Emerging Therapeutic Potential of Mesenchymal Stem/Stromal Cells in Preeclampsia.

PURPOSE OF REVIEW: Preeclampsia is a dangerous pregnancy condition affecting both the mother and offspring. It is a multifactorial disease with poorly understood pathogenesis, lacking effective treatments. Maternal immune response, inflammation and oxidative stress leading to endothelial dysfunction are the most prominent pathogenic processes implicated in preeclampsia development. Here, we give a detailed overview of the therapeutic applications and mechanisms of mesenchymal stem/stromal cells (MSCs) as a potential new treatment for preeclampsia. RECENT FINDINGS: MSCs have gained growing attention due to low immunogenicity, easy cultivation and expansion in vitro. Accumulating evidence now suggests that MSCs act primarily through their secretomes facilitating paracrine signalling that leads to potent immunomodulatory, pro-angiogenic and regenerative therapeutic effects. MSCs have been studied in different animal models of preeclampsia demonstrating promising result, which support further investigations into the therapeutic effects and mechanisms of MSC-based therapies in preeclampsia, steering these therapies into clinical trials.

ADIPONECTIN AS A POTENTIAL BIOMARKER OF LOW BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN WITH METABOLIC SYNDROME.

CONTEXT: Adiponectin is an abundant adipokine, which has antiinflammatory, anti-atherosclerotic and vasoprotective actions, and potential antiresorptive effects on bone metabolism. It seems to be directly involved in the improvement and control of energy homeostasis, protecting bone health and predicting osteoporotic fracture risk. OBJECTIVE: To examine the relationship between adiponectin level and bone mineral density (BMD) in post-menopausal women with metabolic syndrome (MetS) and low BMD, and to estimate the prognostic significance of adiponectin in osteoporosis. DESIGN: Clinical-laboratory cross-sectional study including 120 middle-aged and elder women (average 69.18±7.56 years). SUBJECTS AND METHODS: The anthropometric parameters were measured for all examinees. Lumbar spine and hip BMD, as well as body fat percentage, were measured using a Hologic DEXA scanner. In all subjects serum adiponectin concentration was measured by ELISA method. RESULTS: The level of adiponectin was significantly positively correlated with BMD-total, BMD of the lumbar spine and BMD of the femoral neck (r=0.618, r=0.521, r=0.567; p<0.01). Levels of adiponectin and BMD are significantly lower in post-menopausal women with MetS and osteoporosis compared to patients with osteopenia (856.87±453.43 vs. 1287.32±405.21 pg/mL, p<0.01; BMD, p<0.05), and the highest values in healthy examinees. A cut-off value of adiponectin level for osteoporosis/osteopenia was 1076.22/1392.74 pg/mL. CONCLUSIONS: Post-menopausal women with MetS have significantly lower adiponectin level and low BMD compared to healthy examinees. Adiponectin may be an early, significant and independent predictor of developing osteoporosis in women with MetS, especially in post-menopausal period.

Musculoskeletal Pain and Vitamin D Deficiency in Children: A Pilot Follow-up Study of Vitamin D Therapy in Musculoskeletal/Orthopedic Conditions.

PURPOSE OF THE STUDY: The prevalence of vitamin D deficiency in pediatric populations is high. In the present study we analyzed associations between vitamin D therapy and pain, mobility, fatigue, and daily functioning in children with musculoskeletal/orthopedic conditions suffering from chronic and recurrent pain, but also diagnosed with vitamin D deficiency. MATERIAL AND METHODS: Children with different musculoskeletal/orthopedic conditions and vitamin D deficiency were prescribed to receive vitamin D over 6 months. Thirty-five children (18 males; age 10.48 ± 3.87 years) completed a 6-month follow-up. Self- and parent/proxy rating scales were used to evaluate pain, movement, fatigue, and daily functioning. RESULTS: At a six-month follow-up assessment involving child- and parent-reported scores, worst pain intensity significantly decreased (p ≤ 0.03) after vitamin D therapy, as well as functioning problems related to pain (p ≤ 0.01). The children reported better movement and balance with less fatigue. The parents reported better functioning in everyday activities of their children. CONCLUSION: This pilot study showed that vitamin D therapy possibly reduces pain intensity and improves mobility and daily functioning in children with musculoskeletal/orthopedic disorders, chronic recurrent pain, and vitamin D deficiency. Further follow-up and randomized studies are required in order to assess the validity of clinical recommendations.

