Prevention of cyclophosphamide-induced diabetes in the NOD/WEHI mouse with deoxyspergualin

Ten out of 20 (50%) 17-week-old female NOD/WEHI mice developed an acute form of autoimmune diabetes when injected with two large doses of cyclophosphamide (CY), given at 14-day intervals. If these mice were treated under a prophylactic regimen with 2·5 mg/kg body weight per day of the novel immunosuppressant deoxyspergualin (DSP) the onset of diabetes was completely prevented. Moreover, DSP-treated animals showed reduced signs of pancreatic insulitis, had lower percentages of splenic lymphoid cells (SLC) expressing IL-2 receptors and Ly-6C antigens on their surfaces, and these cells released lower amounts of interferon-gamma (IFN) when stimulated in vitro. These data, providing evidence for the capacity of DSP to protect NOD/WEHI mice from experimental autoimmune diabetes and to modulate histo-immunological pathogenic pathways, indicate DSP as a drug of potential interest in the treatment of human insulin-dependent diabetes mellitus.     

Synergistic mechanisms by which sirolimus and cyclosporin inhibit rat heart and kidney allograft rejection

The studies presented herein examined the mechanism(s) whereby sirolimus (SRL) and cyclosporin (CsA) act synergistically to block allograft rejection. Combination index (CI=1 reflects additive, CI<1 antagonistic, and CI<1 synergistic, effects) analysis documented potent synergism between SRL and CsA to block allograft rejection. Combinations of the two drugs produced synergistic prolongation of heart (CI=0.001–0.2) or kidney (CI=0.03–0.5) allograft survival at SRL/CsA ratios ranging from 1:12.5 to 1:200. Pharmacokinetic analysis of the individual drugs showed that CsA does not affect the blood levels of SRL, and SRL mildly increases the levels of CsA in SRL/CsA-treated rats. Quantitative polymerase chain reaction analysis was used to document that both subtherapeutic (1.0 mg/kg) and therapeutic (2.0 or 4.0 mg/kg) CsA doses inhibited the expression of interferon-gamma (IFN-γ) (P<0.03) and IL-2 (P<0.003) mRNA produced by T helper (Th) 1 cells, as well as IL-10 (P<0.001), but not IL-4 (NS) mRNA produced by Th2 cells. Contrariwise, all tested SRL doses (0.02, 0.04 or 0.08 mg/kg) did not affect cytokine mRNA expression. However, heart allografts from rat recipients treated with synergistic SRL/CsA doses displayed reduced levels of IFN-γ (P<0.01), IL-2 (P<0.001) and IL-10 (P<0.001) mRNA. Thus, because subtherapeutic doses of CsA reduce Th1/Th2 activity, thereby facilitating the inhibition of signal transduction by low does of SRL, the two agents act synergistically to inhibit allograft rejection.     

Chemotherapeutic Interaction Between Khaya Grandifoliola (WELW) CDC Stem Bark Extract and Two Anti-Malarial Drugs in Mice

In malarial endemic countries especially in the tropics, conventional antimalarial drugs are used with herbal remedies either concurrently or successively. Khaya grandifoliola is one of such popular herbs used in the treatment of malaria.Various doses of ethanol extract of K. grandifoliola stem bark (50–400 mg/kg/day) were administered orally to Swiss albino mice infected with Plasmodium yoelii nigerense. A dose of 100 mg/kg/day of the extract was also combined with 2.5 mg/kg/day of chloroquine or 6.25 mg/kg/day of halofantrine in both early and established malaria infection test models. The results showed that in the early malaria infection test, K. grandifoliola in combination with chloroquine or halofantrine elicited enhanced antiplasmodial effect in the established infection, there was significantly greater parasite clearance following administration of the combination when compared to the effects of K. grandifoliola or the conventional drugs alone. The mean survival period of parasitized animals was also enhanced by the extract/halofantrine combination. Lower therapeutic doses of halofantrine may be required to potentiate parasite clearance when used in combination with K. grandifoliola. This may constitute great advantage to halofantrine which is associated with cardiotoxicity at high doses.Key words: Khaya grandifoliola, Antimalarial, Chemotherapeutic interaction, Chloroquine, Halofantrine     

Effect of cyclosporine on 3-methylcholanthrene-induced carcinogenesis and immune responses in the rat.

