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OBJECTIVE AND DESIGN: Inflammatory bowel disease (IBD) is an idiopathic inflammatory condition of the digestive system marked by oxidative stress, leukocyte infiltration, and elevation of inflammatory mediators. In this study, we demonstrate the protective effect of ethyl gallate (EG), a phytochemical, and propyl gallate (PG), an anti-oxidant, given through normal drinking water (DW) and copper water (CW) in various combinations, which had a positive effect on the amelioration of DSS-induced ulcerative colitis in C57BL/6 J mice. MATERIALS AND METHODS: We successfully determined the levels of proinflammatory cytokines and anti-oxidant enzymes by ELISA, tracked oxidative/nitrosative stress (RO/NS) by in vivo imaging (IVIS) using L-012 chemiluminescent probe, disease activity index (DAI), and histopathological and morphometric analysis of colon in DSS-induced colitis in a model. RESULTS: The results revealed that oral administration of ethyl gallate and propyl gallate at a dose of 50 mg/kg considerably reduced the severity of colitis and improved both macroscopic and microscopic clinical symptoms. The level of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, and IFN-γ) in colonic tissue was considerably reduced in the DSS + EG-treated and DSS + PG-treated groups, compared to the DSS alone-treated group. IVIS imaging of animals from the DSS + EG and DSS + PG-treated groups showed a highly significant decrease in RO/NS species relative to the DSS control group, with the exception of the DSS + PG/CW and DSS + EG + PG/CW-treated groups. We also observed lower levels of myeloperoxidase (MPO), nitric oxide (NO), and lipid peroxidation (LPO), and restored levels of GST and superoxide dismutase (SOD) in DSS + EG-DW/CW, DSS + PG/DW, and DSS + EG + PG/DW groups compared to DSS alone-treated group. In addition, we showed that the EG, PG, and EG + PG treatment significantly reduced the DAI score, and counteracted the body weight loss and colon shortening in mice compared to DSS alone-treated group. In this 21-day study, mice were treated daily with test substances and were challenged to DSS from day-8 to 14. CONCLUSION: Our study highlights the protective effect of ethyl gallate and propyl gallate in various combinations which, in pre-clinical animals, serve as an anti-inflammatory drug against the severe form of colitis, indicating its potential for the treatment of IBD in humans. In addition, propyl gallate was investigated for the first time in this study for its anti-colitogenic effect with normal drinking water and reduced effect with copper water.
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Colite Ulcerativa , Colite , Água Potável , Doenças Inflamatórias Intestinais , Humanos , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Galato de Propila/efeitos adversos , Sulfato de Dextrana/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Cobre/efeitos adversos , Água Potável/efeitos adversos , Camundongos Endogâmicos C57BL , Colite/tratamento farmacológico , Colo , Citocinas , Doenças Inflamatórias Intestinais/patologia , Modelos Animais de DoençasRESUMO
Using Health personal protective equipment (PPE) such as face masks, safety foot shoes and protective suits has expanded dramatically due to COVID-19 pandemic leading to a widespread distribution of the PPE, particularly the face masks, in the environments including streets, dump sites, seashores and other risky locations. The environmental degradation of polypropylene, the essential plastic component in single-use face masks (SUM), takes between 20 and 30 years and thus it is essential to develop experimental approaches to recycle the polypropylene or to reuse it in different ways. This paper explores the integration of SUM into concrete structures to improve its mechanical properties. We first to cut the inner nose wire and ear loops, then distribute the PPE material among five different mixed styles. The PPE were applied by volume at 0%, 1%, 1.5%, 2.0%, and 2.5%, with tests focusing on UCS, STS, FS, and PV to determine the concrete's overall consistency and assess the improvement in its mechanical properties. The results showed that adding PPE improves the strength properties and general performance of the concrete specimens. The pattern of rising intensity started to fade after 2%. The findings demonstrated that adding PPE fibers enhanced the UCS by 9.4% at the optimum 2% PPE. The PPE fibers, on the other side, are crucial in calculating the STS and FS of the reinforcement concrete.
