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Liquid-liquid extraction (LLE), the go-to process for a variety of chemical separations, is limited by spontaneous organic phase splitting upon sufficient solute loading, called third phase formation. In this study we explore the applicability of critical phenomena theory to gain insight into this deleterious phase behavior with the goal of improving separations efficiency and minimizing waste. A series of samples representative of rare earth purification were constructed to include each of one light and one heavy lanthanide (cerium and lutetium) paired with one of two common malonamide extractants (DMDOHEMA and DMDBTDMA). The resulting postextraction organic phases are chemically complex and often form rich hierarchical structures whose statics and dynamics near the critical point were probed herein with small-angle X-ray scattering and high-speed X-ray photon correlation spectroscopy. Despite their different extraction behaviors, all samples show remarkably similar critical behavior with exponents well described by classical critical point theory consistent with the 3D Ising model, where the critical behavior is characterized by fluctuations with a single diverging length scale. This unexpected result indicates a significant reduction in relevant chemical parameters at the critical point, indicating that the underlying behavior of phase transitions in LLE rely on far fewer variables than are generally assumed. The obtained scalar order parameter is attributed to the extractant fraction of the extractant/diluent mixture, revealing that other solution components and their respective concentrations simply shift the critical temperature but do not affect the nature of the critical fluctuations. These findings point to an opportunity to drastically simplify studies of liquid-liquid phase separation and phase diagram development in general while providing insights into LLE process improvement.
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BTEX are the consistently found air contaminants in indoor and outdoor environments. In order to investigate the exposure levels of BTEX, the indoor and outdoor air was analyzed during winter season at homes located at four selected sites of Gorakhpur, Uttar Pradesh, India, which comprised residential, roadside, industrial and agricultural areas. BTEX were sampled with a low-flow pump (SKC model 220). Samples were extracted with CS2 and the aromatic fraction was subjected to GC-FID. Mean indoor concentration of BTEX was highest at the agricultural (70.9 µg m-3) followed by industrial (30.0 µg m-3), roadside (17.5 µg m-3) and residential site (11.8 µg m-3). At outdoor locations, the mean BTEX levels were highest at the roadside (22.0 µg m-3) followed by industrial (18.7 µg m-3), agricultural (11.0 µg m-3) and residential site (9.1 µg m-3). The I/O ratios were greater than 1 at all the sites except roadside site, where I/O ratios for toluene, ethylbenzene and xylene were less than unity. Poor correlation between indoor and outdoor levels at each site further indicated the dominance of indoor sources. Factor analysis followed by one-way analysis of variance depicts that the presence of BTEX compounds at all the sites indicate a mixture of vehicular and combustion activities. For benzene, the ILTCR values exceeded the safe levels, whereas ethylbenzene was nearby to the recommended level 1 × 10-6. The HQ values were above unity for agricultural (indoors) and industrial (outdoors) as an exception to all the other sites which indicted the value below unity.
Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Benzeno/análise , Derivados de Benzeno , Monitoramento Ambiental , Índia , Fatores de Risco , Estações do Ano , Tolueno , XilenosRESUMO
OBJECTIVE: The aim of this study was to evaluate the efficacy of anakinra in patients who were admitted to hospital for severe COVID-19 pneumonia requiring oxygen therapy. METHODS: A prospective, open-label, interventional study in adults hospitalized with severe COVID-19 pneumonia was conducted. Patients in the interventional arm received subcutaneous anakinra (100 mg twice daily for 3 days, followed by 100 mg daily for 7 days) in addition to standard treatment. Main outcomes were the need for mechanical ventilation and in-hospital death. Secondary outcomes included successful weaning from supplemental oxygen and change in inflammatory biomarkers. Outcomes were compared with those of historical controls who had received standard treatment and supportive care. RESULTS: A total of 69 patients were included: 45 treated with anakinra and 24 historical controls. A need for mechanical ventilation occurred in 14 (31%) of the anakinra-treated group and 18 (75%) of the historical cohort (p < 0.001). In-hospital death occurred in 13 (29%) of the anakinra-treated group and 11 (46%) of the historical cohort (p = 0.082). Successful weaning from supplemental oxygen to ambient air was attained in 25 (63%) of the anakinra-treated group compared with 6 (27%) of the historical cohort (p = 0.008). Patients who received anakinra showed a significant reduction in inflammatory biomarkers. CONCLUSION: In patients with severe COVID-19 pneumonia and high oxygen requirement, anakinra could represent an effective treatment option and may confer clinical benefit. TRIAL REGISTRATION NUMBER: ISRCTN74727214.
