Percutaneous transluminal angioplasty with stenting for transplant renal artery stenosis at the anastomosis site in a young female patient: A case report.

INTRODUCTION: Transplant renal artery stenosis (TRAS) is one of the major vascular complications and is mostly reported within six months following kidney transplant. CASE PRESENTATION: The present case was a 16-year-old female whose blood urea nitrogen (BUN) and creatinine rose seven days after a kidney transplant. Ultrasound investigation revealed well-prefusion with a 90-degree angle anastomosis, apparent narrowing, and peak systolic velocity of 300 cm/s. Fourteen days after the transplant, with pre-and post-intervention hemodialysis and well hydration, an angiography with diluted iodinated contrast was done for the patient, which revealed >80 % narrowing at the anastomosis site. Percutaneous transluminal angioplasty (PTAS) with stenting was carried out for the patient, resulting in normal levels of BUN, creatinine, and urinary output. CLINICAL DISCUSSION: While the patient did not have any risk factors for TRAS and was young, an early stenosis occurred in her left internal iliac artery one week after the kidney transplant. Due to the lower accuracy of CO2 angiography, diluted iodinated contrast angiography with well hydration and pre- and post-intervention dialysis was preferred. Endovascular treatment was preferred by the patient and attending physician due to possible adhesion and complications of open surgery and the possibility of arterial rupture. CONCLUSION: Performing PTAS two weeks after the renal transplantation at the anastomosis site can be a treatment in patients with early TRAS. However, due to the higher risk of rupture at the anastomosis site, it should be carried out carefully and with consideration of the need for open surgery.

Hybrid surgery of arteriovenous malformation and aneurysm of the sole.

The study describes the successful treatment of a rare type of arteriovenous malformation (AVM) in the sole using hybrid surgery, which consists of open resection and embolization. Moreover, the possibility of utilizing ultrasound during examination in addition to angiography for the diagnosing of AVM of the sole is proposed.

Pelvic arteriovenous malformation (AVM) with recurrent hematuria: A case report.

INTRODUCTION: Arteriovenous malformation (AVM) leads to a direct connection between arterial and venous networks, in which capillary branches are not involved. Pelvic AVM is a benign and rare condition causing severe pain, hematuria, and rectal or vaginal bleeding. CASE PRESENTATION: A 36-year-old woman presented with five months history of hematuria. Her medical history was unremarkable, and laboratory findings were all within normal ranges. Abdominopelvic computed tomography (CT) scan revealed a vascular mass in the left lateral pelvis that extended to the bladder neck and was suggestive of an AVM. The patient underwent a laparotomy for the resection of AVM. The first angiography revealed an AVM in the left internal iliac artery. The patient underwent embolization with coil and gel foam. The second angiography revealed complete obstruction of the left internal iliac artery due to multiple coils and AVM of the right internal iliac artery (RIIA), embolized with glue and lipiodol. A week later, venography revealed another left iliac vein malformation embolized with foam sclerotherapy. Forty days later, the third angiography revealed another AVM in the right iliac artery, embolized with three vials of polyvinyl alcohol (PVA). Following two months of follow-up, the symptoms did not return. DISCUSSION: The present study reported a rare case of recurrent pelvic AVM causing painless hematuria in a female patient. The lesion was treated with several angioembolization sessions. CONCLUSION: Angioembolization is one of the main therapeutic options for AVM. Appropriate material should be precisely chosen for AVM embolization regarding the AVM's location, size, and condition.

Oral contraceptive pill (OCP) treatment alters the gene expression of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) in polycystic ovary syndrome (PCOS) women compared to drug-naive PCOS women.

