Association between antimicrobial consumption and resistance rate of Escherichia coli in hospital settings.

AIMS: This study aims to quantify antimicrobial consumption (AMC) and antimicrobial resistance (AMR) in tertiary care hospitals in Pakistan. METHODS AND RESULTS: This observational study was conducted at two tertiary care hospitals of Pakistan over a 1-year period. The AMC and resistance patterns of Escherichia coli isolates collected from hospitals were observed and analysed using the pearson correlation coefficient. AMC in hospitals varied between 0.00186 and 0.72 (Mean = 0.12 ± 0.191) Defined Daily Dose (DDDs)/1000 patient-days. Fluoroquinolones were the most consumed antimicrobial followed by penicillins, cephalosporins, carbapenems, and aminoglycosides. Antimicrobial-resistant rates in hospitals varied between 92.2% and 34.6%. The highest resistance rate was observed for moxifloxacin, followed by ampicillin, cefotaxime, amoxicillin, ceftriaxone, ciprofloxacin, amoxiclav, and amikacin. Statistically significant association was found between AMC and resistance rate for ampicillin (r = 0.78, P = 0.032), cefotaxime (r = 0.87, P = 0.012), ceftriaxone (r = 0.67, P = 0.042), and ciprofloxacin (r = 0.63, P = 0.031). Additionally, there was a significant association between fluoroquinolone consumption and the resistance rate of third generation cephalosporins (r = 0.61, P = 0.032), and significance was also found when all antimicrobials were combined into 1 analysis (r = 0.721, P = 0.032). CONCLUSION: This data documented a significant association between AMC and resistant rates for multiple antimicrobial agents.

Association of a high-fat diet with I-FABP as a biomarker of intestinal barrier dysfunction driven by metabolic changes in Wistar rats.

BACKGROUND: The epithelial lining of the gut expresses intestinal fatty-acid binding proteins (I-FABPs), which increase in circulation and in plasma concentration during intestinal damage. From the perspective of obesity, the consumption of a diet rich in fat causes a disruption in the integrity of the gut barrier and an increase in its permeability. HYPOTHESIS: There is an association between the expression of I-FABP in the gut and various metabolic changes induced by a high-fat (HF) diet. METHODS: Wistar albino rats (n = 90) were divided into three groups (n = 30 per group), viz. One control and two HF diet groups (15 and 30%, respectively) were maintained for 6 weeks. Blood samples were thus collected to evaluate the lipid profile, blood glucose level and other biochemical tests. Tissue sampling was conducted to perform fat staining and immunohistochemistry. RESULTS: HF diet-fed rats developed adiposity, insulin resistance, leptin resistance, dyslipidemia, and increased expression of I-FABP in the small intestine compared to the control group. Increased I-FABP expression in the ileal region of the intestine is correlated significantly with higher fat contents in the diet, indicating that higher I-FABP expression occurs due to increased demand of enterocytes to transport lipids, leading to metabolic alterations. CONCLUSION: In summary, there is an association between the expression of I-FABP and HF diet-induced metabolic alterations, indicating that I-FABP can be used as a biomarker for intestinal barrier dysfunction.

Anti-arthritic effects of geranium essential oil loaded chitosan nanoparticles in Freund's complete adjuvant induced arthritic rats through down-regulation of inflammatory cytokines.

Geranium essential oil (GEO) has been widely used in aromatherapy and traditional medicines. Nanoencapsulation, a novel technique has emerged to overcome the environmental degradation and less oral bioavailability of essential oils. This work was undertaken to encapsulate geranium essential oil in chitosan nanoparticles (GEO-CNPs) by ionic gelation technique and to explore anti-arthritic and anti-inflammatory potential in FCA-induced arthritic model in rats. The GEO was characterized by gas chromatography flame ionization detector (GCFID) and the nanosuspension was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-rays diffraction (XRD). The Wistar albino rats (n = 32) were separated into four groups; Group 1 and 2 were considered as normal and arthritic controls. Group 3 was positive control that received oral celecoxib for 21 days while Group 4 was treated with oral GEO-CNPs after the induction of arthritis. Hind paw ankle joints diameters were weekly measured throughout the study and significant decrease (5.5 ± 0.5 mm) was observed in GEO-CNPs treatment group in comparison to arthritic group (9.17 ± 0.52 mm). Blood samples were drawn at end for evaluation of hematological, biochemical and inflammatory biomarkers. A significant upregulation of red blood cells and hemoglobin while downregulation of white blood cells, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP) and rheumatoid factor (RF) was observed. Ankles were transected for the histopathological and radiographic examination after animals were sacrificed which confirmed the alleviation of necrosis along cellular infiltration. It was concluded that GEO-CNPs were found to possess excellent therapeutic potential and promising candidates to reduce FCA-induced arthritis.

