Cytological and histopathological correlation of thyroid lesions.

OBJECTIVE: To determine accuracy of cytological diagnosis in comparison with the corresponding histopathological diagnosis of thyroid lesions. METHODS: The retrospective study was conducted at the Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan, and comprised data from January to December 2017 of all in-patient cases of thyroid cytology with their histopathological diagnosis. Both Haematoxylin and Eosin stain slides and cytological smears were reviewed. True negative, true positive, false negative and false positive cases were marked using the criteria defined in Table-1. RESULTS: Of the total 36 cases, 5(13.9%) were non-diagnostic or unsatisfactory for cytological assessment. Cytological diagnosis achieved sensitivity of 82.3%, specificity 64.3%, positive predictive value 73.6%, negative predictive value 75%, false positive rate 35.7% and false negative rate 17.6%. The diagnostic accuracy of cytological diagnosis was 63.9%. CONCLUSIONS: There was significant cytological and histopathological concordance of thyroid lesions.

Prognostic Significance of Percentage Necrosis in Clear Cell Renal Cell Carcinoma.

OBJECTIVES: The consensus conference of the International Society of Urological Pathology (ISUP), held in 2012, made recommendations regarding prognostic parameters of renal tumors. There was a strong consensus that tumor morphotype, pathologic tumor stage, and tumor grade are prognostic indicators of poor outcome. It was also agreed upon that prognostic significance of tumor necrosis is in evolution, and both microscopic and macroscopic tumor necrosis should be documented in percentages. The aim of our study was to explore the impact of tumor necrosis on metastasis-free survival in clear cell renal carcinomas (ccRCCs) in Pakistani patients. METHODS: We retrieved 318 consecutive in-house cases of ccRCC resections from 2014 to 2020 through hospital archives. Histologic slide review was done for assessment of tumor necrosis, tumor stage, and World Health Organization/ISUP grade. The follow-up data to assess metastasis-free survival were available in hospital archives. RESULTS: In multivariable analysis performed by logistic regression model, tumor necrosis was an independent poor prognostic indicator (P = .0001): group 1 (reference group), 0% necrosis; group 2, 1% to 10% necrosis (adjusted odds ratio [AOR], 8.71; 95% confidence interval [CI], 3.62-20.98); and group 3, more than 10% necrosis (AOR, 9.48; 95% CI, 3.99-22.725). CONCLUSIONS: Tumor necrosis is an independent predictor of poor outcome in ccRCCs.

Morphological Spectrum and Survival Analysis of Diffuse Midline Glioma With H3K27M Mutation.

Background Diffuse midline gliomas with the H3K27M mutation are now recognized as separate entities due to their unique molecular signature, clinical features, and adverse outcome. Objective To determine the morphological spectrum and survival rate of diffuse midline gliomas with H3K27M mutation. Material and methods This retrospective study was conducted between January 2015 and January 2021 at Shaukat Khanum Memorial Cancer Hospital and Research Centre. Medical records of 28 cases of H3K27M-mutated midline gliomas were retrieved. Case slides were reviewed and the pertinent histological spectrum was evaluated. Results The mean age of patients was 24.36 ± 14.06 years. There were 21 (75%) males and 7 (25%) females. Biopsy was performed in 22 (78.6%), total resection in 1 (3.6%) while subtotal resection was done in 5 (17.9%) cases. Histologically, a spectrum of morphologies was noted with pilocytic astrocytoma (WHO grade 1) at one end and glioblastoma (WHO grade IV) at the other end. Immunohistochemically, all 28 cases were positive for Histone 3 immunohistochemistry. ATRX was performed in 7 (25.0%) cases with loss of ATRX expression in 3 (10.7%) and retained expression in 4 (14.3%) cases. Ki67 was <5% in 6 (21.4%), 5-10% in 1 (3.6%), 11-15% in 1 (3.6%), 16-20% in 3 (10.7%), 21-25% in 4 (14.3%), and 26-30% in 2 (7.1%) cases. The mean survival was 8.00 ± 9.39 months. Out of 28 patients, 15 (62.5%) patients died of disease. Conclusion Diffuse midline gliomas with H3K27M mutation is an aggressive entity with a broad morphological spectrum.

Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors.

Ependymomas encompass a heterogeneous group of central nervous system (CNS) neoplasms that occur along the entire neuroaxis. In recent years, extensive (epi-)genomic profiling efforts have identified several molecular groups of ependymoma that are characterized by distinct molecular alterations and/or patterns. Based on unsupervised visualization of a large cohort of genome-wide DNA methylation data, we identified a highly distinct group of pediatric-type tumors (n = 40) forming a cluster separate from all established CNS tumor types, of which a high proportion were histopathologically diagnosed as ependymoma. RNA sequencing revealed recurrent fusions involving the pleomorphic adenoma gene-like 1 (PLAGL1) gene in 19 of 20 of the samples analyzed, with the most common fusion being EWSR1:PLAGL1 (n = 13). Five tumors showed a PLAGL1:FOXO1 fusion and one a PLAGL1:EP300 fusion. High transcript levels of PLAGL1 were noted in these tumors, with concurrent overexpression of the imprinted genes H19 and IGF2, which are regulated by PLAGL1. Histopathological review of cases with sufficient material (n = 16) demonstrated a broad morphological spectrum of tumors with predominant ependymoma-like features. Immunohistochemically, tumors were GFAP positive and OLIG2- and SOX10 negative. In 3/16 of the cases, a dot-like positivity for EMA was detected. All tumors in our series were located in the supratentorial compartment. Median age of the patients at the time of diagnosis was 6.2 years. Median progression-free survival was 35 months (for 11 patients with data available). In summary, our findings suggest the existence of a novel group of supratentorial neuroepithelial tumors that are characterized by recurrent PLAGL1 fusions and enriched for pediatric patients.

Insects-plants-pathogens: Toxicity, dependence and defense dynamics.

In a natural ecosystem, the pathogen-plant-insect relationship has diverse implications for each other. The pathogens as well as insect-pests consume plant tissues as their feed that mostly results in damage. In turn, plant species have evolved specialized defense system to not only protect themselves but reduce the damage also. Such tripartite interactions involve toxicity, metabolic modulations, resistance etc. among all participants of interaction. These attributes result in selection pressure among participants. Coevolution of such traits reveals need to focus and unravel multiple hidden aspects of insect-plant-pathogen interactions. The definite modulations during plant responses to biotic stress and the operating defense network against herbivores are vital to research areas. Different types of plant pathogens and herbivores are tackled with various changes in plants, e.g. changes in genes expression, glucosinolate metabolism detoxification, signal transduction, cell wall modifications, Ca2+dependent signaling. It is essential to clarify which chemical in plants can work as a defense signal or weapon in plant-pathogen-herbivore interactions. In spite of increased knowledge regarding signal transduction pathways regulating growth-defense balance, much more is needed to unveil the coordination of growth rate with metabolic modulations in bi-trophic interactions. Here, we addressed plant-pathogen-insect interaction for toxicity as well as dependnce along with plant defense dynamics against pathogens and insects with broad range effects at the physio-biochemical and molecular level. We have reviewed interfaces in plant-pathogen-insect research to show pulsating regulation of plant immunity for attuning survival and ecological equilibrium. An improved understanding of the systematic foundation of growth-defense stability has vital repercussions for enhancing crop yield, including insights into uncoupling of host-parasite tradeoffs for ecological and environmental sustainability.

Green Synthesis of Zinc Oxide (ZnO) Nanoparticles Using Aqueous Fruit Extracts of Myristica fragrans: Their Characterizations and Biological and Environmental Applications.

