Receptor modification as a therapeutic approach against viral diseases

Poliovirus causes flaccid paralysis through the destruction of motor neurons in the CNS. Susceptibility to its infection is mainly due to the interaction in between the surface capsid proteins and its receptors on the host cell surface, important for binding, penetration and other necessary events during early infection. Receptor modification is a new approach to treat viral diseases by the modification of target proteins structure. Binding domains are modified in an effective way to make it difficult for the virus to recognize it. In this study, tolerant and intolerant induced mutations in the poliovirus receptor, VP1 and VP2 were identified and substituted in the seed sequence to get the modified versions. Substitutions causing changes in initial folding were short listed and further analyzed for high level folding, physiochemical properties and interactions. Highest RMSD values were observed in between the seed and the mutant K90F (3.265 Å) and Q130W (3.270Å) respectively. The proposed substitutions were found to have low functional impact and thus can be further tested and validated by the experimental researchers. Interactions analyses proved most of the substitutions having decreased affinity for both the VP1 and VP2 and thus are of significant importance against poliovirus. This study will play an important role for bridging computational biology to other fields of applied biology and also will provide an insight to develop resistance against viral diseases. It is also expected that same approach can also be applicable against other viruses like HCV, HIV and other in near future

Nanomedicines: Nano based Drug Delivery Systems Challenges and Opportunities

Nanomedicine and nano delivery systems, although relatively recent but fast-developing technology is one where nanoscale materials are used to function as diagnostic tools or to deliver therapeutic agents to specifically targeted sites in a controlled manner. It also provides many advantages in the management of human diseases. Recently, there has been a range of excellent uses of nanomedicine as chemotherapeutic agents, biological agents, immunotherapeutic agents, etc., for treatment of different diseases. In this chapter we discuss the recent developments and insights obtained in the field of nanomedicine. It provides a review of the numerous nano-based drug delivery systems that enhance the efficacy of new and old drugs. The new opportunities and challenges arising in the area of nanomedicine from therapeutic viewpoint are also addressed

Comparison of Fine Needle Aspiration Cytology and Thyroid Scan in Solitary Thyroid Nodule

Objective. This was a comparative study between FNAC and thyroid scan used to diagnose the solitary thyroid nodule and histopathology was used as gold standard to compare the results of both modalities. We hypothesized that Fine needle aspiration cytology and thyroid scan diagnose solitary thyroid nodule (STN) as accurately as histopathology. Materials and Methods. This study comprised of 50 patients with solitary thyroid nodules (STN) presented to OPD. After clinical examination these patients were referred to Centre for Nuclear Medicine, Mayo Hospital Lahore for thyroid function tests and thyroid scan (TS). These patients underwent FNAC in the department of Pathology and surgery in Mayo Hospital. The cases were operated and evaluated for histopathological changes. Results. On thyroid scan, 40 patients (80%) having cold nodule were labeled as suspicious 10 patients (20%) had hot nodule. On FNAC 23 patients (46%) had benign lesion, 22 patients (44%) had indeterminate lesion and 5 patients (10%) had malignant lesions. On histopathology, 45 patients (90%) were confirmed to have benign lesions and 5 patients (10%), malignant lesions. After comparison of results of thyroid scan and FNAC with histopathology, the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of thyroid scan were 80%, 20%, 10%, 90% and 26%, respectively whereas those of FNAC were 80%, 97.7%, 80%, 97.7% and 96%, respectively. Conclusion. Fine needle aspiration was a significantly better predictor of malignancy than thyroid scan and resulted in a smaller proportion of excisions for benign nodules

Sero-negative celiac disease with dermatitis herpetiformes: a case report

Introduction:We report a case of sero-negative celiac disease in Pakistan. Case Presentation: A 20-year-old female presented with papulovesicular rash for 15 years, diarrhea for 8 years, spasms of hands and twitching of face for 4-5 months. She had mild anemia, low vitamin-D3 and serum calcium. On exclusion of other causes of malabsorption, anti-tissue transglutaminase antibodies (immunoglobulin-A & immunoglobulin-G), anti-endomysial antibodies, total immunoglobulin-A levels and skin biopsy were performed, which were normal. Intestinal biopsy revealed subtotal villous atrophy. Patient was prescribed gluten-free diet, to which she responded with alleviation of symptoms. Conclusions: Negative serology should not rule out celiac disease, intestinal biopsy should be performed if there is strong clinical suspicion

Conceptos erróneos comunes sobre COVID-19 entre los profesionales de la salud: una encuesta transversal global en línea.