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γ-Irradiation of red blood cell (RBC) concentrates prevents transfusion-associated graft-versus-host disease but may diminish RBC quality. Herein, we show that early γ-irradiation (25 Gy) of RBC units and their subsequent storage in SAG-M additive solution altered membrane microvesiculation, supernatant haemoglobin and cytosolic ATP. γ-Irradiation did not influence phosphatidylserine externalization, a marker of erythrocyte apoptotic cell death (eryptosis), in RBC stored for 42 days. However, shorter periods (4-21 days) of storage accentuated eryptosis in γ-irradiated RBC versus untreated RBCs following energy depletion, suggesting that γ-irradiated RBC is primed for stress-induced eryptosis during storage.
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Preservação de Sangue , Eritrócitos/fisiologia , Apoptose , Eritrócitos/efeitos da radiação , Vesículas Extracelulares/metabolismo , Raios gama , Humanos , SoluçõesRESUMO
This case report chronicles the experience of prompt resuscitation, beginning with the patient, and immediate surgery following the fatal malfunction of a chainsaw. The injuries were atypical for chainsaw injuries and involved total transection of the left subclavian artery and vein, total transection of the left brachial plexus and laceration to the apex of the left lung, among other injuries. A coordinated effort allowed for successful repair of the life- and limb-threatening injuries so that the patient could return to his young family in time for his 40th birthday.
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Lacerações , Humanos , Artéria Subclávia/diagnóstico por imagem , Artéria Subclávia/cirurgia , VeiasRESUMO
The Kohat sub-basin is one of the main hydrocarbon-producing sedimentary basins located in the northwest extension of the Indus Basin in Pakistan. It contains numerous proven and potential petroleum from the Cambrian to the Miocene. Conventional petroleum resources have been depleting rapidly over the last couple of years. Therefore, unconventional resources should be explored using a variety of geochemical and geophysical techniques to address the energy demands. Geochemical techniques, including total organic carbon (TOC) assessment, Rock-Eval pyrolysis, organic petrography, and biomarker studies, are essential for evaluating the potential of shale gas reservoirs to delineate future prospects in a basin. The source rock potential of the Paleocene rocks, including the Patala, Lockhart, and Hangu formations of the sub-basin, is evaluated using geochemical analyses on well cuttings from the Tolanj-01 well. The analyses include estimation of total organic carbon (TOC), Rock-Eval pyrolysis, and organic petrography (vitrinite reflectance) to evaluate the organic richness, thermal maturity, kerogen type, hydrocarbon type, and environment of deposition. Other techniques for extractable organic matter (EOM) include solid-liquid chromatographic separation of fractions, gas chromatography (GC-FID)/whole oil chromatography, and gas chromatography-mass spectrometry (GC-MS). The organic matter (TOC, wt %) analysis reveals that 18 (18) samples of the Hangu formation (0.08-1.8 wt %) show poor values, 12 (12) samples of the Lockhart formation (0.05-0.5 wt %) have poor to fair content, and 26 (26) samples of the Patala formation have poor to fair (0.08-0.19 wt %) TOC content. Rock-Eval pyrolysis studies including hydrogen index, oxygen index, Tmax, quantities of free hydrocarbons (S1, mg/g), and hydrocarbons produced from pyrolysis (S2, mg/g) are determined for the well-cut samples (56) of the Paleocene rocks. The hydrogen index values for the Hangu formation are lower than 200, and those for the Lockhart and Patala formations range between 100 and 250. A maceral analysis is also conducted on these samples, which reveal that the majority of the samples of the Paleocene units present in the basin belong to kerogen types II/III. The thermal maturity of the Hangu and Lockhart formations falls in the late-stage oil window, while that of the Patala formation falls in the peak to late oil window. The genetic potential (GP) for these rock units is also determined based on S1 and S2 values, which reveals that it is generally poor except for a few samples of the Hangu and Lockhart formations, which show fair GP values. For the organic petrography (vitrinite reflectance, R0), one sample from each unit is selected, which shows that the Hangu, Lockhart, and Patala formations fall in the category of the mature oil window with their R0 (%) values being 0.95, 0.89, and 0.82, respectively. The extracts (EOM) from these rock units are also analyzed to assess the depositional settings, biological source input, biodegradation, thermal maturity, etc. The greater values of pristine to phytane (Pr/Ph > 1) ratios for Hangu (1.33), Lockhart (1.23), and Patala (1.8) indicate an intermediate condition (suboxic), while a cross-plot of Pr/n-C17-Ph/n-C18 shows that the organic matter is deposited in a transitional setting. The ratios between C19TCT/C19 TCT + C23 TCT and C24 TeCT/C24TeCT + C23TCT biological source inputs are mainly of marine origin. Similarly, the ternary diagram of regular steranes (C27-C28-C29) shows a greater marine input. Lower values of the carbon preference index (CPI1) for Hangu (0.95), Lockhart (0.91), and Patala (1.04) indicate higher thermal maturity of the Paleocene rocks. Similarly, the methylphenanthrene index (MPI-1) values, Moretane index, and Pr/n-C17 vs Ph/n-C18 plots also show higher thermal maturity for these rock extracts.
