The effect of hepatic steatosis on 18F-FDG uptake in PET-CT examinations of cancer Egyptian patients.

BACKGROUND: Hepatic steatosis is the most common chronic hepatic disease. Imaging diagnosis of hepatic steatosis has been evaluated as an alternative to invasive histological diagnosis. STUDY AIMS: The study aimed to assess the effect of hepatic steatosis on Flourine-18 fluorodeoxyglucose (18F-FDG) uptakes in cancer patients. PATIENTS AND METHODS: Blood samples were collected from 50 cancer patients and analyzed to calculate fatty liver index and Hepatic steatosis index (HIS). Hepatic steatosis examined using high-resolution ultrasound and positron emission tomography-computed tomography (PET-CT). Linear attenuation coefficient, standardized-uptake value (SUV) mean (SUV mean), and SUV maximum (SUVmax) were measured. Accordingly, patients were divided equally into non-fatty liver, and fatty liver groups. RESULTS: A significant increase in SUVmax and SUV mean was observed in the fatty liver group more than in the non-fatty liver group. HSI significantly increased in the fatty liver group compared to the non-fatty liver group. Liver tissue uptake FDG was significantly correlated with HSI values. SUV max significantly correlated with body mass index (BMI) in the non-fatty group only. CONCLUSION: Hepatic changes in cancer patients affect the liver metabolic activity and thus the 18 F-FDG uptake. Therefore, further corrections should be considered when the liver is used as a comparator for PET-CT scans of cancer patients.

Metabolomics analysis of Citrus medica var. sarcodactylis (Siebold ex Hoola van Nooten) Swingle and Limonia acidissima Linn. fruits and leaves in perspective to their antimicrobial potential.

Antimicrobial potential of Citrus medica var. sarcodactylis (Siebold ex Hoola van Nooten) Swingle and Limonia acidissima L. fruits and leaves extracts CMF, CML, LAF and LAL, respectively were evaluated. Gas chromatography-mass spectrometry (GC-MS) analysis for lipoidal matters revealed a high percentage of non-oxygenated compounds. Phytol was the major in LAL. Palmitic and linoleic acid were the major in CML and LAL, respectively. Rutin and P-hydroxy benzoic acid were the main compounds identified by High-performance liquid chromatography (HPLC) analysis. The antibacterial and antifungal activities of the plants extract were determined by the well diffusion method. Antimicrobial investigation for different successive fractions of active methanol extracts of CML, LAL, LAF and CMF showed the highest activity (CML), whereas the petroleum ether (CML PE) and MeOH (CML) fractions exhibit a significant antifungal activity against Candida albicans minimum inhibitory concentration (MIC) 12 and 15 µg/mL, respectively. The antifungal activity prevailed by C. medica leaves may be attributed to its polyphenolics (rutin, chlorogenic and rosmarinic acid) in addition to phenylated hydrocarbon.

Comparison of gdh polymerase chain reaction-restriction fragment length polymorphism and tpi assemblage-specific primers for characterization of Giardia intestinalis in children.

Background: Giardia is a diarrheagenic eukaryotic parasite that consists of at least eight morphologically identical but genetically distinct genotypes. Human giardiasis is caused mainly by A and B assemblages. Aim and objectives: The study aimed to compare the performance of gdh polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and tpi assemblage-specific primers in genotyping of G. intestinalis. Materials and Methods: Stool samples of 315 children were microscopically screened for G. intestinalis. Positive samples were genotyped using tpi assemblage-specific primers and gdh semi-nested PCR-RFLP techniques. Results: The prevalence of Giardia was 18.1%. The detected genotypes using tpi and gdh approaches were assemblage A (15.8% vs. 12.7%) and assemblage B (36.8% vs. 74.5%) as single infections and mixed assemblages A and B (47.4% vs. 12.7%). The two approaches showed a moderate agreement (kappa index = 0.413, P < 0.001). PCR-RFLP of gdh gene revealed that sub-assemblages BIII and BIV were equally detected (30.9% each). The remaining samples were equally divided between sub-assemblage AII, mixed BIII and BIV, and mixed AII and BIII (12.7% each). A significant association was detected between the retrieved sub-assemblages and the presence of symptoms. Conclusions: Although both approaches confirmed the predominance of assemblage B, the use of assemblage-specific primers is more effective in elucidating the true picture of mixed assemblage infection.

Detection of Giardia intestinalis assemblages A and B among children from three villages in the West Delta region, Egypt using assemblage specific primers.

