Marrubium vulgare L.: A Phytochemical and Pharmacological Overview.

Marrubium vulgare is a plant with high bioactive potential. It contains marrubiin, a labdane diterpene that is characteristic for this genus, as well as a complex mixture of phenolic compounds. According to numerous studies, M. vulgare acts as a good antioxidant agent, and due to this, it could potentially be useful in treatments of cancer, diabetes mellitus, and liver diseases. In addition, its anti-inflammatory, wound-healing, antihypertensive, hypolipidemic, and sedative potential are discussed. Apart from that, its antimicrobial activity, especially against Gram+ bacteria, fungi, herpes simplex virus, and parasites such as Toxoplasma gondii, Trichomonas vaginalis, and Plasmodium berghei-berghei was recorded. Additionally, it could be used as a chicken lice repellent, herbicide, and natural insecticide against mosquito larvae and natural molluscicide. In veterinary medicine, M. vulgare can be used as an anthelmintic against the eggs and larvae of bovine strongyles parasites, and as an antibiotic against bovine mastitis caused by resistant bacterial strains. Due to the mentioned benefits, there is a tendency for the cultivation of M. vulgare in order to ensure high-quality raw material, but more firm scientific evidence and well-designed clinical trials are necessary for the well-established use of M. vulgare herb and its preparations.

St. John's Wort Herbal Teas - Biological Potential and Chemometric Approach to Quality Control.

St. John's wort has been used for centuries in traditional medicine of many cultures, and nowadays it is well-known as a clinically important antidepressant drug. Considering the rising market demand for Hyperici herba, quality control of crude drug is of paramount importance. In this paper we performed HPLC-DAD chemical profiling of St. John's wort tea samples obtained at local markets, pharmacies and health food stores in the Balkan Peninsula countries, Austria and Turkey. Furthermore, water alcoholic extracts of the collected samples were evaluated in terms of their antioxidant potential, as well as the ability to inhibit biologically important enzymes such as acetylcholinesterase, monoamine oxidases A and B (MAO-A and MAO-B), α-amylase and α-glucosidase. Significant variability within the samples in the quantities of hypericin, hyperforin, rutin, quercetin, gallic, chlorogenic, caffeic and p-hydroxybenzoic acid was noticed. Chemotaxonomic modelling enabled the identification of three clusters of samples based on the quantities of rutin, hypericin and hyperforin. Generally, the extracts exhibited a significant potential to inhibit MAO-A (median IC50 = 10.01 µg/mL) and α-glucosidase (median IC50 = 12.40 µg/mL). The results of antioxidant potential evaluation suggest strong neutralization of hydroxyl and nitroso radicals, but moderate inhibition of lipid peroxidation process. Overall, the conducted study emphasizes the possibility of St. John's wort teas quality control, taking into account unavoidable variability of chemical profile as well. The stated is of great importance when grinding degree of herbal material excludes taxonomic identification of biological origin as an option within quality control.

Cancer during pregnancy - clinical characteristics, treatment outcomes and prognosis for mothers and infants.

OBJECTIVE: To assess which obstetrical characteristics and treatment improved outcomes and prognosis of pregnant women with malignancy. METHODS: A prospective study, undertaken between 2005 and 2014, involving 35 pregnant women who were diagnosed with malignant tumors during pregnancy. Patients were followed-up for 1 year after delivery. The pregnancy course and outcome and parameters that could influence the condition of mother and fetus were evaluated. RESULTS: Most malignancies were hematological, diagnosed in the second trimester and treated with combined therapy (surgery/adjuvant) after pregnancy. Most fetuses were in good state throughout pregnancy, but were delivered by caesarean section (CS) before term. Adjuvant therapy during pregnancy mostly caused transitory deterioration of fetal conditions. The majority of both mothers and infants were in a good state 12 months postpartum, although numerous mothers were still ill and on therapy. Surviving pregnancy and preventing tumors progression during pregnancy were the best predictors of mothers' future condition (P=0.022). High birthweight and term delivery were the most important factors for good outcome of the infants (P=0.001). CONCLUSIONS: If the tumor is not progressing, pregnancy should be continued as long as possible to obtain adequate birthweight of the infant. Second trimester surgery is safe, while other therapies should preferably be applied after delivery.

