Gingerol nanoparticles attenuate complete Freund adjuvant-induced arthritis in rats via targeting the RANKL/OPG signaling pathway.

Rheumatoid arthritis (RA) is characterized by inflammatory joint pathology leading to the degradation of articular bone and cartilage, primarily triggered by synovial inflammation, resulting in joint discomfort. The metacarpophalangeal and proximal interphalangeal joints are predominantly affected. Treatment typically involves a combination of biological and synthetic disease-modifying antirheumatic drugs (DAMARDs) alongside steroid therapy. The application of nanomedicine has been instrumental in enhancing treatment efficacy by facilitating controlled release of pharmacologically active compounds, thus augmenting bioavailability and enabling targeted drug delivery. Gingerol, a constituent of ginger, possesses multifaceted properties. including anti-inflammatory, anti-oxidant, antidiabetic, and antipyretic effects. In this study, gingerol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), coated with chitosan, were administered orally to rats over a period of 21 days to address RA induced by complete Freund adjuvant (CFA). The rats were segregated into four experimental groups. Upon completion of the treatment regimen, blood samples were collected for the assessment of cyclooxygenase-2 (COX-2), RA factor, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Subsequent gene expression analysis was conducted to evaluate the levels of interleukin-4 (IL-4), interleukin-17a (IL-17a), IL-6, interferon-gamma (INF-γ), TNF-α, interleukin-1 beta (IL-1ß), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL). Statistical analyses utilizing one-way ANOVA followed by Tukey tests were applied to the data. The gene expression profiling revealed significant disparities in mRNA levels of IL-1ß, IL-6, IL-4, IL-17a, RANKL, INF-γ, and TNF-α between the CFA-induced arthritis group and the control group. Consequently, it was inferred that gingerol-loaded PLGA NPs coated with chitosan exhibited heightened therapeutic efficacy in addressing CFA-induced arthritis in rats.

Pathological effects of feeding aflatoxin-contaminated feed on immune status and reproductive performance of juvenile white leghorn males and its mitigation with ∝-tocopherol and Moringa oleifera.

This study was planned to detect the adverse pathological consequences of aflatoxin B1 in White Leghorn (WLH) layer breeder males. Eight-week-old male layer cockerels were separated into six experimental categories: A group was kept as negative control, offered with normal feed only; group B was fed with 400 ppb amount of aflatoxin, while groups F and D fed with normal feed and supplemented with vitamin E 100 ppm and 1% Moringa oleifera, respectively, whereas groups E and C were fed with 400 ppb aflatoxin containing feed and ameliorated with vitamin E 100 ppm and 1% Moringa oleifera, respectively. This study was continued for 2 months and immunologic disorders and reproductive parameters were observed during the trial. To find out immunological status lymphoproliferative response to phytohemagglutinin-P (PHA-P), antibody titers against sheep red blood cells (SRBCs) and carbon clear assay were performed by collecting samples from five birds from each group. The whole data was measured by ANOVA test, and group means were compared by DMR test by using M-Stat C software. Regarding the reproductive status, spermatogenesis, blood testosterone level, testes weight, testes histology, sperm motility, and morphology were negatively affected by aflatoxins, but these deviations positively ameliorated by vitamin E and Moringa. Vitamin E and Moringa found advantageous in boosting the immune status of affected bird. All the immunological parameters including antibody titers against sheed red blood cells, lymphoproliferative response to avian tuberculin and phagocytic potential of macrophages were suppressed by AFB1 however in control, Moringa and vitamin E groups these immunological responses were significantly higher.

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.

Acacia jacquemontii ethyl acetate extract reduces hyperglycemia and pro-inflammatory markers while increasing endogenous antioxidant potential in alloxan-induced diabetic rats.

