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"Insidens insufisiensi adrenal pada pasien renjatan sepsis dilaporkan sekitar 40-65. Sitokin IL-1 dan IL-6 dapat menstimulasi sekresi kortisol sedangkan TNF-? serta MIF berperan dalam menghambat pembentukan kortisol. Penelitian ini bertujuan untuk mengetahui peran IL-1, IL-6, TNF-? dan MIF dalam terjadinya insufisiensi adrenal relatif pada renjatan sepsis.Penelitian eksperimental dilakukan di laboratorium FKH IPB berlangsung selama 6 bulan April-September 2015 . Model anak babi yang dipakai berumur 6-8 minggu dengan berat badan 5-10 kg. Pemilihan sampel dengan consecutive sampling dengan total n = 20. Anak babi diberikan infus endoktoksin dengan dosis 50 ug/kg BB. Sampel darah untuk analisis IL-1, IL-6, TNF-?, MIF, ACTH, kortisol, 17 OHP, DHEA, androstenedion diambil sebelum pemberian endotoksin dan tiap 15 menit hingga terjadi renjatan sepsis, kemudian dilakukan uji synacthen. Pemeriksaan imunohistokimia dilakukan pada kelenjar adrenal, hipofisis, dan hipotalamus.Dari 19 anak babi yang dianalisis mengalami renjatan sepsis dalam waktu 60 menit. Karakteristik sampel tidak berbeda bermakna antara kedua kelompok. Kadar IL-6 pada kelompok IAR dibandingkan dengan kelompok tanpa IAR berbeda bermakna pada menit ke-45 0,65 0,5-4,32 pg/dL vs. 0,54 0,51-0,61 pg/dL , p = 0,008 . Kadar IL-1 antara kelompok IAR dibandingkan kelompok tanpa IAR tidak berbeda bermakna. Kadar TNF-? pada kelompok IAR dibandingkan dengan kelompok tanpa IAR berbeda bermakna pada menit ke-15 1862,5 327,9-4511,14 pg/dL vs. 155,38 24,67-394,10 pg/dL , p = 0,002 dan menit ke-30 4295,76 246,9-5913,37 pg/dL vs. 422,90 101,05-4129,42 pg/dL , p = 0,007 . Kadar MIF kelompok IAR dibandingkan dengan kelompok tanpa IAR berbeda bermakna pada saat renjatan sepsis 25,28 18,45-30,64 ng/dL vs. 11,30 7,1-15,14 ng/dL p = 0,003 . Pemeriksaan imunohistokimia hanya pada hipotalamus yang menunjukkan pewarnaan terhadap IL-1, IL-6, TNF-? dan MIF pada kelompok dengan IAR. Pada renjatan sepsis dan insufisiensi adrenal relatif kadar TNF-? meningkat pada menit-menit awal, kemudian kadar IL-6 meningkat kemudian serta terakhir kadar MIF meningkat pada saat renjatan sepsis. Kadar IL-1 tidak terdapat perbedaan antara kedua kelompok. Kata kunci: IL-1, IL-6, insufisiensi adrenal relatif, MIF, renjatan sepsis, TNF-?

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Incidence of adrenal insufficiency in septic shock ranged between 40 ndash 65 . The mechanism of relative adrenal insufficiency in septic shock is caused by inflammatory mediators. This study aimed to identify the role of IL 6, IL 1 in stimulating ACTH and cortisol release, and the role of TNF and MIF in inhibiting the level of ACTH and cortisol in septic shock with relative adrenal insufficiency RAI in order to develop guidelines for relative adrenal insufficiency marker.Experimental study was conducted in Veterinary Faculty, Bogor Agricultural Institute for 6 months Apri ndash September 2015 . Piglet models Sus scrofa aged 6 ndash 8 weeks weighing 5 ndash 10 kg. Consecutive sampling was used with total 20 piglets. Piglet models were given 50 ug kg endotoxin infusion Escherichia coli O111 B4 Sigma chemical, St. Louis, MO, USA . Blood sample for analysis of IL 1, IL 6, TNF , MIF, ACTH, cortisol, 17 OHP, DHEA, androstenedione was collected before endotoxin administration and every 15 minutes until septic shock occurred. Piglet models were monitored using PiCCO monitor. Stimulation test was then performed using synthetic corticotropin Synacthen and blood sample was collected again along with immunohistochemistry examination of the adrenal, pituitary and hypothalamus glands.From 19 study subjects analized, all subject had septic shock in 60 minutes. Study subject characteristics in each group were similar. The level of IL 6 at 45 minutes had a significant different compared to the group without RAI 0.65 0.5 ndash 4.32 pg dL vs. 0.54 0.51 ndash 0.61 pg dL , p 0.008 . The level of IL 1 during septic shock were not significantly different between both groups. The level of TNF in RAI group had significant different compared to the group without RAI at 15 minutes 1862.5 327.9 ndash 4511.14 pg dL vs. 155.38 24.67 ndash 394.10 pg dL , p 0.002 and at 30 minutes 4295.76 246.9 ndash 5913.37 pg dL vs. 422.90 101.05 ndash 4129.42 pg dL , p 0.007 The level of MIF in group with RAI during septic shock had a significant different compared to the group without RAI t 25.28 18.45 ndash 30.64 ng dL vs. 11.30 7.1 ndash 15.14 ng dL , p 0.003 . Immunohisto chemistry staining of IL 1, IL 6, TNF , and MIF was observed only in the hypothalamus glands of the RAI group. In septic shock and relative adrenal insufficiency, TNF increased in earlier minutes, then IL 6 increased and later MIF increased in septic shock condition. IL 1 level had no difference increment for both group.Keywords IL 1, IL 6, MIF, relative adrenal insufficiency, septic shock, TNF"

