Anti-M₃Muscarinic Acetylcholine Receptor Antibodies in Systemic Lupus Erythematosus

Background: Evidences have shown that anti-M3 muscarinic acetylcholine receptor IgG (anti-M3 mAChR IgG) are clinically useful autoantibody that exert a cholinergic pharmacologic effect binding and interacting with M3 mAChR at the level of exocrine gland (salivary and ocular). Aims: The aim of this study was to determine the associations between serum level of anti-M3 mAChR IgG in patients with systemic lupus erythematosus (SLE) and other autoantibodies, serum prostaglandin E2 (PGE2), and clinical manifestations. Methods: Serum autoantibodies against M3 mAChR synthetic peptide were measured by enzyme-linked immuno absorbent assay (ELISA) using, as an antigen, a 25-mer peptide K-R-T-V-P-D-N-Q-C-F-I-Q-F-L-S-N-P-A-V-T-F-G-T-A-I corresponding to the amino acid sequence of the second extracellular loop of the human M3 mAChR. Serum levels of antinuclear antibodies (ANA), anti-Smith (Sm) antibodies, anti-phospholipid (APL) antibodies, and PGE2 were determined by ELISA in patients with SLE. Results: We found significantly enhanced titers of anti-M3 mAChR IgG in sera from SLE patients compared with healthy individuals (control). In addition, serum levels of PGE2 were significantly higher in SLE patients than in control patients and were significantly higher in active than in non-active SLE. No correlation was found with other autoantibodies present in SLE. By contrast, a positive correlation was found between anti-M3 mAChR IgG and PGE2 serum levels in SLE. Conclusions: As anti-M3 mAChR antibodies present in the sera of SLE patients may be another factor in the pathogenesis of this disease, and the increment of PGE2 in the sera of SLE has a modulatory action on the inflammatory process, suggesting that the presence of these autoantibodies against M3 mAChR may contribute to sustained immune deregulation and the strong inflammatory component observed in SLE.

<i>In Vitro</i>Competitive Metabolism Study of Olmesartan Medoxomil in Rat Liver S9 Fractions Using LC/MS

Olmesartan Medoxomil (OLM), Ramipril (RPL) & Fenofibric acid (FA) are used to treat hypertension and cardiovascular disease. These drugs undergo hydrolytic metabolism by the enzyme liver esterase and converts into their respective active metabolites Olmesartan (OL), Ramiprilat (RPT) and Fenofibric acid (FA) for OLM, RPL and FEN respectively. In this study the competitive metabolism of OLM, in presence of RPL and FEN was investigated in rat liver s9 fractions using a validated LC-MS method. Olmesartan Medoxomil was found to be highly reactive to the rat liver S9 fractions and formation of active metabolite Olmesartan is highest. The rate of formation of active metabolite Olmesartan reduced by 12.68% in the presence Ramipril and 6.56% in presence of Fenofibrate. A marked reduction of 18.96% was found in the formation of active metabolite Olmesartan from Olmesartan Medoxomil when all the three drugs are in combination.

Optimization of Dalbavancin in Patients with Hepatic or Renal Impairment

Dalbavancin is a novel semi-synthetic glycopeptide antibiotic. In this study, we aimed to optimize the dosage regimen of dalbavancin in patients with hepatic or renal impairment by Mote Carlo simulation. Pharmacokinetic parameters and microbiological data were collected about dalbavancin. 10,000 patients with renal or hepatic impairment analyzed by Crystal Ball to calculate probability of target attainment (PTA) and cumulative fraction of response (CFR). We found that all bacterial PTA and CFR were more than 90% for dalbavancin in patients with hepatic or renal impairment, except for Enterococcus faecium. There is no need to adjust the dosage regimen of dalbavancin in patients with hepatic or renal impairment.

