Metformin, Effects Beyond Glycemic Control

Metformin is an appropriate first-line medication, not only for glycemic control, but also in other situations. Most recently, the spectrum of metformin’s target site has expanded to include the endothelium and ovaries. Even if many of these actions are individually modest, they seem to be collectively sufficient to confer therapeutic benefits, not only in cardiometabolism, but also in reproductive aspects related to insulin resistance and proinflammatory states, with promising antitumor and cancer protection properties. The aim of this study was to explain Metformin, Effects Beyond Glycemic Control. In 50 years of its clinical use, there have been no major risks reported with metformin, and serious adverse events attributed to metformin appear to be very low due to some contraindications. The limited use in chronic kidney disease needs to be redefined since many data suggest that metformin may protect against the deleterious consequences of hyperglycemia in the kidneys

FORMULASI BARU PENGEKANGAN HAM DALAM KONTEKS PERBURUHAN

Dari beberapa penjelasan pada Bab II dapat ditarik suatu pemyataan yang tegas bahwasanya eksistensi Undang-Undang Nomor 21 Tahun 2000 tentang Serikat Pekerja per1u dikoreksi dan direvisi, dikarenakan ada beberapa pasal yang sarna sekali tidak memberikan keberpihakan kepada pihak buruh dan kontradiksi dengan konsep per1indungan hak asasi manusia

Anti-inflammatory activity of Agaricus blazei Murill extract in the spleen of mice fed a high-fat diet

Purpose: To examine the effects of A. blazei Murill on the production of  proinflammatory cytokine TNF-α and regulatory cytokine IL-10 in the spleen of mice fed a high-fat diet.Methods: The study was conducted on 25 BALB/c male mice divided into five groups consisting of five mice in each group and utilized three A. blazei Murill extract doses: 100, 200 and 400 mg/kg. The mice were fed a high-fat diet (HFD) and given A. blazei Murill extract for 12 weeks. The relative number of CD4+TNF-α+,  CD11b/c+TNF-α+, and CD4+CD25+IL-10+ were measured using flow cytometry.Results: Oral administration of A. blazei Murill extract (100 mg/kg) in mice fed a high-fat diet significantly decreased (p < 0.05) the level of TNF-α that produced by CD4+ T cells and macrophages (1.64 %), compared with control. The 200 mg/kg dose decreased the level of CD11b/c+TNF-α+ by 5.37 % (p < 0.05) compared to 100 mg/kg dose. The 400 mg/kg dose significantly enhanced regulatory cytokines IL-10 by 17.56 % (p < 0.05) in mice fed a high-fat diet.Conclusion: This findings suggest that Agaricus blazei Murill can inhibits processes in HFD-induced mice by reducing TNF-α production and increasing the  anti-inflammatory cytokine IL-10. These results provide new insight into the pharmacological actions of Agaricus blazei Murill as a medicinal food for potential therapy of atherosclerosis disease.Keywords: Anti-inflammatory agent, Agaricus blazei Murill, Proinflammatory cytokine, TNF-α, IL-1

Three dangerous loops of lipoprotein-associated phospholipase A2 activity on increasing LDL atherogenecity

Background: Hypercholesterolemia is a major classic risk factor for cardiovascular disease; however, there are 35%-40% cases of cardiovascular where patients have normal cholesterol levels. Lp-PLA2 is an enzyme that is produced and secreted by macrophages as a response to the lipid peroxide formation, especially the platelet activating factor compound and phosphocholine peroxide. Lp-PLA2 has been correlated with classic risk factor of cardiovascular disease, although that correlation with number of foam cell at early stage of atherosclerosis is not clear yet. This study aims to determine the lipid profiles, oxidation stress markers and Lp-PLA2 levels at three different initial atherogenesis levels. Methods: This study observed the change of Lp-PLA2, F2-Isp, MDA, TC, LDL, HDL levels in rat serum at three different levels of early atherogenesis; they were Ath-I, Ath-II and Ath-III made on the number of foam cells. The number of cells was observed in all aortic cross sectional surfaces, using the Oil-Red-O staining. The LDL-C content was measured using the Fiedwall formula, whereas the MDA content was measure by using TBA-test. The observation of F2-isoprostane and Lp-PLA2 were exemplified by the procedure of Elisa’s. Results: The one way ANOVA test results between the three initial levels of atherosclerosis showed no significant differences in all lipid profiles both in serum and stress oxidation markers. However, the LSD test results projected significant differences in LDL levels in Ath-I compared to others. There was a significant difference (p<0.01) in the serum of Lp-PLA2 content. The LSD test results displayed a significant increase in Lp-PLA2 enzyme levels since the Ath-II stage. Conclussion: The elevated levels of Lp-PLA2 also increased the atherogenecity of LDL, due to the increased inflammation, stress oxidation and elevated levels of Lp-PLA2, which were interconnected with proatherogenic loops

