Journal - Association of Official Analytical Chemists
A simple and rapid liquid chromatographic method is described for the qualitative and quantitativ... more A simple and rapid liquid chromatographic method is described for the qualitative and quantitative determination of 5 coumarin anticoagulants in tablet composites and individual tablets. Analyses are carried out on a C18 reverse phase column using tetrahydrofuran-methanol-water-acetic acid (35 + 10 + 65 + 0.1) as mobile phase and photometric detection at 311 nm. The coefficients of variation for 10 consecutive injections of a mixed standards solution ranged from 0.28% for ethyl biscoumacetate to 0.78% for acenocoumarol. Standard recoveries were as follows: acenocoumarol, 99.3%; dicumarol, 99.6%; phenprocoumon, 101.6%; and warfarin sodium, 99.0%. The method was linear between 2 and 8 micrograms of drug injected. Assay results agreed favorably with those of the USP XX methods for dicumarol, phenprocoumon, and warfarin, and the NF XIV method for acenocoumarol. In addition, close correspondence was found with the results previously reported for the same drugs by a semiautomated spectrop...
A simple PMR spectroscopic method was developed for the quantitative determination of mechloretha... more A simple PMR spectroscopic method was developed for the quantitative determination of mechlorethamine hydrochloride for injection in commercial unit doses. Deuterium oxide was used as the PMR solvent and tert-butyl alcohol served as the internal standard. The mean +/- SD% recovery value of mechlorethamine hydrochloride from synthetic formulations was 99.5 +/- 0.83, with a coefficient of variation of 0.83%. The mean content of mechlorethamine hydrochloride in a group of ten commercial unit doses was 99.3% by the PMR method and 99.4% by the titrimetric method of U. S. P. XX.
Journal - Association of Official Analytical Chemists
A liquid chromatographic method for the determination of coumarin anticoagulants in tablets was c... more A liquid chromatographic method for the determination of coumarin anticoagulants in tablets was collaboratively studied by 7 laboratories. The method uses an octadecylsilane-bonded microparticulate column, tetrahydrofuran-methanol-water-acetic acid mobile phase, and photometric detection at 311 nm. Each collaborator received samples of warfarin sodium, phenprocoumon, and dicumarol as a synthetic composite and as commercial individual and composited tablets. Pooled average assay values for synthetic and commercial tablet samples of warfarin sodium were 101.6 and 99.5%, respectively, with a combined reproducibility SD of 2.38% (CV = 2.37%) and combined repeatability SD of 1.49% (CV = 1.49%). Pooled average (SD) assay values for dicumarol and phenprocoumon commercial samples were 98.0 (2.27) and 101.3% (4.00), respectively. The content uniformity determinations of 2 mg warfarin sodium and 25 mg dicumarol tablets indicated average tablet contents (range) of 99.5% (91.0-116.0) and 98.0% ...
Abstract A new dihydroindole alkaloid, isodihydroquinamine, has been isolated from the leaves of ... more Abstract A new dihydroindole alkaloid, isodihydroquinamine, has been isolated from the leaves of Isertia hypoleuca Benth. Chemical and spectroscopic data show it to be a stereoisomer of dihydroquinamine, which was previously isolated from the same plant.
... References. ENVIRONMENTAL RESEARCH 19, 112120 (1979) Protective Effects of Zinc Sulfate and L... more ... References. ENVIRONMENTAL RESEARCH 19, 112120 (1979) Protective Effects of Zinc Sulfate and LLysine on Acute Ethanol Toxicity in Mice' IJAZ S. JAMALL,1.3 JOHN E. MIGNANO, VINCENT D. LYNCH, JESSE H. BIDANSET ... 18. Wallace, JE, and Dahl, EV (1966). Amer. ...
