Solubility enhancementofcefixime trihydrate by solid dispersions using hydrotropic solubilization technique and their characterization

Abstract The aqueous solubility of cefixime trihydrate (a water insoluble drug) using different hydrotropic agents was determined and solid dispersions of cefixime trihydrate were prepared by hydrotropic solubilization technique. The drugs content were determined. The aqueous solubility of v was increased many fold in presence of sodium acetate trihydrate as hydrotropic agent. This hydrotropic agent was used to prepare solid dispersion of cefixime trihydrate. Cefixime trihydrate and sodium acetate trihydrate were accurately weighed and taken in a 200 mL beaker. Distilled water 10-15 mL was taken to dissolve hydrotropic agent using heat (48-50 °C). The drug was then added to it and magnetically stirred till whole mass get viscous. The solid dispersions of cefixime trihydrate were characterized by XRD, DSC and IR studies. DSC thermogram, XRD and Infra-Red spectra were studied. Solid dispersions, thus prepared, showed faster release of the drug as compared to pure drug and physical mixture.

Maintenance enteral electrolyte solutions for neonatal calves: sodium acetate and osmolarity effects / Soluções eletrolíticas enterais de manutenção para bezerros neonatos: efeitos do acetato de sódio e da osmolaridade

The use of hypotonic electrolytic solutions in enteral fluid therapy is still understudied in calves. The objective of the present study was to evaluate the effects of maintenance enteral electrolytic solutions with different concentrations of sodium acetate and different osmolarities in calves. For this, 18 Holstein calves, six male and 12 female, 20 days old and weighing around 52kg, were used. The animals were randomly divided into three groups and each group received one of the treatments. The three electrolytic solutions contained the same components in different concentrations, resulting in a hyposmotic, an isosmotic and a hyperosmotic solution. Each animal was maintained in enteral fluid therapy for 12 hours with infusion rate of 15mL kg-1 h-1. Abdominal circumference, body weight, feces consistency, glucose and plasma lactate, pH, pCO2, HCO- 3 and BE were measured at the following times: T0h, T6h, T12h and T24h. The hyposmotic solution did not generate the onset of diarrhea, while the isosmotic and the hyperosmotic did. Regardless of the dose used, acetate did not cause metabolic alkalosis in the evaluated animals. The results suggest that the use of hyposmotic solution in diarrheic calves, dehydrated and without metabolic acidosis, may be clinically important.(AU)

O uso de soluções eletrolíticas hipotônicas na hidratação enteral ainda é pouco estudado em bezerros. O objetivo do presente estudo foi avaliar os efeitos de soluções eletrolíticas enterais de manutenção com diferentes concentrações de acetato de sódio e diferentes osmolaridades em bezerros. Para isso, foram utilizados 18 bezerros, seis machos e 12 fêmeas, holandeses, com 20 dias de nascidos e pesando por volta dos 52kg. Os animais foram divididos aleatoriamente em três grupos e cada grupo recebeu um dos tratamentos. As três soluções eletrolíticas continham os mesmos componentes, mas em diferentes concentrações, resultando em uma solução hiposmótica, uma isosmótica e uma hiperosmótica. Cada animal foi mantido em hidratação enteral durante 12 horas com taxa de infusão de 15mL kg-1h-1. Foram aferidos perímetro abdominal, peso corporal, consistência das fezes, glicose e lactato plasmático, pH, pCO2, HCO- 3 e excesso de base nos seguintes tempos: T0h, T6h, T12h e T24h. A solução hiposmótica não gerou aparecimento de diarreia, enquanto a isosmótica e a hiperosmótica geraram. Independentemente da dose utilizada, o acetato não causou alcalose metabólica nos animais avaliados. Os resultados sugerem que o uso da solução hiposmótica em bezerros diarreicos, desidratados e sem acidose metabólica, pode ser clinicamente importante.(AU)

Development of a LC-MS/MS for Quantification of Venlafaxine in Human Plasma and Application to Bioequivalence Study in healthy Korean Subjects

