Chemical burns represent potentially blinding ocular injuries and constitute a true ocular emergency requiring immediate assessment and initiation of treatment. The majority of victims are young and exposure occurs at home, work place and in association with criminal assaults. Alkali injuries occur more frequently than acid injuries. Chemical injuries of the eye produce extensive damage to the ocular surface epithelium, cornea, anterior segment and limbal stem cells resulting in permanent unilateral or bilateral visual impairment. Emergency management if appropriate may be single most important factor in determining visual outcome. This article reviews the emergency management and newer techniques to improve the prognosis of patients with chemical injuries.
Investigation of drug-DNA interaction is important for understanding the drug action at molecular level and for designing specific DNA targeted drug. Lomustine (CCNU=1-[2-chloroethyl]-3-cyclohexyl-1-nitroso-urea) is an alkylating antineoplastic nitrosourea derivative, used to treat different types of cancer. In the present study, conformational and structural effects of lomustine on DNA are investigated using different spectroscopic approaches. Different drug/DNA molar ratios are analyzed to determine the binding sites and binding mode of lomustine with DNA. Fourier transform infrared spectroscopic (FTIR) results suggest binding of lomustine with nitrogenous bases guanine and cytosine along with weak interaction to the sugar-phosphate backbone of DNA. Circular dichroism (CD) spectroscopic results show perturbation in the local conformation of DNA upon binding of lomustine with DNA helix. These local conformational changes may act as recognition site for alkylating enzymes that further causes alkylation of DNA. Spectroscopic results confirm the formation of an intermediate stage of DNA that occurs during the transition of B-conformation into A-conformation.
A barrier for horizontal gene transfer is high gene expression, which is metabolically expensive. Silencing of horizontally-acquired genes in the bacterium Escherichia coli is caused by the global transcriptional repressor H-NS. The activity of H-NS is enhanced or diminished by other proteins including its homologue StpA, and Hha and YdgT. The interconnections of H-NS with these regulators and their role in silencing gene expression in E. coli are not well understood on a genomic scale. In this study, we use transcriptome sequencing to show that there is a bi-layered gene silencing system - involving the homologous H-NS and StpA - operating on horizontally-acquired genes among others. We show that H-NS-repressed genes belong to two types, termed "epistatic" and "unilateral". In the absence of H-NS, the expression of "epistatically controlled genes" is repressed by StpA, whereas that of "unilaterally controlled genes" is not. Epistatic genes show a higher tendency to be non-essential and recently acquired, when compared to unilateral genes. Epistatic genes reach much higher expression levels than unilateral genes in the absence of the silencing system. Finally, epistatic genes contain more high affinity H-NS binding motifs than unilateral genes. Therefore, both the DNA binding sites of H-NS as well as the function of StpA as a backup system might be selected for silencing highly transcribable genes.
Neurofibromatosis Type I (NFI) is a relatively common hereditary, autosomal dominant neurocutaneous condition. It is a benign peripheral nerve sheath tumour arising from Schwann cells and peripheral fibroblasts. Even though it is a neurocutaneous disorder, NF I has significant skeletal manifestations. Oral and maxillofacial skeletal structures are also often involved in the form of deepening of sigmoid notch, enlarged mandibular canal and notching of inferior border of mandible. In this paper, we are reporting a female patient of NF I who presented with a notching in the posterior border of ascending ramus of mandible.
Saliva of blood sucking arthropods contains compounds that antagonize their hosts hemostasis, which include platelet aggregation, vasoconstriction and blood clotting; saliva of these organisms also has anti-inflammatory and immunomodullatory properties. Perhaps because hosts mount an active immune response against these compounds, the diversity of these compounds is large even among related blood sucking species. Because of these properties, saliva helps blood feeding as well as help the establishment of pathogens that can be transmitted during blood feeding.
Sebaceous gland carcinoma usually arises from the meibomian or Zeis glands within the eyelid, but tumor arising primarily from the conjunctiva, especially bulbar conjunctiva, is a rarity. We hereby report a case of a 50-year-old female who presented with a painless mass in the inferior limbus, encroaching the cornea and hanging over the lower eyelid without involving it. Imprint cytology was suggestive of adenosquamous carcinoma. Management consisted of wide local excision, cryotherapy to tumor bed, and topical 5-fluorouracil (5-FU) 1% preoperatively and postoperatively. Histopathologic analysis was in favor of sebaceous gland carcinoma. This case suggests that although sebaceous gland carcinoma commonly originates as a lid tumor, it can present as a bulbar conjunctival mass. Topical 5-FU is a viable and efficient cost-effective alternative for neo-adjuvant and adjuvant treatment of sebaceous gland carcinoma.
