Core shell methyl methacrylate chitosan nanoparticles: In vitro mucoadhesion and complement activation

BACKGROUND AND THE PURPOSE OF THE STUDY: Studies show that chitosan nanoparticles increase mucoadhesivity and penetration of large molecules across mucosal surface. The aim of the present study was to investigate the use of thiolated chitosan in the development of polysaccharide-coated nanoparticles in order to confer specific functionality to the system. METHODS: Methyl methacrylate nanoparticles were coated with thiolated chitosan using a radical polymerization method. Thiolation was carried out using glutathione (GSH) to improve mucoadhesivity and permeation enhancing properties of chitosan. Mucoadhesion studies were carried out by calculating the amount of mucin adsorbed on nanoparticles in a specific period of time. Complement consumption was assessed in human serum (HS) by measurement of the hemolytic capacity of the complement system after contact with nanoparticles. RESULTS: The FT-IR and (1)HNMR spectra both confirmed the synthesis and showed the conjugation of thiolated chitosan to methyl methacrylate (MMA) homopolymer. Nanoparticles were spherical having a mean diameter within the range of about 334-650 nm and their positive zeta potential values indicated the presence of the cationic polysaccharide at the nanoparticle surface. Increasing the amount of thiolated chitosan led to mucoadhesivity and complement activation. However there was not dose dependent correlation between these phenomenons and the absence of thiolated chitosan led to particles with larger size, and without ability to activate complement process. MAJOR CONCLUSION: It can be concluded that nanoparticles could be used for the mucosal delivery of peptides and proteins. Results show that the thiolated chitosan had higher mucoadhesion and complement activation than unmodified chitosan.     

The relationship between electrophysiological correlates of recollection and amount of information retrieved

The electrophysiological correlates of recollection were investigated with a modified Remember/Know task in which subjects signaled whether they fully or partially recollected visual object information in each study episode. A positive-going ERP deflection--the left parietal old/new effect--was sensitive to the amount of information recollected, demonstrating greater amplitude when elicited by test items associated with full relative to partial recollection. These findings support prior proposals that the left parietal ERP old/new effect is sensitive to the amount of information recollected from episodic memory. An early-onsetting (ca. 150 ms), left frontal old/new effect differentiated items accorded correct old versus correct new responses regardless of whether the items were endorsed as familiar or recollected. This finding extends the range of circumstances under which early, frontally distributed old/new effects occur, and adds weight to previous suggestions that these effects are a neural correlate of familiarity-driven recognition memory.     

Dual nitric oxide mechanisms of cholestasis-induced bradycardia in the rat

1. Cholestatic liver disease is associated with nitric oxide (NO) overproduction and bradycardia. Nitric oxide has a dual effect on sinoatrial node and its effects depend on its concentration. Nitric oxide can increase heart rate by activating hyperpolarization-activated pacemaker current (If) but, at high concentrations, it can potentially decrease heart rate by inhibition of L-type calcium current. In the present study, the responsiveness of isolated atria to CsCl (an inhibitor of the If current) and acetylcholine (ACh; which decreases L-type calcium current through a NO-dependent pathway) were evaluated in bile duct-ligated and sham-operated control rats. 2. Bile duct ligation induced a significant decrease in the negative chronotropic effect of CsCl (0.2-5 mmol/L), but increased the responsiveness of isolated atria to ACh (10-8 to 10-3 mol/L). These effects were restored after incubation of the atria in the presence of the NO synthase inhibitor NG-nitro-l-arginine methyl ester (0.1 mmol/L). 3. Anaesthetized bile duct-ligated rats showed bradycardia and the plasma levels of NO2-/NO3- were significantly higher in bile duct-ligated rats compared with sham-operated animals. 4. Different and opposite responses of atria of cholestatic rats to CsCl and ACh can be explained by NO overproduction in bile duct-ligated animals. A dual role of NO in the regulation of the sinoatrial node may be responsible for this opposite effect and may have a role in the pathophysiology of cholestasis-induced bradycardia.     

Effects of Papaver rhoeas extract on the expression and development of morphine-dependence in mice

The problem of drug dependence still remains unresolved. In the present study, the effects of water-alcohol extract of Papaver rhoeas on the expression and acquisition of naloxone-induced jumping and diarrhea in morphine-dependent mice were investigated. Administration of three daily doses of morphine (12.5, 25 and 50 mg/kg) for three days in order to develop dependence to morphine caused a significant and dose-dependent increase in the number of jumping and diarrhea when the animals were challenged with naloxone (4 mg/kg). On the other hand, administration with the plant extract (25, 50 and 100 mg/kg) did not show any effect. Injection of extract (25, 50 and 100 mg/kg) 30 min before the naloxone administration in morphine-dependent mice decreased the number of jumping and diarrhea. Administration of extract (25, 50 and 100 mg/kg) 30 min before morphine injection increased the number of jumping but decreased the diarrhea. It could be concluded that the extract of Papaver rhoeas can ameliorate the withdrawal syndrome in morphine-dependent mice. Therefore, the extract might be useful to treatment of withdrawal signs in opioid addicts.     

