SAFETY EVALUATION OF STATIN IN YOGYAKARTA, INDONESIA

Background : The 3-hydroxy-3-methylglutaryl-coenzyme (HMG-Co-A) reductase inhibitors, also known as statins, are the most effective class of drugs for lowering serum Low-Density Lipoprotein cholesterol (LDL-c)concentrations. They are first-line agents for patients who require drug therapy to reduce serum LDL-c concentrations. Although these drugs have been very successful in managing the cardiovascular health of many patients, there are also potential adverse effects that have been identified. The most common adverse effects reported include muscle pain or weakness that can progress to rhabdomyolysis and mortality. If detected early, statin-related symptoms are reversible after withdrawal of the statin. Objective : This research was aimed to know the safety of statin used at Public Hospitals in Yogyakarta. Method : This research was observational study with retrospective data collected. The target population are all of diabetes mellitus, cardiovascular and stroke patients that recorded on the medical record of Public Hospitals in Yogyakarta during 2 months. Results : There were 28 patients who used simvastatin and 8 patients who used atorvastatin, experienced adverse effects of statins (n=157). Headache was the most adverse effect which was experienced by the patients. However rhabdomyolysis was not found in this reasearh. Interaction between simvastatin and nifedipine resulted more adverse effects such as headache, insomnia and abdominal pain than with other drugs. Conclusions : Simvastatin, rosuvastatin and atorvastatin were well tolerated use in Yogyakarta, Indonesia. Only 22.9% from 157 patients experienced the adverse effects of statin. Adverse effects because of the interaction between simvastatin and other drugs were experienced by 8.92% patients. The result of this study need to be confirmed with additional study with larger sample sizes and vigilant surveillance to abolish the toxicity of the statin

Peri-implant diseases and metabolic syndrome components: a systematic review

OBJECTIVE: Metabolic syndrome (MetS) is defined as a spectrum of conditions associated with an increased risk of developing CVD and type 2 diabetes. MetS include: hyperglycemia, hypertension, visceral obesity, dyslipidemia with elevated values of triglycerides (TG) and low levels of HDL. The aim of this review is to provide current knowledge of the relationship between MetS, its components and peri-implant diseases. MATERIALS AND METHODS: An electronic literature search was conducted in the English language in several databases. The Newcastle-Ottawa Scale was used for quality assessment of cohort and cross-sectional studies; while systematic reviews were evaluated through AMSTAR; results were reported according to the PRISMA Statement. RESULTS: A total of 272 records were identified through database searching, six studies were included for qualitative analysis. No study directly related to MetS was found, there was inconsistent and controversial evidence regarding association with cardiovascular disease. A higher risk of peri-implantitis was detected in people with hyperglycemia. CONCLUSIONS: Future research should be orientated in assessing the risk of peri-implant diseases, evaluating patient's therapeutic response, analyzing directionality of the relationship between MetS, its components and biologic implant complications. Few studies have investigated the possible relationship between systemic conditions and peri-implant diseases. The aim of this review is to present, in a systematic manner, current evidence and knowledge regarding possible association between cardiovascular disease and implant biologic complications. Out of the one-hundred-eighty-nine studies screened, just five studies were selected for qualitative analysis: three cohort studies (one prospective and two retrospectives) and two cross-sectional studies. According to their results, there is inconsistent and controversial evidence regarding association of cardiovascular disease and implant biologic complications. Future research should be orientated in conducting longitudinal studies, evaluating patients affected by cardiovascular disease rehabilitated with dental implants

Early treatment with a natural antioxidant polyphenolic compound (Resveratrol: trans-3,5,4′- trihydroxystilbene): a new adjuvant therapeutic approach for preventing diabetic cardiomyopathy, in experimental type-1 diabetes