"ABSTRAKInflamasi sistemik pada renjatan sepsis dapat menyebabkan insufisiensi adrenal. Kadar asam lemak bebas ALB yang tinggi diketahui menyebabkan inflamasi steril dan menghambat adrenocorticothropic hormone dan sekresi kortisol. Pemberian hidrokortison pada renjatan sepsis diharapkan memperbaiki hemodinamik, menurunkan ketergantungan terhadap obat vasoaktif dan memperbaiki disfungsi organ.Penelitian bersifat studi eksperimental yang bertujuan menilai pengaruh ALB dan pemberian hidrokortison terhadap hemodinamik, kadar laktat, cedera paru dan kadar kortisol darah pada renjatan sepsis model anak babi. Penelitian dilaksanakan di Divisi Bedah dan Radiologi Departemen Klinik Reproduksi dan Patologi Fakultas Kedokteran Hewan Institut Pertanian Bogor FKH IPB pada April -September 2015 dan telah disetujui oleh Komisi Etik Hewan FKH IPB.Delapan model anak babi Sus scrofa berusia 6-8 minggu dengan berat 5-10 kg dibagi dalam 2 kelompok, yaitu kelompok lipid dan kelompok kontrol. Kelompok lipid diberi lipid 20 sebanyak 3 gram/kgbb intravena dan kelompok kontrol tanpa pemberian lipid sebelum induksi sepsis. Pengukuran parameter hemodinamik dengan Pulse Contour Cardiac Output PiCCO . Pengukuran kadar laktat dengan i-Stat. Cedera paru ditentukan dengan pengukuran extravascular lung water index EVLWI dan rontgen toraks. Tes synacthen dilakukan untuk mengetahui adanya insufisiensi adrenal relatif IAR .Pengaruh ALB terhadap hemodinamik dinilai dengan rerata cardiac index 60 menit setelah pemberian hidrokortison yang berbeda bermakna [2,14 0,06 l/menit/m2 vs. 2,75 0,04 l/menit/m2 p 0,002 ]. Jumlah cairan dan obat vasoaktif yang dibutuhkan kelompok lipid untuk mempertahankan mean arterial blood pressure > 65 mmHg lebih banyak dibandingkan kelompok kontrol. Kadar laktat meningkat sebelum induksi sepsis pada kelompok lipid [2,28 0,52 vs. 1,28 0,45 mmol/L p 0,001 ]. Bersihan laktat pada kelompok lipid lebih buruk dibandingkan kelompok kontrol. Extravascular lung water index kelompok lipid lebih tinggi bermakna dibanding kelompok kontrol setelah 60 menit resusitasi [21 4,04 mL/kg vs. 12,38 2,32 mL/kg p 0,004 ]. Gambaran radiologi efusi pleura dan edema pulmonal terjadi pada seluruh model anak babi kelompok lipid. Insufisiensi adrenal relatif terjadi pada 7 model anak babi di kelompok lipid dan 4 di kelompok kontrol.Kesimpulan penelitian ini adalah kadar ALB yang tinggi memperberat inflamasi dan merupakan faktor risiko terjadinya IAR. Kata kunci: Asam lemak bebas, cedera paru, hemodinamik, hidrokortison insufisiensi adrenal relatif, laktat, renjatan sepsis, sepsis.

