Interactions of metronidazole with other medicines: a brief review.

Metronidazole, a medicine discovered in the late 1950 s is mainly an antibiotic active against anaerobes and protozoa. There are numerous side effects of metronidazole. Some interactions with other medicines enhance its activity, and some cause the decrease in activity and plasma concentration. A short review of its side effects, mechanisms of action and interactions with other medicines is provided. As resistance towards metronidazole occurred, these mechanisms are described as well. The data presented in the review were selected on the basis of relevancy, citation and age of the used references.

Correlation of progesterone levels on the day of oocyte retrieval with basal hormonal status and the outcome of ART.

This study aimed to assess whether basal hormonal levels can predict the levels of progesterone (P4) on the day of oocyte retrieval (OR) and examine the impact of P4 levels on the day of OR on the outcome of assisted reproduction. One hundred sixty-four patients that were enrolled in the assisted reproduction procedure were classified according to their P4 levels on the OR day (< 2 ng/ml vs. ≥ 2 ng/ml). Patients who had P4 levels < 2 ng/ml had significantly higher follicle stimulating hormone (FSH) levels and significantly lower anti-Mullerian hormone (AMH) levels. More than half of patients with P4 levels < 2 ng/ml on the OR day got pregnant and delivered healthy infants. There was a significant correlation between lower FSH values and higher P4 values at OR and between higher AMH values and higher P4 values on the day of OR. Regression analysis showed that high FSH levels are the most important factor that can reliably imply lower P4 levels on OR day. Our study confirmed that lower basal FSH levels can predict the levels of P4 on the OR day. Moreover, lower levels of P4 on the day of OR are associated with a positive outcome in assisted reproduction.

Stimulated electron-acoustic-wave scattering in a laser plasma.

Intense laser-plasma interaction can be a source of various electronic instabilities. Recently, stimulated backscattering from a trapped electron-acoustic wave (SEAS) [Montgomery et al., Phys. Rev. Lett. 87, 155001 (2001)] was proposed to reinterpret spectra previously attributed to stimulated Raman scattering (SRS) from unrealistically low densities. By particle simulations in a uniform plasma layer, which is overdense for ordinary SRS, strong reflection by SEAS at the electron plasma frequency is found. Transient SEAS reflectivity pulsations are followed by strong relativistic heating of electrons. Physical conditions are explained by three-wave parametric coupling between laser light, standing backscattered wave and slow electron-acoustic wave. Regions in which SEAS reflection can dominate over SRS are singled out.

Mechanism and kinetics of synthesis of allicin.

Allicin, allyl-thiosulfinate, a pharmacologically active compound with considerable fungicidal, bactericidal, antioxidant and anticarcinogenic effects, was obtained by oxidizing allyl disulfide with acid hydrogen peroxide. The synthesis mechanism was studied by the ESR spin trap method. The kinetics of allicin synthesis was ascertained by determination of the concentration of the limiting reactant during the synthesis using HPLC and it was found that the allicin synthesis reaction was of zero order. The allicin obtained was determined using UV, FT-IR, MS, 1H and 13C NMR analysis.

Allylthiosulfinate: beta-cyclodextrin inclusion complex: preparation, characterization and microbiological activity.

An allylthiosulfinate: beta-cyclodextrin inclusion complex was synthesized and characterized using X-ray crystallography, IR spectroscopy, thermal analysis and nuclear magnetic resonance. The microbiological activity of the complex was tested on available fungi (Candida albicans ATCC 10231, Aspergillus niger ATCC 16404) and bacteria (Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 9027). In small concentrations, the complex inhibited the growth of the microorganisms tested. The most susceptible microorganism was Candida albicans ATCC 10231, and the least susceptible Pseudomonas aeruginosa ATCC 9027.

Independent complexity patterns in single neuron activity induced by static magnetic field.

We applied a combination of fractal analysis and Independent Component Analysis (ICA) method to detect the sources of fractal complexity in snail Br neuron activity induced by static magnetic field of 2.7 mT. The fractal complexity of Br neuron activity was analyzed before (Control), during (MF), and after (AMF) exposure to the static magnetic field in six experimental animals. We estimated the fractal dimension (FD) of electrophysiological signals using Higuchi's algorithm, and empirical FD distributions. By using the Principal Component Analysis (PCA) and FastICA algorithm we determined the number of components, and defined the statistically independent components (ICs) in the fractal complexity of signal waveforms. We have isolated two independent components of the empirical FD distributions for each of three groups of data by using FastICA algorithm. ICs represent the sources of fractal waveforms complexity of Br neuron activity in particular experimental conditions. Our main results have shown that there could be two opposite intrinsic mechanisms in single snail Br neuron response to static magnetic field stimulation. We named identified ICs that correspond to those mechanisms - the component of plasticity and the component of elasticity. We have shown that combination of fractal analysis with ICA method could be very useful for the decomposition and identification of the sources of fractal complexity of bursting neuronal activity waveforms.

