CASE REPORT: Here, we present a case of collagenofibrotic glomerulopathy in a 49-year-old Indian female, the first to be reported from Singapore. Renal biopsy showed PAS (periodic acid-Schiff), silver and Congo red negative, amorphous extracellular material that expanded mesangial and subendothelial regions. Such materials were strongly positive for anti-collagen III immunofluorescent staining. Under electron microscopy, the mesangial and some subendothelial regions were greatly expanded by abundant collagen fibres which were different from normal collagen III fibres in both appearance and periodicity.
DISCUSSION: The availability of past renal biopsies for reference offered insight into disease progression. From the initial diagnosis of focal segmental glomerulosclerosis to eventually collagenofibrotic glomerulopathy over a time span of more than 10 years, this case highlights the gradual accumulation of collagen fibres in the glomeruli before classical features are apparent. It also emphasises the importance of electron microscopy in the diagnosis of this disease.
OBJECTIVES: To develop a novel in vitro skin glycation model as a screening tool for topical formulations with antiglycation properties and to further characterize, at the molecular level, the glycation stress-driven skin ageing mechanism.
METHODS: The glycation model was developed using human reconstituted full-thickness skin; the presence of N(ε) -(carboxymethyl) lysine (CML) was used as evidence of the degree of glycation. Topical application of emulsion containing a well-known antiglycation compound (aminoguanidine) was used to verify the sensitivity and robustness of the model. Cytokine immunoassay, quantitative real-time polymerase chain reaction and histological analysis were further implemented to characterize the molecular mechanisms of skin ageing in the skin glycation model.
RESULTS: Transcriptomic and cytokine profiling analyses in the skin glycation model demonstrated multiple biological changes, including extracellular matrix catabolism, skin barrier function impairment, oxidative stress and subsequently the inflammatory response. Darkness and yellowness of skin tone observed in the in vitro skin glycation model correlated well with the degree of glycation stress.
CONCLUSIONS: The newly developed skin glycation model in this study has provided a new technological dimension in screening antiglycation properties of topical pharmaceutical or cosmeceutical formulations. This study concomitantly provides insights into skin ageing mechanisms driven by glycation stress, which could be useful in formulating skin antiageing therapy in future studies.
MATERIALS/METHODS: A total of 10 patients with synchronous bilateral breast cancer who were treated with VMAT at our institution were retrospectively analyzed. Clinical target volume (CTV) included chest wall and regional nodes (supraclavicular fossa and internal mammary chain) and prescription dose was 40.05 Gy in 15 daily fractions. HT and IMPT plans were generated for each patient. Dose-volume statistics, including planning target volume (PTV) coverage and dose to OAR: lungs, heart, thyroid, spinal cord, brachial plexus and esophagus, were compared between modalities using a paired T-test.
RESULTS: Mean age of patients was 61 years (43-84). Majority of the patients (80%) were ER+ PR+ and HER2-. 40% of patients underwent breast reconstruction following surgery. All 3 techniques provided adequate target volume distribution and OAR sparing. Compared to VMAT and HT plans, IMPT had better heart and lung sparing effects, resulting in lower mean and V25 Gy heart dose; mean, V20 Gy and V5 Gy lung dose (p<0.0001). There was no significant difference in VMAT and HT plans for mean heart and lung dose. VMAT plans showed significantly lower V25 Gy heart dose on average (p = 0.04). V5 Gy lung dose was slightly lower in HT compared to VMAT plans, approaching statistical significance (p = 0.08). PTV coverage was adequate for all 3 techniques. All techniques fulfilled cord, esophagus, thyroid and brachial plexus constraints.
CONCLUSION: IMPT plans showed significantly better OAR sparing compared to photon techniques. All 3 techniques met OAR constraints, and resulted in adequate target volume coverage. As IMPT is significantly more costly than VMAT or HT techniques, appropriate patient selection is important to deliver treatment in the most resource-effective manner for patients who would derive the most benefit, for example those with young age or existing heart or lung comorbidities.
METHODS: A retrospective cohort study of 200 patients on dabigatran and warfarin from January 2009 till September 2016 was carried out. Data were collected for 100 patients on dabigatran and 100 patients on warfarin.
RESULTS: The mean follow-up period was 340.7±322.3 days for dabigatran group and 410.5±321.2 days for warfarin group. The mean time in therapeutic range (TTR) was 52±18.7%. The mean CHA2DS2 -VASc score for dabigatran group was 4.4±1.1 while 5.0±1.5 for warfarin group. None in dabigatran group experienced ischemic stroke compared to one patient in warfarin group (p=0.316). There was one patient in dabigatran group suffered from ICH compared to none in warfarin group (p=0.316). Four patients in warfarin group experienced minor bleeding, while none from dabigatran group (p=0.043).
CONCLUSION: Overall bleeding events were significantly lower in dabigatran group compared to warfarin group. In the presence of suboptimal TTR rates and inconveniences with warfarin therapy, non-vitamin-K antagonist oral anticoagulants (NOAC) are the preferred agents for stroke prevention in elderly Asian patients for nonvalvular AF.
Materials and Methods: TQ-NLC was radiolabeled with technetium-99m before the administration to the rats. The biodistribution and pharmacokinetics parameters were then evaluated at various time points. The rats were imaged at time intervals and the percentage of the injected dose/gram (%ID/g) in blood and each organ was analyzed.
Results: Oral administration of TQ-NLC exhibited greater relative bioavailability compared to intravenous administration. It is postulated that the movement of TQ-NLC through the intestinal lymphatic system bypasses the first metabolism and therefore enhances the relative bioavailability. However, oral administration has a slower absorption rate compared to intravenous administration where the AUC0-∞ was 4.539 times lower than the latter.
Conclusion: TQ-NLC had better absorption when administered intravenously compared to oral administration. However, oral administration showed greater bioavailability compared to the intravenous route. This study provides the pharmacokinetics and biodistribution profile of TQ-NLC in vivo which is useful to assist researchers in clinical use.