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ABSTRACTCortisol deficiency is associated with increased morbidity and mortality during critical illness. Dysregulation of immune system in septic shock triggers adrenal insufficiency. Free fatty acid FFA is known to induced sterile inflammation and inhibit adrenocorticothropic hormone and cortisol secretion. Hydrocortisone administration is expected to improve hemodynamic, decrease dependency of vasoactive drugs and improve organ dysfunction in septic shock.The aim of this study is to find out the effect of FFA and hydrocortisone administration on hemodynamic parameters, lactate, lung injury and blood cortisol levels in septic shock piglet models, conducted in April September 2015 in the Division of Surgery and Radiology School of Veterinary Medicine, Institut Pertanian Bogor IPB and has been approved by the Animal Ethics Committee of School of Veterinary Medicine IPB. Sixteen piglet models Sus scrofa entered the study. The piglets were 6 8 weeks old, weighing 5 10 kg divided into two groups, lipids and control groups. Administration of 3 g kg BW of lipid 20 were performed intravenously before sepsis induction for lipid group. Hemodynamic measurement by Pulse Contour Cardiac Output PiCCO by Picco. Lactate measurement by i Stat. Lung injury was determined by Extravascular lung water index EVLWI and chest X ray. Synacthen test to determine relative adrenal insufficiency RAI .FFA influences was shown on cardiac index 60 min after adminstration of hydrocortisone in lipid group 2.14 0.06 L min m2 and control group 2.75 0.04 L min m2 p 0.002 . Lipid group require fluids and vasoactive drugs more than the control grup to maintain mean arterial blood pressure 65 mmHg. Lactate levels before induction of sepsis lipid group 2.28 0,52 mmol L and control group 1.28 0.45 mmol L p 0.001 . Lactate clearance in lipid group was worse than the control group. Extravascular lung water index at 60 minutes after resuscitation in lipid group 21 4.04 mL kg and control group 12.38 2.32 mL kg p 0.004 . Pleural effusion and pulmonary edema were found in all piglet models in lipid group. Relative adrenal insufficiency occured to 7 piglet model in lipid gorup and 4 in control group.Conclusion High level FFA aggravate inflammation in septic shock and is a risk factor for RAI. Hydrocortisone administration improve circulation and lactate levels. Keywords FFA, hemodynamic, hydrocortisone, lactate, lung injury, relative adrenal insufficiency, sepsis, septic shock"

"Latar Belakang : Stunting pada anak usia di bawah dua tahun (U₂) menggambarkan kekurangan nutrisi kronis dengan berbagai faktor predisposisi dan prevalensinya masih tinggi di Indonesia. Kurang nutrisi kronis menyebabkan tubuh berdaptasi pada ukuran dan fungsi organ, yang berdampak meningkatnya risiko kardiometabolik (RKM) kemudian hari. Tujuan penelitian ini membuktikan perbedaan faktor predisposisi intrauterin (FPIntra), ekstrauterin (FPEkstra), stres oksidatif (SO), adaptasi metabolik (AM) dan RKM pada anak stunting (AnS) dan tidak stunting (AnTS) usia 6-24 bulan (U_6-24).

Metode : Penelitian nested -kohort, cross-sectional komparatif digunakan untuk menilai peran FPIntra, yaitu antropometri ibu sebelum hamil, asupan dan status gizi ibu hamil, berat lahir (BL) dan panjang lahir (PL) subjek, FPEkstra yaitu ASI eksklusif, berat badan (BB) dan panjang badan (PB) enam bulan pertama (U_6I), antropometri anak, asupan gizi AnS dan AnTS U_6-24. Indikator SO yaitu kadar MDA serum. Indikator AM yaitu ekspresi microRNA -148a. Indikator RKM yaitu ukuran lingkar pinggang (LP), kadar kolesterol-LDL, kolesterol-HDL, trigliserida, dan glukosa darah. Semua subjek merupakan peserta TKA, Bogor dan pengambilan data dilakukan sejak bulan Juli 2017 hingga Februari 2018, dilaksanakan di Rumah Kohort TKA, Bogor. Analisis statistik univariat, bivariat dan multivariat digunakan untuk membandingkan kelompok AnS dan AnTS dengan batas kemaknaan p <0,05.