Conservative treatment vs phonosurgery.

In Phoniatric Dpt. everyday practice we try to keep specific multidisciplinary approach to the communication disorders, that includes an expert team using modern technology. Over the last six years we have treated 110 singers (3% of all new cases) and the results of their diagnostic and therapeutic management are presented here. There were 67 women and 43 men, 41 were smokers and 69 nonsmokers. The singing genres included 24 pop, 41 folk, 8 ethnic, 29 choral and 8 opera singers. The therapy success was compared with the demographic parameters, level of education and music genres across the subjects. A precise history, clinical examination, endovideolaryngostroboscopy and multidimensional computer analysis of voice and speech was carried out by two phoniatricians, two logopeds, two nurses and one clinical psychologist. Additional consultations were carried out by audiologists, allergists, endocrinologists, chest physicians, gastroenterologists and neurologists where necessary. We suggest that the gold standard is conservative therapy, with phonosurgery if conservative measures fail. We also suggest that an annual systematic examination is optimal in preventing disease in professional singers.

Patient with double cancer--successfully treated.

INTRODUCTION: Etiology of thrombosis in malignant diseases is multifactorial, and mechanisms that lead to thrombosis include release of the procoagulants from tumor cells (PC), factor related to bed rest, infections, as well as oncological therapy --chemotherapy, hormones, radiotherapy and surgical treatment. Thrombocytosis has frequently been found to be associated with various malignancies. CASE REPORT: 53 years old female patient hospitalised because of hypopharingeal cancer with metastasis in the left neck. Her state was complicated with deep leg vein trombosis and pseudomonas infection. Persistent thrombocitosis in laboratory monitoring indicated more adequate diagnostic procedures, which led to discovering of Chorioidal Malignant Mellanoma as a second cancer. She was treated: surgically, with antibiotics, with anticoagulants and radiotherapy. Patient was discharged from the hospital in good health condition, free of any other symptom of the malignant disease. CONCLUSION: Presense of thrombocytosis and idiopatic thrombosis can suggest occult malignancy. It would be prudent to further evaluate the relationship of trombotic events, trombocitosis and head and neck tumors. We suggest anticoagulants to prevent thromboembolic complications, affect the angiogenesis and prevent development of metastatic disease. It may lead to lower mortality rate.

[Surgical treatment of destructive diseases of the cornea]. / Hirursko lecenje destrukcionih bolesti roznjace.

The role of surgery in destructive corneal disease is: to protect cornea; remove the cause of the disease; remove the altered tissue and transplant the healthy one; and to repair ocular surface. This can be achieved by penetrating keratoplasty, lamellar keratoplasty, sclerokeratoplasty, keratectomy, peritomy, conjunctival transplantation or keratoepithelioplasty. Some of the combinations of these surgical techniques in our hands are presented, and the relevant literature is reviewed.

[Angiogenesis]. / Angiogeneza.

Angiogenesis, the budding of new vessels from the preexistant capillaries and postcapillary venules, is an important biological phenomenon during reproduction, embryogenesis, and reparation. The sequence of events during angiogenesis includes the proteolysis of basement membranes and extracellular matrix, proliferation, migration and alignment of vascular endothelial cells, and the union of two buds into a vascular loop along the lines of traction and tesselation in the extracellular matrix. This change of phenotype seems to be necessary for the growth of many tumours, and for the enlargement of "dormant" metastases. It is influenced by a change of equilibrium between positive and negative regulators of angiogenesis, largely a family of angiogenic peptides with the affinity for heparin (that may be bond in an inactive state within basement membranes and activated by any lesion) on one side, and circulating suppressors of angiogenesis and tumour growth, thrombospondin and angiostatin, on the other side. Clinical evaluation of some of the two dozen known angioinhibitors for the treatment of age-related maculopathy, certain tumours, metastases and malignang ascites, is underway.

[On the threshold of new treatment of diabetic retinopathy]. / Na pragu drukcijeg lecenja dijabeticke retinopatije?

