RESUMEN
Pyranopyrazole derivatives have a vital role in the class of organic compounds because of their broad spectrum of biological and pharmacological importance. Our current goal is the [3 + 3] cycloaddition of benzoyl isothiocyanate and pyrazolone 1 to undergo oxidation cyclization, producing pyrazoloxadiazine 3. The diol 5 was obtained as a condensation of two equivalents of 1 with thiophene-2-carboxaldehyde in acetic acid above the sodium acetate mixture. When the condensation was carried out in piperidine under fusion, unsaturated ketone 4 was obtained. The pyrazolo pyran derivative 11 resulted from the [3 + 3] cycloaddition of 1 and cinnamic acid, while the Pyrone derivative was prepared by acylation of 12 with two equivalents of acetic anhydride. Phthalic anhydride undergoes arylation using zinc chloride as a catalyst. The cyclic keto acid 23 was synthesized by the action of succinic anhydride on 12 in the acetic medium, while the latter reacted with cinnamic acid, leading to pyrazole derivative 24. All of these reactions were through the Michael reaction mechanism. All the tested compounds showed good antimicrobial activity against pathogenic microorganisms; newly synthesized compounds were also screened for their antioxidant activity. Rational studies were carried out by the ABTs method to allow a broader choice of activities. In addition, similar off-compounds were conducted. Molecular docking studies with the CB-Dock server and MD simulations were created with the default settings of the Solution Builder on the CHARMM-GUI server at 150 nm. A good correlation was obtained between the experimental results and the theoretical bioavailability predictions using POM theory.
Asunto(s)
Pirazolonas , Simulación del Acoplamiento Molecular , Acilación , CiclizaciónRESUMEN
On our way to discovering and developing compounds that have an antioxidant impact compared to ascorbic acid and other biological activities, we designed, synthesized, and evaluated a new series of heterocyclic moieties drugs (1-11) as antioxidants and antimicrobial agents. As starting moieties, these new candidates were derived from two promising heterocyclic compounds, imidazoldin-4-one and thiazol-4-one. Firstly, diphenylimidazol 1 was obtained because of the cyclo condensation one-pot ternary reaction of urea, aniline, and chloroacetic acid under thermal conditions. Out of this starting compound, we could design and create new vital rings such as purine and triazine as in compounds 5 and 6, respectively. Secondly, the start thiazole derivative 7 was obtained from the intermolecular cyclization of thiourea, chloroacetic acid, p-nitobezaldehyde in the presence of sodium acetate. We synthesized various derivatives from this second starting compound 7 by being subjected to different reagents such as aniline, phenylenediamine, phenylhydrazine, and barbituric acid to yield 8, 9, 10, and 11, respectively. Using ascorbic acid as the standard compound, the pharmacological testing for antioxidant activity assessment of the produced derivatives was evaluated against ABTS (2,20-azinobis (3-ethylbenzothiazoline-6-sulfonic acid). Candidate 6 exhibited the best activity as an antioxidant agent compared to ascorbic acid as a reference compound. Moreover, all compounds were evaluated as antimicrobial agents against a series of bacteria and fungi. Among all synthesized compounds, compound 6 achieved high efficiency against two types of fungi and four kinds of bacteria, as Clotrimazole and Ampicillin were used as the reference agents, respectively. All chemical structures of the novel synthesized candidates were unequivocally elucidated and confirmed utilizing spectroscopical and elemental investigations.
Asunto(s)
Antiinfecciosos/farmacología , Antioxidantes/farmacología , Diseño de Fármacos , Imidazolidinas/farmacología , Tiazoles/farmacología , Antiinfecciosos/química , Antioxidantes/química , Bacterias/efectos de los fármacos , Imidazolidinas/química , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Tiazoles/químicaRESUMEN
A rapidly increasing number of mandibular condylar fractures and some complications related to injuries of temporomandibular elements make this study important. Intra-articular disorders lead to secondary pathological findings such as osteoarthritis, deforming osteoarthrosis, and temporomandibular joint ankylosis that limits mouth opening, mastication, swallowing, breathing, and decreased/lost working capacity or disability. Early diagnosis of intra-articular disorders can prevent from long-lasting functional complications caused by temporomandibular joint injuries. This study was performed for the purpose of early detection and investigation of organic pathological changes in the cartilaginous and osseous tissues of the temporomandibular joint caused by traumatic fractures of the mandibular condyle. Twenty patients underwent a general clinical examination, magnetic resonance imaging (MRI), and immune-enzyme testing for biochemical markers of connective tissue injury (pyridinoline and deoxypyridinoline) in urine. Disk dislocation, deformation, adhesion, perforation or squeeze, tension or disruption of ligaments, and injury of articular surfaces are among complications of mandibular fractures that can be revealed on MRI. As regards biochemical findings, we revealed a sharp rise in the levels of pyridinoline and deoxypyridinoline before treatment and a lack of stabilization within 21 days of treatment.