Mitigation potential of individual and combined dietary supplementation of local Bentonite Clay and Distillery Sludge against Ochratoxin-A induced toxicity in broilers.

BACKGROUND: This study aimed to evaluate the ameliorative effects of dietary supplementation of local bentonite clay (BN) and distillery sludge (DS) alone and in combination on ochratoxin-A (OTA) induced toxicity in broilers. For this purpose, day-old-broiler chicks (n = 270) were procured from the local market and reared under standard management conditions. After 7 days of acclimatization, birds were divided into 2 main groups A and B with respect to OTA inclusion level in feed, each with four sub-groups viz. A1-A4, each challenged with OTA at a dietary inclusion level of 250 µg/kg feed and B1-B4, each challenged with OTA at the level of 500 µg/kg feed and a common control group that was fed with basal feed throughout the experiment. In groups A and B, BN and DS were administered with feed at the rate of 10 g/kg of feed and 5 g/kg of feed alone and in combination, respectively. RESULTS: Results showed that OTA administration alone resulted in poor feed conversion ratio (FCR) and immunological responses along with increased serum levels of alanine transaminase (ALT), Aspartate transaminase (AST), urea and creatinine (P < 0.05). A significant decrease (P < 0.05) in serum protein levels (albumin, globulin and total protein) was also observed in OTA-fed groups in a dose-dependent manner. The addition of BN at 10 g/kg of OTA-contaminated feed resulted in better FCR and immunological responses as compared to those fed OTA only. The BN supplementation also conferred protection against elevation of serum biochemical parameters when compared with OTA-fed groups. However, the addition of DS could not provide significant protection (P > 0.05) on alteration of serum biochemical parameters in response to the OTA induced toxicity. The combined supplementation of BN and DS resulted in amelioration of OTA-induced toxicity and showed improved FCR, immunological, hematological and serum biochemical parameters (P < 0.05) when compared with other groups. Similarly, BN and DS resulted in a significant decline (P < 0.05) in the OTA tissue residues compared with other groups and control. CONCLUSION: In conclusion, combined dietary supplementation of BN (10 mg/kg) and DS (05 mg/kg) in feed reduced the toxic effects of OTA contamination at levels of 250 and 500 µg/kg of feed in broilers. So, the combination products of BN and DS may be successfully developed for use in poultry for protection against OTA-induced toxicity in broilers.

Methotrexate-loaded biodegradable nanoparticles exert anti-arthritic effect by downregulating pro-inflammatory cytokines in Freund's complete adjuvant-induced arthritic rats.

Methotrexate (MTX), the first-line drug for the treatment of rheumatoid arthritis (RA), can cause considerable toxicity, which limits effective dosage regimens. Moreover, it has rapid clearance, which leads to poor patient compliance. To mitigate such challenges, this study aimed to validate the use of MTX-loaded chitosan nanoparticles (NPs) in treating Freund's complete adjuvant (FCA) arthritis in rats. Healthy Wistar rats (n = 30) were divided into five groups. The first group served as healthy control, while the second group served as arthritic control. Group 3 was administered methotrexate, while groups 4 and 5 were MTX-loaded NP-treated groups. NPs were prepared by solvent evaporation method and characterized by zeta size, potential, polydispersity index (PDI), and Fourier-transform infrared spectroscopy. NPs were 190 nm in size, and PDI was 0.25, confirming the uniform distribution of NPs. A significant increase in paw thickness was noted up to the 21st day of the study, which was reversed by a high dose of MTX-loaded NPs. MTX NPs significantly reduced the level of pro-inflammatory markers, including TNF-α and IL-6, along with improving control of oxidative stress biomarkers. The findings of biochemical, haematological, radiological, and histopathological investigations further confirmed amelioration of necrosis and cellular infiltration. It can be concluded that MTX-loaded chitosan NPs are promising candidates for treating FCA-induced arthritis in a rat model.