The introduction of ocular photocoagulation, almost thirty years ago, was the first successful prevention of blindness from diabetic retinopathy in some patients. The development of lasers, and the growing knowledge of indications for their application, reached the point at which the growth of new blood vessels could be stopped or reversed, and legal blindness from macular oedema avoided in about half of the treated eyes. The attempts at the very prevention of diabetic retinal microvascular complications at some more physiological, even molecular level, aside from the palliative treatment by photocogulation, brought some new and exciting results which are reviewed here. First, and foremost, is the understanding of the importance of the tight blood glucose control which, if started early and kept long enough, slows down the development of retinal lesions and offers a better prognosis for vision in a substantial number of diabetic patients. Second, the development of a unique animal model of proliferative retinopathy which mirrors human disease both chemically and histopathologically offers a field for investigation of both pathogenesis and therapy of this most dreadful complication of diabetes. Finally, there is a bulk of new evidences about the key role of vascular endothelial growth factor/vascular permeability factor in ocular angiogenesis which will probably result in the new approach to the prevention of neovascular growth by inhibition or modulation of VEGF/VPF activity.

[Electroretinography findings in the other eye in patients with central retinal vein occlusion]. / Elektroretinografski nalaz na drugom oku kod bolesnika s okluzijom centralne vene mreznjace.

ERG assessment in 32 patients with recent OVCR was done over the period of 6 years. The aim was to check the hypothesis whether ERG values in the affected and "healthy" eye of the same patient are same. The control group consisted of patients of the same age but without eye disease. Scotopic "b" wave and photopic b/a ratio, known as indicators of oxygenation of the retina, were studied. In bs wave and b/a ratio the statistically significant difference between the group with OVCR and the other groups was found. Other groups showed no significant differences. The hypothesis that OVCR associated with a systemic disease is necessarily accompanied with changes in the other eye, has been challenged. However, the safety of the other eye is not absolute.

[Inhibition of angiogenesis in the cornea with amiloride]. / Inhibicija angiogeneze roznja ce amiloridom.

INTRODUCTION: For its transparency, avascularity and possibility of measurement of the new vessels ingrowth, cornea is a frequent model for angiogenesis research. New vessels are made in several phases: after the action of the stimulus, there is a localised fragmentation of the basal membrane and the extracellular matrix around the involved capillary. Then, endothelial cells migrate through the openings in the capillary wall and the lysis of the extracellular matrix continues as a new vessel is being formed. Enzymes, plasminogen-activators, convert plasminogen from the blood and tissues to plasmin which starts proteolytic cascade of the lysis of the extracellular matrix. Amilorid, previously known as a diuretic, is found to be a competitive inhibitor of plasminogen activator-urokinase (u-PA). Its effect was shown in the prostaglandin-induced model of corneal vascularization [6]. PURPOSE: The purpose of this work is to show that amilorid acts as an angiostatic in the traumatic model of corneal vascularization. MATERIALS AND METHODS: There were two groups of experimental animals (rabbits, weight 1.5-3 kg). Deepitelisation and trephination were performed on all corneas (traumatic model of vascularisation). The first group of animals (17 eyes) was given 15 mg of amilorid (Sigma) intraperitoneally for five days, while the control group consisted of 7 eyes. Neovascularization was measured after 5 and 15 days. Animals were sacrificed on day 15. Three eyes from each group were tested for corneal wound tensile strength. RESULTS: In the experimental group there was a 0.5 mm ingrowth of the new vessels after the first five days and no further ingrowth till the end of the experiment. In the control group there was a 2 mm ingrowth after five days, and a further 1 mm after the next ten days. No statistical difference was found with regard to tensile strengths of the corneal wounds between the two groups. DISCUSSION: Although the traumatic model is closer to the clinical situation than the prostaglandin-induced vascularization model, more potential angiogenic factors are involved. Trephination damages basal membrane which may liberate angiogenic substances (heparan-sulphate, for example) [9]. Products of damaged cells attract leucocytes by haemotaxis. Also, hyopxia in the depth of the wound may be the site of macrophage induced angiogenesis [10]. It is difficult to say at which point amilorid acts but, considering the new vessel ingrowth for only 0.5 mm, it might be at the beginning of the process (lysis of extracellular matrix). CONCLUSION: Amilorid acts as angiogenesis inhibitor in the traumatic corneal vascularization model without changing the tensile strength of the wound.

[Allergic contact dermatitis in women]. / Kontakni alergijski dermatitis kod zena.

In everyday life, including the professional obligations, women are exposed to a great number of allergens leading to contact sensitization. In order to evaluate the aetiology, frequency and other features of allergic contact dermatitis in women, the results of epicutaneous testing in housewives (I group) and employed women (II group), were analysed. Clear distinctions were observed in relation to the place of residence, the age, the localization of some changes on the skin, the kind of allergens, the frequency of the allergens, etc. Among the women from the second group a significantly high number of allergens to which they were occupationally exposed was recorded.

