Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
1.
Diabet Med ; : e15434, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39255356

RESUMO

BACKGROUND: Pancreatic islet ß-cell mass expands during pregnancy, but underlying mechanisms are not fully understood. This study examines the impact of pregnancy and cafeteria diet on islet morphology, associated cellular proliferation/apoptosis rates as well as ß-cell lineage. METHODS: Non-pregnant and pregnant Ins1Cre/+;Rosa26-eYFP transgenic mice were maintained on either normal or high-fat cafeteria diet, with pancreatic tissue obtained at 18 days gestation. Immunohistochemical changes in islet morphology, ß-/α-cell proliferation and apoptosis, as well as islet cell identity, neogenesis and ductal cell transdifferentiation were assessed. RESULTS: Pregnant normal diet mice displayed an increase in body weight and glycaemia. Cafeteria feeding attenuated this weight gain while causing overt hyperglycaemia. Pregnant mice maintained on a normal diet exhibited typical expansion in islet and ß-cell area, owing to increased ß-cell proliferation and survival as well as ductal to ß-cell transdifferentiation and ß-cell neogenesis, alongside decreased ß-cell dedifferentiation. Such pregnancy-induced islet adaptations were severely restricted by cafeteria diet. Accordingly, islets from these mice displayed high levels of ß-cell apoptosis and dedifferentiation, together with diminished ß-cell proliferation and lack of pregnancy-induced ß-cell neogenesis and transdifferentiation, entirely opposing islet cell modifications observed in pregnant mice maintained on a normal diet. CONCLUSION: Augmentation of ß-cell mass during gestation arises through various mechanisms that include proliferation and survival of existing ß-cells, transdifferentiation of ductal cells as well as ß-cell neogenesis. Remarkably, cafeteria feeding almost entirely annuls pregnancy-induced islet adaptations, which may contribute to the development of gestational diabetes in the setting of dietary provoked metabolic stress.

2.
Int J STD AIDS ; : 9564624241280739, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39259938

RESUMO

OBJECTIVES: Campylobacter spp. has been reported to be a sexually transmissible enteric infection in men who have sex with men (MSM) since the 1980s causing an acute severe diarrhoeal illness and rarely an acute demyelinating polyneuropathy (Guillain-Barré syndrome). The aim of this review was to explore the factors seen in MSM with Campylobacter spp. METHODS: We conducted a systematic review following PRISMA guidelines by searching 7 bibliographical databases in August 2024 for manuscripts in English. Initial screening was conducted by a primary author and then two authors conducted independent full-text reviews to determine the final eligible manuscripts. We only included manuscripts which explored factors seen in MSM with Campylobacter spp.. Two authors independently used the Joanna Briggs Institute critical appraisal tools to assess risk for bias. This review was registered with PROSPERO (CRD42023464803). RESULTS: 25 manuscripts met the inclusion criteria that included 265 MSM with Campylobacter spp.. This review has highlighted demographic factors (living with HIV, living in urban MSM districts, HIV negative MSM using HIV-PrEP), biological factors (antimicrobial resistant Campylobacter spp., having a concurrent or previous sexually transmitted infection [Neisseria gonorrhoeae, Chlamydia trachomatis, Herpes simplex virus, Hepatitis C, Mpox] current/previous enteric infection including non-pathogenic parasites [Shigella spp., Giardia duodenalis, Cryptosporidium, Entamoeba histolytica, Salmonella spp., Entamoeba hartmanii, Entamoeba coli, Endolimax nana, Iodamoeba butchlii]) and behavioural factors (condomless receptive anal sex, oral-anal sex, oral genital sex, multiple/new sexual partners, using sex on premises venues and the internet to meet sexual partners) seen in MSM with Campylobacter spp. CONCLUSION: This review has highlighted some important demographic, biological and behavioural risk factors seen in MSM with Campylobacter spp.. These data can be used to inform future public health interventions and clinical guidelines.

