Efficacy Study of Folic Acid Supplementation on Homocysteine Levels in Adolescent Epileptics Taking Antiepileptic Drugs: A Single Blind Randomized Controlled Clinical Trial.

BACKGROUND: Epilepsy is a chronic medical condition that requires long-term therapy with antiepileptic drugs (AEDs). However, long-term employment of AEDs may lead to the onset of hyperhomocysteinemia, which has been found to modulate imperative metabolic mechanisms and induce cardiovascular disorders (CVDs). Therefore, adolescent population that have been diagnosed with epilepsy and utilize AEDs are among the most vulnerable, exhibiting higher risks of developing CVDs. PURPOSE: The present study was designed to explore the effects of folic acid (FA) supplementation on AED-induced hyperhomocysteinemia and CVD risk factors in adolescent epileptics. METHODS: The randomized clinical trial included adolescent epileptics (i.e., 10-19 years of age) of either sex, on antiepileptic therapy for > 6 months with high homocysteine levels (i.e., >10.9 µmol/L). At the time of enrolment, their baseline BP, lipid and homocysteine levels were recorded. Participants were randomly assigned to either treatment or placebo groups and received the respective treatments. At the end of the first month, BP, lipid and homocysteine levels were recorded and compared to determine the effect of FA on these parameters. RESULTS AND CONCLUSION: A significant fall in homocysteine levels was observed with FA supplementation (P < 0.05). However, this fall was significantly high in valproic acid treated epileptic patients. In addition, we observed an improvement in high-density lipoprotein levels, a risk factor for CVDs, but the change was statistically insignificant (P > 0.05). The study results suggest that FA supplementation in epileptic patients receiving AED therapy may minimize AED-induced hyperhomocysteinemia and other CVD risk factors.

Comparative pre-emptive analgesic efficacy study of novel antiepileptic agents gabapentin, lamotrigine and topiramate in patients undergoing major surgeries at a tertiary care hospital: a randomized double blind clinical trial.

BACKGROUND: Surgical injury leads to postoperative pain hypersensitivity preceded by central nervous sensitization, due to lowered pain threshold in peripheral nociceptors and increased excitability of the spinal neurons. Pre-emptive analgesia is intended to decrease pain perception and overall analgesic need by use of drug regimen seizing central nervous system sensitization before exposure to painful stimuli. Earlier, few studies support pre-emptive analgesic efficacy of novel antiepileptic agent gabapentin. But topiramate and lamotrigine though proven analgesic in animal models of chronic pain and clinical studies of gabapentin resistant neuropathic pain; literature search revealed scarce data on its pre-emptive analgesic efficacy. The present study is designed to study and compare the pre-emptive analgesic efficacy of lamotrigine, topiramate and gabapentin (as control) in postoperative pain control. METHODS: This randomized clinical trial included 90 patients of either sex, between 18 and 70 years undergoing major surgeries. Patients were randomly allocated into control and test groups and received respective treatment 30 min before induction of anesthesia. Aldrete's score and pain score were recorded using visual analogue scale and facial and behavioral rating scales at awakening and at 1, 2, 4, 6 and 24 h. Postoperative rescue analgesic consumption for 24 h was recorded. Data were analyzed using OpenEpi and SciStatCalc statistical softwares. RESULTS: Significantly higher pain scores were observed in the topiramate group postoperatively for 2 h on all pain scales (p<0.05). Lamotrigine-treated patients were more comfortable throughout the study with significantly less (p<0.05) postoperative analgesic requirement comparable to gabapentin. CONCLUSIONS: Study results are strongly suggestive of pre-emptive analgesic efficacy of single oral dose lamotrigine comparable to gabapentin and superior to topiramate in postoperative pain control.

Comparative Pre-Emptive Analgesic Efficacy Study of Novel Antiepileptic Agents Lamotrigine and Topiramate in Patients Undergoing Major Surgeries at a Tertiary Care Hospital: A Randomized Double Blind Clinical Trial.