A simple, rapid and selective liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is developed and validated for quantification of venlafaxine in human plasma with simple liquid-liquid extraction step consisted of extraction with ether and dichloromethane for 10 min and mixing with 1 M sodium acetate in human plasma using fluoxetine as an internal standard (IS). The analyte are separated using an isocratic mobile phase consisted of acetonitrile and 5 mM ammonium formate (4/3, v/v) on a isocratic YMC hydrosphere C18 (2.0x50.0 mm, 3.0 microm) column and analyzed by MS/MS in the multiple reaction monitoring (MRM) mode using the transitions of respective [M+H](+) ions, m/z 278.2-->260.3 and m/z 310.1-->148.1 for quantification of venlafaxine and IS, respectively. The standard calibration curves showed good linearity within the range of 1.0-200.0 ng/mL (r2=0.9986, 1/chi2 weighting). The lower limit of quantification (LLOQ) was 1.0 ng/mL. The retention times of venlafaxine and IS were 0.6 min and 0.7 min that means the potential for the high-throughput potential of the proposed method. In addition, no significant metabolic compounds were found to interfere with the analysis. Acceptable precision and accuracy were obtained for the concentrations over the standard curve range. The validated method was successfully applied to bioequivalence study after 75-mg of venlafaxine sustained-release (SR) capsule in 24 healthy Korean subjects.

Impact of Plasma-Lyte pH 7.4 on acid-base status and hemodynamics in a model of controlled hemorrhagic shock

OBJECTIVE: Intravenous infusion of crystalloid solutions is a cornerstone of the treatment of hemorrhagic shock. However, crystalloid solutions can have variable metabolic acid-base effects, perpetuating or even aggravating shock-induced metabolic acidosis. The aim of this study was to compare, in a controlled volume-driven porcine model of hemorrhagic shock, the effects of three different crystalloid solutions on the hemodynamics and acid-base balance. METHODS: Controlled hemorrhagic shock (40 percent of the total blood volume was removed) was induced in 18 animals, which were then treated with normal saline (0.9 percent NaCl), Lactated Ringer's Solution or Plasma-Lyte pH 7.4, in a blinded fashion (n = 6 for each group). Using a predefined protocol, the animals received three times the volume of blood removed. RESULTS: The three different crystalloid infusions were equally capable of reversing the hemorrhage-induced low cardiac output and anuria. The Lactated Ringer's Solution and Plasma-Lyte pH 7.4 infusions resulted in an increased standard base excess and a decreased serum chloride level, whereas treatment with normal saline resulted in a decreased standard base excess and an increased serum chloride level. The Plasma-Lyte pH 7.4 infusions did not change the level of the unmeasured anions. CONCLUSION: Although the three tested crystalloid solutions were equally able to attenuate the hemodynamic and tissue perfusion disturbances, only the normal saline induced hyperchloremia and metabolic acidosis.

Lead exposure changes gastric acid secretion in rat: role of nitric oxide [No]

Sub chronic exposure to lead in rats slows gastric emptying, but little is known about the effects of lead on gastric secretion. This study was designed to investigate the effects of lead on gastric acid secretion and its possible mechanisms in rats. Lead acetate was dissolved in drinking water in a concentration of 1%. Sodium acetate-containing water with a molar concentration similar to lead was also prepared. We had nine groups of animals [n=8]; four of them were exposed to lead for 1, 2, 3, and 4 weeks [Pbl, Pb2, Pb3 and Pb4 groups, respectively]. Sodium acetate solution was given to another four groups for 1, 2, 3, and 4 weeks [Nal, Na2, Na3 and Na4 groups, respectively]. Gastric secretion was collected by washout technique and its acid output was measured in the basal [Basal Acid Output, BAO], vogotomy [Vagotomized Acid Output, VAO], and vagally stimulated [Vagally Stimulated Acid Output, VSAO] states using titrator instrument. Nitric oxide [NO] metabolite of gastric tissue was determined by Griess micro assay method to evaluate the possible mechanism of lead effect on gastric secretion. VSAO was significantly less in Pbl and Pb2 groups than Nal and Na2 ones respectively [1.75 +/- 0.17, 2.10 +/- 0.30 vs. 5.79 +/- 0.20, 6.18 +/- 0.27 micromol/15min] [P=0.001, P=0.001] BAO was significantly more in Pb3 and Pb4 groups than Na3 and Na4 ones respectively [2.77 +/- 0.37, 2.80 +/- 0.31 vs. 1.73 +/- 0.16, 1.79 +/- 0.34 micromol/15min] [P=0.01, P=0.02], but it was the same after vagotomy. VSAO was more in Pb3 and Pb4 groups than their Na counterparts [P=0.001, P=0.0001] NO metabolite of gastric tissue was more in all Pb groups in comparison to their Na counterparts [P=0.0001]. In this study, it seems that lead exposure, via NO mechanism, has different effects on acid secretion. Nitric oxide in small and large amounts decrease and increase gastric acid secretion, respectively

