Testicular disorders induced by plant growth regulators: cellular protection with proanthocyanidins grape seeds extract

The present study aims to investigate the adverse effects of plant growth regulators : gibberellic acid (GA₃) and indoleacetic acid (IAA) on testicular functions in rats, and extends to investigate the possible protective role of grape seed extract, proanthocyanidin (PAC). Male rats were divided into six groups; control group, PAC, GA₃, IAA, GA₃ + PAC and IAA + PAC groups. The data showed that GA₃ and IAA caused significant increase in total lipids, total cholesterol, triglycerides, phospholipids and low-density-lipoprotein cholesterol in the serum, concomitant with a significant decrease in high-density-lipoprotein cholesterol, total protein, and testosterone levels. In addition, there was significant decrease in the activity of alkaline phosphatase, acid phosphatase, and gamma-glutamyl transferase. A significant decrease was detected also in epididymyal fructose along with a significant reduction in sperm count. Testicular lipid peroxidation product and hydrogen peroxide (H₂O₂) levels were significantly increased. Meanwhile, the total antioxidant capacity, glutathione, sulphahydryl group content, as well as superoxide dismutase, catalase, and glucose-6-phosphate dehydrogenase activity were significantly decreased. Moreover, there were a number of histopathological testicular changes including Leydig’s cell degeneration, reduction in seminiferous tubule and necrotic symptoms and sperm degeneration in both GA₃- and IAA-treated rats. However, an obvious recovery of all the above biochemical and histological testicular disorders was detected when PAC seed extract was supplemented to rats administered with GA₃ or IAA indicating its protective effect. Therefore it was concluded that supplementation with PAC had ameliorative effects on those adverse effects of the mentioned plant growth regulators through its natural antioxidant properties.     

Dapsone-Loaded Invasomes as a Potential Treatment of Acne: Preparation,Characterization, and <Emphasis Type="Italic">In Vivo</Emphasis> Skin Deposition Assay

Dapsone (DPS) is a unique sulfone with antibiotic and anti-inflammatory activity. Owing to its dual action, DPS has a great potential to treat acne. Topical DPS application is expected to be effective in treatment of mild to moderate acne conditions. Invasomes are novel vesicles composed of phosphatidylcholine, ethanol, and one or mixture of terpenes of enhanced percutaneous permeation. In this study, DPS-loaded invasomes were prepared using the thin film hydration technique. The effect of different terpenes (Limonene, Cineole, Fenchone, and Citral) in different concentrations on the properties of the prepared DPS-loaded invasomes was investigated using a full factorial experimental design, namely, the particle size, drug entrapment, and release efficiency. The optimized formulation was selected for morphological evaluation which showed spherical shaped vesicles. Further solid-state characterization using differential scanning calorimetry and X-ray diffractometry revealed that the drug was dispersed in an amorphous state within the prepared invasomes. Finally, the ability of the prepared DPS-loaded invasomes to deliver DPS through the skin was investigated in vivo using wistar rats. The maximum in vivo skin deposition amount of DPS was found to be 4.11 mcg/cm² for invasomes versus 1.71 mcg/cm² for the drug alcoholic solution, representing about 2.5-fold higher for the invasomes compared to the drug solution. The AUC0–10 calculated for DPS-loaded invasomes was nearly 2-fold greater than that of DPS solution (14.54 and 8.01 mcg.h/cm² for the optimized invasomes and DPS solution, respectively). These results reveal that the skin retention of DPS can be enhanced using invasomes.     

First report of detection of the putative receptor of Bacillus thuringiensis toxin Vip3Aa from black cutworm (Agrotis ipsilon)

Black cutworm (BCW) Agrotis ipsilon, an economically important lepidopteran insect, has attracted a great attention. Bacillus thuringiensis (Bt) is spore forming soil bacteria and is an excellent environment-friendly approach for the control of phytophagous and disease-transmitting insects. In fact, bio-pesticide formulations and insect resistant transgenic plants based on the bacterium Bt delta-endotoxin have attracted worldwide attention as a safer alternative to harmful chemical pesticides. The major objective of the current study was to understand the mechanism of interaction of Bt toxin with its receptor molecule(s). The investigation involved the isolation, identification, and characterization of a putative receptor – vip3Aa. In addition, the kinetics of vip toxin binding to its receptor molecule was also studied. The present data suggest that Vip3Aa toxin bound specifically with high affinity to a 48-kDa protein present at the brush border membrane vesicles (BBMV) prepared from the midgut epithelial cells of BCW larvae.     