BACKGROUND: Central nervous sensitization, following surgical injury, leads to postoperative pain hypersensitivity due to lowered pain threshold in peripheral nociceptors and increased excitability of spinal neurons. Pre-emptive analgesia is intended to decrease pain perception and overall analgesic need by use of drug regimen, seizing CNS sensitization before exposure to painful stimuli. Few studies support pre-emptive analgesic efficacy of novel antiepileptic agent Gabapentin. Though Topiramate and Lamotrigine have been proven analgesic in animal models of chronic pain and clinical studies of Gabapentin-resistant neuropathic pain, literature search revealed scarce data on its pre-emptive analgesic efficacy. PURPOSE: This study is designed to study and compare the pre-emptive analgesic efficacy of Lamotrigine, Topiramate, and Diclofenac sodium in postoperative pain control. METHODS: This randomized clinical trial included 90 patients of either sex, between 18 and 70 years undergoing major surgeries. Patients were randomly allocated to control and test groups and received respective treatment 30 min before induction of anesthesia. Aldrete's and pain scores were recorded using the Visual Analog Scale, Facial and Behavioral Rating Scale at awakening and at 1, 2, 4, 6, and 24 h. Postoperative rescue analgesic consumption for 24 h was recorded. RESULTS: Significantly higher pain scores were observed in the Topiramate group postoperatively for 2 h on all pain scales (p < 0.05), whereas in the control group it was significantly higher at 1 h (p < 0.05). Lamotrigine-treated patients were more comfortable throughout the study with significantly less (p < 0.05) postoperative analgesic requirement. CONCLUSIONS: Study results strongly suggest the pre-emptive analgesic efficacy of a single oral dose of Lamotrigine over Diclofenac and Topiramate in postoperative pain control.

A Retrospective Study of Drug Induced Cutaneous Adverse Reactions (CADR) in Patients Attending Tertiary Care Hospital.

OBJECTIVES: Find possible causative agents causing cutaneous adverse reactions; clinical patterns, causality and severity of Drug induced cutaneous adverse reactions (CADR) and treatment outcome. METHODS: Retrospective study was undertaken including cases of CADR. Causality, preventability and severity of Drug Induced cutaneous reactions were judged with the use of Naranjo's algorithm, WHO causality scale, modified Schumock and Thorton scale, and Hartwig's scale respectively. RESULTS: Among 275 total cADRs reported, Antimicrobials (46.55%) were the main drugs involved followed by Non steroidal anti-inflammatory drugs (NSAIDs) (25.09%) and Antifungal (9.82%). Urticaria (63.64%)followed by Erythema multiform(12.36%) was most frequently observed CDRs. Amongst all cADRs 50.18% were certain according to Naranjo's scale, none of them were preventable according to modified Schumock and Thorton scale. All reactions were moderate according to Hartwig's severity scale. CONCLUSION: It was observed that antibiotics and NSAIDs cause maximum number of CADRs. Therefore strict vigilance is required while using them. 
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A Randomized Double-Blind Placebo-Controlled Study to Compare Preemptive Analgesic Efficacy of Novel Antiepileptic Agent Lamotrigine in Patients Undergoing Major Surgeries.

BACKGROUND: If postoperative acute pain remains unrelieved, it may result in significant morbidity and mortality. Preemptive analgesic initiated before surgery offers premature analgesia even before exposure to an initial noxious stimulus bestowing effective postoperative analgesia. In developed countries, it is regularly practiced as a part of well-defined protocol. In our country however, only a few centers practice it and that too irregularly and with undefined protocol. Few studies support preemptive analgesic efficacy of novel antiepileptic agent gabapentin. Though lamotrigine is a proven analgesic in animal models of chronic pain and clinical studies of gabapentin-resistant neuropathic pain, a literature search revealed scarce data on its preemptive analgesic efficacy. AIMS: The present study is designed to study the preemptive analgesic efficacy of lamotrigine in comparison with diclofenac sodium in postoperative pain control. MATERIALS AND METHODS: This randomized clinical trial included 90 patients of both sexes, between 18 years and 70 years undergoing major surgeries. Patients were randomly allocated into placebo, control, and test groups and received the respective treatment 30 min before the induction of anesthesia. Aldrete score and pain score were recorded using visual analog scale (VAS), facial rating scale (FRS), and behavioral rating scale (BRS) at awakening and at 1 h, 2 h, 4 h, 6 h, and 24 h. Postoperative rescue analgesic consumption for 24 h was recorded. RESULTS: Significantly higher pain scores were observed in the placebo group postoperatively for 2 h on all pain scales (P < 0.05), whereas in the control group it was significantly higher at 1 h (P < 0.05). The test group patients were more comfortable throughout the study and postoperative analgesic requirement was significantly less (P < 0.05). CONCLUSIONS: The study recommends the use of single oral dose lamotrigine as preemptive analgesic for effective postoperative pain control.