Neonatal outcome in pregnant patients with antiphospholipid syndrome.

AIMS: The study aim was to evaluate pregnancy outcomes in patients with antiphospholipid syndrome (APS) and to determine which clinical parameters present risk factors for adverse pregnancy outcomes in these patients. METHODS: The study included 55 patients with APS treated at the Clinic for Ob/Gyn, Clinical Center of Serbia, from 2006 to 2012. The control group consisted of 55 healthy pregnant women. Data regarding previous pregnancies and conception method were registered. Immunological and laboratory tests were performed. Pregnancy outcomes, including miscarriage, intrauterine fetal death, hypertensive disorders, diabetes mellitus, phlebothrombosis, fetal growth restriction, premature delivery, delivery method, perinatal asphyxia, respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis were followed. RESULTS: The premature delivery rate in APS patients was 31.8%, and pregnancy loss was 18.2%. Significantly more patients with APS had thrombocytopenia, pregnancy losses, intrauterine growth restriction, and perinatal asphyxia compared with the control group. More miscarriages, preterm delivery, lower birth weight, preeclampsia, and IgM anticardiolipin antibody levels significantly correlated with adverse pregnancy outcomes. Although rare, respiratory distress syndrome can also worsen neonatal health status. According to ROC analysis, previous miscarriages correctly explained 66.3% of adverse pregnancy outcome cases. We generated four equations of adverse pregnancy outcome risk factors. CONCLUSIONS: The most important prognostic factor for pregnancy outcome in APS patients is the number of previous miscarriages. Using appropriate current therapeutic protocol can enable live birth of a healthy newborn in most cases.

The utility of human epididymal protein 4, cancer antigen 125, and risk for malignancy algorithm in ovarian cancer and endometriosis.

BACKGROUND: In women with pelvic mass, cancer antigen 125 (CA125) had not achieved satisfactory sensitivity and specificity in the detection of ovarian cancer, particularly in patients with underlying endometriosis. The aim of this study was to determine the diagnostic potential of human epididymal protein 4 (HE4), the combination of HE4+CA125, and the Risk of Ovarian Malignancy Algorithm (ROMA) for patients with pelvic mass, particularly in differentiating endometriosis from carcinoma. METHODS: A prospective cross-sectional study was conducted at the Clinic for Gynecology and Obstetrics, Clinical Center of Serbia. Serum samples were obtained preoperatively from 108 women undergoing surgery for pelvic mass; 29 of them had ovarian carcinoma, and 79 had a nonmalignant ovarian disease (39 with benign tumor, 20 with endometriosis, 20 healthy controls). Sera were analyzed for the levels of HE4 and CA125 and were then compared with the final pathologic results. The diagnostic performance of HE4 and CA125 was estimated using receiver operating characteristic curve and area under the receiver operating characteristic curve. RESULTS: The level of HE4 and CA125 was significantly higher among the patients with malignant tumors, compared with patients with nonmalignant disease. At the predefined specificity of 95%, HE4 and CA125 showed sensitivity of 65.5% and 58.6%, respectively, whereas the combination of HE4+CA125 reached 68.9% at the same specificity. Importantly, the level of HE4 did not differ significantly between the patients with endometriosis and with other nonmalignant diseases (which was not the case with CA125). Risk of Ovarian Malignancy Algorithm classified 96% of benign premenopausal cases as at low risk for ovarian cancer. CONCLUSIONS: HE4 showed satisfactory capability of distinguishing endometriosis from ovarian cancer, which CA125 lacked. The Risk of Ovarian Malignancy Algorithm score proved to be useful in excluding malignant diagnosis in premenopausal women.

Giant dermatofibrosarcoma protuberans vulvae: rare clinical presentation and literature review.

Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing fibro-cutaneous tumor of low to intermediate grade malignancy. It is characterized by local dermal and subcutaneous infiltration, but also with destructive infiltration of the surrounding tissues (muscle, fascia, and bone). The size of the tumor varies from small nodular to large neglected masses. Males and females are equally affected. The tumor is most often localized in the trunk and the proximal extremities. At a molecular level, more than 90% of all DFSP arise from the translocation of chromosomes 17 and 22. Clinically, it usually occurs in the form of flesh-colored or slightly yellow-brown skin tumor, irregular borders or multinodular appearance. The definitive diagnosis of DFSP is made by biopsy in combination with histological morphology and immunohistochemistry. The standard treatment for DFSP is surgical resection. Radiation treatment is an option for primary inoperable tumors and prior multiple recurrences. There is no consensus about chemotherapy regimens. Imatinib - a tyrosine kinase inhibitor - is approved in Europe for the treatment of inoperable primary tumors, locally inoperable recurrent disease, and metastatic DFSP. The recommended dose is 400-600 mg/daily. DFSP of the vulva is extremely rare, with less than 60 cases reported in the literature. Tumor behavior of DFSP of the vulva does not differ from other DFSP localizations. Spontaneous regressions are common while distant metastases are rare. Multidisciplinary approach requiring wide resection, margin assessment and reconstruction is the therapy of choice.

Analysis of urologic complications after radical hysterectomy.

OBJECTIVE: Injuries of the ureter or bladder or development of vesicovaginal and ureterovaginal fistulas are the most serious complications in gynecological surgery. STUDY DESIGN: This study included 536 women who underwent radical hysterectomy because of invasive cancer of the cervix uteri. RESULTS: During the surgery the ureter was injured in 1.32% of cases, whereas the percentage of bladder injuries was 1.49. In the early postoperative period vesicovaginal or ureterovaginal fistulas appeared in 2.61% and 2.43% of cases, respectively. CONCLUSION: The stage of the disease, obesity, diabetes, and postoperative surgical infection acted as predisposing factors of the urinary tract complications.

The association between IUGR and maternal inherited thrombophilias: A case-control study.

One of the risk factors for vascular obstetric complications, such as intrauterine growth restriction (IUGR), is inherited thrombophilias. Nevertheless, routine screening for thrombophilias is not endorsed in pregnant women due to their low prevalence and conflicting results of published studies regarding the usefulness of screening in these patients. The cause of IUGR remains unknown in almost 1 quarter of cases. There are no published studies evaluating the association of inherited thrombophilias and IUGR in patients with IUGR of unknown origin. Understanding and preventing IUGR is an important public health concern, as IUGR has been associated with fetal mortality and neonatal morbidity, as well as adverse long-standing consequences. This study aimed to evaluate the prevalence of inherited thrombophilias in IUGR of unknown cause and to test the association between the inherited thrombophilias and IUGR of unknown cause.This study included 33 cases of IUGR of unknown cause tested for inherited thrombophilias and 66 controls individually matched for age, ethnicity, and smoking status.Patients with plasminogen activator inhibitor 1 (PAI-1) and methylenetetrahydrofolate reductase (MTHFR) had significantly higher odds for IUGR of unknown cause (P < .001 and P = .002, respectively) with OR 13.546 (CI 95% 3.79-48.37) and 8.139 (CI 95% 2.20-30.10), respectively. A positive association between other inherited thrombophilias (homozygous 20210 prothrombin gene mutation and homozygous factor V Leiden) and IUGR of unknown cause was also found, P = .096, OR 6.106 (CI 95% 0.72-51.30), although it was not statistically significant (P = .096, OR = 6.106, CI 95% 0.72-51.30).Our results indicate that PAI-1 and MTHFR thrombophilias represent risk factors for IUGR of otherwise unidentified cause.

Oxidative Stress Markers in GnRH Agonist and Antagonist Protocols in IVF.

