In Vitro and In Vivo Study of Poly(ethylene glycol) Conjugated Ibuprofen to Extend the Duration of Action

Ibuprofen–polyethylene glycol (PEG) conjugates (PEG-Ibu) were prepared and their potential as a prolonged release system was investigated. Two PEG-Ibu conjugates were synthesized from Ibuprofen and PEG with two different molecular weights by esterification in the presence of DCC and DMAP. The PEG-Ibu conjugates were characterized by FT-IR, 1H NMR, Mass spectroscopy and DSC analysis. The solubility study in aqueous system showed an increase in solubility of conjugates. The dissolution / hydrolysis studies showed a specific acid–base catalysis pattern dependent on the pH of the medium. This indicated a good chemical stability in aqueous buffer solution of acidic medium and the extended release behavior was found in both prodrugs after 9 hour. The results demonstrate that, in the same condition, the rate of hydrolysis for PEG4000-Ibu is slower than other. The Writhing induced by acetic acid experiment and paw edema test after oral administration showed that both conjugates had extended analgesic and anti-inflammatory effects compared with Ibuprofen. These results suggest that PEG-Ibu could be a promising NSAID prodrug with an extended pharmacological effect owing to delayed-release of parent drug

Abordagens avançadas de pró-fármacos para doenças neurodegenerativas

The prodrug technique is still one of the most effective ways to increase hydrophilic substances' medicinal, pharmacodynamic and pharmacokinetic properties. Prodrugs produced in current history have shown good pharmacokinetic characteristics, allowing for a more consistent release and fewer changes in plasma levels. Developing new prodrugs having a desirable ADME (Absorption Distribution Metabolism and Elimination) properties and that still can cross the Blood brain barrier (BBB) and pharmacologically active an appealing task for medicinal chemists. The loss of brain neuron activity characterizes neurodegenerative illnesses, resulting in progressive Gradual cognitive impairment (GCI). Some of the common neurodegenerative diseases are PD (Parkinson's disease), AD (Alzheimer's disease), MS (Multiple sclerosis), ALS (amyotrophic lateral sclerosis) & HD (Huntington's disease) are examples of neurodegenerative illnesses with a variety of etiologies and morphological and pathophysiological aspects. The current review is concerned with current advances in prodrug approaches for the treatment and prevention of the most prevalent neurological illnesses, as well as their absorption, selective CNS targeting and chemical and enzymatic stability.La técnica de los profármacos sigue siendo una de las formas más eficaces de aumentar las propiedades medicinales, farmacodinámicas y farmacocinéticas de las sustancias hidrófilas. Los profármacos producidos en la historia actual han mostrado buenas características farmacocinéticas, lo que permite una liberación más consistente y menos cambios en los niveles plasmáticos. Desarrollar nuevos profármacos que tengan propiedades ADME (Absorción, Distribución, Metabolismo y Eliminación) deseables y que aún puedan cruzar la barrera hematoencefálica (BBB) ​​y farmacológicamente activos es una tarea atractiva para los químicos médicos. La pérdida de actividad de las neuronas cerebrales caracteriza las enfermedades neurodegenerativas, lo que resulta en un deterioro cognitivo gradual (GCI) progresivo. Algunas de las enfermedades neurodegenerativas comunes son PD (enfermedad de Parkinson), AD (enfermedad de Alzheimer), MS (esclerosis múltiple), ELA (esclerosis lateral amiotrófica) y HD (enfermedad de Huntington) son ejemplos de enfermedades neurodegenerativas con una variedad de etiologías y características morfológicas y aspectos fisiopatológicos. La revisión actual se ocupa de los avances actuales en los enfoques de profármacos para el tratamiento y la prevención de las enfermedades neurológicas más prevalentes, así como su absorción, el direccionamiento selectivo del SNC y la estabilidad química y enzimática.A técnica de pró-fármacos ainda é uma das formas mais eficazes de aumentar as propriedades medicinais, farmacodinâmicas e farmacocinéticas de substâncias hidrofílicas. Os pró-fármacos produzidos na história atual, mostraram boas características farmacocinéticas, permitindo uma liberação mais consistente e menos alterações nos níveis plasmáticos. Desenvolver novos pró-fármacos com propriedades ADME (Metabolismo e Eliminação de Distribuição de Absorção) desejáveis e que ainda possam atravessar a barreira hematoencefálica (BBB), e ser farmacologicamente ativos, é uma tarefa atraente para os químicos medicinais. A perda da atividade dos neurônios cerebrais caracteriza doenças neurodegenerativas, resultando em comprometimento cognitivo gradual progressivo (GCI). Algumas das doenças neurodegenerativas comuns são DP (doença de Parkinson), DA (doença de Alzheimer), EM (Eclerose Múltipla), ELA (Esclerose Lateral Amiotrófica) e DH (doença de Huntington), são exemplos de doenças neurodegenerativas com uma variedade de etiologias e alterações morfológicas e aspectos fisiopatológicos. A revisão atual está preocupada com os avanços atuais nas abordagens de pró-fármacos para o tratamento e prevenção das doenças neurológicas mais prevalentes, bem como sua absorção, direcionamento seletivo do SNC e estabilidade química e enzimática