Cyclosporine A (CsA) was used to immunosuppress male Sprague-Dawley rats treated with the chemical carcinogen 3-methylcholanthrene (3MC). Rats treated with low doses of CsA (2.5 or 5 mg/kg) given 2 days prior to an injection of 3MC, and then daily for 2 weeks or twice weekly for 10 weeks did not develop tumors. Rats treated with 2.5 mg/kg CsA for 2 weeks beginning 5 days after a single 3MC injection had tumor incidence similar to rats treated with 3MC only. To further examine the effects of CsA on immune function, groups of rats were then treated with 2.5, 5, 10 or 20 mg/kg CsA daily for 14 days and immune function assessed by measuring delayed-type hypersensitivity (DTH), natural killer cell (NK) activity, and production of interleukin 2 (IL-2), interferon (IFN), prostaglandin E2 (PGE2) and specific IgG antibody. Natural killer cell cytotoxicity was enhanced and antibody production was suppressed in rats treated with all doses of CsA tested. Interleukin 2 production was elevated at the two lower doses, but antibody production, DTH reactions and synthesis of IL-2 and IFN were suppressed with the higher dose treatments (10, 20 mg/kg CsA). The enhanced NK activity seen in rats treated with the lower doses of CsA may be due to the increase in IL-2 production, while enhancement of NK activity at higher doses may be due to other mechanisms. The tumor data suggest that CsA does not prevent tumor formation in our chemical-induced model due to an increase in NK activity, since this enhancement was seen even when tumors did develop normally.     

The sleep-promoting action of ramelteon (TAK-375) in freely moving cats

INTRODUCTION: Ramelteon (TAK-375) is an MT1/MT2 receptor agonist being studied for the treatment of insomnia and circadian rhythm sleep disorders. We compared the behavioral effects of ramelteon and exogenous melatonin in freely moving cats. METHODS: Ramelteon and melatonin were each suspended in a 0.5% (weight per volume) methylcellulose solution and administered orally to freely moving cats. In the control trial, each cat was given vehicle. Each dose of ramelteon or melatonin was compared with the vehicle control in a crossover design. Electroencephalogram, electromyogram, and electrooculogram recordings were assessed. RESULTS: Ramelteon significantly decreased wakefulness at doses of 0.001,0.01, and 0.1 mg/kg, increased slow-wave sleep at doses of 0.001, 0.01, and 0.1 mg/kg, and increased rapid eye movement sleep at a dose of 0.1 mg/kg, compared with the vehicle controls, as assessed by analysis of variance. The effects of ramelteon lasted for up to 6 hours when evaluated by reduction of wakefulness. Exogenous melatonin (0.01-1 mg/kg) significantly increased slow-wave sleep, but the effect was weaker than that of ramelteon and lasted for only 2 hours. The lowest doses of ramelteon (0.0001 mg/kg) and melatonin (0.001 mg/kg) had no significant effect on sleep-wakefulness stage. CONCLUSIONS: Ramelteon was more effective than exogenous melatonin in promoting and maintaining sleep in freely moving cats. Based on its unique mechanism of action, ramelteon should be studied further to evaluate its potential for the treatment of sleep disorders.     