BACKGROUND: Polycystic ovary syndrome (PCOS) presents clinical symptoms of menstrual abnormalities, excessive hair growth (hirsutism), scalp hair loss, acne and infertility. Metabolic abnormalities such as obesity, insulin resistance, glucose intolerance and cardiovascular problems constitute an essential part of PCOS, all of which can have significant long-term health consequences. Low-grade chronic inflammation demonstrated by persistent moderately elevated serum levels of inflammatory and coagulatory markers plays a critical role in the pathogenesis of PCOS. Oral contraceptive pills (OCPs) constitute the mainstay of pharmacologic therapy for women with PCOS to regularize cyclicity and ameliorate androgen excess. On the other hand, OCP use is associated with various venous thromboembolic and proinflammatory events in the general population. PCOS women always carriers the increased lifetime risk of these events. The studies on the effect of OCPs on inflammatory, coagulation and metabolic parameters in PCOS are less robust. Therefore in this study, we investigated and compared the messenger RNA (mRNA) expression profiles of genes implicated in inflammatory and coagulation pathways between drug-naive and OCP-treated PCOS women. The selected genes include intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1). Furthermore, the correlation between the selected markers and various metabolic indices in the OCP group has also been explored. METHOD: The relative amounts of ICAM-1, TNF-α, MCP-1 and PAI-1 mRNA in peripheral blood mononuclear cells from 25 drug-naive PCOS subjects (controls) and 25 PCOS subjects who received OCPs containing 0.03 mg-ethinyl-estradiol and 0.15 mg-levonorgestrel for at least six months (cases) were estimated using real-time qPCR. The statistical interpretation was conducted using SPSS version 20.0 (SPSS, Inc, Chicago, IL), Epi Info version 2002 (Disease Control and Prevention Centres, Atlanta, GA) and GraphPad Prism 5 (GraphPad Software, La Jolla, CA) software. RESULT: Six months of OCP therapy enhanced the expression of inflammatory genes viz ICAM-1, TNF-α and MCP-1 mRNA in PCOS women by 2.54, 2.05 and 1.74 folds, respectively, in this study. However, PAI-1 mRNA in the OCP group showed no significant increase. Furthermore, in cases, ICAM-1 mRNA expression positively correlated with body mass index (BMI) (p = 0.01), fasting insulin (p = 0.01), insulin 2 h p = 0.02), glucose 2 h (p = 0.01) and triglycerides (p = 0.01). TNF-α mRNA expression positively correlated with fasting insulin (p = 0.0007). MCP-1 mRNA expression positively correlated with (BMI) (p = 0.002). CONCLUSION: OCPs helped reduce clinical hyperandrogenism and regularise menstrual cycles in women with PCOS. However, OCP use was associated with increased fold expression of inflammatory markers which positively correlated with metabolic abnormalities.

Association of -675 4G/5G PAI-1 and -2518A/G MCP-1 genetic polymorphisms with polycystic ovary syndrome in Kashmiri women: A case control study.

Background: Polycystic ovarian syndrome (PCOS) is a highly prevalent endocrine disorder among females of fertile age. It has been speculated to be associated with low-grade chronic inflammation like other inflammatory response-driven multifactorial illnesses such as diabetes mellitus (DM) and cancer. Monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) are biomarkers of inflammation and endothelial dysfunction, respectively. These have been found to be elevated in PCOS patients. The current research reveals that single nucleotide polymorphisms (SNPs) in their genes are strongly associated with the elevation of these biomarkers. The goal of this study was to see if there was a link between PAI-1 -675 4G/5G and MCP-1 -2518 A/G polymorphisms with the occurrence of PCOS. Material and Method: This study included 220 PCOS participants and 220 healthy controls. The allele-specific polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods were used to investigate PAI-1-675 4G/5G and MCP-1 -2518A/G SNPs, respectively. Results: The -675 4G/5G SNP in the PAI-1 gene was strongly linked to PCOS. The odds ratio (OR) for the 4G/4G genotype was (OR = 3.2; P = 0.001), whereas the OR for the 4G/5G genotype was (OR = 2.39; P = 0.001). The carriers with the 4G/4G and 4G/5G genotypes showed significantly increasing trends in the triglyceride levels (P < 0.05). The genotypic frequency of the -2518 A/G MCP-1 SNP differed significantly between the PCOS patients and healthy controls; the GG genotype remained a strong predictor of PCOS (OR = 8.7; P = 0.01) and the AG genotype (OR = 2.40; P = 0.01), indicating an elevated risk of predisposing women to PCOS. There was a significant variation in the glucose 2-h levels between -2518A/G MCP-1 genotypes with AG heterozygous and GG mutant genotype showing increasing trends of glucose 2-h levels (P < 0.05). Conclusion: Both PAI-1 -675 4G/5G and MCP-1 -2518A/G polymorphisms are associated with predisposition to PCOS and its complications in Kashmiri women.