3.
J Endocrinol ; 259(2)2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37650517

RESUMO

The present study examines differences in metabolic and pancreatic islet adaptative responses following streptozotocin (STZ) and hydrocortisone (HC) administration in male and female transgenic GluCreERT2/Rosa26-eYFP mice. Mice received five daily doses of STZ (50 mg/kg, i.p.) or 10 daily doses of HC (70 mg/kg, i.p.), with parameters assessed on day 11. STZ-induced hyperglycaemia was evident in both sexes, alongside impaired glucose tolerance and reduced insulin concentrations. HC also had similar metabolic effects in male and female mice resulting in classical increases of circulating insulin indicative of insulin resistance. Control male mice had larger pancreatic islets than females and displayed a greater reduction of islet and beta-cell area in response to STZ insult. In addition, female STZ mice had lower levels of beta-cell apoptosis than male counterparts. Following HC administration, female mouse islets contained a greater proportion of alpha cells when compared to males. All HC mice presented with relatively comparable increases in beta- and alpha-cell turnover rates, with female mice being slightly more susceptible to HC-induced beta-cell apoptosis. Interestingly, healthy control female mice had inherently increased alpha-to-beta-cell transdifferentiation rates, which was decreased by HC treatment. The number of glucagon-positive alpha cells altering their lineage to insulin-positive beta cells was increased in male, but not female, STZ mice. Taken together, although there was no obvious sex-specific alteration of metabolic profile in STZ or HC mice, subtle differences in pancreatic islet morphology emphasises the impact of sex hormones on islets and importance of taking care when interpreting observations between males and females.


Assuntos
Células Secretoras de Glucagon , Ilhotas Pancreáticas , Feminino , Masculino , Camundongos , Animais , Insulina , Glucagon , Camundongos Transgênicos , Hidrocortisona
4.
Mol Cell Endocrinol ; 570: 111932, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37080378

RESUMO

OBJECTIVE: Glucagon receptor (GCGR) antagonism elicits antihyperglycemic effects in rodents and humans. The present study investigates whether the well characterised peptide-based GCGR antagonist, desHis1Pro4Glu9-glucagon (Lys12PAL), alters alpha-cell turnover or identity in mice. METHODS: Multiple low-dose streptozotocin (STZ) treated (50 mg/kg bw, 5 days) transgenic GluCreERT2;ROSA26-eYFP mice were employed. STZ mice received twice daily administration of saline vehicle or desHis1Pro4Glu9-glucagon (Lys12PAL), at low- or high-dose (25 and 100 nmol/kg, respectively) for 11 days. RESULTS: No GCGR antagonist induced changes in food or fluid intake, body weight or glucose homeostasis were observed. As expected, STZ dramatically reduced (P < 0.001) islet numbers and increased (P < 0.01) alpha-to beta-cell ratio, which was linked to elevated (P < 0.05) levels of beta-cell apoptosis. Whilst treatment with desHis1Pro4Glu9-glucagon (Lys12PAL) decreased (P < 0.05-P < 0.001) alpha- and beta-cell areas, it also helped restore the classic rodent islet alpha-cell mantle in STZ mice. Interestingly, low-dose desHis1Pro4Glu9-glucagon (Lys12PAL) increased (P < 0.05) alpha-cell apoptosis rates whilst high dose decreased (p < 0.05) this parameter. This difference reflects substantially increased (P < 0.001) alpha-to beta-cell transdifferentiation following high dose desHis1Pro4Glu9-glucagon (Lys12PAL) treatment, which was not fully manifest with low-dose therapy. CONCLUSIONS: Taken together, the present study indicates that peptidic GCGR antagonists can positively influence alpha-cell turnover and lineage in identity in multiple low-dose STZ mice, but that such effects are dose-related.


Assuntos
Insulina , Receptores de Glucagon , Humanos , Camundongos , Animais , Hiperplasia , Glucagon/farmacologia , Glicemia
5.
Indian J Psychiatry ; 64(4): 354-363, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060721