Asunto(s)
Fracturas Mandibulares/inmunología , Fracturas Mandibulares/patología , Trastornos de la Articulación Temporomandibular/inmunología , Trastornos de la Articulación Temporomandibular/patología , Diagnóstico Precoz , Femenino , Humanos , Técnicas para Inmunoenzimas , Imagen por Resonancia Magnética , MasculinoRESUMEN
The comparative experimental study of osseous tissue regeneration in the createdforaminous mandibular defects being implanted with bioceramics Kergap T-300 and osteoplastic material Osteopor, as well as justifying the possibility ofusing the developed reparative material in the maxillofacial surgery clinics based on the analysis ofhistomorphological research results for are the paper objectives. 78 nonlinearwhite male rats weighing 240-300 g withforaminous mandibular defects were used as models for studying impact on the reparative osteogenesis processes made by the bonegraft material. Reparative changes in the implantation sites were studied in real time with the help of histological drugs under the optical microscopy. The graft components were the morphometry object calculated at the percentage ratio per the graft space unit in three cuts from each section. In 27.7% cases the rats'mandibular defects repair under the natural environment conditions of osseous tissue regeneration achieved with a blood clot was complicated by purulence, the surgical wound dehiscence with pyorrhea or perimandibular abscess. In other cases regeneration caused the development of heterogeneous graft made of chondroid-fibroblastic and osteoid tissues of different organization levels. The comparative experimental morphological and histomorphometric studies of the bone regeneration involving the replacement of created jaw defects with osteoplastic material Kergap-T alone and- in the combination with the lyophilized biological placenta implant Osteopor proved that the latter speeded up the beginning of active regenerative processes promoting the early defect filling with the neogenic organotypic osseous tissue comprising 52(43-63)[46-58]% and 74(57-85)[64-79]% of the bone graft in 60 and 90 days after the surgical intervention correspondingly (being equal to 24(13-29)[20-28]% i 32(27-38)[30-34]% correspondingly in cases when Kergap-Twas applied. According to the morphometric researchfindings, in cases of Osteopor and Kergap-T application the tabular bone element ofthe graft was equal to 53 (43-60) [46-561% and 15(13-18) [14-16]% correspondingly.
Asunto(s)
Regeneración Ósea/efectos de los fármacos , Sustitutos de Huesos/farmacología , Mandíbula/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Plásticos/farmacología , Animales , Regeneración Ósea/fisiología , Implantes Experimentales , Masculino , Mandíbula/patología , Traumatismos Mandibulares/patología , Traumatismos Mandibulares/cirugía , Osteogénesis/fisiología , Ratas , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Efficacy of combined prophylaxis of postoperative pathological cicatrices of facial skin was studied. Application of extracorporeal shockwave therapy and the silicone gel Strataderm have had impacted the clinical characteristics of the facial skin postoperative cicatrix positively: a shockwave therapy promoted a sutural tracks involution, аnd the silicone gel Strataderm normalization of the postoperative cicatrix pigmentation.