Characterization and in vivo evaluation of nanoformulations in FCA induced rheumatoid arthritis in rats.

Rheumatoid arthritis is an inflammatory arthropathy, autoimmune in nature, leading to disability of joints involving structural destruction of articular bone and cartilage due to inflammation in synovium resulting in joint stiffness, swelling and pain. Nanomedicine has played a crucial role in improving the efficacy of treatment by controlling the release of pharmacologically active ingredients to increase bioavailability and achieve uniform and targeted delivery of drug. In this study, we prepared celecoxib, gingerol and oleanic acid loaded PLGA nanoparticles by solvent evaporation method and nanoparticles were characterized by particle size, zeta potential, polydispersity index, entrapement efficiency and FTIR. FCA is induced in right hand paw of rats for induction of arthritis. Celecoxib, gingerol and oleanic acid loaded PLGA nanoparticles coated with chitosan were given orally to rats for the evaluation of anti-arthritic effect of this nanoformulation in rats. Animals were divided into six groups for 21 days trial. On 21st day blood samples were collected for evaluation of hematological and lipid profile parameters. The data was subjected to statistical analysis by applying one way ANOVA and tukey test. At the end of study it was concluded that PLGA loaded celecoxib, gingerol and oleanic acid coated with chitosan have excellent effects in minimizing the side effects and increasing the therapeutic efficacy of drugs.

Hepatoprotective and hypolipidemic activities of Caesalpinia bonduc seed kernels and Gymnema sylvestre leaves extracts in alloxan-induced diabetic rats.

The objective of the current research was to validate the hepatoprotective and anti-hyperlipidemic activities of C. bonduc seed kernels (CBSK) and G. sylvestre leaves (GSL) hydro-methanolic extracts, separately and in combination (CBSKE+GSLE) in alloxan-induced diabetic rat model for 28 days. Diabetes was induced by i.p. injection of alloxan monohydrate (140 mg/kg body weight) to albino Wistar rats. Six groups of rats (n=9) were used. Group 1 was the normal control; group 2 was diabetic control. After induction of diabetes metformin (150mg/kg), CBSKE (400mg/kg), GSLE (400 mg/kg) and CBSKE+GSLE (400mg/kg) were administered to diabetic rat groups 3, 4, 5 and 6 respectively for a period of 28 days. Diabetic rats exhibited an increase in serum blood glucose, liver function markers and lipid profile. Treatment of diabetic rats with metformin, CBSKE, GSLE and CBSKE+GSLE for 4 weeks significantly produced hepatoprotective and hypolipidemic effect via amelioration of raised serum glucose, liver profile, and lipid profile. The outcomes of this study suggest that G. sylvestre leaves and C. bonduc seed kernels have hepatoprotective and hypolipidemic potential which possibly help in managing diabetes-induced liver injury and hyperlipidemia.

Antipyretic and antinociceptive potential of Ricinus communis L. and Withania somnifera L. hydroalcoholic extracts in Wistar rats: A comparative study.

The present study was designed to evaluate the antipyretic and antinociceptive activities of R. communis leaves and W. somnifera roots hydroalcoholic extracts in Wistar rats. To assess the antipyretic activity, Brewer's yeast suspension was used to induce hyperthermia. Antinociceptive activity was observed using acetic acid-induced abdominal writhing, formalin-induced paw licking reflex and heat-induced pain models. R. communis and W. somnifera extracts were used at 150, 250 and 500mg/kg. Results showed that administration of both plants significantly (p<0.001) lowered rectal temperature (°C) in a dose-dependent manner from 1h to 4h of study. R. communis and W. somnifera extracts showed a dose-dependent reduction in abdominal writhing induced by acetic acid and decreased the paw licking reflex in formalin-induced nociceptive response. In the heat test, R. communis and W. somnifera extracts exhibited significant (p<0.001) analgesic effects evidenced as an increase in latency time. However, R. communis exhibited prominent antipyretic and antinociceptive activities at 250 and 500mg/kg as compared to W. somnifera. Conclusively, R. communis and W. somnifera could be a potential source of antipyretic and analgesic agents which require further studies.

Nanoformulations of Nutraceuticals for Cancer Treatment.

