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Cytotoxic effects of some animal and vegetable extracts and some chemicals on liver and colon carcinoma and myosarcoma.

OBJECTIVE: To study, the cytotoxic effects of some biological and chemical agents on G1, S, G2, M and G0 phases of liver and colon carcinomas and myosarcoma cells obtained with chemical carcinogens dimethylbenzanthracene (DMBA) and cadmium chloride. METHODS: Eight rabbit livers, colon carcinoma and myosarcoma cell lines were obtained by injection of DMBA in the Biology Laboratory, of the University of Dumlupinar, Kutahya, Turkey between January 2001 and June 2003. All lines were grown at 37 degrees celsius and 5% carbon dioxide in sterile RPMI-1640 medium with 10% fetal bovine serum after addition of glutamate, penicillin (50 units/ml) and streptomycin (50 ug/ml) (complete medium). Cells were grown on standard tissue culture plastic flasks to 80% confluence and passed by trypsinization. RESULTS: Tortoise (Testudo graeca) shell, sponge (Geodia cydonium), medusa (Aurelia aurita), meat flies (Calliphora erythrocephala) larva, frog (Rana ridibunda) larva and juniper (Juniperus communis) berry extracts killed a large amount of the liver and colon carcinomas and the myosarcoma cells in G2, M and G0 phases (p<0.01). The mistletoe (Viscum album) extract had more effect in only the G0 phase (p<0.05). Genistein, genistin, glycitein, glycitin, daitzein and daitzin have significantly decreased in the cancer cells tests, particularly, genistein and daitzein caused the apoptotic effect in G2, M and G0 phases (p<0.01). Cesium chloride, a mixture of cesium chloride with magnesium chloride had the most effect on tumor cells (p<0.01). AzhexSi, Azhex-AzhepSi, Et-Azhex-AzhepSi, AzhepSi, Hexamine and DL 54 have been inhibited in various levels of the cancer cells (p<0.05, p<0.01). CONCLUSION: This data suggest that some biological extracts and chemicals tested may be useful chemotherapeutic agents to inhibit the growth of cancer cells. This study sheds some light for new anti cancerogenic experiments preventing various cancers on humans.

Animals↗

Magnesium in perinatal care and infant health.

Magnesium, the second most abundant intracellular cation, is essential for life. The consequences of deficiency are severest in the smallest and youngest members of each species and may include sudden unexpected death. Magnesium deficiency, usually diagnosed by hypomagnesemia, may be congenital, as in premature infants, infants of magnesium-deficient mothers and infants with intrauterine growth retardation. It may be acquired or caused by low magnesium intake, the use of magnesium-wasting drugs, illness provoking gastrointestinal or renal losses of the mineral, or high metabolic demands imposed by catch-up growth or postsurgical healing. Finally, the deficiency may be conditioned, caused by excessive dietary calcium, phosphorus or protein in relation to dietary magnesium, especially during a period of rapid growth or tissue repair. Magnesium therapy is safe when a low dosage is given with monitoring of plasma or serum magnesium levels, with occasional checking of calcium and potassium levels. A parenteral dose of 0.1 ml/kg/day of 50% magnesium sulfate USP (approx. 0.2 mmol/kg/day or 0.4 mEq/kg/day) may be given for 5 dose days. An oral dose of 1.0 ml of 10% magnesium chloride solution providing 0.5 mmol/kg/day magnesium or 1.0 ml/kg/day of 10% magnesium chloride USP (0.5 mmol/kg/day) or magnesium magonate (Magonate) 1.0 ml/kg/day (0.45 mmol/kg/day) may be given for extended periods; higher doses may be required for malabsorption syndromes. Hypermagnesemia, which usually results from magnesium overdosage or inadequate renal function, is a potential threat to neonates born to magnesium-treated eclamptic mothers. Most show marked improvement after 36 h of conservative management that includes calcium salts and intravenous infusions of glucose and saline, but obtunded neonates may require dialysis.