Anti-inflammatory potential of dichloromethane leaf extracts of Eucalyptus globulus (Labill) and Senna didymobotrya (Fresenius) in mice

BackgroundInflammation is an immune response characterized by swelling, redness, pain and heat. Inflammation is mainly managed using conventional medicines that are associated with many side effects. Plant-based remedies are considerably better alternative therapies for they have fewer side effects.ObjectiveThis study aimed at determining the anti-inflammatory potential of dichloromethane (DCM) leaf extracts of Eucalyptus globulus and Senna didymobotrya in mice.MethodsFresh leaves of these plants were harvested from Embu County, Kenya. Quantitative phytochemical analysis was done using Gas Chromatography-Mass Spectrometry (GC-MS). Anti-inflammatory test comprised nine groups of five animals each: normal, negative, positive controls and 6 experimental groups. Inflammation was induced with Carrageenan. One hour post-treatment, the different groups were intraperitoneally administered with the reference drug, diclofenac, 3% DMSO and six DCM leaf extracts at doses of 25, 50, 100, 150, 200 and 250mg/kgbw.ResultsGC-MS results revealed α-phellandrene, camphene, terpinolene, and limonene among others. Anti-inflammatory effects showed that extract doses of 100,150,200 and 250mg/kg bw significantly reduced the inflamed paw. Doses of 200 and 250mg/kgbw in both plants were more potent and compared with diclofenac. E. globulus extract dose of 250mg kg bw reduced inflamed paw in the 1^st, 2^nd, 3^rd and 4^th hours, by 2.27,6.52,9.09 and 10.90% respectively while S.didymobotrya at similar dose ranges, inflamed paw reduced by 2.41, 5.43, 8.31 and 9.05% respectively.ConclusionE. globulus and S. didymobotrya have potent anti-inflammatory activities, attributed to their constituent phytochemicals. This study confirms the traditional use of these plants in treating inflammation.     

Changes in the antitumor activity of thiophosphamide (thio-tEPA) due to adrenalin in experimental conditions

Summary The antineoplastic activity of thiophosphamide, administered simultaneously with adrenalin was studied in rats with transplanted sarcoma 45.Thiophosphamide was administered intraperitoneally in dose of 0.5–1.0 mg/kg body weight, whereas adrenalin was given subcutaneously in 3 doses: 2 mg/kg, 1 mg/kg and 0.25 mg/kg. Administration of the preparations was strated on the 7th day after tumor transplantation and continued for 8 days. Thiophosphamide and adrenalin administered simultaneously produced a more marked antineoplastic effect than when given separately in the same doses.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 58, No. 10, pp. 90–92, October, 1964     

Cyclosporin A in the prevention and treatment of experimental autoimmune glomerulonephritis in the brown Norway rat.

Experimental autoimmune glomerulonephritis (EAG) was induced in brown Norway (BN) rats by a single i.m. injection of collagenase-solubilized homologous glomerular basement membrane (GBM) in Freund's complete adjuvant. This model of anti-GBM disease is characterized by the development, over several weeks, of circulating and deposited anti-GBM antibodies, accompanied by albuminuria. We examined the effects of treatment with oral cyclosporin A (CsA) at different doses, starting at the time of immunization and during the course of the disease. Pretreatment with CsA 5 mg kg daily produced a moderate reduction in circulating anti-GBM antibody levels, reduced deposition of antibody on the GBM and decreased albuminuria. Doses of 10 and 20 mg/kg CsA produced a marked reduction in circulating antibody, absence of detectable deposited antibody and virtual absence of albuminuria. Renal function remained normal in CsA-treated and control animals. When CsA treatment was introduced at 2 or 4 weeks after immunization, there were significant effects on the subsequent autoimmune response and albuminuria at 10 and 20 mg/kg daily. These studies demonstrate that CsA in conventional doses has a therapeutic effect in this model of anti-GBM disease, and suggest a role for T lymphocytes in the pathogenesis of EAG.     

Cyclosporin enhances diabetes induced by low-dose streptozotocin treatment in mice

This study concerns the effect of a 12-day cyclosporin A (CsA) treatment (50 mg per kg per day) on "autoimmune" diabetes induced by 5 low doses (40 mg per kg per day) of streptozotocin (SZ). The SZ-treatment period was initiated 4 days after initial administration of CsA. In young (45-day) CD-1 male mice, CsA enhanced hyperglycemia, hypoinsulinemia and beta-cell destruction following a multiple low-dosage SZ. Moreover, CsA did not prevent development of insulitis induced concomitantly by SZ. Similarly, CsA enhanced the "toxic" diabetes produced by a single high dose (160 mg/kg) of SZ. Furthermore, in the absence of SZ, CsA alone induced glucose intolerance, associated with beta-cell degranulation and high pancreatic CsA content. The enhancement of SZ-induced diabetes by CsA may thus be due to toxicity of the immunosuppressive agent for pancreatic beta cells. This side effect is noteworthy because CsA is currently being used in the therapy of human insulin-dependent diabetes.     