Recent studies suggest substantial interactions between opioids and ethanol (EtOH). Both in vivo ... more Recent studies suggest substantial interactions between opioids and ethanol (EtOH). Both in vivo and in vitro experiments indicate that EtOH can regulate opioid systems and that opioids can modify EtOH consumption. In the present studies, we examined if EtOH consumption altered opioid receptors and the potency of opioid analgesics. Mice were given unlimited access to 6-7% EtOH alone for 7 days or were allowed to drink increasing concentrations (3-6%) of EtOH over 13-14 days. Controls had access to water. The EtOH groups drank significantly less volume than controls, although there were no significant differences in body weight or baseline nociception. The analgesic (tail flick) potency of SC morphine was decreased by approximately 1.6-2.0-fold in EtOH-treated mice. A single acute dose of EtOH (1 g/kg) that produced blood alcohol levels in excess of that for 7 day exposure to EtOH, did not change morphine's analgesic ED50, suggesting that chronic exposure to EtOH was necessary for the reduction in potency. The change in morphine potency was not due to pharmacokinetic differences because EtOH consumption did not modify the concentration of morphine in brain and spinal cord. The analgesic potency of a delta-opioid receptor agonist (ICV DSLET) was also decreased by approximately 2-fold. Saturation binding studies indicated no changes in the density or affinity of brain and spinal cord delta-opioid ([3H]DPDPE, [3H]DSLET, [3H]DeltorphinII) and mu-opioid ([3H]DAMGO) receptors. Similarly, there was no significant effect of EtOH on delta-opioid receptor mRNA in either brain or spinal cord preparations. Taken together, these data suggest that EtOH consumption decreases the analgesic potency of opioids in mice through a mechanism that is unrelated to pharmacokinetics or opioid receptor changes in brain and cord.
Journal of biochemical and molecular toxicology, Jan 2, 2017
Ebselen (EB, compound 1) is an investigational organoselenium compound that reduces fungal growth... more Ebselen (EB, compound 1) is an investigational organoselenium compound that reduces fungal growth, in part, through inhibition of the fungal plasma membrane H(+) -ATPase (Pma1p). In the present study, the growth inhibitory activity of EB and of five structural analogs was assessed in a fluconazole (FLU)-resistant strain of Candida albicans (S2). While none of the compounds were more effective than EB at inhibiting fungal growth (IC50 ∼ 18 μM), two compounds, compounds 5 and 6, were similar in potency. Medium acidification assays performed with S2 yeast cells revealed that compounds 4 and 6, but not compounds 2, 3, or 5, exerted an inhibitory activity comparable to EB (IC50 ∼ 14 μM). Using a partially purified Pma1p preparation obtained from S2 yeast cells, EB and all the analogs demonstrated a similar inhibitory activity. Taken together, these results indicate that EB analogs are worth exploring further for use as growth inhibitors of FLU-resistant fungi.
Advances in experimental medicine and biology, 2017
This study has compared the effects of metformin (MET) and taurine (TAU), singly and in combinati... more This study has compared the effects of metformin (MET) and taurine (TAU), singly and in combination, on the oxidative stress caused by diabetes in the rat brain. For this purpose, male Sprague-Dawley rats, 200-225 g in weight, assigned to groups of 6, were intraperitoneally (i.p.) treated with the diabetogen streptozotocin (STZ, 60 mg/kg, in citrate buffer pH 4.5) on day 1 and, after 14 days, orally (p.o.) with either MET, TAU or MET-TAU (each at 2.4 mM/kg, in water). Control rats received only citrate buffer pH 4.5 (2 mL) or only STZ on day 1 by the i.p. route. All the animals were sacrificed by decapitation on day 57 and their brains collected by the freeze clamp technique. Blood samples were placed in heparinized tubes and used for the assay of the plasma glucose (GLC) and blood insulin (INS) levels. Immediately thereafter, the brains were surgically removed and a portion was used to prepare a homogenate in 0.1 M PBS pH 7.4, which was used for the assay of indices of oxidative st...
Advances in experimental medicine and biology, 2017
This study has examined the role of supplementing a treatment of diabetic rats with captopril (CA... more This study has examined the role of supplementing a treatment of diabetic rats with captopril (CAP), metformin (MET) or CAP-MET with the antioxidant amino acid taurine (TAU) on biochemical indices of diabetes-induced metabolic changes, oxidative stress and nephropathy. To this end, groups of 6 male Sprague-Dawley rats (250-375 g) were made diabetic with a single, 60 mg/kg, intraperitoneal dose of streptozotocin (STZ) in 10 mM citrate buffer pH 4.5 and, after 14 days, treated daily for up to 42 days with either a single oral dose of CAP (0.15 mM/kg), MET (2.4 mM/kg) or TAU (2.4 mM/kg), or with a binary or tertiary combination of these agents. Rats receiving only 10 mM citrate buffer pH 4.5 or only STZ served as negative and positive controls, respectively. All rats were sacrificed by decapitation on day 57 and their blood and kidneys collected. In addition, a 24 h urine sample was collected starting on day 56. Compared to normal rats, untreated diabetic ones exhibited frank hyperglyc...
