The effect of different adrenergic blockers on pulmonary edema induced by trauma to skull have been studied in mice. Propranolol (beta blocker) prevented pulmonary edema induced by trauma to skull whereas tolazoline (alpha blocker) as well as guanathedine (adrenergic neuron blocker) did not prevent pulmonary edema. Since propanolol is not having the property to prevent the increase of pulmonary capillary pressure induced by sympatho-adrenal storm due to trauma to skull. possibly It might have prevented the Pulmonary edema by blocking the primary increase of capillary permeability.

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The ICH harmonised tripartite guidelines for good clinical practice, the WHO guidelines for good clinical practice for trials on pharmaceutical products and the FDA's Code of Federal Regulations require that source data verification must be undertaken for all clinical trials in phases I-IV. SDV, which is an evaluation of the conformity of the data presented in case report form with source data, is conducted to ensure that the data collected are reliable and allow reconstruction and evaluation of the study. The responsibilities of the principal investigator, sub-investigator, study coordinator, monitor, quality assurance auditor and the clinical trial manager in SDV must be made clear at the outset of the clinical trial and adequate training should be provided to the personnel involved. Special emphasis should be placed on direct access to data and confidentiality, so that there are no misunderstandings and errors when SDV is undertaken. Meticulous recording of what was done and found, including an evaluation of the findings, must be made to arrive at an indication whether the errors are random or systematic errors and are arising due to carelessness or deliberate actions. All personnel involved must realize that SDV adds to the scientific and ethical integrity of the clinical trial. This review highlights the various aspects governing the conduct, extent, difficulties and stream lining of the process of SDV and gives some suggestions for fast and effective SDV avoiding the common pitfalls observed by the clinical trial monitors.

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Objective: To investigate whether nimodipine (NM), a cerebrovascular selective Ca2+ antagonist, potentiates the anaesthetic effects of ethanol, pentobarbitone and ketamine in rats. Methods: Groups of overnight fasted albino rats received either ethanol (2.5 ml/100g, 25% solution, p.o.), or pentobarbitone (30 mg/kg, i.p.) or ketamine (50 mg/kg, i.p.) along with vehicle (n= 10 in each group). In another experiment, groups of animals were pre-treated with NM (10 mg/kg, i.p.) along with either one of ethanol, pentobarbitone or ketamine. Animals were assessed for loss of righting reflex. The onset and duration of anaesthetic effect in all groups was recorded. Effect of NM alone (10,20 and 40 mg/kg, i.p.) was also observed in normal rats. Results: NM significantly (p <0.01) potentiated the anaesthetic effects of ethanol, pentobarbitone and ketamine in rats. NM pretreatment reduced the onset while prolonged the duration of anaesthetic effects of these agents. NM itself failed to produce any anaesthetic effect. Conclusion: Potentiation of anaesthetic effects of ethanol, pentobarbitone and ketamine by NM may be at least in part, due to modulation of voltage dependent Ca2+ channels.

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Objectives: To evaluate whether Trichopus zeylanicus (active fraction) influences (1) phagocytosis by mice peritoneal macrophages (2) antibody dependent complement mediated cytotoxicity to Ehrlichs ascitic carcinoma (EAC) cells and (3) humoral antibody response in mice. Methods: Phagocytosis of opsonized sheep RBC by peritoneal macrophages obtained from control or T. zeylanicus (active fraction) treated (10-40 mg/kg, daily, p.o., 5 days) mice was determined. The in vitro effect of the drug on macrophage phagocytosis was also studied. The effect of the drug on antibody dependent and complement mediated toxicity (ACC) to EAC cells was carried out using antiserum obtained from drug treated ( p.o., daily for 5 days) mice which were challenged with or without EAC cells. The effect of the drug on humoral immune response in mice was studied by measuring haemagglutination antibody titre and Jerne's plaque forming assay using sheep RBC as antigens. Results: The drug treatment to mice resulted in stimulation of phagocytosis by peritoneal macrophages; but in vitro treatment to macrophages did not influence their phagocytic efficacy. The drug treatment enhanced ACC, haemagglutinating antibody titre and the number of antibody producing spleen cells in mice. Conclusion: The drug stimulates macrophage phagocytosis in mice; but not under in vitro conditions. The drug also enhances ACC mediated cancer cell killing and humoral antibody response in mice.