RESUMO

Background: Literature suggests that the COVID-19 pandemic has resulted in poor sleep quality, especially among the infected population. However, literature regarding the effect of COVID-19 pandemic and SARS-CoV-2 infection on occurrence of insomnia, restless legs syndrome and dream enactment behavior is either scarce or unavailable. Methods: This study was planned to assess the effect of SARS-CoV-2 infection on the occurrence of insomnia, restless legs syndrome (RLS) and dream enactment behavior (DEB). For this cross-sectional study, a questionnaire comprising of items related to demographic details, past medical history, and information related to SARS-CoV-2 infection was distributed through social media. Insomnia was diagnosed using clinical criteria. RLS, DEB, sleep quality, depression and anxiety were assessed using a validated questionnaire. Information regarding the use of hypnotic medications was also gathered. Results: Of the 1596 respondents, 37.2% reported disturbed sleep while insomnia was reported by 22.6% respondents. 27.3% of respondents reported RLS and 17.4% suffered DEB. The odds of insomnia were greater among males (OR = 1.27; 95% CI: 1.03-1.58; P < 0.02) and among those who had SARS-CoV-2 infection (OR = 1.76; 95% CI = 1.42-2.19; P < 0.001). Similarly, SARS-CoV-2 infection was also associated with increased odds of RLS (OR = 2.48; 95% CI = 1.98-3.11; P < 0.001) and DEB (OR = 1.58; 95%CI = 1.21-2.06; P < 0.001). Insomnia, RLS and DEB were more frequent among respondents who required oxygen therapy, those who experienced loss of taste and/or smell, depression and anxiety. Prevalence of insomnia, DEB and RLS was higher than said prevalence among respondents with no history of SARS-CoV-2 infection, but lower than that of those with positive history of SARS-CoV-2 infection. 5.3% of respondents reported taking hypnotic medications before infection, 7% during infection and 5.3% after infection. Conclusion: SARS-CoV-2-infection-related factors in association with environmental factors have increased the prevalence of insomnia, DEB and RLS among subjects having infection. SARS-CoV-2-associated immunological changes, hypoxia and neurotropism may play a role in occurrence of insomnia, DEB and RLS.

6.
Indian J Psychiatry ; 62(4): 370-378, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33165382

RESUMO

INTRODUCTION: To mitigate the spread of the pandemic coronavirus infection (COVID-19), governments across the world have adopted "lockdowns" which have confined many individuals to their homes. This disrupts normal life routines, elements of which are important circadian cues. The pandemic is also associated with new stressors, altered roles, and uncertainties about health and economic security, which are also likely to affect sleep. The current study is an online survey of sleep experience, routines, physical activity, and symptoms of anxiety and depression, to study the alterations associated with the lockdown. MATERIALS AND METHODS: The survey was conducted in early May 2020 using a questionnaire circulated through social media platforms. Questions related to demographic characteristics, current and previous sleep schedules, routine, and working patterns. Insomnia (Insomnia Severity Index - 4), Stress (Perceived Stress Scale - 4), anxiety and depressive symptoms (Patient Health Questionnaire - 4) and physical activity (International Physical Activities Questionnaire) were assessed using standardized instruments. RESULTS: A total of 958 valid responses were received. Compared to the prelockdown period, there was a shift to a later bedtime and waking time, with a reduction in night-time sleep and an increase in day-time napping. These effects were visible across occupational groups, but mostly affected working individuals except health professionals. Sleep quality deteriorated across groups. Reductions in sleep duration were associated with depressive symptoms. CONCLUSIONS: The COVID-19 lockdown is associated with changes in sleep schedule and in the quantity and quality of night-time sleep. Although these changes are associated with elevated rates of emotional symptoms, it is unclear from these cross-sectional results, whether sleep deterioration produces psychological distress, or vice versa.

9.
Ind Psychiatry J ; 23(2): 134-42, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25788803

RESUMO

CONTEXT: Diabetes affects 9.2% of adults in India. About 8-16% of its population also suffer from depression. Both diseases pose a serious health challenge at individual and system level. The prevalence of depression in diabetes is much higher than in the general population. Undiagnosed and untreated depression puts people at higher morbidity and mortality risk. AIM: To study the prevalence of depression in diabetes and to identify associated risk factors. SETTINGS AND DESIGN: Case control study carried out in an outpatient setting of a tertiary hospital in central India. MATERIALS AND METHODS: One hundred and nine type 2 diabetes patients and 91 healthy controls formed the subjects of the study. Sociodemographic data were obtained on seven parameters. Comprehensive clinical data were obtained by means of standard procedures. Blood sugar levels and glycosylated hemoglobin levels were measured to assess glycemic control. Data of diabetic patients and controls as well as that of depressed and nondepressed diabetics were subjected to statistical analysis. RESULTS: About 42.2% of diabetes patients and only 4.39% of controls had depression. About 19% of diabetics had peripheral neuropathy but had much higher neuropathic symptoms. Depression was not related to any sociodemographic or clinical factors but was strongly associated with poor glycemic control. CONCLUSION: Depression is highly prevalent in diabetes. Physical symptoms mask depression. Special attention needs to be paid to diagnose depression in diabetes and treat it appropriately along with effective glycemic control. Diabetes patients need to be treated collaboratively by physicians and psychiatrists.

