ESI-IM-MS characterization of cyclodextrin complexes and their chemically cross-linked alpha (α-), beta (ß-) and gamma (γ-) cyclodextrin particles as promising drug delivery materials with improved bioavailability.

Cyclodextrins (CDs) are natural cyclic oligosaccharides with a relatively hydrophobic cavity and a hydrophilic outer surface. In this study, alpha (α-), beta (ß-) and gamma (γ-) CD particles were prepared by directly using α-, ß-, and γ-CDs as monomeric units and divinyl sulfone (DVS) as a crosslinker in a single-step via reverse micelle microemulsion crosslinking technique. Particles of p(α-CD), p(ß-CD), and p(γ-CD) were perfectly spherical in sub- 10 µm size ranges. The prepared p(CD) particles at 1.0 mg/mL concentrations were found biocompatible with > 95 % cell viability against L929 fibroblasts. Furthermore, p(α-CD) and p(ß-CD) particles were found non-hemolytic with < 2 % hemolysis ratios, whereas p(γ-CD) particles were found to be slightly hemolytic with its 2.1 ± 0.4 % hemolysis ratio at 1.0 mg/mL concentration. Furthermore, a toxic compound, Bisphenol A (BPA) and a highly antioxidant polyphenol, curcumin (CUR) complexation with α-, ß-, and γ-CD molecules was investigated via Electrospray-Ion Mobility-Mass Spectrometry (ESI-IM-MS) and tandem mass spectrometry (MS/MS) analysis. It was determined that the most stable noncovalent complex was in the case of ß-CD, but the complex stoichiometry was changed by the hydrophobic nature of the guest molecules. In addition, BPA and CUR were separately loaded into prepared p(CD) particles as active agents. The drug loading and release studies showed that p(CD) particles possess governable loading and releasing profiles.

Carboxymethyl Chitosan Microgels for Sustained Delivery of Vancomycin and Long-Lasting Antibacterial Effects.

Carboxymethyl chitosan (CMCh) is a unique polysaccharide with functional groups that can develop positive and negative charges due to the abundant numbers of amine and carboxylic acid groups. CMCh is widely used in different areas due to its excellent biocompatibility, biodegradability, water solubility, and chelating ability. CMCh microgels were synthesized in a microemulsion environment using divinyl sulfone (DVS) as a crosslinking agent. CMCh microgel with tailored size and zeta potential values were obtained in a single stem by crosslinking CMCh in a water-in-oil environment. The spherical microgel structure is confirmed by SEM analysis. The sizes of CMCh microgels varied from one micrometer to tens of micrometers. The isoelectric point of CMCh microgels was determined as pH 4.4. Biocompatibility of CMCh microgels was verified on L929 fibroblasts with 96.5 ± 1.5% cell viability at 1 mg/mL concentration. The drug-carrying abilities of CMCh microgels were evaluated by loading Vancomycin (Van) antibiotic as a model drug. Furthermore, the antibacterial activity efficiency of Van-loaded CMCh microgels (Van@CMCh) was investigated. The MIC values of the released drug from Van@CMCh microgels were found to be 68.6 and 7.95 µg/mL against E. coli and S. aureus, respectively, at 24 h contact time. Disk diffusion tests confirmed that Van@CMCh microgels, especially for Gram-positive (S. aureus) bacteria, revealed long-lasting inhibitory effects on bacteria growth up to 72 h.

Biocompatible Glycol Chitosan Microgels as Effective Drug Carriers.

