Albumin grafted coaxial electrosparyed polycaprolactone-zinc oxide nanoparticle for sustained release and activity enhanced antibacterial drug delivery.

One of the most serious issues faced by the healthcare sector is the development of multidrug resistance among various pathogens. It is such that developing new and more capable drugs takes far too long to counter such resistance. In order to overcome these concerns, this study focused on improving upon the coaxial electrospraying process by producing cloxacillin loaded albumin polycaprolactone (PCL) with a ZnO coating for sustained and activity enhanced drug delivery. Albumin-grafted, polycaprolactone-coated, zinc oxide-loaded cloxacillin (APCL-CLOX-ZnO) nanoparticles with a diameter of 85-110 nm were obtained via a coaxial electrospray technique. The encapsulation efficiency of cloxacillin of ZnO-CLOX was found to be approximately 60%. The loading efficiencies of ZnO-CLOX and APCL-CLOX-ZnO were found to be 40% and 28% respectively. Albumin was employed in order to impart immune evasion properties to the formulation. Drug-loaded ZnO NPs were analyzed using SEM, TEM, FT-IR and TGA. This novel formulation was shown to possess sustained release characteristics owing to the PCL and albumin coatings, relative to uncoated counterparts. ZnO-CLOX and APCL-CLOX-ZnO exhibited 72% and 52% cloxacillin release within 24 h. APCL-CLOX-ZnO exhibited potent antimicrobial activity against S. epidermidis, B. cereus and P. aeruginosa and some activity against E. coli with inhibition zones 32 ± 1.4, 34 ± 0.3, 32 ± 0.6 and 11 ± 0.4 mm, respectively. Cytotoxicity studies against murine preosteoblast cells revealed that the albumin-PCL coating served to drastically reduce initial toxicity against healthy mammalian cells. In vitro lung deposition study showed 70% of APCL-CLOX-ZnO particles can reach up to the alveoli level. Therefore, this novel coaxial nanoformulation may serve as a promising drug delivery platform for the treatment of bacterial infections including respiratory tract complications.

An interesting case of adenoviral hepatitis in a cardiac transplant recipient.

Adenoviral infections are commonly described in pediatric transplant populations. However, much less information is available regarding the incidence of infection and clinical spectrum of disease in adult transplant recipients. Moreover, this infection usually manifests as involvement of the transplanted organ in one pathologic form or the other, in addition to other systemic manifestations. We present a case of adenoviral infection of a nontransplanted organ in a solid organ transplant recipient.

Meeting the challenge of preparing undergraduates for careers in cognitive neuroscience.

Preparing students for a career in cognitive neuroscience may be especially challenging due to the expense and complexity of many types of cognitive neuroscience technologies. However, it is possible to train students in cognitive neuroscience at a primarily undergraduate university (PUI) in both the classroom and the laboratory. First, we propose specific methods that can be used in the classroom to make cognitive neuroscience material accessible. We also suggest ways to introduce cognitive neuroscience methodology through lab-based courses or activities. Second, we offer suggestions on how to conduct more complex functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) research with undergraduates at a small school. We hope that these suggestions will be a helpful guide for those wishing to prepare their students for further studies and careers in this exciting and challenging field.

Antimicrobial and Alpha-Amylase Inhibitory Activities of Organic Extracts of Selected Sri Lankan Bryophytes.

Medicinal plants have been the main focus of natural product research. However, recent research has revealed that lower plants including bryophytes are also a major resource of biologically active compounds with novel structures. Sri Lanka is considered as a biodiversity hotspot with a higher degree of endemism flora including bryophytes. In this study, different species of bryophytes were investigated for their antimicrobial and alpha-amylase inhibitory activities. The air-dried plant materials of 6 different bryophyte species, Marchantia sp., Fissidens sp., Plagiochila sp., Sematophyllum demissum, Hypnum cupressiforme, and Calymperes motley, were subjected to sequential cold extraction with 3 different organic solvents. All three types of organic crude extracts were subjected to screening of antimicrobial bioassays using the disc-diffusion method against 3 bacterial strains and 1 fungal strain. According to the results obtained, 6 extracts out of 18 showed antibacterial activity for tested Gram-positive bacteria and 1 active against Gram-negative bacteria. Two extracts showed activity against the pathogenic fungus strain. Extracts from some plants were active against tested bacterial as well as fungal species. TLC-based bioautographic study was carried out to identify the corresponding active bands which is useful for active compound isolation. Furthermore, the ethyl acetate extracts were subjected to evaluate alpha-amylase inhibitory activity where three extracts out of six extracts showed moderate inhibitory activity for alpha-amylase with IC50 ranging 8-30%.

