Pharmacokinetic assessment of rifampicin and des-acetyl rifampicin in carbon tetrachloride induced liver injury model in Wistar rats.

OBJECTIVES: Preclinical evidence is needed to assess drug-metabolite behaviour in compromised liver function for developing the best antitubercular treatment (ATT) re-introduction regimen in drug-induced liver injury (DILI). The pharmacokinetic behavior of rifampicin (RMP) and its active metabolite des-acetyl-rifampicin (DARP) in DILI's presence is unknown. To study the pharmacokinetic behavior of RMP and DARP in the presence of carbon tetrachloride (CCl4) plus ATT-DILI in rats. METHODS: Thirty rats used in the experiment were divided equally into six groups. We administered a single 0.5 mL/kg CCl4 intraperitoneal injection in all rats. Groups II, III, IV, and V were started on daily oral RMP alone, RMP plus isoniazid (INH), RMP plus pyrazinamide (PZA), and the three drugs INH, RMP, and PZA together, respectively, for 21-days subsequently. Pharmacokinetic (PK) sampling was performed at 0, 0.5, 1, 3, 6, 12, and 24 h post-dosing on day 20. We monitored LFT at baseline on days-1, 7, and 21 and sacrificed the rats on the last day of the experiment. RESULTS: ATT treatment sustained the CCl4-induced liver injury changes. A significant rise in mean total bilirubin levels was observed in groups administered rifampicin. The triple drug combination group demonstrated 1.43- and 1.84-times higher area-under-the-curve values of RMP (234.56±30.66 vs. 163.55±36.14 µg h/mL) and DARP (16.15±4.50 vs. 8.75±2.79 µg h/mL) compared to RMP alone group. Histological and oxidative stress changes supported underlying liver injury and PK alterations. CONCLUSIONS: RMP metabolism inhibition by PZA, more than isoniazid, was well preserved in the presence of underlying liver injury.

Scopoletin a potential phytochemical therapy for antitubercular treatment drug induced liver injury (ATT-DILI) model in Wistar rats.

OBJECTIVES: The hepatoprotective properties of scopoletin have been explored in carbon tetrachloride (CCl4) induced liver injury but not in drug-induced liver injury (DILI) scenarios. Only N-acetyl-cysteine (NAC) has proven efficacy in DILI treatment. Accordingly, we conducted a study to assess the hepatoprotective action of scopoletin in the anti-tubercular treatment (ATT)-DILI model in Wistar rats, if any. METHODS: A total of 36 rats were evaluated, with six in each group. A 36-day ATT at 100 mg/kg dose for isoniazid, 300 mg/kg for rifampicin and 700 mg/kg for pyrazinamide were fed to induce hepatotoxicity in rats. Group I and II-VI received normal saline and ATT, respectively. Oral scopoletin (1,5 and 10 mg/kg) and NAC 150 mg/kg were administered in groups III, IV, V and VI, respectively, once daily for the last 15 days of the experiment. LFT monitoring was performed at baseline, days 21, 28, and 36. Rats were sacrificed for the histopathology examination. RESULTS: Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin levels were significantly increased in group II (receiving ATT) compared to normal control on day 28 and day 36 (p<0.05). All three doses of scopoletin and NAC groups led to the resolution of AST, ALT, ALP, and bilirubin changes induced by ATT medications effect beginning by day 28 and persisting on day 36 (p<0.01). An insignificant effect was observed on albumin and total protein levels. The effect was confirmed with antioxidants and histopathology analysis. CONCLUSIONS: The study confirms the hepatoprotective efficacy of scopoletin in a more robust commonly encountered liver injury etiology.

Factors contributing to flares of ulcerative colitis in North India- a case-control study.