Glycol chitosan (GC) is a chitosan (CH) derivative with improved water solubility with regards to CH which affords significant solubility advantages. In this study, microgels of GC as p(GC) were synthesized by a microemulsion technique at various crosslinking ratios e.g., 5%, 10%, 50%, 75%, and 150% based on the repeating unit of GC using divinyl sulfone (DVS) as a crosslinker. The prepared p(GC) microgels were tested for blood compatibility and it was found that p(GC) microgels at 1.0 mg/mL concentration possessed a 1.15 ± 0.1% hemolysis ratio and 89 ± 5% blood clotting index value confirming their hemocompatibility. In addition, p(GC) microgels were found biocompatible with 75.5 ± 5% cell viability against L929 fibroblasts even at a 2.0 mg/mL concentration. By loading and releasing tannic acid (TA) (a polyphenolic compound with high antioxidant activity) as an active agent, p(GC) microgels' possible drug delivery device application was examined. The TA loading amount of p(GC) microgels was determined as 323.89 mg/g, and TA releases from TA loaded microgels (TA@p(GC)) were found to be linear within 9 h and a total amount of TA released was determined as 42.56 ± 2 mg/g within 57 h. According to the Trolox equivalent antioxidant capacity (TEAC) test, 400 µL of the sample added to the ABTS+ solution inhibited 68.5 ± 1.7% of the radicals. On the other hand, the total phenol content (FC) test revealed that 2000 µg/mL of TA@p(GC) microgels resulted in 27.5 ± 9.5 mg/mL GA eq antioxidant properties.

Physically and Chemically Crosslinked, Tannic Acid Embedded Linear PEI-Based Hydrogels and Cryogels with Natural Antibacterial and Antioxidant Properties.

Linear polyethyleneimine (L-PEI) was obtained from the acidic hydrolysis of poly(2-ethyl-2-oxazoline) and employed in the synthesis of physically crosslinked L-PEI hydrogel, PC-L-PEIH, chemically crosslinked L-PEI hydrogel, CC-L-PEIH, and cryogels, CC-L-PEIC. The preparation of L-PEI-based hydrogel networks was carried out in two ways: 1) by cooling the L-PEI solution from 90 °C to room temperature, and 2) by crosslinking L-PEI chains with a crosslinker, glycerol diglycidyl ether = 20 °C for CC-L-PEIC. Furthermore, a polyphenolic compound, tannic acid (TA), with superior antibacterial, antioxidant, and anti-inflammatory properties as an active biomedical functional agent, was encapsulated during the synthesis process within L-PEI-based hydrogels and cryogels, at 10% and 25% (w/w) based on the L-PEI amount. A linear and higher TA release was observed from physically crosslinked PEI-based hydrogels containing 10% and 25% TA-containing PC-L-PEI/TAH within 6 h, with 9.5 ± 05 mg/g and 60.2 ± 3.8 mg/g cumulative released amounts, respectively. A higher antioxidant activity was observed for 25% TA containing PC-L-PEI/TAH with 53.6 ± 5.3 µg/mL total phenol content and 0.48 ± 0.01 µmole Trolox equivalent/g. The minimum bactericidal concentration (MBC) of PC-L-PEIH and CC-L-PEIC networks against both E. coli (ATCC 8739) and Gram-positive B. subtilis (ATCC 6633) bacteria was determined at 5 mg/mL, whereas the MBC value of 10 mg/mL for CC-L-PEIH networks against the same bacteria was achieved.

Poly(Glycerol) Microparticles as Drug Delivery Vehicle for Biomedical Use.

Glycerol (Gly) is a well-known, FDA-approved molecule posing three hydroxyl groups. Since Gly is biocompatible, here, it was aimed to prepare poly(Glycerol) (p(Gly)) particles directly for the first time for the delivery of therapeutic agents. Micrometer-sized particles of p(Gly) were successfully synthesized via the micro-emulsion method with an average size of 14.5 ± 5.6 µm. P(Gly) microparticles up to 1.0 g/mL concentrations were found biocompatible with 85 ± 1% cell viability against L929 fibroblasts. Moreover, p(Gly) microparticles were tested for hemocompatibility, and it was found that up to 1.0 mg/mL concentrations the particles were non-hemolytic with 0.4 ± 0.1% hemolysis ratios. In addition, the blood compatibility index values of the prepared p(Gly) particles were found as 95 ± 2%, indicating that these microparticles are both bio- and hemocompatible. Furthermore, Quercetin (QC) flavonoid, which possessed high antioxidant properties, was loaded into p(Gly) microparticles to demonstrate drug-carrying properties of the particles with improved bioavailability, non-toxicity, and high biocompatibility. The results of this study evidently revealed that p(Gly) particles can be directly prepared from a cost-effective and easily accessible glycerol molecule and the prepared particles exhibited good biocompatibility, hemocompatibility, and non-toxicity. Therefore, p(Gly) particles were found as promising vehicles for drug delivery systems in terms of their higher loading and release capability as well as for sustained long term release profiles.

