Laparoscopic diverticulectomy or laparoscopic-assisted resection of symptomatic Meckel diverticulum in children? A systematic review.

Recent reports have recommended laparoscopic diverticulectomy for symptomatic Meckel diverticulum (MD) rather than laparoscopic-assisted extracorporeal resection. This technique may risk leaving residual ectopic mucosa leading to complications. This systematic review attempts to quantify the relative risks of both approaches. A systematic review was conducted according to PRISMA guidelines. Articles were eligible for inclusion if they reported data on the laparoscopic management of symptomatic MD in children. Eleven reports were identified, all of which were institutional retrospective studies. Pooled outcome data on 248 children showed no statistically significant difference in complications between laparoscopic diverticulectomy (n = 133) and laparoscopic-assisted segmental resection (n = 115) (3% vs. 6.1%, p = 0.39). One patient from the diverticulectomy group re-presented with recurrent bleeding necessitating segmental small bowel resection. Conclusions are limited by the number of patients and variable follow up. Short, wide MD with a height:base ratio of < 2; diverticula with thickening or ischemia at the base and those complicated by volvulus or small bowel obstruction are probably best treated by laparoscopic-assisted extracorporeal resection. For other symptomatic diverticula laparoscopic diverticulectomy is a reasonable approach with a less than 1% risk of leaving residual ectopic gastric mucosa.

Nanosuspensions of hesperetin: preparation and characterization.

Nanosuspensions are a smart formulation principle for dermal applications, as they increase the penetration of poorly soluble substances into the skin. Because microbial stability is a pre-requisite for dermal formulations, water containing formulations need to be preserved. Preservatives are known to possibly impair the physical stability of disperse systems, i.e. by causing agglomeration. These aggregation phenomena might occur during storage of the final product, but can already occur during the production process itself. Therefore, in this study the influence of six different preservatives on the diminution efficiency during the production of hesperetin nanocrystals was investigated. Particles with and without the addition of preservatives were produced by high pressure homogenization (HPH) and the final particle size was analysed and compared to the non-preserved suspension. All preservatives influenced the diminution progress during production and the final particle sizes obtained. The non-preserved suspension yielded a particle size of about 300 nm. Preservation with Hydrolite, Euxyl PE9010, Rokonsal and Phenonip led to sizes of about 400 nm. Preservation with Caprylyl glycol and MultiEx did not lead to nanoparticles (size > 1 microm) and caused a slight agglomeration of the nanosuspensions. Based on zeta potential measurements it was found that the impairment is related to the lipophilicity of the presverative, i.e. the lower the lipophilicity, the less is the impairment. In conclusion, preservatives impair the diminution efficacy during the production of nanosuspensions. Therefore, if possible, preservatives should be added to nanosuspensions after the production process. If preservatives are required during production, highly hydrophilic preservatives, e.g. Hydrolite E, should be used.

Decay score: a guide to the immunoreactivity of human pancreatic islets in autopsy specimen.

BACKGROUND: The pancreas is an exo-endocrine organ that undergoes rapid autolysis soon after death, which limits its utility in academics and research. The timeline of autolytic changes of pancreatic islets and its immunoreactivity is limited in the literature. Decay score has been used to grade the autolytic changes in organs like the brain, lung and liver. However, reports are not available in the pancreas/pancreatic islets. Knowledge regarding the decay score may be used as a torchbearer for the immunoreactivity of human pancreatic islets in autopsy cases. The present study is aimed to provide an optimal cut-off time based on the decay score before which pancreatic specimens should be collected for the purpose of immunohistochemical studies (IHC) of pancreatic islets. MATERIALS AND METHODS: Serial sections of 20 adult human pancreases obtained from the autopsy were subjected to haematoxylin and eosin (H&E) and immunohistochemical staining. Autolytic changes of pancreatic islets were graded by using decay score in H&E sections, which was compared with the results of the immunohistochemical reactivity of pancreatic islets in IHC sections. RESULTS AND CONCLUSIONS: Pancreatic islets immunoreactivity was found to be well preserved in the samples collected early within 9 hours with a decay score of less than 1.4. There was an inverse relation of decay score and immunoreactivity of pancreatic islets. The decay score of less than 1.4 has better-preserved immunoreactivity than having more than 1.4. This knowledge will help researchers working in the field of the endocrine pancreas.