<i>In Vivo</i>Sedative and Anxiolytic Activities of <i>Thunbergia erecta</i>(Acanthaceae) Leaves Activate Gamma-Aminobutyric Acid (GABA) Mediated Hyperpolarization in Swiss Albino Mice

Background: Thunbergia erecta (Acanthaceae) is the most abundant medicinal plant in different parts of Bangladesh where it is known as “nilghonta”. It has been used as traditional medicine for insomnia, depression and anxiety management. However, no scientific evidence of T. erecta belonging to neuropharmacological activity has been reported. The aim of present study was to investigate in vivo sedative and anxiolytic activities of methanol extract from the leaves of T. erecta in Swiss Albino mice. Methods: Sedative activity of METE was investigated using open field, hole cross and thiopental sodium-induced sleeping time test model whereas anxiolytic activity was screened by elevated-plus maze, light-dark box, hole-board and marble-burying test method in mice at 200 and 400 mg/kg doses. The acute toxicity study and phytochemical analysis of METE also carried out. Diazepam used as the positive control for the following behavioral pharmacology test. Results: METE exhibited significant (p Conclusion: The experimental result indicates T. erecta contains phytoconstituents that possess sedative and anxiolytic activity which traditionally used in insomnia, depression and anxiety management.

A Comparative Phytochemical and Biological Study between Different Solvent Extracts of <i>Bombax ceiba </i>Roots Available in Bangladesh

Use of different solvent systems for extraction of plant materials may cause variation in their bioactivities. The present study was conducted to evaluate the presence of different phytoconstituents and to compare in vitro bioactivities of petroleum ether, dichloromethane (DCM) and methanol extracts of Bombax ceiba (B. ceiba) roots available in Bangladesh. Preliminary phytochemical screening was conducted using specific standard procedure. Antioxidant activity of the extracts was evaluated using DPPH radical scavenging assay. Determination of total phenolic and flavonoid content was also carried out. Antibacterial and cytotoxic activities were investigated using disc diffusion method and brine shrimp lethality bioassay, respectively. All the experiments were carried out from February 2016 to September 2016. Phytochemical evaluation revealed the presence of alkaloids, terpenoids, carbohydrates, tannins, flavonoids, saponins and steroids. The methanol extract showed the highest DPPH radical scavenging activity and had the highest phenolic (187.42 ± 3.77 mg/g, GAE) and flavonoid content (74.67 ± 4 mg/g, QE) followed by the DCM and petroleum ether extracts. The extracts showed positive correlation between DPPH radical scavenging activity with the phenolic and flavonoid content. All the extracts showed mild to moderate in vitro antibacterial activity with zone of inhibition ranging from 7 mm to 13 mm. In brine shrimp lethality bioassay, the observed LC50 values for petroleum ether, DCM and methanol extracts were 70.72 μg/ml, 37.72 μg/ml and 22.58 μg/ml, respectively which revealed strong cytotoxic potential of the extracts compared to the positive control. The results indicated that B. ceiba roots could be a very potent source of natural radical scavenger and cytotoxic agent.

Statins and Sepsis Literature Review

Recent data suggest that, in addition to improving dyslipidemia, statin may reduce the risk of infections and infection-related complications. The aim of this study is to make a review of the literature about the effects of statins on clinically relevant outcomes of patients admitted to the hospital and having an infection and/or sepsis, principally in terms of intensive care unit admissions and related death.

The Impact of Clinical Pharmacist Interventions on Drug and Antibiotic Prescribing in a Teaching Hospital in Cairo

Background: The present study was undertaken to investigate the patterns of drug and antibiotics prescribing in a teaching hospital in Cairo, Egypt. Aim: to determine the impact of interventions on such trends in an attempt to rationalize drug use. Method: 1200 prescriptions and patients' records covering the months of January to December, 2011. Prescribing patterns were analyzed using WHO guidelines with regard to prescribing, patient care and health facility indicators. The same parame-ters were again assessed after distributing antibiotic guidelines and holding workshops activities directed towards rational drug use. Results: The number of hospital visits resulting in a prescription was significantly reduced from 94% to 86% (P-value <0.05) and in both cases none of the en-counters contained a generic drug. The average number of drugs per encounter was 2.7 and did not decrease significantly after intervention. A significant reduction was achieved in the number of prescriptions with antibiotics whereas reduction in encounters with injectable drugs was not statis-tically significant. Penicillins was the most commonly prescribed class of antibiotics and amoxicillin was the most frequently prescribed antibiotic. A significant reduction was observed in both en-counters with penicillin and the total of those with antibiotics. Analysis of prescriptions with anti-biotics revealed that penicillins, cephalosporins and erythromycin comprised 94% and 97% of all antibiotics prescribed before and after interventions respectively. Conclusion: The present results clearly indicated that interventions including distribution of antibiotic guidelines and running workshops and seminars on rational drug use to prescribers can lead to significant improvement in prescribing behavior.