Acacia jacquemontii possess has numerous traditional therapeutic uses. The rationale of this study was to investigate the role of Acacia jacquemontii ethyl acetate extract (AJEAE) in the downregulation of hyperglycemia. The current study was performed in two parts, in vitro, through characterization (high-performance liquid chromatography), estimation of total phenolic content, total flavonoid content, antioxidant (2,2-diphenyl-1-picrylhydrazylassay), and α-amylase inhibitory activities of the studied extract, and in vivo using Wistar rats in which animals were divided into five groups NC, DC, GL, AJEAE 250 mg/kg, and AJEAE 500 mg/kg. The effects of AJEAE on fasting plasma glucose, plasma insulin, HOMA-IR, oral glucose tolerance test, glycated hemoglobin (HBA1c), lipid profile, inflammatory cytokines (Interleukin-6, tumor necrosis factor-alpha), and oxidative stress markers (lipid peroxidation, nitic oxide, superoxide dismutase, catalase, glutathione peroxidase) were evaluated. Our findings confirmed the presence of quercetin, kaempferol, gallic acid, vanillic acid, syringic acid, M-coumaric acid, sinapic acid, chlorogenic acid, cinnamic acid, and ferulic acid in AJEAE. Total flavonoid and phenolic contents in AJEAE were 83.83 mg GAE/g and 77.06 mg QE/g, respectively. Significant inhibition of DPPH (69.470%/1 mg/ml) and α-amylase (71.8%/1 mg/ml) activities were exhibited by AJEAE. Alloxan-injected rats showed marked hyperglycemia and hypoinsulinemia, and increased inflammatory marker levels as compared to normal control (p < 0.001). Additionally, raised levels of triglyceride (139.7 ± 2.771), total cholesterol (198.7 ± 1.856), very low-density lipoprotein (33.43 ± 0.2728), low-density lipoprotein (155.5 ± 2.754), lipid peroxidation, and nitric oxide (p < 0.001) and decreased levels of high-density lipoprotein (17.20 ± 0.1732), superoxide dismutase, catalase, and glutathione peroxidase were observed in diabetic rats (p < 0.001). AJEAE significantly (p < 0.05) improved the aforementioned parameters and the protective efficacy was comparable to glibenclamide. Histopathological findings also evidenced the anti-hyperglycemic properties of AJEAE through regeneration of pancreatic ß cells. Conclusively, our findings demonstrated the antihyperglycemic, antihyperlipidemic, antioxidant, anti-inflammatory, and pancreatic beta ß cell regenerative properties of AJEAE against alloxan-induced diabetes.

Amelioration of hyperglycaemia and modulation of pro-inflammatory cytokines by Tamarix gallica fractions in alloxan induced diabetic rats.

Present study is engrossed in identification of phyto-constituents from aerial part extracts of Tamarix gallica and appraisal of its anti-oxidant, anti-diabetic and anti-inflammatory potential based upon its folktale use. The methanol and n-hexane fractions of aerial parts were analysed using high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) respectively. Inhibitory concentration (IC50) showed better results in case of methanolic extract for both in antioxidant (IC50= 15.47 µg/mL) and alpha amylase (IC50=18.75 µg/mL) assays. Significantly higher quantities of phenolic and flavonoid contents were present in methanolic extract. A significant correlation was found to be existed between these contents and IC50 of antioxidant assay. Alloxan induced hyperglycaemia declined along with improvement in lipid profile, C-reactive proteins (CRP), liver function tests (LFTs) and renal function tests (RFTs). Methanolic fraction (500 mg/kg) was also related to significant reduction in levels of inflammatory markers i.e. tumour necrosis factor-alpha, TNF- α (1.28 ± 0.13 g/L) and interleukin-6, IL-6 (98 ± 10.4 pg/L) as observed in diabetic rats. Based upon the above findings, the study suggests that methanolic fraction from aerial parts of the T. gallica has better anti-diabetic profile which might be attributed to its alpha amylase, anti-oxidant and anti-inflammatory potential.

Isolation, characterization and in-vitro antigenicity studies of outer membrane proteins (OMPs) of Salmonella gallinarum coated gold nanoparticles (AuNPs).