Curcumin loaded zinc oxide nanoparticles for activity-enhanced antibacterial and anticancer applications.

Zinc oxide nanoparticles and curcumin have been shown to be excellent antimicrobial agents and promising anticancer agents, both on their own as well as in combination. Together, they have potential as alternatives/supplements to antibiotics and traditional anticancer drugs. In this study, different morphologies of zinc oxide-grafted curcumin nanocomposites (ZNP-Cs) were synthesized and characterized using SEM, TGA, FTIR, XRD and UV-vis spectrophotometry. Antimicrobial assays were conducted against both Gram negative and Gram-positive bacterial stains. Spherical ZnO-curcumin nanoparticles (SZNP-Cs) and rod-shaped ZnO-curcumin nanoparticles showed the most promising activity against tested bacterial strains. The inhibition zones for these curcumin-loaded ZnO nanocomposites were consistently larger than their bare counterparts or pure curcumin, revealing an additve effect between the ZnO and curcumin components. The potential anticancer activity of the synthesized nanocomposites was studied on the rhabdomyosarcoma RD cell line via MTT assay, while their cytotoxic effects were tested against human embryonic kidney cells using the resazurin assay. SZNP-Cs exhibited the best balance between the two, showing the lowest toxicity against healthy cells and good anticancer activity. The results of this investigation demonstrate that the nanomatrix synthesized can act as an effective, additively-enhanced combination delivery/therapeutic agent, holding promise for anticancer therapy and other biomedical applications.

Memory-prediction errors and their consequences in schizophrenia.

Cognitive deficits play a central role in the onset of schizophrenia. Cognitive impairment precedes the onset of psychosis in at least a subgroup of patients, and accounts for considerable dysfunction. Yet cognitive deficits as currently measured are not significantly related to hallucinations and delusions. Part of this counterintuitive absence of a relationship may be caused by the lack of an organizing principle of cognitive impairment in schizophrenia research. We review literature suggesting that a system of memory-based prediction is central to human perception, thought and action , and forward the notion that many of the symptoms of schizophrenia are a result of a failure of this system.

A global partnership in medical education between Duke University and the National University of Singapore.

Duke University and the National University of Singapore (NUS) have partnered to launch a new medical school that brings the American style of postbaccalaureate medical education to Asia. The new institution, called the Duke-NUS Graduate Medical School (GMS) and located in Singapore adjacent to the Singapore General Hospital, admitted its inaugural class of students representing citizens of seven nations in August 2007. The project represents an investment of more than $350 million from three ministries of the Singapore government, and a commitment on Duke's part to provide senior leadership and recruit faculty from Duke, from other international locales, and from within Singapore itself. Graduating students who complete the four-year Duke curriculum will receive an MD degree awarded jointly by Duke and NUS, thereby distinguishing this school from medical education in most Asian institutions that award an MBBS degree after a five-year period of study that follows directly from secondary school. The emphasis of the Duke-NUS GMS is to prepare physician-scientists for academic careers, with plans for 20% of each class to complete a combined MD/PhD degree. This article describes events leading up to this partnership and details of the relationship, including curriculum, organizational structure, milestones, and goals.

Transplantation of a unilateral fused kidney with inferior ectopia: revascularization utilizing donor aorta and vena cava.

We present a case of kidney transplantation utilizing a fused kidney with inferior ectopia. The kidney had three arteries, five veins and two ureters and was procured en bloc with the donor vena cava and aorta. The caudal end of the donor vena cava was anastomosed to the recipient's external iliac vein. The right common iliac artery of the donor, in continuity with the donor aorta, was anastomosed to the recipient's external iliac artery. The two ureters were implanted separately. The patientwas discharged home with a serum creatinine of 0.9 mg/dl. Through innovative techniques, kidneys that may not have been transplantable in the past can now be used with excellent results. This is the first known report of transplantation using a unilateral fused kidney with inferior ectopia.

Drug-Loaded Halloysite Nanotube-Reinforced Electrospun Alginate-Based Nanofibrous Scaffolds with Sustained Antimicrobial Protection.