Giardia intestinalis is a common diarrheagenic parasite infecting children globally. It has been classified into eight morphologically identical but genetically distinct genotypes. Human infection is mainly associated with A and B assemblages with variable geographical distribution. The present work aimed to study the epidemiology of assemblages A and B in children inhabiting different areas in Lower Egypt. Stool samples were collected from 315 children and examined microscopically for parasitic infections. Giardia positive samples were genotyped using tpi assemblage specific primers. The prevalence of Giardia was 18.1% among the examined children. Mixed assemblages A and B was more common (47.4%) than single assemblage B (36.8%) or A (15.8%). The distribution of different genotypes was significantly associated with the residence area, animal contact, and handwashing habits. A non-significant association was observed between Giardia assemblages and the clinical manifestations. Assemblage B is the predominant genotype among Egyptian children. The distribution of different Giardia assemblages is strongly associated with the studied area and the habits of its people.

Radiosensitizing and Phototherapeutic Effects of AuNPs are Mediated by Differential Noxa and Bim Gene Expression in MCF-7 Breast Cancer Cell Line.

To compare the apoptotic efficiency of AuNPs, ionizing and non-ionizing radiotherapy, phototherapy, and AuNPs-ionizing-radiotherapy), MCF-7 cells were used as a model for luminal B subtypes of breast carcinoma. A mixture of AuNPs [66% of Au-nanospheres (AuNSs) and 34% of Au-nanorods (AuNRs)] was synthesized and characterized by optical spectroscopy, zeta potential, and transmission electron microscopy (TEM). MCF-7 were divided into six groups (triplicates); after each treatment, cell viability was tested by MTT assay and relative gene expression levels of Bim and Noxa proapoptotic markers were assayed by qRT-PCR. A dose-dependent significant reduction in cell viability of MCF-7 was detected by all examined treatment protocols. Lower viability detected at extended exposure (48 hours) to AuNPs ( [Formula: see text]/ml) was mediated by the upregulation of Noxa gene expression. AuNS and AuNR in vitro PTTs were mediated by differential expression of Bim and Noxa while AuNPs mixture had a combined effect on both Bim and Noxa. Cellular recovery was observed two days-post x-rays irradiation at does < 3 Gy. AuNPs showed dose enhancement factor (DEF) > 12 indicating a high radiosensitizing effect that was partially mediated by Noxa. In conclusion, AuNPs combined therapies exert better anti-proliferative effects via differential regulation of Noxa and Bim gene expressions.

Permeation Mechanism of Caffeine and Naproxen through in vitro Human Epidermis: Effect of Vehicles and Penetration Enhancers.

BACKGROUND/AIMS: The mechanisms by which permeation enhancers increase human skin permeation of caffeine and naproxen were assessed in vitro. METHODS: Active compound solubility in the vehicles and in the stratum corneum (SC), active compound flux across epidermal membranes and uptake of active and vehicle components into the SC were measured. The effect of vehicle pH on the permeation of caffeine and naproxen was also determined. RESULTS: Oleic acid and eucalyptol significantly enhanced the skin penetration of caffeine and naproxen, compared to aqueous controls. Naproxen permeation was increased from vehicles with pH presenting more ionized naproxen. Caffeine maximum flux enhancement was associated with an increase in caffeine SC solubility and skin diffusivity, whereas for naproxen a penetration enhancer/vehicle-induced increase in solubility in the SC correlated with an increase in maximum flux. SC solubility was related to experimentally determined active uptake, which was in turn predicted by vehicle uptake and active compound solubility in the vehicle. CONCLUSION: A permeation enhancer-induced alteration in diffusivity, rather than effects on SC solubility, was the main driving force behind increases in permeation flux of the hydrophilic molecule caffeine. For the more the lipophilic molecule naproxen, increased SC solubility drove the increases in permeation flux.

Follicular Penetration of Caffeine from Topically Applied Nanoemulsion Formulations Containing Penetration Enhancers: In vitro Human Skin Studies.