The development of biomimetic nanoparticles by combining the natural cellular material with synthetic nanoparticles has inspired innovative therapeutic strategies as compared to traditional line of therapeutics. Therefore, the research was conducted to prepare the outer membrane proteins (OMPs) from Salmonella gallinarum and coated on to the surface of synthetic gold nanoparticles (AuNPs). The size of the final product was characterized by Zeta sizer and Zeta potential. The coating of outer membrane proteins onto the gold nanoparticles (AuNPs) was confirmed by transmission electron microscopy (TEM). The sterility, stability and safety of the prepared antigen was confirmed by standard culture media, in biological buffer solution and in-vitro pyrogenic testing, respectively. In-vitro antigenicity of outer membrane protein alone and coated with gold nanoparticles were observed through macrophage phagocytosis assay. On the basis of results, it was anticipated that bacterial outer membrane protein has immunogenic antigenic properties and coating of bacterial outer membrane protein on the surfaces of synthetic gold nanoparticles not only preserved the complex biological characteristics of bacteria but also provided greater immune responses as compared to outer membrane protein alone. So, it was concluded that the coating of bacterial outer membrane proteins on the surface of synthetic gold nanoparticles have synergistic effects to induce the immune responses and promising potential to develop the effective antibacterial vaccine against salmonellosis in poultry birds.

Comparative characterization of cinnamon, cinnamaldehyde and kaempferol for phytochemical, antioxidant and pharmacological properties using acetaminophen-induced oxidative stress mouse model / Caracterización comparativa de canela, cinamaldehído y kaempferol para propiedades fitoquímicas, antioxidantes y farmacológicas utilizando el modelo de ratón con estrés oxidativo inducido por acetaminofeno

This study was aimed to explore the comparative efficacy of cinnamon bark extract, cinnamaldehyde and kaempferol against acetaminophen (APAP)-induced oxidative stress. Cinnamon bark extract, cinnamaldehyde and kaempferol were utilized or in-vivo analysis. From the results of in-vitro screening tests, cinnamon ethanolic extract was selected for in-vivo study in mouse model. For this, Balb/c albino mice were treated with cinnamon ethanolic extract (200 mg/kg), cinnamaldehyde (10 mg/kg) and kaempferol (10 mg/kg) orally for 14 days followed by single intraperitoneal administration of APAP during 8 hours. Blood and organ samples were collected for biochemical and histopathological analysis. The results showed that cinnamon bark ethanolic extract, cinnamaldehyde and kaempferol ameliorated APAP-induced oxidative stress and organ toxicity in mice. In conclusion, cinnamaldehyde and kaempferol possess comparable antioxidant potential even at 20-times less dose as compared to cinnamon bark ethanolic extract suggesting therapeutic potential in oxidative stress-related disorders.

Este estudio tuvo como objetivo explorar la eficacia comparativa del extracto de corteza de canela, cinamaldehído y kaempferol contra el estrés oxidativo inducido por acetaminofén (APAP). Se utilizaron extracto de corteza de canela, cinamaldehído y kaempferol para el análisis in vivo. De los resultados de las pruebas de detección in vitro, se seleccionó el extracto etanólico de canela para estudio in vivo en modelo de ratón. Para ello, los ratones albinos Balb/c fueron tratados con extracto etanólico de canela (200 mg/kg), cinamaldehído (10 mg/kg) y kaempferol (10 mg/kg) por vía oral durante 14 días, seguido de la administración intraperitoneal única de APAP durante 8 horas. Se recogieron muestras de sangre y órganos para análisis bioquímicos e histopatológicos. Los resultados mostraron que el extracto etanólico de la corteza de canela, el cinamaldehído y el kaempferol mejoraron el estrés oxidativo inducido por APAP y la toxicidad orgánica en ratones. En conclusión, el cinamaldehído y el kaempferol poseen un potencial antioxidante comparable, incluso a una dosis 20 veces menor en comparación con el extracto etanólico de la corteza de canela, lo que sugiere un potencial terapéutico en los trastornos relacionados con el estrés oxidativo.

Mechanistic insights of snake venom disintegrins in cancer treatment.

Snake venoms are a potential source of various enzymatic and non-enzymatic compounds with a defensive role for the host. Various peptides with significant medicinal properties have been isolated and characterized from these venoms. Few of these are FDA approved. They inhibit tumor cells adhesion, migration, angiogenesis and metastasis by inhibiting integrins on transmembrane cellular surfaces. This plays important role in delaying tumor growth, neovascularization and development. Tumor targeting and smaller size make them ideal candidates as novel therapeutic agents for cancer treatment. This review is based on sources of these disintegrins, their targeting modality, classification and underlying anti-cancer potential.