Nutraceuticals are the bioactive chemical compounds, obtained from natural sources, having profound pharmacological activities. The well known phyto-ingredients with fantastic anticancer potential (e.g., curcumin, resveratrol, quercetin, genistein, and epigallocatechin gallate) have been encapsulated in biocompatible and biodegradable polymeric nanoparticles. Currently, anticancer nutraceuticals loaded in biodegradable polymeric nanoparticles demonstrate extraordinary results, revealing maximum solubility, absorption, bioavailability, and anticancer potential in comparison to nutraceuticals alone or in other drug delivery systems. Among these nutraceuticals, curcumin has been extensively studied and established as having optimal anticancer effects after integration in biocompatible and biodegradable polymeric nanoparticles.

Gastroprotective and antioxidant potential of Euphorbia prostrata against aspirin induced gastric ulcers in rabbits.

Present study was planned to estimate the gastroprotective activity of Euphorbia prostrata plant against aspirin induced gastric ulcers in male adult albino rabbits. The ulcer was induced by oral administration of aspirin in all groups except normal control group. Gastric contents were used to estimate total acid output, gastric volume and gastric pH. Results showed that there was a significant decrease in gastric volume, total acid output, ulcer score and ulcer index in groups treated with extract of E. prostrata and it enhanced the pH of gastric mucosa. Blood samples were collected and serum was used for the estimation of total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA) and catalase (CAT). Results suggested that E. prostrata extract significantly (P<0.05) enhanced the TAC and CAT activity comparable to synthetic antiulcer drug cimetidine while it caused a significant (P<0.05) reduction in TOS and MDA levels. Results of this study revealed that extract of E. prostrata at 10, 20 and 40mg/kg showed gastric protection of 33.79%, 53.15% and 70.66% respectively. Cimetidine was used as a synthetic antiulcer drug in the study, which showed 72.85% gastric protection. From the above mentioned results it was demonstrated that E. prostrata extract at dose rate of 40 mg/kg showed gastroprotective activity similar as cimetidine.

Is Cannabidiol a Promising Substance for New Drug Development? A Review of its Potential Therapeutic Applications.

The pharmacological importance of cannabidiol (CBD) has been in study for several years. CBD is the major nonpsychoactive constituent of plant Cannabis sativa and its administration is associated with reduced side effects. Currently, CBD is undergoing a lot of research which suggests that it has no addictive effects, good safety profile and has exhibited powerful therapeutic potential in several vital areas. It has wide spectrum of action because it acts through endocannabinoid receptors; CB1 and CB2 and it also acts on other receptors, such as GPR18, GPR55, GPR 119, 5HT1A, and TRPV2. This indicates its therapeutic value for numerous medical conditions because of its neuroprotective and immunomodulatory properties. Potential therapeutic applications of CBD include, analgesic, anti-inflammatory, anxiolytic, anti-arthritic, anti-depressant, anti-Alzheimer disease, anti-ischemic, neuroprotective, and anti-fibrotic. More promising areas appear to include diabetes and cancer where CBD exhibits lesser side effects and more therapeutic benefits as compared to recent available medical therapies. Hence, CBD is a promising substance for the development of new drug. However further research and clinical studies are required to explore its complete potential.

Diverse Signaling Pathways and Current Status of Molecular Targeted Treatments for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of death associated with cancer. Various molecular mechanisms are involved in HCC development. Alterations in these molecular mechanisms include chromosomal instability, gene mutations, and variations in protein expressions. A number of cell signaling pathways that are associated with the occurrence of apoptosis, cell proliferation, and angiogenesis provide new prospects for the development of HCC treatments. Newly designed, potential therapeutic regimens target specific receptors, kinases, and vital proteins. Sorafenib is the only FDA-approved drug for HCC treatment, and it has been found that the complex genomic aberrations in HCC can be overcome using combination therapy. For example, therapeutic benefits have been gained using sorafenib with doxorubicin, oxaliplatin, cisplatin, and monoclonal antibodies. In addition, elumetinib, carbozantinib, and refametinib may be effective when used in combination with sorafenib. Drugs that target several signaling pathways have shown promising results in phase 3 clinical trials, and clinical studies using these drugs have changed the management strategy for HCC, particularly with the use of combination therapeutic regimens. Such research has improved the current standards of care and influenced clinical decision making.

A review on nanoparticle-based technologies for biodetoxification.