BACKGROUND: Our aim was to study the effect of GnRH agonist and antagonist protocols of ovarian stimulation on oxidative stress parameters in serum and the influence of oxidative stress parameters change on the outcome of IVF cycles. METHODS: This prospective study included 82 patients who underwent IVF procedures. We determined SOD, MDA and SH groups in serum. Serum samples were obtained between the second and fourth day of the cycle and on the day of HCG administration during ovarian stimulation. RESULTS: Patients were divided into two groups depending on the protocol of stimulation. The mean total and mature oocytes number and number of fertilized oocytes were higher in GnRH agonist group. There was no significant difference in biochemical pregnancy, miscarriage and live-birth rate in both groups. Mean serum SOD was significantly lower, while mean serum MDA and SH groups were significantly higher after ovarian stimulation. Delivery rate was higher in patients without OS while miscarriage rate was higher in patients with OS. CONCLUSIONS: Our study confirmed that there is a difference in the concentration of oxidative stress parameters before and after ovarian stimulation. IVF outcome is better in patients without OS after ovarian stimulation. However, the protocol of ovarian stimulation is neither associated with a change in oxidative stress parameters nor with the outcome of ART procedures.

Survivin and VEGF as Novel Biomarkers in Diagnosis of Endometriosis.

BACKGROUND: The aim of this study was to investigate the role of peripheral blood markers as additional diagnostic tools to transvaginal ultrasound (TVU) findings in the diagnosis of endometriosis. METHODS: This study included 40 patients undergoing laparoscopy for suspected endometriosis from January to December 2012. Preoperative levels of serum CA125, CA19-9, CEA and mRNA expression levels for survivin and VEGF were obtained. Real-time PCR was used to determine relative gene expression. A new diagnostic score was obtained by deploying the peripheral blood markers to the TVU findings. Statistical methods used were Chi-square, Fisher's, Student's t-test or the Mann - Whitney test. RESULTS: There was a statistically significant difference in serum CA125, survivin and VEGF levels in patients with endometriosis and those without endometriosis (p<0.001, p=0.025 and p=0.009, respectively). False negative TVU findings were noted in 3/13 patients (23.1%) with peritoneal endometriosis without ovaries involvement. High sensitivity (93.3%), specificity (90.0%), PPV (96.6%), NPV (81.8%) and accuracy (92.5%) were obtained for a diagnostic score based on TVU and significant peripheral blood markers (CA125, survivin and VEGF). CONCLUSIONS: Determination of serum CA125, mRNA expression levels for survivin and VEGF along with TVU can contribute to higher accuracy of the noninvasive diagnostic tools for endometriosis.

An approach for the improved immobilization of penicillin G acylase onto macroporous poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) as a potential industrial biocatalyst.

The use of penicillin G acylase (PGA) covalently linked to insoluble carrier is expected to produce major advances in pharmaceutical processing industry and the enzyme stability enhancement is still a significant challenge. The objective of this study was to improve catalytic performance of the covalently immobilized PGA on a potential industrial carrier, macroporous poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) [poly(GMA-co-EGDMA)], by optimizing the copolymerization process and the enzyme attachment procedure. This synthetic copolymer could be a very promising alternative for the development of low-cost, easy-to-prepare, and stable biocatalyst compared to expensive commercially available epoxy carriers such as Eupergit or Sepabeads. The PGA immobilized on poly(GMA-co-EGDMA) in the shape of microbeads obtained by suspension copolymerization appeared to have higher activity yield compared to copolymerization in a cast. Optimal conditions for the immobilization of PGA on poly(GMA-co-EGDMA) microbeads were 1 mg/mL of PGA in 0.75 mol/L phosphate buffer pH 6.0 at 25°C for 24 h, leading to the active biocatalyst with the specific activity of 252.7 U/g dry beads. Chemical amination of the immobilized PGA could contribute to the enhanced stability of the biocatalyst by inducing secondary interactions between the enzyme and the carrier, ensuring multipoint attachment. The best balance between the activity yield (51.5%), enzyme loading (25.6 mg/g), and stability (stabilization factor 22.2) was achieved for the partially modified PGA.

Clinical Outcome of a FIGO Stage IV Gestational Choriocarcinoma.

Choriocarcinoma is the most malignant tumor of gestational trophoblastic disease arising from any gestation. It has a tendency toward relapse as well as metastasis. Here, a case of relapsed high-risk choriocarcinoma (FIGO stage IV, WHO score 12) in a 37-year-old female presenting with vaginal bleedings is described. Relapse developed at the site of the surgical scar from hysterectomy that had been performed 2 years earlier. Although the patient was treated with aggressive chemotherapy, she was in a bad general condition and died from infection and liver insufficiency.