Background: The COVID-19 pandemic has taken the world by storm, with cases continuously increasing by the hour and with a shortage of information regarding the virus available to the general public. Despite the availability of trusted online sources, there are still misconceptions relating to the virus floating around. This study aimed to find out the level of misconceptions among healthcare professionals (HCPs) worldwide about the ensuing COVID-19 pandemic. Materials and Methods: A descriptive cross sectional study was conducted through a global online survey. The self-administered questionnaire was designed and registered at an online website (Kwiksurveys). A total of 652 participants from 35 different countries across the world responded. Statistical analysis was performed using SPSS version 23. Socio-demographic and discipline characteristics were compared with the help of the chi-square test and univariate and multivariate logistic regression to find significant relationships. Results: Among all HCPs, general physicians (61.2%) were the most common respondents. The responses from females (63.3%) almost doubled those of men, and nearly half of the participants were working in private institutes (49.2%). Additionally, the major source of information used by HCPs about COVID-19 was social media (55.4%). Regarding misconception assessment, 71.6% of participants had correct concepts regarding COVID-19. However, 28.4% had incorrect information. Female HCPs were 1.49 times more likely to have correct concepts compared to males (OR=1.49, 95% CI=1.04-2.14). Conclusions: The majority of the HCPs were keeping themselves up-to-date with current information concerning the knowledge, prevention, and hygiene practices of COVID-19 infection. However, some misconceptions are deeply rooted in the mindsets of HCPs worldwide and need to be addressed by the continuous professional development of HCPs. The availability of reliable sources of information on the pandemic should be encouraged, with adequate explanations also available to the general public in simple terms.Antecedentes: la pandemia de COVID-19 ha asolado al mundo, con casos que aumentan continuamente  y con una escasez de información sobre el virus disponible para el público en general. A pesar de la disponibilidad de fuentes confiables en línea, todavía hay conceptos erróneos relacionados con el virus. Este estudio tuvo como objetivo dilucidar el nivel de ideas erróneas entre los profesionales de la salud (PS) en todo el mundo sobre la pandemia de COVID-19. Material y Métodos: Se realizó un estudio descriptivo de corte transversal a través de una encuesta global en línea. El cuestionario autoadministrado fue diseñado y registrado en un sitio web en línea (Kwiksurveys). Respondieron un total de 652 participantes de 35 países. El análisis estadístico se realizó con el programa SPSS versión 23. Las características sociodemográficas y disciplinarias se compararon con la ayuda de la la prueba de chi-cuadrado y la regresión logística univariada y multivariada para encontrar relaciones significativas. Resultado: Entre todos los profesionales de la salud, los médicos generales (61,2%) fueron los que más respondieron. Las respuestas de las mujeres (63,3%) casi duplicaron las de los hombres, y casi la mitad de los participantes trabajaban en institutos privados (49,2%). Además, la principal fuente de información utilizada por los profesionales de la salud sobre COVID-19 fueron las redes sociales (55,4%). En cuanto a los conceptos erróneos, el 71,6% de los participantes tenían conceptos correctos con respecto a COVID-19. Sin embargo, el 28.4% poseía información incorrecta. Los profesionales de la salud mujeres tenían 1.49 veces más probabilidades de tener conceptos correctos en comparación con los hombres (OR = 1.49, IC 95% = 1.04-2.14). Conclusion: La mayoría de los profesionales de la salud se mantuvieron actualizados con la información actual sobre el conocimiento, la prevención y las prácticas de higiene de la infección por COVID-19. Sin embargo, algunos conceptos erróneos están profundamente arraigados en la mentalidad de los PS en todo el mundoy deben abordarse mediante el continuo desarrollo profesional de los PS. Se debe alentar la disponibilidad de fuentes confiables de información sobre la pandemia, con explicaciones adecuadas también disponibles para el público en general en términos simples