A group of novel N-1-substituted indazole-3-carboxamide derivatives were synthesized and evaluate... more A group of novel N-1-substituted indazole-3-carboxamide derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy was applied to a weakly active unsubstituted 1H-indazole-3-carboxamide 2, by introducing a three carbon linker between 1H-indazole-3-carboxamide and different heterocycles, and led to compounds 4 [1-(3-(piperidine-1-yl)propyl)-1H-indazole-3-carboxamide, IC(50) =36μm] and 5 [1-(3-(2,3-dioxoindolin-1-yl)propyl)-1H-indazole-3-carboxamide, IC(50) = 6.8μm]. Compound 5 was evaluated in rats for its protective action against diabetes induced by a treatment with streptozotocin, a known diabetogenic agent. In addition to preserving the ability of the pancreas to secrete insulin, compound 5 was also able to attenuate the ensuing hyperglycemic response to a significant extent.
A group of novel N-1-substituted indazole-3-carboxamide derivatives were synthesized and evaluate... more A group of novel N-1-substituted indazole-3-carboxamide derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy was applied to a weakly active unsubstituted 1H-indazole-3-carboxamide 2, by introducing a three carbon linker between 1H-indazole-3-carboxamide and different heterocycles, and led to compounds 4 [1-(3-(piperidine-1-yl)propyl)-1H-indazole-3-carboxamide, IC(50) =36μm] and 5 [1-(3-(2,3-dioxoindolin-1-yl)propyl)-1H-indazole-3-carboxamide, IC(50) = 6.8μm]. Compound 5 was evaluated in rats for its protective action against diabetes induced by a treatment with streptozotocin, a known diabetogenic agent. In addition to preserving the ability of the pancreas to secrete insulin, compound 5 was also able to attenuate the ensuing hyperglycemic response to a significant extent.
Protective action of taurine, given as a pretreatment or as a posttreatment, against endotoxin-induced acute lung inflammation in hamsters, 2010
To assess the effect of taurine on lipopolysaccharide (LPS)-induced lung inflammation, oxidative ... more To assess the effect of taurine on lipopolysaccharide (LPS)-induced lung inflammation, oxidative stress and apopto-sis, female Golden Syrian hamsters were intratracheally instilled with bacterial LPS (0.02 mg in phosphate buffered saline (PBS) pH 7.4), before or after a 3-day intraperitoneal treatment with a single dose of taurine (50 mg/kg/day in PBS pH 7.4), and bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected at 24 hr after the last treatment. In comparison to BALF samples from animals receiving only PBS pH 7.4, and serving as controls, those of LPS-stimulated animals exhibited a higher count of both total leukocytes and neutrophils and increased expression of tumor necrosis factor receptor 1. In comparison to lungs from control animals, those from LPS-treated animals showed increased cellular apoptosis, lipid peroxidation, decreased glutathione levels, altered activities of antioxidant enzymes (catalase, glutathione peroxidase, superoxide dismutase) and focal inflammation confined to the parenchyma. A treatment with taurine was found to significantly attenuate all these alterations, with the protection being, in all instances, greater when given before rather than after LPS. The present results suggest that taurine is endowed with antiinflammatory and antioxidant properties that are protective in the lung against the deleterious actions of Gram negative bacterial endotoxin.
Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie, Jan 23, 2015
This study has comparatively evaluated the antiradical and antilipid peroxidizing actions of taur... more This study has comparatively evaluated the antiradical and antilipid peroxidizing actions of taurine (TAU) and its N-pantoyl analog pantoyltaurine (PTAU) in vitro, and has determined the extent to which these findings agree with the in vivo ability of these compounds to prevent changes in plasma glucose and in indices of oxidative stress in the plasma, brain and spinal cord induced by the diabetogen streptozotocin (STZ) in Sprague-Dawley rats. Using free radical-generating and oxidizing systems, PTAU was found more effective than TAU in scavenging DPPH, hydroxyl, peroxyl, and superoxide anion radicals and peroxynitrite, and in preventing lipid peroxidation of a brain homogenate by iron (III)-dopamine and the oxidation of dopamine by iron (III). On the other hand, when administered intraperitoneally (i.p.) at a 1.2mM/kg dose, 75min and 45min before a single i.p., 60mg/kg, dose of (STZ), TAU was about equipotent with PTAU in attenuating STZ-induced increases in glucose, malondialdehyd...