A Review on Phyto-Therapeutic Approaches in Alzheimer's Disease.

Neurodegenerative diseases occur due to progressive and sometimes irreversible loss of function and death of nerve cells. A great deal of effort is being made to understand the pathogenesis of neurodegenerative diseases. In particular, the prevalence of Alzheimer's disease (AD) is quite high, and only symptomatic therapy is available due to the absence of radical treatment. The aim of this review is to try to elucidate the general pathogenesis of AD, to provide information about the limit points of symptomatic treatment approaches, and to emphasize the potential neurologic effects of phytocompounds as new tools as therapeutic agents for disease prevention, retardation, and therapy. This survey also covers the notable properties of herbal compounds such as their effects on the inhibition of an enzyme called acetylcholinesterase, which has significant value in the treatment of AD. It has been proven that phytopharmaceuticals have long-term effects that could protect nervous system health, eliminate inflammatory responses, improve cognitive damage, provide anti-aging effects in the natural aging process, and alleviate dementia sequelae. Herbal-based therapeutic agents can afford many advantages and can be used as potentially as new-generation therapeutics or complementary agents with high compliance, fewer adverse effects, and lower cost in comparison to the traditional pharmaceutical agents in the fight against AD.

Polyelectrolyte Chondroitin Sulfate Microgels as a Carrier Material for Rosmarinic Acid and Their Antioxidant Ability.

Polyelectrolyte microgels derived from natural sources such as chondroitin sulfate (CS) possess considerable interest as therapeutic carriers because of their ionic nature and controllable degradation capability in line with the extent of the used crosslinker for long-term drug delivery applications. In this study, chemically crosslinked CS microgels were synthesized in a single step and treated with an ammonia solution to attain polyelectrolyte CS-[NH4]+ microgels via a cation exchange reaction. The spherical and non-porous CS microgels were injectable and in the size range of a few hundred nanometers to tens of micrometers. The average size distribution of the CS microgels and their polyelectrolyte forms were not significantly affected by medium pH. It was determined that the -34 ± 4 mV zeta potential of the CS microgels was changed to -23 ± 3 mV for CS- [NH4]+ microgels with pH 7 medium. No important toxicity was determined on L929 fibroblast cells, with 76 ± 1% viability in the presence of 1000 µg/mL concentration of CS-[NH4]+ microgels. Furthermore, these microgels were used as a drug carrier material for rosmarinic acid (RA) active agent. The RA-loading capacity was about 2.5-fold increased for CS-[R]+ microgels with 32.4 ± 5.1 µg/mg RA loading, and 23% of the loaded RA was sustainably release for a long-term period within 150 h in comparison to CS microgels. Moreover, RA-loaded CS-[R]+ microgels exhibited great antioxidant activity, with 0.45 ± 0.02 µmol/g Trolox equivalent antioxidant capacity in comparison to no antioxidant properties for bare CS particles.

Travel-associated Legionnaires disease: clinical features of 17 cases and a review of the literature.

We retrospectively investigated patients with Legionnaires disease (LD) who had been admitted to the Baskent University Alanya Teaching and Research Hospital, Ankara, Turkey, from January 2002 to September 2009. Twenty definitive cases were followed as LD, 17 (85%) of which were travel associated. The mean age was 61.5 ± 9.5 years (range, 39-77 years). Diabetes mellitus was found in 7 (41.2%) of those patients. Gastrointestinal or neurologic abnormalities were found approximately in two-thirds and relative bradycardia in 9 (52.9%). LD was severe in 11 (64.7%) patients, which required intensive care unit follow-up. Although appropriate antibiotic therapy was initiated in all patients on admission day, 4 (23.5%) deaths occurred. In conclusion, clinicians should remain vigilant about the diagnosis of LD in patients with community-acquired pneumonia, especially in the presence of extrapulmonary involvement, risk factors for LD, and a history of recent travel. As in our cases, mortality is still high in sporadic cases despite early appropriate treatment.