Antidepressant-like activity of flunarizine in modified tail suspension test in rats.

BACKGROUND: Flunarizine, a Ca(2+) channel blocker, crosses blood brain barrier (BBB), antagonizes calcium influx and interferes with neurotransmitter system. Flunarizine 20 mg/kg exhibited significant antidepressant activity in our previous study using forced swim test (FST) in mice, which was contradictory to the findings of other authors. Hence, the present study was designed to strengthen the results of our previous study, using the modified tail suspension test (TST) in rats. AIM: Aim of this study was to evaluate the antidepressant activity of flunarizine versus standard antidepressant drug fluoxetine in modified TST in rats. MATERIALS AND METHODS: The study approved by Institutional Animal Ethics Committee was conducted using 24 adult albino rats (n = 6 in each group). Antidepressant effect of normal saline (0.1 ml/100 g), fluoxetine (10 mg/kg, intraperitoneally (ip)), and flunarizine (2 and 10 mg/kg, ip) was evaluated by using modified TST in rats. Thirty minutes after administration of all test drugs the duration of immobility was recorded for a period of 5 min in all rats by using modified TST. The data was analyzed by Student's t-test and one-way analysis of variance (ANOVA) and P < 0.05 was considered significant. RESULTS: Mean duration of immobility was significantly reduced in fluoxetine and flunarizine (10 mg/kg, ip) group as compared to the normal saline, that is, 160.33, 175.17, and 226.83 s, respectively (P < 0.05). Decrease in immobility with flunarizine (10 mg/kg, ip) was statistically significant compared with normal saline, but was not found to be significant when compared to fluoxetine (P > 0.05). Also, currently used human dose of flunarizine when extrapolated to rats (i. e., 2 mg/kg, ip) failed to show significant antidepressant effect in modified TST in rats. CONCLUSION: The results of the present study indicate antidepressant-like activity of flunarizine.

A comparative study to evaluate the cardiovascular risk of selective and nonselective cyclooxygenase inhibitors (COX-Is) in arthritic patients.

BACKGROUND: During the past 2 years, a great deal of evaluation has been accomplished on the cardiovascular (CV) effects of nonsteroidal anti-inflammatory drugs (NSAIDs), nonselective and selective cyclooxygenase-2 inhibitors (COX-2-Is). Clinical trial databases for nonselective and selective COX-2-Is have shown variable effects on CV risk. There is much controversy regarding the CV safety of these selective and nonselective COX inhibitors (COX-Is). This study was therefore conducted to assess and compare the CV risk of COX-Is in arthritic patients over a period of time. METHODS: In this prospective comparative study, adult arthritics of either sex who were freshly diagnosed or taking COX-Is for <3 months were included. Patients were grouped into nonselective and selective COX-2-I groups with reference to the treatment they received, whereas arthritics with no history of COX-I treatment were included as controls. CV risk factors like blood pressure (BP), blood sugar level (BSL), lipid profile, and body mass index (BMI) were assessed and compared; the demography of CV risk factors was also studied. Data obtained were analyzed with Student's t-test using OpenEpi statistical software (Andrew G. Dean and Kevin M. Sullivan, Atlanta, GA, USA). RESULTS: The study clearly revealed that all NSAIDs exhibit potential CV risk; however, selective COX-2-Is were found to exhibit more CV risk. BMI, BP and lipid profile, the potential CV risk factors, showed significant impairment in a selective COX-2-I group: p<0.01, p<0.001 and p<0.05, respectively, vs. baseline and p<0.05 for BMI and triglycerides vs. nonselective COX-Is. CONCLUSIONS: This study depicts the impending CV risk of selective COX-2-Is and confirms and reevaluates the results of earlier studies in this regard.

