Evaluating serum level of thymidylate synthase in post burn keloid patients before and after intralesional injection of 5-fluorouracil

Background Keloids are fibrous lesions formed at the site of trauma due to types I and III collagen irregular production. The presence of thymidylate synthase (TS) is a must for DNA synthesis and repairs causing cell death. 5-fluorouracil (5-FU) is a fluorinated pyrimidine analogue acting as an anti-metabolic agent that inhibits thymidylate synthase and interferes with ribo-nucleic acid (RNA) synthesis. Objectives we aimed to evaluate the level of thymidylate synthase in post burn keloid patients before and after intralesional injection of 5-fluorouracil. Methods The study included 20 keloid patients and 20 healthy subjects as a control. Serum TS was estimated using commercially available enzyme-linked immunosorbent assay (ELISA) kits before and after treatment with 5-fluorouracil. Results There was a statistically significant difference in TS levels before and after 5-FU treatment (p < 0.05). Also, results have shown that 5-FU injection has good satisfactory results in treatment of keloid causing reduction in scar volume and symptoms improvement (90% of the patients improved). On the other hand, there was no statistically significant difference in TS levels and the outcomes of the treatment. Conclusion Our findings suggest that intralesional 5-FU injection in keloid has very satisfactory results. However, thymidylate synthase enzyme has a minimal role in evaluating the treatment of keloid, so further studies are required to elaborate the relation between this enzyme and keloid scars.

Photophysical Deactivation Mechanisms of the Pyrimidine Analogue 1-Cyclohexyluracil

The photophysical relaxation mechanisms of 1-cyclohexyluracil, in vacuum and water, were investigated by employing the Multi-State CASPT2 (MS-CASPT2, Multi-State Complete Active-Space Second-Order Perturbation Theory) quantum chemical method and Dunning’s cc-pVDZ basis sets. In both environments, our results suggest that the primary photophysical event is the population of the S11(ππ*) bright state. Afterwards, two likely deactivation pathways can take place, which is sustained by linear interpolation in internal coordinates defined via Z-Matrix scans connecting the most important characteristic points. The first one (Route 1) is the same relaxation mechanism observed for uracil, its canonical analogue, i.e., internal conversion to the ground state through an ethylenic-like conical intersection. The other route (Route 2) is the direct population transfer from the S11(ππ*) bright state to the T23(nπ*) triplet state via an intersystem crossing process involving the (S11(ππ*)/T23(nπ*))STCP singlet-triplet crossing point. As the spin-orbit coupling is not too large in either environment, we propose that most of the electronic population initially on the S11(ππ*) state returns to the ground following the same ultrafast deactivation mechanism observed in uracil (Route 1), while a smaller percentage goes to the triplet manifold. The presence of a minimum on the S11(ππ*) potential energy hypersurface in water can help to understand why experimentally it is noticed suppression of the triplet states population in polar protic solvent.

A COMPARATIVE STUDY OF INTRALESIONAL TRIAMCINOLONE ACETONIDE ALONE VERSUS COMBINATION OF 5-FLUOROURACIL AND TRIAMCINOLONE ACETONIDE IN THE TREATMENT OF KELOID

Background: Keloids are benign proliferative condition of dermal broblast. Intralesional corticosteroid improves keloid but associated with signicant adverse effects like dyspigmentation, tissue atrophy and telengectasia and contraindicated in certain conditions like hypertension and diabetes. 5-Fluorouracil (5-FU), a pyrimidine analogue with an inhibitory effect on TGF-β induced broblast proliferation is useful in treatment of keloids but is associated with ulceration and pain. A low dose of Triamcinolone if added to 5-FU injection overcomes these issues. Approach: This study was conducted in a tertiary care hospital. Sixty patients; thirty in each group were included. In group A, once weekly intralesional Triamcinolone and in group B, intralesional injection of Triamcinolone mixed with 5-Flurouracil in 1: 9 dilution were injected for 8 sessions. Parameters of Vancouver scale were noted at the baseline and at the end of treatment. Results: Out of 60 patients enrolled in this study. The combination group was better in improving height (62.11% vs 78%), pliability (44.14% vs 8.81%), and vascularity (55.78% vs 61.30%) and results were statistically signicant (P valve <0.05) however it was not better in improving pigmentation (43.47% vs 20%) and volume (69.79% vs 80.76%) (P valve > 0.05). Pain and pruritus improved completely (100%) in both the groups at the end of the treatment. Excellent improvement in patient and observer assessment score was seen in 96.67% vs 3.33% in combination group and TAC group respectively. The difference was statistically signicant (P valve<0.05). Combination was better irrespective of age of the patient, duration, site, and origin of keloid. All patients treated with 5 FU develop ulceration and pain. Conclusion: Both the therapies are effective but combination is superior to TAC alone. We advocate that 5-FU should be used alone, addition of TCA does not have any added advantage in therapeutic outcome rather it increases the cost of treatment.