[Role of electroretinography in the prognosis of central retinal vein occlusion]. / Uloga elektroretinografije u prognozi okluzije centralne vene retine.

UNLABELLED: The aim of the study is to evaluate the role of electroretinography in diagnosis of central retinal vein occlusion CRVO. There are two forms of this entity, each of them having a different prognosis. While haemorrhagic form has a better outcome, with fairly good prognosis for vision, ischaemic form usually develops many complications: macular oedema, neovascularisation of the retina or optic disk, neovascular glaucoma, and possible blindness. Three months after the onset, when oedema and retinal haemorrhages are usually resolved, it is possible to perform fundus fluorescein angiography (FFA) and make differentiation between the two forms of the disease. However, neovascular glaucoma may challenge the vision even before the diagnosis of ischaemic form becomes possible by observing the fundus or by performing FFA. Trying to foresee the course of the disease, and thus to help a patient with panretinal photocoagulation, we performed electroretinography (ERG) in each patient just after the onset of the disease. The prospective study included 40 patients with CROV which lasted less than three months and without any complication. Two parameters were examined: scotopic "b" wave and photopic b/a ration. By ERG action potentials from the retina after its stimulation with light, are recorded. Scotopic "b" wave generates in bipolar layer from Muller's and bipolar cells. Photopic b/a ratio is a ration of two waves, "b" and "a" in photopic conditions and is a good indicator of saturation of the retina with blood and oxygen. Visual acuity, applanation tonometry, examination of the fundus after dilatation of pupils with Sol. Mydriacili were performed in each patient. Each patient was examined by ERG in scotopic and photopic conditions. The results were as follows: Scotopic b wave per se could not indicate potential complications, while b/a ratio was a good predictor of possible complications when its value was less than 1.25. CONCLUSION: Electroretinography, which can be performed at any time after the onset of the disease may be a good indicator of retinal perfusion and oxygen saturation, by giving the ratio of b and a waves under photopic conditions. The status of Muller's cells and bipolar cells is reflected in the scotopic b wave. In a prospective study forty patients with CRVO of less than three months duration and without neovascularisation were studied with the use of ERG, both in scotopic and photopic conditions. Our results suggest that the b/a ratio may be a good predictor of the development of retinal, disk and iris neovascularisation by showing the degree of retinal ischaemia, while the scotopic b wave cannot be used for such evaluation. Predicting the new vessel development by ERG may save the useful vision and prevent a disastrous outcome, blinding and painful neovascular glaucoma by performing panretinal photocoagulation.

[Ipsilateral surgery of primary pterygium, sensory esotropia and conjunctival autotransplantation in a single procedure]. / Ipsilateralna operacija primarnog pterigijuma, senzorne ezotropije i konjuktivalni autotransplantat u istom aktu.

The purpose of this study was to find out whether a conjunctival autograft over the recessed bulbomotor muscle can prevent a recidive of an inflammatory internal pterygium associated with strabismus. The fast growing internal pterygium (crossing corneoscleral limbus of the right eye 3-4 mm towards the centre of the cornea) in a 42 years old patient, was removed by superficial keratectomy, while strabismus was corrected by the recession of the internal rectus muscle and covered with an autograft of the upper bulbar conjunctiva. Neither collagen vascular diseases, nor dry eye were present. Horizontal deviation was lessened from +12 to +6, after surgery, and the regrowth of the inflammatory pterygium was not observed during a five years follow up. The risk of the reappearance of pterygium at the site of muscle surgery for strabismus might have been avoided by creating a smooth ocular surface over a thin conjunctival autograft without Tenon's capsule. We believe that conjunctival autograft in such eyes, carrying a higher risk for pterygium regrowth, may help in the avoidance of the use of cytostatic drugs and on their untoward effects.

[Optimal standard series of allergens--a condition of successful detection of etiology of allergic contact dermatitis]. / Optimalna standardna grupa alergena--uslov uspesnog otkrivanja etiologije kontaktnog alergijskog dermatitisa.

Standard series of allergens should enable a successful detection of etiology of allergic contact dermatitis (ACD), the intention, to detect allergens occuring in performing the largest number of professions that would sooner approach the results and patients would most commonly be saved of additional testing procedures. There are standard series of allergens recommended by the official associations detecting ACD, as well as many modifications, depending on research workers' experience in certain living and working surrounding. The aim of this work is to point to necessity of creation of optimal standard series of allergens which would be accepted by all those who deal with this problems on our areas. Constitution of various standard series applied both elsewhere and with us is analyzed,comparison to own previously gained experiences is made, and so on. An agreement about edoption of unique standard series of allergens is suggested by which further follow-up of results and inprovement of the same would be enabbed.