Randomized, double-blind, placebo-controlled study to investigate the pharmacodynamic interaction of 5-HT3 antagonist ondansetron and paracetamol in postoperative patients operated in an ENT department under local anesthesia.

BACKGROUND: The preclinical incision pain models and clinical studies in healthy volunteers have demonstrated the central serotonergic analgesic mechanism, paracetamol analgesia. This has been evidenced by raised serotonin concentrations in the brain following paracetamol administration in a few studies. The inhibition of paracetamol analgesia by 5-HT3 antagonists suggests that this analgesia is 5-HT3 mediated. However, in a few studies, 5-HT3 antagonists themselves exhibited an analgesic action. Various studies in this context stated intricate results. The present study was intended to understand the pharmacodynamic interaction between paracetamol and ondansetron in postoperative patients. METHODS: This randomized clinical trial included 32 postoperative cases of either sex, ages between 18 and 70 years. The patients were randomly allocated into the placebo and test groups and received respective treatment at the end of surgery. The pain score was recorded using Visual Analogue Scale (VAS) and Face, Legs, Activity, Cry, Consolability (FLACC) behavioral scale at awakening and every 30 min for the next 3 h. The postoperative rescue analgesic consumption for 24 h was recorded. The data were analyzed using OpenEpi and SciStatCalc statistical software. RESULTS: A significantly higher pain score was observed in the placebo group postoperatively for 60 min on VAS (p<0.05 and p<0.01), whereas the FLACC behavior scale score was significantly higher at 120 and 150 min (p<0.05). The test group patients were more comfortable throughout the study, and the postoperative analgesic requirement was significantly lesser (p<0.05). CONCLUSIONS: The pharmacodynamic interaction between paracetamol and ondansetron coadministration does not block but instead increase paracetamol analgesia, reduce the postoperative analgesic requirement, and improve the postoperative comfort level.

A cohort study to evaluate cardiovascular risk of selective and nonselective cyclooxygenase inhibitors (COX-Is) in arthritic patients attending orthopedic department of a tertiary care hospital.

BACKGROUND: Cyclooxygenase-2 inhibitors (COX-2-Is) have recently been concerned in the occurrence of adverse cardiovascular (CV) events. Rofecoxib and valdecoxib has been withdrawn from the market, but celecoxib, etoricoxib and parecoxib continues to be used. Other nonsteroidal anti-inflammatory drugs (NSAIDs) may also increase the risk of CV events. However, clinical trial databases for COX-2-Is had created lots of controversies regarding cardiovascular safety of selective and nonselective cyclooxygenase inhibitors (COX-Is). This study was, conducted to assess and compare the CV risk of COX-Is in arthritic patients over a period of time. MATERIALS AND METHODS: In this prospective cohort study adult arthritics of either sex those were freshly diagnosed or taking COX-Is for < 3 months; were included. Patients were grouped into nonselective and selective COX-2-I groups with reference to treatment they received. The CV risk factors like blood pressure (BP), blood sugar level (BSL), lipid profile, body mass index (BMI) were assessed and compared; demography of CV risk factors was also studied. Data obtained was analysed using Student's 't'-test of OpenEpi statistical software. RESULTS: Study clearly revealed that all NSAIDs exhibit variable CV risk; however, selective COX-2-Is found to exhibit more CV risk. BMI, BP and lipid profile; the potential CV risk factors, showed significant impairment in selective COX-2-Is group; P < 0.01, P < 0.001 and P < 0.05, respectively, compared to baseline and P < 0.05 vs. nonselective COX-Is for BMI. CONCLUSIONS: This study portrays the potential CV risk of selective COX-2-Is; confirms and re-evaluate the results of earlier studies in this regard.

Attitude, perception and feedback of second year medical students on teaching-learning methodology and evaluation methods in pharmacology: A questionnaire-based study.