Emerging evidence suggests that both adult cardiac cell and the cardiac stem/progenitor cell (CSPC) compartments are involved in the patho-physiology of diabetic cardiomyopathy (DCM). We evaluated whether early administration of Resveratrol, a natural antioxidant polyphenolic compound, in addition to improving cardiomyocyte function, exerts a protective role on (i) the progenitor cell pool, and (ii) the myocardial environment and its impact on CSPCs, positively interfering with the onset of DCM phenotype. Adult Wistar rats (n=128) with streptozotocin-induced type-1 diabetes were either untreated (D group; n=54) or subjected to administration of trans-Resveratrol (i.p. injection: 2.5 mg/Kg/day; DR group; n=64). Twenty-five rats constituted the control group (C). After 1, 3 or 8 weeks of hyperglycemia, we evaluated cardiac hemodynamic performance, and cardiomyocyte contractile properties and intracellular calcium dynamics. Myocardial remodeling and tissue inflammation were also assessed by morphometry, immunohistochemistry and immunoblotting. Eventually, the impact of the diabetic “milieu” on CSPC turnover was analyzed in co-cultures of healthy CSPCs and cardiomyocytes isolated from D and DR diabetic hearts. In untreated animals, cardiac function was maintained during the first 3 weeks of hyperglycemia, although a definite ventricular remodeling was already present, mainly characterized by a marked loss of CSPCs and adult cardiac cells. Relevant signs of ventricular dysfunction appeared after 8 weeks of diabetes, and included: 1) a significant reduction in ±dP/dt in comparison with C group, 2) a prolongation of isovolumic contraction/relaxation times, 3) an impaired contraction of isolated cardiomyocytes associated with altered intracellular calcium dynamics. Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function. These findings indicate that RSV can constitute an adjuvant therapeutic option in DCM prevention and treatment

Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program

Background: The Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval. Methods: Pts with previously treated advanced or mRCC were eligible to receive nivolumab 3 mg/kg every 2 weeks. Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for drug-related adverse events (drAEs) using CTCAE v.4.0. Immune-related (ir) AEs were defined as AEs displaying a certain, likely or possible correlation with immunotherapy (cutaneous, endocrine, hepatic, gastro-intestinal and pulmonary). The association between overall survival (OS) and irAEs was assessed, and associations between variables were evaluated with a logistic regression model. Results: A total of 389 pts were enrolled between July 2015 and April 2016. Overall, the objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7-6.2) and the 12-month overall survival rate was 63%. Any grade and grade 3-4 drAEs were reported in 124 (32%) and 27 (7%) of pts, respectively, and there were no treatment-related deaths. Any grade irAEs occurred in 76 (20%) of patients, 8% cutaneous, 4% endocrine, 2% hepatic, 5% gastro-intestinal and 1% pulmonary. Of the 22 drAEs inducing treatment discontinuation, 10 (45%) were irAEs. Pts with drAEs had a significantly longer survival than those without drAEs (median OS 22.5 versus 16.4 months, p = 0.01). Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8 months, p = 0.002), confirmed at the landmark analysis at 6 weeks. The occurrence of irAEs displayed a strong association with OS in univariable (HR 0.48, p = 0.003) and multivariable (HR 0.57, p = 0.02) analysis. Conclusions: The appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab

Alterações do filme lacrimal e da superfície ocular no diabetes mellitus

Diabetes mellitus and its clinical association with dry eye and ocular surface are becoming a frequent and sometimes complicate problem in Ophthalmology. Epidemiological data show that an increase in the number of patients with this association is expected following the trend to rise of the disease. The present work reviews the clinical and functional aspects of this problem. The observations indicate that metabolic, neuropathic and vascular tissue damages lead to an inflammatory process and functional degeneration. The physiopathological mechanism include hyperglycemia, advanced glycated end product accumulation, oxidative stress and inflammation mediated by NF-κB signaling pathways. Potential treatments enlightened by those findings would include antioxidant, anti-inflammatory, secretagogues and/or anabolic agents that would mimic insulin effects.O diabetes mellitus e sua associação clínica com olho seco e doença da superfície ocular estão se tornando um problema freqüente e muitas vezes complicado em oftalmologia. Os dados epidemiológicos mostram que o número de casos deve crescer acompanhando a tendência de aumento da incidência da doença. Esse trabalho revê seus aspectos clínicos e funcionais. As observações indicam que as lesões metabólicas, neuropáticas e vasculares levam a um processo inflamatório e degeneração funcional. Os mecanismos fisiopatológicos incluem hiperglicemia, acúmulo de produtos finais de glicosilação avançada, estresse oxidativo e inflamação mediada pelas vias de sinalização do NF-kB. Os tratamentos potenciais sugeridos por essas observações incluiriam antioxidantes, antiinflamatórios, secretagogos e/ou agentes anabólicos com efeitos miméticos ao da insulina.Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)CNPqFAPES