Humans↗

[Study of the mitochondrial Ca2+-transport system on lipid bilayer membranes (LBM)].

Electrical properties of BLM formed from lipid components of rat liver mitochondria were studied. The lipids were obtained after preliminary 40 second incubation of mitochondria in the medium containing succinic acid. BLM electroconductivity in the medium with calcium chloride (8--20 mM) is 10--100 times higher than the initial electroconductivity in tris-HC1 at pH 7.5, and in the presence of potassium chloride and magnesium chloride it differes little from the initial value. The transmembrane potential difference per 10-fold concentration gradient of Ca2+, Mg2+, and K+ is approximately 27 mV, approximately 15 mV and approximately 22 mV correspondingly. By means of biionic potential method the following selectivety line for cations is formed: Ca2+ greater than Sr2 greater than or equal to Mg2+ greater than K+. La3+ ions inhibit the transport of Ca2+ through the BLM studied.

Animals↗

The effect of diet, intraruminal pH and osmolarity on sodium, chloride and magnesium absorption from the temporarily isolated and washed reticulo-rumen of sheep.

Six mature sheep fitted with rumen fistulae underwent four consecutive feeding periods, of 15 weeks each, i.e. (1) hay only; (2) 36% hay, 64% concentrate; (3) 10% hay, 90% concentrate; and (4) hay only again. The net absorption of sodium, chloride and magnesium from the washed rumen filled with artificial rumen fluids was tested during each feeding period. The artificial rumen fluids varied either in osmolarity (315 and 422 mosmol l-1) or in pH (6.78 and 4.79). Further, the surface area of rumen papillae was determined. The feeding of increasing proportions of concentrate resulted in an increase of the surface area of rumen papillae and in an elevated net absorption of sodium, chloride and magnesium. Hypertonicity (422 mosmol l-1) of the artificial rumen fluid caused net influx of water into the rumen but did not influence net absorption of the electrolytes irrespective of the feeding regimen. When the pH was lowered this led to a decrease in net absorption of sodium, chloride and magnesium and in transmural potential difference. The extent of the pH-induced decrease in net ion transport and potential difference was less in sheep receiving high-concentrate diets. When only hay was fed after the period of feeding 90% concentrate diets the surface area of the papillae, the absorptive capacity of the rumen epithelium and the resistance against low pH returned to control levels. The findings show a reversible adaptive response of rumen epithelial functions to different diets.

Adaptation, Physiological↗

Salivary calcium, magnesium, phosphate, chloride, sodium and potassium in pregnancy and labour.

Pregnancy and labour produce significant changes in salivary calcium, magnesium, phosphate and chloride when pregnant patients in labour are compared with non-pregnant patients. There is a decrease in concentration of these constituents in the 3rd trimester of pregnancy followed by a marked increase when labour occurs. Magnesium and chloride are the constituents most significantly affected and show the largest increase during labour. Changes in saliva flow rate were accounted for and are not responsible for these changes noted. Sodium and potassium follow a similar pattern. When their levels are corrected for saliva flow rate changes, both show a significant increase with the onset of labour.

Adult↗

Modulation of the discriminative stimulus and rate-altering effects of cocaine by competitive and noncompetitive N-methyl-D-aspartate antagonists.