BACKGROUND: To assess the student's attitude, perception and feedback on teaching-learning methodology and evaluation methods in pharmacology. MATERIALS AND METHODS: One hundred and forty second year medical students studying at Smt. Kashibai Navale Medical College, Pune, were selected. They were administered a pre-validated questionnaire containing 22 questions. Suggestions were also asked regarding the qualities of good pharmacology teachers and modification in pharmacology teaching methods. Descriptive statistics were used and results were expressed as percentage. RESULTS: Majority of the students found cardiovascular system (49.25%) as the most interesting topic in pharmacology, whereas most of the students opined that cardiovascular system (60.10%), chemotherapy (54.06%) and central nervous system (44.15%) are going to be the most useful topics in internship. 48.53% students preferred clinical/patient-related pharmacology and 39.13% suggested use of audiovisual-aided lectures. Prescription writing and criticism of prescription were amongst the most useful and interesting in practical pharmacology. Students expressed interest in microteaching and problem-based learning, whereas seminars, demonstrations on manikin and museum studies were mentioned as good adjuvants to routine teaching. Multiple Choice Question (MCQ) practice tests and theory viva at the end of a particular system and periodical written tests were mentioned as effective evaluation methods. Students were found to have lot of interest in gathering information on recent advances in pharmacology and suggested to include new drug information along with prototype drugs in a comparative manner. CONCLUSION: There is a need of conducting few microteaching sessions and more of clinical-oriented problem-based learning with MCQ-based revisions at the end of each class in the pharmacology teaching at undergraduate level.

Effect of aqueous extracts of Achyranthes aspera Linn. on experimental animal model for inflammation.

BACKGROUND: Achyranthes aspera is known as Chirchita (Hindi), Apamarga (Sanskrit), Aghedi (Gujarati), Apang (Bengali), Nayurivi (Tamil), Kalalat (Malyalam) and Agadha (Marathi) in our country. It possesses valuable medicinal properties and used in treatment of cough, bronchitis and rheumatism, malarial fever, dysentery, asthma, hypertension and diabetes in Indian folklore. Present study was designed to evaluate anti-inflammatory activity of an aqueous extracts of Achyranthes aspera (AEAA). MATERIALS AND METHODS: AEAA leaves and whole plant (i.e. Aqueous extracts of Achyranthes aspera leaves (AEAAL)/Aqueous extracts of A. aspera whole plant (AEAAW) were studied in albino mice using carrageenan induced left hind paw edema. Both extracts were subjected to preliminary phytochemical analysis and acute toxicity of the extracts was also studied using Organization for Economic Co-operation and Development OECD guidelines 423. RESULTS: Acute toxicity study confirmed toxic dose of AEAA to be more than 2,000 mg/kg. Flavonoids, alkaloids, saponins and triterpenoids were the major constituents found in extracts. AEAA reduced the edema induced by carrageenan by 35.71-54.76% on intraperitoneally administration of 400 mg/kg and 800 mg/kg as compared to the untreated control group. Diclofenac sodium at 10 mg/kg inhibited the edema volume by 42.85%. The results indicated that the AEAA 800 mg/kg body weight shows more significant (P < 0.01, P < 0.001) anti-inflammatory activity when compared with the standard and untreated control respectively. CONCLUSION: Both AEAA exhibit promising anti-inflammatory activity attributed to flavonoids, alkaloids, saponins and triterpenoids phytoconstituents.

Study of central nervous system depressant and behavioral activity of an ethanol extract of Achyranthes aspera (Agadha) in different animal models.

BACKGROUND: Achyranthes aspera Linn., an indigenous herb, has been reported to have antifertility, antihyperlipidemic, antidiabetic, immunomodulatory, anticarcinogenic, diuretic, cardiotonic, analgesic anti-inflammatory, hypnotic, antifungal, antibacterial, and central antinociceptive activities. AIMS: This study was designed to evaluate depressant effects on central nervous system (CNS) and behavioral effects of ethanol extract of A. aspera (EEAA) and to find the phytochemical responsible for these activities. MATERIALS AND METHODS: The pharmacological assays used to study CNS depressant effect in albino mice were rota rod and actophotometer performance test. Effects on behavioral activity were studied using open field test. The extract was given intraperitoneally (i.p.) at a dose of 400 mg/kg. Diazepam (2 mg/kg body weight i.p.) was used as standard. STATISTICAL ANALYSIS USED: Data were analyzed by using analysis of variance followed by Dunnett's test. P < 0.05 was considered significant. RESULTS: Phytochemical screening revealed presence of triterpenoids, saponins, alkaloids (betaine, achyranthine), and steroids as major constituents. The result of this study reflected that EEAA (400 mg/kg i.p.) decreased locomotor activity, produced muscle relaxation, and showed anxiolytic activity. CONCLUSIONS: EEAA exhibit CNS depressant and significant anxiolytic activity comparable to diazepam.