SiRNA delivery: challenges and role of carrier systems.

Gene silencing by RNA interference is a rapidly growing therapeutic area for managing diseases. Despite research advances in this direction, the poor cellular uptake of synthetic small interfering RNAs is a major impediment to their clinical applications. Polymer and lipid-based systems are attractive carrier systems for delivery of siRNA and provide options for desirable engineering of carrier particles. In this review, there is a detailed discussion of RNAi delivery systems and recent advances in the field.

On the synthesis and characterizations of TiO2 nanotubes.

In the present work, aligned TiO2 nanotubes have been synthesized by a simple method of electrochemical anodization of high purity, well cleaned, etched and ultrasonicated Ti-sheet (Purity approximately 99.99%) in a fluoride mediated electrolytic media consisting of a solution of 0.14 M NaF and a solution of 0.5 M/1.0 M H3PO4. Studies on the effects of anodization voltage, time and electrolyte concentration on the formation of TiO2 nanotubes have been carried out. The TiO2 nanotube arrays have been synthesized at applied anodization voltages of approximately 10 V and approximately 20 V. The anodization was carried out for 1 hour and 2 hours at each applied voltage. Structural/microstructural characterizations of TiO2 nanotubes have been carried out through scanning electron microscopy (SEM) and transmission electron microscopy (TEM). SEM images of TiO, nanotubes showed interesting features relating to morphology, the pore size (diameter of the tubes) and the lengths of the tube. TEM investigations revealed that the as synthesized nanotubes are amorphous in nature and on electron beam annealing, these transformed to crystalline phases (rutile and brookite). The optical characterizations through UV-Visible spectroscopy exhibited that the band gap are approximately 3.03 eV and approximately 2.87 eV for tubes synthesized at applied anodization voltages of approximately 10 V and approximately 20 V respectively. A tentative mechanism for the growth of TiO2 nanotube has been put forward.

Impact of involvement of non-formal health providers on TB case notification among migrant slum-dwelling populations in Odisha, India.

BACKGROUND: Migrant labourers living in the slums of urban and industrial patches across India make up a key sub-population so far controlling Tuberculosis (TB) in the country is concerned. This is because many TB patients from these communities- remain under reached by the Revised National Tuberculosis Control Programme (RNTCP) of India. This marginalized community usually seeks early-stage healthcare from "friendly neighbourhood" non-formal health providers (NFHPs). Because, RNTCP has limited capacity to involve the NFHPs, an implementation research project was conceived, whereby an external partner would engage with the NFHPs to enable them to identify early TB symptomatics from this key sub-population who would be then tested using Xpert MTB/RIF technology. Diagnosed TB cases among them would be referred promptly to RNTCP for treatment. This paper aimed to describe the project and its impact. METHODS: Adopting a quasi-experimental before-after design, four RNTCP units from two major urban-industrial areas of Odisha were selected for intervention, which spanned five quarters and covered 151,400 people, of which 30% were slum-dwelling migrants. Two similar units comprised the control population. The hypothesis was, reaching the under reached in the intervention area through NFHPs would increase TB notification from these traditionally under-notifying units. RNTCP notification data during intervention was compared with pre-intervention era, adjusted for contemporaneous changes in control population. RESULTS: The project detected 488 Xpert+ TB cases, of whom 466 were administered RNTCP treatment. This translated into notification of additional 198 new bacteriologically positive cases to RNTCP, a 30% notification surge, after adjustment for 2% decline in control. This meant an average quarterly increase in notification of 41.20(20.08, 62.31; p<0.001) cases. The increase was immediate, evident from the rise in level in the time series analysis by 50.42(10.28, 90.55; p = 0.02) cases. CONCLUSION: Engagement with NFHPs contributed to an increase in TB notification to RNTCP from key under reached, slum-dwelling migrant populations.

Formation and microstructural characterization of coaxial carbon cylinders consisting of aligned carbon nanotube stacks.