Molecular Epidemiologic Study of Male Trichomoniasis in Hamadan, Western Iran.

BACKGROUND: Trichomoniasis, caused by Trichomonas vaginalis protozoan, may lead to clinical or subclinical urethritis or prostatitis in men. Despite the importance of men in the epidemiology of trichomoniasis, there is little information about this topic. This epidemiological study was performed on men in Hamedan, western Iran. METHODS: During Oct 2018 to Mar 2019, 214 male individuals, presenting to the Urology Clinic of Shahid Beheshti Hospital in Hamadan, were enrolled and evaluated for trichomoniasis. First-voided urine specimen was used for detection of T. vaginalis infection using molecular and parasitological methods. RESULTS: Trichomoniasis was detected in 10 of 214 male participants (4.7%, 95% CI: 7.5-1.8%) using PCR assay. Culture and wet mount preparation of urine sediment were unable to isolates any T. vaginalis parasite. Nine of the 10 infected men were married, and six of them were ≥49 yr of age. Urinary frequency and dysuria were the most complaints (80%) among infected individuals. CONCLUSION: Given the notable prevalence of the infection, the prevalence of male trichomoniasis will be underestimated if only conventional diagnostic methods are used. Therefore, the risk of infection as well as the molecular survey of T. vaginalis infection should be considered in men with or without clinical symptoms.

Gas Chromatographic-Mass Spectrometric Analysis, Antibacterial, Antioxidant and Antiproliferative Activities of the Needle Essential Oil of Abies pindrow growing wild in Kashmir, India.

The essential oil composition of the leaves of Abies pindrow, growing in Kashmir, India, along with its antioxidant, antibacterial and anticancer activity is reported for the first time. Gas chromatography coupled with mass spectrometry (GC-MS) revealed the presence of 12 constituents, representing 99.9% of the total oil. The major constituents of the oil were limonene (38.9%), α-pinene (36.5%), ß-pinene (6.9%), and α-selinene (4.4%). The essential oil was dominated by the presence of monoterpene hydrocarbons (90.2%), followed by sesquiterpene hydrocarbons (6.761%), oxygenated sesquiterpenes (2.096%) and oxygenated monoterpenes (0.942%). The monoterpene rich essential oil was subjected to antibacterial activity against 4 Gram negative bacteria and 2 Gram positive bacteria at three different concentrations using Agar Well Diffusion Method taking streptomycin sulphate as reference. The oil displayed significant and broad spectrum antibacterial activity against different bacteria used. The minimum inhibitory concentration (MIC) of the active essential oil was determined using Agar Dilution Method. Highest antibacterial activity was shown by the oil against E. Coli (25 mm), and the lowest by Bacillus subtilis (14 mm) and Pseudomonas aeruginosa (14 mm). The oil was subjected to cytotoxic activity by MTT assay against human mammary carcinoma (MCF), human ductal breast epithelial tumour (T47D), human lung adeno-carcinoma epithelial (A549) and rat glial (C6) cell lines at three different concentrations. The results revealed significant sensitization of the cell lines with highest inhibition against human ductal breast epithelial cell line (51%) and the lowest against rat glial cell line (33%) at a concentartion of 50 µg/mL. The oil displayed a significant free radical scavenging activity with DPPH.

Combined gas exchange characteristics, chlorophyll fluorescence and response curves as selection traits for temperature tolerance in maize genotypes.