Microbial keratitis in ITU staff: an occupational hazard?

Microbial keratitis is a potentially blinding corneal infection; the infection may progress rapidly if untreated and result in corneal perforation. The breakdown of the innate ocular defences is known to predispose to corneal infection. We present three cases of microbial keratitis in intensive therapy unit (ITU) staff each of whom had compromised corneal immunity. Anaesthetists and nurses regularly perform high-risk procedures, such as tracheal suctioning, which have been known to cause ocular infections by aerosol inoculation. We suggest that although the absolute risk of infection is low, susceptible individuals may be at increased risk of corneal infection from exposure to potentially pathogenic organisms in such environments. We stress the need for ITU staff, particularly those who wear contact lenses, to wear eye protection when performing procedures likely to cause infected aerosols.     

A case of prenatally detected left isomerism and hemiazygos continuation of inferior vena cava

Heterotaxy syndromes are defined as the disorders that involve abnormal arrangement of viscera. We present a case of prenatally diagnosed left isomerism in a 30‐year‐old primigravida woman referred to our hospital for complex cardiac abnormality. Sonographic findings included heart block, unbalanced atrioventricular septal defect, interruption of the inferior vena cava with hemiazygos continuation, double superior vena cava, a right‐sided stomach, and biliary atresia. The hemiazygos vein drained into the right atrium by the persistent left superior vena cava. This type of inferior vena cava interruption and continuation is rarely reported in prenatally detected cases of left isomerism. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45 :430–433, 2017     

An update on plexiform fibrohistiocytic tumor and addition of 66 new cases from the Armed Forces Institute of Pathology, in honor of Franz M. Enzinger, MD

The seminal article of Drs Franz Enzinger and Renyuan Zhang in 1988 defined plexiform fibrohistiocytic tumor (PFHT) as a distinctive entity. They described 65 cases (from 1965 to 1985) in children and young adults, with female and upper extremity predominance. These tumors were morphologically divided into 3 groups: fibroblastic, histiocytic (often with osteoclast-type giant cells), and mixed. Most tumors exhibited a plexiform and infiltrative arrangement of cells at the dermal/subcutaneous junction. Two fibroblastic PFHT had a metaplastic bone formation. Absence of cellular pleomorphism, low mitotic activity, dense hyalinization, hemorrhage, and chronic inflammation were observed. Vascular invasion was present in 1 recurrent, yet nonmetastatic, case. Tumors were negative for S100 protein, desmin, cytokeratin, factor VIIIrag, and lysozyme. Most patients were without disease up to 60 years after excision; 32 (37.5%) cases with follow-up recurred and 2 of those patients had regional lymph node metastasis at 9 and 36 months, respectively, yet there were no systemic metastases. In the interim, there have been additional studies on PFHT. We wanted to update the literature and add 66 new PFHT cases (1986-present) from the Armed Forces Institute of Pathology, since this seminal article, in honor of Dr Franz Enzinger. There were 37 men and 29 women; patient age ranged from 1 to 77 years (median, 20 years; 53% of patients were younger than 20 years). Twenty-eight cases occurred in the upper extremity (mostly forearm), 16 in lower extremity, 11 in trunk, 9 in head and neck, and 2 of unknown site. Although most cases were observed at the dermal/subcutaneous interface, 22 cases were predominantly dermal, and the rest predominantly subcutaneous, with 4 superficially involving skeletal muscle. Except for 12 predominantly dermal cases, most cases had an infiltrative growth pattern. Thirty-four cases were predominantly histiocytic, 16 predominantly fibroblastic, and the remaining 16 mixed. Two fibroblastic cases demonstrated the microfat cells (probably secondary to subcutis infiltration). All cases exhibited a plexiform growth pattern of small- to medium-sized nodules; 41 cases had giant cells, mainly osteoclast type, often the predominantly histiocytic type. The purely fibroblastic often had surrounding inflammation, 2 cases with marked inflammation. Perineural growth was observed in 5 cases, peri-Pacinian corpuscle growth in 2 cases, adnexal trapping in several, and, increased hyalinized collagen in 17 cases. Eight cases demonstrated focal myxoid change. Only 1 case, a histiocytic, had bone formation. Although increased cytologic atypia and mitotic activity were noted in a few cases, an atypical mitosis was only observed in 1 case. No cases demonstrated vascular or lymphatic invasion or necrosis. The tumors were generally positive for CD68 and SMA, occasionally for MSA, and negative for keratin, desmin, HMB45, S100 protein, and CD34. Overall, the findings were very similar to the original observations made by Dr Enzinger and his colleague, with the minor exceptions of roughly equal sex distribution (possibly due to timely referral bias), and additional morphologic features of myxoid change, adnexal sparing, increased inflammation, and microfat similar to recently described lipofibromatosis. The relationship between PFHT and cellular neurothekeoma is also explored.