Safety and Efficacy in Early Insulin Initiation as Comprehensive Therapy for Patients with Type 2 Diabetes in Primary Health Care Centers

Aim: to analyze the safety and efficacy of early insulin initiation therapy for patients with type 2 diabetes mellitus (T2DM) in primary health care provided by general practitioners (GPs) in Surabaya, East Java, Indonesia. Methods: pre-post study of ninety nine diabetic patients without previous insulin treatment with HbA1c levels >8% were involved in this study. The study was conducted in 10 primary health care centers in Surabaya between October 2011 to June 2012. Each patient received insulin therapy for 12 weeks. Laboratory examination was performed for each patient including fasting plasma glucose (FPG), 2 hours post-prandial plasma glucose (2hPPG) and HbA1c examination before and after the study. Self monitoring blood glucose (SMBG) examination was conducted in order to adjust the insulin dose and prevent the incidence of hypoglycemia. Data was statistically analyzed using paired-T test. Results: FPG level was decreased from baseline data (209 mg/dL) to 152.07 mg/dL at the end of the study (Δ56.93 mg/dl; p=0.0001). The average of 2hPPG level was also decreased from 313.00 mg/dl to 220.72 mg/dL (Δ 92.28 mg/dL; p=0.0001). HbA1c was reduced from 11.60% at baseline to 8.95% at the end of study (Δ 2.65%; p=0.0001). Hypoglycemia was found in 6 patients (6.06%) in this study, but all events were mild and did not need to be admitted to hospital. Conclusion: the safety of insulin therapy iniatiation might be provided by GPs at primary health centers with significant efficacy and minimal side effects. Key words: insulin, general practioner, primary health center

Profil oksitocina u serumu u ženki štakora nakon okota i ženki štakora koje nisu skotne

Oxytocin is primarly secreted in the brain as a neuromodulator that affects numerous neurophysiological and behavioral processes. It is also produced in the ovaries and uterus to stimulate delivery and lactation. Oxytocin mRNA is found in the endometrial epithelial cells of non-pregnant women during ovulation and menstruation. Until recently, there have been no data on scientific-level oxytocin in virgin female rats. This study aimed to compare the level of oxytocin in different physical biology between postpartum and non-pregnant experimental animals (virgin or had never given birth). This experimental study was conducted on 19 female white rats (Rattus norvegicus) allocated to two groups: T1 and T2. The ten rats in group T1 (nulliparous virgin) and the nine in group T2 (postpartum) were sacrificed on day two, except for group T1, which were sacrificed following vaginal delivery. Blood was collected intracardiacally, and serum oxytocin levels were evaluated using an ELISA assay. The T-test was used for statistical data analysis. The serum oxytocin level in the T2 group (628.06 ± 168.72 pg/mL) was significantly higher than in the T1 group (366.71 ± 185.03 pg/mL; P < 0.05). In conclusion, oxytocin levels were higher in postpartum animals than in virgin animals. Thus, oxytocin plays a greater role in female reproduction than in normal physiological condition.Oksitocin se, prije svega izlučuje u mozgu kao neuromodulator koji utječe na brojne neurofiziološke i bihevioralne procese. Isto tako proizvodi se i u jajnicima i maternici da bi se potaknuo porođaj i laktacija. mRNK oksitocina se tijekom ovulacije i menstruacije može se pronaći i u endometrijskim epitelnim stanicama žena koje nisu trudne. Do nedavno nije bilo podataka o znanstvenoj razini oksitocina u djevica. Cilj je ove studije bio usporediti razinu oksitocina u različitoj fizičkoj biologiji između ženki eksperimentalnih životinja nakon porođaja i onih koje nisu skotne (koje se nisu prethodno parile ili nikada nisu kotile). Ova eksperimentalno istraživanje provedeno je na 19 ženki bijelog štakora (Rattus norvegicus) podijeljenih u dvije skupine: T1 i T2. Deset ženki u skupini T1 (nikada nisu kotile; nikada se nisu parile) i devet u skupini T2 (nakon okota) žrtvovano je na dan dva, osim skupine T1 koja je žrtvovana nakon vaginalnog porođaja. Prikupljena je krv intrakardijalno te su procijenjene razine oksitocina u serumu pomoću ELISA testa. T-test je rabljen za analizu statističkih podataka. Razina oksitocina u serumu u T2 skupini (628,06 ± 168,72 pg/mL) bila je značajno veća od one u T1 skupini (366,71 ± 185,03 pg/mL; P < 0,05). Zaključno, razine oksitocina u životinja nakon okota bile su veće od razina u ženki koje se nikada nisu parile. Nakon naših istraživanja zaključak je da oksitocin ima veću ulogu u reprodukciji ženki nego u normalnom fiziološkom stanju