In the present work, bioaugmented zinc oxide nanoparticles (ZnO-NPs) were prepared from aqueous fruit extracts of Myristica fragrans. The ZnO-NPs were characterized by different techniques such as X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, ultraviolet (UV) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and thermogravimetric analysis (TGA). The crystallites exhibited a mean size of 41.23 nm measured via XRD and were highly pure, while SEM and TEM analyses of synthesized NPs confirmed their spherical or elliptical shape. The functional groups responsible for stabilizing and capping of ZnO-NPs were confirmed using FTIR analysis. The ζ-size and ζ-potential of synthesized ZnO-NPs were reported as 66 nm and -22.1 mV, respectively, via the DLS technique can be considered as moderate stable colloidal solution. Synthesized NPs were used to evaluate for their possible antibacterial, antidiabetic, antioxidant, antiparasitic, and larvicidal properties. The NPs were found to be highly active against bacterial strains both coated with antibiotics and alone. Klebsiella pneumoniae was found to be the most sensitive strain against NPs (27 ± 1.73) and against NPs coated with imipinem (26 ± 1.5). ZnO-NPs displayed outstanding inhibitory potential against enzymes protein kinase (12.23 ± 0.42), α-amylase (73.23 ± 0.42), and α-glucosidase (65.21 ± 0.49). Overall, the synthesized NPs have shown significant larvicidal activity (77.3 ± 1.8) against Aedes aegypti, the mosquitoes involved in the transmission of dengue fever. Similarly, tremendous leishmanicidal activity was also observed against both the promastigote (71.50 ± 0.70) and amastigote (61.41 ± 0.71) forms of the parasite. The biosynthesized NPs were found to be excellent antioxidant and biocompatible nanomaterials. Biosynthesized ZnO-NPs were also used as photocatalytic agents, resulting in 88% degradation of methylene blue dye in 140 min. Owing to their eco-friendly synthesis, nontoxicity, and biocompatible nature, ZnO-NPs synthesized from M. fragrans can be exploited as potential candidates for biomedical and environmental applications.

Secretory Carcinoma Of Salivary Gland: A Clincopathological Analysis.

BACKGROUND: Secretory carcinoma of the salivary gland (SC) is a new entity that harbours a specific ETV6 gene rearrangement. The clinical behaviour of this tumour is not well-known as it is a relatively new entity but it is generally considered as a tumour of low malignant potential. The objective of the study was to find out the frequency of ETV6 translocation in cases diagnosed based on histology and immunohistochemistry, to study morphological features and immunohistochemical findings of our cases and to determine the survival and disease-free status of our patients. METHODS: Twenty-five diagnosed cases of SC were retrieved from the archives of SKMCH and RC. Diagnosis was made primarily based on morphology and immunohistochemistry. Immunohistochemistry includes S100, p63, mammaglobin, DOG 1, GCDFP-15, TTF-1, GATA3, SMA, AMA, and AR. The diagnosis was further confirmed by molecular testing, i.e., Fluorescence in situ hybridization (FISH) studies to observe specific ETV6 gene break. Follow up of the patients was done by developing a questionnaire. Statistical analysis of the data was done using SPSS-23.0. RESULTS: The mean age of diagnosis was 41±17.4 and the male to female ratio was 1.5:15. The mean size of the tumour was 45.48±27.35. The most common site of the tumour was parotid gland (60%). On morphology, SC showed a wide range of morphological patterns, most common being the tubular, microcystic, intraductal, and papillary. Immunohistochemical stains mammaglobin (22/22), GCDFP-15(15/15) and GATA3 (10/10) showed 100% positive result. However, all cases were negative for p63 (0/18) and DOG 1(0/11). ETV6 break was seen in 17/17 cases (100%). The mean disease-free survival was 75 months and the overall survival was 51.90±2.80 months. CONCLUSIONS: This study highlights the presence of specific molecular alteration in all cases, which were diagnosed based on morphology and immunohistochemistry.

Androgen Receptor Expression In Endometrial Carcinoma And Its Correlation With Estrogen Receptor And Progesterone Receptor And Clinicopathological Findings.