Asunto(s)
Cicatriz/prevención & control , Procedimientos Quirúrgicos Dermatologicos/métodos , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Traumatismos Faciales/terapia , Procedimientos Quirúrgicos Ortognáticos , Geles de Silicona/uso terapéutico , Adulto , Cicatriz/patología , Cara/patología , Cara/cirugía , Traumatismos Faciales/patología , Traumatismos Faciales/cirugía , Femenino , Humanos , Maxilares/lesiones , Maxilares/patología , Masculino , Piel/lesionesRESUMEN
The Clostridium thermocellum lichenase (endo-ß-1,3;1,4-glucan-D-glycosyl hydrolase) displays a high thermostability and specific activity and has a compact protein molecule, which makes it attractive, in particular, for protein engineering. We have utilized in silico analysis to construct circularly permuted (CP) variants and estimated the retained activity and thermostability. New open termini in the region of residues 53 or 99 in two lichenase CP variants (CN-53 and CN-99) had no effect on their activity and thermal tolerance versus another variant CP variant, CN-140 (cut in the region of residue 140), which displayed a dramatic decrease in the activity and thermostability. Construction and further activity and thermostability testing of the modified lichenase variants (M variants) and CP variants with peptides integrated via insertion fusion have demonstrated that the N-terminal regions in the lichenase catalytic domain (53 and 99 amino acid residues) that permit circular permutations with retention of activity and thermostability of the enzyme as well as the region between the C and N termini of the native lichenase in thermostable and active lichenase variants (CN-53 and CN-99) may be used for integrating small peptides without the loss of activity and thermostability. These findings not only suggest that CP predictions can be used in search for internal integration sites within protein molecule, but also form the background for further enzymatic engineering of the C. thermocellum thermostable lichenase aiming to create new fusion proteins.
Asunto(s)
Proteínas Bacterianas/metabolismo , Clostridium thermocellum/enzimología , Glicósido Hidrolasas/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Dominio Catalítico/genética , Clostridium thermocellum/genética , Electroforesis en Gel de Poliacrilamida , Estabilidad de Enzimas , Glicósido Hidrolasas/química , Glicósido Hidrolasas/genética , Calor , Datos de Secuencia Molecular , Mutación , Péptidos/química , Péptidos/genética , Péptidos/metabolismo , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Homología de Secuencia de AminoácidoRESUMEN
A set of module vectors for stable or transient gene expression in plants was constructed with regard to the majority of factors ensuring efficient heterologous gene expression in plants. The vectors are convenient to clone new regulatory elements and genes of interest via simple molecular cloning procedures. The vectors can be used to obtain transgenic plants with stable heterologous gene expression as well as to achieve transient expression because one vector includes the gene for the tomato bushy stunt virus p19 protein, which acts as a suppressor of posttranscriptional gene silencing.
Asunto(s)
Regulación de la Expresión Génica de las Plantas , Vectores Genéticos , Plantas Modificadas Genéticamente , Secuencia de Bases , Genes Reporteros , Datos de Secuencia Molecular , Plásmidos/genética , Interferencia de ARN , Nicotiana/genética , Proteínas Virales/genéticaRESUMEN
The basic methods used in current practice for stable and transient expression of heterologous genes in plants are presented and compared. The key areas of research in the heterologous expression of genes in plants have been identified by analyzing literature and experimental data: modeling of metabolic pathways; creation of marker-free transgenic plants; the search for new regulatory elements and plant genes influencing the efficiency of expression of heterologous genes in plants; development of new methods for analyzing of transgenic plants and new approaches to the expression of heterologous genes in plants.
Asunto(s)
Expresión Génica , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Marcadores GenéticosRESUMEN
Lysophosphatidic acid (LPA) is a lipid mediator required for maintaining homeostasis of numerous physiological functions and also involved in development of some pathological processes through interactions with G protein-coupled receptors. Recently many data have appeared about the role of this phospholipid in humans, but pathways of LPA biosynthesis and mechanisms of its action remain unclear. This review presents modern concepts about biosynthesis, reception, and biological activity of LPA in humans. Natural and synthetic LPA analogs are considered in the view of their possible use in pharmacology as agonists and/or antagonists of G protein-coupled receptors of LPA.