Tracheobronchopathia osteochondroplastica: an unusual presentation.

A 24-year-old woman presented with chronic cough and noisy breathing. Chest x-ray revealed diffuse irregularity and narrowing of the tracheal lumen. Thorax computed tomography showed irregularity, stenosis, and areas of ossification throughout the trachea and both main bronchia. Flexible bronchoscopy revealed multiple nodules protruding into the tracheal lumen. Histopathology of the nodules confirmed the diagnosis of "tracheobronchopathia osteochondroplastica." Tracheobronchopathia osteochondroplastica is a rare, benign disease that is characterized by multiple cartilaginous and osseous submucosal nodules protruding through tracheal lumen and large bronchia. The etiology is still unexplained.

Recurrent posterior reversible encephalopathy syndrome in a hypertensive patient with end-stage renal disease.

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiologic entity characterized by headache, variable mental status, epilepsy, visual disturbances, and typical transient changes in the posterior cerebral perfusion. Recurrence of PRES is not common, but increasingly in recent years, studies demonstrate recurrence of this syndrome in populations with different diseases. In this report, we describe recurrent PRES in a hypertensive patient with end-stage renal disease, and discuss recurrence as the least-characterized feature of PRES. This condition can cause neurological sequelae such as persistent brain damage and epilepsy, arising from delays in diagnosis and therapy. To the best of our knowledge, this is the first report demonstrating recurrent PRES in a patient on hemodialysis for end-stage renal disease.

[A case of endobronchial aspergilloma]. / Endobronsiyal aspergilloma olgusu.

Infections caused by Aspergillus spp. in immunocompromised or atopic patients may present as invasive aspergillosis, allergic bronchopulmonary aspergillosis and aspergilloma. In this report a 69 years old female patient admitted to the hospital with the complaints of intermittent cough and sputum and diagnosed as endonbronchial aspergilloma, has been presented. The patient was not immunocompromised, however she has bronchial asthma for 10 years and the disease is now under control. The chest radiography and computed tomography revealed lung infiltration with undefined borders, and bronchoscopy demonstrated the presence of a mass at left lower lobe. In the pathologic examination of biopsy specimen with the use of methenamine silver and PAS methods, hyphae formations concordant with Aspergillus were detected. The direct microscopic examinations of biopsy material and sputum obtained after bronchoscopy, have also revealed the presence of hyphae. A. fumigatus was isolated from the cultures of biopsy material and sputum specimen. The patient was diagnosed as endonbronchial aspergilloma, however the follow-up was failed since she has not accepted medical or surgical treatment. In conclusion, aspergilloma should be considered in the differential diagnosis of mass lesions in the endobronchial area.

Mediastinal thymolipoma: an analysis of 10 cases.

Thymolipoma is a benign tumour composed of thymic elements and adipose tissue. It may be associated with myasthenia gravis or immune disorders. We aimed to evaluate the clinical and radiological features of thymolipoma. The clinical data from 10 cases of thymolipoma, diagnosed at our centre between 2002 and 2004, were analysed retrospectively. There were six female and four male patients, whose ages ranged from 16 to 67 years, with a mean age of 34.1 years. All but two patients had pulmonary or extrapulmonary symptoms. Five patients also had myasthenia gravis. All thymolipomas were localized in the anterior superior mediastinum. The surgical approach was sternotomy in nine cases and thoracotomy in one case. Thymectomy was performed on all patients. Thymolipomas are unusual tumours and may be associated with myasthenia gravis. Surgical resection is the most appropriate treatment modality.

Giant carcinoid tumor mimicking pulmonary sequestration.