Halloysite nanotube (HNT)-reinforced alginate-based nanofibrous scaffolds were successfully fabricated by electrospinning to mimic the natural extracellular matrix (ECM) structure which is beneficial for tissue regeneration. An antiseptic drug, cephalexin (CEF)-loaded HNT, was incorporated into the alginate-based matrix to obtain sustained antimicrobial protection and robust mechanical properties, the key criteria for tissue engineering applications. Electron microscopic imaging and drug release studies revealed that CEF had penetrated into the lumen space of the HNT and also deposited on the outer walls, with a total loading capacity of 30 wt %. Moreover, the diameter of alginate-based nanofibers of the scaffolds ranged from 40 to 522 nm with well-aligned HNTs, resulting in superior mechanical properties. For instance, the addition of 5% (w/w) HNT improved the tensile strength (σ) and elastic modulus by 3-fold and 2-fold, respectively, compared to those of the alginate-based scaffolds without HNT. The fabricated scaffolds exhibited remarkable antimicrobial properties against both Gram-negative and Gram-positive bacteria, and the cytotoxicity studies confirmed the nontoxicity of the fabricated scaffolds. Drug release kinetics showed that CEF inside HNTs diffuses within 24 h and that the diffusion of the drug is delayed by 7 days once the CEF-loaded HNTs are incorporated into the alginate-based nanofibers. These fabricated alginate-based electrospun scaffolds with enhanced mechanical properties and sustained antimicrobial protection hold great potential to be used as artificial ECM scaffolds for tissue engineering applications.

Antimicrobial activities of endophytic fungi of the Sri Lankan aquatic plant Nymphaea nouchali and chaetoglobosin A and C, produced by the endophytic fungus Chaetomium globosum.

Twenty distinct endophytic fungi were isolated from the surface-sterilized plant parts of Nymphaea nouchali and were identified using morphological and molecular techniques. At 300 µg/disc concentration, eight of the 20 fungal extracts exhibited antimicrobial activities against Staphylococcus aureus (ATCC 25923) and Bacillus cereus (ATCC 11778) while two within the eight showed activity against Pseudomonas aeruginosa (ATCC 9027) and Escherichia coli (ATCC 35218). Furthermore, investigation of the crude extract of Chaetomium globosum resulted in the isolation of two known cytochalasans, chaetoglobosin A and C, and their structures were elucidated and confirmed by mass and nuclear magnetic resonance (NMR) (1H, 13C, COSY, HSQC, HMBC and tROESY) spectral data. Chaetoglobosin A showed antibacterial activities against Bacillus subtilis (MIC 16 µg mL-1), Staphylococcus aureus (MIC 32 µg mL-1) and methicillin-resistant Staphylococcus aureus (MRSA, MIC 32 µg mL-1). This is the first study to report the isolation, identification and antimicrobial properties of endophytic fungi of N. nouchali in Sri Lanka.

Preliminary study of thyrotrophin releasing hormone stimulation test in chronic low back pain patients.

Chronic pain has been considered as a variant of depression or as a masked depression. In an attempt to unravel the complex relationship between chronic pain and depression, we administered the TRH stimulation test to a uniform group of chronic pain patients classified into those with and without major depression using DSM-III criteria. Eighteen percent showed blunting of TSH response to TRH. There was no significant difference between the two groups.

Chronic pain and depression. III. Family history study of depression and alcoholism in chronic low back pain patients.

In an attempt to unravel the relationship between chronic pain and depression, the authors studied the incidence of depression, alcoholism, and chronic pain in first degree relatives of 100 chronic pain patients with and without depression. A higher incidence of major depression was found in first degree relatives of those patients with depression than those without depression. Familial incidence of alcohol dependence was similar in both groups of patients. These findings confirm an earlier report and raise questions about the notion of considering chronic pain simply as a variant of depression and suggest the possibility that the occurrence of major depression in chronic back pain might be related to genetic vulnerability to depression in these patients.

Molecular cloning and expression of two HSP70 genes in the prawn, Macrobrachium rosenbergii.