Ciprofloxacin Cardiotoxicity and Hepatotoxicity in Humans and Animals

Ciprofloxacin is generally well tolerated;the most common adverse effects include gastro intestinal tract, central nervous system and hematological system effects. Recently rising cases of Ciprofloxacin associated toxicity have been reported. Experiment using animal models and clinical experience showed that Ciprofloxacin induced cardiotoxicity is marked by increase QT and QTC interval and prolonged action potential duration. This increases the risk of arrhythmia (tosarde de pointes). Ciprofloxacin induced cardiotoxic effect could be associated with blocking cardiac voltage—gated potassium channels particularly the rapid component (IKr) of the delayed rectifier potassium current. Drug interaction with inhibitors of Cytochrome P450 (CYP) mediated metabolism could be one of the underlying mechanisms. Several cases of Ciprofloxacin induced hepatoxicity have been also reported. These were characterized by extensive hepatocellular necrosis, mixed inflammatory infiltrate and abundant esinophils in the liver. Elevated liver enzymes which include serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gramma-glutamyltranferase and prolong prothrobin time were reported. The hepatotoxic effect of Ciprofloxacin as reported could be due to oxidative stress induced in the liver by Ciprofloxacin through the generation of oxidative radicals leading to depletion of protein content in hepatocytes as a consequence of nucleic acids diminution and DNA damage. This may lead to significant decrease in the number and degeneration in mitochondria which is responsible for energy supply. Conclusion: Ciprofloxacin induced cardiotoxicity and hepatotoxicity is relatively low in humans but patients’ liver and cardiac function may be considered before Ciprofloxacin use.

Serum Chlorine Level as a Possible Predictive Factor for Oxaliplatin-Induced Peripheral Neuropathy

Peripheral neuropathy is a major adverse event associated with oxaliplatin-based chemotherapy and is a major dose-limiting adverse event in clinical practice. However, some patients treated with oxaliplatin may show no or minimal peripheral neuropathy. These differences are still poorly understood. The data on patients with colorectal cancer who received oxaliplatin-based regimens between January 2005 and June 2010 at South Miyagi Medical Center were retrospectively retrieved from the medical records. We selected 51 patients, and factor analysis was performed. The serum chlorine (Cl) level at baseline was significantly higher in patients with a high frequency of peripheral neuropathy (106;range 104 - 107 vs. 104;range 101 - 104 mEq/L, p = 0.02). Principal component analysis showed the variables Cl, body mass index, status of liver metastasis, and status of lymph node metastasis were related to the incidence of peripheral neuropathy. Discriminant analysis showed the model had predicted 72.5% of peripheral neuropathy. An understanding of the patient’s characteristics could be useful for preventing or predicting oxaliplatin-induced peripheral neuropathy.

Binary and Ternary Complexes of Arteether β-CD - Characterization, Molecular Modeling and in Vivo Studies

The purpose of the present work is to improve the antimalarial activity of arteether through enhancing its solubility subsequently bioavailability by incorporating the drug into the cyclodextrins cavity. The effect of hydrophilic polyvinyl propylene (PVP) polymer on the complexation and solubilizing efficiencies of cyclodextrins (CDs) is also elucidated. Inclusion of arteether molecule in solid state was evidenced by Differential scanning calorimeter (DSC), Powder X-ray diffractometery (PXRD), and in solution state by NMR and solution calorimetry. A 1:1 stoichiometry was proposed by the phase solubility studies both in presence and absence of PVP. The most plausibe mode of inclusion of arteether into the CD cavity is revealed by molecular modeling studies utalizing Fast Rigid Exhaustive Docking acronym. Solution calorimetry was used further to confirm 1:1 stiochiometry in presence or absence of PVP by determining the enthalpy of interaction between the drug and cyclodextrins. The inclusion of drug was found to be exothermic process accompanied by small positive value of entropy (ΔSo). The methylated-β-CD showed the best ability to solublize arteether which is approximately at par with β-CD in the presence of PVP. Better complexation efficiency of β-CD in presence of PVP is also reflected by the higher numerical values of stability constant (K). Compelete eradication of the parasite from the blood and highest anti-malarial pharmacological activity was observed in the complexes of arteether with M-?-CD while 83.7% was observed for ternary complexes of β-CD in presence of PVP.