A 42-year-old woman who previously underwent two consecutive thoracotomies for a lower lobe mass in her right lung was referred to our clinic for further management. Both procedures were abandoned due to excessive bleeding. Computed tomographic angiography demonstrated an infra-diaphragmatic systemic arterial supply of the mass similar to pulmonary sequestration. However the lobe had a normal venous drainage to the left atrium. Then a right lower lobectomy was undertaken through a hemi-clamshell incision, and histopathology revealed an atypical carcinoid tumor. The patient was discharged home after a satisfactory postoperative period. She still remains disease free at 14 months follow-up.

Rhabdomyolysis-induced acute renal failure associated with legionnaires' disease.

Legionnaires' disease (LD) is a systemic infectious disease primarily involving the lungs. Rhabdomyolysis, with subsequent acute renal failure, is an infrequently recognized entity associated with high mortality rates in LD patients. As in the case presented herein, initial respiratory signs and symptoms may not be prominent. Early diagnosis and appropriate treatment can be life-saving.

Orgasm-induced seizures: a study of six patients.

PURPOSE: Reflex seizures are known as the epileptic seizures triggered by some specific stimuli in sensitive patients. They are often classified according to the stimuli that trigger them rather than by the type of the seizure. Epileptic seizures induced by sexual orgasm are very rare in the literature. METHODS: We report six patients with different epileptic syndromes who experienced seizures after sexual intercourse and orgasm. RESULTS: All patients are women whose epileptogenic focus was in the right temporal in four and left frontal in one patient. One patient had pure generalized reflex epilepsy. CONCLUSIONS: Seizures induced by orgasm are very rare, with female and right hemisphere dominance requiring complex mechanisms to occur.

Computed tomography-guided transthoracic fine-needle aspiration in diagnosis of lung cancer: a comparison of single-pass needle and multiple-pass coaxial needle systems and the value of immediate cytological assessment.

OBJECTIVES: The aim of the present study was to compare single-pass needle and multiple-pass coaxial needle systems and to evaluate the value of immediate cytological assessment during the procedure in the diagnosis of lung cancer with CT-guided transthoracic fine-needle aspiration. METHODOLOGY: One hundred and forty-three consecutive patients who underwent CT-guided transthoracic fine-needle aspiration were divided into three groups. In the first group (group A, 48 patients), a single-pass needle was used for aspiration, but immediate cytological examination was not performed. In the second group (group B, 48 patients), a single-pass needle was used for aspiration and a pathologist immediately assessed the adequacy of the sample obtained. In the third group (group C, 47 patients), a multiple-pass coaxial needle was used for aspiration and a pathologist immediately assessed the adequacy of the sample obtained. RESULTS: The mean number of fine-needle aspirations was 1.25 in group A, 1.39 in group B and 1.34 in group C (group A vs group B, P = 0.08). The diagnostic accuracy was 83.3, 97.9 and 100.0%, respectively (group A vs group B, P = 0.03; group B vs group C, P > 0.05). Although immediate cytological assessment resulted in adequate samples being obtained from all patients in groups B and C, adequate samples were obtained in 41 of 48 patients (85.4%) in group A (P = 0.004). There was no statistically significant difference among the groups with respect to the rate of pneumothorax. CONCLUSIONS: A single-pass needle technique in transthoracic fine-needle aspiration is preferred because there is no significant difference between single-pass needle and multiple-pass coaxial needle systems with respect to the diagnostic accuracy and the complication rate and, in addition, the single-pass needle has a lower cost. The results of the present study suggest that immediate cytological assessment during the procedure reduces an inadequate sampling rate, thus increasing the diagnostic accuracy of the procedure.

Suspected lamotrigine-induced toxic epidermal necrolysis.

Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare, life treating cutaneous reactions. Most cases of toxic epidermal necrolysis are drug induced. The drugs with the highest estimated incidence include co-trimoxazloe (trimethoprim-sulfamethoxazole), sulfadoxine-pyrethamine, and carbamazepine. Among other drugs, the reported reaction rates are relatively low for lamotrigine and sulbactam-ampicillin. We describe a patient who developed toxic epidermal necrolysis after either administration of lamotrigine or of ampicillin.