Is Time to Reach EDSS 6.0 Faster in Patients with Late-Onset versus Young-Onset Multiple Sclerosis?

MethodsThis cross-sectional cohort study was conducted to identify LOMS and YOMS patients’ with relapsing remitting course at MS diagnosis. Time (years) to reach sustained EDSS 6.0 was compared between LOMS and AOMS patients. Cox proportional hazards model was used to evaluate the demographic and clinical predictors of time to EDSS 6.0 in these cohorts.ResultsLOMS and YOMS cohorts comprised 99 (10.7%) and 804 (89.3%) patients respectively. Spinal cord presentation at MS onset was more common among LOMS patients (46.5% vs. 32.3%). The proportions of LOMS and YOMS patients reaching EDSS 6.0 during the follow-up period were 19.2% and 15.7% respectively. In multivariable Cox proportional hazards model, older age at MS onset (adjusted hazard ratio (aHR) = 3.96; 95% CI: 2.14–7.32; p < 0.001), male gender (aHR = 1.85; 95% CI: 1.22–2.81; p = 0.004) and spinal cord presentation at onset (aHR = 1.47; 95% CI: 0.98–2.21; p = 0.062) were significantly associated with shorter time to EDSS 6.0.ConclusionsLOMS patients attained EDSS 6.0 in a significantly shorter period that was influenced by male gender and spinal cord presentation at MS onset.     

Preparation and Properties of Antibodies to GD3 and GM1 Gangliosides

Abstract: Gangliosides G_D3 and G_M1 were coupled to proteins by their car-boxyl groups and antisera were raised against the complexes. Anti-ganglioside antibodies were isolated by affinity chromatography on ganglioside-amino-propyl silica gel columns and the specificity of the antibodies was determined by a quantitative microcomplement fixation assay. Antibodies to G_D3 were highly specific and did not crossreact with G_M3, lactosyl ceramide, or other glycolipids. Purified antibodies to G_M1, in contrast, crossreacted with asialo-G_M1, G_D1b and to a lesser extent, G_M2 and asialo-G_M2. A derivative of G_M1, containing a C-7 sialic acid residue produced by periodate oxidation, reacted with the anti-G_M1 antibodies almost as readily as with G_M1. The specificities of anti-G_M1 antibodies elicited by the covalent ganglioside-protein complexes were similar to those produced by immunization with noncovalent complexes of G_M1 and methylated bovine serum albumin. The ganglioside-protein complexes described here should be useful for preparing antibodies to polysialo-gangliosides that contain neuraminidase-sensitive linkages.     

Metabolites of PGF2α in Blood Plasma and Urine as Parameters of PGF2α Release in Cattle

The metabolism of PGF2α in cattle results initially in the formation of 15-keto-13,14-dihydro-PGF2α (15-ketodihydro-PGF2α) and later the 11-ketotetranor PGF metabolites. Both types of metabolites appear in the peripheral circulation and finally the 11-ketotetranor PGF metabolites are found in large quantities in the urine in a species-related pattern. Several approaches can be made to the quantitative analysis of PGF2α release during reproductive studies. First, assay of the 15-ketodihydro-PGF2α metabolite in the peripheral circulation; second, analysis of the longer-lived 11-ketotetranor PGF metabolites in the peripheral circulation; and finally analysis of the latter metabolites in the urine. The antibodies used in radioimmunoassays of both types of metabolites of PGF2α were found to be specific and the results agree well with those obtained earlier by mass spectrometric analysis. The assay of 11-ketotetranor PGF metabolites was used to study the excretion of urinary metabolites in the cow after i.v. infusion of PGF2α and also during the normal estrous cycle and early pregnancy. These studies suggest that 11-ketotetranor PGF metabolites in cow urine serve as a good parameter of PGF2α release, especially for long–term studies, but when a precise pattern of PGF2α release is required, measurement of 15-ketodihydro-PGF2α levels in frequently collected plasma samples is preferable.     

