Zainy M. Banjar

Mitochondrial dysfunction induced impairment of spermatogenesis in LPS-treated rats: modulatory role of lycopene.

The current study investigates the potential toxicity of lipopolysaccharide (LPS) on the mitochondrial fraction of rat testis and the possible protective efficacy of lycopene. Adult male Wistar rats were categorized into four groups. Two groups were administered LPS (0.1mg/kg/day for 7 days i.p.); one of these groups received lycopene treatment (4 mg/kg/day by oral gavage, 24h before LPS treatment) (Group IV) and the other received LPS alone (Group III). A vehicle-treated group (Group I) and a lycopene drug control group (Group II) were also included. Sperm count and motility were significantly decreased in Group III. The testicular mitochondrial fraction of Group III showed significant increase in basal and Fe(2+)-induced lipid peroxidation, along with a significant increase in hydrogen peroxide (H(2)O(2)) level. Moreover, the activities of mitochondrial enzymic (SOD, CAT, GPx, GR and ADH) and non-enzymic (GSH and ascorbate) antioxidants levels were decreased. Group III also showed decline in the activities of TCA enzymes such as SDH, MDH and ICDH. Pretreatment with lycopene showed normal sperm parameters, lipid peroxidation, H(2)O(2) level, antioxidant defenses and TCA enzyme activities. In conclusion, this study indicates that LPS-induced oxidative stress leads to functional damages in the testicular mitochondria. Lycopene pretreatment provided a marked normalization in these parameters.

Optimization of self-nanoemulsifying systems for the enhancement of in vivo hypoglycemic efficacy of glimepiride transdermal patches.

Objectives: To optimize and use of glimepiride (GMD)-loaded self-nanoemulsifying delivery systems (SNEDs) for the preparation of transdermal patches. Methods: Mixture design was utilized to optimize GMD-loaded SNEDs in acidic and aqueous pH media. Optimized GMD-loaded SNEDs were used in the preparation of chitosan (acidic) and hydroxypropyl methyl cellulose (HPMC) (aqueous) films. The prepared optimized formulations were investigated for ex vivo skin permeation, for in vivo hypoglycemic activity and for their pharmacokinetic parameters using animal model. Results: The optimized formulations showed flux value of (2.88 and 4.428 μg/cm2/h) through rat skin for chitosan and HPMC films, respectively. The pattern of GMD release from both formulations was in favor of Higuchi and approaching zero order models. The n values for Korsmeyer–Peppas equation were characteristic of anomalous (non-Fickian) release mechanism. Moreover, HPMC patches have shown significant reductions (p < 0.05) in blood glucose levels; (213.33 ± 15.19) mg/100 ml from the base-line measurement after 12 h of application. Conclusions: Optimized GMD SNEDs patches were found to improve GMD skin permeability and the essential pharmacokinetic parameters. Further extensive pre/clinical studies are necessary prior to use transdermal GMD as a valuable alternative to peroral dosage forms with improved bioavailability, longer duration of action and more patient convenience.

The formulation of a nasal nanoemulsion zaleplon in situ gel for the treatment of insomnia

Background: Zaleplon is a drug used for the treatment of insomnia and is available in tablet form; however, it has two major problems. First, the drug undergoes extensive first pass metabolism, resulting in only 30% bioavailability, and second, the drug has a poor aqueous solubility, which delays the onset of action. Objective: The objective of this study is to utilise nanotechnology to formulate zaleplon into a nasal in situ nanoemulsion gel (NEG) to provide a solution for the previously mentioned problems. Methods: The solubility of zaleplon in various oils, surfactants and co-surfactants was estimated. Pseudo-ternary phase diagrams were developed and various nanoemulsion (NE) formulations were prepared; these formulations were subjected to visual characterisation, thermodynamic stability study and droplet size and conductivity measurements. Carbopol 934 was used as an in situ gelling agent. The gel strength, pH, gelation time, in vitro release and ex vivo nasal permeation were determined. The pharmacokinetic study of the NEG was carried out in rabbits. Results: Stable NEs were successfully developed with a droplet size range of 35 to 73 nm. A NEG composed of 15% Miglyol, 30% Labrasol and 10% PEG 200 successfully provided the maximum in vitro and ex vivo permeation and enhanced the bioavailability in the rabbits by eightfold, when compared with the marketed tablets. Conclusion: The nasal NEG is a promising novel formula for zaleplon that has higher nasal tissue permeability and enhanced systemic bioavailability.