Suppression of Growth and Metastasizing of T-Cell Lymphoma in Mice Infected with American Trypanosomiasis at Different Stages of Experimental Infection

Study was performed by counting cells with chromosomal aberrations in C57Bl/6 mice. Bark dry extract was given perorally in doses of 50, 150, 450, and 1500 mg/kg. Mutagens dioxidine and cyclophosphamide were injected intraperitoneally in doses of 200 and 20 mg/kg, respectively. Bark dry extract in doses of 150 and 1500 mg/kg did not possess cytogenetic activity. Bark dry extract in doses of 50, 150, and 450 mg/kg significantly decreased the cytogenetic effect of mutagens under various regimens of treatment with the preparation (single combined administration, 5-day pretreatment, and 5-day combined administration). Our results indicate that bark dry extract possesses antimutagenic properties.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 11, pp. 535–539, November, 2004     

Protection from Experimental Autoimmune Thyroiditis in CBA Mice with the Novel Immunosuppressant Deoxyspergualin

The effects of the novel immunosuppressant Deoxyspergualin (DSP) on the development of experimental autoimmune thyroiditis (EAT) in CBA mice were studied. For EAT induction, the mice were immunized with 100 μg of porcine thyroglobulin (p Tg) emulsified in CFA on day 0 and in IFA, for boosting, on day 14. Twenty-eight days after primary immunization, histological and serological signs of EAT occurred in control mice treated with PBS which showed marked lymphoid infiltration of the thyroid glands along with increased serum titres of anti-pTg antibodies. Development of both these EAT features was significantly suppressed when the mice were treated with 2.5 mg/kg body weight DSP, given daily, five times a week, from day —2 to day + 28 after immunization. The effect appeared to be dose-dependent and DSP was ineffective when given under the same experimental conditions at the dose of 0.5 mg/kg body weight. No DSP-toxic effects could be observed during the experiment. These results provide further evidence for the powerful immunosuppressive properties of DSP and suggest that this drug may be used in the treatment of autoimmune thyroid diseases and other T-cell mediated autoimmune disorders in humans.     

Induction of micronuclei in mouse bone marrow after combined X-rays-cyclophosphamide and X-rays-mitomycin C treatments.

The induction of micronuclei in polychromatic erythrocytes of bone marrow of Pzh:SWISS mice after combined treatment with X-rays and cyclophosphamide (CP) or X-rays and mitomycin C (MMC) were investigated. Combinations of high (1.00 Gy + 100 mg/kg bw CP and 1. 00 Gy + 5.25 mg/kg bw MMC) and low (0.25 Gy + 25 mg/kg bw CP and 0. 25 Gy + 1.75 mg/kg bw MMC) doses were used. Both chemicals enhanced the mutagenic effects caused by irradiation. After combined treatment with high doses of X-rays + CP and X-rays + MMC at different sample times increases in frequency of micronuclei were observed. Mutagenic effects were found also after treatment with two low doses, when irradiation alone produced no effects. The effects of combined treatments are generally similar to the additive effect of the single treatments.     

Effects of sodium fusidate in animal models of insulin-dependent diabetes mellitus and septic shock.