A Study on Association of XRCC3 Gene Polymorphism in Gastric cancer risk

Gastric Cancer (GC) is among the common and fatal cancer in the world. DNA repair plays a critical role in protecting the genome of the cell from insults of cancer-causing agents. Inherited polymorphisms of DNA repair genes may contribute to variations in DNA Repair capacity (DRC) and genetic susceptibility to different c ancers. Mammalian cells are constantly exposed to a wide variety of genotoxic a gents from both endogenous and exogenous sources. In human beings, 70 genes are involve d in the five major DNA repair pathways: direct repair, NER, BER, mismatch repa ir and double-strand break repair. The X-ray repair complementing defective repa ir in Chinese hamster cells 3 (XRCC3) gene is a member of the RAD51 gene fami ly. It encodes an important protein that functions in the homologous rec ombination repair of DNA double-strand break. The Kashmir valley has an eleva ted incidence of GC and its etiology is not understood fully yet, though, we are ethni cally and demographically different from the other states of the country and world. The aim of this study was to determine whether single nucleotide poly morphism (SNP) of XRCC3 gene (Thr241Met) of exon7, can influence the risk of gastric cancer in Kashmiri population. About 80 histopathologically confirmed GC case s and 70 healthy controls, age ,gender, ethnicity matched for known genotypes of XRCC3 exon7 were analyzed. Patients medical history and dietary habits were taken for the study as well. The ge notype for this variant was determined using polymerase chain reaction- restriction fra gment length polymorphisms (PCR-RFLP) in 80 histologically confirmed GC patients and 70 frequency-matched healthy controls in Department of Biochemistr y, Government Medical College srinagar. The XRCC3 genotype and allele frequencies were not significantly different between cases and controls (P= 0.92 for ge notype; P= 0:72 for allele). The XRCC3 241Met allele frequency (6.6%) was signifi cantly lower in healthy Kashmiri controls than previously reported healthy US Caucasian controls (38.9%). Compared with the XRCC3241Thr/Thr genoty pe, the variant XRCC3241Thr/Met and Met/Met genotypes were not associated with an increased risk of gastric cancer (adjusted odds ratio (ORa), 1.19; 95% confiden ce interval (CI), 0.44-3.18). These finding s suggest that polymorphisms of XRCC3 Thr241Met may not play a role in the etiology of GC. Further studies with a larger number of subjects and simultaneous measurement of different pol ymorphisms in DNA repair genes in the same pathway are needed

In Vitro

Arnebia benthamii is a major ingredient of the commercial drug available under the name Gaozaban, which has antibacterial, antifungal, anti-inflammatory, and wound-healing properties. In the present study, in vitro antioxidant and anticancer activity of different extracts of Arnebia benthamii were investigated. Antioxidant potential of plant extracts was evaluated by means of total phenolics, DPPH, reducing power, microsomal lipid peroxidation, and hydroxyl radical scavenging activity. The highest phenolic content (TPC) of 780 mg GAE/g was observed in ethyl acetate, while the lowest TPC of 462 mg GAE/g was achieved in aqueous extract. At concentration of 700 µg/mL, DPPH radical scavenging activity was found to be highest in ethyl acetate extract (87.99%) and lowest in aqueous extract (73%). The reducing power of extracts increased in a concentration dependent manner. We also observed its inhibition on Fe2+/ascorbic acid-induced lipid peroxidation (LPO) on rat liver microsomes in vitro. In addition, Arnebia benthamii extracts exhibited antioxidant effects on Calf thymus DNA damage induced by Fenton reaction. Cytotoxicity of the extracts (10–100 µg/mL) was tested on five human cancer cell lines (lung, prostate, leukemia, colon, and pancreatic cell lines) using the Sulphorhodamine B assay