Solid lipid nanoparticles loaded with iron to overcome barriers for treatment of iron deficiency anemia.

According to the World Health Organization, 46% of the world’s children suffer from anemia, which is usually treated with iron supplements such as ferrous sulfate. The aim of this study was to prepare iron as solid lipid nanoparticles, in order to find an innovative way for alleviating the disadvantages associated with commercially available tablets. These limitations include adverse effects on the digestive system resulting in constipation and blood in the stool. The second drawback is the high variability in the absorption of iron and thus in its bioavailability. Iron solid lipid nanoparticles (Fe-SLNs) were prepared by hot homogenization/ultrasonication. Solubility of ferrous sulfate in different solid lipids was measured, and effects of process variables such as the surfactant type and concentration, homogenization and ultrasonication times, and charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release and in vivo pharmacokinetics were studied in rabbits. Results indicated that Fe-SLNs consisted of 3% Compritol 888 ATO, 1% Lecithin, 3% Poloxamer 188, and 0.2% dicetylphosphate, with an average particle size of 25 nm with 92.3% entrapment efficiency. In vivo pharmacokinetic study revealed more than fourfold enhanced bioavailability. In conclusion, Fe-SLNs could be a promising carrier for iron with enhanced oral bioavailability.

Genetic and Antigenic Analysis of Human Rotavirus Prevalent in Al-Taif, Saudi Arabia

The subgroup, serotype and electropherotype diversity of human rotavirus strains was investigated in Al-Taif, Saudi Arabia. Out of 349 faecal samples collected from diarrhoeic children, 150 (43 percent) tested rotavirus positive by a group-A specific enzyme-linked immunosorbent assay (ELISA). The majority (87 percent) of the infected children were below 2 years of age. Subgrouping and serotyping of rotaviruses with specific monoclonal antibodies showed that of the 150 rotavirus positive specimens, 17 percent belonged to subgroup I, 59 per cent belonged to subgroup II, and 24 percent were neither subgroup I nor subgroup II. The specimens were typed, as serotype 1 (43 percent), serotype 2 (5 percent), serotype 3 (11 percent), serotype 4 (10 percent) or mixed serotypes (3 percent). The remaining 41 (27 percent) specimens were untypeable. None of the serotypes showed association with a particular age group. An electrophoretic analysis of viral RNA revealed 11 distinct patterns (six long and five short). The majority, 78 percent were long patterns and 22 percent were short patterns. Analysis of the specimens for which subgroups, serotypes and electropherotypes were available indicated that a given RNA pattern does not correspond to a particular subgroup or serotype.

Mangostanaxanthones III and IV: advanced glycation end-product inhibitors from the pericarp of Garcinia mangostana

Advanced glycation end-products (AGEs) are associated with a non-enzymatic reaction between the amino group of a protein and the carbonyl group of a sugar during hyperglycemia. The precipitation of AGEs in different tissues leads to many complications, such as endothelial dysfunction, cardiovascular complications, atherosclerosis, retinopathy, neuropathy, and Alzheimer’s disease. Garcinia mangostana L. (Clusiaceae) (GM) was selected owing to the ability of its polar and non-polar fractions to inhibit AGE formation. For the first time, the bioguided fractionation of its pericarp MeOH extract (GMT) gave rise to two new xanthones, namely, mangostanaxanthones III (1) and IV (3), in addition to six known compounds, β-mangostin (2), garcinone E (4), rubraxanthone (5), α-mangostin (6), garcinone C (7), and 9-hydroxycalabaxanthone (8), from the non-polar faction. Their structures were verified by various spectroscopic methods, including 1D and 2D NMR studies and high-resolution MS data. All of the isolated xanthones significantly inhibited both sugar (ribose) and dicarbonyl compound (methylglyoxal)-induced protein glycation in a dose-dependent manner. This is explained by the ability of the isolated xanthones to inhibit protein oxidation, as indicated by the decreases in dityrosine and N′-formylkynurenine formation.

Human rotavirus genomic RNA electropherotypes in Jeddah, Saudi Arabia from 1988 to 1992.

