Magnetic nanoformulation of azidothymidine 5’-triphosphate for targeted delivery across the blood–brain barrier

Despite significant advances in highly active antiretroviral therapy (HAART), the prevalence of neuroAIDS remains high. This is mainly attributed to inability of antiretroviral therapy (ART) to cross the blood–brain barrier (BBB), thus resulting in insufficient drug concentration within the brain. Therefore, development of an active drug targeting system is an attractive strategy to increase the efficacy and delivery of ART to the brain. We report herein development of magnetic azidothymidine 5′-triphosphate (AZTTP) liposomal nanoformulation and its ability to transmigrate across an in vitro BBB model by application of an external magnetic field. We hypothesize that this magnetically guided nanoformulation can transverse the BBB by direct transport or via monocyte-mediated transport. Magnetic AZTTP liposomes were prepared using a mixture of phosphatidyl choline and cholesterol. The average size of prepared liposomes was about 150 nm with maximum drug and magnetite loading efficiency of 54.5% and 45.3%, respectively. Further, magnetic AZTTP liposomes were checked for transmigration across an in vitro BBB model using direct or monocyte-mediated transport by application of an external magnetic field. The results show that apparent permeability of magnetic AZTTP liposomes was 3-fold higher than free AZTTP. Also, the magnetic AZTTP liposomes were efficiently taken up by monocytes and these magnetic monocytes showed enhanced transendothelial migration compared to normal/non-magnetic monocytes in presence of an external magnetic field. Thus, we anticipate that the developed magnetic nanoformulation can be used for targeting active nucleotide analog reverse transcriptase inhibitors to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat neuroAIDS

Investigation of features of May, 2001 tropical cyclone over the Arabian Sea through IRS-P4 and other satellite data

In this paper, utility of satellite derived atmospheric motion vectors and geophysical parameters is brought out to discern appropriate signals for improving short-range forecasts in respect of development/dissipation of tropical cyclones over the Indian region. Results of a particular case study of May, 2001 cyclone, which formed in the Arabian Sea are reported. Analysis of wind field with input of modified cloud motion vectors and water vapour wind vectors is performed utilizing Optimum Interpolation (OI) technique at 850 and 200 hPa for finding dynamical changes such as vorticity, convergence and divergence for the complete life period of this cyclone. Simultaneously, variations in geophysical parameters obtained from IRS-P4 and TRMM satellites in ascending and descending nodes are compared with dynamical variations for discerning some positive signals to improve short range forecasts over the Indian region. The enhancement of cyclonic vorticity at 200 hPa over larger area surrounding center of cyclone was observed from 26 to 28 May 2001 which gave a positive signal for dissipation of storm

Proper depiction of monsoon depression through IRS-P4 MSMR

In this paper, daily variations of satellite-derived geophysical parameters such as integrated water vapour (IWV), cloud liquid water content (CLW), sea surface temperature (SST) and sea surface wind speed (SSW) have been studied for a case of monsoon depression that formed over the Bay of Bengal during 19th-24th August 2000. For this purpose, IRS P4 MSMR satellite data have been utilized over the domain equator - 25°N and 40°-100°E. An integrated approach of satellite data obtained from IRS-P4, METEOSAT-5 and INSAT was made for getting a signal for the development of monsoon depression over the Indian region. Variations in deep convective activity obtained through visible, infrared and OLR data at 06 UTC was thoroughly analyzed for the complete life cycle of monsoon depression. Geophysical parameters obtained through IRS-P4 satellite data were compared with vorticity, convergence and divergence at 850 and 200 hPa levels generated through cloud motion vectors (CMVs) and water vapour wind vectors (WVWVs) obtained from METEOSAT-5 satellite. This comparison was made for finding proper consistency of geophysical parameters with dynamical aspects of major convective activity of the depression. From the results of this study it is revealed that there was strengthening of sea surface winds to the south of low-pressure area prior to the formation of depression. This indicated the possibility of increase in cyclonic vorticity in the lower troposphere. Hence, wind field at 850 hPa with satellite input of CMVs in objective analysis of wind field using optimum interpolation (OI) scheme was computed. Maximum cyclonic vorticity field at 850 hPa was obtained in the region of depression just one day before its formation. Similarly, with the same procedure maximum anticyclonic vorticity was observed at 200 hPa with WVWVs input. Consistent convergence and divergence at 850 and 200 hPa was noticed with respect to these vorticities. In association with these developments, we could get lowest values of OLR (120W/m 2) associated with major convective activity that was consistent with the maximum values of integrated water vapour (6-8 gm/cm 2) and cloud liquid water content (50-60 mg/cm 2) persisting particularly in the southwest sector of the monsoon depression