Gitelman's syndrome as a cause of poorly controlled hypokalemia.

Gitelman's syndrome is a rare autosomal recessive tubulopathy caused by a defect of the thiazide-sensitive sodium chloride co-transporter at the distal tubule, leading to hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria and low-to-normal blood pressure. Clinical features include transient periods of muscle weakness and tetany, dizziness, abdominal pains and constipation. Patients can also present with convulsions due to severe metabolic alkalosis or hypomagnesemia. Therefore, early recognition and treatment are important. Diagnosis of Gitelman's syndrome is usually made incidentally during adolescence or early adulthood based on clinical and biochemical findings. In this paper we present the case of a 23-year-old female patient referred to our nephrology department for severe hypokalemia. Complementary evaluation revealed hypokalemia, hypomagnesemia, metabolic alkalosis, increased chloride and sodium urinary excretion and reduced urinary calcium excretion with normal renal function. A diagnosis of Gitelman syndrome was established. Treatment included magnesium and potassium salts and potassium saving diuretics. In general, the long-term prognosis of Gitelman's syndrome is good if the patient adhere with the treatment.

The glassy behaviour of poorly crystalline Fe2O3 nanorods obtained by thermal decomposition of ferrous oxalate.

Nanorod ferrous oxalate dihydrate (FeC2O4 × 2H2O) which had been synthesized by the microemulsion method, was used as a precursor in the thermal decomposition process performed in air atmosphere. The formation of nanocrystalline hematite as the final product was preceded by the appearence of an intermediate product. Comprehensive study comprising several complementary techniques (x-ray diffraction, transmission electron microscopy, selected area electron diffraction, thermogravimetric/differential thermal analyses and SQUID magnetometry) confirmed that the intermediate product corresponds to the poorly crystalline Fe2O3. Due to the specific nanorod shape and poorly crystalline structure, the investigated Fe2O3 showed high coercive field value of ~0.5 T at 5 K. Special attention in this study was devoted to the peculiar magnetic properties of poorly crystalline Fe2O3, which were thoroughly investigated by employing sophisticated experimental procedures such as relaxation of thermoremanent magnetization for different cooling fields, zero field and field cooled memory effects as well as aging experiments for different waiting times. At low temperatures and weak applied magnetic fields, the investigated system behaves similarly to spin glasses, manifesting slow, collective relaxation dynamics of magnetic moments through memory, rejuvenation and aging effects.

Genetic detection of Dobrava-Belgrade hantavirus in the edible dormouse (Glis glis) in central Serbia.

Hantaviruses are endemic in the Balkans, particularly in Serbia, where sporadic cases and/or outbreaks of hantaviral human disease have been reported repeatedly, and evidenced serologically. Here, we present genetic detection of Dobrava-Belgrade virus (DOBV) hantaviral sequences in wild rodents trapped in central Serbia. All the animals were pre-screened serologically by indirect immunofluorescence (IF) test and only those with a positive finding of hantaviral antigens were further tested by polymerase chain reaction. Of the total of 104 trapped animals, 20 were found to be IF positive and of those three were positive for hantaviral RNA: one Microtus arvalis for Tula virus, and one each of Apodemus agrarius and Glis glis for DOBV. Phylogenetic analysis of the obtained sequences implies putative DOBV spillover infection of A. agrarius and G. glis from Apodemus flavicollis. However, future investigations should help to identify the most common natural host and geographical distribution of DOBV in its reservoir hosts in Serbia.

Genetic analysis of Dobrava-Belgrade virus from western Serbia--a newly detected focus in the Balkan Peninsula.

