Sertraline with desvenlafaxine and sertraline with mirtazapine as treatment initiation in MDD patients with moderate to severe depression and effect on inflammatory markers.

BACKGROUND: This study evaluated the effect of sertraline with desvenlafaxine and sertraline with mirtazapine on HAM-D score and inflammatory markers (IL-6 and TNF-α levels) in major depressive disorder. METHODS: Patients (18-60 years) with MDD diagnosed by DSM-V criteria and HAM-D score 18 or more were included (n = 60). Group A patients (n = 30) received sertraline 50 mg/day and desvenlafaxine 50 mg/day. Group B patients (n = 30) received sertraline 50 mg/day and mirtazapine 30 mg/day. All patients were followed up for 8 weeks for the evaluation of clinical efficacy, safety, serum IL-6, and TNF-α levels. RESULTS: Our study showed a comparatively similar and statistically significant (p < 0.05) reduction in HAM-D score in both groups in the 4th and 8th week of the treatment. Both drug combinations significantly (p < 0.05) decreased serum IL-6 and TNF-α after 8 weeks of treatment. CONCLUSION: The present study suggests that the combination therapy (as treatment initiation) with sertraline and desvenlafaxine, and sertraline with mirtazapine is effective and well tolerated in MDD patients with moderate to severe depression, and their therapeutic efficacy is accompanied by decreased inflammatory markers (serum IL-6 and TNF-α).

Recent evidence indicates that combination therapy of antidepressant drugs started as treatment initiation produces superior treatment outcomes in patients of MDD with moderate to severe depression.MDD is associated with increased inflammatory markers.Combination therapy of sertraline with desvenlafaxine and sertraline with mirtazapine as treatment initiation is effective and well tolerated in MDD patients.The therapeutic efficacy of sertraline with desvenlafaxine and sertraline with mirtazapine is associated with a significant decrease in serum levels of IL-6 and TNF-α.

Increased Pill Burden and Adverse Effects of Psychotropics Correlated with Poor Quality of Life and Medication Nonadherence: A Cross-sectional Drug Utilization Study at a Tertiary Care Hospital in Delhi during COVID-19 Pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to an increase in mental health problems such as depression and anxiety. This study aims to investigate the prescribing pattern of psychotropic drugs in patients with common mental disorders which might be altered during the pandemic and also whether the pandemic could alter their quality of life (QOL) and medication adherence. MATERIALS AND METHODS: After prior ethical approval, a descriptive cross-sectional drug utilization study (DUS) of 200 prescriptions was undertaken to evaluate the pattern of psychotropic drug usage as per WHO (World Health Organization)/International Network of Rational Use of Drugs (INRUD) guidelines. The correlation of the average number of drugs per prescription with QOL was observed. The correlation of adverse drug reactions (ADRs) with medication adherence was also analyzed. RESULTS: The average number of drugs per prescription during the pre-COVID-19 and COVID-19 period was estimated to be 2.48 and 2.96. The percentage of drugs prescribed by generic name in the two different periods (pre-COVID-19 and COVID-19) was 97.40 and 95.77%. The percentage of drugs prescribed from the list of essential medicines was 89.40 and 85.12%, respectively. The percentage of prescriptions with injections was 0.45% and 0.53%, respectively for the two periods. The QOL during the COVID-19 pandemic was found to be negatively correlated to the average number of drugs per prescription (correlation coefficient = -0.61) and medication adherence was found to be poor in patients who developed ADRs with the drugs prescribed (p-value of 0.001). CONCLUSION: In the tertiary care hospital described, rational drug prescribing was followed. Increase in the number of drugs per prescription was found to be associated with poor QOL and the development of ADRs led to medication nonadherence in the patients. Further studies with larger sample sizes are needed to confirm these results. How to cite this article: Kumar A, Halder S, Srivastava S, et al. Increased Pill Burden and Adverse Effects of Psychotropics Correlated with Poor Quality of Life and Medication Nonadherence: A Cross-sectional Drug Utilization Study at a Tertiary Care Hospital in Delhi during COVID-19 Pandemic. J Assoc Physicians India 2023;71(9):14-18.

Association of serotonin transporter gene polymorphism with efficacy of the antidepressant drugs sertraline and mirtazapine in newly diagnosed patients with major depressive disorders.