BACKGROUND: Ulcerative colitis is a relapsing and remitting disease that may be associated with flares. The causes of flares in the Indian setting are not well recognized. METHODS: The present prospective case-control study was conducted at a single center in North India. Cases were defined as patients admitted for flare of ulcerative colitis, while controls were patients in remission enrolled from the outpatient department. The basis of the diagnosis of flare was a simple clinical colitis activity index (SCCAI) of ≥ 5 and endoscopic activity, while remission was based on SCCAI < 4 and a normal fecal calprotectin. A questionnaire evaluating recent infections, stress, drug intake (antibiotics, pain medication), adherence to therapy, and use of complementary and alternative therapy (CAM) was administered. RESULTS: We included 84 patients (51 with flare and 33 in remission) with a median age of 38 years, of whom 47 (55.9%) were males. The two groups were similar for baseline parameters, including age (38, 23-50 and 38, 25.5-48.5 years), male gender (52.9% and 60.6%), extent of disease, extraintestinal manifestations (21.6% and 12.1%), use of 5-aminosalicylates (76.5% and 90.9%). The thiopurine use was lower in those having a flare (15.7% and 36.4%). Amongst the predictors of flare, the recent infections (39.2% and 30.3%), recent travel (31.4 and 27.3%), eating outside food (47.1% and 39.4%), consumption of milk products (88.2% and 75.8%), use of pain medication (43.1% and 33.3%) and recent stress (62.7% and 60.6%) were similar between cases and controls. The rates of antibiotic use (29.4% and 6.1%), lack of adherence (50.9% and 15.2%), and intake of CAM (70.6% and 33.3%) were higher in those with flare. Patients attributed a lack of adherence to the cost of therapy, presumed cure (due to lack of symptoms), and fear of adverse effects. CONCLUSION: Lack of adherence to inflammatory bowel disease therapies and recent CAM and antibiotic intake was higher in patients with flares of UC. The study makes ground for educational intervention(s) promoting knowledge and adherence to IBD therapies.

The Effects of Statins on Bone Formation Around Implants Placed in Animal Bones: A Systematic Review and Meta-Analysis.

Background: Implants are preferred for replacement of missing teeth by the clinicians as well as the patients. Lesser alveolar bone density doesn't preclude any individual for choosing this option but warrants for extra caution. Preclinical studies have explored the osteoinductive potential of statins, but results should be analyzed vigorously before implementing them in humans. There is no meta-analysis to document effect of statins on bone formation around implants in osteoporotic animals. Methods and material: PubMed, Embase and Cochrane were searched for studies investigating the effect of statins on bone implant contact (BIC %), bone mineral density (BMD %) and bone volume (BV %) around implants at 2, 4 and 12 weeks. Meta-analysis was performed on subgroups with osteoporotic animals which were administered statins through different routes. Results: Quantitative data from 12 studies showed favorable effect of statins on bone around implants. Positive difference was observed at 4 weeks in BIC (parenteral [SMD = 4.33 (2.89, 5.77); I 2 = 3%)], BMD (local [SMD = 1.33 (0.51, 2.15); I 2 = 0%] and BV (local [SMD = 1.58 (0.76, 2.40); I 2 = 0%]. BIC [SMD = 1.40 (0.89, 1.90); I 2 = 0%] and BV [SMD = 3.91 (2.33, 5.50); I 2 = 43%] were higher in experimental group after 12 weeks of oral administration. Conclusions: Statins can be investigated as potential bone graft materials to increase the predictability of osseointegration especially in osteoporotic individuals. Future research should focus to reproduce homogeneous data and conclusive recommendations which can be applied in clinical trials. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-023-01873-z.

Dose-Response Evaluation of Scopoletin, a Phytochemical, in a High-Fructose High-Fat Diet-Induced Dyslipidemia Model in Wistar Rats.

The putative hypolipidemic properties of scopoletin have not been fully confirmed due to a lack of validation in an irreversible chronic hyperlipidemia animal model. The druggability also needs to be studied in terms of bioavailability in the vascular compartment. Accordingly, we conducted a study to assess the hypolipidemic and pharmacokinetic behavior of scopoletin in the high-fructose high-fat diet (HFHFD)-induced dyslipidemia model in Wistar rats. A total of 42 rats were studied, with 6 in each of the 7 groups. A 60-day HFHFD opted for induction of dyslipidemia. Group I and groups II-VII received normal rat chow diet and HFHFD, respectively. Oral scopoletin (1, 5, 10 mg/kg) and atorvastatin 5 mg/kg were administered in groups III-VI, respectively, once daily for the next 15 days. A separate group, group VII, was used for the pharmacokinetic assessment comparing the scopoletin 10 mg/kg intraperitoneally (IP) in group VII versus the oral (group V). Pharmacokinetic blood sampling was performed on the 10th day of continuous once-daily therapy. Rats were sacrificed for the histological examination. All three scopoletin dosages significantly decreased the total cholesterol, low-density lipoproteins, and triglycerides (P < .05 for all), but not in a dose-dependent manner. Atherogenic Index of plasma, Castelli's risk indices, and histopathological findings confirmed the protective effect of scopoletin. The IP administration showed a 23.18% higher exposure than the oral route (P < .001 for area under the curve and P < .05 for concentration-maximum). This study confirms the hypolipidemic efficacy of scopoletin in a more robust irreversible model of dyslipidemia. Scopoletin's gut absorption in the disease state may also boost the initial phase exploratory clinical trial.