The purpose of this study was to determine the extent to which N-methyl-D-aspartic acid (NMDA) antagonists modified the discriminative stimulus effects of cocaine in rats trained to discriminate 5 mg/kg cocaine from vehicle on a fixed-ratio schedule of food presentation as well as the rate-altering effects of cocaine in rats maintained on a fixed-interval schedule of food presentation. NMDA-associated ion channel blockers (dizocilpine, phencyclidine, and magnesium chloride) and competitive NMDA antagonists (NPC 17742 and CGP 37849) displayed similar behavioral effects when administered alone: each drug engendered intermediate levels of cocaine-appropriate responses and rate-dependent effects on food-reinforced operant responding. Selected doses of dizocilpine, magnesium chloride, and phencyclidine given in combination with 1 mg/kg cocaine produced more cocaine-appropriate responses than this dose of cocaine alone. In addition, dizocilpine and magnesium chloride each attenuated the discriminative stimulus effects of higher doses of cocaine. The competitive NMDA antagonists did not appreciably modify the discriminative stimulus effects of any dose of cocaine. Under the fixed-interval schedule, each NMDA antagonist attenuated the effects of 3 mg/kg cocaine, which normally produced maximal increases in response rate. Attenuation of the rate-decreasing effects of the highest dose of cocaine (30 mg/kg) also were observed after pretreatment with dizocilpine and magnesium chloride. These findings demonstrated differences in the way that NMDA-associated ion channel blockers and competitive NMDA antagonists interact with cocaine, and suggest that some NMDA-associated ion channel blockers may either enhance or antagonize the effects of cocaine, depending on the dose and type of behavioral procedure.

2-Amino-5-phosphonovalerate↗

Nickel chloride/chlorides of divalent metal interactions in nickel-sensitive subjects.

To verify if the counter-ion Cl- permits the same interactions between nickel and divalent metals with physicochemical similarities as the counter-ion SO4- does, 50 sensitive subjects to nickel sulfate 5% pet. who previously gave positive patch test reactions either to 8 mu 1 of aq. nickel sulfate 0.1 M or to 8 mu 1 of aq. nickel chloride 0.1 M, or to both, were patch retested simultaneously to 8 mu 1 of, respectively, aq. nickel sulfate 0.1 M and aq. nickel chloride 0.1 M, and to 8 mu 1 of aq. mixed solutions containing, respectively, nickel chloride 0.1 M+magnesium chloride 0.3 M, nickel chloride 0.1 M+zinc chloride 0.3 M, nickel chloride 0.1 M+zinc chloride 0.5 M, nickel chloride 0.1 M+manganese chloride 0.3 M, and nickel chloride 0.1 M+manganese chloride O.5 M. Whilst 4 subjects gave a positive patch test response to only nickel sulphate, 8 gave a positive response to nickel chloride alone and the remaining 38 gave a concomitant positive response to both. In all subjects who gave positive responses to nickel chloride, the chlorides of divalent metals were not able to inhibit or reduce the positive reaction. 25 healthy subjects patch tested to both single salts and mixed solutions, and all gave negative responses. 9 of the 50 subjects, 4 who previously gave positive reactions to only nickel chloride 0.1 M, and 5 with concomitant reactions of equal intensity to both nickel chloride and nickel sulfate 0.1 M, were patch retested simultaneously to 8 mu 1 of, respectively, aq. nickel sulfate 0.1 M, aq. nickel chloride 0.1 M and aq. mixed solutions containing nickel sulfate (0.1 M) mixed with sulfates (0.3 M) and nickel chloride (0.1 M) mixed with chlorides of Mg, Zn, Mn (0.3 M). Whilst the mixed sulfate solutions were able to reduce nickel sulfate, 0.1 M patch test positive reactions, those containing chlorides, at all concentrations tested, did not inhibit the nickel chloride reactions in any of the subjects. The results of the tests to chlorides, compared to those reached on testing to sulfates of the same metals, lead us to hypothesize that the anion probably affects the uptake and local tissue distribution of the metal, modulating in this way, together with the individual cutaneous ligands, its effects.

Adult↗

Cardiovascular consequences of magnesium deficiency and loss: pathogenesis, prevalence and manifestations--magnesium and chloride loss in refractory potassium repletion.