Journal - Association of Official Analytical Chemists
Optimum experimental conditions were developed for determination of the optical purity of samples... more Optimum experimental conditions were developed for determination of the optical purity of samples of tranylcypromine sulfate by proton magnetic resonance spectroscopy after complexation with the chiral lanthanide chelate Eu(hfc)3. At a substrate concentration of 0.25M (0.125M as sulfate) in CDCl3 and an Eu(hfc)3 to substrate molar ratio of 1, the methine proton geminal to the amino group in the cyclopropane ring showed the largest induced shift and largest enantiomeric induced shift difference. From the relative intensities of the resolved (+)-CH-NH2 protons (15.77 ppm) and (-)-CH-NH2 proton (16.04 ppm), the enantiomeric purity and percentage compositions were readily calculated. The mean +/- SD recovery of (+)-tranylcypromine sulfate from synthetic enantiomeric mixtures was 101.02 +/- 2.59 (n = 6).
Research communications in chemical pathology and pharmacology
The administration of a single, 100-300 mg/kg ip, dose of a B6 vitamer to rats resulted in an alm... more The administration of a single, 100-300 mg/kg ip, dose of a B6 vitamer to rats resulted in an almost immediate and gradual mobilization of the liver glycogen and a concomitant elevation of the serum glucose, with the order of potency being pyridoxal greater than pyridoxamine greater than pyridoxine. Since the B6 vitamer also stimulated the secretion of adrenal catecholamines and the accumulation of liver cAMP, and a pretreatment with selected blocking agents conferred significant protection against the glycogen depletion in the order of potency propranolol + phentolamine greater than propranolol greater than verapamil greater than phentolamine, a role for an adrenomedullary catecholamine-stimulated, beta-adrenoceptor-mediated, activation of the glycogen cascade system was suggested. This assumption was confirmed by verifying pyridoxal to possess virtually no effect on the liver glycogen of adrenalectomized rats.
We present a simple, accurate, stability-indicating nuclear magnetic resonance (NMR) method for d... more We present a simple, accurate, stability-indicating nuclear magnetic resonance (NMR) method for determining active (S,S) and inactive (R,S) epimers of S-adenosyl-L-methionine (SAM) in tablets. The SCH3 resonances of SAM epimers were well resolved at 300 MHz. Individual assays of 5 SAM tablets gave SAM values of 101.3 +/- 1.7% of declared amounts. Tablet solutions were assayed at a level of 8.0 mg/mL, but the method was linear for SAM concentrations ranging from 64 to 1 mg/mL (correlation coefficient, 0.9996). Reproducibility was indicated by a relative standard deviation of 0.33% for 6 replicate assays for total SAM at a concentration of 8 mg/mL. In contrast to the propietary liquid chromatographic (LC) method, which requires SAM as an external standard, the NMR method uses sodium trimethylsilylpropionate-d4 (TSP) both as an internal standard and as a chemical shift reference. The method was used to test the stability of SAM analytes under various pH levels and temperatures. We found 8% inactivation of SAM due to epimerization over a 24 h period at room temperature and pH 5. SAM solutions showed no detectable inactivation after 14 days when stored below 0 degrees C.
Research communications in chemical pathology and pharmacology
The daily ip administration of pantethine (500 mg/kg), pantothenic acid (100 mg/kg) or cystamine ... more The daily ip administration of pantethine (500 mg/kg), pantothenic acid (100 mg/kg) or cystamine (50 mg/kg) for 5 days conferred significant protection against the hepatotoxic and peroxidative actions of a 0.5 mL/kg ip dose of CCl4 in rats. All three treatments lessened the increases in serum ALT and liver TBARS values, and the reductions in serum triglyceride levels, and prevented the development of hepatic steatosis caused by the halocarbon. Pantethine was found to offer the greatest protection.