Scopoletin Improves Glucose Homeostasis in the High-Fructose High-Fat Diet-Induced Diabetes Model in Wistar Rats.

Antihyperglycemic action of scopoletin needs to be validated before considering it for clinical trials. The present study explored antihyperglycemic action of scopoletin in high-fructose high-fat diet (HFHFD)-induced diabetes in rats. The animal study was performed using 48 rats, 6 in each group. HFHFD was administered for model induction for 74 days. Rats in Group I (normal control [NC]) and group II (experimental control [EC]) received normal saline and HFHFD, respectively, throughout the study. Groups III, IV, V, and VI received oral scopoletin (1 mg/kg [low dose, LD], 5 mg/kg [medium dose, MD], 10 mg/kg [high dose, HD]), and metformin (250 mg/kg; positive control [PC] for efficacy), respectively, once daily from day 60 to 74, in addition to HFHFD. Group VII (10 mg/kg oral scopoletin safety group) and VIII (0.1 mg/kg oral warfarin; PC for safety) were separately used for bleeding time-clotting time (BTCT) assessment on days 60, 68, and 74. Groups I, VII, and VIII rats were studied for safety assessment. Later, animals were sacrificed for histological examination. Scopoletin-treated groups showed a significant decline in glucose levels, especially in the MD (5.18 ± 0.12) and HD group (5.271 ± 0.11) in comparison to the EC (6.37 ± 0.05) on day 74 (P < .05). Two weeks after scopoletin treatment, ß-cell function significantly improved (53.073 ± 4.67) in the MD group versus 29.323 ± 8.505 in the NC group (P < .05). A statistically significant difference was observed when the MD group (53.07 ± 4.67) was compared to the metformin-treated group (24.80 ± 3.24; P < .05). The safety assessment in the form of BTCT findings did not observe a difference among groups I, VII, and VIII (P > .05). The study showed that scopoletin dose-independently reversed insulin resistance. Consequently, scopoletin can be a potential candidate for antidiabetic drug development.

Dental Anxiety Assessment through the Drawings of Children and Influence of Art Therapy.

Background: Assessment of dental anxiety in children is difficult because of their immature cognitive and emotional development. Drawings are well well-established emotion assessment tool. These can be used as nonverbal methods of communication for expressing the children's anxiety and emotions. Art therapy utilizes creative therapy interventions to deal with children suffering from emotional problems. Aims and Objectives: The aim of the study is (1) To assess the drawings of children for the presence of dental anxiety. (2) To study the effectiveness of art therapy on dental anxiety in children. Materials and Methods: One hundred and twenty children within the age group of 6-12 years were part of this study. The pretest assessment of dental anxiety was done using Frankl and Five facial anxiety scales. All the participants received local anesthesia during their first treatment session. At the end of the treatment session, all the participants were asked to draw a picture of their experience. The drawn figures were assessed by a psychologist. The children were allotted randomly into the study group (n = 60) and control group (n = 60). Art therapy was given to 60 children in the study group for three consecutive appointments. The posttest assessment of dental anxiety was done using Frankl and Five facial anxiety scales after completion of the entire dental treatment. Results: The pretest scores revealed very high level of dental anxiety in 33 (55%) children in study group and 34 (56.67%) children in control group. The posttest scores of study group, who received the art therapy, revealed that 24 (40%) children had little anxiety and 32 (53.33%) children had some anxiety. Whereas in the control group, the posttest scores showed 20 (33.33%) children had high anxiety and 39 (65%) children had very high anxiety scores. There was a significant correlation between the objective score of dental anxiety and the subjective scores of CD: H. Conclusion: Drawings can be used as an assessment tool for the detection of dental anxiety and art therapy effectively reduces the anxiety in pediatric patients undergoing dental treatment.

Essential oil nebulization in mild COVID-19(EONCO): Early phase exploratory clinical trial.