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OBJECTIVES: HIV infection is associated with higher than expected cardiovascular event rates and lowered platelet counts. These conditions are associated with an elevation of mean platelet volume (MPV). The present study compared MPV in HIV-infected and uninfected women and identified factors influencing MPV values in HIV-infected women. METHODS: A total of 234 HIV-infected and 134 HIV-uninfected participants from the Women's Interagency HIV Study (WIHS) had MPV values obtained. HIV-infected women were older, were more likely to have diabetes and had higher triglyceride levels than HIV-uninfected women. RESULTS: The mean platelet count was lower in HIV-infected vs. uninfected women [249 cells/µL (95% confidence interval (CI) 238, 259 cells/µL) vs. 276 cells/µL (95% CI 265, 287 cells/µL), respectively; P < 0.01]. Adjusted mean MPV values were lower in the HIV-infected than in the uninfected group [8.66 fL (95% CI 8.52, 8.79 fL) vs. 9.05 fL (95% CI 8.87, 9.24 fL), respectively]. In multiple regression analysis, after adjusting for other covariates, MPV was positively associated with platelet count, and negatively with HIV infection (model R² = 0.20; P < 0.01). In multiple regression analysis confined to HIV-infected women, a lower MPV was independently associated with a history of AIDS-defining illness (R² = 0.28; P = 0.03), but not with nadir CD4 count or highly active antiretroviral therapy (HAART) use. CONCLUSIONS: HIV-infected women had lower MPV values than uninfected women, suggesting impaired production rather than increased destruction. Higher than expected cardiovascular event rates cannot be attributed to greater platelet reactivity as measured by MPV.
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Infecções por HIV/sangue , Volume Plaquetário Médio , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Estudos de Casos e Controles , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Barium copper sulfur fluoride (BaCuSF) is a p-type transparent conductor (p-TC) that, when doped with potassium, exhibits exceptionally high conductivity. The results of a detailed optical and electronic characterization of BaCuSF thin films deposited at a substrate temperature of 100 °C are presented. X-ray diffractometry shows the presence of a cubic BaCuSF phase. Spectroscopic measurements demonstrate that the films transmit from the visible through the mid-infrared with a band gap of 1.8 eV. Hall measurements indicate that the material is a degenerate semiconductor. As deposited, the films exhibit conductivity at room temperature of approximately 260 S/cm - among the highest reported room temperature conductivities for p-TCs. After post-deposition treatment in water, their conductivity increases to as high as 800 S/cm, and their band gap is reduced to 1.5 eV. The potential for low temperature deposition of p-type films with high conductivity and optical transmittance makes BaCuSF promising for several applications including flexible electronics and photovoltaics.
