Development of Single Vial Kits for Preparation of 68Ga-Labelled Peptides for PET Imaging of Neuroendocrine Tumours

Purpose

The present work was aimed at the formulation and evaluation of freeze-dried kits of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-peptides for the preparation of ⁶⁸Ga-labelled peptides for PET imaging of neuroendocrine tumours. The ⁶⁸GaCl₃ was obtained from the locally produced nanoceria-PAN, composite-sorbent-based ⁶⁸Ge/⁶⁸Ga generator.

Procedures

Single vial kits of somatostatin analogues DOTA-[Tyr³]-octreotide (DOTA-TOC), DOTA-[NaI³]-octreotide (DOTA-NOC) and DOTA-Tyr³-Thre⁸-octreotide (DOTA-TATE) were formulated. Optimization of radiolabelling with ⁶⁸Ga from the in-house generator, characterization, long term evaluation of stability of kits and bioevaluation studies in animals was carried out.

Results

DOTA-TOC, DOTA-NOC and DOTA-TATE kits could be successfully formulated. Consistently high radiochemical yields (>95 %) were obtained on radiolabelling with ⁶⁸Ga. The radiolabelled peptides exhibited excellent in vitro stability. Biodistribution studies in normal non-tumour bearing Swiss mice revealed fast clearance of activity via renal route as reported for the respective peptides.

Conclusion

Availability of ready to use DOTA-peptide kits in conjunction with ⁶⁸Ge/⁶⁸Ga generators would pave way for the establishment of ⁶⁸Ga radiopharmacy, a long-felt need of the nuclear medicine community.     

Newborn survival in Nepal: a decade of change and future implications

Nepal is on target to meet the Millennium Development Goals for maternal and child health despite high levels of poverty, poor infrastructure, difficult terrain and recent conflict. Each year, nearly 35,000 Nepali children die before their fifth birthday, with almost two-thirds of these deaths occurring in the first month of life, the neonatal period. As part of a multi-country analysis, we examined changes for newborn survival between 2000 and 2010 in terms of mortality, coverage and health system indicators as well as national and donor funding. Over the decade, Nepal's neonatal mortality rate reduced by 3.6% per year, which is faster than the regional average (2.0%) but slower than national annual progress for mortality of children aged 1-59 months (7.7%) and maternal mortality (7.5%). A dramatic reduction in the total fertility rate, improvements in female education and increasing change in skilled birth attendance, as well as increased coverage of community-based child health interventions, are likely to have contributed to these mortality declines. Political commitment and support for newborn survival has been generated through strategic use of global and national data and effective partnerships using primarily a selective newborn-focused approach for advocacy and planning. Nepal was the first low-income country to have a national newborn strategy, influencing similar strategies in other countries. The Community-Based Newborn Care Package is delivered through the nationally available Female Community Health Volunteers and was piloted in 10 of 75 districts, with plans to increase to 35 districts in mid-2013. Innovation and scale up, especially of community-based packages, and public health interventions and commodities appear to move relatively rapidly in Nepal compared with some other countries. Much remains to be done to achieve high rates of effective coverage of community care, and especially to improve the quality of facility-based care given the rapid shift to births in facilities.     

Pre-surgery immune profiles of adult glioma patients

Journal of Neuro-Oncology - Although immunosuppression is a known characteristic of glioma, no previous large studies have reported peripheral blood immune cell profiles prior to patient surgery...     

Metachronous Occurrence of Multifocal Phaeochromocytoma

The authors report an 8-yr-old boy who presented with hypertension, psychosis, and visual disturbances due to a left adrenal phaeochromocytoma which was excised. After 4 years, the child developed multifocal phaeochromocytomas in the left suprarenal area, right adrenal gland, and left para-aortic region. The tumors were excised along with re-implantation of normal adrenal tissue from the right adrenal into the omentum. The course of the disease and the family history were suggestive of von Hippel-Lindau (VHL) disease.     

Gastric mucormycosis: Diagnosis by imprint cytology

The fungi in the order of Mucorales commonly target diabetics and other immunocompromised hosts, producing fatal respiratory and or CNS infections. Gastrointestinal mucormycosis is uncommon and seldom diagnosed in living patients due to nonspecific clinical manifestations. We report a case of gastric mucormycosis in an immmunocompetent male patient, diagnosed by imprint cytology—a rare site and a rare setting. To the best of our knowledge, this is only the second report of gastric mucormycosis being diagnosed on cytology. As the disease is rapidly progressive and often fatal, early diagnosis is critical to the patient survival. Imprint cytology or brush cytology is extremely useful for the rapid diagnosis of gastric mucormycosis as these organisms are morphologically distinct. Familiarity with the cytomorphology of these organisms assists in the correct diagnosis of this disease. Diagn. Cytopathol. 2016;44:820–822. © 2016 Wiley Periodicals, Inc.     

