Exploration of sialic acid receptors as a potential target for cancer treatment: A comprehensive review.

The potential to target anticancer drugs directly to cancer cells is the most difficult challenge in the current scenario. Progressive works are being done on multifarious receptors and are on the horizon, expected to facilitate tailored treatment for cancer. Among several receptors, one is the sialic acid (SA) receptor by which cancer cells can be targeted directly as hyper sialylation is one of the most distinguishing characteristics of cancer cells. SA receptors have shown tremendous potential for tumor targeting because of their elevated expression in a range of human malignancies including prostate, breast, gastric cells, myeloid leukemia, liver, etc. This article reviews the overexpression of SA receptors in various tumors and diverse strategies for targeting these receptors to deliver drugs, enzymes, and genes for therapeutic applications. It also summarizes the diagnostic applications of SA-grafted nanoparticles for imaging various SA-overexpressing cancer cells and technological advances that are propelling sialic acid to the forefront of cancer therapy.

Adverse drug reaction profile of daily regimen antituberculosis treatment.

Objectives: The objective was to estimate the proportion of adverse drug reactions (ADRs) to daily regimen antituberculosis treatment (ATT) among the ADRs received in the ADR monitoring center (AMC) of the institution and to describe its pattern. Materials and Methods: This was a descriptive study conducted in the Department of Pharmacology of a Government Medical College in Central Kerala and the period under study was October 2017-June 2020. The data on ADR were entered into a structured pro forma and data were analyzed using SPSS for Windows Version 16.0 (SPSS Inc., Chicago, USA). Results: Of the 643 ADRs, 98 (15.24%) were suspected to be due to the daily regimen of ATT. The most common organ system affected was hepatobiliary 46 (46.9%) namely hepatitis in 35 and asymptomatic elevated liver enzymes in 11 followed by eye with 26 reports of decreased vision. In 96 (97.95%), the suspected ADR had probable causality and in 2 (2.04%) it was possible. Seventy-seven (78.6%) ADR reports were serious as well as moderate-level 4b in severity and 57 (58.16%) were probably preventable. The mean days of onset of ADR after starting the ATT regimen were 56.40 ± 58.29 days (range 1-180). Decrease in vision with a mean duration of 125.23 ± 55.46 days had the longest latency in onset among all the ADRs. Conclusions: Of all the ADRs reported to AMC 15.24% were due to the daily regimen of ATT. Hepatitis was the most common ADR encountered followed by decrease in vision. The majority of the ADRs were probable in causality, serious, moderate-level 4b in severity, and probably preventable.

Vulval Intraepithelial Neoplasia 3: A Clinico-Pathological Review in a Tertiary Care Centre Over 10 Years.

Objectives: Vulval Intraepithelial Neoplasia 3 (VIN) is a chronic, premalignant condition affecting the vulval skin. The age standardised incidence is approximately one per 100,000 women, with a peak at 30-49 years of age, and has risen over recent decades. This study would analyse the pattern of presentation, diagnosis, treatment and follow up of patients diagnosed with VIN 3 over a period of ten years at a tertiary care centre in India. Materials and Methods: This was a retrospective study conducted on all patients diagnosed to have VIN 3 between 1 January 2010 to 30 November 2019 in the Department of Gynaecologic Oncology, Christian Medical College, Vellore were included in this study. The outpatient records of the patients were obtained from an electronic registry. Results: A total of 18 patients were diagnosed of VIN 3 during this time period. Sixteen patients were older than 50 years. Abnormal PAP was noted in 10 patients (HSIL-7, LSIL-2, ASC-H-1). Four patients had coexisting VAIN 3. About 16 patients underwent primary simple vulvectomy or wide local excision. Two patients were managed conservatively. Nine patients had recurrence with mean disease free interval of 12.5 months (4-36 months). Cryotherapy was used in 2 patients. Imiquimod was used in 3 patients. Surgical margins was achieved in 7 patients out of which 5 patients had recurrence. About 50% of patients with involved margins on biopsy had recurrence. Mean duration of follow up was 17 months (4-105 months). About 8 patients developed squamous cell carcinoma of genital tract on follow up. Conclusion: VIN 3 has a high rate of progression to invasive SCC. Regression of VIN is rare. Proper follow up and treatment of VIN 3 goes a long way in preventing the morbidity associated with vulval cancer.

Chemical constituents from Chonemorpha fragrans roots and antibacterial activity studies of sarcorucinine D.