The Porcine Pulmonary Surfactant Protein A (pSP-A) Immunogenicity Evaluation in the Murine Model

This paper investigated the porcine surfactant protein A (pSP-A) immunogenicity in murine model. Many elegant stu-dies about SP-A therapeutic applications are available however specific studies about its exogenous immunogenicity were not easily assumed. Therefore, we investigated the immunogenicity of this porcine protein in mice. The mice re-ceived pSP-A subcutaneously on days 0 and 7. The animals were observed during 90 days and the blood was collected on days 30, 60 and 90 for assessment the immunogenic potential of pSP-A. Some animals showed circulating antibodies above the screening cut point, which was calculated based on control mice sera signals. However, those antibodies were considered false positive read-outs by the performed competitive inhibition assay. Also no neutralizing antibodies were detected able to avoid the porcine protein ability to promote lipid aggregation. So far in this model, porcine surfactant protein-A could be considered not immunogenic.

Investigation of Patients’ Mood on Their Distance from the Pharmacist during Medication Instruction

Background: Pharmacists must adjust their distance from patients to facilitate communication during interviews and gain their trust. The distance between the patients and the pharmacists varies depending on many factors, such as gender, posture and the patients’ mood. Only a few of these papers have actually measured and validated distance with patients. In this study, we validated our method of assessing mood and measuring distance before beginning a survey with patients. Methods: We measured comfortable interpersonal distance among men and women using an ecological scenario, in which a pharmacist approaches the subject, and the subject is asked to stop the pharmacist at the distance he/she feel comfortable with. Five pharmacists and 33 subjects participated in the study. The Japanese version of the Brief Mood Questionnaire Checklists (BMC-J) was used to quantify the subject’s mood for the day, and then the distance from the pharmacist that the subjects considered comfortable was measured at the bedside. The relationship between the mood and distance obtained was examined. Results: The comfortable distance of subjects was influenced by gender, posture, and mood. The shortest distance was 94.7 ± 11.1 cm (mean ± SD), for the male subjects versus the female pharmacists in the sitting position. The distance of male subjects shorted when they had positive emotions and lengthened when they were worried. Female subjects maintained a long distance from both male and female pharmacists when they had positive emotions and a short distance when they were worried. Conclusion: Findings show that the distance changes depending on the subjects’ mood at the time of measurement. It was found that the present measurement method can be used to determine the psychological state of the patient and measure the comfort distance at that time, and can be used as a simple method to examine these relationships. Therefore, it is also considered a practical method for the next step, which is a clinical study on patients.

Antioxidant, Cytotoxic, Thrombolytic and Antimicrobial Activity of <i>Zanthoxylum rhetsa</i>Root Bark with Two Isolated Quinolone Alkaloids

The background of this study was to investigate the antioxidant, cytotoxic, thrombolytic and antimicrobial activity of the petroleum ether (PE), carbon tetrachloride (CTC), chloroform (CF) and aqueous (AQ) soluble fractions of crude methanolic Zanthoxylum rhetsa root bark with two isolated quinolone alkaloids, 8-methoxy-n-methylflindersine (1) and zanthodioline (2). Structures were characterized by 1D NMR analyses. Antioxidant activity was assessed by using DPPH assay and antimicrobial activity was screened by disc diffusion method. An in vitro thrombolytic model was used to evaluate the clot lysis effect of different extracts of root bark of Z. rhetsa along with streptokinase as a positive control and distilled water as a negative control and the cytotoxic activity of different extracts of Z. rhetsa root bark was evaluated by Brine Shrimp Lethality Bioassay. AQ fraction exhibited strongest antioxidant, cytotoxic and thrombolytic activity among four fractions. The CTC and CF soluble fractions exhibited significant antioxidant, cytotoxic and thrombolytic activity. CTC and AQ fractions gave highest anti-bacterial activity against Vibrio cholera and Klebsiella pneumonia respectively. Compound 1 showed significant activity at a concentration of 100 μgm/disc against Sarcina lutea, Staphylococcus aureus and Salmonella paratyphi-A, Shigella dysenteriae, Shigella boydii and Shigella sonnei with high antioxidant activity. The antioxidant, thrombolytic and antimicrobial activity of 8-methoxy-n-methylflindersine and zanthodioline are the first record from root bark of this plant.