Dobrava-Belgrade virus (DOBV) is a hantavirus species that causes the most severe form of haemorrhagic fever with renal syndrome (HFRS) in Europe. DOBV has been detected in three Apodemus rodents: A. flavicollis, A. agrarius and A. ponticus. These emerging viruses appear throughout the Balkan Peninsula including Serbia as its central part. In this study, we examined the seroprevalence, molecular epidemiology and phylogenetics of DOBV from A. flavicollis captured at six Serbian localities. Furthermore, we applied microsatellite typing of host animal genome to analyse the role of host kinship in DOBV animal transmission. The overall IgG seropositivity rate over 3 years (2008-2010) was 11.9% (22/185). All seropositive samples were subjected to RT-PCR and DNA sequencing for S and L genome segments (pos. 291-1079 nt and 2999-3316 nt, respectively). DOBV was genetically detected in three samples from mountain Tara in western Serbia, a newly detected DOBV focus in the Balkans. No sequence data from human cases from Serbia are available for the studied period. However, collected DOBV isolates in this work phylogenetically clustered together with isolates from Serbian human cases dating from 2002, with 1.9% nucleotide divergence. We determined the level of kinship between seropositive and seronegative animal groups and found no significant difference, suggesting that horizontal virus transmission in the studied population was the same within and among the hatches. Our findings are the first genetic detection of DOBV in rodents in Serbia. We confirm wide and continuous hantavirus presence in the examined parts of the Balkans, underlying the necessity of continual monitoring of hantavirus circulation in A. flavicollis.

Is there a correlation between molecular markers and response to neoadjuvant chemoradiotherapy in locally advanced squamous cell esophageal cancer?

PURPOSE: To evaluate the expression of epidermal growth factor receptor (EGFR), p53, p21 and thymidylate synthase (TS) in a pretherapy biopsy specimen of locally advanced squamous cell esophageal cancer and correlate these markers with response to neoadjuvant chemoradiotherapy. METHODS: Sixty-two patients with histopathologically proven locally advanced (T3 or greater) squamous cell esophageal cancer were enrolled. The expression of EGRF, p53, p21 and TS markers was assessed with immunohistochemistry. Semiquantitative assessment of expression of these markers was performed based on the percent of the stained cells. Radiotherapy (45-50.4 Gy) was delivered concomitantly with 5-fluorouracil (5-FU)/leucovorin (LV)/cisplatin (CIS) chemotherapy. Five to 6 weeks after chemoradiation, response to treatment was assessed. Medically fit and operable patients were operated. The resected material underwent histopathological evaluation of tumor expansion, histological classification after initial multimodality treatment (yp TNM), residual status and tumor regression grade (TRG). RESULTS: Out of 62 patients enrolled, 41 (66%) were evaluated for molecular markers. Clinical response rate was 43.9%. Out of 41 patients, 12 (29%) underwent surgery. TRG 1 was noted in 58% of the patients. In a pretherapy tumor specimen, positive expression was noted in 80, 90, 80 and 71% for EGFR, p53, p21 and TS, respectively. We noted no statistically significant difference neither between tumor marker expression and clinical response to chemoradiation, nor between tumor marker expression and TRG. CONCLUSION: We registered no difference in response to treatment between EGFR, TS, p21 and p53 positive and negative staining.

Volume changes of corpus striatum, thalamus, hippocampus and lateral ventricles in posttraumatic stress disorder (PTSD) patients suffering from headaches and without therapy.

BACKGROUND AND AIM: In the present study, we have hypothesized that volume changes of the caudate nucleus, putamen, globus pallidus, hippocampus, thalamus, and lateral ventricle in newly-diagnosed, male PTSD patients without therapy are more pronounced in those with headaches. To confirm or reject our hypothesis, we have undertaken an extensive study of forty-nine PTSD patients. PATIENTS AND METHODS: To confirm or reject our hypothesis, we have undertaken an extensive study of forty-nine PTSD male patients that underwent MRI scanning immediately upon admittance for the treatment. Based on headache frequency, they were classified into three groups: group 1 included patients with headaches at least twice a week; group 2 consisted of patients with headaches less than twice a week; and group 3 consisted of patients without headaches. All MRI scans underwent software-based volume compute and statistical processing. RESULTS: 39 out of 49 patients with PTSD suffered from headaches. Bilaterally, volume decreases were noted in groups 1 and 2 compared to group 3 for the caudate nucleus, putamen, hippocampus and lateral ventricle. Differences in globus pallidus and thalamus among groups appeared to be insignificant. CONCLUSION: The present study revealed a bilateral volume decrease of the caudate nucleus, putamen and hippocampus in PTSD male subjects without therapy. Intensity of volume alterations correlated with Hamilton's depression rating score; regression analysis uncovered correlated changes in the caudate nucleus, putamen and hippocampus, and an inverse correlation with the volume of the lateral ventricle in the PTSD patients.