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BACKGROUND: A spontaneous mutant rat with a hairless phenotype and an intact thymus was discovered in a long-standing Sprague Dawley-National Institute of Nutrition (SD/NIN) rat colony at a national animal resource facility. OBJECTIVE: We conducted extensive phenotypic and biochemical analyses on this mutant strain to determine its suitability as a preclinical model for immunocompetent testing in noncommunicable disease research. MATERIALS AND METHODS: We subjected the mutant rats to strict and frequent phenotypic and genetic surveillance to accomplish this objective. The animals were assessed for food intake, body weight, blood cell profile, clinical chemistry, adipose tissue deposition, and bone mineral density (BMD) using total electrical body conductance (TOBEC) and dual-energy X-ray absorptiometry (DXA) analysis. RESULTS: Initially, only two hairless mutant rats, a male and a female, were born from a single dam in the SD/NIN rat strain. However, the results indicate that the mutant colony propagated from these unique pups displayed distinct phenotypic features and exhibited differences in feeding behavior, weight gain, and clinical biochemistry. The food conversion rate was significantly higher in nude females (2.8-fold) while 26% lower in nude males. Both sexes of nude rats had significantly higher triglycerides and lower glucose levels in females. However, glucose levels did not change in male nude rats. Furthermore, nude female and male rats had significantly lower fat (TOBEC) and bone mineral content (DXA). Nonetheless, BMD was only slightly lower (7%-8%) compared to the heterozygous groups. CONCLUSIONS: These findings indicate that the spontaneous mutant rat has the potential to serve as an immunopotent and modulatory testing system in pharmacokinetics/pharmacodynamics and toxicology, which can be further explored for therapeutic drug discovery.
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Doenças não Transmissíveis , Ratos , Masculino , Feminino , Animais , Ratos Sprague-Dawley , Ratos Nus , Densidade Óssea , GlucoseRESUMO
Current article illustrates the data of body weight, biochemical, haematological profile, and organ weights of rats and rabbits administered with recombinant human papilloma virus (HPV) vaccine, along with genotoxicity effect. The data was collected from nonclinical safety/toxicity and immune response evaluations of recombinant Salmonella typhi expressing the HPV 16 and 18 L1 proteins as vaccine. The intended clinical route of vaccine administration is through oral route, whereas it is established fact that attenuated S. typhi could not colonize in laboratory animals. In view of this it is challenging to undertake the nonclinical safety/toxicity evaluations following the regulatory guidelines. Hence sub chronic safety/toxicity testing was carried out in rat and rabbits by administration of HPV vaccine through oral (intended clinical route) and innovative intranasal routes. The prophylactic dose derived from adult human clinical dose (2â¯×â¯109CFU/70â¯kg) was administered to SD rats (PD: 0.18â¯×â¯109CFU/kg) and New Zealand White (NZW) rabbits (PD: 0.09â¯×â¯109CFU/kg) through oral and intranasal routes. Similarly, average dose (AD:5xPD) was administered to rats (AD:0.9â¯×â¯109CFU/kg) and rabbits (AD: 0.45â¯×â¯109CFU/kg) through intranasal route only. The repeated doses were administered on 3rd and 5th days of post-exposure of 1st dose through specified routes and test compound effects in relation with time of exposure was assessed by euthanizing animals and data collection at different time points i.e. 15th (25% of animals), 29th (25% of animals) and 93rd days (50% of animals) of post-exposure of 1st dose. The retro-orbital plexus blood was collected before euthanizing animals to unveil the biochemical and haematological profile. The data on genotoxicity effect of test compound, if any, was obtained by assessing the bone-marrow micronucleus assay. The immune response and allergenicity in terms of specific IgG and IgE levels against HPV 16 and 18 L1 proteins were determined in mice. The raw data of various parameters collected at different time points were compiled and computed according to the groups. The haematological profile and organ weights data can be used as reference data for SD rats and NZW rabbits for future studies.