Hypersensitivity to Etoposide in case of metastatic gestational choriocarcinoma.

Etoposide is commonly used in the treatment of a variety of neoplasms. Hypersensitivity reactions to etoposide are infrequently reported and include hypotension, hypertension, flushing, diaphoresis, chest discomfort, dyspnea, bronchospasm and loss of consciousness. We report the case of a 39-year-old woman who experienced acute bronchospasm, tachycardia, hypoxia and hypotension. The symptoms resolved within an hour after administration of intravenous fluids, methylprednisolone, diphenhydramine and oxygen. Subsequently, the patient was given etoposide phosphate without incident.

[Term pregnancy after minimally invasive surgical treatment of Herlyn-Werner-Wunderlich syndrome].

INTRODUCTION: Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis represents a complex congenital anomaly, also known in the literature as Herlyn-Werner-Wunderlich (HWW) syndrome. CASE OUTLINE: A 16-year-old patient presented with secondary amenorrhoea and abdominal pain. Her history revealed anorexia nervosa; she had menarche at the age of 14; her menstrual cycles were regular, with progressive dysmenorrhoea. Nine months after the explorative laparotomy performed at the regional healthcare center there was no a definitive diagnosis. Pelvic examination showed a paravaginal pelvic mass located on the right side. Magnetic resonance imaging of the abdomen and pelvis confirmed the diagnosis of HWW syndrome. Transvaginal excision and marsupialisation of the vaginal septum were performed. Regular menstrual cycles were resumed after four years following the treatment of anorexia nervosa. Twelve years after the operation, the patient conceived spontaneously; pregnancy developed in the left non-obstructed uterus. She underwent Cesarean section at the 37th gestational week and gave birth to a healthy female infant. CONCLUSION: HWW syndrome is an uncommon cause of abdominal pain and progressive menstrual discomfort shortly after menarche. It is therefore essential to maintain a high index of suspicion of the existence of this syndrome in such cases, since prompt and adequate treatment prevents the development of complications and allows for preservation of the reproductive potential of both hemi-uteri.

Madelung disease: a rare case associated with gynaecomastia and scrotal involvement.

Madelung disease is rare, and characterised by accumulation of fatty non-encapsulated tissue in the head, neck, shoulders, and upper extremities. The aetiology is not completely known, but the association with alcohol intake is clear. We present a neglected case that was associated with bilateral asymmetrical gynaecomastia. To the best of our knowledge, this is a pattern of involvement not previously reported. The treatment of choice is lipectomy for severe cases and liposuction for less extensive accumulations of fat.

[Application of radial forearm free flap in extraoral soft tissue head and neck reconstruction].

BACKGROUND/AIM: Radial forearm free flap, highly regarded in head and neck reconstructive surgery, is known to be one of the most reliable and versatile flaps. The aim of this study was to illustrate the versatility and reliability of a radial forearm flap in reconstruction of a variety of extraoral head and neck defects. METHODS: During a period 2001-2007 at the Clinic for Maxillofacial Surgery, Faculty of Dentistry and the Center for Burns, Plastic and Reconstructive Surgery in Belgrade, 19 patients underwent microsurgical reconstructions after extraoral tumor ablation in the head and neck region, using fasciocutaneous radial forearm free flap. RESULTS: The overall flap survival rate was 89.5%. The complications that appeared were one partial necrosis and one venous thrombosis that in spite of reanastomosis resulted in a complete flap failure. The donor site healed uneventfully in all patients, except one, who had a partial skin graft failure, that ended in a secondary skin grafting. CONCLUSION: For reconstruction in head and neck surgery, with the need for thin, pliable tissues and a long vascular pedicle, radial forearm flap still remains a primary choice. Because of their multiple advantages, free flaps from the radial forearm is a safe method for reconstruction of a variety of extensive extraoral soft tissue defects in the head and neck region.

Atypical proliferating mucinous tumors of gigantic dimensions.