We have evaluated the effects of the novel immunosuppressant sodium fusidate (fusidin) in the non-obese diabetic (NOD) mouse and in D-galactosamine (D-Gal)-presensitized BALB/c mice challenged with the bacterial superantigen, Staphylococcus aureus enterotoxin B (SEB) or with the endotoxin, Escherichia coli lipopolysaccharide (LPS). The NOD mouse model has clinical and histoimmunological features similar to those of human insulin-dependent diabetes mellitus (IDDM). The SEB- and LPS-treated BALB/c mouse models exhibit pathogenic similarities with human septic shock conditions. In the NOD mouse, fusidin suppressed the spontaneous development of insulitis (mean inhibition 73%) and hyperglycaemia (IDDM incidence 25% versus 0%) when administered at 40 mg/kg five times weekly for 8 consecutive weeks from the fourth week of age; concurrently treated animals exhibited reduced percentages of splenic T lymphocytes. This anti-diabetogenic effect was confirmed in the accelerated model of diabetes induced in the NOD mouse with cyclophosphamide (CY) (IDDM incidence 55% versus 21-6% using dosages of fusidin from 40 to 80 mg/kg five times weekly); protection from IDDM development was achieved even when the drug (80 mg/kg/day) was first administered 7 days after CY challenge. In contrast, fusidin did not reverse hyperglycaemia when administered to CY-treated animals within 3 days of IDDM development. In the two models of septic shock, prophylactic treatment with fusidin, 80 mg/kg given three times for 2 days prior to D-Gal/SEB or D-Gal/LPS challenge, drastically reduced the lethality compared with D-Gal/buffer-treated mice. This effect may depend on the inhibitory action of fusidin on the secretion of cytokines such as interferon-gamma and tumour necrosis factor-alpha, the serum levels of which were greatly diminished in the fusidin-treated mice (mean inhibition 50-90%). These results demonstrate that fusidin may have a role in the treatment of cell-mediated autoimmune diseases and cytokine-mediated infectious diseases in humans.     

Intestinal nutrients elicit satiation through concomitant activation of CCK(1) and 5-HT(3) receptors

Previous studies demonstrate that cholecystokinin type-1 (CCK(1)) and serotonin type-3 (5-HT(3)) dependent pathways are independently involved in intestinal nutrient-induced meal termination. In the current study, we employed selective antagonists to investigate the relative contribution of CCK(1) and 5-HT(3) receptors in mediating the anorexia produced by duodenal infusion of Polycose or Intralipid in rats. Combined administration of 1 mg/kg ondansetron (Ond) and 1 mg/kg devazepide (Dev) reversed 132 mM Polycose-induced suppression to the level of control intake and significantly attenuated 263 mM Polycose-induced suppression greater than either antagonist alone. Similar results were observed when subthreshold doses of Ond (500 microg/kg) and Dev (5 microg/kg) were co-administered prior to 263 mM Polycose infusion. Suppression of intake resulting from 130 mM Intralipid was reversed to the level of control when Ond and Dev were co-administered at both independent effective doses (1 mg/kg each) and subthreshold doses (500 microg/kg and 5 microg/kg, respectively). Finally, combined administration of the antagonists increased sucrose intakes beyond intakes following control or treatment with either antagonist alone when rats were infused with saline. These data demonstrate that intestinal carbohydrates and lipids inhibit food intake through simultaneous CCK(1) and 5-HT(3) receptor activation and that these receptors appear to completely mediate the Intralipid-induced suppression of intake.     

Antithymocyte globulin and cyclosporin A are synergistic in an experimental transplantation tolerance model in the rat

The aim of the present investigation was to study the possible synergistic effect between cyclosporin A (CsA) and antithymocyte globulin (ATG), using the potent immunostimulator, Linomide. DA rats were transplanted with a PVG/c heart to the neck vessels, and the recipients were treated for 10 days with oral CsA (10mg/kg), oral Linomide (160mg/kg) and/or ATG, which was given as a single dose of either 0.02 ml, 0.1 ml or 0.2 ml prior to transplantation. Rats given a combination of ATG and Linomide or CsA and Linomide were used as controls. Synergism between CsA and ATG was tested using the two immunosuppressive drugs given in combination in order to override the challenge of Linomide. CsA or ATG treatment alone resulted in rats with long-term surviving grafts. Addition of Linomide to CsA-treated recipients was followed by early graft rejection. Similarily, Linomide triggered rejection in rats given a low dose of ATG and in recipients given a high dose of ATG if Linomide treatment was prolonged to 21 days. The combination of ATG, CsA and 21 days of Linomide resulted in a significantly prolonged graft survival compared with either ATG + Linomide or CsA + Linomide. These findings demonstrate the synergistic capacity of ATG and CsA in combined immunosuppressive therapy.     