BACKGROUND: The objective of the study is to analyze the expression of androgen, estrogen and progesterone receptor in different types of endometrial carcinomas and to correlate the androgen receptor expression with estrogen and progesterone receptor and the clinicopathological parameters like lymphovascular invasion, grade of the tumour, size of tumour and extent of myometrial invasion.. METHODS: It is a cross-sectional analytical study design with a simple random sample of a total of 54 cases of different types of endometrial carcinomas from the year 2017. Immunohistochemical stains androgen receptor, estrogen receptor, and Progesterone receptor were applied in all the cases. The Pearson Chi-square test of independence was applied to measure association and P-value is calculated to check the significance of the results. RESULTS: Androgen receptor expression was observed in 73% of low-grade endometrioid carcinomas, 62.5% of high-grade endometrioid carcinomas, 62% of serous, 20% of clear cell and 18% of carcinosarcomas, respectively. Androgen positive tumours were also positive for estrogen and progesterone in most of the cases, except 3 serous carcinomas and one low-grade endometrioid carcinoma. However, no significant relation was observed between androgen expression and prognostic parameters like the lymphovascular invasion, size of the tumour and myometrial invasion. CONCLUSIONS: Maximum expression of androgen receptor was observed in endometrioid and serous carcinomas, while carcinosarcomas and clear cell carcinomas showed minimum expression with no significant correlation between androgen receptor expression and clinicopathological parameters.

The Hot Pleura: Isolated Pleural Metastases From Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is the most common solid renal malignancy that metastasizes typically to lungs, bones, liver, adrenals, and lymph nodes. Isolated pleural metastases of RCC are extremely rare, with only few cases reported in the literature. We report one such case of a 60-year-old woman, a known case of RCC of the left kidney who underwent nephrectomy, and on follow-up, PET/CT scan revealed diffuse thick nodular hypermetabolic left pleural thickening, which was later biopsied and turned out to be pleural metastases from RCC. No other site of metastases was found.

Lhermitte-duclos disease (dysplastic cerebellar gangliocytoma): A case report.

Lhermitte-Duclos disease (LDD) is a relatively uncommon condition of the cerebellum. It is generally characterised as a hamartomatous lesion of posterior fossa and is common in the third and fourth decades of life. According to the World Health Organisation, it is classified as a grade I tumour with potential for recurrence. Otherwise, this disease is generally associated with good prognosis. Malignant transformation of LDD has not yet been reported. However, genetic counselling of the patient is recommended with active surveillance. Since LDD is believed to be a pathognomonic feature of Cowden syndrome, which is a multi-system autosomal dominant hereditary disorder characterised by multiple hamartomas and an elevated risk of benign and malignant neoplasms, we decided to report this important entity considering its rarity and high clinical significance.

Efficacy of intra-articular autologous platelet rich plasma injection in primary knee osteoarthritis: A quasi-experimental study.

OBJECTIVE: To observe the efficacy of platelet rich plasma on pain improvement in knee osteoarthritis patients and to explore the impact of various facotrs on pain reduction with such a treatment. METHODS: The quasi-experimental study was conducted at the Armed Forces Institute of Rehabilitation Medicine, Rawalpindi, Pakistan, from October 2017 to April 2018 and comprised patients with primary knee osteoarthritis. The sample was sub-grouped into "normal", "overweight" and "obese" on the basis of body mass index. Two age-based sub-groups were also formed at ≤ 60 years and >60 years. Three injections of calcium gluconate activated 2.5ml platelet rich plasma were given in the knees at an interval of two weeks each. The pain score was calculated using the numerical rating scale at the 6th week. Data was analysed using SPSS 20. RESULTS: Of the 50 patients, 26(52%) were females and 24(48%) were males. The overall mean age was 59.6±9.6 years (range: 42-75 years), with 22(44%) aged ≤ 60 years. There were 21(42%) patients who were overweight, 7(14%) had normal weight and 22(44%) were obese. There was significant pain reduction post-treatment compared to the baseline (p<0.001). The reduction in pain was not significantly related to gender, age, knee osteoarthritis grade, or body mass index (p>0.05). CONCLUSIONS: Platelet rich plasma significantly improved pain in knee osteoarthritis patients regradless of all age, gender, grade and body mass index.

Diagnostic Utility of BCOR Antibody in Clear Cell Sarcomas of Kidney.

