Incidence and Prevalence of Vaginal Infections in Women of Reproductive Age in North Macedonia.

In the available literature on this subject there are many studies which describe the effects of sexually transmitted infections on pregnancy and fertility of women. Because of the frequency of the infections with the atypical bacteria of the Ureaplasma Spp., Mycoplasma Spp., Chlamydia Trachomatis, as well as HPV infections in women of reproductive age, it is easy to underestimate their importance when establishing the basis of the genital health of women of reproductive age. In this prospective analysis, conducted from 2014 to 2018 in the laboratory for HPV and Molecular diagnostics at the University Clinic of Gynaecology and Obstetrics in Skopje, North Macedonia, we analysed the results of 10,387 patients of all ages, of which 973 patients were of reproductive age. A Panel analysis was also conducted (including the above-mentioned pathogens). An HPV analysis was also conducted on 643 patients in this group. Within the group of 643 patients, there was a positive result for HPV in 26.7% of them, while in 40.9% there was a positive result for one or more pathogens on the Panel analysis of bacterial pathogens. The statistical analysis of the results showed that the most frequent of all bacterial pathogens within the Macedonian population of women of reproductive age is Ureaplasma Spp, with an incidence of 33%, followed by Mycoplasma Spp., with 7.8%, while Chlamydia Trachomatis was present in 6.4% of the cases. We should highlight that a co-infection with HPV was present in 18.5% of all the patients where there was analysis of both diagnostic procedures. The analysis of the results in the patients co-infected with HPV and at least one bacterial pathogen on the Panel Analysis, showed a very high statistical correlation (p<001).

Nephrinuria and podocytopathies.

The discovery of nephrin in 1998 has launched a new era in glomerular diseases research, emphasizing its crucial role in the structure and function of the glomerular filtration barrier. In the past 20 years, substantial advances have been made in understanding podocyte structure and function as well as the discovery of several podocyte-related proteins including nephrin. The glomerular filtration barrier is comprised of podocytes, the glomerular basement membrane and endothelial cells. Podocytes, with their specialized slit diaphragm, form the essential backbone of the glomerular filtration barrier. Nephrin is a crucial structural and functional feature of the slit diaphragm that prevents plasma protein, blood cell and macromolecule leakage into the urine. Podocyte damage results in nephrin release. Podocytopathies are kidney diseases in which podocyte damage drives proteinuria, i.e., nephrotic syndrome. Many kidney diseases involve podocytopathy including congenital nephrotic syndrome of Finnish type, diffuse mesangial sclerosis, minimal change disease, focal segmental glomerulosclerosis, collapsing glomerulonephropathy, diabetic nephropathy, lupus nephropathy, hypertensive nephropathy and preeclampsia. Recently, urinary nephrin measurement has become important in the early detection of podocytopathies. In this chapter, we elaborate the main structural and functional features of nephrin as a podocyte-specific protein, pathomechanisms of podocytopathies which result in nephrinuria, highlight the most commonly used methods for detecting urinary nephrin and investigate the diagnostic, prognostic and potential therapeutic relevance of urinary nephrin in primary and secondary proteinuric kidney diseases.

Role of urinary podocalyxin in early diagnosis of diabetic nephropathy.

Introduction. Podocyte injury has been reported as an early feature of DN therefore, the assessment of podocyte injury can be accomplished by estimation of podocalyxin in urine. This study aimed to estimate the urinary podocalyxin levels and to determine the sensitivity and specificity of this biomarker for early detection of DN.Materials and methods. A total of 90 patients with type 2 diabetes mellitus (T2DM) were included in this cross-sectional study. Sixty of them were without diagnosed DN, and 30 with diagnosed DN. A control group consisted of 30 healthy subjects. All patients with T2DM were divided into three subgroups according to urinary microalbumin/creatinine ratio (UM/CR): normoalbuminuric, microalbuminuric and macroalbuminuric patients. Urine samples, were used for measurement of podocalyxin by ELISA, creatinine and microalbumin. Fasting venous blood samples was collected for biochemical analyses.Results. The levels of urinary podocalyxin (u-PDX) were higher in patients with T2DM compared to control subjects and a statistically significant difference among studied subgroups regarding u-PDX was found (p < 0.05). Levels of u-PDX are increasing gradually with the degree of DN (p < 0.029). u-PDX levels were positively correlated with UM/CR (r = 0.227, p = 0.002). A cut-off level of 43.8 ng/ml u-PDX showed 73.3% sensitivity and 93.3% specificity to detect DN in early stage. A cut-off level of 30 mg/g UM/CR showed 41.5% sensitivity and 90% specificity in predicting DN. u-PDX was elevated in 48,2% of normoalbuminuric patients.Conclusion. Urinary podocalyxin be useful and more sensitive and specific marker in early detection of DN than microalbuminuria.

NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN AS AN EARLY BIOMARKER OF ACUTE KIDNEY INJURY IN NEWBORNS.

The aim of the study was to determine the incidence, risk factors and efficiency of the neutrophil gelatinase-associated lipocalin (NGAL) biomarker in early diagnosis of acute kidney injury (AKI) in newborns. The study was designed as a prospective, clinical, epidemiological investigation conducted in the period of three years, which included 50 newborns with AKI hospitalized in the Neonatal Intensive Care Unit, University Children's Hospital in Skopje. The estimated prevalence of AKI was 6.4%, while the prevalence according to RIFLE classification was 8.7%. Perinatal asphyxia was a common predisposing factor associated to kidney injury. The mortality rate was 32% and was significantly higher in the group of newborns with congenital heart diseases. There was a significant difference between NGAL values and creatinine values on the day of admission. There was a significant difference in NGAL values between newborns with AKI and lethal outcome and newborns without lethal outcome (p<0.001). In conclusion, AKI is a life-threatening condition. It is an independent contributor to mortality. Urinary NGAL is an early predictive biomarker of AKI in critically ill newborns.

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.

The Spectrum of Kidney Diseases in Children Associated with Low Molecular Weight Proteinuria.

BACKGROUND: Proteinuria, in addition to haematuria, is the most important laboratory parameter in patients with nephro-urological diseases. Low molecular weight proteinuria (LMWP) is of particular importance because some diseases genetic and tubulointerstitial are diagnosed based on its presence. AIM: The purpose of this study is to describe the clinical features, the course and outcome of pediatric patients with a renal disease associated with LMWP. MATERIAL AND METHODS: This retrospective observational study included 250 pediatric patients with various kidney diseases in which the type of proteinuria was defined by 4-20% gradient gel sodium dodecyl sulphate polyacrylamide gel (SDS-PAG) electrophoresis. RESULTS: Isolated LMWP was detected in 12% of patients, while mixed glomerulotubular proteinuria was detected in 18% of patients. It was detected in all patients with the Dent-1/2 disease, Lowe's syndrome and secondary Fanconi syndrome. Transient LMWP was also detected in a series of 12 patients with distal renal tubular acidosis. In patients with nephrotic syndrome, it was associated with corticoresistence and unfavourable clinical course. CONCLUSION: This study contributes to the understanding of the clinical spectrum of various kidney diseases associated with LMWP, their natural course, and the effect of therapy.

Incidental Detection of Dent-2 Disease in an Infant with Febrile Proteinuria.

OBJECTIVE: Febrile proteinuria is functional proteinuria and is seen as a transitory phenomenon during acute febrile illness, mainly viral infections. It is a benign phenomenon and clears promptly with resolution of the infection. CLINICAL PRESENTATION AND INTERVENTION: In this report, we present a patient who was thought to have febrile proteinuria. Persistence of significant proteinuria after resolution of the infection prompted biochemical and genetic workup which led to the diagnosis of Dent-2 disease. CONCLUSION: We recommend the use of SDS-PAGE (sodium dodecyl sulfate electropheresis) for the detection of low molecular weight proteinuria.

Effect of two laparoscopic techniques for treatment of ovarian endometrioma on ovarian reserve.

INTRODUCTION: Operative laparoscopy is the most common used technique for treatment of patients with ovarian endometriomas, because of many positive effects in comparison with laparotomy. There are many laparoscopic techniques, but most used are cystectomy and puncture with endocoagulation (ablation) of the cyst's capsule. The aim of this study was to evaluate the effect of two laparoscopic techniques for treatment of ovarian endometriomas on ovarian reserve. We used two ultrasonographic markers for ovarian reserve: ovarian volume and antral follicle count (AFC). MATERIALS AND METHODS: Sixty patients in reproductive age (18-42 years) were treated for a chronic pelvic pain or infertility in a tertiary hospital (University Clinic for Gynecology and Obstetrics in Skopje, R. Macedonia). The study was prospective and two laparoscopic techniques were used. All patients were with confirmed ultrasound diagnosis for ovarian endometriomas with diameter between 3 and 8 cm. Complete cystectomy was done in 30 patients (group A) and puncture with endocoagulation was done in other 30 patients (group B). Ovarian reserve was analyzed before surgery and was controlled one and three months after laparoscopic surgery. RESULTS: In group A (operated with cystectomy) ovarian volume was 53.46±29.97 cm³ before surgery, which fell to 13.06±7.34 cm³ after one month, and 13.28±7.17 cm³ after three months. Statistical analysis showed a significant reduction in ovarian volume one and three months after surgery (p≤0.01). In group B (operated with puncture and endocoagulation) the ovarian volume was 58.34±37.99 cm³ before surgery, which fell to 18.96±7.90 cm³ one month and 17.38±6.86 cm³ three months after surgery. In both groups there was a significant reduction in ovarian volume one and three months postoperatively (p≤0.01). In the first group AFC was 3.03±1.27 before surgery, 4.8±1.30 one month after surgery and 6.23±1.57 after three months. Statistical analysis showed a significant increase in AFC after laparoscopic cystectomy (p≤0.01). In the second group AFC was 3.07±1.05 before surgery, 5.33±1.60 after one month and 7.0±1.62 after three months. The comparison of AFC showed high statistically significant difference (p≤0.001), e.g. increase of AFC after one and three months in comparison with AFC before surgery. CONCLUSIONS: Ovarian reserve decreases after laparoscopic surgery using both laparoscopic techniques. But, this decrease was more frequent using cystectomy in comparison with ablation of the endometriotic cyst.

