Colon-specific delivery and enhanced colonic absorption of [Asu(1,7)]-eel calcitonin using chitosan capsules containing various additives in rats

The objective of this study was to estimate the colon-specific delivery of [Asu1,7]-eel calcitonin (ECT) using chitosan capsules in rats. The intestinal absorption of ECT was evaluated by measuring the plasma calcium levels after oral administration of the chitosan capsules containing ECT and different combinations of additives. The same combinations were investigated by an in situ absorption experiment prior to in vivo administration of capsules. A marked decrease in plasma calcium levels was observed following the oral administration of chitosan capsules containing ECT, S-nitroso-N-acetyl-dl-penicillamine (SNAP), sodium glycocholate, bacitracin and aprotinin (pharmacological availability (PA)% = 6.344%), as compared with capsules containing only ECT (PA% = 0.551%) or capsules containing ECT with SNAP only (PA% = 1.651%). The hypocalcemic effect started 6-8 h after oral administration of capsules and sustained for 24 h. These findings suggest that colon-specific delivery of ECT can be achieved using chitosan capsules and these additives may be useful for improving the colonic absorption of ECT in rats.     

Abdominal obesity and endometrial cancer in egyptian females with postmenopausal bleeding

Endometrial cancer is the most common type of female genital tract malignancies. We intended to assess the relation between different measures of obesity and the risk to develop endometrial cancer in Egyptian females with postmenopausal bleeding (PMB). The study was conducted in Alexandria, Egypt and included all postmenopausal females presenting to the University Hospital of Gynecology and Obstetrics with PMB within the study period (from January 1 to September 30). A questionnaire was completed, and data about anthropometric measurements including weight, height, and waist circumference were collected. Vaginal sonography, dilatation and curettage, and pathological examination were done by experts for all participants. Endometrial cancer was diagnosed in 38% of females presenting with PMB. Using ROC curve analysis, only the measure of abdominal obesity (waist circumference) showed significant accuracy in predicting endometrial cancer (area = 0.63, P < .05). The best cutoff point that maximizes accuracy was 88 cm. Body mass index (≥30 vs. ≤30) showed no significant relation (OR = 1.1, 95%CI 0.5-2.3), and the ratio between upper and lower body obesity (W/H ratio) showed border line significant relation (OR = 2, 95% CI 1-4.1), whereas waist circumference (≥88 vs. ≤88 cm) showed strikingly high OR (OR = 13.6, 95%CI 4-46.6). The risk of abdominal obesity on endometrial cancer remains very high (OR = 15.8, 95%CI 4.1-60.9) even after adjustment, in a logistic model, for other risk factors such as age at presentation, age at menarche, age at menopause, family history of malignancy, and gravidity. Abdominal obesity (waist circumference >88 cm) is the best measure of obesity to be used in predicting the risk of endometrial cancer in Egyptian females with PMB.     

The effect of unsaturated fatty acids in benzyl alcohol on the percutaneous permeation of three model penetrants

The model penetrants butyl paraben (BP), methyl paraben (MP) and caffeine (CF), because of their different octanol/water partition coefficients and postulated routes of permeation through human skin, were selected to assess the enhancing activity of pre-treatment solutions consisting of monounsaturated (oleic (OA) and palmitoleic (PA)) and poly-unsaturated (linoleic (LA)) fatty acids in benzyl alcohol (BA) using Franz diffusion cells and HPLC detection. Prior to assessing the effect of penetrant lipophilicity, MP was chosen to investigate the concentration-dependent effect of fatty acids in pre-treatment solutions. At 5% (w/w) fatty acids in BA, only pre-treatment solutions containing palmitoleic acid (PA) increased the permeation of MP when compared to pre-treatment with BA alone, whereas at higher concentrations (10 and 20%, w/w), all pre-treatment solutions except 10% OA produced a significant increase in MP flux (P<0.05). The general order of fatty acid effectiveness at any concentration was PA>LA>OA. At 20% (w/w) fatty acids in BA, all pre-treatment solutions significantly enhanced the permeation of all three penetrants (P<0.05) and an inverse relationship between penetrant lipophilicity and enhancement effect was observed. The permeation of BP was enhanced to a similar extent by all three fatty acids, whereas PA caused a significantly greater enhancement in the flux of both MP and CF when compared to OA, LA and controls (P<0.05). It was proposed that the synergetic enhancement mechanisms of fatty acids and BA in pre-treatment solutions were augmenting the polar route by way of interactions with both polar and non-polar regions of stratum corneum lipids. Furthermore, the combination of PA and BA appears to be a good candidate as a penetration enhancer for hydrophilic molecules.     

Doxycycline in the treatment of bleeding with DMPA: a double-blinded randomized controlled trial

BackgroundIncreased matrix metalloproteinase (MMP) activity in the endometrium is a predisposing factor for bleeding with depot medroxy progesterone acetate (DMPA) injectable contraception. Doxycycline (DOX) has been proven in vitro to inhibit MMP-mediated degradation of stromal matrix. The current study examined the effect of DOX compared to placebo in treating a current bleeding episode during DMPA use.Study DesignA double-blinded randomized controlled trial was conducted in Assiut, Egypt. DMPA users with current bleeding episode were counseled to participate. Women who agreed to participate were randomly assigned to receive 100 mg DOX twice daily for 5 days (34 patients) or an identical placebo (34 patients). All participants were asked to report bleeding and spotting days in a menstrual diary. All participants were followed for 3 months after treatment. This trial was registered (NCT01254799).ResultsThe relative risk to stop a bleeding episode within 10 days of starting treatment was 0.88 (confidence interval 0.64–1.21) in the treatment group compared to the control. DOX treatment caused no significant difference compared to placebo in the number of bleeding and/or spotting days in the 3 months following the treatment.ConclusionDoxycycline as MMP inhibitor is not effective in stopping a current attack of bleeding with DMPA. It also does not improve the bleeding characteristics of women for the subsequent 3 months following the treatment.     