Purpose. Clear cell sarcoma of the kidney (CCSK) is an uncommon malignant renal tumor. It is the second most common renal pediatric renal malignancy after Wilms tumor. It exhibits a heterogeneous morphology, with overlapping features with its close differentials, which results in diagnostic challenges. There was no specific immunohistochemical marker in the past, to help in this regard. BCOR antibody has recently been suggested to be helpful in the differential diagnosis. We aim to study the utility of the BCOR antibody in the diagnosis of CCSK. Methods. We selected a total of 27 cases of CCSK (n = 12), Wilms tumor (n = 12), and congenital mesoblastic nephroma (n = 3). All cases were evaluated for the extent and intensity of nuclear labeling for BCOR antibody by immunohistochemistry (IHC). Results. We found that BCOR IHC was positive in 11 out of 12 cases with diffuse and strong staining in 8 of the cases. None of the cases of Wilms tumor and congenital mesoblastic nephroma were positive. Only 2 cases of Wilms tumor showed minimal and weak staining in <5% of cells. Conclusion. Diffuse and strong nuclear staining for the BCOR antibody is highly specific for CCSK among common pediatric renal malignancies. Our study confirms that BCOR IHC is a good IHC marker for the diagnosis of CCSK.

Absence of the TRIP13 c.1060C>T Mutation in Wilms Tumor Patients From Pakistan.

BACKGROUND AND AIM: Wilms tumor (WT) is the most common childhood malignant renal tumor. Germline mutations in several WT predisposition genes have been identified. However, the fundamental cause of most WT patients remains unexplained. Recently, a founder mutation, c.1060C>T (p. Arg254X) in a mitotic spindle checkpoint gene, TRIP13, was reported in 5 unrelated children with WT from the United Kingdom, of Pakistani descent from Azad Kashmir region. This observation suggests other children with WT in Pakistan may also harbor this mutation. We conducted the first study to assess the contribution of TRIP13 c.1060C>T mutation to WT in Pakistan. MATERIALS AND METHODS: Constitutional genomic DNA from 68 Pakistani individuals including unrelated WT cases (n=26) and one (n=10) or both (n=32) of their parent(s) were screened for the TRIP13 c.1060C>T mutation using DNA sequence analysis. We also included positive controls in the analyses. RESULTS: The median age of WT diagnosis was 3.0 years (range, 0.75 to 10). The TRIP13 c.1060C>T mutation was not found in any WT patient (n=26) or their parents (n=42). Twenty-four patients (92.4%) presented with unilateral tumor and 2 patients (7.7%) were diagnosed with synchronous bilateral WT. Thirteen patients (50%) reported parental consanguinity. Thirteen patients (50.0%) belonged to the Punjabi ethnicity and 1 patient (3.8%) had a Kashmiri background. Four patients (16.7%) reported a family history of WT or other malignancies. The predominant histologic subtype was stromal (46.2%). The majority of patients presented with >5 cm of tumor size (81%). None of the patients had a personal or family history of congenital anomalies, or associated genetic syndromes. CONCLUSIONS: Our findings suggest that TRIP13 c.1060C>T mutation may be infrequent in Pakistani WT cases. Further evaluation of this mutation in a large number of WT patients of Kashmiri heritage and various ethnic backgrounds from Pakistan is warranted.

Assessment of Cucumber Genotypes for Salt Tolerance Based on Germination and Physiological Indices.

Soil salinity is one of the primary problem for agricultural crops which causes a great loss in crop production in Pakistan and worldwide. Various approaches have been implemented to overcome salinity problem. Assembly of crops for the enhancement of salt tolerance is a good strategy to achieve cost-effective yields. Cucumber is considered as one of the leading vegetable crop around the world for the nourishment of human being as source of nutrients, minerals, and vitamins. Screening of 12 cucumber genotypes using some physiological indices, that is, seedling germination stress tolerance index, plant height stress tolerance index, root length stress tolerance index, shoot and root dry weight stress tolerance index, and shoot and root fresh weight stress tolerance index were performed for the identification of salt tolerance. Using the above characteristics genotypes, Valley and HC-999 were categorized as tolerant, Safaa and Debra as medium tolerant, while Thamin-II identified as medium sensitive and NSC-CM1 and Akbar are classified as sensitive genotypes of cucumber. According to the current study findings, the screened cucumber genotypes for salinity tolerance can also be suggested to farmers for the improved production and yield of crop at saline soil.