Background: Medications studied for therapeutic benefits in coronavirus disease 2019 (COVID-19) have produced inconclusive efficacy results except for steroids. Objective: A prospective randomized open-label, parallel-arm Phase I/II clinical trial was planned to compare essential oil (EO) blend versus placebo nebulization in mild COVID-19. Methods: A Phase I safety evaluation was carried out in a single ascending and multiple ascending dose study designs. We assessed Phase II therapeutic efficacy on COVID-19 and general respiratory symptoms on days 0, 3, 5, 7, 10, and 14 on the predesigned case record form. Viremia was evaluated on day 0, day 5, and day 10. Results: Dose-limiting toxicities were not reached with the doses, frequencies, and duration studied, thus confirming the formulation's preliminary safety. General respiratory symptoms (p < 0.001), anosmia (p < 0.05), and dysgeusia (p < 0.001) benefited significantly with the use of EO blend nebulization compared to placebo. Symptomatic COVID-19 participants with mild disease did not show treatment benefits in terms of symptomatic relief (p = 1.0) and viremia clearance (p = 0.74) compared to the placebo. EO blend was found to be associated with the reduced evolution of symptoms in previously asymptomatic reverse transcription polymerase chain reaction (RT-PCR)-positive study participants (p = 0.034). Conclusion: EO nebulization appears to be a safer add-on symptomatic relief approach for mild COVID-19. However, the direct antiviral action of the EO blend needs to be assessed with different concentrations of combinations of individual phytochemicals in the EO blend.

Appropriate chemopreventive strategy for anti-tubercular therapy related liver injury is unsettled: Results from a systematic review and network meta-analysis.

BACKGROUND: Role of chemoprophylaxis for prevention of antitubercular therapy-related drug-induced liver injury (ATT-DILI) is uncertain. METHODS: Electronic databases were searched for randomized trials reporting on chemoprophylaxis agents for prevention of ATT-DILI. We included studies evaluating the role of a drug in comparison to controls/placebo. The primary outcome was the occurrence of ATT-DILI. We performed a Bayesian random-effects network meta-analysis to calculate odds ratios (ORs) and 95% credible intervals (CrI) for those arms where at least two studies were available. Additional comparative studies for these arms were also identified. RESULTS: Fourteen studies were identified and seven included in the meta-analysis. The agents used for prevention of ATT-DILI were silymarin/silibinin (4 trials), N-acetylcysteine (NAC) (3 studies), herbal preparations (5 studies) and one study each for cholecalciferol and carnitine. Compared with controls/placebo, the odds of occurrence of hepatotoxicity with NAC was 7 * 10-17 (95% CrI: 2.8 * 10-53, 0.0053) and Silymarin was 0.68 (95% CrI: 0.084, 4.6). NAC had the highest probability of rank 1 (0.99) which was followed by Silymarin (0.004). CONCLUSION: N-acetyl cysteine, but not Silymarin/Silibinin, appears to be beneficial in prevention of ATT-DILI. However, the results were limited by the possible risk of bias in included studies, variable definitions of ATT-DILI and limited number and category of patients.

Protective role of Convolvulus pluricaulis on lipid abnormalities in high-fat diet with low dose streptozotocin-induced experimental rat model.

BACKGROUND: The methanolic extract of Convolvulus pluricaulis had earlier shown lipid lowering activity in Triton induced reversible hyperlipidemia model, but, the hypolipidemic activity in irreversible models and hypoglycaemic activity are not investigated so far. OBJECTIVE: This study was designed to validate the lipid and glucose-lowering actions of C. pluricaulis methanolic extract (CPME) by using ingredients from the Indian diet for induction of hyperlipidemia and diabetes on experimental rats. MATERIALS AND METHODS: Experimental animals were divided into four groups having six animals in each group (n = 6). Animals of Group I II, III and IV received - no treatment, 0.9% NaCl, Glipizide (GPZ) 5 mg/kg and CPME 400 mg/kg once daily for two weeks respectively. Animals of all groups except group I were fed a high fat-based Indian diet for 21 days followed by a single STZ (35 mg/kg) i.p. administration in model induction phase. Afterwards, animals were sacrificed, and the pancreas was dissected for histological changes, and blood was collected for measuring lipid parameters, FBS, insulin levels, and HOMA scores. RESULTS: CPME significantly ameliorate the lipid abnormalities in HFD-STZ-treated experimental model (p < 0.001) but fails to reverse the hyperglycaemia developed in diabetic rats with no protective effect on islet architecture (p > 0.05) as compared to experimental group while, GPZ showed protective effect on both lipid abnormalities and hyperglycemia by modulating the levels of lipid parameters and insulin respectively. CONCLUSION: In conclusion, the study confirm that CPME possesses significant hypolipidemic activity but fails to reverse the hyperglycaemia developed in diabetic rats.

Randomized controlled trial of cefazolin monotherapy versus cefazolin plus azithromycin single dose prophylaxis for cesarean deliveries: A developing country's perspective.