The macroscopic coaxial carbon cylinders (dia. approximately 0.5 cm with varying lengths approximately 2-5 cm) consisting of aligned carbon nanotube (CNT) stacks have been prepared by spray pyrolysis of benzene-ferrocene solution in argon atmosphere at approximately 850 degrees C-900 degrees C temperature. The coaxial carbon cylinders of CNT stacks have been formed directly inside the quartz tube. We attempted to prepare superimposed multi carbon cylinder configurations, each consisting of ordered and aligned CNTs stacked over each other. For this, we have terminated the spray of precursor after run of about 25 minutes, for a short interval (approximately 5 min), and then the solution was sprayed again over the already deposited hot CNT stack. Gross structural characterization of CNTs was done through X-ray diffraction technique (XRD). Microstructural characterizations of as prepared coaxial carbon cylinders with CNT stacks were done by scanning electron microscopic (SEM) techniques. SEM studies show that the CNTs are well aligned along the periphery of the cross section of coaxial carbon cylinder, each consisting of CNTs of the type described in the above. Comparisons have been made between the present macroscopic coaxial carbon cylinders with CNT stacks studied earlier by several other workers. Plausible explanation for the synthesis of CNT stacks will be put forward.

P-gp modulatory acetyl-11-keto-ß-boswellic acid based nanoemulsified carrier system for augmented oral chemotherapy of docetaxel.

In spite of being a very potent and promising drug against many types of cancer, docetaxel suffers the disadvantage of low solubility and poor bioavailability rendering it unsuitable for oral administration. Also, the available marketed formulation for intravenous administration has its inherent drawbacks owing to the presence of polysorbate 80. Here, we exploited the anticancer and P-gp inhibitory potential of naturally occurring frankincense oil to fabricate a stable docetaxel loaded nanoemulsified carrier system for oral delivery. The nanoemulsion possessing desirable particle size (122±12nm), polydispersity (0.086±0.007) and zeta potential (-29.8±2.1mV) was stable against all type of physical stresses and simulated physiological conditions tested. The formulation showed higher uptake in Caco-2 cells and inhibited P-gp transporter significantly (P<0.05). In MDA-MB-231 cells, it showed less IC50, arrested cells in G2-M phase and exhibited higher degree of apoptosis than marketed formulation Taxotere®. The 182.58±4.16% increment in relative oral bioavailability led to higher in vivo anti-proliferative activity manifesting 19% more inhibition than Taxotere®. Conclusively, it is revealed that the developed nanoemulsion will be a propitious approach towards alternative docetaxel therapy.

Dual functioning microspheres embedded crosslinked gelatin cryogels for therapeutic intervention in osteomyelitis and associated bone loss.

In the present research,we simultaneously addressed the condition of osteomyelitis and osteoporosis by developing a gelatin based chemically cross linked cryogel system embedded with CaCO3 microspheres and ciprofloxacin hydrochloride was incorporated in both the microspheres and the 3D matrix of cryogel. The fabricated cryogel was characterized for the swelling ratio, swelling kinetics, porosity, pore volume, compression strength and in vitro rate of degradation which were found to be dependent on the concentration of gelatin, duration of freezing and number of freeze-thaw cycles. The sustained release of drug was obtained up to 21days after the initial burst, and the concentration was maintained above the MIC for the entire duration of the study. The in vitro antibacterial study in Staphylococcus aureus and Escherichia coli exhibited 33mm, 30mm, 28mm, 27mm and 43mm, 37mm, 37mm, and 36mm zone of inhibition respectively at day 1, 3, 5 and 7. The cell viability, number of cells in the growth phase and alkaline phosphatase levels were found to be significantly higher in rat osteoblasts cultured in cryogel as compared to 2D surface. All these results demonstrate the propitious potential of this microsphere incorporated, ciprofloxacin-loaded, industrially scalable cryogel system for therapeutic intervention in osteoporosis and associated osteomyelitis.

En bloc Pancreaticodudenectomy with Colectomy for Locally Advanced Right Sided Colon Cancer.

