cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.6503096.v1
title: Star anise extracts modulation of reproductive parameters, fertility potential and DNA fragmentation induced by growth promoter Equigan in rat testes

description: ABSTRACT Equigan is an anabolic steroid that has been developed for veterinary use and derived from endogenous sex hormone testosterone that plays a key role in the development of male reproductive tissue as well as in puberty and spermatogenesis. The current study is aimed to investigate the possible prophylactic effect of star anise extracts (SAE) on the toxicity of rat testes, sexual hormones alternations, sperm count, sperm abnormalities and testicular DNA damage by Equigan. Forty adult male rats were equally divided into four groups (1st Control group, 2nd SAE group, 3rd Equigan and 4th Equigan+SAE group). Food and fluid intakes, relative body weight, potassium, chloride, phosphorous, non-progressive and immotile sperms were significantly increased in Equigan group as compared to control group. In contrast; relative testes weight, sodium, magnesium, total calcium, testosterone, FSH, LH, PRL, sperm count, progressive motility, and viability showed a significant decrease in Equigan group as compared to control groups. The relative weight of epididymis, seminal vesicles, prostates and serum calcium ions didn’t change significantly in different studied groups. Co-administration of SAE with Equigan improved the sexual toxicity, electrolyte alternations, sperm count, abnormalities and DNA damage induced by Equigan.
DOI: 10.6084/m9.figshare.6504302
title: Development of self-nanoemulsifying tablet (SNET) for bioavailability enhancement of sertraline

description: Abstract The purpose of the study was to combine the advantages of self-nanoemulsifying drug delivery systems and tablets as a conventional dosage form. Self-nanoemulsifying drug delivery system (SNEDDS) was prepared to enhance the solubility and thus oral bioavailability of sertraline. Aqueous titration method was used to prepare the liquid SNEDDS; ternary phase diagrams were constructed and based on smaller droplet size (24.8 nm), minimum viscosity (153.63 cP) and polydispersity index (0.182), higher percentage transmittance (95%) and in vitro drug release (97%), an optimum system was designated. Liquid SNEDDS was transformed into free-flowing powder by solid adsorption technique followed by compression into tablets. In vitro release of sertraline from liquid and solid SNEDDS was found to be highly significant compared to plain sertraline (p&lt;0.01). Pharmacokinetic studies after oral administration of liquid and solid SNEDDS in rats showed about 6-and 5-fold increased absorption of sertraline compared to the aqueous suspension of sertraline. These studies demonstrate that the solid SNEDDS are promising strategies for successful delivery of poorly water-soluble drug like sertraline.
DOI: 10.6084/m9.figshare.6504302.v1
title: Development of self-nanoemulsifying tablet (SNET) for bioavailability enhancement of sertraline

description: Abstract The purpose of the study was to combine the advantages of self-nanoemulsifying drug delivery systems and tablets as a conventional dosage form. Self-nanoemulsifying drug delivery system (SNEDDS) was prepared to enhance the solubility and thus oral bioavailability of sertraline. Aqueous titration method was used to prepare the liquid SNEDDS; ternary phase diagrams were constructed and based on smaller droplet size (24.8 nm), minimum viscosity (153.63 cP) and polydispersity index (0.182), higher percentage transmittance (95%) and in vitro drug release (97%), an optimum system was designated. Liquid SNEDDS was transformed into free-flowing powder by solid adsorption technique followed by compression into tablets. In vitro release of sertraline from liquid and solid SNEDDS was found to be highly significant compared to plain sertraline (p&lt;0.01). Pharmacokinetic studies after oral administration of liquid and solid SNEDDS in rats showed about 6-and 5-fold increased absorption of sertraline compared to the aqueous suspension of sertraline. These studies demonstrate that the solid SNEDDS are promising strategies for successful delivery of poorly water-soluble drug like sertraline.
DOI: 10.6084/m9.figshare.6504038
title: Guideline values and human risk assessment for the presence of anti-inflammatory drugs remaining in drinking water after lab scale treatment

