Challenging Treatment of a Female Patient with Extensive Fournier's Gangrene - Case Report.

Fournier's gangrene (FG) is a necrotizing fasciitis of the genital, perianal and perineal regions, caused by multiple anaerobic/aerobic infection. It is a rare but very serious condition with multiple long-term complications and high mortality rate. Early diagnosis and multidisciplinary approach in treatment of complicated cases of FG are crucial to the successful outcome. We report a case of an extensive FG in a 59-years-old female patient with multiple risk factors such as obesity, type 2 diabetes and hypertension. She was hospitalized as an emergency case with diabetic ketoacidosis, sepsis and extensive necrotic lesions located perineal, perianal, genital and spread to inguinal, hypogastric, gluteal and sacrococcygeal region. Fournier's gangrene was diagnosed, and after prompt resuscitation, intravenous fluids, broad-spectrum antibiotics, insulin infusion, emergency aggressive surgical debridement was performed. Several aerobic and anaerobic bacteria were isolated from wound culture and hemoculture. Patient has second debridement after four days. After second debridement was applied metabolic control, broad-spectrum antibiotics coverage, dressing the wound and negative pressure wound therapy (NPWT). Patient was discharged home five weeks after a second debridement in good condition. One month later she underwent reconstructive surgical treatment. Besides extensive FG and multiple comorbidity she was successfully managed with good outcome. Fournier's gangrene remains a life-threatening and fulminant disease which need urgent diagnosis and aggressive medical and surgical treatment, to achieve a reduction in long term complications and mortality rate.

Urinary Nephrin and Podocalyxin Levels as Predictors of Pre-eclampsia in High-Risk Pregnant Women.

INTRODUCTION: Pre-eclampsia (PE) is characterized by new-onset hypertension and proteinuria. Damage of podocyte cells has been reported in pre-eclamptic women, thus podocyte specific proteins such as nephrin and podocalyxin could be useful biomarkers in PE. AIM: To investigate the role of urinary nephrin (u-nephrin) and urinary podocalyxin (u-PDX) levels in predicting PE in women with a high-risk pregnancy. MATERIALS AND METHODS: We included 101 pregnant women in this study and allocated them into three groups: group 1 included pregnant women at high risk of developing PE (n=41), group 2 - pregnant women with PE (n=30), and group 3 was the controls including healthy pregnant women (n=30). The inclusion criteria for women with PE were de novo hypertension >140/90 mm Hg, proteinuria >300 mg/24 hours, and presence of edema after 20 weeks of gestation, while the exclusion criteria were a history of renal diseases and pregnant women younger than 18. Inclusion criteria for the group of women with a high-risk pregnancy was gestational week >15, a history of PE in a previous pregnancy, pre-existing diabetes type 1 or 2, pre-existing hypertension, multiple gestations, prior placental abruption, obesity women, nulliparity, maternal age >35 years, and a family history of PE. The study was conducted from March 2016 to May 2017 in the Medical Faculty at the Institute of Medical and Experimental Biochemistry in Skopje. Urine samples were used to measure the nephrin and podocalyxin levels using immunoenzyme assay, creatinine and microalbumin. Blood samples were collected for biochemical analyses. RESULTS: U-nephrin levels were elevated in 96.7% of women with PE, and 73% of women with a high-risk pregnancy. U-PDX levels were elevated in 63% of the women with PE and 100% of the women with a high-risk pregnancy. U-nephrin and u-PDX levels were significantly increased in women with a high-risk pregnancy and women with PE compared with a control group (p.

Urinary nephrin is earlier, more sensitive and specific marker of diabetic nephropathy than microalbuminuria.