BACKGROUND/AIMS: This study aimed to investigate transfollicular delivery enhancement of caffeine from nanoemulsion formulations incorporating oleic acid (OA) and eucalyptol (EU) as chemical penetration enhancers. METHODS: Caffeine permeation was evaluated from nanoemulsions containing OA or EU and an aqueous control solution through excised human full-thickness skin with hair follicles opened, blocked, or left untreated. Differential tape stripping was performed, followed by cyanoacrylate skin surface biopsies to determine the amount of caffeine in the hair follicles, and skin extraction to determine the retention of caffeine in the skin. RESULTS: Nanoemulsions significantly increased caffeine permeation through open and untreated skin over control (untreated: 36- and 42-fold for OA and EU, respectively; open: 40- and 49-fold). The follicular route contributed 53.7% of caffeine permeation for the OA nanoemulsion and 51% for EU when follicles were opened. Nanoemulsions promoted 4- and 3.4-fold increases in caffeine retention in open follicles, for OA and EU, respectively. Retention of caffeine in the stratum corneum and skin was almost equal in all cases. CONCLUSIONS: This study demonstrated effective delivery of caffeine as a hydrophilic model drug into and through hair follicles and showed that follicles and surrounding regions may be targeted by optimised formulations for specific treatments.

Post-irradiation protective effects of ectoine on brain and testicles in male mice.

BACKGROUND: The present study aimed to investigate the possible post-irradiation protective effects of ectoine on CNS and testes of male mice. METHODS: The study included thirty male Swiss albino mice (20-22 gm). Mice were divided into five groups (six each); controls (injected intraperitoneally with 0.2ml saline), irradiated group 1 (received six Gy whole body x-irradiation single dose, injected with saline, and sacrificed after one day), irradiated group 2 (x-irradiated, injected with saline, and sacrificed after one week), ectoine group 1 (x-irradiated, injected with 200mg/kg ectoine, and sacrificed after one day), and ectoine group 2 (x-irradiated, injected daily with 200mg/kg ectoine, and sacrificed after one week). IL-1ß, IL-6, IL-10, PGE2, MDA, GSH, GSSG, and GSH/GSSG ratio were evaluated in CNS and testes. RESULTS: IL-1ß, IL-6, IL-10, PGE2, and MDA are significantly elevated in the CNS and testes of x-irradiated groups when compared with controls. IL-1ß, IL-6, IL-10, and PGE2 significantly elevated at one week than one day while MDA significantly decreased. A significant decrease in the concentration of GSH and in the GSH/GSSG ratios coupled with an opposite effect on GSSG was noted. Ectoine treatment significantly ameliorated the biochemical effects induced by whole body x-irradiation. All the tested parameters tended to go back to near control values. It was noted that the modulating action was dependent on the accumulation of ectoine as it was more effective after repeated administration. CONCLUSION: Ectoine has post-irradiation protective effects on CNS and testes via its action on inflammatory and oxidative stress pathways.

Minoxidil Skin Delivery from Nanoemulsion Formulations Containing Eucalyptol or Oleic Acid: Enhanced Diffusivity and Follicular Targeting.

In this work, we examined enhanced skin delivery of minoxidil applied in nanoemulsions incorporating skin penetration enhancers. Aliquots of fully characterized oil-in-water nanoemulsions (1 mL), containing minoxidil (2%) and the skin penetration enhancer oleic acid or eucalyptol as oil phases, were applied to full-thickness excised human skin in Franz diffusion cells, while aqueous solutions (1 mL) containing minoxidil were used as controls. Minoxidil in the stratum corneum (SC), hair follicles, deeper skin layers, and flux through the skin over 24 h was determined, as well as minoxidil solubility in the formulations and in the SC. The nanoemulsions significantly enhanced the permeation of minoxidil through skin compared with control solutions. The eucalyptol formulations (NE) promoted minoxidil retention in the SC and deeper skin layers more than did the oleic acid formulations, while the oleic acid formulations (NO) gave the greatest hair follicle penetration. Minoxidil maximum flux enhancement was associated with increases in both minoxidil SC solubility and skin diffusivity in both nanoemulsion systems. The mechanism of enhancement appeared to be driven largely by increased diffusivity, rather than increased partitioning into the stratum corneum, supporting the concept of enhanced fluidity and disruption of stratum corneum lipids.

Development and Evaluation of Lipid Nanoparticles Containing Natural Botanical Oil for Sun Protection: Characterization and in vitro and in vivo Human Skin Permeation and Toxicity.

