Hypovitaminosis D in Patients with Ankylosing Spondylitis: Frequency and Consequences.

OBJECTIVES: This study aimed to assess the frequency of hypovitaminosis D in patients with Ankylosing Spondylitis (AS) compared to healthy controls and evaluate its association with disease activity, structural damage and Bone Mineral Density (BMD). METHODS: Serum 25(OH) D in 30 AS male patients was compared to 30 matched healthy controls. AS disease activity was assessed using AS Disease Activity Score and C - reactive protein (ASDAS- CRP). Bath AS Functional Index (BASFI) and Bath AS Metrology Index (BASMI) were used to assess the functional impairment and the spinal mobility, respectively. Radiological damage was scored according to modified Stoke AS Spine Score (mSASSS) and BMD was measured in the lumbar spine and femoral neck. RESULTS: The mean serum 25(OH)D levels in AS patients were significantly lower compared to healthy controls (27.73 ± 14.27 vs. 38.46 ± 8.11ng/ml, P <0.001). Among the patients, 60% exhibited hypovitaminosis D. AS patients with hypovitaminosis D had significantly higher ASDAS-CRP (p<0.001), BASFAI (p=0.0003) and mSASSS (p=0.04) scores. Additionally, BMD and Z scores at lumbar and femoral sites were significantly reduced in patients with hypovitaminosis D (P < 0.05). Serum 25(OH)D was positively correlated with BMD (lumbar and femoral; p=0.002 and p=0.01 respectively) and Z scores (lumbar and femoral; p<0.001and p=0.01 respectively), whereas, negatively correlated with ASDAS-CRP (p<0.001), BASFI (p<0.001), and mSASSS (p=0.003). ASDAS - CRP was the only significant predictor of hypovitaminosis D in AS patients. CONCLUSION: Hypovitaminosis D is prevalent among AS patients and is associated with increased risk of active disease, impaired function, radiographic severity and bone mineral loss. Future studies with a larger sample size are recommended to assess the impact of vitamin D deficiency on radiological progression in AS and to address whether or not vitamin D supplementation will help control the active disease.

Novel lipid-polymer hybrid nanoparticles incorporated in thermosensitive in situ gel for intranasal delivery of terbutaline sulphate.

AIM: The present work aimed to improve the bioavailability of terbutaline sulphate (TS) and to prolong its nasal residence time for the treatment of asthma. METHODS: Chitosan/pectin polyelectrolyte complex nanoparticles (CS/PC) were prepared by ionic gelation method and coated with phospholipid (PL) and then incorporated into optimised thermosensitive in situ gel. RESULTS: The optimal PL-coated nanoparticle formulation (LP1) showed the smallest particle size (345.5 nm), the highest zeta potential (32.9 mV) and the greatest percent drug released after 6 h (71%). The optimum in situ gel loaded with LP1 (NG3) showed three times greater permeation through nasal mucosa than aqueous solution of TS and revealed about 94% and 92% of the effect of IV injection of drug solution on tidal volume and peak expiratory flow in histamine treated rats, respectively. CONCLUSION: The developed PL-coated CS/PC/in situ gel could be considered as a promising intranasal formulation of TS for asthma management.

Chemical composition and protective role of Pulicaria undulata (L.) C.A. Mey. subsp. undulata against gastric ulcer induced by ethanol in rats.

Pulicaria undulata subsp. undulata (Family; Asteraceae) is a medicinal plant used to treat inflammation. The objective of this study is to explore the protective effect of the ethanol extract of P. undulata subsp. undulata aerial parts against ethanol induced gastric ulcer in rats. The chemical composition of plant extract, the unsaponifiable matter and the fatty acid methyl esters were analyzed. The biological evaluation was carried out through measuring ulcer indices, oxidative stress markers, certain marker enzymes, inflammatory index and the histopathological assessment of the stomach in rats. The total unsaponifiable matter (94.29%) and the fatty acid methyl ester (82.96%) content were identified. Gastric ulcer recorded significant increase in gastric volume and lesion counts (p < 0.0001). Drastic changes in all biochemical parameters under investigation were observed. Protection with plant extract reversed the action of ethanol by variable degrees of improvement in comparison with the reference drug. The presence of carbohydrates and proteins that acted as a mucilage lining the stomach inner wall give its protective action. In conclusion, P. undulata subsp. undulata succeeded to have anti-ulcerative protective effect. The measured biomarkers served as a good mirror to predict gastric ulcer and the presence of carbohydrates, protein and fibers present in the plant extract acted as a mucilage lining the inner intestinal wall and protect against ethanol induced gastric ulcer. Future study will be carried out to identify the biologically active compounds responsible for plant protection against the gastric ulcer.