Nine non-alkaloid constituents viz., sitostenone (1), ß-sitosterol (2), naringenin (3), aromadendrin (4), matairesinol (5), vanillic acid (6), ferulic acid (7), protocatechuic acid (8) and sitosterol-3-O-ß-D-glucopyranoside (9) were isolated from the acetone extract as well as five alkaloids viz., japindine (10), sarcorucinine D (11), dictyophlebin (12), chonemorphine (13) and N-formylchonemorphine (14) were isolated from the ethanol extract of Chonemorpha fragrans roots. Except ß-sitosterol, all other non-alkaloid compounds and the alkaloid sarcorucinine D are being reported for the first time from C. fragrans. From the MIC and MBC values, it has been found that sarcorucinine D shows most promising antibacterial activity. Quantification of antibacterial activity as well as killing curve determinations were performed in order to confirm the efficacy of the compound. The cytotoxic activity studies revealed that it is nontoxic up to 100 µM concentration.

Mapping the Fibril Core of the Prion Subdomain of the Mammalian CPEB3 that is Involved in Long Term Memory Retention.

Long-term memory storage is modulated by the prion nature of CPEB3 forming the molecular basis for the maintenance of synaptic facilitation. Here we report that the first prion sub-domain PRD1 of mouse CPEB3 can autonomously form amyloid fibrils in vitro and punctate-like structures in vivo. A ninety-four amino acid sequence within the PRD1 domain, PRD1-core, displays high propensity towards aggregation and associated amyloid characteristics. PRD1-core is characterized using electron microscopy, X-ray diffraction, and solution-state NMR deuterium exchange experiments. Secondary structure elements deduced from solid-state NMR reveal a ß-rich core comprising of forty amino acids at the N-terminus of PRD1-core. The synthesized twenty-three amino acid long peptide containing the longest rigid segment (E124-H145) of the PRD1-core rapidly self-aggregates and forms fibrils, indicating a limited aggregation-prone region that could potentially activate the aggregation of the full-length protein. This study provides the first step in identifying the structural trigger for the CPEB3 aggregation process.

Treatment Outcomes of Early Carcinoma Cervix Before and After Sub-specialization.

This study aimed to compare the treatment outcomes in carcinoma cervix before and after gynecologic oncology sub-specialization at a tertiary care hospital, in India. This was a retrospective cohort study comparing women with operable cervical cancer who underwent radical hysterectomy before and after gynecologic oncology sub-specialization. Electronic medical records of women operated for early carcinoma cervix between 2001 and 2010 and 2011-2015 were reviewed and compared for treatment and oncological outcomes. Seventy-four patients were operated over 5 years after sub-specialization as against 59 over 10 years before sub-specialization, with similar clinical characteristics. After surgical-pathological examination, both cohorts were comparable with regard to mean tumor size, lymph nodes retrieved, deep stromal invasion, and involvement of lymph nodes, parametrium, and vaginal margins. After sub-specialization, the rate of intraoperative (3% versus 14%, p = 0.018) and postoperative complications (15% versus 46%, p < 0.001) was lower. Adjuvant radiation was used more after sub-specialization (50% versus 24%, p < 0.001). The follow-up rates were similar in both groups with comparable 5-year recurrence-free survival and overall survival rates. The hazard ratio for death after sub-specialization was 0.39 (95% CI 0.12 to 1.22) after adjusting for histology, stage, grade, and presence of intermediate or high risk factors. Gynecological oncologic sub-specialization decreased intraoperative and postoperative complications, improved pathological reporting, and enabled appropriate tailoring of adjuvant therapy.

Nonlinear absorption and scattering of a single plasmonic nanostructure characterized by x-scan technique.

Nonlinear nanoplasmonics is a largely unexplored research area that paves the way for many exciting applications, such as nanolasers, nanoantennas, and nanomodulators. In the field of nonlinear nanoplasmonics, it is highly desirable to characterize the nonlinearity of the optical absorption and scattering of single nanostructures. Currently, the common method to quantify optical nonlinearity is the z-scan technique, which yields real and imaginary parts of the permittivity by moving a thin sample with a laser beam. However, z-scan typically works with thin films, and thus acquires nonlinear responses from ensembles of nanostructures, not from single ones. In this work, we present an x-scan technique that is based on a confocal laser scanning microscope equipped with forward and backward detectors. The two-channel detection offers the simultaneous quantification for the nonlinear behavior of scattering, absorption and total attenuation by a single nanostructure. At low excitation intensities, both scattering and absorption responses are linear, thus confirming the linearity of the detection system. At high excitation intensities, we found that the nonlinear response can be derived directly from the point spread function of the x-scan images. Exceptionally large nonlinearities of both scattering and absorption are unraveled simultaneously for the first time. The present study not only provides a novel method for characterizing nonlinearity of a single nanostructure, but also reports surprisingly large plasmonic nonlinearities.