Assessment of Rational Prescribing in General Outpatient Department of Kampala International University Teaching Hospital, Western Uganda

Introduction: Prevention of irrational use of medicines may reduce healthcare costs and potentially save lives. Aim: The aim of this study was to assess rational drug prescribing using World Health Organization (WHO) and International Network of Rational Use of Drugs (INRUD) indicators on prescribing in the General Outpatient Department of Kampala International University Teaching Hospital, Ishaka-Bushenyi, Western Uganda. Methodology: The study design was retrospective, descriptive and cross-sectional. A total of 884 prescriptions were selected by systematic sampling using an interval of 27 from 23,868 prescriptions available in the medical records of the General Out-Patient Department (GOPD) of Kampala International University Teaching Hospital (KIUTH) from April, 2016 to March, 2017. The selected samples were analyzed using Microsoft Excel 2013, to assess for conformity with the prescribing indicators. Results: The results showed that the percentage of recording of diagnosis was 90.72% (index of diagnosis—0.91). The average number of drugs per encounter was 2.6 (index of non-polypharmacy—0.77), and the percentage of drugs prescribed with the generic name was 90.21% (index of generics—0.9). Percentages of encounters with antibiotics and injectable drugs prescribed were 61.88% (index of antibiotics—0.48) and 5.43% (index of injectable drugs—1) respectively. Only 78.96% (index of EMSLU—0.79) of the medicines prescribed were from the Essential Medicines Supplies List of Uganda (EMSLU) or Uganda Clinical Guidelines 2016. The index of rational drug prescribing (IRDP) was found to be 4.85. Conclusion: The findings showed that only the percentage of encounters with injectable drugs was in line with WHO/INRUD prescribing indicators. On the over all, the index of rational drug prescribing (IRDP) was poor (observed 4.85 versus optimum 6). The authors recommended continuous sensitization, counselling and education of prescribers in KIUTH in order to achieve rational prescribing.

Study of Factors Affecting Medical Incident: 2 Powdered Medication Dispensing

Medical incidents have been collected, analyzed and built up preventive measures by each medical institution for a long time. For powdered medication, there is the problem that it is difficult to tell at a glance the quantity of the active ingredient in the medication that has been dispensed and the quantities that have been mixed together. Therefore, special prevention measures are considered essential. In this study, we examined the work content of pharmacists’ powdered medication dispensing, using an eye-tracking technology of measuring a human eye movement, and studied on factors that affect medical incident. Participants were five pharmacists with 8 to 26 years of working experience (expert), and five pharmacists with less than one year of working experience (newcomer). Gaze measurement experiments were implemented for powdered medication dispensing during regular work activity. The gaze measurement equipment used was Tobii Pro Glasses 2. Based on the results of the eye tracking, newcomer had a longer dispensing time than expert for all powdered medication dispensing. In particular, it was suggested that there is a close relationship to “years of experience” and “weighing and mixing skills.” Experts did unwasted and efficient movements, when preparing the dispensing apparatus, taking medications from the shelves, and scanning the barcode in the powders dispensing checking system. These movements led to shorter working time in experts. In contrast, newcomer had individual differences at the dispensing. Even with the same pharmacist, the work progression differed depending upon the prescription. Therefore, it is thought that the factor of common error was inadequate check and overlooked. The state that it’s messy on the workplace is also considered highly likely to cause dispensing mistakes. At the weighing, expert started weighing after the inspection of the prescription and checking weighed amount. However, certain newcomer dispensed to depend on the powders dispensing checking system only for the weighing process, without the inspection of the prescription or checking weighed amount. Irregular doses for infants and older patients require fine adjustments;therefore, the powders dispensing checking system may not find all dispensing errors. It is important for a pharmacist to, first, be written calculated weight on the prescription and checked by themselves, and next to begin dispensation work. In the future, as well as the powdered medication dispensing, it is necessary to make use of measures for preventing errors in the various dispensing process, such as the medication inspection, sterile products preparation, clinical practice et al.