Fabrication of Ag and Ni Nanocatalyst with Enhanced Efficiency

Metal nanoparticles (NPs) have received significant attention in last decade because of their unique properties. In this work, two different metal NPs have been prepared and their catalytic activities are compared with conventional catalyst. In first case, Ag NPs were synthesized by chemical reduction method in ethanolic medium. Synthesized Ag NPs were characterized by scanning electron microscope (SEM) images which indicated an average particle size of Ag around 250 nm. The catalytic activity of Ag NPs was investigated for the oxidative mineralization of methylene blue dye. Comparative studies suggested that Ag NPs possess enhanced catalytic activity compared to bulk Ag. In second approach, supported Ni NPs were fabricated using Al2O3 as supporting surface; that is, Ni NPs get adsorbed on Al2O3 through in situ reduction reaction. Oxidative degradation of methylene blue indicated that catalytic activity of supported Ni/Al2O3 is about five times higher than simple Ni as catalyst

Antimicrobial and Antioxidant activities of Arnebia benthamii (Wall ex. G. Don Johnston) - A Critically Endangered Medicinal plant of Kashmir

Plants used in traditional medicines contain a vast array of substances that can be used to treat chronic and infectious diseases and the present study was carried out with the same intentto appraisethe possible medicinal value of Arnebia benthamii L. (Wall. ex G. Don) Johnston [Syn Macrotomia benthamii (Wall.) DC.] a threatened medicinal plant of Kashmir valley by examining its phyto-chemical constituents and evaluating the antimicrobial and antioxidant activity. Preliminary phytochemical screening was carried out to detect the presence of phyto-chemicals that add to the medicinal value of the plant. The antimicrobial assay was carried out by Disc diffusion and Micro-broth dilution methods. The crude plant extracts (both root as well as aerial parts) exhibited significant antimicrobial activity on majority of test organisms tested. The highest occurrence of secondary metabolites was of alkaloids and phenolic substances. The tannins and saponins were absent in all plant extracts. The total phenolic content that was quantitatively estimated showed highest presence in methanol extracts of the aerial parts. The antibacterial results revealed that methanol extracts of aerial parts were found to exhibit significant antibacterial activities against all tested bacterial strains except Staphylococcus aureus which was found resistant. The highest inhibition zone diameter (30mm) was recorded for Pseudomonas aeruginosa and Escherichia coli with respect to control i.e. Gentamycin (16 and21mm) followed by Salmonella typhimurium (28 mm). Chloroform extract also showed good inhibitory activity against all the tested bacterial strains likeE. coli (22mm) followed by Klebsella pnuemonie (20 mm) and P. aeruginosa (17mm). The aqueous extract didn’t show any inhibitory activity against the tested bacterial strains. The root extracts were separately tested for antibacterial activity against pathogenic strains and it was apparent from the results that they were less active than aerial part extracts. Among the strains tested, S. aureus was found susceptible to chloroform, ethyl acetate and methanol root extracts with an average inhibition zone diameter (10 mm) with respect to control and rest of extracts showed no activity against it. The Shigella flexneri was found susceptible to all the root extracts and the highest inhibition zone diameter was recorded for methanol (20mm) followed by ethanol (15 mm)against the control (Erythromicin 30 mm). Among all the strains, E. coli was highly susceptible towards the methanol root extracts followed by chloroform and ethyl acetate extract while the rest of the extracts did not exhibit any inhibitory activity. Most of the root extracts exhibit highest antibacterial activity against S. typhimurium compared to aerial parts. The screening served a s an indicator f or the selection of bacterial strains that displayed antibacterial activity for further testing to determine the MIC’s of plant extracts. Four bacterial strains S. fle xnerii, K. pneumonia, E. coli and P. aeruginosa were found viable for testing with the specific plant extracts. S. flexnerii