Immunohistochemical Analysis of Vimentin in Oral Submucous Fibrosis

Background. Oral submucous fibrosis (OSF), a precancerous condition, is characterized by abnormal accumulation of collagen fibers in oral submucosa. Vimentin is a Class 2 intermediate filament (IF) and primarily expressed in cells of mesenchymal origin. Vimentin is also found to be involved in cell growth, cell cycling, and tumour differentiation. Objective. The purpose of the study was to compare the expression of vimentin in various histological grades of OSF. Materials and Methods. To assess the immunohistochemical expression of vimentin in 20 mild cases of OSF, 20 severe cases of OSF, and ten cases of normal oral buccal mucosa. Results. The overall staining intensity of vimentin significantly increased statistically (P<0.01) in OSF cases over normal control. A significant increase in the staining intensity of vimentin was also noted in the fibroblasts of severe cases of OSF (P=0.03). Conclusion. Considering the marked vimentin expression in the present study, future studies should include cytoskeleton IF and other filaments in the fibroblasts of OSF

IRS-IC applications for coastal zone management

IRS-1A and 1B data have been found to be useful in providing information on the extent and condition of coastal habitats, coastal processes and water quality of coastal waters. These inputs formed major elements for preparing coastal zone management plans. IRS-1C data having improved spatial resolution (5.6 m PAN data), extended spectral range inclusion of middle infra-red band in LIAA-III) and increased repetitivity (5 days for WiFS data have opened up new vistas of applications in the coastal zone. Preliminary analysis of IRS-1C data indicates that coral reef zonation, identification of tree and shrub mangroves, seaweed/sea grass beds, improved delineation of coastal features such as fringe mangroves, mudflats, beach, dune vegetation, saline areas, etc. as well as better understanding of suspended sediment patterns are now possible. These additional information will certainly form vital remote-sensing-based input for preparing coastal zone management plans

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Application of remote sensing data to monitor mangroves and other coastal vegetation of India

195-213Remote sensing data, because of its repetitive, synoptic and multi-spectral nature, has proved to be of an immense value in monitoring of coastal vegetation. Indian Remote Sensing Satellite (IRS) data have been extensively used to map mangroves and other coastal vegetation for the entire country’s coastline. Large database on spatial extent of mangroves and their condition has been created on 1:250,000, 1:50,000 and 1:25,000 scale using IRS data (the database provides information for the first time on the mangrove areas of the entire Indian coast). Based on this study, it was observed that the Kori creek, Gujarat, has large area under mangroves. The repetitive nature of the data has helped in monitoring vital and critical areas, periodically. In one such study, on the Marine National Park, in the Gulf of Kachchh, mangrove areas were monitored for the last 25 years. The degradation of mangroves continued up to 1985 and the condition significantly improved due to the adoption of conservation measures. This has helped in planning various management actions to conserve this vital ecosystem. IRS data have been used in identifying dominant plant communities in many mangrove areas such as Bhitarkanika, Coringa, Mandovi estuary in Goa and the Gulf of Kachchh, etc. This is a unique approach for providing spatial information at plant community level and can be seen as a first step towards bio-diversity assessment. Along with the mangroves, seaweed, seagrass beds and dune vegetation have also been mapped with reasonable accuracy. With the better sensors planned for future, remote sensing-based information is going to be one of the major inputs in the preparation of management action plans

Application of remote sensing data to monitor mangroves and other coastal vegetation of India

Remote sensing data, because of its repetitive, synoptic and multi-spectral nature, has proved to be of an immense value in monitoring of coastal vegetation. Indian Remote Sensing Satellite (IRS) data have been extensively used to map mangroves and other coastal vegetation for the entire country’s coastline. Large database on spatial extent of mangroves and their condition has been created on 1:250,000, 1:50,000 and 1:25,000 scale using IRS data (the database provides information for the first time on the mangrove areas of the entire Indian coast). Based on this study, it was observed that the Kori creek, Gujarat, has large area under mangroves. The repetitive nature of the data has helped in monitoring vital and critical areas, periodically. In one such study, on the Marine National Park, in the Gulf of Kachchh, mangrove areas were monitored for the last 25 years. The degradation of mangroves continued up to 1985 and the condition significantly improved due to the adoption of conservation measures. This has helped in planning various management actions to conserve this vital ecosystem. IRS data have been used in identifying dominant plant communities in many mangrove areas such as Bhitarkanika, Coringa, Mandovi estuary in Goa and the Gulf of Kachchh, etc. This is a unique approach for providing spatial information at plant community level and can be seen as a first step towards bio-diversity assessment. Along with the mangroves, seaweed, seagrass beds and dune vegetation have also been mapped with reasonable accuracy. With the better sensors planned for future, remote sensing-based information is going to be one of the major inputs in the preparation of management action plans