Study of CNS depressant and behavioral activity of an ethanol extract of Achyranthes Aspera (Chirchita) in mouse model.

BACKGROUND: Achyranthes Aspera Linn., known as Chirchira (Hindi), Agadha (Marathi) is an indigenous herb found in India. The herb has been reported to have variety of activities like antifertility, antihyperlipidemic, antidiabetic, immunomodulatory, anticarcinogenic, diuretic and cardiotonic, analgesic, anti-inflammatory, hypnotic, antifungal and antibacterial activity. It has been also reported to have central anti-nociceptive activity in thermal induced pain methods in our earlier studies. We wanted to study its neuropharmacological effects, which may throw light on understanding the underlying mechanism for its central activity. PURPOSE: The present study was designed to evaluate CNS depressant and behavioral effects of A. Aspera extract and to study the phytochemical responsible for these activities with possible mode of action. METHODS: The effects on behavioral activity was studied using open field test (OFT). The extract was given intraperitoneally at a dose of 400 mg/kg. Diazepam (2mg/kg body weight i.p.) was used as standard. Data was analyzed by ANOVA test followed by Dunnett's test. All the results were expressed as Mean (±SEM). P <0.05 was considered significant. RESULTS: Phytochemical screening revealed presence of triterpenoids, saponins, alkaloids (betaine, achyranthine) and steroids as major constituents. The result of the study demonstrated that ethanol extract of A. Aspera (400 mg/kg i.p.) decreased locomotor activity, produced muscle relaxation and showed antianxiety activity. CONCLUSIONS: Ethanols extract of A. Aspera exhibit CNS depressant action and significant anxiolytic activity comparable to diazepam.

A comparative study of the glycemic control of various antidiabetic agents and the role of homocysteine in the therapy of type 2 diabetes mellitus.

OBJECTIVES: The objectives of this study were to evaluate and to compare the glycemic control of various antidiabetic agents and the role of homocysteine in type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: Two hundred forty patients with type 2 diabetes mellitus, divided into Groups 1-6 (n=40), received glipizide, glipizide-SR, glimepiride, glibenclamide, metformin, and insulin followed by an oral hypoglycemic agent, respectively. They were evaluated with respect to glycemic control, serum insulin, safety, and quality of life (QoL) for 24 weeks. Furthermore, poorly controlled patients with elevated serum homocysteine were divided into two groups, of which received folic acid for 4 weeks. RESULTS: Glipizide-SR significantly improved glycemic control at lower serum insulin levels, was well tolerated, and improved QoL. Metformin improved glycemic control and reduced insulin resistance in obese type 2 diabetes mellitus patients. Initial insulin therapy led to rapid reduction in hyperglycemia with reduced insulin resistance. Folic acid therapy significantly (P<.001) lowered elevated serum homocysteine levels in poorly controlled patients. CONCLUSIONS: Glipizide-SR emerged as the sulfonylurea of choice in lean type 2 diabetes mellitus patients, while metformin was preferable for obese type 2 diabetes mellitus patients. Short-course insulin therapy with subsequent oral hypoglycemic agent could obviate the need for continuous insulin therapy in poorly controlled type 2 diabetes mellitus patients. Folic acid constitutes an inexpensive and safe therapy for hyperhomocysteinemia in patients with type 2 diabetes mellitus.

Chronotherapeutic dose schedule of phenytoin and carbamazepine in epileptic patients.