A 57 year old male presented to our outpatient clinic with history of on and off melena, weight loss and decreasing appetite for 10 months duration and a noticeable mass on the right upper quadrant. Abdominal examination revealed an intra-abdominal lump in right upper quadrant which was subsequently evaluated by colonoscopy, which revealed an ulcero-proliferative growth in the hepatic flexure and the biopsy from it confirmed well-differentiated adenocarcinoma. Contrast enhanced computed tomography demonstrated hepatic flexure mass with possible invasion into adjacent duodenum without features of advanced disease. After completion of necessary preoperative assessment and investigations, patient was explored with curative intent and underwent extended right hemicolectomy with en bloc pancreaticodudenectomy. Patient was discharged on 10th postoperative day and at 14 months follows up; he was doing well without any evidence of recurrence.

An insight into functionalized calcium based inorganic nanomaterials in biomedicine: Trends and transitions.

Over the recent years the use of biocompatible and biodegradable nanoparticles in biomedicine has become a significant priority. Calcium based ceramic nanoparticles like calcium phosphate (CaP) and calcium carbonate (CaCO3) are therefore considered as attractive carriers as they are naturally present in human body with nanosize range. Their application in tissue engineering and localized controlled delivery of bioactives for bones and teeth is well established now, but recently their use has increased significantly as carrier of bioactives through other routes also. These delivery systems have become most potential alternatives to other commonly used delivery system because of their cost effectiveness, biodegradability, chemical stability, controlled and stimuli responsive behaviour. This review comprehensively covers their characteristic features, method of preparation and applications but the thrust is to focus their recent development, functionalization and use in systemic delivery. On the same platform mineralization of other nanoparticulate delivery system which has widened their application drug delivery will be discussed. The emphasis has been given on their pH dependent properties which make them excellent carriers for tumour targeting and intracellular delivery. Finally this review also attempts to discuss their drawback which limits their clinical utility.

Anticonvulsant effects of ivermectin in genetically-epileptic chickens.

In genetically-photosensitive epileptic chickens, the anti-parasitic agent ivermectin, at 1.0 and 5.0 mg/kg, decreased or prevented seizures induced by intermittent photic stimulation without any side-effects on the central nervous system. The latency and duration of this anti-convulsant effect was dose-dependent. When combined with diazepam, ivermectin prolonged the anti-convulsant action of diazepam.

DNA loss in the developing cerebellum of nervous mouse: a flow cytometric study.

Flow-cytometry of cerebellar EGL cells of nervous (nr) mouse revealed a reduction in DNA quantity per cell accompanied by an increase in the DNA dispersion during 6-8 days of postnatal life. This loss of DNA is due to a partial degeneration of the cells of EGL during the first week of postnatal life. The surviving cells later on achieve a DNA content equivalent to their bone marrow cells. The flow-cytometric technique also facilitates an early detection of the homozygous nervous mutant, almost 2 weeks before the clinical manifestation of the disease, which to date was not possible.

Dual coated erodible microcapsules for modified release of diclofenac sodium.

Diclofenac sodium was formulated as novel enteric microcapsules for improved delivery to the intestine using the polymers cellulose acetate phthalate (CAP) and ethyl cellulose (EC). The enteric coating was given using an innovative technique combining the wet granulation and thermal change methods. The novel process was analysed for its capability to produce microcapsules of uniform size, good flowability, uniform drug loading and maximum entrapment efficacy and the absence of interaction between drug and process parameters as well as the polymers. In vitro release study was carried out in simulated gastric fluid (SGF) for first 2 h and simulated intestinal fluid (SIF) for next 6 h. The best formulation that contained cellulose acetate phthalate and ethyl cellulose in the concentration of 10:90 at 1:1.5 drug-polymer ratio (B3) was further evaluated using in vivo for its pharmacodynamic efficacy and ulcerogenicity. In addition to sustained and uniform release of drug, the formulation B3 showed better anti-inflammatory activity than the marketed formulation and retarded drug release in the gastric medium. The biological examination of incised stomach showed no histological alterations in term of mucous surface cells and glands.

Surface modified methotrexate loaded erythrocytes for enhanced macrophage uptake.