Isodeoxyelephantopin, a Sesquiterpene Lactone Induces ROS Generation, Suppresses NF-κB Activation, Modulates LncRNA Expression and Exhibit Activities Against Breast Cancer.

The sesquiterpene lactones, Isodeoxyelephantopin (IDET) and Deoxyelephantopin (DET) are known to exhibit activities against some cancer types. The activities of these lactones against breast cancer and the molecular bases is not known. We examined the efficacy of lactones in breast cancer preclinical model. Although both lactones exhibited drug like properties, IDET was relatively effective in comparison to DET. IDET suppressed the proliferation of both invasive and non-invasive breast cancer cell lines. IDET also suppressed the colony formation and migration of breast cancer cells. The assays for Acridine Orange (AO)/Propidium Iodide (PI) staining, cell cycle distribution, phosphatidylserine externalization and DNA laddering suggested the apoptosis inducing potential of IDET. The treatment with IDET also induced an accumulation of cells in the sub-G1 and G2/M phases. The exposure of breast cancer cells to the lactone was associated with a depolarization in mitochondrial membrane potential, and cleavage of caspase and PARP. The lactone induced reactive oxygen species (ROS) generation in breast cancer cells. Further, the use of N-acetyl cysteine (NAC) suppressed IDET induced ROS generation and apoptosis. The NF-κB-p65 nuclear translocation induced by okadaic acid (OA) was suppressed by the sesquiterpene. IDET also suppressed the expression of NF-κB regulated tumorigenic proteins, and induced the expression of proapoptotic gene (Bax) in cancer cells. While the expression of oncogenic lncRNAs was suppressed, the tumor suppressor lncRNAs were induced by the sesquiterpene. Collectively, the modulation of multiple cell signaling molecules by IDET may contribute to its activities in breast cancer cells.

Angiomyoma - A requisite in differential diagnosis of palatal growths.

Vascular variant of leiomyomas termed angioleiomyomas rarely present in the oral cavity. They present themselves as well-circumscribed, slow-growing, superficial lesions covered by normal mucosa and sometimes bluish or purple in color. Clinicians often tend to overlook this entity due to the rarity and asymptomatic nature of the lesion. Scrupulous knowledge of this entity and a thorough examination is of value, as the lesion can impersonate or transform to malignancy, as a malignant counterpart exists. We present a case of angiomyoma of hard palate in a 46-year-old patient with a detailed review.

Pharmacovigilance of Cutaneous Adverse Drug Reactions among Patients Attending Dermatology Department at a Tertiary Care Hospital.

CONTEXT: Cutaneous adverse drug reactions (CADRs) are the most frequent of all manifestations of drug sensitivity that present with varied and diverse morphology and therefore, awareness about them is essential for diagnosis and prevention. Aims: To evaluate the clinical spectrum, morphology, causality, severity and preventability of cutaneous adverse drug reactions in a tertiary care hospital. SETTING AND DESIGN: Descriptive study for six months in the Dermatology Department of a tertiary care hospital in Kerala. METHODS AND MATERIALS: All patients of any gender and age who presented with visible skin lesions and were diagnosed or suspected cases of cutaneous adverse drug reactions were included in the study. All the relevant information was recorded using pre-structured proforma and ADR reporting form. STATISTICAL ANALYSIS: Data were analyzed using descriptive statistics. The quantitative variables were expressed as mean ± standard deviation and qualitative variables as frequencies and percentages. Odds ratio (OR) was calculated to assess the risk factors for severe cutaneous adverse drug reactions using SPSS 16. RESULTS: Total 124 cutaneous adverse drug reactions were reported with mean age 39.22 ± 20.47 years, male:female ratio being 1:1.4. Most common cutaneous adverse drug reaction was maculopapular rash. Antibiotics accounted for maximum cases, of which beta-lactams were the most common. About 55.6% cutaneous adverse drug reactions occurred within 24 hours of drug administration. Mean hospital stay duration was 4.89 ± 6.23 days. Most reactions were either mild or moderate. Risk analysis revealed that concomitant use of more than one drug, delayed onset, oral route, more generalized area of involvement and medications prescribed for CNS indications were risk factors for severe cutaneous adverse drug reactions. All reactions were preventable. Majority got fully recovered. No fatality was observed. CONCLUSION: Identification and reporting of cutaneous adverse drug reactions reduces their future occurrences and encourages rational prescribing. The study emphasizes on having a deeper understanding of risk factors for serious cutaneous adverse drug reactions that may contribute significantly in improving their outcomes.

