Helicobacter pylori: past,current and future treatment strategies with gastroretentive drug delivery systems

Helicobacter pylori have been subject to intense investigation since its discovery from gastric biopsy in 1982. This gastropathogen has been regarded as serious public health problem due to its association with dyspepsia, gastritis, gastroduodenal ulcers, mucus-associated lymphoid tissue lymphoma and gastric carcinoma. In vivo eradication of established H. pylori infections is difficult due to several factors such as gastric niche, coccoid form due to sub-minimum inhibitory concentration of antimicrobials, bacterial load, primary antibiotic resistance, patient compliance and stability of therapeutics in gastric acid secretion. Considering these factors, a logical way to improve the outcome of the treatment is to develop dosage forms which are able to deliver the anti-helicobacter agents in the gastric niche for both local and systemic actions, simultaneously taking care of stability of therapeutics in acidic environment. Such dosage forms, which are popularly known as gastro retentive drug delivery systems (GRDDS), have the immense potential to effectively counter the problem of high bacterial load; prevent induction of coccoid bacteria thereby improving treatment outcome and compliance. This review describes efficacy of various therapeutic agents, treatment strategies and status of different GRDDS until now.     

Survival estimates and risk factors for failure of palatal and buccal mini-implants

ObjectivesThe primary objective was to compare the success and survival rates of palatal and buccal mini-implants for different locations and treatment requirements. The secondary objective was to evaluate risk factors influencing the survival of mini-implants.Materials and MethodsIn this retrospective cohort, records of 127 orthodontic patients with 257 mini-implants were included after imposing inclusion/exclusion criteria. Along with the implant failure data, factors such as age, sex, transverse location, anteroposterior location, and purpose of mini-implants were recorded. Kaplan–Meier survival analysis was used to draw the curves and a Nathan Mantel-David Cox test to compare variables.ResultsThe failure rate of palatal mini-implants was 8.5%, whereas the failure rate for buccal shelf mini-implants was 68.7% (P < .0001). A significant difference was that the survival rates of palatal mini-implants were dependent on the purpose of the mini-implants and, for the buccal mini-implants, they were dependent on the skeletal malocclusion and location type of mini-implants (P < .05).ConclusionsThe overall survival rate of palatal mini-implants was high, at 91.5%. Of the buccal mini-implants, inter-radicular mini-implants had the highest survival rate for 12 (75.5%) and 24 (71.9%) months, while buccal shelf mini-implants had the lowest success and survival rates for 12 (31.3%) and 24 (20.8%) months. Class III malocclusion had the lowest survival rate for the buccal mini-implants (65.3% and 54.2%) for 12 and 24 months.     

In vitro antiviral activity of neem (Azardirachta indica L.) bark extract against herpes simplex virus type‐1 infection

Herpes simplex virus type 1 (HSV‐1) causes significant health problems from periodical skin and corneal lesions to encephalitis. We report here that an aqueous extract preparation from the barks of neem plant Azardirachta indica acts as a potent entry inhibitor against HSV‐1 infection into natural target cells. The neem bark extract (NBE) significantly blocked HSV‐1 entry into cells at concentrations ranging from 50 to 100 μg/ml. The blocking activity of NBE was observed when the extract was pre‐incubated with the virus but not with the target cells, suggesting a direct antiHSV‐1 property of the neem bark. Further, virions treated with NBE failed to bind the cells which implicate a role of NBE as an attachment step blocker. Cells treated with NBE also inhibited HSV‐1 glycoprotein‐mediated cell–cell fusion and polykaryocytes formation suggesting an additional role of NBE at the viral fusion step. These findings open a potential new avenue for the development of NBE as a novel antiherpetic microbicide. Copyright © 2009 John Wiley & Sons, Ltd.     