The unique property of macrophages to distinguish between 'mature self' and 'senescent self' was applied for the enhanced macrophage uptake upon loading drugs into erythrocytes and provoking environment within which it gets translated into senescent cells. Two different approaches were applied one by depleting the sialic acid from the surface of cells and another by inducing hemichrome formation in the cells. Erythrocytes encapsulation of methotrexate was carried out by preswell dilution technique. Surface modification of erythrocytes was performed using desialation and hemichrome induction by treating with trypsin (Tt) and phenylhydrazine (PhT) respectively. Desialation technique was optimized in terms of concentration of trypsin, incubation temperature and time period. Both of these surface modified erythrocytes were characterized for in vitro macrophage uptake. In vivo organ localization was assessed by recording amount of drug present in different organs. The macrophage uptake of both surface modified erythrocytes was enhanced by almost 3-5 and 5-6 times with Tt and PhT cells, respectively. These new surface modified carriers are found to be excellent candidate for enhanced macrophage uptake and anticipated to be useful for any RES tumors.

Biotinylated methotrexate loaded erythrocytes for enhanced liver uptake. 'A study on the rat'.

To serve as liver specific delivery system, methotrexate (MTX) loaded erythrocytes were modified by attachment with N-hydroxysuccinimide ester of biotin (NHS-biotin) and in vitro macrophage uptake and in vivo studies were carried out in the rat. Surface bound biotin was quantitated indirectly using an avidin support and measuring the change in absorbance at 500 nm by the interaction with 2-(4' hydroxyazobenzene) benzoic acid (HABA). A concentration course study of biotin binding reaction showed biotin molecules bound to the erythrocytes as a function of the NHS-biotin concentration. Glycerol lysis time study revealed enhanced stability of biotinylated cells (BT) compared with nonbiotinylated drug loaded cells (NB). These surface modified erythrocytes were characterized for in vitro macrophage uptake. The macrophage uptake and phagocytic index of these modified erythrocytes were enhanced by more than two-fold compared with NB cells (P<0.05). In vivo organ localization was assessed by recording amount of drug present in different organs. The modified carrier induces substantial liver targeting as drug therapeutic index in liver was found to be 3.1. These findings support the use of carrier erythrocytes, exploiting the targeting properties imparted by biotinylation. Consequently, it can spare surgical intervention to place hepatic arterial catheters for locoregional treatment of liver neoplasms.

Folate conjugated doxorubicin-loaded membrane vesicles for improved cancer therapy.

The new concept developed in this study is the preparation of a new derivative of erythrocyte ghosts, i.e., membrane vesicles loaded with doxorubicin (Dox) HCl and coupled to folic acid to improve cancer chemotherapy. N-hydroxysuccinimide (NHS) folate was then conjugated to membrane vesicles. These membrane vesicles were extensively characterized for in vitro and in vivo performance. The vesicle size obtained was in the range of 1.2-1.5 microm and in vitro release profile showed 51.8 and 38.7% of drug release in case of Dox-V and Dox-FV, respectively, in 16 hr. The stability studies were performed at 4 degrees C by assessing the effect on vesicle size and leakage after 7, 15, and 21 days. The stability study showed negligible leakage and no appreciable change in the vesicle size after storage for several days in both formulations. The cytostatic activity was assessed and found that IC50 was decreased 3.2 and 2.1 times for Dox-FV compared with free drug and Dox-V, respectively. The cytotoxic activity showed similar profile among the formulations: order of toxicity was Dox-FV > Dox-V > free drug. The mean survival time was found in order of Dox-FV > Dox-V > free drug > control (FV). The increase in life for Dox-FV was 212.9%. Overall, this folic acid conjugated vesicle system proved to be a potential delivery system for improved cancer therapy.

Reverse biomembrane vesicles for effective controlled delivery of doxorubicin HCl.

A new derivative of erythrocyte ghosts--reverse biomembrane vesicles (RBVs)--was developed, loaded with doxorubicin HCl (Dox RBVs), and extensively characterized both in vivo and in vitro. The formulation of reverse biomembrane is based on budding of membrane into the ghost interiors (endocytosis) leading to accumulation of small vesicles within each parent ghost. The system was evaluated in vitro for entrapment efficiency, membrane orientation, vesicle size, release profile, and centrifugal stress. The stability studies were performed at 4 degrees C by assessing the effect on vesicle size and leakage after 7, 15, and 21 days. The stability study showed negligible leakage and no appreciable change in vesicle size after storage for several days--an indication of good stability of RBVs formulation. The formulation and process variables were optimized to obtain vesicles of 1.2-1.8 microm. The amount of doxorubicin entrapped in RBVs was 0.75 mg/ml of packed vesicles. The in vitro release profile showed 52.86% of drug release in 16 hr. A membrane orientation study revealed inversion of membrane surface because only 10% of sialic acid was accessible on trypsin treatment. The plasma clearance data revealed an increase in half-life and bioavailability of drug. Tissue concentration data suggest that liver and spleen remain the major organs for clearance of these drug-loaded RBVs, which suggests preferential uptake by the reticuloendothelial system. On the whole, this vesicle system proved to be of potential application in cancer chemotherapy.