Journal - Association of Official Analytical Chemists
A simple and rapid liquid chromatographic method is described for the qualitative and quantitativ... more A simple and rapid liquid chromatographic method is described for the qualitative and quantitative determination of 5 coumarin anticoagulants in tablet composites and individual tablets. Analyses are carried out on a C18 reverse phase column using tetrahydrofuran-methanol-water-acetic acid (35 + 10 + 65 + 0.1) as mobile phase and photometric detection at 311 nm. The coefficients of variation for 10 consecutive injections of a mixed standards solution ranged from 0.28% for ethyl biscoumacetate to 0.78% for acenocoumarol. Standard recoveries were as follows: acenocoumarol, 99.3%; dicumarol, 99.6%; phenprocoumon, 101.6%; and warfarin sodium, 99.0%. The method was linear between 2 and 8 micrograms of drug injected. Assay results agreed favorably with those of the USP XX methods for dicumarol, phenprocoumon, and warfarin, and the NF XIV method for acenocoumarol. In addition, close correspondence was found with the results previously reported for the same drugs by a semiautomated spectrop...
A simple PMR spectroscopic method was developed for the quantitative determination of mechloretha... more A simple PMR spectroscopic method was developed for the quantitative determination of mechlorethamine hydrochloride for injection in commercial unit doses. Deuterium oxide was used as the PMR solvent and tert-butyl alcohol served as the internal standard. The mean +/- SD% recovery value of mechlorethamine hydrochloride from synthetic formulations was 99.5 +/- 0.83, with a coefficient of variation of 0.83%. The mean content of mechlorethamine hydrochloride in a group of ten commercial unit doses was 99.3% by the PMR method and 99.4% by the titrimetric method of U. S. P. XX.
Journal - Association of Official Analytical Chemists
A liquid chromatographic method for the determination of coumarin anticoagulants in tablets was c... more A liquid chromatographic method for the determination of coumarin anticoagulants in tablets was collaboratively studied by 7 laboratories. The method uses an octadecylsilane-bonded microparticulate column, tetrahydrofuran-methanol-water-acetic acid mobile phase, and photometric detection at 311 nm. Each collaborator received samples of warfarin sodium, phenprocoumon, and dicumarol as a synthetic composite and as commercial individual and composited tablets. Pooled average assay values for synthetic and commercial tablet samples of warfarin sodium were 101.6 and 99.5%, respectively, with a combined reproducibility SD of 2.38% (CV = 2.37%) and combined repeatability SD of 1.49% (CV = 1.49%). Pooled average (SD) assay values for dicumarol and phenprocoumon commercial samples were 98.0 (2.27) and 101.3% (4.00), respectively. The content uniformity determinations of 2 mg warfarin sodium and 25 mg dicumarol tablets indicated average tablet contents (range) of 99.5% (91.0-116.0) and 98.0% ...
Abstract A new dihydroindole alkaloid, isodihydroquinamine, has been isolated from the leaves of ... more Abstract A new dihydroindole alkaloid, isodihydroquinamine, has been isolated from the leaves of Isertia hypoleuca Benth. Chemical and spectroscopic data show it to be a stereoisomer of dihydroquinamine, which was previously isolated from the same plant.
... References. ENVIRONMENTAL RESEARCH 19, 112120 (1979) Protective Effects of Zinc Sulfate and L... more ... References. ENVIRONMENTAL RESEARCH 19, 112120 (1979) Protective Effects of Zinc Sulfate and LLysine on Acute Ethanol Toxicity in Mice' IJAZ S. JAMALL,1.3 JOHN E. MIGNANO, VINCENT D. LYNCH, JESSE H. BIDANSET ... 18. Wallace, JE, and Dahl, EV (1966). Amer. ...