OBJECTIVE: We examined the association of serotonin receptor transporter gene polymorphism in patients with MDD with the clinical efficacy of mirtazapine (MZ) and sertraline (ST). METHOD: Newly diagnosed, treatment naïve, 80 MDD patients (aged 18-45) diagnosed using DSM-5 criteria and with Beck's depression inventory score (BDI) score ≥21 were included and randomly divided into two groups of 40 participants and were administered MZ 15-45 mg/day or ST 25-200 mg/day respectively. Patients were followed up for 6 weeks for evaluation of BDI scores. Genotypic evaluation was done and three allele variants were identified based on the polymerase chain reaction fragment sizes: short (S; 486 bp), long (L; 529 bp), or extralong (XL; 612 or 654 bp) and classified into five genotypes: S/S,S/L, L/L, S/XL, and L/XL. RESULT: We found that 32.5% patients belonged to the S/S genotype, suggesting that individuals with the SS genotype are at higher risk of developing MDD. No statistically significant association was seen with ST or MZ groups on the basis of genotypes. Clinically significant improvement was observed with a more than 50% reduction in BDI scores at 6 weeks of treatment with both drugs. CONCLUSION: Identification of risk population can be carried out by genotype testing. Prior genotyping in MDD patients might help to predict a better clinical outcome with antidepressants.

Correlation between telomere length and efficacy of oral and long-acting injectable antipsychotics on severity and cognitive impairment of schizophrenia.

OBJECTIVE: To study the correlation between telomere length (TL) and long-acting injectable (LAI) and oral atypical antipsychotic (OAA) efficacy on schizophrenia (SCZ) severity and cognitive impairment. METHODS: Sixty Schizophrenia patients of 18-50 years and of either sex were included in a 12-week study. Thirty patients were recruited in each group, LAI and OAA. Positive and Negative Syndrome Scale (PANSS) and National Institute of Mental Health and Neuro-Sciences (NIMHANS) neuropsychological battery tests were evaluated at baseline and 12 weeks. TL was estimated at baseline. RESULTS: Both groups showed a significant improvement in PANSS and NIMHANS battery test scores after treatment (p < 0.001) within the group, though not between the groups. Mean TL at baseline was 407.58 ± 143.93 and 443.40 ± 178.46 in LAI and OAA groups respectively. A significant negative correlation (r = -0.28, p = 0.03) of TL was seen with the mean change in negative PANSS score after treatment. CONCLUSIONS: LAI antipsychotics are similar to OAA in decreasing the disorder severity and improving the cognitive impairment in schizophrenia. Also, patients who have shorter TL show greater improvement in the negative PANSS score. Hence, TL holds the potential of predicting antipsychotic drug response in schizophrenia patients.KEY POINTSLong-acting injectable antipsychotic was comparable to oral atypical antipsychotics in bringing out improvement in disorder severity, cognitive functions over 12 weeks.Shorter telomere length has been found to be associated with a greater response in negative symptoms of schizophrenia.

Elderly Population Has Higher Prevalence of Polypharmacy Associated with Poor Quality of Life and Low Compliance after Recovery from COVID-19.

Background: Long term effects of COVID are not fully understood yet. The geriatric population has been badly affected. The impact of COVID-19 on the health-related quality of life after recovery and patient compliance is a matter of concern especially in the geriatric population where polypharmacy is often prevalent. Aims and Objectives: This study intended to observe the occurrence of polypharmacy (PP) among COVID-19 recovered older patients with multimorbidity and explore its association with health-related quality of life and compliance in these patients. Materials and Methods: Total 90 patients, above 60 years of age having two or more co-morbidities and recovered from COVID-19 infection were included in this cross-sectional study. Number of pills taken daily by each patient was noted, to determine the occurrence of PP. WHO-QOL-BREF was used to assess the effect of PP on health-related quality of life (HRQOL). Medication adherence was measured using a self-reported questionnaire. Results: PP was found in 94.4% while hyper polypharmacy was found in 45.56% of patients. The overall mean score of HRQOL in patients with PP was 187.91 ± 32.98, indicating poor quality of life with PP (p value 0.0014) whereas the overall mean score of HRQOL in patients with hyper polypharmacy was 177.41 ± 26.11, showing poor quality of life with hyper polypharmacy (p value 0.0005). Increased number of pills corelated with poor quality of life (r =0.49). The medication adherence was found to be poor in patients who received mean number of pills 10.44 ± 2.62 whereas the adherence was good if the mean number of pills was 8.20 ± 2.63, (p value of 0.0001). Conclusion: Polypharmacy is highly prevalent among COVID-19 recovered patients and is associated with poor quality of life as well as poor medication adherence.