description: Abstract This study aimed to determine whether the anti-inflammatory drugs that are most commonly consumed in Brazil, including diclofenac, ketoprofen, naproxen, indomethacin, ibuprofen and acetaminophen, are present in drinking water and to derive guideline values to characterize the human risk. These pharmaceuticals were quantified in surface waters by LC-MS/MS with solid phase extraction, both before and after conventional treatment on a laboratory scale, using a jar test assay. The methods used to quantify these drugs showed good results: the chromatographic analysis obtained correlation coefficients between 0.9952 and 0.9991, with limits of quantification of 0.5 ng.mL-1 - 50 ng.mL-1 and precision standard deviations (0.08 - 2.08). Only ketoprofen and ibuprofen were not completely removed through the jar test. Environmental samples were collected and handled by the same method; the values for ketoprofen and ibuprofen after treatment were 18.67 - 19.65 ng.L-1 (±17%) and 166.70 - 244.73 ng.L-1 (±14%), respectively. Human risk was assessed by comparing the guideline values for each compound to the concentrations obtained in the environmental samples, considering the toxicological backgrounds, following WHO (2011) method. The results suggest that the concentrations of ketoprofen and ibuprofen found in drinking water do not pose a risk to human health, even with chronic consumption.
DOI: 10.6084/m9.figshare.6504038.v1
title: Guideline values and human risk assessment for the presence of anti-inflammatory drugs remaining in drinking water after lab scale treatment

description: Abstract This study aimed to determine whether the anti-inflammatory drugs that are most commonly consumed in Brazil, including diclofenac, ketoprofen, naproxen, indomethacin, ibuprofen and acetaminophen, are present in drinking water and to derive guideline values to characterize the human risk. These pharmaceuticals were quantified in surface waters by LC-MS/MS with solid phase extraction, both before and after conventional treatment on a laboratory scale, using a jar test assay. The methods used to quantify these drugs showed good results: the chromatographic analysis obtained correlation coefficients between 0.9952 and 0.9991, with limits of quantification of 0.5 ng.mL-1 - 50 ng.mL-1 and precision standard deviations (0.08 - 2.08). Only ketoprofen and ibuprofen were not completely removed through the jar test. Environmental samples were collected and handled by the same method; the values for ketoprofen and ibuprofen after treatment were 18.67 - 19.65 ng.L-1 (±17%) and 166.70 - 244.73 ng.L-1 (±14%), respectively. Human risk was assessed by comparing the guideline values for each compound to the concentrations obtained in the environmental samples, considering the toxicological backgrounds, following WHO (2011) method. The results suggest that the concentrations of ketoprofen and ibuprofen found in drinking water do not pose a risk to human health, even with chronic consumption.
DOI: 10.6084/m9.figshare.20039269
title: Antinociceptive local effect of the combination of dexketoprofen trometamol and chlorhexidine gluconate in a formalin test: an additive effect

description: ABSTRACT A drug delivery system (DDS) with analgesic and antibacterial properties would be desirable for the local control of post-operatory pain and the prevention for surgical site infection (SSI). The objective of the present study was to evaluate the antinociceptive effect of the combination between dexketoprofen trometamol (DXT) and chlorhexidine gluconate (CHX) in the formalin pain model. Different doses of CHX were combined with DXT and were locally administered in rats paw simultaneously with 5% formalin dilution. Flinches were documented and the antinociceptive effect was calculated. The area under the curve of each experimental group were calculated and the % of antinociception were compared. The groups of CHX and DXT showed similar antinociceptive effect. The combination groups (DXT-CHX) showed higher antinociceptive effect that the one obtained with individual molecules. Besides the confirmation of DXT local antinociceptive properties, CHX also showed a positive effect; and an additive effect when combined with DXT.
DOI: 10.6084/m9.figshare.20039269.v1
title: Antinociceptive local effect of the combination of dexketoprofen trometamol and chlorhexidine gluconate in a formalin test: an additive effect

description: ABSTRACT A drug delivery system (DDS) with analgesic and antibacterial properties would be desirable for the local control of post-operatory pain and the prevention for surgical site infection (SSI). The objective of the present study was to evaluate the antinociceptive effect of the combination between dexketoprofen trometamol (DXT) and chlorhexidine gluconate (CHX) in the formalin pain model. Different doses of CHX were combined with DXT and were locally administered in rats paw simultaneously with 5% formalin dilution. Flinches were documented and the antinociceptive effect was calculated. The area under the curve of each experimental group were calculated and the % of antinociception were compared. The groups of CHX and DXT showed similar antinociceptive effect. The combination groups (DXT-CHX) showed higher antinociceptive effect that the one obtained with individual molecules. Besides the confirmation of DXT local antinociceptive properties, CHX also showed a positive effect; and an additive effect when combined with DXT.
DOI: 10.6084/m9.figshare.6504317.v1
title: Simultaneous determination of candesartan and hydrochlorothiazide in human plasma by LC-MS/MS

