Investigation of a new horizon antifungal activity with enhancing the antimicrobial efficacy of ciprofloxacin and its binary mixture via their encapsulation in nanoassemblies: in vitro and in vivo evaluation

The main goal of this study was to prepare and evaluate nanosponges containing ciprofloxacin (CIP) or its binary mixture with N-acetyl carnosine (NAC). Nanosponges were prepared by ultrasound-assisted synthesis technique using hydroxypropyl βeta-cyclodextrin (HPβ-CD), as the polymer and diphenyl carbonate (DPC) as the crosslinker. Entrapment efficiency (EE%) of CIP or its binary mixture with NAC in nanosponges was deduced spectrophotometrically. Nanosponges were characterized using several methods. EE% of CIP or its binary mixture with NAC inside nanosponges ranged from 98.63 ± 3.1 to 100 ± 0.07%. Particle size of nanosponges ranged from 66.7 to 90.1 nm. Release of drugs from nanosponges was biphasic and the release pattern followed Korsmeyer–Peppas model. Ex vivo and in vivo studies results showed that the antibacterial effect was enhanced with encapsulation of drugs in the nanosponge system. Furthermore, a potent antifungal activity was obtained from all examined formulae against Candida albicans (10231). The study revealed that successful encapsulation of CIP or its binary mixture with NAC in nanosponge formulations has innovated a new promising therapeutic activity for both drugs.     

Doxycycline hydrochloride-metronidazole solid lipid microparticles gels for treatment of periodontitis: development,in-vitro and in-vivo clinical evaluation

Objective: To formulate solid lipid microparticles (SLMs) encapsulating doxycycline hydrochloride (DH) and metronidazole (MT) for the treatment of periodontal diseases.

Methods: SLMs were prepared applying hot homogenization method, using different types of lipids and stabilized with various types and concentrations of surfactants. The optimized formula was subjected to freeze-drying followed by incorporation into poloxamer gel. Microbiological and clinical evaluation of the selected SLMs on patients suffering from periodontal diseases was performed.

Results: SLMs could entrap high percentage of both drugs (81.14% and 68.75 % for doxycycline hydrochloride and metronidazole respectively). Transmission electron microscopy images of SLMs showed nearly spherical particles. Freeze-dried SLMs showed satisfactory stability for three months. Combined drugs were molecularly dispersed in SLMs. Incorporation of the freeze-dried SLMs powder in poloxamer gel could control the drugs release for 72 h. In-vivo study revealed effective and safe use of SLMs gel for periodontitis treatment. Significant improvement in both microbiological and clinical parameters was observed as compared to scaling and root planing alone.

Conclusion: The formulated SLMs gel offers an applicable dosage form that can be injected directly into the periodontal pocket as adjunctive to scaling and root planing.     

Design,synthesis, biological evaluations,molecular docking,and in vivo studies of novel phthalimide analogs

A series of novel phthalimide analogs containing an indole or brominated indole moiety were synthesized and their antimicrobial activity was evaluated. Compound 8 showed a broad spectrum activity, revealing 53–67% of erythromycin activity on the tested bacteria and 60–70% of miconazole activity on the tested fungi. Anticancer activity was evaluated on the cell lines HepG2, MCF‐7, A549, H1299, and Caco2. The results revealed that the new phthalimide analog 8 has broad‐spectrum anticancer activity toward all the tested cancer cell lines, followed by compound 11 , which showed good activity toward all the tested cell lines except for MCF‐7. The ability of the promising analogs 5 , 8 , and 11 to bind to topoisomerase II DNA gyrase was investigated. Caspase‐3 activation and Bcl‐2 assay of the best active derivatives 8 , 11 in addition to compound 5 were evaluated. The antifibrotic activity was studied in an in vivo model and the histopathological studies revealed that treatment with the new compound 8 improved the fibrotic liver tissues to normality.

     

Diagnostic potential of magnetic resonance imaging (MRI) of the first carpometacarpal joint in hand osteoarthritis

Aim of this workTo assess the magnetic resonance imaging (MRI) findings compared to plain X-ray in patients with primary nodal osteoarthritis (OA) of first the carpometacarpal (CMC) joint of the thumb.Patients and methodsThis study included 35 Egyptian patients with primary nodal hand OA (HOA) and 15 healthy subjects of matched age. Each subject had plain X-rays graded by Kellgren and Lawrence (K–L) score for HOA. MRI testing of both hands done by using T1/T2 weighted axial and coronal images.ResultsThe mean age was 57.2 ± 8.3 years (45–72 years) and they were 24 females and 11 males. Disease duration of patients ranged (8 months to 10 years, 2.04 ± 1.06 years). In all HOA patients there were signs of knee OA involvement; synovial thickening in 51.4% of patients, knee effusion in 8.6%, limited knee ROM in 28.6% and night pain in 60%. There was a superiority of the MRI in detecting synovitis (71.4%), flexor tenosynovitis (71.4%), collateral ligament (60%), bone marrow lesion (85.7%) and cysts (57.1%) compared to the X-ray which could not detect them. MRI significantly detected osteophytes (88.6%), joint space narrowing (91.4%), erosions (85.7%) and malalignment (57.1%) compared to X-ray (51.4%, 62.9%, 34.3% and 14.3% respectively) (p < 0.001, p = 0.004, p < 0.001 and p < 0.001).ConclusionMRI is superior in detecting HOA changes compared to conventional radiography. As OA is recognized to involve the whole joint, modern imaging techniques such as MRI could be a valuable tool for better evaluation of HOA.     