Effect of complicated ocular surgery in stress-related parameters: A novel outlook into surgeon’s health

Purpose:To assess the stress-related physiological parameters of ophthalmic surgeons during complicated cataract surgery and compare them with uncomplicated routine cataract surgery.Methods:In this cross-sectional observational study, 110 patients of various types of cataract were divided into two groups: Group 1 included 55 patients with simple cataract (Grade ≤3) with no ocular or systemic comorbidities, whereas Group 2 included 55 patients with complicated cataracts (Grade >3) and ocular/systemic comorbidities. All patients underwent phacoemulsification with intraocular lens implantation in the right eye only. The outcome measures were systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), and saturation of peripheral oxygen (SpO₂).Results:The average SBP, DBP, MAP, and HR were significantly higher in the surgeon operating Group 2 (complicated cataract) compared with Group 1 (uncomplicated cataract; P < 0.05). The average SBP of the surgeon while operating Group 1 patients preoperatively and postoperatively was 125.42 ± 2.49 mmHg and 122.45 ± 2.10 mmHg, respectively, whereas in Group 2, the average SBP of the surgeon taken preoperatively and postoperatively was 145.98 ± 3.80 mmHg and 137.44 ± 3.45 mmHg, respectively (P < 0.05). The surgeon’s SpO₂ showed no significant difference between the two groups.Conclusion:There is a significant level of increase in stress-related parameters of operating surgeons while doing complicated cataract surgery.     

The feasibility of task-sharing the identification,emergency treatment,and referral for women with pre-eclampsia by community health workers in India

Background

Hypertensive disorders are the second highest direct obstetric cause of maternal death after haemorrhage, accounting for 14% of maternal deaths globally. Pregnancy hypertension contributes to maternal deaths, particularly in low- and middle-income countries, due to a scarcity of doctors providing evidence-based emergency obstetric care. Task-sharing some obstetric responsibilities may help to reduce the mortality rates. This study was conducted to assess acceptability by the community and other healthcare providers, for task-sharing by community health workers (CHW) in the identification and initial care in hypertensive disorders in pregnancy.

Methods

This study was conducted in two districts of Karnataka state in south India. A total of 14 focus group discussions were convened with various community representatives: women of reproductive age (N = 6), male decision-makers (N = 2), female decision-makers (N = 3), and community leaders (N = 3). One-to-one interviews were held with medical officers (N = 2), private healthcare OBGYN specialists (N = 2), senior health administrators (N = 2), Taluka (county) health officers (N = 2), and obstetricians (N = 4). All data collection was facilitated by local researchers familiar with the setting and language. Data were subsequently transcribed, translated and analysed thematically using NVivo 10 software.

Results

There was strong community support for home visits by CHW to measure the blood pressure of pregnant women; however, respondents were concerned about their knowledge, training and effectiveness. The treatment with oral antihypertensive agents and magnesium sulphate in emergencies was accepted by community representatives but medical practitioners and health administrators had reservations, and insisted on emergency transport to a higher facility. The most important barriers for task-sharing were concerns regarding insufficient training, limited availability of medications, the questionable validity of blood pressure devices, and the ability of CHW to correctly diagnose and intervene in cases of hypertensive disorders of pregnancy.

Conclusion

Task-sharing to community-based health workers has potential to facilitate early diagnosis of the hypertensive disorders of pregnancy and assist in the provision of emergency care. We identified some facilitators and barriers for successful task-sharing of emergency obstetric care aimed at reducing mortality and morbidity due to hypertensive disorders of pregnancy.

     

Virostatic potential of micro-nano filopodia-like ZnO structures against herpes simplex virus-1