Assuntos
COVID-19/terapia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Oxigênio/uso terapêutico , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração ArtificialRESUMO
The advent of high-speed x-ray photon correlation spectroscopy now allows the study of critical phenomena in fluids to much smaller length scales and over a wider range of temperatures than is possible with dynamic light scattering. We present an x-ray photon correlation spectroscopy study of critical fluctuation dynamics in a complex fluid typical of those used in liquid-liquid extraction (LLE) of ions, dodecane-DMDBTDMA with extracted aqueous Ce(NO_{3})_{3}. We observe good agreement with both static and dynamic scaling without the need for significant noncritical background corrections. Critical exponents agree with 3D Ising values, and the fluctuation dynamics are described by simple exponential relaxation. The form of the dynamic master curve deviates somewhat from the Kawasaki result, with a more abrupt transition between the critical and noncritical asymptotic behavior. The concepts of critical phenomena thus provide a quantitative framework for understanding the structure and dynamics of LLE systems and a path forward to new LLE processes.
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The dewetting dynamics of a supported bilayer polymer thin film on a solid substrate is investigated using grazing incidence x-ray photon correlation spectroscopy. We find that the top layer dewets via the spinodal mechanism. The kinetics of the dewetting is studied by monitoring the time evolution of the surface diffuse x-ray scattering intensity. We study the time evolution of fluctuations about the average surface structure by measuring the two-time x-ray intensity fluctuation correlation functions. Using these two-time correlation functions we quantify the crossover from early-time diffusive dynamics to hydrodynamics. The early diffusive regime satisfies dynamic universality. The two-time correlation functions also quantify the onset of hydrodynamic effects. The hydrodynamic regime is observed during the spinodal dewetting process as these interactions are not screened.
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Polymer mediated drug delivery system represents a novel promising platform for tumor-targeting with reduced systemic side effects and improved chemotherapeutical efficacy. In this study, we report the preparation and characterization of herceptin targeted, diglycolamic acid (DGA) functionalized polyamidoamine (PAMAM) dendrimer as a potent drug carrier for cisplatin. DGA dendrimers carrying cisplatin demonstrated enhanced anticancer activity when targeted with herceptin. In vitro cell line studies with herceptin-DGA-G4-cisplatin in HER-2 +ve and HER-2 -ve human ovarian cancer cell lines showed that these nanoparticles possessed remarkable features such as lower IC50 value, improved S-phase arrest, and enhanced apoptosis due to increased cellular uptake and accumulation than the untargeted DGA-G4-cisplatin and free cisplatin. Furthermore, in vivo results in SCID mice bearing SKOV-3 tumor xenografts, herceptin-DGA-G4-cisplatin, appeared to be more effective in inducing tumor regression as compared to free cisplatin. Collectively, these results indicate that herceptin targeted DGA functionalized PAMAM-cisplatin conjugates serve as better anti-tumor agents than individual therapeutic agents.
Assuntos
Acetamidas/química , Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Dendrímeros/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Neoplasias Ovarianas/tratamento farmacológico , Trastuzumab/química , Absorção Fisiológica , Animais , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/metabolismo , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Composição de Medicamentos , Excipientes/química , Feminino , Humanos , Concentração Inibidora 50 , Camundongos SCID , Nanopartículas/ultraestrutura , Neoplasias Ovarianas/metabolismo , Distribuição Aleatória , Fase S/efeitos dos fármacos , Propriedades de Superfície , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Chlamydia trachomatis (CT) infections in women can result in tubal pathology (TP). Worldwide 10-15% of all couples are subfertile, meaning they did not get pregnant after 1 year. Part of the routine subfertility diagnostics is the Chlamydia Antibody Test (CAT) to decide for laparoscopy or not in order to diagnose TP. The CAT positive and negative predictive value is such that many unneeded laparoscopies are done and many TP cases are missed. Addition of host genetic markers related to infection susceptibility and severity could potentially improve the clinical management of couples who suffer from subfertility. In the present study, the potential translational and clinical value of adding diagnostic host genetic marker profiles on the basis of infection and inflammation to the current clinical management of subfertility was investigated. This review provides an overview of the current state of the art of host genetic markers in relation to CT infection, proposes a new clinical diagnostic approach, and investigates how the Learning-Adapting-Leveling model (LAL, a public health genomic (PHG) model) can be of value and provide insight to see whether these host genetic markers can be translated into public health. This review shows that the preliminary basis of adding host genetic marker profiles to the current diagnostic procedures of subfertility is present but has to be further developed before implementation into health care can be achieved. CT infection is an example in the field of PHG with potential diagnostic to be taken up in the future in the field of subfertility diagnosis with a time line for integration to be dependent on enhanced participation of many stakeholders in the field of PHG which could be advanced through the LAL model.