Effect of valproate and add-on levetiracetam on inflammatory biomarkers in children with epilepsy.

BACKGROUND: Contemporary research indicates the role of neuroinflammation/inflammatory markers in epilepsy. In addition, comorbidities such as anxiety and poor health-related quality of life are vital concerns in clinical care of pediatric patients with epilepsy. This open-label, prospective, observational study evaluated the effect of valproate and add-on levetiracetam on serum levels of C-C motif ligand 2 (CCL2) and Interleukin-1 beta (IL-1ß) in pediatric patients with epilepsy. We also studied effect of valproate and add-on levetiracetam on anxiety and health-related quality of life (HRQoL) in specified age subgroups. METHODS: Children aged 1 to 12 years, diagnosed with epilepsy (generalized or focal seizures), treated with valproate (n = 40) and valproate with add-on levetiracetam (n = 40) were included. All patients were followed up for 16 weeks and assessed for changes in serum CCL2 and IL-1ß levels. Spence Children Anxiety Scale short version (SCAS-S) and QOLCE-16 scales were used to measure anxiety and HRQoL, respectively, in specific age groups. RESULTS: The serum CCL2 level decreased significantly (p < .001) from 327.95 ±â€¯59.07 pg/ml to 207.02 ±â€¯41.50 pg/ml in the valproate group and from 420.65 ±â€¯83.72 pg/ml to 250.06 ±â€¯46.05 pg/ml in the add-on levetiracetam group. Serum IL-1ß level did not change significantly in both groups. Spence Children Anxiety Scale short version scores were decreased and QOLCE-16 scores were increased significantly (p < .001) in both valproate and add-on levetiracetam groups. CONCLUSIONS: The results of our study suggest that valproate and levetiracetam led to decrease serum CCL2 levels without any change in serum IL-1ß levels in children with epilepsy. Anti-inflammatory property of valproate and levetiracetam might underlie their antiepileptic effect and CCL2 could be a potential marker of drug efficacy in epilepsy. Also, valproate and levetiracetam reduced anxiety and improved quality of life in children with epilepsy in the age groups evaluated.

Chromium Exposure in Late Gestation Period Caused Increased Levels of Cr in Brain Tissue: Association with Alteration of Activity and Gene Expression of Antioxidant Enzymes of F1 and F2 Generation Mice.

Chromium is a micronutrient which has found frequent use as supplements during pregnancy and could have a role in altering the antioxidant status in the brain. The present study was undertaken to estimate chromium levels in the brain, antioxidant enzyme activity with their gene expression, and learning and memory parameters on F1 and F2 generation mice when the F0 was exposed to chromium. The chromium levels in the brain were estimated using atomic absorption spectrophotometer. The enzyme activity of glutathione-s-transferase (GST) and catalase (CAT) was estimated and their gene expression was evaluated using RT-PCR. The spatial memory was tested using Morris water maze. The learning and recall memory was tested using the step down latency paradigm. The chromium levels were significantly raised in animals treated with Cr per se in F1 generation and quercetin cotreatment reduced the Cr levels in brain significantly. The enzyme activity of GST was significantly less in Cr-treated animals of both generations and this effect was significantly reversed on cotreatment with quercetin. The gene expression of GST matched the enzyme activity. However, catalase activity did not show significant decrease with Cr but cotreatment with quercetin resulted in significant decrease compared with control and this effect was not matched by its gene expression. We observed no significant change in learning and memory parameters in both generations following Cr exposure. Thus, this study demonstrates that chromium exposure in gestation causes changes in enzyme activity especially GST and this change was matched by change in gene expression in GST but not CAT. There was no effect on memory at the given dose.

Cadmium level in brain correlates with memory impairment in F1 and F2 generation mice: improvement with quercetin.