Dietary magnesium (Mg) deficiency is more prevalent than generally suspected and can cause cardiovascular lesions leading to disease at all stages of life. The average American diet is deficient in Mg, especially in the young, in alcoholic persons, and in those under stress or with diseases or receiving certain drug therapies, who have increased Mg needs. Otherwise normal, Mg-deficient diets cause arterial and myocardial lesions in all animals studied, and diets that are atherogenic, thrombogenic and cardiovasopathic, as well as Mg-deficient, intensify the cardiovascular lesions, whereas Mg supplementation prevents them. Diuretics and digitalis can intensify an underlying Mg deficiency, leading to cardiac arrhythmias that are refractory unless Mg is added to the regimen. Potassium (K) depletion in diuretic-treated hypertensive patients has been linked to an increased incidence of ventricular ectopy and sudden death. K supplementation alone is not the answer. Mg has been found to be necessary to intracellular K repletion in these patients. Because patients with congestive heart failure and others receiving diuretic therapy are also prone to chloride loss leading to metabolic alkalosis that also interferes with K repletion, the addition of Mg and chloride supplements in addition to the K seems prudent.

Cardiovascular Agents↗

Effects of magnesium and chloride ions on light-induced electron transport in membrane fragments from a blue-green alga.

The effects of magnesium and chloride ions on photosynthetic electron transport were investigated in membrane fragments of a blue-green alga, Nostoc muscorum (Strain 7119), noted for their stability and high rates of electron transport from water or reduced dichlorophenolindophenol to NADP+. Magnesium ions were required not only for light-induced electron transport from water to NADP+ but also for protection in the dark of the integrity of the water-photooxidizing system (Photosystem II). Membrane fragments suspended in the dark in a medium lacking Mg2+ lost the capacity to photoreduce NADP+ with water on subsequent illumination. Chloride ions could substitute, but less effectively, for each of these two effects of Chloride ions could substitute, but less effectively, for each of these two effects of magnesium ions. By contrast, the photoreduction of NADP+ by DCIPH2 was independent of Mg2+ (or Cl-) for the protection of the electron transport system in the dark or during the light reaction proper. Furthermore, high concentration of MgGl2 produced a strong inhibition of NADP+ photoreduction with DCIPH2 without significantly affecting the rate of NADP+ photoreduction with water. The implications of these findings for the differential involvement of Photosystem I and Photosystem II in the photoreduction of NADP+ with different electron donors are discussed.

Cell Membrane↗

Cytotoxicity and mutagenicity of dimethylnitrosamine in mammalian cells (CHO/HGPRT system); enhancement by calcium phosphate.

The cytotoxicity and mutagenicity of dimethylnitrosamine (DMN) was determined in the CHO/HGPRT system. Metabolic activation of the promutagen was achieved by use of liver homogenate supernatant (S9) prepared from Aroclor 1254-induced Sprague-Dawley rats. The cytotoxic and mutagenic effects of DMN were enhanced by the inclusion of calcium chloride in the incubation mix, and this enhancement was dependent on the presence of sodium phosphate. Under conditions that yielded maximal activity (10 mM calcium chloride, 10 mM magnesium chloride, 50 mM sodium phosphate), an apparent calcium phosphate precipitate was observed. DMN activity increased with increasing amounts of S9 protein over the range of 0.3-3.0 mg/ml in the S9 mix and appeared to plateau at higher concentrations. The mutagenicity of DMN can be described as 110 mutants/10(6) cells per mM DMN per mg/ml S9 protein per hour.

Animals↗

Cerebral palsy and experimental hypoxia-induced perinatal brain injury: is magnesium protective?

Recent retrospective, observational studies describe an association between maternal administration of magnesium and a reduction in cerebral palsy in low birthweight infants. Cerebral palsy is thought to result mainly from hypoxia-induced brain injury, and its incidence is increasing due to recent advances in obstetric and newborn intensive care. The findings of the observational studies raise the promising possibility that magnesium treatment may protect the immature brain from hypoxia-induced injury and thus decrease the incidence of cerebral palsy. Despite this promise, a critique of clinical studies indicates that a definitive answer is dependent on the outcome of prospective clinical trials. A critique of experimental animal studies indicates that a neuroprotective role for magnesium prior to, or after, immature hypoxic-ischemic brain injury is currently not supported by the available evidence. Most clinical and animal studies in this field have used magnesium sulphate as a possible therapeutic agent. Based on evidence that magnesium chloride is a preferable salt to use, the inclusion of magnesium chloride in future clinical and experimental studies is worthy of consideration.