Antinociceptive,Anti-Inflammatory and Antipyretic Activities of the Leaf Methanol Extract of Ruta Graveolens L. (Rutaceae) in Mice and Rats

Background

Ruta graveolens has been used to treat toothache, earache, rheumatism and fever with little scientific evidence corroborating these uses.

Materials and Methods

The leaf methanol extract of Ruta graveolens was evaluated for antinociceptive activity using the acetic acid writhing and hot-plate tests in mice, also anti-inflammatory and antipyretic activities using the carrageenan-induced oedema and E. coli-induced pyrexia tests in rats, respectively.

Results

R. graveolens (100 mg/kg, i.p.), significantly reduced the number of acetic acid-induced writhes by 54 %. R. graveolens (400 mg/kg, i.p.), significantly delayed the reaction time in mice to thermal stimulation 15, 30, 45, and 60 min after treatment. Combined treatment of the lowest and sub-effective doses of the leaf methanol extract (25 mg/kg, i.p.), and indomethacin (10 mg/kg, i.p.) significantly reduced the number of acetic acid-induced writhes in mice. The leaf methanol extract of R. graveolens (50 – 400 mg/kg, i.p.), significantly reduced carrageenan-induced oedema over the 4 h period of testing. Combined treatment of the lowest doses of R. graveolens (25 mg/kg, i.p.) and indomethacin (2 mg/kg, i.p.) produced a significant reduction in carrageenan-induced oedema over the 4 h period of testing. R. graveolens (100 -400 mg/kg, i.p.) significantly reduced E. coli-induced pyrexia over the 5 h period of testing. Given together, the lowest dose of R. graveolens (25 mg/kg, i.p.) and pentoxifylline (10 mg/kg, i.p.) produced a significant reduction in pyrexia induced by E. coli (50 µg/kg, i.m.) over the 5 h period of measurement. The LD₅₀ value obtained for R. graveolens was greater than 4000mg/kg (p.o), suggesting that the plant species may be safe in or nontoxic to mice.

Conclusion

The data obtained indicate that R. graveolens has antinociceptive, anti-inflammatory and antipyretic activities, justifying the use of the plant species by traditional medicine practitioners in the management and treatment of pain, inflammation and fever.     

Evaluation of the Toxicological Profile of the Leaves and Young Twigs of Caesalpinia Bonduc (Linn) Roxb

Acute and sub-acute toxicological effects of ethanolic extract of the leaves and young twigs of Caesalpinia bonduc were carried out on albino rats. Single extract doses from 2000 to 5000 mg/kg body weight were administered orally and monitored for 14 days in acute study, while extract doses from 200 to 1600 mg/kg body weight were orally administered daily for 28 days in sub-acute study and recovery was assessed 14 days after dosing. Biochemical, haematological and histopathological examinations were carried out. There was no mortality in the experimental animals in all acute treatment doses. However, there were significant alterations in the biomarkers and induced cellular damage to the liver in all acute treatment doses. In the sub-acute toxicity treatment, the assessed biomarkers were unaffected at extract dose of 200 mg/kg body weight compared to control, while significant changes were observed in rats administered with extract doses of 400 mg/kg body weight and above. No significant difference was observed between the tested groups and the recovery groups in the sub-acute toxicity study. In conclusion, the ethanolic extract of C. bonduc could be toxic to selected organs of the rat body in acute and sub-acute treatments.     