The present work reports the compositional analysis of thirteen different packed fruit juices using high performance liquid chromatography (HPLC). Vitamin C, organic acids (citric and malic) and sugars (fructose, glucose and sucrose) were separated, analyzed and quantified using different reverse phase methods. A new rapid reverse phase HPLC method was developed for routine analysis of vitamin C in fruit juices. The precision results of the methods showed that the relative standard deviations of the repeatability and reproducibility were <0.05 and <0.1 respectively. Correlation coefficient of the calibration models developed was found to be higher than 0.99 in each case. It has been found that the content of Vitamin C was less variable amongst different varieties involved in the study. It is also observed that in comparison to fresh juices, the packed juices contain lesser amounts of vitamin C. Citric acid was found as the major organic acids present in packed juices while maximum portion of sugars was of sucrose. Comparison of the amount of vitamin C, organic acids and sugars in same fruit juice of different commercial brands is also reported.
The binding of vincristine with DNA has been investigated using Fourier transform infrared spectroscopy. Various changes in the double helical structure of DNA after addition of vincristine have been examined. It is evident from Fourier transform infrared results that vincristine-DNA interaction occurs through guanine and cytosine base pairs. External binding of vincristine with phosphate backbone of the DNA is also observed. Vincristine perturbs guanine band at 1714 cm(-1), cytosine band at 1488 cm(-1), and the phosphate vibrations at 1225 and 1086 cm(-1). The UV-visible spectra of vincristine-DNA complex show hypochromic and bathochromic shifts, indicating the intercalation of vincristine into the double helical structure of DNA. Both intercalative and external binding modes are observed for vincristine binding with DNA, with an estimated binding constant K = 1.0 × 10(3) M(-1).
Metastatic tumors are the most common intra-ocular malignancies and choroid is by far the most common site for intra-ocular malignancies. Multiple foci are usually involved, and bilateral involvement is frequently seen. The primary sites for choroidal metastasis in decreasing order and by gender are: breast, lung, unknown primary, gastrointestinal and pancreas, skin melanoma and other rare sources in females, and lung, unknown primary, gastrointestinal and pancreas, prostate, kidney, skin melanoma and other rare sources in males. Available treatment options are external beam radiotherapy and plaque radiotherapy, while new methods like surgical resection, transpupillary thermotherapy and intravitreal chemotherapy offer promises for the future. The use of chemotherapy alone for choroidal metastases is not widely reported.
The incidence of multiple primary cancers is reported to be between 0.3% and 4.3%. The second primary lesion is identified either simultaneously with the primary lesion (synchronous) or after a period of time (metachronous). Few cases of metastasis of breast carcinoma to the esophagus and vice versa have been reported in the past.
Nelfinavir mesylate is the first nonpeptidic protease inhibitor available in pediatric formulation. In the present paper the stability of nelfinavir mesylate under different stress conditions is evaluated using Fourier transform infrared spectroscopy. The drug is subjected to thermal degradation, photodegradation, acid hydrolysis, base hydrolysis and oxidation as per ICH guidelines. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD) and high performance liquid chromatography (HPLC) are carried out to support the implementation of infrared spectroscopy for the stability studies of nelfinavir mesylate. Significant changes are observed in the IR spectra collected after exposing the drug to thermal radiations, acid and base hydrolysis and oxidative degradation. No change is observed in the spectra of the drug after exposing it to sunlight indicating the good photostability of nelfinavir mesylate. The results of infrared spectroscopy agree well with that of other complementary techniques as DSC, TGA, XRD and HPLC.
The determination of moisture content in pharmaceuticals is very important as moisture is mainly responsible for the degradation of drugs. Degraded drugs have reduced efficacy and could be hazardous. The objective of the present work is to replace the Karl Fischer (KF) titration method used for moisture analysis with a method that is rapid, involves no toxic materials and is more effective. Diffuse reflectance infrared (IR) spectroscopy, which is explored as a potential alternative to various approaches, is investigated for moisture analysis in 5-fluorouracil, an anticancer drug. A total of 150 samples with varying moisture content were prepared in laboratory by exposing the drug at different relative humidities, for different time intervals. Infrared spectra of these samples were collected with a Fourier transform infrared (FTIR) spectrophotometer using a diffuse reflectance accessory. Reference moisture values were obtained using the Karl Fischer titration method. A number of calibration models were developed using the partial least squares (PLS) regression method. A good correlation was obtained between predicted IR values and reference values in the calibration and validation set. The derived calibration curve was used to predict moisture content in unknown samples. The results show that IR spectroscopy can be used successfully for the determination of moisture content in the pharmaceutical industry.