10.
Chem Biol Drug Des ; 80(4): 598-604, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22716235

RESUMO

Some hybrid 1,3,4-thiadiazole-1,3,5-triazine derivatives tethered via -S- bridge were synthesized and characterized with the aid of spectroscopic and elemental analysis. These hybrid conjugates were then investigated for their antibacterial activity against selected Gram-positive and Gram-negative bacteria. Excellent to moderate antibacterial activity was presented by the target compounds.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Tiadiazóis/química , Tiadiazóis/farmacologia , Triazinas/química , Triazinas/farmacologia , Antibacterianos/síntese química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Humanos , Tiadiazóis/síntese química , Triazinas/síntese química
11.
Chem Biol Drug Des ; 80(4): 572-83, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22702334

RESUMO

Some novel hybrid 1,3-thiazine-1,3,5-triazine derivatives were synthesized and tested for antibacterial activity. Compounds 8c and 8f were found active against Gram positive and Gram negative microorganisms. Molecular docking studies have been performed on eubacterial ribosomal decoding A site (Escherichia coli 16S rRNA A site) to rationalize the probable mode of action, binding affinity, and orientation of the molecules at the active site of receptor. The structures of all these newly synthesized compounds were confirmed by their elemental analyses and spectral data techniques viz. IR, ¹H NMR, ¹³C NMR, and mass.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Tiazinas/química , Tiazinas/farmacologia , Triazinas/química , Triazinas/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/genética , Infecções Bacterianas/tratamento farmacológico , Humanos , Simulação de Acoplamento Molecular , Biossíntese de Proteínas/efeitos dos fármacos
12.
J Drug Target ; 19(4): 258-69, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20604740

RESUMO

The present investigation was aimed at targeting indinavir, a protease inhibitor to cells of mononuclear phagocyte system (MPS) via mannosylated liposomes. ß-d-1-thiomannopyranoside residues were covalently coupled with dimyristoyl phosphatidylethanolamine (DMPE) to generate mannosylated-DMPE (Man-DMPE) conjugate which was further incorporated with disteroyl phosphatidyl choline and cholesterol to prepare mannosylated liposomes. The optimized mannosylated liposomes were nanometric in size (142 ± 2.8 nm) with optimum entrapment efficiency (88.7 ± 2.3%). Less than 20% cumulative drug release was observed from the prepared formulations in 24 h in phosphate buffer saline (pH 7.4). Cellular uptake studies performed on J774.A1 macrophage cell line via flow cytometric analysis depicted enhanced uptake of mannosylated liposomes as compared to plain liposomes. Annexin-V-fluorescein isothiocyanate/propidium iodide apoptosis assay delineated marginal cytotoxicity in macrophages from the developed formulation. Plasma and tissue distribution studies performed to assess the drug reach to macrophage rich regions depicted a significant level (P < 0.05) of indinavir in macrophage rich tissues like liver, spleen, and lungs from mannosylated liposomes as compared to plain liposomes and free drug. The conducted studies suggest the potential of indinavir loaded mannosylated liposomes for anti-human immunodeficiency virus therapy.


Assuntos
Antivirais/administração & dosagem , Antivirais/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Indinavir/administração & dosagem , Indinavir/uso terapêutico , Lipossomos/química , Animais , Área Sob a Curva , Linhagem Celular , Portadores de Fármacos , Meia-Vida , Macrófagos/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
13.
Nanomedicine ; 6(4): 590-6, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20093197

RESUMO

Indinavir, as a protease inhibitor with a short biological half life, variable pH-dependent oral absorption, and extensive first-pass metabolism, presents a challenge with respect to its oral administration. The current work aims to formulate and characterize indinavir-bearing ethanolic liposomes (ethosomes), and to investigate their enhanced transdermal delivery potential. The prepared ethanolic liposomes were characterized to be spherical, unilamellar structures having low polydispersity, nanometric size range, and improved entrapment efficiency over other delivery formulations. Permeation studies of indinavir across human cadaver skin resulted in enhanced transdermal flux from ethanolic liposomes that was significantly (P < 0.05) greater than that with ethanolic drug solution, conventional liposomes, or plain drug solution. Additionally, the ethanolic liposomes showed the shortest lag time for indinavir, thus presenting a suitable approach for transdermal delivery of this protease inhibitor. From the clinical editor: This study characterizes indinavir bearing ethanolic liposomes (ethosomes), and investigate their enhanced transdermal delivery potential, demonstrating a potentially a suitable approach for transdermal delivery of this protease inhibitor for HIV treatment, which typically has been associated with limited bioavailability via the oral route.