Polyacrylamide gel electrophoresis was used to analyze the double-stranded RNA of rotavirus recovered from stool specimens collected between March 1988 and December 1992 from children with acute diarrhoea admitted to the central hospital in Jeddah, Saudi Arabia. Rotavirus was detected by ELISA in 523 specimens of the 1242 collected during the study, giving an overall prevalence of 42.2% for the 5 years of investigation. Out of 523 rotavirus-positive specimens, 263 (50.3%) were successfully electropherotyped. Eighteen different electropherotypes were observed, 12 long patterns and six short patterns. Eighty-seven per cent of the electropherotypes were of the long RNA pattern. The remaining were short electropherotypes. The predominant electropherotypes were two long patterns and maintained dominance over 5 years of the study. The third most predominant pattern was a short electropherotype. The remaining electropherotypes made minor contributions every year. These predominant electropherotypes were different from the predominant patterns detected in many countries. Temporal distribution was observed for 5 successive years for the predominant electropherotypes, with an increase in the incidence during the cooler months of the year.

Protective effect of zingerone on increased vascular contractility in diabetic rat aorta.

The aim of the present study was to investigate the effect and possible mechanism of action of zingerone, the main constituent of ginger, on vascular reactivity in isolated aorta from diabetic rats. The results show that incubation of aortae with zingerone alleviates the exaggerated vasoconstriction of diabetic aortae to phenylephrine, as well as the impaired relaxatory response to acetylcholine in a concentration-dependent manner. Furthermore, Zingerone directly relax phenylephrine-precontracted aortae. The vasorelaxatory response is significantly attenuated by the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester hydrochloride and the guanylate cyclase inhibitor methylene blue but no effect of either the potassium channels blocker tetraethylammonium chloride, or the cyclooxygenase inhibitor indomethacin was observed. Zingerone had no effect on advanced glycation end product formation as well. In conclusion, zingerone ameliorates enhanced vascular contraction in diabetic aortae which may be mediated by its vasodilator effect through NO- and guanylate cyclase stimulation.

Crystallization of a new polymorph of acetohexamide from 2-hydroxybutyl-β-cyclodextrin solution: Form VI with a high aqueous solubility

A new polymorph of acetohexamide (Form VI) was prepared via the formation of a complex with 2-hydoxybutyl-β-cyclodextrin (HB-β-CD) in aqueous solution. An alkaline solution of acetohexamide and HB-β-CD was adjusted to pH 4.0 by titration with hydrochloric acid. The resulting opaque solution was filtered through paper and allowed to stand at 4°C for 24h. The resulting precipitate was isolated on a filter and analyzed for polymorph content by powder X-ray diffractometry and thermal analysis. The diffraction pattern and thermal behavior of the precipitate was different from those of previously reported acetohexamide polymorphs (Forms I, III, IV and V), indicating that a new polymorph of the drug, i.e. Form VI was produced. This new polymorph was fairly stable against conversion to a stable form even at accelerated storage conditions. Crystalline Form VI was highly soluble in water and dissolved more rapidly than the other known polymorphs. This property was reflected in the blood concentrations of the drug after oral administration to rats.

2,3-Seco-2,3-dioxo-lyngbyatoxin A from a Red Sea strain of the marine cyanobacterium Moorea producens

Chemical investigation of the organic extract of a Red Sea strain of the cyanobacterium Moorea producens has afforded 2,3-seco-2,3-dioxo-lyngbyatoxin A (1). Five known compounds including lyngbyatoxin A (2), majusculamides A and B (3 and 4), aplysiatoxin (5) and debromoaplysiatoxin (6) were also isolated. Their structures were elucidated by using HR-FAB-MS, 1D and 2D NMR analyses. The compounds were evaluated for antiproliferative activity against HeLa cancer cells. Lyngbyatoxin A (2) showed potent activity, with an IC50 of 9.2 nM, while 5 and 6 displayed modest activity with IC50 values of 13.3 and 3.03 μM, respectively. In contrast, compounds 1, 3 and 4 were inactive, with IC50 values greater than 50 μM. The lack of cytotoxicity for 2,3-seco-2,3-dioxo-lyngbyatoxin A (1) demonstrates that the indole moiety in lyngbyatoxin (2) is essential for its cytotoxicity, and suggests that detoxification of 2 may be carried out by biological oxidation of the indole moiety to yield 1.