The role of graft reperfusion sequence in the development of non-anastomotic biliary strictures following orthotopic liver transplantation: A meta-analysis

Background

Liver transplant is a potential cure for liver failure and hepatic malignancy but there are many techniques which have been described for vascular reconstruction. This study was to compare the prevalence of non-anastomotic biliary stricture and other surgical complications based on Clavien-Dindo scoring system, in initial portal reperfusion (sequential) versus simultaneous or initial artery reperfusion.

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Introduction: With clinical trials underway, our objective was to construct a composite score of global function that could discriminate among people with spinal muscular atrophy (SMA). Methods: Data were collected from 126 participants with SMA types 2 and 3. Scores from the Hammersmith Functional Motor Scale—Expanded and Upper Limb Module were expressed as a percentage of the maximum score and 6‐minute walk test as percent of predicted normal distance. A principal component analysis was performed on the correlation matrix for the 3 percentage scores. Results: The first principal component yielded a composite score with approximately equal weighting of the 3 components and accounted for 82% of the total variability. The SMA functional composite score, an unweighted average of the 3 individual percentage scores, correlated almost perfectly with the first principal component. Conclusions: This combination of measures broadens the spectrum of ability that can be quantified in type 2 and 3 SMA patients. Muscle Nerve 52 : 942–947, 2015     

Phrenic Nerve Conduction Abnormalities Correlate with Diaphragmatic Descent in Chronic Obstructive Pulmonary Disease

Diaphragmatic weakness in chronic obstructive pulmonary disease (COPD) is ascribed to hyperinflation-induced diaphragm shortening as well as impairment in cellular and subcellular structures. Although phrenic neuropathy is known to cause diaphragmatic weakness, phrenic neuropathy is rarely considered in COPD. This work aimed at assessing phrenic nerve conduction in COPD and its relation to radiographic hyperinflation and pulmonary function. Patients and methods: Forty COPD patients were evaluated. Radiographic parameters of lung hyperinflation were measured on postero-anterior and lateral chest x-ray films. Flow volume loop parameters were obtained from all patients. Motor conduction study of the phrenic nerves was performed and potentials were recorded over the xiphoid process and the ipsilateral 7th intercostal space. Twenty-seven healthy subjects were enrolled as controls. Results: Parameters of phrenic nerve conduction differed significantly in patients compared to controls. Phrenic nerve abnormalities were detected in 17 patients (42.5%). Electrophysiological measures correlated with diaphragmatic angle of depression on lateral view films and with lung height on postero-anterior films. They did not correlate with the flow volume loop data or disease severity score. Conclusion: Phrenic nerve conduction abnormality is an appreciated finding in COPD. Nerve stretching associated with diaphragmatic descent can be a suggested mechanism for nerve lesion. The presence of phrenic neuropathy may be an additional contributing factor to diaphragmatic dysfunction in COPD patients.     

Growth factor release and enhanced encapsulated periodontal stem cells viability by freeze-dried platelet concentrate loaded thermo-sensitive hydrogel for periodontal regeneration

Periodontium regeneration is a highly challenging process as it requires the regeneration of three different tissues simultaneously. The aim of this study was to develop a composite material that can be easily applied and can sufficiently deliver essential growth factors and progenitor cells for periodontal tissue regeneration.Freeze-dried platelet concentrate (FDPC) was prepared and incorporated in a thermo-sensitive chitosan/β-glycerol phosphate (β-GP) hydrogel at concentrations of 5, 10, or 15?mg/ml. The viscosity of the hydrogels was investigated as the temperature rises from 25?°C to 37?°C and the release kinetics of transforming growth factor (TGF-β1), platelet-derived growth factor (PDGF-BB) and insulin-like growth factor (IGF-1) were investigated at four time points (1?h, 1?day, 1?week, 2?weeks). Periodontal ligament stem cells (PDLSCs) were isolated from human third molars and encapsulated in the different hydrogel groups. Their viability was investigated after 7?days in culture in comparison to standard culture conditions and non FDPC-loaded hydrogel.Results showed that loading FDPC in the hydrogel lowered the initial viscosity in comparison to the unloaded control group and did not affect the sol-gel transition in any group. All FDPC-loaded hydrogel groups exhibited sustained release of TGF-β1 and PDGF-BB for two weeks with significant difference between the different concentrations. The loading of 10 and 15?mg/ml of FDPC in the hydrogel increased the PDLSCs viability significantly compared to the unloaded hydrogel and was comparable to the standard culture conditions.Accordingly, it may be concluded that loading FDPC in a chitosan/β-GP hydrogel can offer enhanced injectability, a sustained release of growth factors and increased viability of encapsulated stem cells which can be beneficial in periodontium tissue regeneration.