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.

Ovarian reserve after laparoscopic treatment of unilateral ovarian endometrioma.

AIM: To evaluate the effect of laparoscopic treatment of unilateral ovarian endometrioma on ovarian reserve using ultrasonographic markers, ovarian volume and antral follicle count (AFC), and two biochemical markers, serum levels of Follicle-stimulating hormone (FSH) and Estradiol (E2). MATERIAL AND METHODS: This prospective study included 40 patients in their reproductive age, between 18 and 40 years old. They were treated laparoscopically for unilateral ovarian endometrioma. Markers of ovarian reserve were investigated before and three months after surgery. Transvaginal ultrasound examination was used for measurement of ovarian volume and AFC. Biochemical markers (FSH and E2 levels) were determined by chemiluminescent tests. RESULTS: Ovarian volume was significantly reduced after surgery. There was significant increase of AFC and non-significant increase of E2 levels in treated patients after three months. CONCLUSIONS: Laparoscopic cystectomy of unilateral ovarian endometrioma decreased ovarian reserve immediately after surgery with decrease of ovarian volume. But ovarian reserve was increased after three months with increase of AFC and estradiol levels.

Oral findings in end-stage renal disease.

The aim of the study was to analyse and compare the most frequent clinical oral symptoms, signs and lesions at end-stage renal disease (ESRD), before kidney transplantation (BKT) and after kidney transplantation (AKT). A total of 35 subjects with ESRD were included, 19 in group A (BKT) and 16 in group B (AKT). Oral lesions were classified according to referent clinical diagnostic criteria: Serum albumins, urea, creatinine and salivary urea, creatinine uremic acid were determined by standard biochemical spectrophotometric methods (Human, Germany). For serum albumin concentration measurement (g/L) the method of bromcresol green assay was used while serum and salivary uric acid determination (µmol/L) was performed according the uricase/PAP method. Serum creatinine concentration was measured (µmol/L) with the Jaffe kinetics method, without deproteinization. Oral signs, symptoms and lesions were higher in group A: metallic taste (O.R. = 6.61/ ± 95% CI : 1.13 < O.R. < 38.69), dry mouth (O.R. = 30/ ± 95% CI : 3.15 < O.R. < 285.71), uremic stomatitis (O.R. = 6.5/ ± 95% CI : 1.47 < O.R. < 28.80 and coated tongue (O.R. = 11.73/ ± 95% CI : 2.31 < O.R. < 59.54). On the other hand, in group B, gingival enlargement (O.R. = 59.5/ ± 95% CI : 7.41 < O.R. < 478.05) was more common. High statistically significant differences were recorded between group A and B for dry mouth and gingival enlargement (p > 0.001). Blood urea, creatinine and albumin levels, as well as salivary urea creatinine and uraemic acid values, were significantly higher in group A. Chances of the appearance of all symptoms, clinical signs and lesions, except gingival enlargement, were greater in group A as against group B. Some of our findings correspond with the stage of the disease and some with the use of medicaments in treatment.

Extracts from the history and medical properties of garlic.

At the time when antibiotics and other pharmacy products did not exist, a bulb of garlic itself represented a whole pharmacy industry due to the broad spectrum of effects. Most different suppositions involving this herb are mentioned; some of them were so pointless that they disappeared in time, but some of them have remained until the present days. The garlic was given different names that are still in use such as 'Russian penicillin', 'natural antibiotic', 'vegetable viagra', 'plant talisman', 'rustic's theriac', 'snake grass' etc. Presentation of the development of ideas associated with garlic and the evolution of the notions increased the ability of the pharmacists and physicians to respond to the challenges of their professional services in facilitating human life.