The increased exposure to cadmium (Cd) through environmental pollutants, food and cigarette smoke is a concern worldwide. The association of Cd with impaired learning disabilities led us to hypothesise that cadmium levels in brain tissue could be dose-dependently related to the extent of memory impairment and oxidative stress. In this study, we proposed to study whether cadmium exposure to dams could alter the brain Cd levels, memory parameters, antioxidant enzymes in brain and their gene expression in the F1-F2 generation mice and whether quercetin could modulate this effect. Animals were administered Cd alone and in combination with quercetin for 7 days during their gestation period. Their newborn pups (F1 and F2 mice) were reared until adulthood and were tested for memory using Morris water maze and step-down latency test. The brain tissue of F1 mice was collected. Cd levels were estimated using the atomic absorption spectrophotometer. G-S-transferase (GST) and catalase (CAT) activity were measured and fold increase in their respective gene expression was observed using the RT-PCR method. Cd levels were significantly increased in the brain tissue of animals exposed to Cd but cotreatment with quercetin showed decreased levels in both generations. Memory impairment was observed in animals of F1 generation exposed to Cd and cotreatment with quercetin (100 mg/kg) reversed this effect. Cd exposure significantly enhanced both activity and expression of GST and CAT in the brain tissue of F1 generation mice and quercetin attenuated this effect. In F2 generation, results were variable. GST activity and expression increased with Cd and decreased with quercetin cotreatment. However, CAT activity showed no significant change despite a decrease in gene expression. Quercetin cotreatment enhanced activity as well gene expression in F2 generation. Our study insinuates that Cd levels could act as a predictor of memory impairment and altered enzyme activity and gene expression in brain tissue. Quercetin helped to reduce Cd levels in brain tissue of F1 and F2 generation and modulated the antioxidant system of the cell by affecting expression of antioxidant enzymes at the transcription level.

Alteration in cognitive behaviour, brain antioxidant enzyme activity and their gene expression in F1 generation mice, following Cd exposure during the late gestation period: modulation by quercetin.

We investigated whether in-utero Cd(II) chloride exposure of the dams between 14th to 21st day of gestation affects memory and learning, oxidative stress, antioxidant enzyme activity and their gene expression in brain of the pups in their adulthood. In the Morris water maze, cadmium (Cd) exposure impaired spatial memory which was reversed following co-treatment with quercetin (100 mg/kg). In the passive avoidance paradigm, retention memory was adversely affected but was significantly reversed by co treatment with quercetin (25, 50, 100 mg/kg). The malondialdehyde and catalase (CAT) levels and glutathione-S-transferase (GST) activity were increased significantly in Cd-treated group, but were reversed by quercetin (all doses). The gene expression for CAT and GST in brain tissue of Cd treated animals also increased many folds as compared to the control, and this effect was decreased on co-treatment with quercetin (all doses), thus matching with the respective enzyme activities. Quercetin (25 mg/kg) when co-treated with Cd caused a decrease in GST activity compared to control, which points towards a complex interplay with oxidative free radicals and promoters and transcription factors. Thus, Cd exposure during late gestation causes impaired spatial and retention memory in the next generation which may be due to alteration of activity as well as gene expression of the antioxidant enzymes, CAT and GST. Quercetin may offer some protection of memory impairment probably by modulating these effects.

Role of Survivin and p53 Expression in Response of Primary Culture of Ovarian Cancer Cells to Treatment With Chemotherapeutic Agents.

BACKGROUND: Ovarian cancer is associated with a high relapse rate and is the fifth leading cause of cancer deaths in women. The genetic profile of a tumor is responsible for deciding response to chemotherapeutic agents. In this study, we investigate the relation between survivin and p53 expression and response to chemotherapeutic agents of primary cultures of ovarian cancer cells established from ascitic fluid. MATERIALS AND METHOD: Ascitic fluid and Dulbecco's modified Eagle medium was mixed in equal proportion in culture flasks and incubated to establish primary culture. The cells were treated with different combinations of carboplatin and paclitaxel with and without survivin small interfering RNA transfection. Cell survival was estimated by MTT assay. Survivin and p53 expression was quantified by real-time polymerase chain reaction. RESULTS: Out of 19 ascitic fluid samples, 13 primary cultures of ovarian cancer cells were established. The half maximal inhibitory concentration doses of carboplatin (≥70 µg/mL) and paclitaxel (≥18 µg/mL) were high for 10/13 and 5/13 patients, respectively. Survivin messenger RNA expression was significantly downregulated on treatment with carboplatin (100 µg/mL), paclitaxel (12.5 µg/mL), and a combination of carboplatin (50 µg/mL) and paclitaxel (6.25 µg/mL). Only paclitaxel-treated ovarian cancer cells showed decrease in expression of p53. Survivin small interfering RNA increased sensitivity of the primary cultures to chemotherapeutic agents. CONCLUSIONS: The present study highlights the fact that establishing primary cultures from ascitic fluid may help to develop personalized treatment regime for individual patients based on their molecular profile. Our study also shows that supplementing taxols drugs with survivin inhibitors may prove to be beneficial in the treatment of ovarian cancer patients.

