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"Latar BelakangSleep deprivation (SD) merupakan gangguan tidur dalam hal berkurangnya kuantitas maupun kualitas tidur. SD terjadi pada 20-30% anak-anak, di mana terjadi dampak buruk pada fungsi kognitif, termasuk memori. Saat ini, belum ada pengobatan standar untuk gangguan tidur ini. Dari berbagai studi pada hewan coba dan manusia, N-acetylcysteine (NAC) diketahui memiliki efek neuroprotektif. Akan tetapi, belum ada penelitian terkait efek NAC pada tikus muda yang mengalami SD.Metode48 ekor Sprague-Dawley jantan usia 21 hari dibagi empat kelompok. Kelompok satu merupakan tikus normal tanpa SD. Kelompok dua, tiga, dan empat diinduksi SD dengan metode multiple platform yang dilakukan selama 3 hari. NAC diberikan secara intraperitoneal dengan dosis masing-masing 100 mg/kgBB atau 500 mg/kgBB pada kelompok tiga dan empat selama 5 hari (dimulai sejak 2 hari sebelum perlakuan SD). Fungsi kognitif dinilai dengan y-maze dan NOR. Dilakukan pemeriksaan kadar kortisol dan IL-1β pada darah. Pada hipokampus, dilakukan pemeriksaan aktivitas enzim AChE, kadar ACh, BDNF, CREB, p-CREB, dan penilaian densitas neuron. Ekspresi mRNA dari IL-1β, TNF-α, dan NLRP3 dari jaringan PFC juga dinilai.HasilPada kelompok SD tanpa NAC, terjadi penurunan alternasi spontan dan rasio diskriminasi secara signifikan (p<0.05) dibandingkan kelompok normal. Hal tersebut diikuti pula dengan penurunan kadar BDNF yang bermakna, serta tendensi peningkatan aktivitas AChE dan penurunan ACh dibandingkan kelompok normal. Kadar kortisol dan ekspresi mRNA TNF-α pada kelompok tersebut juga meningkat secara signifikan dibanding kelompok normal. Pemberian NAC terutama pada dosis 500 mg/kgBB memberikan hasil yang bermakna pada peningkatan alternasi spontan, rasio diskriminasi, dan kadar BDNF, serta penurunan kadar kortisol, aktivitas enzim AChE, dan ekspresi mRNA TNF-α.KesimpulanNAC dapat mencegah defisit memori yang diinduksi SD dengan menurunkan ekspresi mRNA TNF-α, aktivitas AChE, kadar kortisol, dan meningkatkan kadar BDNF.

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Introduction

Sleep deprivation (SD) is a sleep disorder in terms of reduced quantity or quality of sleep. SD occurs in 20-30% of children, with negative impacts on cognitive function, including memory. Currently, there is no standard treatment for this condition. From various studies on experimental animals and humans, N-acetylcysteine ​​(NAC) is known to have neuroprotective effects. However, no research related to the effects of NAC in juvenile rats with SD.

Method

48 male Sprague-Dawley rats aged 21 days were divided into four groups. Group one was normal rats without SD. Groups two, three, and four were induced with SD using the multiple-platform method for 3 days. NAC was administered intraperitoneally at a dose of 100 mg/kgBW or 500 mg/kgBW in groups three and four for 5 days (starting 2 days before SD treatment). Cognitive function was assessed using y-maze and NOR. Blood cortisol and IL-1β levels were examined. In the hippocampus, AChE enzyme activity, ACh, BDNF, CREB, p-CREB levels, and neuron density were measured. mRNA expression of IL-1β, TNF-α, and NLRP3 from PFC tissue was also assessed.

Results

In the SD group without NAC, there was a significant decrease in spontaneous alternation and discrimination ratio (p<0.05) compared to the normal group. This was also followed by a significant decrease in BDNF levels and a tendency to increase AChE activity and decrease ACh compared to the normal group. Cortisol levels and TNF-α mRNA expression in this group also increased significantly compared to the normal group. Administration of NAC, especially at a dose of 500 mg/kg BW, gave significant results in increasing spontaneous alternation, discrimination ratio, and BDNF levels and decreasing cortisol levels, AChE enzyme activity, and TNF-α mRNA expression.

Conclusion

NAC prevents SD-induced memory deficits by decreasing TNF-α mRNA expression, AChE activity, and cortisol levels, and increasing BDNF levels"