Maize is a low-temperature (LT)-sensitive plant and its physiological responses towards LT of temperate regions developed is an adaptive trait. To further our understanding about the response of maize to LT at the physiological and photosynthesis level, we conducted Infrared Gas Analysis (IRGA using LICOR6400-XT in 45-day-old grown two maize genotypes, one from temperate region (Gurez-Kashmir Himalayas), viz., Gurez local (Gz local), and another from tropics (Gujarat), viz., GM6. This study was carried out to evaluate the underlying physiological mechanisms in the two differentially temperature-tolerant maize genotypes. Net photosynthetic rate (A/PN), 18.253 in Gz local and 25.587 (µmol CO2 m-2 s-1) in GM6; leaf conductance (gs), 0.0102 in Gz local and 0.0566 (mmol H2O m-2 s-1) in GM6; transpiration rate (E), 0.5371 in Gz local and 2.9409 (mmol H2O m-2 s-1) in GM6; and water use efficiency (WUE), 33.9852 in Gz local and 8.7224 (µmol CO2 mmol H2O-1) in GM6, were recorded under ambient conditions. Also, photochemical efficiency of photosystem II (PSII) (Fv/Fm), 0.675 in Gz local and 0.705 in GM6; maximum photochemical efficiency (Fv'/Fm'), 0.310234 in Gz local and 0.401391 in GM6; photochemical quenching (qP), 0.2375 in Gz local and 0.2609 in GM6; non-photochemical quenching (NPQ), 2.0036 in Gz local and 1.1686 in GM6; effective yield of PSII (ФPSII), 0.0789 in Gz local and 0.099 in GM6; and electron transport rate (ETR), 55.3152 in Gz local and 68.112 in GM6, were also evaluated in addition to various response curves, like light intensities and temperature. We observed that light response curves show the saturation light intensity requirement of 1600 µmol for both the genotypes, whereas temperature response curves showed the optimum temperature requirement for Gz local as 20 °C and for GM6 it was found to be 35 °C. The results obtained for each individual parameter and other correlational studies indicate that IRGA forms a promising route for quick and reliable screening of various stress-tolerant valuable genotypes, forming the first study of its kind.

Study of the genus Bracon Fabricius, 1804 (Hymenoptera: Braconidae) from Iran: new subspecies, new records and an updated checklist.

The present study is based on the genus Bracon Fabricius collected from the Khuzestan province in the southwestern part of Iran during 2016-2017. In total, 35 species including one subspecies were collected and identified, of which 10 species are recorded for the first time from Iran and Bracon (Osculobracon) pelliger rumezensis Samartsev Zargar ssp. n. is described. In addition, 24 species are recorded for the first time from Khuzestan province in southwestern Iran. Brief diagnoses with illustrations for new records from Iran and a faunistic list with distribution data are provided.

Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance.

Early-stage detection of leukemia is a critical determinant for successful treatment of the disease and can increase the survival rate of leukemia patients. The factors limiting the current screening approaches to leukemia include low sensitivity and specificity, high costs, and a low participation rate. An approach based on novel and innovative biomarkers with high accuracy from peripheral blood offers a comfortable and appealing alternative to patients, potentially leading to a higher participation rate.Recently, non-coding RNAs due to their involvement in vital oncogenic processes such as differentiation, proliferation, migration, angiogenesis and apoptosis have attracted much attention as potential diagnostic and prognostic biomarkers in leukemia. Emerging lines of evidence have shown that the mutational spectrum and dysregulated expression of non-coding RNA genes are closely associated with the development and progression of various cancers, including leukemia. In this review, we highlight the expression and functional roles of different types of non-coding RNAs in leukemia and discuss their potential clinical applications as diagnostic or prognostic biomarkers and therapeutic targets.

Recent Advances in Head and Neck Tumor Microenvironment-Based Therapy.

Head and neck squamous cell carcinomas (HNSCCs) are a group of heterogeneous aggressive tumors affecting more than half a million patients worldwide annually. While the tobacco- and alcohol-associated HNSCC tumors are declining, human papillomavirus (HPV)-induced tumors are on rise. Despite recent advances in multimodality therapeutic interventions including surgery in combination with chemoradiation therapy (CRT), the overall 5-year survival has not improved more than 50%. The underlying reasons for this dismal prognosis is the intrinsic or acquired resistance to CRT. While previous studies were focused to target tumor cells, recent findings have implicated the involvement of tumor microenvironment (TME) on tumor progression and response to therapy. HNSCC TME includes cancer-associated fibroblasts (CAFs), endothelial cells, immune cells, endocrine cells, and the extracellular matrix (ECM) proteins including collagen and fibronectin. Understanding the crosstalk between TME and cancer cells is important to formulate more effective novel therapies and to overcome resistance mechanisms. Here, we summarized the current literature on recent advances on HNSCC TME with special emphasis on novel cell-cell interactions and therapies currently under development.

Elucidating Critical Proteinopathic Mechanisms and Potential Drug Targets in Neurodegeneration.