Asunto(s)
Lisofosfolípidos/metabolismo , Humanos , Lipasa/genética , Lipasa/metabolismo , Lisofosfolípidos/biosíntesis , Lisofosfolípidos/fisiología , Complejos Multienzimáticos/genética , Complejos Multienzimáticos/metabolismo , Fosfodiesterasa I/genética , Fosfodiesterasa I/metabolismo , Hidrolasas Diéster Fosfóricas , Pirofosfatasas/genética , Pirofosfatasas/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
The molecular biological features of the eutopic and ectopic endometrium were studied in 46 patients with adenomyosis, 44 with endometrioid cysts in the ovaries, and 34 with disseminated mixed forms of genital endometriosis. Reproductive-aged patients with the eutopic endometrium in a proliferation phase with hyperplastic or inflammatory changes were selected. Ten samples of the endometrium in a phase proliferation, which had been obtained at medicolegal autopsy of women without reproductive disorders, were studied as a control group. Both the glandular and stromal components of the ectopic and eutopic endometrium in different forms of endometriosis were shown to differ from the intact endometrium in their molecular biological features (the expression of Ki-67, Bcl-2, Bax, vascular endothelial growth factor, transforming growth factor-beta1, matrix metalloproteinases 2 and 10, matrix metalloproteinase-2 inhibitor, the enzyme cytochrome P450 aromatase.
Asunto(s)
Endometriosis/metabolismo , Endometrio/metabolismo , Adulto , Aromatasa/biosíntesis , Femenino , Humanos , Antígeno Ki-67/biosíntesis , Metaloproteinasas de la Matriz/biosíntesis , Persona de Mediana Edad , Quistes Ováricos/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Inhibidor Tisular de Metaloproteinasa-2/biosíntesis , Factor de Crecimiento Transformador beta/biosíntesis , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Adulto JovenAsunto(s)
Antibacterianos/uso terapéutico , Sinusitis/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Vacunas Estafilocócicas/uso terapéutico , Staphylococcus aureus/aislamiento & purificación , Adolescente , Adulto , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Sinusitis/microbiología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/inmunología , Supuración/tratamiento farmacológico , Supuración/microbiología , Resultado del Tratamiento , Adulto JovenRESUMEN
The induction, regeneration, and biolistic sensitivities of different genotypes of common wheat (Triticum aestivum L.) have been determined in order to develop an efficient system for transformation of Russian cultivars of spring wheat. Short-term (two days) cold treatment (4 degrees C) has been demonstrated to distinctly increase the frequency of morphogenetic callus induction. The optimal phytohormonal composition of the nutrient medium ensuring an in vitro regeneration rate of the common wheat cultivar Lada as high as 90% has been determined. The optimal temporal parameters of genetic transformation of wheat plants (10-14 days of culturing after initiation of a morphogenetic callus) have been determined for two transformation methods: biolistic without precipitated DNA and transformation with the plasmid psGFP-BAR. Analysis of the transient expression of the gfp gene has confirmed that 14 days of culturing is the optimal duration.
Asunto(s)
Plantas Modificadas Genéticamente/genética , Transformación Genética , Triticum/genética , Genotipo , Plantas Modificadas Genéticamente/citología , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Regeneración/genética , Federación de Rusia , Triticum/citología , Triticum/crecimiento & desarrolloRESUMEN
Variability of C-structural heterochromatin segments in chromosome 1,9 and 16 has been studied in lymphocyte cultures of peripheral blood taken from the patients with the hypertrophy (HC) and dilatate (DC) forms of cardiomiopathy and their 1st degree relatives (32 individuals, in total). 10 healthy individuals composed the control group. C-segments were sorted according to Patil and Lubs: a<0.5 x 16p; b>0.5-1 x 16p; c>1.5 x 16p; d>1.5-2 x 16p; e>2 x 16p. The total amount of C-heterochromatin in all the studied chromosomes was tended to increase for DC patients and the relatives of the patients with the two forms of cardiomiopathy. Individual specificity within the group was found when the c-variants were assessed in chromosomes. In particular, the results obtained in cells of HC patients and their relatives did not differ from the control values, while the distribution pattern of C-segments within the group of DC patients and their relatives underwent changing. The elevated induces of pericentromeric inversion were found in all the patients with both forms of the disease and their relatives indicating C-structural heterochromatin polymorphism in the tested individuals.