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Objective: To study the effectiveness of famotidine and sucralfate in the prophylaxis of stress ulcers and upper gastrointestinal bleed in patients of head injury. Methods: Seventy five consecutive patients, who had sustained head injury within the previous 24 hours, were randomly allocated to three groups to receive either no regular prophylactic anti-ulcer treatment (Group I) or prophylactic famotidine (FM) 20 mg twice daily (Group II) or prophylactic sucralfate (SC) 2 g twice daily (Group III). Escape anti-ulcer treatment was allowed in case of three positive tests for occult blood in nasogastric aspirate. Results: Incidence of upper gastro-intestinal bleeding was significantly lower in group II (p < 0.05) as compared to groups I and II. A higher incidence of bleeding was seen in patients with lower Glasgow Coma Scale (GCS) scores, particularly in those receiving no prophylactic treatment (Group I), against which both famotidine and sucralfate were not effective. The most commonly observed type of bleeding was occult bleeding. Both famotidine and sucralfate decreased the Grade Day Product significantly, famotidine being more effective than sucralfate. Conclusion: Famotidine is more effective than sucralfate in preventing and controlling stress-related upper gastrointestinal haemorrhage of moderate intensity in patients of head injury.

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Objective: The effects of Bonny light crude oil on the smooth and skeletal muscles contraction and pain were investigated. Methods: Analgesic effect of Bonny light crude oil was tested in mice using acetic acid (0.75%)- induced writhing model. Its effects on histamine-, and Ach-induced smooth muscle contraction were studied in guinea pig ileum. The effects of crude oil on Ach-induced contraction of rat duodenum and frog rectus abdominis muscle were also studied. Results: The crude oil caused complete inhibition of histamine - induced smooth muscle contraction, while producing only a partial inhibition of the acetylcholine - induced contraction. It had no effects on the acetylcholine-induced skeletal muscle contraction, but showed good analgesic effect comparable to aspirin. Conclusion: The Bonny light crude oil possesses inhibitory action on smooth muscle contraction induced by histamine, and analgesic property.

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Objective: To probe whether locomotor activity (LA) affects passive avoidance response (PAR) in mice Methods: PAR and LA were studied in mice treated with known amnesic (scopolamine, diazepam) and nootropic (piracetam, Bacopa monniera extract) drugs. For PAR, the step-down latency (SDL), step-down errors (SDE) and time spent in shock zone (TSZ) were measured. A videopath analyzer was used for recording LA. Results: An increase in LA augmented SDE scores and vice-versa, indicating a direct correlation. No such correlation was seen between LA and the other two parameters viz SDL and TSZ. The latter increased with amnesic agents and decreased in nootropic treated animals. Conclusion: LA affects parameters for evaluation of cognitive function by the PAR test. TSZ appears to be the best indicator for nootropic/amnesic activity.

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The D2 dopamine receptor antagonism of antipsychotic drugs and their ability to upregulate striatal D2 sites are the corner stones of the dopaminergic hypothesis of schizophrenia. The question of the role of D2 receptors in schizophrenia, however, has been reopened by the development of clozapine, which, while being the best known antipsychotic medication has low affinity for most subtypes of D2 receptor class. To explain this atypical action of clozapine, involvement of many other receptor subtypes namely 5-HT2 , D1 , D5 and D4 has been postulated. However, most studies hitherto, have not been able to demonstrate any direct involvement of these other receptor subtypes in the action of atypical antipsychotics. The most popular theory to explain the atypical nature of the newer antipsychotics is, their selectivity for the dopamine receptors in limbic area, as compared to the nigrostriatal area of the CNS. Thus, D2 receptor occupancy measurements still provide the best predictor of antipsychotic response, extrapyramidal side effects and elevation of prolactin levels.

