A STUDY ON SANGUINARINE AS AN ANTILEUKEMIC AGENT- INVOLVEMENT OF REACTIVE OXYGEN SPECIES-CERAMIDE-AKT APOPTOTIC SIGNALING PATHWAY

Dysregulation of apoptosis is a prime hallmark of leukemia. Therefore, drugs which restore the sensitivity of leukemic cells to apoptotic stimuli are promising candidates in the treatment of leukemia. The main objective of this dissertation was to examine the antileukemic effect of sanguinarine, in vitro, and to further examine the signaling mechanisms that may be involved. This study demonstrates that in human leukemic cells, sanguinarine activates a caspase-dependent apoptotic cell death pathway that is characterized by reactive oxygen species-dependent ceramide generation, and subsequent inhibition of Akt signaling pathway. In addition, sanguinarine also induces reactive oxygen species-dependent glutathione depletion and activation of extracellular signal-regulated kinase1/2. Moreover, inhibition of reactive oxygen species generation, using reactive oxygen species scavengers and antioxidants, significantly abrogates sanguinarine-induced ceramide generation, Akt dephosphorylation, extracellular signal-regulated kinase1/2 activation, and apoptosis. Sanguinarine-induced ceramide generation is mediated via reactive oxygen species-dependent activation of acid sphingomyelinase in Jurkat cells and inhibition of acid ceramidase and glucosylceramide synthase in both Jurkat and Molt-4 cells. Furthermore, the involvement of ceramide-activated protein phosphatase-1 in sanguinarine-induced Akt dephosphorylation and apoptosis is demonstrated. Altogether, this study underscores the critical role for reactive oxygen species-ceramide-Akt signaling pathway and reactive oxygen species-dependent extracellular signal-regulated kinase1/2 activation in the antileukemic action of sanguinarine. Understanding the molecular signaling mechanism of sanguinarine induced apoptosis undoubtedly should have a great impact on future sanguinarine based antileukemic drug development

Retrospective Assessment and Management of Neonetal Jaundice Cases in Government Hospital Tirupur

Retrospective studies are conceived after some people have already developed the outcomes. The investigations find the subjects and begin collect information about them after outcomes have already occurred. These studies are very efficient for studying rare or unusual exposure, but there are many potential problems. Sometimes exposure status is not clear when its not necessary to go back, in time and use whatever data is available, especially because the data being used was not designed to answer a health question. A cohort is identified and classified as to exposure to the risk factor at some date in the past and followed up to the present to determine incidence rate. This is called a retrospective cohort studies/ historical prospective study prospective study of past data. Retrospective study is an epidemiological study in which participating individuals are classified as either having some outcomes (cases) or lacking (control); the outcome may be a specific disease, and the person histories are examined for specific factors that might be associated with the outcomes. Cases and controls are often matched with respect to certain demographic or other variables but need not be. NEED FOR THE STUDY: The role of developmental assessment is to see that the child is progressing as per norms set by a large majority of children of the same age. It is by no means a predictor of future intelligent quotient and any deviation from the normal is brought to the notice of the parents, only in reassuring ways. The cause and effect relation between developmental deficits and risk factors can be much more complicated than we imagine. We cannot presume that neonatal jaundice will lead to mental retardation, fine and gross motor abnormalities, hearing loss and vision problems. But most of the children have developmental disabilities after neonatal jaundice. Hence it is ideal to have some sort of developmental evaluation for all babies like measuring length, Head Circumference, Chest Circumference, Midarm Circumference, weighing weight & reflexes of the neonates. The Preliminary analysis and statistics from many child developmental centers and out-patient departments in hospitals have showed that babies with neonatal hyperbilirubinemia have higher incidence of delayed developmental milestones and other associated problems. Hence the investigators were prompted to follow the children who suffered from neonatal jaundice in order to identify the complications very early and promote optimum growth & development of the children. AIM OF THE STUDY: The aim of this study is provides recommendations aimed to improve management of neonatal hyperbilirubinemia in infants. 0BJECTIVES: 1. To study the treatment used in the management of neonatal jaundice. 2. To study the sign, symptoms and duration of the diseases. 3. Collect information on the diagnosis, and treatments. 4. To assess the diagnosing methods. 5. Observe the entire treatment methods. 6. To establish the most effective treatment methods for neonatal jaundice. METHODOLOGY: Study site: The study is conducted in Government district headquarters hospital, Thirupur district, Tamil Nadu. Study period: November 2017 - June 2018. Study type: Retrospective study. Sample size: 80 patients. Study population: babies attended in neonatal intensive care unit, case sheets from medical record department. Inclusion criteria: • New birth babies diagnosed with neonatal jaundice • Patients those willing to give their consent. Exclusion criteria: • Patient above 6 month years old. • addult. Study procedure: The present study was conducted at Government district headquarters hospital, Thirupur for the retrospective assessment of neonatal jaundice cases The study involves mainly 3 steps. CONCLUSION: Neonatal jaundice was found to be more prevalent in male infants compared to females. This reflects male gender is an important risk factor for neonatal jaundice. • The primipara mother is one of the most risk factor of neonatal jaundice. Near 50 % of infants found to be poor feeding. That is the main symptom of neonatal jaundice. • Sepsis effected to 35 % of the neonates. That is it’s also one of the most risk factor of neonatal jaundice. • Most of the infants about 65% of neonates effected to medium level of neonatal jaundice the range of bilirubin concentration is shown in to 10-15 mg/dl. • Birth weight of infants are affected .low birth weight of infants are also one of the risk factor. And gestational age of infants is effected rarely only 10% of pre term neonates are effected neonatal jaundice. • Bilirubin concentration is a highly sensitive parameter in detection of cases of neonatal jaundice. • Recommendation for the duration of photo therapy can be decided based on the results of visual assessment and total serum bilirubin concentration. • The phototherapy is the main treatment method of neonatal jaundice. It is an effective treatment method normally.drugs is not ordinarily used