Assuntos
Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/genética , Genômica/métodos , Infertilidade Feminina/diagnóstico , Saúde Pública/métodos , Algoritmos , Chlamydia trachomatis , Citocinas/metabolismo , Feminino , Marcadores Genéticos , Antígenos HLA/metabolismo , Haplótipos , Humanos , Infertilidade Feminina/microbiologia , Inflamação , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Gravidez , Receptores Toll-Like/metabolismo , Pesquisa Translacional BiomédicaRESUMO
Specific ligation states of hemoglobin are, when crystallized, capable of taking on multiple quaternary structures. The relationship between these structures, captured in crystal lattices, and hemoglobin structure in solution remains uncertain. Wide-angle X-ray solution scattering (WAXS) is a sensitive probe of protein structure in solution that can distinguish among similar structures and has the potential to contribute to these issues. We used WAXS to assess the relationships among the structures of human and bovine hemoglobins in different liganded forms in solution. WAXS data readily distinguished among the various forms of hemoglobins. WAXS patterns confirm some of the relationships among hemoglobin structures that have been defined through crystallography and NMR and extend others. For instance, methemoglobin A in solution is, as expected, nearly indistinguishable from HbCO A. Interestingly, for bovine hemoglobin, the differences between deoxy-Hb, methemoglobin and HbCO are smaller than the corresponding differences in human hemoglobin. WAXS data were also used to assess the spatial extent of structural fluctuations of various hemoglobins in solution. Dynamics has been implicated in allosteric control of hemoglobin, and increased dynamics has been associated with lowered oxygen affinity. Consistent with that notion, WAXS patterns indicate that deoxy-Hb A exhibits substantially larger structural fluctuations than HbCO A. Comparisons between the observed WAXS patterns and those predicted on the basis of atomic coordinate sets suggest that the structures of Hb in different liganded forms exhibit clear differences from known crystal structures.
Assuntos
Carboxihemoglobina/química , Metemoglobina/química , Espalhamento a Baixo Ângulo , Regulação Alostérica , Animais , Bovinos , Cristalografia por Raios X , Humanos , Modelos Moleculares , Soluções , Difração de Raios XRESUMO
X-ray magnetic circular dichroism (XMCD) and Small Angle Neutron Scattering (SANS) measurements were performed on thiol capped Au nanoparticles (NPs) embedded into polyethylene. An XMCD signal of 0.8 x 10(-4) was found at the Au L3 edge of thiol capped Au NPs embedded in a polyethylene matrix for which Superconducting Quantum Interference Device (SQUID) magnetometry yielded a saturation magnetization, M(S), of 0.06 emu/g(Au). SANS measurements showed that the 3.2 nm average-diameter nanoparticles are 28% polydispersed, but no detectable SANS magnetic signal was found with the resolution and sensitivity accessible with the neutron experiment. A comparison with previous experiments carried out on Au NPs and multilayers, yield to different values between XMCD signals and magnetization measured by SQUID magnetometer. We discuss the origin of those differences.
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The effect of mangiferin, a naturally occurring xanthone glucoside on cyclophosphamide-induced immunotoxicity and its mode of action in the immune system were investigated. To induce immunotoxicity, adult male Wistar rats were injected weekly with cyclophosphamide intraperitoneally at 100 mg/kg bodyweight. Mangiferin was injected intraperitoneally at 10 and 20 mg/kg daily for 14 days. Levamisole (3 mg/kg, i.p., daily for 14 days), a known immunostimulant that acts in immunosuppressive conditions was used as a standard drug. The effect of mangiferin on the primary immune response to ovalbumin (200 microg/rat, s.c.) was assessed at weekly intervals by measuring the serum ovalbumin-specific IgM levels. The organ weights and cellularity of spleen, thymus and bone marrow, haematology, T and B cell-dependent mitogen stimulation of splenocytes were assessed for the cellular response. Oxidative changes in lymphocytes, neutrophils and macrophages were measured at the end of the study. As well, the in vitro effect of mangiferin on cytotoxicity caused by H2O2 in primary lymphocytes was studied. The decrease in the lymphoid organ weights, cellular responses and antigen-specific IgM levels by cyclophosphamide treatment were significantly increased by repeated intraperitoneal administration of mangiferin. The enhanced lipid peroxidation and decreased catalase and superoxide dismutase activities found in lymphocytes, polymorphonuclear cells (PMN) and macrophages from cyclophosphamide treated rats were significantly ameliorated in mangiferin treated groups. The tissue injury caused by cyclophosphamide treatment was significantly suppressed by mangiferin as shown by the decrease in serum creatine phosphokinase (CPK) activity. In vitro experiments showed that pretreatment of lymphocytes with mangiferin protected from the toxicity induced by H2O2, further confirming the in vivo findings. From this study, it is evident that mangiferin exhibits an immunoprotective role mediated through the inhibition of reactive intermediate-induced oxidative stress in lymphocytes, neutrophils and macrophages.