Nanotechnology has gained significant penetration to different fields of medicine including drug delivery, disease interrogation, targeting and bio-imaging. In recent years, efforts have been put forth to assess the use of this technology in biodetoxification. In this review, we will discuss the current status of nanostructured biomaterials/nanoparticle (NP)-based technologies as a candidate biodetoxifying agent. Patient hospitalization due to illicit drug consumption, suicidal attempts and accidental toxin exposure are major challenges in the medical field. Overdoses of drugs/toxic chemicals or exposure to bacterial toxins or poisons are conventionally treated by voiding the stomach, administering activated charcoal or by using specific antidotes, if the toxin is known. Because of the limitations of these methods for safe and effective detoxification, advancements in nanotechnology may offer novel ways in intoxication support by using nanostructured biomaterials, such as liposomes, micellar nanocarriers, liquid crystalline nanoassemblies and ligand-based NPs.

Influence of some plant extracts on the transdermal absorption and penetration of marker penetrants.

CONTEXT: Plant extracts are commonly used in a number of cosmetics and topical pharmaceuticals. The effects on such extracts on the subsequent dermal absorption and penetration of other cosmetic ingredients needs to be evaluated. OBJECTIVE: This study demonstrates the effect of some natural extracts routinely found in cosmetics on the dermal absorption and penetration of marker penetrants. METHODS: Aqueous ethanolic extracts of Gingko biloba, Lavendula angustifolia, Rosmarinus officinale, Mentha piperita, Matricaria recutita, Persea Americana, Avena sativa, Zingiber officinale were prepared. 14C-caffeine and 14C-salicylic acid were topically dosed with either 10% solutions of natural extracts or ethanol (control) using a flow through in vitro porcine skin diffusion system. Samples were analyzed with liquid scintillation counter. The parameters of flux, permeability, and percent dose absorbed/retained were calculated and compared. RESULTS: The dermal absorption of 14C-caffeine was significantly higher (p ≥ 0.05) with avocado, chamomile, ginger and peppermint extract as compared to the control ethanol; while dermal absorption of 14C-salicylic acid was significantly greater with ginkgo and chamomile extract as compared to ethanol. Over four fold increase in flux and permeability of caffeine with avocado extract was observed while chamomile and peppermint extracts increased the flux and permeability of caffeine over three fold. Gingko and chamomile extracts increased salicylic acid's flux and permeability by two fold. Sum of %dose skin residue + %absorption in receptor fluid for different extracts exhibited the similar trend as shown by flux and permeability. The other natural extracts tested did not produce statistically significant effects on dermal penetration parameters for both caffeine and salicylic acid (p ≥ 0.05). CONCLUSION: These results emphasize the influence of natural plant extracts on the transdermal penetration of hydrophilic (caffeine) and hydrophobic (salicylic acid) penetrants and thus warrants the consideration as to their safety in cosmetics and topical pharmaceuticals containing natural extracts.

Modulation of chemical dermal absorption by 14 natural products: a quantitative structure permeation analysis of components often found in topical preparations.

A large number of cosmetics and topical pharmaceuticals contain compounds of natural origin. There is a rising concern if these compounds can interact with the activity of other topically applied components in these formulations. The current study demonstrates modulation of dermal absorption of model components often found in topical preparations (14C caffeine and 14C salicylic acid) by a set of 14 compounds of natural origin using a flow through in vitro porcine skin diffusion system. The parameters of flux and permeability were calculated and quantitative structure permeation relationship (QSPR) analysis conducted on different molecular descriptors of modulator compounds. Terpinyl acetate was the greatest permeability/flux enhancer for caffeine followed by s-perillyl acetate and limonene 1,2-epoxide. The permeability/flux of salicylic acid was highest with hydroxycitronellal followed by limonene 1,2-epoxide and s-perillyl acetate. The optimum descriptors using stepwise regression analysis for predicting additive modulation on penetrant permeability/flux were polar surface area, log P for caffeine and Henry's Law constant, number of freely rotatable bonds, and water solubility for salicylic acid. In parallel with the experimental techniques, a novel mathematical model was developed to estimate the permeability coefficients and improve the stepwise regression analysis for assessing modulator effects. The r2 values significantly increased for multicomponent QSPR models. Notably, limonene 1,2-epoxide and s-perillyl acetate were excellent enhancers for both caffeine and salicylic acid. These results confirm that some natural products incorporated into topical formulations will enhance absorption of other components which could affect their safety and efficacy profiles.