Effect of Peptidase Inhibitors on Dynorphin A (1-17) or (1-13)-Induced Antinociception and Toxicity at Spinal Level

Our group has earlier demonstrated that three enzymes sensitive to peptidase inhibitors (PIs), amastatin (A)-, captopril (C)-, and phosphoramidon (P), played an important role in inactivation of enkephalins at the spinal level. Dynorphin-converting enzyme (DCE) hydrolyzes dynorphin (Dyn) A (1-17) or Dyn A (1-13) mainly at the Arg6-Arg7 bond. Dynorphin A and its derived peptides interact with opioid and glutamate receptors at their N- and C-terminals, respectively. The purpose of the present study was to evaluate the antinociceptive potency and toxicity of intrathecal administered Dyn A (1-17), Dyn A (1-13), or Dyn A (1-6) under pretreatment with ACP and/or the DCE inhibitor p-hydroxymercuribenzoate (PHMB). The effect of these PIs on Dyn A (1-17)-induced inhibition of electrically-evoked contractions in mouse vas deferens was also investigated. The inhibitory potency of Dyn A (1-17) on electrically-evoked contractions in mouse vas deferens under pretreatment with ACP was higher than that with AC, AP, or CP. Pretreatment with ACP augmented Dyn A (1-17) or (1-13)-induced antinociception by approximately 50- or 30-fold with no sign of allodynia when administered intrathecally at low doses. Pretreatment with ACP and PHMB induced neuropathy. These findings showed that intrathecal administration of low-dose Dyn A (1-17) or DynA (1-13) increased antinociception under pretreatment with ACP, but without signs of allodynia in rat.

<i>In Vitro</i>Antibacterial, Antifungal and Other Medical Properties of Endangered Medicinal Plant Seeds

The risk created by infectious microorganisms to humans attracted the development of common medicine. To find an alternative source, medicinal plants with diverse metabolites play an important role in curing the diseases and human disorders caused by microbial pathogens. Medicinal plants namely, Citrullus colocynthis, Hyoscyamus muticus, Ocimum basilicum, Amaranthus lividus, Salvia aegyptiaca and Ruta chalepensis are commonly used as a traditional medicine in Gulf countries. The present study aimed to investigate the antibacterial, antifungal and antioxidant potential of the organic crude extracts obtained from the seeds. Besides, the possible antimicrobial mechanisms of the extracts were evaluated by determining the enzyme activities. The antibacterial and antifungal activities of the crude extracts were evaluated by the broth micro dilution method and the effect of the extracts on the pathogens were determined by quantifying the alkaline phosphatase (ALP), lactate dehydrogenase (LDH) enzymes and intracellular protein leakage. Besides, the antioxidant properties were determined using hydroxyl radical scavenging assay, DPPH radical scavenging assay, reducing power assay and superoxide radical scavenging assay. Results indicated that the extracts of C. colocynthis showed promising activity against all the tested pathogens, especially the MIC values were ranged from 100 to 150 μg/ml for Gram positive bacteria and 100 to 250 μg/ml for Gram negative bacteria respectively. The MIC values of H. muticus, O. basilicum and R. chalepensis against the fungal pathogens were ranged from 100 to 500 μg/mL respectively. The ALP activity was higher in extract treated Klebsiella pneumoniae compared with control, whereas the LDH and protein concentrations for Escherichia coli and Staphylococcus aureus were comparatively higher. Furthermore, all the studied seed extract showed good antioxidant activities. In conclusion, the studied plant seed extracts documented good antimicrobial and antioxidant activities. Therefore, the medicinal plants would be the excellent source for natural antioxidant and antibacterial agents for medical and applications.