The effects of rutin and quercetin on ECG parameters in 5-FU-induced cardiotoxicity rat model

5‐fluorouracil (5-FU), a pyrimidine analogue anticarcinogenic agent, is widely used in the solid tumors treatment. Use of the 5-FU causes cardiotoxicity. Our aim in this study investigations effects of Quercetin and Rutin on ECG parameters in the 5-FU-induced cardiotoxicity in rats. In the present study used male rats. Rats were divided randomly to eight group. The control group was given intragastric corn oil for 14 days. The 5-FU group rats were given ig corn oil for 14 days and injected intraperitoneal the single dose of 5-FU(50 mg/kg) on the eleventh day. The Q50+5-FU and Q100+5-FU groups were given ig 50 mg/kg and 100 mg/kg Q for 14 days, respectively and these groups were injected single dose of 5-FU(50 mg/kg) on the 11th days of Q application. The group Q100 was Q(100 mg/kg-ig) for 14 days. The Rutin50+5-FU and Rutin100+5-FU groups were injected ig 50 mg/kg and 100 mg/kg of the Rutin for 14 days, respectively. These groups were injected single dose of 5-FU(50 mg/kg) in the 11th days of Rutin application. The Rutin 100 group was given Rutin(100 mg/kg-ig) for 14 days. In the end of experimental application recorded to ECGs of the rats. 5-FU administration rats were observed that it was caused sinus tachycardia and ST elevation. Also, in the 5-FU group QRS segment was shorter and the duration and amplitude of the P was different from other groups. In both doses of Q and Rutin were prevented these changes and our findings were seen the consistent with the literature.

Acute cerebellar toxicity induced by high dose of cytarabine (HiDAC): A case report

Cytarabine is a pyrimidine analogue that is used for the treatment of acute myeloid leukemia at different doses. Standard doses of cytarabine are used for induction therapy, while high doses are used for post-remission (consolidation) and relapsed/refractory treatment. One of the major side effects of its high doses is acute cerebellar toxicity occurring in 10 to 25% of patients. We report a case that developed this side effect after receiving two doses of high-dose cytarabine. The patient’s symptoms improved after withholding the drug. Thereafter, the patient tolerated treatment continuation with lower doses.

Inhibitory Effect of Oat Bran Ethanol Extract on Survival and Gemcitabine Resistance of Pancreatic Cancer Cells

Pancreatic cancer (PC) is one of the most aggressive malignancies in the world. Gemcitabine (Gem), a nucleoside pyrimidine analogue, is a first-line chemotherapeutic drug for PC, but the tumor response rate of Gem is very low and resistance to Gem has emerged as a major problem in the treatment of PC. Oat bran, used as animal and human food, has been found to be beneficial to health. In this study, effects of oat bran ethanol extract (OBE) on PC cells and Gem-resistant PC cells were investigated in vitro. OBE decreased cell survival and colony forming ability of PC cells, without any cytotoxicity on the normal pancreatic cells. Flow cytometry analysis and TUNEL assay showed that the OBE reduced G1/S phase transition and induced death in PC cells through AMPK activation and downregulation of JNK. Additionally, OBE could overcome Gem resistance through reduction in RRM1/2 expression and showed synergistic effect by combinatorial treatment with Gem on Gem-resistant PC cells. Additionally, LC-MS data showed that avenacoside A was a component of OBE. Thus, this study elucidated the anti-proliferative effect of OBE and synergistic effect of OBE with Gem on PC cells and Gem-resistant cells.

The Role of Antifungals in Pediatric Critical Care Invasive Fungal Infections

Invasive fungal infections (IFIs) have seen considerable increase in pediatric intensive care units over the past several decades. IFIs are predominantly caused by Candida species, and candidemia is the third most common cause of healthcare-associated bloodstream infections (BSIs) in children. IFIs are opportunistic infections that affect pediatric patients in critical care resulting in significant morbidity and mortality especially in those with a compromised immune system. IFIs are the leading cause of death in children with comorbidities such as immunosuppression, and pediatric ICU admission has been shown to be an independent risk factor for mortality. Management of IFI and fungal sepsis is broad and encompasses several key components that include prompt initiation of therapy and rapid source identification and control. This study reviews important antifungals in the pediatric critical care setting including the pharmacologic properties, antifungal spectrum, adverse effects, and clinical uses of agents belonging to the four major classes of antifungals—the polyenes, azoles, echinocandins, and pyrimidine analogue flucytosine. The polyenes and azoles are the most often used classes of antifungals. The echinocandins are a relatively newer class of antifungal agents that offer excellent Candida activity and are currently recommended as the first-line therapy for invasive candidiasis.

Decitabine Induced Delayed Cardiomyopathy in Hematologic Malignancy

Decitabine is a pyrimidine analogue of nucleoside cytidine, used for the treatment of myelodysplastic syndromes, chronic myelogenous leukemia, and acute myelogenous leukemia. We present a case of cardiomyopathy associated with decitabine used for secondary acute myelogenous leukemia. The patient presented with new heart failure symptoms and an ejection fraction decline.