Recent studies suggest substantial interactions between opioids and ethanol (EtOH). Both in vivo ... more Recent studies suggest substantial interactions between opioids and ethanol (EtOH). Both in vivo and in vitro experiments indicate that EtOH can regulate opioid systems and that opioids can modify EtOH consumption. In the present studies, we examined if EtOH consumption altered opioid receptors and the potency of opioid analgesics. Mice were given unlimited access to 6-7% EtOH alone for 7 days or were allowed to drink increasing concentrations (3-6%) of EtOH over 13-14 days. Controls had access to water. The EtOH groups drank significantly less volume than controls, although there were no significant differences in body weight or baseline nociception. The analgesic (tail flick) potency of SC morphine was decreased by approximately 1.6-2.0-fold in EtOH-treated mice. A single acute dose of EtOH (1 g/kg) that produced blood alcohol levels in excess of that for 7 day exposure to EtOH, did not change morphine's analgesic ED50, suggesting that chronic exposure to EtOH was necessary for the reduction in potency. The change in morphine potency was not due to pharmacokinetic differences because EtOH consumption did not modify the concentration of morphine in brain and spinal cord. The analgesic potency of a delta-opioid receptor agonist (ICV DSLET) was also decreased by approximately 2-fold. Saturation binding studies indicated no changes in the density or affinity of brain and spinal cord delta-opioid ([3H]DPDPE, [3H]DSLET, [3H]DeltorphinII) and mu-opioid ([3H]DAMGO) receptors. Similarly, there was no significant effect of EtOH on delta-opioid receptor mRNA in either brain or spinal cord preparations. Taken together, these data suggest that EtOH consumption decreases the analgesic potency of opioids in mice through a mechanism that is unrelated to pharmacokinetics or opioid receptor changes in brain and cord.
Journal of biochemical and molecular toxicology, Jan 2, 2017
Ebselen (EB, compound 1) is an investigational organoselenium compound that reduces fungal growth... more Ebselen (EB, compound 1) is an investigational organoselenium compound that reduces fungal growth, in part, through inhibition of the fungal plasma membrane H(+) -ATPase (Pma1p). In the present study, the growth inhibitory activity of EB and of five structural analogs was assessed in a fluconazole (FLU)-resistant strain of Candida albicans (S2). While none of the compounds were more effective than EB at inhibiting fungal growth (IC50 ∼ 18 μM), two compounds, compounds 5 and 6, were similar in potency. Medium acidification assays performed with S2 yeast cells revealed that compounds 4 and 6, but not compounds 2, 3, or 5, exerted an inhibitory activity comparable to EB (IC50 ∼ 14 μM). Using a partially purified Pma1p preparation obtained from S2 yeast cells, EB and all the analogs demonstrated a similar inhibitory activity. Taken together, these results indicate that EB analogs are worth exploring further for use as growth inhibitors of FLU-resistant fungi.
Advances in experimental medicine and biology, 2017
This study has compared the effects of metformin (MET) and taurine (TAU), singly and in combinati... more This study has compared the effects of metformin (MET) and taurine (TAU), singly and in combination, on the oxidative stress caused by diabetes in the rat brain. For this purpose, male Sprague-Dawley rats, 200-225 g in weight, assigned to groups of 6, were intraperitoneally (i.p.) treated with the diabetogen streptozotocin (STZ, 60 mg/kg, in citrate buffer pH 4.5) on day 1 and, after 14 days, orally (p.o.) with either MET, TAU or MET-TAU (each at 2.4 mM/kg, in water). Control rats received only citrate buffer pH 4.5 (2 mL) or only STZ on day 1 by the i.p. route. All the animals were sacrificed by decapitation on day 57 and their brains collected by the freeze clamp technique. Blood samples were placed in heparinized tubes and used for the assay of the plasma glucose (GLC) and blood insulin (INS) levels. Immediately thereafter, the brains were surgically removed and a portion was used to prepare a homogenate in 0.1 M PBS pH 7.4, which was used for the assay of indices of oxidative st...
Advances in experimental medicine and biology, 2017
This study has examined the role of supplementing a treatment of diabetic rats with captopril (CA... more This study has examined the role of supplementing a treatment of diabetic rats with captopril (CAP), metformin (MET) or CAP-MET with the antioxidant amino acid taurine (TAU) on biochemical indices of diabetes-induced metabolic changes, oxidative stress and nephropathy. To this end, groups of 6 male Sprague-Dawley rats (250-375 g) were made diabetic with a single, 60 mg/kg, intraperitoneal dose of streptozotocin (STZ) in 10 mM citrate buffer pH 4.5 and, after 14 days, treated daily for up to 42 days with either a single oral dose of CAP (0.15 mM/kg), MET (2.4 mM/kg) or TAU (2.4 mM/kg), or with a binary or tertiary combination of these agents. Rats receiving only 10 mM citrate buffer pH 4.5 or only STZ served as negative and positive controls, respectively. All rats were sacrificed by decapitation on day 57 and their blood and kidneys collected. In addition, a 24 h urine sample was collected starting on day 56. Compared to normal rats, untreated diabetic ones exhibited frank hyperglyc...