Pulicaria crispa mitigates gastric ulcer induced by ethanol in rats: role of treatment and auto healing.

Context: Stomach ulcers are the common gastrointestinal disorders worldwide. Objective: This study aimed to investigate the therapeutic impact of Pulicaria crispa aerial parts ethanol extract against gastric ulcer in rats. Materials and methods: Ulcer was induced by one oral dose of ethanol (0.5 ml/100g body weight) on 24 hours empty stomach, then the plant extract (500 mg/kg b.wt.) was orally administered daily for one week. Ranitidine (100 mg/kg b.wt.); as a reference drug was evaluated. Stomach acidity and volume, as well as lesion counts were measured. Levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) were estimated. Assay of different marker enzymes; succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), glucose-6-phosphatase (G-6-Pase), acid phosphatase (AP) and 5'-nucleotidase (5'NT) were determined. Interlukin-10 (IL-10), intracellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor alpha (TNF-α) were also determined. Stomach histopathological assessment was detected. Results: Gastric ulcer showed drastic changes in oxidative stress, cell organelles and inflammatory markers. These biomarkers served as good tools to identify the presence of gastric ulcer. Treatment with P. crispa recorded amelioration in most parameters exceeding the auto healing effect. Conclusion: Healing potency of P. crispa is possibly related to its content of glycosides, coumarins, flavonoids, tannins, sterols and triterpenes.

Formulation and In Vitro and In Vivo Evaluation of Lipid-Based Terbutaline Sulphate Bi-layer Tablets for Once-Daily Administration.

The objective of this study was to prepare and evaluate terbutaline sulphate (TBS) bi-layer tablets for once-daily administration. The bi-layer tablets consisted of an immediate-release layer and a sustained-release layer containing 5 and 10 mg TBS, respectively. The sustained-release layer was developed by using Compritol®888 ATO, Precirol® ATO 5, stearic acid, and tristearin, separately, as slowly eroding lipid matrices. A full 4 × 2(2) factorial design was employed for optimization of the sustained-release layer and to explore the effect of lipid type (X 1), drug-lipid ratio (X 2), and filler type (X 3) on the percentage drug released at 8, 12, and 24 h (Y 1, Y 2, and Y 3) as dependent variables. Sixteen TBS sustained-release matrices (F1-F16) were prepared by melt solid dispersion method. None of the prepared matrices achieved the targeted release profile. However, F2 that showed a relatively promising drug release was subjected to trial and error optimization for the filler composition to develop two optimized matrices (F17 and F18). F18 which consisted of drug-Compritol®888 ATO at ratio (1:6 w/w) and Avicel PH 101/dibasic calcium phosphate mixture of 2:1 (w/w) was selected as sustained-release layer. TBS bi-layer tablets were evaluated for their physical properties, in vitro drug release, effect of storage on drug content, and in vivo performance in rabbits. The bi-layer tablets showed acceptable physical properties and release characteristics. In vivo absorption in rabbits revealed initial high TBS plasma levels followed by sustained levels over 24 h compared to immediate-release tablets.

Role of traditional healers in the pathway to care of patients with bipolar disorder in Egypt.

BACKGROUND: A large number of mentally ill patients prefer to visit non-medical practitioners such as traditional healers because of the confidence in the system, affordability and accessibility of the service. This may lead to delay in seeking psychiatric services and has prognostic impact. AIM: To assess the rate of bipolar affective disorder (BAD) patients seeking traditional healers, the sociodemographic and clinical correlates of those patients. METHODS: We assessed 350 patients with BAD after confirmation of diagnosis with Structured Clinical Interview for DSM-IV Axis I Disorder (SCID-I) research version and assessment of functioning with Global Assessment of Functioning scale. They were assessed for percent, rate and timing of seeking traditional healers. RESULTS: In all, 40.8% sought traditional healers, with 34.9% more than four times. Of those, 62.2% were before seeking psychiatric services and 37.8% after. Lower educational level, less impairment of functioning and presence of hallucinations were significant correlates. CONCLUSION: This study shows that most of the patients suffering from mental illness prefer to approach faith healers first, which may delay entry to psychiatric care and thereby negatively impact the prognosis of BAD. This highlights the importance of mental health education and developing a positive collaborative relationship with traditional healers.