Hyperglycemia triggers HIPK2 protein degradation

Homeodomain interacting protein kinase-2 (HIPK2) is an evolutionary conserved kinase that modulates several key molecular pathways to restrain tumor growth and induce p53-depending apoptotic cell-death in response to anticancer therapies. HIPK2 silencing in cancer cells leads to chemoresistance and cancer progression, in part due to p53 inhibition. Recently, hyperglycemia has been shown to reduce p53 phosphorylation at serine 46 (Ser46), the target residue of HIPK2, thus impairing p53 apoptotic function. Here we asked whether hyperglycemia could, upstream of p53, target HIPK2. We focused on the effect of high glucose (HG) on HIPK2 protein stability and the underlying mechanisms. We found that HG reduced HIPK2 protein levels, therefore impairing HIPK2-induced p53 apoptotic activity. HG-triggered HIPK2 protein downregulation was rescued by both proteasome inhibitor MG132 and by protein phosphatase inhibitors Calyculin A (CL-A) and Okadaic Acid (OA). Looking for the phosphatase involved, we found that protein phosphatase 2A (PP2A) induced HIPK2 degradation, as evidenced by directly activating PP2A with FTY720 or by silencing PP2A with siRNA in HG condition. The effect of PP2A on HIPK2 protein degradation could be in part due to hypoxia-inducible factor-1 (HIF-1) activity which has been previously shown to induce HIPK2 proteasomal degradation through several ubiquitin ligases. Validation analysed performed with HIF-1α dominant negative or with silencing of Siah2 ubiquitin ligase clearly showed rescue of HG-induced HIPK2 degradation. These findings demonstrate how hyperglycemia, through a complex protein cascade, induced HIPK2 downregulation and consequently impaired p53 apoptotic activity, revealing a novel link between diabetes/obesity and tumor resistance to therapies

Asuhan Keperawatan Pada Klien Tn. I Dengan Diabetes Mellitus (Hiperglikemia) Di Instalasi Rawat Intensif RSUP Dr. Soeradji Tirtonegoro Klaten

Diabetes mellitus merupakan sekelompok kelainan heterogen yang ditandai oleh kenaikan kadar glukosa dalam darah atau hiperglikemia. Menurut Organisasi Kesehatan Dunia (WHO) dan Federasi Diabetes International (IDF) 177 juta penduduk dunia yang menderita diabetes mellitus. Diabetes Mellitus merupakan suatu keadaan hiperglikemia yang ditandai oleh keadaan absolute insulin yang bersifat kronik yang dapat mempengaruhi metabolisme karbohidrat Tujuan karya tulis ilmiah ini mengetahui dan mampu menerapkan teori kedalam praktek asuhan keperawatan pada klien dengan kegawat daruratan diabetes mellitus (hiperglikemia) di RSUP Dr. Soeradji Tirtonegoro Klaten. Teknik pengambilan data pada karya tulis ilmiah ini antara lain menggunakan observari, wawancara, partisipatif. Diagnosa yang muncul antara lain pola nafas tidak efektif b.d penurunan ekspansi paru, kekurangan volume cairan b.d poliuri dan dehidrasi, PK: infeksi, resiko injuri b.d kerusakan neuromuskuler, tekanan dan disease, kelelahan b.d ketidakberdayaan, deficit self care b.d kelemahan dan PK : hiperglikemi. Implementasi yang sudah dilakukan antara lain Implementasi yang telah dilakukan adalah mengobservasi keadaan umum klien disertai mengukur tanda-tanda vital klien ( tekanan darah, nadi, suhu, dan pernafasan), memberikan terapi sesuai program, mengecek GDS,memberikan posisi semifowler pada klien, mengkaji pola nafas klien, memantau intake dan output klien, merestrain klien, membantu klien dalam pemenuhan ADL. Dari masalah – masalah tersebut setelah dilakukan tindakan keperawatan selama 3 hari ternyata 7 masalah dapat teratasi Kata kunci : Asuhan Keperawatan, diabetes mellitus dan hiperglikemi