Neurodegeneration entails progressive loss of neuronal structure as well as function leading to cognitive failure, apathy, anxiety, irregular body movements, mood swing and ageing. Proteomic dysregulation is considered the key factor for neurodegeneration. Mechanisms involving deregulated processing of proteins such as amyloid beta (Aß) oligomerization; tau hyperphosphorylation, prion misfolding; α-synuclein accumulation/lewy body formation, chaperone deregulation, acetylcholine depletion, adenosine 2A (A2A) receptor hyperactivation, secretase deregulation, leucine-rich repeat kinase 2 (LRRK2) mutation and mitochondrial proteinopathies have deeper implications in neurodegenerative disorders. Better understanding of such pathological mechanisms is pivotal for exploring crucial drug targets. Herein, we provide a comprehensive outlook about the diverse proteomic irregularities in Alzheimer's, Parkinson's and Creutzfeldt Jakob disease (CJD). We explicate the role of key neuroproteomic drug targets notably Aß, tau, alpha synuclein, prions, secretases, acetylcholinesterase (AchE), LRRK2, molecular chaperones, A2A receptors, muscarinic acetylcholine receptors (mAchR), N-methyl-D-aspartate receptor (NMDAR), glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) and mitochondrial/oxidative stress-related proteins for combating neurodegeneration and associated cognitive and motor impairment. Cross talk between amyloidopathy, synucleinopathy, tauopathy and several other proteinopathies pinpoints the need to develop safe therapeutics with ability to strike multiple targets in the aetiology of the neurodegenerative disorders. Therapeutics like microtubule stabilisers, chaperones, kinase inhibitors, anti-aggregation agents and antibodies could serve promising regimens for treating neurodegeneration. However, drugs should be target specific, safe and able to penetrate blood-brain barrier.

A review of the Iranian species of genus Iconella Mason (Hymenoptera: Braconidae: Microgastrinae) with description of two new species.

The present study was carried out in the Khuzestan province of Iran during 2016-2017. In total, five species of the genus Iconella were collected and identified, of which two new species are described and illustrated: Iconella mongashtensis Zargar Gupta sp. nov., and I. similus Zargar Gupta sp. nov. One species, Iconella meruloides (Nixon 1965), is recorded for the first time from Iran and two species, Iconella myeloenta and I. subcamilla, are new provincial records. The number of Iconella species in Iran is now raised to eight. An identification key to all Iranian species of the genus Iconella is provided.

Association of Protein Expression and Methylation of DAPK1 with Clinicopathological Features in Invasive Ductal Carcinoma Patients from Kashmir

Aims: Death-associated protein kinase-1 (DAPK1) is a pro-apoptotic Ser/Thr kinase that participates in cell apoptosis and tumor suppression. DAPK1 is frequently lost in many different tumor types including breast cancer. The aim of this study was to evaluate the promoter methylation status of DAPK1 and a possible correlation with the expression of DAPK1 and standard clinicopathological features in invasive ductal breast carcinoma patients (IDC). Methods: Methylation Specific PCR (MSP) was carried out to investigate the promoter methylation status of DAPK1 from 128 breast cancer patients. The effect of promoter methylation on protein expression was evaluated by immunohistochemistry (n=128) and western blotting (n=56). Results: We found significant difference in DAPK1 promoter methylation frequency among breast tumors when compared with the corresponding normal tissues. Hypermethylation of DAPK1 is significantly correlated with the loss of DAPK1 protein expression (P < .001, rs= -0.361). The loss of DAPK1 protein was significantly associated with estrogen receptor (ER) negativity (p= 0.003), triple negative breast cancer (TNB) (p= 0.024) and advanced tumor stages (P = 0.001). Moreover, age at diagnosis (p= 0.041), tumor stage (p= 0.034), ER negativity (p= 0.004) and TNB cancers (p=0.003) correlated significantly with the hypermethylation of the DAPK1 promoter. Coclusion: This study indicates that DAPK1 is methylated in IDC and promoter hypermethylation could be attributed to silencing of DAPK1 gene expression in breast cancer. Thus, we consider DAPK1 inactivation by promoter hypermethylation likely plays a role in the development and progression of breast cancer.

Modulation of Oxidative Stress and Hyperglycemia by Rheum spiciformis in Alloxan Induced Diabetic Rats and Characterization of Isolated Compound.