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Advancement in technology led to development of live attenuated Salmonella typhi Ty21a as enteric vector for expression of foreign proteins. Such vector platform is inevitable for development of vaccine candidate against human papilloma virus (HPV), the etiological agent of cervical cancer with high prevalence in developing nations. The high risk HPVs like type 16 and 18 contributes to 70% of cervical cancer, hence Indian Immunologicals Limited (IIL), Hyderabad, India developed a recombinant HPV vaccine by introducing HPV 16 and 18 L1 protein coding genes into attenuated S. typhi Ty21a vector. Being a genetically engineered enteric vector vaccine, it would be less expensive, with an ease of oral administration, instead of injectable that needs trained personale, is an added advantage for low socioeconomic setup compared to existing HPV vaccines. Establishing the nonclinical efficacy and safety/toxicity as per the national/international regulatory guidelines has become major constrain for such recombinant S. typhi HPV (rSt.HPV) vaccine. Since, the intended clinical mode of rSt.HPV is through oral route, whereas the live attenuated S. typhi Ty21a doesn't colonize in gut of laboratory animals to be used for nonclinical experiments. Hence, an alternate and unconventional method of 'intranasal drug testing', was followed for nonclinical efficacy and toxicity evaluations. An array of parameters specified by regulatory agencies were investigated in mice, rat and rabbits administered with rSt.HPV through, intra-peritoneal, intranasal and oral routes, the intended clinical route.â¢Current unconventional and innovative nonclinical testing procedures helps in exploring the alternate methods by pharmacologist/toxicologist.â¢Ultimately, such new drugs developed through technology must serve the humankind justifying the guidelines of regulatory agencies.
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AIM: The human papilloma virus (HPV) type 16 and 18 causes nearly 70% of uterine cervical cancers. Oral administration of live Salmonella typhi Ty21a, expressing major capsid proteins (L1) of HPV 16 and 18 is a potential choice for immunization in adolescent girls under low resource settings. Present study aimed to assess the nonclinical safety of recombinant S. typhi expressing HPV 16 and 18 (rStHPV) proteins. METHODOLOGY: The acute toxicity of rStHPV was tested by intranasal single dose administration, of 10 and 50 folds higher than clinical prophylactic dose, in mice and rat followed by monitoring their survival for 14 days. Sub-chronic toxicity was evaluated in rats and rabbits with prophylactic and 5 times (average) to clinical prophylactic dosages on scheduled days (1st, 3rd & 5th day) through oral and intranasal routes. The immune/allergic response of rStHPV was assessed in mice through intranasal and intra-peritoneal routes. Experimental animals were daily monitored for live phase, and clinical chemistry, haematology, immunotoxicology, immunogenic response and histopathological examination of vital organs on 15th, 29th and 93rd days. RESULTS: No abnormal changes were noticed in live phase activity, clinical chemistry and haematology profile. The gross necropsy, organ weights and histopathology were found to be normal. No immunotoxicity was recorded as evaluated by tier I tests. Allergic immune response, as evaluated with IgE levels was also negative irrespective of test routes. On the other hand, a significant (P < 0.01) increase of anti-HPV IgG levels was noted in mice exposed through intranasal route. Though the pre-terminal mortality was noted in mice (6-15%), rats (10%) and rabbits (15%), the autopsy revealed no signs of toxicity related to rStHPV, as the changes neither significant nor dose dependent; and even noted in vehicle control also. CONCLUSION: The study results suggested 'no observable adverse effects' of rStHPV even at higher dosages (5, 10 & 50 folds) than intended clinical dose. A significant increase of anti-HPV specific IgG suggests the immunogenicity of vaccine. The innovative approach of current study is nonclinical toxicology evaluation of vaccine through intra-nasal route, an alternate route apart from stipulated regulatory guidelines.
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Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Animais , Proteínas do Capsídeo , Feminino , Papillomavirus Humano 16 , Humanos , Camundongos , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/efeitos adversos , Coelhos , Ratos , Salmonella typhiRESUMO
An adult case of shunt malfunction presenting with acute quadriparesis as a manifestation of foramen magnum syndrome with acquired Chiari type I malformation is described in this study. The corticospinal function was restored after shunt revision. MRI showing considerable ascent of cerebellar tonsils after surgery is shown. Theories regarding the formation of acquired Chiari I malformations, alongside the possible synergistic roles of intracranial pathologies and cerebrospinal fluid drainage in the development of this entity are discussed.