BACKGROUND: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. Progressive damage and decline in the number of podocytes often occur in the early stages of DN. Thus, nephrin as a podocyte-specific protein may be regarded as a potential biomarker of early detection of DN. The aim of this study is to determine whether urinary nephrin is an earlier marker in DN than microalbuminuria and to test the significance of urinary nephrin as a marker for early detection of DN. METHODS: Our cross-sectional study included 90 patients with type 2 diabetes mellitus (T2DM), 30 patients with diagnosed DN and 60 patients without diagnosed DN. As a control group, we used 30 healthy subjects. All patients with T2DM were classified into three subgroups according to urinary microalbumin/creatinine ratio (UMCR): normoalbuminuric, microalbuminuric and macroalbuminuric patients. Nephrin in urine was measured by immunoenzyme assay, microalbumin with turbidimetric and creatinine with the photometric method. In blood sera, we measured a few standard biochemical parameters. RESULTS: Nephrinuria was found to be present in 100% of patients with T2DM and macroalbuminuria, in 88% with microalbuminuria, as well as 82% of patients with T2DM and normoalbuminuria. A concentration of urinary nephrin was significantly increased in all groups of subjects with T2DM compared to the control group (p<0.05). Nephrinuria correlated statistically negative with eGFR (r=-0.54). ROC analysis showed that nephrin has a total predicted probability of 96% in patients with DN. CONCLUSIONS: Urinary nephrin is earlier, more specific and sensitive marker than microalbumin in early detection of DN.

Lipoprotein(a) - Link between Atherogenesis and Thrombosis.

Lipoprotein(a) - Lp(a) - is an independent risk factor for cardiovascular disease (CVD). Indeed, individuals with plasma concentrations of Lp(a) > 200 mg/l carry an increased risk of developing CVD. Circulating levels of Lp(a) are remarkably resistant to common lipid lowering therapies, currently available treatment for reduction of Lp(a) is plasma apheresis, which is costly and labour intensive. The Lp(a) molecule is composed of two parts: LDL/apoB-100 core and glycoprotein, apolipoprotein(a) - Apo(a), both of them can interact with components of the coagulation cascade, inflammatory pathways and blood vessel cells (smooth muscle cells and endothelial cells). Therefore, it is very important to determine the molecular pathways by which Lp(a) affect the vascular system in order to design therapeutics for targeting the Lp(a) cellular effects. This paper summarises the cellular effects and molecular mechanisms by which Lp(a) participate in atherogenesis, thrombogenesis, inflammation and development of cardiovascular diseases.

Establishment of an EC50 database of pesticides using a Vibrio fischeri bioluminescence method.

An EC50 database was established to assess the acute toxicity of 16 PESTANAL pesticide standards and of seven pesticide commercial formulations using a Vibrio fischeri bioluminescence method. Half maximal effective concentration (EC50 ) is defined as the concentration of pollutant (in this case, pesticide) destroying 50% of the bacteria population and causing 50% bioluminescence inhibition, after a specified exposure time. Linear curves of bioluminescence inhibition versus pesticide concentration and EC50 values were obtained for exposure times (t) of 5 or 15 min for these pesticides. The EC50 values ranged from 6.90 × 10-4 to 0.83 mg/ml (t = 5 min), and from 9.00 × 10-4 to 0.37 mg/ml (t = 15 min) for pesticide standards, plus from 0.0077 to 0.74 mg/ml (t = 5 min), and from 0.0076 and 0.57 mg/ml (t = 15 min) for pesticide commercial formulations. The EC50 database allowed classification of the pesticides under study into three categories according to their toxicity: very toxic, toxic and moderately toxic. These results demonstrated that the establishment of an EC50 database and of linear curves of bioluminescence inhibition versus the pesticide concentration resulted in very important and irreplaceable tools to estimate the global and individual toxicity of pesticides present in environmental samples.

High-density lipoprotein metabolism and reverse cholesterol transport: strategies for raising HDL cholesterol.