AGE AND BODY MASS INDEX IN TYPE I ENDOMETRIAL CANCER GRADE

Highlights: 1. The major risk factors for type I endometrial cancer, namely age and obesity, play a major role in the increase in this case and are thought to be related to the grade in these cancer patients. 2. Type I endometrial cancer patients at Dr. Soetomo General Academic Hospital 2019-2020 are dominated by patients diagnosed at the age of 56-65 years, having an overweight body mass index (23-24.9 kg/m2). 3. The patient's age and body mass index did not correlate with endometrial cancer type I grade. Abstract Background: The increase in obesity and life expectancy has contributed to type I endometrial cancer cases worldwide. Increased risk factors play a role in the increase of these cases. Objectives: To determine the relationship between age and BMI with the cancer grade. Material and Method: This research was a cross-sectional study. The data were obtained from the patient’s medical records. The sampling technique was total sampling. The analysis used was Spearman Rho correlation test for the relationship between age and BMI with cancer grade. Results: This study recorded 54 patients with type I endometrial cancer in Dr. Soetomo General Academic Hospital, Surabaya, Indonesia, from 2019 to 2020. The patients were from the age group 56-65 years 25 patients (46.30%), 46-55 years 17 patients (31.48%), 36-45 years 8 patients (14.81%), 26-35 years 2 patients (3.7%), and >65 years 2 patients (3.7%). For BMI, the patients were overweight (23-24.9 kg/m2) 21 patients (38.89%), normal (18.5-22.9 kg/m2) 14 patients (25.93%), obesity (25-29.9 kg/m2) 12 patients (22.22%), and obesity II (≥30 kg/m2) 7 patients (12.96%). For grade, grade III were 22 patients (40.75%), grade II  20 patients (37.04%), and grade I 12 patients (22.22%). There was a weak, insignificant positive correlation between age with grade (ρ=0.116, 0.405>α=0.05) and a weak, insignificant negative correlation between BMI with grade (ρ=-0.206, 0.135>α=0.05). Conclusion: A total of 54 patients with type I endometrial cancer at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia, from 2019-2020 aged 56-65 years and overweight (23-24.9 kg/m2) with grade III cancer. The patient's age and BMI did not correlate with the patient's grade

Adiponectin and ADMA Level in Type-2 Diabetes Patients After 12 Weeks of Treatment with Glimepiride and Metformin Fixed Dose Combination (DIAGRAM Study)

Background: Recent published study on glimepiride showed remarkable increase of plasma adiponectin while metformin was associated with a decrease in asymmetric dimethylarginine concentrations. A fixeddose combination of glimepiride and metformin available in Indonesia with limited local data on plasma hba1c adiponectin and asymmetric dimethylarginine concentrations. Objective: This clinical trial aimed to evaluate the effect of fixed-dose combination of 1 mg glimepiride and 250 mg metformin Immediate Release on the level of plasma adiponectin, circulating asymmetric dimethylarginine, ankle-brachial pulse wave velocity, as well as fasting blood glucose and hba1c change in 40 patients with type 2 diabetes mellitus after 12 weeks of therapy. Methods: Diagram was an open label study. We compared pre- and post-treatment values of high molecular weight adiponectin and asymmetric dimethylarginine level after 12 weeks treatment period with fixeddose combination glimepiride/metformin. Forty patients with type 2 diabetes mellitus aged 40 – 60 years who were not currently treated with any Oral Anti Diabetic agents, statins, angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers for at least 8 weeks and the hba1c value between 7% and <10% have been enrolled for this clinical trial. Results: Fixed Dose Combination glimepiride/metformin is proven effective for treating forty patients with type-2 diabetes who were included in this study, even though plasma adiponectin was not significantly increased (34 ng/mL; p=0.201) by the administration of this fixed-dose combination for a 12 weeks treatment period as expected, however the treatment effect in increased adiponectin was shown in subjects with adiponectin dysfunction. Significant increase of asymmetric dimethylarginine median value (0.14 μmol/L, p<0.001) and decrease of ankle-brachial pulse wave velocity (-110.4 cm/sec, p=0.016) were shown in this study accompanied by the decrease in hba1c from 8.52% to 7.38% (p<0.001) and fasting blood glucose from 165.9 mg/dL to 123.1 mg/dL (p<0.001). Mild adverse events were reported in 7.5% patients, while serious adverse event was reported in one subject and was not related to study drug. Conclusion: It can be concluded that treatment with fixed-dose combination glimepiride/metformin has effect in improving endothelial function by increasing adiponectin and lowering ankle-brachial pulse wave velocity level significantly. Meanwhile, the administration of fixed-dose combination glimepiride/metformin may not have effect in decreasing ADMA level. Further studies which included larger population with more varied parameters are needed to confirm the relationship of this fixed-dose combination with other factors