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Malformação de Arnold-Chiari/cirurgia , Forame Magno/cirurgia , Quadriplegia/cirurgia , Derivação Ventriculoperitoneal/métodos , Adulto , Humanos , Masculino , Quadriplegia/etiologia , Síndrome , Resultado do TratamentoRESUMO
Introduction: To compare short- and midterm outcomes of the first 55 patients undergoing robot-assisted kidney transplant (RAKT) with patients undergoing open kidney transplant (OKT) during the same period in a tertiary care hospital. Materials and Methods: Data of all end-stage renal disease patients undergoing renal transplant were prospectively maintained. All graft kidneys were harvested laparoscopically. Both RAKT and OKT were performed using standardized techniques, and all RAKTs were performed by a single experienced robotic surgeon. Chi-square test/Fisher exact test was done for categorical data, and Mann-Whitney U test was done for continuous data. Discrete variables were expressed in absolute numbers and percentages. For all tests, p < 0.05 was considered significant. All results were expressed as mean ± standard deviation or median with range. Results: Between April 2016 and September 2018, 55 patients underwent RAKT. The same was compared with 152 patients who underwent OKT. The two groups were comparable in terms of age, gender, and body mass index. Duration on hemodialysis was significantly higher in the RAKT group, and hemoglobin and donor kidney glomerular filtration rate was significantly better in the RAKT group. Requirement of perioperative analgesia was significantly less in the RAKT group. Rewarm ischemia time was significantly longer in the RAKT group. The fall in serum creatinine was slower in RAKT group till 3 months. The serum creatinine levels were statistically similar in the two cohorts at 3 months (p = 0.082), which was maintained at median 29 months of follow-up (p = 0.067). Tacrolimus levels on postoperative day 2 were found to be significantly higher in RAKT cohort (17.98 ± 14.41) vs OKT cohort (11.38 ± 6.93). Surgical-site infections were rare in the RAKT group. Conclusions: RAKT confers advantage of decreased wound morbidity with similar functional outcomes compared with OKT in midterm. It looks promising; however, long-term follow-up of larger numbers of patients is needed.
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Transplante de Rim , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Duração da Cirurgia , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Mass gathering (MG) events are associated with public health risks. During the period January 14 to March 4, 2019, Kumbh Mela in Prayagraj, India was attended by an estimated 120 million visitors. An onsite disease surveillance was established to identify and respond to disease outbreaks. METHODS: A health coordination committee was established for planning. Disease surveillance was prioritized and risk assessment was done to identify diseases/conditions based on epidemic potential, severity of illness, and reporting requirement under the International Health Regulations (IHR) of 2005. A daily indicator and event-based disease surveillance was planned. The indicator-based surveillance (IBS) manually and electronically recorded data from patient hospital visits and collected MG area water testing data to assess trends. The event-based surveillance (EBS) helped identify outbreak signals based on pre-identified event triggers from the media, private health facilities, and the food safety department. Epidemic intelligence was used to analyse the data and events to detect signals, verify alerts, and initiate the response. RESULTS: At Kumbh Mela, disease surveillance was established for 22 acute diseases/syndromes. Sixty-five health facilities reported 156 154 illnesses (21% of a total 738 526 hospital encounters). Among the reported illnesses, 95% (n = 148 834) were communicable diseases such as acute respiratory illness (n = 52 504, 5%), acute fever (n = 41 957, 28%), and skin infections (n = 27 094, 18%). The remaining 5% (n = 7300) were non-communicable diseases (injuries n = 6601, 90%; hypothermia n = 224, 3%; burns n = 210, 3%). Water samples tested inadequate for residual chlorine in 20% of samples (102/521). The incident command centre generated 12 early warning signals from IBS and EBS: acute diarrheal disease (n = 8, 66%), vector-borne disease (n = 2, 16%), vaccine-preventable disease (n = 1, 8%), and thermal event (n = 1, 8%). There were two outbreaks (acute gastroenteritis and chickenpox) that were investigated and controlled. CONCLUSIONS: This onsite disease surveillance imparted a public health legacy by successfully implementing an epidemic intelligence enabled system for early disease detection and response to monitor public health risks. Acute respiratory illnesses emerged as a leading cause of morbidity among visitors. Future MG events should include disease surveillance as part of planning and augment capacity for acute respiratory illness diagnosis and management.