Effects of cyclosporin A and a rapamycin derivative (SAR943) on chronic allergic inflammation in sensitized rats

Immunomodulators such as cyclosporin A (CsA) and SAR943 (32-deoxorapamycin) inhibit single allergen-induced allergic inflammation such as eosinophilic and lymphocytic infiltration and mRNA expression for interleukin (IL)-4 and IL-5. We examined the effects of CsA and SAR943, administered orally, on asthmatic responses in a rat model of chronic allergic inflammation. Sensitized Brown-Norway (BN) rats were exposed to ovalbumin (OVA) aerosol every third day on six occasions. CsA (5 mg/kg/day), SAR943 (2.5 mg/kg/day) or vehicle (Neoral) was administered orally, once a day, from days 10 to 21 (a total of 12 doses). We measured eosinophilic and T-cell inflammation in the airways, proliferation of airway cells by incorporation of bromodeoxyuridine (BrdU) and bronchial responsiveness to acetylcholine. CsA had no effects, while SAR943 inhibited airway smooth muscle (ASM, P < 0.05) and epithelial cell (P < 0.01) BrdU incorporation, and the number of CD4+ T cells (P < 0.05), without effects on BHR. ASM thickness was not significantly increased following chronic allergen exposure. Therefore, CsA and SAR943 have no effect on chronic eosinophilic inflammation, while SAR943, but not CsA, had a small effect on the proliferation of ASM and epithelium.     

A single dose of celecoxib 200 mg improves postoperative analgesia provided via patient-controlled epidural technique after caesarean section

Introduction

Celecoxib in a dose of 200 mg is safe for the breast feeding mother, as its milk levels are extremely low. We investigated the efficacy of celecoxib in improving postoperative pain management in parturients under patient-controlled epidural analgesia (PCEA).

Material and methods

We studied 64 healthy parturients undergoing elective caesarean section under combined spinal-epidural anesthesia. Postoperative analgesia was performed via PCEA with ropivacaine 0.15% and fentanyl 2 µg/ml (4 ml bolus administration, lock-out 15 min). Patients were randomly allocated to receive either only PCEA (n = 32) or PCEA plus celecoxib 200 mg orally (n = 32). Paracetamol 500 mg was given orally as rescue analgesia. We recorded visual analogue scale (VAS) scores for pain at rest and movement, attempted and given PCEA doses, Bromage scores, level of sensory blockade, rescue doses of paracetamol, maternal side effects during the first 24 h after the PCEA instrumentation, and the overall patient satisfaction.

Results

Fifty-six patients completed the entire protocol. Patient demographics, duration of surgery, side effects, attempted and given PCEA doses, and motor and sensory blockade did not differ between the groups. Significantly lower VAS scores at rest and movement, fewer paracetamol doses (p = 0.039) and increased patient satisfaction (p = 0.001) were found in the celecoxib group compared to controls.

Conclusions

A single dose of 200 mg of celecoxib effectively improved pain management in parturients with PCEA, limited the need for supplemental analgesics and improved efficacy of analgesia, increasing patient satisfaction.     

Anti-Ulcerogenic Activity of the Methanol Root Bark Extract of Cochlospermum Planchonii (Hook f)

Cochlospermum planchonii (Hook f) is a common medicinal plant used in Nigeria traditional medicine for treatment of different ailments including ulcers. The anti ulcer activity of the root bark methanol extract of Cochlospermum planchonii was evaluated using different [ethanol, acetylsalicylic acid (aspirin), cold/restraint stress and pyloric ligation/histamine - induced ulcers and acid production] ulcerogenic models in rats at the doses of 250, 500, and 1000 mg/kg body weight using cimetidine (100 mg/kg) as a standard reference drug. The different doses of the extract and the reference drug significantly (p < 0.01) decreased all the ulcer parameters in a dose dependent manner in all the models used. The total number of ulcers were significantly (p < 0.05) decreased. The ulcer index was significantly (p < 0.004) reduced by the extract. Similarly, the percentage ulcer preventive index was also increased from 0% in the negative control up to 93.2% at the dose of 1000 mg/kg, while the percentage ulcer severity was dose dependently reduced by the extract. Furthermore, the extract significantly (p < 0.02) decreased free gastric HCl and total gastric acid. In conclusion, Cochlospermum planchonii methanolic root bark extract showed significant antiulcer activity in this study which may be as a result of its cytoprotective, antioxidant or antisecretory properties.