Asunto(s)
Cardiomiopatía Dilatada/genética , Cardiomiopatía Hipertrófica Familiar/genética , Variación Genética/genética , Heterocromatina/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 16/genética , Cromosomas Humanos Par 9/genética , Humanos , Mutación Puntual/genética , Polimorfismo Genético/genéticaRESUMEN
An immunoperoxidase test was used to reveal the expression of cytochrome P-450 aromatase in the eutopic and ectopic endometrium of 14 patients with ovarian endometriosis and 26 with adenomyosis, whose age ranged from 21 to 47 years (38+/-2.0 years). Five endometrial samples taken at autopsy from the women who had died from injuries at ages of 32 to 47 years and who had no uterine or ovarian abnormities served as the control. Control observations revealed no aromatase expression by endometrial epithelial and stromal cells. Aromatase expression in the eutopic endometrium was found in patients with ovarian endometriosis and adenomysis in 80 and 58% of cases, respectively; while that in the ectopic endothelium was in all cases in both groups. In external genital endometriosis, the sensitivity and specificity of the test were 75 and 100%, respectively. In the glandular and stromal epithelium of both the ectopic and eutopic endometrium, aromatase expression increased with the higher extent of endometriosis.
Asunto(s)
Aromatasa/biosíntesis , Endometriosis/enzimología , Endometrio/enzimología , Quistes Ováricos/enzimología , Ovario/enzimología , Adulto , Femenino , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
Expression of the desC gene coding for acyl-lipid delta(9) desaturase of thermophilic cyanobacterium Synechocystis sp. PCC6803 was studied in Escherichia coli cells. In a hybrid gene constructed (desC-licBM3), a sequence of the native acyl-lipid delta(9) desaturase was fused in frame with the reporter gene coding for thermostable lichenase. Lichenase contained in the hybrid protein simplified selection and analysis of the expression of membrane desaturase in the heterologous host. Comparisons of the expression for the native and hybrid genes in bacterial cells showed that lichenase remained active and thermostable in the hybrid protein, while desaturase retains the capability of introducing a double bound in the corresponding position of fatty acids.
Asunto(s)
Proteínas Bacterianas/biosíntesis , Cianobacterias/enzimología , Escherichia coli/metabolismo , Ácido Graso Desaturasas/biosíntesis , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Bacterianas/genética , Clonación Molecular , Escherichia coli/genética , Ácido Graso Desaturasas/genética , Genes Reporteros , Glicósido Hidrolasas/genética , Proteínas Recombinantes de Fusión/genética , Estearoil-CoA DesaturasaRESUMEN
Cerebral dysfunction due to epilepsy is not currently well-understood and needs to be further investigated. We have observed patients with static encephalopathy (cerebral palsy) of nearly equal severity with epileptic encephalopathy and symptomatic epilepsy and have had carried out comparative analysis of prognosis among these groups. The work is based on the results of investigation of 121 patients admitted to the Center of child neurology and neurorehabilitation during the period 2000-2005. 69 patients with epileptic encephalopathies were included into the study groups according to following criteria: I group -- cases with early starting seizures (before 1 year of life) and II group -- starting seizures after 1 year of life. The control group involved 52 patients with associated cerebral palsy of different severity and symptomatic epilepsy. The study and control groups were compared prognostically. According to our data, prognosis and outcome of epilepsy was closely associated with the time of onset of epilepsy syndromes: early started (within the first year) epileptic encephalopathies display the highest correlation with poor prognosis; the risk of development of epileptic encephalopathies is the highest in patient with cerebral palsy and early starting of seizures.
Asunto(s)
Parálisis Cerebral/complicaciones , Parálisis Cerebral/fisiopatología , Epilepsia/complicaciones , Epilepsia/fisiopatología , Espasmos Infantiles/complicaciones , Espasmos Infantiles/fisiopatología , Encéfalo/fisiopatología , Preescolar , Epilepsia/diagnóstico , Femenino , Humanos , Lactante , Masculino , Pronóstico , Índice de Severidad de la Enfermedad , Espasmos Infantiles/diagnósticoRESUMEN
Comparative studies on spontaneous and induced by two agents (mytomycin C and Nickel chloride) chromosome instability have been conducted in cultured lymphocytes derived from patients with hypertrophic and dilated forms of cardiomyopathy (HCMP and DCMP) and their relatives compiling a high-risk group to develop mentioned pathologies. In patients with HCMP and DCMP, as well as in their relatives higher levels of spontaneous chromosome instability were found in comparison with the control group (comprising healthy individuals without cardiomyopathic anamnesis). Almost all the affected patients and their relatives revealed tendency to increased aneuploidy and significant elevation of polyploidy when compared with control values. It was demonstrated that nickel chloride-induced chromosome disorders registered more frequently in lymphocytes of the patients and their relatives than in cells of control subjects, but mytomycin C did not have such an affect. We assume to explain the similarity of studied parameters in patients with cardiomyopathy and their relatives as a consequence of identical rearrangements in genome functioning. The revealed analogy should be interpreted as a pre-illness condition for the individuals included in the risk-group.