Assuntos
Etanol/química , Inibidores da Protease de HIV/administração & dosagem , Indinavir/administração & dosagem , Lipossomos/química , Administração Cutânea , Inibidores da Protease de HIV/química , Inibidores da Protease de HIV/farmacologia , Indinavir/farmacologia , Microscopia Eletrônica de Transmissão , Pele/metabolismo , Absorção Cutânea
14.
J Pharm Pharm Sci ; 13(4): 495-509, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21486527

RESUMO

PURPOSE: Solid lipid nanoparticles (SLN) have emerged as carriers for therapeutic peptides, proteins, antigens and bioactive molecules. We have explored the potential of SLN as carrier for Hepatitis B surface antigen (HBsAg) by surface modifications to enhance their loading efficiency and the cellular uptake, using subcutaneous route. METHODS: Four different formulations of SLN were prepared by solvent injection method and characterized for various physical properties: particle size, surface morphology, shape, zeta potential, polydispersity, X-ray diffraction analysis, release profile and entrapment efficiency. HBsAg loaded SLN were studied for their functional characteristics, in vitro cellular uptake and internalization studies by human dendritic cells, macrophages and fibroblasts, T cell proliferation and TH1/TH2 response. Humoral immune response elicited by subcutaneously administered HBsAg containing SLN formulations were studied in vivo in mice. RESULTS: Compared to soluble HBsAg; SLN, particularly the mannosylated formulation, showed better cellular uptake, lesser cytotoxicity and induction of greater TH1 type of immune response. They also showed better immunological potential by producing sustained antibody titer. CONCLUSION: Mannosylated SLN appears to be promising as carrier for vaccine delivery against hepatitis B as ascertained by in vitro and in vivo studies, however further investigations on humans are required to establish their potential as vaccines against hepatitis B infection.


Assuntos
Antígenos de Superfície da Hepatite B/administração & dosagem , Vacinas contra Hepatite B/administração & dosagem , Nanopartículas , Animais , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/metabolismo , Feminino , Fibroblastos/metabolismo , Hepatite B/imunologia , Hepatite B/prevenção & controle , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/imunologia , Humanos , Injeções Subcutâneas , Lipídeos/química , Macrófagos/metabolismo , Manose/química , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Linfócitos T/metabolismo , Células Th1/imunologia , Células Th2/imunologia , Difração de Raios X
15.
J Drug Target ; 18(2): 93-105, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19640212

RESUMO

The present study evaluates the potential of surface functionalized gelatin nanoparticles (f-GNPs) for efficient macrophage-specific delivery of amphotericin B (AmB) in the treatment of visceral leishmaniasis (VL). Further, the effect of spacer for macrophage targeting was also evaluated. Gelatin was functionalized either through conjugation to mannose via direct coupling (mGelatin) or via PEG spacer (m-Gelatin), and the synthesis was confirmed by FTIR. AmB-loaded f-GNPs, that is, mGNPs and m-GNPs prepared from mGelatin and m-Gelatin conjugates, respectively, were characterized. In vitro concanavalin A (Con-A) agglutination assay confirmed the availability of mannose on the surface of these f-GNPs. Kinetics of cellular uptake of AmB-loaded f-GNPs by J774A.1 macrophage cells assessed through flow cytometry demonstrated a steady increase and maximum cell-associated fluorescence was observed at 4h for m-GNPs and 6 h for m-GNPs. Measurement of cytotoxicity using Annexin-V-FITC/PI apoptosis assay delineated marginal changes (7-9%) in treated macrophages following 48 h incubation, establishing the safety of f-GNPs. m-GNPs showed a 5.4-fold reduction in IC(50) in comparison with plain AmB suggesting significant enhancement of antileishmanial activity. Our results indicate that f-GNPs could be a promising carrier for specific delivery of AmB to macrophages for effective treatment of VL. Furthermore, spacer contributed significantly in reducing the cytotoxicity as well as increasing the uptake and activity of f-GNPs.