This study evaluates the ameliorative potential of Rheum spiciformis methanolic (RS-MeOH) extract in reducing oxidative stress and hyperglycemia in albino rats along with characterization of possible therapeutic compound(s). Groups treated with 50 and 100 mg/kg bw plant extract (RS-MeOH ) decrease blood glucose levels from 359.9±8.2 to 209.5±8.5 mg/dl (50 mg/kg bw) and 354.7±13.3 to 162.5±7.4 mg/dl (100 mg/kg bw) on the 0th and 14th day (P<0.001) respectively. This reduction in blood glucose was significant as compared to glibenclamide (20 mg/dl) which reduced glucose levels from 297.7±11.39 to 132.9±8.74 mg/dl on 0th and 14th day respectively. Biochemical parameters triglycerdies, cholesterol, low density lipoprotein (LDL) and creatinine were also reduced in a dose dependent manner. Liver marker enzymes were positively modulated by administration of RS-MeOH (P<0.001). Antioxidant enzyme profile showed an enhanced/better pattern after the administration of RS-MeOH extracts for reduced glutathione, reduced glutathione (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and superoxide dismutase (SOD) in both liver and pancreas. Moreover pancreatic histopathology reports revealed ß-cell restorative effects with RS-MeOH, thereby potentiating its role in improving blood glucose levels. RS-MeOH purification and isolation studies involving GC-MS and NMR techniques revealed presence of emodin type compounds in RS-MeOH. Overall Rheum spiciformis showed ameliorative action on oxidative stress and hyperglycemia, however further studies to explore the mechanism of action of possible therapeutic compound in invivo clinical trials will prove beneficial for the advancement of new oral antidiabetic drug.

Exploring Proteomic Drug Targets, Therapeutic Strategies and Protein - Protein Interactions in Cancer: Mechanistic View.

Protein-Protein Interactions (PPIs) drive major signalling cascades and play critical role in cell proliferation, apoptosis, angiogenesis and trafficking. Deregulated PPIs are implicated in multiple malignancies and represent the critical targets for treating cancer. Herein, we discuss the key protein-protein interacting domains implicated in cancer notably PDZ, SH2, SH3, LIM, PTB, SAM and PH. These domains are present in numerous enzymes/kinases, growth factors, transcription factors, adaptor proteins, receptors and scaffolding proteins and thus represent essential sites for targeting cancer. This review explores the candidature of various proteins involved in cellular trafficking (small GTPases, molecular motors, matrix-degrading enzymes, integrin), transcription (p53, cMyc), signalling (membrane receptor proteins), angiogenesis (VEGFs) and apoptosis (BCL-2family), which could possibly serve as targets for developing effective anti-cancer regimen. Interactions between Ras/Raf; X-linked inhibitor of apoptosis protein (XIAP)/second mitochondria-derived activator of caspases (Smac/DIABLO); Frizzled (FRZ)/Dishevelled (DVL) protein; beta-catenin/T Cell Factor (TCF) have also been studied as prospective anticancer targets. Efficacy of diverse molecules/ drugs targeting such PPIs although evaluated in various animal models/cell lines, there is an essential need for human-based clinical trials. Therapeutic strategies like the use of biologicals, high throughput screening (HTS) and fragment-based technology could play an imperative role in designing cancer therapeutics. Moreover, bioinformatic/computational strategies based on genome sequence, protein sequence/structure and domain data could serve as competent tools for predicting PPIs. Exploring hot spots in proteomic networks represents another approach for developing targetspecific therapeutics. Overall, this review lays emphasis on a productive amalgamation of proteomics, genomics, biochemistry, and molecular dynamics for successful treatment of cancer.

Hepatoprotective Potential of Elsholtzia densa Against Acute and Chronic Models of Liver Damage in Wistar Rats.