5-Fluorouracil is one of the oldest chemotherapy drugs and it has been in use for decades. It is an active medicine against several types of cancer and effectively blocks the replication of DNA viruses. The present study assessed the potential of diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy to determine the thermal stability of 5-fluorouracil. Infrared spectra of the drug before and after exposure to thermal radiation at different temperatures were collected in diffuse reflectance mode using a Fourier transform infrared (FTIR) spectrophotometer. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis were carried out simultaneously to confirm and support the results of infrared spectroscopy. The DRIFT spectra reveal that the drug shows good thermal stability up to 275 degrees C and undergoes complete thermal breakdown at about 285 degrees C. The results of DSC and XRD analysis also give the same information, which support the implementation of diffuse reflectance infrared spectroscopy for the determination of thermal stability of 5-fluorouracil.
DNA methytransferases (MTs) in bacteria are best understood in the context of restriction-modification (R-M) systems, which act as bacterial immune systems against incoming DNA including phages, but have also been described as selfish elements. But several orphan MTs, which are not associated with any restriction enzyme, have also been characterized and may protect against parasitism by R-M systems. The occurrence of MTs in these two contexts, namely as part of R-M systems or as orphans, is poorly understood. Here we report the results of a comparative genomic survey of DNA MTs across ?1000 bacterial genomes. We show that orphan MTs overwhelm R-M systems in their occurrence. In general, R-M MTs are poorly conserved, whereas orphans are nearly as conserved within a genus as any average gene. However, oligonucleotide usage and conservation patterns across genera suggest that both forms of MTs might have been horizontally acquired. We suggest that many orphan MTs might be degradation products of R-M systems, based on the properties of orphan MTs encoded adjacent to highly diverged REs. In addition, several fully degraded R-M systems exist in which both the MT and the RE are highly divergent from their corresponding reference R-M pair. Despite their sporadic occurrence, conserved R-M systems are present in strength in two highly transformable genera, in which they may contribute to selection against integration of foreign DNA.
Choroidal melanoma is the most common primary intra-ocular malignant tumor and second most common site of ten malignant melanoma sites in the body. Current diagnosis of choroidal melanoma is based on both the clinical experience of the specialist and modern diagnostic techniques such as indirect ophthalmoscopy, A- and B-ultrasonography scans, fundus fluorescein angiography, and transillumination. Invasive studies such as fine needle aspiration cytology can have significant morbidity and should only be considered if therapeutic intervention is indicated and diagnosis cannot be established by any other means. Several modes of treatment are available for choroidal melanoma. Multiple factors are taken into account when deciding one approach over other approaches, such as visual acuity of the affected eye, visual acuity of the contralateral eye, tumor size, location, ocular structures involved and presence of metastases. A comprehensive review of literature available in books and indexed journals was done. This article discusses in detail epidemiology, diagnosis, current available treatment options, and prognosis and survival of choroidal melanoma.
MicroRNAs (miRNAs) have emerged as new class of RNA molecules which are short in length, less in number but play bigger role in regulation of cellular events. miRNAs keep cellular homeostasis in tight control by fine tuning expression of protein coding genes at post-transcriptional level. Neurogenesis and neurodegeneration are two complex processes which are regulated by dynamic expression of regulatory proteins like transcription factors and signaling proteins. Evidences are accumulating that expression of miRNAs play major role in fate determination of neuronal cells undergoing neurogenesis or neurodegeneration. Neurodegeneration either induced by genetic factors or environmental chemicals results in development of neurodegenerative disorders like Parkinsons or Alzheimers. With increasing acceptance of adult neurogenesis, it seems possible that inducing neurogenesis in adult brain can help in fighting with neurodegenerative disorders. Regulatory RNA molecules, like miRNAs are presenting them as potential therapeutic targets for inducing neurogenesis and controlling neurodegeneration. In the current review, we are exploring the link between neurodegeneration and adult neurogenesis regulation by focusing on miRNAs.
Related JoVE Video
Journal of Visualized Experiments
What is Visualize?
JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.
How does it work?
We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.
Video X seems to be unrelated to Abstract Y...
In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.