Assuntos
Anfotericina B/uso terapêutico , Gelatina/química , Leishmaniose Visceral/tratamento farmacológico , Macrófagos/fisiologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Anfotericina B/administração & dosagem , Animais , Antiprotozoários/administração & dosagem , Antiprotozoários/uso terapêutico , Linhagem Celular , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/uso terapêutico , Manose/química
16.
Nanomedicine ; 6(1): 110-8, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19446655

RESUMO

The aim of the present study was to evaluate two vesicular carrier systems, ethosomes and elastic liposomes loaded with hepatitis B surface antigen, for in vitro qualitative and quantitative uptake by human dendritic cells (DCs) and ability to stimulate T lymphocytes. Quantitative uptake of antigen-loaded carriers was documented by flow cytometry, and internalization of the systems by the DCs was studied using spectral bioimaging. Ability of antigen-pulsed DCs to stimulate autologous peripheral blood lymphocytes and levels of TH1/TH2 cytokines were also examined using flow cytometry. Both vesicular carrier systems as antigen delivery modules and DCs as antigen-presenting cells were able to generate a protective immune response. However, ethosomes were found to have higher internalizing ability and immunogenicity in comparison with elastic liposomes. These properties of ethosomes coupled with their skin-navigating potential, make it an attractive vehicle for development of a transcutaneous vaccine against hepatitis B in preference to elastic liposomes. FROM THE CLINICAL EDITOR: Two carrier systems for more potent vaccine administration - ethosomes and elastic liposomes loaded with hepatitis B surface antigen - are compared. Ethosomes demonstrated higher internalizing ability and immunogenicity. Due to their known skin-navigating potential, ethosomes may represent an attractive vehicle for development of a transcutaneous vaccine against hepatitis B.


Assuntos
Células Dendríticas/imunologia , Portadores de Fármacos/química , Antígenos de Superfície da Hepatite B/imunologia , Lipossomos/química , Animais , Apoptose , Bromodesoxiuridina/metabolismo , Bovinos , Núcleo Celular/metabolismo , Proliferação de Células , Citocinas/metabolismo , Elasticidade , Citometria de Fluxo , Fluoresceína-5-Isotiocianato/metabolismo , Humanos , Indóis/metabolismo , Cinética , Camundongos , Células NIH 3T3 , Necrose , Rodaminas/metabolismo , Soroalbumina Bovina/metabolismo , Células Th1/citologia , Células Th1/metabolismo , Células Th2/citologia , Células Th2/metabolismo , Fatores de Tempo
17.
Nanomedicine ; 5(4): 432-42, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19341818

RESUMO

This work presents a novel cascade of chemical functionalization of multiwalled carbon nanotubes (MWCNTs) through chemical modification by a carbohydrate, D-galactose. Galactose-conjugated or galactosylated MWCNTs were synthesized involving the sequential steps of carboxylation, acylation, amine modification, and finally, galactose conjugation. The modification of MWCNTs with galactose was investigated by elemental analysis, x-ray diffraction analysis, Fourier transform-infrared spectroscopy, Raman spectroscopy, and zeta potential measurements, at every sequential step of functionalization. Size and surface characteristics of chemically modified MWCNTs were monitored by transmission electron microscopy and scanning electron microscopy. That galactosylation improved the dispersibility of MWCNTs in aqueous solvents was confirmed by investigation of their dispersion characteristics at different pH values. Thus, the galactosylated MWCNTs as developed could be used for delivery of different bioactive(s) as well as active ligand (galactose)-based targeting to hepatic tissue. FROM THE CLINICAL EDITOR: This work presents a novel cascade of functionalization of multiwalled carbon nanotubes (MWCNTs) through chemical modification by a carbohydrate. Galactosylation improves the dispersibility of MWCNTs in aqueous solvents. The galactosylated MWCNTs could be used for delivery of different bioactive(s) as well as active ligand-based targeting to hepatic tissue.