The use of sunscreen products is widely promoted by schools, government agencies, and health-related organizations to minimize sunburn and skin damage. In this study, we developed stable solid lipid nanoparticles (SLNs) containing the chemical UV filter octyl methoxycinnamate (OMC). In parallel, we produced similar stable SLNs in which 20% of the OMC content was replaced by the botanical urucum oil. When these SLNs were applied to the skin of human volunteers, no changes in fluorescence lifetimes or redox ratios of the endogenous skin fluorophores were seen, suggesting that the formulations did not induce toxic responses in the skin. Ex vivo (skin diffusion) tests showed no significant penetration. In vitro studies showed that when 20% of the OMC was replaced by urucum oil, there was no reduction in skin protection factor (SPF), suggesting that a decrease in the amount of chemical filter may be a viable alternative for an effective sunscreen, in combination with an antioxidant-rich vegetable oil, such as urucum. There is a strong trend towards increasing safety of sun protection products through reduction in the use of chemical UV filters. This work supports this approach by producing formulations with lower concentrations of OMC, while maintaining the SPF. Further investigations of SPF in vivo are needed to assess the suitability of these formulations for human use.

Topical Nano and Microemulsions for Skin Delivery.

Nanosystems such as microemulsions (ME) and nanoemulsions (NE) offer considerable opportunities for targeted drug delivery to and via the skin. ME and NE are stable colloidal systems composed of oil and water, stabilised by a mixture of surfactants and cosurfactants, that have received particular interest as topical skin delivery systems. There is considerable scope to manipulate the formulation components and characteristics to achieve optimal bioavailability and minimal skin irritancy. This includes the incorporation of established chemical penetration enhancers to fluidize the stratum corneum lipid bilayers, thus reducing the primary skin barrier and increasing permeation. This review discusses nanosystems with utility in skin delivery and focuses on the composition and characterization of ME and NE for topical and transdermal delivery. The mechanism of skin delivery across the stratum corneum and via hair follicles is reviewed with particular focus on the influence of formulation.

Plasma TuM2-PK correlates with tumor size, CRP and CA 15-3 in metastatic breast carcinomas; short versus long term follow up study of the Egyptian breast cancer patients.

BACKGROUND: The key regulator of tumor metabolome is the glycolytic isoenzyme M2-PK which favors the generation of nucleic acid via glutaminolysis as hypoxic adaptive mechanism in the tumor cells. AIM: The study aimed to evaluate the prognostic role of M2-PK, CRP, and CA 15-3 in preoperative and metastatic breast carcinomas. PATIENTS AND METHODS: The study included 70 females; 15 controls, 33 preoperative primary breast carcinomas clinically metastasis free, and 22 clinically diagnosed metastatic breast carcinomas. M2-PK and CA 15-3 were detected by ELISA. CRP was quantified using the CRP LATEX kit. RESULTS: TuM2-PK significantly increased in metastatic and preoperative groups when compared to controls (p= 0.049, p= 0.001); respectively. Both CRP and CA 15-3 were significantly increased in metastatic than the preoperative group (p= 0.002). CA 15-3 was significantly increased in both groups when compared to controls (p= 0.016; p< 0.001; respectively). TuM2-PK level significantly related to tumor size in metastatic group (p= 0.006) and with menstruation status (p= 0.039), and liver metastasis (p= 0.036) in preoperative group. TuM2-PK significantly correlated with CRP (r= 0.793, p= 0.004), and CA 15-3 (r= 0.568, p= 0.006) in the metastatic group.Metastatic group with TuM2-PK ⩽ 15 U/ml had significantly higher survival rate than those with > 15 U/ml (χ2= 13.841, p< 0.001) within 3.3-4.2 but not after 10-20 years follow up period. Metastasis to bone and lymph nodes significantly increased in the metastatic than the preoperative group (p= 0.002, p= 0.013; respectively). Within 3.3-4.2 years, CA15.3 has the highest prognostic performance in metastatic group while both TuM2-PK and CRP have same specificity. On the other hand, TuM2-PK has the highest prognostic performance in preoperative group. After 20 years follow up period, there was neither significant difference in the performance of the three markers in predicting mortality in metastatic and preoperative groups nor in predicting metastasis in preoperative group. CONCLUSION: Current results document for the first time, a cross-talk between TuM2-PK and each of CRP and CA 15-3 in metastatic breast cancer.

Skin models for the testing of transdermal drugs.

The assessment of percutaneous permeation of molecules is a key step in the evaluation of dermal or transdermal delivery systems. If the drugs are intended for delivery to humans, the most appropriate setting in which to do the assessment is the in vivo human. However, this may not be possible for ethical, practical, or economic reasons, particularly in the early phases of development. It is thus necessary to find alternative methods using accessible and reproducible surrogates for in vivo human skin. A range of models has been developed, including ex vivo human skin, usually obtained from cadavers or plastic surgery patients, ex vivo animal skin, and artificial or reconstructed skin models. Increasingly, largely driven by regulatory authorities and industry, there is a focus on developing standardized techniques and protocols. With this comes the need to demonstrate that the surrogate models produce results that correlate with those from in vivo human studies and that they can be used to show bioequivalence of different topical products. This review discusses the alternative skin models that have been developed as surrogates for normal and diseased skin and examines the concepts of using model systems for in vitro-in vivo correlation and the demonstration of bioequivalence.