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Objective: To find out the possible role of lipid peroxidation and glutathione in the pathogenesis of myocardial infarction and the protective role of Abana, a polyherbal drug. Methods: The effect of Abana pretreatment (75 mg /100 g ) for a period of 60 days on isoproterenol (20 mg/100g s.c. twice at an interval of 24 hrs) induced lipid peroxidation was studied in rats. Marker enzymes levels such as creatine kinase, lactate dehydrogenase, alanine transaminase and aspartate transaminase were assessed in serum and heart homogenate. Glutathione content and lipid peroxide level were also estimated. Results: In isoproterenol administered rats, a significant decrease was observed in the levels of marker enzymes in the heart with a corresponding increase in their levels in serum. Lipid peroxide level measured in terms of "TBA reactants" increased significantly in serum and heart. In rats pretreated with Abana, the alterations observed in the marker enzymes and lipid peroxide level were minimum on isoproterenol administration, and the levels were retained at near normal values. Conclusion: Abana pretreatment may offer protection in experimental myocardial infarction induced by isoproterenol.

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Objectives: To entrap methotrexate (MTX) in thermosensitive liposomes, to characterise liposomes for different physicochemical properties and to investigate the potential of liposome entrapped MTX and localised hyperthermia (HT) in management of melanoma B16F1. Methods: Thermosensitive liposomes, made of synthetic lipids (distearoylphosphatidylcholine, DSPC and dipalmitoyl phosphatidyl choline, DPPC) showing gel to liquid phase transition at 41o C, were used for encapsulation of methotrexate. The liposomes were prepared by reverse phase evaporation method. The entrapment efficiency of the drug within the liposomes was determined by gel filtration on Sephadex G-50 column. The in vitro release studies of the vesicles were conducted by incubating the drug encapsulated liposomes in saline at various temperatures for 15 min. The vesicle stability was assessed by storage at room temperature, 37o C and under refrigeration (4o C) for a period of three months. The MTX containing liposomes were administered intravenously to C57BL/6J mice bearing melanoma B16F1 tumour at 12 mg kg-1 dose. Immediately after the drug administration, localised hyperthermia treatment was applied by placing the tumours in water bath at 43o C either for 30 min. or 1 hr. The volume doubling time and growth delay of the tumour were taken as parameters to assess the antitumour efficacy. Results: The thermosensitive liposomes encapsulated about 52% of the MTX. Comparison of the drug release profile at various temperatures revealed that maximum drug release (83%) occurred at 42o C compared to less than 5% release at 37o C. Better stability on storage was also observed with thermosensitive MTX liposomes. The thermosensitive liposomes and localised hyperthermia produced an improved anticancer activity as evident by enhanced volume doubling time and growth delay. Conclusion: These results suggest that localised hyperthermia in combination with temperature sensitive liposome encapsulated MTX may serve as a useful targeted drug delivery system for more effective management of melanoma B16F1.

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Objective: To evaluate the cardioprotective actions of two angiotensin converting enzyme (ACE) inhibitors, enalapril and lisinopril on myocardial infarction in normal and salt loaded rats. Methods: Myocardial infarction was produced by occlusion of left coronary artery for 30 minutes followed by 4 hours of reperfusion. Infarct size was measured by using triphenyl tetrazolium chloride (TTC) stain method. Results: Infarct size, expressed as percent myocardial infarction (PMI) was found to be 34.84 with untreated control animals, whereas PMI was significantly reduced to 14.78 and 13.54 with enalapril (3 mg/kg) and lisinopril (3 mg/kg) pretreatment respectively. In salt loaded animal groups, PMI was found to be 37.20 with control untreated and reduced to 13.41 with enalapril pretreatment (3 mg/kg) and 13.19 with lisinopril pretreatment (3 mg/kg) respectively. Conclusion: The results suggest a possible cardioprotective role for ACE inhibitors.

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Objective: To investigate the role of central nitrinergic system in Brewer's yeast induced peripheral inflammation in rats. Methods: Permanent icv cannulation in rats was performed stereotaxically into the right lateral ventricle under ketamine hydrochloride anaesthesia. NO modulators viz NO synthase inhibitors, NO precursor, NO donors and NO scavengers were administered icv 30 min prior to induction of paw oedema by injecting 0.1 ml of 20% (W/V) Brewer's yeast below the planter aponeurosis of hind paw in rats. Paw volume up to the ankle joint was recorded plethysmographically. Results: NO synthase inhibitors and NO scavenger haemoglobin (Hb) were found to be potent inhibitors of paw volume increase in the late phase (1-5 h) than early period (15-60 min). NO donors SIN-1, SNP and NO precursor L-arginine were found to increase the oedema volume. D- arginine and methylene blue were without any effect. Conclusion: Central nitrinergic system modulates the Brewer's yeast induced peripheral inflammation in rats. Both endogenous and exogenous NO are involved in the inflammatory process.