[Challenges and advances in the care of injuries in the Republic of Serbia].

There are many problems that trauma care system in Serbia is facing today. Few of them are: 1) Lack of categorization of trauma centers; 2) Diversity in managing of trauma patients among institutions; 3) There is no trauma management training, 4) Inappropriate cooperation between pre hospital trauma care and hospital trauma care; 5) There is no standard in managing of trauma patients as well as procedures. To improve trauma care quality throughout the country we must learn from the experiences of other countries. The aim of this paper was to report representative data about organization, management, stuff and equipment of ambulance and emergency services in Serbia. We analyzed 12 out of 138 parameters we obtained from the relevant institutions.

[Damage control surgery in abdominal trauma].

The damage control laparotomy is an advancement in the management of massively injured trauma patients. Massive liver injuries, pelvic trauma and some retroperitoneal injuries are some of the indications for this approach. The damage control laparotomy is the phased approach to severe abdominal injury that might best be described with the acronym STIR (Staged Trauma Injury Repair). The initial procedure requires rapid abdominal exploration with hemorrhage and contamination control, using suture repair combined with abdominal packing. Temporary abdominal wall closure without tension is recommended. After abrevated initial surgical procedure, the patient is transferred to the intensive care unit where continued resuscitation is performed. Careful replacement of blood and blood products along with correction of hypothermia, acidosis and optimalization of oxygen transport represents a critical phase in this management approach. Once the coagulation profile has normalized, planned re-intervention, with repeat abdominal exploration to remove the packs and perform definitive surgical repair and reconstruction takes place. When applied judiciously, the damage control laparotomy with the staged abdominal repair and reconstruction for severe trauma is associated with an improved outcome in the selected group of patients.

[Current trends in surgical treatment of radial nerve injuries associated with injuries of the humerus].

Radial nerve is the most common injured peripheral nerve after bone and wrist injuries in human body. Radial nerve can be injured by force causing fracture of the humeral shaft, due to compound fracture of the bone or by direct injury with small fragments of the bone. This happen in of cases and in remaining caseswas caused by manipulation during the treatment of the fracture of the humeral shaft. Because of the possibility of spontaneous recovery, indication and timing of surgical treatment of the radial nerve still remain controversial. There is contradictory approach in the treatment of the injured radial nerve. In a period betwen 1979 and 2005 year we have operated 193 patients with injury of radial nerve. Among them, 97 (50.2%) have had combined injury of the humeral shaft or proximal part of radius. Rest of injuries of the radial nerve were associated with manipulation during treatment. Surgical treatment has been performed in a period between three and four months after neurological deficit. Analysing our result regarding recovery of the motor function we have used combination of gradation including British Medical Council Score and modified Highet Scale to obtain satisfactory analysis of useful functional recovery of motor function after surgical procedure. We have classified results as bad M O-2 for all muscles innervated by the radial nerve; satisfactory M3, for extensors of the wrist and fingers and M O-2 for abductor of the thumb, good M 4-5 extensors of the wrist and fingers and M3 for abductor of the thumb, and excellent M 4-5 for all muscles.

[Postoperative use of nonsteroidal anti-inflammatory agents in orthopedic surgery].

Nonsteroidal antiinflamatory drugs (NSAIDs) lead to satisfactory acute and chronic pain relief. Besides that, they exert potent antiinflamatory effect. Their analgesic potency is dose related and limited. Orthopedic patients are often on these medications preoperatively and experience opioid-sparing effect in the postoperative period. Chronic NSAIDs use is related to higher rate of sistemic adverse effects, but even short time exposure in the postoperative period is not risk-free. Although Coxibs reduce GIT bleeding incidence due to prolonged use of NSAIDs, there has to be judicious decision considering their cardiovascular adverse effects. There is evidence that NSAIDs producing moderate, dose-dependent increased bleeding time within normal values. High risk of bleeding have patients with established coagulopathy, alcohol abuse and on anticoagulant treatment. There is no strong evidence on influence of NSAIDs on bone growth. Nevertheless, there is evidence that NSAIDs do prevent heterotropic ossification. Prostaglandins are vital contributors for maintainig tissue homeostasis and NSAIDs use can lead to many unwanted effects. Those adverse effect are more common with prolonged exposure, are dose-related and risks have to be carefully and individually assesed in the postoperative pain management.