Diagnostic Accuracy of Frozen Section and Its Influence on Intraoperative Management of Indeterminate Epithelial Ovarian Tumors.

The objective of this study is to determine the diagnostic accuracy of frozen section in detecting epithelial ovarian tumor histological types and its effect on management. A retrospective review was done of all patients who had an intraoperative frozen section for an indeterminate ovarian tumor over a six-year period. The reference standard was final histology. The validity indices for frozen section in diagnosing benign, borderline, and malignant lesions were determined. One hundred thirty-five intraoperative frozen section-diagnosed epithelial ovarian tumors were reviewed. The mean age was 44.9 ± 14.2 years, the median parity was 2, and 57% (77/135) of patients were post-menopausal. The commonest histological subtype was mucinous 48.1% (65/135) on frozen section and 46.7% (63/135) on final histology. The overall concordance rate of frozen section to final histology was 81.5% (ƙ = 0.719, p = 0.0001). The accuracy, sensitivity, specificity, and positive predictive value of frozen section to diagnose benign lesions were 86.7%, 85.7%, 97.2%, and 79.2% respectively. In borderline tumors, the diagnostic test characteristics were 88.1%, 81.2%, 90.3%, and 72.2%. For malignant lesions, these values were 88.1%, 77.8%, 95.1%, and 91.3% respectively. The odds ratios for frozen section being correct were 40.9 (95% CI 14.8-113.5) for benign lesions, 40.3 (95% CI 13.4-121.3) for borderline tumors, and 67.4 (95% CI 20.5-222.0) for malignancy. Over-treatment or under-treatment occurred in 19.3% of patients. Intraoperative frozen section is useful in situations where the nature of the ovarian tumor is uncertain. However, borderline ovarian tumors are more likely to be over-diagnosed. About a fifth of patients received inappropriate treatments based on the frozen section report.

Quetiapine-induced Diabetic Ketoacidosis.

Psychomotor retardation and extrapyramidal symptoms have limited the conventional antipsychotic use. Atypical antipsychotics though widely prescribed with good tolerability and efficacy, the metabolic complications associated with them are of clinical importance. Diabetic ketoacidosis (DKA) is a fatal complication of atypical antipsychotic use. We report a case of new-onset diabetes presenting as DKA with quetiapine use.

Relative Efficacy of Quercetin Compared with Benzydamine Hydrochloride in Minor Aphthae: A Prospective, Parallel, Double Blind, Active Control, Preliminary Study.

BACKGROUND AND OBJECTIVES: Recurrent aphthous stomatitis is an inflammatory condition present since ancient era wherein numerous treatment modalities have been tried. But complete eradication of the disease has not been possible and hence newer agents are being introduced. One such agent is a flavonoid named quercetin with proven antioxidant, anti-inflammatory, and ulcer healing properties. METHODS: 40 patients with minor aphthous ulcers were divided equally into two groups: A and B. Group A patients were advised to apply quercetin gel and Group B patients were advised to take benzydamine hydrochloride mouth wash. Clinical evaluation including assessment of ulcer size and pain score and questionnaire about the acceptability of both the drugs in terms of taste and ease of application was carried out. Each criterion was compared and statistically analyzed. RESULTS: There was statistically significant reduction in the mean score of pain sensation and ulcer area in both the groups. Quercetin showed statistically highly significant ulcer size reduction as compared to benzydamine hydrochloride. CONCLUSION: From the present study, it is evident that quercetin is safe, well tolerated, and effective therapy which promotes complete ulcer healing in a short duration of time.

Zn2+ Interrupts R4-R3 Association Leading to Accelerated Aggregation of Tau Protein.