Herpes simplex virus type-1 (HSV-1) entry into target cell is initiated by the ionic interactions between positively charged viral envelop glycoproteins and a negatively charged cell surface heparan sulfate (HS). This first step involves the induction of HS-rich filopodia-like structures on the cell surface that facilitate viral transport during cell entry. Targeting this initial first step in HSV-1 pathogenesis, we generated different zinc oxide (ZnO) micro-nano structures (MNSs) that were capped with multiple nanoscopic spikes mimicking cell induced filopodia. These MNSs were predicted to target the virus to compete for its binding to cellular HS through their partially negatively charged oxygen vacancies on their nanoscopic spikes, to affect viral entry and subsequent spread. Our results demonstrate that the partially negatively charged ZnO-MNSs efficiently trap the virions via a novel virostatic mechanism rendering them unable to enter into human corneal fibroblasts - a natural target cell for HSV-1 infection. The anti-HSV-1 activity of ZnO MNSs was drastically enhanced after creating additional oxygen vacancies under UV-light illumination. Our results provide a novel insight into the significance of ZnO MNSs as the potent HSV-1 inhibitor and rationalize their development as a novel topical agent for the prevention of HSV-1 infection.     

Limb lead interchange in thorough QT/QTc studies

The investigators analyzed 85,133 electrocardiograms (ECGs) recorded in 484 subjects from 5 thorough QT/QTc studies (3 using Holter devices, 2 using 12-lead ECGs) for inadvertent limb lead interchanges using a dedicated quality control process in a central ECG laboratory. Limb lead interchanges were present in 2919 (3.4%) ECGs in 17.9% of subjects and were more frequent with Holter devices (7.5% vs 0.8%, P < .0001), where leads remain connected for prolonged periods, affecting data from several time points. Left arm-left leg interchange was seen in 54% of 12-lead ECGs and right arm-left arm interchange in 38%. The ECG device itself could identify 21.7% of interchanges, whereas experienced readers blinded to subject and visit identified 79% of interchanges; 21% of interchanges were identified only during the quality control process. If correctly identified, QT measurement could be performed in a precordial lead. If undiagnosed, incorrect QT interval measurements and morphological diagnosis may confound results.     

Effect of nonselective and selective COX-2 inhibitors on memory dysfunction, glutathione system, and tumor necrosis factor alpha level against cerebral ischemia reperfusion injury

Involvement of the glutathione system is well established in stroke-induced memory dysfunction. The aim of the present study was to investigate the effects of celecoxib (a selective cyclooxygenase-2 [COX-2] inhibitor), nimesulide (a preferential COX-2 inhibitor), and ibuprofen (a nonselective COX-2 inhibitor) against bilateral common carotid artery occlusion (BCCAO)-induced memory dysfunction. BCCAO for 30 minutews, followed by 24-hour reperfusion, significantly delayed transfer latency in the plus-maze performance task and shortened fall-off time in the hanging-wire experimental test. Besides significant alterations in glutathione defense (i.e., glutathione S-transferase and redox ratio), increased acetylcholinesterase activity and proinflammatory marker (tumor necrosis factor alpha TNF-α) in the hippocampus was seen. Seven days of treatment with celecoxib (3 and 10?mg/kg, p.o.), nimesulide (10?mg/kg, p.o.), and ibuprofen (30?mg/kg, p.o.) significantly improved behavioral alterations and glutathione defense and attenuated acetylcholinesterase activity and TNF-α levels, as compared to the control (i.e., ischemic reperfusion) group. The present study highlights the neuroprotective effect of celecoxib and nimesulide against ischemia reperfusion injury-induced memory dysfunction, neuroinflammation, and oxidative damage.     

Telemedicine security: a systematic review

Telemedicine is a technology-based alternative to traditional health care delivery. However, poor security measures in telemedicine services can have an adverse impact on the quality of care provided, regardless of the chronic condition being studied. We undertook a systematic review of 58 journal articles pertaining to telemedicine security. These articles were selected based on a keyword search on 14 relevant journals. The articles were coded to evaluate the methodology and to identify the key areas of research in security that are being reviewed. Seventy-six percent of the articles defined the security problem they were addressing, and only 47% formulated a research question pertaining to security. Sixty-one percent proposed a solution, and 20% of these tested the security solutions that they proposed. Prior research indicates inadequate reporting of methodology in telemedicine research. We found that to be true for security research as well. We also identified other issues such as using outdated security standards.