description: Abstract A simple, sensitive, rapid and highly efficient LC-MS/MS method was developed for the determination of Candesartan and Hydrochlorothiazide simultaneously in human plasma. The method employed Zorbax eclipse C18 (150 X 4.6 mm, 5µ) column using acetate buffer: acetonitrile (25:75%, v/v) as the mobile phase. The mobile phase flow rate is 1 mL/min which was delivered into the mass spectrometer electron spray ionization chamber. The Liquid/liquid extraction procedure was used in the method for the extraction of analytes. The chromatograph was attached to a negative ion mode tandem mass spectrometer and the method was validated for all the parameters as per the guidelines of US-FDA. The ions were detected in multiple reaction monitoring mode and the transitions are m/z 439.00®309.10 and 295.80®268.80 for candesartan and hydrochlorothiazide respectively. Isotopic standards were used as internal standards for effective recovery of the analytes. The drugs were analyzed over a calibration range of 1.027-302.047 ng/mL for candesartan and 1.044-306.945 ng/mL for hydrochlorothiazide respectively with regression coefficient greater than 0.99. The mean extraction recoveries are 96.95±5.61 and 100.55±4.82 for candesartan and hydrochlorothiazide respectively. The precision and accuracy values for all the studies were within the range of ≤15% and 85-115%. The performed stability studies indicate that the developed method is stable in plasma for 15 h at room temperature (bench top); 52 h (in injector); for 112 days at -70 ºC for long term stability; five successive freeze and thaw cycles. The developed method could be successfully employed for the determination of selected drugs in biological samples.
DOI: 10.6084/m9.figshare.6504317
title: Simultaneous determination of candesartan and hydrochlorothiazide in human plasma by LC-MS/MS

description: Abstract A simple, sensitive, rapid and highly efficient LC-MS/MS method was developed for the determination of Candesartan and Hydrochlorothiazide simultaneously in human plasma. The method employed Zorbax eclipse C18 (150 X 4.6 mm, 5µ) column using acetate buffer: acetonitrile (25:75%, v/v) as the mobile phase. The mobile phase flow rate is 1 mL/min which was delivered into the mass spectrometer electron spray ionization chamber. The Liquid/liquid extraction procedure was used in the method for the extraction of analytes. The chromatograph was attached to a negative ion mode tandem mass spectrometer and the method was validated for all the parameters as per the guidelines of US-FDA. The ions were detected in multiple reaction monitoring mode and the transitions are m/z 439.00®309.10 and 295.80®268.80 for candesartan and hydrochlorothiazide respectively. Isotopic standards were used as internal standards for effective recovery of the analytes. The drugs were analyzed over a calibration range of 1.027-302.047 ng/mL for candesartan and 1.044-306.945 ng/mL for hydrochlorothiazide respectively with regression coefficient greater than 0.99. The mean extraction recoveries are 96.95±5.61 and 100.55±4.82 for candesartan and hydrochlorothiazide respectively. The precision and accuracy values for all the studies were within the range of ≤15% and 85-115%. The performed stability studies indicate that the developed method is stable in plasma for 15 h at room temperature (bench top); 52 h (in injector); for 112 days at -70 ºC for long term stability; five successive freeze and thaw cycles. The developed method could be successfully employed for the determination of selected drugs in biological samples.
DOI: 10.6084/m9.figshare.20039272.v1
title: Oral lactate intensifies insulin toxicity during severe insulin-induced hypoglycemia in mice