Assuntos
Galactose/química , Nanotubos de Carbono/química , Elementos Químicos , Nanotubos de Carbono/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Temperatura , Fatores de Tempo , Difração de Raios X
18.
Int J Diabetes Dev Ctries ; 29(3): 133-8, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20165651

RESUMO

This study was conducted to find out the association of diabetes mellitus with cognitive functioning and depressive features. We included 50 diabetic and 30 control subjects who were screened on the basis of various inclusion and exclusion criteria. Then, a history of variables under study was taken and respective laboratory investigations were noted. First, the Becks Depression Inventory (BDI) was administrated to the patients. The cognitive function was then assessed using the digit span test, stroop Test, controlled oral word association test, visual target cancellation test, digit symbol substitution test, and visuospatial working memory matrix. The composite score on all tests was used to make cognitive index. The data was compiled and appropriate statistical methods were used. We found that 48% of elderly diabetic patients showed cognitive impairment. Poor metabolic control (hyperglycemia) was associated significantly and negatively with cognitive index in diabetic patients. Hyperglycemia was significantly and negatively correlated with immediate memory and attention, verbal memory, psychomotor functioning (DSST), and visuospatial memory. In conclusion, genesis of cognitive deficits in diabetic patients is complex. However, it appears from the study that such deficits do exist and may be associated with chronically poorly controlled diabetes.

19.
Curr Drug Deliv ; 5(3): 199-206, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18673263

RESUMO

In order to get across the intact skin, drug-laden carriers have to pass through narrow, confining pores of 50 nm or less diameter, under the influence of a suitable transdermal gradient. Novel ultradeformable carriers, the elastic liposomes achieve this target via its deforming and self-optimizing property. The main goal of this work was to prepare and characterize, elastic liposomes bearing melatonin, an anti-jet lag agent for its efficient transdermal delivery. Elastic liposomes bearing melatonin were prepared by modified extrusion method and characterized for shape, lamellarity, size distribution, percent drug loading, turbidity profile by Transmission electron microscopy (TEM), Dynamic light scattering (DLS), Mini-column centrifugation and Nephelometric techniques. The effect of different formulation variables like type of surfactant and concentration of surfactant on the deformability of vesicles, turbidity changes, transdermal flux across human cadaver skin, amount of drug deposited into the skin were investigated. Confocal laser scanning (CLS) micrographs revealed that probe (Rhodamine Red) loaded elastic liposomes were able to penetrate much deeper than the probe loaded conventional rigid liposomes. Out of the three surfactants utilized namely, Span 80, Sodium cholate and Sodium dodecylsulphate, formulation bearing Span 80 at an optimum lipid: surfactant ratio of 85:15% w/w proved to be the best in all parameters studied. The optimum skin permeation profile including greater transdermal flux and lower lag time of melatonin from optimized elastic liposomes via human cadaver skin was observed. Our results of the present study demonstrated the feasibility of elastic liposomal system for transdermal delivery of this anti- jet lag agent, which provides better transdermal flux, higher entrapment efficiency, greater skin drug deposition and possesses the ability of a self-penetration enhancer as compared to conventional liposomes.


Assuntos
Administração Cutânea , Síndrome do Jet Lag/tratamento farmacológico , Lipossomos , Melatonina/uso terapêutico , Absorção Cutânea/fisiologia , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Composição de Medicamentos , Elasticidade , Excipientes , Humanos , Técnicas In Vitro , Melatonina/administração & dosagem , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Pele/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier
20.
Crit Rev Ther Drug Carrier Syst ; 25(2): 169-206, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18540838

RESUMO

Carbon nanotubes (CNTs) are considered for use in numerous technological applications, including as biocompatible modules for the delivery of bioactives. However, there are unique properties of CNTs that limit their use as vehicles for various purposes. This review highlights the various challenges to a pharmaceutical scientist while exploring CNTs as bioactive delivery vehicles. The lack of solubility, nonbiodegradability, circulation half-life of 3-3.5 hours, biocompatibility, and immunogenicity limitations of CNTs are discussed in this review. These limitations indicate the need for modifications in order to explore the feasibility of CNTs as delivery vehicles.


Assuntos
Materiais Biocompatíveis , Nanotecnologia , Nanotubos de Carbono , Animais , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Meia-Vida , Humanos , Solubilidade , Vacinas/administração & dosagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA