Comparative study of oral mifepristone and endocervical prostaglandin-E2 gel as pre-induction cervical ripening agents in parturition

Background: Intracervical instillation of prostaglandin E2 is a well-known and widely practiced method of pre-induction cervical ripening. Mifepristone, due to its anti-progesterone action has been found to be a potential cervical ripening agent. This study was conducted to compare the safety, efficacy and outcome of these two drugs in pre-induction cervical ripening.Methods: One hundred antenatal women were recruited for the study; 50 in mifepristone arm and 50 in PG-E2 gel arm. Any singleton term pregnancy in vertex presentation with intact membranes and bishop’s score of <4 was included in the study. Any contraindication for vaginal delivery and any contraindication for mifepristone or PG-E2 were considered as exclusion criteria. Participants in the mifepristone arm were given tablet mifepristone 200 mg orally and those in PG-E2 gel group received endocervical instillation of PGE2 gel 0.5 mg, two doses 6 hours apart (if necessary). Induction of labour was considered successful if the parturient delivered within 48 hours of administration of mifepristone or first dose of PG-E2 gel, with or without labour augmentation with oxytocin. Delivery after 48 hours and caesarean delivery were considered unsuccessful induction.Results: There was a significant improvement in bishop’s score in mifepristone group 5.0±1.55 as compared to PG-E2 gel group 3.64±2.14; p value 0.001.Conclusions: Oral administration of 200 mg mifepristone is a safe, effective and convenient alternative to intracervical instillation of prostaglandin-E2 gel for pre-induction cervical ripening.

Anti-granuloma activity of Coriandrum sativum in experimental models.

Background: Coriandrum sativum has been used in the traditional systems of medicine for management of arthritis and other infl ammatory disorders. Objectives: In this study, we have evaluated the anti-infl ammatory and anti-granuloma activities of Coriandrum sativum hydroalcoholic extract (CSHE) in experimental models. Materials and Methods: The anti-infl ammatory activity of CSHE was evaluated using carrageenan-induced paw edema model and the anti-granuloma activity of CSHE was evaluated using the subcutaneous cotton pellet implantation-induced granuloma formation and stimulation of peritoneal macrophages with complete Freund’s adjuvant. Serum tumor necrosis factor- (TNF-), IL-6, IL-1  levels, and peritoneal macrophage expression of TNF-R1 were evaluated as markers of global infl ammation. Results: CSHE at the highest dose tested (32 mg/kg) produced a signifi cant reduction (P0.05) in paw edema after carrageenan administration. CSHE treatment also reduced dry granuloma weight in all treated animals. Serum IL-6 and IL-1  levels were signifi cantly (P0.05) lower in the CSHE (32 mg/kg)-treated group as compared to control. Although there was an increase in serum TNF- level in the CSHE-treated group as compared to control, TNF-R1 expression on peritoneal macrophages was found to be reduced. Conclusion: Thus, the result of this study demonstrates the anti-infl ammatory and anti-granuloma activities of CSHE in experimental models, and validates its traditional use for the management of arthritis and other infl ammatory disorders.

Evaluation of disease modifying activity of Coriandrum sativum in experimental models.

Background & objectives: Coriandrum sativum (CS), has been widely used in traditional systems of medicine for treatment of rheumatoid arthritis. However, the mechanism of action for its antiarthritic effects is not clearly known. Therefore, the present study was carried out to evaluate the antiarthritic activity of CS in rats in two experimental models. Methods: The antiarthritic activity of CS seed hydroalcoholic extract (CSHE) was evaluated in adult Wistar rats by using two experimental models, viz. formaldehyde and Complete Freund's adjuvant (CFA) induced arthritis. The expression of pro-inflammatory cytokines (predominantly contributed by macrophages) was also evaluated. TNF-α level was estimated in serum by ELISA method. TNF-R1, IL-1 β and IL-6 expression in the synovium was analysed by immunohistochemistry. Results: CSHE produced a dose dependent inhibition of joint swelling as compared to control animals in both, formaldehyde and CFA induced arthritis. Although there was a dose dependent increase in serum TNF-α levels in the CSHE treated groups as compared to control, the synovial expression of macrophage derived pro-inflammatory cytokines/cytokine receptor was found to be lower in the CSHE treated groups as compared to control. Interpretation & conclusions: Our results demonstrate that the antiarthritic activity of CSHE may be attributed to the modulation of pro-inflammatory cytokines in the synovium. In further studies CSHE could be explored to be developed as a disease modifying agent in the treatment of RA.

Antiarthritic activity of Majoon Suranjan (a polyherbal Unani formulation) in rat.

Background & objectives: Majoon Suranjan (MS) is a polyherbal formulation used in Unani system of medicine for the treatment of rheumatoid arthritis (RA). The present study evaluates the antiarthritic efficacy of this formulation in three different experimental models. Methods: The anti-inflammatory activity of MS (in doses of 450, 900 and 1800 mg/kg body wt) was evaluated using the turpentine oil induced paw oedema model and the antiarthritic efficacy was evaluated using the formaldehyde and complete Freund's adjuvant (CFA) induced arthritis models. Aspirin (100 mg/kg body wt) was used as the standard drug in all the models. In order to assess the safety of the test drug, oral acute and 28 day toxicity studies were also carried out. Results: MS produced a dose dependent protective effect in all the experimental models. Its antiarthritic efficacy was comparable to aspirin in formaldehyde induced arthritis and was superior to aspirin in turpentine oil induced paw oedema and CFA induced arthritis. MS also inhibited the delayed increase in joint diameter as seen in control and aspirin treated animals in CFA induced arthritis. Oral LD50 of MS was found to be >5000 mg/kg in rats. Chronic administration did not produce any significant physiological changes in the tested animals. Interpretation & conclusions: Results of the present study suggest that the antiarthritic activity of MS was due to the interplay between its anti-inflammatory and disease modifying activities, thus supporting its use in traditional medicine for the treatment of RA.

Effect of acorus calamus on electrical and chemical induced seizures in mice.

Acorus calamus Linn. (Family: Araceae) is an aromatic semi-aquatic perennial marshy herb. Experimental studies have indicated the efficacy of this plant against various types of epileptic seizures, but the results vary with the models and the type of extract used. These conflicting reports and the unavailability of the data regarding the effects of aqueous extract of Acorus calamus (AEAC) prompted us to evaluate the efficacy of AEAC on electrical and chemical induced seizures in albino mice. Either normal saline or sodium valproate or AEAC was given sixty minutes prior to the experiment in acute study, whereas in chronic study, they were given twice daily for ten days and the last dose was given one hour prior to the exposure of the animal either to maximal electrical shock (MES) or pentylenetetrazole (PTZ) administration. On acute administration, AEAC dose dependently reduced the duration of tonic hind limb extension in MES induced seizure which was comparable to that produced by sodium valproate. Whereas, in PTZ induced seizures, the test drug decreased the latency and increased the duration of seizures as well as mortality. On repeated administration (chronic study) the test drug significantly reduced the duration of tonic hind limb extension and also the clonus phase of MES induced seizures. However, in PTZ induced seizures, results were similar to that obtained in acute study. Results indicates that AEAC has protective effect against MES, but not against PTZ induced seizures.

Antidepressant activity of aqueous extract of fruits of emblica officinalis in mice.

Depression is a widespread psychiatric disorder affecting around 5% of the population. Furthermore, it is difficult to predict which patient will respond to any given treatment. In the traditional systems of medicine, many plants and formulations have been used to treat depression for thousands of years. Emblica officinalis (EO) contains tannic acid as its main ingredient and this compound has been shown to have non-selective mono-amine oxidase activity. Therefore, the present study was undertaken to evaluate the antidepressant potential of acute and chronic administration of EO in forced swim test (FST) and tail suspension test (TST). Inbred adult male Swiss Albino mice weighing 25-30g were used in the study. Standard drug (imipramine) and test drug (EO) were suspended in 1% gum acacia. The vehicle (10ml/kg, p.o), imipramine (10mg/kg, p.o) and EO (0.8mg/kg, 2mg/kg, 4mg/kg, p.o. respectively) were administered 1hour prior to acute study. In chronic study, all drugs were given for 10 days and the last dose was given 1hour before the experiment. Duration of immobility was noted in both the models. In our study, both imipramine and EO significantly reduced the duration of immobility in both experimental models as compared to the animals in the control group. The antidepressant activity of EO was comparable to that of standard drug imipramine. The results of the present study indicate the potential for use of EO as an adjuvant in the treatment of depression.

Evaluation of the anti-ulcer activity of NR-ANX-C (a polyherbal formulation) in aspirin & pyloric ligature induced gastric ulcers in albino rats.