Biotransformation and toxicity evaluation of functionalized manganese doped iron oxide nanoparticles.

Safe inorganic nanomaterials are tremendously used for diagnosis and therapies. However, essential processing in the microbiological environment changed the physical properties and in situ degradability, which is evaluated meticulously. In this research article, bare, Polyethylene glycol, and citrate coated manganese doped iron oxide nanoparticles are synthesized through the coprecipitation route. Structural, magnetic, optical, and morphological analyses are performed through different characterization tools. X-ray diffraction confirmed the formation of single-phase FeMnO3 with a crystallite size of 48.91 nm. Vibrating sample magnetometer analysis confirmed the formation of soft ferromagnetic behavior of bare and coated nanoparticles (NPs). Scanning electron microscopy and transmission electron microscopy confirmed the formation of spherical shaped nanoparticles. Single-dose in vivo acute toxicity testing is performed through the intraperitoneal route of administration on groups of healthy albino rats. Elevated enzyme levels of kidney and liver are observed at day 1 but a transient decrease is observed at later stages. Through optical follow-up, degradation effects are studied by adding prepared NPs in lysosomal like medium. Finally, metabolization of degraded products based on manganese/iron ions is studied by adding apoferritin into a lysosome like solution. These studies showed partial storage of manganese ions from NPs, while no substantial transfer is observed in the case of manganese salt.

Antioxidant and Wound Healing Potential of Essential Oil from Citrus reticulata Peel and Its Chemical Characterization.

BACKGROUND: Fruit peels are considered as waste and contribute to a major proportion of the biomass. They can be a good source of various therapeutic benefits. Peels biomass of citrus fruits is usually considered as garbage. Such peels may have many important and valuable medicinal components with pharmacological activities. Citrus reticulata, (Rutaceae family, local name tangerine) is a local seasonal fruit in Pakistan, a very good example of wastage of its peels. OBJECTIVE: The study is based on the exploration of a citrus fruit peel derived essential oil, its chemical characterization, identification of various bioactive components and the exploration of pharmacological potentials (antibacterial and wound healing activity). METHODS: Essential oil was recovered by hydro-distillation of freshly collected peels. Chemical constituents of oil were determined by Gas Chromatography-Mass Spectroscopy (GC-MS) analysis. Antioxidant activities were evaluated by total phenolic contents, total flavonoid content, DPPH scavenging activity and reducing power assay. Antibacterial activity was determined using disc diffusion assay. In vivo wound healing potential was determined in rabbits after topical administration of oil. Wound scoring was calculated followed by histological study. RESULTS: GC-MS analysis showed the presence of various components with the greatest proportion of D-Limonene (89.31%). Total flavonoid and phenolic contents were found to be 14.63 ± 0.95 mg CE/g and 17.03 ± 3.24 mg GAE/g respectively, while DPPH activity was found to be 73.32%. A better antibacterial activity was shown against E. coli. In vivo studies showed significant reduction in wound diameter in essential oil treatment groups. Further, the essential oil was found non-irritant in draize scoring. CONCLUSION: The study concluded that essential oil of this fruit peel might be used for antibacterial and wound healing purposes.

In vitro Antioxidant Activity and In vivo Anti-inflammatory Effect of Ricinus communis (L.) and Withania somnifera (L.) Hydroalcoholic Extracts in Rats