Two complementary deoxyribonucleic acid (cDNA) clones encoding 2 different 70-kDa heat shock proteins (HSPs) were isolated from the prawn Macrobrachium rosenbergii. The cDNA clones were 2448 and 2173 bp in length and contained 1950- and 1734-bp open reading frames (ORFs), respectively. The ORFs encoded 649- and 577-amino acid polypeptides, which were named Mar-HSC70 and Mar-HSP70, respectively, according to the sequence identities with other known HSC70s and HSP70s and based on their inducibility in response to heat shock stress (at 35 degrees C). Genomic DNA sequence analysis revealed no introns in either gene. The major structural differences between the 2 proteins were a 60-amino acid segment and a 14-amino acid segment present in the N-terminal and C-terminal, respectively, of Mar-HSC70 that were not found in Mar-HSP70. Northern blotting and semiquantitative reverse transcription-polymerase chain reaction analyses indicated that the Mar-HSP70 gene was expressed under heat shock (35 degrees C) stress in a non-tissue-specific manner. In contrast, Mar-HSC70 messenger ribonucleic acid was constitutively expressed in every tissue except muscle, and its expression in response to heat shock (at 35 degrees C) changed only in muscle.

Clinical experience with substance P receptor (NK1) antagonists in depression.

Substance P (SP) belongs to the neurokinin (NK) family of neuropeptides and exerts its biological effects via interaction with the NK1 receptor. The SP-NK1 receptor system is one of the best-characterized neurotransmitter pathways in both the central and peripheral nervous systems. It has been postulated that this pathway may have important roles in a variety of centrally regulated pathophysiologic conditions, including depression. In animal models, central injection of SP was associated with a series of anxiety-like behaviors, and this response could be abolished by pretreatment with SP (NK1) receptor antagonists (SPAs). On the basis of these and other encouraging preclinical results, several clinical trials have examined the potential of SPAs in the treatment of depression. In phase 2 trials, therapy with the SPAs aprepitant (MK-0869) and compound A resulted in improvements in depression and anxiety symptoms that were quantitatively comparable with those seen with selective serotonin reuptake inhibitors (SSRIs) and significantly greater than those seen with placebo. These positive results have established a proof of concept that the inhibition of the SP-NK1 receptor pathway may be a potentially useful novel treatment option for management of patients with depression. The apparent lack of benefit with SPAs versus placebo in subsequent dose-finding studies with aprepitant and compound A is not surprising, considering the fact that the outcomes with an active control (SSRI) in these trials were also similar to those observed with placebo. Future trials with SPAs will focus on the identification of appropriate patients and drug regimens and will also define the role of these agents in the treatment of depression.

Funeral mania in recurrent bipolar affective disorders: reports of three cases.

Anniversary reactions as precipitants of manic episodes are reported to be relatively common, while manic onset within a week of bereavement ("funeral mania") has been considered rare. Three cases of funeral mania are described to illustrate that this phenomenon may be more frequent than has been thought.

Correlates of suicidal ideation among an elderly depressed sample.

BACKGROUND: Suicidal ideation has been shown to be strongly associated with suicide completion and elders take their own lives more than any other age group. METHODS: The present study examined clinical and phenomenological correlates of suicidal ideation among an elderly sample (n = 167) derived from subjects enrolled in the Duke Clinical Research Center for the Study of Depression in Late Life. RESULTS: Bivariate results indicated that clinical variables associated with psychomotor retardation, a history of dysthymia, a previous psychiatric in-patient stay, and being a 'younger' elder were related to greater suicidal ideation. Multivariate analyses indicated that feeling guilty, sinful, or worthless was associated with over six times greater odds of having suicidal thoughts. LIMITATIONS: Findings are based on correlational analyses, and thus, the direction of causality cannot be inferred. CONCLUSIONS: This study provides evidence for clinicians of some of the 'red flags' associated with the presence of suicidal ideation among depressed older adults.

New onset and remission of suicidal ideation among a depressed adult sample.

BACKGROUND: Previous research has demonstrated that suicidal ideation often predicts suicide completion. METHODS: The present study examined clinical and phenomenological variables associated with the presence, development and remission of suicidal ideation among depressed adults. The sample (n = 81) was derived from subjects enrolled in the Duke Clinical Research Center for the Study of Depression in Late Life. RESULTS: Greater pessimistic thinking at baseline predicted the development of suicidal ideation one year later and the older a person was when he or she first experienced depression, the more likely he or she was to report remission from suicidal ideation one year following onset. LIMITATIONS: Longitudinal analyses were based on relatively small samples. Variables that were not significant in these analyses might be in a larger sample. CONCLUSIONS: The longitudinal design of this study mitigates limitations associated with cross-sectional or retrospective designs and advances our understanding of a clinical profile associated with the development and remission of suicidal thoughts.