A group of novel N-1-substituted indazole-3-carboxamide derivatives were synthesized and evaluate... more A group of novel N-1-substituted indazole-3-carboxamide derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy was applied to a weakly active unsubstituted 1H-indazole-3-carboxamide 2, by introducing a three carbon linker between 1H-indazole-3-carboxamide and different heterocycles, and led to compounds 4 [1-(3-(piperidine-1-yl)propyl)-1H-indazole-3-carboxamide, IC(50) =36μm] and 5 [1-(3-(2,3-dioxoindolin-1-yl)propyl)-1H-indazole-3-carboxamide, IC(50) = 6.8μm]. Compound 5 was evaluated in rats for its protective action against diabetes induced by a treatment with streptozotocin, a known diabetogenic agent. In addition to preserving the ability of the pancreas to secrete insulin, compound 5 was also able to attenuate the ensuing hyperglycemic response to a significant extent.
A group of novel N-1-substituted indazole-3-carboxamide derivatives were synthesized and evaluate... more A group of novel N-1-substituted indazole-3-carboxamide derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy was applied to a weakly active unsubstituted 1H-indazole-3-carboxamide 2, by introducing a three carbon linker between 1H-indazole-3-carboxamide and different heterocycles, and led to compounds 4 [1-(3-(piperidine-1-yl)propyl)-1H-indazole-3-carboxamide, IC(50) =36μm] and 5 [1-(3-(2,3-dioxoindolin-1-yl)propyl)-1H-indazole-3-carboxamide, IC(50) = 6.8μm]. Compound 5 was evaluated in rats for its protective action against diabetes induced by a treatment with streptozotocin, a known diabetogenic agent. In addition to preserving the ability of the pancreas to secrete insulin, compound 5 was also able to attenuate the ensuing hyperglycemic response to a significant extent.
Protective action of taurine, given as a pretreatment or as a posttreatment, against endotoxin-induced acute lung inflammation in hamsters, 2010
To assess the effect of taurine on lipopolysaccharide (LPS)-induced lung inflammation, oxidative ... more To assess the effect of taurine on lipopolysaccharide (LPS)-induced lung inflammation, oxidative stress and apopto-sis, female Golden Syrian hamsters were intratracheally instilled with bacterial LPS (0.02 mg in phosphate buffered saline (PBS) pH 7.4), before or after a 3-day intraperitoneal treatment with a single dose of taurine (50 mg/kg/day in PBS pH 7.4), and bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected at 24 hr after the last treatment. In comparison to BALF samples from animals receiving only PBS pH 7.4, and serving as controls, those of LPS-stimulated animals exhibited a higher count of both total leukocytes and neutrophils and increased expression of tumor necrosis factor receptor 1. In comparison to lungs from control animals, those from LPS-treated animals showed increased cellular apoptosis, lipid peroxidation, decreased glutathione levels, altered activities of antioxidant enzymes (catalase, glutathione peroxidase, superoxide dismutase) and focal inflammation confined to the parenchyma. A treatment with taurine was found to significantly attenuate all these alterations, with the protection being, in all instances, greater when given before rather than after LPS. The present results suggest that taurine is endowed with antiinflammatory and antioxidant properties that are protective in the lung against the deleterious actions of Gram negative bacterial endotoxin.
Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie, Jan 23, 2015
This study has comparatively evaluated the antiradical and antilipid peroxidizing actions of taur... more This study has comparatively evaluated the antiradical and antilipid peroxidizing actions of taurine (TAU) and its N-pantoyl analog pantoyltaurine (PTAU) in vitro, and has determined the extent to which these findings agree with the in vivo ability of these compounds to prevent changes in plasma glucose and in indices of oxidative stress in the plasma, brain and spinal cord induced by the diabetogen streptozotocin (STZ) in Sprague-Dawley rats. Using free radical-generating and oxidizing systems, PTAU was found more effective than TAU in scavenging DPPH, hydroxyl, peroxyl, and superoxide anion radicals and peroxynitrite, and in preventing lipid peroxidation of a brain homogenate by iron (III)-dopamine and the oxidation of dopamine by iron (III). On the other hand, when administered intraperitoneally (i.p.) at a 1.2mM/kg dose, 75min and 45min before a single i.p., 60mg/kg, dose of (STZ), TAU was about equipotent with PTAU in attenuating STZ-induced increases in glucose, malondialdehyd...