Effect of Autologous Platelet-rich Plasma on Appearance of Tenocytes at Injured Achilles Tendon Entheses in Rabbits.

OBJECTIVE: To determine the effects of autologous platelet-rich plasma on appearance of tenocytes at injured Achilles tendon entheses in rabbits. STUDY DESIGN: Laboratory-based experimental study. PLACE AND DURATION OF STUDY: Department of Anatomy and Pathology, Army Medical College, Rawalpindi, in collaboration with National Institute of Health, Islamabad, from March to May, 2018. METHODOLOGY: Forty healthy male, 4-6 months old New Zealand white rabbits, weighing 2000-2500 gm, were randomly divided into four equal groups A, B, C and D. Group A served as control, while B, C and D were experimental groups. Injury was surgically induced at left Achilles tendon entheses of experimental groups, which were treated with injections of autologous platelet-rich plasma, at the time of induction of injury in group C and two weeks after injury in group D, while no treatment was given in group B. Animals were euthanised at the end of 12 weeks. Specimens were taken and processed for histological observations. Bonar's modified score was used to assess the appearance of tenocytes. SPSS version 21 was used for statistical analysis. Chi-square test was applied and p-value of <0.05 was taken as significant. RESULTS: Experimental group B showed marked deterioration in Bonar's score as compared to the control group A. The scores were significantly improved in treatment groups C and D as compared to group B. CONCLUSION: Injection of autologous platelet-rich plasma effectively improved the Bonar's modified score for appearance of tenocytes at injured entheses, 12 weeks after injury.

Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis.

OBJECTIVE: The colonic inner mucus layer protects us from pathogens and commensal-induced inflammation, and has been shown to be defective in active UC. The aim of this study was to determine the underlying compositional alterations, their molecular background and potential contribution to UC pathogenesis. DESIGN: In this single-centre case-control study, sigmoid colon biopsies were obtained from patients with UC with ongoing inflammation (n=36) or in remission (n=28), and from 47 patients without colonic disease. Mucus samples were collected from biopsies ex vivo, and their protein composition analysed by nanoliquid chromatography-tandem mass spectrometry. Mucus penetrability and goblet cell responses to microbial stimulus were assessed in a subset of patients. RESULTS: The core mucus proteome was found to consist of a small set of 29 secreted/transmembrane proteins. In active UC, major structural mucus components including the mucin MUC2 (p<0.0001) were reduced, also in non-inflamed segments. Active UC was associated with decreased numbers of sentinel goblet cells and attenuation of the goblet cell secretory response to microbial challenge. Abnormal penetrability of the inner mucus layer was observed in a subset of patients with UC (12/40; 30%). Proteomic alterations in penetrable mucus samples included a reduction of the SLC26A3 apical membrane anion exchanger, which supplies bicarbonate required for colonic mucin barrier formation. CONCLUSION: Core mucus structural components were reduced in active UC. These alterations were associated with attenuation of the goblet cell secretory response to microbial challenge, but occurred independent of local inflammation. Thus, mucus abnormalities are likely to contribute to UC pathogenesis.

Ex-vivo antihypertensive and calcium channel blocking activity of Androsace foliosa n-hexane leaves fraction on isolated rabbit aorta.

Hypertension is persistent elevation in blood pressure for 3-4 weeks. Estimated global prevalence of hypertension suggested that by the Year 2025 (29%) of adult worldwide are suffering from hypertension (1.56 billion). Hypertension complications are hemorrhage, atherosclerosis, renal artery stenosis, angina pectoris end organ damage, cardiomyopathy, myocardial infarction and retinopathy. Along with other drug class Calcium channel blocker are also used for the treatment of hypertension. In this study the possible action of the n-hexane leaves fraction of the Androsace foliosa on isolated rabbit aorta was examined. Antihypertensive activity was examined in the existence of standard agonist like phenylephrine and antagonist like Verapamil. Phenylephrine (PE 1µM) high K+ was used to steady the tissue materials. Additionally to observe the calcium channel blocking effect the tissues were treated with n-hexane segment of A. foliosa leaves. Aortic tissues were treated 4-5intervals with Ca+2- free preparation earlier to control calcium reaction curve (CRCs). Verapamil is utilized as standard calcium channel inhibitory mediator and is used as an antagonist. The Af. n-hexane leaves fraction completely inhibited the precontractions induced by Phenylephrine (1µM) and K+ (80 mM) precontractions, with EC50 standards of 1.0mM (0.3-1.0mg/mL) and 4.90mM (1-3mg/mL), respectively. Androsace foliosa n-hexane leaves fraction was tested for calcium channel inhibitory effect on isolated rabbit aorta. A. foliosa n- hexane leaves segment at the dosage of 1mg/mL block the calcium channel approximately (35±5%). Consequence indicates that A. foliosa n-hexane leaves segment block calcium channel in the similar manner as compared to the standard calcium channel blocker drug (verapamil).