Formulation, characterization, and clinical evaluation of microemulsion containing clotrimazole for topical delivery.

The objective of the present study was to formulate and evaluate microemulsion systems for topical delivery of clotrimazole (CTM). The solubility of CTM in various oils was determined to select the oil phase of the microemulsion systems. Pseudoternary phase diagrams were constructed to identify the area of microemulsion existence. Five CTM microemulsion formulations (M1-M5) were prepared and evaluated for their thermodynamic stability, pH, refractive index, droplet size, viscosity, and in vitro release across cellulose membrane. Among the prepared microemulsion formulations, M3 (lemon oil/Tween 80/n-butanol/water) and M4 (isopropyl myristate/Tween 80/n-butanol/water) microemulsion systems were found to be promising according to their physical properties and CTM cumulative percentage release. Gel form of M3 and M4 were prepared using 1% Carbopol 940 as the hydrogel matrix. Both formulations were evaluated in the liquid and gel forms for drug retention in the skin in comparison to the marketed CTM topical cream and their stability examined after storage at 40°C for 6 months. Microemulsion formulations achieved significantly higher skin retention for CTM over the CTM cream. Stability studies showed that M4 preparations were more stable than M3. The in vitro anti-fungal activity of M4 against Candida albicans was higher than that of the conventional cream. Moreover, clinical evaluation proved the efficacy and tolerability of this preparation in the treatment of various topical fungal infections.

Antimicrosporidial activities of fumagillin, TNP-470, ovalicin, and ovalicin derivatives in vitro and in vivo.

Therapies for microsporidiosis in humans are limited, and fumagillin, which appears to be the most broadly effective antimicrosporidial drug, is considered to be moderately toxic. The purpose of this study was to apply an in vitro drug screening assay for Encephalitozoon intestinalis and Vittaforma corneae and an in vivo athymic mouse model of V. corneae infection to assess the efficacy of TNP-470 (a semisynthetic analogue of fumagillin), ovalicin, and eight ovalicin derivatives. TNP-470, ovalicin, and three of the ovalicin derivatives inhibited both E. intestinalis and V. corneae replication by more than 70% in vitro. Another three of the ovalicin derivatives inhibited one of the two microsporidian species by more than 70%. None of the treated athymic mice survived the V. corneae infection, but they did survive statistically significantly longer than the untreated controls after daily treatment with fumagillin administered at 5, 10, and 20 mg/kg of body weight subcutaneously (s.c.), TNP-470 administered at 20 mg/kg intraperitoneally (i.p.), or ovalicin administered at 5 mg/kg s.c. Of two ovalicin derivatives that were assessed in vivo, NSC 9665 given at 10 mg/kg i.p. daily also statistically significantly prolonged survival of the mice. No lesions associated with drug toxicity were observed in the kidneys or livers of uninfected mice treated with these drugs at the highest dose of 20 mg/kg daily. These results thus support continued studies to identify more effective fumagillin-related drugs for treating microsporidiosis.

GPx-1 modulates Akt and P70S6K phosphorylation and Gadd45 levels in MCF-7 cells.

Selenium has been shown to prevent cancer in animal models, and recent data indicate it is likely to be effective in humans as well. One selenium-containing protein, the cytoplasmic form of glutathione peroxidase (GPx-1), has been implicated in cancer risk and development by genetic studies identifying at-risk alleles and loss of heterozygosity in tumors. In order to evaluate the biological consequences of GPx-1 overexpression, human MCF-7 cells were stably transfected with a GPx-1 expression construct and the effects of GPx-1 on protein kinases associated with stress responses were determined. GPx-1 overexpression affected phosphorylation of p70S6K, whereas Erk1/2 and p38 MAPK were not affected. Site-specific phosphorylation of Akt declined and the levels of Gadd45, a DNA damage response protein, increased significantly as a consequence of elevated GPx-1 expression. Effects on p70S6K and Gadd45 after selenium supplementation have been reported, and given previous data demonstrating a role for GPx-1 in cancer etiology, these results support the concept that the chemopreventive properties of selenium may be due, at least in part, to its role in regulating GPx-1.