Survival of Enterococcus faecalis in root canals ex vivo

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72532/1/j.1365-2591.2005.01009.x.pd

Quality of antimalarial drugs and antibiotics in Papua New Guinea: A survey of the health facility supply chain

Background: Poor-quality life-saving medicines are a major public health threat, particularly in settings with a weak regulatory environment. Insufficient amounts of active pharmaceutical ingredients (API) endanger patient safety and may contribute to the development of drug resistance. In the case of malaria, concerns relate to implications for the efficacy of artemisinin-based combination therapies (ACT). In Papua New Guinea (PNG), Plasmodium falciparum and P. vivax are both endemic and health facilities are the main source of treatment. ACT has been introduced as first-line treatment but other drugs, such as primaquine for the treatment of P. vivax hypnozoites, are widely available. This study investigated the quality of antimalarial drugs and selected antibiotics at all levels of the health facility supply chain in PNG.Methods and Findings: Medicines were obtained from randomly sampled health facilities and selected warehouses and hospitals across PNG and analysed for API content using validated high performance liquid chromatography (HPLC). Of 360 tablet/capsule samples from 60 providers, 9.7% (95% CI 6.9, 13.3) contained less, and 0.6% more, API than pharmacopoeial reference ranges, including 29/37 (78.4%) primaquine, 3/70 (4.3%) amodiaquine, and one sample each of quinine, artemether, sulphadoxine-pyrimethamine and amoxicillin. According to the package label, 86.5% of poor-quality samples originated from India. Poor-quality medicines were found in 48.3% of providers at all levels of the supply chain. Drug quality was unrelated to storage conditions.Conclusions: This study documents the presence of poor-quality medicines, particularly primaquine, throughout PNG. Primaquine is the only available transmission-blocking antimalarial, likely to become important to prevent the spread of artemisinin-resistant P. falciparum and eliminating P. vivax hypnozoites. The availability of poor-quality medicines reflects the lack of adequate quality control and regulatory mechanisms. Measures to stop the availability of poor-quality medicines should include limiting procurement to WHO prequalified products and implementing routine quality testing

Prevalence of apical periodontitis and endodontic treatment in a Kosovar adult population

<p>Abstract</p> <p>Background</p> <p>Despite numerous studies on the prevalence of apical periodontitis (AP) and endodontic treatment in diverse geographical populations, there are currently no data on the prevalence of these conditions in populations of adults native to Kosovo. Therefore, little is known about how widespread these conditions are, and whether there is any correlation between root canal treatment and AP. The purpose of our research was to address this anomaly by investigating AP and endodontic treatment in an adult Kosovar population based on radiographic examination.</p> <p>Methods</p> <p>The sample used for this study consisted of randomly selected individuals referred to the University Dentistry Clinical Center of Kosovo in the years 2006-2007. Orthopantomographs of 193 patients were evaluated. The periapical status of all teeth (with the exception of third molars) was examined according to Ørstavik's Periapical Index. The quality of the root canal filling was rated as 'adequate' or 'inadequate' based on whether all canals were filled, the depth of fill relative to the radiographic apex and the quality of compaction (absence/presence of voids). Data were analyzed statistically using the Chi-square test and calculation of odds ratios.</p> <p>Results</p> <p>Out of 4131 examined teeth, the prevalence of apical periodontitis (AP) and endodontic treatment was 12.3% and 2.3%, respectively. Of 95 endodontically-treated teeth, 46.3% were associated with AP. The prevalence of AP increased with age. The prevalence in subjects aged over 60 years old (20.2%) was higher than in other age groups. A statistically significant difference was found for the frequency of endodontically-treated teeth associated with AP in the 40-49 year age group (P < 0.001). Of some concern was the discovery that only 30.5% of the endodontically-treated teeth examined met the criteria of an acceptable root canal filling. Inadequately root-filled teeth were associated with an increased AP risk.</p> <p>Conclusions</p> <p>The prevalence of AP and the frequency of endodontically-treated teeth with AP in this Kosovar population are higher than those found in other countries. Inadequate root canal fillings were associated with an increased prevalence of AP.</p