[Topographic localisation of insertion of the anterior cruciate ligament].

INTRODUCTION: Determining the center of tibial insertion of the anterior cruciate ligament is important during reconstruction ligament. AIM: Determining the center of insertion of the anterior cruciate ligament on the anterior intercondylar area relate to anterior and medial edge of the upper end of tibia. MATERIAL AND METHODS: The messurement has been done on 102 tibia. We measured distance from the center of ACL to anterior and medial edge of the uper part of tibia, and the lenght and the width of the tibial insetion. Also, we showed the procentual ratio these distances with medio-lateral and anteroposterior diametar of upper tibial part. RESULTS: The distance between the centre of attachment and medial edge is at 39% from entire latero-medial diametar, while the distance from anterior edge is at 31% from entire anterio-posterior diametar. The possitive correlation between the distance of centar of the anterior cruciate ligament from anterior and inner edge (r = 0.366, p) was found. CONCLUSION: The center of the attachment of the ACL at anterior intercondylarl area is at 1/3 of antero-posterial diametar behind the anterior edge of the upper part of tibia and 2/5 of latero-medial diametar inside from the medial edge.

[The position of anterior cuciate ligament in frontal and sagittal plane].

INTRODUCTION: Position of the anterior cruciate ligament (ACL) represents one of the anatomical factors which can lead to the rupture of the ligament. AIM: The aim of this study was to overview and compare gender and age differences of the position of the ACL and its relation with the medial aspect of the lateral femoral condyle. METHOD: The measurements were performed on the fifty cadaver knees (32 male and 18 female) aged between 15 - 53 years with intact ACL. We were measuring the angle of the ACL in sagittal and frontal plane and the angle of the medial aspect of the lateral condyle in frontal and horizontal plane. RESULTS: Measurements of the ACL in sagittal plane and measurements of the angle of the medial aspect of the lateral femoral condyle in horizontal plane showed statistically significant variations with the age (p < 0.05 and p < 0.01, respectively). The angle of the medial aspect of the lateral femoral condyle in frontal plane was statistically significant higher than the same measured angle in the horizontal plane ( p < 0.01). CONCLUSION: ACL fomis narrower angle with medial aspect of the lateral femoral condyle in extension of lower leg than in flexion as a result of smaller angle of the medial aspect of the lateral femoral condyle in frontal compared to horizontal plane.

[Open fracture of the shin as an occupational injury and work capacity evaluation--case report].

Injuries at work (occupational injuries) represent a big social and economic problem. This case report presents the patient who suffered occupational injury--open fracture of the left shin. He has been hospitalized for several times at Orthopedic-Surgical Hospital "Banjica" and underwent several surgical procedures, physical therapy and Hyperbaric Oxygen Therapy. After this treatment, he was hospitalized at Institute of Occupational Health for disability evaluation and work capacity evaluation.

[Morphometric parameters of the intercondylar notch, gender and age differences].

INTRODUCTION: Narrow intercondylar notch of femur can lead to lean anterior cruciate ligament on femur's condyle, constraint and rupture. PURPOSE: Purpose of this study is description and comparasion gender and oldage differencies of morphometric factors of intercondylar notch important for rupture LCA. METHOD: The measurements were taken on 50 cadaverous knees (32 male and 18 female) with intact anterior cruciate ligament, aged from 15 to 53 years. We measured intercondylar height and epicondylar width, intercondylar width, width of lateral and medial condyle in level of popliteal sulcus and on the widest place of the distal part of femur. We calculated notch width (NWI) and notch shape (NSI) indices from absolute measurements. RESULTS: Notch width and epicondylar width, have larger values (p < 0.01) on the male (22.3 i 79.6 mm) than the female (18.2 i 68.7 mm). There is no statistical significant differences (p < 0.05) about notch width and notch shape indices between male (NWI: 0.28; NSI: 0.77) and female (NWI: 0.27; NSI: 0.68). Aging epicondylar width rise.