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Objective: To evaluate the effect of pretreatment of CNS specific calcium channel blockers (CCB) nimodipine and nitrendipine on some dopaminergically mediated behaviours like haloperidol induced catalepsy, methamphetamine induced stereotypy and conditioned avoidance response. Methods: Catalepsy was induced by haloperidol (1mg/kg, i.p.) and scoring was done by the method of Costall and Naylor. Catalepsy score of each rat in the group (n=10) was taken to compute mean value. Onset time was noted. Similarly stereotypy was induced by methamphetamine (5 mg/kg, i.p.) and scoring was done by the method of Watanbe et al and effect on conditioned avoidance response (CAR) was noted using Cook's pole climbing apparatus. Test drugs nimodipine (4, 8 mg/ kg, i.p.) and nitrendipine (2.5, 5 mg/kg, i.p.) were given 1 hr. prior to the experiment. Results: Nimodipine (4, 8 mg/kg, i.p.) and nitrendipine (2.5, 5 mg/kg, i.p.) reduced the onset of haloperidol induced catalepsy and potentiated catalepsy at different time intervals. Onset of methamphetamine induced stereotypy was delayed and score was inhibited significantly. There was blockade of CAR but unconditioned response was not affected by these drugs in the doses used in this experiment. Conclusion: Nimodipine and nitrendipine may act through dopaminergic mechanism to potentiate catalepsy, inhibit stereotypy and block CAR.

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Objective: To study the effect of sodium arsenite exposure on the functions of murine leukocytes and humoral immune response. Methods: Male (BALB/c) mice were continuously exposed to sodium arsenite (NaAsO2 ) for two weeks. Fractions of peritoneal macrophages were separated and their functional activities were determined. To test the effects of arsenic on the humoral immune response heat killed S.aureus was injected and the titre of the antiserum was measured. Results: The mean phagocytic index (P.I) of control macrophage (M() is decreased from 25571.43 ( 1126.26 to 4905.30 ( 556.70 after Sodium arsenite treatment, whereas the mean P.I of S. aureus primed M( (47147.44 ( 666.36) is also decreased to 15965.91 ( 1185.95 in case of arsenite exposure followed by S.aureus immunization (P<0.001). Intracellular killing capacity in control cell is (68.4%) which is found to be 77.3% in case of NaAsO2 treatment and they can kill only 22.7% bacteria. The chemotactic index also decreases significantly in case of arsenic treated cell (2.5( 0.02) with respect to that of control cell (9.83( 0.22) at 60 min. In S.aureus immunized serum, agglutination titre was obtained at lowest antibody conc(1:512), whereas serum from pre-exposure of arsenite followed by S.aureus immunization showed early agglutination (1:32). Conclusion: Sodium arsenite exposure interferes with the immunological functions and antibody raising capacity of peritoneal macrophages in BALB/C mice.

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Objective: To screen for the pharmacological effects of S. scabrida on behaviour, temperature and blood coagulation. Methods: Aqueous leaf extract of S. scabrida (55-440 mg/kg, p.o.) was given to albino mice to test for the central effects, while the aqueous and ethanol extracts mixed with fresh normal human blood were used for the blood coagulation study. Results: The aqueous extract produced slight motor activity but gave rise to transient hyperthermia, while prolonging the prothrombin time of human blood. Conclusion: Aqueous extract of S. scabrida produces transient hyperthermia, but no motor activity. It also possesses some anticoagulant properties.

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Objective: To study the therapeutic efficacy of histone H1 as an antitumour agent in rats. Methods: Animals were induced for breast cancer using 9, 10 dimethyl benz(a) anthracane (DMBA). Histone H1 was injected intratumourally in experimental breast tumour. Tumour volume was measured after treatment and regression was observed. The levels of carcino embryonic antigen (CEA) were estimated using ELISA kit. Results: The animals bearing tumour had high levels of carcino embryonic antigen but the levels decreased following treatment. Conclusion: Histone H1 mediated cytotoxicity could prove useful for therapy for mammary carcinoma.

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