Lead exposure changes gastric motility in rats: role of nitric oxide [no]

Abdominal colic, constipation and delay in gastric emptying are symptoms of lead poisoning, but there is scant information about the effect of lead on gastric motility. In the present study, we investigated the effect of lead acetate on gastric motility in rats. Animals were divided into nine groups [n=8]; four groups were exposed to lead acetate solution [1%] for 1, 2, 3, and 4 weeks [Pb1, Pb2, Pb3, and Pb4 groups, respectively]. Sodium acetate solution was given to another four groups for 1, 2, 3, and 4 weeks [Na1, Na2, Na3, and Na4 groups, respectively] and the control group had free access to tap water. Gastric motility was measured in the basal and acetylcholine [Ach]-stimulated states using a physiograph instrument. Nitric oxide metabolite of gastric tissue was determined by Griess micro-assay. There were no significant differences between basal and Ach-stimulated gastric motility in Pb1, Pb2, Na1, and Na2 groups. However, it was significantly greater in Pb3 and Pb4 groups when compared with Na3 and Na4 groups in both basal and Ach-stimulated states [P<0.05]. In addition, nitric oxide metabolite of gastric tissue was more in all Pb groups in comparison with their Na counterparts [P<0.05]. We found that lead exposure could affect gastric motility via the nitric oxide pathway

Synthesis and applications of coumarin

In this work, coumarin was synthesized by Perkin reaction using salicylaldehyde, acetic acid and sodium acetate. Due to the misuse of acetic anhydride in narcotics synthesis, acetic acid was substituted for acetic anhydride in Perkin reaction. On the basis of this substitution a hypothesis was proposed that "acetic acid could be substituted as an acetylating agent in place of acetic anhydride in coumarin synthesis via Perkin reaction". In the present research project, salicylaldehyde was prepared from phenol, sodium hydroxide and chloroform for further procedure. Then four different coumarin samples were synthesized by changing the parameter of reactants proportions. From this parameter, we designed a trend of high product yield. Yields of Coumarin samples will lead towards either acception or rejection of the above proposed hypothesis. In the next step, these Coumarin samples were characterized by age yield [%], solubility and melting points. At last Antibacterial activities of all the four coumarin samples were evaluated against two bacterial strains; E.coli and S.aureus. As a consequence of all above, it was inferred that the yields of all coumarin samples obtained were low as compared to the yield obtained by the use of acetic anhydride in previous reports. This led to the rejection of proposed hypothesis. Among four Coumarin samples, sample-4 obtained by taking equal amounts of all the reactants had shown maximum yield, best characterization and excellent antibacterial activity. In spite of low yields obtained, the remarkable antibacterial activities of Coumarin samples have enabled us to suggest coumarin as a strong antibacterial agent and it must be employed for further applications

Deshidratación hipernatremica en recién nacido por sales de rehidratación oral reporte de un caso / Hypernatremic deshydration in newborn by salts of oral rehydration: a case report

La deshidratación hipernatremica se define como una concentración sérica de sodio mayor de 150 mEq/L, representa el 20 por ciento de las deshidrataciones y refleja un déficit de agua extracelular con relación al contenido corporal de sodio con edema cerebral, hemorragia intracraneal, hidrocefalia y gangrena. Los factores de riesgo para deshidratación hipernatrémica son: niños menores de un año por inmadures renal y aumento del líquido extracelular, fiebre que aumenta la pérdida de agua libre y, fundamentalmente el ingreso incrementado de solutos con relación al contenido de agua libre, producto de la reshidratación oral con soluciones con alto contenido de sodio, formulas mal preparadas o alimentación al pecho exclusiva en madres con una aporte insuficiente de líquidos. Se trata de recién nacido de 13 días de vida quien presenta clínica de deshidratación y acidosis por síndrome diarreico agudo con antecedente de mala administración de Sales de rehidratación oral por parte de la madre con dilución inadecuada hiperosmolar. Hallazgos paraclínico, Hipernatremia, Hiperkalemia, acidosis metabólica e hipoxemia. Tratamiento: corrección de acidosis con solución 75 y rehidratación en 48 horas con solución hipoosmolar 0.22 por ciento. Presentamos este caso por ser una de las causas más frecuentes de deshidratación hipernatrémicas en recién nacidos, es importante exponer la necesidad de educación a las madres para la adecuada preparación de las sales de rehidratación oral, como método eficaz de prevenir la deshidratación. Y en aquellos casos de presentarse tal complicación, los médicos debemos conocer la adecuada correlación de las misma a modo de evitar las complicaciones.