Letharia vulpina,a vulpinic acid containing lichen,targets cell membrane and cell division processes in methicillin-resistant Staphylococcus aureus

Context: Antibiotic resistance in humans is a major concern. Drugs that target traditional sites and pathways are becoming obsolete; thus, compounds affecting novel targets are needed. Screening lichen metabolites for antimicrobials has yielded promising antimicrobial compounds, yet their mode of action is poorly understood. Letharia vulpina (L.) Hue (Parmeliaceae) has traditionally been used to poison predators, and treat stomach disorders; more recently L. vulpina extracts have demonstrated promising antimicrobial properties.

Objective: This study investigates the mode of action of L. vulpina acetone extract against a methicillin-resistant Staphylococcus aureus (MRSA).

Material and methods: We treated MRSA with L. vulpina extracts at 1×, 5×, and 10?×?MIC values (MIC?=?31.25?µg/ml) for 24?h and optical density (OD₆₆₀) was measured over time to determine bacteriolytic activity; counted colony forming units (CFUs) to determine time kill dynamics; the propidium iodide (PI) assay and transmission electron microscopy were used to assess membrane-damage potential, and thin-layer chromatography was used to identify secondary compounds.

Results: Bacteriolytic assays showed that L. vulpina extracts, containing only vulpinic acid, do not cause cell lysis, even at 10?×?MIC values but there was 92% reduction in bacterial CFUs when treated with increased concentrations of lichen extracts over 24?h at 4?h intervals. Our data indicate that the L. vulpina extract compromises membrane integrity of the MRSA isolate and disrupts cell division processes.

Discussion and conclusion: Based on this study, detailed examination of acetone extracts of L. vulpina as well as pure extracts of vulpinic acid as potential antibacterial compounds merit further study.     

Adaptations in a Community-Based Family Intervention: Replication of Two Coding Schemes

Although program adaptation is a reality in community-based implementations of evidence-based programs, much of the discussion about adaptation remains theoretical. The primary aim of this study was to replicate two coding systems to examine adaptations in large-scale, community-based disseminations of the Strengthening Families Program for Parents and Youth 10–14, a family-based substance use prevention program. Our second aim was to explore intersections between various dimensions of facilitator-reported adaptations from these two coding systems. Our results indicate that only a few types of adaptations and a few reasons accounted for a majority (over 70 %) of all reported adaptations. We also found that most adaptations were logistical, reactive, and not aligned with program’s goals. In many ways, our findings replicate those of the original studies, suggesting the two coding systems are robust even when applied to self-reported data collected from community-based implementations. Our findings on the associations between adaptation dimensions can inform future studies assessing the relationship between adaptations and program outcomes. Studies of local adaptations, like the present one, should help researchers, program developers, and policymakers better understand the issues faced by implementers and guide efforts related to program development, transferability, and sustainability.     

Comparison of two different methods of preoperative marking for toric intraocular lens implantation: bubble marker versus pendulum marker

AIM: To compare the accuracy of two different methods of preoperative marking for toric intraocular lens (IOL) implantation, bubble marker versus pendulum marker, as a means of establishing the reference point for the final alignment of the toric IOL to achieve an outcome as close as possible to emmetropia. METHODS: Toric IOLs were implanted in 180 eyes of 110 patients. One group (55 patients) had preoperative marking of both eyes done with bubble marker (ASICO AE-2791TBL) and the other group (55 patients) with pendulum marker (Rumex(3-193). Reference marks were placed at 3-, 6-, and 9-o''clock positions on the limbus. Slit-lamp photographs were analyzed using Adobe Photoshop (version 7.0). Amount of alignment error (in degrees) induced in each group was measured. RESULTS: Mean absolute rotation error in the preoperative marking in the horizontal axis was 2.42±1.71 in the bubble marker group and 2.83±2.31in the pendulum marker group (P=0.501). Sixty percent of the pendulum group and 70% of the bubble group had rotation error ≤3 (P=0.589), and 90% eyes of the pendulum group and 96.7% of the bubble group had rotation error ≤5 (P=0.612). CONCLUSION: Both preoperative marking techniques result in approximately 3 of alignment error. Both marking techniques are simple, predictable, reproducible and easy to perform.