Structure-based pharmacophore models to probe anticancer activity of inhibitors of protein kinase B-beta (PKB ß).

Protein kinase B-beta (PKBß/Akt2) is a non-receptor kinase that has attracted a great deal of attention as a promising cancer therapy drug target. In mammalian cells, hyperactivation of Akt2 exclusively facilitates the survival of solid tumors by interfering with cell cycle progression. This definite function of Akt2 in tumor survival/maintenance provides the basis for the development of its antagonists with the aim of desensitizing cell proliferation. In order to find novel and potent Akt2 inhibitors, structure-based pharmacophore models have been developed and validated by the test set prediction. The final pharmacophore model was used for hits identification using public chemical databases. The hits were further prioritized using drug-like filters which revealed 14 potential hit compounds having novel chemical scaffolds. Our results elucidate the importance of three hydrogen bond acceptors (A), one hydrogen bond donor (D), one hydrophobic group (H), and one positive ionic charge (P) toward inhibition of the Ak2. One of our selected hits showed 68% cell apoptosis at 8 µg/ml concentration. We proposed various chemical scaffolds including benzamide, carboxamide, and methyl benzimidazole targeting Akt2 and thus may act as potential leads for the further development of new anticancer agents.

Diagnostic accuracy of glypican-3 in differentiating hepatocellular carcinoma from metastatic liver tumours.

OBJECTIVE: To determine the diagnostic accuracy of Glypican-3 in differentiating hepatocellular carcinoma from metastatic liver tumours while taking histopathology as the gold standard.. METHODS: The cross-sectional study was conducted at Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan, from January 1 to June 30, 2016, and comprised cases of malignant liver tumours. Samples were collected from the pathology department. Glypican-3was applied on them. Tumours were classified as positive when they showed >5% positivity and negative when showing <5% positivity. Frequencies and percentages of cases showing GPC3 positivity and negativity along with frequency and percentages of hepatocellular carcinoma and metastatic tumours were calculated. RESULTS: Of the 240 patients, 143(59.58%) were males and 97 (40.42%) were females. Overall mean age was 54.65 ± 13.46 years. On histopathology, 134 cases were hepatocellular carcinoma (55.83%) and 106 (44. 17%) cases turned out to be metastatic carcinoma. Glypican-3staining was positive in 116 (48.33%) cases and negative in 124(51.67%). Sensitivity was 82%, Specificity 94.33%, positive predictive value 94.82% and negative predictive value 80.64%. Diagnostic accuracy was 87.5%. CONCLUSIONS: Glypican-3 was found to be a highly sensitive and specific Immunohistochemistry stain distinguishing hepatocellular carcinoma from the clear majority of metastatic carcinomas of the liver.

Granulomatous Interstitial Nephritis: A Rare Cause of Acute Kidney Injury.

Acute granulomatous interstitial nephritis (GIN) is a rare cause of acute kidney injury (AKI) but treatable. It is present in 0.5 to 0.9% of native renal biopsies. Treatment with moderate dosage of steroids is associated with good prognosis. We herein review a case of a 48-year lady having AKI following drug-induced damage [non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics]. Her renal functions did not improve after one month of drug withdrawal, so renal biopsy was done that showed acute GIN. She was treated with intravenous then oral steroids that completely resolved AKI.