Cadmium exposure during lactation causes learning and memory-impairment in F1 generation mice: amelioration by quercetin.

Cadmium (Cd) is a known pollutant present in the environment at low levels and is reported to affect reproduction in many ways. The present study was undertaken to explore the effect of Cd in F1 generation mice on cognitive parameters, and to further investigate whether quercetin could modulate these effects. In this study, female lactating mice were exposed to cadmium for seven days just after delivery. The new born pups in their adulthood were tested for learning and memory parameters by passive avoidance task and Morris water maze (MWM) test. It was observed that pups exposed to Cd showed significant impairment of memory in step down latency test, which was reversed by quercetin (100 mg/kg). In MWM test for spatial memory, animals exposed to Cd exhibited increased escape latency, which was reversed by quercetin (50 mg/kg) significantly. Quercetin alone (50 and 100 mg/kg) also demonstrated improved spatial memory, and showed improved retention memory in the passive avoidance paradigm at dose 50 mg/kg. On testing oxidative stress parameters, we observed significantly increased malondialdehyde (MDA) levels in brain tissue of Cd-treated mice. Moreover, co-treatment with quercetin (50 mg/kg) and Cd significantly reduced these MDA levels. The other doses (25 and 100 mg/kg) also showed reduction in MDA levels as compared to the group exposed to Cd alone, though the difference was not statistically significant. Hence, this study highlights the possibility of cognitive impairment in adulthood if there is Cd exposure during lactation and oxidative stress could possibly attribute to this effect.

Quercetin Modulates the Effects of Chromium Exposure on Learning, Memory and Antioxidant Enzyme Activity in F1 Generation Mice.

In the present study, we investigated whether chromium (Cr) administered to the dams (F0) during lactation period could affect memory and oxidative stress in F1 generation mice in their adulthood and whether quercetin could modulate these effects. Morris water maze (MWM) was used to test for spatial memory. Passive avoidance task and elevated plus maze were used to test for acquisition and retention memory. Oxidative stress was evaluated by measuring glutathione-S-transferase (GST), catalase activity and malonaldehyde (MDA) levels in the brain tissue. The results of MWM showed that the animals in the Cr-treated group compared to control have better spatial memory that was further enhanced when Cr was administered along with quercetin (50 mg/kg). The elevated plus maze test also showed the Cr-treated group to improve acquisition as well as retention memory compared to control. Co-treatment with quercetin (all doses) also exhibited enhanced acquisition and retention memory compared to control. The passive avoidance task demonstrated no significant improvement in memory in the Cr-treated mice but co-treatment with quercetin (100 mg/kg) showed improved acquisition memory compared to control which was significantly better than the animals treated with chromium alone. GST activity was significantly increased in the Cr-treated animals, and this was further increased in groups treated with Cr and quercetin (all doses). Chromium when administered alone and in combination with quercetin (all doses) significantly reduced MDA levels. However, Cr treatment did not show significant change in catalase activity. Nevertheless, co-treatment with quercetin (25 and 50 mg/kg) resulted in significant decrease in catalase activity. Thus, our study demonstrates that Cr exposure during lactation could be beneficial for pups with respect to augmentation of cognitive function and reduction of oxidative stress. Quercetin could probably enhance this effect to some extent.

Protective effect of melatonin on propoxur-induced impairment of memory and oxidative stress in rats.

Propoxur (a carbamate pesticide) has been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. This study was designed to explore the modulation of the effects of propoxur over cognitive function by melatonin (MEL). Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus, and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and reduced glutathione (GSH) levels and catalase (CAT) activity. A significant reduction in SDL and prolongation of TL was observed for the propoxur (10 mg/kg/d; p.o.) treated group at weeks 6 and 7 when compared with control. One week treatment with MEL (50 mg/kg/d; i.p.) antagonized the effect of propoxur on SDL, as well as TL. Propoxur produced a statistically significant increase in the brain MDA levels and decrease in the brain GSH levels and CAT activity. Treatment with MEL attenuated the effect of propoxur on oxidative stress. The results of the present study thus show that MEL has the potential to attenuate cognitive dysfunction and oxidative stress induced by toxicants like propoxur in the brain.