Abstract Ricinus communis L. and Withania somnifera L. have traditionally been used as analgesic and anti-inflammatory remedies. The current study was aimed to evaluate the in vitro antioxidant potential and anti-inflammatory activity of hydroalcoholic extract of R. communis leaves (RCE) and W. somnifera roots (WSE) in Wistar rats. Total phenolic and flavonoid contents were quantified and in vitro antioxidant activity of extracts was determined through DPPH* scavenging, superoxide anion scavenging and reducing power activities, while anti-inflammatory activity was observed by xylene-induced ear edema and paw edema induced by egg albumin and carrageenan. RCE and WSE demonstrated considerable antioxidant activity in DPPH* scavenging (IC50: 250.10 and 309.42 µg/mL), superoxide anion scavenging (IC50: 193.42 and 206.81 ug/mL), and reducing power (maximum absorbance: 1.47±0.01 O.D and 1.28±0.01 O.D at 500 ug/mL) activities, respectively, with high phenolic and flavonoid contents. Both extracts showed dose-dependent edema inhibition in inflammation models. A maximum ear edema inhibitions by RCE (51.49±2.54%) and WSE (49.28±1.90%) at 500 mg/kg were observed when compared to indomethacin (56.42±13.17%) in xylene-induced ear edema. RCE and WSE showed a maximum percentage of paw edema inhibitions of 46.62±8.98% and 43.00±12.44%, respectively as compared to chlorpheniramine (62.02±12.21%) after 4 h in the egg albumin model. In carrageenan-induced paw edema, RCE (72.88±13.79%) significantly inhibited paw edema in comparison to WSE (57.81±17.43%) against diclofenac (89.93±18.53%). Conclusively, both plants have shown plausible antioxidant and anti-inflammatory activities that might be due to high phenolic and flavonoid contents. Moreover, RCE demonstrated more promising effects than WSE.

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.

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.

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.

Histopathological evaluation of gastro protective effect of Berberis vulgaris (Zereshk) seeds against aspirin induced ulcer in albino mice.

The present study was carried out to investigate the antiulcer activity of Berberis vulgaris (Zereshk) seeds in albino mice. After acclimatization, animals were divided into six equal groups. Aspirin 150 mg/kg was used to induce gastric ulcer in all groups except normal control. Omeprazole 20mg/kg was used as synthetic anti ulcer drug in study. Three dose levels of B. vulgaris seed powder 300 mg/kg, 600 mg/kg and 900 mg/kg were used respectively orally. Histopathological analysis was carried out to evaluate the gastroprotective activity of B. vulgaris seed powder. Results of the study showed that in case of aspirin treated mice gastric luminal mucosa villi were decreased in height or were absent. In the glandular region there was connective tissue proliferation and also infiltration of cells. Similar infiltration of cells was present on muscularis mucosa. In esophageal region tumor cells were present. However three dose levels of B. vulgaris significantly reduced the tissue proliferation, infiltration of cells and sloughing induced by aspirin. Highest dose of B. vulgaris (900 mg/kg) showed similar results as synthetic antiulcer drug omeprazole.

Breast cancer: major risk factors and recent developments in treatment.

Breast cancer is the most common in women worldwide, with some 5-10% of all cases due to inherited mutations of BRCA1 and BRCA2 genes. Obesity, hormone therapy and use of alcohol are possible causes and over-expression of leptin in adipose tissue may also play a role. Normally surgery, radiation therapy and chemotherapy allow a good prognosis where screening measures are in place. New hope in treatment measures include adjuvant therapy, neoadjuvant therapy, and introduction of mono-clonal antibodies and enzyme inhibitors.

Quantitative structure activity relationship and risk analysis of some pesticides in the goat milk.

The detection and quantification of different pesticides in the goat milk samples collected from different localities of Faisalabad, Pakistan was performed by HPLC using solid phase microextraction. The analysis showed that about 50% milk samples were contaminated with pesticides. The mean±SEM levels (ppm) of cyhalothrin, endosulfan, chlorpyrifos and cypermethrin were 0.34±0.007, 0.063±0.002, 0.034±0.002 and 0.092±0.002, respectively; whereas, methyl parathion was not detected in any of the analyzed samples. Quantitative structure activity relationship (QSAR) models were suggested to predict the residues of unknown pesticides in the goat milk using their known physicochemical characteristics including molecular weight (MW), melting point (MP), and log octanol to water partition coefficient (Ko/w) in relation to the characteristics such as pH, % fat, specific gravity and refractive index of goat milk. The analysis revealed good correlation coefficient (R2 = 0.985) for goat QSAR model. The coefficients for Ko/w and refractive index for the studied pesticides were higher in goat milk. This suggests that these are better determinants for pesticide residue prediction in the milk of these animals. Based upon the determined pesticide residues and their provisional tolerable daily intakes, risk analysis was also conducted which showed that daily intake levels of pesticide residues including cyhalothrin, chlorpyrifos and cypermethrin in present study are 2.68, 5.19 and 2.71 times higher, respectively in the goat milk. This intake of pesticide contaminated milk might pose health hazards to humans in this locality.