AIM: To compare the efficacy of pre-incision intravenous single doses of cefazolin versus cefazolin plus azithromycin as an antibiotic prophylaxis in cesarean delivery (CD). METHODS: This was a single-center, double blind, randomized controlled trial conducted in the PGIMER, Chandigarh. 200 women undergoing elective/emergency cesarean section were randomized. Group A received single dose of cefazolin plus placebo while Group B received single dose of cefazolin plus azithromycin. Primary outcome evaluated was occurrence of surgical site infections (SSI); secondary outcomes included incidence of febrile morbidity, UTI, endometritis, neonatal outcome, total cost of antibiotics, and duration of hospital stay in both the study arms. Descriptive statistics and χ2 tests were used for analysis of the data. RESULT: There was an overall significant reduction in the incidence of SSI (15% vs 3%; P = 0.03), endometritis (8% vs 2%; P = 0.048), and post-operative febrile morbidity (17% vs 3%; P = 0.001) with the addition of azithromycin to cefazolin. Duration of hospital stay was almost two days lesser for the cefazolin plus azithromycin group. Subgroup analysis of patients with SSI showed the age, duration of ruptured membranes, and type of anesthesia as important predictors of infection rate. Study observed statistically significant reduction in requirement of additional post operative antibiotics, phototherapy for neonates, hospital stay and cost of therapy in cefazolin plus azithromycin group (P < 0.05). CONCLUSION: Tertiary care hospitals in developing countries such as India can opt for the cefazolin plus azithromycin as antimicrobial prophylaxis during CD to maximize the efficacy as well as for decreasing the cost burden of postoperative infections.

Characterization of stable and reactive metabolites of piperine formed on incubation with human liver microsomes.

Black pepper, though commonly employed as a spice, has many medicinal properties. It consists of volatile oils, alkaloids, pungent resins, etc., of which piperine is a major constituent. Though safe at low doses, piperine causes alteration in the activity of drug metabolising enzymes and transporters at high dose and is known to precipitate liver toxicity. It has a potential to form reactive metabolite(s) (RM) owing to the presence of structural alerts, such as methylenedioxyphenyl (MDP), α, ß-unsaturated carbonyl group (Michael acceptor), and piperidine. The present study was designed to detect and characterize stable and RM(s) of piperine formed on in vitro incubation with human liver microsomes. The investigation of RMs was done with the aid of trapping agents, viz, glutathione (GSH) and N-acetylcysteine (NAC). The samples were analysed by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS) using Thermo Scientific Q Exactive Plus Orbitrap. Full scan MS followed by data-dependent MS2 (Full MS-ddMS2 ) mode was used to establish mass spectrometric fragmentation pathways of protonated piperine and its metabolites. In total, four stable metabolites and their isomers (M1a-c, M2a-b, M3a-c, and M4a-b) were detected. Their formation involved removal of carbon (3, M1a-c), hydroxylation (2, M2a-b), hydroxylation with hydrogenation (3, M3a-c), and dehydrogenation (2, M4a-b). Out of these metabolites, M1, M2, and M3 are reported earlier in the literature, but their isomers and two M4 variants are novel. In addition, six novel conjugates of RMs, including three GSH conjugates of m/z 579 and three NAC conjugates of m/z 435, were also observed.

Pharmacological evaluation of Convolvulus pluricaulis as hypolipidaemic agent in Triton WR-1339-induced hyperlipidaemia in rats.

OBJECTIVE: The aim of the study was to evaluate the effect of Convolvulus pluricaulis (CP; C. pluricaulis) methanolic extract on Triton WR-1339-induced hyperlipidaemia in rats. METHODS: The study comprised of six groups namely normal control, experimental control and treatment groups (100, 200 and 400 mg/kg of C. pluricaulis, and 65 mg/kg of Fenofibrate). Hyperlipidaemia was induced by a single intraperitoneal injection of Triton WR-1339 400 mg/kg in rats. Parameters such as lipid profile, oxidative stress, histological analysis and atherogenic index were evaluated. The plant extract was further studied by HPLC and LCMS, for analyses of active phytochemicals. KEY FINDINGS: The result of the study showed that C. pluricaulis significantly decreased total cholesterol, triglycerides, LDL-c, MDA levels and atherogenic index while the levels of HDL-c and GSH were found to be raised. Plant extract at the dose of 400 mg had a consistent effect on all lipid profile parameters. Lower doses (100 and 200 mg) did not produce a statistically significant reduction in LDL-c. In addition, the protective effect of C. pluricaulis was confirmed by histological analysis. Further, the findings of the study were found to be comparable with fenofibrate. CONCLUSIONS: Therefore, the present study suggests that C. pluricaulis has the potential for the treatment of hyperlipidaemia.