Animals↗

Fe(II) speciation and its uptake by free and immobilized cells of Pseudomonas fluorescens from industrial waste water.

Studies are carried out to remove Fe(II) from wastewater using free and immobilized cells of Pseudomonas fluorescens. Experiments are carried out with free cells between 6 and 8 pH and the uptake of Fe(II) is observed to be maximum at pH 7. Further experiments are done at pH 7. Studies with free and immobilized cells revealed that immobilized cells are more efficient for the removal of Fe(II) than free cells. Fe(II) uptake with Pseudomonas fluorescens is also investigated after the addition of NaCl and MgCl2 to the cells. It is found that the uptake has increased when Sodium chloride (NaCl) and Magnesium Chloride (MgCl2) mixed cells are used. Effect of deficiency of nutrients is also studied. It is found that glucose deficient conditions inhibit Fe(II) uptake more than yeast extract deficient ones. pH also plays an important role in the transport of Fe(II) across the membrane of the cells.

Biodegradation, Environmental↗

Increased buffer pH enhances sensitivity and specificity of human papillomavirus detection using consensus primer based PCR.

Polymerase chain reaction (PCR) buffers were optimized for the specific detection of human papillomavirus (HPV) sequences. The effect of pH, potassium chloride concentration and magnesium chloride concentration of three different consensus primers were examined. Several phylogenetically distinct HPVs (HPV1, HPV2, HPV6, HPV8, HPV16, HPV18, and HPV20) were used to determine the optimal buffer components. Genital types were less sensitive to changes in pH than cutaneous types. Higher buffer pH, with a few exceptions, led to increased sensitivity and specificity of HPV detection.

Base Sequence↗

Calcium participation in thyroid function in fowl (Gallus domesticus).

The effects of the calcium antagonists ethyleneglycol-bis-(beta-aminoethylether)-N,N,N',N'-tetraace tic acid (EGTA), cobalt chloride (CoCl2), and magnesium chloride (MgCl2) on the concentrations of plasma thyroxine (T4) and triiodothyronine (T3) and on the basal and stimulated release of T4 from incubated thyroid glands have been determined in the domestic fowl. Plasma T4 levels were consistently reduced 2 hr after the administration of each calcium antagonist, although only EGTA and CoCl2 lowered the concentration of plasma total calcium. Concentrations of plasma T3 were increased following MgCl2 treatment but reduced after CoCl2 administration. The basal release of T4 by incubated thyroid glands was reduced following in vivo EGTA and CoCl2 treatment, but increased after MgCl2 injection. The addition of bovine thyroid stimulating hormone (TSH, 200 mU) to the incubation consistently stimulated in vitro T4 release, although the magnitude of the stimulation was increased following in vivo EGTA or CoCl2 treatment and reduced after MgCl2 administration. These results demonstrate the involvement of calcium dependent mechanisms in the control of T4 release in fowl.

Animals↗

Protection of Measles Virus by Sulfate Ions Against Thermal Inactivation.

Rapp, Fred (Baylor University College of Medicine, Houston, Tex.), Janet S. Butel, and Craig Wallis. Protection of measles virus by sulfate ions against thermal inactivation. J. Bacteriol. 90:132-135. 1965.-The infectivity of measles virus in water is rapidly destroyed at temperatures of 37 C and above. More than 50% of the infectivity is lost after 1 hr at 25 C, and almost 90% loss of infectivity occurs within 24 hr at 4 C. Magnesium chloride enhances the inactivation of the virus at all temperatures tested. Addition of either magnesium or sodium sulfate protects the virus against thermal inactivation. The stabilizing effect is demonstrable at temperatures ranging from 4 to 56 C, but is especially pronounced through 45 C. Prolonged storage (up to 6 weeks) of the virulent virus at 4 C in 1 m magnesium sulfate permits retention of substantial infectivity, whereas storage at 4 C in either water or 1 m magnesium chloride results in a loss of infectivity approximating 99% after 2 weeks. Magnesium chloride also enhances inactivation of the attenuated vaccine strain of measles virus. The attenuated virus, however, is strongly protected by magnesium sulfate against thermal inactivation, and retention of infectivity for long periods of time at 4 C seems feasible when the virus is kept in 1 m magnesium sulfate.