Functional characterization of the muscarinic receptors involved in endothelium-dependent relaxation in isolated canine uterine artery.

Acetylcholine interacts with endothelial muscarinic receptors releasing nitric oxide and causing vasodilatation. To identify the receptor subtype responsible for acetylcholine-induced relaxation in canine uterine artery, the usual organ bath method for in vitro investigation on isolated blood vessels was applied. Using a range of muscarinic receptor antagonists such as atropine (nonselective), pirenzepine (M(1)-selective), methoctramine (M(2)-selective) and p-fluoro-hexahydro-sila-difenidol (p-FHHSiD) (M(1)/M(3)) and determining pA2 value of those antagonists through Shild analysis, we aimed at establishing a precise receptor mechanism underlying acetylcholine-induced relaxation in isolated canine uterine artery. The relaxation of uterine arterial rings in response to acetylcholine in the presence or absence of selective muscarinic receptors antagonists was calculated using concentration response curves. Acetylcholine induced concentration-dependent and endothelium-dependent relaxation of arterial rings precontracted with phenylephrine (pEC(50) = 6.90 +/- 0.02). Muscarinic receptors antagonists atropine, pirenzepine, methoctramine and p-FHHSiD competitively antagonized the response to acetylcholine and obtained pA(2) values were 9.91 +/- 0.06, 6.60 +/- 0.04, 6.21 +/- 0.08 and 8.05 +/- 0.1, respectively. This study showed that acetylcholine induced endothelium-dependent relaxation of canine uterine artery by stimulation of muscarinic receptors localized on the endothelial cells. On the basis of differential antagonist affinity, we suggest that the muscarinic receptors involved in the acetylcholine-induced relaxation of canine uterine artery are predominantly of M(3) subtype.

[Preoperative chemoradiotherapy in locally advanced esophageal cancer].

Preoperative or definitive chemoradiotherapy defines today the standard treatment of patients with localized or locally advanced esophageal cancer. Preliminary results of our study are presented. 46 patients with locally advanced squamous cell esophageal cancer (T3-4, N0-1, M0) were enrolled. All patients recieved concomitant chemotherapy (Cisplatin/5FU/LV) and radiotherapy (45-50, 4Gy). Clinical response rate was 59% (3 patients (7%) complete response, 24 patients (52%) partial regression, 13 (28%) stabile disease, 6 patients (13%) disease progression). Out of 46 patients, 12 were operated (26%), all with R0 resection. Complete patohistolgical regression (TRG 1) was noted in 5 patients (42%). TRG 2 i TRG 3 in one (8%) and 3 patients (25%), and TRG 4 in 3 patients (25%). Mean survival time in operated group of patients was 9.3 months, and in nonoperated group 5.5 months. Studies show improved survival rate in patients with complete response to chemoradiotherapy and R0 resection. Individualy tailored therapy is essential.

[Influence of morphometric intercondylar notch parameters in ACL ruptures].

The most important anatomic risk factors in ACL lesions are the morphometric parameters of intercondylar notch. In the morphometric studies index of notch width and index of notch shape (NWI and NSI) are commonly used. The certain morphologic parameters of distal femoral part are used in calculation. Beside standard parameters we measured the maximal width of intercondylar notch and distal part of femur, which we used for calculation of maximal index of notch width and maximal index of notch shape (NWI max and NSI max). We compared two different methods of calculation of intercondylar notch indexes to find out which one represent anatomic risk factor and influence the ACL lesions. The indexes were measured in the two groups of patients (33) who have the history of knee injuries, the first group has document of ACL injuries and the second without ACL injuries (control one). The important difference between two groups was founded in NWI (p < 0.01) and NSI (p < 0.05). NWImax and NSImax do not show the difference (p > 0.05). The NWI and NSI importance is higher in males, and smaller in females. There is no difference in NWImax and NSImax (p > 0.05) comparing to the gender.