporters and enzymes in pathways of the nitrogen and carbon metabolism. In contrast, the addition of ammonium to organic matter had relatively minor effects on the expression of transcripts and the decomposition of litter material, occurring only when glucose was present. On the basis of spectroscopic analyses, three major types of chemical modifications of the litter material were observed, each correlated with the expression of specific sets of genes encoding extracellular enzymes. Our data suggest that the expression of the decomposition and nitrogen assimilation processes of EMF can be tightly regulated by the host carbon supply and that the availability of inorganic nitrogen as such has limited effects on saprotrophic activities.