Journal - Association of Official Analytical Chemists
Optimum experimental conditions were developed for determination of the optical purity of samples... more Optimum experimental conditions were developed for determination of the optical purity of samples of tranylcypromine sulfate by proton magnetic resonance spectroscopy after complexation with the chiral lanthanide chelate Eu(hfc)3. At a substrate concentration of 0.25M (0.125M as sulfate) in CDCl3 and an Eu(hfc)3 to substrate molar ratio of 1, the methine proton geminal to the amino group in the cyclopropane ring showed the largest induced shift and largest enantiomeric induced shift difference. From the relative intensities of the resolved (+)-CH-NH2 protons (15.77 ppm) and (-)-CH-NH2 proton (16.04 ppm), the enantiomeric purity and percentage compositions were readily calculated. The mean +/- SD recovery of (+)-tranylcypromine sulfate from synthetic enantiomeric mixtures was 101.02 +/- 2.59 (n = 6).
Research communications in chemical pathology and pharmacology
The administration of a single, 100-300 mg/kg ip, dose of a B6 vitamer to rats resulted in an alm... more The administration of a single, 100-300 mg/kg ip, dose of a B6 vitamer to rats resulted in an almost immediate and gradual mobilization of the liver glycogen and a concomitant elevation of the serum glucose, with the order of potency being pyridoxal greater than pyridoxamine greater than pyridoxine. Since the B6 vitamer also stimulated the secretion of adrenal catecholamines and the accumulation of liver cAMP, and a pretreatment with selected blocking agents conferred significant protection against the glycogen depletion in the order of potency propranolol + phentolamine greater than propranolol greater than verapamil greater than phentolamine, a role for an adrenomedullary catecholamine-stimulated, beta-adrenoceptor-mediated, activation of the glycogen cascade system was suggested. This assumption was confirmed by verifying pyridoxal to possess virtually no effect on the liver glycogen of adrenalectomized rats.
We present a simple, accurate, stability-indicating nuclear magnetic resonance (NMR) method for d... more We present a simple, accurate, stability-indicating nuclear magnetic resonance (NMR) method for determining active (S,S) and inactive (R,S) epimers of S-adenosyl-L-methionine (SAM) in tablets. The SCH3 resonances of SAM epimers were well resolved at 300 MHz. Individual assays of 5 SAM tablets gave SAM values of 101.3 +/- 1.7% of declared amounts. Tablet solutions were assayed at a level of 8.0 mg/mL, but the method was linear for SAM concentrations ranging from 64 to 1 mg/mL (correlation coefficient, 0.9996). Reproducibility was indicated by a relative standard deviation of 0.33% for 6 replicate assays for total SAM at a concentration of 8 mg/mL. In contrast to the propietary liquid chromatographic (LC) method, which requires SAM as an external standard, the NMR method uses sodium trimethylsilylpropionate-d4 (TSP) both as an internal standard and as a chemical shift reference. The method was used to test the stability of SAM analytes under various pH levels and temperatures. We found 8% inactivation of SAM due to epimerization over a 24 h period at room temperature and pH 5. SAM solutions showed no detectable inactivation after 14 days when stored below 0 degrees C.
Research communications in chemical pathology and pharmacology
The daily ip administration of pantethine (500 mg/kg), pantothenic acid (100 mg/kg) or cystamine ... more The daily ip administration of pantethine (500 mg/kg), pantothenic acid (100 mg/kg) or cystamine (50 mg/kg) for 5 days conferred significant protection against the hepatotoxic and peroxidative actions of a 0.5 mL/kg ip dose of CCl4 in rats. All three treatments lessened the increases in serum ALT and liver TBARS values, and the reductions in serum triglyceride levels, and prevented the development of hepatic steatosis caused by the halocarbon. Pantethine was found to offer the greatest protection.
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Papers by Cesar Lau-cam