Hasil : Sebanyak 38 AnS dan 46 AnTS U_6-24 memenuhi kriteria penelitian dan didapatkan FPIntra AnS lebih rendah secara bermakna dibanding AnTS, yaitu kategori kadar seng serum ibu hamil, tinggi badan ibu, BL dan PL subjek (p = 0,047, p < 0,001, p = 0,009, p = 0,025). Asupan mangan (p= 0,007), isoleusin (p =0,015), pertambahan BB U_6-I (p =0,002), rerata pertambahan BB/bulan U_6-I (p =0,002), pertambahan PB U_6-I (p <0,001), rerata pertambahan PB/bulan U_6-I (p <0,001) dan kadar Hb anak (p =0,005) lebih rendah secara bermakna pada AnS, sementara RDW-CV lebih tinggi pada AnS (p =0,009). Tidak ditemukan perbedaan SO pada kedua kelompok, tetapi gambaran adanya AM pada usia dini terlihat pada normalized expression ratio microRNA -148a AnS sebesar 2,6 kali lebih cepat dibandingkan dengan AnTS, yang mengakibatkan kolesteol-LDL di sirkulasi lebih tinggi pada AnS. Ditemukan dua indikator RKM berbeda bermakna yaitu ukuran LP AnS lebih kecil bermakna, namun kadar trigliseridanya lebih tinggi pada AnS. Kadar kolesterol-LDL cenderung lebih tinggi pada AnS.

Kesimpulan : FPIntra dan FPEkstra terbukti memberikan dampak terhadap kejadian stunting anak U_6-24. Adaptasi metabolik dan RKM pada AnS sudah terdeteksi pada U_6-24.

Saran : Penting untuk memantau status gizi ibu sebelum hamil dan memberikan intervensi nutrisi dalam 1000 hari awal kehidupan untuk mengurangi RKM di kemudian hari.

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Background : Stunting children under two years of age (U2) illustrates chronic nutritional deficiency with various predisposing factors and the prevalence is still high in Indonesia. Chronic malnutrition causes the body to adapt organ size and function, which results in increased cardio metabolic risk (CMR) in adulthood The aim of this study was to prove differences in intrauterine predisposition (PFIntra), extra uterine (PFExtra), oxidative stress (OxS), metabolic adaptation (MetAdapt) and CMR in stunting children (StC) and non stunting children (NStC) aged 6-24 months (U6-24).

Methods : A nested-cohort, comparative cross-sectional study was used to assess the role of PFIntra, namely maternal anthropometry before pregnancy, nutrition intake and nutritional status of pregnant women, birth weight (BW) and birth length (BL) of subjects, PFExtra namely exclusive breastfeeding, weight and body length in the first six months (U6I), pediatric anthropometry and nutritional intake in StC and NStC U6- 24. Indicator of OxS was serum MDA level. MetAdapt indicator was microRNA-148a expression. The CMR indicators were waist circumference (WC), LDL-cholesterol levels, HDL-cholesterol, triglycerides, and blood glucose. All subjects were participants in Bogor Longitudinal Study Child Growth and Development (BLSCGD), in Bogor Tengah sub-district. Univariate, bivariate and multivariate statistical analyzes were used to compare StC and NStC groups with significant p value <0.05.

Results : There were 38 StC and 46 NStC U6- 24 fulfilled the study criteria and obtained significantly lower PFIntra in StC compare to NStC, namely the serum zinc level category of pregnant women, maternal height, BW and BL subjects (p = 0.047, p <0.001, p = 0.009, p = 0.025). Manganese intake (p = 0.007), isoleucine intake (p = 0.015), increase in weight U6-I (p = 0.002), weight gain per month U6-I (p = 0.002), increase in length U6-I (p <0.001), length increase per month U6-I (p <0.001) and Hb levels of children (p = 0.005) were significantly lower in StC, while RDW-CV was higher in StC (p = 0.009). There were no significant differences in OxS between two groups, but MetAdapt at an early age was seen in the StC as show in normalized expression ratio of microRNA-148a was 2.6 times faster than NStC, which resulted in higher circulation of LDL in StC. Two of five CMR indicators were significantly different, namely the size of WC in StC was significantly smaller, but the triglyceride level was higher in StC. LDL-cholesterol levels tend to be higher in StC.

Conclusion : PFIntra and PFExtra proved to have an impact on the incidence of stunting children U6- 24. Metabolic adaptation and CMR in StC have been detected in U6- 24.

Suggestion: It is important to monitor the nutritional status of the mother before pregnant and provide nutritional interventions within the first 1000 days of life to reduce cardio metabolic risk in the future."