The effect of the essential oil of Eugenia caryophyllata in animal models of depression and locomotor activity.

OBJECTIVE: The essential oil of Eugenia caryophyllata (clove oil; Family: Myrtaceae) is used in dental care as an antiseptic and analgesic. The present study investigates the effect of clove oil on animal models of depression and locomotion. METHODS: Clove oil was administered in doses of 0.025, 0.05, and 0.1 ml/kg/day, intraperitoneally (i.p.) for 3 weeks. The forced swim test (FST) and the tail suspension test (TST) were used to assess depression. To evaluate locomotor activity, the rota rod test and the photoactometer procedure were performed. RESULTS: In the FST, it was observed that the duration of immobility was significantly decreased (P < 0.01) in animals treated with clove oil (0.05 and 0.1 ml/kg); however, the clove oil dose of 0.025 ml/kg showed an insignificant increase in the immobile period. The TST demonstrated that pretreatment with clove oil decreases (P < 0.01) the immobile period significantly at all the three administered doses. Similarly, the photoactometer procedure showed increased locomotor activity at all the three doses, although significant (P < 0.05) only at 0.1 ml/kg. In addition, the rota rod test showed that animals treated with clove oil (0.1 ml/kg) enhanced muscle coordination as demonstrated by a significant increase (P < 0.05) in the latency to fall from the rota rod as compared to the control. However, the lowest administered dose (0.025 ml/kg, i.p.) decreased the latency to fall from the rota rod significantly (P < 0.05) compared to the control. Clove oil (0.05 ml/kg) also showed a decrease in the latency to fall from the rota rod although the result was not statistically significant. DISCUSSION: Thus, it can be concluded that pretreatment with clove oil decreases depression and enhances locomotor activity similar to that exhibited by psychostimulants.

Aloe vera improves memory and reduces depression in mice.

OBJECTIVE: Aloe vera (barbadensis Mill., Family Liliaceae) since ancient times has been used for the treatment of skin disorders, infection, and as a laxative. The present study was undertaken to explore the effect of A. vera (Family Liliaceae) in animal models of learning and memory, depression, and locomotion. METHODS: To assess learning and memory, the passive avoidance task and elevated plus-maze were used. For evaluating depression, the forced swim test and tail suspension test were performed, and to assess locomotor activity, the rota rod test and photoactometer were used. RESULTS: A. vera (200 and 400 mg/kg, p.o.) was found to significantly increase the acquisition and retention step-down latency as compared to control in the passive avoidance task. In the elevated plus-maze, the highest administered dose (400 mg/kg, p.o.) of A. vera significantly reduced the transfer latency as compared to control. The forced swim test as well as tail suspension test showed that A. vera at all administered doses (100, 200, and 400 mg/kg, p.o.) decreased the period of immobility significantly. However, the locomotor activity did not show any significant change in the rota rod test and photoactometer. DISCUSSION: Thus from the above observations, it can be proposed that A. vera enhances learning and memory, and also alleviates depression in mice.

Role of NMDA and opioid receptors in neuropathic pain induced by chronic constriction injury of sciatic nerve in rats.

BACKGROUND: The efficacy of opioids in neuropathic pain is still controversial. Earlier studies have suggested that N-methyl-D-aspartate (NMDA) receptor binding can be affected by opioids and vice versa. The present study aims to explore the interactions between NMDA and opioid receptors using various combinations of drugs acting on these receptors. METHODS: We used an animal model of sciatic nerve ligation to induce neuropathic pain, and a hot-plate test was used to assess pain response. RESULTS: It was observed that NMDA and naloxone increased the pain response. Ketamine reduced the pain response, which was further reduced when ketamine was administered in combination with naloxone, but not with NMDA, thus highlighting the activity of the NMDA receptor system. In addition, morphine was also found to increase latency to hind-paw lick, which was further reduced when given in combination with naloxone. Furthermore, triple drug combinations using ketamine+morphine+naloxone and ketamine+NMDA+naloxone demonstrated some significant interactions at these receptors. CONCLUSIONS: Thus, our study establishes that neuropathic pain can probably be overcome using higher doses of opioids, and there exists some intimate relationships between NMDA and opioid systems that lead to pain modulation.

Augmented humoral immune response and decreased cell-mediated immunity by Aloe vera in rats.