The objective of this study was to compare the efficacy and safety of a chronotherapeutic dosing schedule of phenytoin and carbamazepine versus a conventional dosing schedule for the treatment of tonic-clonic epileptic patients. Of 148 epileptic subjects found to have subtherapeutic trough drug levels (subtherapeutic group, STG), 103 subjects who completed the study were randomized to either STG I (n=51) for treatment by the conventional dosing schedule (tablet phenytoin 100-400 mg/day OD or BD, tablet carbamazepine 200-800 mg BD, or both, equally divided doses with no fixed time of drug intake), with a dose increment but no change in usual time of drug administration allowed; or to STG II (n=52), with no dose increment permitted but a shift in all or most (two-thirds or three-fourths) of the daily dose of one or both medications to 20:00 h. The 62 patients who experienced drug toxicity reactions (toxicity group, TG) and who had serum drug levels in the toxic range were assigned to TG I for dose reduction or TG II for dose reduction and drug administration at 20:00 h. Those 16 subjects in STG I and 47 subjects in STG II who initially evidenced subtherapeutic trough drug concentrations exhibited therapeutic drug levels by the end of four weeks of treatment (p<0.01). A significantly greater number of TG II, as compared to TG I, subjects who experienced toxic reactions showed improved drug tolerance. There were no poor responders and more good responders (control of epilepsy for one year) in STG II compared to STG I subjects. The findings of this study indicate that a chronotherapeutic dosing schedule of phenytoin and carbamazepine involving the administration of most or all the daily dose of medication(s) at 20:00 h can improve the response of diurnally active epileptic patients not responding to standard doses, achieve therapeutic drug levels, and reduce toxic manifestations in subjects having drug concentrations beyond the therapeutic range.

Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 levels in acute myocardial infarction.

The cause of the circadian variation in the incidence of acute myocardial infarction (AMI) has not been identified. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) have opposing effects on thrombi. Hence, the extent of the clot, the size of the infarct and outcome of patients could depend on t-PA and PAI-1 levels. In an effort to elucidate the pathophysiologic basis of circadian variation of AMI, we investigated the presence of a possible corresponding circadian variation in the levels of endogenous t-PA and PAI-1 in patients diagnosed to have AMI and the effects of hypertension, diabetes and site of the infarct on these levels. We estimated the levels of t-PA and PAI-1 in platelet-poor plasma of 42 patients with AMI on admission, using the enzyme-linked immunosorbant assay. Although not statistically significant, patients having an AMI in the morning hours had the highest t-PA:PAI-1 ratio. The normal circadian variation in PAI-1 levels was lost in patients with AMI, probably due to the disease process. Also, the t-PA levels in hypertensive patients were significantly lower than in nonhypertensives. PAI-1 levels were also significantly lower in patients with anteroseptal than in inferior and anterolateral AMI. This relationship between the fibrinolytic potential and the site of infarction needs further study. Furthermore, t-PA levels on admission were significantly lower in survivors and may have a predictive value in determining the outcome.

Immunomodulatory activity of septilin, a polyherbal preparation.

Septilin is a polyherbal preparation, claimed to be effective in conditions such as chronic stubborn URTI, tonsillitis, cutaneous infections, dental infections and also prescribed as a health supplement. In view of this, the present experimental study was undertaken to evaluate the effect of Septilin on different arms of the immune system. The experimental animals (male albino rats and mice) were divided into three groups. Group I received distilled water; group II received Septilin in a dose of 1 g/kg (rats) or 1.5 g/kg (mice); group III received Septilin 2 g/kg (rats) or 3 g/kg (mice) orally for 28 days. They were evaluated for immunological function on day 29 by studying weight gain, resistance against E. coli sepsis, haemogram, phagocytic activity of PMN cells and reticuloendothelial system, delayed hypersensitivity to oxazolone and the plaque forming cell response of splenic lymphocytes to sheep erythrocytes. Neither of the doses of Septilin altered weight gain, absolute lymphocyte counts, or host resistance against E. coli sepsis. The higher dose of Septilin reduced phagocytic activity of the PMN cells/reticuloendothelial system, but both doses increased the percentage and absolute number of circulating neutrophils, stimulated humoral immunity and suppressed cellular immunity. Thus, Septilin has dual effects on the immune system, with lower doses showing greater stimulant and higher doses showing predominantly suppressant effects.