description: ABSTRACT We investigated whether oral lactate could prevent seizures and deaths in mice with severe hypoglycemia induced by a high dose of insulin. For this purpose, mice were fasted for 15 h and then given an intraperitoneal injection of regular insulin (5.0 U/kg or 10.0 U/kg). Immediately after insulin injection, the mice received an oral dose of saline (control), glucose (5.5 mmol/kg), or lactate (18.0 mmol/kg). Glucose and lactate levels were measured in the blood and brain before and after the seizures began. Glucose and lactate delayed (p &lt; 0.05) the onset of seizures associated with severe insulin-induced hypoglycemia. Elevated (p &lt; 0.05) brain levels of lactate were associated with an absence of seizures in mice that received glucose or lactate, suggesting that lactate could prevent convulsions associated with severe insulin-induced hypoglycemia. However, the same oral dose of lactate that delayed the onset of convulsions also increased the mortality rate. In contrast, diazepam (3.0 mg/kg) prevented seizures and markedly decreased the frequency of death during severe insulin-induced hypoglycemia. The results demonstrated that in contrast to oral glucose, oral lactate intensifies insulin toxicity.
DOI: 10.6084/m9.figshare.20039272
title: Oral lactate intensifies insulin toxicity during severe insulin-induced hypoglycemia in mice

description: ABSTRACT We investigated whether oral lactate could prevent seizures and deaths in mice with severe hypoglycemia induced by a high dose of insulin. For this purpose, mice were fasted for 15 h and then given an intraperitoneal injection of regular insulin (5.0 U/kg or 10.0 U/kg). Immediately after insulin injection, the mice received an oral dose of saline (control), glucose (5.5 mmol/kg), or lactate (18.0 mmol/kg). Glucose and lactate levels were measured in the blood and brain before and after the seizures began. Glucose and lactate delayed (p &lt; 0.05) the onset of seizures associated with severe insulin-induced hypoglycemia. Elevated (p &lt; 0.05) brain levels of lactate were associated with an absence of seizures in mice that received glucose or lactate, suggesting that lactate could prevent convulsions associated with severe insulin-induced hypoglycemia. However, the same oral dose of lactate that delayed the onset of convulsions also increased the mortality rate. In contrast, diazepam (3.0 mg/kg) prevented seizures and markedly decreased the frequency of death during severe insulin-induced hypoglycemia. The results demonstrated that in contrast to oral glucose, oral lactate intensifies insulin toxicity.
DOI: 10.6084/m9.figshare.20039275.v1
title: Antidiabetic, antihyperlipidemic and antioxidant influences of the spice cinnamon ( Cinnamomum zeylanicumon ) in experimental rats

description: ABSTRACT The present study investigates the effect of cinnamon (Cinnamomum zeylanicumon) powder supplementation on glucose levels, lipid profiles, and oxidative stress parameters in alloxan-induced diabetic rats. Diabetes was induced in adult male Wistar rats via a single subcutaneous alloxan injection (15 mg/kg). Cinnamon powder was mixed with the standard feed of the rats in an amount of 5% for 28 consecutive days. Serum concentrations of total cholesterol (TC) and triglycerides (TG) were assayed at the end of the experimental period in all investigated groups. Anti-oxidative enzymes such as glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) were sought in the serum and pancreas. Alloxan caused the fasting blood sugar level to increase. The administration of cinnamon blocked the increase of blood glucose. There was also a significant difference in the TG and TC levels between control and treated diabetic rats. In diabetic rats, cinnamon treatment restored the activities of SOD, CAT and GPx. These findings suggested that cinnamon has an anti-hyperglycemic effect, improves lipid profiles, and protect against damage induced by oxidative stress in the diabetic state.
DOI: 10.6084/m9.figshare.20039275
title: Antidiabetic, antihyperlipidemic and antioxidant influences of the spice cinnamon ( Cinnamomum zeylanicumon ) in experimental rats

description: ABSTRACT The present study investigates the effect of cinnamon (Cinnamomum zeylanicumon) powder supplementation on glucose levels, lipid profiles, and oxidative stress parameters in alloxan-induced diabetic rats. Diabetes was induced in adult male Wistar rats via a single subcutaneous alloxan injection (15 mg/kg). Cinnamon powder was mixed with the standard feed of the rats in an amount of 5% for 28 consecutive days. Serum concentrations of total cholesterol (TC) and triglycerides (TG) were assayed at the end of the experimental period in all investigated groups. Anti-oxidative enzymes such as glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) were sought in the serum and pancreas. Alloxan caused the fasting blood sugar level to increase. The administration of cinnamon blocked the increase of blood glucose. There was also a significant difference in the TG and TC levels between control and treated diabetic rats. In diabetic rats, cinnamon treatment restored the activities of SOD, CAT and GPx. These findings suggested that cinnamon has an anti-hyperglycemic effect, improves lipid profiles, and protect against damage induced by oxidative stress in the diabetic state.
DOI: 10.6084/m9.figshare.20039277.v1
title: Monocyte Activation Test (MAT) as a possibility of replacement for the rabbit pyrogen test in hyperimmune sera