OBJECTIVE: The present study was performed to explore the effect of aqueous extract of Aloe vera on parameters of humoral and cell-mediated immunity. MATERIALS AND METHODS: Delayed-type hypersensitivity was assessed by measuring foot pad thickness following sensitisation by keyhole limpet haemocyanin injection and subsequently challenged by the same. Humoral immunity was assessed by measurement of haemagglutination titre to sheep red blood cells. RESULTS: Aloe vera (400 mg/kg, p.o.) produced a significant decrease in foot pad thickness compared with the control group, and also significantly enhanced the secondary humoral immune response. CONCLUSION: Thus, these findings suggest that A. vera can modulate immune response by augmenting secondary humoral immunity and decreasing cell-mediated immunity.

Acute effect of essential oil of Eugenia caryophyllata on cognition and pain in mice.

The essential oil of Eugenia caryophyllata (clove oil; Family: Myrtaceae) is used in dental care as an antiseptic and analgesic. The study aims to evaluate the effect of clove oil on experimental models of pain and cognition in mice. To observe the acute effects of clove oil at different doses, the elevated plus maze was used for the assessment of cognition, and the tail flick and formalin tests were used for the study of pain. The formalin test showed that clove oil (0.1 ml/kg, i.p.) demonstrated significantly reduced pain response in both the phases. The lower doses (0.025 and 0.05 ml/kg, i.p.) reduced the formalin-induced pain response significantly in the second phase only. The tail-flick test showed variable response. The dose 0.1 ml/kg, clove oil, significantly decreased the tail-flick latency at 30 min and this effect was reversed by naloxone (1 mg/kg). On the contrary, the dose 0.025 ml/kg of clove oil, at 30 and 60 min increased the mean tail-flick latency compared to control group, but this effect was not statistically significant. Yet naloxone significantly (p < 0.05) reversed the effect of clove oil 0.025 ml/kg at 30 min. Clove oil (0.025 and 0.05 ml/kg, i.p.) significantly reversed the scopolamine-induced retention memory deficit induced by scopolamine, but clove oil (0.1 ml/kg, i.p.) significantly reversed both acquisition as well as retention deficits in elevated plus maze induced by the scopolamine. Clove oil exhibits reduced pain response by a predominantly peripheral action as evidenced by formalin test and the tail flick test showed the involvement of opioid receptors. Clove oil also significantly improved scopolamine-induced retention memory deficit at all doses.

Essential oil of clove (Eugenia caryophyllata) augments the humoral immune response but decreases cell mediated immunity.

The present study was undertaken to explore the effect of the essential oil isolated from the buds of Eugenia caryophyllata on some immunological parameters. Humoral immunity was assessed by measuring the hemagglutination titre to sheep red blood cells and delayed type hypersensitivity was assessed by measuring foot pad thickness. Clove oil administration produced a significant increase in the primary as well as secondary humoral immune response. In addition, it also produced a significant decrease in foot pad thickness compared with the control group. Thus, these results suggest that clove oil can modulate the immune response by augmenting humoral immunity and decreasing cell mediated immunity.

Clove oil reverses learning and memory deficits in scopolamine-treated mice.

The present study was performed to examine the effect of Eugenia caryophyllata (Myrtaceae) on learning and memory, and also evaluate whether it can modulate oxidative stress in mice. Passive avoidance step-down task and elevated plus-maze were used to assess learning and memory in scopolamine-treated mice. Oxidative stress parameters were also assessed in brain samples by estimating the malondialdehyde (MDA) and reduced glutathione (GSH) levels at the end of the study. Scopolamine (0.3 mg/kg, i. p.) produced impairment of acquisition memory as evidenced by a decrease in step-down latency and an increase in transfer latency on day 1, and also impairment of retention of memory on day 2. Pretreatment with clove oil (0.05 mL/kg and 0.1 mL/kg) for 3 weeks significantly reversed the increase in acquisition latency and all the doses (0.025, 0.05, 0.1 mL/kg, i. p.) reversed the increase in retention latency induced by scopolamine (0.3 mg/kg, i. p.) in elevated plus-maze. However, 0.05 mL/kg clove oil attenuated memory deficits in the passive avoidance step-down task. Brain samples showed a significant decrease in MDA levels in the group treated with clove oil (0.05 and 0.025 mL/kg). GSH levels were also increased in clove oil-treated mice though the results were not significant. Thus, it can be concluded that clove oil can reverse the short-term and long-term memory deficits induced by scopolamine (0.3 mg/kg, i. p.) and this effect can, to some extent, be attributed to decreased oxidative stress.