Journal Article↗

Fetal exposure to magnesium chloride-adenosine triphosphate (MgCl2-ATP) results in alterations in cerebral blood flow and a metabolic acidosis.

OBJECTIVE: Magnesium chloride-adenosine triphosphate (MgCl(2)-ATP), advocated as an adjunct treatment in shock resuscitation, might be useful for pregnant women who develop hypovolemia secondary to conditions such as placental abruption. The effects of this treatment on the fetus, however, have never been investigated. This study determined the direct, acute effects of MgCl(2)-ATP on fetal organ blood flow, hemodynamic measurements, and metabolic parameters before and after maternal hemorrhage. DESIGN: Experimental, randomized, nonblinded, control study. SETTING: Animal laboratory at a university research facility. SUBJECTS: This study was performed on 11 chronically instrumented, 123-day gestational age, pregnant ewes (term = 147 days) and their fetuses. INTERVENTIONS: Ewes were randomly allocated to either experimental (Expt, n = 5) or control (Cntl, n = 6) groups. After a 60-min baseline period, Expt fetuses received a 60-min iv infusion of MgCl(2)-ATP (150 &mgr;mole/hr each of MgCl(2) and ATP; at 3 mL/hr), and Cntl fetuses received an equivalent volume of 0.9% NaCl. After this infusion-only period, the infusion was continued, and ewes were intermittently bled over 1 hr for a total blood loss of 20 mL/kg (hemorrhage-plus-infusion period). After this, the infusions were continued, and ewes and fetuses were monitored for 1 additional hr (posthemorrhage period). Measurements: At the end of all periods, fetal and maternal blood pressures, blood gases, oxygen saturation, hemoglobin, serum electrolytes, and serum glucose concentrations were measured. At the end of the baseline, infusion-only, and hemorrhage-plus-infusion periods, fetal organ blood flows were determined using a fluorescent microsphere technique. Nonparametric statistics were used for comparisons (2-tailed, p </=.05). MAIN RESULTS: Maternal hemorrhage caused maternal hypotension, resulting in a decrease in fetal oxygen content and an increase in fetal hemoglobin and glucose concentrations. The changes were similar in both groups. In both groups, a progressive fetal metabolic acidosis developed during the hemorrhage period and it continued through the posthemorrhage period. This metabolic acidosis was more severe in the Expt fetuses and appeared to have started during the infusion-only period. There were no fetal deaths in either group. In the Cntl fetuses, there were increases from baseline after the hemorrhage-plus-infusion period in fetal adrenal (71%), brain (89%), and thymus (18%) blood flow and a decrease in muscle (-28%) blood flow. In the Expt fetuses, there were increases during the infusion-only period in adrenal (332%), myocardial (142%), and pancreatic (219%) blood flow and decreases in kidney (-25%) and skin (-75%) blood flow. These changes persisted during the hemorrhage-plus-infusion period. Most strikingly, regional cerebral blood flow in the Expt fetuses did not increase from baseline in any of the 10 brain areas sampled during the infusion-only period or following maternal hemorrhage. In Cntl fetuses, however, there was increase in blood flow in all 10 brain areas sampled following maternal hemorrhage. CONCLUSIONS: In healthy fetuses, direct MgCl(2)-ATP exposure caused metabolic acidosis and a redistribution of cardiac output to different organs. When the MgCl(2)-ATP fetuses were then subject to the effects of maternal hemorrhage, the expected increase in cerebral blood flow was not observed. Although an earlier study suggests that ATP may be beneficial to stressed fetuses when administered to mothers in labor, the direct effect of MgCl(2)-ATP appears to be potentially harmful by producing an acidosis and altering the normal fetal cerebral blood flow response to maternal hemorrhage.

Journal Article↗