Haematopoietic effects of Angelica sinensis root cap polysaccharides against lisinopril-induced anaemia in albino rats.

CONTEXT: Angelica sinensis L. (Umbelliferae) has medicinal properties. OBJECTIVES: The present study evaluates the haematopoietic effects of A. sinensis polysaccharides (ASP) against lisinopril-induced anaemia. MATERIALS AND METHODS: Thirty healthy adult male albino rats were randomly divided into five groups (n = 6). Group I was control group. Group II was treated with angiotensin-converting enzyme inhibitor (ACEI, 20 mg/kg/day) to induce anaemia. In group III, erythropoietin (EPO, 100 IU/kg/each) was administered in combination with ACEI. Group IV was treated with ASP (1 g/kg/day), extracted from A. sinensis root caps. In Group V, ASP (1 g/kg/day) was treated with ACEI. After 28 days, blood and tissue samples were collected for haematological and histopathological analysis, respectively. RESULTS: The results showed that ACEI significantly reduced the haemoglobin (Hb, 10.0 g/dL), packed cell volume (PCV, 39.5%), red blood cells (RBCs, 6.2 million/mm3), mean corpuscular volume (MCV, 53.5 fL) and mean corpuscular haemoglobin (MCH, 16.2 pg/cell) values. In the group treated with ASP, the Hb (13.7 g/dL) and RBCs (7.8 million/mm3) increased significantly (p < 0.05). The combination of ASP and ACEI led to the significant (p < 0.05) reduction in Hb (10.7 g/dL), PCV (33.3%), RBCs (6.0 million/mm3), MCV (54.42 fL) and MCH (16.44 pg/cell) values. While histopathological examination of the liver and kidney cells showed a mild degree of toxicity in the ASP-treated group. CONCLUSION: ASP has a potentiating effect on haematological parameters when given alone. However, when administered simultaneously with lisinopril, it showed an unfavourable effect with more complicated anaemia so it should not be used with ACEIs.

Determination of florfenicol residues in broiler meat and liver samples using RP-HPLC with UV-visible detection.

BACKGROUND: Broilers are vulnerable to various types of microorganisms, including Salmonella, Escherichia coli and Staphylococcus aureus, resulting in multiple infections. Broad-spectrum antibacterial drugs such as florfenicol (FF) are widely used in the treatment of such infections. Suspected residues of these drugs in body tissues of treated birds can be passed to humans through meat consumption and thus lead to serious ill effects on human health. The present study was designed to estimate the presence of FF residues in broiler meat and liver samples. RESULTS: The mean residual concentrations of FF in broiler meat and liver samples were 311.42 ± 186.56 and 2585.44 ± 1759.71 µg kg(-1) respectively, which are higher than their respective maximum residual limits (MRLs). The results showed that 126 and 24 samples were FF-positive and FF-negative respectively. Of the positive samples, 84 and 42 samples were above and below the MRL respectively. CONCLUSION: The results indicate the presence of FF residues in broiler meat and liver samples. Usage of this contaminated meat causes resistance in consumers and poses a public health threat. Thus there is a need to educate farmers about the ill effects of residual drugs on human health and their withdrawal times in poultry. © 2015 Society of Chemical Industry.

In vitro and in vivo toxicological evaluations of methyl ferulate, methyl p-coumarate, and pulegone 1,2-epoxide.