Role of ceramide in diabetes mellitus: evidence and mechanisms

Diabetes mellitus is a metabolic disease with multiple complications that causes serious diseases over the years. The condition leads to severe economic consequences and is reaching pandemic level globally. Much research is being carried out to address this disease and its underlying molecular mechanism. This review focuses on the diverse role and mechanism of ceramide, a prime sphingolipid signaling molecule, in the pathogenesis of type 1 and type 2 diabetes and its complications. Studies using cultured cells, animal models, and human subjects demonstrate that ceramide is a key player in the induction of β-cell apoptosis, insulin resistance, and reduction of insulin gene expression. Ceramide induces β-cell apoptosis by multiple mechanisms namely; activation of extrinsic apoptotic pathway, increasing cytochrome c release, free radical generation, induction of endoplasmic reticulum stress and inhibition of Akt. Ceramide also modulates many of the insulin signaling intermediates such as insulin receptor substrate, Akt, Glut-4, and it causes insulin resistance. Ceramide reduces the synthesis of insulin hormone by attenuation of insulin gene expression. Better understanding of this area will increase our understanding of the contribution of ceramide to the pathogenesis of diabetes, and further help in identifying potential therapeutic targets for the management of diabetes mellitus and its complications

PREVALENCE OF DENGUE VIRAL INFECTION IN PESHAWAR, KPK, PAKISTAN

Background: Dengue is a widespread mosquito-borne viral infection in human beings, which is a major public health concern all over the world. In recent years, dengue is predominant in the tropics and subtropics with a high incidence and increased considerably over the last three decades. Objective: To investigate the prevalence of dengue in Peshawar, Khyber Pakhunkhwa, Province of Pakistan. A total of 823 samples were collected from 823 patients by puncturing the vein in aseptic condition. Serum of patient was analyzed by Immunochromatography technique (ICT). Results: Out of patients, 671 were male and 152 were female. Among the total of 823 samples, 196 (23.81%) patients were positive for Dengue Non-Structure 1 (NS1) while 627 (76.18%) were negative. In male patients 147 (21.90%) were positive for Dengue NS1 while 524 (78.09%) were negative. Out of 152 (18.46%) female patients 49 (32.23%) were positive for Dengue NS1 and remaining 103 (67.76%) were negative. Conclusion: It is concluded that the prevalence of dengue infection is higher in male than in female due to susceptibility of male to certain risk of dengue. Key Words: Prevalence, Dengue viral infection, Peshawa

INCIDENCE OF NEPHROPATHY IN DIABETIC PATIENTS

Objective: To determine the burden of diabetes mellitus (type I and II) and incidence of nephropathy in diabetic patients Peshawar. Methodology: A cross-sectional study carried out on known diabetic patients in Peshawar. This study was conducted on 267 diabetic patients in duration of one year (from January 2018 to February 2019). Both diabetes mellitus type I and type II patients was included in study. Informed consent was taken from all patients before sample collection. Collected samples were further processed in pathology department. Collected data was analyzed by statistical package for social sciences software version 21. Results: Out of total 267 diabetic patients, diabetes mellitus type I was observed in 43 (16.1%) patients while diabetes mellitus type II was examined in 224 (83.9%) patients. The incidence of nephropathy was found in 33 (12.4%) patients with highest percentage in female (57.5%). Conclusion: Diabetes mellitus type II was three times more common than diabetes mellitus type I. Nephropathy incidence is manageable but high risk to female diabetic patients. Key words: Incidence, Nephropathy, Diabetes mellitus, Peshawar

One- and Two-Dimensional Hydrological Modelling and Their Uncertainties

Earth processes, which occur in land, air and ocean in different environment and at different scales, are very complex. Flooding is also a part of the complex processes, which need to be assessed accurately to know the accurate spatial and temporal changes of flooding and their causes. Hydrological modelling has been used by several researchers in river and floodplain modelling for flood analysis. In this chapter, factors affecting flash flood, possible options of basic input parameters in one- and two-dimensional hydrological models in data sparse environment, some case studies and uncertainty in hydrological modelling were discussed. This discussion will help the readers to understand the flooding factors, selection of input parameters in data sparse environment, a brief insight of one- and two-dimensional hydrological models and uncertainties in their input and model parameters and model structures

Exploring the nutritional and health benefits of pulses from the Indian Himalayan region: A glimpse into the region’s rich agricultural heritage