Development of silica-coated rare-earth doped strontium aluminate toward superhydrophobic,anti-corrosive and long-persistent photoluminescent epoxy coating

Long-persistent phosphorescent smart paints have the ability to continue glowing in the dark for a prolonged time period to function as energy-saving products. Herein, new epoxy/silica nanocomposite paints were prepared with different concentrations of lanthanide-doped aluminate nanoparticles (LAN; SrAl₂O₄:Eu²⁺,Dy³⁺). The LAN pigment was firstly coated with silicon dioxide (SiO₂) utilizing the heterogeneous precipitation technique to provide LAN-encapsulated between SiO₂ nanoparticles (LAN@SiO₂). The epoxy/silica/lanthanide-doped aluminate nanoparticles (ESLAN) nanocomposite paints were coated on steel. The prepared ESLAN paints were studied by transmission electron microscopy (TEM), Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), X-ray fluorescence (XRF) analysis, and energy-dispersive X-ray spectroscopy (EDS). The transparency and coloration properties of the nanocomposite coated films were explored by CIE Lab parameters and photoluminescence spectra. The ultraviolet-induced luminescence properties of the transparent coated films demonstrated greenish phosphorescence at 518 nm upon excitation at 368 nm. Both hardness and hydrophobic activities were investigated. The anticorrosion activity of the nanocomposite films coated onto mild steel substrates immersed in aqueous sodium chloride (NaCl_(aq)) (3.5%) was studied by electrochemical impedance spectroscopy (EIS). The silica-containing coatings were monitored to exhibit anticorrosion properties. Additionally, the nanocomposite films with LAN@SiO₂ (25%) exhibited the optimized long-lasting luminescence properties in the dark for 90 min. The nanocomposite films showed highly reversible and durable long-lived phosphorescence.     

Liposomes as an ocular delivery system for acetazolamide: In vitro and in vivo studies

The purpose of this study was to formulate topically effective controlled release ophthalmic acetazolamide liposomal formulations. Reverse-phase evaporation and lipid film hydration methods were used for the preparation of reversephase evaporation (REVs) and multilamellar (MLVs) acetazolamide liposomes consisting of egg phosphatidylcholine (PC) and cholesterol (CH) in the molar ratios of (7∶2), (7∶4), (7∶6), and (7∶7) with or without stearylamine (SA) or dicetyl phosphate (DP) as positive and negative charge inducers, respectively. The prepared liposomes were evaluated for their entrapment efficiency and in vitro release. Multilamellar liposomes entrapped greater amounts of drug than REVs liposomes. Drug loading was increased by increasing CH content as well as by inclusion of SA. Drug release rate showed an order of negatively charged > neutral > positively charged liposomes, which is the reverse of the data of drug loading efficiency. Physical stability study indicated that approximately 89%, 77%, and 69% of acetazolamide was retained in positive, negative, and neutral MLVs liposomal formulations up to a period of 3 months at 4°C. The intraocular pressure (IOP)-lowering activity of selected acetazolamide liposomal formulations was determined and compared with that of plain liposomes and acetazolamide solution. Multilamellar acetazolamide liposomes revealed more prolonged effect than REVs liposomes. The positively charged and neutral liposomes exhibited greater lowering in IOP and a more prolonged effect than the negatively charged ones. The positive multilamellar liposomes composed of PC:CH:SA (7:4:1) molar ratio showed the maximal response, which reached a value of −7.8±1.04 mmHg after 3 hours of topical administration. Published: January 5, 2007     

Isolation and enzyme-inhibition studies of the chemical constituents from Ajuga bracteosa

Bractin A (=(2S,3S,4R,5E)-2-{[(2R)-2-hydroxydodecanoyl]amino}triacont-5-ene-1,3,4-triol; 1) and bractin B (=(2S,3S,4R,5E,8E)-2-{[(2R)-2-hydroxyhexacosanoyl]amino}pentadeca-5,8-diene-3,4,15-triol 1-O-beta-D-glucopyranoside; 2), new sphingolipids, and bractic acid (=(5Z,10Z,15Z)-2-decyl-4,7,8,12,13,17,18-heptahydroxy-20,23-dioxopentacosa-5,10,15-trienoic acid; 3), a long-chain polyhydroxy acid, were isolated from the whole plant Ajuga bracteosa along with four known diterpenoids 4-7. Their structures were deduced by spectral studies including 1D- and 2D-NMR spectroscopy. Compounds 1-3 displayed inhibitory potential against enzyme lipoxygenase, while compounds 4-7 inhibited cholinesterase enzymes in a concentration-dependent manner with IC(50) values in the range 10.0-33.0, 14.0-35.2, and 10.0-19.0 microM for lipoxygenase, acetylcholinesterase, and butyrylcholinesterase, respectively. Lineweaver-Burk, and Dixon plots, and their secondary replots indicated that all compounds exhibit non-competitive type of inhibition with K(i) values in the range of 9.5-35.2, 15.2-36.0, and 11.6-20.5 microM, for lipoxygenase, acetylcholinesterase, and butyrylcholinesterase, respectively.