"Kondisi hipertiroidisme berkorelasi dengan kejadian atherosclerosis cardiovascular disease (ASCVD). Hal ini dapat terjadi melalui jalur resistensi insulin, metabolisme lipid, dan inflamasi yang dapat menyebabkan disfungsi endotel. Sebaliknya, pemberian obat antitiroid seperti propiltiourasil (PTU) atau metimazol memiliki potensi untuk memperbaiki disfungsi endotel yang terjadi. PTU memiliki keunggulan dibandingkan metimazol dalam hal menghambat migrasi dan proliferasi otot polos vaskular. Studi ini bertujuan untuk mempelajari peran hormon tiroid dan pengobatannya pada pasien Graves terhadap penanda dini aterosklerosis.Studi ini merupakan uji klinis tersamar tunggal yang dilakukan di RSUPN Dr. Cipto Mangunkusumo (RSCM) pada pasien Graves baru yang diberikan PTU atau metimazol selama 3 bulan. Kedua kelompok diperiksakan HOMA-IR,LDL-R, NF-kB, sICAM-1, sVCAM-1 dan sE-selektin serta pulse wave velocity (PWV) dan carotid intima media thickness (cIMT) saat sebelum terapi, setelah terapi 1 bulan dan 3 bulan. Dilakukan uji Pearson atau Spearman untuk menilai korelasi antar variabel. Perubahan variabel dalam 3 bulan dinilai dengan uji repeated ANOVA. Perbedaan pada kelompok PTU dan metimazol dinilai dengan uji general linear model.Selama bulan Juli 2019 hingga Agustus 2020, didapatkan 36 pasien Graves baru. Pada uji korelasi didapatkan konsentrasi T4 bebas berkorelasi dengan sICAM-1(r = 0,41; p = 0,013) dan sVCAM-1 (r = 0,458; p = 0,005), begitu juga T3 total berkorelasi dengan sICAM-1 (r = 0,513; p = 0,001) dan sVCAM-1 (r = 0,567;p < 0,001). Pada tindak lanjut 3 bulan, didapatkan 24 subjek (13 kelompok PTU dan 11 kelompok metimazol) yang menyelesaikan pemeriksaan dan mencapai eutiroid. Pada kelompok PTU, didapatkan penurunan LDL-R (p = 0,017),sICAM-1 (p = 0,001), sVCAM-1 (p < 0,001) dan sE-selektin (p = 0,045). Pada kelompok metimazol terjadi penurunan hanya pada LDL-R (p = 0,011) dan sVCAM-1 (p = 0,001). Namun pada perbandingan kedua kelompok tidak berbeda bermakna. Parameter PWV dan cIMT juga tidak berbeda bermakna.Simpulan: Pada penelitian ini kondisi hipertiroid pasien Graves berkorelasi dengan peningkatan sICAM-1 dan sVCAM-1 sebagai penyebab aterosklerosis. Pemberian obat antitiroid dapat menurunkan LDL-R, sICAM-1, sVCAM-1 dan sE-selektin. PTU memiliki mekanisme yang berbeda dari metimazol dalam patofisiologi aterosklerosis. Akan tetapi, belum didapatkan bukti pada perubahan PWV dan cIMT

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Hyperthyroidism is correlated with atherosclerosis cardiovascular disease (ASCVD). The basic mechanisms are through insulin resistance, lipid metabolism, and inflammation resulted in endothelial dysfunction. On the other hand, antithyroid drugs such as propiltiourasil (PTU) or methimazole have the potential to improve the endothelial dysfunction. PTU is believed to have a better profile than methimazole in reducing smooth muscle cells migration and proliferation. This study aims to investigate the effect of thyroid hormone and its treatment in Graves’ disease to early marker of atherosclerosis.

This study is a single-blinded clinical trial conducted in dr. Cipto Mangunkusumo General Hospital (RSCM) to newly diagnosed Graves’ patient treated with PTU or methimazole for 3 months. Both groups were examined for LDL-R, NF-ĸB, sICAM-1, sVCAM-1, sE-selectin, pulse wave velocity (PWV) and carotid intima media thickness (cIMT) at baseline, after 1 month and 3 months treatment. Pearson or Spearman test was done to analyze correlation between tested variables. Repeated ANOVA test was done to analyze the changes in those variables during 3 months treatment. Difference between PTU and methimazole groups was analyzed with general linear model test.

From July 2019 to August 2020, 36 newly diagnosed Graves’ patients were included in the study. Correlation test showed free T4 concentration correlated to sICAM-1 (r = 0.41; p = 0.013) and sVCAM-1 (r = 0.458; p = 0.005), and total T3 also correlated to sICAM-1 (r = 0.513; p = 0.001) and sVCAM-1 (r = 0.567; p < 0.001). After 3 months follow up, 24 subjects (13 from PTU group and 11 from methimazole group) reached euthyroid state and included in the analysis. In PTU group, we found reduction in LDL-R (p = 0.017), sICAM-1 (p = 0.001),

sVCAM-1 (p < 0.001) and sE-selectin (p = 0.045). While in methimazole groups, we only found reduction in LDL-R (p = 0.011) and sVCAM-1 (p = 0.001). However, after comparing both groups, the differences were not statistically significant. We found no significant changes in PWV and cIMT parameter.

In conclusions, this study found that hyperthyroidism in Graves’ patient correlated with increase in sICAM-1 and sVCAM-1, which are the early markers of atherosclerosis. Antithyroid drugs can lower LDL-R, sICAM-1, sVCAM-1 and sE-selectin. PTU had a different mechanism in pathophysiology of atherosclerosis compared to methimazole. However, we found no evidence in PWV and cIMT changes"