HIV infection and drugs of abuse: role of acute phase proteins

Background HIV infection and drugs of abuse such as methamphetamine (METH), cocaine, and alcohol use have been identified as risk factors for triggering inflammation. Acute phase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA) are the biomarkers of inflammation. Hence, the interactive effect of drugs of abuse with acute phase proteins in HIV-positive subjects was investigated. Methods Plasma samples were utilized from 75 subjects with METH use, cocaine use, alcohol use, and HIV-positive alone and HIV-positive METH, cocaine, and alcohol users, and age-matched control subjects. The plasma CRP and SAA levels were measured by ELISA and western blot respectively and the CD4 counts were also measured. Results Observed results indicated that the CRP and SAA levels in HIV-positive subjects who are METH, cocaine and alcohol users were significantly higher when compared with either drugs of abuse or HIV-positive alone. The CD4 counts were also dramatically reduced in HIV-positive with drugs of abuse subjects compared with only HIV-positive subjects. Conclusions These results suggest that, in HIV-positive subjects, drugs of abuse increase the levels of CRP and SAA, which may impact on the HIV infection and disease progression

Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder

Background HIV-associated neurocognitive disorder (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occurs in approximately 50% of HIV infected individuals. In the United States, the prevalence of cigarette smoking ranges from 35-70% in HIV-infected individuals compared to 20% in general population. Cognitive impairment in heavy cigarette smokers has been well reported. However, the synergistic effects of nicotine and HIV infection and the underlying mechanisms in the development of HAND are unknown. Results In this study, we explored the role of nicotine in the progression of HAND using SK-N-MC, a neuronal cell line. SK-N-MC cells were infected with HIV-1 in the presence or absence of nicotine for 7 days. We observed significant increase in HIV infectivity in SK-N-MC treated with nicotine compared to untreated HIV-infected neuronal cells. HIV and nicotine synergize to significantly dysregulate the expression of synaptic plasticity genes and spine density; with a concomitant increase of HDAC2 levels in SK-N-MC cells. In addition, inhibition of HDAC2 up-regulation with the use of vorinostat resulted in HIV latency breakdown and recovery of synaptic plasticity genes expression and spine density in nicotine/HIV alone and in co-treated SK-N-MC cells. Furthermore, increased eIF2 alpha phosphorylation, which negatively regulates eukaryotic translational process, was observed in HIV alone and in co-treatment with nicotine compared to untreated control and nicotine alone treated SK-N-MC cells. Conclusions These results suggest that nicotine and HIV synergize to negatively regulate the synaptic plasticity gene expression and spine density and this may contribute to the increased risk of HAND in HIV infected smokers. Apart from disrupting latency, vorinostat may be a useful therapeutic to inhibit the negative regulatory effects on synaptic plasticity in HIV infected nicotine abusers

Long term survival after coronary endarterectomy in patients undergoing combined coronary and valvular surgery – a fifteen year experience

<p>Abstract</p> <p>Background</p> <p>Coronary Endarterectomy (CE) in patients undergoing coronary artery bypass graft (CABG) surgery has been shown to be beneficial in those with diffuse coronary artery disease. There are no published data on its role and benefit in patients undergoing more complex operations. We present our experience with CE in patients undergoing valve surgery with concomitant CABG.</p> <p>Materials and methods</p> <p>Between 1989 and 2003, 237 patients underwent CABG with valve surgery under a single surgeon at our institution. Of these, 41 patients needed CE. Data was retrospectively obtained from hospital records and database. Further follow-up was obtained by telephone interview. All variables were analyzed by univariate analysis for significant factors relating to hospital mortality. Morbidity and long term survival was also studied. There were 29 males and 12 females with a mean age of 67.4 ± 8.1 and body mass index of 26.3 ± 3.3. Their mean euroscore was 7.6 ± 3.2 and the log euro score was 12.2 ± 16.1.</p> <p>Results</p> <p>Thirty-two patients were discharged from the intensive therapy unit within 48 hours after surgery. Average hospital stay was 12.7 ± 10.43 days. Thirty day mortality was 9.8%. Six late deaths occurred during the 14 year follow up. Ten year survival was 57.2% (95% CL 37.8%–86.6%). Three of the survivors had Class II symptoms, with one requiring nitrates. None required further percutaneous or surgical intervention. We compared the result with the available mortality figure from the SCTS database.</p> <p>Conclusion</p> <p>Compared to the SCTS database for these patients, we have observed that CE does not increase the mortality in combined procedures. By accomplishing revascularization in areas deemed ungraftable, we have shown an added survival benefit in this group of patients.</p