The cancer targeting potential of D-α-tocopheryl polyethylene glycol 1000 succinate tethered multi walled carbon nanotubes.

Our main aim in the present investigation was to explore the in vitro and in vivo cancer targeting potential of the doxorubicin (DOX) laden d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) tethered surface engineered MWCNTs nanoformulation (DOX/TPGS-MWCNTs) and compare it with pristine MWCNTs and free doxorubicin solution. The developed MWCNTs nanoformulations were extensively characterized by Fourier-transform infrared, Raman spectroscopy, x-ray diffraction, electron microscopy, and in vitro and in vivo studies using MCF-7 cancer cell line. The entrapment efficiency was determined to be 97.2 ± 2.50% (DOX/TPGS-MWCNTs) and 92.5 ± 2.62% (DOX/MWCNTs) ascribed to π-π stacking interactions. The developed formulations depicted the sustained release pattern at the lysosomal pH (pH 5.3). The DOX/TPGS-MWCNTs showed enhanced cytotoxicity, cellular uptake and were most preferentially taken up by the cancerous cells via endocytosis mechanism. The DOX/TPGS-MWCNTs nanoconjugate depicted the significantly longer survival span (44 days, p < 0.001) than DOX/MWCNTs (23 days), free DOX (18 days) and control group (12 days). The obtained results also support the extended residence time and sustained release profile of the drug loaded surface engineered nanotubes formulations in body as compared to DOX solution. Overall we can conclude that the developed MWCNTs nanoconjugate have higher cancer targeting potential on tumor bearing Balb/c mice.

Coating doxorubicin-loaded nanocapsules with alginate enhances therapeutic efficacy against Leishmania in hamsters by inducing Th1-type immune responses.

BACKGROUND AND PURPOSE: The aim of the present study was to evaluate the immunomodulatory and chemotherapeutic potential of alginate-(SA) coated nanocapsule (NCs) loaded with doxorubicin (SA-NCs-DOX) against visceral leishmaniasis in comparison with nano-emulsions containing doxorubicin (NE-DOX). EXPERIMENTAL APPROACH: NE-DOX was prepared using low-energy emulsification methods. Stepwise addition of protamine sulphate and SA in a layer-by-layer manner was used to form SA-NCs-DOX. SA-NCs-DOX, NE-DOX and Free DOX were compared for their cytotoxicity against Leishmania donovani-infected macrophages in vitro and generation of T-cell responses in infected hamsters in vivo. KEY RESULTS: Size and ζ potential of the NE-DOX and SA-NCs-DOX formulations were 310 ± 2.1 nm and (-)32.6 ± 2.1 mV, 342 ± 4.1 nm and (-)29.3 ± 1.2 mV respectively. SA-NCs-DOX was better (1.5 times) taken up by J774A.1 macrophages compared with NE-DOX. SA-NCs -DOX showed greater efficacy than NE-DOX against intramacrophagic amastigotes. SA-NCs-DOX treatment exhibited enhanced apoptotic efficiency than NE-DOX and free DOX as evident by cell cycle analysis, decrease in mitochondrial membrane potential, ROS and NO production. T-cell responses, when assessed through lymphoproliferative responses, NO production along with enhanced levels of iNOS, TNF-α, IFN-γ and IL-12 were found to be up-regulated after SA-NCs-DOX, compared with responses to NE-DOX in vivo. Parasitic burden was decreased in Leishmania-infected hamsters treated with SA-NCs-DOX, compared with NE-DOX. CONCLUSIONS AND IMPLICATIONS: Our results provide insights into the development of an alternative approach to improved management of leishmaniasis through a combination of chemotherapy with stimulation of the innate immune system.