UNLABELLED: BACKGROUND; Ovarian tumors of low malignant potential (LMP) are also known as atypically proliferating tumors. Ovarian tumors of LPM account for approximately 15% of all epithelial ovarian cancers. Mean age of occurrence is 40 years and they are 15-20 cm in diameter. CASE REPORT: A 32-year-old female patient was hospitalized as an urgent case with a large tumor mass that filled the entire abdomen. Cyst was 100 x 70 cm dimensions belonging to the right ovary and filled with 18 liters of content. Right adnexectomy, resection of the second ovary, as well as biopsy of the omentum were performed. Lymphadenectomy of the right iliac and obturator area was also performed. After receiving definitive histopathological results it was decided to perform a radical reoperation. On the 10th postoperative day relaparotomy, total hysterectomy and left adnexectomy were performed. The patient was released on the 6th postoperative day. She used to come to regular examinations up to date. CONCLUSION: This case is a proof that LMP tumors have low malignant potential, they grow slowly and can reach great proportions.

[Successful application of recombinant activated factor VII in a patient with HELLP syndrome and disseminated intravascular coagulation].

INTRODUCTION: HELLP syndrome represents the form of preeclampsia characterized by moderate hypertension, often with absence of proteinuria and oedema. The frequency of HELLP syndrome in pregnant women with preeclampsia is 10-20%. The clinical course of the disease is characterized by the progressive worsening of mother and fetus condition, which can be stopped only by delivery. Disseminated intravascular coagulation is present in 8% of patients with HELLP syndrome and causes significant morbidity and mortality. CASE OUTLINE: We present a case of HELLP syndrome complicated by intrauterine fetal demise and disseminated intravascular coagulation in trigemelar pregnancy. After all surgical and medicamentous methods to establish haemostasis were exhausted, the patient was treated by recombinant activated factor VII (rFVIIa) in intravenous bolus dose of 90 microg/kg twice, which resulted in satisfactory haemostasis. Side effects of the drug were not registered. CONCLUSION: The application of rFVIIa reduced haemorrhage in our patient, both after the Caesarean section and after hysterectomy, contributing to the patient's full recovery, without neurological sequelae and with preserved renal function. RFVIIa is not an alternative to surgical haemostasis, but its administration should surely be considered before deciding to perform hysterectomy, especially in patients who want to preserve fertility. In cases of postpartum haemorrhage, when bleeding persists even after adequate surgical haemostasis, the administration of rFVIIa is to be considered not only as an alternative to hysterectomy, but also an effort to prevent significant maternal morbidity and mortality.

Tibolone and osteoporosis.

BACKGROUND: We conducted a 5-year prospective, observational, controlled study to assess the effects of tibolone 1.25 mg/day on bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis. METHODS: The subjects were 420 women, an average of 66.4 years old, who had been postmenopausal between 8 and 19 years when enrolled in the study. Of the 420 women enrolled, 346 agreed to take tibolone for 5 years. The 74 who refused tibolone took only calcium/vitamin D supplements and served as the control group. BMD was measured in the lumbar spine and total hip region at baseline and annually by dual-energy X-ray absorptiometry (DXA). RESULTS: At the first two follow-up visits, women taking tibolone had a significant increase in BMD at the spine (P < 0.001) and at the hip (P < 0.001) when compared to baseline values and when compared to BMD values for the control group, which decreased from baseline. In the final 3 years of the study, BMD values (spine and hip) continued to decrease in the control group and also tended to decrease in the tibolone group, but at the end of the fifth year, mean BMD in the tibolone group was still higher than BMD before the start of tibolone treatment (P < 0.05). Calculations showed that if women taking tibolone continued to lose BMD at the same rate as during the final 3 years of the study, after 11 years of tibolone treatment the average patient would have the same BMD as she had when treatment started. CONCLUSION: This 5-year observational study provides evidence that tibolone is effective in increasing BMD in postmenopausal women with osteopenia and osteoporosis during the first 2 years of treatment, but because BMD starts to decline in the third year, it is vital that postmenopausal women start treatment with tibolone as early as possible, so that bone mineral density levels are kept high as long as possible.