Assuntos
Adjuvantes Imunológicos/farmacologia , Linfócitos/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Xantonas/farmacologia , Animais , Formação de Anticorpos/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Contagem de Células , Ciclofosfamida/toxicidade , Peróxido de Hidrogênio/toxicidade , Linfócitos/imunologia , Linfócitos/metabolismo , Tecido Linfoide/efeitos dos fármacos , Tecido Linfoide/imunologia , Tecido Linfoide/metabolismo , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Masculino , Neutrófilos/imunologia , Neutrófilos/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ovalbumina/imunologia , Estresse Oxidativo/imunologia , Ratos , Ratos WistarRESUMO
Ethanolic extract (70%) of Caesalpinia bonducella seed kernel has been subjected for its antipyretic and antinociceptive activities in adult albino rats or mice of either sex at 30, 100 and 300 mg/kg orally. The extract demonstrated marked antipyretic activity against Brewer's yeast-induced pyrexia in rats. The extract had significant central analgesic activity in hot plate and tail flick methods. It also exhibited marked peripheral analgesic effect in both acetic acid-induced writhing test in mice and Randall-Selitto assay in rats. It also significantly inhibited the formalin-induced hind paw licking in mice. In conclusion, the present study suggests that the ethanolic extract of Caesalpinia bonducella seed kernel possesses potent antipyretic and antinociceptive activities and thus, validates its use in the treatment of pain and pyretic disorders.
Assuntos
Analgésicos não Narcóticos/farmacologia , Analgésicos/farmacologia , Caesalpinia , Dor/prevenção & controle , Fitoterapia , Extratos Vegetais/farmacologia , Ácido Acético , Administração Oral , Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/uso terapêutico , Animais , Temperatura Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Formaldeído , Temperatura Alta , Masculino , Camundongos , Dor/induzido quimicamente , Medição da Dor/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , SementesRESUMO
Small-angle neutron scattering was used to characterize the solution behavior of charged carboxylic acid terminated "cascade" dendrimers (Z-Cascade/methane [4]/3-oxo-6-oxa-2-azaheptylidyne/3-oxo-2-azaheptylidyne/propanoic acids) of third (G3) and fifth (G5) generations as a function of dendrimer concentration, pH, and ionic strength. An increase in dendrimer concentration leads to a single broad peak in the scattering profile arising from interdendrimer interaction. The dissociation of terminal carboxylate groups also gives rise to an interdendrimer interaction peak, which could be suppressed by the addition of excess salt. The results of contrast matching measurements indicate the accumulation of an excess concentration of tetramethylammonium counterions around the surface of these highly charged particles, and the thickness of these counterions lies somewhere between 4 and 6 A. This conclusion is consistent with our previous potentiometric titration (Zhang, H.; et al. J. Phys. Chem. B 1997, 101, 3494) and capillary electrophoresis (Huang, Q. R.; et al. J. Phys. Chem. B 2000, 104, 898) data.
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In the present study, the effect of mangiferin (a xanthone glucoside, isolated from the leaves of Mangifera indica) on the atherogenic potential of streptozotocin (STZ)-diabetes was investigated. In addition, the effect of mangiferin on oral glucose tolerance in glucose-loaded normal rats was also determined. The chronic intraperitoneal (i.p.) administration of mangiferin (10 and 20 mg/kg) once daily (o.d.) for 28 days exhibited antidiabetic activity by significantly lowering fasting plasma glucose level at different time intervals in STZ-diabetic rats. Further, mangiferin (10 and 20 mg/kg, i.p.) showed significant antihyperlipidemic and antiatherogenic activities as evidenced by significant decrease in plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) levels coupled together with elevation of high-density lipoprotein cholesterol (HDL-C) level and diminution of atherogenic index in diabetic rats. In addition, the chronic administration of mangiferin (10 and 20 mg/kg, i.p.) for 14 days significantly as well as markedly improved oral glucose tolerance in glucose-loaded normal rats suggesting its potent antihyperglycemic activity. The accumulating evidences suggest that both pancreatic and extrapancreatic mechanisms might be involved in its antidiabetic or antihyperglycemic action. In conclusion, the present study demonstrates that mangiferin possesses significant antidiabetic, antihyperlipidemic and antiatherogenic properties thus suggesting its beneficial effect in the treatment of diabetes mellitus associated with hyperlipidemia and related cardiovascular complications.