was found highly susceptible towards methanol aerial part extract with MIC and MBC value of 200μg/ml and 750 μg/ml respectively as compared to reference (Erythromycin75 and 100 μg/ml) followed by methanol root extract { MIC 300 μg/ml and500 MBC μg/ml}. Methanol aerial part extract exhibited the MIC value 500 μg/ml and MBC 750 μg/ml against K. pneumonia. However the root extracts showed co mparatively higher value of MIC against the tested organism ranging f rom400-500μg/ml with respect to positive control (MIC-150 μg/ml).The MIC value for E . coli ranged between 150 to 500 μg/ml towards aerial part extracts w ith lowest MIC observed for methanol aerial part extract with respect to Erythromycin (175 μg/ml), and for root extract MIC value ranged between 225 -425 μg/ml. P. aeruginosa was found to be most susceptible towards all aerial part extracts with MIC value ranged between 75 μg/ml and 425 μg/ml and MBC value from 100 to750 μg/ml. All the fungal strains except Candida parapsilosis were more or less inhibited b y both aerial and root part extracts of the plant. The aqueous extract of both root as well as aerial parts did not show any antifungal activity. Asperigillus flavus was found to be highly susceptible to butanol aerial part extract with inhibition zone diameter (25mm) followed by ethyl acetate extract(22 mm) and chlorof orm extract (14 mm) compared to the control (Nystatin 35mm) used. The methanol aerial part extract showed highest inhibitory activity against Asperigill us versicolor with inhibition zone diameter (22 mm) and Acremonium spp (25 mm). The petroleum ether, ethyl acetate and chloroform extracts of aerial part did not exhibit any inhibitory activity against Candida spp . Only methanol extract followed by ethanol and butanol extract exhibited antif ungal activity against Candida spp. Among the Candida spp, the highest inhibition zone diameter (14 mm) of methanol extract was seen against C. albicans whereas C. parapsalosis was found completely resistant against the all aerial part extra cts. The ethanol and aqueous root extracts didn’t exhibit any inhibitory activity against any tested fungal strains. Meanwhile the ethyl acetate extract sho wed highest inhibition zone diameter(33mm) against C. albicans f ollowed by Acremonium spp (18mm).The methanol root extract showed good inhibitory activity with an average inhibition zone diameter (12mm) against A. versicolor, C. albicans and C. kruesie with respect to reference used. The four in-vitro tests i.e. DPPH radical scavenging action, riboflavin photo- oxidation method, hydroxyl scavenging and the lipid peroxidation assay for antioxidant activity were used. Together all the methods provide a better assessment of antioxidant properties and results revealed that inhibitory activity was concentration dependent. Free radical scavenging potential of aerial and root part extracts at different concentrations was tested by the DPPH method. Highest inhibition of 86% and 94% was recorded for both methanol extracts of aerial as well as root parts with respect to reference (Ascorbic acid 90%) at the higher concentration (300 μg/ml) followed by ethyl acetate (60%) and chloroform extract (63 %) of aerial parts. The superoxide radical scavenging activity of aerial parts was observed in the following order butanol extract (85%) >ethyl acetate (79%)> methanol extract (70%) however Petroleum ether, ethanol and aqueous extracts didn't exhibit any scavenging activity. The root extracts were also effective in scavenging the superoxide radicals and the order of scavenging was as butanol (91%)> methanol (88%)>aqueous (79%) extracts. As far as the protective effect of deoxyribose was concerned, the highest inhibition of radicals was observed for methanol extract of root part and aerial part (~85% inhibition). The ethanol extracts of both parts were found to be ineffective. The overall inhibition of FeSO4 induced lipid peroxidation was high in presence of positive control (ascorbic acid 95.78±1.0%) compared to the plant extracts of A. benthamii. However, the ethyl acetate extract of aerial parts (95 %) showed almost the same activity as compared to the reference antioxidant. The ethyl acetate (87%) of root parts also exhibited significant inhibitory activity followed by ethanol extracts (78%)