Asunto(s)
Cardiomiopatías , Linfocitos/metabolismo , Mutación Puntual/genética , Aneuploidia , Cardiomiopatías/sangre , Cardiomiopatías/epidemiología , Cardiomiopatías/genética , Aberraciones Cromosómicas , Humanos , Linaje , PoliploidíaRESUMEN
This study was carried out for improvement of extracorporeal detoxication results. Distribution of middle-mass molecules (MM) in various media and vascular beds in patients with acute general peritonitis (AGP) and correlation between central hemodynamics (CH) and level of MM-intoxication were studied. Results of treatment were analyzed in 72 patients with AGP. Ultraviolet irradiation of autoblood (UVIA) had negative influence on circulation in patients with AGP in terminal stage who had more severe primary disorders of CH. Therefore, UVIA without hemosorption (HS) in these patients is potentially dangerous because of undesirable hemodynamic effects due to increase of MM-concentration in blood plasma. HS was performed 1.5-2 hours after UVIA and resulted in decrease of MM-concentration in caval system blood by 28.1% with subsequent slow increase, MM-level restored 24 hours after HS. If HS and UVIA were carried out simultaneously, MM-concentration in caval system blood decreased by 13.9% only, an in 3 of 7 cases MM-concentration didn't change. Combination of UVIA and HS with 1.5-2 h interval is most effective.
Asunto(s)
Albúminas/uso terapéutico , Peritonitis/complicaciones , Peritonitis/terapia , Sustitutos del Plasma/uso terapéutico , Desintoxicación por Sorción/métodos , Toxemia/complicaciones , Toxemia/terapia , Terapia Ultravioleta/métodos , Enfermedad Aguda , Sangre/efectos de la radiación , Dextranos/uso terapéutico , Endotoxinas , Hemodinámica , Humanos , Peritonitis/tratamiento farmacológico , Factores de TiempoAsunto(s)
Albendazol/síntesis química , Albendazol/uso terapéutico , Antihelmínticos/síntesis química , Antihelmínticos/uso terapéutico , Albendazol/efectos adversos , Albendazol/farmacología , Animales , Antihelmínticos/efectos adversos , Antihelmínticos/farmacología , Ensayos Clínicos como Asunto , HumanosRESUMEN
OBJECTIVE: To study the effect of oral magnesium supplementation on blood pressure, platelet aggregation and platelet calcium handling in deoxycorticosterone acetate (DOCA)-induced hypertension in rats. DESIGN AND METHODS: Rats were divided into four groups of 20 each. Drug treatments were given for a 6-week period. Control rats were vehicle treated. In the second group, DOCA, 15 mg/kg, was injected subcutaneously twice weekly with 1% NaCl used instead of drinking water. The third group was given magnesium oxide (MgO), 1 g/kg daily, orally by gavage. The fourth group was given MgO along with DOCA and 1% NaCl. Blood pressure and heart rate were measured weekly. Platelet aggregation, intracellular calcium, calcium uptake and calcium efflux studies were performed at the end of sixth week. Serum magnesium concentration, plasma levels of reactive nitrogen intermediates (RNI) and citrulline were also measured RESULTS: There was a significant rise in blood pressure in the DOCA-treated rats. Magnesium prevented the gradual rise in blood pressure when given along with DOCA, but had no effect in normotensive rats. Heart rate did not show any significant change. Platelet aggregation was significantly reduced in all the treatment groups compared to the control group. DOCA treatment produced a significant increase in the intracellular calcium concentration as well as the calcium uptake compared to the control group. Magnesium supplementation inhibited the increased intracellular calcium concentration and calcium uptake in DOCA-treated rats. RNI and citrulline levels were elevated in all the treatment groups. Serum magnesium levels were significantly higher in the magnesium-treated and DOCA plus magnesium-treated rats. CONCLUSIONS: Magnesium supplementation prevents blood pressure elevation in DOCA hypertensive rats. These effects are associated with inhibition of platelet calcium uptake and decreased intracellular free calcium concentration.