Immunostimulatory and protective effects of Aloe vera against coccidiosis in industrial broiler chickens.

This paper reports the immunostimulatory and protective effects of Aloe vera extracts (aqueous and ethanolic) against coccidiosis in industrial broiler chickens. The study was divided into two experiments. Experiment-I was conducted for the evaluation of immunostimulatory activity of A. vera and experiment-II demonstrated the protective efficacy of A. vera extracts against coccidiosis in chickens. Results of the experiment-I revealed significantly higher (p<0.05) lymphoproliferative responses in chickens administered with ethanolic extract of A. vera as compared to those administered with aqueous extract and control group. Microplate haemagglutination assay for humoral response on day 7th and 14th post primary and secondary injections of sheep red blood cells (SRBCs) revealed significantly higher (p<0.05) anti SRBC antibody (total Igs, IgG and IgM) titers in chickens of experimental groups as compared to the control group. None of the extracts, however, demonstrated significant effects on the development of lymphoid organs. Results of experiment-II revealed maximum protection (60%) in chickens administered with aqueous Aloe extract as compared to the ethanolic extract administered chickens (45%). Mean oocysts per gram of droppings in the control group was significantly higher (p<0.05) as compared to the chickens in both the experimental groups. Chickens administered with aqueous Aloe extract showed a minimal mean lesion score (2.3) followed by those administered with ethanolic Aloe extract (2.6) and control chickens (3.05) for caeca, and a similar pattern was observed for intestinal lesion scoring. Further, significantly higher weight gains and antibody titers (p<0.05) were observed in chickens administered with A. vera extracts as compared to those in the control group. It was concluded that A. vera may be a potential and valuable candidate to stimulate the immune responses and can be used successfully as an immunotherapeutic agent against coccidiosis in industrial broiler chickens.

Dermatotoxic effects of orally administered ciprofloxacin in sweating and nonsweating animal models.

CONTEXT: Some drugs, such as ciprofloxacin (CFX), that are excreted in sweat may produce some effects/toxicities in the skin structure. In order to differentiate the dermatotoxic effects of drugs due to excretion in sweat, it is essential to perform simultaneous studies in sweating and nonsweating animal models. OBJECTIVE: To determine the dermatotoxic effects of CFX in sweating (goats) and nonsweating (rabbits) animals and to determine whether there is a relationship between dermatotoxicity and the blood CFX concentration. MATERIALS AND METHODS: CFX was administered orally at the dose rate of 20 mg/kg body weight to goats (n = 16) and rabbits (n = 16) for 1 and 2 weeks, while control animals were given vehicle (water). Skin biopsies were taken after 1- and 2-week administration of CFX and processed histologically. Similarly, the CFX concentration in the plasma samples was analyzed by high-performance liquid chromatography (HPLC). RESULTS: Mean ± standard error (SE) epidermal thickness (µm) was 26.2 ± 0.2, 38.6 ± 2.05, and 37.8 ± 1.8 for the control, 1-week-treated, and 2-week-treated goats and 16.06 ± 2.39, 50.67 ± 6.61, and 34.03 ± .12 for the control, 1-week-treated, and 2-week-treated rabbits, respectively. Mean ± SE epidermal cell layers were 2.08 ± 0.08, 3.42 ± 0.16, and 3.25 ± 0.21 in the control, 1-week-treated, and 2-week-treated goats and 1 ± 0, 3.08 ± 0.37, and 1.83 ± 0.35 in the control, 1-week-treated, and 2-week-treated rabbits, respectively. Mean ± SE plasma concentration (µg/mL) of CFX was 0.37 ± 0.06 and 0.30 ± 0.05 in the 1- and 2-week-treated goats and 0.13 ± 0.04 and 0.14 ± 0.09 in the 1- and 2-week-treated rabbits, respectively. CONCLUSION: Microscopically, increases in epidermal thickness, number of cell layers, and cell infiltration were observed in both sweating and nonsweating animals, indicating that the dermatotoxic effects may not be due to CFX excretion in sweat. No relationship was found between dermatotoxicity and blood CFX concentration in both animal models.