Glorisa superba Hydroalcoholic Extract from Tubers Attenuates Experimental Arthritis by Downregulating Inflammatory Mediators, and Phosphorylation of ERK/JNK/p-38.

Glorisa superba (GS) is a medicinal plant that has been traditionally used in the treatment of joint pain and rheumatoid arthritis (RA). The present study was carried out to investigate the antiarthritic activity of Glorisa superba hydroalcoholic extract (GSHE) in an adjuvant-induced arthritis (AIA) rat model. Arthritis was induced by sub-plantar administration of complete Freund's adjuvant (CFA) and GSHE (25, 50, or 100 mg/kg/day) was administered orally for 21 consecutive days. Joint diameter was measured on Days 0, 3, 7, 14, and 21. GSHE dose dependently attenuates the increased joint diameter and serum tumor necrosis factor (TNF)-α level following induction of arthritis by adjuvant. This attenuation was well substantiated with reduced mRNA expression of interleukin (IL)-1ß, IL-6, TNF-α, and NF-κB. Additionally, GSHE inhibited phosphorylation of the mitogen-activated protein kinases (MAPK) signaling pathway as there was decreased protein expression of MAPK (p-p38/p38 and p-ERK/ERK p-JNK/JNK ratio). Moreover, GSHE in a dose-dependent fashion normalized the redox status of ankle joint (GSH, malonaldialdehyde [MDA], and NO levels and superoxide dismutase [SOD] and catalase [CAT] activities) and displayed decreased inflammatory cell infiltration in histopathological findings. Taken together, these findings indicate that GSHE protects against AIA by modulating MAPK.

Anticonvulsant activity of Aloe vera leaf extract in acute and chronic models of epilepsy in mice.

OBJECTIVES: The effect of Aloe vera in epilepsy has not yet been explored. This study was done to explore the effect of aqueous extract of Aloe vera leaf powder on three acute and one chronic model of epilepsy. METHODS: In acute study, aqueous extract of Aloe vera leaf (extract) powder was administered in doses 100, 200 and 400 mg/kg p.o. Dose of 400 mg/kg of Aloe vera leaf extract was chosen for chronic administration. Oxidative stress parameters viz. malondialdehyde (MDA) and reduced glutathione (GSH) were also estimated in brain of kindled animals. KEY FINDINGS: In acute study, Aloe vera leaf (extract) powder in a dose-dependent manner significantly decreased duration of tonic hind limb extension in maximal electroshock seizure model, increased seizure threshold current in increasing current electroshock seizure model, and increased latency to onset and decreased duration of clonic convulsion in pentylenetetrazole (PTZ) model as compared with control group. In chronic study, Aloe vera leaf (extract) powder prevented progression of kindling in PTZ-kindled mice. Aloe vera leaf (extract) powder 400 mg/kg p.o. also reduced brain levels of MDA and increased GSH levels as compared to the PTZ-kindled non-treated group. CONCLUSIONS: The results of study showed that Aloe vera leaf (extract) powder possessed significant anticonvulsant and anti-oxidant activity.

An evaluation of the effects of nonselective and cardioselective ß-blockers on wound healing in Sprague Dawley rats.

OBJECTIVES: To investigate the effect of a nonselective ß-blocker (propranolol) and cardioselective ß-blocker (metoprolol) on wound healing in rats using incision and excision wound models and to compare the effect of these drugs on wound healing. MATERIALS AND METHODS: Propranolol and metoprolol were given orally. Sprague Dawley rats of either sex were used. Incision and excision wound models were used to evaluate the wound-healing activity. Effects of metoprolol and propranolol on tensile strength, period of epithelialization, and hydroxyproline content were observed. Histological analysis was done to see collagen deposition and inflammatory infiltrate. STATISTICAL ANALYSIS USED: The data was subjected to analysis of variance (ANOVA) followed by Scheffe's test. P < 0.05 was considered to be statistically significant. Statistical analysis was done using SPSS software version 15.0. RESULTS: Administration of propranolol or metoprolol was shown to decrease tensile strength, delay wound contraction and re-epithelialization, increase inflammatory infiltrate, and reduce collagen density and hydroxyproline levels. CONCLUSIONS: The results suggest that nonselective and cardioselective ß-blockers delay wound healing and these effects are mediated by ß1-receptors.