description: ABSTRACT The use of a commercial kit for the monocyte-activation test (MAT) was evaluated for assessing pyrogenic contamination of hyperimmune sera . Three batches of sera, two pyrogen free and one pyrogenic, were tested. Endotoxin spike recover indicated that sample dilutions from 1/2 to 1/10 are suitable. Kit transport and storage conditions were also evaluated, proving that an adequate cold chain must be assured to achieve good results. Furthermore, the commercial MAT kit seemed suitable to replace the rabbit pyrogen test (RPT) for pyrogen testing of hyperimmune sera, although further tests are needed to a full validation.
DOI: 10.6084/m9.figshare.20039277
title: Monocyte Activation Test (MAT) as a possibility of replacement for the rabbit pyrogen test in hyperimmune sera

description: ABSTRACT The use of a commercial kit for the monocyte-activation test (MAT) was evaluated for assessing pyrogenic contamination of hyperimmune sera . Three batches of sera, two pyrogen free and one pyrogenic, were tested. Endotoxin spike recover indicated that sample dilutions from 1/2 to 1/10 are suitable. Kit transport and storage conditions were also evaluated, proving that an adequate cold chain must be assured to achieve good results. Furthermore, the commercial MAT kit seemed suitable to replace the rabbit pyrogen test (RPT) for pyrogen testing of hyperimmune sera, although further tests are needed to a full validation.
DOI: 10.6084/m9.figshare.20039278
title: Complexation and enhancement of temozolomide solubility with cyclodextrins

description: ABSTRACT Temozolomide is a poorly soluble anti-cancer drug used in the treatment of some brain cancers. Following literature reports about the enhancement of solubility and stability for these kinds of drugs upon complexation with cyclodextrins, we aimed to form an inclusion complex between temozolomide and the different types of cyclodextrins (CDs) to enhance its solubility. In this study, three different cyclodextrins (β -CD, hydroxyl-β-CD and γ-CD) were used, and changes in solubility was measured by UV-Vis Spectroscopy and HPLC. Morphological changes upon complexation were shown by the Scanning Electron Microscope (SEM), and weight loss profiles with respect to temperatures which were unique to the compounds were shown by Thermogravimetric Analysis. Changes in heat release profiles were shown by Differential Scanning Calorimeter (DSC). Drug solubility was measured to be increased to around 25% for 1:1 molar ratio for all used CD complexations. Changes of morphology, heat release and weight loss profiles are consistent with the formation of an inclusion complex between CDs and temozolomide. In this study, success was shown in the enhancement of temozolomide solubility upon complexation with different types of CDs. It has been demonstrated that cyclodextrins can be used as complexing agents for poorly soluble anti-cancer drugs, increasing their solubility and hence drug availability.
DOI: 10.6084/m9.figshare.20039278.v1
title: Complexation and enhancement of temozolomide solubility with cyclodextrins

description: ABSTRACT Temozolomide is a poorly soluble anti-cancer drug used in the treatment of some brain cancers. Following literature reports about the enhancement of solubility and stability for these kinds of drugs upon complexation with cyclodextrins, we aimed to form an inclusion complex between temozolomide and the different types of cyclodextrins (CDs) to enhance its solubility. In this study, three different cyclodextrins (β -CD, hydroxyl-β-CD and γ-CD) were used, and changes in solubility was measured by UV-Vis Spectroscopy and HPLC. Morphological changes upon complexation were shown by the Scanning Electron Microscope (SEM), and weight loss profiles with respect to temperatures which were unique to the compounds were shown by Thermogravimetric Analysis. Changes in heat release profiles were shown by Differential Scanning Calorimeter (DSC). Drug solubility was measured to be increased to around 25% for 1:1 molar ratio for all used CD complexations. Changes of morphology, heat release and weight loss profiles are consistent with the formation of an inclusion complex between CDs and temozolomide. In this study, success was shown in the enhancement of temozolomide solubility upon complexation with different types of CDs. It has been demonstrated that cyclodextrins can be used as complexing agents for poorly soluble anti-cancer drugs, increasing their solubility and hence drug availability.