Background & objectives: The aetiology of gastric ulcers is not completely understood and continuous use of anti-ulcer agents leads to many side effects. In this study we evaluated the anti-ulcer efficacy of a polyherbal formulation with potent antioxidant activity in aspirin and pyloric ligature induced gastric ulcers in rats. Methods: The efficacy of the polyherbal formulation NR-ANX-C (composed of the extracts from Withania somnifera, Camellia sinensis, Ocimum sanctum, shilajith and triphala) was evaluated in terms of antioxidant potential as assessed in terms of protection from lipid peroxidation and the antiulcer activity as seen by the area of gastric lesions, gastric juice volume, gastric pH, total acidity and total adherent gastric mucus content. Results: In our study, NR-ANX-C (25 and 50 mg/kg) was more efficacious than ranitidine in reducing ulcer index in both the models. At the highest dose tested (50 mg/kg), NR-ANX-C was comparable to omeprazole in preventing ulcer formation in the pyloric ligature model. NR-ANX-C showed a dose- dependent decrease in gastric juice volume and total acidity in both the models. A dose-dependent increase in gastric pH and total adherent gastric mucus was also seen in NR-ANX-C treated groups. The extent of lipid peroxidation was also reduced in the test drug treated groups. Interpretation & conclusion: Based on our findings, we presume that the cytoprotective, anti-secretary and antioxidant properties of NR-ANX-C were responsible for its anti-ulcer activity. These findings suggest the potential for use of NR-ANX-C as an adjuvant in the treatment of gastric ulcer.

Evaluation of anti-inflammatory activity of plant lipids containing alpha-linolenic acid.

Two groups of fatty acids are essential to the body, the omega6 (n6) series derived from linoleic acid (18:2, n-6) and the omega3 (n3) series derived from alpha-linolenic acid (18:3, n-3). Fatty acids provide energy, are an integral part of the cell membranes and are precursors of prostaglandins, thromboxanes and leukotrienes collectively known as eicosanoids. Eicosanoids participate in development and synthesis of immunological and inflammatory responses. The fixed oils (1, 2, 3 ml/kg) containing alpha-linolenic acid, obtained from the seeds of Linseed (Linum usitatissimum), Soyabean (Glycine max) and Holy basil (Ocimum sanctum) were screened for their antiinflammatory activity using carrageenan, leukotriene and arachidonic acid induced paw edema models in rats and the antiinflammatory effects were compared with the standard drug indomethacin. Significant inhibition of paw edema was produced by all the oils in the highest dose (3 ml/kg) in all the models. While O. sanctum oil produced the maximum percentage inhibition in leukotriene induced paw edema, L. usitatissimum oil produced maximum percentage inhibition in carrageenan and arachidonic acid induced paw edema models. The results show that oils with higher alpha-linolenic acid content (L. usitatissimum and O. sanctum) produced a greater inhibition of paw edema suggesting that modulation of the course of inflammatory disorders may be achieved by altering the eicosanoid precursor (i.e. poly unsaturated fatty acids: PUFA) availability through dietary manipulation.

Effect of NR-ANX-C (a polyherbal formulation) on haloperidol induced catalepsy in albino mice.

BACKGROUND & OBJECTIVE: Use of typical antipsychotics like haloperidol in treatment of schizophrenia is associated with a high incidence of extrapyramidal side effects. In rodents, administration of haloperidol leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we evaluated the anticataleptic efficacy of NR-ANX-C, a polyherbal formulation containing bioactives of Withania somnifera, Ocimum sanctum, Camellia sinensis, triphala and shilajit in haloperidol induced catalepsy in mice. METHODS: Five groups (n = 6) of male albino mice were used in the study. Catalepsy was induced by ip administration of haloperidol (1mg/kg). The degree of catalepsy (cataleptic score) was measured as the time the animal maintained an imposed posture. We compared the anticataleptic efficacy of NR-ANX-C (10, 25 and 50 mg/kg) with scopolamine (1 mg/kg). The superoxide dismutase (SOD) level in brain tissue was also estimated to correlate the levels of oxidative stress and degree of catalepsy in the animal. RESULTS: Significant (P<0.01) reduction in the cataleptic scores was observed in all NR-ANX-C treated groups and maximum reduction was observed in the NR-ANX-C (25 mg/kg) treated group. Significant (P<0.05) reduction in SOD activity was observed in NR-ANX-C (25 and 50 mg/kg) treated groups and maximum reduction was observed in NR-ANX-C (25mg/kg) treated group. INTERPRETATION & CONCLUSION: In our study, maximum reduction in cataleptic score was observed in NR-ANX-C (25 mg/kg) treated group. The maximum reduction in SOD activity was also observed in the same group. These findings suggest a possible involvement of the antioxidant potential of NRANX- C in alleviating haloperidol induced catalepsy.

Squamous cell carcinoma of the scalp arising from chronic cutaneous lupus erythematosus: report of two Indian patients.

Squamous cell carcinoma (SCC) usually arises in skin damaged by actinic rays. Exposure to chemicals like coal tar, soot, arsenic and a variety of oils and distillation products is also implicated in its pathogenesis. It occasionally occurs in scars following inflammatory or degenerative processes. It is an end stage complication of a wide array of inflammatory skin conditions. SCC complicating chronic cutaneous lupus erythematosus (CCLE) in Indian patients is rarely reported. Here we report two such Indian patients with long standing CCLE in whom the diagnosis of CCLE and SCC was confirmed by histopathology.