Formulation and <i>In-Vitro</i>Release Pattern Study of Gliclazide Matrix Tablet

In current decade, pharmaceutical industries of Bangladesh are giving much emphasize on the formulation of time release preparation to treat various chronic diseases in order to decrease the frequency of administration and to improve patient compliance. Objectives: The objective of this investigation is to design and evaluate sustained release matrix tablet of Gliclazide by direct compression method employing polymers of hydroxypropylmethyl cellulose (HPMC) derivatives (K15M CR and K4M CR) and to select the optimized formulations and compression process by performing a comparative release kinetic study with a reference product, Diamicron MR (one of the worldwide brand of Gliclazide sustain released tablet manufactured by Servier one of the French pharmaceutical company) tablet. Methods: Release kinetics of Gliclazide matrix tablets were determined using USP paddle method at Phosphate buffer (pH 7.4). The release mechanism was explored and explained with zero order, first order, Higuchi and Korsmeyer model. Result: It is found that formulation with lower polymeric concentration follows Higuchi release kinetics and that the formulation with higher concentration best fits with zero order release kinetics. Among the formulations, F1 and F6 show almost similar dissolution profile with Diamicron MR Tablet, which can be suitable candidates for further in-vivo bioequivalence study. Conclusion: Findings of this investigation suggest that F1 and F6 formulations are potential candidates for further bioequivalence study among other formulations.

Torsadogenic Index: Its Chinese Medical Origin

The foundational chronology of Torsadogenic Index is introduced to explain the relationship between impending death situations and drug prescription, combination, self-indication, or abuse of torsadogenic pharmacological products. The pathophysiological basis of Torsade de Pointes is presented with the most frequent causes of Long QT syndrome. Traditional Chinese Medical principles are exposed in order to help people to understand its para-logical sequence, providing another view of medical explanations upon scientific evidence. Development of Torsadogenic Risk Management Project and Torsadogenic Traceability concepts derived from these Chinese Medical perpetual axioms are presented in this paper.

Hepatoprotective Effect of Vitamin C (Ascorbic Acid)

Human and animal studies have shown that some drugs and chemical agents have potential hepatotoxic effects. The hepatotoxic effect of drugs and some chemical agents is reported to be associated with the generation of reactive oxygen species (ROS). These ROS are reported to be associated with lipid peroxidation in the liver. This mechanism has led to continuous evaluation of the hepatoprotective effect of antioxidants in humans and animals. Among the antioxidants been evaluated is vitamin C which is a water soluble antioxidant. Reports have linked vitamin C with hepatoprotective property in animals and humans. It synergistic hepatoprotective effect with other antioxidants was also reported. Due to these reports a comprehensive literature review on the hepatoprotective property of vitamin C in humans and animals was performed. It was observed that vitamin C exhibited a reputable hepatoprotective effect in humans and animals. Research showed that vitamin C inhibited hepatotoxicity induced by drugs, heavy metals, organophosphate insecticides and some chemical agents. Vitamin C was reported to normalized levels of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamine, alkaline phosphatase, lactate dehydrogenase and malondialdehyde and serum bilirubin in intoxicated animals. It potentiates the activities of free radical scavengers, superoxide dimutase, and catalase glutathione peroxidase thereby preventing microsomal lipid peroxidation, liver fibrosis, liver necrosis and hepatic inflammation. In humans vitamin C was reported to be beneficial in non alcoholic steatohepatitis and in patients with fatty liver disease. Hepatoprotective property of vitamin C is attributed to it antioxidant property. Vitamin C (ascorbic acid) which is a major water-soluble antioxidant is believed to decrease lipid peroxidation either directly or indirectly by regenerating vitamin E. Vitamin C is an important free radical scavenger in extracellular fluids, trapping radicals and protecting biomembranes from peroxide damage. Vitamin C effectively scavenges singlet oxygen, superoxide, hydroxyl, water soluble peroxyl radical and hypochlorous acid. It is also reported to be an excellent source of electrons and therefore can donate electrons to free radicals such as hydroxyl and super oxide radicals and quench their activity. Vitamin C is an essential co-factor involved in many biochemical functions and acts as an electron donor or reducing agent. In this review it is observe that vitamin C has hepatoprotective effect which increases when co administered with other agents precisely antioxidants.