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Doenças Transmissíveis/epidemiologia , Religião , Adolescente , Adulto , Criança , Diarreia/epidemiologia , Surtos de Doenças , Feminino , Febre/epidemiologia , Gastroenterite/epidemiologia , Humanos , Índia/epidemiologia , Masculino , Vigilância da População , Saúde Pública , Medição de Risco , Adulto JovemRESUMO
Metallic filaments with submicrometer diametere have been fabricated. Standard diffraction techniques with conventional x-ray sources were unsuccessful in identifying the structure of these materials. However, with the use of synchrotron radiation produced on a wiggler beam line, diffraction data were obtained in measurement periods as short as 10 milliseconds. Two cylindrical single crystals of bismuth were studied, each with a diameter of 0.22 +/- 0.02 micrometer. The volume of sample illuminated for these measurements was 0.38 cubic micrometer, less than 0.5 femtoliter. The crystals are grown in glass capillaries, and, because bismuth expands on solidification, they are under a residual hoop stress. The crystallographic data indicate the presence of a linear compressive strain of about 2 percent, which is assumed to be the result of a residual stress of about 2 gigapascals.
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Evidence of structural inhomogeneities in two high-transition-temperature superconductors, YBa(2)Cu(3)O(7-delta) and Nd2-xCexCuO4-y, is presented. When samples were illuminated by highly collimated x-rays produced on a synchrotron wiggler, small changes in the lattice were detected over a spatial scale of 10 micrometers. These changes are interpreted as evidence of variations in the oxygen content in one case and in the cerium content in the other; both affect the superconducting properties. The existence of such structural inhomogeneities brings into question whether exotic experimental results obtained from superconducting materials with high transition temperatures actually reflect intrinsic properties.
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Sphingosine-1-phosphate (S-1P) is a key sphingolipid involved in the pathobiology of various respiratory diseases. We have previously demonstrated the significance of S-1P in controlling non-pathogenic mycobacterial infection in macrophages, and here we demonstrate the therapeutic potential of S-1P against pathogenic Mycobacterium tuberculosis (H37Rv) in the mouse model of infection. Our study revealed that S-1P is involved in the expression of iNOS proteins in macrophages, their polarization toward M1 phenotype, and secretion of interferon (IFN)-γ during the course of infection. S-1P is also capable of enhancing infiltration of pulmonary CD11b+ macrophages and expression of S-1P receptor-3 (S-1PR3) in the lungs during the course of infection. We further revealed the influence of S-1P on major signaling components of inflammatory signaling pathways during M. tuberculosis infection, thus highlighting antimycobacterial potential of S-1P in animals. Our data suggest that enhancing S-1P levels by sphingolipid mimetic compounds/drugs can be used as an immunoadjuvant for boosting immunity against pathogenic mycobacteria.
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Lisofosfolipídeos/metabolismo , Macrófagos/imunologia , Mycobacterium tuberculosis/fisiologia , Esfingosina/análogos & derivados , Células Th1/imunologia , Tuberculose/imunologia , Adjuvantes Imunológicos , Animais , Diferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Humanos , Imunidade Inata , Interferon gama/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Transdução de Sinais , Esfingosina/metabolismoRESUMO
Accidental exposure to lethal doses of Gamma radiation leads to the systemic inflammatory syndrome which causes mortality. In view of this, management of hemopoietic syndrome by modulating pro-inflammatory response in clinically manageable time period seems to be the most appropriate strategy for encountering radiation induced damage and recovery. As both tissue and peripheral macrophages are critical for the management of radiation induced injuries, we have unraveled the immunomodulatory potential of radioprotective formulation (G-003M) on peripheral macrophages populations in this study. G-003M inhibited lethal radiation induced NO and Th1 effector cytokines in the exposed macrophages indicating its M1 dim polarizing capacity. In similar lines, conditioning of mice with G-003M before lethal irradiation (LR) inhibited LR induced titre of Th1 effector cytokines in both serums as well as in lung, small intestine, and spleen tissue confirming its immunomodulatory potential. G-003M potentially down modulated inflammatory response in LPS induced inflammatory model and enhanced M2 polarization of iNOS+ M1 effector macrophages providing a molecular hint on G-003M mechanism of action on macrophages. These observations revealed that G-003M potentially modulate pro-inflammatory programming of macrophages and mitigate radiation-induced inflammatory stress which is believed to contribute significantly to radioprotective attribute of G-003M. In this study, we demonstrate that Rutin and Podophyllotoxin drive M1dim/M2 polarization of LR primed macrophages apart from protecting DNA from radiation. These drugs have the capacity to programme innate immune cells like macrophages which may be involved in homeostasis during recovery.