CONTEXT: Toxicological screening of natural compounds for medicinal purposes. OBJECTIVES: The objective of this study is to evaluate the toxicity of methyl ferulate (MF), methyl p-coumarate (MpC), and pulegone 1,2-epoxide (PE) with in vitro and in vivo assays. MATERIALS AND METHODS: The in vitro toxicity of MF, MpC, and PE was assessed at a concentration of 10 mg/ml with the Ames assay using two strains of Salmonella typhimurium TA98 and TA100. Human red blood cells (RBC) were used to determine the hemolytic activity of these compounds. The cytotoxicity of above compounds was determined with brine shrimp lethality bioassay (BSLB) at the concentrations of 0.1-20 mg/ml. While dermal and ocular irritation studies were conducted on healthy rabbits (n = 8) for 96 and 12 h post-topical application of test compounds, respectively. RESULTS: PE produced 6-8% hemolysis of RBCs at all the tested concentrations while MF and MpC produced 10-5% hemolysis up to 20 mg/ml, and 50-85% hemolysis at concentrations of 40 and 80 mg/ml, respectively. The Ames assay indicated that MF, MpC, and PE were non-mutagenic as the test values were not significantly higher as compared with background values of the assay. BSLB suggested the lethal concentration (LC50) values of MF, MpC, and PE as 4.38, 6.74, and 25.91 mg/ml, respectively. In vivo ocular and dermal irritation scores of MF, MpC, and PE were comparable with ethanol (control) in rabbits indicating the non-irritant nature of these natural compounds. CONCLUSION: The present studies suggest that these compounds are non-toxic/non-irritant and might be used for medicinal purposes.

Dermatoprotective effects of some plant extracts (genus Ficus) against experimentally induced toxicological insults in rabbits.

AIM: Present study was conducted to evaluate the dermatoprotective effects of plant extracts (Ficus religiosa, Ficus benghalensis, and Ficus racemosa) against known irritants such as sodium dodecyl sulfate (SDS), atrazine, and petrol. METHODS: The study was conducted in adult male rabbits. Ethanol extracts of plants were obtained through Soxhlet. All irritants and Ficus extracts were topically applied to the backs of rabbits daily for 4 days, while pure ethanol served as control. Skin was examined after 24, 48, and 96 h for erythema. Skin biopsies were taken on 5th day for microscopic examination. RESULTS: Erythema produced by irritants reduced significantly with the simultaneous application of Ficus extracts. The mean ± SEM epidermal thickness (micrometer) with SDS was 45.40 ± 1.89, F. religiosa + SDS was 18.60 ± 0.51, F. benghalensis + SDS was 18.40 ± 0.25, F. racemosa + SDS was 18.80 ± 0.37, and mixture of three Ficus species + SDS was 16.80 ± 0.37. Similar findings were revealed after using plant extracts with atrazine and petrol. The mean ± SEM epidermal layer count for SDS was 3.60 ± 0.25, atrazine was 3.40 ± 0.25, petrol was 3.40 ± 0.25, and ethanol (control) was 1.00 ± 0.20. This count reduced to 1.20 ± 0.20 for three Ficus species + SDS, 1.40 ± 0.25 for Ficus species + atrazine, and 1.40 ± 0.25 for Ficus species + petrol. CONCLUSION: Ficus species demonstrated the potential to block the dermatotoxic effects of topical irritants and could be used successfully to prevent skin toxicity.

Effect of oxytocin on serum biochemistry, liver enzymes, and metabolic hormones in lactating Nili Ravi buffaloes.

Studies reporting the effects of oxytocin on the health of lactating animals are lacking and still no such data is available on Nili Ravi buffalo, the most prominent Asian buffalo breed. The present study was conducted to investigate the effect of oxytocin on physiological and metabolic parameters of lactating Nili Ravi buffaloes. Healthy lactating buffaloes (n = 40) of recent calving were selected from a commercial dairy farm situated in the peri-urban area of district Faisalabad, Pakistan. These buffaloes were randomly allocated to two equal groups viz experimental and control, comprising 20 animals each. Twice-a-day (morning and evening) milking practice was followed. The experimental and control buffaloes were administered subcutaneously with 3 mL of oxytocin (10 IU/mL) and normal saline respectively, prior to each milking. Serum biochemical profile including glucose, total cholesterol (tChol), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), total proteins (TP), C-reactive protein (CRP), liver enzymes aspartate transaminase (AST), alanine transaminase (ALT), and metabolic hormones triiodothyronine (T3) and thyroxine (T4) were studied. Results revealed significantly higher (P ≤ 0.01) levels of glucose, total cholesterol, LDL-C, triglycerides, total proteins, and C-reactive protein in experimental (oxytocin-injected) lactating buffaloes compared to control group. Liver enzymes AST and ALT as well as serum T4 concentration was significantly higher (P ≤ 0.01) in oxytocin-injected lactating buffaloes as compared to control animals. It was concluded that oxytocin had the key role in increasing the metabolic parameters and hormones, resulting in the optimization of production. But, at the same time, it may pose a threat to the animal health.