A key to effective treatment of cardiovascular disease is to understand the body's complex lipoprotein transport system. Reverse cholesterol transport (RCT) is the process of cholesterol movement from the extrahepatic tissues back to the liver. Lipoproteins containing apoA-I [highdensity lipoprotein (HDL)] are key mediators in RCT, whereas non-high-density lipoproteins (non-HDL, lipoproteins containing apoB) are involved in the lipid delivery pathway. HDL particles are heterogeneous; they differ in proportion of proteins and lipids, size, shape, and charge. HDL heterogeneity is the result of the activity of several factors that assemble and remodel HDL particles in plasma: ATP-binding cassette transporter A1 (ABCA1), lecithin cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), hepatic lipase (HL), phospholipid transfer protein (PLTP), endothelial lipase (EL), and scavenger receptor class B type I (SR-BI). The RCT pathway consists of the following steps: 1. Cholesterol efflux from peripheral tissues to plasma, 2. LCAT-mediated esterification of cholesterol and remodeling of HDL particles, 3. direct pathway of HDL cholesterol delivery to the liver, and 4. indirect pathway of HDL cholesterol delivery to the liver via CETP-mediated transfer There are several established strategies for raising HDL cholesterol in humans, such as lifestyle changes; use of drugs including fibrates, statins, and niacin; and new therapeutic approaches. The therapeutic approaches include CETP inhibition, peroxisome proliferator-activated receptor (PPAR) agonists, synthetic farnesoid X receptor agonists, and gene therapy. Results of clinical trials should be awaited before further clinical management of atherosclerotic cardiovascular disease.

Acute Kidney Injury in Newborns.

OBJECTIVE: Acute kidney injury is common condition in the neonatal intensive care unit and it is associated with poor outcome. The incidence of neonatal AKI is the highest one followed by adults and children, depending on different factors such as the gestational age, birth weight, contributing conditions and the facilities of the neonatal intensive care unit. The aim of the study was to determine the incidence, risk factors and the outcome of the neonatal acute kidney injury. SUBJECTS AND METHODS: This was a clinical, prospective study that was performed in a referent NICU at the University Children's Hospital in Skopje. All neonates admitted from January 2012 to December 20014 with documented acute kidney injury were included. The medical data records of the admitted neonates with AKI were analyzed. The material was statistically processed using methods of the descriptive statistics. RESULTS: During the study period 770 newborn infants were admitted to the NICU and 50 (6.5%) infants developed acute kidney injury. The male to female ratio was 2.1:1. Most of the neonates involved in the study were neonates born at term (62%). Oliguric AKI was found in 28 cases (56%) and no oliguric in 22 cases (44%). The prevalence of prerenal, renal and post renal AKI were 78.5%, 19.5% and 2.0% respectively. Perinatal asphyxia was the most common predisposing factor for AKI and was evaluated in 38% of the cases with predominance of term infants and male. The mortality rate was 32% and was significantly higher in the group of patients with congenital heart diseases. CONCLUSION: AKI is a life threatening condition with still high mortality rate. Early recognition of the risk factors and the rapid effective treatment of the contributing conditions will reduce AKI in the neonatal period.

Chlamydia pneumoniae and helicobacter pylori serology - importance in patients with coronary heart disease.

BACKGROUND: Chronic infections in CHD are due to one or both of the organisms Chlamydia pneumoniae and Helicobacter pylori. AIM: To examine the association between serum markers of Chlamydia pneumoniae and Helicobacter pylori infection and markers of myocardial damage. in patients with acute coronary syndrome (ACS), with chronic coronary artery disease (CAD) and in-control group. MATERIAL AND METHODS: Sera were taken from a total of 153 subjects. Subjects were divided in three groups: 64 patients with ACS; 53 patients with CAD and a group of 35 conditionally healthy individuals. Analysis of patients' sera for IgG antibodies to H. pylori and markers for myocardial damage was done on the Immulite system. The presence of specific IgG and IgA antibodies to C. pneumoniae was determined with MIF, Sero FIA (Savyon Diagnostics, Israel). Statistical analysis of data was done using the statistical program SPSS (Statistical Package for Social Sciences), version 13. RESULTS AND DISCUSSION: There was a high significant difference in troponin levels between the three groups of subjects (p=0.0000). Levels of creatine kinase isoenzyme (CK-MB) were highest in the ACS group (500.0 ng/mL). There was a statistically significant difference between CG subjects and ACS patients due to more frequent detection of antichlamydial IgA antibodies in patients with acute coronary syndrome. Positive serum immune response for Helicobacter pylori was 17 (53.1%) and 29 (80.6%), respectively. CONCLUSION: Increased IgA antibody titers for C. Pneumoniae, increased CRP values as well as classic markers of myocardial damage are risk factors for coronary events.