The effect of carbon as an energy source for biological denitrification through Pseudomonas stutzeri.

The biological denitrification processes possess many advantages in comparison to other denitrification processes. The present study was undertaken to observe the effect of quantity of carbon on biological denitrification with Pseudomonas stutzeri at different C/N ratios. The results obtained in the present investigations show that the pH and alkalinity of the effluent increased with increase in C/N ratio due to alkalinity generated during denitrification. The COD of the influent was increased with increase in C/N ratio. The effluent COD was nil under pseudo-steady state condition up to the C/N ratio of 2.5. Above this C/N ratio, the organics started entering in the treated water. The maximum feasible economic reduction of NO(3-)N from 51.6 mg/l to 1.2 mg/l occurred at C/N ratio of 2.5 and the obtained concentration of NO(3-)N was found to be lower than the tolerance limit (10 mg/l) prescribed by the WHO. The present work provides a feasible approach for a more efficient NO(3-)N removal process.

Bicarbonate versus acetate dialysate in long term haemodialysis: impact on acid-base status, delivered Kt/V and protein nutritional status. A prospective crossover study

We selected 40 cases of chronic renal failure [CRF] [25 males and 15 females] on thrice weekly haemodialysis [HD] using acetate for at least 1 year before study onset. All cases were allowed unrestricted protein intake starting one month before they were randomly divided into 2 groups matched for age, gender, body weight [BW] and socioeconomic status, Group 1 were shifted to bicarbonate dialysis while Group 2 patients were kept on acetate dialysis for 3 months then cross over was done for the following 3 months. Both biocarnonate and acetate were used at a fixed concentration of 36 mmol/L. Prescribed Kt/V was kept constant throughout the 6 months. Pre and post dialysis [Dx] blood pH and serum bicarbonate [Sbic].predialysis serum prealbumin [Spalb], and transferring [Stf], triceps skin fold thickness [TSF], mid arm muscle circumference [MAMC] as well as protein catabolic rate [PCR and nPCR] and urea reduction ratio [URR] were estimated at the onset and at the end of each 3 month period. Delivered kt/V was estimated from URR. Pre Dx Sbic and pH were significantly higher during bicarbonate dialysis compared to acetate dialysis [p<0.001]. Spalb increased significantly in Group 1 during bicarbonate and decreased significantly during acetate dialysis [p<0.00011 and 0.06,respectively] while in Group 2 it increased significantly in both periods [p<0.05 and 0.004.respectively]. Stf didn't show any significant change throughout the study. TSF, MAC and MAMC increased significantly in Group 1 during bicarhonate dialysis and decreased significantly during acetate dialysis [p<0.001,0.02.0.001,0.05,0.004 and 0.03,respectively for TSF, MAC and MAMC at 0,3 months and MAMC at 0,3 months and 6 months] while in Group 2 they did not change during acetate dialysis and increased significantly during bicarbonate dialysis [p<0.05,<0.002.>0.05, <0.03, >0.05 and <0.05, respectively]. nPCR increased significantly in Group 1 during bicarbonate dialysis and did not change during acetate dialysis [p<0.001 and >0.05, respectively] while in Group 2 nPCR did not change during acetate dialysis and increased significantly during bicarbonate dialysis [p>0.05 and >0.05, respectively]. Although prescribed Kt/V did not change throughout the study, delivered Kt/V increased significantly in Group 1 during bicarbonate dialysis and decreased significantly during acetate dialysis [p<0.001 and < 0.02, respectively]. In Group 2 delivered Kt/V did not change during acetate dialysis and increased significantly during bicarbonate dialysis [p>0.5 and <0.0001, respectively]. Conclusions: 1. Bicarbonate dialysis offers better blood pH and Sbic levels 2. Optimized serum pH and bicarbonate offers improvement in protein intake evidenced by increased nPCR associated with improved protein anabolism as evidenced by increased Spalb, TSF, MAC and MAMC. 3. Increased delivered Kt/V is likely due to better patient compliance during bicarbonate haemodialysis