Magnetic resonance imaging signal hypointensity and iron content of putamen nuclei in elderly depressed patients.

We previously introduced a semiquantitative scale for assessment of iron content of putamen nuclei as determined by magnetic resonance imaging (MRI)--the Signal Hypointensity in the Putamen (SHIP) scale. Such hypointensity may be related to putamen nuclei iron content, although this suggestion remains controversial, especially in the elderly. In the present study, we apply the SHIP scale to a sample of 68 elderly depressed patients (diagnosed with DSM-IV major depression using the Diagnostic Interview Schedule and clinical interview) and a group of 28 age-matched non-depressed control subjects. MRI scans were conducted on a single 1.5-T General Electric Signa system with axial acquisitions obtained parallel to the canthomeatal line. Technical parameters were as follows: (1) repetition time (TR) = 500 ms and echo time (TE) = 15 ms for T1-weighted images; (2) TR = 2500 ms and TE = 30 ms for proton-density-weighted images; and (3) TR = 2500 ms and TE = 80 ms for T2-weighted images. Among depressed patients, older age of depression onset and greater severity of depression were associated with increased putamen nuclei iron deposition. When depressed patients were compared with control subjects, the patient group demonstrated greater putamen nuclei iron, but the finding was significant only for the left hemisphere. Our findings support previous neuroimaging studies linking both changes in the basal ganglia and greater left-sided brain pathology to late-life depression.

Accuracy and reproducibility of brain and tissue volumes using a magnetic resonance segmentation method.

Magnetic resonance (MR) imaging now allows the qualitative and quantitative assessment of the human brain in vivo. As MR imaging resolution has improved, precise measurement of small brain structures has become possible. Methods of measuring brain regions from MR images include both manual and semiautomated methods. Despite the development of numerous volumetric methods, there have been only limited attempts so far to evaluate the accuracy and reproducibility of these methods. In this study we used phantoms to assess the accuracy of the segmentation process. Our results with simple and complex phantoms indicate an error of 3-5% using either manual or semiautomated techniques. We subsequently used manual and semiautomated volumetric methodologies to study human brain structures in vivo in five normal subjects. Supervised segmentation is a semiautomated method that accomplishes the division of MR images into several tissue types based on differences in signal intensity. This technique requires the operator to manually identify points on the MR images that characterize each tissue type, a process known as seeding. However, the use of supervised segmentation to assess the volumes of gray and white matter is subject to pitfalls. Inhomogeneities of the radiofrequency or magnetic fields can result in misclassification of tissue points during the tissue seeding process, limiting the accuracy and reliability of the segmentation process. We used a structured seeding protocol that allowed for field inhomogeneity that produced reduced variation in measured tissue volumes. We used repeated segmentations to assess intra- and inter-rater reliability, and were able to measure small and large regions of interest with a small degree of variation. In addition, we demonstrated that measurements are reproducible with repeat MR acquisitions, with minimal interscan variability. Segmentation methods can accurately and reliably measure subtle morphometric changes, and will prove a boon to the study of neuropsychiatric disorders.

Amygdala activity at encoding corresponds with memory vividness and with memory for select episodic details.

It is well known that amygdala activity during encoding corresponds with subsequent memory for emotional information. It is less clear how amygdala activity relates to the subjective and objective qualities of a memory. In the present study, participants viewed emotional and neutral objects while undergoing a functional magnetic resonance imaging scan. Participants then took a memory test, identifying which verbal labels named a studied object and indicating the vividness of their memory for that object. They then retrieved episodic details associated with each object's presentation, selecting which object exemplar had been studied and indicating in which screen quadrant, study list, and with which encoding question the exemplar had been studied. Parametric analysis of the encoding data allowed examination of the processes that tracked with increasing memory vividness or with an increase in the diversity of episodic details remembered. Dissociable networks tracked these two increases, and amygdala activity corresponded with the former but not the latter. Subsequent-memory analyses revealed that amygdala activity corresponded with memory for exemplar type but not for other episodic features. These results emphasize that amygdala activity does not ensure accurate encoding of all types of episodic detail, yet it does support encoding of some item-specific details and leads to the retention of a memory that will feel subjectively vivid. The types of episodic details tied to amygdala engagement may be those that are most important for creating a subjectively vivid memory.