Direct binding of divalent metal ion, especially Zn2+ , have been shown to increase the rate of tau aggregation and enhance tau toxicity in cells. Hence, understanding the molecular basis of the Zn2+ -accelerated tau aggregation can potentially determine the molecular interactions modulating tau aggregation. Herein, we show that Zn2+ coordinates through the cysteine in R3 repeat and significantly accelerates the aggregation rate of the three repeat tau constructs (K19) but that the coordination is incapable of increasing the aggregation rate of the 20 amino acid peptide derived from the R3 repeat (R3) of tau. The NMR characterization of the binding of Zn2+ to K19, together with the aggregation studies with K19, R3 and R4 peptides, reveal the presence of an aggregation-inhibitory interaction between the R3 and R4 repeat of K19. Our data show that binding of Zn2+ to R3 repeat of tau, weaken the aggregation-inhibiting influence between R3 and R4 repeats, leading to faster aggregation of tau protein.

Evaluation of diagnostic value of AgNOR and PAP in early detection of dysplastic changes in leukoplakia and lichen planus - a preliminary case-control study.

BACKGROUND AND OBJECTIVES: Early detection of oral cancer has been the most effective approach to reduce morbidity and mortality of cancer patients. If a lesion is clinically considered suspicious, an easily practicable, non-invasive, painless, safe, and accurate screening method for detection of the dysplastic changes is necessary. In an attempt to procure this, a study was conducted with the aim of determining the diagnostic accuracy of rapid Papanicolaou stain (PAP) and silver-stained nucleolar organizer regions (AgNOR) in brush biopsies of potentially malignant lesions for early detection of oral cancer. METHODOLOGY: Brush biopsies taken from 25 cases of leukoplakia and lichen planus each were stained with rapid PAP and silver nitrate stains. Histopathological correlation was performed and further compared with rapid PAP and AgNOR for its diagnostic validity. RESULTS: Statistically significant increase in the mean AgNOR count was seen from normal epithelium to lichen planus to that of leukoplakia. When compared with rapid PAP, a linear correlation was seen in AgNOR counts and stages of dysplasia in leukoplakia which was also found to be statistically significant. Diagnostic accuracy for AgNOR in leukoplakia was found to be 84%, lichen planus 73%, whereas RAPID PAP showed 72% accuracy. CONCLUSION: AgNOR analysis may be useful as a quantitative marker of incipient cellular alterations and hence would be helpful in assessing suspicious lesions and thus can be regarded as a valuable adjunct.

Cheiloscopy as an additional forensic parameter : a review

@#Criminal activities involving human life always puts lives at stake. Newer advances in other fields especially medicine and dentistry is essential in solving the mysteries of death. Different disciplines insert a part of the puzzle until it is complete. Fingerprints, DNA profiling, Forensic anthropology are commonly employed in personnel identification, mass disasters and others. Investigators may also rely on lip prints to identify possible suspects or to support evidence gained in specific investigations. A lip print at scene of crime can be the basis for inference as to the number of people involved, gender, habits, occupational traits, and others, based on the pathological changes present. This review deals with lip prints and their possible acquisition and usage.

Verrucous carcinoma-an enigma: Case report and review.

Verrucous hyperplasia, verrucous keratosis, and VC may not be distinguished clinically or may coexist. Though it appears remarkably harmless, the histopathological diagnosis of VC should be accompanied with careful identification of tumors with a greater chance to become frank cancers. Here, we report two cases of OVC, referring all the diagnostic intricacy occurring in the clinicopathological examination along with a review of the scientific literature.

Is H Atom Abstraction Important in the Reaction of Cl with 1-Alkenes?

The relative yields of products of the reaction of Cl atoms with 1-alkenes (C4-C9) were determined to see whether H atom abstraction is an important channel and if it is to identify the preferred position of abstraction. The presence of all the possible positional isomers of long chain alkenones and alkenols among the products, along with chloroketones and chloroalcohols, confirms the occurrence of H atom abstraction. A consistent pattern of distribution of abstraction products is observed with oxidation at C4 (next to allyl) being the lowest and that at CH2 groups away from the double bond being the highest. This contradicts with the higher stability of allyl (C3) radical. For a better understanding of the relative reactivity, ab initio calculations at MP2/6-311+G (d,p) level of theory are carried out in the case of 1-heptene. The total rate coefficient, calculated using conventional transition state theory, was found to be in good agreement with the experimental value at room temperature. The preferred position of Cl atom addition is predicted to be the terminal carbon atom, which matches with the experimental observation, whereas the rate coefficients calculated for individual channels of H atom abstraction do not explain the observed pattern of products. The distribution of abstraction products except at C4 is found to be better explained by reported structure activity relationship, developed from experimental rate coefficient data. This implies the reactions to be kinetically dictated and emphasizes the importance of secondary reactions.