[Occurrence of changes in the eye in diabetic retinopathy with significant myopia]. / Ucestalost promena dijabetesne retinopatije na oku sa znatnom miopijom.

The optic disc and retinal neovascularization are less prominent and less frequent in myopic eyes in patients suffering from diabetes mellitus. The exact mechanisms of this phenomenon are not well known, but there is some evidence that there is a reduced blood flow in myopic eyes which is associated with less damaged microcirculation in eyes of patients with diabetes mellitus. The aim of our study was to evaluate the correlation between myopic refractive error and degree of diabetic retinopathy. We conducted a retrospective study in a group of randomized patients, divided into the following groups according to their refractive error: emmetropia (30 eyes), myopia simplex (30 eyes) and high myopia, over -6.5 dsph (21 eyes). Among patients with high myopia, seven had monocular myopia. All patients suffered from non insulin dependent diabetes mellitus for more than ten years, and their average age was 52.37-3.48 years. We did not observe patients with rubeosis iridis and neovascular glaucoma or patients with myopia less than -2.0 dsph. Our results indicated that there was no significant difference in the appearance of fundus between the studied groups. In all patients the incidence rate of non proliferative and proliferative diabetic retinopathy was the same as well as the absence of retinopathy (Fisher's test). The only exception were the patients with monocular myopia over -13.o dsph who had no signs of diabetic retinopathy in myopic eye, while the other, emmetropic eye, showed various stages of retinopathy, from severe non proliferative to proliferative. Some of the risk factors which influence the incidence rate of ocular complications in diabetic patients are well known, as are duration of diabetes mellitus, blood sugar level, blood pressure, ocular pressure and eye perfusion. On the other hand, it is also known that amblyopia, optic atrophy, low blood pressure in central retinal artery and retinitis pigmentosa are ocular conditions which are not associated with proliferative diabetic retinopathy. It was also noticed that complications of diabetes in high myopic eyes are less prominent than in emmetropic eyes. This finding is in harmony with our results. Sultanov et al. observed diabetic changes in the retina in 40.9% of myopic refraction patients, 65.2% of emmetropia cases and 70.4% of hypermetropia cases. The severity of involvement was less in myopia than in other types of refraction. In medium severe myopia, no proliferative diabetic retinopathy was observed, and in high myopia (10 eyes) no diabetic involvement of the fundus oculi was found. In anisometropia diabetic symptoms on the myopic side were either absent or poorly manifest. The possible cause of such findings could be the changes in retinal perfusion in myopic eyes and eyes in patients with diabetes mellitus. In 1973 a lower blood flow was detected in the retina and the choroid, proportionally to the degree of myopia. In 1982, Perkins indicated that the circulation time and pulsation rate in the central retinal artery in myopic eyes were reduced proportionally to the degree of myopia. In cases with early diabetic retinopathy Coscas detected a lesser blood flow in retinal veins. On the other hand, it has been found that high blood pressure increases the risk of diabetic retinopathy. These data suggest that the reduced blood flow in high myopia is a protective factor regarding the occurrence of complications in diabetes. Anisometropia and amblyopia in cases with monocular myopia, which presents a particular group in our study, could be factors which also prevent the occurrence of proliferative diabetic retinopathy. Instead of conclusion, we would like to point out that pathophysiologic mechanisms of these phenomena are not discussed enough. It is, nevertheless, important to appropriately examine the fundus in patients with high myopia and diabetes mellitus, because if the complications appear, they may be disastrous and must be treated immediately.

[Human placental lactogen levels in normal pregnancy monitored by serial ultrasound]. / Nivoi humanog laktogena (HPL) u fizioloskim trudnocama monitorovanim serijskim ultrazvucnim pregledima.

Parallel to the great use of ultrasound in diagnostical purposes the interest for biological effects of ultrasound is growing every day. The present studies of the biological action of ultrasound concerned the cytogenetic investigations as well as those of animals and men. Taking into account that the extrapolation of results from animals to men is uncertain all data obtained in human population are of utmost importance. We tried to define the possible biological action of routine diagnostical ultrasound on foetoplacental unit. Women with physiological pregnancy were exposed to ultrasound during regular antenatal control-examinations in the 20th, 30th and 38th week of gestation. The follow-up concerned HPL levels in the serum 1 hour before and 1 hour after exposure to ultrasound. There was no significant difference in concentrations of the examined hormone in both blood samples.