The aim of the present study was to evaluate the hepatoprotective activity of methanolic extract of Elsholtzia densa against experimentally induced acute (CCl4) and chronic (paracetamol) liver injury in albino wistar rats. Activity was measured by monitoring the serum levels of ALT, ALP AST and LDH, total protein levels, bilirubin and albumin. The results of the CCl4 and paracetamol-induced liver toxicity experiments showed that the rats treated with the methanolic extract of Elsholtzia densa exhibited a significant decrease in biochemical parameters as well as the proteins, which were all elevated in the CCl4 and paracetamol group. The extract at a concentration of 300 mg/kg body wt. showed a significant decline (P≤0.05) in the levels of AST, ALT, ALP and LDH to 69.50±2.23IU/L, 60.01±2.25IU/L,46.20±2.24 IU/L and 150.21±5.68IU/L in CCl4 injected animals and 51.12±2.20 IU/L,49.15±3.25 IU/L, 44.12±2.56 IU/L and 125.15±4.45 IU/L in paracetamol-treated animals when compared to the control group. The activities of tissue antioxidants GSH, GPx, GR, GST and CAT was significantly (P≤0.05) restored in dose dependent manner in animals treated with extracts as with acute and chronic hepatotoxic models. The current study confirmed the hepatoprotective effect of methanolic extract of Elsholtzia densa against the model hepatotoxicant CCl4 and paracetamol.

Effect of six-month use of oral contraceptive pills on plasminogen activator inhibitor-1 & factor VIII among women with polycystic ovary syndrome: An observational pilot study.

Background & objectives: Polycystic ovary syndrome (PCOS) is an endocrinopathy warranting lifelong individualized management by lifestyle and pharmacological agents mainly oral contraceptive pills (OCPs). This study was aimed to report the impact of six-month OCP use on plasminogen activator inhibitor-1 (PAI-1) and factor VIII (FVIII) in women with PCOS. Methods: PCOS women diagnosed on the basis of Rotterdam 2003 criteria, either treated with OCPs (ethinyl estradiol-0.03 mg, levonorgestrel-0.15 mg) for a period of six months (n=40) or drug-naïve (n=42), were enrolled in this study. Blood was drawn to estimate glucose, insulin levels and lipid profile. Chemiluminescence immunoassays were used to measure hormones (LH, FSH, PRL, T4). Plasma levels of PAI-I and FVIII were measured by commercially available kits. Results: Menstrual regularity, Ferriman-Gallwey score and serum total testosterone significantly improved in the OCP group compared to drug-naïve group (P<0.01). No significant difference was observed in PAI-1 levels of the two groups; however, significant decrease in FVIII levels was observed in OCP group as compared to drug-naïve group. PAI-1 levels of OCP group correlated positively with blood glucose two hours, triglycerides and insulin two hours, while FVIII levels of OCP group correlated negatively with fasting insulin and homoeostatic model assessment-insulin resistance. Interpretation & conclusions: OCPs use has differential effect on pro-coagulant markers among women with PCOS. Well-designed, long-term, prospective, large-scale studies are prerequisite to elucidate the efficacy and safety of OCP in the treatment of PCOS.

Modern Computational Strategies for Designing Drugs to Curb Human Diseases: A Prospect.

Drug discovery is an exhaustive and time-consuming process involving numerous stages like target identification, validation, lead optimization, preclinical trials, clinical trials and finally postmarketing vigilance for drug safety. The application of computer-aided drug designing (CADD) is an indispensable approach for developing safe and effective drugs. Previous methods based on combinatorial chemistry (CC) and high throughput screening (HTS) consumed a lot of time as well as expenditure. CADD based approaches including pharmacophore modeling (PM), molecular docking (MD), inverse docking, chemical similarity (CS), quantitative structure-activity relationship (QSAR), virtual screening (VS) and molecular dynamics simulations have been quite productive in predicting the therapeutic outcome of candidate drugs/compounds besides saving precious time. CADD tools exploit structural and other information available regarding the target (enzyme/receptor) and the ligands to identify the compounds with the ability to treat diseases notably cancer, neurodegenerative disorders, malaria, Ebola, HIV-AIDS and many more. Computational approaches have led to the discovery of many drugs that have passed preclinical and clinical trials and become novel therapeutics in the treatment of a variety of diseases. Some notable examples of CADD derived novel drugs include dorzolamide, saquinavir, ritonavir, indinavir, captopril and tirofiban. CADD plays important role in predicting absorption, distribution, metabolism, excretion and toxicity (ADME/T) of candidate drugs. Overall, CADD represents an effective and much-needed strategy for designing therapeutically effective drugs to combat human diseases.