MATERIALS AND METHODS: Thirty five female Sprague Dawley rats at age 21-day old were divided into 4 groups; Group 1 (control, n=10), Group 2 (PF4, n=5), Group 3 (rapamycin, n=10) and Group 4 (rapamycin+PF4, n=10). MNU was administered intraperitionally, dosed at 70 mg/kg body weight. The rats were treated when the tumors reached the size of 14.5 ± 0.5 mm and subsequently sacrificed after 5 days. Rapamycin and PF4 were administered as focal intralesional injections at the dose of 20 μg/lesion. The tumor tissue was then subjected to histopathological examinations for morphological appraisal and immunohistochemical assessment of the pro-apoptotic marker, Bax and anti-apoptotic markers, Bcl-2 and survivin.
RESULTS: The histopathological pattern of the untreated control cohort showed that the severity of the malignancy augments with mammary tumor growth. Tumors developing in untreated groups were more aggressive whilst those in treated groups demonstrated a transformation to a less aggressive subtype. Combined treatment resulted in a significant reduction of tumor size without phenotypic changes. Bax, the pro-apoptotic marker, was significantly expressed at higher levels in the rapamycin-treated and rapamycin+PF4-treated groups compared to controls (p<0.05). Consequently, survivin was also significantly downregulated in the rapamycin-treated and rapamycin+PF4-treated group and this was significantly different when compared to controls (p).
CONCLUSIONS: In our rat model, it could be clearly shown that rapamycin specifically affects Bax and survivin signaling pathways in activation of apoptosis. We conclude that rapamycin plays a critical role in the induction of apoptosis in MNU-induced mammary carcinoma.
DESIGN AND METHODS: This is a retrospective study. We reviewed medical records of six patients diagnosed with CACT and CPT2 deficiencies. They were identified from a selective high-risk screening of 50,579 patients from January 2010 until Jun 2020.
RESULTS: All six patients had either elevation of the long chain acylcarnitines and/or an elevated (C16 + C18:1)/C2 acylcarnitine ratio. SLC25A20 gene sequencing of patient 1 and 6 showed a homozygous splice site mutation at c.199-10 T > G in intron 2. Two novel mutations at c.109C > T p. (Arg37*) in exon 2 and at c.706C > T p. (Arg236*) in exon 7 of SLC25A20 gene were found in patient 2. Patient 3 and 4 (siblings) exhibited a compound heterozygous mutation at c.638A > G p. (Asp213Gly) and novel mutation c.1073 T > G p. (Leu358Arg) in exon 4 of CPT2 gene. A significant combined prevalence at 0.01% of CACT and CPT2 deficiencies was found in the symptomatic Malaysian patients.
CONCLUSIONS: The use of the (C16 + C18:1)/C2 acylcarnitine ratio in dried blood spot in our experience improves the diagnostic specificity for CACT/CPT2 deficiencies over long chain acylcarnitine (C16 and C18:1) alone. DNA sequencing for both genes aids in confirming the diagnosis.
AIM: Aim of the present study is to fabricate nanofilm embedded with simvastatin loaded chitosan nanoparticles (CS-SIM-NPs) has been reported herein to explore the efficacy of SIM in diabetic wound healing.
METHODS: The NPs, prepared via ionic gelation, were 173nm ± 2.645 in size with a zeta potential -0.299 ± 0.009 and PDI 0.051 ± 0.088 with excellent encapsulation efficiency (99.97%). The optimized formulation (CS: TPP, 1:1) that exhibited the highest drug release (91.64%) was incorporated into polymeric nanofilm (HPMC, Sodium alginate, PVA), followed by in vitro characterization. The optimized nanofilm was applied to the wound created on the back of diabetes-induced (with alloxan injection 120 mg/kg) albino rats.
RESULTS: The results showed significant (p < 0.05) improvement in the wound healing process compared to the diabetes-induced non-treated group. The results highlighted the importance of nanofilms loaded with SIM-NPs in diabetic wound healing through angiogenesis promotion at the wound site.
CONCLUSION: Thus, CS-SIM-NPs loaded polymeric nanofilms could be an emerging diabetic wound healing agent in the industry of nanomedicines.
DISCUSSION: It is a set of various methodologies which are used to capture internal or external images of the human body and organs for clinical and diagnosis needs to examine human form for various kind of ailments. Computationally intelligent machine learning techniques and their application in medical imaging can play a significant role in expediting the diagnosis process and making it more precise.
CONCLUSION: This review presents an up-to-date coverage about research topics which include recent literature in the areas of MRI imaging, comparison with other modalities, noise in MRI and machine learning techniques to remove the noise.
SIGNIFICANCE: A strong need exists for the development of transdermal patch having improved bioavailability at the site of action with fewer side effects at off-target organs.
METHODS: The patches were physically characterized by texture analysis (color, flexibility, smoothness, transparency, and homogeneity), in vitro dissolution test and FTIR analysis. Furthermore, functional properties essential for TDDS, in vitro percentage of moisture content, percentage of water uptake, in vitro permeation by following different kinetic models, in vivo drug content estimation and skin irritation were determined using rabbit skin.
RESULTS: The optimized patches were soft, of uniform texture and thickness as well as pliable in nature. Novel transdermal patch showed ideal characteristics in terms of moisture content and water uptake. FTIR analysis confirmed no interaction between TZH and cellulose acetate phthalate (CAP). The patch showed sustained release of the drug which increased the availability of short acting TZH at the site of action. The patch also showed its biocompatibility to the in vivo model of rabbit skin.
CONCLUSIONS: The results demonstrated that topically applied transdermal patch will be a potential medicated sustain release patch for muscle pain which will improve patient compliance.
METHODS: We retrospectively evaluated the surgical outcome of the BGI with Supramid© 3/0 ripcord stent in patients with NVG. No tube ligation or venting slits were performed. Supramid was removed after 3mo if the target intraocular pressure (IOP) was not achieved. Surgical success was defined as IOP≤21 mm Hg with (qualified success) or without IOP-lowering medications (complete success).
RESULTS: Twenty-six eyes from 24 patients were included in the study. The median duration of follow-up was 4 [interquartile range (IQR)=1-5]y, ranging from 0.5 to 5y. IOP decreased by a mean of 24.2 mm Hg (59.7%); from a mean of 40.5±12.6 mm Hg at baseline to 16.3±11.9 mm Hg, P≤0.001. The number of glaucoma medications reduced from a median of 5 (IQR=5-6) to 1 (IQR=0-2, P≤0.001) at the final follow-up. Overall success rates were 88.0% at 1y, 34.8% at 3y, 66.7% at 4y, and 50% at 5y. Hypertensive phase (HP) in the first 3mo occurred in 15/26 eyes (57.7%) with a mean IOP of 31.1 mm Hg.
CONCLUSION: BGI with Supramid© ripcord stent gives close to 90% of the overall survival rate at the final follow-up without significant early hypotony. However, early HP is still a challenge.