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Macrófagos/imunologia , Podofilotoxina/uso terapêutico , Lesões por Radiação/imunologia , Rutina/uso terapêutico , Animais , Diferenciação Celular , Células Cultivadas , Citocinas/metabolismo , Raios gama/efeitos adversos , Humanos , Imunomodulação , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Lesões por Radiação/tratamento farmacológico , Células Th1/imunologia , Equilíbrio Th1-Th2/efeitos dos fármacos , Células Th2/imunologiaRESUMO
The economy of Ca utilization is under the control of vitamin D(3), particularly its active metabolite 1,25-dihydroxy cholecalciferol [1,25(OH)(2)D(3)]. In sufficient Ca absorption leads to tibial dyschondroplasia resulting in not attaining optimum body weight. Our earlier studies [T.P. Prema, N. Raghuramulu, Phytochemistry 37 (1994) 167] have shown that the Cestrum diurnum (CD) leaves contain vitamin D(3) metabolites. It was felt whether incorporation of CD as a source of 1,25(OH)(2)D(3) could improve the Ca absorption in broilers. Four groups of 60 birds each were fed with either normal diet or normal diet+0.25% CD or normal diet without vitamin D(3) or normal diet without vitamin D(3)+0.25% CD leaf powder for 45 days. In subsample of six birds it was observed that incorporation of CD leaves in the feed had the maximal effect on all the parameters studied. The results indicate that the intestinal Ca transport as represented by Serosa/Mucosa (S/M) ratio was found to be significantly (p<0.01) higher in broilers fed diet with CD leaf powder and the 1alpha hydroxylase activity in kidney is significantly (p<0.001) higher in negative controls. On the other hand the supplementation of CD leaves enhanced the serum Ca, body weight, tibia weight, density and strength resulting in the disappearance of tibial dyschondroplasia. No lesions of toxicity were observed in any of the soft tissue examined. The results suggest that the incorporation of CD leaf powder in poultry feed could be beneficial to the poultry.
Assuntos
Cálcio/metabolismo , Cestrum , Mucosa Intestinal/metabolismo , Ração Animal , Animais , Transporte Biológico , Peso Corporal , Galinhas , Rim/enzimologia , Tamanho do Órgão , Folhas de Planta , TíbiaRESUMO
We have developed a novel approach for layer-by-layer growth of tissue-engineered materials using a direct writing process known as matrix assisted pulsed laser evaporation direct write (MAPLE DW). Unlike conventional cell-seeding methods, this technique provides the possibility for cell-material integration prior to artificial tissue fabrication. This process also provides greater flexibility in selection and processing of scaffold materials. In addition, MAPLE DW offers rapid computer-controlled deposition of mesoscopic voxels at high spatial resolutions. We have examined MAPLE DW processing of zirconia and hydroxyapatite scaffold materials that can provide a medical device with nearly inert and bioactive implant-tissue interfaces, respectively. We have also demonstrated codeposition of hydroxyapatite, MG 63 osteoblast-like cells, and extracellular matrix using MAPLE DW. We have shown that osteoblast-like cells remain viable and retain the capacity for proliferation when codeposited with bioceramic scaffold materials. Our results on MG 63-hydroxyapatite composites can be extended to develop other integrated cell-scaffold structures for medical and dental applications.