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Arteriosclerose/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Xantonas/uso terapêutico , Animais , Arteriosclerose/sangue , Diabetes Mellitus Experimental/sangue , Hiperglicemia/sangue , Masculino , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Folhas de Planta , Ratos , Ratos Wistar , Xantonas/isolamento & purificaçãoRESUMO
The model system of poly(ethylene-oxide) or PEO, where the changing hydrogen-bond connectivity of the water has large effect on the conformation of the polymer chain, in mixtures of water and acetonitrile, is experimentally studied. The results show the existence of a threshold water content in the system at which the 3d connectivity of the water network begins. Unusual expansion of the polymer chain, an effect larger than that observed in either of the pure solvents, is seen. Upon addition of small amounts of a monovalent salt, binding of ion to polymer takes place in pure acetonitrile solutions. Salt ions begin to co-ordinate with water molecules at the same solvent ratio as the threshold for water network formation. Ions now no longer complex to PEO; instead, hydrogen bonding of water to the polymer strongly dictates conformation in this regime.
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Materiais Biocompatíveis/química , Polietilenoglicóis/química , Água/química , Absorção , Ligação de Hidrogênio , Íons , Substâncias Macromoleculares , Sais/química , Espalhamento de RadiaçãoRESUMO
A sensitive and selective liquid chromatography-tandem mass spectrometry method (LC-MS-MS) for the simultaneous estimation of bulaquine and primaquine has been developed and validated in monkey plasma. The mobile phase consisted of acetonitrile/ammonium acetate buffer (20 mM, pH 6) (50:50 v/v) at a flow-rate of 1 ml/min. The chromatographic separations were achieved on two spheri cyano columns (5 microm, 30 x 4.6 mm I.D.) connected in series. The quantitation was carried out using a Micromass LC-MS-MS with an electrospray source in the multiple reaction monitoring (MRM) mode. The analytes were quantified from the summed total ion value of their two most intense molecular transitions. This is another novel method leading to increased sensitivity and precision. A simple liquid-liquid extraction with 2 x 1.0 ml n-hexane/ethyl acetate/dimethyloctyl amine (90:10:0.05, v/v) was utilized. The method was validated in terms of recovery, linearity, accuracy and precision (within- and between-assay variation). The recoveries from spiked control samples were >or=90 and 50% for bulaquine and primaquine, respectively. Linearity in plasma was observed over a dynamic range of 1.56-400 and 3.91-1000 ng/ml for bulaquine and primaquine, respectively.
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Antimaláricos/sangue , Primaquina/análogos & derivados , Primaquina/sangue , Espectrometria de Massas por Ionização por Electrospray/métodos , Animais , Haplorrinos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND OBJECTIVES: Controversial reports are available regarding the effect of magnesium (Mg) on lipid profile and glycaemic control in diabetic patients. The present study was designed on 1) compare serum Mg levels in diabetic patients with those of non-diabetic controls and 2) to assess the effect of oral Mg supplementation on lipid profile and blood glucose of these patients. METHODS: The study included 40 patients of type 2 diabetes mellitus (DM) and 54 age and sex matched non-diabetic controls. After the baseline investigations of all the subjects (n=94) including blood glucose, serum lipid and magnesium, the diabetic patients (study group) were supplemented with 600 mg of Mg oxide daily for 12 weeks. They were followed up every four weeks (for a total duration of twelve weeks) and investigated for the above parameters. RESULTS: Mean serum magnesium at baseline in the diabetic patients was significantly lower than that in controls (1.44 +/- 0.48 mg/dl Vs 2.29 +/- 0.33 mg/dl; p < 0.001). A significant fall in serum total cholesterol, LDL cholesterol and triglycerides and a rise in HDL cholesterol levels was observed 4 to 8 weeks after initiation of magnesium supplementation and continued till the end of the study i.e. 12 weeks. Fasting and post-prandial blood glucose levels did not show any significant change after twelve weeks of magnesium supplementation when compared with baseline. CONCLUSIONS: A significant hypomagnesemia was observed in diabetic patients as compared to controls and Mg supplementation resulted in a beneficial effect on the lipid profile of these patients with no significant effect on blood glucose levels.