Hemoglobin A1C as the Strongest Influencing Factor in relation to Vascular Stiffness in Type 2 Diabetes Mellitus - Metabolic Syndrome Patients

The risk of cardiovascular disease in type 2 diabetes mellitus (T2DM) will be high despite intensive glycemic control. This is because T2DM is often accompanied by the condition of metabolic syndrome (MetS). Endothelial dysfunction can be assessed by non-invasive pulse wave velocity (PWV) measurement, which is an arterial stiffness influencing factor. This research aimed to determine the correlation of influencing factors in regard to metabolic syndrome and HbA1c in relation to vascular stiffness as measured by baPWV value in T2DM-Mets. The research was conducted at the Diabetes Outpatient Clinic of Dr. Sutomo General Hospital Surabaya and six Primary Healthcare clinics in Surabaya from December 21, 2010 - March 21, 2012. Subjects fulfilling the inclusion and exclusion criteria were measured with regard to blood pressure, BMI, waist circumference, laboratory examination: Fasting plasma glucose, Post prandial glucose, Hemoglobin A1c and ba-PWV measurements with V Serra-1000 devices. A total of 33 patients with T2DM met the inclusion and exclusion criteria. The result of the statistical analysis shows that there is a significant correlation between the HbA1c value and ba-PWV (p = 0.036). Other influencing factors exhibited a non-significant correlation with vascular stiffness (p >0.05). The contribution of metabolic syndrome and HbA1c influencing factors was 4.6% with respect to vascular stiffness (Adjusted R2 = 0.046). Together the influencing factors in regard to metabolic syndrome and HbA1c had no significant effect on vascular stiffness (p = 0.584). HbA1c is the influencing factor that has the greatest effect on vascular stiffness. There was a significant correlation between HbA1c and vascular stiffness as measured by baPWV compared with other metabolic syndrome components. The contribution of influencing factors in regard to metabolic syndrome and HbA1c was 4.6% against vascular stiffness. Hemoglobin A1c is the influencing factor that has the greatest effect on vascular stiffness

In-Vitro Differentiation Adipose-Derived Mesenchymal Stem Cells into Pancreatic Progenitor Cells

Background: Adult stem cells are currently reliable sources of mesenchymal stem cells for regenerative therapy, include diabetes mellitus. The aim of this study is to develop endocrine pancreatic progenitor cells characterized by Pdx1 and insulin expression from rat adipose-derived mesenchymal stem cells using two steps in-vitro differentiation. Methods: In this experimental study, ADMSCs were isolated from rat adipose tissue and exposed to insulinogenic differentiation medium containing nicotinamide, activin A and glucagon-like peptide-1 (GLP1). After induction, the existence of pancreatic progenitor cells (PPCs) was confirmed by immune-staining assay of Pdx1 and insulin. Results: After three weeks of in-vitro differentiation, expression of Pdx1 and insulin proteins showed up as green in the immunofluorescence assay. Immunofluorescence intensity of Pdx1 was higher in PPCs than in ADMSCs control (p<0.05). Immunofluorescence intensity of insulin was also higher in PPCs than in ADMSCs control (p<0.05). Therefore, in-vitro differentiation was successful to develop PPCs from rat ADMSCs Conclusion: This study has demonstrated the in-vitro differentiation of ADMSCs into PPCs that expressed Pdx1 and insulin