SSRIs for Hot Flashes: A Systematic Review and Meta-Analysis of Randomized Trials

Background

Hot flashes are the most commonly reported vasomotor symptom during the peri- and early post-menopausal period.

Objectives

To systematically review, appraise and summarize the evidence of the impact of different SSRIs on peri-menopausal hot flashes in healthy women in randomized, controlled trials.

Methods

A comprehensive literature search was conducted of MEDLINE?, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science and Scopus through March 2013. Two independent reviewers selected studies and extracted data. Random effects meta-analysis was used to pool outcomes across studies, and Bayesian mixed treatment methods were used to rank SSRIs in terms of effectiveness.

Results

We included a total of 11 randomized controlled trials with good methodological quality enrolling 2,069 menopausal and post-menopausal women (follow-up 1–9 months, mean age 36–76 years, mean time since menopause 2.3–6.6 years). Compared with placebo, SSRIs were associated with a statistically significant decrease in hot flash frequency (difference in means ?0.93; 95 % CI ?1.46 to ?0.37; I² = 21 %) and severity assessed by various scales (standardized difference in means ?0.34; 95 % CI ?0.59 to ?0.10; I² = 47 %). Adverse events did not differ from placebo. Mixed treatment comparison analysis demonstrated the superiority of escitalopram compared to other SSRIs in terms of efficacy.

Conclusion

SSRI use is associated with modest improvement in the severity and frequency of hot flashes but can also be associated with the typical profile of SSRI adverse effects.     

Morphological development of testes in ostrich (Struthio camelus) embryo

Although the histological structure of ostrich testis has been studied, very little information is currently available on the embryonic development of this organ. The aim of this study was to determine the sequence of the histological changes in diverse components of the testis in ostrich embryo from embryonic day (E) 20 to E42. The main findings were categorized into four histological features, i.e., development of sex cords, interstitial tissue and rete ducts, and the appearance of defective septa. While the lumen of sex cords, tunica albuginea, capsular rete ducts and Leydig cell precursors appeared at E26, the filum-shaped defective septa were visible at E36. The emersion of the lumen in the primary sex cords and formation of capsular rete ducts in the ostrich embryo is considerably different from that in other birds. However, tunica albuginea and Leydig cell precursors appeared in a similar pattern to those of other birds. An interesting observation was that the primordial germ cell (PGC)-like cells were completely distinct, while the capsular rete ducts were formed by trapping of some Sertoli cell aggregations in the tunica albuginea. This suggests that similar to the primary sex cords, the capsular rete ducts may originate from the Sertoli cell aggregations which had corralled some PGCs. Stereological estimations in the ostrich embryo testis showed the major proportion of testis is occupied by the seminiferous tubules, which is unlike the fowl embryo testis.     

Misoprostol decreases oxidative stress and liver injury in bacterial lipopolysaccharide-induced endotoxemia in mice

The effect of misoprostol, a synthetic prostaglandin E1 analog, on the development of oxidative stress induced in mice with lipopolysaccharide (LPS) endotoxin was investigated. Misoprostol was administered by intraperitoneal route (i.p.) at doses of 10, 100, or 1,000 μg/kg at the time of LPS injection (200 μg/kg, i.p.). Mice were euthanized 4 h later. Lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH), nitric oxide (nitrite/nitrate) levels as well as paraoxonase activity were measured in brain and liver. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities as well as DNA fragmentation were determined in the liver. The administration of LPS increased oxidative stress both in the brain and liver tissue. There were significantly increased MDA and nitrite and decreased GSH and PON1 activity in the brain and liver, respectively. In addition, LPS was associated with markedly elevated plasma ALT and AST level as well as increased liver DNA fragmentation. The administration of misoprostol at 100 or 1,000 μg/kg decreased brain MDA by 17.6 and 30 %, increased GSH by 29.8 and 33.3 %, and decreased nitric oxide by 21.74 and 42.5 %, respectively, compared with the lipopolysaccharide control group. Liver MDA decreased by 27 %, GSH increased by 47.7 %, and nitric oxide decreased by 37.2 % with misoprostol at 1,000 μg/kg. Paraoxonase activity increased in both the brain and liver by misoprostol administration. The increase in liver AST and ALT and DNA fragmentation after endotoxin administration was normalized by misoprostol. These results indicate that misoprostol can alleviate oxidative stress in the presence of a mild systemic inflammatory illness, indicating a new and potentially important therapeutic application for the drug.