A Comparison of the Penetration and Permeation of Caffeine into and through Human Epidermis after Application in Various Vesicle Formulations.

BACKGROUND/AIMS: A range of vesicles is now widely used to carry various solutes into and through the epidermis. These usually have the active solute encapsulated within and may be modified to confer flexibility and skin penetration enhancement. Here, we compared the ability of five different vesicle systems to deliver a model hydrophilic drug, caffeine, into and through excised human skin. METHODS: In addition to lipids, the vesicle excipients included eucalyptol or oleic acid as penetration enhancers, and decyl polyglucoside as a non-ionic surfactant. Vesicle particle sizes ranged between 135 and 158 nm, and caffeine encapsulation efficiencies were between 46 and 66%. Caffeine penetration and permeation were measured using high-performance liquid chromatography. RESULTS: We found that niosomes, which are liposomes containing a non-ionic surfactant, and transferosomes (ultraflexible vesicles) showed significantly greater penetration into the skin and permeation across the stratum corneum. Significant enhancement of caffeine penetration into hair follicles was found for transferosomes and those liposomes containing oleic acid. CONCLUSIONS: We conclude that targeted delivery of the hydrophilic drug caffeine into the skin compartments can be modified using optimized vesicular formulations.

Synergistic Skin Penetration Enhancer and Nanoemulsion Formulations Promote the Human Epidermal Permeation of Caffeine and Naproxen.

We examined the extent of skin permeation enhancement of the hydrophilic drug caffeine and lipophilic drug naproxen applied in nanoemulsions incorporating skin penetration enhancers. Infinite doses of fully characterized oil-in-water nanoemulsions containing the skin penetration enhancers oleic acid or eucalyptol as oil phases and caffeine (3%) or naproxen (2%) were applied to human epidermal membranes in Franz diffusion cells, along with aqueous control solutions. Caffeine and naproxen fluxes were determined over 8 h. Solute solubility in the formulations and in the stratum corneum (SC), as well as the uptake of product components into the SC were measured. The nanoemulsions significantly enhanced the skin penetration of caffeine and naproxen, compared to aqueous control solutions. Caffeine maximum flux enhancement was associated with a synergistic increase in both caffeine SC solubility and skin diffusivity, whereas a formulation-increased solubility in the SC was the dominant determinant for increased naproxen fluxes. Enhancements in SC solubility were related to the uptake of the formulation excipients containing the active compounds into the SC. Enhanced skin penetration in these systems is largely driven by uptake of formulation excipients containing the active compounds into the SC with impacts on SC solubility and diffusivity.

Modulation of bone turnover in orchidectomized rats treated with raloxifene and risedronate.

Osteoporosis is a reduction in bone mineral density (BMD). It develops less often in men than in women. This study aimed to evaluate the bone protective effects of raloxifene (RAL), risedronate (RIS), and their combination on osteoporotic male rats. Forty male Wister rats (12 weeks) were randomly divided into five groups: sham-operated group (n = 8), orchidectomized (ORX) group (n = 7), RAL group (n = 9), RIS group (n = 7) and RAL + RIS group (n = 7). RAL was orally administered at 3 mg/kg three times/week, and RIS was given subcutaneously at 5 µg/kg, twice weekly. After 6 weeks of treatment, serum cathepsin-K, alkaline (ALP) and acid phosphatase activities, serum osteocalcin, serum Ca²âº, and Pi were determined. Urinary Ca²âº and deoxypyridinoline levels, BMD, and Ca²âº content of femur ash were estimated. Histochemical localization of ALP activity of tibia and histomorphometry was examined. As compared to sham, ORX rats showed a significant increase in bone turnover markers, and histochemical activity of ALP was increased markedly in proximal tibia of ORX rats, whereas BMD and Ca²âº content of femur ash were reduced after ORX. These changes were modulated after treatment with RAL and RIS or both to ORX rats; BMD of femur was improved by each treatment, and bone turnover markers were reduced as compared to ORX vehicle group. We concluded that orchidectomy induced osteoporosis and increased bone turnover in male rats because of withdrawal of sex hormones. Both RAL and RIS could treat osteoporosis in ORX rats; they reduced bone turnover markers and maintained BMD.