Pengaruh Pemberian Ketotifen terhadap Jumlah Sel Fibroblas dan Kepadatan Sel Kolagen pada Luka Insisi Tikus Wistar

Ingga Hadian, S-501202027. PENGARUH PEMBERIAN KETOTIFEN TERHADAP JUMLAH SEL FIBROBLAS DAN KEPADATAN SEL KOLAGEN PADA LUKA INSISI TIKUS WISTAR. Pembimbing I : DR. Untung Alfianto, dr, Sp.Bs, Pembimbing II : dr. Ardana Tri Arianto. Msi. Med. Sp.An-KNA. Program studi Magister Kedokteran Keluarga, Minat Utama Ilmu Biomedik, Fakultas Kedokteran Universitas Sebelas Maret, Surakarta, 2016. Latar Belakang : Sel mast merupakan salah satu yang berperan dalam proses inflamasi pada penyembuhan luka. Sel mast dikaitkan dengan kejadian luka kronis, sehingga sel mast diduga ikut memelihara proses inflamasi secara berlebihan. Hambatan pada degranulasi sel mast diharapkan akan mempercepat penyembuhan luka yang ditandai dengan meningkatnya jumlah sel fibroblas dan kepadatan sel kolagen. Ketotifen mampu mengurangi dreganulasi sel Mast dan mengurangi pelepasan Histamin, protease sel Mast, myeloperoxidase, leukotriens, PAF dan bermacam-macam Prostaglandin. Ketotifen juga menghambat agregasi polimorfonuklear serta mengurangi respon inflamasi dan mempercepat migrasi fibroblas di fase proliferasi. Tujuan :Mengetahui perbedaan jumlah sel fibroblas dan kepadatan sel kolagen pada tikus wistar yang diberikan Ketotifen oral dosis 0.3 mg/kg dibandingkan plasebo pada penyembuhan luka insisi tikus wistar. Metode : Penelitian ini termasuk true eksperimental laboratorik dengan desain Randomized Controlled Trial yang menggunakan tikus wistar sebagai obyek penelitian. 14 tikus Wistar dibagi dalam 2 kelompok, masing masing kelompok terdiri atas 7 tikus Wistar. Kelompok 1 merupakan kelompok kontrol yang dilakukan insisi sepanjang 2cm pada kulit punggung tikus dan diberikan plasebo per oral selama 6 hari. Kelompok 2 merupakan kelompok perlakuan yang dilakukan insisi sepanjang 2cm pada kulit punggung tikus dan diberikan Ketotifen 0,3 mg/kgBB per oral setiap 12 jam selama 6 hari. Analisis data untuk membandingkan rerata antar kedua kelompok yaitu kelompok perlakuan dan kelompok kontrol menggunakan uji independent samples t-test, dengan tingkat kemaknaan p < 0,05 (dikatakan bermakna secara statistik). Hasil : Pada kelompok kontrol didapatkan rerata persentase kepadatan sel kolagen sebesar 26,05 %, sedangkan pada kelompok Ketotifen didapatkan rerata persentase kepadatan sel kolagen sebesar 36,13 %. Untuk jumlah sel fibroblas pada kelompok kontrol didapatkan rerata sebesar 423 per lapang pandang, sedangkan pada kelompok Ketotifen didapatkan rerata sebesar 555,43 per lapang pandang. Kesimpulan : Ketotifen mempercepat penyembuhan luka ditandai dengan peningkatan sel fibroblas dan sel kolagen. Kata Kunci : Sel Mast, Ketotifen, Sel fibroblas, Serabut Kolagen. ABSTRACT Ingga Hadian, S-501202027. EFFECTS OF KETOTIFEN ON FIBROBLAST CELL COUNT AND COLLAGEN DENSITY ON INCISED WISTAR RATS. DR. Untung Alfianto, dr., Sp.BS, dr. Ardana Tri Arianto, Msi, Med, Sp.An-KNA. Background: Mast cells have a pivotal role in every healing process that involves inflammation of the cells, usually in wounds of chronic nature. If the degranulation process of the mast cells are inhibited, the healing process of the wound will accelerate, indicated by a raise in fibroblast cells and collagen density. Ketotifen are shown to inhibit the degranulation process and decreasing the release of histamin, mast cells proteases, myeloperoxidases, leukotriens, PAF, and various prostaglandins. Ketotifen can also inhibit the aggregation of polymorphonuclear cells, increasing the rate of fibroblast migration in the proliferation phase. This study was aimed to identify the effects of ketotifen on fibroblast cell count and collagen density tested on a wistar rats model. Methods: This study was a true laboratoric experimental study with randomized controlled trial using wistar rats model as objects. 14 rats were divided into two groups, each group contained seven rats. The first group was the control group, where the rats were incised 2 cm above the back skin, and were given per oral placebo for 6 days. The second group were given the same treatment, only the rats were given ketotifen 0.3 mg/kg per oral, every 12 hours lasting 6 days. The data were then collected and tested with independent sample t-test, with p value less than 0,05 is statistically significant. Results: In the control group, the mean percentage of the thickest collagen density were marked at 26.05%, whereas in the treatment group collagen density were marked at 36.13%. The mean fibroblast cell count were marked at 423 and 555.43 each viewing field, on the control group and the treatment group respectively. Conclusion: Ketotifen can accelerate the healing process, marked by the significant increase in collagen density and fibroblast cell count. Keywords: mast cells, ketotifen, fibroblast cells, collagen fibers

Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis

An integrative approach to assess non-native iguana presence on Saba and Montserrat: Are we losing all native Iguana populations in the Lesser Antilles

Invasive alien species are among the main drivers of the ongoing sixth mass extinction wave, especially affecting island populations. Although the Caribbean is well-known for its high species richness and endemism, also for reptiles, equally important is the regional contribution of non-native species to island biodiversity. The Lesser Antilles encompass high genetic diversity in Iguana, though most native populations either have gone extinct or are declining following competitive hybridization with invasive non-native green iguanas. Here, we assessed non-native presence in two poorly-studied native melanistic Iguana iguana populations using available genetic tools and explored utilizing size-dependent body measurements to discriminate between native and non-native iguanas. Genetic samples from Saba and Montserrat were genotyped across 17 microsatellite loci with STRUCTURE, and multivariate analyses indicating non-native iguana presence only on Saba. This was corroborated by mtDNA and nDNA sequences, highlighting a non-native origin in Central America and the ABC islands. We identified preliminary evidence suggestive of hybridization. Morphological variation among size-dependent characteristics showed that non-native iguanas have significantly larger subtympanic plates than native iguanas. Non-native individuals also differed in scalation and coloration patterns. Overall, our findings demonstrate the need for continuous monitoring of non-native iguanas within remaining native Iguana populations in the Lesser Antilles, as those not directly threatened by non-native green iguanas are restricted to only 8.7% of the historic range. Although genetic data allow for the identification of non-native or hybrid iguana presence, this field-to-lab workflow is time-consuming. Rapid in-situ identification of non-native individuals is crucial for conservation management. In addition to patterns of scalation and coloration, we have highlighted the utility of size-dependent variables for rapid diagnosis. We urge regional partners to build morphometric databases for native Iguana populations allowing the quick detection of future incursions of non-native green iguanas and the rapid implementation of effective countermeasures during the early phase of invasion

Long Term Observations of B2 1215+30 with VERITAS

We report on VERITAS observations of the BL Lac object B2 1215+30 between 2008 and 2012. During this period, the source was detected at very high energies (VHEs; E > 100 GeV) by VERITAS with a significance of 8.9σ and showed clear variability on timescales larger than months. In 2011, the source was found to be in a relatively bright state and a power-law fit to the differential photon spectrum yields a spectral index of 3.6 ± 0.4stat ± 0.3syst with an integral flux above 200 GeV of (8.0 ± 0.9stat ± 3.2syst) × 10–12 cm–2 s–1. No short term variability could be detected during the bright state in 2011. Multi-wavelength data were obtained contemporaneously with the VERITAS observations in 2011 and cover optical (Super-LOTIS, MDM, Swift/UVOT), X-ray (Swift/XRT), and gamma-ray (Fermi-LAT) frequencies. These were used to construct the spectral energy distribution (SED) of B2 1215+30. A one-zone leptonic model is used to model the blazar emission and the results are compared to those of MAGIC from early 2011 and other VERITAS-detected blazars. The SED can be reproduced well with model parameters typical for VHE-detected BL Lac objects

Investigating Broadband Variability of the TeV Blazar 1ES 1959+650

We summarize broadband observations of the TeV-emitting blazar 1ES 1959+650, including optical R-band observations by the robotic telescopes Super-LOTIS and iTelescope, UV observations by Swift Ultraviolet and Optical Telescope, X-ray observations by the Swift X-ray Telescope, high-energy gamma-ray observations with the Fermi Large Area Telescope, and very-high-energy (VHE) gamma-ray observations by VERITAS above 315 GeV, all taken between 2012 April 17 and 2012 June 1 (MJD 56034 and 56079). The contemporaneous variability of the broadband spectral energy distribution is explored in the context of a simple synchrotron self Compton (SSC) model. In the SSC emission scenario, we find that the parameters required to represent the high state are significantly different than those in the low state. Motivated by possible evidence of gas in the vicinity of the blazar, we also investigate a reflected emission model to describe the observed variability pattern. This model assumes that the non-thermal emission from the jet is reflected by a nearby cloud of gas, allowing the reflected emission to re-enter the blob and produce an elevated gamma-ray state with no simultaneous elevated synchrotron flux. The model applied here, although not required to explain the observed variability pattern, represents one possible scenario which can describe the observations. As applied to an elevated VHE state of 66% of the Crab Nebula flux, observed on a single night during the observation period, the reflected emission scenario does not support a purely leptonic non-thermal emission mechanism. The reflected emission model does, however, predict a reflected photon field with sufficient energy to enable elevated gamma-ray emission via pion production with protons of energies between 10 and 100 TeV