Cardioprotective Effect of Ischemic Preconditioning: Relationship between Intracellular Glycogen and Protein Kinase C

BACKGROUND: Recent studies suggest that the cardioprotective effect of ischemic preconditioning (IPC) is related to intracellular glycogen content in rat hearts, however, controversies still remain. METHODS: To test this hypothesis, isolated Langendorff-perfused rabbit hearts were subjected to 45 min global ischemia followed by 120 min reperfusion with IPC (n=0) or without IPC (ischemic control, n=). IPC was induced by one cycle of 5 min global ischemia and 10 min reperfusion. In the glucose (G)-free preconditioned group (n=0), G depletion-repletion was induced by perfusion with G-free Tyrode solution for 5 min and then G-containing Tyrode solution for 10 min followed by 45 min ischemia and 120 min reperfusion. For glycogen depletion or loading, hearts were treated with sodium acetate (NA, 5 mM, n=) or insulin (Ins, 1 unit/L, n=) for 15 min before 45 min ischemia. Left ventricular function and coronary flow (CF) were continuously recorded during experiments. Myocardial cytosolic and membrane protein kinase C (PKC) activities were measured by 32P-gamma-ATP incorporation into PKC-specific pepetide; glycogen content in the cardiac myocytes was determined by spectrophotometry with amyloglucosidase; expression of PKC isozymes was determined by Western blot with monoclonal antibodies. Infarct size was determined by staining with tetrazolium salt and planimetry. Data were analyzed by ANOVA and Tukey's post-hoc test. RESULTS: IPC or G-free preconditioning enhanced LV functional recovery; NA did not influence on functional recovery but Ins depressed it. Infarct size was significantly reduced by IPC, G-free preconditioning, and NA treatment (35.3+/-2.1% in the ischemic control, 18.7+/-1.2% in the IPC, 22.1+/-1.2% in the G-free preconditioned, 16.3+/-1.2% in the NA-treated group, and 32.8+/-1.6% in the Ins-treated group, p<0.05). Membrane PKC activities significantly increased by IPC, IPC and 45 min ischemia, G-free preconditioning, and G-free preconditioning and 45 min ischemia; especially, expression of membrane PKC-epsilon increased by IPC and G-free preconditioning. Glycogen content decreased by 45 min ischemia, IPC, G-free preconditioning, and by NA treatment, but increased by Ins treatment. CONCLUSION: These results suggest that in rabbit heart, intracellular glycogen may not significantly be related with the cardioprotective effect of IPC; G-free preconditioning could not improve post-ischemic contractile dysfunction but it has an infarct size-limiting effect; this cardioprotective effect may be related in part to activation of PKC, especially epsilon isozyme.

Labeling and Biodistribution of Re-188-DTPA ( Diethylenetriaminepentaacetic acid ) / 대한핵의학회잡지

Re-188 is useful candidate for therapeutic radionuclide because it has a physical half life of 17 hours, contains beta ernissions suitable for therapy(maximum energy 2.12MeV) and emits a garnma ray that is suitable for quantitative diagnostic scanning(155keV). To use He-188 as a radionuclide compound of angioplasty balloon radiotherapy, we investigated the labelling method and biodistribution of Re-188- DTPA. We postulated that labeled Re-188-DTPA is preferable because it would be excreted via urinary system more easily than other compounds. To label Re-188 with DTI'A, 1ml of 222MBqI(6mCi) of Re-188 was added to DTPA solution(DTPA 20mg, SnC4 2HsO 10mg, pH 3.5) and boiled at 100C for 120min in water bath. pH was adjuted to 5 with 2.3Fo sodium acetate. I.abeling efficiency was measured using TLC-SG(acetone, saline). We evaluated biodistribution of Re-188-DTPA in sacrificed mice at 10 and 60 minutes after injection. We acquired images of kidneys, and drew tirne-activity r.urves in normal dogs and rats and calculated Trnax and Tl/2 in rats. The labelling efficiency was 95.7Yo on average. Labelling of Re-188-DTPA was stable(90% after 5hours) in vitro at room temperature. According to time-activity curves of dogs and rats, it took 15 to 20 minutes after injection for Re-188-DTPA to be washed out through kidneys. In conclusion, Re-188-DTPA was successfully labeled, Re-188-DTPA was stable in vitro and was excreted early via kidneys in animals. We could recornmend Re-188-DTPA as radionuclide of potential use in angioplasty balloon radiotherapy.