Pulses have been consumed worldwide for over 10 centuries and are currently among the most widely used foods. They are not economically important, but also nutritionally beneficial as they constitute a good source of protein, fibre, vitamins and minerals such as iron, zinc, folate and magnesium. Pulses, but particularly species such as Macrotyloma uniflorum, Phaseolus vulgaris L., Glycine max L. and Vigna umbellate, are essential ingredients of the local diet in the Indian Himalayan Region (IHR). Consuming pulses can have a favourable effect on cardiovascular health as they improve serum lipid profiles, reduce blood pressure, decrease platelet activity, regulate blood glucose and insulin levels, and reduce inflammation. Although pulses also contain anti-nutritional compounds such as phytates, lectins or enzyme inhibitors, their deleterious effects can be lessened by using effective processing and cooking methods. Despite their great potential, however, the use of some pulses is confined to IHR regions. This comprehensive review discusses the state of the art in available knowledge about various types of pulses grown in IHR in terms of chemical and nutritional properties, health effects, accessibility, and agricultural productivity.Universidade de Vigo/CISU

Green finance and foreign direct investment–environmental sustainability nexuses in emerging countries: new insights from the environmental Kuznets curve

The primary objective of the present study is to identify the asymmetric relationship between green finance, trade openness, and foreign direct investment with environmental sustainability. The existing research utilizes the asymmetric approach to evaluate annual data from 1980 to 2021. The findings of this study show heterogeneous results. Therefore, the outcomes of the study confirm the nonlinear (NARDL) association between the variables in Pakistan. Moreover, the study describes the positive shock of foreign direct investment (FDI) as a significant and positive relationship with environmental degradation, while the negative shock of FDI shows a negative and significant relationship with the environment. Furthermore, the study scrutinizes the positive shock of green finance as a significant and negative relationship with environmental degradation; the negative shocks also show a negative relationship with environmental degradation in Pakistan. In addition, the consequences of the study suggest that the government should implement taxes on foreign investment and that investors should use renewable energy to produce goods. Furthermore, the results suggest that the government should utilize fiscal policy and fiscal funds to enhance carbon-free projects. Moreover, green securities should be used for green technologies. However, Pakistan can control its carbon emissions and achieve the target of a sustainable environment. Therefore, Pakistan’s government should stabilize its financial markets and introduce carbon-free projects. Furthermore, the main quantitative achievement according to the outcomes suggests that policymakers make policies in which they suggest to the government to control foreign investment that causes carbon emissions because of trade openness and also invest the funds in renewable energy, which helps to control the carbon emissions

Spatial estimation of average daily precipitation using multiple linear regression by using topographic and wind speed variables in tropical climate

Complex topography and wind characteristics play important roles in rising air masses and in daily spatial distribution of the precipitations in complex region. As a result, its spatial discontinuity and behaviour in complex areas can affect the spatial distribution of precipitation. In this work, a two-fold concept was used to consider both spatial discontinuity and topographic and wind speed in average daily spatial precipitation estimation using Inverse Distance Weighting (IDW) and Multiple Linear Regression (MLR) in tropical climates. First, wet and dry days were identified by the two methods. Then the two models based on MLR (Model 1 and Model 2) were applied on wet days to estimate the precipitation using selected predictor variables. The models were applied for month wise, season wise and year wise daily averages separately during the study period. The study reveals that, Model 1 has been found to be the best in terms of categorical statistics, R2 values, bias and special distribution patterns. However, it was found that sets of different predictor variables dominates in different months, seasons and years. Furthermore, necessities of other data for further enhancement of the results were suggested

An investigation on 3-acetyl-7-methoxy-coumarin Schiff bases and their Ru(II) metallates with potent antiproliferative activity and enhanced LDH and NO release†

New cyclometallated ruthenium(ii) complexes of 3-acetyl-7-methoxycoumarin-4N-substituted thiosemicarbazones were synthesized and characterized by analytical and spectral techniques. The crystal structures of the ligands H2L1-3 and complexes (1, 2 and 4) were confirmed by X-ray crystallography. The analysis showed that the ligands have undergone C-H activation at the C(4) carbon of the pyrone ring and acted in a tridentate fashion by binding through C, N and S atoms. CT-DNA and protein (BSA/HSA) binding studies were carried out to analyze their interaction with biomolecules. Good binding affinity with DNA was observed with intercalative binding mode, which was further confirmed by EB displacement and viscosity measurement studies. The quenching mechanism with BSA/HSA was found to be static. Three dimensional (3D) fluorescence measurements were carried out to validate the micro environmental changes in the serum albumins. Their antioxidant propensity and antimicrobial study insisted that the compounds displayed good spectrum of activity. Evaluation of their anticancer potential against MCF-7 (human breast cancer) and A549 (human lung carcinoma) cell lines revealed that the complexes exhibited better activity than the ligands and cisplatin. Further, the results of LDH and NO release assays supported the cytotoxic nature of the compounds. The non-toxic nature of the compounds was established by testing against the non-cancerous cell line HaCaT (human normal keratinocyte). © 2018 The Royal Society of Chemistry